108th ACNW Meeting U.S. Nuclear Regulatory Commission, March 23, 1999

UNITED STATES OF AMERICA
NUCLEAR REGULATORY COMMISSION
***
108TH ADVISORY COMMITTEE ON NUCLEAR WASTE
(ACNW)

Nuclear Regulatory Commission
Room 2B3
Two White Flint North
11545 Rockville Pike
Rockville, Maryland

Tuesday, March 23, 1999

The above-entitled meeting, commenced, pursuant to notice at
8:32 a.m.

MEMBERS PRESENT:
DR. JOHN B. GARRICK, Chairman, ACNW
DR. GEORGE W. HORNBERGER, Vice Chairman, ACNW
DR. CHARLES FAIRHURST, Member, ACNW
DR. RAYMOND G. WYMER, Member, ACNW
. PARTICIPANTS:
DR. ANDREW CAMPBELL
MS. MARY L. THOMAS
DR. OTTO RAABE, ACNW Consultant
DR. KIM KEARFOTT, ACNW Consultant
MR. RICHARD P. SAVIO, ACNW Staff
MR. RICHARD K. MAJOR, ACNW Staff
MR. MICHAEL HALUS, Facilitator
GRETA JOY DICUS, Commissioner
DR. ARTHUR UPTON, NRCP Scientific Committee
MARVIN FRAZIER, Department of Energy
EVAN DOUPLE, NAS Board on Radiation Effects
Research
DR. EDWARD J. CALABRESE, University of
Massachusetts
CHARLES MEINHOLD, ICRP
MYRON POLLYCOVE, NMSS
KEITH DINGER, Health Physics Society
ALEX FLINT, Senator Domenici's Staff
PETE LYONS, Senator Domenici's Staff
JERRY PUSKIN
RALPH ANDERSEN
CHARLES LAND, National Cancer Institute
THEODORE ROCKWELL, Radiation Science and Health,
Inc.. P R O C E E D I N G S
[8:32 a.m.]
DR. GARRICK: Good morning. The meeting will now come to
order. This is the first day of the 108th meeting of the Advisory
Committee on Nuclear Waste. My name is John Garrick, Chairman of the
ACNW. Other members of the committee include George Hornberger, Ray
Wymer and Charles Fairhurst.
We are pleased to have with us today Dr. Dana Powers,
Chairman of our sister committee, the Advisory Committee on Reactor
Safeguards.
The ACRS and the ACNW have identified a number of areas of
interest to both Advisory Committees, and while we will be working
together on all such issues, we agreed that the ACNW should take the
lead on the issue of low levels of ionizing radiation because of the
impact on managing nuclear waste.
In addition to Dr. Powers, we are pleased to have two
consultants, Dr. Otto Raabe and Dr. Kim Kearfott. We are glad you made
it.
The entire meeting will be open to the public. During
today's meeting, the committee will hear presentations on the status of
the linear nonthreshold model from representatives of national and
international radiation protection advisory groups, government and
academic research groups and the nuclear power industry. Following
these presentations will be a panel discussion.
Because of the controversial nature of this topic, and
strongly held positions, an impartial facilitator, Mr. Michael Halus, on
my right here, is available to ensure that this meeting remains
collegial and that all views can be heard.
Mr. Halus will be helping us keep track of time for all
presentations and statements from the floor. Any statements from the
floor that run longer than the suggested time of five minutes can be
supplemented by a statement in writing to the committee. And please be
advised that these statements will become a part of the official record
of this meeting.
Again, we ask the participants to conduct themselves
professionally, display courtesy and respect for all presentations and
views expressed.
Howard Larson is the designated federal official for today's
session. The committee wishes to acknowledge the efforts of the ACNW
staff in organizing what we believe will be an outstanding meeting. In
addition to Howard, we especially want to recognize Mary Thomas for her
excellent assistance in pulling this together. The meeting is being
conducted in accordance with the provisions of the Federal Advisory Act.
We have received a request from Theodore Rockwell of
Radiation Science and Health, Inc. to make an oral statement regarding
today's session. One written statement has been received from James
Muckerhyde and Myron Pollycove. Should anyone else wish to address the
committee, please make your wishes known to one of the committee's
staff. And, as usual, it is requested that each speaker use one of the
microphones, identify himself or herself and speak with sufficient
clarity and volume so that they can be heard.
Also, I am told that not everybody in the room has signed
in. Please, we ask you to do that in the interest of an accurate
record.
It is now my privilege to introduce Commissioner Greta
Dicus, who will provide some opening remarks. Commissioner Dicus is a
two-term Commissioner who has extensive experience as a heath physicist,
research scientist, medical school instructor, radiation health
director, and corporate board member. Commissioner Dicus.
COMMISSIONER DICUS: Thank you very much. I am clearly
pleased to be able to spend a few moments with you at the beginning of
what I think we will all find, and I think you certainly will find, to
be two days of rather thoughtful and challenging debate on this very
important but somewhat controversial subject, which is the role of the
linear nonthreshold theory, and the role of that theory is radiation
protection.
I would also like to add my congratulations to the committee
staff. I think you have done a marvelous job of assembling an
outstanding group of speakers who are all well qualified to discuss the
theory and the arguments concerning the use of this theory versus the
use of other theories. So, for that reason, in my prepared comments, at
least, I am not going in any depth into the theory itself, I want to
talk more on how it impacts those of us who must develop radiation
protection standards in a regulatory environment.
I just want to say a few words about why I think this
subject is so very important to the Nuclear Regulatory Commission, to
our licensees, and, of course, to the public that we serve. Let me say
at the onset that the NRC is pledged, and we are repeatedly making this
pledge, to move towards a risk-informed, ultimately performance-based
regulatory approach.
If this approach is applied to the setting of radiation
protection standards for the public and the environment for protection
from the risk resulting from radiation exposure, then there are two
things that we must assure: (1), that the standards will be protective;
and, (2), that the costs for complying with those standards are
justified by the risk that would result if the standards were not met.
Now, although there are some in the radiation protection
community who will argue that present radiation protection standards are
not sufficiently protective, this is a minority view and it is not the
source of the present controversy. Most radiation protection officials,
professionals, will agree that the present standards are protective, and
some will even say that they are over-protective.
The controversy arises from the plain economic fact that
there are costs associated with compliance with radiation protection
standards. As the compliance cost rises, the numerical standards are
lowered. Worse, the costs rise at a nonlinear, and some would say
exponential rate. There is no mystery about why this occurs.
For example, examine what it means to demonstrate compliance
of a decontaminated site with license termination standards.
Demonstrating compliance means distinguishing within an acceptable
degree of statistical uncertainty the radiation from the residual
activity from background radiation. The lower the standards, then the
smaller is the standard relative to background levels of radiation.
Worse, background radiation itself, as we all know, is not consistent,
because, obviously, it varies with location, it varies with time, it
varies with other situations.
Therefore, attaining an acceptable degree of statistical
uncertainty in compliance measurements at near background levels
requires extensive, complex sampling and analyses, with the attendant
costs.
Now, I would recommend to you, and I think many of you are
familiar with this, but the reading of a summary of these difficulties
and their associated costs that was written by former Commissioner, Gail
De Planque, who, prior to joining the commission, was director of the
DOE's Environmental Measurement Laboratory and is a world-renowned
expert on environmental radiation. I am referring to her paper, "In
Search of Background," which was in "Radiation Protection Measurements,"
May-June 1995. It is an excellent thesis on this subject.
Then when you add to the costs of demonstrating compliance
the cost of designing and operational activities such as decontamination
to meet the standards, it becomes even more expensive. To paraphrase
Senator Everett Dirksen, a few million here for design and operations to
meet the standard, a few million there to demonstrate compliance with
the standard, and after a while, you are talking about some real money.
But whose money is it? Well, ultimately, it is yours and
mine, the public's. Whether we pay for it as electric rate-payers for
the decommissioning of nuclear power plants, or as taxpayers to fund
cleanup of DOE sites, there is no uncertainty that these costs exist,
and there is no uncertainty about who ultimately pays for them.
But what about the risk of health effects from low level
radiation? There is no uncertainty about them. If there is uncertainty
about the risk of health effects from low level radiation, how then
should this commission factor this into our decisions on radiation
protection standards as we seek to pursue the risk-informed,
performance-based regulatory approach?
So, I am going to summarize briefly, and, as I have
promised, I have not spoken, in my prepared comments at least, about the
scientific details with the linear-nonthreshold controversy. But what I
am trying to emphasize to you in your deliberations is the seriousness
of the controversy. I have tried to explain why it is serious to those
who must implement radiation protection programs, and I have left you
with a fundamental question about how the commission should deal with
the controversy in the context of our pursuit of a risk-informed,
ultimately, performance-based regulatory structure.
Applying this approach to the setting of radiation
protection standards is perhaps its most fundamental application and
quite probably its most challenging. It could however provide to be its
most rewarding application.
As I have said, I have been extremely brief this morning. I
have you well ahead of schedule, but I thought with those opening
comments if you wanted to get into some discussions or question-answer
it would be useful to have the time to do that, so I thank you.
DR. GARRICK: Excellent. I think there might be a question
or two. Yes, go ahead.
DR. RAABE: I am Otto Raabe. Greta, that's a very good
introduction. I have one question.
If it's not possible to estimate the risk with any degree of
certainty at low doses, how can you have a risk-informed approach?
COMMISSIONER DICUS: I think that is one of the obviously
good questions, one of the things that we are struggling with ourselves,
but I think it is what we are attempting to do. If we cannot with
certainty know what the risks are at these extremely low levels, and we
are approaching getting the area background, then it drives to a large
measure the NRC's desire to be careful about going to extremely low
levels when we know the risk is small.
We may not know exactly what it is but we know that it is
small. The problem is the error bars in trying to determine what that
risk is are rather large especially in the area of background but our
ability to measure these levels is much better so we have this aspect
trying to find its way around inside here.
It becomes difficult. That is partly driving us not to want
to lower radiation standards beyond where we have them at the moment and
given the fact that it may not be truly -- well, it's not risk-based, it
is risk-informed. I think we can deal with the risk inside that
uncertainty, so long as we don't go too much lower.
DR. GARRICK: I think there is a comment there that I would
like to just add to that.
I think there is a great deal of confusion outside the risk
assessment community about what is meant by quantification. If in fact
by quantification you embrace uncertainty -- in other words, if you
display what your uncertainty is to the best of your ability, it is
quantifying, so in principle then you can always quantify the
uncertainty. You just may not like the answer or the outcome, but you
can quantify it.
You very often find that even though the uncertainty is
great, as it is with things we calculate routinely like core damage
frequency, the core damage frequency in a reactor's uncertainties, if
you account for model uncertainty as well as information uncertainty,
maybe as much as 10 to 100, and yet that is hardly ever discussed but
that is the way it is.
There are no absolutes, so the uncertainty is always there
and what we are trying to do a better job of with the point of view of
risk-informed is to recognize that rather than just wring our hands
about it, I am talking about uncertainty, let's see if we can put down
what it really is and let's see if we can display the uncertainties in a
manner that communicates what it is, so I think that is part of the
problem. Yes, go ahead.
DR. KEARFOTT: I have two questions. My first question is
what degree of improvement in uncertainty, in risk estimates, would be
acceptable in order to effect a change in standards or regulatory
approach?
COMMISSIONER DICUS: I don't know if I can give you -- I
can't give you a quantitative answer. I don't know what the degree that
we would want. To better understand perhaps the mechanisms would lead
us to being able to have a greater comfort level and maybe narrow down
some of the uncertainties in the risk estimates so that the error bars
are not quite as large as they are at the moment, so I think mechanisms
might drive us a little bit more than some quantification of the degree
of reduction or improvement in absolute known risk.
Now obviously if somehow or the other in this we continue to
study the issue we are able to better answer the question of whether the
linear non-threshold theory is accurate or rather what really happens at
these low dose rates or if we are able to get better information on the
dose and dose rate effectiveness factor and what that might be. This
will help us too. Anything that might be able to narrow the uncertainty
limits is always going to be helpful.
You had a second question.
DR. KEARFOTT: Yes. It is kind of unrelated but it seems
the cost issue could also be approached by doing research and attacking
the cost of both the remediation aspects and the measurements aspects,
and I wondered if anyone was looking at that or how that would also
enter into this, that you could actually reduce through technologies the
cost of cleanup, the cost of measuring compliance.
COMMISSIONER DICUS: I think we can get to the point where
we can do that. That is certainly another way to attack the issue, but
right now I think trying to demonstrate the compliance with the
technology that we do have available, it simply is very costly and that
hasn't changed.
DR. GARRICK: Thank you. Other questions? Ray?
DR. WYMER: Nope.
DR. GARRICK: One of the things that I did want to comment
on, the cost issue -- given that you have suggested that the controversy
is economic-based or at least driven to a large extent by economic
considerations, and given the fact that the NRC has a tendency to be
criticized whenever they do anything in the name of economics. Do you
see that as a problem in any direction that the NRC might take with
respect to implementation of risk-informed, performance-based
philosophy?
COMMISSIONER DICUS: Let me first make a comment about that.
I actually think the controversy is more steeped scientifically. It may
have implications of cost though for the NRC, as has been pointed out.
DR. GARRICK: Right.
COMMISSIONER DICUS: And from that perspective we have to
deal with it. If society is willing to pay the cost then we pay it and
we go to a standard that society has agreed that it will pay for, but if
society is not willing to pay the cost then we do have to take that into
consideration.
DR. GARRICK: Yes. Dana?
DR. POWERS: There's some interesting work done in the
systems engineering field on decontamination and decommissioning of
facilities and when you are confronted with stringent regulatory
restrictions on your dosage that you can have to your working population
you almost immediately conclude that the biggest cost in decontaminating
and decommissioning a facility is cutting big things up into little
things, and when you foreclose the ability to move big things into a
disposal facility you force those costs on to the engineering corps, so
you have a problem in what the public is wiling to pay.
They are willing to pay to cut big things up into little
things and they are not willing to pay the societal costs of disposing
of big things.
I think somehow you have to -- that there is a color to this
money that the society is paying that has to be recognized because it
really forecloses a lot of engineering options that a systems engineer
could envision when he has to confront these stringent regulations.
COMMISSIONER DICUS: That's a good point. Of course, we
know that the Trojan Reactor Vessel Society was willing to pay the
societal cost so that that could go intact and we were careful with the
Commission in our deliberations that this was not necessarily
precedent-setting, that as each one of these came in and other requests
it would be looked at individually and all aspects of it considered but
that was one case where we were able to move something big without
cutting it up.
DR. POWERS: Just in that regard, any time you are cutting
things up the Department of Energy seems to spend half of its life
cutting up things. If they could just do it wholly, you can handle
things so much easier and so much lower worker dose that really those
options make it relatively inexpensive to cut up facilities.
You still have a societal cost in that when you dispose of
big things you have got to have a big place to put them.
DR. GARRICK: Other questions?
[No response.]
DR. GARRICK: Well, thank you very much. That was a good
way to kick off this subject. We hope that you can -- we would like you
to spend some time with us --
COMMISSIONER DICUS: Actually, I am going to stay until the
break.
DR. GARRICK: Excellent, excellent. I would like to stay a
little while anyway.
Very good. In keeping with our -- excuse me, is there
somebody that wanted to --
COMMISSIONER DICUS: Excuse me, do you have a question?
SPEAKER: No, no, no.
DR. GARRICK: In keeping with our practice, on major topics
we usually assign one of the committee members to be the lead and we
have done so on this one and Dr. Wymer drew the right straw --
DR. WYMER: I wouldn't say that.
[Laughter.]
DR. GARRICK: From my point of view he did and he will
conduct the meeting from this point on as far as the LNT issue is
concerned, so Ray, I turn it over to you.
DR. WYMER: Thank you. I want to add my thanks, too, to
Commissioner Dicus for making those introductory comments. We
appreciate your coming and giving it that level of attention this
morning.
In the past we have had formal presentations from the
NCRP -- Ron Catherine regarding the NCRP Report 121 and James
Muckerheide regarding low level radiation health effects during a joint
subcommittee meeting with the ACRS in 1996. We had an informal update
by Vincent Holohan regarding the BIER-7 report and from the NMSS, by
Myron Pollycove, regarding hormesis in 1997, and the committee has
requested an update now in light of new developments, we think,
regarding the LNT model. Previous ACNW correspondence on this issue
consisted of a letter to the Commission and some memoranda.
I have some ground rules for the meeting. As you know, the
validity of the LNT hypothesis has very large implications, as we have
heard for the entire nuclear enterprise. The principal purpose of this
meeting is to obtain an update on the research related to LNT and a
review of recent past activities and advice on this topic from various
national and international bodies.
We hope also to get from this meeting an idea of the key
research areas that need additional study and we hope to gain some
perspective on the validity as experimental verification and
interpretation of the studies and conclusions to date.
There will be a summary report and meeting minutes.
The ultimate product of this meeting will be a report by the
ACNW, the Advisory Committee on Nuclear Waste, to the NRC Commissioners
recommending NRC actions related to the LNT hypothesis as it is applied
to risk from low level ionizing radiation.
Some of the questions related to the LNT hypothesis or
theory that you might be thinking about during the course of the meeting
are can this -- you have heard this before -- can the impact of the LNT
hypothesis be quantified, perhaps in terms of avoided cost, and would
the establishment of clearance levels, radiation levels, result in a
more risk-informed performance-based decommissioning cost, and finally,
are there significant gaps in research that might prove to be critical
in helping resolve this issue.
Now this meeting, as John Garrick has already said, is to be
collegial and that means even though there are strongly held opinions
pro and con on this hypothesis, let's be collegial and no arguments.
There will be no speeches from the floor during the presentations
although questions will be permitted. We will try to hold those to four
minutes per question, and they should be aimed specifically at
clarification of things presented rather than any further discussion,
because you will have an opportunity for that later.
Questions will be taken in an order. The committee members
will be given the first shot and then the consultants will be given the
next opportunity, and then the presenters, and then the ACNW staff, and
then members of the audience, and we will try to do it in that order.
There will be time for questions and discussion from the
floor during the panel discussion and people desiring to make short
position statements will be permitted to do so during the panel
discussion, time permitting, and statements may be submitted, and
several already have been, in writing to the committee and all such
statements, oral and written, will be part of the official record of the
meeting.
During the
panel session, each presenter will be encouraged to make a brief
observation on the presentations and the main thrust of the panel
discussion, we hope, will be identification of potential gaps in the
research being carried out.
We have a facilitator who has already been introduced,
Michael Halus, who will help me keep speakers on schedule today and will
facilitate the panel discussion when it comes up. Michael Halus sits
over there.
The guidelines for the speakers are to allow about half of
their time for questions. In my experience, that has never happened.
People use all of their time, but we want you to shoot for that.
In any event, the speakers will be turned off five minutes
before the end of their allotted time so there will be time for some
questions, so those are the ground rules. Let's hope we can adhere to
them reasonably well.
With that, the first presentation will be by Dr. Arthur
Upton, who was the Chairman of the recent NCRP Scientific Committee 1-6
draft report, which is entitled, "Evaluation of the Linear Non-Threshold
Dose Response Model."
Dr. Upton.
A fellow alumnus of Oak Ridge.
DR. GARRICK: We won't hold that against him.
DR. UPTON: Is the P.A. system working?
I'm pleased and honored to be here this morning. I feel a
bit humble, because I represent the Scientific Committee 1-6 of the
NRRP. I'm not a statistician, I'm not an epidemiologist, I'm not a
molecular biologist. I'll do my best to convey what I think is the
thrust of the committee's draft report.
It is an ideal time for discussion of the report because it
is still in draft form. It's on the Internet, on the NCRP Web site.
You perhaps have all seen it. But on behalf of the committee, I would
welcome any comments you might care to offer. The ink is not yet dry,
so this is a timely occasion in that sense.
If I could begin with that first slide, please. I'm not
sure how to turn it on. Oh, thanks.
The members of the committee are listed here. I shan't take
time to speak about all of them. It is a committee that represents all
of the disciplines that have to be involved, epidemiology, molecular
biology, genetics, et cetera.
Our concern of course is that we're trying to look at the
low end of the dose-response curves down where there are perhaps no more
than a single traversal per cell nucleus or per target, whatever it is.
And as has been emphasized by Goodhead, the data we have really, whether
they're high LET or low LET, leave us orders of magnitude above the
range in which we really want information. So we're confronted with the
necessity to extrapolate on the basis of models. And the issue really
is what is the appropriate model.
The consensus would appear to be that it is the DNA double
helix that is the most sensitive or critical macromolecular target, and
here there is good evidence that for low LET radiation, there's a small,
perhaps only finite chance that enough energy is going to be left behind
on a single traversal to produce a significant biological lesion,
whereas along a high LET track there's a very much greater likelihood of
such an event.
We know that there are an enormous number of strand breaks,
base lesions, every day in every cell. We wouldn't be here today, any
of us, if there weren't the capacity to deal with these. What is less
clear is how frequent the double-strand breaks or the complex lesions in
DNA are, the locally multiply damaged sites. There is a controversy
about the frequency with which they occur. At the dose levels where
they're readily measured, repair seems to be error-prone on the whole.
So there is this dichotomy, if you will, between the spontaneous
background and the radiation-induced lesions.
The unrepaired or misrepaired lesions may be expressed in
the form of mutations. Some years ago at Brookhaven, Arnold Sparrow and
his coworkers demonstrated dose-response curves for pink mutant events
and tradescantia, and as you can see with neutrons the curves were
linear, well down into a low-dose range, and with X rays, linear in the
lower to intermediate dose range, and quadratic at higher ranges up to
the saturation point.
There are lots of data like this for mammalian cells. I can
vividly recall Bill Russell's work at Oak Ridge and his astonishment
when he discovered that mice irradiated daily continuously in a low dose
rate field showed fewer mutations in spermatagonia than did those
animals exposed acutely over a single brief exposure period.
This was before we knew about DNA repair. This was to my
knowledge the first evidence for repair of ionizing-radiation-induced
damage to DNA, and it was controversial at the time. Russell went to
lower and lower dose rates, down to a rad per day in continuous
irradiation, and failed to eliminate this positive slope.
We know in human lymphocytes irradiated in vitro -- this is
the work of the Harvard group, Little and coworkers -- again the curves
look reasonably linear over a fairly low dose range, and the mutations
that are induced are not all expressed in the first generation. In
successive cell generations, new mutations appear which have the
molecular fingerprints characteristic of spontaneous mutations,
suggesting that the initial exposure induced a genetic instability, a
genomic instability in the cells leading to successive new mutations on
subsequent divisions.
Radiation can also damage chromosomes, chromosome break
illustrated here. The broken chromosomes can be restituted and the
result then can be a perfectly normal chromosome following restitution,
but various aberrations can also result. I'm not sure that's well
focused. Please let me hear from you if the focus -- good thing I'm not
a surgeon.
Now the frequency of two-event aberrations, dicentrics
plotted against dose here by Lloyd and Peritz some years ago,
characteristically linear with the densely ionizing radiation, linear
quadratic with low LET radiation, and as one drops the dose rate, the
curve gets less steep. If the cell has enough time between production
of successive breaks, one break will heal before the second break is
formed, and a two-event aberration will not occur.
These kinds of aberrations are of biological consequence not
only for the survival of the cell but as we see here the Philadelphia
chromosome, which involves a translocation of the able oncogene from 9
to the chromosome 22 in juxtaposition with the promoter, this is the
lesion responsible for chronic myelogenous leukemia, and such an
aberration has been shown to be producible by X-radiation in vitro. So
there's no reason to suppose that these kinds of chromosome aberrations
resulting from radiation in cells won't set the stage for cancer.
Because of our concern with models, we sought in the
committee to look at the various stages of cancer. What do we know
about carcinogenesis, how can we model, if you will, the effects of low
doses? So we looked at transformation in vitro, and the curves are
complex. They are far from simple. They tend to saturate at high
doses. But there is a dose rate dependency for low LET radiation seen
again and again, low dose rates are less transforming than high dose
rates, densely ionizing radiations are more potent than sparsely
ionizing radiation in transforming cells in culture.
Paradoxically, with densely ionizing radiations, as one
drops the dose rate, the radiation becomes more potent, for some reason.
If repair of the DNA damage or some other form of damage is responsible
for dose-rate dependency of low LET radiation, there seems to be less if
any such repair if anything successive increments of dose seem to
promote earlier exposures with the densely ionizing radiations. And
there are models that seek to try to explain this.
What is radiation doing? Again, the Harvard Group, Kennedy,
Fox & Little, have sought to cartoon, if you will, schematically what's
happening in the cells. One irradiates and then eventually gets a
transformed focus, a cancer-like proliferation of cells in the culture
dish.
It seems to involve more than a single event. It takes some
time for this process to develop. The initial event -- call it
initiation, if you will -- occurs far too commonly to be attributable to
mutation at any one locus. In fact, there are some suggestions that
there may be bystander effects, that irradiated cell may influence its
neighbor in some fashion. So we really don't understand this process as
yet.
Whatever it does in the first step, it can be promoted
through this metastable state by an appropriate promoting agent, phorbol
ester, so-called tumor promoting agent, TPA, or it may be inhibited by
an appropriate inhibitor, protease inhibitors.
The second event, whatever it is, would appear to have the
same frequency as in mutation.
Now in modern molecular biology, one is beginning to map the
road to cancer, and this is the work of the Hopkins School, Theron
Vogelstein and co-workers.
In the human bowel, there appear to be a succession of
mutational changes necessary for the road to cancer from a normal cell
to a highly malignant metastasizing cancer. Not that every tumor goes
through this same sequence of specific changes, but this is the kind of
sequence that appears to be involved.
As we learn more and more about genes, a larger and larger
number of different kinds of genes appear to be implicated, some of
which are responsible for policing, if you will, the genome, repairing
damage as it occurs. When one affects those genes, genomic instability
is the result in the probability of successive events.
What do we know from studies of laboratory animals, looking
at the whole animal. One size doesn't fit all. Reticulin cell sarcomas
tend to get less common in animals as one irradiates. Relatively
frequent in the control, one can almost eliminate them in irradiated
animals, whole body irradiation. Irradiation is therapeutic in that
sense.
Some tumors appear to have real thresholds, looking at Otto
Raabe, bone tumors; some may have little if any evidence of threshold;
some appear over the dose range where we have data perhaps
non-thresholding.
Years ago, Marion Finkle and her coworkers, at the Argonne
Laboratory, published this curve where you see evidence for substantial
thresholds for osteosarcoma induction in mice. The thresholds may be
somewhat smaller with the alpha emitters than with the beta emitters,
but responses look pretty thresholded there, and as Raabe pointed out
some years ago with his coworkers, at low dose rates, if one puts a
small amount of radioactivity into the skeleton so it takes a long time
for that radioactivity to be deposited, the doses to be expressed,
eventually the time it takes for tumor induction exceeds that mean
survival time of the species. So one is dealing in this case at low
dose rates with an effective if not absolute threshold, a practical
threshold. I think it was Raabe-Evans years ago who also had this same
idea.
Another feature of the experimental system is the
susceptibility of tumor induction to manipulation by cofactors of
various kinds. Years ago in Israel, Barablum and Tranen irradiated
mice, whole body irradiation, and they could produce lymphomas, but it
took a fairly substantial dose. There was a threshold here; no tumors
in 84 mice. As they increased the dose, they got some tumors. But if
they injected urethane after whole-body irradiation, urethane by itself
doing nothing to affect tumor induction, at each dose level, they
boosted the frequency of tumors. And now, instead of getting what looks
like threshold response, they had a response they thought looked like a
linear non-threshold response. They inferred from this that leukemia
induction might behave like a mutation, radiation inducing and mutation,
which wasn't expressed unless it was unmasked by subsequent exposure to
a promoter.
This kind of promotion is most dramatically evident with the
hormone sensitive tumor types. Salabager and coworkers at the
Brookhaven Laboratory years ago showed that with diethyl stilbestrol and
neutron irradiation, one gets a synergistic interaction. Neutrons are
tumorigenic to the rat memory gland; diethyl stilbestrol promotes the
expression of the tumors.
This is our work at Oak Ridge with myeloid leukemia in the
mouse. The open symbols are low LET radiation, x-rays, gamma rays, and
the shaded symbol is neutrons, acute, chronic -- acute, chronic. With
neutrons, it doesn't seem to matter whether the dose is delivered in a
single sitting or spread out over weeks. With the low LET radiation,
much of the effectiveness is lost, perhaps not all. These data don't
prove threshold, but there's enough statistical uncertainty so that we
really don't know for sure there's an effect.
Again, some years ago, Thompson and coworkers at Argonne
published this curve. The tumorigenic effects in animals are expressed
in shortening of the life-span. You irradiate the whole body, you
produce tumors in various organs, not all, and you shorten the life
span.
Again, with low LET radiation, as one drops the dose rate,
much of the effect is lost, perhaps not all. Conversely, with high LET
radiation, you drop the dose rate, you don't lose the effect. If
anything, you increase the tumorigenic effect.
These are data published from UNSCER simply showing that in
general, over a variety of different mouse systems, with whole-body
radiation, one gets life-shortening. At the low dose end of the curve,
the data are uncertain -- may be life-shortening, may not be
life-shortening. And it doesn't seem to matter whether one is dealing
with the mouse, the rat, the guinea pig, the dog. As Sacher pointed out
years ago with whole-body, radiation, one shifts the Gombertz's curve to
the left to about the same degree in every species, and I would venture
to guess that that will also be seen in the Japanese A-bomb survivors.
If you irradiate at very low dose rates, again Sacher and
coworkers found that as they dropped the dose rate down from ten rad,
ten-R per day, down to less than an R per day, they seem to be on the
linear slope. At higher dose rates, the curve became a quadratic.
Now let's look at the human. A-bomb survivors show cancer
at the dose of a grade. Not all. Again, one size doesn't fit all. The
relative risk of leukemia seems to be displaced more markedly than that
of other tumors, and the leukemias were the first to appear. We really
don't know what's going on down here. The data are consistent l a
threshold response. They're also consistent with linearity. The best
fit, I'm told, is linear quadratic. I'm not a biostatistician.
The problem with leukemia is that one is dealing with many
diseases. The chronic granulocytic leukemias peaked early, within ten
years after exposure, irrespective of age. That was true in the younger
age group as well as in the adult. The acute leukemias took much longer
to appear in the adult than in the kids, and it's questionable in my
mind, therefore, whether it's legitimate to lump these together.
There's no evidence that chronic lymphatic leukemia is induced by
radiation in any of the studies that have been done thus far. These are
age distributions of different types of leukemia in the population of
England and Wales. Irradiated children, this seems to be the disease
you get. You multiply the risk, which is already high at this age
group. You radiate the adults, you get predominantly one of these
others. And again, no evidence that you induce this disease at all.
Well, how about other kinds of cancer. We said not all were
induced. In the low dose range, there does appear to be some excess,
and if one plots the data, one gets a curve that is consistent with a
linear non-threshold response. A threshold cannot be excluded. David
Hall and his coworkers have emphasized that. The data are consistent
with linearity, but they don't exclude the threshold either.
Emphasis has been placed on the fact that in women whose
breasts were radiated incidently years ago in the treatment of pulmonary
tuberculosis with artificial pneumothorax in the days before
antibiotics. Small doses in repeated fluoroscopic examinations seemed
to have a cumulative effect on the risk of breast cancer essentially
indistinguishable from the excess in women surviving atomic bomb
radiation or women whose breasts were treated therapeutic for acute
postpartum mastitis.
The similarity in the four sets of data, when one adjusts
for aged exposure and duration of follow-up, was interpreted to indicate
that even a tiny dose of radiation to the female breast leaves behind a
carcinogenic imprint so that successive doses are essentially fully
additive. Little evidence for repair; argument for linearity. Again,
the data don't exclude a threshold. They support the interpretation of
linearity.
Another example -- thyroid cancer. This is the work of Roy
Shore. Thyroid cancer in children irradiated in substantial excess in
the low dose range, ten rads, consistent with linearity, again don't
prove the absence of threshold, don't prove threshold.
How about low dose rates? Well, if you look at different
cohorts, as Cardist and coworkers have done, there really isn't any
consistent excess. The data bob around a good bit. But if you fit a
linear response to all of the data, pool data, one does see an excess
consistent with what one would predict from the linear quadratic
function fitted to the A-bomb survivor data.
Another body of evidence comes out of the study of children
whose mothers were exposed to diagnostic radiography, abdominal
radiography, when the children were in utero. This used to be a popular
procedure in obstetrics. When one suspected a twin pregnancy or an
abnormality in the female pelvis that might interfere with normal
delivery, one radiographed the mama. As Alice Stewart and coworkers
pointed out years ago, the excess of childhood cancer appears to be
linear as a function of the number of x-ray films.
Now, another concern has to do with susceptible subgroups.
We've just emphasized that the infant in utero might be a susceptible
subgroup. This little girl had the nevoid basil cell syndrome, a
genetic disease often associated with the brain tumor. She was treated
with radiation therapy for midular glastoma of the brain, and within six
months after treatment, shows this crop of basil cell carcinomas at the
margin of the treatment field. We know now that this hereditary trait
is associated with exquisite sensitivity to radiation carcinogenesis.
So what can we make of all this? Well, there's increasing
evidence for adaptive responses, the capacity of cells exposed to
conditioning doses of radiation, to withstand more effectively
subsequent test doses, and there's no evidence that radiation does
up-regulate the genes that are responsible for the repair of DNA damage.
There's evidence that radiation can accelerate cell
proliferation, augment the healing of fractures, for example,
enhancement of immunological reactions in low dose levels, and some
experiments have shown what appears to be protection against
intercurrent mortality early in life, presumably through enhanced immune
responses.
These are the data from the Harvard Group, Kelsey, Little
and coworkers. Mutation frequency in human lymphocytes exposed to 300
rad, you see substantial increase above the control level; one rad, a
small increase. If one conditions cells with a priming dose before
irradiation and then gives them the test dose, one gets a smaller yield
than one gets with the test dose alone, pointing again to up-regulation
of DNA repair capability through the conditioning effect. This was
observed some years ago by Wolfe and coworkers for chromosome aberration
induction, and Jerry Puskin, who is sitting out there, published this
figure from work by Shadley and Weincke. The adaptive response that
protects against chromosome aberration induction appears to require a
test dose -- a priming dose at a fairly high dose rate. If one drops
the dose rate, one loses the protective effect. The protective effect
is also fairly fleeting. So it's not clear whether such a protective
effect is applicable under conditions of low dose chronic irradiation.
We mentioned that some experiments have suggested or
actually demonstrated improved survival of irradiated animals. One of
the first to do so was this -- the data shown here published by Lorenz
and coworkers. When the mortality rate of mice plotted against age or
time after exposure was presented in this forum, in the control animals,
the mortality rate was actually higher than in the irradiated animals up
until the very end of life, so that in many -- in most of the dose
groups, the mean survival time was actually better in the irradiated
animals than in the controls.
More recently, of course, we have seen the study of Bernie
Cohen's at Pittsburgh in which the relative risk of bone cancer and of
lung cancer in many counties across the country, plotted against the
radon levels, appears to go down, pointing to a hormetic effect, if you
will, in contrast to the case control studies with indoor radon which
appear to be consistent with the data for miners.
The issue then is, what information does one lean on here?
Is this approach more credible, more reliable than this one? There are
many arguments against the linear-nonthreshold model. Low doses of
radiation have not consistently been observed to raise mortality rates,
cancer rates, mutation rates, as predicted by the model.
There is no question that radiation can induce adaptive
responses in cells and organisms that may enhance their capacity to
withstand subsequent exposures. That is not controversial. The effects
of low level radiation have appeared under certain conditions to be
beneficial to the exposed cells and organisms. There are indications of
radiation hormesis.
What are the counter arguments? Double-strand DNA breaks,
locally multiply damaged sites, complex lesions appear to increase
linearly with the radiation dose in the low to intermediate dose range.
Repair of such lesions, where we can measure repair, thus, have been
able to measure repair, appears to be error prone. Whether it is error
prone down in the really low dose range, a single traversal, we don't
know. If the lesions are unrepaired or misrepaired, they may be
expressed as mutations or chromosome aberrations, and the frequency of
these effects appears to increase as linear nonthreshold functions of
the dose in the low dose domain.
Cancer usually arises as a single cell -- in a single cell
as result of mutation or chromosomal changes, that is the prevailing
notion, and although multiple such changes appear typically to be
necessary to transform a cell, a single such change in a cell that is
already appropriately susceptible may tip the balance. And for that
reason, the risk of cancer may be expected to increase with the
frequency of mutation. The increase is apparently nonlinear --
apparently a linear nonthreshold function of the dose. And in keeping
with this hypothesis, frequency of some types of cancer does appear to
increase as linear nonthresholds functions of the dose in humans and in
laboratory animals.
So there are arguments pro and con, and if one wants to
measure these tiny effects, one is dealing with enormous variations in
the natural baseline frequency. So trying to measure small effects
against such a noise level, I think is virtually impossible. So I think
we are stuck. We have data that point in this direction. We have some
data that point in this direction, in this direction. I don't know
myself of any strong evidence for supra-linearity, but I don't think,
from what I know, or what the committee has been able to determine, that
we can really settle the issue at this point in time.
There is no one model that appears to be so overwhelmingly
consistent with all the data that we have to say that's it, but,
certainly, the linear-nonthreshold model for some forms of cancer, for
some mutations, appears to be plausible, appears to be consistent with
the data as we have it. And so I will stop there. Thank you.
DR. WYMER: Thank you very much. That certainly sets the
stage for both points of view that will come later I think in the
discussion. Let me ask, are there any questions from the committee
members first here? John.
DR. GARRICK: Well, I would like to reveal quickly that I am
not an expert in this area by asking a question. One of the things that
strikes me about this whole debate that is very interesting is the
different perspectives of research, and let me characterize it by the
fact that I will call one research that deals with what I will call
micro-mechanisms, individual cell behavior and phenomena, single cell
behavior phenomena, versus macro manifestations, and when you look at
your list of arguments against LNT versus arguments for LNT, just
quickly, and I may be wrong on this pickup, it looks like that the
arguments against LNT are mostly what I would call based on macro
observations, whereas the list of arguments that you presented for LNT
seem to be more at the mechanistic or single cell level. Am I missing
something here?
And I guess my question really is that, trying to draw an
analogy between this and something I know more about, it strikes me that
if we had made decisions about the use of some phenomena, such as
electricity, on the basis of complete understanding of the
micro-mechanisms, we wouldn't be using electricity today. And I am just
wondering if we are into sort of a parallel situation here with respect
to this issue.
DR. UPTON: Good question. I am not sure I can answer it
effectively. If we look at macro, I sought to point out that there are
in the human epidemiological data, in the whole animal radiobiological
data, in the area of genetics, indications of linear-nonthreshold
responses. None of the data prove linearity, but the data are
consistent with linearity.
If we look at the molecular or micro, there are comparable
but lines of evidence that are consistent with the linear-nonthreshold
hypothesis.
If we look at the arguments against the linear-nonthreshold
model, again, I think, with whole animals, there are some indications of
hormetic effects. With epidemiological data, there are some exceptions
to the predictions you would make. None to my knowledge that are so
powerful that they essentially clinch the argument against linearity,
but they are troublesome, they are provocative.
I am not conscious of strong arguments at the molecular
level. I know that there have been a number of -- I am searching for
the proper number. A number of people have argued that there is an
enormous background level of DNA damage in every cell, and that the
body, the living cell has to deal with this somehow to survive, and one
can measure the up-regulation of DNA damage control genes and processes
by test doses.
Whether this adaptive response to low level radiation deals
effectively with all of the genetic damage is, I think, the unknown
question and if one of the objectives of this session of the committee
is to pinpoint research needs, I would say that is an important research
need, from my point of view. How effective is the genetic repair
mechanism at low levels of exposure, especially with concern about the
multiply -- locally multiply damaged sites, the complex lesions. Base
damage, I don't think -- I think that is pretty well resolved, but the
complex lesions, I am not aware have had the kind of attention that they
deserve.
DR. GARRICK: Well, I think, clearly, we would all prefer to
have an explanation at the micro level. One of the things I have never
fully understood, and maybe it will come in later presentations, is that
we keep making this point that we don't have sufficient data. Again,
looking at it between micro and macro, I would think that we have an
enormous amount of data at the macro level.
We know that this phenomena is location dependent. We know
where people live. We know what they do. We know even the frequent
flyers. There's all kinds of information available to us to isolate
populations, at least in a macro sense. And so it would seem to me,
that from an analysis standpoint, there is an opportunity, at least at
the macro level, to do a great deal of work in illuminating, at least
from these global considerations, what the cancer case discrepancies or
differences are as a function of these conditions.
Are we doing -- when we talk about doing research, are we
recognizing that component of the research as much as we ought to be?
And, as I say, I preface my remarks by saying I would much rather
understand the micro-mechanisms, of course, but we deal in a lot of
things where we don't understand the micro-mechanisms, and, yet, because
of understanding something about the macro effects, we move forward, but
we don't seem to be doing that in this case.
DR. UPTON: I would certainly not want to argue that we are
doing all we can do and all that we should do. I don't, myself, think
that we have over-estimated the importance of epidemiological studies or
radiant populations. I think it is crucial that we continue to follow
the Avon survivors, thoughtfully, carefully, in-depth.
I was disappointed that my colleague, Roy Shore at NYU, who
had demonstrated the feasibility of a study of nuclear workers across
the country wasn't able to persuade the industry to mount such a study.
Perhaps out of fear of litigation, I don't know why the study wasn't
undertaken. But I think, as you point out, we have got a lot of
information, we have got a lot of experience, we should use this
information, we shouldn't squander it.
DR. GARRICK: Thank you, Art.
DR. WYMER: George? Charles?
DR. FAIRHURST: Just a little follow-up on what John was
saying. I have heard it said that the variation in natural background
worldwide is quite significant, a factor of two, three or more, and,
yet, there is apparently no correlation with cancer rates, and that if
one were to really pursue that from a research point of view, and
demonstrate statistically that there is no effect over that range,
wouldn't that indicate that a threshold must exist, and, in fact, that
the whole human species has been evolving throughout in a environment
where a certain level of radiation was always present? That must be
able to come in as a piece of strong evidence in favor or contrary to --
DR. UPTON: You are absolutely right, Charles. To my
knowledge, there have not been any consistent indications that
populations residing at elevated levels of natural background radiation
have shown any increased cancer rates attributable to such backgrounds.
The problem, as I see it, and Charles Land, others in the
room, are better qualified than I to comment on this, the problem, as I
see it, is that there are so many confounding variables that --
threshold, yes, but threshold for detectability. Threshold may not mean
that there isn't an effect, the effect may be masked by the influence of
confounding variables.
I attempted to show in one of my figures that there is
enough difference just among the cities of this country, irrespective of
background, natural background, so that any attempt to identify small
differences, and the differences are going to be small, of the order of
a few percent at most, such differences, I think, are likely to defy
detection. But this is not a field in which I am expert. I think some
of the epidemiologists or biostatisticians are better qualified to speak
about this than I am.
But if you are talking about thresholds for detection, I
think they are there. But that wouldn't satisfy those who are saying,
well, we are not concerned about detecting 1 percent, 20 percent of us
will die of cancer. If you are talking about a one in a million risk,
it is way, way, way down below the level of detection.
DR. WYMER: Okay. We'll go to our consultants next.
DR. KEARFOTT: I hope you ignore my ignorance and indulge my
curiosity. I'm going to kind of touch on some of these earlier issues.
When I was looking in all these data that tended to support the
epidemiology things, that tended to support but not prove a linear
hypothesis, one thing -- it was going pretty fast for me. But one thing
I noticed is that most of the data went up to the 10 Gray range with
only one or two points below the 1 Gray range, and mainly nothing in the
centigray range. So these were really not in the dose range of
interest.
And I'm puzzled and wondering if animal or epidemiological
work of statistical significance is actually possible in the centigray
range. For all this sort of animal work doesn't go down lower, the
epidemiological work doesn't go down where we want. Is it really
possible to do meaningful work in that lower range?
DR. UPTON: Some years ago, Charles Land published an
article on the numbers of individuals needed to demonstrate risks down
in that low dose range. And Charles is sitting back there. He's much
better qualified to speak about this. You're really asking a question
that deals with statistics. And this is out of my realm. But my
recollection, Charles, and you correct me if I'm mistaken, you're
talking about hundreds of thousands if not millions of individuals to
demonstrate risks down in the region of a rad.
Now the only evidence that I know of that goes down into
this -- well, there are two bodies of evidence that I'm aware of. One
for all solid cancer of the A-bomb survivors, one is down in the region
of 5 to 10 rads. If you look at the excess of childhood cancer in
children exposed to diagnostic X radiation in utero, there would appear
to be significant elevation in the region of a rad. But again I would
defer to someone like Charles Land, who has a better grasp for the
statistics than I do.
But I'm trying to recall now a paper that Richard Doll and
Richard Wakeford published years ago in which they sought to analyze the
data on prenatal radiation in childhood cancer. And there's a problem
there in that the A-bomb survivors who were irradiated in utero don't
show an excess of childhood cancer. There weren't many of them, so the
absence of the excess doesn't negate the case control data, but there
are cohort studies that don't agree with the case control data. So
again you've got a half full glass, a half empty glass.
DR. WYMER: Dr. Raabe?
DR. RAABE: I read your draft reports and actually submitted
some written comments on behalf of the Scientific and Public Issues
Committee of the Health Physics Society, and of course I participated in
the collection of information, and I thought your talk this morning as
previous talks that you've given was very balanced. It's a very
complicated issue, and I think you showed that there are lots of factors
that have to be considered. And, yes, you know what's going on at the
micro level may not tell us what's happening at a macro level. But the
report itself, I came from it thinking it was kind of a defense of the
linear no-threshold approach. And the linear no-threshold has two parts
to it, the linear and the no-threshold, and sometimes it gets confusing.
Now the first question I have relates to something in your
report, something which you presented this morning, and this idea that
if you can demonstrate that there must be some risk because, you know,
there's some unrepaired DNA or there's some mutations at any level, that
if you can demonstrate there must be some risk, the risk is not zero,
that for some reason therefore you have to accept the linear
no-threshold. And I have trouble with that, because I don't know if
there are any zero risks in this world from anything, so if we have to
prove zero risk to eliminate the linear no-threshold, we never can do
that. But the risk can get quite small, can't it.
Now what do you think about this idea -- it's in your
report -- this argument you presented that you have -- if you can show
that there's got to be some kind of effect because there's a mutation
expected or there's some DNA that's not repaired, that therefore you
have to jump to the idea that there's a linear response?
DR. UPTON: Well, let me say first of all that I'm most
grateful on behalf of the committee for your comments and for the
comments of many others. The committee approached its task with a great
deal of humility, recognizing that the literature is vast and many
colleagues out there in the community are knowledgeable, insightful. We
published an appeal for data, and received a mountain of information
from all over the world, and the report itself was circulated widely on
the Internet, and again, many, many very helpful comments have come
back.
I take your point, Otto. I think it is unreasonable to be
overly concerned with vanishingly small risks. I empathize with those
who are trying to promote the idea of a negligible individual dose, or a
dose below regulatory concern, for the reasons you indicate. We were
asked as a committee not to get into policy but to try to stay on the
science: What are the scientific data? Do they support a linear model?
Do they not support a linear model? Where does the science come out?
And leave the policy issues to others. And that's what we sought to do.
DR. RAABE: I have just one second question that's a
followup. The report mentions but really doesn't delve into some of the
counterissues that you brought up this morning. For example, Luckey's
two books were not even referenced. And one of his articles was
referenced, but it was passed off in one sentence. And I think -- and
Dr. Pollycove gave a very good presentation that I witnessed to your
committee that I thought should have had a little bit more coverage. I
mean, you can't just write this off as a footnote.
Also Bernard Cohen's work is really -- I think it needs to
be given a little bit more attention, because it certainly is an
ecological study. He did not attempt to show that radiation was good
for you, necessarily, but he did show that the linear no-threshold model
is very much in doubt. And I think that in your scientific committee's
report that was also kind of written off kind of briefly. And I think
the kind of presentation you gave this morning that really goes into a
little bit more of these other issues and tries to scientifically review
them would be more helpful to us.
DR. UPTON: Well, thank you, and others have made the same
comments, and I can assure you the committee will strive very hard to
correct these deficiencies.
I'm impressed with Luckey's books. I've got them. I've
read them. It's a very extensive review of the literature. And I've
recently been fortunate to receive from Ed Calabrese some draft
manuscripts that he has prepared on the history of radiation releases
which are very illuminating, very helpful.
DR. WYMER: Dr. Kearfott, do you have a followup question?
DR. KEARFOTT: Yes. Dr. Upton, can you fantasize wildly for
me, because what I'd like you to try to answer is we've got all these
different kind of biological mechanistic research going on. They show
different kinds of things. They show threshold, no threshold, they show
repair, they show hermesis, adaptive response, there are hints of
anything. Can you wildly fantasize for me how you would reconcile
without constraints these models?
DR. UPTON: Golly, I wish I were Galileo.
[Laughter.]
I think really that's the task that confronts the research
community today. Policy makers can't do this. These are really
technical issues, and I think the research community must address these
carefully, thoroughly, and it may take some time.
When I was at the National Cancer Institute, I frequently
had to defend NCI against the critics who were arguing that you were
losing the war on cancer. Nixon signed a bill and there was the
expectation that a few billion dollars and we'd have the problem solved.
And I was there some years later and the problem wasn't solved, and
there were those who were arguing we were losing the war. I had to
emphasize that the war on cancer was not like the Manhattan Project or
the Apollo Project. We really didn't know how to solve the problem. We
weren't putting a man on the Moon. We had to work at the science. I
had no reason to think that the problem defied solution, and I would say
today I'm not confident that we'll ever completely eliminate cancer.
But we're making headway.
I don't -- as I fantasize, in response to your question, I'm
not pessimistic about this. I don't really see that there's necessarily
a contradiction between the adaptive response and some residual
component of damage that may defy repair. The cell, after all, only has
a moment in which sometimes to repair the lesion. It's about to divide,
it's about to complete the replication of its DNA, and then the damage
takes place. To eliminate that altogether may go too far. But to say
for that reason that we can't allow any radiation is ridiculous. This
has been pointed out already, that the world is full of risks. It's a
matter of balancing one ideal, one need, against another.
DR. RAABE: One quick followup. On the basis of your
studies now on this -- all the work that was done by your committee --
do you think you could assign a risk of developing cancer from an
exposure of 1 millisievert per year, 100 millirems per year? Could you
assign a risk and even come up with any kind of uncertainty? Could the
risk be zero?
DR. UPTON: When I was involved with the BIER VI
committee -- the BIER V committee, I chaired the BIER V committee --
there was an elegant review of uncertainty, but as the report came down
the homestretch, there was no statement anywhere that at natural
background levels the risk could be zero. And I insisted that the
report say that. And I think it's unscientific, Otto, for anyone to
argue today that we know that there's going to be a risk at zero
background levels. Background may be beneficial, for all we know.
Hormesis may in fact be the valid model. We don't know. But to say
that we've got enough evidence now to throw linearity out the window and
say there are no risks down there, to me that's not scientific either.
DR. WYMER: Dr. Powers, do you have any questions?
DR. POWERS: I'm going to delve into the policy area, so my
question probably isn't directed toward the scientific study, maybe more
toward the chair and to Commissioner Dicus.
You remind us that there are a lot of different types of
cancers and that there is a lot of progress made in the medical
treatment of those cancers.
But when in the reactor world, we consider accidents. We
focus on fatal cancers, acute and delayed, and I am wondering whether
that is really as we move into a risk-informed regulatory area whether
we really ought to be constraining our view of risk that narrowly.
Should we not? I mean after all, these cancers are much like the
thyroid cancers that are reported to develop following Chernobyl are no
walk in the park and they do impose societal costs.
We can attempt to hide or compensate for neglect of those by
the -- where we set our standards for protection against fatal cancers
but that is going to become increasingly difficult as the medical
community becomes better and better at treating those, yet they still
impose a societal cost on us, so I guess my question really is ought we
not think about expanding our measures of risk as we move into a
risk-informed regulatory arena?
DR. GARRICK: My opinion about that is a simple answer --
yes. I think one of the things that handicaps that a little bit is that
with the emphasis that we have had on using surrogates of risk like core
damage frequency, there has been little attention given to the upgrading
of what I will call the health effects models that would better
represent the good work that has been done in the last decade.
I am not sure the health effects models are in very good
shape for adding to the arsenal of expanding the risk measures but the
principle of the idea and in keeping with the notion of a risk-informed
approach seems to me to be an excellent one.
I have always preached that when you choose a single measure
of risk it's like looking into a single window of a very large building
that has many rooms and windows. You see something about what is in the
building but you don't see very much and so I am a strong supporter of
expanded measures of risk.
COMMISSIONER DICUS: And it's wonderful to be able to agree
with a simple answer. I say yes as well.
I would also like to maybe just mention something else too.
It is along the lines of micro as opposed to macro and this idea of risk
and looking at risk in different ways and I am reminded of the
discussion -- I think it is in ICRP-60, it may be in NCRP as well, I am
not sure -- of distinguishing between change that may or may not lead to
damage, that may or may not lead to harm, that may or may not lead to
detriment, and whether we look at risk, we discuss risk. Are we really
concerned of the risk of detriment as opposed to -- or the risk of
change that might ultimately lead to detriment, so it is just simply
another way to look at the question.
DR. UPTON: In that context, I think in talking about risk
one really, as the committee sought to do, has to look at the coherence
of the various relevant lines of evidence until they come together in a
coherent fashion -- the contradictions that are troublesome.
COMMISSIONER DICUS: If we are dealing with very low levels,
if we do find change and damage we have a hard time getting to
detriment. How do deal with that, particularly in a regulatory
environment?
DR. UPTON: Yes. good question.
DR. POWERS: Having gotten an answer of yes from both
Garrick and Dicus, now I can turn to how do I engineer it?
You give me multiple measures that are not commensurate.
How do I use that in designing either regulations or responses to
regulations?
DR. GARRICK: Well, I don't think we can answer that today,
but I will say that --
DR. POWERS: I just wanted to toss some complexity back into
it. Simple answers are nice but there are complexities still hidden in
that simple answer.
DR. GARRICK: I think part of the answer to your question,
Dana, is provided by the Chairman's adoption of a risk-informed concept
rather than risk-based.
I think that what we are really suggesting is that we ought
to move in the direction of informing us increasingly about what the
risk is, and to do that multiple measures of risk are very useful.
I think if we practice that awhile, it will probably shake
out what are the best measures and how many of them. I don't think you
can speculate on that without some experience.
I wanted to ask one thing, and then I will shut up about
this. There was one viewgraph or slide that you had up there that was a
reading test kind of slide that was only there for a few seconds but I
seemed to notice that -- and this was a slide having to do with cancer
rates as a function of location -- the bars. I seemed to pick up
something on that that caught my attention that suggested that it is
quite location-dependent and there are some locations where the cancer
rates are lower than other places and that you might be able to draw
some conclusions from that.
The one I picked out in particular was Utah, and so my
question is if that information is reasonably valid, doesn't this
suggest that maybe cancers are so driven by things like dietary
considerations, environments, that it is very difficult to at the macro
level see behind what the real drivers of risk are to something that is
perhaps as subtle as the effects of low level radiation?
DR. UPTON: That is the point that I was trying to make.
DR. GARRICK: Yes.
DR. UPTON: And your eyes are sharp. The rates in Utah tend
to be lower, the Rocky Mountain states --
DR. GARRICK: Right.
DR. UPTON: -- and some have emphasized that this means that
elevated levels of radiation there from cosmic rays --
DR. GARRICK: Yes.
DR. UPTON: -- are really not detrimental.
DR. GARRICK: Yes that is -- because I know most of the
elevation -- most of the people live at around the 4000 to 5000 foot
elevation level.
DR. UPTON: Yes, and they seem to do better than the rest of
us.
DR. GARRICK: Yes. Okay.
MR. HALUS: We have planned about five more minutes for this
topic.
DR. UPTON: Right.
DR. WYMER: Let me ask now if the ACNW staff has any
questions or clarifications with respect to the notes they are taking
and trying to get the gist of what is going on here?
[No response.]
DR. WYMER: Okay. I would like to ask in the remaining five
minutes if there are any of the people who are making presentations in
the audience who would like to ask any questions at this point? There
is a microphone up here by this pillar. Please identify yourself.
MR. MUCKERHEIDE: This is Jim Muckerheide, Radiation Science
and Health.
Dr. Upton, as was alluded to, there was a very quick
coverage of a number of very heavy slides. There were a couple of notes
that I had about the content and I don't -- I appreciate that you
probably can't answer all of these right off, but just a couple of
minutes of some questions.
One, there seems to be just as a start-off that there's
really not a very substantial consideration of most of the scientific
literature that you were provided from those of us who were trying to
get you to look more in depth and participation in the report didn't
seem to reflect participation by people who have done the thousands of
studies that are typically referenced.
In the linear effects in cells and organisms there wasn't a
very good sense of when you were dealing with cells and culture and
artifacts that don't really have full immunological response modes and
there wasn't a consideration in some instances where there were whole
animal studies that an effect in a cell doesn't necessarily lead to a
health effect.
We know from the radiation workers in the UK that the high
dose group, the effects don't necessarily lead to any adverse health
effects.
In the data that demonstrate at the molecular level some of
that information, there was no recognition that much of the work that
has gone on in the last 15-20 years in molecular biology and radiation
effects has stimulated a lot of the repair mechanisms that have been
identified as being -- causing the kind of repair and response so that
there is a net active response and there's an enormous amount of science
on that and this only had seemed to do with what is the hit on the
radiation without any other consideration of the cellular response.
The neutron responses I would beg is all kind of irrelevant
to the real issue of LET response that we have to deal with in the issue
of radiation protection policies. The data that shows linear down to
about an r a day or sometimes lower where there is a whole consistent
missing of doing studies at low doses while there are thousands of
studies at low doses seems to me almost disingenuous, to not address the
studies that do specifically deal with doses below about an r a day.
We know for example in May of '98 when we talked about all
this stuff, about how big a population do you have to have, there was a
publication in Gerontology of a study of 300 mice as controls, 300 mice
at 7 r per year and 300 mice at 14 r per year, highly statistically
significant life extension to the exposed populations, information about
the typical -- consistent with going back to the Manhattan Project --
life extension that goes on in whole animal systems.
The representation of whole animal systems or animal systems
that didn't show life extension ignored the fact that we know some of
the reasons why some populations didn't have life extension with low
levels of radiation. They were not whole animals. They were
tumorigenic. They didn't have immune systems to function with and some
that didn't have doses of that were really low dose populations.
DR. WYMER: This is getting close to a presentation from the
floor -- sort of questions or clarification?
MR. MUCKERHEIDE: Okay. Well, let me just ask two more
questions of clarification.
DR. WYMER: Okay.
MR. MUCKERHEIDE: On the Cohen data, it would really be
helpful if instead of only treating Cohen as some nut from the
hinterlands that we recognize that his enormous database has been
assessed in various combinations, very independent studies, and that
there are dozens of other studies that show the similar results.
The Frigerio study by the AEC in 1973 was killed by AEC in
'73 and it was not picked up by the NRC when it was formed when it was
still trying to be -- still pointing out that in the U.S. population
when you talk about needing to have millions of people, this is a
population that has been studied and it does show the adverse effect
does not apply, and I think part of the response that we need in this
report as its further work is, as has been mentioned, to really address
some of the substantive information that has challenged the LNT instead
of just kind of defining how we work ourselves around it.
DR. WYMER: Thank you. I am sorry, Dr. Upton, but there
won't be time for you to respond.
[Laughter.]
DR. WYMER: Maybe you are glad for that.
DR. UPTON: Well, let me just say on behalf of the committee
I am thankful for the comments and we'll do our best to address them.
DR. WYMER: Thank you very much for that very good
introductory lecture.
The next presentation is by Dr. Marvin Frazier, from the
Department of Energy.
DR. WYMER: I should also say that we have had an unusually
long period for questions after this first talk, which will not be
possible after all these subsequent talks.
DR. GARRICK: Yes, and I also want to acknowledge for Art's
sake that the first speaker usually gets it the hardest, so maybe there
was a reason for choosing Art to lead off this discussion.
MR. FRAZIER: Well, I'd like to thank you for your
invitation to speak today about our new program that's starting out, and
I'd also like to thank Dr. Upton for the introduction, because I think a
lot of the questions that you asked are similar to the kinds of
questions that this program is trying to address over the course of the
next few years.
We've just started a new low-dose-radiation program at the
Department of Energy and the Office of Health and Environmental
Research. That's the home of much of the research that's been done over
the last 50 years in radiation biology, and we're very proud of that,
and we're hoping to build on the wonderful work that's gone before in
trying to address some of these questions that you're asking.
Unfortunately, we are not going to have any answers for you today, but
we hope that in the future as this group meets that we'll be able to
provide more and more insight.
This is a program not only in the Office of Science, which
is the basic research arm of the Department of Energy, but also in the
Office of Environmental Management. And so it's a program that's
collocated. This was done by Congress in the appropriations, and it
seems to be working out quite well, because I think it makes both
groups -- we're a very basic oriented group, and the other group is very
applied. And so it makes us talk together, and I think it shows some
insight on the part of the
congressional people.
Senator Domenici -- I mention this because they're the ones
who put this language into our budget and put this program together, has
made a couple of statements over the last couple of years. He has
interests and concerns in many areas associated with research, waste,
cleanup, nuclear energy production, and so forth. And as an offshoot of
those interests, he started a dialogue with our office about three years
ago in terms of trying to determine what the future of radiation biology
research might be, where we should be going, and so forth. And he
wanted us to improve the scientific basis of risk assessment in a way
that would be useful for policy development.
Another statement by Senator Domenici, as we started he made
several speeches last year -- these were taken from his speeches in
1998. That's the year whenever we initiated our low-dose program.
There wasn't funding in the budget for it, but we restructured some of
our funding and started the program with RFA last spring, small RFA, and
then this year additional budgets were added. We're expecting that this
program will be able a $22 million to $24 million a year program over
the course of the next ten years.
The fundamental question then that we're being asked to
address is are there safe levels of exposure to radiation, and that's
obviously a difficult if not impossible question to answer, as Dr. Raabe
pointed out. But if we put this "safe" in quotes and -- what we're
trying to do really is find out if there are practical kinds of levels
where we don't need to be concerned. So we felt to put this in proper
perspective we really needed to look at endogenous processes.
The processes that are used to repair, to process radiation
damage and so forth are processes that were developed to handle
endogenous damage within the cell. I think that's -- everybody talks
about well, we evolved in these low-level radiations. I just don't
think that's the driver here. I think it's really these endogenous
processes. You've got oxidated damage that's very similar to low-level
radiation damage. Our question is, is it the same, qualitatively and
quantitatively.
We know that certain kinds of high LET radiation are
qualitatively different from oxidated damage, but what we don't know if
at these low levels are you just talking quantitative differences. And
that's one of the things we want to address. And I think if you put the
radiation problem in the perspective of endogenous processes, start to
look at those processes and see how this perturbs above and below those,
that's really going to give you the crux to the kinds of answers that
you're searching for.
So as I say, you know, we know that aspects are different,
but what we're looking for is clearly quantitative sort of thing in this
question: Are there thresholds for low-dose radiation? I think these
are simple questions. They're very difficult to approach. We're going
to tell you about how we're trying to go forward with that and other
genetic factors, susceptibility issues, and how should we communicate
this risk.
I think this is an area where this whole field has really
had problems in the past, and we're going to try to address some of
those problems as we go along in this process rather than waiting to the
end and coming to the people and saying oh, you know, DOE's got the
answer for you, you don't need to worry anymore. That just doesn't
work, as you know. And so what we have to do is we have to engage
people as we go through this process, get feedback, and try to address
their concerns as we go along. And that's part of the plan.
As a result of developing this program, we put together a
research program plan which we sent out. Many of you in this room I
think have had opportunities to comment on it. We went through a
process, our advisory board is the Biological and Environmental Research
Advisory Council. It's a FACA board. Put together a subcommittee that
had a couple of workshops. David Thomason, who's in the room, is the
program manager here, he worked very hard with the BERAC advisory group
to develop this plan.
The plan is a ten-year research program plan. It's at a
high level that's meant to be accessible to policy makers, to
scientists, to legislatures. So it's an overall plan of what are we
trying to do.
The implementation plan is going to be more difficult.
We're going to be -- that's going to be an ongoing process, as is this
plan. This is a living document. We're going to have to modify it.
We're going to have to follow this program very carefully over the
course of the next ten years, because we have a budget that we're trying
to meet and deadlines we're trying to meet. So we're going to work very
hard to try to keep to those deadlines and actually make some progress
on these issues.
So anyway, so this group drafted a plan earlier this year,
sent it out for review, sent it to most of the major groups that would
be interested in this sort of thing. We're in the process of starting
to go around and tell people about the plan. We're here today. We're
going to be at Radiation Research this year, American Nuclear Society, I
think Health Physics, as people are interested. We hope to do that and
give yearly or every other year updates to these groups. And they're
welcome to come to us and meet with us at any time.
We're very interested in going forward. We have been also
working on other workshops. We had a joint workshop with NCI last year
on biomarkers, NCI and NASA. We had a workshop that we held last spring
in California where we looked at endogenous processes. I think there's
a publication coming out of that. Dr. Pollycove and Feinendegen I think
are -- that whole group's authoring that paper that we tried to define
what the background endogenous damage is. We're having a joint workshop
with NIH in April on low-dose effects. So we're trying to constantly
provide information and input into this process.
As a result of the process we had as I said RFA last year.
There's a current call for proposals. We got some, around 183
proposals, which we reviewed, sent back to people our comments, and
full-blown proposals are coming in. So we're not going to describe for
you the kinds of research in detail today because that program is just
being starting to be funded. But in the future we'll be happy to give
you updates on that. But I just kind of give you the process and where
we are.
We're going to be studying the effects at many levels. I
think one of the comments made in the earlier talk was that you really
need to look at across all levels from DNA to whole organisms, look at
tissue effects, whole organism effects. There are some very critical
issues that are associated with each of those, and as I say, we're
really trying to build on prior studies.
There's, you know, a lot of studies on DNA damage and cell
transformation in labs and some whole organism studies, and what we
really want to do is look at a lot of mechanistic studies as best we can
and try to develop mechanistic understandings, but those mechanistic
understandings have to at some level be quantified. If they can't be
quantified, then they're going to be very difficult to use in models.
But they can be hypothesis-generating, they can help us to understand
things.
A lot of these endpoints that you see up here are familiar,
but one of the keys that we are asking our researchers to do are to look
at these endpoints and look at them at dose levels of interest here. We
are not really interested in dose levels, the higher dose levels. That,
I think, has been done quite well historically. So we are pushing in
the center -- centigray range for these kinds of things, down. If your
measurements are above about 10 or 20 centigray, we are really not
interested unless those are for comparative purposes, so that we can
look at, you know, how the data -- there can be a control, for example,
that is high level radiation to see how low level effects compare with
high level effects, to see how the extrapolation model works, things
like that. But we are really pushing people to utilize these endpoints
and to develop new endpoints for measuring radiation effects at the low
levels, at the centigray levels and below, wherever we can.
You can't -- with regard to the program, there has been
quite a bit of talk about epidemiology. This program really won't have
any epidemiology in it. We are counting on other studies to provide
some of that. But what we are trying to do is work with mechanisms and
molecular components, try to put those together to feed -- quantify
those, put them together so that they can feed and help interpret the
epidemiology studies that have been done.
I think we talked a little bit earlier, someone mentioned
that it takes hundreds -- it would take hundreds of thousands of people
at the one centigray level to get you an answer. That gets you an
answer, but it may not give you the answer. It is one study, and so it
would have to be repeated time and time again. So, we, in our program,
don't have the resources or technical capabilities to be running
epidemiology studies, but we think if we work with the epidemiologists
and other people on these issues, and if we have specific kinds of
studies, such as susceptibility, we can look at aspects of these, so we
are building some of those tools.
We can't presume at this point what kinds of data, how this
data is going to work with risk modelers, risk assessors, so we are
going to have to work with them on a routine basis, to make certain they
are going to come to -- we are going to have yearly workshops,
contractors' workshops, where our people make presentations. We are
going to bring in advisors, we are going to bring is risk modelers and
try to get them to help tell us the kinds of data that would help them
in this process.
So it is -- I think, you know, we are treading on new
ground, but we do have a lot to build on. And we are going to talk
about some of the things we think will help us get to that in a second.
Another issue that we want to try to sort out is the human
susceptibility to radiation. This was already mentioned in the morning
talk about how important this might beat low dose levels.
Susceptibility, there might be highly susceptible groups that are
driving the low dose responses. We think we have tools to start to
answer this question. When we get the answer, what we do with that
answer is another problem. There are all sorts of ethical
considerations and so forth as to how you would handle that problem.
But we think understanding the problem is really important to this. How
it is used, that is going to be for policy makers and others to decide.
Again, we think communication of research results here, and
by communication, we two-way streets, interacting with the public to
some degree. We are going to have web sites describing the work. We
are going to try to think about education modules for schools as we go
forward. Try to get the scientists to interact, to help us make sure we
are giving out the right information. Work with regulators and
legislators to try to develop this process over the course of the next
10 years so that it really does make a sea change in our risk estimation
processes.
We are very interested in just getting to the base of the
problem. Why do we think now is better than why has been done in the
past? Well, as you say this morning, there's a lot of radiation biology
information already out there. We want to build on that. But there is
a lot of new technology and data from the human genome program. One of
the rationales that our office used for starting the human genome
program was to address these problems. And so Domenici happens to
remember that and he came back and said, well, you guys said you are
going to do this, and you are getting close to having the human genome
project done, so don't you think it is appropriate that we try to
address this.
In fact, the human genome program, which is about 18 months,
I think, from 90 percent of all the human DNA pretty well set up -- you
will be able to do a lot of chip technology for looking at induction of
these various response genes and things like that in the human, and the
mouse is basically -- well, the human is a non-furry mouse or something
like that. But wherever you look at the genes, they are very closely
related. It may be things like how much of a gene is expressed and
things like that.
There is a lot of new instrumentation. One of the reasons
we started -- another reason we started the human genome program was we
needed different instrumentation to try to address these low level
problems and so forth. And, of course, there is the Congressional
interest, which allowed us to fund this. As you know, our program has
been hit pretty hard over the years, and I think now they feel that it
is time to try to move forward on this.
But there is also a lot of really interesting technology
that allows us to do this. I have alluded to some of this. We can do
transgenics not only in mice, but you can do transgenic in flies. We
know we can do a lot of hypothesis generating potentially in flies and
yeast. It has to move very quickly out of those systems and into human
systems, but they are so quick that you can get -- you can generate
really nice hypotheses in these systems.
Genetics are well worked out in yeast and flies, and, again,
a fly has all the homologs for humans, they have about one-fifth the
genome, but there are certain genes that cause limb deformities in
flies. If you look in humans, those same genes -- their homologs cause
the same kinds of deformities in humans. Low side associated with
Down's Syndrome. If you trace back, there is a related gene in the fly
that causes flies that can't -- that have learning disabilities in terms
of being able to train for sugar, water and things like that.
So there's a lot of things that can be done with these. We
have sequencing techniques that we can very rapidly -- we are getting to
where sequencing, by the end of the year, we think sequencing costs will
be about 10 cents a base pair. Whenever I started sequencing a few
years ago, it was $10 a base pair. And so looking at mutants, looking
at mutations and things like that was prohibitively expensive. It is
going to be, by the middle of this program, it is going to be a very
cheap way to look at mutations.
There are also leverage kinds of ways, a leverage sequence
where you don't have to do sequencing, it is even cheaper than that.
Resequencing is cheaper than sequencing, and will become even more so.
Microarrays to look at gene expression, as I mentioned,
those are very nice and cute, but they are going to become very powerful
when we have all the genes. And particularly, you can already get
microarrays for yeast. You will very shortly be able to get them for
the fly, and shortly after that for the human. So they are very
powerful techniques.
You can now with FISH independently label each chromosome in
the human. So you can look at mechanisms and things, you know, some of
these complex translocations, we didn't even know existed before FISH
came along. Now we know they exist and we have got better and better
ways to track them, and really powerful, powerful new tools, and I think
it is time we put them to work on this very important problem.
One aspect of this program we still think is instrumentation
development. Some of the instruments, capillaries are just starting to
reach the market for sequencing and they are very, very powerful. We
have people at the national labs and in industry who know a lot about
capillaries. This is potentially a very strong way to measure damage.
It has got to be tweaked, it has got to be changed, but it has got
tremendous power to look at this.
We have single molecule fluorescent detection techniques
where you can see expression of a single molecule. That wasn't possible
a few years ago. Mass spectrometry, if you have a genome, you can take
a cell like -- they are doing it with microbial cells now. You have got
the microbial genome, you can irradiate that cell like we doing
dynocaucus, irradiated versus non-irradiated, you can blow it apart in a
mass spec, and when you know the genome, you can see what genes are
being expressed, because you can find the pieces.
And we have very powerful mass spec, one at Pacific
Northwest Laboratory, 11.2 test to the mass spec. And, sure, that is a
one of a kind instrumentation, but what you can do with that is you can
do the very sensitive experiments, then with just a benchtop mass spec,
you can go back and repeat this and do all kinds of things, once you
know what the peaks are and what you are looking for, once the thing has
been defined.
We have got microbeams, we have had those for a few years,
but we also have -- people have developed electron guns, things for
single cell irradiation. You can not only irradiate a single cell, but
you can pick out whether you are going to irradiate the cytoplasm or
things. Powerful ways to get at things like bystander effects, if you
couple that with single molecule detection for looking at gene
expression and things.
So I think we are really on the verge of being able to look
at these mechanistic things in very, very powerful ways and put that
together with the macro kinds of approach and really try to come up with
new ways of figuring out what the real -- what is really going on in
terms of risk? Are there things like thresholds?
The science is going to drive this, but I think we need to
have the scientists address these questions. And this is going to be
very much a principal investigator driven program, within the
constraints of what we tell them our needs are. And so we, again, in
this document, are saying very simply, we want you to address these very
simple questions. Sure, the way they address them is going to be
complex, but individual investigator initiative is quite strong, I
think, if you give them the right cues.
So that is kind of where we are. I think a last Domenici
quote -- I am having a senior moment here. I had something I wanted to
say with this, but I -- anyway. I think, you know, that sort of defines
where the program is. As I have laid it out to you, you see it is kind
of an umbrella under which we are trying to go forward. It is a new
program. We can give you more specifics as it unfolds, as we get our
projects in.
We are working very hard on the management of this program
between the two offices, the Office of Science, the Office of
Environment Management. We are going to work -- stay on top of this.
We are going to interact with you, with the scientific groups like
health physics, radiation research, American Nuclear Society, anybody
else, the Academy, NCRP. Everybody who wants to help in this process,
we are interested in getting your input. We tried to get as much
comment on our plan as possible. As I mentioned, it is a living plan.
If there are problems still with it, we will address those. And as we
go forward, we are going to try to put together a plan that will really,
we hope help you over the course of the next few years.
Thank you for the opportunity.
DR. WYMER: Thank you. Well, both of the speakers so far
are a very good example of allowing enough time for questions after
their presentations.
First, let me ask again the committee if they have any
questions.
DR. GARRICK: I want to just ask one or two.
If I look at your key question, and I like the idea of
establishing a project or a research program against a set of
questions -- I think in a way that makes it focused -- but your key
question is is low dose, low dose radiation a greater health hazard than
normal physiological processes?
Let me ask on the basis of what we now know how would you
answer that question?
MR. FRAZIER: Well, my feeling would be at very low levels
it is -- my intuition tells me it is not much different, low levels of
low LET radiation.
DR. GARRICK: So most likely what is going to happen --
MR. FRAZIER: But the science is going to answer it, not me.
DR. GARRICK: Yes, I understand, but most likely what we are
going to see here is a change in your uncertainty with regard to that
question. It is probably going to be no, but with uncertainty.
I guess the real question here is what has to happen here in
order for there to be a basis for change? We know that the end result
here is -- at best is going to be no, but there's uncertainty. How can
we use that information? What are your thoughts about what to do with
the results of the research?
I think it is awfully interesting when you engage in a
research program to on the basis of the question you are trying to
answer put forth the answer to that question based on the current
evidence and then speculate if you wish on "so what?" -- so if you get
that answer, what does that mean?
MR. FRAZIER: Well, I think one of the reasons we are trying
to quantitate as we go forward is to find out if by quantifying, you
know, at certain doses of radiation you don't vary from what is going on
in endogenous in the cell. Then that could be used by modelers, risk
modelers and so forth, and I think that the way for assessing radiation
risk might fundamentally change if we have those kinds of information
and we have quantitative information.
Whenever the process that is used today was set up, I think
it was done as a first cut, and there was -- I think that's what the
people who did it sort of intended. The did a damn good job of taking
the first cut but what we need if we are going to go beyond that is new
ways to utilize cellular and molecular data and if we are going to use
it, it's got to quantifiable and if it is quantifiable then I think it
can help you to answer some of these questions and change the risk
paradigm.
DR. GARRICK: I guess a part of my comment here is that one
of the valuable resources that I think would come out of this and would
be short term would be your best shot at the answers to these questions
in a forum that you -- that it will be consistent with where you are
headed.
MR. FRAZIER: Yes. I agree.
DR. GARRICK: Including a forum that displays the critical
parameters that are involved and the uncertainties associated with those
parameters.
MR. FRAZIER: I agree with that, and that is really I think
what we envision is to try to give it a shot so that we can then go to
various groups and say okay, is this -- are you going to be able to use
this kind of information or how do you need it changed to use it. I
think we have to do that. We have to -- this has to be some sort of an
iterative process and if it is iterative that means we have got in a
fairly short time to come out with some information and try to bounce it
off of people who are making these kinds of -- policy-makers.
DR. GARRICK: A final question. I am a great believer in
competition, even in the arena of research. Who is your competition in
this arena? Where are other research programs trying to answer the same
questions?
MR. FRAZIER: I don't know that -- there are other groups
trying to do basic research. NASA is looking at similar kinds of
questions. I interact with Walter Schimmerling on a fairly routine
basis. Of course they have a different set of critical questions but
some of them are the same. We also interact with NCI's low dose group.
They are both doing basic kinds of research.
We also interact with the group at Uniformed Services --
AFRRI. On a routine basis those four groups meet every couple of
months, I think, and discuss our programs, what is going forward, how we
are interacting.
As I mentioned, we have had several workshops with them, so
it is a competition in a sense but it is also -- they have different
bits and pieces of same -- but across that spectrum we are trying to
interact and drive the whole field forward as a group, so we don't have
any direct competition on these questions per se, but we do have good
competition and coordination between NASA, NCI and the DOD.
DR. GARRICK: I think one of the things you will have to be
very on-guard for, it seems to me, given the enthusiasm that you had
about some of these other issues such as instrumentation and the
broadness of scope, is keeping this thing under control, keeping it
extremely focused and aimed at the questions that really do illuminate
the low level radiation issue.
MR. FRAZIER: Absolutely.
DR. GARRICK: Thank you.
MR. FRAZIER: Couldn't agree more.
DR. WYMER: George? Charles?
DR. FAIRHURST: I had question but it slipped my mind.
DR. WYMER: Commissioner Dicus, do you have a question?
COMMISSIONER DICUS: No.
DR. WYMER: Let's go to Dr. Kearfott.
DR. KEARFOTT: Is there really anything missing in terms of
funding of research in this area?
MR. FRAZIER: Is there anything missing?
DR. KEARFOTT: I mean it seems there are four groups funding
research and do you see any gaps among all your programs?
MR. FRAZIER: Well, I think this was a gap before we
started. I think this was clearly a gap. We are constantly monitoring
and trying to address those gaps, but that is something we are going to
have to follow along, and one of the things when we have our first
contractors' meeting is to bring some advisors in and say, hey, you
know -- and some of those people will have somebody from NCI and
somebody who is familiar with the NASA programs and so forth so that
they will be able to say whether there are gaps that we need to close,
but that is a real concern and getting a balanced portfolio is a real
concern here, and it is something I think that if you look at what we
funded last year you would say it is far from a balanced portfolio but
it was just getting a foot in the door and trying to get some projects
funded, but by the end of our next round after this round we hope to
have a very balanced portfolio, moving forward, and constantly
monitoring for gaps.
This is going to be a very difficult project to monitor and
we are going to try to keep on top of it and use as much of the
expertise in the field as we can to do that.
DR. KEARFOTT: Also, do you have any suggestions for the
best way of integrating all existing and future results in this area and
reviewing them and sort of condensing them -- of all of these four
funding sources? We have got all this stuff coming up. Do you have any
suggestions as to who or how this ought to be integrated?
MR. FRAZIER: Well, again, with DOD, DOE and NASA, there are
some things we could have -- I am sure that we could arrange a joint
contractors workshop at some point where we could get -- but NCI is a
little bit more difficult to bring the grantees in, but in the three
agencies I mentioned we have some strings where we can bring people in
and look at all groups.
In lieu of that, what we are trying to do is have constant
communications with the people who are leading each of those groups and
then attending -- I am going to NASA's meeting, contractors meeting,
present our program, get in a panel discussion this year. Walter, and
as I said, some NASA representatives, some of the researchers will come
to our meeting, talk about what is going on in the NASA program, things
like that, so we're going to work that very well, but we are welcome to
any other suggestions.
DR. KEARFOTT: Thank you.
MR. FRAZIER: That is something we are very concerned about.
DR. RAABE: I think we owe a debt of gratitude to Senator
Domenici for stimulating this program and obtaining the funding because
I think it is going to be a very valuable program.
I have just a couple of questions about it.
It is very strong on the micro and mechanistic aspects of
the problem and I am not quite as clear about the macro aspect. Are you
visualizing additional studies with animals at below 10 rem, 10
centigray? What about alternative analyses of existing data? We have a
lot of existing data. Maybe we can do something in alternative
analysis. Is that part of your program?
MR. FRAZIER: Yes, I think we would be interested in other
analysis of some of the existing data. We have tried to preserve a lot
of that data through our radiobiological archive, for example, that we
have in Richland, Washington at Washington State University, so I think
if you can make that case, we have tried to do some of that as we have
gone along even though our funding has dribbled out. We have tried to
do some analyses of existing data.
I think where we are going to work with whole animals though
is not in large mega-animal studies, as was done in the past, but rather
directed studies where we have a hypothesis that we are generating and
using some of the new tools to say, okay, we observed this in a cell
culture system situation. We observed these kinds of interactions. Now
can we make those kind of measurements in an animal and what does it
amount -- what is going on?
There are other things that are going on in animals that are
really quite interesting and one of our researchers, Mina Bissell at
Berkeley, has done a lot of work with extra-cellular matrix, for
example, and extra-cellular matrix is really an important key concept
here, because she can show -- she has shown that structure, tissue
structure, is dominant over function.
Well, we all know that because we have eyeballs and we have
arms and the genome type of all these cells is the same but the
structure, surrounding structure, then is the dominant feature and
allows certain genes to be expressed and other genes not to be
expressed.
She has shown that with tumor cells, mammary tumor cells,
that if she puts them in an appropriate structure they look perfectly
normal and if you take normal cells and put them in an abnormal thing,
they look like tumor cells, and so these are the kinds of issues that
you have to take into account beyond adaptive responses and things.
There's a lot of new science out there that we can bring to bear on this
problem and we intend to do that.
DR. RAABE: Okay. Just one more follow-up, quick question.
It relates to management. I see RFAs going out and you have all these
proposals come in from scientists and that kind of represent a patchwork
of different ideas, and I wonder how you are going to manage this
integrated program to make sure there are no holes. How do you get
research funded that isn't even proposed, for example?
MR. FRAZIER: Well, what we do there is we write, we hold
some of the funding and we write RFAs to direct those questions and we
try to go to meetings and stimulate ideas and we have to reach outside
of the radiation biology community in some of these instances. Some of
the people who are going to address this may be working in other fields
that are really key to this, and so we have got to reach outside of what
was just the radiation biology.
The other thing is we have to have good dosimetry in all
this. That is part of the thing -- whenever we send back things --
proposals -- that we have got to do quantitation here. There's got to
be good dosimetry associated, good exposure systems, well characterized,
and so those are all important elements and we are trying to address all
those. I didn't get into them all today but I think as you see the
program unfold you will see that those elements are int there.
DR. WYMER: Thank you.
MR. HALUS: We have got about five minutes remaining for
this topic.
DR. WYMER: Thank you. Dr. Powers.
Dr. Powers? Okay.
Do any of the future speakers have comments with respect to
clarification or additional information on this topic? Anybody in
general from the audience who would like to say a few words?
MR. ROCKWELL: Yes. Theodore Rockwell from Radiation
Science and Health.
I had a question. You program seems to be aimed entirely at
clarifying the mechanisms of radiation damage, and isn't it true that
the mechanism of radiation damage, in clarifying that understanding, is
really different from developing risk analysis, because in risk
analysis, you have all these confounded confounding factors, and if you
look at data such as the epidemiological data, you will see the real
people with the real problem and all of their confounding factors.
I've heard people say, I want to go live where the radon
level is high because those confounding factors will protect me, you
know. You don't have to put the confounding factors in from the
mechanism if you start looking at the epidemiological data, and there
are some very excellent epidemiological data with very large numbers of
people, very detailed studies. And it seems to me that if you do not
look at that aspect of the thing, you're leaving this great leap of
getting from the mechanism to the risk evaluation. Isn't that true?
MR. FRAZIER: Well, you know, the epidemiology studies and
so forth are an important component. They're not something that we're
going to be able to address in this study.
MR. ROCKWELL: Why not?
MR. FRAZIER: I think some of the --
MR. ROCKWELL: Why not? If your study --
MR. FRAZIER: Because of the scope of it.
MR. ROCKWELL: But if your purpose of your program is to
develop risk analysis, that's what the agency is all about, isn't it?
And if you leave out that big step of how do you get from the mechanism
to the risk analysis and say that's not our job, then I don't see how
the NRC can develop risk analysis.
MR. FRAZIER: I don't think we're leaving out that step of
getting from mechanisms to risk analysis. What the are leaving out, we
are not doing additional epidemiology and looking at some -- I think in
the mechanism studies, we can address some of the confounding factors,
and we'll try to do that; but what we're trying to do is provide
additional information to risk assessment.
You're not going to get at these kinds of low levels by
epidemiology studies alone, and we're trying to provide the --
MR. ROCKWELL: I just don't think that's true. I just don't
think that's true and I don't think you've given adequate attention to
those studies which do involve hundreds of thousands of people and very
high statistical significance.
MR. PUSKIN: I would like to ask a question. Jerry Puskin
from UPA.
I have a question about -- you say that it has to do with
this question of whether radiation is the same as endogenous oxidated
damage. I thought it's been pretty well shown that radiation is
different because the damage is clustered, and --
MR. FRAZIER: Well -- I'm sorry.
MR. PUSKIN: -- and that, in fact, that someone like -- some
of the work of Dudley Goodhead has shown that the damage even at tens of
rads is dominated by single effects, and that really the issue is more
one of how much of this damage can be repaired, and it's not really the
same. It's more complex damage than you get with just oxidative damage.
MR. FRAZIER: Well, I don't think we know the answer to
that. First of all, we do, first, that a high LET -- that you get these
multiple locally damaged sites, you do get very complex things.
But at a low LET, I -- you may get some of that, but we
don't know whether endogenous damage causes similar kinds of things, you
get a burst, oxidated burst, you've got a strong chance to be getting,
in a localized area around DNA, older cells, leaky mitocondrhia or
something. We don't know that you don't get that kind of damage. Those
kinds of things haven't been measured.
I mean, we know what we get with radiation. That's been
measured, it's been modelled. But endogenous processes, we need to look
at that and see are we getting that same kind of thing and how is it
handled in an endogenous situation. I don't think we know the answer to
that, in other words.
DR. WYMER: I doubt if there's time for another question.
If there's more discussion, there's time during the break, which we'll
take now. We will start at ten minutes after eleven. If you're not
back by then, you'll miss part of the next talk.
[Recess.]
DR. WYMER: Okay. It's time to get started. Please take
your seats. Let's get this show on the road.
Our next speaker is Dr. Charles Land, Radiation Epidemiology
Branch of the National Cancer Institute.
Dr. Land.
DR. LAND: Well, I am a biostatistician and I know a little
about epidemiology. I don't know a whole lot about other things, so
this is going to be fairly short.
I'm only going to talk about the epidemiology part and the
statistical part, and the first -- this first slide here is actually
wrong, but it's --
[Laughter.]
DR. LAND: It's wrong because these numbers are too large.
This is not women; this is everybody in the life span study sample of A
bomb survivors. But the point is proportionally, it's right.
There are a lot of people at zero dose; there are a lot of
people at one to five rads; and then it just goes sort of down
exponentially. And at the really high doses, where all the good
information is, there aren't very many people at all. That's just --
that's the whole thing. I just want to get that across.
And these are epidemiological data, breast cancer. It's a
summary dose response analysis adjusted for city and age at the time of
the bombings and detained age in calendar time, and it just expresses
the excess relative risk as a function of dose, and even though there
are very few people out here, few hundreds, the -- and relatively few
cases, where most of the cases, the breast cancer cases are down here in
the low dose range, I think you can see here that this is where you get
the big excess risks, of course, and so these are estimates of excess
relative risk, and these are confidence bounds on this estimate. So
there's a lot of error there, but it all ties together very well, and
actually these data fit -- happen to fit a linear model extremely well.
I understand, by the way, that the linear -- the question of
the linear no -- low dose, no threshold hypothesis is not about
linearity as a function for describing the whole thing; it's about what
happens down in here.
So here's what happens down in here, and the main point here
is that if -- well, first place, there is an excess -- a significant
excess at around 15 rads. But if we only had these data here, if we
only had the data below a tenth of a cevert, we would have no reason to
believe that there was -- there is an excess risk associated with
radiation. And we have all the rest of the stuff, so we do know that
it's true.
Basically, the thrust of my talk is going to be that as you
are interested in what goes on at really low doses -- that is, as
divorced from this -- it may be that the shape of the dose response sort
of changes drastically, or that there is a threshold down here -- you're
not going to get there. You can't get there from here. This is -- from
the epidemiological data, you can't do it, you can't answer it.
DR. HORNBERGER: Could you just clarify for me what the
measure excess risk is? Is that a --
DR. LAND: Oh, excess relative risk. Okay. You take --
actually, I'll be clarifying that in just a little -- in a little bit.
All right.
Essentially, what you do is you take the risk here and you
divide it by the risk here, and you get a relative risk and then you
subtract one from it, and that's the excess relative risk. But I'll
explain that a little more later.
Risk estimation is all about the slope of the fitted curve;
that is, you take the excess risk, excess relative risk, you divide it
by the dose, and then you get -- and you get this slope. And this is a
fitted line, and so this is the same line, the same fitted line as this
one. The slope of this curve is what matters, it's the excess risk per
unit dose, and these are confidence bounds based on the regression.
Now, what I'm going to do here is I'm presenting the slope.
So this value here is the slope of the line in the previous graph, and
these limits here are the confidence bounds on the slope of the previous
graph. This -- what this is about, then, is what happens if you start
taking away the high dose data. Actually, these are pretty strong data.
And so as you take away the very highest dose points, just keep moving
across, it doesn't change very much, but you're losing data, and so the
confidence bounds get a bit wider. They get a bit wider. That's not
only because you're losing data, but it's because you don't have this
angular business, you have -- if you have the same -- if you have the
same data point as that and you moved it down here, the angle becomes
much wider. That's, I think, pretty obvious.
So we get down here and the -- get more instability because
you're having to -- you have less signal and more noise proportionally.
And down here, below ten rads, you don't have any information at all.
So really, it's these data are -- the higher dose data are what drive
things.
DR. POWERS: Could I just ask you on this, you indicate
error bounds for the relative risk.
DR. LAND: Yes.
DR. POWERS: But you -- is there something that indicates
the error bound for the dose?
DR. LAND: I'm ignoring that.
DR. POWERS: I wondered why.
DR. LAND: Because the -- the error in the dose estimates
for the A-bomb survivors is not -- it's not something that affects so
much the error in the -- it doens't increase error, it introduces a bias
in the estimate, and the way to correct for that is to essentially you
increase -- no, you decrease the doses against which you plot things,
and it changes the estimate, but it really has very little effect on the
doses. This has been explained pretty well by Don Pierce and a number
of other people. It's a statistical issue and it really doesn't -- it's
taken into -- that particular -- the error introduced by error in the
dose is taken into account here as a bias -- as a change -- as a bias
adjustment.
So there is nothing here to support an increased risk per
unit dose at very low doses, say, below 5 centisieverts or a decrease,
and it can still be true, but resolution of this question is going to
have to come from other kinds of studies. That's basically -- basically
the message and I could just stop there, except that I am compulsive and
I would like to explain more to you. But maybe you really -- there
probably would be some resistance to this.
But this is -- okay. This is some statistical theory, and
now I am not talking about -- I am not going to be talking about
estimates any more, now I am talking about the statistical process, the
probabilistic process, and, generally, when you are dealing with cancer
rates, you are talking poisson random variation. And so we have a count
of number of cancer cases, and we say -- and it will be essentially
poisson, or approximately poisson in its variance and its mean will be a
rate times the number of people, or times the number of person years.
And this is a pretty good approximation. If you take the
log of the ratio of the number of cases divided by the number of people,
or the number of person years, you get something that is approximately,
normally distributed, and its mean is approximately the log of the rate,
and its variance is the inverse, approximately the inverse of the number
times the rate.
And if you have another independent poisson variable, like
another -- like number of cancers in another population with the same
basic rate, but an excess that is due to radiation, so it has this mean
but times 1 plus alpha D, where alpha D is the excess risk that is
related to radiation. It doesn't have to be linear, it just -- it is
simpler if I do it this way.
So the ratio of these two, and that's the sort of points you
saw on the first graph, or the second graph, that is approximately
normal. The log of the ratio and its mean is what you want to estimate,
and it has a variance that depends on -- proportional to the inverse of
NP, times a ratio of 2 plus alpha D, actually, it is divided by 1 plus
alpha D. So, now this ratio, as D goes to zero, or as alpha D goes to
zero, approaches 2, and if alpha D gets very large, it approaches 1, so
you have really -- really, you are dealing with this. The main thing
that dominates this is this 1 over NP.
Any resistance yet to this? Now, let's say that, and I have
already said it, actually, is that X is the number of cancers that are
observed in N, unexposed people, from a population with cancer rate P.
That is what -- and that X sub D is the number of cancers also in N
people, from the same population, that are exposed to a particular dose,
D, and their cancer rate is P times 1 plus alpha D.
The relative risk of cancer in the population exposed to
dose D, compared to the population with no exposure, is 1 plus alpha D,
and it is estimated by the ratio of these two counts, the numbers of
cancers. And that is -- I am making it simpler because, generally, you
don't have identical Ns, but that's -- believe me, it is better this
way.
Okay. Now, the next -- the graphs that I showed you before
concerned estimates of excess relative risk. An excess relative risk is
just relative risk minus one. So that when you don't have any effect at
all, you have zero.
Now, here is an example where you have approximate doubling
of risk at one sievert or one gray, and that the baseline rate is
one-and-a-quarter percent, and you have a thousand observations. Now,
this is not a data graph like the one I showed you earlier. This is the
distribution, the mean of the distribution of estimates, and this is
sort of the upper and lower 90 quantiles that correspond to 95 percent
of the distributions, all right. And -- well, I guess I should point
rather than there. So there is -- if I had -- if D is 1, then this
ratio has mean here and 95 percent of the time it is between these
bounds.
And then, finally, if you had an estimate here, this would
be the upper 95 percent confidence limit, and if you had an estimate
here, this would be the lower 95 percent confidence limit. So your
observation -- your confidence bounds, you can be fairly sure that the
risk is going to be somewhere in here. And as you -- as the dose gets
lower and lower and lower, these intervals shrink somewhat, but not a
whole lot, because they are really governed by 1 over NP. It is the
sample size and the rate that governs it.
And here is the point I was trying to make earlier, that the
value of alpha, or the estimated value of alpha is between these two
lines here, but when you have got -- when your data are down here, the
ratio is -- I mean the range is a lot wider. So these, if you did a
study with data down in here, you would have less information about the
excess risk than you would from a study out here, at a higher dose. And
that is the crux of the problem.
Well, here is what I am -- here it is all written out again.
Based on log normal distribution theory, the estimate of the excess
relative risk at dose D should be between these two values, and that is
the -- that is these limits there. And for estimates within that
interval, the lower and upper confidence limits correspond to these two
equations, you just multiply by another variance, roughly, and that is
where these things came from.
And then, well, the business about the line between the
origin and the point of -- on which the risk estimate was plotted has
slope alpha, and I have already told you that.
This is the same thing, but with 10,000 people at each --
again, this is not a regression. This is the whole study right here,
and you are just drawing lines back here, and this is what happens if
the study is out here, is at 1 sievert or 1 gray, at a half a gray, at a
quarter of gray, an eighth, sixteenth and so forth. It gets very
crowded in here and there is not much information. It looks a lot
better at 100,000, 100,000 is -- well, it is bit better than the A bomb
survivor studies.
So, as I said, what really drives this uncertainty is the
number of people and the baseline rate.
Well, I don't think this is -- I really can't believe that
this is working very well, but I am just going to carry on. If you --
DR. GARRICK: Can I ask a question?
MR. LAND: Sure. Go ahead.
DR. GARRICK: Rather than going through an exercise of
fitting data to, say, classical distributions and doing regression
analysis and what-have-you, what if you were to represent the data in
the form of discrete histograms and let the data completely drive the
distributions by inferring from the data in, say, a Bayesian sense,
would you get the same kind of results?
MR. LAND: If it worked, yes, you would more or less, but
except that when you say Bayesian, you raise the possibility --
DR. GARRICK: Talking to an expert statistician, I would
expect that response.
[Laughter.]
DR. GARRICK: But I am just curious what would happen if we
tried to analyze this data in what, from an engineering perspective
might be a little more visible than curve fitting and regression
analysis? If you represented it in some sort of a discrete form --
because data comes to you in a discrete form. It comes to you in
whatever distribution these discretized histograms suggest, and if you
manipulated that in some way, and if I were to do it, I would do it
Bayesian, would you expect to, in your experience, get the same kind of
results?
MR. LAND: Okay. I am hearing what I expect to hear when
you say Bayesian, and when you say Bayesian, that means that you
actually have a prior distribution and you are putting prior information
in there as well.
DR. GARRICK: Right.
MR. LAND: And the ratio, and, of course, if you don't
really have much information, especially down at low doses, much
statistical information, what you are going to get is your prior.
DR. GARRICK: All that means is that the evidence is going
to control the distribution.
MR. LAND: No, in that case, it means that if you are
talking about the information, a study at low doses, it means that there
isn't very much information and that your conclusion is going to reflect
exactly your prior. But I think maybe you were talking about something
a little differently.
DR. GARRICK: Yes. Yes. Yes.
MR. LAND: But, actually, there isn't a philosopher's stone
here. I really do sincerely believe that. I think that the most
efficient way, statistically, the most efficient way to do things is to
always argue in terms of, given these basic assumptions, then this
follows, and that is why one uses models like linear dose response or a
linear quadratic and so forth. You get can get better conclusions
about, if it is linear, what is the slope. If it is linear, then it
looks as if the slope is this. If it is quadratic, if it is a general
quadratic, what is the linear slope and the curvature?
And your answer to that is not going to be as good.
Yes.
MR. LAND: And say well, let's suppose it's a linear
quadratic and you use the ICRP, low dose and dose rate reduction factor
of 2, you'll get a better answer, because you're putting in that
assumption that that DD REF is 2.
Well, what I'm trying to get at here is that if -- oh, let's
see, okay -- this actually is the wrong graph. I don't want that there
at all. I changed it. Okay. Right.
Suppose -- oh, I want to show another graph as well. This
is -- I just showed you this curve. Now I'll show you this one, which
is the low dose detail. This is -- all right. And I think that even
with 100,000 -- and again, this is 100,000 here, not spread out over the
whole thing. This is 100,000 here or 100,000 here or 100,000 here or
100,000 here. And the point I want to make is that at the very low
doses if you have a study here it doesn't tell you anything, because of
this uncertainty here, that is, the observations could be anyplace,
could be anyplace in here, and the confidence limits could be anyplace
in here.
And this would be an estimate if -- what the estimate would
look like if the excess risk were actually zero. All right? Now, take
this and let's take this distribution here and move it out here. Let's
say that you actually have a dose of 20 rads and there isn't any excess
risk. You have a threshold above 20 rads. You've still got all this
uncertainty, and you're very unlikely to get an upper confidence limit
that's less than zero. So even if there is a threshold, it's going to
be very difficult to show. And if I -- I can increase the numbers from
100,000 to a million, I can increase them to 10 million, and all it does
is it changes the scale of this drawing. Instead of here between 0 and
20 rads we get down to zero to 5 rads or zero to 2 rads. There aren't
enough -- it's just not possible to do studies large enough to solve
this problem.
You have to do it a different way. You have to do it with
molecular studies -- epidemiology is not going to do it. Even though --
and I don't think you're going to do it with experimental animal
studies, because people feed themselves and they house themselves, where
animals don't. So there is this enormous problem of expense.
So the bottom line is it's extremely difficult to
demonstrate the existence of a low dose threshold epidemiologically.
I think it's probably a lot easier to demonstrate the
existence of a high dose threshold, especially if at even higher doses
you have a big response because you see this big difference between
risks. But when you're down in this area, it's really difficult.
That's it. That's really all I have.
DR. WYMER: Okay. Thank you very much. Again, we do have
time for questions. It looks like the people pushing for
epidemiological studies have just been shot out of the saddle. Maybe
there are some counterarguments?
John?
DR. GARRICK: Oh, I don't think I have any questions.
DR. WYMER: George?
DR. HORNBERGER: You want us to go along with you on this
conclusion for all studies? I mean, you started showing some data on
breast cancers, but then you went on, and given your assumption of a
Poisson distribution, you showed us basically the sampling distribution
for that process.
Are your results at all sensitive to those -- the
assumptions of a Poisson process, or is this a robust conclusion?
MR. LAND: It's robust. Yes. And the Poisson -- Poisson is
one of these natural distributions when you have counts and you have
large numbers and small rates, that's Poisson. And it's -- I mean it's
just -- it's not something that you can say well, maybe it isn't,
because it just about has to be.
There is one other thing that I should have said and --
should not have said, and missed, and that is that all of this is based
on the assumption that the high dose that the exposed population and the
nonexposed population are identical except in the fact that they were
exposed. And that is extremely difficult to show. If you're dealing
with large doses where you have big effects, it doesn't matter. But if
you're dealing with real small doses, when you're looking at really
small effects, those -- the little differences that might occur between
the population for some reason would probably dominate things. And so
you might get -- you might very well get an estimate that's very low,
it's negative, or when it's positive, but it probably would be
determined by the difference between the populations rather than the
dose response.
I don't know how you could control for that, because
generally when we're dealing with little bitty excesses, there is all
kinds of things. We don't generally study little -- very small
excesses, and so we don't know anything about them.
DR. WYMER: Dr. Kearfott.
DR. KEARFOTT: Two quickies, just to clarify for me, at one
time I was challenged to write a paper that had no words in it and only
equations, so I want a little words.
Is there anything then -- number 1, am I understanding
correctly that this argument applies not just to detecting a threshold
or the shape, but the uncertainty and the risk estimate at these levels?
MR. LAND: Yes.
DR. KEARFOTT: Okay. So it applies to both.
Secondly, is there anything at all to be gained by
reanalyzing in a broad sense all the work that's been done to date
epidemiologically on this issue?
MR. LAND: Well, that's one of the things I do, you know,
and so I --
[Laughter.]
I don't really want to say -- but you have to be real
careful when you do this sort of thing. But actually yes, when you have
different studies on the same -- let's say on, for example, on breast
cancer in irradiated women, there is something to be gained, and one of
the things you gain is you get information on what else influences the
radiation-related risk.
Sometimes -- for example, if you compare Japanese women and
American women who have very different baseline rates, you learn a lot
there. You learn -- you do get more stable risk estimates.
DR. KEARFOTT: So that new studies would mean millions or
even that wouldn't help?
MR. LAND: No, I don't think it would help. Because of --
well, do you have any idea how expensive these things are to do? They
really are. They really are expensive. But I think that what the most
interesting things in radiation epidemiology after one has established
that there are risks and wants to quantify them reasonably well, is that
here you have a known cause of radiation, and what influences it besides
the dose. That's where the excitement is.
DR. KEARFOTT: Thank you.
MR. LAND: You're welcome.
DR. WYMER: Dr. Raabe?
DR. RAABE: I have a couple of quick questions about some of
the data you presented. On the breast cancer data that you presented,
did you attempt to fit a threshold model mathematically to those data to
see what kind of effect you got like ratio tests or something to see if
it was better or poorer than --
MR. LAND: Have I done it? I know that Dale Preston has
done that with some other data. I tried fitting quadratics, and the
result of the quadratic was that there really wasn't much evidence of
any curvature at all, that whatever curvature there was was really
small. One can do -- I know that if I were to fit a model with a
threshold around here, it would fit pretty well if I just had a linear
that went out -- a dose response that went out to there and then went up
from there, it would fit every bit as well as this one.
DR. RAABE: Dr. Upton mentioned David Hall's study where he
took the life span and fit threshold models and said they were equally
good, maybe better than linear models.
MR. LAND: Well, yes, if the threshold is really low, is a
low-dose threshold, sure, you betcha, because there isn't any
information down here.
DR. RAABE: Well, just one last question. When you get this
relative risk, you have a -- it's anchored at the zero there, excess
relative risk. Is that based upon some independent population, Japanese
living outside of Hiroshima?
MR. LAND: No, it's based on the A-bomb survivors that had
really low doses.
DR. RAABE: Right. Now I heard a rumor, and I don't know
this for a fact, I've heard a rumor that if you look at the cancer rates
or life span incidences of Japanese people who were not in Hiroshima and
Nagasaki, that the people who were there actually have lower cancer
rates and longer life span than Japanese who didn't happen to be in
Hiroshima or Nagasaki at the time.
MR. LAND: Okay. That's -- that has been said, and it has
been -- it probably is true or it might be true. It's been explained
one thing, well, the people who were -- let's see, are they really --
then the people who were -- at first we did not -- okay, in terms of
breast cancer, the women who were not in city and who are in the LSS
sample actually have lower breast cancer rates than the women who had
very low doses. However, in other studies they have -- let's see, I'm
trying to remember a particular study that was done in Nagasaki, and I
can't remember the outcome, but it was the opposite way, and it was
explained that this might be because A-bomb survivors have free medical
care. But, you know, these are all post hoc explanations and you know
what that's worth.
DR. RAABE: Healthy survivor effect or something.
MR. LAND: Well, it's possible, quite possible that that's
going on too.
DR. RAABE: Well, I wonder if you could, you know, this is
an interesting question. I wonder if you could just come up with a
reference where somebody has looked at the independent control group.
There's no independent control group in these studies. It's just all
internal comparisons, right, the way you did this?
MR. LAND: Oh, I would not want to do an independent --
okay, there is -- the LSS sample has 120,000 people, of whom 26,000 are
people who were resident in Hiroshima or Nagasaki around October 1950 or
maybe a little later, and they were added to the population because they
weren't there, they weren't there at the time of the bombing, they
were -- and so that was considered to be a control. And that sort of
passed out of fashion using them because they seemed to have a little
bit different rates, which might be explained by the fact that say many
of them were -- their socioeconomic status is somewhat higher or was
somewhat higher. A lot of them were living in Korea or China or they
had been farmers. But I've actually from breast cancer I've started
using them because it makes very little difference to the risk
estimates.
MR. HALUS: We had planned about five more minutes --
MR. LAND: Oh, sure.
MR. HALUS: For this presentation.
DR. WYMER: Dr. Powers, anything?
DR. POWERS: What you have shown is a classic result of
experimentation, always use a high variable when you want a
statistically powerful result.
MR. LAND: Yes. Yes.
DR. POWERS: Does the same thing -- if you inject additional
information into the process that as I've done a high one and now as I
do a second study with a second population in there, do you retain the
high one still being just totally dominant and it really doesn't matter
where you do the second variable, or does that give you information on
curvature?
MR. LAND: You know these are actual data points.
DR. POWERS: Yes, I understand that.
MR. LAND: There's a whole lot of people --
DR. POWERS: I was speaking more of your theoretical stuff.
MR. LAND: More theoretically.
DR. POWERS: Yes.
MR. LAND: If you have -- well, in epidemiology -- unlike
experimental stuff, in epidemiology you take what you can get.
DR. POWERS: That's right.
MR. LAND: So that is what is there and with an experimental
study you can design them. In this other stuff I was just talking about
a two group -- a zero-dose group and a higher-dose group -- and with
that design you could not estimate curvature. You need three points to
do that, to estimate curvature, and you need four points to do more
complex things.
Have I understood your question?
DR. POWERS: Well, what I am wondering is two things. One is
what is the statistical power for validating a linear model, of
introducing a third point, a third study?
MR. LAND: You don't have any power at all unless you do it,
unless you introduce this third point.
DR. POWERS: And if you are trying to validate a curve
model, which I presume the people advocating thresholds would -- it's
easier to detect curvature than it is to detect thresholds --
MR. LAND: Yes, right.
DR. POWERS: -- does the third study that you introduce give
you any power for detecting curvature, since threshold is just going to
be impossible to detect?
MR. LAND: Well, of course it does. Yes.
DR. POWERS: And are there any characteristics of where that
third study should be in order to optimize your detection of curvature?
MR. LAND: I would think you would want to be right about in
the middle.
DR. POWERS: I would think so too.
MR. LAND: Yes, but I mean I have thought about it a little
bit. I haven't thought very hard, I guess. I don't know exactly, but
that seems about right, in the middle.
DR. WYMER: I think we have time probably for one more
question and one more answer to that question from the floor.
MR. ROCKWELL: I'll make it a real short one. Ted Rockwell
again.
But we are still left to explain the fact that when we look
at 700,000 nuclear shipyard workers, the lifespan situation -- .76 --
the mortality is down. The atomic bomb survivors are outliving the
controls. The soldiers who participated in atomic weapons tests are
outliving the controls. I mean every one of these massive studies all
is anomalous in the same direction. Isn't that rather curious?
MR. LAND: I don't actually accept what you have said. I
don't think that these conclusions are that strong.
MR. ROCKWELL: Have you looked at the nuclear Naval shipyard
studies, because that is very good statistics and very good control of
dose.
MR. LAND: But in occupational studies you actually do
find -- it's called the healthy worker --
MR. ROCKWELL: No, no, this is matching up welders with
welders, ship fitters with ship fitters, painters with painters in the
same shipyard and you are taking the only variable then is the
radiation, and this is very good radiation control, individual dosimetry
monitor every day and the mortality difference was .76.
MR. LAND: No, I haven't looked at that.
MR. MUCKERHEIDE: Just one quick question.
DR. WYMER: Okay -- you've got a minute.
MR. MUCKERHEIDE: Jim Muckerheide again.
When you said that the issue of very small differences in
terms of doing the study, if you take background at 300 millirem, just
for sake of argument, are you talking about differences of 100 millirem
or less or up to a rem, or are you talking about up to 10 or 20 rem, as
you had indicated? There were some of the issues about the range in
which you would do studies in terms of the relative difficulty in
finding the results.
MR. LAND: The lower the dose -- it's actually an effect
thing. The lower the effect, the lower the excess risk, the harder it
is.
MR. MUCKERHEIDE: But you are implying that no matter how
big the data got if you are talking about small effects it would be
almost impossible.
MR. LAND: If it's real small, yes. If you are talking on
the order of --
MR. MUCKERHEIDE: And I wondered if you were talking only
really down to your background or whether you are talking about
multiples of rem.
MR. LAND: It all depends on -- it depends on the baseline
rate. It depends on the slope of the line you might say or the shape of
the curve. It depends on the baseline rate and the excess rate, and the
number of people and it also depends on this other problem, which we
really don't address much statistically is that it is of differences
that are not due to dose -- but the short answer is, yes, I was talking
about doses on the order of a few, let's say a milligray to a few
centigray, that sort of thing.
MR. MUCKERHEIDE: Okay. The other conclusion that you
seemed to reach is that if you seem to reach is that if you don't know
any more than you know from the kind of low dose effect, it seems to me
that we live our lives on medical and pharmacological data that are all
driven by these kinds of studies, and you are kind of implying that if I
look at all of those millions of studies that have justified medical and
pharmacological results, they have no power of information because in
many cases they are talking about relatively low doses changing what we
know about nutrition and many other things.
They are not using large populations and so they are
obviously of no epidemiological benefit.
MR. LAND: You are talking about clinical trials?
MR. MUCKERHEIDE: Clinical trials and other studies, yes.
MR. LAND: Well, they are generally not looking for really,
really small differences, the clinical trials. they are looking for big
differences, differences that are worth, you know, spending money to buy
drugs --
MR. MUCKERHEIDE: -- big differences in dose or just in
results?
MR. LAND: In results, sure.
MR. MUCKERHEIDE: And yet we have statistics that get
reported all the time where the differences in results are very small
between one group and another group and yet we are making decisions on
medical treatments on the basis of those results.
DR. WYMER: May I suggest the two of you continue this
discussion over lunch.
We will resume exactly one hour from now.
[Whereupon, at 11:57 a.m., the meeting was recessed, to
reconvene at 1:00 p.m., this same day.]. A F T E R N O O N S E S S I O N
[12:58 p.m.]
DR. WYMER: Take your seats, if you will. We are ready to
begin this afternoon's session. Our first speaker is Evan Douple from
the National Academy of Sciences' Board on Radiation Effects Research,
who will be talking about biological effects of ionizing radiation, as
soon as he gets wired up.
[Pause.]
DR. WYMER: While he is adjusting his projector, let me
point out one more time that there will be opportunity during the panel
discussion for the people in the audience to ask questions that they
might not have time to do after the speakers, so keep that in mind as
you frame your questions.
MR. DOUPLE: It is a pleasure to be here. I have been asked
to talk a little bit about the National Academy of Sciences BEIR VII
study which has just begun, and to do that, I would like to basically
focus on three aspects, and perhaps save the last one for the panel
discussion.
First, I would like to talk about our scoping study. This
time the Environmental Protection Agency asked the Academy to begin with
a phase one scoping study to ask the question -- Is there enough new
information available since BIER V in 1990 that would enable a BEIR VII
committee to do a reassessment of risk that would be perhaps different
or more rigorous than what been done almost ten years prior to this
time?
In addition, I would like to talk a little bit about a
workshop that was held in conjunction with the phase one study, it was
sponsored by the Department of Energy and it was to look at the biology
that had been developing in the last few years, and it was titled, "The
Impact of Biology on Risk Assessment." DOE had actually supported two
workshops. Two years prior to this time we had done a workshop to
assist the BEIR VI committee looking at high LET low dose radiation, and
the purpose of this workshop was to look at low LET low dose radiation.
Thirdly, I would like to tell you about our plans for BEIR
VII, the phase two that was recommended by the phase one scoping study,
the goals and the work scope of the committee, how we are composing the
membership of the committee, its timeline, and how we expect the
committee to do its work.
The phase one committee produced a report that was called,
"Health Effects of Exposure to Low Levels of Ionizing Radiations, Time
for Reassessment." And this report was published last year about this
time and it is a summary of the scoping committee's recommendations.
That scoping committee consisted -- it was a relatively small committee,
it was chaired by Dick Setlow from Brookhaven. It included Ken Chadwick
from Europe, Phil Hanawalt from Stanford, Jeff Howe from Columbia
University, Albrecht Kellerer from Germany, Charles Land from the NCI,
Nancy Ollinick from Case Western Reserve and Bob Ullrich from the
University of Texas, Medical Branch at Galveston.
The bottom line, the conclusions of that committee and its
scoping study is summarized in this paragraph. They came to the
conclusion that information has become available since 1990 that makes
this an opportunity to proceed with a BEIR VII phase two, a
Comprehensive Reanalysis of Health Risks Associated with Low Levels of
Ionizing Radiations. Such a study should begin as soon as possible and
is expected to take about 36 months to complete.
Now, that report of the scoping committee provides the
justification for their conclusions, and that justification is
summarized here. The committee based its judgment on the following five
major considerations.
First, there is a lot of new epidemiologic evidence. In
fact, at least 49 of those studies -- or, I am sorry, 39 of those
studies are summarized in the scoping committee's report. Some of these
are updates of the very rich RARF data from Japan, but, in addition,
there are nuclear worker studies and many other epidemiology studies
that were not available to the committee in 1990.
Some of the new data is an area where information had been
sparse. An example is cancer mortality for those exposed to whole body
irradiation in childhood. Studies of carcinogenesis completed since the
BEIR V have focused on mechanisms and the cellular and molecular events
that are involved in the neoplastic process. And if BEIR VII follows
BEIR VI in terms of considering and looking and evaluating all of the
biology that is available in the published literature, then this would
be an important consideration for BEIR VII to do the same.
Over the next few years, investigators will be applying two
closely linked approaches using animal models of carcinogenesis. This
is using the new technology of knockout mice, it is genetic studies, and
this should be very, very important, particularly in terms of looking at
susceptible subpopulations. Those two experiments should be available
within a year or two at the very latest.
And, finally, there is evidence regarding specific biologic
events that can affect the shape of the dose response curve at low
doses. This is accumulating and a BEIR VII committee would be expected
to be following this biology, and some of this may come from the DOE
program, or at least we hope that it does, and that it might come in
time for this committee to consider that new information.
The scoping study recommended that a BEIR VII could do at
least the following five things. One, it could include a comprehensive
review of all relevant epidemiologic data related to low LET and
sparsely ionizing radiation. The committee should define and establish
principles on which quantitative analyses can be based, including
requirements for epidemiologic data and cohort characteristics that they
would use in their analyses.
The group should consider biologic factors such as the dose
and dose rate effectiveness factor, relative biological effectiveness,
genomic instability and adaptive responses, and other factors that may
become better known in the next two or three years. And, finally, they
would use appropriate models, favoring simple as opposed to complex, to
develop either etiologic models or estimates of population detriment and
attribute causation in specific cases.
So the committee was directed to look at the data in a
manner which would provide information that could be used for risk
assessment.
To assess the current status and relevance to risk models of
biologic data, there are those who feel that they have been able to
model the Hiroshima, Nagasaki data and those modelers, with additional
biology input and information, might produce a risk analysis that may be
very important and certainly would not have been able to have been done
10 years ago, in particular, evidence of thresholds or the lack thereof
in dose response relationships, and the influences of things such as
adaptive responses and radiation hormesis.
They should consider potential target cells and problems
that might exist in determining dose to the target cell. And, finally,
they should consider any recent evidence regarding genetic effects that
are not related to cancer. And those of you who have been following the
RARF data know that there is considerable new data from Japan indicating
non-cancer endpoints, particularly at higher doses and in populations as
they age, but that is information that certainly was not available, and
it is still not clear whether that material is going to turn out to
stand up to statistical scrutiny and analysis.
MR. DOUPLE: The categories of information that is available
since BEIR 5, some of it is summarized here to give you a flavor of the
types of human data that will become -- or is available. There's
non-leukemia cancer mortality the RARF group has published through --
analyzed the data and published in 1996 which models mortality to the
end of 1990. They're currently working on the next five-year extension.
Mortality in a British series of patients treated with
x-rays for ankylosis spondylitis, and this data has been updated a few
years ago. There's several radiation worker studies, typically those
that have been coordinated in Europe by Elizabeth Cartis and others, and
of course in this country Ethel Gilbert and her analyses.
Site-specific analyses for most cancer sites -- again
primarily in the RARF data but in many other populations for specific
cancer sites, there is new data for a variety of different cancer types.
Finally, new data on radiation related risk in patients
known to be genetically susceptible to cancer. This committee has been
charged that they should consider very carefully the potential influence
of sub-populations that might be sensitive, the retinoblastoma patients
that have been studied, the Swift hypothesis regarding the ATM and
breast cancer and increased susceptibility to radiation related breast
cancer, and finally the ICRP has summarized the genetic susceptibility
to radiation related cancer, and that's work done by Roger Cox and his
colleagues.
So those are just some examples of epidemiologic data that
should be very important to a reassessment of risk, and it's information
that was not available when BEIR 5 was done.
So the considerations would be that the new data should
permit the development of a richer risk model and perhaps alternatives
to models, and furthermore, there have been methodologic developments
such as the incorporation of dose measurement errors into fitting for
risk models that was not applied in BEIR 5.
The committee could develop a generalized strategy for risk
modelling and illustrate it with specific examples. The models should
provide a good fit to the empirical epidemiologic data, be biologically
plausible, be readily understood by the scientific community in general,
and that argues in favor of simple rather than complex models, and
finally should take into account all the relevant epidemiologic and
biologic data. That's a big task to chew off, but it's the kind of
thing that the committee should at least begin as its optimistic goal,
and it will depend on many factors as to whether or not they successful
achieve that goal.
That report is available from the Academy, and it includes
some examples of modeling that could be used that would take biologic
data and try to model the epidemiology results.
I mentioned that DOE asked us to conduct two workshops, and
the one on the impact of biology on risk assessment was held July 21, 22
in 1997. We had 47 attendees, and the five topics of focus were DNA
damage, inducible responses, situ genetics and chromosomal instability,
individual susceptibility and sensitivity, and modeling. And these are
all terms that you heard this morning. My overall impression of this
workshop was that I was very surprised that these distinguished
scientists, all of whom have in their introduction to their grant
applications, I'm sure, the statement that what we propose to do is
important to risk assessment. But I was surprised to see that they
really had not thought about the implications of what their work and
their results had done. So if anything, I think it was good to get
these people in the same room with people from DOE and EPA and other
risk assessment bodies to be forced to start to think about the
implications of their results.
I noticed there is some additional gatherings now of these
-- some additional workshops being planned. They're basically many of
these same people, but I think perhaps by bringing them together again,
they will have thought about the impact of their results, and hopefully
we have a dialogue going here that will be very beneficial.
The results of with workshop were published in Radiation
Research in December, and the first author on that was Michael Frye.
Most of you have probably seen that manuscript, and it basically
summarizes all of those five sessions that were the focus of the
workshop.
In terms of the workshop conclusions, I've pulled out I
think these five major points. The first is that there are differences
between spontaneously occurring oxidative damage and ionizing
radiation-induced damage. At least the multiply damaged sites is
something that is rather unique compared to the endogenous oxidative
damage that we hear so much about and we know is repaired so well. I
think, as we heard this morning, additional work has to be done in this
area. There are those who claim that at the lowest low LET, the lowest
dose in a single traversal, you will have clusters where even a low LET
particle has at its end, whether it's the final beta track, there is
this potential for a high LET type of an effect and a clustering of
radiation damage.
Secondly, factors were identified which, if they occurred in
the intact human organism, could lower risk -- for example, adaptation
or adaptive responses in hormesis -- but then there were other effects
that could increase risk, such as bystander effects and genomic
instability. You really have to realize that this could work on both
sides of the coin, and if it isn't applicable in the intact organism,
then it's something that's not going to apply to risk assessment. So
we're still at a very primitive stage relative to these new effects that
are being identified, and we really have to understand how they would
impact on risk.
Further investigation, verification and mechanistic
understanding, particularly in animal models, is needed to clarify their
relevance to risk assessment. While the effects of individual
susceptibility on risk to populations might be small, such effects are
of interest to affected persons. And this was a point that I thought
was driven home, that there may not be a big impact of this susceptible
population in terms of the overall population, but those who are
affected, it is a big impact, and it's something that when it becomes
personal, it would be important to know what that -- how that risk might
be amplified in that population.
Finally, more biologic data will be needed to improve the
multi that should be step mathematical models of radiation tumor
genesis. There's a lot of biology that the modelers don't know, and
even if that biology is provided, it's not clear that they know how to
incorporate that from a plausible point of view into their modeling and
into their equations.
So we found it to be a very informative workshop, and I
think it certainly indicated that these people must be speaking to each
other. We need a dialogue between our biologists and the risk assessors
and epidemiologists.
The report called for -- or justified a BEIR 7 phase 2, and
the primary sponsors are the EPA and the Nuclear Regulatory Commission,
although I understand this is in cooperation with other agencies since
it came out of the inter-agency subcommittee.
The goal is to consider all data and information available
since the 1990 BEIR 5 study, and I do emphasize all data, and it's to
conduct a comprehensive reassessment of health risks resulting from
exposure to low levels of low LET ionizing radiation.
Time line is 36 months, three years, to the year -- fall of
the year 2001, and we have been talking both with the EPA and the
Nuclear Regulatory Commission in that one thing that might be prudent
would be that after about two years, when the committee is at a point
where it's really wrestling, has a better feel for what data is
available and its responsibility, it might be good at that point to take
a stop and look at where things are, particularly in the new DOE
program, any new data that's coming in, any studies that are expected to
be reported or released within a short period of time. It might be
worthwhile for the committee to take a hiatus of a year or so to see
whether it would be prudent to wait until something that's very special
that's right around the corner might be coming due.
On the other hand there is a tremendous interest in trying
to get an improved risk assessment and it might not be prudent to delay
at that period of time.
We propose a 16-person committee, and these are the
expertise areas that we at minimum want to have represented:
epidemiology, biostatistics, of course, radiation biology at the
molecular, cellular, and animal level, radiation physics and dosimetry,
risk communication we feel is very important, molecular biology, risk
assessment experts, somatic cell genetics, DNA damage and repair, cell
cycle regulation and apoptosis, and carcinogenesis.
Some committee members will represent more than one of these
areas of expertise, but we feel that all those aspects have to be
considered.
The work scope is the following. The committee would be
expected to review low-dose human cancer risk estimation for single or
multiple acute doses or for continuous lifetime exposure to estimate if
possible the DDREF, the status of that information, evidence for or
against thresholds, evidence for or against adaptive responses or
irradiation hormesis that might modify the risk.
In terms of numerical risk estimation the committee is
expected to estimate radiation-induced cancer risks from all sources
including background and variations in background and estimation of
uncertainties in radiation risk estimates including dosimetric
uncertainties in the studies upon which the risk models would be based.
And finally, the area of subpopulation sensitivity to try to
identify subpopulations that might be more sensitive to the effects of
radiation, and to the extent possible, estimate the number of people in
that subpopulation and the expected impact it might have on the risk
assessment.
In terms of the data that the committee will be looking at,
it will be all published data since the BIER V. It'll look heavily at
the Japanese atomic bomb survivor data, of course. Other
epidemiological data, including medically irradiated cohorts, the former
Soviet Union data as it becomes available, including both Chernobyl and
Chelyabinsk, and nuclear workers, airline flight crews, and other
studies that are under way, particularly in Europe, and any other
suitable population groups such as residents of high background areas
such as in Taiwan or Kerala, India, and other locations.
And the third area would be laboratory studies pertaining to
mechanisms of radiation-induced carcinogenesis including DNA damage and
repair, the efficiency of the repair processes, and the importance of
specific genetic changes caused by radiation or other agents in
carcinogenesis.
Finally, the influence of the cell cycle on
radiation-induced cellular changes and repair.
So these are the kinds of things the committee would be
expected to evaluate and take into consideration.
We expect the committee to meet three to four times each
year. All information gathering will be done in public, all
deliberations of conclusions in private, because we are subject to the
FACA 1997 amendment. We want to have workshops and public testimony and
try to encourage people to bring their latest data and present to the
committee. We'd like to hold some of our meetings in association with
scientific society meetings, and we're already planning to participate
in this year's health physics society meeting in Philadelphia.
We feel that there's a large body of scientists there who
have been thinking about this for a long time, and we would like them to
have the opportunity to provide input to the committee. Rad Research
will be next year, since they don't have a national meeting this year,
and perhaps we will see whether maybe the American Nuclear Society would
also be another meeting where we would have our committee meeting in
association with the society meeting.
The Academy has a current projects Web site where you can
follow the agendas and all the material that's distributed to the
committee, but in addition we want to set up a BIER VII Web site. It
might be a little easier to find than going through the Academy's
extensive project listing. The study director, Rick Jostes, who is here
in the room, has already been setting up an electronic mailing list.
You can simply e-mail to rjostes@nas.edu and get on that mailing list
where you will receive all updates and information and material as it's
presented to the committee.
The goal is to produce a consensus report with conclusions
and recommendations. It'll be reviewed and widely disseminated in
accordance with the Academy policies, and this includes, of course,
posting on the Internet.
Just to give you an idea, our advisory board of the Board on
Radiation Effects Research is composed of about typically 12 to 15
distinguished scientists with expertise in areas related to our studies.
And I must say we're very concerned that we've been receiving a lot of
through e-mail and other -- and through letters the impression has been
perpetuated that all BEIR studies and reports are done by the same group
of people and they're the same people who do NCRP, ICRP, UNSCER, and so
forth.
I can assure you that this BIER VII committee which we don't
have final approval yet to release, but it will not have the same people
who have been very involved in the past with most of the risk
assessment. We are looking for people that will bring new ideas and new
perspective to this committee, but still maintain a high level of
expertise and the standards relative to both conflict of interest and
bias that we think is crucial to our committee process.
In the same way, our BRER board, Board on Radiation Effects
Research, has not been a longstanding body. We turn over three or four
members every year. There have been over 36 members of BRER in the last
decade, and you will see on this committee some people who have
experience on this board, experience with the BEIR process such as Jim
Adelstein and -- no, I don't think there is another individual. So they
are people who are not wedded to the past BEIR series of studies, and we
hope that their advice will be very beneficial as well to the committee.
So I think at that point I will stop to try to keep with the
excellent precedent that the other speakers this morning established
that we are trying to keep on time, and if you have any questions about
either the Phase I scoping study, the rad research summary of the
workshop, or our proposed plans for BIER VII, I'm willing to answer
those now.
DR. WYMER: Thank you for your presentation and thank you
for allowing us about 12 minutes for discussion here.
Let's start with the committee again and start with our
chairman. John?
DR. GARRICK: I don't have any questions, just a comment.
If the previous speaker is correct, a lot of the questions that you
raised in the earlier slides that are epidemiologically based appear to
be answered.
MR. DOUPLE: Well, let me perhaps rephrase your question a
bit. Will epidemiology be able to provide anything new? And I think
there are several things, some of which were answered by Charles Land.
One is that the data base is far richer than it was ten
years ago, and so refining the dose-response curve will be a very
important task for this committee. In addition, reducing the
uncertainties is very, very important, because that also will tell how
much reliability one can attribute to the curve. And if anything I
think this committee should be able to explain to the public how low you
can go by measuring effects in humans, and I think that's something I
hope the committee will endorse and try to see how low it can force that
information.
As Charles mentioned, you also learn a lot of things about
biology and carcinogenesis and confounders and other effects by taking a
more rigorous analysis of the population data base. So there's no
question -- I don't think epidemiology is going to tell us what exactly
is happening at the very lowest doses. But in addition there is the
biology that should be summarized here, and I think just being able to
explain what is the latest biology, how does it impact on risk
assessment, what influence should it have, and what types of experiments
and gaps still remain, I think that will be very, very important.
I must note that BEIR VI was in a situation, a very similar
situation. It had a very rich, robust dataset of lung cancers from
radon at high doses in uranium miners but by its reanalysis it also had
for the first time in 10 years a significant number of miners whose
doses overlapped with the ranges of high doses in homes.
In addition, the committee had access to a case control
study and a meta analysis where it could look at the higher doses in
homes and see how that compared to the miners and they came together,
and then finally it took the biology, the latest biology that was
available and let that provide guidance as to how you could do some
extrapolation down at least to a certain level and so I think that alone
would be a very significant contribution of BIER VII if it were able to
provide a quantification of uncertainty and also provide guidance as to
how low the doses could be extrapolated based on the epidemiology and
the impact of the biology and bring that all together in one document.
DR. WYMER: George.
DR. HORNBERGER: Yes, a similar question. I guess a
follow-up, Evan. In your Phase 1, as you had on one of your slides,
there's a statement, "Evidence regarding specific biologic events that
can affect the shape of the dose response curve at low doses is
accumulating" and again as a non-specialist in this field, can you give
me some idea of how one might go from this evidence, how the shape of
the dose response curve at the low end might be affected and how the
biologic information gets translated somehow over into a population
response.
MR. DOUPLE: Well, one example of course will be the key
issue of the lesions that might be unique to radiation at very low
doses, and if in fact multiply damaged sites and double-strand breaks
and so forth persist and their response in vitro is well characterized
in the biology experiments, that would suggest that the response in
terms of carcinogenesis might in fact be, if it is linear, it might be
more linear, if it is quadratic, it might give some advice that you
might be wanting to look at a quadratic modeling, but I think it will be
important to look at the biology, the impact of subpopulations, the
sensitivity. If that gets well characterized in cellular studies and in
animals, and estimates can be superimposed on the population of the
United States, then one could again begin to let that influence the
modeler in terms of fitting and extrapolating from higher doses, so I
think there's several examples that could impact on the model that is
selected.
MR. HALUS: We have got about five more minutes for this
topic.
DR. WYMER: Otto?
DR. HORNBERGER: If I may, just real quick --
DR. WYMER: Please.
DR. HORNBERGER: -- do I understand you to say then that the
biology suggests the shape, quadratic, or whatever, exponential, and
then the modelers fit the epidemiological data using that particular
form of the model? Is that the procedure?
MR. DOUPLE: Well, that is a possibility. The committee
could take the epidemiology data at relatively moderate and higher doses
and have a very good idea of the way things are responding at that
point. When they determine at what low dose this begins to -- where
uncertainty begins to prevail to a point where it is unrealistic to
continue, the biology might suggest at that point how one could continue
to estimate beyond that dose, so it is really a fusion of the biology
and the epidemiology.
The other approach is there are modelers who feel that we
are now knowing enough about the steps of carcinogenesis that given key
biology input they are going to be able to create a model of what they
predict happens in that area. They will never be able to prove it by
epidemiology but that in itself may become strong enough to provide
guidance or a rationale for the regulators to make a different decision.
DR. WYMER: Dr. Kearfott?
DR. KEARFOTT: No questions.
DR. RAABE: Thank you. I have a couple of quick ones.
Will this BIER VII include information about radiation
exposure from internally deposited radionuclides?
MR. DOUPLE: Yes. There will be some assessment. Thyroid
cancer and Iodine-131 is an area where we need to bring together and
summarize a lot of new data and so I think that is something that would
be very valuable.
As to others such as high LET emitters, plutonium and other
isotopes, that will not be within the jurisdiction of this committee,
but I think I-131 is an example where the world needs to have an update
and there's a lot of new data and new evidence that will be coming in.
DR. RAABE: What about low LET radionuclides, internally
deposited radionuclides?
It seems to me that these would be an important adjunct.
Are you just going to do external radiation?
MR. DOUPLE: Well, it is something we could discuss with our
sponsors but I would consider I-131 for example to be a low LET
radiation but --
DR. RAABE: But there are lifetime exposures from low LET
radionuclides that you could consider, for example.
Okay. Another question. Animal studies -- are they going
to be incorporated into this evaluation in some way?
MR. DOUPLE: By all means.
DR. RAABE: Lifetime studies with animals?
MR. DOUPLE: Yes. There are some new animal experiments
too, which I alluded to, that are very critical, but there are others
that will probably be available in the next two years and will certainly
be considered, yes.
DR. RAABE: Okay, and the final question is there some
mechanism for your committee to receive input from the scientific
community?
MR. DOUPLE: Yes. The first five or six meetings will have
designed in their agenda an open session for input from the scientific
or the non-scientific community, and I mentioned by meeting at least
three times in association with scientific societies, we hope that that
will especially bring out contributions from the scientific community.
Also, by scheduling one or two workshops, or small workshops
where we would invite specific scientists to come and present their
information, that will be a third element.
Finally, with the website and particularly the e-mail
listing, we expect that scientists will contribute information via that
format and that the committee will be literally deluged with input in
that sense, so yes, in this day and age we don't think input and
information will be a problem. We think there will be a lot of input.
DR. RAABE: Thank you very much.
DR. WYMER: We'll take one more short question and then a
very quick answer. Dana?
DR. POWERS: I am a little concerned about the use of the
word "consensus report" -- and whether it has any relationship to the
consensus process we have standards, and I will also say that this study
is very likely to have regulatory impact and I am a little distressed at
the sharp dissociation you are making in your presentation between
what's gone on in the past and what would go on here -- that is, I can
see the potential for whiplash to the regulators here that could be
difficult to tolerate.
DR. WYMER: Can we have a very quick response to that?
MR. DOUPLE: We will take great care to provide a committee
that has balance and I don't think just by having different people
bringing a fresh look -- I don't think that is going to necessarily
create any -- these are going to be very careful scientists and
consensus is the bread and butter of that's what you buy with an Academy
of Sciences report, the fact that your conclusions and recommendations
are going to be agreed to by every committee member and that means that
the final results are very important.
DR. POWERS: But that is quite different than a consensus
standard process.
MR. DOUPLE: I'm sorry?
DR. POWERS: That is quite different from a consensus
standard process.
MR. DOUPLE: That's right.
DR. POWERS: So I mean the terms are not the same and it
might be good for you to think about adopting at least some of the
features of the consensus process as you seek input from the outside
world.
DR. WYMER: Okay. We probably have to quit at that point.
Thank you very much.
Our next speaker is Dr. Edward Calabrese, who will talk
about "The Development of a Database on the Effects of Low Doses of
Ionizing Radiation and Its Application for Assessing Radiation Hormesis
as a Biological Hypothesis." That will be interesting.
DR. CALABRESE: Okay. Thank you very much. My name is Ed
Calabrese and I am from the University of Massachusetts, and I am here
in conjunction with a project which is currently being funded by the
NRC, which is to develop a database dealing with ionizing radiation.
And I want to give you a little bit of background on the
project and, really, a little bit with respect to myself, because the
topic is unique, it is controversial, and even though the word was
mentioned several times in some of the presentations today, I suspect
that there surely is little agreement on whether hormesis exists or
doesn't exist, I think, within the scientific community. If anything at
all, I think it would be considered negative, and that is both on the
chemistry side, as well as perhaps on the radiation side. And I think
that you should have a feel for where this is coming from and where I am
coming from and see what you think.
Basically, the story for me starts with hormesis.
Thirty-two years ago when I was undergraduate taking a course in plant
physiology, and doing probably 35 or 40 little experiments with a group
of four, and many little groups of four in this one particular class,
and at the end of the semester, or most of the way through, the
professor comes in and he says, gee, the group that is evaluating the
effects of this particular chemical on peppermint growth, something is
acting very unusually because this is a growth inhibitor, and in walking
through the greenhouse and seeing your treatments and so forth, it
appears to be performing in a stimulatory fashion. And that is really
contrary to what happened in the last three years. This is, in all
honesty, fellows, this is somewhat of a demonstration experiment, and it
is supposed to be an inhibition and you are -- you are not responding
this way at all.
And so he said either you used the wrong chemical or you
have something -- there is an error in here. So he says if anybody is
interested in following up on this, see me after the semester.
Well, as the story goes, I was the only one who was
interested to follow up on it. And I went back and saw this gentleman
and he asked me to repeat the study all over again after the semester
was over, and he said, exactly as his instructions were, and he would be
with me when I made up the solutions and follow exactly what we did.
Well, as it turns out, what we did first semester, we
actually made a dilution error and actually exposed the plants to
approximately, you know, ten to fifty-fold lower than his instructions
were. And so, as it turns out, when we repeated the study with the same
doses that we did as students, and that he instructed us, we actually
got a high dose inhibition as his demonstration experiment was supposed
to have demonstrated, and the low dose stimulation that we observed.
And so we went back and repeated that study three or four
times in soil, pretty much getting the same results each time. He then
encouraged me to conduct the same study in hydroponics, which I did, and
saw the same low dose stimulation, high dose inhibition.
We published the study in a plant physiology journal and I
was through of plants, I felt, and was on to obtain a Ph.D. in pesticide
toxicology. And I didn't know the word hormesis then, I called it a
biphasic dose response relationship, and as it would -- I guess as life
would have it, 20 years later, about 1986, I saw -- I received a flyer
in the mail that was sent to me concerning a conference on radiation
hormesis to be held in Oakland, I think it was in 1986, that the
Electric Power Research Institute was conducting, and it was on
something called radiation hormesis.
And from the description that I saw, it looked a little bit
like what I had remembered when I was 20 years younger. And so I called
and spoke to a fellow whom you may know, who passed away a year or so
ago, Leonard Sagan, and introduced myself and told him that I had seen
this shape of the dose response. I thought it was similar to what he
was talking about in this flyer, but I wasn't sure, and asked him if it
was. And he said that he wasn't sure either, but he said it looked like
a so-called hormetic curve.
And then he asked me if I had troubles getting my paper
published because of bias. And I said, well, I had trouble getting it
published, but it was actually because it was my first attempt to
publish a paper and I pretty well got chewed up by the reviewers, but
they stayed with us through several major revisions, minor revisions,
and it got in. But I said they were only really biased against a poorly
written first draft.
And so as it turns out, he said, okay, let's go on to the
next issue. And so I attended this meeting, we attended the meeting out
in Oakland. He encouraged me to write a review paper on the chemical
side of these dose response relationships, since I wasn't coming in from
a radiation perspective. And the next thing I know, it was a year or so
later, and the papers were published in "Health Physics," and I was not
really maintaining an intellectual thought process on the concept of
hormesis, I was following my own funded research line. It was kind of
an interesting little excursion.
And then 1989 came and I noticed in the journal "Science"
that Sagan and Shelly Wolfe were debating radiation hormesis and upon
reading it pretty carefully, it seemed to me that that was the same
debate that those two had at the conference. And so I called up
Leonard, and I said, Leonard, I said, it was great to see you published
in "Science" with Shelly, I said, but -- and it would be one of my great
dreams some day to actually get into "Science" with a publication. But,
I said, in all honesty, I said, this debate that you are having in
"Science," it hasn't gone beyond where we were in 1986 at the
conference.
So, I said, is there something we can do? And he said,
well, Ed, he said, I guess you are right. He said it is pretty much
rehashing what we did back there several years ago. What do you
suggest? And so what I suggested was bringing about 16 people together
from different professional organizations, but interested in low dose
effects and thinking independently about the concept of hormesis, to
bring them together to see if we can actually move this analysis ahead
rather than have the same rehash eight years later, and see what would
happen.
So, in May of 1990, 15 or 16 people came to U Mass, Amherst.
We had a two or three day meeting, and within the context of that, an
entity called BELLE was created, which stands for the Biological Effects
of Low Level Exposures, and we decided to take a role in forcing an
evaluation of the issue of the understanding of the biology of low dose
effects.
It really wasn't focused on hormesis. Hormesis was one of a
variety of things that could have been looked at. And we went forth to
publish scholarly newsletters three times a year, every other year a
national meeting. And I would say for the first three or four years,
there were probably no papers exclusively or even predominantly on the
concept of hormesis.
Then a major change took place, which will get me into this,
and that is I received a telephone call from an industry funded group
that I hadn't heard of before, down in Texas, called the Texas Institute
for Advanced Chemical Technology, TIACT, which is based at Texas A&M in
their research foundation. And they were quite taken with some aspects
of some BELLE newsletters and the general concept of hormesis, and they
wanted to somehow come up or no, yes and no, it exists or it doesn't
exist, let's resolve this issue.
And so they asked if I was interested in taking this on,
and, of course, that is an academic stream with somebody calling you to
do what you have felt you were, you know, desiring to evaluate for the
last X number of years. So we got a contract to look at chemical
hormesis as compared to what, obviously, the group here is focused in on
as ionizing radiation hormesis.
And as it turns out, I think that they felt they wanted to
look at two or three papers and see if they were legitimate and really
go into them in detail, and come up or down on these things. And as I
began to look at it, I didn't think that one could really look at it in
that fashion because I felt that there was a much broader framework to
evaluate this in, and it really needed to be looked at not as a single
study, but as a biological hypothesis.
And also I felt that people who were looking at this especially from
more of an ideological, political, or otherwise viewpoint were seeing
hormesis as beneficial, always beneficial, defining it as a beneficial
effect at low doses. I wasn't defining it that way. I was really
defining it in more biological terms, which is low-dose stimulation,
high-dose inhibition. I can think of many situations where that might
be beneficial or harmful, depending upon the circumstances, and we'll
look at some of those.
So I was more or less trying to understand how cells and
organisms respond at low doses and whether in fact there is something
that is biphasic with respect to dose.
Now what I want to do is to tell you what we've been doing,
because it's going to fit into this, and how it fits in is that we made
a lot of progress on the chemical side. We have essentially identified
several thousand papers in the literature that I believe are consistent
with an hormetic hypothesis from the chemical side.
We began to analyze this with what I'm going to share with
you, which I believe are rigorous objective a priori criteria for
evaluation. Upon sharing this with the broader community, it became
evidence that this type of activity should be applied to the field of
radiation with the same criteria.
And so what happened was that we were essentially trying to
merge these two concepts and at the same time go forth with several
meetings that related the concept of hormesis, but running BELLE, trying
to get funding for the newsletter, and other things takes a lot of time
and effort, and I had taken -- it had taken me 3-1/2 years to raise
money for our last BELLE conference.
So I was at this meeting and this fellow from the Air Force
came over and said Ed, I like the conference. It's serving a great
purpose, he said, but my biggest criticism, you waited 3-1/2 years for
you to get this next conference going. And I said well, you know, I had
to raise money from this point and that point and make it all come
together, and the other things one has to do in their professional life.
And he says well, he says, what about if we funded the next
two or three meetings so you wouldn't have to do all that scrambling
around, and then we could combine this chemical and radiation into one
merging point of view so that we can evaluate this in toto. And so
that's what we decided to do. We were clearly a year ahead,
year-and-a-half ahead on the chemical side. The ionizing radiation
funding came through, and that is being developed in an advanced way and
with the same type of criteria. And so that's kind of where things are
historically and how that's worked out.
Now in terms of trying to understand where this is -- see if
I can get this right -- where this is coming from, these are
dose-response relationships. You see a typical J curve, an inverted U,
inverted J. These are typical hormesis curves. Low-dose stimulation,
high-dose inhibition, if I had my original plan data with you, it's
pretty well superimposed right there. Its growth is stimulated at low,
inhibited at high, where you see the J curve in theory, if you had
carcinogenesis, if you had mutagenesis, if you had perhaps membrane
stabilization, you would see a decrease at low doses followed by an
increase at high. I believe this is the same phenomenon, at least
mathematically, it's just that the -- whether it's a J or whether it's
an inverted U is a function of what end point that you're dealing with,
if you're dealing with the concept of hormesis.
Now the question here is how can people of good will,
objective people, claim that hormesis exists or conclude that hormesis
exists or doesn't exist. There's an awful lot of my opinion, your
opinion, in the literature, and I really can't deal with my opinion,
your opinion, because it doesn't get us anywhere. We really have to
have objective, agreeable criteria that we can move ahead on.
And so what I tried to do was to come up with some criteria
that would be guiding so that we could evaluate criteria, and if I sat
down in a room with others, then perhaps we would have substantial
agreement. And so I said that I would try to develop criteria based
upon whether there was low-dose stimulation, whether there was
consistency with the so-called beta curve, would have to take into
account study designed features like number of doses, the range of the
dose, the number of doses in the hormetic zone, the end point measured
statistical power. There may be other factors, but these are things
that I would want to consider if I were to evaluate whether hormesis was
real or not.
Now in terms of trying to actually judge this, I think the
problem is is that, you know, you see data control, three doses, the low
dose has a blip, the other doses are inhibitory, the research you see is
the stimulation and believes it's real, the study is not replicated,
somebody says it's a hormetic effect, maybe it's background variability,
maybe it's just an unexplained phenomenon, really. And so what we tried
to do was we tried to say well, what would make me believe that this was
real.
And I said well, what's really going on here if the theory
makes sense is it's going on below the traditional NOEL or ZEP. That's
where this phenomenon is taking place. And that's where you have to
have your doses to evaluate it. Having one or two doses below the ZEP,
while useful, you really need more information to define a dose response
in that zone. So we felt that you really had to have very strict study
design criteria for evaluating hormesis.
And so what we wanted to do was we wanted to say we wanted
studies that could define the upper portion of the curve and where you
could have a NOEL or a threshold, and then we wanted to evaluate studies
and essentially assess them on the basis of how many doses below the
NOEL, because that's where we were really looking to see if there was
stimulation or not. And then we were also interested in was the
response criteria, the number of statistically significant doses, and
then the magnitude of the response was also important, because sometimes
people do not do statistical analysis of a hypothesis-testing nature,
and we wanted to give credit to both the magnitude of response and the
number of statistically significant doses in that stimulatory zone. So
study criteria and response criteria were important.
We also wanted to include in this, and that is replication
criteria, if a study could be replicated or not. Now here we are
combining the last slide with the present slide. It really is the same
up here, except above it was really a U-shaped dose-response curve.
Here we had to make a comparable numerical scale when we have a J-shaped
curve. And so we can see the point values here, they're comparable
numerically to what we have above.
Now the question that I would have next is, okay, how do we
actually make some sort of judgments? And so we wanted to say well, if
we summed points from our criteria, we could begin to make at least
semiquantitative judgments as to what extent the evidence was consistent
with the hormetic hypothesis or consistent with the beta curve or
J-shaped curve. And these are point totals that I arbitrarily gave
these types of rankings. You could certainly come up with ones that are
different, but -- and I'd be open certainly to that. We have argued
quite a bit internally on that.
Now the next thing is let's see how it works. Okay. If you
take three dose-response relationships, these three dose responses would
not be that different than what you might find in other papers. Perhaps
you might say well, which ones of these are most convincing with regards
to the hormetic hypothesis without having the investigator involved,
because the investigator might believe that their data represents that.
And so what we're trying to do here now is to take a look at doses below
the NOEL, count the number of doses below the NOEL, the number that are
statistically significant, and the magnitude of their response. And I'm
going to evaluate each of these three stylistic responses in light of
our criteria.
Now you can see here that in the first dose response there
was one dose below the NOEL. The NOEL was determined, yes, so we have
now two points. The number of doses statistically significant was one,
so we gave it two points. The magnitude of response was approximately
200 percent, so it gets two points. There was no reproducible data.
The total points were six, and the evidence in our system was six. The
investigator may have been convinced that that one little blip was real.
It may well have been real, but you'd have to go back in and do more
doses in the low-dose zone to see what that relationship was.
In the second one over here, if you recall it, this was the
dose response in the middle that has the rather modest response but
three significant dose responses. We're evaluating that one. And you
can see here that number of doses below the NOEL was three, so it gets
three points, NOEL was determined yes, so we give it one, three
statistically significant doses, we give it eight. The magnitude of
response is relatively low, so it gets a relatively low value. And we
tabulate it, get to 13.5. That fits into a moderate range.
The last one is just chuck full of doses that are
statistically significant with a higher magnitude of response, and you
can see here that that study does pretty well with seven doses, gets
five points, seven that are statistically significant. It eventually
comes up with 34 points and gets a high value.
I can tell you that this is a hard scoring system and I
think a lot of people -- unless you have a lot of doses that are below
the NOEL that are statistically significant it is hard to get scores
that are essentially going to be high.
I think this field has such a tendency to advocacy that you
have to make sure that you don't fall victim to advocacy. You actually
have to say if you want to test hormesis, that's fine. You are going to
have to pay the price for doses in the low dose zone and then you are
going to have to pay the price for reproducability and maybe that is not
fair, to lay it on that particular hypothesis but the reason for this
from what we have seen, and I will tell you the basic problem with
hormesis as a hypothesis. It's not that it's not biologically
conceivable or evolutionarily conceivable. To me it has those things.
The problem that I have seen in looking at now thousands of
papers on hormesis is in fact that the response is modest. When we see
responses, we typically see responses, and I will show you basically --
this is what I find after looking at thousands of papers. For the most
part, we find that the dose response range is about ten to twentyfold,
and that that is okay but this is the real problem is that the maximum
response is only about 30 to 60 percent above background.
Now when you have 30 to 60 percent above background, well, I
mean I work with rats and rat livers and enzyme changes and other
changes and variability is high in my system, much higher than 30 to 60
percent I would have to say -- sometimes it's severalfold in my system,
so you need to try to deal with that, but when you see a change by 30
percent or 10 percent, 60 percent, that's why it is so important to have
many doses in the low dose range so you can see your trends and you can
see your reproducability.
That is where the hormesis issue I think has been -- why
people of good will could dismiss it -- because one dose in 60 percent
above background could easily be explained by variability, but that is
why in laying out these criteria, the criteria are tough. They are
pretty rigid and they demand -- well, they are very demanding.
But the other issue too is that this nature of this response
can also be to biologists of good will ignoring something that is real.
It could have major and profound implications on risk assessment and
perhaps on other aspects of application in the clinical and other world
and so this is why it is important not to dismiss things very summarily.
Another issue too, and that is hormesis -- and the reason
why I think, another compelling reason why I think that it is real is
that you have to begin to follow it not just -- you know, these numbers
aren't just fixed. It is a very dynamic system. For example, this is a
look at bacterial response to phenol over time. Now if you look at
phenol over time, if you just look at it when the study was completed at
five hours you see a low dose stimulation which is modest, about 40 to
60 percent, and then it drops off at high doses, but you really have to
start with hour one, two, three, four, five, and what you find with hour
one, two, three, four, five is you find initially a dose response,
inhibition, and then you see some type of adaptation taking place, and
ultimately with your beta curve displaying itself. It has been
interpreted by others and I support this interpretation that it is
initially a disruption in homeostasis followed by an overcompensation
response that essentially results in the excess or stimulation that you
see.
I have to tell you that we published our -- go back to my
original story when this started -- we published our original plant
research and we measured our plants over time. I would have to say I
just published the six-week data. When I saw these findings that other
people had published about hormesis and time I went back to this
notebook that I have carried around with me for 32 years, known the data
longer than I have my wife, and basically dug things out this past year
and re-evaluated the data over time.
I really should have done it at that time but I just didn't
do it, so I went back in and I wanted to see what happened. Now I would
have to tell you that these are the data at Week 5 with these peppermint
plants that we published. We never published the information over time.
But when I went back and looked I was actually pretty shocked because
what I found was a dose-dependent inhibition at Week 1 that was very
much like that work with bacteria, then followed by what appears to be
this overcompensation response. I have seen this in a lot of different
biological systems, bacteria, plants. I have seen it in immune function
tied into ionizing radiation exposure. I have seen it in a variety of
situations and basically what happened was that this to me is very
helpful in explaining the biology of what I see, and that is if you have
a modest decrement or stress on a system, there will always be an
overcompensation or some sort of push-it-back-to-the-middle, and that
takes energy and that takes time.
What actually happens is that if you are going to do it
right, you are probably going to edge a little bit over what you need
and so what happens is because you don't want to push back so far it
goes tenfold over, you would like to push back to make sure it covers it
with a little bit of change, a little bit extra. That little bit extra
translates into 30 to 60 percent in most biological systems, as I see
it, and that is why it biologically -- if I saw hormetic effects and
they were tenfold over, so it would be easy to believe, I would say that
is not very believable to me -- it is a different mechanism.
That is why the hormetic response and why -- and
historically if you go back into why it has been a problem in ionizing
radiation -- you go back into the early years of the twentieth century
and the debate was over whether it was a direct stimulation or it was a
stimulation in response to damage, and people would blow off the fact
that it was in response to damage and blow off the fact that it was a
minor response and yet I think that therein lies an explanation to me
which actually makes biological sense and has an evolutionary component
and a dose response component that are real.
I would also have to tell you too that in looking at our
data, and when we submittted it to the people in Texas they told me that
my theory, while compelling, could not explain all of our data, and so
of course I have -- and I had blinders on and I couldn't see all our
data as well as perhaps external reviewers could see, because not all of
our data fit this beautiful little story I am telling you right now.
Some of the data actually was -- if you take a look for
example at DES, now DES causes an increase in prostate weight over a
broad range of concentrations and at high doses causes it to become
inhibited or reduced in size, and this is about 30 percent of control,
just like what we are seeing, but the strange thing here is that it is
over about a 1500-fold range of dose, which is quite a bit different
than what we are talking about.
I also have seen some other situations where the response is
upwards of -- it's an old piece of work but it was a good piece of
work -- where the response was actually over 4000-fold and up by a
factor of 1000 percent, and so I have seen these kinds of phenomena not
as commonly and it has led me to understand that one size doesn't fit
all, that some of these responses, which I believe are quite real, are
probably a range of different types of mechanisms. Some may be my
definition of hormesis being an overcompensation to a disruption in
homeostasis.
I found the field of receptor chemistry particularly
important in this respect. It may ultimately be important along the
lines of the radiation angle as well, but we have -- for example, if you
take a look at membrane active agents, and you take a look at such a
variety of compounds, most of these are alcohols, but I will show you
things with detergents and things with steroids. What you have if you
are looking at hemolysis and what this is really measuring is a measure
of essentially a decrease in the risk of hemolysis on membrane
stabilization, you find it goes down beautifully, like a J-shaped curve,
and then goes up again, and this is the lysis side of the curve.
We are not showing you the lysis side because it would be
too confusing here, but for all these different compounds it shows
protection at low doses, lysis at high doses. This was actually
discovered in the 1950s and 1960s dealing with the issue of membrane
stabilization and they are actually using the red blood cell membrane to
try to understand the nature of anesthetics and how they work in people
and you actually can predict the mole concentration that is effective in
anesthesia based upon the dose, the 50 percent protective dose in the
erythrocyte -- it is actually quite a striking relationship.
But what I am trying to point out here is when you talk
about membrane active compounds, I don't know of too many things that
really aren't, but the same relationship holds for whether you have
steroids. The same investigator actually then tried to tabulate
essentially this protection and lysis and tried to measure the number of
molecules finally adhering to the membrane where you would begin to get
the effects.
To see this with Vitamin A -- high doses causes lysis of
membranes; low doses, stabilization -- but it is not just on membranes.
It is argonel membranes as well as cell membranes.
The field of -- I know you are here for the radiation
side --
DR. WYMER: If there are additional really key things you
want to present, now would be a good time.
DR. CALABRESE: Right. What I want to share with you is
where we are. This project is designed to end the end of this year. We
have identified the key features -- we have identified, as I said, about
several thousand papers on the chemical side and we have analyzed about
800 of those, which show evidence of hormesis.
On the radiation side we have identified and have evaluated
500 articles in the radiation side that show evidence consistent with
hormesis that have gone through the same process. It is my belief that
there are probably four chemical papers in the literature for every one
on radiation and it may be more. The ratio may even be higher than that
due to all the pharmaceutical and other aspects, but there's still a lot
of radiation that is out there.
For every paper that you have, we have about a little more
than two endpoints per paper, so if you were to look at where we stand
right now on the evidence of hormesis within radiation aspect of the
database, we have about 500 papers and about 1093 endpoints that have
been evaluated within our system -- 117 or 11 percent have scored high
in our system, 573 have scored low. You might think that that is not
very convincing and it may not be given our criteria. I would say our
criteria are extraordinarily hard to get an A in our criteria.
You can see moderate high and so forth and so on that we
have, looking at this. The range of endpoints are -- how this breaks
down in terms of some of these aren't ionizing radiation but basically
you can see that this is being driven by gamma ray research and x-rays
and then there are other examples within the literature that we have
used.
In addition, you might want to see the endpoints that
comprise these 1,093. This is driven strongly by growth because there
are an awful lot of plants that are involved in this. It is not all
plants that are a growth but plants are dominating, but you can see that
metabolic cancer, reproductive survival, and disease incidents and other
are also broadly represented here.
I also have to tell you too that this is not an easy project
to do or defined and this is perhaps maybe the most important thing that
you can get away, take away with you.
We have used every conceivable strategy to find articles
with computer databases. We get papers and I go through the papers and
we do two or three or four generations of cross-referencing with every
single paper, so you read the paper, you get references that might be
leading you to other papers and then those to others and those to
others. We go through three or four generations of those.
I can tell you that on the chemical and radiation side that
what we have found is that doing it that way we come up with about 25 to
30 percent of our papers. How we got the rest of our papers, I
literally have gone to our library 8 o'clock in the morning to 10:00
five days a week for "x" number of months and I go through from day one
of a journal to the present time and literally scan the journal
visually, and I have found in certain journals we have gone back and a
number of them really, but generally speaking we are missing 75 percent
by going through the computer database searches.
Most investigators don't understand the dose-response
relationship. They certainly don't look at it in the context of what we
look at it. They never use -- I can't say never -- they often don't
use --
MR. HALUS: There are approximately five minutes remaining.
DR. CALABRESE: -- don't use a term that is effective, so
it's very difficult to find these. It's very costly with respect to
time in going forth at it. Nonetheless, the issues --
DR. WYMER: I think in fairness to you with this very
interesting discussion we ought to allow time for --
DR. CALABRESE: Oh, I'm sorry --
DR. WYMER: -- for some questions.
DR. CALABRESE: Absolutely. You got it.
DR. WYMER: John?
DR. GARRICK: The NRC is a stickler for quality assurance
when it comes to licensing anything and particularly with regard to the
databases that are supporting that license. Have they imposed any kind
of a quality assurance program on your development of this database?
DR. CALABRESE: Other than I think being aware of what the
criteria were, and I think being supportive of the criteria, I would say
no.
DR. GARRICK: Okay.
DR. KEARFOTT: Two real quickies. What is the numerical
value of the NOEL for radiation that you are using in this work?
DR. CALABRESE: The NOEL for radiation would be really
study-dependent and endpoint dependent, so it would actually be a dose
response derived NOEL value for every single endpoint in every study
that you would look at, so it would be very different.
DR. KEARFOTT: Got it. Also, is there any attempt
whatsoever to review the technical credibility or presence of
confounding factors or improvements in technology including papers in
your dataset, or is it just based upon what you see?
DR. CALABRESE: Well, every paper is evaluated within the
context of I would say an overall weight of evidence evaluation. If you
felt that the paper was lacking in methods or lacking in other types of
basic study design components, then it may not qualify for review in
your situation.
DR. KEARFOTT: Who does that?
DR. CALABRESE: Myself and my research team.
DR. WYMER: Otto.
DR. RAABE: Yes, I have one question.
Did you see any toxic chemicals for which there was no
stimulatory effect below the NOEL?
DR. CALABRESE: There are chemicals that we have not seen
any effect below the NOEL. I would have to say that we have looked and
carefully considered why we see it sometimes and why we don't see it.
It is difficult to prove a negative.
For example, if you don't see it, you can easily kind of
skirt the issue by saying well maybe they didn't do their timing
correctly or it was an endpoint issue, or the dose spacing wasn't
appropriate to see it, and so it is easy to -- you know, there are many
situations where we haven't seen it and some of those may be legitimate
that it just doesn't exist. There are other circumstances where it
could be an artifact of the study design including temporal and other
reasons.
DR. RAABE: Thank you.
DR. WYMER: We'll take one more question from the floor
here. Mr. Meinhold.
MR. MEINHOLD: I am sure that you are aware of the UNSCEAR
review of 94 and I think that their conclusion pretty much was there is
no question about hermetic effects -- having been demonstrated much
along the lines that you are saying.
What concerned them was whether or not any of those hermetic
effects applied specifically to carcinogenesis.
DR. CALABRESE: Okay. In terms of -- yes, we have a number
of examples in our database, more so on the chemical but also some on
the radiation which apply directly to the process of carcinogenesis.
I have a paper that has just been published in Regulatory
Toxicology and Pharmacology that speaks to the generalizable aspects of
the concept of hormesis to cancer, but quickly there we took a look at
early stages of carcinogenesis, promotional stages of carcinogenesis and
later stages of carcinogenesis and actually had substantial numbers of
examples with underlying explanations for -- which would be phenomena
that display the hormetic effect, and then we would have -- I'm not sure
if had on that paper -- but we would have then how they performed with
our evaluation, with our criteria for them, and so, yes.
DR. UPTON: How did they do?
DR. CALABRESE: Well, it depends on the study. Some
studies, you know, they scored high and others scored less than
whatever, but I would not have included them if I didn't think it was
credible, consistent, and so forth -- and I would be more than happy to
share and send reprints to anybody who would want those but yes, we have
not seen -- this phenomenon seems to be independent of endpoint, so
cancer, mutation, birth defects, size of organ growth, maybe even
behavioral performance.
It is independent of endpoint, independent of animal model,
independent of chemical class and I believe physical stressor agent.
It is my belief that it is a very broadly generalizable
phenomenon.
DR. WYMER: Thank you very much.
The next speaker is Dr. Charles Meinhold, who is the Vice
Chairman of the International Commission on Radiological Protection.
MR. MEINHOLD: All right. I guess I am going to call this
ICRP and the LNT, I thought that was kind of a clever way to do it
because that is what Mary Thomas asked me to do. I am not sure that I
know what it means, but I am going to try anyhow.
There are a number of things that ICRP is doing even now. I
think it was already mentioned previously that we are looking at this
radiation sensitivity issue about whether or not there are specific
individuals. Also, a lot of work is being done by the UNSCEAR and ICRP
on the genetic aspects, that there are two issues there. One has to do
with the non-Mendelian effects, that is, it is easy to do the Mendelian
effects, you know, the blue eyes, brown eyes kind of thing. We think
there, there is a serious over-estimate to the genetic risk there, but
even more importantly is how we handle the other genetic impacts on
health and whether or not we really understand, as well as we need to,
how that comes down. So I think you will see changes in both of those
aspects in upcoming ICRP and UNSCEAR reports.
But I wanted to talk just a little bit about sort of the
approach that we have taken, and I think -- this is out ICRP-60, which
is mentioned earlier, which gives these detriments, which I think are
now being used by the NRC as their risk estimates. And an earlier
question had to do with whether or not there were other effects being
taken into account when you talked of total detriment. And what ICRP
publication 60 did do was look at that genetic -- I mean the non-fatal
component and the severe genetic component. That's the one that I say
will probably change quite dramatically.
This one is interesting because we have tried to say, how do
you account for the non-fatal cancers? And what we did there was
essentially multiply by the fatality fraction to do that. Let me
explain what that means. It merely says that if you take a cancer like
skin cancer, where the fatality fraction is .001, you multiply that by
the total number of cancers, you greatly reduce what you think the
detriment is. You take something like pancreatic cancer with a fatality
ratio of .97, you multiply the number by .97, you don't change it very
much.
So, essentially, we just said if we multiply it by the
fatality fraction, we can then get some estimate of the severity. And
it had to do -- that approach had to do with something somebody
mentioned earlier, that if you have had a pancreatic cancer, you might
as well have died in terms of what it has done to your family and your
friends, and your ability to make a living. Whereas, if you have got
something like basal cell carcinoma, like I had on my nose, it doesn't
make a very big effect, other than it costs a lot of money to get it
taken care of.
So I gave you those, and then I am going to add just some of
the words, because I think -- oh, and I want to keep this up for a
minute, because I think the word nobody ever reads here is this one,
"nominal." That is a very important word for us, because these aren't a
presentation of what we think are the point estimates that are
absolutely true.
Let me give you some words out of publication 60 which
reflects that. One of the points that they made was that we may have
made it look silly when there is a value of 5 times 10 to the minus 2
per sievert or 5 times 10 to the minus 4 per rem for the population of
all ages, and yet it is 4 times 10 to the minus 2 or 4 for the worker.
And the point is that we probably don't know it that well, but all we
really know is that it is different between workers and the general
public because young people are more sensitive, and so we had to make an
account for that. But I think that is the kind of reflection in that
report which I think a lot of people have missed.
I want to insert, just for a moment, an uncertainty paper
that NCRP published based on those ICRP numbers in which -- I think
Charles Land was part of these. Charles Land gets into a lot of these
things, you have got to be a little careful. But we have the nominal
value, but when you look really at how -- what we believe about it, what
we believe about it is something between 1 and 10. The biggest errors
here are probably in the DREF, which I think -- I guess the Academy is
going to solve this problem for us, that would be very good. But,
anyhow, the fact is that we don't know that very well, and so when you
really look at it, you understand that you have got a very wide
confidence level in those numbers.
However, what we did say was a little bit what you heard
from Dr. Upton as well, is that our problem comes about is that -- this
problem of the defense mechanisms are unlikely to be error-free. I mean
that is the real problem that the commission faced when it was making
its recommendations back in 1990. And, in fact, it is the from one cell
concept which drove that estimate.
Now, I would point out, before I move on, that I had been
concerned for years over these simple statements in our reports. As a
matter of fact, in our publication from NCRP, we merely say that it is
prudent to assume. And that was when we decided that we ought to have a
committee, that we asked Dr. Upton to chair, to look at the scientific
basis. That was driven by essentially our own concern that we hadn't
really laid out the science, and that is what I think Dr. Upton's
committee have attempted to do, and have done an admirable job.
Now, let's look what ICRP is doing. They said, well, let's
put together a task group. This was done about a year-and-a-half ago,
Charles? And you notice we have got Charles Land again. And we have
put together a group of national, international folks to look at this
question, again, with their corresponding members. More importantly,
what did we ask them to do? They had -- not unlike the Academy and Art
Upton's committee, of course, to review all of the information on the
stochastic effects, the cancer and genetic effects, and what has been
learned subsequently -- sounds very familiar.
And then, in particular, whether it is true or not true that
studies at low doses have a limited value for risk estimates. Charles
answered that already, but he is going to chair a committee that is
going to examine it again, and then any new information on the dose
threshold including whether the threshold question is solvable, which is
an important question all by itself, and whether a threshold can be
demonstrated conclusively by anything less than hormesis.
And then, in particular, C&D, new information on linearity
at low doses, including implications, radiation induced genetic
instability. I might add this genetic instability has been mentioned a
couple of times. One of the problems you have when you are out talking
about what ICRP and NCRP think, if I am talking to you about it, we are
going to hear about hormesis, I am going to hear about the fact that we
aren't paying attention to all of these things. When I go out and talk
to the people at Rocky Flats, I am told that we aren't paying enough
attention to genomic instability, and that if we were really taking care
of the people, we would increase our risk estimates by about a factor of
10.
A very interesting point on that was that at a recent CEC
hearing, when they were reviewing the reports from the CEC to the
European community, the European community brought a bunch of people
together and the Secretary of ICRP was there, and when he went away, he
wrote us a report that said he couldn't tell when he left whether the
Parliament was going to increase the risk by a factor of 10 or decrease
it by a factor of 10, he only knew they weren't going to leave them the
way they were.
Now, this task group is a task group of ICRP's Committee I,
which is on the biological effects, has the responsibility for all the
biological effects work that ICRP does. And when they looked at this
layout of work for this group, they thought there should be more
activities looking at the DDREF, the epidemiological data at low doses,
and, again, the genomic instability and hormesis, follow up on the
UNSCEAR report. And then examine whether age and temporal factors might
compound the dose relationships and the epidemiological data, and then
looking at the importance of fundamental judgments on DNA damage and
carcinogenesis.
And then the last one is important, because they hadn't seen
the NCRP report when they made this decision. Now that they have seen
it, they aren't sure that one of the questions that Charles' group has
to answer is whether Charles' group should do the report.
I did want to add one little bit on something that I sent up as a white
paper through NRC because I think it's a very different problem, to show
you some of the details that we get messed up with in this whole
business.
As I said earlier, the NRC has adopted the original risk
values that are in this table, the 4 and the 5 times 10 to the minus 4
per rem. However, if we look at this -- let me tell you one of the
problems that's come up. The risk level here was 1 times 10 to the
minus 4 if the risk variable used in Publication 26, which forms the
basis of 10 CFR Part 20. This is based on a risk estimate of 5 times 10
to the minus 2 per rem, the 1990 data.
These tissue weighting factors here are really no more than
estimates of the fraction of that risk that can be assigned to each one
of these tissues. For instance, if I look at the breast, which is an
easy one to examine here, 15 percent of the risk of 1 times 10 to the
minus 4 was in the breast. That's what that says. And it says that 3
percent was in the thyroid and whatever. Now if I come over here to
1990 and I see that it's -- where did the breast go? Lost the breast;
can't lose breasts -- .05. So the first thing -- and I'll tell you that
senior radiobiologists said to me, why have you reduced the risk
estimates for the breast?
Well, we haven't. This is 5 percent of 4 times 10 to the
minus 4; this is 15 percent of 1 times 10 to the minus 4.
The point I'm making is that it's entirely inappropriate to
use those tissue weighting factors with 4 times 10 to the minus 4 per
rem. It's a very important little point, and it's I think right now a
mistake that's being made.
Another one, a good example is the bone marrow, which was 12
percent of 1 times 10 to the minus 4, and all of a sudden it's 12
percent of 4 times 10 to the minus 4. Does that mean the risk is the
same? No, it means that we think the risk has gone up by a factor of
four. And this has been I think a very important thing for those who
deal with these issues to be aware of, because I think a lot of mistakes
can be made if you start trying to derive the risk in these tissues
based on that 4 times 10 to the minus 4.
Well, I wanted to go real fast because I don't want to get a
lot of questions. I don't want to hear what Art Upton had to hear, so
I'll stop it now and take whatever questions you'd like to have.
DR. WYMER: Actually going fast gave you more time for
questions.
MR. MEINHOLD: Yes. Well, I like questions better than this
anyhow.
DR. GARRICK: Thank you very much.
John?
Charles?
Otto?
DR. RAABE: I have a question.
MR. MEINHOLD: That's good.
DR. RAABE: You knew I'd have a question, Charlie.
MR. MEINHOLD: No, I didn't know that, Otto.
DR. RAABE: Okay. Let me try this out on you. The ICRP 60
says the nominal risk for developing fatal cancer for the population is
5 times 10 to the minus 2 per sievert.
MR. MEINHOLD: Right.
DR. RAABE: There are 270 million people in the United
States, and all of us today will get an average of about 10
microsieverts or 1 millirem of exposure. So that means 270 million
millirem, 270,000 rem, 2,700 sieverts today --
MR. MEINHOLD: Um-hum.
DR. RAABE: Five times 10 to the minus 2, 135 people are
going to die of cancer because of the 1 millirem that we got today. Do
you believe that's correct?
MR. MEINHOLD: Let me go -- I want to go a little further,
Otto.
But for any one of those people, the risk is 1 times 10 to
the minus 8.
DR. RAABE: No, but do you believe there are actually going
to be around 135 people develop --
MR. MEINHOLD: I think that it's a possibility. I thought I
told you about uncertainty. I believe it's very -- I think we have a
lot of uncertainty. Do I believe that there will be no effect from
that? Do I believe that there is no cancer created by the natural
background? Answer that question. Do you believe --
DR. RAABE: No, do you think it's possible that the risk is
actually zero for the 1 millirem --
MR. MEINHOLD: Possible. Possible. But I don't know that
it is, and I don't know that it isn't close to the extrapolation you
just did. The point is, Otto -- and you and I both know we will never
know that. That's the problem. We will never know whether or not those
cancers occurred. We can only make guesses at the probability that it
occurs. And that's what we're talking about. And there's no other way
to handle this.
I mean, the question that you're asking is -- that's why I
turned it around on you. I don't think it's very important, all right?
I don't think that dose is important. I don't think that the number
that you take when you multiply by 200 millions of Americans and you
come up with 130 has any value. I think that that's a societal
question. How much does society have to do to take care of 130 fatal
cancer cases in the United States? It doesn't add more doctors. It
doesn't add more hospitals. It doesn't add more medical schools. It
don't do nothin'. And it shouldn't. That's the real point. It's a
trivial risk. But that doesn't mean it doesn't exist.
DR. RAABE: I think the problem is people using those
numbers think they can count bodies, and I don't think there's that kind
of certainty.
MR. MEINHOLD: Well, it's only a probability question, and
it would be hard to find the bodies. When you start looking for them,
it would be hard to find them.
DR. WYMER: Kim, have you got a question?
DR. KEARFOTT: Yes, it's a broad -- you're not going to like
me after this question.
MR. MEINHOLD: That's all right.
DR. KEARFOTT: The credibility of the NCRP and the
acceptance of your reports I think over the last ten years has been
diminishing, and there are various professionals who attack the
composition and the process NCRP is using to generate these reports.
Could you please address that?
MR. MEINHOLD: Okay. First of all, I think that we have to
separate the reports. For instance, I thought that the Report 121 was
embraced by almost everybody because it said look, collective dose, you
can calculate certainly collective dose. What you can't do is decide
how you're going to use it. That's a different issue.
Now what you're saying is they don't like -- for instance,
the recommendations in Publication 126, let me tell you about 116; 116
was our basic recommendation document, and it went out to all of our
collaborating organizations, who looked at it. And one of them came
back and said that they were going to have trouble with our limit, which
was -- we said rather than use the ICRP, essentially 20 millisieverts a
year, we would recommend 50 millisieverts a year but at no more than
your age in rem or 50 tens of millisieverts.
We made a comment like that. I think that we can be very
responsive when the issue is clear and it doesn't violate the principle
upon which we wrote the report.
Now you asked about whether it is open. I think I would
answer the same that the Academy answers it, that the strength of our
reports for the Federal agencies really is that they don't have anything
to do with it. Once they ask us to do it, we do the report, we put it
out for general comment -- that is one of the things that has changed in
the past 10 years -- is that it now goes out to 60 collaborating
organizations, 30 honorary members, 30 international groups and of
course the Council members themselves, the 80 Council members.
As a matter of fact, some organizations have even set up
committees to do that review and we always pay attention to -- and that
is how that came in.
This last one, 121, as Otto says, he got invited to come and
talk about it. That doesn't happen by accident. That is because the
committee looked at the materials that Otto could offer and said they
ought to know more about it and asked Otto to come in and talk about it
and that was essentially how we handled that.
Art said he had a mountain of material. He actually had a
pile of reports that was that tall. That is what he had when he ended
up and in fact I thought -- I had criticisms of the draft you saw. I
hadn't seen that draft. You should know that I do not see the draft
until the members see it. I don't sit in on Art's committee. Art never
saw me during this process -- and the committee writes its report and
then it goes to the Council and to everybody else at the same time.
I had some things I didn't like and I am sure that Otto had
things he didn't like and there were going to be Council members that
had things they didn't like, and that is why poor Art is going to be
working like a slave for the NCRP for the next three months, because
that is part of the review process.
What it all comes down to though, it is a consensus of the
80 members of the Council. They decide, and I might say that what I
think about it very often has very little to do with how it comes out.
It is how they can resolve all of those comments which come to them, and
that is the best we can do.
I mean criticism is one of those things you have to deal
with, but what we are trying to do is just be as open as we can with the
process that we have, and I think it's been very successful.
I have been disappointed that we haven't had a lot of
comments from the web page itself, which had the whole document on it,
but we have certainly had a lot of comments from the people that
reviewed the report.
DR. WYMER: Dana? We are open to comments, questions from
the floor.
[No response.]
MR. MEINHOLD: Thank you.
DR. WYMER: Thank you very much. Gee, we are ahead of
schedule.
That gives Dr. Pollycove a little extra time. Our next
speaker is Dr. Myron Pollycove from the Nuclear Materials Safety and
Safeguards Division of the NRC.
MR. POLLYCOVE: I appreciate the opportunity to make some
comments and particularly I would like to start off by seconding what
Dr. Raabe, Otto Raabe, stated, essentially that Dr. Upton presented a
very balanced presentation this morning and that the tenor however of
the draft report did not seem as objective and balanced as your
presentation, and it is this effort to defend the LNT hypothesis and
discount anything that contradicts it as being inconsistent with what we
know basically, gives it a flavor being defensive and very protective of
the position that has been maintained since 1959 when ICRP first adopted
the hypothesis that was proposed by UNSCEAR in 1958.
So I would like to just read excerpts from a letter that a
previous Chairman of the Advisory Committee on Nuclear Waste, Paul
Pomeroy, wrote to the Chairman -- and this letter is being
distributed -- July 16th, 1986, so that was quite awhile ago, almost
three years ago.
This letter reiterates some of the comments that have
already been made, namely "The basic principle of risk-informed
regulation is to prevent a situation in which scarce resources are
misspent to avoid negligible risks while significant risks remain
unattended for want of resources to deal with them. Owing to the
potentially significant costs of the present conservatism, we conclude
that a re-examination of the regulatory model is appropriate. It is
obvious that agreement on an appropriate dose response model is made
more difficult by differing voices on this subject within the scientific
community and those outsiders outside of this community including
regulators, policymakers and members of the public. The first task
required to reach such an agreement is an impartial review" -- I'll try
to stress impartial -- "of the data and their quality in the face of the
extensive application of the LNT model in regulations and scientific
opinion."
"We recommend" -- this is the conclusion of the letter -- "
We recommend that the need for special attention be conveyed to the NCRP
regarding its study. Such attention should include (1) assurance that
the study includes scientists other than those who are `recognized
experts'" -- that's in quotes -- "with a reputation built on the LNT
model, and (2) an evaluation of the data by an entity with expertise in
statistics or information science, but no prior position on LNT such as
NIST, National Institute of Standards and Technology, as well as the
NCRP Study Committee, and consideration of essentially all studies that
could relate to LNT."
Now the response by Jim Taylor, who at that time was the
EDO, on behalf of Chairman Jackson includes these statements -- "A
critical review of the LNT hypothesis must be conducted by an expert
multidisciplinary committee whose scientific views are objective and the
biases balances."
The flavor of the report is that the bias is unidirectional.
"As indicated previously, the NCRP is tasked to conduct a
comprehensive review of the scientific literature relevant to the LNT
hypothesis, particularly as it applies to low dose and low dose rate
radiation exposures, and as you heard this morning, a good view of the
evidence is high dose and extrapolation from high dose."
In addition, "Scientists with diverse opinion on the effects
of ionizing radiation at low doses will be asked to present their views
to the committee at a workshop to be convened early next year." That
would be '97. Well, actually, that was convened in early '98 but again,
as Dr. Raabe pointed out, that some of the data that was presented then
was not given a balanced, unbiased consideration.
In fact, as I remember, Dr. Raabe even pointed out that in
his beagle data there was statistically evidence of hormesis in those
that received Strontium-90.
Finally, "All relevant data will be reviewed and
incorporated into the NCRP Council Report and this report will receive a
comprehensive and critical review by the NRC and other collaborating
organizations before it is submitted, so that" -- I am reading this just
to make the next three months even more miserable -- to try to
incorporate some of the data that's been rejected out of hand.
As an example of this rejection is the nuclear shipyard
workers study which was -- a great deal of time was spent on that and
yet in the report it was rejected because it showed that the mortality
from all causes was decreased in the nuclear workers and such a finding
obviously points out to the fact that the groups, that is the nuclear
and non-nuclear groups, were not properly matched.
And this despite the fact that the report says that they
were well matched with regard to age of entry, the kind of work they
did, the kind of medical care they received and so forth. But on the
basis that this hormetic effect appeared, it must be concluded that they
were not matched. Well, that is scarcely, to me, it seems like an
unbiased, objective point of view. I mean there was a high statistical
power, a great deal of effort went into matching them and then to say,
well, when you get a result like this, obviously, they weren't matched.
So it is just these thoughts that -- and that have serious
consideration of some of the comments that you will be receiving, I
think would be -- will come closer to fulfilling the requests of the
NCRP. Thank you. Any questions?
DR. WYMER: John.
DR. GARRICK: I don't have any questions, no.
DR. WYMER: George? Charles? Kim?
DR. KEARFOTT: Given the presentations of Dr. Land, and also
the fact that --
MR. POLLYCOVE: Dr. who?
DR. KEARFOTT: Land.
MR. POLLYCOVE: Land, yes.
DR. KEARFOTT: Yes. And given the fact that the
Massachusetts study does not really seem to have any real strong peer
review of the data, although they look at data that they enter into
their database, do you still feel that this independent rereview and
reanalysis are necessary? The review that you are proposing, do you
still think it is necessary in light of Dr. Land's presentation?
MR. POLLYCOVE: Oh, yes. I think that it is clear that
epidemiology can furnish a great deal of information if it is not
restricted to one-sided P values. In other words, if you say that, as
the Cardis report did, that it is inconceivable that radiation could be
of any benefit, and, therefore, we are going to use one-sided P values,
then it is true what Dr. Land says, is that if you are looking and
talking into account only harmful effects and not beneficial ones, then
you need so many subjects that are very well controlled, into the
millions, that you are not going to get anything out of it.
But you don't have to limit it to one-sided P values. You
can take into account, and then you have groups that are much smaller,
such as the nuclear shipyard workers. Here is a study which compared
30,000 badged workers who received more than a half centigray
accumulative dose, with 33,000 non-nuclear workers who weren't badged.
You don't need millions. This comes out and with a tremendous amount of
statistical power. So that I disagree with that comment, only agree
with it in the sense that if you reject all hormetic effects, then that
statement is true. But there is no necessity for doing that.
DR. KEARFOTT: If a peer review of all existing data, or
even a reanalysis of this data were justified, then I would maintain
that NRC has a conflict of interest in being the actual people who do
that peer review -- repeer review and reanalysis. Given that, who
really would be a credible group to those outside all these interest
groups to do this?
MR. POLLYCOVE: Well, I --
DR. KEARFOTT: Who would be acceptable to review this?
MR. POLLYCOVE: Well, I think there are scientists who have
done very good work, who have not been previously aligned with
developing and defending LNT, and such scientists are exactly the people
that we would like to have involved. We are not talking about NRC doing
any of the work and NCRP could, just as apparently BEIR VII is making a
great effort to do, is to pick people who have not been part of NCRP and
part of their consultants for many years, and have been involved with
grants that are supported -- that support this position. Not everyone
is involved in defending and generating data that supports the linear
no-threshold hypothesis.
Did I misunderstand your question?
DR. KEARFOTT: Yes, you did.
MR. POLLYCOVE: I'm sorry I misunderstood.
DR. KEARFOTT: I have sort of a corollary question. If a
rereview were indicated, then what agency or group would be acceptable
to the broad cadre of scientists to oversee that work where it wouldn't
come out with a report that would just be -- say, oh, that is biased?
Who would oversee it? What agency, scientific organization or group
would you view as being not biased? Not the individuals, but the group.
MR. POLLYCOVE: An organization who would be the proper
judge of whether it is biased or not biased, is that what you are
saying?
DR. KEARFOTT: Yes.
MR. POLLYCOVE: Okay. I finally get your point.
MR. HALUS: We have about five minutes left.
MR. POLLYCOVE: Okay. Well, for one thing, I have always
respected NIST. I think that that is a group that has been not
committed one way or another, and they probably have very good
statisticians that could evaluate the data. I think NIST would be a
good. Let me think. I think that, although in the past, I think some
-- for instance, I will be very specific, BEIR V, I think was -- ignored
some of the data and did stress other parts of the data. I think that
at the present time Dr. Douple presented an approach which is going to
do its best. What you are saying is who going to judge whether, in
fact, they do it. In other words, who is going to bell the cat? Right.
As I say, I think of NIST, but there are probably other
organizations who have not been involved.
DR. KEARFOTT: Would you believe the Surgeon General,
irrespective of what result they found?
MR. POLLYCOVE: I think that would be good. I think the
Surgeon General would be good. A good suggestion. yes.
MR. MEINHOLD: Myron, listening to this, I was just bemused
for a moment, because I guess you know that one of the people who
believes they should review every single epidemiological study before it
is accepted is John Guffman.
MR. POLLYCOVE: Is who?
MR. MEINHOLD: John Guffman. He believes that no study
should be published, sponsored by the federal government unless --
MR. POLLYCOVE: Are you trying to put me into John's
bailiwick?
MR. MEINHOLD: I am just saying --
MR. POLLYCOVE: No, I am just asking you.
MR. MEINHOLD: No.
MR. POLLYCOVE: No. Good.
MR. MEINHOLD: I am just saying, though, that that is, I
think, the problem, is that -- where do you go? The place probably to
go is NCI. They are the country's recognized epidemiological
organization. Right? Well, they are.
MR. POLLYCOVE: Well, let me put it this way -- let me put
it this way, I think you need somebody like the Surgeon General, who
does not have a financial interest in this. Let me be blunt. If you
are asking me bluntly, I will tell you bluntly, when I contacted the NCI
to participate in this study by the University of Massachusetts to look
into hormesis, radiation hormesis and so forth, I was told bluntly, over
the telephone, we don't want any part of it, that isn't the way any of
our younger people are going to get tenure. That's a direct quote.
Now, when I get that kind of a response, I can't feel that
the NCI is an unbiased position.
DR. WYMER: Well, I would like to give Otto Raabe a chance
to --
MR. RAABE: Just on a different topic, a little bit. I just
wanted -- I was kind of surprised when you started off and said that I
had suggested that the Scientific Committee 1-6 was biased. I don't
think I said that.
MR. POLLYCOVE: No, no, no. You said that the report had a
flavor --
MR. RAABE: The report.
MR. POLLYCOVE: -- that defended LNT in contrast to Dr.
Upton's balanced presentation. Maybe I misunderstood you.
MR. RAABE: No, I did say that. Yeah, the report --
MR. POLLYCOVE: That's all I meant.
MR. RAABE: I didn't say it was biased, or that --
MR. POLLYCOVE: No, but it was defending it. Well, I
translated defended LNT as biased. But maybe I misspoke.
MR. RAABE: I think that that committee could have done a
better job of perhaps going into some of the other material.
MR. POLLYCOVE: That is what I mean by biased. I meant
nothing more than that.
MR. RAABE: But I didn't say that they were biased.
MR. POLLYCOVE: No -- well, no. But that is what I meant.
By not going into the other side of the equation as thoroughly as they
went into the side that protects LNT -- I don't want to get you into
trouble. No, that is what I meant by biased, and perhaps that is too
harsh a word.
DR. WYMER: There is about a half a minute left. There is
not time for another question, but there may be time for a concluding
remark.
MR. POLLYCOVE: Okay. Concluding remark. So I think that
what Dr. Douple presented is very encouraging. They are making every
effort to rotate the people, to examine all the data, to get comments as
we go along, not at the last moment from four individuals who are known
to have opposing views.
And I think that, you know, that when all statistically significant data
that shows radiation hormesis is discounted a priori, because that's
improbable, there must be something wrong, to me that does not show an
equitable objective. So we'd like to see an effort made to look at some
of the data such as your own nuclear shipyard worker and find out if
indeed they were poorly matched, explain the poor match. If you can't
explain the mismatch, then include the data.
DR. WYMER: I think that's a good way to conclude the
discussion.
Thank you very much.
Our final speaker in the formal presentation part of this --
MR. POLLYCOVE: Don't want to walk away with the house here.
DR. WYMER: Our final speaker is Keith Dinger, who is the
president of the Health Physics Society, and he'll discuss the Health
Physics Society policy on expenditure of funds for ionizing radiation in
health effects studies, I believe.
MR. DINGER: Thank you. Well, I do want to thank the
committee very much for inviting the Health Physics Society to
participate in this dialogue on this very important topic.
As you indicated, our primary purpose for being here in this
discussion is to present and discuss a policy that was approved by our
board of directors last November entitled "The Health Physics Society
Policy on Expenditure of Funds for Ionizing Radiation Health Effects
Studies."
Now I have provided background material to the committee
members prior to the meeting explaining in some detail our policy, as
well as some background material on the society's position on LNT in
general. For those who would like to see our policy, because I will not
go into detail of the entire policy in this short presentation, but
those that would like to see the policy, it is posted on our Web site,
hps.org, if you'd like to check that out after the meeting.
I do have a disclaimer. The disclaimer is a little bit
different than normal disclaimers. The disclaimer is that my intent in
this discussion is to present to you the views of the society policy
makers and spokespersons on this issue of funding and research for
ionizing radiation health effects. Therefore, the disclaimer is that it
does represent the society policy makers and does not therefore
necessarily represent the views of all the members of the society.
For those in the room who are not familiar with the Health
Physics Society, we are a scientific, professional, nonprofit
organization of about 6,000 members who are involved in both the study
of radiation and its effects and also and more importantly, becoming
more importantly, in the use of radiation and its applications in the
beneficial use for the public.
We not only study the issue of low-level radiation effects,
but we are the ones who then have to take and accommodate the
uncertainties and the questions that that study raises into radiation
safety programs, and our job is to take the questions and issues that
we've been delving with all day today to figure out how to put them into
radiation safety programs which do more good than harm.
And so I guess what I'd like to do is to take you out of the
laboratory a little bit, now that we've delved into the laboratory I
think for most of the day, and get you out in the field for those of us
that have to wrestle and accommodate the problems that we've been
investigating and talking about today.
Now the Health Physics Society policy, why did we write it?
Well, last fall we became aware of the fact that the Congress had
chartered the Department of Energy to "determine the biological effect
of exposure to low doses of ionizing radiation." Because of our
society's members' interest and active involvement in this very issue,
the society leadership decided we were obligated to in fact make input
to the Department of Energy on this very charter. And so that was the
reason for the policy.
The policy's purpose then could best be summed up by saying
that we intended to provide the advice of our society on the judicious
expenditure of public money for the purpose of improving public health.
In this context then this policy is intended to address this
very specific issue of spending the public's money on investigation of
the issue and implementation of the answers to the issue of low-dose
responses. It was not intended to be and was not written as a wholesale
commentary on all research and study related to radiation effects.
The premise of the study is briefly summarized here as being
the fact that first of all funds -- and we are talking about public
funds -- are limited.
The specific issue of responses at low doses will be decided
by biological considerations. We do not feel that it can be decided by
epidemiology or epidemiology alone, and the policy goes on to say that a
second priority -- the first priority being to define the response at
low doses -- there is a second priority that is important to the society
that we define, in addition to defining low doses, that we establish
reasonable radiation protection criteria.
With that premise, the policy lays out six recommendations.
Summary phasing of the recommendations are that recommendations 1 and 2
provided criteria that we felt needed to be met by an epidemiological
study before we spent money on that study.
Recommendation number 3 was a recommendation to continue
funding the Japanese atomic bomb survivor studies.
Recommendations 4 and 5 dealt with the funding of basic
research, the basic molecular biology research.
Recommendation 5 was funding of animal research. Both of
those being basic research directed specifically at the issue of
mechanistic effects of carcinogenesis from radiation.
Recommendation number 6 was a recommendation that there also
be funding to work on the establishment of a regulatory framework for
reasonable radiation regulations.
Now as much as I would like, and in fact I am looking
forward to in the question period and also in the panel session
discussing all six of these recommendations, I've chosen to take the
next few minutes of my presentation time to concentrate on or to expand
upon our recommendation number 6, that associated with the establishment
of reasonable regulations.
As a lead-in to this, let me give you a little background on
the Health Physics Society's positions on LNT to this point, and I
should say that the society takes positions in a formal manner by a
committee. It's the Scientific and Public Issues Committee of the
society, which is made up of the current president, the president-elect,
the immediate past president, and then the last two immediate past
presidents. So it's a succession of five presidents.
That committee is entrusted by rules, and according to our
by-laws to be spokespersons for the society, to make statements which
are in fact representative of the society's position. So when I speak
of society positions, it's in that manner that I'm referring to.
There are four formal position statements out of the society
that address directly LNT issues. The summary of those statements are
that first of all the society has not taken a position on whether
exposure to low-level ionizing radiation results in a health outcome, or
if it does result in any type of health outcome, we have not taken a
position on whether we feel that is an adverse or beneficial outcome.
All the position statements do recognize the uncertainties
of low-dose response and therefore acknowledge the possibility of LNT,
as well as acknowledging the possibility of other dose responses.
And then all four of our statements deal directly with
implementation of radiation protection standards in light of these
uncertainties in the low-dose region.
MR. DINGER: And so that's what really leads us to
Recommendation Number 6. It is addressing what is the overriding
emphasis for our society and that is the establishment of a reasonable
regulatory framework in which the uncertainties are accommodated and
that we ensure that we have radiation safety standards which in fact do
more good than harm.
I would offer to you that it is this issue, reasonable
regulatory framework, that certainly seems to me to be most directly of
interest to the committee that we are addressing today.
Now I want to say that the emphasis on our recommendation is
with the judicious expenditure of money, such that it does more good
than harm, and our concern for the possible misappropriation of
expenditures of money rests with the public, general public, standards.
The current United States, occupational standards of the United States
are not at issue within our society, so we are speaking about public
exposure standards.
The society has written in its position statements what we
feel are reasonable regulations and form a reasonable regulatory
framework for exposure to the public. However, these positions of the
society have not been accepted by all regulatory agencies and therefore
it is this inconsistency and the lack of acceptance of the types of
recommendations that we made for a regulatory reason that has driven us
to include Recommendation 6 in our policy.
We are frankly asking for a piece of the pie to get on with
figuring out how to reasonably regulate while we are off looking at the
biology and science of low dose response, and that is exactly what
Recommendation Number 6 is asking for.
Now the question is what would you put money into? What do
you mean? What do you research? Reasonable regulations? One
suggestion is for example to examine the possibility of finding a
scientifically founded basis for a statistical threshold, a statistical
threshold which would be acceptable to all regulatory agencies because
of its scientific basis and its basis for science would be based upon
our scientific knowledge of the uncertainties of the dose estimates and
the risk estimates at low doses, and that this statistical threshold
then would define an area below which I would call the area of "I don't
know."
Now in presenting this presentation to a number of our
members last year as President-Elect in my travels, the quick assumption
was that I was talking about a de minimis or a negligible individual
risk. It is not. A de minimis is a bound on an area that says "I don't
care." I am speaking of a level below which I say "I don't know" and an
interest is what is it I don't know?
I don't know whether I am doing good or harm to regulate
quantitatively below that level, and that is at issue, whether I don't
know whether I am doing good or harm, and there are two distinct risks
for which we have to be worried as to whether we are doing good or harm
as we continue to lower our regulatory standards.
One is the biological risk, and that is what has consumed
you today is the biological risk. If I continue to reduce exposures, in
fact is there still a biological risk, which I need to keep reducing for
the good of the exposed person?
The answer to that is we don't know, because there may in
fact be a biological benefit, there may in fact be no biological effect
at all and there may be a biological risk, so then we have to consider
the other very important risk in a regulatory framework and that is the
societal risk, and that societal risk comes from spending money.
We have to be aware that every time we spend the public's
dollar we are in fact imposing a risk upon them. Our cost benefit
analysis from the personal basis now at this point deviates from any
position statement but I offer to you that in our cost benefit analysis
we are always evaluating the number of dollars that a life is worth. I
offer to you that we really ought to be looking at the number of lives
that a dollar is worth and that if we did that then we would recognize
that the continued expenditure of money is in fact taking that money
away from potential expenditures in more beneficial manners, and that is
the crux of the Recommendation Number 6. It is the crux of the Health
Physics Society's position on this issue and in fact it comes with a
plea, a strong plea, that we evaluate how we can get to this research
effort and get to reasonable consistent regulations in a much shorter
timeframe than the 10 year timeframe that the DOE research plan for
example is investigating.
MR. HALUS: You have about five more minutes.
MR. DINGER: Thank you. With that, I will give you two
minutes of summary remarks on the other five recommendations.
Recommendations 1 and 2 address epidemiology. They
establish criteria we think needs to be met to fund them. They are not
in fact the wholesale accommodation -- condemnation -- thank you -- nor
is it a rejection of epidemiology.
Recommendation Number 3 is to continue funding the RERF. It
does carry a caveat that we think there needs to be a multi-stakeholder
body that is incorporated in the RERF process to infuse in the data
analysis -- to look at alternative data analysis techniques as a part of
their process.
Numbers 4 and 5 are funding basic research and we think that
is self-explanatory, although Recommendation 5, which has to do with
animal research does carry a caveat that we feel that there is a lot of
animal data which exists but which has not been adequately or completely
analyzed to this point from which there is some information to be
gained.
With that, I would like to stop and open to questions.
DR. WYMER: John?
DR. GARRICK: I was a little confused by your reference to
your "I don't know" threshold.
MR. DINGER: Okay.
DR. GARRICK: Can you explain that to me a little more?
MR. DINGER: Yes -- well, I can try.
The threshold is one that we are referring to as a
statistical threshold, that being a threshold which is established by
the limitations of our ability to detect an effect below that dose
level, and right now we are limited in our ability by human epidemiology
knowledge.
Now microbiology advances will help us advance that ability,
to reduce that statistical threshold but right now if you offered to
me -- in fact, Dr. Land did this for us already -- offered to Dr. Land a
population of people that I say I want to protect with the dose limit,
and it is 100,000 people, and I want to protect them such that if I did
the best experimental epidemiological study that can be done on those
100,000 people through their lifetime, when they were all done, I want
to know whether I did harm or good, he will tell you the dose level
below which he will not be able to say whether you have done good or
harm at the end of their lifetime because of the limitations of
statistical epidemiological studies.
DR. GARRICK: Yes. I have a little problem with that from a
risk perspective because, first off, I think it is a bad concept from a
risk communication standpoint because you are suggesting to the public
that you don't have any evidence that you can make a judgment one way or
the other, which I really doubt.
Secondly is that I don't believe in these speed limits and
thresholds and limit lines anyhow. It is all a matter of likelihood and
the likelihood is what changes. It is not a matter of one side you are
okay and on the other side you are not okay, so from a risk perspective
it is sort of an illogical concept. I just wanted to make that
observation.
The other thing I wanted to ask is that apparently the
Health Physics Society is doing a very constructive thing by sticking
its neck out from time to time and getting involved in issues and taking
positions and so forth.
What kind of position have you taken or involvement have you
had with respect to the ongoing debate with respect to the radiation
standard for Yucca Mountain?
MR. DINGER: We do not have a position statement on the
Yucca Mountain standard.
We have been following it. We have for example Mr. Mills is
our liaison, society liaison to regulatory agencies. He has been
involved in the review of the Yucca Mountain feasibility studies, so the
short answer is we have not made a position statement on it.
DR. GARRICK: I think when you start talking about
detectability and levels below which and you start talking about a
radiation standard that is rooted into the groundwater standard it seems
to me you are getting into a situation where all of these issues come
into play.
MR. DINGER: Thank you. Actually let me say that we have a
position statement on general public standards and I would offer to you
that we feel that that is in fact also applicable to Yucca Mountain as a
source of exposure to the general public.
A very quick summary of those standards is that we believe
in the NCRP 100 millirem and if I may I will use traditional units since
NRC still does --
DR. GARRICK: Yes.
MR. DINGER: -- that in their regulations -- 100 millirem
per year constraint for the individual dose. We believe that that
constraint should be a committed effective dose and effective dose
equivalent unit, which means we believe in all pathway exposures.
We also then carry on in the general public with some
recommendations and position statements on risk assessments. We believe
that the individual doses should only be applied to individuals. We do
not believe in collective dose and also we have some positions on risk
assessments, quantitative risk assessments, so I would offer that that
applies to the Yucca Mountain issue also.
DR. GARRICK: Thank you.
DR. WYMER: In light of the fact that we have a 25 minute
break scheduled, I am going to surprise everybody and say that we should
take until 3:30, which will allow time for a little bit more discussion
on this.
And then we'll have a 20-minute break instead of a 25-minute break.
Charles?
DR. FAIRHURST: I'm interested in your recommendation 6,
this question about doing harm.
MR. DINGER: Um-hum.
DR. FAIRHURST: Has anybody taken that up, or is it just a
recommendation on your part?
MR. DINGER: Well, at this point it's a recommendation. The
recommendation is being made for the purpose of hoping that somebody
will take it up.
DR. FAIRHURST: I see. Well, the basis to say you have a
finite amount of resources to do good, and it's the allocation of those
to where they can do the most good is the --
MR. DINGER: That is --
DR. FAIRHURST: General underlying philosophy?
MR. DINGER: Very much so. And I would offer that that's
exactly the philosophy that Commissioner Dicus in fact opened this
meeting --
DR. FAIRHURST: Yes, I agree.
MR. DINGER: As her concern. And it's been taken up only in
the form that it has been embedded in our society communications, and so
we're talking among ourselves, and frankly we saw this policy to DOE as
being the first place to formally make a recommendation that somebody
act on it.
DR. FAIRHURST: Do you have any doubt that if that were done
that there would be other areas would not appear where it would be much
more cost-effective from a lifesaving point of view to apply money?
MR. DINGER: I guess I'm not sure I understand the question.
DR. FAIRHURST: Well --
MR. DINGER: Do I think there are better ways and other ways
that the money can be spent?
DR. FAIRHURST: Well, is there anybody who doubts that?
Anybody who feels that the money that's being put into reduction of this
is going to lead to more, how should I say, eventually giving you more
informed decision which will save enough money to offset what it is
costing in other areas?
I've confused the question even more, I know.
DR. POWERS: It seems to me that the problem boils down to
you can't do the analysis. I mean, anytime you try to do the
opportunity cost of money in an analysis, you quickly run into the
problem you can't do the analysis except to call it the cost of money.
That's the only value you can put into it unless you're very fortunate
or very imaginative and the problem is it's not reviewable or it's
not -- it won't pass review because other people will say no, no,
putting it in oil rigs is not nearly as good as putting it in highways
or something like that. Putting opportunity costs for money expended
into an analysis, cost-benefit analysis, always causes major headaches.
DR. WYMER: Let's just ask our consultants here if they have
any short comments.
DR. KEARFOTT: Real quick, your reasons for recommending 1
through 3, given that your belief is that it's biology that will unveil
low-level effects, is that to improve and get more certainty in the risk
number that we do have?
MR. DINGER: The recommendations 1 through 3 is not to fund
studies which in fact cannot improve our knowledge, if I understood your
question. Our recommendation is do not fund studies that don't meet
criteria, and the purpose of that is not to fund studies who in fact is
not going to add to our scientific knowledge of the risk estimate or of
the biological response at low doses.
DR. KEARFOTT: So these would be by epidemiological studies
at higher doses?
MR. DINGER: The only epidemiological study that we
recommendation at higher doses is the Japanese survivors.
DR. WYMER: One final question.
DR. RAABE: Keith, the society does have a position
statement on estimation of risk at doses -- radiation risk in
perspective. Maybe you could elaborate on that, because you didn't
actually mention the numerical values there.
MR. DINGER: No. At the end of the question about Yucca
Mountain, I mentioned that we do have position statements on doing risk
assessments. The most recent statement that was issued 2 years ago,
"Risk in Perspective" is the title, recommends that there not be
quantitative risk estimates performed at less than 5 rem per year
individual dose or a 10 rem lifetime individual dose, but rather that at
lower than those doses risk estimates only be explained in a qualitative
relative manner. So that's what he's referring to.
And if I may have just two seconds to wrap up --
DR. WYMER: Sure.
MR. DINGER: In response to Chairman Garrick's concern about
the statistical thresholds as being a risk-associated thing, I haven't
explained it very well in that the determination of that statistical
threshold uses our scientific knowledge of the uncertainties, so in fact
I offered you that such a threshold if properly constructed in fact is
using what we do know and it keeps us then from having to anguish over
that which we don't know. And in constructing the formula I would offer
that just as EPA and many agencies have figured out a dollar value per
life, I would offer that perhaps we switch that around and in our
analysis figure out a life value per dollar, and then we look at the
life value that's spent in billions of dollars on DOE cleanup could also
buy in other arenas, if that helps clarify those two comments.
DR. WYMER: Okay. Thank you very much. I have a short
announcement to make. I want to remind the panel members that when they
come back from the break, each of them will be asked to make a
five-minute presentation of their impressions of what they've heard so
far. So you can be thinking about that for 20 minutes, and you've got
five minutes to summarize six hours' worth of discussion.
[Recess.]
MR. HALUS: The next portion of the agenda calls for a panel
discussion, and after considerable thought, what we thought we would do
is have each panel member reflect on the information that was presented
today and respond for about a five minute period of time. And what I
will do, so I don't verbally interrupt you, I have got a little
countdown timer that will go beep-beep, and when you hear that, for the
panel members, if you would not mind then wrapping up your comments for
that particular time.
After we do that then, we will be going through the same
sequence before where the panel will be responding to questions, the
questions coming from the committee members, consultants, presenters,
staff, and then other interested people. And we will continue that to
the duration for the presentation this afternoon, or until 6:00.
DR. WYMER: We will have a presentation after the meeting.
MR. HALUS: Immediately after the panel members make their
discussions, we will have a presentation by Mr. -- or Dr. Rockwell, I
believe, will make a brief presentation then we will go to the question
and answer period after that.
Are there any questions before we start?
MR. FRAZIER: We are not going to meet tomorrow, right,
again, or are we?
DR. GARRICK: Yes.
MR. HALUS: The question came up, we are scheduled to meet
tomorrow.
MR. FRAZIER: I mean this group, this panel continues
tomorrow for a half day, what?
MR. HALUS: There is an opportunity for that to occur, and I
think what Ray's thinking is on that is if there is a need for the panel
to reconvene tomorrow morning and continue the process, we will do that,
and that decision will be made as we wrap up this evening, and I think
Ray will decide at that time. Is that correct, Ray?
DR. WYMER: We have allowed tomorrow morning to continue the
panel discussion, depending on how spirited it is and how much we think
we can accomplish by doing it. So we will try to decide later on.
MR. HALUS: Are there any other questions before we start?
[No response.]
MR. HALUS: Okay. Well, let's start with Evan. What I
would ask each of you to do, since we have some people here now who were
not here earlier today, if you wouldn't mind briefly just giving your
name and your position, and then go into the remarks that you have based
upon the presentations made today.
MR. DOUPLE: I am Evan Douple, I am Director of the Board on
Radiation Effects Research at the National Academy of Sciences. Our two
most visible, ongoing projects have been a series of BEIR, Biological
Effects of Ionizing Radiation, reports, and today I commented on our
plans for -- well, justification for and plans for BEIR VII.
In addition, I should point out that the National Academy of
Sciences is responsible for the management of the Radiation Effects
Research Foundation program, at least the U.S. funding for the
Department of Energy in Japan. And the first thing that comes to my
mind when I saw the comments that were presented by Mr. Dinger, a
position statement from the Health Physics Society. Of course, I was
pleased to see that they recommend continued funding of the RARF in
Japan.
However, I should point out that two weeks ago, we received
word that our fiscal year 2000, that is this October, budget was cut
$500,000 by the Department of Energy, so I think it is important that I
make that statement that Keith can take back in terms of a response to
one of his recommendations.
I think it was very interesting today to hear the presenters
get right to the point in terms of some of the limitations associated
with the whole LNT issue. That isn't probably new to you, because you
know who difficult this whole issue is. And it takes me back to when I
first started teaching radiation risk in my courses at Dartmouth 30
years ago when I was saying that this may be a trans-scientific problem.
That wasn't an original statement, I think I was quoting somebody when I
used that in one of my lectures. And I think my students at one time
that the only way the issue would be solved is if they delayed the
Houston baseball team two years and used that Astrodome and filled it
with mice and irradiated them, and they could answer this question. Of
course, I didn't have the courage 30 years ago to say anything like that
as a recommendation to those who have much more wisdom.
So I think the key issues were mentioned. The fact that we
now -- we know epidemiology's limitations, and, yet, we must continue to
refine our knowledge in epidemiology because it is the effect, the
endpoint in people, and, despite what we are going to learn in the next
three to ten years from the DOE's program with molecular and cellular
effects, not all of these effects are going to be directly transferrable
or understood in human beings.
So I think, my only reaction is that I think you have heard
key issues put out on the table. It was interesting to know that the
Department of Energy has readdressed some issues that should have been
continued to be researched in the last decade. That is very
encouraging. And I also am impressed that all of the -- if we are all
multi-stakeholders in the sense that we want to see the science done to
the best and correct, I like to see the idea that we are collaborating
and discussing amongst ourselves, and will keep each other informed.
Those are my only comments.
MR. HALUS: Thank you very much. Art, please.
DR. UPTON: I am Arthur Upton, Chair of the NCRP Scientific
Committee 1-6, charged with review of the scientific basis for the
linear nonthreshold dose response model. I am pleased at the discussion
that I have heard today. The model obviously is a model with many
uncertainties. There are now growing numbers of new data that point to
adaptive responses that call the model into question more and more, and
as Chairman of the committee that has been evaluating the model, I am
very pleased at the quality of the discussion I have heard today. The
interchange has been informative and constructive, and we can take back
to the committee comments that will be helpful as we try to complete our
work.
Obviously, we are dealing with an evolving subject, it is a
moving target, and it is very important that the kind of interchange
that we have had today continue to occur. The process not only is
important scientifically, but I think, from the standpoint of risk
communication, credibility, general understanding, it is very important
that this be transparent.
MR. HALUS: Thank you, Art. Charles, please.
MR. MEINHOLD: Well, I do want to thank everybody for
listening to what we had to say today, and I enjoyed very much all of
the presentations. I am concerned about one aspect of the meeting, in
that -- and I expressed the same thing at the Pacific Basic Conference
that I went to, which was an ANS international meeting.
That is, we are only listening to one side of the NCRP's
problem. As I mentioned earlier, when we go out to the hinterlands, the
people that are going to -- Yucca Flats and WIP, are not the NCRP and
not any of you. It is going to be those other people we are not
listening to. And until we understand where they are coming from, we
aren't going to get very far with this. And so I only caution you that
way.
That's why I made a few snide remarks about John Goffman and
things like that, because it is just a level of awareness. I don't feel
John Goffman is very helpful and, in fact, he wasn't on our committee
either. But you should be aware that he is there. And I think that is
one of the things I worry about.
I do think what I learned, very much, is that I think
everybody is on the same page here, that low dose epidemiology is not
going to help us with the public limitation issue. That is not going to
help us for that issue. But I am not sure that it is not going to help
us with the level of the worker. I mean it would help a lot more to
have better data in the range of 50 millisieverts a year or 20
millisieverts a year, and the epidemiology studies may help us to do
that, particularly some of the worker studies and things of that kind.
For the public numbers, for the numbers that are going to
help us get out from under the cleanup criteria and the rest of it, I
don't think we are going to get there from epidemiology, and I think
that was what we heard. And I think we do have a shot at a better
model, which is essentially the work of what DOE is trying to do. It is
going to help a little bit with what Art's committee has done, perhaps
with the ICRP committee, with the Academy committee. It is the model
that is going to help us with that. How good can we make that model?
And I think this question of hormesis adaptive response may
well have an influence on what that looks like. And I know that Art and
I are both interested in getting the papers that were mentioned by one
of those speakers. So, altogether, I think it has been a very helpful
discussion. And, by the way, I am very proud of having Art Upton chair
that committee for us, you should all know that, because that was hard
work. Art was having a good time out in Santa Fe, New Mexico. To get
him to think that he would do this work was incredible, and I can't
think of anybody with greater -- that I could have greater confidence in
and that everybody could have more confidence in. Thank you.
MR. HALUS: Okay, Charles. Thank you very much. Marvin,
please.
MR. FRAZIER: My name is Marvin Frazier, I am with the
Department of Energy's Office of Biological Environmental Research, I am
head of the Life Sciences Division. We have just been charged by
Congress to launch a new program in the low dose area. We are very
excited about this. We think that modern biology has a lot to offer
with this question. We think that the low dose problem, radiation is --
like any kind of research, is an iterative process, and we are starting
to iterate at this point on a whole new way of looking at some of this
data.
I think what I heard today, the NCRP report is trying to
summarize very well what has been done in the past. We have a similar
effort ongoing by BEIR VII. I think it may be too late to ask NCRP to
do this, but we would very much like to ask BEIR VII, in their
deliberations, if they would look to see where some of the gaps are and
how, as they are looking at models, developing the biological model,
trying to find out what kinds of data they are missing that we could
help them with. That would really help us in this kind of iterative
process. So not just to make recommendations based on what is known,
but make some recommendations about the process that we need to help you
in BEIR VIII or BEIR IX or whatever it is.
We certainly want to help as much as we can with BEIR VII
but we think that BEIR VII can help us to make for a better program. We
also think that our plan going forward is in synch with what the Health
Physics Society recommendations are. I believe that. I hope they do.
We certainly want that kind of interplay from the Health Physics
Society, from Radiation Research, American Nuclear Society.
We at the Department of Energy I think have a fairly strong
group in understanding how to put the biology packages together. We are
not so strong in how to relate this to risk assessments. We are not so
strong in communicating to the public, so we are going to have a lot of
outreach in those areas and we think those are extremely important
components of this program and we are very serious about bringing those
aspects into it because if you don't communicate, you are wasting a lot
of good science, I believe.
So we are looking forward to the challenge and we are
expecting all of you to help us. Thank you.
MR. HALUS: Thank you, Marvin. Keith, please.
MR. DINGER: I am Keith Dinger, the President of the Health
Physics Society.
I guess what I would like to start by doing is in my
presentation I felt like there was an important summary that I would
like to summarize that with, and like all good instructors, I had my
entire script scripted in front of me and I left in the book while I
presented the presentation so what I would like to do is read to you the
script that I had for my concluding remarks that I hope will answer some
of the questions from Chairman Garrick and others about this
recommendation for a reasonable regulatory framework.
My personal contention is that if we achieve reasonableness
in regulating general public exposures we will lose interest in solving
the biological question. In a recent paper by Professor Roger Clark of
the NRPB in which he proposes a change in the ICRP protection
philosophy, he observed that, quote, "Perhaps there is no need to
destroy the credibility of the profession in arguments for or against a
threshold."
I think that this should be an overriding goal in setting
our radiation protection standards with our current state of knowledge.
We need to determine how to proceed with reasonable regulations that do
not impose more societal harm than good. We should use that which we do
know and not anguish over that which we don't know.
Clearly we know enough to ensure the reasonable health and
safety of our workers and the public while receiving the tremendous
public benefits available for the use and application of radiation and
radioactive materials. Direct testimony to this fact is the excellent
safety record that exists in the use and handling of radiation and
radioactive materials to date.
So that we my concluding scripted remark. I hope that helps
put perspective on what it was I was trying to say, and that leads me to
the point of keeping perspective on what we are here to do and talk
about.
In instructing occupational workers, I spent the last 18
years of my employed life as the Director of Radiation Health at the
Portsmouth Navel Shipyard, and one of my largest challenges was to face
the occupational worker and explain what all these epidemiological
studies meant that they read about in the paper. In there I developed
the message that turned out to be fairly effective in my opinion, and
the message was this. I said, you know, friends, the bad news is we
don't know what happens at low doses of radiation but the good news is
we don't know what happens at low doses of radiation.
There is a reason we are anguishing over what the low dose
response is and the reason is because if it is there it is not very bad,
and I don't think we should lose perspective on that. My concern is as
we start looking at genomes and pictures of them breaking that we lose
that kind of perspective.
I have been extremely pleased at being able to be a
participant so far in this forum and I really thank you for the Health
Physics Society's opportunity to do this.
I would like in further questions -- I thank Marvin for
pointing out that we do support the funding of the RES study. There are
caveats with that and before I run out of my five minutes if you are
interested in those, I would be glad to discuss them in the discussion
period, and with that I would just like to say that I look forward to
the continuing discussions.
MR. HALUS: Keith, thank you very much. Jerry, please.
MR. PUSKIN: I am Jerry Puskin and I am with the Radiation
Protection Division of the Environmental Protection Agency. I am also
the Project Officer on BEIR VII.
There are quite a number of things that sort of made an
impression on me today. One thing I would like to mention is I think
one point that wasn't brought out is that I think there is perhaps some
places where the epidemiological studies can help close the gap in our
knowledge. What we have is a lot of data on acute exposures and what we
are interested -- acute high exposures -- and we are very interested of
course in chronic low level exposures.
One thing, as Charles pointed out, if you look at very low
doses you are not going to see anything. The issue though is not really
whether there is a threshold at low doses, because after all we get a 10
rem or so during our lifetime anyway. The real issue is whether there
is a threshold at low dose rates, whether if you get a small dose as
long as this dose is -- there is some high window in which you have to
get -- there may be a time window in which you have to get a dose larger
than something in order to have an effect, so what we are interested in
is what that might be.
Some of the studies of chronic radiation where the
cumulative dose may be very high may give you the statistical power to
detect an effect, so that for example -- especially let's say the
studies in the former Soviet Union where people may have gotten of the
order of 100 millirads a day that over a period of years could give you
the statistical power to show an effect or not. You still need some
radiobiology to tell you whether that is the right dose range to be
interested in. That will tell you whether there is risk at 1 millirem a
day but I think there is -- it is quite likely that that is the case,
that if there is going to be a threshold it is likely to occur at a much
lower dose than 100 millirads a day because that is not much more than 1
or 2 tracks of low level LET radiation a day, so I think that is worth
looking at.
I don't know how much more time I have.
Another issue is the cost benefit and certainly we would
like to allocate resources in the most efficient way, but you always get
back to the issue of equity and acceptance. It doesn't do much good to
tell somebody who lives on a site that may get a few hundred millirads a
year that the money would better be spent on cancer treatment or
something like that. You just won't convince them so you have to
have -- to consider the public acceptance and we can't just by fiat say
we are going to spend money to get maximal health protection. It just
doesn't work that way.
So I think you have to look at can we spend the money -- if
we have a pool of money, how wide of a universe can we distribute this
money? Can we spend the money for radiation protection in the most
efficient way or can we spend the money in environmental protection in
the most efficient way -- given that I think you have to say that
people's risks have to be -- I think the people have a right to have
reasonable individual protection. I don't think anyone would say, well,
it's okay to expose a worker to 25 or 50 rads a year in order to protect
hundreds of thousands of people to get a certain -- maybe a cumulative
dose that was larger because that one person doesn't have -- I don't
think we have a right to expose someone to a very high risk either. So
that's -- I wanted to make those comments.
MR. HALUS: Okay, Jerry. Thank you very much. Ralph,
please.
MR. ANDERSON: My name is Ralph Anderson. I am Senior
Project Manager for Radiation Protection and Nuclear Waste at the
Nuclear Energy Institute. The Nuclear Energy Institute is a
Washington-based policy organization for the nuclear energy industry.
I didn't speak this morning, for those of you that weren't
here, but I was very impressed by both the scope of the presentations
and actually the way that they seemed to logically fit together. At
this point I would really like to commend the ACNW for elevating this
issue on its priority list for the year and for holding a workshop like
this.
I had commented earlier to the Chairman that it is too bad
after this meeting that there isn't a photo opportunity to capture this
moment in history, because once we know all the answers, then we won't
be as important on this landscape when the research is completed.
[Laughter.]
MR. ANDERSON: But what did strike me, listening to the
presentations, is that the tremendous value that we have the opportunity
to grasp is probably in integrating the diverse approaches that are
being taken and the actual appropriate resources that are being
committed now to carry some research to conclusion. Where that really
hit home with me is in listening to Dr. Douple's presentation as to
where the BEIR VII committee was going and the very innovative
suggestion that he made that the BEIR VII might even take a hiatus at a
certain point if it looked of value to wait for some additional
information to emerge.
It persuades me even more that maybe we are really on the
verge of something here.
I would like to say though that from our point of view of
course we look on the research with a very pragmatic approach. I think
research in its own right is probably going to lend value far beyond the
practicality of setting radiation standards -- for instance, maybe
helping us better understand the nature of cancer and how to cure it.
But nevertheless in the short term I would look at all this
effort with how it might better improve the situation for formulating
reasonable and appropriate radiation standards and a couple of thoughts
come to mind.
As someone who has practiced radiation safety for a lot of
years before I moved inside the Beltway I will say that the linear model
does simplify dose management. It allows you to set radiation limits on
the idea of acceptable risk, even though it is a presumed risk and it
allows you to use a construct of ALARA where you can involve cost
benefit analysis for decisionmaking.
What is missing and maybe what this research can provide,
and certainly it will be the topic of conversation tomorrow, is some
reasonable lower bound for applying those resources. You know, we sort
of apply them ad infinitum and then we end up with interesting
situations -- and no fault intended to either party -- but you have two
agencies arguing about the difference between 25 millirem and 15
millirem, which seems to me to be in a realm of absurdity that there's
some actual quantitative difference between the two.
So I greatly encourage the thought of how this research may
better inform risks associated with clearance levels as a topic that is
on the plate soon, certainly for cleanup standards and other things, but
missing that lower bound makes radiation protection elusive with the
lower model.
I think I am going to break off at that point and just say
again that I really appreciate the opportunity to be here and commend
you for this effort.
MR. HALUS: Ralph, thank you very much. Charles, please.
MR. LAND: I am Charles Land. I am a statistician in the
Radiation Epidemiology Branch of the National Cancer Institute.
I would like to continue with what you were just saying.
This idea -- this seems ridiculous to me too, to be arguing over a
quarter of a millirem or 25 millirem or 15 millirem and I think this is
not so much a scientific problem as a society problem, a matter of
coming to some kind of consensus about what kind of risks are important
and what kind of risks can be ignored.
I don't think the way to get at it is to research on and
argue the question of, well, there is some dose below which there isn't
any risk at all. I just don't think you will ever get there. The
question of whether there are thresholds or whether there is hormesis,
they are very interesting scientific ideas but I think they are really
bad for public policy.
I just don't see how that is ever going to get the sort of
people that I talk to in other venues, people who are very concerned
about radiation and related risk and who actually tend to exaggerate it
out of all reasonable proportion. I don't see how you are ever going to
connect with these people and these people are very influential.
Actually epidemiology is pretty good for testing models. I don't think
it's so good for developing them. And one thing that Jerry mentioned
here was that the people who are -- studies of people who have been
exposed to fairly high total doses in little bits, and I'm just thinking
that there are studies of people who were exposed to multiple chest
fluoroscopies and they have been studied for breast cancer, these are
individual doses separated by a fair amount of time, weeks, in which the
individual dose is less than a rad. And they have substantial breast
cancer risks, and this means -- or maybe somebody could explain why this
might not be true, but to me this means that if there's a threshold dose
for breast cancer, it's certainly less than a rad, maybe less than a
half a rad.
We come to this point again, well, how big a risk has to be
before it can maybe -- it's not very important, rather than how small a
dose has to be before there isn't any risk at all. And it seems to me
the first is much more -- you can deal with it much more easily.
And finally I'd just like to comment on something that Evan
said. See, I'm just commenting on what everybody else says. I don't
have views of my own.
[Laughter.]
And this keeps -- and this is a second reaction to Keith's
talk. You know, the RERF studies are partially funded by the U.S., and
now we fund less than half of them. And what this means is that we now
only have one-third of the directors. So these various things that you
might think would be a good idea to have the data looked at by other
people and so forth, I don't know that we could get the Japanese to do
that, because I feel very strongly that this is quite a bad thing, that
we're losing control of the organization.
That's all I have.
MR. HALUS: Well, gentlemen, thank you very much.
We have Ted Rockwell, who had requested some time to make a
presentation. He's got an overhead projector. So we're going to break
momentarily. I encourage you to take a stretch break, those of you up
in front may want to get a seat back, and we'll listen to what Ted has
to say.
Immediately following that we'll come back and we'll go with
the questions starting with the committee members.
MR. ROCKWELL: I'm Ted Rockwell from Radiation Science and
Health. I just had a couple of quick things to close off this question
of the nuclear shipyard study. This was a study that was committed by
the UNSCEAR group in 1994 noting that this was excellent work and that
statistically significant decrease in standardized mortality ratio for
deaths from all causes cannot be due to the healthy-worker effect alone,
since the nonnuclear workers and the nuclear workers were similarly
selected for employment and were afforded the same health care
thereafter. And this is a study that was done by the Department of
Energy over about a ten-year period, maybe $10 million. It's been
commended as one of the very best studies of this sort, and it's really
important.
Let me just show you what the data look like on longevity,
where the red is the badged nuclear workers, 29,000 nuclear workers, the
blue is the nonnuclear controls that had the same kind of work, same
kind of history, and so forth, and you can see in each case that there
is a very significant difference in the thing. And if you look at all
causes in particular, look at the statistics there, there's a tremendous
difference.
I don't want to dwell on that, but the main point that I
want to get across here, and I'll do it very briefly, is that this work
that we're discussing, our message is not that we have the right answer
and everybody else has the wrong answer. What we're concerned about is
that this work raises very serious and very specific technical
questions, and it's true that the various groups have been open in
inviting people in, but then when they get here, they listen to the
comments and you look at the report, and if you judge the thing by its
fruits, you look at the latest NCRP report, and it says the same thing
the previous one said, which is the same thing the one before that one
said. So that you find that the data and the questions raised have
never been faced and have never been resolved.
That's the whole point that we're pushing. We've gotten
together -- I said that there was a vast amount of data. This is the
compilation of the data that Radiation Science and Health Group has
pulled together, a very large amount of stuff. This is all
single-spaced, both sides. This is the update. This is both sides,
which makes it twice as fat. But it is a tremendous amount of data, and
this is condensed, analyzed, you know, a paragraph or two on each of
these several thousand reports on the specifics.
I have put on the back table there, and John, I understand
that this can go into the record -- is that right, the stuff that we've
provided? Because what we have here is the conclusions of a wide
variety of prominent scientists from all over the world as to the
significance of all of these data on the LNT, and I agree that the LNT
as a theory is not the target. The question is how do we get out of
this business of quibbling over numbers that are less than the
background.
I say if you push the whole question of radiation science
aside altogether and you say does it make sense to try to work on a
number, to try to control to a number that is not only a small fraction
of the background but is a small fraction of the variation in natural
background from one place to another and from one time to another, and
you say no other industry, no other activity do people try to control
below a natural background to that extent.
And in the BIER VII -- BIER VI report on the radon, a
statement was made that most scientists would be reluctant to abandon a
useful theory just because there's some data that disagree with it, I
respectfully suggest that's got the thing backwards.
Let's look at this LNT and how useful and strong a theory
this is. I'm going to quote from the report that Charlie Meinhold just
mentioned earlier, NCRP Number 121 of November '95, and here is the
basis for the LNT as put forward by its proponents:
Few experimental studies -- I'm quoting directly now -- and
essentially no human data can be said to prove or even to provide direct
support for the concept of collective dose with its implicit
uncertainties of nonthreshold linearity and dose-rate interdependence
with respect to risk. The best that can be said is that most studies --
not all studies, most studies -- do not provide quantitative data that
with statistical significance contradict the concept of collective dose.
It is conceptually possible with a vanishingly small probability that
any of these effects could result from the passage of a single charged
particle causing damage to the DNA. It is for this reason that the
linear nonthreshold dose relationship cannot be excluded.
Now that is the basis for this theory that is so impregnable
to discussion and change. But two pages later in this same report it
says cheerfully:
Since it is generally accepted that a dose of ionizing
radiation, however small, has associated with it a risk of eliciting
deleterious biological response, there is no conceptual basis to exclude
even the individuals receiving the lowest dose from a calculation of
collective dose.
So that's the basis on which we have a discussion. So what
we are concerned about is the fact that the people who are providing
this data, none of them are here today, none of them were invited to
this meeting. I think that's really important. The guys who are doing
this research are not here to talk about it. What you heard was a
restatement of the thing that we've all presumably read and come here to
comment on. And what you have not heard is the basis on which people
are challenging it.
Our plea is, for gosh sakes, let's look at it. That's all
we're saying. If we're wrong -- I say "we" not in a sense that I'm the
researcher, we're just doing some collecting of this information, trying
to do some intelligent compilation of it, and to present it for
review -- if we're wrong, for Pete's sake, dispose of this nonsense
then, all this problem that we're giving you. Show where we're wrong.
But very, very specific questions are being raised, and these are
unanswered. These are unanswered.
Dr. Upton said that he had both of Luckey's big two thick
books on radiation hormesis, but they're not even listed in the
bibliography. There's 52 pages of single-spaced titles of reports that
they looked at to reach their data. Those two books on radiation
hormesis aren't even mentioned. There's lots of references to Lubin's
complaints about Cohen's work; no references to the various places in
which Cohen thoroughly answered each of those questions.
So this is our whole point. We're not saying we want you to
walk out of here saying these guys are right, the other guys are wrong,
and that's the answer. We're saying for gosh sakes look at it. We're
supposed to be here today to raise questions concerning this draft
report and to see whether there are parts of it that ought to be revised
or reexamined. And I think it's really important that we give people a
chance to do that.
I certainly hope it carries over till tomorrow morning.
There are people that may be able to make it tomorrow. The president of
the ANS is here tonight, for instance, to address the local chapter.
I'm hoping that he and some of the people from that meeting will be able
to get here tomorrow. So we certainly hope that you'll give us a chance
to get some of that information.
We have tried not only to get this data into the published
literature and the peer-reviewed scientific literature, which it is, but
also it's been presented to the bodies that are responsible for it. We
have a report to this committee from RSH officially, very briefly
commenting on the thing. And in closing an example, just one group of
stuff here, just one slice of the data. This is 22 pages single-spaced,
both sides, on just reports that have been given to the American Nuclear
Society on this subject. You don't see any of this stuff referenced,
either, but these are the data that have to be answered, that haven't
been evaluated.
Then Radiation Science and Health wrote a letter, and to
make sure everybody who wanted to -- have an interest, we sent it to the
Chair of the Nuclear Regulatory Commission, the Administrator of the
Environmental Protection Agency, the Secretary of Energy, the President
of the NAS, and the American Academy of Engineering, the National
Institute of Medicine, the Surgeon General, with copies to NCRP and BRER
and the various Senate, House Committees who were involved in the thing.
MR. HALUS: Ted, if you could please wrap up in the next two
minutes or so, we would appreciate it.
MR. ROCKWELL: All right. But this is on the record. It is
on the record. And you people have been informed, the NRC has been
informed, and it remains to be responded to. And I think you also noted
that in your '96 meeting, Dr. Pollycove read the letter that was turned
in. That was sent on saying that we were concerned that this
information was not looked at and that this committee would be looking
at the result and seeing that that happened.
I think it is really important now that you now that it
hasn't happened. Here is your chance to make a statement, that is what
you are called for, to express your concerns and, you know, the time is
now. The thing is right before you, and I urge you to raise your
concerns now before the whole thing becomes just one more report,
because these reports do have the force of unrepealable law.
When the EPA or the NRC puts out their rulings, and they are
open for public discussion, and if you try to discuss the use of the LNT
or the collective dose concept, they will tell you flat out, those are
not -- we are not free to deviate from those, we are bound by law to
follow. So these Advisory Committees are really creating unrepealable
law. I think it is important that that context be understood. Thank
you.
MR. HALUS: Ted, thank you very much for your comments.
Will the panel please reassemble?
[Pause.]
MR. HALUS: What we would like to do now is provide the
committee opportunity to ask questions to the various panel members, get
their thoughts, their insights, give them an opportunity to respond to
questions, concerns, any aspect that you would care to ask them.
DR. GARRICK: Yes. Let me address this I think to Keith
Dinger, Health Physics Society. I think we would all agree that maybe
their ought to be a way we could put the focus on protecting the health
and safety of the public, good regulations, good standards, with respect
to this issue, rather than just the LNT.
I guess a number of questions come to my mind on that
strategy. One of the reasons, of course, the LNT keeps coming into
focus is that every time there is any sort of discussion about a
threshold or about a cut-off point, or about a clearance rule, or about
a limit below regulatory concern, there is an avalanche of mail that we
are allowing people to be killed.
I remember the safety goals, when they were first published
for reactors, the first thing that hit the Washington Post the next day
were calculations by intervenor groups on how many people the government
has allowed to be killed by populating nuclear power plants around the
country.
So even though that sounds like a very sound principle, to
talk about protecting the public and so forth, it seems to inevitably
come back to what constitutes a good set of regulations. Those
regulations, to be good ones in the spirit of what we are talking about,
would seem to have to be regulations that have some sort of a limit,
some sort of a threshold, and the moment we do that, then we are right
back where we started, and the LNT is back on front and center as the
major issue.
So I guess I need some advice on how to switch the emphasis,
and at the same time get something done. And I also liked your comments
on what in your judgment constitutes some of the elements of good
regulations that are not now in place.
MR. DINGER: Okay. Thank you. It is a rather complex
question. Let me see if I can address your points. First of all, I
think the point that we want to recognize is the inter-relation and the
feedback loop that we have in what we do with what the public perceives,
and what the public makes us do. And, so, embodied in all this is the
problem that we are very definitely, as a society, and as a regulatory
agency, driven by the public's understanding, perception and orders to
us on what to do. And so these are all tied together.
I think we have to -- in the right world, if I were king,
what I would do is say, look, I am going to set some standards which are
safe, and I am going to look at all of my knights around here and say --
aren't they all safe? And all the knights are going to say, yes, king,
these are all safe. Then go forth and tell the multitude.
The problem is is that the knights that sit around our
regulatory table don't all say, yes, king, when there is a suggestion or
a basis presented to us for a safe regulation. So out of that, let's
get into specifics.
The NCRP gives us guidance, scientific guidance on what safe
protective actions are, 100 millirem per year constraint on all sources,
all constrainable sources, that is everything other than medical and
background, 100 millirem per year individual dose. Heck, if there is a
problem or a good reason, let it go to 500 in a year or two, but don't
keep it at that. Okay.
There is a scientific body that is telling us what is
reasonable. And with that reasonableness, okay, we need to go implement
that. So we say this is a constraint on all sources, somebody may get
exposed to a couple of them, so let's have a level below that by which
we design our programs around, by which we evaluate them against, to see
that we have some assurance that we are not going to reach the safe
level of 100 that Charlie has told us about. That's 25 millirem.
And, so, to me, there is the basic -- the basis of a
program. The NRC has bought into 100 millirem per year to the general
public as being a protective, safe dose. So now if all the knights
would get in the line and say, okay, we go forth in everything that we
regulate to in the general public, when we go to our public hearings and
tell about the decommissioning standards, about our Superfund cleanup
laws, about whatever regulatory thing I need a public hearing on, when
we go there we say we are setting the level at 100 millirem, except we
are going to evaluate against 25. And then people stand up and say, but
how many deaths are you allowing? The answer is we don't think we are
allowing any, at least none that we can count. And if that were the
answer, then the public starts to say, oh, okay, so there is something
that we can accept. And then they can get on with their business and
start worrying about alar and dioxins and the other stuff. Okay.
My point is is that it is -- I think an important point is
the inconsistency in our regulatory framework across our regulatory
agencies that adds fuel to the fire. That gets back to the point that
Charlie made, which is extremely important, and that is when he goes out
to talk about WIP in the Yucca Mountain, that it is not the NCRP that is
at issue, it is those people who say -- but a millirem -- the diminimus
issue, a millirem per year can cause some deaths. You know why?
Because they can pull out a regulatory agency's document that has a
calculation for how many deaths a millirem causes.
Dr. Raabe did the calculation for us in trying to trip up
Charlie. And so long as there is that calculatable number, then we are
not going to reach reasonable regulations that support us being able to
get on with the business of protecting the public in all aspects of the
thing.
Now, I don't know if I answered all your questions, John.
DR. GARRICK: That sort of brings me back to what I was
saying, that, inevitably, we seem to have to come back to that you
either kill people or you don't, below a certain level.
MR. DINGER: Okay. My short answer is is that we get
agreement among the scientific and regulatory agencies that we are not
killing people at all levels.
DR. GARRICK: I probably have some more questions, but I
want to spread the --
DR. HORNBERGER: It sounds like a threshold.
MR. DINGER: No, it is an area of I don't know. I don't
know if I am killing anyone. I don't know whether I am helping anyone.
DR. GARRICK: See, the point here is if you really take a
risk perspective, the real answer there is that maybe, but not likely.
And the truth is there are no absolutes about anything that we are
subjected to from a risk standpoint, it is just that we are measured
more in this industry than we are others.
MR. DINGER: Thank you. And I agree wholeheartedly. And,
in fact, I am over-characterizing the 100 millirem, it sounds like a
threshold. The right verbiage that goes along with that articulation is
that it is much more likely that I am not causing you any harm than that
I am.
The problem we have to be careful of, though, is in
communicating to the public, because let's be -- I mean we are driven by
the public, and it is in the communication within, and they hear it is
more likely than probable, or more likely than not. There are those
that will pick up on -- oh, but there is some likelihood. And we have
to figure out how to handle that kind of issue.
DR. GARRICK: But you also hear the public from time to time
speak the rational view, that there is always risk, and maybe we just
have to play that strategy a little more.
MR. DINGER: If I may offer, I was a part of the public
speaking up and saying we are ready to accept some risk. In my
community in New Hampshire, our landfill was dubbed to be on the
national priorities list and a Superfund site, and the EPA came in with
their reclamation plan, which was going to cost our town, our city, the
equivalent of five years of our annual budget. And that was going to be
our cost and share in cleaning up the Superfund site. Our public, our
town said I am willing to accept that risk and, in fact, we got them
turned around doing a pump and cap. And so one way to do it is to start
hurting them where it hits you, and that is your pocketbook. But I
don't know that that adds to the conversation.
DR. GARRICK: I have some questions for Charles and Art, but
I will defer those until later.
DR. HORNBERGER: Okay. I have a question, I guess I will
direct it to Art, although maybe Evan could chip in as well in the
response. The question is, well, we just heard Ted Rockwell offer some
very disguised criticisms of your work, of the report, and I know
earlier you just made the point, well, thanks for this information, we
will take it to heart. Do you have anything else that you could add to
the defense of the report as it stands that you did, in fact, take this
into consideration?
And the extension to Evan is, what kind of steps are you
going to take to try to avoid having Ted beat you up when your report
comes out?
DR. UPTON: Honestly, I would have to say we did strive to
take the concerns into account. That we didn't do a completely adequate
job is obvious today, and I am not pleased that there are criticisms of
the report, but I am not astonished. I have served on other committees
and I have seen projects evolve step by step. I emphasized at the
outset that I am really very happy that we had an opportunity today to
get this kind of criticism because the report is still in the process of
being finalized, and these comments can be helpful to us in improving
the version that finally emerges.
I was somewhat surprised a moment ago to hear that Luckey's
books weren't cited in our bibliography. I thought I, myself, cited
them in the part of the text that I drafted. If they didn't appear in
the bibliography, that must be some oversight.
MR. RAABE: There is just one paper by Luckey in your
bibliography.
DR. UPTON: Well, that is an oversight. And I accept
responsibility for not proofing that bibliography more carefully. But
--
DR. HORNBERGER: Do you think that on a more substantive
level -- you can correct the bibliography and whatnot, but do you
anticipate that some of these criticisms might actually make any kind of
substantive change?
DR. UPTON: I do, yes. Yes. I think we owe it to the
community, the scientists who are here and others, to address these
issues, to do so in a way that is considered adequate.
MR. DOUPLE: Ted already beat up on us in BEIR VI, so he
didn't have to do that again today. In all fairness, the Bernie Cohen
data was reviewed very thoroughly in BEIR VI, because it was a radon
report. And several paragraphs and pages were devoted to that
discussion. It occupied a lot of our committee's time and there must
have been eight or nine of his references cited in the bibliography.
So in that sense we think that we were very considerate of
that information.
On BEIR VII however we must again start the same process.
We must make sure that we spend ample time listening to presentations,
not just from RSH but from others, the entire spectrum of the public and
that includes Dr. Goffman. His book is getting a lot of reading around
this country and so our committee is going to have to or will invite him
to make a presentation and we'll also have to listen to the other
presentations that we expect to hear so we are going to do everything we
can to make sure that that information is heard by the committee, that
their material is added to our public record that we now keep and the
public has access to come in and review and all I can do is promise that
our committee will definitely pay attention and take that into
consideration in its report.
DR. HORNBERGER: Charles?
DR. FAIRHURST: I am trying to think through -- I have not
been involved with this debate as long as many people but if I sense a
change, if there is any change, it is more that initially what one said
was we don't know so let's be ultra-conservative or let's be as
conservative as possible. What I have heard is some people who are
strongly supporting that moving a little and saying there may be some
hormesis efforts which may mean there are some movement -- I don't know
whether you mean to the right or the left -- and then hearing that
certain epidemiological studies are not going to contribute at these
ultra low dose effects and the only way that the effects can be
construed to be significant is on the population basis, that the
individual level is likely to be very small and the comment by Roger
Clark that we're perhaps thrashing around here and will never get very
far in the eyes of the public and what we need is a different policy
strategy to say these levels are all compared to other risks that we
take, and are demanding of public attention and public funds, this is
not an optimum use of resources.
So that if we are going make any move in this direction is
it going to be in the direction of really thinking through carefully
what is the correct policy, not pin all our hopes on a major
break-through in any of these research studies.
DR. UPTON: That would be my take-home message, Charles. I
think, on the other hand, there is a chance, and I can't put a
probability estimate on this but there is a chance that radiation injury
leaves a fingerprint behind, a molecular fingerprint which can be
identified and that the radiation effects at some future time can be
identified as such and the cancer caused by radiation can be identified
as radiation-induced cancer or a precancerous change in a gene or a
chromosome or some other cellular organelle may bear the fingerprint of
radiation injury.
If that should happen, then one might be able to be much
more specific in quantifying risks of small doses.
I suspect it won't happen but it could happen. For that
reason I think the studies of the molecular nature of radiation injury,
the molecular pathway between the exposure to radiation or some other
carcinogen and ultimate development of cancer or the disease deserves to
be pursued. It is not totally without promise.
DR. FAIRHURST: Let me ask a follow-up. If one is able to
do that from the research, presumably you could go back and test that
hypothesis on the apparent insensitivity to background.
DR. UPTON: Right. Separate out the background.
DR. WYMER: I have one observation and then a fairly broad
question. One is that I have heard from several of you that the
communication of risk is very important. That is about as hard to do as
deciding whether or not there is a LNT threshold to really find a way to
effectively communicate to people at large and not just to select groups
who attend select meetings, and the ACNW has undertaken the task of at
least more effectively communicating what we do to the public and what
we can do. We hope to do that in the coming year, so that is
observation number one, and if there is any help on that score from this
group of people who probably are not communications experts we would be
glad to hear that.
The second was I heard some discussion from several of you
trying to find some way to separate the extraordinary complexity of this
whole LNT issue from the issue of setting some sort of practical
reasonable regulations, maybe with some guidance from research related
to the LNT. I have an idea that this thought will be an important part
of the report that we will ultimately draft from this meeting and I
would like to hear any observations from you on that, preferably
initially from the people who haven't already expressed their views on
that topic, so those two issues are open.
MR. MEINHOLD: If I could respond to the first one, one of
the old-timers of ICRP was a Professor Lindell from Sweden, and he got
very much involved in risk as he got out of the radiation business and
became more of a risk person than a radiation person.
The point he made in a presentation he gave to the NCRP at
one of its meetings, and he's given it in other places, is that people
don't care about the risk associated with this or that thing in a
comparative risk, what they care about is the thing that causes the
risk. If they like the thing that causes the risk, then the risk
doesn't matter. If they don't like the thing that causes the risk, then
they don't accept it.
That's why your job is so tough. They don't like waste, and
they don't like abandoned nuclear powerplants. I mean, that's the
problem you have, and it's not trivial, and it's a very big part of this
problem, that perception of risk is tied to the people's accepting of
the thing, and not to the absolute measure of the risk.
DR. GARRICK: But isn't that where we've really let the
public down?
MR. MEINHOLD: Yes.
DR. GARRICK: Because you can't talk about communication
without talking about risk and benefit. The reason they'll accept the
risk of an automobile, to pick up on your example, is they like
automobiles. And to talk about the reason they don't like radiation is
because they don't like nuclear waste is a total distortion of the
concept. The concept is that what does mankind benefit from nuclear
technology, and somehow we have lost that connection. We're not getting
the message across about the hundreds of thousands of people that are
saved every day because of nuclear technology, and so we've decoupled
it.
MR. MEINHOLD: Yes.
DR. GARRICK: And we've decoupled it not only into clumps
but into little pieces and parts to where the most horrible image is
conjured up in the public's mind such as Chernobyl when we talk about
the risk of radiation. So we have as a scientific community miserably
failed in terms of telling the -- as one famous newscaster would say --
the rest of the story. So when we talk about risk communication you
can't talk about risk communication without talking about benefit
communication or you're never ever going to be successful in addressing
this issue at least at that level it seems to me.
DR. UPTON: May I comment?
DR. GARRICK: Yes.
DR. UPTON: I'm reminded, Mr. Chairman, of a meeting I
attended after the Three Mile Island accident. I was invited to take
part in a symposium that was purported as an educational effort for
people in the community, and my assignment was to talk about radiation
injury. And I went to some considerable pains to emphasize that so far
as we were able to determine, people downwind from Three Mile Island or
in the surrounding area received tiny amounts of radiation, if any. The
largest dose anyone might have received was close to what they would
have had from natural background in a year anyway. The average dose was
a tiny fraction of that. And although we weren't confident that there
were no risks at low doses, the risks if they existed were vanishingly
small and could be dismissed. And a woman in the -- after I gave my
remarks stood up and said, "Dr. Upton, you've reassured me greatly. My
husband and I have always raised our own vegetables in a garden, and
we've been concerned that we couldn't do that anymore because of the
contamination. But what you've told me is reassuring indeed."
And I was pleased to hear that, that my effort had been to
be reassuring. The next day in the New York Times there was an article
on this symposium headlined "Expert Says No Threshold." That was the
headline. Nothing about the qualifications, totally out of context,
flagrant distortion.
DR. GARRICK: Yes. Well, that's the root problem.
MR. DINGER: If I might, the Health Physics Society has been
wrestling over the last ten years I would say with their mission
statement, and at the heart of a lot of that has been the idea that a
number of people want to put the word "promote" into our mission, and we
to date have not let that happen. Now that's reflective of the society
being very protective that we are always understood to be and perceived
to be a scientific and professional society. And so we wrestle with the
idea how is the public going to perceive us as being scientific,
independent, professional, if we're out promoting something that's
self-serving.
So I think you -- Nuclear Regulatory Commission, the
regulators of all types, wrestle with that same problem with the public
communication of how can you go out and tell the truth and not be seen
as somewhat self-serving, if you will, if I can put it in that manner.
And I think that's something that we need to wrestle with.
Frankly, I think the society is moving towards the -- we're
just going to bite the bullet and see what happens, and we've done that
in that we've commissioned Dr. Mills is going to -- been chartered with
writing a position paper, formal position paper for the society on the
benefits of radiation.
It leads to the second comment I wanted to make on
communications. Once we get a position paper like that, provided we get
one that's acceptable, what do we do with it? Well, the public doesn't
read our position papers, but we have stumbled, or at least we are
trying to enhance our public communication by realizing who is it that
really sets the tone of what the public thinks and does. And we've
decided that's the legislators.
We have started an active program last year under Otto
Raabe's presidency actually of going on the Hill and realizing if we can
educate the legislators to the face where they understand the benefits
and it's good for their people to have the benefits of radiation uses,
then they're going to go educate the people why that is. Senator
Domenici is an excellent example of that. He understands the benefits
and we don't need to educate New Mexico anymore, because he's doing the
education for us. So maybe you can use that.
DR. GARRICK: Except Santa Fe.
MR. DINGER: Oh, yes, except Santa Fe. I agree.
But those are my comments.
DR. GARRICK: I have some more questions, but I want to
yield to Dr. Powers and the consultants.
DR. POWERS: You posed a lot of questions about the
specifics. I guess I'm sitting here saying okay, suppose these guys are
all successful in their research efforts and their studies and what not,
what changes, what do I have to change in the regulations, things like
that. And things that come to mind, a lot of things come to mind with
respect to decommissioning, decontamination of facilities. But I guess
I'm more from a reactor world and I live and die on risk assessments and
things like that. And I said gee, a threshold could have an impact on a
risk assessment, but I see another thing that comes up, and that is
sensitive individuals. And all of a sudden my ability to define an
average person becomes a lot more complicated now.
Would anybody like to comment on if you've thought about the
implications of some of these research efforts, and particularly has DOE
thought about have part of their program implications that, I think you
have risk communication as part of your objectives, communications of
that nature that might come from all of this good work that you're
planning to do?
MR. FRAZIER: Yeah, we had thought about this. We had a
model and we may be going ahead with aspects of this in our human genome
program and our bioremediation programs.
We have a component of the research that's involved in
dealing with ethical, legal and social implications of the research, and
I think a component of that associated with this program might be
worthwhile.
We're already faced with just the issue you're talking about
with verilium in DOE workforce, where we have some indication that there
might be very sensitive individuals in the workforce, in the population,
and we have -- there's some tests, you know, genetic tests to look at
that. These are very, very hot buttons in the public, and so we're
faced with trying to -- with these problems already.
DR. POWERS: Marvelous ethical issues there as well.
MR. FRAZIER: Yes. Absolutely.
MR. MEINHOLD: I would like to just, you know, the ACRP has
-- is about ready to print a document on this very topic, and we spent a
lot of time with this very -- this is a very different question.
The first thing that was important was that from the level
of the impact that has on a population, it doesn't look like it would
have an impact on the risk estimates from Japan. That's the first
question. Because, of course, if you thought that, then all of a
sudden, you could say, well, the whole risk estimate is based on the
sensitive of the people and it doesn't appear that it can do that.
The second one was that most of this sensitivity, although
it gets averaged over the population, is centered on a few people who
exhibit this because they don't live past about age 20. I mean, that's
where the big burden is. Even though you spread it out and it sounds
like it's just some kind of a percentage number, but it's really a small
number of people who are highly sensitive.
In fact, having a separate regimen for those people doesn't
look sensible because it's not going to be a big part of what's going to
cause them to exhibit some future cancer which they're likely to have
anyhow.
The third one was that although that's true, it does seem to
have an implication for radiation therapy because this is a person who
has exhibited a sensitivity because they've got a tumor, and they are
then suspect as being a person that might have an enhanced sensitivity,
and the course of therapy, depending on whether it's going to be, you
know, surgery or chemicals or radiation, may in fact be important.
Those were the three conclusions, actually, that are in that
report. So the other thing that's there, though, is a very serious
warning. This is an emerging field. It's just really beginning to come
out. And there may well be changes in this has time goes on. This is
just a snapshot at this time about what the situation is.
MR. FRAZIER: I would disagree with those conclusions from
the standpoint that if you're talking about homozygous situation, that
is a very small part of the population. But if you're talking about a
situation where people carry one normal gene and one sensitive gene, we
don't know the scope of that. We do know that those may be in double
digits in the population. That's a significant number. You start
talking, you know, up around ten percent or 15 percent of the population
with just a couple of different sensitivities, it could be a significant
number of the population.
Now, if you -- if you're dealing with populations in your
calculations and you're not doing that, you probably don't see that.
But I think if we can tease those differences out, this is again a place
where epidemiology could play a significant role, I think, to try to
look at these kinds of sensitivities and see are these people who are
heterozygous, who have one normal and one sensitive gene, and are they
more sensitive, substantially more sensitive. I think -- I don't think
we know the answer to that at all, and that's part of what we're trying
to address.
So I would disagree with the conclusions of that group. I
think they're based on too narrow of a focus on the sensitivity problem.
MR. PUSKIN: I would say this could have really major
implications for regulation because I think what drives regulatory
actions is mainly the maximum individual risk. I never can understand
all this concern about calculating collecting dose; it usually makes no
difference. What happens is you set a standard, you can't have more
than 25 millirems, or you can't have more than ten to the minus four
risk or something like that. Hardly ever do you take an action below
that because the collective dose is so high that it looks like it's
worth it from a cost/benefit standpoint. You're already -- the
cost/benefit is not very good at that level.
So if you now say, okay, we've got five percent of the
population or something like that that has three times as much risk or
four times as much risk as we thought before, there would be pressure to
tighten standards. So I think -- and particularly the, you know,
cleanup criteria and all that kind of thing, there would be -- there
would certainly be a problem, especially, I know, in Superfund, their
guidelines are the risk should be no more than ten to the minus four.
Now, the way it's normally calculated at EPA now is you sort of say,
well, let's taken an average individual in terms of their biology and
you say, what's the worst kind of exposure that person might have. Now
you say, oh, we've got also now -- we know -- we can kind of identify
that there's five or ten percent of the population out there that's got
higher sensitivity. Now, how that might get factored in is --
MR. ANDERSON: I would like to address that from a more
pragmatic point of view. Given where you sit, I can't really comment
with regard to safety goals or potential consequences from accidents
because that probably falls more in the realm of more significant doses,
and therefore that sensitivity might play some role. But I do want to
address issues like setting standards for the public and for cleanup and
so forth.
I've no doubt that scientific reports on sensitivity are
going to promote controversy and probably are going to promote people to
approach agencies to reduce standards in some cases. But for
perspective, I think firs and foremost, you've got to remember the
standards are set at very small fractions of the amount of radiation
those people are definitely receiving, which is background radiation.
So first of all, I would say that incrementally, you're
adding very little to the risk they're already being exposed to if
they're hypersensitive to radiation.
Secondly, fortunately, some agencies don't believe that when
they set a limit, that everyone in the universe gets exposed right at
the level of that limit. Risk-informed and performance-based regulation
recognizes that, in fact, the experience is that people are exposed to
actually rather modest fractions of where limits are set in reality, and
that includes site cleanup.
So, you know, what I would offer is if you approach it
pragmatically, I really don't think that plays a significant factor even
if you are talking about ten or 15 percent of populations. Occupational
workforce -- different question; you have to approach it quite
differently. But as far as setting public standards, I just don't see
it.
We're talking about doses to real people that are fractions
of a millirem, and I'm hard-pressed to believe that playing around with
standards at 25 or 15 or whatever the going number is going to be is
really going to affect what doses real people receive. So I don't see
it an issue in that context, if you stay risk informed rather than risk
based. And I congratulate the NRC for going that direction, by the way.
MR. PUSKIN: Let me just clarify. I think that -- I'm not
saying that the standards would automatically get tightened, but I just
think that the kinds of issues you brought up would have to be
considered, but there would be that kind of a discussion happening and
it's not clear where it would end up.
DR. POWERS: The next question or next point is that when we
think about risk, or protecting the public, the NRC, certainly in the
reactor world, sets safety goals, goals that sometimes are called how
safe is safe enough. Those goals refer to prompt and latent fatalities.
Now, we're in the process of wrestling with should we think
about other kinds of safety goals. It seems like the science is moving
in a direction where we can talk about health effects that are not just
fatalities but also talk about injuries and things like that.
I think in the course of doing your research programs, it's
going to be important to give us as much of a technical handle on
anticipating and predicting those kinds of non-fatalities because I have
no idea where the date on changing safety goals will go or if we'll
change them at all or if we'll try to move away from biology because it
has a lot of sticky wickets associated with it that maybe engineers
don't like so much. But it could move in the direction of taking into
account -- not fatalities, but injuries as well as fatalities.
DR. HORNBERGER: I guess we're ready for the consultants.
MR. HALUS: Yes. Any response to comments here from the
panel?
MR. PUSKIN: Just one thing is that for most radionuclides
of interest, an appreciable fraction of the injuries would be fatal.
The one major exception is iodine, radioiodine where this --
DR. POWERS: But it's a non-trivial exception. The
difficulty comes that if we talk about accidents that are mitigated but
not -- radioiodine might be the only thing that we released to any
significant effect, and so it's a non-trivial exception.
MR. PUSKIN: I think you can't ignore the non-fatal effects.
MR. HALUS: Okay. From the consultants, please, your
questions for the panel.
DR. RAABE: I wonder if we could discuss a little bit the
ideas that we get from looking at background radiation. I live in
California, I get about 300 millirem per year from background radiation,
including radon effective does equivalent. If I were to move to
Colorado, that would go up to 900 millirem per year.
Now, is that really a risk? If I move to Colorado, am I
presenting a terrible risk by increasing my annual dose by 600 millirem
per year effective dose equivalent?
If I look at other places in the world, say Kara, India
where the background levels are maybe 20 times what it is in California,
and can I find any measurable effects. Doesn't that have some impact on
how we view the safety of the standards that we're setting? I just open
that up to the panel for discussion.
MR. LAND: Can I just say something about the premise that
you look at Kara and you can't find it and you can't find anything. I
don't think that the public health statistics in Kara are that good. I
don't think they have --
DR. RAABE: There have been some very detailed studies that
have been done, been published, and in China. But, you know, just take
Colorado. We have -- the dose to the lung for the average person living
in Colorado from high LET alpha particles from radon is on the order of
eight rem per year, and, you know, for the average person in the United
States, it's only about two. Now, that's a big difference.
So let's go look at Colorado. What do we see about lung
cancer. Well, lung cancer is pretty low in Colorado, it's 47th, 48th in
the Nation on lung cancer risk.
Now, you can think of all kinds of confounding factors that
might, you know, cause lung cancer to be lower in Colorado than -- well,
the highest is Washington, D.C., as a matter of fact. The highest lung
cancer risk in the Nation is in Washington, D.C.
Okay. Now, you can think of all sorts of things that might
-- confounding factors that might influence this, you know, the
so-called ecological kind of analysis. You look and say, hey, the doses
are high, the observed effects are low. But it seems to imply that if
there is a risk associated with this giant dose, it's lost in everything
else that's going on in daily life. You can't see it. And if you -- in
fact, it's very consistent.
New Mexico, Colorado -- the states with high doses -- Utah
-- they all have very low cancer rates. They're 47th, 48th, 49th out of
the states in terms of cancer rates of all types, and they have the
highest doses -- people living in -- the one -- it's not a general rule
background one state that has very low radiation also has low cancer,
that's Hawaii.
But I think that, you know, I think about, well, is there a
hundred millirem standard? The Health Society recommends the 100
millirem standard for the public. Is there any known or meaningful risk
associated with that? If there were, we would have to evacuate
Colorado.
MR. DINGER: Just a couple of comments related to
background. I think the lesson that we really learn from -- that I take
away from looking at cancer rates or risk rates versus the variation of
background is exactly the one that you've summarized or said, and that
is what it tells us is if there's a risk there, it's not large enough to
make a difference in all the other risk that faces. So that used to
help add into the communications that I had on the good news, and that
is, you know, the good news is it's not bad enough to cause a problem if
you double your dose by going to Colorado.
There -- I would like to pick on the idea of background,
though, and I'm extremely hesitant to do this because I'm not a
toxicologist and I'm going to start stepping way outside my bounds. But
I have an observation, and I'll do this is a dumb citizen.
If you look at -- what I am interested in looking at is the
dose standards that we set versus background for radiation versus
chemicals. What I look at is if you take nominal background at 100
millirem, which, you know, I'm going to eliminate the radon out of the
background, 100 millirem nominal background, and we are regulating at
fractions of that level, and that's where the regulatory discussions
are, but then you look at the chemicals, and I talked to my toxicology
friends at school, at Harvard, and they say, okay, arsenic is probably
going to be your controlling one to look at, and here in arsenic, the
background levels, natural background levels in arsenic in water is
something like five micrograms per liter, and maybe I have the units
wrong, but I think that's right. But the regulatory levels on that is
-- used to be 50. I don't know whether it got lowered to 25 recently or
not, but it's still multiples of the background levels.
I think -- help me with this, Otto, you're the toxicologist
-- I think that we are talking about stochastic results effects of
arsenic, so what I have been thinking is, boy, I wish I was lucky enough
to be talking about multiples of natural background as the levels we
ought to be regulating at, and I don't know if there isn't something in
there that we ought to be seeing whether it makes sense or not.
DR. POWERS: They know there's a threshold effect for
arsenic, don't they? I think there is.
DR. RAABE: Arsenic is treated as a carcinogen with a linear
-- it's a, you know, a two-stage, typical two-stage model, but they use
linear portion. So they use basically a linear no-threshold model for
arsenic regulation.
DR. POWERS: Kim, you've got a question?
DR. KEARFOTT: It's just a little question about all the
radon data and the radon epidemiology and that. Not being an
epidemiology expert, I can't comment on that, but it's occurred to me
that the radon in homes is in a different space in the homes and the
progeny are in a different space, and what might be going on, and this
is sheer speculation, is that the radon is not really getting into the
person.
I wondered if I could ask a question of the other
consultant, is whether anyone in these radon studies has looked at, in a
domestic situation where you're above ground, are the progeny actually
getting into the lungs of the individuals?
DR. RAABE: Yes, of course, the radon decay products are --
not the radon, but the radon decay products, and they're certainly
present on airborne particles in the home.
MR. FRAZIER: Yes, there were a lot of studies done in our
radon program to look at a comparison between homes and where you
actually did measurements in homes. They looked at the effective of
cooking all sorts of things.
DR. RAABE: It changes a little bit the dosimetry, but it
doesn't change the fact that the dose is there.
MR. FRAZIER: That's right.
DR. WYMER: Are there any further questions from the
consultants -- comments?
MR. MEINHOLD: Well, I think that this background thing is
kind of interesting because it's part of -- somebody mentioned Roger
Clark's paper -- I guess you did. Roger Clark is trying an idea out in
general about what he calls controllable dose. What he's saying is,
let's suppose that what we have for the public is a, you know, a level,
an upper bound, that's composed of natural background and whatever else,
and anything else.
So now we would set this at some level, like say, well, 400
millirem in traditional use. But I had a very interesting discussion
again with my friends in Rocky Flats, because he said to me, look, he
says, Charlie, the problem is, here we are, we get 400 already. He
writes 400 on the blackboard. He says, and they want to add 85. And he
says, we want to add 15. So I told him, that's a good one. I said, so
we use 415. He said yes. I said, so we can go to New York where it's
100 and allow them to have 315. Oh, no, he says. So I said, well,
you're not talking about 415 and 485, you're talking about 15 and 85.
They don't care. I mean, it's this whole problem. They do not view
that risk the same.
I think the other way, too, is that even Roger's proposal
controllable is part of the issue. So you can control radon, but you
can't control cosmic rays. You know, you can control some of the
terrestrial things, you can't control other parts. It gets very
complicated. But whether the public will ever allow this question to
even be raised is a serious, serious problem.
DR. RAABE: There is also the issue of protraction. We base
a lot of what we're doing on acute exposure, especially the RARF
studies, and earlier, I think Dr. Land mentioned the fluoroscopy studies
with breast cancer.
Now, Jeff Howell also did a study of lung cancer in those
people, and he found that when you looked at the lung cancer risk that
you predict from the atomic bomb survivor models at one sievert, you
predict a 60 percent increase in lung cancer, it wasn't there. I'm sure
you're familiar with that study; maybe you can comment on it.
MR. LAND: Maybe it's just different.
DR. RAABE: I beg your pardon?
MR. LAND: Maybe lung is different.
DR. RAABE: Well, it suggests to me that when you get down
to lower protraction, and this was not really chronic exposure,
obviously, it's multiple exposures, but when you get down to
protraction, that looks like there's a non-linearity, because if you
spread out the dose in time, if the linear and no-threshold level is
correct, spreading it out in time wouldn't have too much of an effect,
and here we have complete elimination effect, at least in that organ.
MR. LAND: There's also radiation therapy for breast cancer
which doesn't seem to have much of an effect on lung cancer. Part of
the same picture.
MR. HALUS: I believe the chairman has got some more
questions.
DR. GARRICK: Yes. I wanted to talk to Art while he's here.
We've talked a lot today about the merits of looking at the basis for a
departure from LNT from the macro level, overall dose level, to the
molecular single cell level. Would you comment on the issue of --
supposing we wanted to really launch a Manhattan Project effort at the
molecular level to solve this problem in three years with $20 billion.
What's the prognosis of the molecular level experts as to the
feasibility of approaching it from that level and finding the answers
we're looking for?
DR. UPTON: I'm going to disappoint you because I'm really
not a molecular biologist, but I would think that as we heard from Dr.
Frazier, the field of molecular biology is exploding, and techniques are
becoming available now that allow one very much more effectively,
cheaply, quickly, to examine effects on DNA, on genes, on chromosomes.
I think it behooves us, given the opportunities that beckon,
to look systematically at the effects of small doses, doses protracted
in time, on the genome.
If it turns out that small doses -- I'm talking about single
track low LET events -- up-regulate DNA repair systems and repairs not
just repair of base damage, but of the more complex legions in DNA, then
this seems to me to argue very strongly that the old linear model has to
be modified to take account of these kinds of phenomena.
On the other hand, if it turns out that these effects do not
exist, that sure, there are adaptive responses, there are some hermetic
responses in the sense that we heard from Dr. Calibrese earlier, but the
complex lesions in DNA are not affected by these protective mechanism, I
think that's a sobering finding.
But the stage is set to make those determinations now, and
I'm not aware that they have been made in the past, and I think that
kind of information would be very relevant and probably obtainable in
the next several years. Dr. Frazier would know better than I.
MR. FRAZIER: Yes. I think when we had our discussions with
Dr. Domenici, that was one of the questions he asked, is, you know, if
we pour more money on this, can we get the answer faster? And our
feeling was that this was a process where you had to do some
instrumentation development, some iterative kinds of studies where you
asked questions using new tools, develop new tools. And so we tried to
put together what we thought would give us a reasonable shot at getting
an answer or at least opening it up so we know whether we were going to
get an answer this way or not, and so we tried to propose it that way in
terms of resources and in terms of time, and I don't think, you know,
$30 billion on this in three years would be -- I think that would be a
total waste of resources. I think kind of a measured response of where
we're going, trying to get input as to how the information we're
developing is useful, where it's not useful, how do we have to modify
that kinds of information, it's going to have to be a measured process.
I'm sorry, but I really think that.
But I also believe, as Dr. Upton has stated, that we have a
new opportunity to get at those answers with the technology and
advancements, and I really think it's worth this sort of investment to
go forward.
MR. DOUPLE: Sitting in liquid nitrogen in Hiroshima and
Nagasaki is the world's most valuable resource relative to this
particular issue. These are tissue samples from tumors of patients,
survivors who were exposed, and thousands of those samples and thousands
of immortalized lymphocyte samples that have been frozen, and when the
technology is ready, that information could be very valuable in terms of
a range of known doses or known estimated doses, that could be very,
very valuable. I just want to point out the importance of that
resource.
MR. FRAZIER: There might come a time when there are more --
you know -- but I think that should be self-evident to a broader
population, and it shouldn't just be me saying it, it should be -- you
know, because it's our program, it should be other people saying, hey,
more resources are needed at this point. We have enough to know that we
really have to do this large study, and it's going to take whatever it
takes. But -- and then people can decide whether they want to do it.
But I think a sort of measured, going-forward, iterative approach is the
right pace at this point.
DR. GARRICK: I wanted to also pick up on Ted Rockwell's
observations of a few moments ago. He had in front of him an impressive
amount of documentation of references and source material of work that
was, as he put it -- kind of punched us in the nose -- was not
represented at this meeting.
So I'm going to also pass the question on to the National
Academy of Sciences, the NCRP, and ask, in your collective judgment,
Charles and Evan, is that a knowledge base represented in the committees
and projects that you have underway?
MR. DOUPLE: Let me start by saying that we have received
those materials and we appreciate that. One has to be very careful that
one also looks at the other information that is available, and too
often, the presentations have stressed pooling an assortment of studies
that have shown the types of effects that that individual is endorsing,
and these committees must look at all the information, they must look at
many feet thick documents, and that information is there, we appreciate
all the hard work that has gone into collating that information, and we
will examine that information.
DR. GARRICK: Dr. Meinhold.
MR. MEINHOLD: The box itself came after Art's committee had
completed its work. It's available to them now. However, most of the
issues that are in it have been addressed by the committee because those
aren't new issues that Ted's bringing forward or others; they're all
issues that have been on the table for four or five years, and as such,
they've been reviewed by the material that's come in.
I wasn't -- I didn't participate with the committee, but I
saw the materials that did come in to the committee, and I think that
almost everything that was in those reports has been seen by Art's
committee.
I don't know if you want to respond to it, but it's -- it's
the whole package of materials that would call the LNT into question.
So every one of those studies was there, and I think -- I'm not sure
that any of them have not been reviewed by the committee.
DR. UPTON: I would not want to argue that we've reviewed
them all. We found ourselves confronted with an enormous literature and
made the determination that it really wasn't feasible to produce a
bibliography that contained everything in the literature. We would have
to limit ourselves.
What we tried to do was to build on existing reviews where
they were relevant. The UNSCEAR '94 report had an extensive review of
the adaptive responses and hormesis. We cited that. We may well have
erred in neglecting other pertinent key pieces of information. I'm
dismayed to discover today for the first time that Luckey's books
weren't cited in our bibliography. Those are errors, those are
deficiencies that we'll have to correct. And to the extent that some of
the material that Ted referred to isn't adequately dealt with, Dr.
Pollycove had similar concerns -- we'll address those concerns and
attempt to rectify the situation.
DR. GARRICK: In a kind of a related question, Evan gave an
impressive accountability of the committee makeup and how you're
rotating committee members and changing people and reaching out for
different and new experts for your committees. I'm very familiar with
that since I chair a couple of Academy committees. I wonder, is the
NCRP motivated in the same way?
One of the criticisms that you often hear is the
institutional commitment that exists to the LNT.
MR. MEINHOLD: The turnover on the council itself -- the
council itself turns over about six new people each year. But this
committee, for instance, that was formed for this purpose is one that I
discussed the mission with Art, and then Art worked out the people he
would like to have, and it went to the board of directors, who approved
it.
I don't think that anybody ever turns down a suggestion for
that. And in fact, I could probably go through that committee, but less
than half of that committee had history with the NCRP. I mean, we
deliberately didn't put our stellar linearity people on the committee,
okay. I mean, Warren Sinclair, who is an excellent scientist but who
has that reputation, would have loved to have been on the committee, but
he is not on the committee. And we took a lot of steps to make sure
that was true.
For instance, Kelly Clifton has never had an assignment with
the NCRP before, who is on the committee, or Stewart Finch, or Howard
Lieber or Robert Painter. These are all people that have nothing to do
with this. And even people like Brenner, who came on the council a year
ago primarily because of the outstanding work he did on this committee.
DR. GARRICK: Yes.
MR. MEINHOLD: So these aren't institutional people that
made up this committee. That was the point that I would make about
that. And it was our intent not to be. As a matter of fact, if it had
been up to me, John Goffman would have been on the committee, just so
you know that I don't decide. But if I decided, John Goffman would have
been on the committee. My point is that we tried to be as
middle-of-the-road as we can, but the fact is that if you think we're
biased in one direction, I ought to try to bias it in the other to make
some balance.
DR. GARRICK: One final question. Is either the BEIR 7
committee or the 1-6 committee, is there any representation on either of
those committees of somebody that would be considered extremely
knowledgeable or associated with the shipyard worker study?
DR. UPTON: Well, I chaired the committee.
DR. GARRICK: Thank you.
MR. HALUS: It's been suggested that I ask people, in the
advantage of time, as you to hold your comments or questions to a
five-minute period.
But is there anyone in the audience who has some questions
for the panel or would like to make a comment at this time?
Please, sir.
MR. JOHNSON: My name is Raymond Johnson, I'm the
president-elect of the Health Physics Society, so I'll be following in
Keith Dinger's footsteps here shortly in a few months. Keith's
following in Otto Raabe's footsteps from a year ago, so we have the
whole succession here.
What I wanted to raise as a point for consideration, I
believe one of the committee members raised a question a few minutes ago
about, okay, so we've done all the studies, where does that bring us to?
And the concern being one of how does that help us in our communication
with the public, who perhaps is not reacting just to their technical
understanding of risks, but rather their perceptions.
What I would like to add to that for consideration and
perhaps ask of the panel members what's being done in the area of risk
communication. What I would offer as an observation is that as we
attempt to develop our technical understanding of radiation risks and
refine our knowledge of the linear non-threshold model, that, in fact,
what the public is reacting to is not the technology, but rather their
images of the consequences of what radiation can cause, and, you know,
in particular, I think people, if they think about the risk, they
general think about cancer, which is quite a scary prospect because --
and it's an insidious disease, it suddenly afflicts itself on you with
no warning, and if that's the result of radiation, and that's what
people have in their mind as an image, then they don't want any part of
it.
I guess what I would like to ask is, is there any thought
being given perhaps in DOE in your research programs to the risk
communication aspect of, you know, we're developing more knowledge, are
we also developing our ability to present that in ways that address
images that people have which are not a function just of technology, but
a function of their fears, their perceptions, their values, their
beliefs, and all of these factors are what are determining how we
implement our regulations today, and I don't know if we're dealing
enough with that.
MR. FRAZIER: Well, I think it's a good point. It is
clearly a part of our RFA that's on the street. We asked for proposals
in the area of risk communication and we got some responses in that
area. So we -- those will be reviewed by a special panel, I think. We
didn't get very many responses, and we have to develop interest in that
area. But we clearly see it as a critical part of the program, and we
have a group at Oak Ridge that got an award in an earlier panel that's
actually trying to do some of that. They've got some expertise in the
area of chemicals which is not desirable, but we're trying to bring in
some people in radiation to help with that. But they have very good
risk communication kinds of backgrounds. Very important area. We're
trying to address it, as I say, and we'll continue to throughout the
whole program.
MR. JOHNSON: Thank you.
MR. MEINHOLD: I would like to respond to that. I think
this is a serious problem raised, as you know, that one of the
difficulties is that we don't know how to do it. The scientist and
engineer community do not know how to do this, and our biggest mistake
is thinking we do.
For years, we've had the Health Physics Society write things
for educating the public or whatever. It's not us, it's other people.
And we realize that on the NCRP, too -- we don't know how to do it. So
we did try to start to do something. We started with Paul Slovic
chairing a committee for us, who understands about risks and public
communication, and we're trying again with Susan Wilshire, now chairing
that same committee, with Granger Morgan and a few other people who deal
with public issues.
It's just an ongoing issue to try to bring even us up to how
to do this. I mean, I think it's an absolute mystery that we just don't
know how to deal with.
I was enlightened by the fact that they could point out just
the way we say things in our reports gives wrong impressions about what
we mean, you know, not what they understand but what we mean isn't
correct in the way we say it from a public perspective.
DR. GARRICK: Let me give a classic example. The classic
example that's going on right now is the debate between the US NRC and
the EPA on the Yucca Mountain standard, where the one argument seems to
be rooted in protecting the groundwater, whereas the public perception
is that the Nuclear Regulatory Commission is not interested in
protecting the groundwater, a total, total miscommunication.
MR. MEINHOLD: Right. Absolutely.
But one of the critical things that people we've talked to
-- we had risk communicators helping develop our plan -- is that, you
know, really the wrong people ask what the issues are. You've got to go
to the public and find out what they perceive is the issues and what
they perceive is the risk questions they want to ask. And we always
have this top-down approach where the scientists are trying to tell the
people and the people are saying, you know, I don't care about that
point, my real concern is this, but nobody is listening. We've got to
listen.
MR. HALUS: Are there other people -- yes -- who have
questions? Yes, sir, please go ahead.
MR. JOUSTES: Actually, I have a comment. I'm Rick Joustes,
I work with Evan Douple and I'll be the study director on BEIR 7.
I was in Dr. Frazier's radon program for a number of years,
and one of the perceptions in that program or one of the public
perceptions that I experienced on occasion was that a portion of the
population wasn't that concerned about radon because it was a natural
thing emanating from the earth.
I now have a study where I'm looking at a large electric and
magnetic field program, and one of the public perceptions is that it's a
dangerous thing because it's being done to you, the power lines are
being done to you. I guess I'd tie that comment together by saying that
we are including a risk communication person on the BEIR 7 study, and I
talked to this person that we're going to propose and I hope that that's
going to be, you know, valuable to the process.
MR. HALUS: Other questions or comments from the audience,
please?
MR. MUCKERHEIDE: Jim Muckerheide.
Public perception and risk communication is always an
interesting topic. We tend to blame the poor, uninformed public. When
I talk to the public, they don't feel quite so uninformed. They feel
quite informed, and unfortunately, it seems as though they're informed
by you and me, that we have gone at this issue of risk by radiation from
the LNT perspective and it colors everything we say.
The public believes you. Can you get past the idea that if
you can address risk communication from the perspective that risk
doesn't necessarily exist at zero doses, at insignificant doses, that
somehow the public will being to believe you.
Now, of course, you're going to look very -- be looked at
very askance, but how can we approach the question of talking to the
public after 40 to 50 years of telling them that any amount of radiation
is hazardous because it helped us with the arguments to stop
above-ground nuclear testing to tell them that fallout was hazardous.
So if we use a linear model, we can start going from our simple approach
on the linear model, apply to occupational exposures to tiny doses over
the whole country, which has again, of course, now come back 40 years
later to haunt us as an issue that could eat up lots of resources for
absolutely no public health benefit.
If we can't get past the idea that we are telling them
something they believe, we'll never get past the issue.
The other question I would ask about risk communication is
in working with Paul Slovic in the '70s and DOE on a waste management
program, the perception that I always had of the risk communicators was
we know there is a risk, but it's small. However they approach the
question, we know there's a risk. You can't tell people there is no
risk.
Paul Slovic was one of the people in 1976, 1977 who built
the public perception that there was significant risk from waste. He
built the public perception that says, we don't have to just take care
of the waste tanks at Hanford, we have to clean up levels that are below
background. And of course, now many years later, we're looking at even
more extreme conditions of the levels at which we are trying to address
cleanup. But can we get to the point where we are prepared to tell
people that the amount of radioactivity that would be released from the
Hanford site, just as hypothesis thrown out here, we could release all
of that radioactivity over the number of years, we could imagine all of
this inventory being dispersed, and going through the groundwater into
the Columbia River, and I would venture to propose that if we did a
quantitative analysis, we would say there was a million times more
radioactivity down that river from 1946 to 1972 or 1980, and I'll bet
you that over the period of time that that waste would be released from
the Hanford site to that river, there is a trillion times more
radioactivity going down that river from natural sources.
Now, unless we killed people in Oregon in 1980 from the
releases from 1940 to 1972, unless we know that those high releases
caused damage, the idea that we should spend $5 billion a year not to
take care of the concentrated waste that we should have responsibility
for, but to go into the whole process of that cleanup is something that
the public is going to get zero benefit for, zero benefit, not a
hypothetical very small benefit, they will get zero benefit. There is
no significance to the issue of how much radioactivity within the
natural noise level of natural background that is going to be affecting
anybody downstream from Hanford. You may want to clean up specific
areas; on the other hand, we need places to sequester materials.
There's a place on that site that could be set up as a place where we
are going to sequester materials.
But I think unless we in this business start telling the
truth to the public about the nature of the risk and the quantification
of the risk, the idea that we can convince the public that they can
understand something that we look at and say is a high risk is not going
to happen.
I would appreciate any views by anybody that says that in
our institutional approach to this, from the agencies or from the
radiation protection committees, that the change that we have to address
is how we look at the nature of the problem we face.
DR. POWERS: I would just comment quickly that I've done the
calculation on putting it down the Columbia River, and you're right --
background dominates whatever you do if you spread it out over 40 years
by a huge amount.
DR. GARRICK: And that's another example of the rest of the
story.
MR. HALUS: Further responses to Jim?
MR. PUSKIN: I guess I just don't see how -- unless you can
-- you're sort of making the assumption that we can tell people that
there is no risk from very low doses, and until there's a consensus in
the scientific community that that's the case, I don't see how you could
be very convincing because they're going to be scientists who are going
to say the opposite.
MR. POLLYCOVE: That's right. And so what we've got to do
is get that consensus and quit worrying about the public's irrational
fear when, in fact -- you're exactly right that until the public --
until the scientific community involved in this problem can agree that
this is not a risk that we're imposing, until we can agree on that,
there is no point in worrying about how we're going to communicate to
the public that they shouldn't worry.
If I believed that the LNT was true, I'd be marching with
Green Peace. I don't think it's at all irrational for the public to
fear a thing that says if one gamma ray gets out, it's going to kill
you, and trust us, we're not going to let that one gamma ray out.
That's -- I don't care how you phrase it. You can get the tobacco
advertisers or anybody else you want to try to sell that story.
[Laughter.]
MR. POLLYCOVE: You're not going to sell it because it's not
rationale.
So you're absolutely right, the scientific community has got
to get its act together. That's why RSH has been focusing its attention
on the scientific community rather than on the public, because we've got
to get our thing together, and until we can say, no, we are not imposing
a risk anymore than that arsenic is a risk, then I think until we can do
that, I wouldn't worry about trying to communicate to the public. We're
not ready to communicate with the public.
MR. PUSKIN: I don't entirely agree. I think that obviously
we would be in a much better position to communicate if we had that kind
of scientific knowledge, but we do have enough knowledge in terms of
what's the maximum risk it could be and we can put that into
perspective. Not everyone is going to accept it, but I think that's
what you can do right now.
MR. MEINHOLD: I guess I want to come back to -- I think the
most important thing that's happening here is Marvin Frazier's program.
All of the stuff that Ted has written for us, we've seen. All of the
stuff that John Goffman has written for us, we've seen. Now let's find
out about it, okay? Let's do the research and see if we can sort it
out.
I don't think we're going to get anywhere continuing to talk
about it without more information. I mean, that's where it is. And I
think that the DOE research program is the only option we have, together
with the ongoing genome project and other things, to get us the answers.
And we can sit here and call each other names and get excited about it,
but there's not going to be any consensus until we've done our science.
That's where we are. And I feel sorry for your committee. Your
committee has got Art's problem. I mean, we just don't have those --the
definition we need that hopefully you'll have.
MR. FRAZIER: Hopefully.
MR. MEINHOLD: Hopefully. I know. I mean, it's the only
hope.
Now, the only other thing I want to add is that your answer
could be just exactly opposite of what you hope it is. Just so you
understand about this money that's going to be spent here, it's very
possible that they will endorse in a scientific way the assumptions that
have gone into all of these other assessments. That's the other danger
to this program.
DR. GARRICK: If the evidence supports that, sobeit.
MR. MEINHOLD: That's right. Exactly. But I think talking
about it without much more on that doesn't hep us very much, to be
honest with you.
MR. ANDERSON: I would just like to add a point in this
communication with regards to what Charlie said.
My understanding, Charlie, is that all of the
recommendations emanating out of NCRP, ICRP, and, in fact, those
recommendations are utilized virtually verbatim in NRC's regulations --
MR. MEINHOLD: Well, it may be, but it takes them an awful,
awful long time.
MR. ANDERSON: Well, that being said, I think a very
important part of the communication is to stress that -- I'm thinking
about probabilities, Dr. Garrick -- the probability is exceedingly small
that we're going to find out that the standards have been placed too
high. The greater probability is we'll find out that the frame work is
either appropriate or perhaps too conservative.
I think, as I listen to the discussion and try to think
about somebody that's not quite so tuned into all the nuances, it would
be easy to walk away with an impression that we just don't know what
we're doing at all, that we're just fumbling around with arbitrary
standards, and I think that we need to communicate very strongly as we
move forward with this research that that's not the case. I'm not
looking for Dr. Frazier to come back in ten years with the answer in his
hand and say, oh, my god, you know, we've got to decrease the standards
by a factor of ten.
So I think that's very important to convey over in
communication, that we already have a suitable scientific knowledge base
to formulate appropriate safe standards for public health and safety,
and we do so.
I don't expect much, getting back to the pragmatic approach,
out of the research as far as standard-setting is concerned.
MR. MEINHOLD: The only way I see it, though, is the low
dose question, the model that we're talking about. It's not going to
change the upper one because it's -- the epidemiology there is all right
as it is. It's the -- it's not the worker, it's the public, and whether
or not -- there's still the uncertainty. When you read Art's report,
even if you think it's prejudiced and biased, when you read it, you
realize that there is an awful lot of uncertainty in every section of
that report. Uncertainty is the name of this game. It really is. And
so it's really narrowing that uncertainty that can help us.
I don't expect to see a big change because I think that the
models can't be -- I've said the biggest uncertainty I see in all of
this is the drift. I mean, Chuck and all of the -- Charles and all of
the epidemiologists thinks it's one, and the animal biologists think
it's five, and we've settled on two. I mean, it could be ten. It's
probably the biggest area that we don't know very much about but we're
guessing anyhow because we don't know the molecular biology and all the
rest of it down there.
DR. GARRICK: See, there's another example of risk
communication. The public having -- if they had just heard you and you
had waved your arms about uncertainty and how great it is and what have
you, there is a sense of hopelessness and what have you -- what you're
talking about is uncertainty about the details.
MR. MEINHOLD: Right.
DR. GARRICK: There is not much uncertainty about the
ability to protect the safety of the public.
MR. MEINHOLD: Absolutely.
DR. GARRICK: There's not much uncertainty about the global
impacts of these things. And I think these are examples of where we
screw up. We don't really -- we don't really keep things in proper
context.
There is uncertainty in understanding some of the
fundamental mechanisms that are going on to be sure, but there's not
uncertainty as far as having high confidence that we're protecting --
MR. MEINHOLD: Right.
DR. GARRICK: -- the health and safety of the public.
DR. WYMER: It's six o'clock. We have a fairly fundamental
decision to make -- whether or not we come back in the morning and
pursue this.
Let me start by probing the panel. Are you pretty well
talked out? Have you presented things that you think are pertinent?
Are we reaching the point of diminishing returns?
MR. DOUPLE: Yes.
DR. WYMER: We have a yes. Maybe we're getting unanimity
here.
How about the audience? There's a yes.
I suspect we are --
DR. GARRICK: I think the one useful thing that we could do
tomorrow would be to talk in specifics about things that we think have
not been properly considered, giving some examples, because I think
we've got a dichotomy here on saying, on the one hand, gee, we've looked
at all this stuff, and we're saying, no, you haven't really. I think we
owe it to you to be more specific about where we feel things have not
been properly considered, and we could be very specific on a number of
details on that, and I think that might be helpful.
MR. DOUPLE: I'm not sure, though, that we will have a
committee that wants to do that. It is a question of diminishing
return.
DR. WYMER: I think it's important to really deliver that
message to the committees that are going to be reviewing this, so I'm
not so sure that it's appropriate here. But you have to make that
decision. I think that that kind of input is valuable. Whether or not
it's valuable to us right now is -- that's pretty negative sounding.
DR. GARRICK: Well, I was mumbling and didn't hear the last
comment. My impression is we got a lot of information today and a lot to
think about and probably enough to formulate some sort of a letter.
DR. WYMER: That really is my view, too. I think maybe
we've heard the right answer down here from Dr. Douple that those people
who want to present a more detailed discussion probably ought to do it
through a different medium than this meeting here than -- rather than
bring everybody back tomorrow when most of the panel thinks that they
would rather not because they've pretty much said what they want to say
and heard what they want to hear.
I assume, Ray, you were thinking of still bringing the
consultants back so that we --
DR. GARRICK: I think we'll need the help from the
consultants in formulating our -- the frame work for our report, yes.
DR. WYMER: Yes. Right.
DR. GARRICK: But unless -- I'm sorry?
DR. FAIRHURST: Could I just ask a very -- do you have any
examples of successful risk communication efforts? You don't need to
answer now; I'm just -- everywhere I've heard, people are very negative
about the ability to do it. Is there any concrete examples of where
it's been --
MR. PUSKIN: I think with the WIPP project, I think --
DR. FAIRHURST: I was involved in that for a long time.
MR. MEINHOLD: I thought one of the better examples was the
stuff that John Teal did out at the Hanford reservation. He did a very
clever thing, which is the thing we have to learn how to do was, that he
gave a format of how you would work out your dose. You know, did you --
if the item came from a plant, did you live in the Richson area from
1949 to 1948, from '48 to '52? Yes. Did you live south of the plant?
Yes. Did you have a cow? Yes. Did you drink that unpasteurized milk
from the cow. And each one of these was a fault tree.
So the people worked out their own doses, right, which was
one of the best risk communication things I had ever seen, because most
of it ended up with nothing, you know. They didn't have a cow, you
know, all of this stuff. So there were about six people that turned out
to have important exposures, and most of them found out who they were
themselves. I thought it was a very, very successful communication
exercise.
DR. WYMER: Let's hear another comment from -- back here.
MR. MUCKERHEIDE: Having been in Hanford from '46 to '49,
I'd wonder about the value of having done that considering where it's
gotten us even as recently as this thyroid study that got a bunch of bad
press.
I'm sorry, I just wanted to make two quick points about
tomorrow, and one is, I spent the whole day here taking a lot of notes
and a lot of questions about hopefully an opportunity to ask questions,
and, of course, if you're just not going to do this tomorrow, then
that's all a waste.
The other point was we did mention to several people that
this would continue tomorrow. Conceivably you have people coming back.
The third is I would just like to observe that one of the
difficulties of having set this up without the participation of people
who would be more critical of the substance of this material is that you
have a lack of discussion other than a few questions from the floor that
has any of the merit of what's missing, what needs to be done, and I
think you're missing the other side of the coin, I think there have been
some very good points about the other things you have to think about,
but you don't have people who have made presentations, nor even really
asked serious questions about the material that has not been addressed,
especially in the NCRP report.
If you're going to take a position without having another
meeting or an opportunity for people to speak, I think that's going to
be very detrimental.
DR. GARRICK: One thing that we should observe is that this
is about the third meeting we've had on this issue in the last couple of
years. We had -- we had meetings where we heard at length from some of
these people. In fact, James, I think you were --
MR. MUCKERHEIDE: I was.
DR. GARRICK: -- a participant in some of those. And I
think that we were accused last time around of over-favoring the other
side. So I think if you take all three meetings together, probably the
balance is greater than maybe it would be perceived as being on the
basis of just today's meeting.
The other thing is even today, I think we've given an
opportunity to anybody in the room to express themselves on whatever
their hot buttons were with respect to this issue, and as the day grows
longer, I think we're beginning to hear recycling of some of those
issues, which suggests to me that maybe we are pretty close to having
run the gamut here.
Obviously, this is a very fascinating subject and I myself
would like to discuss it all day and ask questions for all week, but I
do think there is a lot to do and that maybe we have gotten close to
that point of diminishing return. That's at least my impression.
DR. WYMER: Well, we only had two hours scheduled for the
morning. I think in light of the panel thinking that they've had
enough, for two hours in the morning, it's quite a thing to ask them to
come back in light of the fact they've already expressed an interest in
not coming back. So I think we'll declare it done.
DR. GARRICK: That doesn't mean we're not going to have a
discussion in the morning among the committee and its consultants about
this. That's right.
MR. HALUS: And information can still be provided in writing
if someone cares to do that; is that correct?
DR. WYMER: That's exactly right.
MR. MUCKERHEIDE: Does that mean that's not an opportunity
to speak to the committee if you don't have the panel back? Are you
asking us not to show up?
DR. GARRICK: It's a public -- it's an opening meeting.
MR. MUCKERHEIDE: No, I understand, but I mean, are we -- is
it going to be the two hours of an opportunity to ask questions or are
you saying, you know, we can sit here --
DR. GARRICK: I'll speak out of turn here, but if you have
some constructive observations to make that we haven't heard, I think
the committee, if you notify the staff, would be pleased to hear from
you tomorrow.
DR. WYMER: I think it's fair enough to say that we'll be
available for those two hours we had scheduled in the morning to be open
for additional discussion, but the panel does not need to --
DR. GARRICK: Participate in that.
DR. WYMER: -- attend unless they scheduled their planes
such that it wouldn't make any difference to them.
MR. MUCKERHEIDE: Can I just add one point in reference to
my previous participation?
DR. GARRICK: Yes.
MR. MUCKERHEIDE: And that is that while you've had three
meetings on this subject, this is the one and only meeting one product
of the NCRP review. The other two meetings, to the extent that there
were identified issues that said, this is an issue that has to be
addressed in this report, has in essence a record that says, would we
have concluded that the issues that were identified in those earlier
meetings have been addressed in this report? And I would ask you, on
your own, that in your record, recognize that those earlier meetings
were without the product of the NCRP report effort, and that the
question of whether or not the identified issues have been addressed is
something that isn't going to be undertaken by this committee in the
absence of your own private initiative.
MS. THOMAS: Excuse me. Jim, correct me if I'm wrong,
Charlie and Art, but at the NCRP annual meeting, April 7th and 8th, Art
will be up making a presentation on the report and there will be time
for comment from the floor?
MR. MEINHOLD: Not very much; about 15 minutes for each
speaker, like it was here.
DR. WYMER: At any rate, let's leave it for the two hours we
have scheduled in the morning for the panel discussions, that we can
hear from the audience their comments about what was and what was not
included that should have been included, and that will be input to our
report certainly.
MR. MUCKERHEIDE: Thank you.
DR. WYMER: That's sort of a compromise.
MR. MUCKERHEIDE: Thank you.
DR. GARRICK: And we should point out, this is a continuing
issue. This is not going to be solved on the basis of a single
recommendation as a result of this meeting.
Furthermore, we have had presented to us a great deal of
information that we've not even touched on today, like the stack in
front of me is all information that was generated in preparation for
this session.
So I think that the channels are still open for discussion,
dialogue, as Ray said. We've got a couple hours in the morning to wrap
up a few things. But I want to assure you that this is not something
we're closing the book cover on, that this is a continuing issue and we
will have future meetings, won't we, Dana?
DR. POWERS: Well, especially if the research starts
yielding products that we can take regulatory action --
DR. GARRICK: Right.
DR. POWERS: -- or suggest regulatory actions on.
DR. GARRICK: Right.
DR. WYMER: I want to take this opportunity to thank the
panel. We certainly appreciate their input and their discussion. We've
taken a lot of notes. I hope we can translate those into some kind of a
meaningful report with some meat in it. I thank the consultants, which
we will see again in the morning, and the audience for participating,
and we expect to see several of you in the morning.
[Whereupon, at 6:14 p.m., the meeting was recessed, to
reconvene at 8:30 a.m., Wednesday, March 24, 1999.]

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