September 8, 2006
COUNCIL MEMBERS PRESENT
Edmund Pellegrino, M.D., Chairman
Floyd E. Bloom, M.D.
Scripps Research Institute
Benjamin S. Carson, Sr., M.D.
Johns Hopkins Medical Institutions
Nicholas N. Eberstadt, Ph.D.
American Enterprise Insitute
Daniel W. Foster, M.D.
University of Texas, Southwestern Medical School
Robert P. George, D.Phil., J.D.
Alfonso Gómez-Lobo, Dr. phil.
William B. Hurlbut, M.D.
Peter A. Lawler, Ph.D.
Johns Hopkins University School of Medicine
Gilbert C. Meilaender,
Carl E. Schneider, J.D.
University of Michigan
WELCOME AND ANNOUNCEMENTS
CHAIRMAN PELLEGRINO: Good morning. Good morning. Thank
you very much for joining us on time to provide an opportunity for
everyone who wishes to speak to speak.
I would like to start out first by stepping out of the
agenda for one second, and it won't take very long, and asking
Professor Eberstadt to give us a report on a question that was posed to
him yesterday by Dr. George having to do with the economic literature.
DR. EBERSTADT: Thank you very much, Dr. Pellegrino.
I wasn't prepared for Robby's friendly
interrogatory about the state of the economics literature yesterday.
And so I don't think I was as informative as I could be to fellow
I went back last night to do a little bit of homework on
this as I guess your sometime economist on the Council. And I can
report very briefly to you the state of the literature.
As I mentioned, there are indeed only about a literal
handful of professional studies on questions bearing on organ donation
or organ transplants. However, that handful of studies has been
offered by a very high quality of economist. Of the maybe half a dozen
studies I came across, two were by Nobel Laureates in economics. A
third is by a winner of the John Bates Clark prize, which is the prize
that's given to the most promising economist under 40 years of age
every 4 years.
Not all of the work was on the question of marketization or
commoditization of donor markets. Some of the work was on trying to
quantify, for example, what the impact of presumed consent laws might
be by looking at European data. Like those laws or not, the conclusion
of that work, the suggestion of that work was that this would
substantially increase the supply of cadaveric organs.
Other work was analyzing the disparate impact or the
disparities in areas with respect to waiting lines and other things
under existing situations. But I suppose the study which I would bring
to your most immediate attention here was one by Gary Becker at the
University of Chicago, not known, like Richard Epstein, as a famous
libertarian, a person, very eminent economist, associated with work in
human capital and crime and the family and many other areas.
He has attempted to model the impact of marketizing.
It's somewhat speculative, but he has attempted to estimate the
impacts of marketizing organ donations, organ transplants.
In his approach, he comes up with the suggestion or the
quantified hypothesis that an equilibrium price of about $30,000 might
be expected for a market in human kidneys in the United States. Now,
how does he arrive at this conclusion? He draws upon a literature in
economics, so-called cost of life literature.
To many of us, the idea that you would put a price on human
life may seem offensive or repulsive, but this, of course, happens all
the time in the insurance industry and in many walks of life.
By drawing upon some findings in this cost of human life
literature, he goes about the speculation which ends up with this
suggested equilibrium price.
I am certainly no Nobel Laureate in economics. It looks to
me as if he is equating the marginal cost of a human kidney in the
sense of the risk to a donor plus hospital expenses as being equal to
its marginal price. There is a different sort of economic perspective
that might suggest that people have what economists call a reservation
price, not just simply a marginal cost, for organ donations. This
shows the beginning of the work that is being done in this area.
I would also bring your attention to a popularized article
that Steve Levitt, the winner of the John Bates Clark Medal and the
author of the best-selling book, Freakonomics, did in the New York
Times last summer. It's a popular article, not a scholarly one.
He makes the observation that there is no serious economist
who would agree with the way that the U.S. current organ donation
arrangements are working. And he mentions work being done by — he
does, however, at the same time acknowledge what he calls the
repugnance factor in what one would think about the somewhat ghoulish
aspect of a market in human organs and brings attention to work that is
being done at Harvard University and in New England by an economist
named Roth, who is simulating some of the effects of a market through a
kidney exchange program, the New England Kidney Exchange Program, thus
CHAIRMAN PELLEGRINO: Thank you very much.
Could I make you a request? Would you submit that in
writing so all of us can take a look at it and think about it? It was
very, very appropriate to our comments yesterday. We do not have time
Moving to the first part of the agenda, which — welcome,
Paul, delighted to have you back.
DR. McHUGH: There was some bomb package that delayed me
getting here this morning.
CHAIRMAN PELLEGRINO: Delighted to have you.
SESSION 5: THE COUNCIL'S FUTURE AGENDA
CHAIRMAN PELLEGRINO: The first morning session we have dedicated to the question
of our future agenda. That came up yesterday. And I think this is the
time to discuss it in some detail.
As we said yesterday, we have been operating now on a
number of different topics for a period of about six or eight months
and I think would like to know the mind of the Council with reference
to what direction we ought to take in the future.
Dan Davis has done a wonderful job of collating your
responses to the survey, which you were good enough to participate in.
And he has set that before you. And I suggest you use that as a guide
to whatever remarks you have in mind to make.
I would like to come out at the end of this with some
notion of the preferences of the group. And let me forewarn you. I
would like to have an open discussion for a period. And then unless
you rebel, I would like to go around the table and ask each of you to
tell me what your thoughts are about — go ahead and put it right out.
What do you think is the direction we should be taking?
I ought to tell you what you know, I'm sure, that
we'll try to take that under advisement and then come back with
something that looks like an agenda but get started as soon as
So let me then throw it open for discussion. You have seen
the grid. Maybe Dan will take a second to tell you what the meaning of
the gradation of colors is, although I think it's quite obvious.
Nonetheless, he can make it clearer.
DR. DAVIS: Okay. There were two topics that received the
highest votes in terms of interest, number 4 and number 8, the ends and
goals of medicine and citizens' personal responsibilities for
Those two were then followed by four topics that were neck
and neck: number 5, genetic information and knowledge; number 6,
health care, which special interest or focus on obligations of society
towards its members; and then nanotechnology; and, number 11,
commercialization of clinical research.
And then following that there were two topics: ethical
formation of health professionals and the patient-physician
relationship. So that is how things sifted out with the tally.
And then two Council members have suggested other topics
that were not on the list. And those are at the bottom of the page.
And when we get into the swim of the discussion perhaps they would like
to join the discussion and explain why they have offered those
CHAIRMAN PELLEGRINO: Thank you very much, Dan.
Now I would like to throw it open for general discussion
and again repeat what is in the back of our mind of eventually getting,
not so eventually getting, to your own personal opinions of what we
should be doing.
First, general comments on the results of the survey and
your own feelings about what would be appropriate and best directions
for us to go. Anyone?
CHAIRMAN PELLEGRINO: If the silence continues, I think we
will just start. A few more moments of silence would be useful, but
then if it goes on, we will start with individuals. And I think that
probably will be much more productive, frankly. It looks like you
Now the problem is who goes first. And I will be accused
either of partiality or of malevolence wherever I start, but — very
good. Thank you.
DR. EBERSTADT: May I ask a question?
CHAIRMAN PELLEGRINO: Yes, you may ask a question.
DR. EBERSTADT: It's pertinent to the future
agenda. Where is the disposition of our deliberations on organ
donations and organ transplants in re: the future agenda? Is this —
CHAIRMAN PELLEGRINO: Dan?
DR. DAVIS: Well, we ended yesterday with a statement
against, I think, continuing to pursue the topic. And we also had a
proposal for at least an outline of a report that we may issue on this
topic. So that is where I think the state of the debate is at this
CHAIRMAN PELLEGRINO: And I think that should be part of
PROF. LAWLER: Let me relate Nick's report to that.
I read the article in the New York Times by the Freakonomics guy.
And he reported what I already knew, that no serious economist can
figure out why we don't have a market in kidneys. And from
the point of view of a political scientist, serious economist might
be kind of an oxymoron or something.
But from another point of view, this economic way of
thinking is ever more pervasive in our society. So I think the fact
that people who really think along these lines are perplexed.
I would suggest that a market in organs is a much more serious
possibility than Carl was saying at the end of the meeting yesterday.
And with respect to the Professor Becker, who is a great economist
report, he's so abstracted from the political context and coming
up with that number... That study is worthless because obviously,
as we talked about yesterday, the price of the kidney will be set
in terms of the Medicare entitlement, which would make it much higher
than that. And, as you were alluding very gently, common sense
would tell you $30,000 wouldn't be enough to generate many kidneys
unless you globalized the market, which would be disgusting in certain
So, strictly speaking, you didn't answer Robby's
question, which was, do we have any data that shows how many more
kidneys a market would generate, what they're really worth.
And the studies you brought us by eminent economists
don't really address that question and, I would even suggest, are
incapable of addressing that question, but the fact that they're
thinking along these lines and these guys have so much influence on
public policy and they are frequently on the cutting edge of public
policy would suggest the importance of the kidney issue because I think
any — I don't think like an economist, but if I did, I would think
this is a problem that would have a market solution. And this allows
the libertarians in a certain way for the first time ever to be
compassionately conservative. This would be a compassionate market
solution to a real human problem.
So I agree with Carl on many points, but on this particular
point I disagree. I think we need to rush in a deliberate sort of way
to get this kidney thing done, this organ transplant thing done because
I think it is an urgent issue facing the country.
CHAIRMAN PELLEGRINO: Thank you.
I think we will undertake the procedure of going around and
getting individual opinions about what would be the direction in which
we ought to go as a Council. So, Robby, would you be willing to kick
us off in that direction?
PROF. GEORGE: Sure. I will be happy to make a few
opening remarks perhaps. And then I would like to weigh in a little
later, if I could, after hearing some of the discussion from other
CHAIRMAN PELLEGRINO: All right.
PROF. GEORGE: Before beginning, can I say how wonderful
it is to have our colleague Dr. McHugh back and looking so hale and
DR. McHUGH: I want to thank the members of the Council
for their kind thoughts and messages when I was ill. I can tell you
they were most welcome and brought cheer to me.
PROF. GEORGE: It is wonderful to have you back, Paul.
Well, in addition to the matters that are laid out here, I
would like to propose, Dr. Pellegrino, one other thing but not a major
thing, on a small scale, a project on a small scale.
I think one of the most important instruments that we have as a
Council produced over the four-plus years' life of the Council
was our White Paper on Alternative Sources of Pluripotent Stem Cells.
I think that really had a wonderful impact that is
stimulating thought and work among people who are qualified to search
for alternative sources of pluripotent cells. And it continues to have
In part, because of the report, work has now been done that
renders our report out of date, work by people like Dr. Eggan at
Harvard, Dr. Jaenisch at M.I.T., Dr. Trounson in Australia, Dr.
Yaminaka from Japan. And I noticed just yesterday a report of what
looks like some very important work by Dr. Cibelli.
So what I would propose as a small project for the staff
and for the Council is simply an updating of that white paper to take
into account all the work that has been done and, of course, to treat
some of the work that has come into the public in the form of a kind of
controversy, such as the ACT exploration of the embryo biopsy proposal,
which was one of the proposals that we outlined among the four
proposals in the report. So I think that would be a very useful
contribution for the Council to make at this stage.
Well, let me also say that I think that a reflection on the
ends and goals of medicine is just a very, very worthy and timely
topic. I think it's an area where the Council really does have an
important contribution to make because we can sit back and reflect on
just what it is that we're aiming at when we're aiming at
So many of these issues came onto the floor yesterday
during our discussion. Is health purely to be understood in a physical
sense? If that's true, what do we do with Professor McHugh's
profession? But if it's not true, where are the limits? Is
medicine in the business of making people happy?
We have, of course, already explored some of these issues
in our "Beyond Therapy" report, but there is certainly more
to be said. And we have gained some strength, not least the addition
of Dr. Pellegrino, who spent a lifetime reflecting on these issues
since that report was issued. So I think we probably would have some
new and important things to say there.
I myself am very concerned about the eugenics issue. I do
notice that five members of the Council indicated that they have little
interest in that and one member of the Council said no interest. I was
somewhat surprised by that, but people have different perceptions of
the situation that we're in.
It hasn't been published yet, but Dr. Kass gave a
wonderful, if disturbing because of the analysis of our current
situation that he offered, talk at the Holocaust Museum. It must have
been about a year ago. The paper hasn't yet been published.
He noted in that talk — and I can't remember the
title, but it was the talk that he gave at the Holocaust Museum. The
ways in which what might be called the eugenics mentality has
reappeared in a somewhat different form at the end of the Twentieth and
the beginning of the Twenty-First Century from the form it took in the
1920s and '30s that although the form is different, the substance
is similar or even the same.
And he brought to light some social facts that I myself had
perceived only dimly, but, of course, Leon's powerful, illuminating
intellect really did bring them into the light of day.
I hope that that talk will be published soon, but, even if
it's not, I hope that it could be made available. Perhaps we could
ask Leon to do that. And I wonder if it might shift some sentiment on
the Council to move the eugenics issue further up the table.
So those are my remarks for now, Dr. Pellegrino. Thank
CHAIRMAN PELLEGRINO: Thank you very much.
I will point out that each of you as you do make your own
preferences known, it doesn't mean that you have had your last say
so we can come back. And only time will limit your participation.
PROF. LAWLER: My tendency is to be a follower in these
matters and just go along with what others suggest, but I will still
I agree with Robby that we should update the white paper on the
acquisition of pluripotent stem cells. And if you want to connect
that with the issue we faced yesterday of something like this: it
would be a disaster, disaster we are going through, for the country
to change its understanding of life and related issues in response
to a stage of science that will be very soon surpassed.
What the white paper has shown and recent studies have
shown is that eventually we won't — and eventually could be any
day now in a way — have to kill embryos to get pluripotent stem
cells. How this resolves itself is unclear. But that it will resolve
itself somehow I think is pretty clear.
In the same way, with respect to kidneys, the crisis or
alleged crisis with respect to kidneys depends upon a very specific
stage in science that, as Leon Kass pointed out, will be superseded
eventually. So it would be a disaster perhaps to have a market in
kidneys given that eventually we will have another and better way with
dealing with end-state renal disease.
With respect to the issues here, the ends and goals,
medicine, the issue there is something like this. Should we address
this directly, look right square in the eyes of the ends and goals of
medicine, or should we consider our present procedure of looking at it
indirectly through specific issues?
So many of the reports deal with the ends and goals of
medicine but in the context of organ transplantation and so forth. So
we're talking about freedom, talking about dignity, but not
abstracted from particular issues.
One Council member yesterday and quite well said, "We
don't want to speak too abstractly." By looking at the ends and
goals of medicine straight on, we might be accused of speaking too
abstractly." So I'm not sure about this.
I myself am interested in investigating nanotechnology;
first, because it's become so important; and, secondly, to tell the
truth because I know nothing about it. And so this would be like a
graduate education for me in an emerging issue that I am pretty murky
on right now.
With respect to eugenics, I think Robby was right. This is
a powerful issue. The change between the eugenics that caused the
Holocaust and the eugenics today is the science that caused the
Holocaust was simple baloney. The late Nineteenth Century eugenics was
simple baloney. The eugenics around the corner may actually work. And
that is the scary thing. So it might actually have a positive eugenics
plan that might actually produce results. And this is what is totally
unprecedented about it.
The citizens' personal responsibilities for health, I
agree with Floyd we have neglected this in certain ways. But it might
be a mistake there again to address this straight on but to include
this as a component of reports issued in other specific topics.
And I guess that's what I have to say for now.
CHAIRMAN PELLEGRINO: Thank you very much.
DR. HURLBUT: Maybe since I have some additions, maybe I
should come later. What do you think?
CHAIRMAN PELLEGRINO: You want the Fifth Amendment for the
DR. HURLBUT: What?
CHAIRMAN PELLEGRINO: You want the Fifth Amendment for the
DR. HURLBUT: I think maybe that's easier.
CHAIRMAN PELLEGRINO: Okay. Gil?
PROF. MEILAENDER: Well, I would make two general comments
and then a brief comment on the specifics. The first general comment
is that I think that we should think of whatever we turn toward as a
supplement to finishing the organ project.
We have worked on several tracks on many occasions over the
past four years. I think we can do it. The organ project is a very
rich one. We're well along. I mean, we're in position for the
staff to begin to take that stuff and turn it into the draft of a
report now. And I would hate to see us not complete what we have
already put a lot of work in on. So whatever we turn to in my mind is
an additional topic that supplements the finishing of that one.
The second thing I would say is — I think I said something
like this yesterday maybe, but to me the best topics for a body like
ours are ones that are not purely theoretical; that is to say, that may
at least result in some recommendations, some fairly focused
recommendations, of one sort or another but that aren't just
solving a practical question either, that, really, once you start to
work on them compel us to think about deeper issues that bioethics
raises about the nature of human life and the nature of the universe
So I always look for an issue or issues that, on the one
hand, there might be something specific to say about, but, on the other
hand, in order to get there and say that you'll just be forced to
think in richer ways. Lest we be too pedestrian along the way, I
don't see why we should bother to do that. There are plenty of
other people that will see to that.
So when I look at the sheet here — and, to be honest, I
realize that I can't even quite remember what my own rankings were
at the time. I wish I had made a copy of them or something so I could
But if I look at the things that more or less rose to the
top of the chart, I myself probably would incline in the direction of
the number 5, the genetic information and knowledge.
We have already talked — I mean, we are not starting from
scratch on that because we have done a few things that connect us with
that. We are actually going to be dealing with that in a second
session this morning. It has the character that I just described that,
on the one hand, there are some very specific questions that arise
that, you know, one might or might not make a recommendation about.
On the other hand, it raises some very deep questions that
the Council on Bioethics ought to think about in a way about human
life. So that it has that kind of dual quality that I think has
enriched our work over the four years.
And so whatever my original preferences may have been that
I can no longer remember, if I were looking at the ones that seemed to
rise highest, that is the one that stands out to me.
It would I think — Peter — I guess Peter is right. Just
as the organ project does, it would force you to think a little about
things like the ends and goal in medicine, even about citizens'
personal responsibility and so forth, though it would get at those
questions, not for their own sake but through a somewhat more narrow
prism. And so that is where I turn.
I would be happy to have us try to, as it were, update the
white paper also. And that I think would not have to be a major
undertaking. We would need as few sessions that simply brought us up
to speed on it in ways. And then we would have to have a session
deciding what having been brought up to speed, if anything, we wanted
But I don't think it would be a major output of
energy. So that would be fine, too, as far as I'm concerned. But
that is sort of the direction that I would see us heading.
CHAIRMAN PELLEGRINO: Thank you very much, Gil.
DR. BLOOM: Well, I am very happy with the list as it
came out. I would say that these are the issues that were in my mind
when I was interviewed to ask whether I could join this Council. And
so I think how we carve it up is the critical issue.
Genetics and health care seem to me to be the major problem
that our nation is facing unaware that there is a problem. Most people
are healthy. And so they don't understand that the capacity of our
system is so strained that any major even modest disaster could
compromise the health of the nation.
I think unless we start to train our new physicians to be
aware of the genetic information that their patients bring to them and
to be able to use that in a way to improve their health in the long
term, we are pretending that our system is better than it is. And to
me that is the major ethical issue that we face.
I should have said yesterday that I support Gil's
proposal that we finish off the organ transplant, even though to me
that was not as pressing an idea as some of these that are on the
list. But because we have invested so much in it and we have so many
good papers to inform others, certainly I was unaware of many of these
issues. And I think that we would do a service to the country by
making those views public.
How we carve this up I think is a major step because we
need to be able to take on something where we can have an impact,
rather than just talk about it. But I think these are the major
CHAIRMAN PELLEGRINO: Thank you very much, Dr. Bloom.
DR. CARSON: I agree that we need to spend a little more
time updating the paper on pluripotent cells. I think that is a very
important contribution we could make.
Now that we have an esteemed economist on the Council, you
know, the ideal of looking at resources in health care I think is very
important, recognizing that there are 45 million people in this country
who have no health care insurance, which is a travesty. And I think
there are ways that that can be addressed with the amount of money that
is currently in the system. And I don't think anybody has really
been taking very serious looks at it. They just complain about it.
Also, the whole concept of health care reform, which
obviously is discussed at every national election, but nothing ever
gets done about it. I wonder if perhaps this body might be able to
make some real recommendations because it is such an important issue
for all of us, maybe even looking at a governmental role and taking
care of such things as catastrophic health care, which completely skew
the system and allow for all kinds of inequities to occur. And
it's not been looked at in any rational fashion.
So I think if we concentrated some energy on those areas,
we could make a major contribution.
CHAIRMAN PELLEGRINO: Thank you very much, Dr. Carson.
Thank the speakers thus far for being very much to the point and very
much in the direction I was hoping you would take. That is not to say
a particular subject but to give you your own views on what you thought
were critical for us to be doing.
I would like to go now to Professor Gómez-Lobo. Thank you.
DR. GÓMEZ-LOBO: I find myself in general agreement with
many of the proposals that have been expressed. First of all, I think
it's wise to finish up the organ transplant project. We have
worked on that. And I think there is so much that is real clear
information that should be made public.
However, I do think that we have to come down one way or
the other on the question of market for organs. I mean, I think we
would be remiss if we don't do that. I think we have to have a
position of that whatever it is or more than one position because I
think that's what many people are going to be expecting from us.
In this case, it would be the odd thing of a moral judgment
on an institution which is supposed not to be moral at all, but let it
Second, I strongly favor the idea of updating the
alternative sources document. That has to be done. It is a pressing
issue today. It's almost every day in the press. We all know
about the Nature article a few days ago. And it's important for
people to know that we had thought about some of the problems long ago
and that the science is moving forward.
I see a certain urgency there. I would even say in terms
of timing, maybe we should let it run ahead of the final organ
Then with regard to new material, I tend to see certain
things as connected. For instance, the eugenics question to me seems
very important. I think it's of vital importance to call to mind
what is being done and certain kinds of procedures and that they are
eugenic in nature.
Interestingly enough, I see it connected to the question of
under-treatment of pain. And both I see as subsets of the question of
the ends and goals of medicine; for instance, in the case of eugenics, to
make clear that it cannot be a goal of medicine to eliminate the weak
and just favor the strong or it cannot be a goal of medicine to leave,
say, suffering and pain untreated. So my tendency would be to
incorporate those two topics under the ends and goals.
And, finally, it seems to me that what Ben has mentioned is
extremely important as a public issue: the question of the dismal
health care resources for millions of Americans. I mean, that just
I would say even if we cannot provide something like a
technical or a political solution, I mean, how do you get health care
insurance for all of these people? Even if we couldn't get to that
point, just pressing the issue seems to me extremely important. Now,
if we could make some concrete recommendation, that would be great, but
just bringing the issue to the floor seems to me important.
CHAIRMAN PELLEGRINO: Thank you very, very much.
PROF. SCHNEIDER: Yes. I agree with the last two people
that there probably is no single thing that you could do that would
make more difference to Americans' health and well-being in any way
that we're connected with more than looking at this problem of the
42-45 million people who are uninsured.
I just spent several days in North Carolina interviewing
people who have no way of paying for their health insurance. And these
were people who had virtually no education. They had no way of even
using the resources that were supposed to be made available to them
because they didn't have the sophistication to call on those
They were people who had no jobs because they were so ill.
And they were multiply ill and never taking care of themselves, not
because of a moral failing but because they simply weren't being
given the equipment to do that.
And since one of my criteria for selecting topics is doing
good in the world in a reasonably perceptible way, I would be very
enthusiastic about that topic.
Some of the other topics are probably more important than I
realize. And I am glad to learn how.
CHAIRMAN PELLEGRINO: Thank you very much.
DR. FOSTER: Also the most important thing I think we
can do has to do with the economics of health care. Ben and I had
lunch yesterday. And we already solved the problem about what needs to
DR. FOSTER: But we think that that would be number
one. Also, my number two thing, I think we do need to upgrade the
discussion, including the ethical issues of stem cell work that we have
There are huge changes coming along. For example, just
yesterday two of these things that I haven't even had a chance to
read yet, particularly the three papers in Nature, yesterday as all of
you — if you read the Times yesterday, you saw that this famous tumor
suppressor gene, which is called P16 INC 4A, has dual effects that are
very interesting. Its protein is made in huge amounts as we age.
And the teleological reason that these three labs that put
this together and did not compete with each other on it — they all
found exactly the same thing — think that because cancer increases as
aging, that the universe has made it that one would try to keep you
from getting cancer by producing this — it's not the most famous
of the tumor suppressor genes, but it will do it.
But simultaneously it causes a disappearance of adult stem
cells. So that you have this Catch-22. I mean, you make this
protein. And it will help you escape cancer. But at the same time, it
probably means that all the concerns about adult stem cells are very
real. And we have known for a long time that bone marrow transplants
in older people don't work as well.
And so to readdress the issue of embryonic stem cells, as
opposed to adult stem cells, would be a very important issue. So I
think that we need to look at that.
We came down on the view that biopsying an eight-cell
morulae for pre-implantation genetics was fine for genetics but
probably was not worth the risk of doing it to get stem cells and so
forth. So that would be my second view.
The third thing that Floyd was talking about that is in the
new Science, which I haven't seen, is from the Vogelstein lab at
Johns Hopkins. You remember, to put this in perspective, they worked
out the genetics of colon cancer. And it came out that there were
probably eight or nine genetic changes that lead to you.
Now, this new paper apparently says that when they look at
the — they use examination of the whole genome — that cancer is
involved with two or three hundred genes in every cancer. And they
found only five genes that would be crossed from one version of a colon
cancer to the next.
So the idea of being able to attack specific genetic
changes in the treatment of cancer, I mean, that's a remarkable
thing when you think there are maybe 25,000 genes or something like
that and 200 or 300 of them give you a fingerprint of a single cancer
in you or me and that if — let's say Gil and I both had a colon
cancer and you did the genomic evaluation. We would maybe share only
five genes involved in that. So these are — I mean, the tremendous
advance in the greatness of science is that it gives you new
information to do that.
So, in summary, I am in favor, first of all, to say
something about what I think is — the word I think you used was a
"travesty" of health care that we're the last or next to
last in all the developed countries in the world, the richest country
in the world. And we have this shameful, ethically shameful, fact
about the care.
And, secondly, I would like to upgrade the ethics of stem
cells and look at those things again; and, thirdly, the whole problem
of the genomics for the future of health.
CHAIRMAN PELLEGRINO: Thank you very much.
DR. McHUGH: I agree with much of what has been said, of
course, here, but I want to remind the group that the method that we
have used as a successful body, not only in the reports that we have
taken but also for each of us as members after the meetings, we have
become quite a well-informed body of people in relationship to
contemporary science. And much of our discussions and much of our
learning and much of even our disagreements have come and have been
based upon the growth of knowledge in this committee of contemporary
I want to encourage whatever method, whatever thing we do
from this point on, since we have a relatively short life perhaps ahead
of us, that we should continue this.
And so I am, first of all, very much in favor of what Robby
and Dan and others have said about the follow-up and the contemporary
discoveries related to stem cells to build up what we have done.
We can again, as we did before, bring in the world's
experts. It's wonderful. They look forward to coming and talking
to us and explaining the details, much as Dan has just done in
relationship to Bert Vogelstein's new work. I would like the
opportunity again to see whatever ethical positions that I have that
they have a certain scientific foundation and derive from real life.
I am concerned that if we go out and try to solve our big
problems in our nation, all of us I think agree that the health problem
of lack of insurance is a big one, but I'm not sure that we as a
group will do anything more than add to the political process in one
way or another, joining the red states or the blue states in
relationship to that. And I would rather leave that to others.
And then, finally, in relationship to the contemporary
science, I believe that the genetic world and the world of genetics as
it's emerging permit us to get the best scientists here. We are
very lucky to have Nancy here today and to see the direction things go
Let me just make a point. Bert's work has been
emphasized here today, but George Uhl just a few weeks ago was talking
about the genes in relationship to alcoholism and other addictive
substances in which he said, you know, "Look, now there are
32" or "52." I can't remember exactly what George
sid the number was, but it was clear that there are, again, a huge
number of genes that come into play in relationship to behavior.
And the place of genetics, you know, people have been talking about
alcoholism is a disease and there is a gene for it or there is a
gay gene or an anorexia gene or other kinds. Well, there's
obviously that this is not true. And we should perhaps have some
of these behavioral geneticists come and talk to us about just the
place of genes in relationship to behavior given that behavior is
the essence of our ethical dilemmas often.
So, in essence, what I would like to say is I suppose what
has been coming. I would like in this list to emphasize the genetic
information and knowledge as a place where we would get good traction
in relationship, really, to many of the other things that come up.
CHAIRMAN PELLEGRINO: Thank you very much, Paul.
DR. EBERSTADT: I would mention three items. I would
second Dr. McHugh's vote for genetic information and knowledge, but
I would say that an exploration of genetic information and knowledge I
think naturally dovetails with Robby's questions about eugenics
because the technological innovations in this area I think will
naturally raise questions about eugenic interventions or, conversely,
if we were to explore the question of eugenics, I think that would
naturally lead us to the question of genetic information and
knowledge. It seems to me those two questions may be somewhat wed.
A second item of interest to me at least is the question of
citizens' personal responsibilities for health. Now, this fails
Paul's test of new scientific knowledge. I don't think,
however, it fails entirely our mission of ethical reasoning.
We do know that personal behavior figures very strongly in
health outcomes in the United States. We do know that there is an
enormous goal for preventive interventions that's currently not
being made use of. We know that what we might call irresponsible
personal behavior imposes an enormous mortality burden in the
humanitarian sense on our society and also an enormous economic burden
on our society.
How do we think about this question without ending up as a
nanny state and as health police and as all of the rest? Where is the
line that we can tread in there? I mean, I would think that our
Council members might be able to illuminate this question for the
public very profitably.
Finally, I would get back to some of the things that have
been said about the still unfinished question of organ donation and
marketization. From my own perspective, I think we could explore a
little bit more in this area the whole relationship between economic
reasoning and the organ shortage.
I don't happen to believe the organ shortage is a
crisis. My own perspective is that it's a problem. For many
families, it is a tragedy. But until there is the technological fix
that Peter described, it looks as if it's going to be a growing
problem. And it coincides with the relentless march in our society of
market-like thinking. These two things are conflating.
It may seem fanciful at this point to imagine that there
will be an organ market in the United States or in the world, but this
is not a completely fanciful possibility. And, again, I think that our
Council members are positioned at this point to examine and discuss and
opine upon this possibility in a way that I do not see other groups
So I think there could be great comparative advantage, a
great contribution to the public. It will be a public service to have
the input from our group on this evolving question.
CHAIRMAN PELLEGRINO: Thank you very much.
PROF. GEORGE: Thanks. Two points. First, I remembered
the title of Leon's magnificent and profoundly disturbing talk at
the Holocaust Museum.
CHAIRMAN PELLEGRINO: Yes.
PROF. GEORGE: The title is "A More Perfect
And then the second point was I have a question for Dan. I
don't think that the Council has endorsed cell biopsy for purposes
of pre-implantation genetic diagnosis. Have we? I thought your
comment suggested that we had. And I don't remember that we did.
Did we do that?
DR. FOSTER: I didn't mean to imply that.
PROF. GEORGE: Oh, okay.
DR. FOSTER: I simply said that that methodology was
available and it had been done. You know, the guy in Chicago had
already done this. This new thing, they don't reference those two
What we did say is that we thought that under any
circumstance that that seemed too risky for us. That was all —
PROF. GEORGE: Yes. So we didn't really say anything
about it one way or another, but we did address the cell biopsy
question in relation to attracting —
DR. FOSTER: Just in terms of the methodology that was
already going on there.
PROF. GEORGE: Yes.
CHAIRMAN PELLEGRINO: Thank you.
Dr. Hurlbut, we have not heard from you as yet.
DR. HURLBUT: In reflecting on what we should do in
terms of topics, I would like to just suggest that, at some point at
least, we talk a little bit more broadly about the mandate of the
Council because I feel like, in retrospect, some of what we were
mandated to do we haven't done.
And one of those dimensions was to engage and educate the
public. I just think it's worth at least having a discussion to
see if there's a way we can get our reports out there a little
better and our engagement and interaction with the American public
I remember when the Canadian person came and talked to us
about how they engaged the stem cell issue. They had public forums
specifically around the country. I know we're all very busy, but I
also feel like there is some great value in at least discussing those
kinds of possibilities. So that's something I just wanted to add
to the mix at some point in our discussions.
I also feel like there's an awful lot of
misrepresentation, misunderstanding in the public arena, including
through the media, of some of what our Council has said and done and
also just of the general issues themselves. It's very obvious from
the last week's coverage of the stem cell announcement that there
is a lot of misunderstanding in what the Council had said or inadequate
assimilation of it.
Before I say a couple of subjects that I think we should
also address, I want to make a plea for one of them that only got a
four. And that is international collaboration.
Now, I don't think we should go into that extremely
complicated issue of the cross-cultural meaning of bioethics in a deep
and serious way. That could consume an entire lifetime of a Council.
But I do think there are a couple of valences that are
really important for us to at least acknowledge and perhaps make some
preliminary statement on. I have traveled quite a bit in my adult
life. I have been in half the countries of the world. And I have
traveled a lot in the last four years while on the Council. I'm
very aware of how different the dialogue is in different countries.
For example, in the organ transplantation field, I was in
Japan a few years ago and took a three-day trip with a physician from
Tokyo who is a hepatologist, is a very profound thinker on the issues
of transplantation. And he and I had a long-running conversation on
the different views of the body and why cadaveric transplantation is
not done primarily. They have only done something like 18 cadaveric
kidney transplants in Japan in the whole history of the country.
And this is worth at least acknowledging how foundational
the concepts of the body, the perspectives on broader metaphysical
questions play into this. It's an element our report ought to
include, an acknowledgement at least.
But what worries me more than trying to solve all the
different cultural variations on these kinds of themes is the practical
issue that I think we can all see coming: first, medical tourism; and,
second, what I have been calling the outsourcing of ethics.
Clearly we have got a dilemma coming with the globalization
of rapid transmission knowledge, the disbursement of research centers,
the collaborations between both commercial and university-based
research programs in the United States and those in other nations.
We should at least reflect on the potential dilemmas of
getting things done elsewhere that we in our nation find unacceptable
to do. And I think we should acknowledge that there are commercial
values and scientific advantages in terms of competition to be gained
by violating ethical standards.
I mean, you could test drugs more quickly if you didn't
have to worry about human subjects concerns. You could get organs more
readily if you didn't worry about some dimensions of human
dignity. Well, it is worth touching on.
But what I really wanted to say is this. When I look out
— I think you can see this — any day when you pick up Science
magazine, read through it, you can see that the two major fields of
scientific advance right now, all building on the foundations of a
range of advances across biology but especially genetics, the two major
fields of advance right now, and the two major fields of challenging
ethical questions are developmental biology and neurobiology. And
it's notable that none of our 14 topics focused in very strongly on
either of those.
So I have been trying to formulate in my mind how we would
approach those very broad and difficult subjects, but first let me make
a plea for why we need to.
Nancy and I have been involved in — this is Nancy Wexler I
am referring to here, our next speaker — have been involved in
thinking about the issues of genetics for a long, long time. And I
think we are probably both aware — I will speak for you a little,
Nancy, and you can say not or yes, but I think we are both aware that
had people talked about some of these issues before they became
practical issues, it would have been helpful. And we tried.
But we have a unique opportunity now with regard to some of
the issues of development biology and neurobiology to anticipate the
ethical questions, to define the terms and the concepts of the
conversation, and to set a frame for the future. Even if we can't
precisely adjudicate some of the difficult issues, we could help frame
them and make a big difference in the way they play out.
Just let me give as an example two specifics that I would
like the Council to take up. I admit that my case in making these
isn't fully formed and so, therefore, a little inarticulate. So I
would actually like to have a chance to prove, maybe over the next few
months, to the Council members why both of these issues are extremely
important and we shouldn't dismiss them for their abstractness.
They might be summarized as an inquiry into what you might
call the boundaries of humanity issues in developmental biology. Most
specifically, what is it that defines life, organism, human? Let's
just say those categories.
We obviously are going to have really valuable tools in
biological inquiry if we can mix species cells together, chimeras.
And, yet, obviously there are great ethical challenges involved in
that. I think we have already done some on that, and I think it would
be very valuable for us to continue. But that is just a subset of a
larger category defining what the boundaries of our moral concern
This has both basic principled concerns and, as I said
yesterday, sort of semiotics. What are the signs and symbols of
humanity? It may be that even just the appearance of humanity is
enough, even if we don't think something is operating in a humanly
conscious way. Therefore, we might not want to create a sheep with a
human face or with hands if that were possible.
So that borders on the issue we discussed yesterday a
little bit of the definition of organism in relationship to organ
transplantation and definition of death.
There is a whole industry emerging, as I said yesterday, of
production of human parts apart from the human normal developmental
process. And somebody should address some of those issues.
The second thing I think is very important — and here I
probably can't make a very compelling case, but I think there is a
compelling case to be made. And that is the subject of a
neurobiologically related subject. It could perhaps be covered under
the ends and goals of medicine and maybe to some degree under genetic
information and knowledge, but it's the subject of what you might
call desire and disproportion.
In its most extreme form, it's not a subject of only
specific advances in biology. It's known as the subject of
addiction. But addictive behaviors in the broadest sense, broadly
construed, are becoming an obvious problem in our civilization.
And here let me just outline briefly what I am concerned
about. I think that in the natural environment of our evolution or
creation, whatever you want to frame it, desires have operated within
natural constraints. And, therefore, they have been stronger than what
one might in the modern world consider necessary in order to get the
Hunger is a very compelling drive. So is sexual desire.
Fear is very powerful. Now as we gain control and the ability to kind
of manage our pains and pleasures or to bypass the natural constraints,
we're looking at some very troubling potential dimensions.
And on a practical level, it's obvious that the
biological revolution in a way, the first dramatic and unnoted
milestone was perhaps the contraceptive pill, which separated off
procreation from the unitive and pleasureful act of sexual intercourse.
And without passing any kind of moral judgment on
contraception itself, it certainly raised important social questions
and personal questions and challenging issues because the technology
essentially disconnected and bypassed a natural connection in life.
We're going to do this on so many levels. Already you
can see that the abundance of food is creating a challenge. Our
society has a great many people suffering from obesity. Our society
has learned to promote and to commercialize dimensions of sort of
managed experience, like the stimulation of gambling high or even
commercialized recreation that stimulates the release of adrenaline.
And we should face the fact that we have short-circuited
the connection between sexual stimulation and actual human encounter
through internet pornography.
Those are perhaps a little beyond our purview, but there
are some very important connections with advancing biotechnology and
the potential to engage in and manage human pains and human pleasures.
There are also some very real social issues emerging. You
probably know there is now a movement to sue the fast food industry on
the same grounds as the tobacco industry was sued. And somebody needs
to make some inquiry from a deep ethical perspective onto what the
justification for such a perspective of how we should think about this
As you probably all know, there are quite a lot of
children's foods that have caffeine in them. And I think there are
some moral issues there.
And then one of the larger issues involved in this field of
inquiry would be some kind of comment on the social dimensions of
engaging in bypassing the constraints on impulsivity; in other words,
what traditionally has been called indulgence, self-indulgence, of
people. And this leads, indulgence always leads, to injustice.
And in a world where the U.N. estimates that 30,000 kids a
day on average die from starvation and diseases related to
malnutrition, the over-engagement and over-stimulation of desire and
its disproportions in the conduct of both individual and collective
life has I think a compelling case to be at least clarified and brought
out to help our society be aware that primary human desires are now
being managed in such a way that might be disruptive of human life.
CHAIRMAN PELLEGRINO: Thank you very much, Bill.
Dr. Lawler, did you want to make a comment?
PROF. LAWLER: I am not going to address any of that,
although I think many of those concerns could be folded into some of
the topics we have here.
With respect to the stem cells, let me just emphasize
something that emerged. Robby's emphasis is on the innovations and
acquisition of stem cells. Paul's and Dan's emphasis is on
innovations in the use of stem cells. I don't see any reason why
we couldn't bring those together in another white paper.
With respect to the issue of taking a position against
market forces, the use of the market, in acquiring organs, I'm in
favor of doing this, but I'm also in favor of giving the strongest
possible case for the market to understand in a certain way, as Nick
pointed out, how compelling it is and why we have to take a stand
against it. It's precisely because the case for it is so
non-trivial. I mean, there is actually something there. We have to
take a stand against it.
And obviously it emerged that there is a connection
between, number five, genetics and, number nine, eugenics. And they
could easily be handled at the same time.
Obviously innovations and acquiring genetic information
have eugenic implications. And a lot of our wilder thoughts about
eugenics depend upon, as Paul said, really overestimating how important
genes are for human behavior.
In general, with respect to the health care, the economic
side of health care, I was changing my mind every 30 seconds here
concerning whether we should address this.
On the one hand, now that we have an economist, maybe we
should. To add to that some health care professionals throughout the
country commented to me on our care-giving report, "There was a
lot of beef there but no talk about money." I mean, they said the
whole report distracted from the economic dimension of the issue.
So it's not just that a large number of Americans
don't have insurance. Even the social safety net we have now is
going to fall victim to harsh demographic realities, as we have an
aging and frail population. How exactly are we going to pay for their
care? We sort of abstracted from that in our report.
So there is an argument that we should address this that
came from some of our M.D.'s and then an argument that we
shouldn't address it that came from another one. The argument
against it would be it's too big technically and too dividing
politically. We would have to be on the red side or the blue side.
But there is an argument that we could just lay out the
fact that we're not going to pay for it. We have no way of paying
for what we need to be able to pay for. And I think that is sort of a
nonpartisan part. Even if you have a minimalist safety net, it's
unclear how we're going to pay for it in the future.
That's all I have to say.
CHAIRMAN PELLEGRINO: Thank you very much, Dr. Lawler.
I want to congratulate the Council members again for very,
very promptly and concisely giving your thoughts on what are the agenda
items of importance. I think you have a fair return.
We have asked you for your comments. And I think Dan and I
will just give you ours very, very quickly. Just to add to them, I, in
particular, as a member of the Council, ought to at least express my
I think you know, I hope, from my behavior since I have
taken over as Chairman, that I do not use this position to impose my
views. So, therefore, as I express them, they will be thrown into the
pot with all of the others. And I want to make that very, very clear.
The other point is that after we have expressed our views,
I would like to have more discussion on what you want to go into in
detail. Peter had a comment. Others have comments of others.
And then, finally, I'm sure you know we don't
necessarily decide such things by plebiscite but, rather, looking at
the strength of the arguments pro and con for these particular
I will ask Dan to give you his preferences or his thoughts
and then mine very, very quickly. And then we will go back to
discussion because you have been so prompt and so responsive that we
have the time for further discussion.
DR. DAVIS: Let me talk about organ transplantation first.
To address some of the concerns that Professor Schneider raised
yesterday, one of the things that the staff has been engaged in doing
is talking with those divisions of the federal government that are
engaged in this issue, the Institute of Medicine, the various
societies, the American Society of Transplantation, et cetera, and
attempting to figure out where is their play with regard to proposed
We're still engaged in this activity. We're going
to meet on Monday with the Division of Transplantation at the Health
Resources and Services Administration, which staffs the advisory
committee to the Secretary of HHS on organ transplantation.
I think based on the survey thus far, there is something
very important for this Council to say. And it does deal with the
market issue for the most part. There is an expectation, I think,
within the transplant community that we are going to issue a report on
this issue because we can all tell you we are being lobbied by both
There's not a week that goes by that I do not hear from Ben
Hippen, Arthur Matas, who are very vocal proponents of markets,
also from Frank Delmonico, from whom we have heard. So I think
there is an expectation that the Council is going to weigh in on
this issue, that it's going to use its bully pulpit. So I think
if we say nothing, we will fail those expectations.
So I am glad to hear that there is a clear sentiment for
doing a report on organ transplantation. I think we need to capitalize
on the investment that we have already made on the topic.
Genetics. We have been engaged in this conversation about
newborn screening. And I think that the conversation by its very
nature has pushed us beyond that particular point in the life cycle.
So I think, although we might consider doing something
along the lines of a white paper on newborn screening, there is an
immediate issue on the table and it's the proposal for a uniform
approach across the 50 states. I think we need to go beyond that. And
so I am also happy to hear that there is some sentiment in that favor.
And I agree with Floyd. I think that if we ignore this
issue, we should be taken to task for that. And I hope that Dr. Wexler
when she gives us her remarks can help us perhaps begin to understand
what that broader inquiry might look like.
Obviously there is clear interest in updating the white
paper. And so I think you should consider that task done. We'll
walk away from here and begin to figure out how we wrap our heads
So those would be my responses, at least at the time.
CHAIRMAN PELLEGRINO: Thank you very much, Dan. I will be
as brief as I can as well.
First, I very much am in agreement with Paul McHugh's
statement — and I think every member of the group shares that — of
securing the scientific base of whatever we do. Over and over again I
have to in my debates and discussions point out that poor science makes
poor ethics, not that science determines ethics, but the scientific
foundations, the factual foundation is absolutely essential.
So I think a continuation of doing what we have been doing,
perhaps even more in depth, on the scientific foundations of the
questions we're dealing with is critical. And I think that is
uppermost, at least in my mind.
With respect to specific topics, I think we have invested a
lot in transplantation. And I think probably we should say something
about that. My own inclination is to take selected topics. This topic
has been discussed by other groups, other reports. And I think we
should take the difficult ones that have not been addressed, one of
them being the question of paying for organs, et cetera, et cetera, but
not the only thing. But surely I think we should address that from the
ethical point of view as well as the economic.
The third issue that is very much in my mind as well is the
question of genetics. And I'm not going to speak of a particular
aspect of it. It's so broad. But we need to focus on it.
Particularly I think someone used the term — I believe it
was my colleague on the left — "genetic medicine," the
question of when it comes to the bedside. As a clinician, I am always
interested in the bedside and the gurney. Some people find that rather
stressing, but that is where my initial concerns about ethics lie. And
so I think that particular topic deserves consideration.
I very strongly believe that we need to bring up to date
the stem cell situation, again, here because of the first point that I
made, that the science is changing so rapidly. And we are always in
our ethics trying to catch up with science, kind of like, as I pointed
out once or twice, those of you remember the movie and the story of
Pinocchio, Jiminy Cricket running after Pinocchio and always trying to
catch him. And I think that ethics looks kind of like Pinocchio and
never quite gets there.
So I think it is extremely important that we do address
that topic because it is very much in the public mind, and there's
no question that they will be looking for something from us, I believe.
And the way we have done it before I very much support the
statements that have been made about the techniques we have followed,
the idea of laying out the issues. I think that is the most important
function we can make. When we can come to an agreement on a policy
recommendation, we ought to do so but granting the disparate nature of
this group, the different perspectives and so on, we can't always
But we do a great service in the hopes that the
policy-makers will, in fact, read what we have put out and use it as a
starting point for their discussions, rather than the usual emotiveness
that runs through all of the discussions.
I am very much disposed to an examination at the health
care reform. I don't use that terminology. My concern, at least,
— we're not necessarily going to follow up because it's my
concern — to establish a moral foundation of a good society for the
health of the system. And that is a topic in its own.
And I think we could not get into at that point the
economics, the mechanics, or any of those aspects. We need to first
answer the question, does a good society owe something to its sick
members and its disabled members? And what is the moral foundation for
that? That would be my preferred approach.
I think on the international cooperation, Bill, that you
brought up, you might want to know that I am a member of the UNESCO —
the only American on it, UNESCO International Bioethics Committee. And
I was a member of the drafting group that put out the universal
declaration, which has its ups and downs and so on, but for a
discussion at the international level, I think it's probably a
pretty good document, particularly for those countries that don't
have well-developed programs in bioethics or an interest in it, which
was one of the foci.
Also, Dan has been associated with a group that met in Strasbourg.
And he has connections there. So both of us at least are providing
information to these international groups on where our Council is,
not our opinions, I assure you, but what we have published and where
the thinking is at the present moment. And they have found it most
They haven't had that in the past. And they have been very,
very interested in the fact that we are willing to share. And,
as a matter of fact, I was overwhelmed by the reception I received
as the United States representative, particularly in this world
when everybody is feeling a little bit negative about the United
States outside our own borders and sometimes inside our borders.
So I think that is an important issue, but I don't
think it would involve the whole Council except to the extent that you
want to tell us what to tell those people abroad but keeping them going
because I think ultimately — and I think, Bill, you made a point —
there is no way we can keep these issues from being global issues. The
boundaries do not limit the implications of the ethical advances and
the ethical problems that biotechnology is producing.
The other subjects are important. I don't mean to
depreciate them in any way, but since I have put you on the spot, I put
myself on the spot. And these are my own inclinations.
The last one that I am very, very much interested in as
well personally, as Robby pointed out, of course, is the state of the
health professions. And I think the transformation of the offices that
has been occurring is not necessary in the interest of patients.
And, after all, going back once again, — I don't
defend myself. I'll assert it. Every policy we make, every
decision we make, ultimately has an effect on someone on the gurney or
someone in the bed if it's health care we're talking about.
And, therefore, I am very concerned about that translation.
And, finally, with reference to the point that you made,
Robby, I am concerned about occult genetics, not about the overt, which
is still unpopular but the occult genetics that occur whenever you
begin to get into genetic questions and the selection and how you make
it and who gets the model of the acceptable.
That will tie in with our coming report that Adam Schulman is handling
on dignity, the human person, where there will be a variety of difference
perceptions. Nonetheless, we will be making our contribution to
looking at that complex concept because I think, as we said in the
UNESCO document and as the U.N. said 50 years ago, the dignity of
the human person gets to be the foundation for much of what we decide
in the ethical realm, end of speech.
Now, we have time left. And we open it cone again to the
members to add to, amend, expand on their comments, limited only by the
fact that have a break at 10:00 o'clock and time to get to Dr.
Wexler at 10:15.
PROF. SCHNEIDER: I think I am obliged to say a couple of
things. And since the time really is limited, let me just mention a
couple of the additional topics that I had in mind.
I was under the impression that everybody was supposed to
come up with several of them. And so I did. And I discovered that I
was rate-breaker and apologized.
Now that I have put myself out that far and committed
myself, Dan let me go ahead and name a couple of topics. The first one
partly grows out of an experience I had on the hospital a number of
I was visiting. A patient was transferred in from another
hospital, actively dying of cancer, with pain wholly untreated. He had
ripped out the various tubes that were in him. Blood was spilling
everyplace and staining the sheets. And he was writhing on the gurney
and shouting over and over and over again, "Don't let your
children die in pain like this."
I was unable to visit a hospital professionally for six
months after that because I found this experience so wrenching. And it
made me feel obliged to try to bring to the attention of anybody who
would listen thee facts that I have discovered on investigation, which
are hardly secret but not well-known.
Those facts are that pain is very dramatically
under-treated in American hospitals and by American doctors, very
dramatically under-treated. Let me very briefly give you a couple of
samples of data.
The SUPPORT study, which was quite elaborate and careful,
found that half of the very seriously ill patients with whom they did
their research, were complaining of pain. One-sixth of the patients
were in moderately severe pain, at least half of the time, and/or were
in extremely severe pain at some times.
There is another estimate that patients in nursing homes
are suffering from unrelieved pain, much of which is persistent for at
least 80 percent of the people who are in nursing homes.
If it were scientifically impossible to treat these people,
it would be a misfortune. The fact is that almost all of this pain
that we're talking about is very much treatable.
One of the tantalizing things is that this is a solvable
problem. Patients at the worst hospitals dealing with pain suffer pain
75 percent more than those patients at the best hospitals.
Now, this isn't to say that is an early problem because
there are an awful lot reasons why pain is untreated, starting with
problems in medical education. We can always attribute our problems to
medical education or whatever you are interested in.
Doctors and nurses are very dramatically under-educated,
not just in medical schools but in their own work with patients. There
is a complicated and important relationship between our drug policies
and our pain policies. And those cut in many different ways.
There are ethical questions about the willingness of many
doctors to decline to give their patients adequate pain treatment
because they say they are afraid of a legal response, a legal response
which in statistical fact is almost impossible.
And even if it were a much more serious threat, it seems to
me it is a real ethical questions that doctors face about saying,
"I'm going to let my patient suffer because I feel some kind
of legal response."
This is also an issue where the law is at a formative
stage. There are beginning to be tort suits in which physicians in
nursing homes are being sued and in two cases losing cases. One of the
cases, for example, was a nursing home.
The physician had ordered a quite adequate pain treatment
for the patient. The nurse in the nursing home decided the patient was
likely to become addicted. And the nurse, therefore, refused to
provide the medication. And the nursing home did nothing about it.
That was a case in which there was a very considerable damage award.
In addition, of course, issues like physician-assisted
suicide are in no small part driven by the fear of patients that they
will die in pain, the very realistic and reasonable fear of patients
that they will die in pain.
So this is an important, not simple but workable problem in
ethics that would profit by being understood as an actual issue by
Americans as I think most Americans do not realize that it is an issue,
but repeatedly when I tell people about it, they have a story to
illustrate the case.
It is a problem that can be solved, but it isn't an
easy problem, which if solved would make a big difference in the lives
of millions and millions of people.
The other thing that I should mention is informed consent.
And it must be hard to believe that anybody wants to say anything more
about informed consent. It is certainly an issue that has been beaten
to death. But I should tell you that it is also now an issue that
somebody needs to speak about honestly because the sorry fact is that
we know now beyond peradventure that informing consent in anything like
the forms in which it was intended is a failure. It does not work.
Patients do not get the information that they need, do not get in the
sense of actually getting into their minds the information they need
for making decisions.
Let me give you an example from a study that a colleague of
mine named Angela Fagelin is about to publish. She took one of the
classic issues in informed consent, which is treatment for breast
cancer. And she found that fewer than half of the patients knew that
the chance of survival after 5 years were the same for mastectomy and
breast-conserving surgery with radiation and that only 19 percent knew
that recurrence rates for the 2 treatments are different. If you have
only 19 percent of the people knowing a fact as basic as that, you have
people who do not understand the decisions they are asked to make.
This study is not a sport. It's not a freak, as she
says. Other analyses over many years in a considerable number of
studies have reached similar conclusions. I have read, I think,
probably now hundreds of these studies. They are all for the same
effect: Failure, failure.
Indeed, we know that in other areas, where the solution to
a social problem is to try to give information to people in an unequal
power relationship so that they will make good decisions, that
everywhere that is tried, that fails.
The classic example for you is the Miranda rule.
You're worried about the disproportionate power that police have
over suspects so that you say to the police, "Give the suspect the
information they need to make a good decision."
I have heard the Miranda rule described as the most
ignored, commonly heard warning in American life outside of what you
read on cigarette packages.
We knew two things. We know that, no matter how hard
experimenters have tried to communicate information successfully, they
have failed. We also know — this is the Braddock study — that in
only nine percent of the hundreds, if not thousands, of interactions
between doctors and patients that they listened to, that in only nine
percent of those cases given for making a decision.
Now, there are a lot of reasons why this doesn't work.
One of the reasons this doesn't work is because people don't
listen. And one of the interesting things that one encounters on
trying to probe more deeply into the transplantation question, as I
have been doing, is that when prospective donors are told about the
possibility of donating, they very commonly decide instantly to donate
or not to donate.
They decide before they have heard any of this information
that we pour upon them. And once they have decided, they are like all
of us. And they interpret every other datum they get as confirming the
wise decision they have already made.
Now, if informed consent were not the solution to almost
everything, it wouldn't matter that informed consent doesn't
work. But, of course, informed consent is the basis for our definition
of how doctors and patients ought to deal with each other.
Currently there is a lot of writing that talks about the
doctor-patient relationship and medical decisions in terms of what is
now called shared decision-making. What that means depends on who you
are reading, but it, too, is essentially based on ideas about informed
Human subject research is a very large problem, a very
large part of which is solved by trying to give research subjects
information. And I suspect that all of you have heard and even seen
the 25-page consent forms that IRBs now feel it wise to give to
patients. I don't know if you have ever tried giving such a form
to a patient. The patient or the subject will not read a two-page
form. And there is an interesting study of the forms proposed by IRBs
themselves that suggest that they can only be read by people with a
college education, which does not describe most of the people who are
The latest idea in health care reform now that managed care
is thought to have been rejected is consumer-driven health care. The
idea is that consumers are going to buy health insurance shrewdly and
then are going to spend their own money in making medical decisions.
And that, too, depends on informed consent.
There are many other areas that I could list. I will not
because time is out. But at some point we are going to have to
acknowledge that our solution to so many things is a solution that has
CHAIRMAN PELLEGRINO: Thank you very much. I think we have
reached the time now for intermission. Let's return at 10:20,
instead of 10:15. Thank you very much, Dr. Schneider.
(Whereupon, the foregoing matter went off the record at
10:06 a.m. and went back on the record at 10:20 a.m.)
SESSION 6: GENETIC INFORMATION: ITS SIGNIFICANCE FOR PATIENTS, HEALTH PROFESSIONALS, ETHICS, AND POLICY DEVELOPMENT
CHAIRMAN PELLEGRINO: Our next topic will be on genetic
information. And we have the opportunity and the pleasure to hear from
Dr. Nancy Wexler, who is Professor of Clinical Psychology at Columbia
I told her and for the benefit of those of you who haven't
been here before, we do not provide extensive autobiographies.
The people who come here are distinguished by their very presence
and by their titles. And so we find it unnecessary and gilding
the lily to go into the rest of it. I hope that's a good excuse
for not going into it. Dr. Wexler, will you please take over?
We're at your service.
DR. WEXLER: I am honored to speak here today and delighted
that the President's Council is taking on the serious challenge
both of newborn screening and potentially genetic testing in general.
This is a critical area in which we need to tread cautiously and with
your advice. I give you my biases right up front. What we do today
will have repercussions for many years to come.
I also appreciate your willingness to consider broadening your mandate
to include genetic information and knowledge, whether obtained before
or after birth in terms of its existential significance for individuals,
families, society at large, its implications for policy, particularly
insurance and employment.
I was asked to answer some specific questions in Dr. Davis'
letter, which I will address somewhat throughout the presentation
and come back to at the end. Particularly I was asked to look at
the question posed by Dr. Alexander and colleagues at your last
meeting, whether the so-called dogma governing newborn screening
— that is, not to screen unless you have a treatment, an effective
treatment — should be discarded. And I was also asked to
really focus on the impact of the completion of the Human Genome
The completion of the Human Genome Project I believe has placed
us in a hitherto almost unimagined era of possibility, responsibility,
and liability. There will certainly be affordable gene chips, customized
gene chips, beads, micro array technology, and genetic technologies
which we have not yet fathomed, even nanotechnologies. So I think
that fits with one of your other topics. We need to be ready for
In the light of public acknowledgement of my own biases, I
would like to also say that my grandfather, two uncles, and mother died
of Huntington's disease. And my family has been very invested and
involved in trying to find a cure for this particular disorder. So I
would like to use some of the experiences from our Huntington's
world to address some of these issues specifically.
In 1968 — I would like to actually talk about finding the
gene and how that reflects on where we are now with respect to the
human genome and the future.
In 1968, my father began the Hereditary Disease Foundation when
my mother was diagnosed. We held small interdisciplinary workshops
because at that point no one was really interested in looking at
this tiny disorder.
In October 1979, 27 years from next month, we had a workshop entitled
"Can You Use DNA Markers to Find the Huntington's Disease
Gene?" This was organized by David Housman of M.I.T. The
workshop included Ray White and David Botstein at the very beginning
of their careers. If you can imagine, remember back to that time.
There was nothing yet published about using DNA markers to find
human diseases, that you could even find a marker.
We were talking about whether this was method or madness.
There were heated arguments, scribbles of calculations on the board,
how many postdoc years it would actually take to even consider mapping
the human genome. And David Housman said he had a very talented
graduate student named Jim Gusella and we should do it in Gusella
Now, at that point, there was a ferocious argument about
whether or not we should actually look for the HD gene or wait until
the human genome was finished. Ray White and David Botstein felt
strongly that the whole human genome had to be mapped first before we
could look for a marker segregating with the HD gene. They felt, in
fact, it was unethical to do it any other way because we were
over-promising. That's how far away. It had taken Ray about two
years to find the first marker.
David Housman, on the other hand, said, "Look, why
don't you look for markers segregating in a family? Maybe you will
get lucky. You won't have to wait until the entire genome is
mapped. You'll be ahead of the game. And every time you find a
new marker, run it through a family."
In fact, David Housman encouraged me. I had already been in Venezuela
in a small study. He encouraged me to go to Venezuela to study
what turned out to be the largest kindred known anywhere with Huntington's
disease to look for a marker segregating with the HD gene.
In 1981, I began traveling to Venezuela, which,
unfortunately, still has many families living in the most unbelievable
poverty, to collect pedigree information, clinical data, and DNA.
Astonishingly — this was in 1981 we started — in 1983,
together with David Housman, Jim Gusella, Mike Conneally, we actually
discovered a DNA marker which was 4 million base pairs beneath the
Huntington's disease gene on the top of chromosome 4.
The jubilation and elation — you can remember that, Paul,
right? Remember that? Nobody could believe that. It was just
shocking. So the jubilation and elation were not only for
Huntington's, which is an appalling disorder, but really that this
was a proof of principle that you could use these strategies to find
any genes, deleterious or not.
The Hereditary Disease Foundation then organized a collaboration
of many of the early pioneers of the genetics world to go from this
linked marker to actually finding the gene because without the gene,
we still were sort of in Never Never Land.
David Housman; Jim Gusella; Francis Collins; Hans Lehrach; the
late John Wasmuth; Peter Harper; Robert Horvitz, Nobel Prize winner;
and many talented postdocs and graduate students worked for a decade
of really arduous work to isolate the gene itself.
Its abnormality turns out to be an expansion of a CAG repeat that
makes too much of the amino acid glutamine in the protein called
"huntingtin." When the research began, looking for the
gene, the equipment — if you went to anybody's lab at
that time, the equipment were these gel boxes literally put together
with massive giant clips like that, paper towels, jolts of electricity,
and radioactivity. The thing just looked like a death trap.
And at that time, there was no PCR. And the first gene-sequencing
machine had just been discovered, which was almost like a kind of
aesthetic work of art. That's the technology 27 years ago,
not that long ago.
So when the genome project began in earnest in 1990, it
required innovative technology in order to succeed. It also
necessitated worldwide collaborations, cooperation in both public and
private sectors, informatics previously unheard of, an unknown scale.
And, astonishingly, the project came in ahead of schedule and under
budget, which astonishes everybody.
So as soon as the genome was finished, all the same groups got
together to set up a HapMaps project to look at human variability.
So an example of the genetics of the future is now at the Broad
Institute Center for Genotyping and Analysis at M.I.T. and Harvard.
The Broad Institute has brand new sequencing capability. In a
matter of weeks, you can put your DNA in. They have new chips with
100,000 SNPs, which are sort of the RFLPs of today. And the difference
is shocking between where we started and what the capability is
So let me say a word again about some of the advances in HD
to just talk about what is happening now, not only for Huntington's
but many other different diseases.
In 1983, when we isolated the gene, we observed that the
size of the expansion correlates extremely closely with the age of
onset. We also learned that the larger the repeat, the earlier the age
of onset. If you have about 40 repeats, the disease is fully
If you live a normal life span, this disease will inevitably appear
and is invariably fatal, over a course of 10 to 20 grueling years
of loss of physical and mental capacities. Uncontrollable movements
envelop the body. Cognition is profoundly impaired. Severe psychiatric
problems, such as depression, suicide, even hallucinations and delusions,
The typical age of onset is the 30s or 40s, but the disease
can appear as early as 2 and as late as 80. If a person inherits a CAG
size of 60, the disease starts at 12 or younger.
So once we had discovered the HD gene, we learned, much to
our surprise, that some people with repeats between 35 and 39 may or
may not get sick. Sometimes they do. Sometimes they don't. But
those people invariably give rise to new mutations. When you pass on
the gene from generation to generation, it expands, particularly in
sperm. Why this happens we don't know.
Huntington's is one of the most fully genetically
determinant diseases known. If you carry an expanded repeat of a
certain size, you will get sick and die. And, yet, there is this
tremendous variability in when the disease appears, from 2 to 80.
So we were very interested to see whether or not there were
modifiers that affect when the disease shows up because these could
also be therapeutic targets pushing the disease out of the life span.
We went back to our Venezuelan data and started looking
very closely at different families. We found that in certain families
who had 44 repeats, they had an onset in their 20s. Other families
with 44 repeats had an onset in their 50s, same repeats. So obviously
there was something else besides repeats.
We took the DNA. We took this information. We sent it off
to the Broad Center. And just a couple of weeks ago, after less than a
month — the Broad Center sends you back all of this data. And we have
clear evidence of the presence of modifying genes which influence the
age of onset of Huntington's.
The analysis points to certain regions on chromosomes as
hot spots, which most likely contain modifying genes. And, even more
amazing, we can dial up the computer and actually look at the area in
the chromosome and say, "Well, what genes should we pay attention
to?"; which is astonishing.
I mean, when you start out in 1979 thinking that there's no
way you're going to actually find this gene and you're dialing
up to say, "Hey, can you just get that little tip of the chromosome
a little bigger because that's the gene that's causing it
to be starting at 2 or starting at 80?", that's shocking.
I mean, that is so mind-boggling that it's almost beyond comprehension
how fast this field is moving.
Now, it's entirely thanks to the Human Genome Project
that we're in this happy position. And if Huntington's can be
unraveled in the same way, if the rate of change is happening so
rapidly, there's no doubt about what we can anticipate in the
Whatever our wild imagination about what could happen, it
is going to happen. And if we stop until it happens, we are going to
be totally missing the boat. We are going to be in serious, serious
I mean, if you walk down in the Broad Institute now, in the old
labs where we were doing the work, you think you're on a different
planet. The driving motivator behind the Human Genome Project was
to look for new diagnostics, treatments and cures for human disorders.
And that push is the same for technological advances in genetic
So I think we can assume that future tests will be
DNA-based and accurate. That was one of the questions posed to me. I
think we can posit that the same drivers that forced the cost of
sequencing to tumble sufficiently to make large-scale sequencing
feasible will also be dramatically lower, will lower the cost for
accurate diagnostic testing, making it possible, not only throughout
the states but probably throughout the world, to take advantage of
these new technological advances.
The world, which welcomed the completion of the Human
Genome Project, will certainly welcome its increasing medical
relevance. In my opinion, we are woefully unprepared as a society to
deal with these changes.
The challenges span the range of issues from scientific to social
to ethical. Unless we prepare now, we won't be ready to take
advantage of the benefits of technological advances. We are like
a freight train on a collision course with our future.
Let me try to get at some of these examples. Certainly
there's a huge amount of variability when you actually start
looking at any of these diseases. They're much more variable than
you thought, even with Huntington's. It turns out to have another
disease, looks exactly like it, called HDL2, which is present in Africa
and African Americans, another chromosome entirely.
So I always recommend that somebody get two genetic tests.
Everybody yells at me and says, "Oh, no." You know,
they're impugning the labs if you actually say, "Get one blood
test and send it to this lab and another blood test, send it to that
lab and make sure you get the same result because the importance of the
data is much, much, much too critical."
One of the other problems we really have also is how the results
are described and interpreted. So with Huntington's, if you
have an expansion at the DNA level, that can be picked up if you
have newborn screening. It's exactly the same when you have
an embryo as when you have somebody that is actually diagnosed.
When people are given their diagnostic information, it's usually
extremely unclear. They say to somebody who is in their 30s, "You
have been diagnosed with Huntington's disease," meaning
that when they looked at the DNA, they found an expanded repeat
but not that the person clinically had symptoms. And so there is
a huge amount of just lack of clarity and necessity for education
about what actually these diagnostic terms mean.
The Human Genome Project is providing us with an
opportunity to have personalized medicine. I think that's one of
the benefits of the information gained, but for me we're not ready
to take advantage of these discoveries.
My personal view of personalized medicine is rather idiosyncratic.
I think that we look at each disease in an individualistic way as
if the disease itself is a person. In other words, the disease
has its own personality based on symptoms, prognosis, treatment,
or lack thereof, age of onset, and other characteristics. And each
individual in society is also distinctive.
Let me again use Huntington's as an example. We know
precisely the nature of the molecular mistake. We have an accurate
test, could be given at any time from conception to death. Where do we
stand clinically? We are actually no different now than when my mother
was diagnosed almost four years ago. We have better medicines to treat
the psychiatric aspects but really not very much else.
Tetrabenazine, which is the drug of choice, used for chorea for
40 years and Europe and elsewhere, has not yet been licensed by
the FDA. And we don't know whether it is going to be. So there's
nothing now to prevent, retard, or cure the disease, only the most
meager symptomatic relief.
We are not really that different from when George
Huntington described the disease in the 1800s. So we need a tremendous
amount more research, funding at every level, particularly at the NIH
level, where it is being cut, which has the magnitude to make a
difference, to develop new treatments and cures.
But having the gene in hand, you know, certainly has
changed research. We have in vitro systems, in vivo systems. But,
really, we don't know when any kind of really therapeutic
breakthrough is going to happen.
And so what do patients and families do in the meantime while science
is working hard at a slow, unpredictable pace? For families, the
experience of the expanded repeat means definite inexorable death.
When we discovered the HD marker in 1983, families and health professionals
alike realized that we needed guidelines to help define how the
test should be given.
I was part of a committee to develop guidelines formed by the major
international organizations of families at the International HD
Association and the major scientific group, the World Federation
We published a series of guidelines. And it had to be
revised slightly when the gene was found. In fact, I think that the
latest guideline publication is at your table. We sent it around.
That was published in Neurology in 1994.
We realized that we were in a unique, unprecedented
situation. The HD DNA marker test could accurately diagnose, both
pre-symptomatically and prenatally, the appearance of a disease decades
before its onset, a disease which inexorably ravages body and mind.
Some even suggested we shouldn't give the test until there was a
treatment, but others felt that it would be helpful to have it in
order to help people, particularly for family planning and to resolve
The guidelines explicitly reject the notion of including
Huntington's as part of newborn screening. The guideline states,
"The test is available only to individuals who have reached the
age of maturity according to the laws of their respective
The committees and family professional groups adopting the guideline
felt strongly that the choice to take the test should be only made
when the person has the capacity to fully understand all of the
ramifications and implications of the knowledge on his or her life.
For an individual to be tested prior to the age of majority was
an invasion into the privacy of the child. It violated the child's
confidentiality and was not acceptable.
A related guideline states, "The decision to take the
test is solely the choice of the individual concerned. No requests
from third parties, family members, or otherwise will be considered.
The individuals must freely choose whether to be tested and must not be
coerced by family, friends, partners, or potential partners,
physicians, insurance companies, employers, government, or others.
"Testing for adoption purposes will also not be
permitted since the child to be adopted cannot decide for his or her
self whether to be tested. The privacy of children is an area as
crucial as the confidentiality of adults with respect to insurance and
So the committee felt that by the time you were 18, you
were able to make some of these informed choices and to understand the
tremendously serious repercussions that this information can have. You
cannot take back information once it's revealed.
What has been the experience of some of these people who
actually have been tested? So let me read a couple of excerpts from
some of the people who have actually gone through testing. And then I
want to address some of the specific questions, and we'll stop.
"When you ask what it is like to be tested, you can
prepare for testing cognitively. You can have a support person that
you talk to for 23 out of the 24 hours each day. And that's the
only thing you think about.
"You go to counseling to get prepared for testing. And that
can go smoothly. And you think you have all of your ducks in a
row. But when you are delivered that information, you know, you
have to remember to breathe again. And then you have to figure
out how to go on. And for me, it was extremely difficult to assimilate
that information while the world continues to go on.
"Initially I was prepared that this would be very difficult
should I receive the results I was positive. So my husband and
I anticipated that I might need a period of time where I'm not
accountable. We would play it by ear.
"We cognitively prepared for that. What we couldn't prepare
for, though, was that the weight of that would be so grave. So
I think for a period, I was going through the motions and had my
ducks in a row, but it was a huge struggle. I was trying to put
on a good front for my daughter.
"I thought it was a personal decision for me to get
tested. I largely did it for me, but an awful lot was done for my
family, what I could offer. I was hoping to say to my ten-year-old
daughter, 'Sweetheart, you don't have to worry. We're
going to end this right here,' but I didn't choose to tell her
I was getting tested. We had all kinds of scenes about where I was
going and why I would be away. That wore down my energy keeping up a
front for my daughter.
"I came home, trying to be a happy, normal mother so my daughter
wouldn't worry, which is my big fear from childhood. I didn't
want my child ever taking care of me and having to do what I did
for my own mother. I didn't want her to deal with Huntington's.
I didn't want her to give up her childhood or early adulthood
for me. I wanted to spare her that grief.
"It was quite dysfunctional in my family after we had been
such an open unit not to talk about it, very honest before. So,
of course, that didn't work. One day she held me hostage and
said to me, 'I know something is wrong. Are you getting divorced?
Are you dying? Is Grandma dying? Don't you love me anymore?'
"I mean, it was horrible. So I thought 'It's
obvious I needed to tell her what had happened.' I had been
tested, and my results were positive. I wasn't really prepared for
that conversation either, but it was a relief.
"At that point, I had no choice but just to give up my life
for six weeks and do nothing. I didn't get paid for six weeks.
We relied on my income entirely. My husband worked three jobs,
did laundry, cooked dinner. I walked the dog, went to the beach,
and went to therapy three times a week. I did nothing else. And
it was an accomplishment just to get up and walk the dog on the
beach. That's all I did for six weeks because that is all I
could do. And cry.
"I felt that part of me completely vanished and that I had died.
I was stuck in my dead body to figure out how to pick up the pieces
and go on because it wasn't over, but a large part of me was.
"I really thought after living in the dysfunctional
household that I had grown up in, that I had pulled myself up by my
bootstraps. It was high time for me to live the way I wanted to live.
"I put myself through school. I moved away. I was on
my road. I was marching to my parade. And, you know, the conductor
stopped. I really thought I worked very, very hard to offer myself and
my daughter a life we deserved to live. And now we were challenged
with something that was much, much, much more devastating than I could
possibly ever imagine.
"I knew whether I was gene-positive or gene-negative,
it wasn't going to be over. If I were gene-positive, in terms of
my aspirations and my future, what I would do with my family, that
would be terrible. But if I received the information that I was
gene-negative, it certainly would not be over either.
"I was scared of being gene-negative, too, because I know
what it is like to have to take care of my mother. So how much
more would be expected of me to be even more strong?
"So I think there is no good news for this testing. I
don't think it's for everyone, but I think truly if you need to
know, there are no two ways about it. One must know. And I don't
I asked her if she ever wished she hadn't pursued it.
She said, "No, never."
I said, "Would you ever like to take it back?"
She said, "Maybe that. I was as very, very prepared, as possibly
you could be. I mean, years of being at different functions, having
a lot of information, all the information possible in making a choice.
And still at the point when the information was real, it was painful.
It was deep. It was almost like a death but not yet totally. It
was like a loss, a really big loss, of dreams."
The opportunity to do prenatal testing has been
extraordinarily beneficial, a unique outcome of having the HD gene in
hand, even though no new treatments have been forthcoming.
There are several options for prenatal testing through
amniocentesis, chorionic villus sampling, or also through
pre-implantation genetic diagnosis, PGD. This procedure, as you know,
involves selecting a single cell from an embryo at approximately the
eight-cell stage. PGD permits a critically important variant on
prenatal testing, which is very appealing to many HD families, called
Many at-risk individuals don't want to know their own genotype,
but they also don't want to pass on this horrific illness to
the next generation.
Non-disclosing PGD provides an excellent solution to the
dilemma. People at risk for Huntington's have embryos.
They're guaranteed to be having a normal size allele implanted
without knowing the genotypes either of the embryos or themselves.
This means that the IVF physicians performing the services are
instructed not to say how many embryos there are since that could give
One woman was also diagnosed inadvertently by a lab tech doing
the sonogram who said to her, "Gee, isn't it good that
your expanded repeat isn't so big?" She was doing non-disclosing.
She didn't want to know her genotype.
With all the advantages that PGD can provide, there are
some external disadvantages that must be overcome. IVF is required for
PGD, and IVF is still expensive and not covered by insurance, even if
it's being utilized to avoid a lethal disease.
Privacy is a critical issue for HD families as well as
families affected by other genetic diseases. Health insurance,
disability insurance, life insurance, people suffering from or even at
risk from Huntington's are, in the words of the insurance industry,
considered uninsurable unless they're part of a large group.
There is a Medical Information Bureau in Boston, which is a bank,
which keeps a lot of health information. And people have been denied
insurance by having somebody in the family with Huntington's
linked in the database and denied.
One of the problems about having these guidelines is that
they are just guidelines and there is no way, really, to enforce them.
Who is to be the gatekeeper and enforcer?
The clinicians should know about the guidelines, but they
don't. The laboratories had been actually very helpful to enforce
the guidelines, but they were chastised because they were losing money
because they were not accepting certain samples. So, really, one of
the problems, even if you have beautiful guidelines, is who is actually
going to enforce them?
Another problem is that the people's motivation to be
tested is so great that sometimes they want to take the test but they
do it anonymously. And there is a protocol for being able to be tested
anonymously. If you just give a false name, sometimes the center will
call up a telephone number. And, all of a sudden, the anonymity is
In one instance, a woman who was the sole support of her
young son went to a general practitioner to get tested because the
general practitioners haven't a clue about guidelines and just
said, you know, "Test me for Huntington's disease."
When the results came back, she called me up in a panic.
And she said, "The doctor said to me, 'You have two als. One
is big. One is little. I don't know what this means. Call for
What do you mean two als? Well, an al was an allele. And
it turned out she had an expanded allele, but the GP didn't have a
clue what that was. And I had to tell her over the phone that she was
going to get Huntington's in the future. And I didn't know her
name, and there wasn't any possibility of follow-up. And doing
that over the phone is a definite violation of any guideline.
Another problem, even in the best of circumstances, part of
the guideline is to have a clinical examination, a neurological
examination. My cousin had two growing-up children, had two children
who were in their teens. She decided that she wanted to get tested
just to clarify the risk for her children. Left to her own devices,
she wouldn't have gotten tested. So I call her sort of the
When she went to the center, part of this evaluation is the neurological
exam. They said, "No, you won't get feedback. That's
not part of the guideline."
She went on her own. The neurologist took one look at her
and said, "Why are you bothering to pay for a DNA test? You
obviously have clinical Huntington's disease. Go home. And
don't see me."
After a year, she decided maybe she would go back and get
the DNA test since she had given the blood just for completeness'
sake. And the result came back perfectly normal. So mistakes happen.
And these are in the best of circumstances.
Some of the people's concerns were with respect to
acquiring genetic information. Is this concern a valid impact on their
insurance and employment?
When I was chairing the Ethical, Legal, Social Issues Working Group,
we established a task force on insurance, health insurance, to look
at these issues. Very often in the course of those discussions,
I would say very openly as a person at risk for Huntington's,
I'm uninsurable, that uninsurable category. People at risk
even for one of the BRCA1 genes, that's an uninsurable category.
Now, if that were not true, you can believe me that nobody
would want to have gone on record having that blur, that slight on the
health insurance industry. So it is definitely an issue which is
chilling people's participation in research, people's
participation even in the genetic testing, which potentially could be
beneficial for their future health.
This is not just that people are concerned that there is
going to be discrimination. There actually is discrimination.
Sometimes very often it's very hard for people to be honest about
it because they're getting insurance in other ways.
So until issues of universal access to affordable insurance and
genetic privacy are guaranteed and until insurance and employment
discrimination is banned, the public won't be able to take advantage
of the benefits of the Human Genome Project. We have created social
and economic barriers that impede the way to improved health care
for our citizenry.
Let me just in closing try briefly to address a couple of
the other points raised by Dr. Davis. I do not believe that we should
be guided by dogma but that each disorder should be reviewed in a case
by case basis.
It's critical to involve family members who suffer from or
are familiar with the ramifications of the disease in any decision-making
process. In 1983, some doctors immediately wanted to go ahead with
HD testing, but because this was such a delightful new technology.
And the family members said, "No, no, no. Put on the brakes."
And I think that the guidelines have stayed in place.
So I personally do not believe that failing to screen for
currently untreatable diseases will deprive children or family of
benefits. We're not doing a sufficiently good job in screening for
the diseases for which we can treat. We're following up on
diseases for which we have some remedy.
I do think we potentially do more harm by including at the moment
all diseases for which we can test, especially if they have a very
late onset. Families are concerned about some other entity, like
the state or even the state Public Health Department, having confidential
information about them that they cannot control, that this information
will be misused.
There is also the issue that diagnosis of one individual with a
genetic disease spreads. It would be extremely problematic to have
your entire life from birth clouded by an early diagnosis of Huntington's
and then have a treatment or cure intervene before the disease actually
You suffered needlessly for decades. We know that in many
of these families, there are already issues of depression, alcohol, and
drug abuse just from the stress of being at risk. So to include HD
tests as part of newborn screening, which was suggested, I think only
adds to that torture.
I disagree that the default position should be to include,
rather than exclude. If the dogma is going to be broken, each
situation must be evaluated on its own merits. There should be no
default position. There are not so many diseases that we can't
look at them one by one.
I would recommend that late-onset diseases, such as
Huntington's, the hereditary forms of Alzheimer's,
Parkinson's, ALS, and others be excluded from any newborn screening
programs; in fact, that these disorders merit being treated as genetic
tests, rather than genetic screens. So a testing program provides a
more individualistic approach.
I definitely think that multiplex genetic screening of newborns
is likely to become standard of practice. I also believe strongly
that diseases should not be routinely multiplexed just because it's
more economical. You can't lump Huntington's and Alzheimer's
along with PKU because it's cheaper. A more complex problem
might be CF.
There are certain disorders that can be routinely screened
for newborns and for which informed consent is not necessary. It may
be more beneficial to protect the health of the child from a treatable
disorder than spending time acquiring informed consent from a parent.
But exempting informed consent should be the exception for genetic
tests, not the norm. Truly informed consent is not a luxury item.
I think that the discussion, the quote "right to
remain ignorant" mischaracterizes the situation. The word
"ignorant" has a pejorative connotation in our culture and
Ignorance is not well-regarded. And, really, the choice
often involves when to know a piece of information. If people choose
not to take a genetic test for Huntington's, they are often
choosing not to cloud years when they are young and healthy with
foreknowledge of their doom. If they develop symptoms, they will take
a genetic test and also get appropriate clinical diagnosis. If a
disease never appears, they will know that, too.
Sometimes people consent to genetic testing after death
just to confirm the lack of a genetic risk to offspring. Having a one
in two risk of developing Huntington's is sufficiently high to
guide people to plan appropriately financially and lead their lives
Testing involves timing. There are different developmental
stages when testing can be relevant, others when it's not. Jim
Watson once told me that he would not like to know if he was going to
get Alzheimer's in the future if there wasn't anything he could
do about it. I would not call Jim somebody who lacks curiosity.
We're in severe danger of running over the abyss in
terms of our ability to provide the kind of meaningful genetic services
that we're required to deliver on the promise of the humane genome
Even in the 1990s, there was a lack of appropriately
trained personnel. There were only approximately 1,000 trained genetic
counselors. Medical education was sadly lacking in teaching the kind
of sophisticated genetics and probability theory necessary to help
families cope with genetic decision-making.
There is still a severe shortage of genetically trained
individuals at any level: physicians, nurses, counselors, allied
health professionals. Even the general public still has a huge amount
to learn to avail itself of the latest genetic information. They need
guidance and training to integrate new genetic risk factors and
decision-making into their lives.
It will be tragic if our choices as a society are merely
hijacked by the technological imperative. We can predict that more and
more diseases will be able to be accurately diagnosed, often prior to
being able to treat or intervene. We will be flooded by more and more
genetic information, but our capacity to interpret and handle that
information is strained, even today, as Floyd would say.
We currently have a unique opportunity to develop the
policies and procedures that we need to have in place in the future to
help people benefit from genetic information and minimize harm. We
know we need trained personnel. We have a tremendous paucity of them.
We also know that research is a moving target. You know,
people are looking at RNA interference as a cure for Huntington's.
Well, obviously when the disease becomes treatable, then you reconsider
when you want to introduce testing because it may be a good idea to
prevent a disease, rather than trying to backtrack after it has begun.
So we need flexibility. We need to look at all of these things.
I just want to end with one note from someone who also was tested,
who I think is a spur to both having these kinds of mechanisms in
"To those of us who have been told we have the gene, we are
facing such a black, uncertain future. The worst part about testing
positive is the uncertainty. When will the symptoms start? And
what will they look like? We're talking about suicide. For
us, suicide isn't an if but a when and a how. We plan the logistics
and whether it should be staged as an accident. The big question
is, how do you (or your designated loved one if you even enlisted
help) know when it's time.
"What is shaking up my frame of reference is the idea that
a cure could be possible. If that happens, then I have a future.
That's a little spooky. I'm used to looking at my life
and seeing nothing after age 50 or 55 because I will have ended
it by then."
CHAIRMAN PELLEGRINO: Thank you very much, Dr. Wexler. We
have among the Council members Dr. William Hurlbut to open up the
discussion. And then we'll have a general examination of the
DR. HURLBUT: Well, I think, actually, most of what I
wanted to say has been said, explicitly or implicitly. Let me maybe
put a couple of words on labels on categories that I think we should be
First of all, I want to thank Nancy for her typical
penetrating and poignant comments. I've known Nancy a long time
and just want to say how extraordinary her contribution has been to
this whole field over the years. She has come to my classes at
Stanford and again today showed how humanly sensitive her comments are.
I am struck again by the deep human significance of this
subject. It just goes to the core, I mean, where we come from and
where we're heading. I am also struck by the immense positive
value of the Human Genome Project and its implications, this exciting
opportunity to step in, understand more deeply the significance of
where disease comes from and our new possibilities for intervening.
Just wonderful possibilities lie ahead.
Just to put a few labels on the potential problems that
have been mentioned by Nancy in this whole realm of knowledge, the word
"toxic" knowledge was used for this years ago. It captures
the potential problem here.
Knowing kind of more than you wanted to know or more than
you can handle is summed up by that term. I don't need to go into
it because it was so clearly stated.
Well, just to put one further explication on it that Nancy
had in her writings, some people may actually kill themselves when they
find out this information. And it puts an imperative on our society
for managing the playing out of this kind of testing and the danger
that this will be mismanaged, either in a commercialized context or
just misunderstood by individuals, in spite of our best efforts. And
Carl has pointed out the danger of informed consent, which implies the
difficulty of even communicating to people what is actually at issue or
what the meaning of it is.
It is obvious that, as Nancy implied, this is going to go
from very powerful and compelling autosomal dominance all the way down
to what they call multi-trace loci, the complex interweaving of
numerous genes with only statistical probabilities of what goes from
disease all the way through just human variation and what we will be
tested for and what will come forward, as I said, only as a statistical
That blends over into the second label we might give, which is
the problem of what has been called micro-eugenics, the one at a
time individual choice. If we have been well-warned about letting
the state take over guidance and governance of our genetics, we
might be persuaded by our ignorance or by our false ambitions to
take control over family lineages in ways that could be tragically
The question of pre-implementation genetic diagnosis is not
a simple one at all. You put into the hands the future of not just the
individual lineage but to some extent the species itself. And whereas
this has some powerful ramifications for specific diseases, it also has
implications for the broader prevailing — what they call flavor of the
month preferences for what people should be like.
There's a very interesting historical moment where —
I'm trying to remember who it was now — Haldane or maybe it was
Mueller, one of the two, called for programs of eugenics where people
would be made more and more like ideal members of the society.
And, first, he was a communist at that time, like many
intellectuals in America. And he called for making people more like
Lenin and Stalin. And then he got disenchanted with it. Who was
this? Was this Herman Mueller — have I got that right — or J. B. S.
Haldane? In any case, he said, "Well, we should make people like
Lenin and Stalin." And then he got disenchanted, and he retreated
to Lincoln and Pasteur.
So not that we will easily do this, but there could be a
lot of misunderstanding, which I think is the other side of it, immense
human ignorance about the meaning of this knowledge and
over-interpreting, over-determination of human existence.
I know of a case of Huntington's disease where
identical twins have manifested the early symptoms of the disease at a
lag of ten years. So even where the genetics are identical, the
individual manifestation is dramatically different.
And then just one final comment on this. The amazing
complexity of this is not just a complexity in the biological level but
on the social interpretive level. I'm good friends with Baruch
Blumberg, who discovered hepatitis B. He and I taught a class
together. He used to say, "For the most part, there are no good
genes, bad genes. The biology is an immense balance." And Nancy
pointed that out well.
Let me, just for the interest of it, highlight one what I
see as kind of a poignant problem. You take an allele like the sickle
cell allele, which everybody knows has a balancing benefit in the
carrier state and a disease in the homozygous state. And you ask
yourself, "Well, we're doing selections now for traits like
And who knows? Cystic fibrosis may very well have some
balancing benefits, too. There are theories that it is there in our
genome in such a high density, the CF trait, because it may have
conferred some benefit during cholera epidemics or — there are a
variety of theories on this.
Well, the image of selecting either prenatally through
pre-implantation genetic diagnosis, pre-implantation or prenatally, and
then eliminating the individual who is the homozygous or even the
carrier, is sort of a poignant problem. If the gene confers some
benefit to the society as a whole, the individual who got the
homozygous state is, in fact, an unfortunate recipient of a problem
that occurs because there's also a benefit.
I bring this up because it seems to me in all cases but
especially, as pointed out, by those where the individual has a disease
because there's a benefit to society, we owe something to the
person who carries the burden of genetic disease. We owe something
because they're part of our human family for which the balance of
genes is not a simple issue. It's not like there's good genes,
We should be very, very careful before we endorse projects that,
either explicitly or implicitly involve an agenda of purifying the
Well, I think that says it all, says enough. Just to end
with one statement, I think this is a level of knowledge at a
profoundly fundamental level biologically. And at the same time, it
raises very fundamental ethical questions worthy of our council.
CHAIRMAN PELLEGRINO: Thank you very much, Bill.
Dr. Wexler, would you like to respond?
DR. WEXLER: One of the potential inequities about using
PGD is that only people who can afford it are going to be able to
ensure that their children aren't suffering.
I mean, I take your point that we don't really know
what these genes do and we sort of struggle with "Is there a
benefit to Alzheimer's or Huntington's or these genes?"
On the other hand, the person that's suffering is
really devastated, the person who is watching them suffer. And so if
there is an opportunity, at least so that that person who kind of has a
double dose by accident or is suffering the manifestations doesn't
have to, then I think that gives us an opportunity to ease the burden.
However, most people can't afford it. And so that is
going to be putting, again, too much of it — I mean, we already were
talking before about just people who have insurance, people who are
afraid of losing their insurance because of genetic discrimination,
people who are totally uninsured, and then people who can pay cash out
of pocket for genetic tests so they won't lose their insurance,
some people who can pay cash out of pocket for IVF and PGD so that
their children won't suffer.
I think we need to have a better equity about these issues.
CHAIRMAN PELLEGRINO: Open to Bill unless you want to say
anything further. Dr. Hurlbut?
DR. HURLBUT: Well, just one little comment on that.
Sometimes I think maybe you're lucky if you're poor in some
ways in this field. That's a strange statement, but you may not
get drawn into some of the errors that the rich might get drawn into.
And you may accept some fundamental human realities that are in the
large play of things meaningful human experiences and don't place
you in what may be called the options glut.
I have students who — I have a set of twins I taught who
have cystic fibrosis and who are genetic counselors now at Stanford
Medical Center ten years after my classes. And I'm not saying I
got them there, but that was a very interesting experience.
When I first met Francis Collins, who discovered the gene
for cystic fibrosis, I said to him, "Francis" — he was a
practicing clinician. Most of you know that. And he had been working
with cystic fibrosis patients. And I said to him, "Francis, have
you ever taken care of a patient with cystic fibrosis who said they
wished they had never been born?" And he said that he hadn't.
So along with whatever we think about this subject, let's remember
that genetics is not going to solve all the problems. Genetic knowledge
is not going to solve all the problems of human suffering and that
in the mix of thinking about what to do with this, we need a more
profound understanding of the meaning of human suffering and what
it calls us as a society to do by way of solidarity amid suffering,
not just cooperative efforts to eliminate it.
CHAIRMAN PELLEGRINO: Thank you, Bill.
Now we open it up to general comments of the Council
members. Does anyone wish to? Dr. Carson?
DR. CARSON: I just had a question, actually. Has
it been considered by the committee making the guidelines for the
molecular genetic testing to advise people not to have testing done
unless they have non-terminable health and life insurance?
CHAIRMAN PELLEGRINO: Dr. Wexler?
DR. WEXLER: In fact, that is part of this specifically.
And all of the genetic counselors or other people in the advocacy
groups are all really instructed before they even begin testing, have
done the testing protocol, to talk to people about their insurance.
People have put the testing on hold, in fact, so that they
could work out issues of insurance. And that's either, implicitly
or explicitly, exactly your suggestion. Some people do that.
CHAIRMAN PELLEGRINO: Thank you very much.
Further comments? Further comments? Dr. McHugh? Dr.
DR. McHUGH: Hello, Nancy. It's wonderful to see
you. I do have a question. Before I get to my question, I want to
reinforce what Bill has said and why you are such a heroine to all of
us, Nancy. I think many of us in the group know that Nancy has been
the spirit behind the development of so much in the science, the
practice, and ultimately in the ethics of Huntington's disease and
the care and treatment and understanding of those patients.
You know, I've known Nancy since the '70s, when
our Huntington's program got started, but she always was a sharp
and contributing leader for the field and led us to see things more
deeply than we would have otherwise.
Just take, for example, her point about not letting testing be
done on people before they're [age of] majority. If only other
scientists in other conditions, like, for example, children born
with ambiguous genitalia, had followed a similar thought process
that Nancy illuminated for all of us, a great deal of suffering
in later life for those people would have been avoided.
And so, Nancy, I just reiterate everybody's theme that it's wonderful
to see you here and have us get a chance to thank you and with deep
gratitude for the energies and spirit that you brought to our understanding
of Huntington's disease.
Now, when I know that and say that, I appreciate, of
course, as well that as you're thinking of Huntington's
disease, you think about the other genetic disorders and the ones that
As it turns out, Huntington's, of course, is a very
specific disease in more senses than one. I mean, it's a dominant
genetic disorder. It's fully penetrant.
We now understand a lot more, not completely yet, about the
biochemical mechanisms that direct the development of it and the timing
of it in life. And we are making steady progress towards the
understanding of Huntington and things of that sort.
The lessons that we have learned here, are they completely
translatable into our understanding and management of the polygenetic
disorders who are much more common, certainly amongst our
I mean, our Department of Psychiatry turned to
Huntington's disease because of the things that Nancy has pointed
out, including the fact that these patients, a very sizeable number of
them, suffer from clear mental disorders and the like. And from that,
we had thought it would be an easy step into understanding
schizophrenia, manic depressive disorder, and the like. It has turned
out to be a lot harder.
What lessons from a single genetic disorder are there for
us to appreciate in relationship to polygenetic disorders? And if
possible, what ethical principles do you want to translate in that way,
CHAIRMAN PELLEGRINO: Dr. Wexler?
DR. WEXLER: Thank you. Well, first, I just want to thank
you for all of your kind words. I am also glad that you are feeling
better and that you are here today. And I salute you.
DR. McHUGH: Thanks.
DR. WEXLER: I can always count on Paul to ask me an
impossible question. I think it's a really crucial question. In
fact, one of our hopes for looking for modifiers, even at the genetic
level, is to look at some of the families where there are tremendous
psychiatric problems, OCD, depression, hallucinations — you know,
people say, "Our family, we go crazy" — to see if we
can't find genes, actually, even in the Venezuelan Huntington's
families that produce that kind of psychiatric characteristics.
I think that there is a lot of generalizability because the
problems given the fact that there isn't a treatment other than the
psychiatric treatment for Huntington's, the problems for the
families are very, very similar. A lot of Huntington's families
have sort of some of the apathy, the negative kinds of schizophrenia.
So some of the family members are constantly trying to
figure out in terms of taking care of the patients. They're almost
always with other people with psychiatric problems, rather than
neurological problems. I mean, I think it's really a false
distinction. You know, we talk about neuropsychiatric, but it really
is one brain.
Since I think there is also a tremendous misunderstanding in the
general public about how predictive genes are — you know,
even recently I was with somebody with Alzheimer's disease who
had two doses of apoE4. And she was crying about how obviously
her children were doomed because it was so predictive.
And I said to her, "It's not predictive. It
isn't predictive." And it was the first time anybody actually
had talked to her about the genetics, that sometimes you yourself can
— if you have these genes, they can be more diagnostic. But if you
pass them on, they're not predictive.
People, even in cancer, if you say, something is hereditary
or something is genetic, it means something totally different because
genetic can be just some surprise explosion in a cancer cell, but it
isn't passed on to your children. But since people sort of
interchangeably will use hereditary and genetic, everybody is
completely panicked that they now are passing down these genetic
diseases to their children.
Certainly there are many genetic influences in psychiatric
diseases, some clearly more than others. So we need to do a tremendous
amount of educating in families. In genetic counseling, really, what
is the risk if people want to have children or if people have a child
with autism, what is the risk to other children in allaying
There's a tremendous amount we could do with collecting
pedigree information that people will often have huge family histories
and nobody even knows about them. So getting a lot of that information
just accessible in a way helps people even understand what is going on,
though, in family, sometimes for research but also just in terms of
Destigamatizing. All of these diseases have a horrendous
stigma. And if they're hereditary, there is a kind of a peculiar
sort of — in a certain way it becomes, you know, not stigmatized. You
can't help it because it's in your genes.
On the other hand, it's even more stigmatized because
it's considered a stain. I mean, some of the social Darwinism,
some of the laws, which actually permitted people to be sterilized if
they had schizophrenia, epilepsy, Huntington's disease, they
weren't so long ago. And I think that many of the families kind of
carry this notion that "There is something wrong with me."
I think having the idea of genetic variability is very
helpful because I say to people, you know, "Your DNA got too
enthusiastic, you know, just got fancy and expanded" because
people feel that "There is something wrong with me. I have a bad
gene. I am a mutation." And I think that also generalizes to
other diseases in general.
So in terms of the genetic counseling, in terms of the
research issues, in terms of having these diseases included, much more
integrated into family practice, and understood, I think we have a huge
amount, you know, a ways to go.
CHAIRMAN PELLEGRINO: Dr. Meilaender?
PROF. MEILAENDER:I want to sort of take a risk. I
don't wish to underplay what is new in the challenge that this kind
of knowledge faces us, but I would like to think just a little about
I am conscious of the fact that there may be a certain kind
of teutonic temperament at work here, and I apologize in advance for
At least if one has a certain kind of philosophical bent,
we live every day toward death. In order to be a parent, I have to
know that my children are all doomed. I have no idea how much of a
future I have. I may walk out of here and keel over. This may be the
day I make a foolish left turn. I've made one of those in my life,
but I survived it.
And we all at different points — again, it may be different depending
on what sort of philosophical bent we have, but we may begin to
notice declining powers. People make jokes, but they're not
just jokes about forgetting where their car keys were and things
like that. You know, we don't know where life is headed.
One of the things it leads me to conclude is that knowing
where life is headed isn't so important or special, that life has
to be lived in a certain way toward death, toward oblivion, but without
certain knowledge of what that is.
And I just wonder. As I say, I mean, I don't wish to
deny that there is something new and special going on here, but I just
wonder if we might not let the amazing possibilities that increasing
genetic knowledge offers us to know certain things about the future
cause us to forget what human life well-lived is actually like. And if
we didn't forget it, it would seem to me it would reinforce some
things that you said that the best life is lived with a great deal of
uncertainty and that there are a lot of things that we think we might
like to know but that, actually, we don't need to know in order to
Now, as I say, I don't know. And if that is
unnecessarily gloomy, I am sorry. But it just seems to me that this is
a very focused problem and a really dramatic one, of course, for people
who face it, but I'm not sure that it's so different from what
life is like once we really start to think about it.
I don't know if that makes sense to you or not.
CHAIRMAN PELLEGRINO: Dr. Wexler?
DR. WEXLER: It absolutely makes sense to me. And I think
that our capacity to have those choices be our own is very crucial.
Somebody that I know recently, very, very sophisticated, sort of a
scion of business, went to see his doctor. And he said to his doctor,
"Please don't do the PSA test because I don't intend to do
anything about it," got thoroughly worked up.
And at the end of his visit as he was walking out, his
doctor said, "By the way, your PSA was normal." Now, on the
one hand, he was delighted it was normal. On the other hand, he was
furious because here was a person who had thought extremely carefully
about his therapeutic options and didn't want to be tested and
didn't want his doctor overruling how he chose to live his life.
So I think that and I know that people are saying, "I
don't want to take the Alzheimer's test because my mother has
"Oh, you know, the apoE4 test."
So people are constantly sort of going into their
doctor's office and having genetic conversations of some sort.
They are asked, "Do you want to take the BRACA1 test? Do you
want to take this test? Do you want to take that test?"
And so the fact that as we have more and more knowledge and
as that knowledge is more and more predictive, I mean, it's not
going to all be like Huntington's, but there will be things. For
Alzheimer's disease, I mean, there is certain autosomal dominant
Alzheimer's disease or autosomal dominant ALS, which is just
exactly like Huntington's and no treatment, 1 and 2, and if you
have the gene, you get it and you die.
Now, we need, I think, to as a society be able to educate
ourselves about these genes and what they do but also educate ourselves
about the choices and that — I mean, when we first started having the
Huntington's test, there was a lot of, you know, press interest in
it. And so people would call up and say to me, "Well, so are you
going to take the Huntington's test?"
And I said, "Well, you know, that's
And they would say, "Well, my editor told me that I
had to ask you."
And to that I would say, "Don't you have anything
genetic in your family?"
"No. My family is perfect."
"Well, what did your parents die of?"
"Oh, they died of cancer and heart disease."
"So you mean you don't really have anything
genetic in your family?"
So there's like a gradual sort of understanding of, you
know, what really these genes can and can't do. And if we want to
live our lives so that we're taken out by the next Mack truck,
that's our prerogative.
But one of the difficulties I think is that for certain
diseases, if they get lumped into, for example, prenatal screening,
about which you have no choice, cystic fibrosis — I mean, in certain
ways it makes a lot of sense to have an early indication of cystic
fibrosis because you can treat better, you can intervene, you can do
On the other hand, cystic fibrosis can also be a disease
for which people are concerned at least about losing their insurance.
So they don't want people to know that they have it in the family.
They have a sort of schizophrenic attitude toward in my
institution, they require you to be pregnant before they test you for
CF. So the only option you have is termination if it turns out that,
actually, you and your husband have a baby that's affected.
So why don't they pay for it prior? Well, the
insurance is really basically driving the whole pregnancy because the
insurance won't pay before you get pregnant.
Then the genetic counselors don't say, "Hey, you
have a CF gene. Talk to your parents. Talk to your brothers and
sisters. Talk to your cousins." Nobody discusses it.
So everything is just kind of happening in this little
vacuum and void except that on occasion somebody will write down, for
example, you know, "She told her doctor 'Don't talk about
Huntington's' because I don't want to lose my
But you want to be candid with your doctor so you can have
an intelligent conversation. So the doctor wrote on the outside on a
manila folder "Huntington's in the family." When it got
returned to this woman's work, somebody noticed that there was
something written on the outside, Xeroxed the piece of paper, put it
inside. The woman lost her insurance.
So these things happen all the time. Someone whose wife
was pregnant, at risk for Huntington's, wanted to get insurance,
was told they couldn't get insurance, discovered, in fact, that
what was in his family wasn't Huntington's, another disorder
very similar. So he called up the insurance agency and said, "If
I test negative for Huntington's, will you insure me and my
They said, "Yep." So he tested negative for
Huntington's because it wasn't in his family. And then in the
meantime, he also tested for what was in his family, and he was
So people are forced into these kinds of distorted
relationships that I think a lot of it really has to do with the
question that you were talking about earlier, you know, what kind of
health care system do we want to have for our nation as an ethical
nation. And how does this get perverted and distorted by information,
by gaming the system? And I think it is something that it is being
distorted for us so that we are not able to make the kinds of choices
that I agree with you we ought to be able to make ourselves.
CHAIRMAN PELLEGRINO: Thank you, Dr. Wexler.
I have two requests for speakers. And we are running close
to the end of our time. So may I ask for brevity and conciseness. I
first have Dr. George and then Dr. Bloom. And may I, Dr. Wexler, ask
them to provide the questions in sequence and then you respond to
both. Dr. George?
PROF. GEORGE: Dr. Wexler, thank you for your
presentation, which was not only informative but very moving. I'm
grateful, as I'm sure the other members of the Council are, to you
not only for sharing your expertise with us but also your very personal
I hope you will excuse me for raising the very sensitive
question of eugenic abortion. I ordinarily wouldn't do it in this
context except for the fact that in the guidelines, which you have
kindly provided us, there seems to be a recommendation at 7.2, together
with a comment at 7.2, that relates directly to it. And I would like
to ask you about those.
The recommendation says that the couple requesting antenatal testing
must be clearly informed that if they intend to complete the pregnancy,
if the fetus is a carrier of the gene defect, there is no valid
reason for performing the test. And I think it's clear that
by "complete the pregnancy," that means not have an abortion,
not do something that will destroy the fetus.
And then at 7.2 in the "Comments" column, there
is an indication that testing a fetus carries with it a small
additional risk of miscarriage and possibly of congenital abnormality.
Is it correct to conclude from the combination of the
recommendation and the comments here that the test carried out on the
fetus couldn't benefit the fetus, himself or herself, in any way?
It would either be positive, in which case the expectation would be
that an abortion would be performed, or it would be negative, in which
case the fetus is carrying a small additional risk imposed by virtue of
the test but no benefit, therapeutic benefit, to the fetus himself or
Is that right? Have I understood this correctly? Oh,
CHAIRMAN PELLEGRINO: Thank you.
PROF. GEORGE: And then the second point, second question,
is that obviously on the question of abortion in the case of fetal
defect, there is a wide descensus. There is a dispute in the society.
Americans and others are divided over the question of the legitimacy of
that, whether that is a legitimate option.
And I wondered if the committee that put together the
ethical guidelines that you have shared with us had a spectrum of views
sort of reflecting the broader society on the question represented or
whether all of the members of the committee or the overwhelming
majority of members of the committee took the view that abortion for
fetal defect, leading, quite possibly, to a serious disease, such as
Huntington's, was a legitimate option.
CHAIRMAN PELLEGRINO: Thank you.
DR. BLOOM: I will try to be very brief.
CHAIRMAN PELLEGRINO: Dr. Bloom?
DR. BLOOM: It is always inspiring to hear Nancy speak,
as it was when she and her dad came out of the Congressional Caucus and
said, "What is good for neuroscience will be good for
Huntington's disease." It was the first disease-focused
agency to make that kind of generalization.
In the early days of HIV, we said since we can't treat
it, there's no point in testing for it. Eventually we recognized
that there were people who were HIV-positive in whom there was no
Your mentioning of the Broad Institute's finding of
modifier genes at least creates the possibility that someone could be
HD, Huntington, mutation-positive, and, yet, never show the disease.
Would that change your attitude towards prenatal screening, antenatal
CHAIRMAN PELLEGRINO: Thank you very much.
DR. WEXLER: Let me try to address the first question. If
I am not understanding your question, please correct me. There was a
lot of discussion about the issue of prenatal discussion — I want to
answer your second question first — and what it actually meant.
There was as an international group a tremendous range of
different beliefs, philosophies, religions. And, again, I think having
family members as well as professionals made a real contribution. And
there were people who felt very strongly for religious reasons that
they did not in any way support abortion or terminating the fetus.
There were other people who felt that just as an at-risk
person, they didn't want to feel that someone would choose to end
the life of someone like them. So there was a whole, really, an array
of different points of view.
The intent of the guideline — it may not be that clear the
way it is expressed — is that if some people just one said, "I
want to have a baby, but I also want to know if it is going to have
And the point of view of the guideline was to say,
"That is an invasion of the privacy of the child, of the minor in
the same way that testing somebody under the age of 18 is an invasion.
That baby in utero is not giving informed consent. And so since you
intend to keep the pregnancy and there is no medical benefit, we
can't treat in utero" — I mean, obviously, if there was a
treatment, it would be different.
But since there is nothing you can do and there is some
potential risk of harm by doing any kind of amnio, then there
wasn't a cause for testing the fetus in terms of the well-being of
the fetus and the child to be, that if they wanted to have the child,
that was fine, but the position of the guideline was that the only
reason, really, that someone would have the test prenatally was if they
then intended to terminate that pregnancy, if they find that the fetus
is carrying expanded repeat and they wanted to terminate the fetus.
So it wasn't that people were saying, "Yes. I
promise to do this." And obviously people change their minds all
the time. And you can't say, you know, "You promised. We did
this test. And now you're keeping the baby. If people change
their mind, they change their mind."
Sometimes, interestingly enough, people change their
minds. Sometimes if they were pregnant and they went home and visited
a relative who was sick, just seeing the reality of the disease, they
said, "Well, you know, I am not going to carry this pregnancy
without testing" or the husband got diagnosed with a repeat the
size of a juvenile. So they knew that the baby would be affected as a
juvenile. And they decided to terminate.
So people have very varied reasons for doing it. For the
most part, HD families are just having children. They're not
testing themselves. And they're not testing the children. And I
think partly this is because, by and large, the testing centers, many
of them, don't advocate abortion. They don't even suggest it.
And sometimes people who have had multiple terminations
because they are trying not to have children who will carry this
terrible disease, but they can't afford IVF and PGD, so they're
having multiple terminations, they finally just say, "I can't
stand it anymore. I can't bear. I want to have children."
You know, they're not people who want to terminate. They just
don't want their children to suffer.
And, finally, they just give up and say, "Okay.
I'm not going to test the baby. I'm just going to have a
baby." And then very often they are absolutely castigated by the
health care system that says, "How could you be so selfish? How
can you do it?" They don't even know, you know, what they
went through to even get to that point.
So that has been, really, a difficulty. And, again, I
think for people for whom PGD is an option, that that helps some of the
stress of that.
Did I answer your question or not quite?
PROF. GEORGE: Yes. It is quite clarifying. And, if I
have understood the answer correctly, it sounds as though the committee
is working with just a very difficult problem because you're trying
to protect the rights of the baby in utero, who may very well become a
person who would like to decide for himself or herself whether these
tests are performed. But you are trying to protect the rights of the
baby in utero while you don't know whether the baby will be
terminated or not as a result of the testing.
So it's difficult. I see the dilemma that the
committee is in.
DR. WEXLER: What we are asking the couple is, "Do
you" — I mean, the couple has to say to us, "Our
intention is to terminate if we find that that baby is positive.
Our intention is not to continue the pregnancy and to try again."
If they don't have that intention, then there's no
reason to test the fetus because it is an invasion of privacy. So the
couple has to come to us saying, "This is what we intend to
Now, the couple can always change their mind if the baby
tests positive and they say, "Well, we're going to keep it
PROF. GEORGE: Well, just to be clear, the invasion of
privacy is the invasion of the privacy of the child.
DR. WEXLER: Exactly.
PROF. GEORGE: And the invader, who is violating the
rights of the child, is the parents.
DR. WEXLER: Exactly. Yes, you are exactly right.
PROF. GEORGE: This is a real paradox here.
DR. WEXLER: That's right. That's right. But
that's why, you know you wouldn't even begin to take on the
challenge unless the parents are coming to you and saying, you know,
"Our option at the moment is to try not to have a baby that is
going to suffer in the long run."
To go to Floyd —
CHAIRMAN PELLEGRINO: Dr. Bloom's question.
DR. WEXLER: Right. I think that we were extremely
enthusiastic when we found out about both the HIV, that there could be
people that had these protective factors that would enable them to
never develop AIDS. It also gave a kind of window on the cause and the
treatment for AIDS because you could figure out how were they getting
It certainly is our hope that with these modifiers, that —
I mean, there are people who get the disease and it's almost
unnoticeable. They get it in their 80s, in their 90s. And it's
usually completely misdiagnosed because the people just think
they're kind of old until it is passed down. And then the younger
generations get it earlier often.
So it certainly is our hope to find these modifiers. Now,
whether that would make enough of a difference, you know, I am open. I
think that is why we need to take a flexible attitude, both towards
what we are going to find as modifiers, you know, doing RNA
interference or any other kind of small molecule treatment. The
likelihood is if you don't intervene early, it's going to be
much harder to reverse the process.
I mean, certainly there is a mouse that had
Huntington's and got sick. And the gene was stopped. And it got
reversed and got cured. So there are examples in mice of the brain
being able to handle this kind of toxic load as long as has toxic
information. Probably it would be better to prevent the disease than
to have to reverse it.
So then, of course, you would absolutely say, "Let's start
over from scratch and figure out what is the best thing for patients,
to protect them."
So that's why I think what you are doing is so crucial
because you can raise these as issues of how you would introduce them
flexibility, how would you introduce these kinds of protections, and
also the kinds of research that really needs to be pushed because this
research is going to change the future of all of these diseases.
CHAIRMAN PELLEGRINO: Thank you very much, Dr. Wexler.
SESSION 7: PUBLIC COMMENTS
CHAIRMAN PELLEGRINO: Now we move into the last part of our
program, the opportunity for members of the audience to ask a question
or make a statement.
I have only one person who has requested the possibility of
speaking. And that is Dr. Torsten Trey, representing Falun Gong. And
I will ask Dr. Trey to speak and be aware of the fact that there is a
time limit. I hope that has been made clear to you. I'm sure it
has by Dan. We are delighted to hear from you and anything you want to
submit in terms of written material later we welcome.
DR. TREY: Thank you very much. I will try to be fast.
DR. TREY: My name is Torsten Trey. I am a medical doctor
with a German background. I would like to address some comments on
organ transplantation's policies that the Council has discussed
earlier. And the reason is that transplantation medicine has developed
into a global business. This requires that we, among other things,
look after an international ethical standard for transplantation.
Some countries don't follow such standards. I would like to
express my concerns about the legal transportation practices in
China. You may have heard about the systematic organ harvesting
of Falun Gong practitioners.
The recent report of Kilgour and Matas is a thorough investigation,
which provides significant hints that organs are systematically
removed from living Falun Gong practitioners, of course, without
their consent. The victims were procured for transplantation reasons.
One Falun Gong inmate mentioned that after an injection of
an unknown substance, she experienced a tachycardia and a burning
sensation in the arm. This may indicate that potassium was injected to
the victims in order to cause heart failure before surgeons removed the
A few days ago, Dai Ying from Norway, whose eyes were
shocked to blindness with electric buttons in a Chinese detention
center, described what she witnessed, "One day in May 2004, all of
approximately 160 Falun Gong practitioners were gathered in a
conference hall. All equipment brought from a Fushan hospital was set
up in a bus. Doctors from the hospital conducted forceful physical
examinations and injected an injection of all the Falun Gong
"When a doctor did an electrocardiogram from me, he
asked me in detail whether I had anything wrong with my health. Blood
was drawn from each practitioner. After the examination, some
practitioners disappeared. And nobody knew where they went."
In July I attended the World Transplant Congress in
Boston. I had the opportunity to talk to a Chinese transplant surgeon
from Tianjin City. We talked about liver transplantations. He said
that his hospital is one of three hospitals that performs liver
transplantations in Tianjin City. He further said that in his hospital
alone, they would perform 2,000 liver transplantations per year.
In comparison, in the entire country of Germany, with a
population of 80 million people, there are approximately 700 liver
transplantations per year; in Argentina, only 200 per year.
The number of liver transplantations in Tianjin City is
even more concerning if we take into consideration that the Asian
population is traditionally reluctant to donate organs. So I wonder
where all of these organs come from.
The Kilgour report provides an additional 18 significant
hints about this unethical malpractice. This practice is not only
inhuman but anti-human.
I had the opportunity to talk to Mr. Kilgour in Boston.
Many attendees of the World Transplant Congress listened to his
presentation and were shocked about his data.
In fact, after his presentation, a huge amount of posters
about transplantation findings generated in China, according to an
attendee of WTC, at least 40 posters, didn't show up in the poster
section. At this point it is not clear if these posters were withdrawn
because the findings may have been generated through illegal organ
harvesting or the authors didn't want to expose their
The data about organ harvesting and simultaneously
increasing the number of transplantation in the recent years in China
should be concerning to all medical professionals.
The malpractice in China can undermine the trust of our
patients in transplantation, let alone of a new type of phobia related
to the received organs in the patients.
In the growing global transplantation medicine, we cannot
turn a blind eye to China's malpractice. We should realize that
the Chinese government uses our medical profession as part of the
persecution of Falun Gong.
Seventy years ago we faced the situation with Germany when
the Nazi dictatorship used medical staff, like Dr. Mengele, in the
Auschwitz concentration camp to perform medical experiments on Jewish
Due to the courageous stance of the U.S. government and the Allies,
fortunately, the systematic killing was stopped. But, unfortunately,
six million Jews were already killed before the intervention.
We don't know how many Falun Gong practitioners have
already lost their lives due to the persecution in China and due to the
organ harvesting. But with approximately 70 million Falun Gong
practitioners in China, we should take it seriously.
The chronicles will observe our acting and will assess our
ethical stance. Financial interests without ethical values will not
When the U.S. government took a stand against the
Holocaust, it has established a reputation of justice in the whole
world. It may be once more time to refresh the justice by speaking up
against the illegal organ harvesting in China. I believe at this time
the medical professionals worldwide are requested to speak up as well.
Coming Thursday, September 14th, Mr. Kilgour will be in
Washington, D.C. to present his data. Please feel free to come to his
presentation or invite him to your institution or the NIH so that more
and more people and medical professionals will be able to take a
stand. The Twenty-Firth Century requires a high moral and ethical
standard in the medical profession worldwide.
CHAIRMAN PELLEGRINO: Thank you very much.
Are there questions the members of the Council would like
to put to Dr. Trey? I'm sorry. Do we have a second? Question
first for Dr. Trey?
DR. EBERSTADT: Could I ask you a question, Dr. Trey?
Where will Dr. Kilgour be making his presentation and when on the 14th
DR. TREY: We are still in the process to organize, to
finalize the date and the time and the location. Most likely it will
be in the Congressional Building. But I have my telephone number and
e-mail address. I could send the detailed information later.
MS. YANG: I am sorry. I just want to add a few
things from a Chinese perspective following Mr. Trey's comment.
I am originally from China. Actually, I have friends who have been
tortured to death in China's labor camp because he refused to
sign a paper from the Chinese government saying that he would give
up his practice. I also have several friends who have been missing
in the past few years. And family don't know where they are.
That's why after reading the report from Mr. Kilgour
and the two Canadian investigators who released their report this July
— I am sorry.
CHAIRMAN PELLEGRINO: Take your time.
MS. YANG: I am very worried for my friends here.
Actually, the story about the live organ harvesting from practitioners
was — first, it broke out in Chinese media here in the United States
early this year, in March.
And following that, I noticed an article by Knight Ridder
Beijing correspondent Tim Johnson. He interviewed somebody who was
doing organ transplant in China. And this businessman is from
Pakistan. According to him, about every nation is here. There
isn't one single hospital in Tianjin, said he. There are Korean,
Japanese, Arabs, the whole Persian Gulf region. There are a few guys
from Israel as well.
I also know that lots of Americans go to China for organ
transplant because you know the waiting time here is — it takes time
to wait for an organ matching you, but in China, the official Web site
even advertised, "Come. You can get a kidney in two weeks or a
month." How can they promise in that way?
The only explanation is that they have a large live organ
bank somewhere. That's why I hope everyone do something to help.
CHAIRMAN PELLEGRINO: Does anyone want to make a comment or
question? And could I have your name for the —
MS. YANG: Sorry. If you want more information, I do have
the Web site, where you can download the report by the two Canadian
investigators. One is the human rights lawyer. The other is a former
Canadian Parliament member. I read the report. It is really good,
CHAIRMAN PELLEGRINO: Could I have your name for the
transcript? I'm sorry.
MS. YANG: My name is Ms. Yang. Is that okay? It's
spelled as Y-a-n-g, last name.
CHAIRMAN PELLEGRINO: Thank you very much. Question? Yes?
PROF. GEORGE: Yes. Thank you, both, for those very, very
Dr. Pellegrino and Dr. Davis, in the report that we will be
going forward with, I gather, or likely go forward with on organ
transplantation, will we be addressing the issue of travel to China for
organ transplantation? Is that something that the staff has looked
into thus far? I mean, it's been put on the table here, but, of
course, it's also something that has been written about in the
CHAIRMAN PELLEGRINO: Dan, do you want to respond to that
DR. DAVIS: We are going to be meeting with David Kilgour
next week to talk with him about his report. And in Sam's policy
paper, there is some mention of that. Robby, you may not have been
here for the meeting when this came up on the periphery of the
discussion about markets. And the argument was that if we had markets
in this country, we would not be forcing Americans to go abroad.
So I think certainly it will arise within the context of
that discussion. How thoroughly we treat it we'll have to see as
yet, but yes, we will be dealing with that.
PROF. GEORGE: Good. Thank you, Dan.
CHAIRMAN PELLEGRINO: If there are no other comments,
again, I want to thank the members of the Council for their
participation, particularly this morning. I think it was most
And I want to thank the speakers, particularly Dr. Wexler, this afternoon
and also those who have made the public presentations. You have
brought an extraordinarily important problem before us. Thank you
(Whereupon, the foregoing matter was concluded at 12:05