COUNCIL MEMBERS PRESENT
R. Kass, M.D., Ph.D., Chairman
American Enterprise Institute
University of California, San Francisco
S. Dresser, J.D.
Washington University School of Law
W. Foster, M.D.
University of Texas, Southwestern Medical School
Johns Hopkins University
Ann Glendon, J.D., L.LM.
B. Hurlbut, M.D.
F. May, Ph.D.
Southern Methodist University
Johns Hopkins University School of Medicine
C. Meilaender, Ph.D.
Janet D. Rowley,
The University of Chicago
J. Sandel, D.Phil.
Q. Wilson, Ph.D.
University of California, Los Angeles
WELCOME AND OPENING REMARKS
CHAIRMAN KASS: Could I ask Council Members to take their seats
so that we can get started?
Good morning. Welcome Members of the
Council to this, our twelfth meeting. Welcome also to members of the
public. I'd like to recognize the presence of Dean Clancy, our
Executive Director, the Designated Federal Officer, in whose presence
we have a legal and proper meeting.
And I would also like to take this
opportunity on behalf of the Council to express our congratulations to
Jim Wilson who yesterday received the Presidential Medal of Freedom.
Congratulations to you, Jim.
A word of thanks to Council Members for
your loyalty and devoted service and especially this time for the
heroic amount of material that you have, I would assume, read or will
have read before long. I warn you there is more to come, but we are in
your debt for your attention and comments, of course. Welcome.
The first session of this meeting,
"The Research Imperative: Is Research a Moral Obligation?"
does double duty in this Council. First, it's part of our ongoing
effort at what we call a richer bioethics and second, it does have
something to contribute to the on-going discussions of the ethics of
stem cell research. It will continue our effort to lift up to view
some of the unstated assumptions that lie behind the debates, say about
stem cell research or cloning for biomedical research, assumptions that
rarely get the attention and scrutiny that they deserve. We've
paid some attention to the assumptions about the moral status of the
At the next meeting we want to look at
the ethical and political meaning of funding or not funding ethically
controversial research in a pluralistic society. And today, we're
going to look at the so-called imperative of research, especially
research in biomedical science that could lead to cures for diseases.
No one doubts the great value of such
research and no one should have anything but admiration and gratitude
to the generations of scientists who have pushed back the frontier
against ignorance and who provide knowledge and techniques fruitfully
used to alleviate human suffering.
The question is, rather, what kind of a
good is such research and what kind of an obligation do we have to
Is it an unqualified obligation, a so-called perfect duty that
takes precedence over possible objections and concerns, especially
ethical ones? Such seem to be, at least the implicit view of at
least one scientist who presented to this Council, who in so many
words indicated that this Council would be held morally responsible
for any lives that were lost should we erect any legal barriers
to cloning for biomedical research and similar opinions have been
voiced many times in the public debate in recent years.
Others have argued that there is no moral
or social obligation to medical research at all, even if such research
were a social good and good for us, but rather an optional goal to be
pursued, one among many and by no means supreme.
To help us continue to think about this
question, is there an imperative to research and if so, of what sort?
We're very fortunate to have with us Daniel Callahan, the
co-founder and for 27 years the Director and President of the first
bioethics think tank of the United States, The Hastings Center. Dan
Callahan has a nose for all the tough big questions in the field, as
the titles in his résumé will show. And moreover, the courage to try
to make other people face up to them.
It is the tough question of the research
imperative that is the topic of his forthcoming book, What Price
Better Health: Hazards of the Research Imperative and that makes
him the perfect person to get us thinking about this today.
If I might add a note of personal
pleasure, I was a young researcher at NIH almost 35 years ago when Dan
Callahan was starting The Hastings Center and he invited me to the
first organizing meeting of what would become that center and in an
ill-fated writing venture Dan and I were co-editors of a volume called
Freedom, Coercion and the Life Sciences for which I had written
a chapter on "Freedom, Coercion and Asexual Reproduction"
whose arguments I've been cloning ever since.
Dan, it's a great pleasure to have you here. We look forward
to your presentation and discussion.
SESSION 1: "THE RESEARCH IMPERATIVE":
IS RESEARCH A MORAL OBLIGATION?
DR. CALLAHAN: Leon and I have worked
together for a long time and I can remember my first discussion with
you, I think, at my house on Summit Drive, and we talked and you seemed
exactly the sort of person I was looking for. You were suggested to me
by Paul Ramsey who many of you knew.
It's a double pleasure being here
then to be with Leon and this particular Council and also because I
think I know at least two thirds of the people on the Council and
it's so nice to see you collected here.
The term research imperative first arose
for me with an article that was in The Hastings Center Report and Paul
Ramsey used the phrase. He engaged in really a most interesting debate
with the Jesuit theologian Richard McCormick on the question of human
subject research on children, particularly what's called
nontherapeutic research, for the sake of knowledge, rather than direct
therapeutic treatment of children.
And McCormick argued that children should
be available for nontherapeutic research. Their parents should be
willing to make them available as a sort of a noble sacrifice for the
good of humanity and the advancement of research. Paul Ramsey rejected
that notion altogether, felt children should not be used in that way
and accused McCormick of falling prey to the research imperative.
I had no particular interest in research
at that time and it had passed out of my head, but shortly thereafter I
did run across Joshua Lederberg, Nobel Laureate, former President of
the Rockefeller University who said to me at a meeting, I gather
something similar to what Leon quoted at another meeting saying
"If we don't carry out research, the blood of those who die
will be on our hands."
I wondered at the time whether that was
true, but again had no particular interest in research and didn't
pay much attention to it, so it faded away. But in recent years, all
of that sort of came back to me for a variety of reasons. I got
interested in the whole enterprise of biomedical research in this
country, particularly in this country, although obviously it goes on in
other countries as well.
And there were a number of things that caught my eye. First of
all, the NIH budget is something of a federal marvel. So far as
I know it is the only budget that hasevery year without fail gone
up rather than down. A researcher went through all the transcripts
of hearings of the National Institutes of Health and it has always
had complete bipartisan support. There's never been any serious
dissent of any kind.
There has been some discussion in recent years about the priorities
of NIH, but basically no objection to an increased budget and typically
the President each year, whether Democrat or Republican, has put
in for a certain amount for the budget. Congress has always found
that inadequate and forced the NIH to take more money and they were
happy enough, of course, to take it. So the NIH budget caught my
eye as an interesting phenomenon in American life.
I got interested also in the escalation
of what I think is escalating history of medical research in this
country where research was a worthy cause in the late 19th century when
it first was taken seriously in this country, particularly in medical
schools. But the kind of shift from a worthy cause to a kind of
imperative, necessary cause which really came into play after the
Second World War and I suppose nicely symbolized by President
Nixon's declaration in 1970 of a "War Against Cancer."
And thereafter, language of the imperative of research became stronger
More recently the stem cell debate caught
my eye since many people have argued and you may hear it in your
discussion, but a moral duty to pursue such research. Simultaneously,
more or less, the pharmaceutical industry, for those of you who follow
it you can't help following it a bit these days, pharmaceutical
industry has long claimed that they, the main reason they need the high
profits is in order to carry out research which is going to save future
lives and relieve future suffering. Hence, they have used a very
strong research imperative argument in justifying their drug pricing
and the like.
Now to me, the interesting question is,
why has this happened? What has been the reason for this kind of
increased interest? It's rather striking, if perhaps unusual, that
health care, I suppose—particularly NIH research, but it is a budget
that has gone up despite the fact that health is getting better. It
seems to me there's some straight line correlation between the
better health we have, the more money we spend on health care and
particularly the more we think we ought to spend on research and the
argument there is, of course, the prospects of new breakthroughs are
greater than they've ever been historically and therefore we should
go after them.
In any case, as health gets better, the
budget goes up and spending on health care continues to go up as well.
Now I think that there are a number of
things culturally that have happened. First of all, I think
there's a very strong feeling in this country that illness and
disease, which have always been considered human evils have taken a
kind of transcendent status as evils in our country. They are seen as
among the worse things that can happen to people, one of the most
important things we can spend money on, and that there is really
nothing better we can do for each other than to invest money in
research to promote better health.
I think also, as part of that, is that
one shift that I think has taken place since the Second World War has
been a kind of abolition of fatalism. It's been argued that in the
past we reconciled ourselves to aging and death simply because we could
nothing. People could do nothing about it and then it had to be
rationalized, it had to be given a place in human life, but fatalism,
many would, in effect, argue should be put behind us. Now we can do
something about the evils of illness and disease.
The political scientist, Michael Walzer,
I think very perceptively made this point about 20 years ago when he
said, "What has happened in the modern world is simply that
disease itself, even when it is endemic rather than epidemic, has come
to be seen as a plague. And since the plague can be dealt with, it
must be dealt with. People will not endure what they no longer believe
they have to endure." That was from his book, Spheres of
I think it's also the case that the
pursuit of health through research is seen as not only a good in
itself, morally and socially, but also of great economic benefit, both
in the lives saved and the future productivity of those lives, but also
in the jobs and profit that research generates. A strong argument
behind the annual NIH budget is that the research is exportable.
It's one of America's great products. People need it. They
love it. And they will spend money for it.
Most importantly, I think, and an issue
that's worth a side discussion, but we won't have time to get
into today, a strong argument that medical research offers the greatest
promise of eventually reducing our escalating health care costs. A
number of economists, David Cutler and the new Commissioner of the Food
and Drug Administration, Mark McClellan, have argued very strongly that
research and biomedical investment is the greatest investment that has
been made on anything in this country, that has been worth trillions of
dollars to our economy. And both the pharmaceutical industry and from
time to time the NIH itself has argued that better research is what
will beat the problem of rising health care costs. I would add as a
footnote, it hasn't happened yet. It seems to me a wonderful idea,
but the historical record is not encouraging. Anyway, the argument has
Now I want to really make three basic
contentions in this talk. I'm going to make them and let's see
if I can defend them and make them quasi-persuasive.
First of all, I want to argue that, in
general, there is no moral research, no moral imperative or duty to
pursue medical research, or in particular, to pursue any specific line
of research. Research, I want to argue, is a moral good to be weighed
against other human goods, but not an overriding moral obligation.
That's the first contention.
The second is that in the absence of what
I will call a common metric, there is no rationally justifiable or
viable way of balancing the moral good of research against other
claimed moral goods.
And my third contention is that in the
legal and ethical policy, international policy now in human subject
research that has developed since the Nuremburg Trials in 1947, the
principle of informed consent for competent patients has come
decisively to overcome any and all claims of research benefits that
could come from violating the principle of informed consent. I think
this has great historical significance.
Let me go to my first contention, why is
there, with one exception I will shortly mention, no moral obligation
or duty to carry out biomedical research, but at the same time one can
say that research is clearly a moral good? I offer you three
considerations for that.
First of all, this is a point that
philosophers sometimes make about the very notion of obligation.
Philosophers distinguish between perfect and imperfect obligations. A
perfect obligation is one which is based on a specific promise we have
made. We're then obliged to keep it. Or an obligation that flows
from certain types of roles we take on such as doctor, policeman,
lawyer, what have you, obligations that typically are called role
obligations and they go with the carrying out of particular
So an imperfect obligation by contrast is
one where no one in particular has any obligation to carry it out. We
talk about it as an obligation, but one cannot say that any given
individual has a duty to carry out the obligation. In that sense,
it's a very weak kind of obligation. Indeed, it's not clear
when you talk about imperfect obligation whether you ought to use it at
all, talk about obligation at all, but nonetheless that has typically
And here I would want to argue that medical research falls in the category
of an imperfect obligation, imperfect in the sense that it's
not clear whose duty it is in particular to carry out such research.
One can't even claim that of the researcher. If a researcher
decides to do basic research with no interest in therapy, one would
hardly accuse that researcher of being irresponsible or to say that
any given researcher had a particular obligation to pursue this
or that line of research.
So in that sense, medical research itself
would be a classic case of an imperfect obligation. Now it might well
be the case that someone in say the field of genetics who took on
particular issues pertinent to society or therapy would have some moral
obligation to carry through on that if the person had chosen to do that
research it would then begin to take on some of the characteristics of
a perfect obligation. But there's no obligation in the first place
that a person become a particular kind of researcher.
Now this may seem like a rather
technical, indeed, precious point, the kind of thing philosophers have
lots of fun with, but don't persuade many others. I think the
question is pertinent because if we're going to talk about a duty
to carry out research, and obligation of research, we really then have
to ask, in what sense are we supposed to carry out research and what
moral sense is there a claim upon us?
I simply want to argue that it is
perfectly possible to talk about it as a good. It's an ideal of
our culture, a very strong ideal. It is based on the notion of a duty
of empathy, mercy, of the relief of suffering, the virtue of
beneficence, the virtues of mercy. And in that sense, one can make a
very strong case that it is a good thing to do, but not necessarily a
Now by calling it a good thing to do, it
seems to me one then has to raise the question well, how does it
compare with other good things we might do? As an economist might say,
what are some of the optional ways we might spend a similar amount of
money? How do you compare the value and need for man's educational
needs, national defense, jobs, all sorts of other things that societies
need in order to function well?
It seems to me then once one has said it
is a good, and simply a good and not necessarily the highest good, then
one is in a situation of trying to juggle budgets, juggle moral
priorities and make a determination of where we want to locate health
over against other things we might do with our money and with our
I think it is fairly obvious in this country, as at least symbolized
by the NIH, that we have given it an uncommonly high status and
this is clearly not the case in other countries. The British, the
French, the Germans all spend money on medical research, but they
don't put nearly the amount of money into it as we do in this
But I would point out that we don't
consider it morally objectionable that they spend less money on
research and more money say on other things, since it seems to me once
one begins talking about comparative goods for society, this will be
determined by the politics, the values, the history, culture and a lot
of other things.
So basically, I have a very modest kind
of goal here, which is simply to use an old fashioned term from
theology, demythologize the notion of a research imperative by simply
saying sure, it's an absolutely good thing to do, but once
we've said it's a good thing to do, then it has to be compared
with and compete with other goods in society, whereas to talk about it
as a duty seems to act for many as a kind of a trump care which then
allows people to not only ask for more money than they might for other
things, but also to argue that somehow we have an inescapable duty and
I want to argue with that.
Now I would make one exception which I
think is important in our world. I think one can make a very strong
case that there is something pretty close to a duty when you're
talking about infectious diseases and particularly disease such as
AIDS; diseases that don't simply kill people, but mainly kill
younger people and in particular kill those who are responsible for the
running of the society. And one of the great problems in sub-Saharan
Africa is not simply a high death rate although that, of course, is
horrible, but the point is that what we're seeing is the
destruction of the health care workers, the police force, government
administrators, all the people that make society run, and of course,
leaving thousands of children as orphans. So it's very destructive
on the family.
So it seems to me that plagues and
particularly those that affect younger generations and affect the
infrastructure of society and not simply the death rate stand out as a
particular exception, which is only to say in a way that there is a
difference between what was called the endemic diseases, cancer, heart
disease and the like and contagious diseases that seem to fall into a
Now let me respond to the Lederberg
argument. I think when we think about the Lederberg argument, the idea
that somehow it's a sin of omission not to support research and
therefore we will bear responsibility for the results of failing to
support the research, this will certainly be true if we consider a very
hard and specific obligation a duty, therefore, we will have seen,
failed in our duty and thus to be condemned. But it seems to me one
has to really ask about all the other needs of society and ask is it
really wrong to decide in a given society, at a given time that
education, say, is more important than health care.
In this country, we have more or less
spent around 6 percent of our gross domestic product on health care for
nearly 30 years or so. We now spend about 14 percent on health care
and around 3 and 4 percent on defense. Thirty-five years ago we spent
about 6 percent on each. So one can really raise the question whether
it makes a great deal of sense or there leads to a balanced society to
allow one sphere, namely health care to so remarkably outpace all of
the others, as if somehow our education system is terrific, we
needn't put more money in that, but only health care deserves the
constant escalating budget that it typically gets.
Now I think in trying to ask the question
of research as a good and comparing it with other goods, we really are
forced to ask what kind of an evil disease, suffering, and death are.
Clearly, they are very important evils. All societies have considered
them evils. As I suggested maybe earlier fatalistic societies had to
develop rationalizations and ways of making sense of them. Many of
these, I believe, still make sense, but we have at least entered a
period where there is not much pleasure taken in arguments that seem to
have a fatalistic flavor to them.
So that pushes us really back to the
question of let's take, for instance, the question of death. I
think it's very pertinent to ask what kinds of death are comparably
more or less evil. There's death by disease. There's death by
social violence, war, domestic violence and the like. There's
death by accidents. There is death by poverty. Can we rank in some
sense, even if very crudely and roughly, can we rank those deaths in
terms of evils? I myself would say that the greatest, the worst kinds
of deaths are those that come from social violence and deaths that are
unexpected, unnecessary and are a function of human evil, rather than
We can obviously argue about that matter,
but it seems to me it's important when we begin thinking about the
comparative good that medical research can bring, what are the
comparative evils we are trying to overcome and how do we want to
understand and rank those evils?
To my mind, premature death is something
to be worked against. Threats to public health are to be worked
against. This would particularly include infectious diseases and
threats to sanitation, air and the like, and I suppose anything that
threatens the ability, particularly of people in their adult years, to
run families and to manage societies.
I would want myself to classify the
endemic diseases of modern society, particularly those that primarily
affect older populations, as comparatively low priority. That is to
say they are terribly important. People—it would be a good thing to
cure cancer, heart disease and the like, but it seems to me in terms of
social priority, I would want to argue that they have a comparatively
low priority and it's very difficult, I believe, to say that we
have an obligation to overcome cancer and heart disease as much as they
cause individuals suffering. I use that as an example because my
family has a history of cancer as a cause of death and certainly that
brought suffering to our family as to many other families, but I think
if one takes a social perspective on, say, death from cancer, one would
have to say that while a source of great pain and suffering for
individuals, it is not a disease that threatens the very structure of
society or the overall functioning of society.
I might mention a very interesting quote
by Harold Varmus. Harold Varmus, many people will recall, was the
Director of the National Institutes of Health, a Nobel Laureate and I
think considered a particularly effective Director. He retired—he
left that position in the year 2000 and is now president of Memorial
Sloan-Kettering in New York. In his last talk he gave to the staff at
NIH, he said something very interesting that was not picked up by the
press, but I thought was very radical for a Director of NIH. He said
first of all, he said I think we pay too much attention to health in
our society, an interesting thing for an NIH Director to say; and the
second thing he said was he was concerned that too much of the research
they were carrying out was going to produce products that Americans
would not be able to afford to buy.
And it seemed to me that was what I
thought was the very first time that anyone in a position like that
began to question some of the very basic work that the NIH has been
Now let me bring in a third consideration
here. It seems to me that if one cannot say that health is an
overriding good as I would want to say, but it is one of many goods,
then the question is really how do we balance the ensemble of human
goods necessary to make up a society? Obviously, a society where you
have a very low death rate from the endemic diseases, but is one marked
by social violence, corruption and other things will be a lousy society
to live in, however healthy physically people may be. And for that
society a priority would want to be given to dealing with the social
problems of the society.
The question always would be, if one
wants to say health is a basic necessity for human beings, obviously
the same thing can be said for food, clothing and shelter and maybe a
slightly less sense of the importance of jobs and other things for
society. So the question then is to find a way to decide what priority
to give to health compared to the other goods and at the same time to
recognize that the aim of a society is to find a way to get a good
balance between all the needs and not just one.
I am particularly interested in this
issue because while the research drive has received an awful lot of
money and great attention, we have done less well with the delivery of
health care in this country. We've spent a lot of money on
research, but we have spent less money doing research on how to better
deliver health care and there has been far less public debate, much
less agreement on the value of say achieving universal health care in
Harold Varmus said something rather
radical for somebody in his position. Floyd Bloom, who is the recently
retired President of the American Association for the Advancement of
Science and before that editor of the journal Science, said very
interestingly he thought we should spend less money on medical research
and more money on the delivery of health care, because we have a
paradoxical problem in this country. Namely, we have a research agenda
that's going forward to find cures for disease, but there is by no
means any guarantee that all Americans will be able to receive the
results of those disease. There are some 41 million uninsured in this
country. There are many people who can't afford the drugs that are
coming out of the research enterprise, the pharmaceutical industry and
yet somehow we can't seem to find unanimity to deal with that
problem the way we can in putting money into research itself.
Okay, so much for my thoughts on the obligation to do research.
Let me turn to the issue of balancing research against other goods
and values. Here I mean to talk very generally about balancing
research against other human needs and goods, but here I want to
particularly look at the language of balancing when, in the moral
debate, because it is often said and has been said in many government
reports that we must balance various considerations.
Let me give you some obvious examples.
In the human subject debate, the question has been one of balancing
potential, harm to subjects against potential research benefits.
I'll come back to that issue. In the stem cell debate, a very
common use of balancing language there; namely, the destruction of
balancing the destruction of early embryos against the potential
benefits of stem cell research. A third area that has received some
attention lately, the protection of privacy against the public health
benefits that would come from epidemiological and collecting
information on people's health behavior and other items concerning
In short, in each of those debates, the
issue has arisen, how do we balance the potential harms of doing the
research and what harms of different kinds over against the potential
values. Now I find this very interesting, first of all because it
seems to me one can't really use the language of balance in any
meaningful way unless one has a kind of common metric, that is to say,
it's the old question of sort of comparing apples and oranges. In
that case, the issue you can talk about is the fruit, but in many of
these other cases, the differences are very great between the values to
Now it seems to me that unless you have a
common metric, you really can't do that in any meaningful way. For
instance, by a common metric, I mean if your physician says look, you
have a very painful condition, we have some surgery that will relieve
the condition, but the surgery is very painful, then, of course, you
have a common metric of pain and you can do some serious balancing.
But in the cases I've mentioned, the human subject research stem
cell debate, protection of privacy, we don't have anything that
works in such a tidy manner.
Now my own observation is that, lacking
this common metric, and despite the language of balancing, the de facto
results of efforts to do so have pretty much reflected the ideological,
prior ideological commitments of the people doing the balancing. I
look at the language of balancing in previous national commissions
beginning with the National Commission for the Protection of Human
Subjects in the mid-1970s through three other federal commissions and
finally this President's Council, I'll leave out this one, but
the other ones use the language of balancing, but pretty much the
balancing would typically go in the direction of the known policies,
attitudes, ideologies of the Commission Members.
And it seems to me there's probably
no other way of doing it. People will bring to bear on balancing
questions their previous commitments. Hopefully, they may have been
influenced by arguments and debate they heard, but nonetheless, they
are likely to act out some of their deepest values and that will tip
the balancing one way or the other.
And of course, one way you achieve balancing, there are a variety of
ways. One is simply decide that on the balancing of a see-saw,
one value really isn't such a high value after all and you get
rid of it entirely and thus getting rid of the problem or you find
some way to make one of less value than the other, but in point,
all I want to argue is I don't think there's any very rational
way of doing this. It ends up a matter of politics, maybe in a
good sense, but still politics rather than any form of rational
The third issue I'd like to look at is that of human subject research.
I think the history of human subject research offers a very interesting
perspective on the question of balancing and also on the research
imperative. Although the famous physician William Osler, at Johns
Hopkins over a century ago insisted on the importance of gaining
informed consent from human subjects, and even a German Commission,
interestingly, in the early 1930s made it a moral requirement, it
was only slowly and fitfully accepted by medical researchers. Their
objection over the decades, as one might guess, was that research
requires human subjects, that medical progress cannot take progress
without the use of medical subjects and that the cure of disease
took priority over any claimed rights of subjects to be free of
having their bodies invaded by researchers.
In short, there was an effort—an effort
was made to look at the problem of balancing, but by and large, in
earlier decades, probably the Second World War, the balance was always
typically in favor of the researcher and again, the arguments are
rather familiar ones. You can't do the research unless we go
forward without the consent and in any case the saving of lives and the
relief of suffering is something that is of higher value than the
protection of human subjects.
A friend of ours, Leon remembers him
well, Robert Morrison, a physician, said of his medical training in the
1930s, it was hard to take the idea of informed consent seriously when
so many of our patients were dying all around us, particularly young
Well, all of that changed with the
Nuremburg Trials in 1947, trials of the Nazi doctors accused and
correctly indicted for many horrible medical crimes, particularly
crimes involving human subject research. Out of that trial came the
Nuremburg Code which at its very core had the idea of informed consent
as a necessity.
Nonetheless, despite the blessing of the
Nuremburg Code, it took many years for the report really just to sink
in and again the arguments against it were the necessity of the
research, the value of the research, and one that became increasingly
common, the fact that your average lay person would simply be too
incompetent, too ignorant to make informed judgments.
In any case, over a period of time, by virtue of the Nuremburg
Code, and by other codes that were developed, the principle of informed
consent was accepted and accepted in the face of many rationalizations
to evade it. And it's very interesting because I think the
rule at present, in effect, says competent subjects have a right
to make, give informed consent and without their informed consent,
no research may go forward, regardless of how many lives might be
saved, how much suffering might be relieved. It is a hard and fast
rule. We basically get rid of the problem of balancing all together
and said this is not an area where balancing is appropriate, patients
must be protected.
Now this was, I think, a very important
precedent. It said something about the research imperative. It said
something about the competence of people, even lay people, to make
informed judgments and it certainly said something about the necessity
to bring in regulation of something very important. A number of people
who believed in informed consent such as Henry Veatch, one of the
people who blew the whistle in the mid-1960s on the problem, said it
would be certainly important that there be a moral requirement for
informed consent, but the government ought not to enter in and try to
regulate this area. It should be left to the integrity of the
researcher. Well, that view was rejected. The institutional review
boards were born in the late 1960s and it is now a firm regulatory
requirement that research be protected by informed consent.
Now I might mention that, of course, as
many of you are familiar with earlier Commissions, the issue never gets
totally solved. Efforts to this day still go on to evade informed
consent. The work of institutional reviews is endlessly being
reviewed, criticized. Nonetheless, I think it very striking that this
one principle did endure a lot of criticism and particularly criticism
from those who argued for a research imperative to do the research.
Let me end—I'm not charged to say
anything about the stem cell debate, but let me try to make a few
applications of what I've said generally to that debate. First of
all, if there's anything to what I've said, it is not
appropriate to talk about a duty to carry out stem cell research, even
if you believe it extraordinarily valuable, even if you believe there
aren't any terrible moral objections against it. It seems to me
inappropriate to talk about it as a duty. It certainly doesn't
meet the standards I've suggested.
Now even if we want to say, however, it
is not a duty, but simply a high good, then the question is high how a
good and how are we to think within that context. The thing that has
certainly caught my eye is that it is claimed to be promising
research. But I'm struck by the fact that the National Institutes
of Health over the past few decades has spent literally hundreds of
millions of dollars on other promising research for the very same
diseases that stem cell research is supposed to help.
In the case of Parkinson's disease,
an article a couple of years ago listed 10 different research lines
being pursued for the cure of or relief of Parkinson's disease and
certainly that's the case with heart disease, spinal cord injuries
and lots of other things as well.
Therefore, one can hardly argue that stem
cell research is the only possible way of—unless someone once said
the NIH has been wasting lots of money on everything else over the
years, I don't think they would want to say that. One would have
to say the stem cell research is promising, but other things are
promising as well and that this might be even comparatively more
promising, but promising in and of itself is not enough to constitute a
duty to carry it out, particularly when there are alternative lines of
I would notice something else that people
haven't noticed which I found at least amusing. Christopher Reeve
who has been a great proponent of stem cell research, as you know,
there's been a couple of stories about him over the past year, one
that he is now able to have some movement in his limbs that he
didn't have earlier and this came from recent research on
rehabilitation. And secondly, that he is gradually being weaned from a
ventilator and this was cited as a sign of research progress on weaning
people from ventilators. In short, some of these other alternative
lines of research are working on his very condition and bearing some
I think on the question of balancing and
here, this is where the balancing issue has come in very strongly, how
do you balance the claims of an embryo against the potential of
benefits from the research itself? Well, I guess the question is one
thing is pretty clear, embryos are killed in order to carry out the
research for research that is promising, its hypothetical benefits
over against at least some real harm. Now unless one believes that
embryos have no moral standing whatever, which some do, of course, one
is then left with—or believes that they have such moral standing that
they shouldn't be used at all, but if you're like many of us in
sort of muddling around in the middle there, then the question is how
do you balance off the decisive harm done to embryos against
It seems to me that at least from the way
I think about the issue, there is one kind of common metric here, that
is to say we're talking about the potential value of the life of
the embryo over against the lives of future victims of disease. But it
seems to me the question is again, it's not a very good metric
because it's still a hypothetical benefit. We don't know the
stem cell research will, in fact, work. We do know that lots of harm
can do lots of harm to embryos to get there. So I suppose I would want
to try to think about the matter in terms of how likely are the
benefits and even if we don't believe that there's full human
life present in embryos, what do we mean when we say, as many former
Commissions have, that embryos deserve respect. I think that is a kind
of way on the part of the embryos a certain insecurity about the way we
talk about embryos, even among those who don't believe embryos
should be considered a full human life worthy of full protection. I
think the language of respect has been invoked as a kind of middle
level term, if you will, to help us say well, we don't think
they're nothing, but at the same time we don't think they have
quite enough standing to merit their non-use for the sake of research.
I suppose I would want to end by saying
on this issue and here I will simply end by saying this, I think
embryos have a fairly weak moral claim, but on the other hand I think
the research claim is even weaker. Thank you.
CHAIRMAN KASS: Thank you very much, Dan.
Let me just simply throw the floor open
for comment. Elizabeth, is that half a hand, Elizabeth Blackburn?
PROF.BLACKBURN: I would like to
address the points that you raised in the last part of your
presentation. With respect to stem cell research, you point out that
the NIH has, of course, spent very much more money on different kinds
of research avenues from stem cell research. But I think we should
acknowledge that the reason for that has been partly because there has
not been the possibility to do very much stem cell research because of
the situation being so limited right now.
So it's not that the stem cell
research has been abandoned. It's being sufficiently useful
compared with other avenues to pursue it. It's simply that we at
this stage haven't had the opportunity, we as a society, to look
I think it's early days. And you
pointed out that there hasn't been a whole lot of evidence about
how useful it can or could not be, but again, the only way to find out
that is to gain the knowledge.
So I think I was getting from you words
somewhat of a sense that you were thinking that extensive research was
the inferior mode of research. And I was just going to point out that
we really don't know that at this point because we have not had the
Another quick point I wanted to raise
about Christopher Reeve. I think that the news is wonderful that the
injuries that he had were in some way not completely irreversible, but
I think that what he acknowledges is that he was in a rather unusual
position of having a lot of resources. And he could devote enormous
resources, financial, into having the very, very intensive sorts of
effort put into his rehabilitation, which I think is not commonly the
situation for most people.
And so if there were alternatives to this
route that he was able to take, which was heroic and very encouraging,
I think that would be better because these people do not have
Christopher Reeve's large amount of resources that he could sink
into his rehabilitation.
So those are the couple of points I just
wanted to raise.
DR. CALLAHAN: Well, let me first point
out I in no sense meant to imply that stem cell research is inferior,
in fact, it may be superior to all the others. I was simply making the
point that NIH already is pursuing other things that they consider very
promising as well.
Stem cell would be one more thing added
to the list. It might be better than the others, but unless we think
they have been wasting money over the years, the NIH has believed that
other things are valuable and worth pursuing as well.
With Christopher Reeve, you may well be right, but much of that
research, the benefits came out of NIH-sponsored research. How
it got paid for with him, I haven't the faintest idea.
But, again, this gets back to Harold Varmus' point. It may well
be that a lot of the research will develop things that only well-positioned,
affluent people will be able to afford. But that is a side issue.
PROF.BLACKBURN: I think the point
was that his current one was such an expensive kind of therapy. And if
there were cheaper ones that might be more readily accessible, that
DR. CALLAHAN: Sure, sure.
CHAIRMAN KASS: At the risk of perhaps
deflecting people from where they would like to go, it seems to me the
real challenge that Dan's paper and presentation throws out for us
is to think really about the large theme, which is the moral imperative
And I wonder what people think of the
general thesis of the presentation as stated. And the use also of
informed consent at least indicates that, if I understand Dan's
argument, there were certain kinds of trumping limitations that
indicated that the imperative to research, if there were one, or at
least the pursuit of research, if there were one, simply wasn't the
sort of thing that trumped all other kinds of considerations, including
moral considerations. I wondered what people make of the general
thesis that has been presented.
PROF. FUKUYAMA: Well, I appreciated
that presentation because it really made me think about a lot of
things, but it does seem to me that fundamental to your argument is
actually not the question of the value of research per se, but the
value of biomedicine directed towards basically curing diseases in old
people that will add, say, another five years of life expectancy to a
population whose life expectancy has already been pushed to a fairly
And the value of that compared to other
things because you are willing to say, well, infectious diseases that
affect younger people I guess in your mind actually do trump quite a
lot of other moral considerations.
DR. CALLAHAN: Not informed consent,
PROF. FUKUYAMA: Not informed
consent, but you're willing to concede that. So it seems to me
that that is really the focus of the issue, the relative value of
biomedical research directed towards that particular population. And
that becomes, then, a kind of metric by which you can value one type of
research over another. Isn't that the basic—
DR. CALLAHAN: I guess to me the
fundamental question is, what are appropriate goals of medicine at this
stage in history given the fact that we have already made great
progress, given the fact that most people now die in old age, rather
than as young people. Where ought we to be going? That's the
And at the same time, though, I want to
say that I think it's been given an excessively high evaluation.
And I would simply want to bring it down a little bit and put it on a
par with a lot of other things we could usefully spend money on.
CHAIRMAN KASS: Frank, do you want to
PROF. FUKUYAMA: Yes. I think that
that's really in a way a core issue that we ought to discuss much
further. I remember once hearing the director of HHS saying that heart
disease is down, mortality from heart disease is down, and a number of
other diseases, but, unfortunately, mortality from these other diseases
Now, it seems to me even the director of
HHS should be able to figure out that the total of mortalities from all
diseases have to sum to 100. So that if you actually cure some
diseases, you will be raising the rates of mortality from other
diseases unless you can presume that they are not going to die.
So, really, what you are talking about is, in a way, this whole
life extension issue and the kind of value that.
DR. CALLAHAN: Implicitly, that certainly
arises, yes. Well, it's also there's another issue, which I
have written about in another case and gotten in trouble for writing
about, namely, what is our obligation to the elderly given the fact
that the average age of cancer deaths is at age 69 or 70 now. So it is
clearly a disease of the aging.
Should we continue giving it the high
priority it had by virtue of the fact that it's mainly older people
who have it, as with spending on money on young people to improve the
schools? Which is the greater social contribution?
PROF. FUKUYAMA: And I would just
point out that among the complexities of that, you get into all of
these quality of life issues. One of the reasons that there has been
this explosion in rates of Alzheimer's is that you have actually
succeeded in other areas of biomedicine, keeping people alive long
enough that they can get to an age where they are much more susceptible
So it seems to me the total good that is
being delivered to society by some of these advances is much more
problematic. And I think that's a perfectly reasonable issue to
CHAIRMAN KASS: Alfonso Gómez-Lobo and then Bill May.
DR.GÓMEZ-LOBO: I have a concern and a
question, but I would like to preface that with a broad agreement on
your approach. I think there's deep wisdom in placing the question
within the ranges of goods.
And I totally agree. I seem to see an
emphasis on health, which may not be reasonable in the long run. I
mean, we are surrounded by other goods. And we may be neglecting lots
of other social goods by emphasizing that.
Now, what I think is very important is to
say there is a limit to the balancing. In other words, that balancing
goods is something that is reasonable when the pursuit of those goods
is morally permissible. And there I think—and I totally agree with
you—the notion of informed consent plays a very important role
because that's the nonnegotiable limit, right? You don't
balance that in any way.
Now, here is my concern and my question.
I have seen since I have been on the Council and reading some stuff
that informed consent is sometimes extended to the treatment of
children and then also to the disposal of, say, frozen embryos.
What I am doubtful about here is whether
there can be valid informed consent for actions that will not benefit
the subject. And I would love to hear some clarification of that.
And, of course, that ties into your last
remark, the remark about the embryos having a weak moral claim. And I
want to ask you, what does that mean? And if it's weak, how does
it become stronger and say how strong would that be in an infant? In
other words, does the notion of varying moral claim for drastic action,
like the action of killing, really make philosophical sense?
That's the question I would like to raise.
DR. CALLAHAN: Well, your last question
bears on the whole discussion, the rest of this meeting. I mean, I
could say a lot, but let me say very briefly I think by "weak
moral claim," I mean a claim where we are uncertain about the
moral status and we are uncertain about how great the harm being done
to that moral status might be.
By "weak claim," I mean a claim
somewhere in between saying embryos are worth nothing and embryos are
full of life we claim is one that is somewhere in between. It is
something. It has some value, but we are not quite sure how much
And we may on occasion be willing to say
it might be overridden by other considerations. That's all I will
say on that. I would just as soon not have to get further into that.
I'm sorry. You're first—
DR.GÓMEZ-LOBO: The other point was
about consenting to an action performed, say, on a child or on an
embryo that would not benefit that child in—
DR. CALLAHAN: Well, that's a hot
area that has been disputed ever since the Nuremburg trials because
there are incompetent people doing research and somebody with
Alzheimer's disease doing research and children, people who are not
in a position.
I think it's generally agreed that
you may have to indeed do the research, it's valuable research, but
there you have to depend upon a surrogate giving you permission,
somebody you believe is competent and capable of giving permission for
the research to be carried out on that person, the condition being that
the person is not able to carry out the research and that the research
would be beneficial.
Now, on your question of non-therapeutic research, I don't see any
reason why a competent person can't agree to be part of research.
It is not going to particularly help that person. I was part of
a research project on amphetamines myself at one point. It had
nothing to do with my health at all. And I think I was able to
give informed consent on that subject.
So the question of consent for embryos,
well, that's a whole totally murky kind of area. I don't think
obviously you can give consent for an embryo because you have no idea
what that embryo might have wanted, where it's going, or anything
else. I am going to put that question aside and not even try to mess
my way through that, which would be a confusing business anyway for me.
DR.GÓMEZ-LOBO: Yes. I'm a little
bit disappointed, because that is exactly the kind of guidance—
DR. CALLAHAN: That's not my charge
at this meeting. And I will give you references I have written on
that, but I can't do it in three or four quick sentences.
CHAIRMAN KASS: Bill May?
DR. MAY: The paper and the presentation
are offered with your characteristic reasonableness. I would simply
like to explore the question of the place that you give to research
imperative in the setting of a metaphor, a fight against death and
understanding of death as a contingent, accidental fact and, therefore,
the tension between that research imperative driven by that military
metaphor with what you call the clinical imperative, at least the old
clinical imperative. You're talking about an imperative directed at
doctors. I'm not sure if that is what you mean or patients where
the imperative is to accept death as a biological fact.
Now, it seems to me what this leaves out, that gives heft to the research
imperative, is a further structural characteristic of death, that
death is uncertain but uncertain as to time when— Heidegger
worked all of that out. And behind that was Kierkegaard.
Uncertain as to time when creates a huge
opening that allows one to give the impression that one is fighting
against death. But one really creates space for the avoidance of
We send people to hospitals so often
because that is where the battleground is located and where we have got
people equipped to fight against that. And if they don't have all
the resources behind them, it's research so that if it isn't
successful with this patient, it will be successful with future
patients, all of that.
But the other deep response to death is
not simply fight but flight or avoidance. And so the military
establishment fighting against death offers an important psychological
service to patients.
Yes, it's certain but in a sense
uncertain as to time when this is going to happen. And there are still
tricks that the doctor will have and so forth, so that push in the
direction of orienting even what goes on in the clinical setting, to if
not curative efforts, delaying efforts and so forth.
Now, what this leads me to think about is
a huge shift in the religious landscape from earlier centuries, a West
shaped by a notion of a creative and nurturant God.
And purportedly the authentic life was to
be open to this deity and then two forms of reaction to this deity,
which were defined as sin, fighting against God, Luciferian revolt
against God, and avoidance of his presence. That was Philistine
flight. So you had a fight and flight response in relationship to the
One might argue that the religious
landscape of the last couple of hundred years has shifted over that the
encompassing reality is not a creative, nurturant God but what James
Joyce referred to as dio boia in "Ulysses," the hangman God,
or Camus said, "The whole world is organized by death. In the
end, we're all done in."
And then you get people like Kubler-Ross saying, "Hey, let's
be open to this. And, indeed, being open to death, finally we're
open to ourselves at our deepest level." And she gave, in
a way, Heidegger-on-the-cheap there.
But, on the other hand, the terrific
attraction of fighting against death and, further, the compounding of
that that you set up an apparatus of fighting against death that offers
people the sense that we don't get heft to face it. So avoidance,
at a deep level, helps drive and give heft to the research imperative.
The way you have written this chapter, it seems as though the research
imperative is driven by the military metaphor and then spills over
into the clinical setting when I think the existential setting is
quite the reverse for people, that it is certain but uncertain as
to time-when. And there were things to be done in the hospital
that I can't do at home. So you put them there and so forth.
So it allows one not to have to face it yet.
Now, yes, medicine ought to recover that
old, old imperative, learning how to accept finitude and death. It was
very difficult to do in a setting where one really feels that
ultimately one is facing a hangman God.
The kind of religious background, it
seems to me, would ask one to talk about the drive behind the research
imperative. That may be at a deeper level and more complicated level
of our attraction to it and the temptation to it.
DR. CALLAHAN: Well, just a quick
response. It seems to me that, even if one accepts the reality of
death, it's seemingly understandable that we would like to stall
things a bit, take our time.
But this is true of a lot of things that
are rather unpleasant. We avoid and we flee. When the doctor says,
"Well, you have to have your tooth pulled," we say,
"Well, how about next week, rather than tomorrow?" and so
forth and so on.
I think the question of the research
imperative is—the way I like to put it is whether we ultimately
believe that death is kind of a biological accident, a contingent event
that ultimately can be overcome as distinguished from simply
And it seems to me that the whole
trajectory of modern medical research has been basically to treat it as
if it were an accident. As far as I know, there are no fatal diseases
that the NIH finds acceptable. The NIH is not in favor of immortality,
at least officially, but there are no diseases that kill people that it
is prepared to tolerate. And it puts money into research, any and all
lethal diseases. So the logic of that whole movement is—
DR. MAY: Long before there was modern
research, you got Frazer and "The Golden Bough" talking in
traditional societies, a tendency to look upon death as an accident; or
in Freud, the eagerness to find out the cause of death because it is an
accident that befell somebody else and not me or you get the same thing
again in Tolstoy's "Death of Ivan Ilych."
DR. CALLAHAN: But I think with
contemporary medicine, we get a new plausibility to thinking that way.
That's the difference.
CHAIRMAN KASS: Rebecca Dresser, then
PROF. DRESSER: I share many of your
views and concerns. And I think I am so happy that you are writing
about this in your usual eloquent and elegant way.
I had two questions. One is, you alluded
to this but didn't speak to it directly. Something that I think
goes on is the equation of provision of proven health care with money
for research in the political setting and sort of public ethical
I take it you would see those both as
goods. And so then the question would be weighing and saying which
should have priority, but I wonder if you can comment on how you might
weigh those two, the provision of proven health care to more people who
don't get access to it, versus money for research that might
improve the health care we have available now, but at the same time
leaving more people without it.
And then my other question was about procedures, sort of at a practical
level. If we are to try to make progress toward revising priority-setting
in these social programs, any ideas how we might go about doing
that and the role of lobbying and all of this? Any thoughts in
DR. CALLAHAN: Well, let me begin with your second question.
I like the system used by the British government. Of course, they
have the National Health Service. It's financed by the government
and run by the government. But I gather that a part of their annual
budget-setting is that the different social areas have to compete
against each other. They have an open debate: education versus
health versus economic development.
I would love to see that. Even if done
informally, I think it would be terrific if somebody could have a great
television program getting people, leaders from the different sectors
and say, "Okay. You want more money for education. Are you
prepared to say less money for health?" That would really put
everybody on the spot. I think if we could get that in open debate, it
would be very valuable.
I think on your first question, I think one major reform that I am in
favor of in the priority-setting area and in support of research
is that we really now need to look very carefully at the economic
consequences of research.
Right now recently Medicare had some
hearings to look into new heart technologies that are going to very
radically increase the costs of treating heart disease. And the
question is, which ones should Medicare cover?
Now, typically that is done more
informally, rather than as a public debate. I would like to see that
done openly. I suppose my most radical suggestion would be that those
companies that manufacture new devices and new drugs must, at the same
time as they are doing safety studies and efficacy studies, be doing
economic studies and saying, "This is our projection of the
economic impact of doing this" and before the technology is
The typical procedure now is technologies
are developed. And they're sort of thrown out of the window. And
they say, "Okay. You health care administrators sort of deal with
it. That's not our problem." And I would want to say we
should make it their problem.
And I suppose if you want to go really
far, you would say no technology or at least to be reimbursed by the
government until it has had a very solid economic analysis and debate
and some consensus on whether this is economically worth advancing.
Now, the typical attitude of researchers
is, well, a) that's not really their problem; and, b), after a
while, we find ways to pay for things anyway. And this will hold up
Well, it probably would hold up research,
but, an issue that didn't come up at all, I happen to believe that
research is one of the main things that drives up costs, that right now
we are seeing cost inflation 10 to 15 percent a year.
The estimate is 40 to 50 percent.
It's coming from new technologies or intensified use of old
technologies. If that's the case, then I think we have to very
squarely face the problem of the research behind those technologies and
learning how better to evaluate the new technologies that come on
line. And all of that is set within the larger context of comparing
health with other things in society.
But I think more generally, it seems to me a really tragic situation
when we have — to me, the worst arguments around are those
on the part of the pharmaceutical companies that say, "We need
these high profits to save future lives" when, by God, if they
bring the price down, they could save lots of lives here and now
in Africa by making their drugs available.
So that this notion of these wonderful
lives in the future somehow comes at a discount rate for the future.
They're basically saying, "Oh, no. These lives are worth more
in the future than the present lives we could save now." And the
drug companies simply dodge that issue altogether.
CHAIRMAN KASS: Paul McHugh? I have a
long queue. I will try to get to everybody before the break.
DR. McHUGH: Well, I also want to thank
you very much and was looking forward to your presentation because I
have read your work for a long time and expected, actually, to find
just what I found this time, that I agree with so much I am surprised
at what I disagree with.
Let me develop my disagreements, at least
to the point of talking about them in practical terms. I speak now as
a person who has run a laboratory and also a person who has been a
director of a clinical academic department.
In this arena that you have laid out for
us of discussing the value and the value of research in relationship
to, is it a moral good, or is it an imperative, you first wanted to
talk about it in relationship to cost. And it's that point I want
to bring up first, that even if it's a good, just a small good,
anyone who has had any experience with research, basic science research
or clinical research, knows what the problem for our country is in
relationship to its financial support.
The growth of investigators and the
growth of reimbursement is a Malthusian problem because laboratories
grow and replicate themselves with their students in an exponential
And anyone who has run a laboratory
begins to notice that he or she has many of these wonderful
postgraduate students. They grow. They become directors of their own
departments. And they become steadily more expansive in bringing many
more opportunities to our world because of that. But tax money and
money from the country can only grow arithmetically.
So there is always going to be this
problem that you raise. Why is it that the legislature, the things
closest to the people, closest to the citizenry, will always overrule
the executive, ask for more money because more money is going to be
needed for whatever, whether it is an imperative or a good, only to do
that to our country?
On the other hand as well, it may just be
my perspective about your work and your presentation here, and it might
be just a prejudice on my part. And so we'll accept that at the
beginning, but you've got to begin somewhere with a prejudice. And
that is, how would I, who think of research as an obligation, a moral
obligation, approach that from my experience? And what is research or
why research or how to judge research are the issues before us in
relationship to is it a good or a moral obligation? And I would like,
of course, as you would, to produce, for example, one piece in this
scale, namely the achievements in research over these years.
Now, you mentioned the wonderful
achievements we have had, at least in recognizing the cause of the AIDS
epidemic and developing very effective medications for them. I lived,
like any doctor who has lived, with the AIDS epidemic from its earliest
beginnings right now, when everyone thought that nothing could be done
because it was a viral illness, and now out to a place where I am
taking care of a vary large number of people who carry the HIV virus
but are protected from the things which were discovered.
In my area of work, of course, in
psychiatry, the results have equally been remarkable, really, with
research that is sometimes developed by accident but sometimes
developed out of reason.
Those results are not just the reason for
wanting to speak about it. I also feel that both attitude and
educational communities do not thrive unless there is research going on
Again, I ran a clinical department. And
the very great importance of mingling investigators with the clinicians
was to raise the standards of care offered to the patients and very
much raise the standards of discourse amongst the clinicians about what
they were doing and why they were doing it.
Now, in psychiatry, we have this in vivid
terms described to us, demonstrated to us by the neglect of research
during the psychoanalytic era, what Ed Shorter has referred to in his
book on the history of psychiatry as the great hiatus in psychiatry
when during the psychoanalytic era, essentially no research was done
because everybody thought they knew the answer. Okay?
The result of that era was the neglect of
patients, the development of snake pits, the concentrations purely on
the worried well, and the loss of opportunities in neuroscience and
pharmacological work to do it.
And for psychiatrists like myself, I have
come to believe that there really is an absolute moral obligation to
have this in our discipline and in our departments.
And, finally, the very attitude that all
of this ultimately produces for us is an attitude of not only optimism
for the future but also an attitude of criticism for our views at the
So for all of that, I think you have laid out a very interesting point.
I have to say that there are some fairly fundamental disagreements
that I have with the conclusions you came to draw. I hope you will
accept it in —
DR. CALLAHAN: Well, I guess if you want to continue to
use the word "obligation," fine. But then I would ask
you, is the obligation to do research in your field — and
it is not a coincidence that you feel it in your field and not my
field. I feel an obligation for philosophical research probably
as strongly as in psychiatric medicine.
DR. McHUGH: Oh, I think that —
DR. CALLAHAN: I put that aside. But how
do you compare with the obligation better housing, community, national
defense, safety nets? I mean, my question is, do you want to give it
an overriding priority? Do you say that this is worth far more money
than anything else or it ought to be put on the scale and compared with
the other obligations?
DR. McHUGH: Well, you know, once again,
in a democracy, we have issues of competing obligations, competing with
values. And my assumptions are going to be that we should be trying to
meet all of those obligations as we see them and as we interpret them.
That is how I am going to do it. And
that is why I am in America, where we can earn the money to do it.
CHAIRMAN KASS: Michael Sandel?
PROF.SANDEL: Well, this follows,
Dan, on your discussion with Paul just now. I think there is something
needlessly puzzling, confusing about the pieces you present that
obstructs what I think is really a very important insight that you are
directing us toward.
So let me first say what I take to be one of the really interesting
directions that you have given us and then say what I think is puzzling
and wrong-headed about the way you have put the thesis.
By calling into question the research
imperative, you have raised a bigger question lying in the background,
which you mentioned at the beginning of your talk, about the inflation
of health as a moral and social good in our society. And Bill May gave
I thought a fascinating interpretation about the existential landscape
that might partly account for this dynamic.
There may also be — and this is just a speculation—a
shift in the moral and public culture that contributes to this.
It might be that the more reluctant we become to pass judgment or
publicly to affirm what makes lives worthy or good, the more likely
we become to affirm what we take to be all-purpose means to any
So the inflation of health may be a reflection of a non-judgmental impulse
that has entered into the moral and public culture over the past
40 years, roughly the time that you detect this inflation of health.
Health is something we in a pluralist
society can agree on because we take it to be necessary to the
realization of just about any ends that people might pursue, against
the background desire not to affirm any particular ends as aims of
And you have directed us to this whole
question. That may not be the best or the only explanation. But you
have directed us, I think rightly, to this very important phenomenon
about the inflation of health as a social and moral good.
The thesis, what makes the thesis
confusing and puzzling, even to those of us who want to sympathize with
it, is that you really, as I understand, are saying two things. First,
there is no moral obligation to pursue medical research. That seems to
me wrong. There is a moral obligation to pursue medical research.
Then you are also saying another thing,
which you take to be the same, which is medical research is not an
overriding good. It doesn't trump all other goods. It has to be
balanced. Well, that is surely right. And I suspect everyone would
agree with that, but those two claims aren't the same. It's
perfectly possible for something to be a moral obligation and still, as
Paul says, for there to be competing moral obligations.
Consider other examples outside of
medical research. There is an obligation to educate the young, to
prevent starvation, to save innocent lives where we can, to oppose
injustice, to protect the security of the country. Those are all
obligations. But to call them and to recognize them as such isn't
to say that any of them is an overriding good in the sense that its
pursuit trumps all other considerations.
So I think that you could win wide
support for your thesis that medical research is not an overriding
good. It has to be balanced against other competing goods without
making what seems to me a puzzling and unnecessary claim that it is not
a moral obligation.
DR. CALLAHAN: Well, the reason I was
trying to deal exactly with that confusion, which is the difference
between a perfect and an imperfect obligation, when people say there is
a duty to do stem cell research, they're giving it a very special
status. They are saying that somehow: a) we ought to do it; and b)
others can make a claim against us that they have a right that the duty
I would want to say most of these
obligations are rather nonspecific. Yes, we have an obligation to
raise children well. We have an obligation to our national defense and
so forth and so on.
But I guess I want to say that you
can't use the language. You can't make it a very specific kind
of obligation because you then have to say, who is the one who has to
carry it out?
If you want to say there is an obligation
to carry out research, who has the duty to do that research? Do we as
citizens have a duty that we must put up the money for it? Does the
researcher, young researcher, have a duty that he must go into the
field that will deal with XYZ problem?
It's narrow and very specifically goal-directed. The imperfect
obligation it seems to me is the more general one. So I put it
in the category of the imperfect, not the perfect.
CHAIRMAN KASS: Very quickly, Michael,
we're at the break time. Let me ask the remaining people. Dan,
are you okay for another ten minutes? I know you have a plane to
DR. CALLAHAN: Yes. Unfortunately, I
came from vacation on an island in Maine. You can't get there from
here or back to there from here without leaving soon.
CHAIRMAN KASS: Seven minutes?
DR. CALLAHAN: Yes.
CHAIRMAN KASS: We'll ask people not
to run over so the people in the queue can speak. I have Gil, Mary
Ann, Janet, and Dan Foster.
PROF. MEILAENDER: Just quickly, Dan,
I wonder if I can get you to think with us just a little bit about the
structure of your argument because it seems to me there are a couple of
aspects to it.
The one aspect that flows out of the
language of imperfect obligations is to start from goals, really,
aspirations that we seek to realize. And there are many such goals
that we think of as goods. And we often, contrary to Paul's
American optimism, we can't fulfill all of them.
That in some ways becomes a process of
political argument, then. And that's, in fact, what you have
advocated. You would like to see more overt political argument. There
is not necessarily any single answer that has to be given to how we
should weigh defense and medicine and education and so forth.
It is also true, your talk about informed
consent suggests that in terms of the means to those goals, that there
are occasions when, even when a clear good could perhaps be realized,
one has to forego it simply because the means to it is prohibited. And
that's what the principle of informed consent accomplishes.
I just wonder if that doesn't need a
little more emphasis than you gave it, in a sense. If there is not a
research imperative, to use that language, then I don't think the
primary reason is that we have a number of goals which we have to weigh
and that sometimes health care might come out not at the top.
The primary reason is that we have
accepted, and I think in some ways the research community has accepted,
the fact that there are certain things that ought not be done even to
achieve a certain kind of undisputed good. That's where you simply
can't claim that there is an imperative to do it because there is
some other imperative that really does trump it and is overriding.
So, insofar as there is not a research
imperative, it seems to me that that fact grows primarily out of
prohibited means, rather than simply out of conflicting ends or goals.
DR. CALLAHAN: Well, it seems to me that
you can say that informed consent itself is a kind of moral
imperative. And it's over against the research imperative.
I guess I want to argue that the research
imperative is troublesome when it is taken to have the power to
overcome those moral obstacles. That's when it seems to me it
causes trouble, moral trouble. And it basically says it is such a high
goal that the means don't matter, that it is worth achieving
because what you are doing is of such ultimate good.
PROF. MEILAENDER: But you've
actually got a duty of perfect obligation in the requirement that you
respect informed consent.
DR. CALLAHAN: Well, in that particular
case, because you have a trust relationship between a doctor and a
researcher and a research subject, in that case, you have a situation
of perfect obligation because it is a much more narrow contractual
PROF. MEILAENDER: Not just because
of the narrow relation. Because every human being has a right to claim
that over against potential researchers.
DR. CALLAHAN: But that's exactly the
point. They have a right to claim it against researchers because we
agree that there is a particular relationship that ought to obtain
between researcher and subject. And we, therefore, have put it into
the category of a perfect obligation; whereas, earlier, I think it was
not seen that way. That was what the whole debate was about.
CHAIRMAN KASS: Mary Ann and Janet.
PROF.GLENDON: I want to thank you
very much for giving us your expansive vision of bioethics as
including, among other things, the ethical dimensions of the choices we
make about what social goods to pursue, and I just want to see if I can
make a little extension of your argument. You have told us that
research is a good to be pursued among other goods and that there are
difficult problems of choosing among those goods.
The extension I would like to make is
that in setting priorities among those goods, if you don't set them
thoughtfully, and after deliberation, then they are going to be set by
default or by the influence of special interests. Would you accept
DR. CALLAHAN: Oh, absolutely.
PROF.GLENDON: And so some of the
references you made to what happens in other countries suggests that
there is more of a process of deliberation and balancing in some other
countries than there is here within the democratic forum.
Of course, a cynical side of me says,
"Well, yes, European countries can, just as they do with defense
spending, let us spend the big bucks on medical research. And then
they have the luxury of democratic deliberation about education,"
Nevertheless, the question I come to is,
why do you think it is that it is so difficult in these discussions to
get a public debate or even a legislative debate of the type that you
mentioned happens in England, a discussion of the pros and cons of
pursuing the various good things in a world of scarcity?
DR. CALLAHAN: Well, to me the great
difference between Europe and the United States is, at least as far as
health is concerned and a lot of welfare programs, the government
actually runs everything.
They either control the financing or
financing and delivery as well. And that means they have to work
within a closed budget. And once you're forced to work within a
closed budget, you then are forced to deal with priorities. You're
then forced to deal with rationing, saying some things are
comparatively more or less important.
By virtue of our strange mixture of the
public and the private, we have no way to have a rational discussion
because you have so many different actors with different rules of the
I mean, the whole private sector can go
out and develop all sorts of things medically and technologically,
which are absolutely beyond the control of any government or any
regulation; e.g., private stem cell research, private human cloning if
Under those circumstances, it is very
hard to set a budget. It is very hard to have a rational discussion.
And it is very hard to have any kind of unified outlook that enables
you to set priorities.
Now, the National Institutes of Health
has set a priority discussion and for a very simple reason. They have
to live within a budget. They get a certain amount of money. And they
then have to decide how to spend that money. So priorities are forced
upon them. But we don't have a country that is run like the
National Institutes of Health.
So that's why I happen to think
government is a good thing in this area because the market does not
enforce discipline. The market forces profligacy; whereas, it is the
government's and closed budgets for discipline and
priority-setting. We don't have it.
CHAIRMAN KASS: Janet Rowley and Dan
DR. ROWLEY: Well, I appreciate the
thoughtfulness with which you have prepared the material. I have to
say that I have very serious reservations, some of which were already
expressed in a sense by Paul.
To me, the use of research imperative
implies that there is some direction of this imperative and an
agreement to its goals, even unstated. And it seems to me this does
not reflect the real world of science or biomedical science as I have
lived it for over 40 years.
Your statement just now about who is
going to tell a scientist to do stem cell research, that is not the way
science is carried out at all. It is true it is carried out that way
in companies, but in the academic world, which is where fundamental
research is really flourishing, the scientists are the ones who have
the intellectual curiosity and the creativity to say, "Isn't
this an interesting question?" and to follow up on it.
I think Liz Blackburn is a wonderful
example of somebody who was studying how the ends of chromosomes in
yeast were formed and maintained and discovered the enzyme telomerase.
And now this turns out to be a very important enzyme in cancer. But
who would have expected research in yeast to then have that kind of
So there is no direction necessarily in
medical research. It is what scientists find interesting. Now, it is
absolutely true that many of the interests are channeled by research
questions that are considered to be very important or research areas
that are the hot topics. And if you are a young scientist, that is
what you want to do because that is where the action is.
But I just don't think that there is
a research imperative. So I think that your example of NIH and their
following many different ways of Parkinson's, in part, that is
because there is no good answer. So you try all of the options, hoping
that one or a combination of options will really give you greater
insight that will allow you, then, the next step to go beyond.
And I realize you have a plane to catch, but I want to come back to
Alfonso's question of non-therapeutic research on children.
I want to point out that our understanding now of how babies learn,
of how infants learn, of how different aspects of the nervous system
mature at different stages and allow infants to gradually respond
and observe, is all done by research, non-therapeutic research.
And it has led to enormous changes on how we look on babies and
how we look on intelligence.
So you have to put these in the context
of what it is that you are doing, what is the goal. It may not benefit
that baby, but it sure is going to benefit babies down the line.
CHAIRMAN KASS: Dan Foster. Why
don't we take both questions, Dan, and then we'll let you
DR. FOSTER: Well, I will give it to you
that the Council seems to have their loquacious genes fully on this
morning. As a consequence, I am going to bring it back towards the
mean by depriving the Council of my remarks, which were really of
eternal significance, but I am not going to—
CHAIRMAN KASS: Do you want to follow
that? Why don't you respond to Janet?
DR. CALLAHAN: Okay. I certainly
wasn't claiming that the research imperative has goals. The
research imperative in its benign sense I simply mean has a very strong
sense within the scientific community supported by the American public
that research is a good thing that ought to go forward. And we ought
to put money into it. And that's what I mean by the imperative,
that this is a valuable thing that should be carried out. That's
The goals are all over the place. People
have different goals at different levels and so forth, so on. And, of
course, you are someone who spoke for the research imperative. Your
scientific colleague said exactly sort of what I was saying.
CHAIRMAN KASS: Council members, we have
run over. We have a guest waiting to speak. Let's return at five
minutes of 11:00. Dan Callahan, thank you very much for being with
us. We're adjourned for 15 minutes.
(Whereupon, the foregoing matter went off the record at 10:41 a.m.
and went back on the record at 10:58 a.m.)
SESSION 2: STEM
CELL RESEARCH: CURRENT ETHICAL LITERATURE
CHAIRMAN KASS: This is the second session, "Stem Cell Research:
Current Ethical Literature." As Council members surely recall,
the formation of this council was connected to President Bush's
decision announced in his address to the nation in August of 2001
to permit for the first time the use of federal funds to support
research on human embryonic stem cells, this despite the existence
of congressional statute, the Dickey-Wicker Amendment that prohibited
the use of federal funds for research in which a human embryo or
embryos are destroyed, discarded, or knowingly subjected to injury
or death, risks of injury or death, greater than that allowed for
research on fetuses in utero.
Among its other functions, this Council
was charged with monitoring stem cell research; that is, following and
keep abreast of all developments, scientific, medical, ethical, and
legal, in this exciting area of research, embryonic and adult. The
rest of today's meeting is given over entirely to helping us
fulfill that charge.
We are following and monitoring
developments in the ethical argumentations on stem cell research,
developments in the basic scientific research and clinical application,
developments in the state laws, as these have taken place over the past
two years under the current federal policy.
To aid us in these monitoring tasks, we
have commissioned seven review papers: one on recent developments of
the discussions of the ethics of stem cell research, five on recent
scientific and clinical developments in five separate areas of
embryonic and adult stem cell research, one on recent developments in
state law regarding stem cell research.
The ethics review paper was prepared by
our guest for this session, Professor Paul Lauritzen, who is professor
of the Department of Religious Studies and the director of the Program
of Applied Ethics at John Carroll University in Cleveland. Speaking
only for myself, I would note with gratitude that Professor Lauritzen
has tried in his paper to expand our horizon of the relevant ethical
issues to include matters beyond the one that has so preoccupied us,
namely the important issue of the moral status of the embryo.
I would like to welcome Professor
Lauritzen, who will offer a beginning presentation, after which both
the presentation and his paper will be open for our discussion. Thank
you very much for joining us. We look forward to hearing from you.
DR. LAURITZEN: Thank you.
Let me begin by saying I made the mistake
of sending the slide show ahead of time and got a call from Dean Clancy
last night wondering what the slide show and my presentation had to do
with my report because I had decided not to simply summarize my report
but to just highlight a few themes in my presentation.
And I suspect that Dean is a better and
keener observer of human nature because he pointed out that perhaps not
everyone would have read the report as carefully as I might have
assumed. But I wasn't going to write another presentation at nine
o'clock last night. And so I am going to give the one I wrote,
which really takes some themes of my report and tries to highlight them
by way of some additional data. Mostly I am just going to read this.
Several people who have read the draft of
my report have commented that for someone who argues that we should
move beyond the debates about embryos and the status of the embryo, I
spend a lot of time in the report talking about embryos.
At the risk of inviting that objection
today, I want to begin with of slide that reproduces data reported
recently from a study conducted jointly by the Society of Assisted
Reproductive Technology and the RAND Corporation on the number and
dispositions of frozen embryos in the country. Forgive me if you have
already considered this data, but it wasn't clear to me whether you
As you can see from the slide maybe and
based on a survey of 340 of the 430 assisted reproductive technology
practices in the United States, the documented number of embryos in
frozen storage as of April 11, 2002 is approximately 400,000.
Moreover, the study was able to document
the use to which these frozen embryos were designated by the IVF
couples from whom they came. Indeed, one point of the study was to
determine how many frozen embryos are, in fact, available for use in
the derivation of stem cell lines.
Despite the fact that many advocates of stem cell research call for
deriving stem cells from embryos left over from IVF procedures,
the authors of the study contend that so-called "spare embryos"
are not a ready source of stem cell lines.
Of the nearly 400,000 frozen embryos in
storage, apparently only 11,000 are available for possible use in
deriving stem cells. Although this seems like a large number of
embryos, according to the authors, in fact, it is not. And they break
down that 11,000 along these lines.
Of those 11,000 or approximately 11,000,
only 65 percent will survive the thawing process, leaving roughly 7,000
embryos. Only 25 percent of that 7,000 will develop to the blastocyst
stage, leaving roughly 2,000 blastocysts. And only 15 percent of those
blastocysts will yield viable cell lines, leaving roughly 275 cell
According to this study, then, despite
the large number of embryos frozen in this country, the number of
potential stem cell lines available from their use is relatively small.
This is clearly an important study. For
one thing, it gives empirical grounding to the claim that we can derive
stem cell lines from frozen embryos. It is less likely to be widely
My reason for beginning with it, however,
is quite different. I wish to highlight not the number of frozen
embryos cited in the study but, rather, the date of the study's
publication, namely May 2003.
As the study points out, the first live birth in this country
from a cryo-preserved embryo was in 1986. That means for nearly
20 years, we have had almost no idea of the scope of embryo cryo-preservation
in this country. Let me make two observations about this fact.
First, I believe it supports my claim
that talk about respecting the embryo from conception is frequently
more rhetorical than anything else. If the early embryo is really to
be treated as a being who deserves serious respect, you would think
that we would at least know how many embryos are routinely frozen,
discarded, or otherwise lost through IVF. Not to put too sharp a point
on it, but if each embryo were equivalent in value to a dollar bill, we
would have lost track of nearly half a million dollars.
Second, the fact that until recently we
knew almost nothing about the numbers or the dispositions of frozen
embryos highlights just how unregulated the world of reproductive
As this Council knows well and as the staff working paper to be discussed
tomorrow highlights, the world of reproductive medicine is almost
entirely unregulated. Cryo-preservation of embryos is just one
of the many developments in reproductive medicine that has been
introduced as therapy without any sort of clinical trials and without
any real oversight. The significance of this fact in relation to
stem cell research is that we have in reproductive medicine a model
for what happens when commerce is wedded to desperation, when research
is privatized, and when there is essentially no regulation.
More than one commentator has invoked the
image of the Wild West to capture this scene. The image strikes me as
particularly apt, not least because the wild West was notoriously
dangerous, at least as it has been conceived in the popular
There are clear dangers in the
unregulated world of reproductive medicine. I know there is some
controversy about this point, but consider the report in the New
England Journal of Medicine last year on the risks of major defects
after ICSI and in vitro fertilization.
According to this study, infants
conceived of reproductive technology were more than twice as likely as
naturally conceived infants to have major birth defects diagnosed
during the first year of life and were also more likely to have
multiple major defects. These were the odds ratios after the numbers
were adjusted for maternal age, multiple births, and other factors that
might have skewed the data upward.
Moreover, the increased risks were not
confined to just one organ system. They were found in cardiovascular,
urogenital, musculoskeletal, and gastrointestinal systems.
Again, my point is not to focus on
specific problems with reproductive medicine, as it is currently
practiced, but to highlight a pattern. Just as opposition to embryo
research has led to the privatization of work on in vitro
fertilization, with virtually no oversight or regulation of IVF, so,
too, has it led to the privatization of stem cell research with similar
This is one reason I have noted the
relation of IVF and stem cell research in my report. The other is that
I do not think we have fully appreciated the deep tensions between the
widespread acceptance of IVF and a widespread profession of respect for
the early embryos.
A foolish consistency may be the
hobgoblin of little minds. And Emerson may be right that such a
consistency is adored by statesmen, philosophers, and divines. But
consistency in ethics is rarely foolish.
I have no quarrel with Emerson's advice to speak your mind forcefully
today, even if it flatly contradicts what you thought and said yesterday.
My concern is that we speak out of both sides of our mouths simultaneously
when we say that destroying an embryo is killing a person or that,
indeed, the early embryo deserves profound respect and also say
or act as if discarding embryos in IVF is non-problematic.
I tried to illustrate this point in my
report by drawing attention to the cartoon comparing reactions to a
stem cell clinic and an abortion clinic and then asking the reader to
imagine that an IVF clinic is substituted for the stem cell clinic.
Here is the cartoon.
As you can see, the cartoon depicts protesters in front of a stem
cell research lab, condemning those who worked there as being anti-life.
Down the street at the abortion clinic, the workers are noting how
quiet things have gotten at the facility since the stem cell lab
The point of the cartoon, of course, is that opposition to stem cell
research appears to be almost as passionate as opposition to abortion
and that there is perhaps an irony in the fact that pro-life advocates,
thus, appear to be committed to demonstrating against research being
done to find treatments for Alzheimer's, Parkinson's, and
other devastating illnesses.
Now, try to imagine protesters standing
outside an IVF clinic or, even better, outside maternity wings,
condemning couples who use IVF as murderers or at least complicit with
murder. It is almost impossible to imagine this scene. And it is
worth asking why.
If the early embryo is fully a person,
shouldn't we condemn IVF and work to prohibit it? Is condemning
stem cell research but accepting IVF not inconsistent?
Of course, one response to this alleged
inconsistency would be to say that we should, in fact, be consistent in
trying to prohibit both IVF and embryonic stem cell research. I do not
subscribe to that position myself, nor do I think it is a politically
viable option. But it would at least be consistent.
Notice, however, that a ban on embryonic
stem cell research will not eliminate the many issues raised by the
prospect of regenerative medicine. And that is another theme from my
report that I wish to highlight.
Although the ethics debate has mostly
focused on the status of the early embryo and has, therefore, tended
almost exclusively to issues raised by embryonic stem cell research, we
need to take a closer look at issues raised by the prospect of adult
stem cell research as well.
I have discussed some of these issues in my report. And I merely
list some of them here. They include issues of social justice;
of commodification or of commerce; issues about the conception of
nature and what nature might mean; issues about human embodiment;
issues raised by the erosion of species boundaries, so-called hybridization;
and issues for implications of personal identity and moral responsibility.
Worries about eroding the boundaries
among species, about destabilizing the concept of nature, and about
treating human bodies merely instrumentally are related.
I believe that this cluster of issues
deserves special attention going forward. And, again, my point is that
it's a cluster that is raised for adult stem cell research as well
as for embryonic. So that while we ought to continue debating the
status of the embryo, we also ought to move beyond that debate to focus
on these other issues as well.
I also think that we might do well, at
least initially, to think about these issues outside of the contested
question of human nature. For example, I wonder whether there is some
merit in considering the pervasive human manipulation of nonhuman
For example, it may be useful to take as more than a curiosity
the so-called transgenic art of Eduardo Kac. Several years ago
Kac made headlines around the world with his public art intervention
that included Alba, the green fluorescent protein bunny.
As you may recall, Alba was an albino
rabbit that glowed green under certain light because it had been
genetically altered and carried a gene from a jellyfish.
Kac defined transgenic art as "a new
art form based on the use of genetic engineering to transfer natural or
synthetic genes to an organism to create new living beings." And
here is a slide of Kac with Alba.
Many people were outraged at Kac's
creation. And many dismissed his work as a publicity stunt. But, in
fact, part of the point of the Alba project was to generate a public
conversation on the cultural and ethical implications of genetic
According to Kac, "The creation of a
chimeric animal forces us to examine notions of normalcy,
heterogeneity, purity, hybridity, and otherness." Here is Alba
The claim that I just read is a bit too jargon-filled for my taste.
That he did not use "alterity," instead of "otherness,"
is astonishing. But Kac's work invites us to reflect on the
implications of turning nonhuman animals into artifacts. Of course,
we have been doing that for a very long time. Still, it's worth
thinking carefully about our reaction to the creation of Alba.
It is worth asking whether our reaction
to Alba is different from our reaction to, say, the creation of the
Harvard oncomouse and if so, why.
I began my written report with a passage
from C. S. Lewis. And so it's perhaps fitting to draw my
presentation to a close with another passage from the "Abolition
of Man." Lewis writes, "Now, I take it when we understand a
thing analytically and then dominate it and use it for our own
convenience, we reduce it to the level of 'nature' in the sense
that we suspend our judgments of value about it; ignore its final
cause, if any; and treat it in terms of quantity. The repression of
elements in what would otherwise be our total reaction to it is
sometimes very noticeable and even painful. Something has to be
overcome before we can cut up a dead man or a live animal in a
Although it is perhaps justifiable to
reduce the world of nature to mere nature, as Lewis puts it, I am
inclined to agree with him that something is lost when we do so.
When I reread the "Abolition of
Man" in working on this presentation, I was struck by the fact
that the sort of dynamic Lewis describes here is very close to that
recorded in Jonathan Glover's impressive work "Humanity, A
Moral History of the 20th Century."
Glover writes, "Human responses are
the core of the humanity which contracts within humanity. They are
widely distributed. But to identify them with humanity is only partly
an empirical claim. It remains also partly an aspiration."
As Glover powerfully argues, morality
must be rooted in human needs and values. And these needs and values
are both rooted in human nature and grounded in human aspiration.
As we move forward to wrestle with issues
of stem cell research, we ought to be conscious of what is at stake in
the possibility of redefining either our natures or our aspirations,
for, as Glover makes clear, the inhumanity of humans is a frightening
and all too familiar thing.
CHAIRMAN KASS: Thank you very much. I
assume, Professor Lauritzen, that both the presentation and the paper
are fair game in the discussion.
DR. LAURITZEN: Sure, absolutely.
CHAIRMAN KASS: Does someone want to
start? Jim Wilson, please?
PROF. WILSON: I wanted to be clear, Professor
Lauritzen, in your views. You displayed the differences in the
cumulative prevalence of diagnosed major birth defects singled in
infants resulting either from natural conception or IVF and pointed
out that the data suggest that that incidence is roughly twice as
high with IVF as it is with natural conception.
Do you conclude from that that we should
be opposed to IVF?
DR. LAURITZEN: No. I mean, first let me
say that data is somewhat controversial, I gather, in that there are
other studies that don't show that kind of risk. Rather, my point
is that we don't have the data. I mean, that is part of the issue
I have to go back and look, but I think
that data actually came from western Australia. So it doesn't even
reflect data in this country. I think that is right. I would have to
go back and look.
The point is we are not tracking the
potential health consequences of in vitro fertilization in
anything like the way we should. And it seems to me part of the reason
is that this is an area, reproductive medicine is, which has almost no
oversight. And it obviously also has almost no federal funding.
Had there been federal funding, there
might have been more oversight. But even apart from the issue of
federal funding, it is an issue of one area of medicine where the move
from a novel idea, like intracytoplasmic sperm injection, moves very
quickly into clinical practice when it is really a therapeutic modality
that has been largely untested.
And then it is offered as a therapy when
it is really, in fact, experimental and not tracked in any significant
way. So we don't know, long term, what the genuine health risks
So that one of the issues here I think a staff working paper—the Council may have flagged that. The little regulation there
is tends to be sort of consumer protection regulation so that prospective
couples using IVF should be protected in some way, get adequate
information about success rates of clinics and things of that sort
when, in fact, there may be larger public health issues about the
long-term implications for women and children, for the women undergoing
high-dose hormones to induce hyperovulation and for the children
to see if there are long-term health consequences or, for that matter,
PROF. WILSON: Could I make one follow-up?
DR. LAURITZEN: Please?
PROF. WILSON: I certainly agree with you about
the unfortunate lack of longitudinal research that will track babies
from these processes. My view is that we should encourage this.
But let's suppose there is this
longitudinal research to the extent that we can. And let's
suppose, in effect, it replicates the data you have presented for the
United States over the long term. Would such data lead you to question
the value of IVF?
DR. LAURITZEN: Well, I think it raises certainly issues about
which there is a significant literature in the philosophical side
of things about so-called harm to future children.
And there are folks like John Robertson
who have argued a variation of the point that essentially you can't
harm by bringing that into existence because without the technology,
this child would not exist or the adults that might come from the
So that even if it turned out that there
were significant health risks, much higher rates of cancer in children,
in vitro fertilization procedures, that you haven't, in
fact, harmed those children because they wouldn't have existed
My own view is that that is not the right
approach to frame it entirely in terms of harm to the specific child
and compare that to nonexistence, which obviously is a difficult
So I'm dodging your specific
question, I think, a bit except to say we ought to sort through it. I
mean, obviously there is no regulation preventing couples to reproduce
who are carriers of known genetic effects with a certain percentage
likelihood of problems for their children.
So I am not saying necessarily that that
would mean we should shut down IVF programs, but it's information
we need. It's, frankly, information that ought to be a kind of
obviously a fairly detailed part of the informed consent process for
couples considering using IVF. And I don't think that any of those
things are true now.
PROF.WILSON: Thank you.
CHAIRMAN KASS: Janet Rowley?
DR. ROWLEY: I would like to follow up on both your comment and
then Jim's question because I think that it is extraordinarily
important that we emphasize, as we have in previous Council meetings
and in the document we have under consideration, the lack of reliable
long-term data on the outcome of IVF and ICSI and other procedures.
I think we have to emphasize that that is
because there has been no money available to gather such data. And
such data is going to be very, very costly to obtain.
I know just in terms of our own research projects of tracking
down cancer patients and what's the long-term outcome of their
treatment, that to try to find these individuals is extremely difficult.
The laws have just been changed, the
Privacy Act. So I would think that before you can contact any
individual, you have to go to the clinic. The clinic has to go to that
patient and say that they're trying to collect information and
would the patient be willing to provide that information before you can
even begin the collection process.
So this is no small task that we have set and that apparently CDC is
embarking on because it is a two or a three-stage process before
you get it.
And you say research is privatized. This
is the only area of medicine in which research is privatized. And,
again, that leads to the problems that we are currently facing.
CHAIRMAN KASS: Thank you.
DR. LAURITZEN: Can I just make one
observation on that?
CHAIRMAN KASS: Please?
DR. LAURITZEN: I think there is going to
be that difficulty of getting consent. There is also I think in the
case of reproductive medicine the additional difficulty that the
prospective parents in giving that consent would have to be
acknowledging in a way that is different from cancer, where the
expectation is that there is going to be certain morbidity and
Well, the assumption that most infertile couples have is that
if we go forward with this, we are going to have a healthy child
and there aren't going to be long-term problems. So I think
to some degree, reproductive docs are going to be a bit reluctant
to raise the specter of potential long-term harms going in.
DR. ROWLEY: Can I make two comments?
One, my impression is that most infertile couples who live in states
where there is no insurance and, therefore, they are paying 30 to 50
thousand dollars for this procedure are pretty sophisticated and, as a
consequence, know the risks that they face.
What we are trying to get is data on children 5 or 10 years old or older
now and what is their status so that the individuals involved in
IVF 5, 10, or 15 years ago gave no such consent for this follow-up
information. And that is the first step of running a survey, to
get their permission to even contact them to get the information.
CHAIRMAN KASS: Thank you.
Just as one fact, I understand that the
NIH is gearing up for a massive study on children, a prospective
study. And it might be of interest to us to explore the ways in which
some of the things that we would be interested in might be incorporated
in the planning of this study as it goes forward. But that's for a
I had myself in the queue. Let me deal
with things in the paper, rather than in the presentation. A couple of
comments and then a question. First, I guess it's fair to say you
criticize what you take to be the excessively individualistic treatment
of the ethical questions, especially as they are concerned with the
matters of the embryo or even the language of rights in this area.
I would simply observe that in questions
of life and death, which, after all, are things that befall
individuals, a certain individualistic focus ought not to be pejorative
but is somehow necessary, that there might be other kinds of goods that
are here that don't concern individuals, but the people who care
about whether or not embryonic life is destroyed will, in fact, care
about the death of individuals. And that can't be avoided.
Whenever you are dealing with a question of death, you can't sort
of avoid that. That would be an observation. I don't imagine you
would dissent from it. I would take that as a friendly amendment.
Second, on the questions of economics and
commerce, it seems to me there are three things potentially that are
bothering you here. One is the notion of commerce in the body
altogether. Second are questions having to do with distributive
justice and unequal access to the benefits that are available. And
third is a kind of faint whiff of a dislike of profit, although it
doesn't come out very strongly.
These are questions that have come up
around the table before. And I am sometimes sympathetic to these
arguments, but reading your paper made me less so for these reasons.
It seemed to me that the mere assertion
of inequality is not ipso facto a demonstration of injustice, though
the question of equal access is important. The remarks about the truck
company said, after all, why should they be able to profit from the
embryos when the people whose embryos they were don't? The answer
to that is they have mixed their labor with it extracting the stem
cells. The embryos as such are not by themselves valuable until
somebody has done something to them. So at least there is a prima
facie case for saying that there is some claim for profit.
And then on the question of commerce in
the body, I am not so sure whether it is the money changing hands that
bothers us as much as it is sort of the free alienation of body parts.
We don't object to people selling their labor, although people have
done so. And, therefore, I wonder whether what might bother us is even—if there was something that was somehow disquieting simply about the
giving of an embryo for research, we would be bothered by the fact that
someone might be paid for it. I think the commercial aspect of this is
a sign that there is something beneath the commerce that is troubling
I have got more, but that is too much.
Let me stop. I would be interested in your comment, really, on this
nest of the economic questions. It's not the first time that we
have taken them up, but we haven't taken up in the stem cell
context. And I think it would be useful to spend a few minutes on
DR. LAURITZEN: Sure. Well, my first
reaction is to say that I'm not sure your nose for the smell of the
concern about profit is on target. I would be happy to accept a larger
stipend for my work here. So we can talk about that afterwards.
CHAIRMAN KASS: People make exceptions to
their own case.
DR. LAURITZEN: I mean, I do think
it's a fair observation. And it depends, I suppose. One point
about the embryo, the difference between the researcher who mixes his
or her labor to produce the product and the embryo is going to depend,
of course, what stage we're talking about with embryo research.
And, arguably, women have mixed the labor of their body in producing
either the eggs and going through the hormone regimens to generate
the embryos or if we're talking about an embryo then subsequently
brought to term, obviously there is the work of gestation, though
I don't like that kind of language particularly. And that may
just be my anti-profit convictions of some sort.
As you were talking, I was trying to
think of some comparisons. Here I am just trying to mine an intuition
in a way that as I thought about surrogacy, for example, in the past, I
have always found the prospect of surrogacy more troubling in a case
where there is a paid surrogate than in a case where there might be a
family member who has stepped forward to carry a child.
So I am not sure quite how you put the
point, but there is something about the commercial aspect of paying the
surrogate that seems problematic in a way that a sister or a cousin or
something who might offer to gestate a child doesn't invoke. So I
am not sure—
CHAIRMAN KASS: Why is that?
DR. LAURITZEN: Yes. I think it is a
good question. In part—well, I'm not sure. Let me say that my
inclination at this point is to draw on the story of the minister who
had gone to seminary and had training in doing sermons, which I
haven't had the benefit of. This guy was giving a talk at the
university. And he had a written text. I went up afterwards. In the
margin throughout, there were a couple of marginal notes that were
So I was puzzled by this. And I asked him what they referred
to. And he said, "Pound the pulpit." So he always pounded
the pulpit at the weakest point in his argument. And I'm inclined
to pound the pulpit here.
I'm not sure that's the best
response, but it may be all I can come up with right now.
CHAIRMAN KASS: Gil Meilaender and
PROF. MEILAENDER: At the risk of
dismaying our chairman, although perhaps not to your surprise, I want
to come to a question about the structure of your paper, the way you
work it out, where you suggest that there has been too much attention
paid to the embryo status question and not enough to this other range
of things. Leon congratulated you on that, and I want to worry about
that a little bit. Well, okay, Leon, I am just having a little fun
I haven't at the moment come up with
a great analogy, but if in the instance of warfare, for instance, we
were using all sorts of very large, powerful weapons with very little
concern about the collateral damage that came to people apart from the
military targets themselves and I was worried about that and you said,
"Well, yeah, but let's don't focus too much on that.
Let's worry about the fact that we are probably stereotyping our
enemies when we think we can do this to them," that we may coarsen
our sensibilities in pursuing warfare in this way, that acquiescing too
quickly in this may keep us from developing other better kinds of
weapons and those are the things that we really ought to worry about
while proceeding to bombing the living daylights out of them in this
way, it would strike me that—and you will recognize that this is a
version of a different formulation—that would be an argument for
sort of unlimited casualties always with tears.
We should always feel bad about these
casualties because of all of these other reasons involved while we
continue to inflict them. It seems to me that that is sort of the
structure of your argument. And while I don't wish to deny that
one or another of the issues that you raise might be important to think
about, indeed, that they are all important and that taken as a package,
they bear considerable weight, I can't imagine that we would worry
so much about them if we had entirely set aside the issue that you say
we have worried too much about, namely what we ought to think about the
And so I guess what I want to know is,
will you accept my description of the structure of your argument as
sort of unlimited stem cell research always with tears? And if you
will, are you really prepared to defend that kind of moral argument?
DR. LAURITZEN: What you need to know is
that Gil has accused me of this once before. I think I denied it in
that context and will probably deny it again here.
It seems to me that in urging in some way
the expansion of the moral discussion, I don't want to suggest that
we not attend to the status of the embryo. There may be a way in which
I put my point too rhetorically sharply to try to suggest that.
So I don't want to suggest that we
stop talking about the embryos, the status of the embryo. We are going
to have sharp disagreements around the room. And there is a sense in
which what I said in the report was suggestive of the fact that, look,
it's hopeless. We're never going to make any progress on
this. So let's just stop talking about it.
And I may have come close to saying
something like that. I didn't mean to. After all, we have made
progress on moral status questions in the past. I mean, we certainly
in this country have made progress with regard to African American
status and the status of women historically.
I think there is some reason to suggest
that we have made at least some progress with regard to thinking about
the status of nonhuman animals. So I think their status questions are
important and we should continue to talk about them.
But my point, instead—and I suppose
this is something of a structural issue. My point is to say, why
don't we bracket for a moment that which divides us and focus on
that about which we are united? There may not be universal agreement
about those thing we're united about, but I think we would find
more commonality around the table if we started focusing on some of the
issues that I identified that apply to both embryonic stem cell
research and adult stem cell research, which might, in fact, lead us to
hesitate to do embryonic stem cell research, not because we share the
conviction that their early embryo is a person with a full moral status
but because we agree on a cluster of other values.
So that I don't think I am
necessarily suggesting that we continue doing, necessarily doing,
embryonic stem cell research and just wringing our hands about it,
though I do say in the end, just to try to weigh my own position out,
in fairness, that I think it is justified to go forward with both
embryonic stem cell research and adult stem cell research in a
carefully regulated way.
PROF. MEILAENDER: As long as
we're haunted by it. Is that the language?
DR. LAURITZEN: Yes, that we will be
haunted by it, we will be wringing our hands about it and I will be
crying and tearful. But I could easily be persuaded that part of the
regulation would be, for example, moratorium on embryonic stem cell
research until we do more adult stem cell work but, even there, be
awfully careful about how we are doing it.
So I don't entirely accept your
characterization, but it's not entirely unfair either.
CHAIRMAN KASS: I have Alfonso. Bill, do
you want on this point or—
DR. MAY: Not directly.
CHAIRMAN KASS: Okay. Then I'll put
you on the queue. Alfonso?
DR.GÓMEZ-LOBO: I'm going to refer
to the paper as well, but I'll preface that by saying that,
unfortunately, it seems to me on certain moral issues, we just have to
have sharp disagreements, the idea focusing on what we have in common.
That papers over the deeper question, will it not serve the American
I read your paper over a couple of times
because I don't see in the paper the presentation of the
arguments. I see descriptions. I see appeals. But, for instance, to
put embryonic stem cell research and adult stem cell research as
closely connected it seems to be obscures an argument that some of us
have against one and in favor of the other. That's why, for
instance, I would say I am all for stem cell research.
My only concern, my single concern is that we not use, destroy,
or instrumentalize human beings to do that. That is why, for instance,
one of the great challenges I see for the scientist is just try
to figure out how to get those stem cells without destroying the
It's a challenge from someone who is
viewing this from the point of view of moral philosophy. And
that's why I am very interested in your arguments for your final
statement that you think that an embryo is not a person.
And just to go out on a limb, let me give
you an argument. And you please try to refute it. I would say the
following. I have a twin brother. I was conceived 64 years ago. I
got my genetic inheritance from my father presumably at the time.
Genetically I am the same individual I
was back then. And spatio-temporally also, I have the relationship of
saying this with that early embryo. If you pursue me in time and
space, it turns out that I am the same individual.
And then my second premise, well, I am a
person now. I am a human being now, and I should be respected now.
Why should I not have been respected then?
DR. LAURITZEN: Well, a couple of things,
first about your earlier point. I guess what I want to press you on is
why your only concern about stem cell research, adult or embryonic, is
that it may destroy human beings.
I think there is certainly a range of
issues that I think have come up in other Council deliberations that I
would urge you to take up going forward about the social implications
of profoundly enhancing human characteristics in various ways, perhaps
radically increasing the human life span. Whether that is realistic or
not is another matter. But if, in fact, it is, it seems to me to raise
important moral issues.
Already this morning we have had some
discussion. Dan talked about Harold Varmus' concern about access
to therapies. All of those issues are I think terribly pressing moral
ones. And they don't have anything at all to do with destroying
embryos or necessarily destroying human persons.
So in a way, that's what I mean to
say. I think we would have a very interesting conversation about that
when we didn't talk about embryos at all.
The second part has to do with embryos. There is some material
in the report that I think is at least intriguing to talk about
the developmental potential of that early embryo as if it was, in
effect, a kind of little homunculus that just is going to develop
in a set way is just biologically inaccurate, that it's the
interaction of a complex set of systems that in your case, in fact,
led to an arc that 64 years later is you. And you can trace back
that arc. But that doesn't mean that there was the potential
in that early embryo or only one natural kind of teleology that
leads to you.
In a different environment, it would have
led to some other. Well, if we derive stem cells and then grow an
organ from them, say, well, we say that heart, we can trace back to
that embryo that was then disaggregated to produce the stem cells.
I didn't jot down everything you said but genetic relation,
spatio-temporal relations, you could trace the same arc backwards
if the environment were such that it produced something else.
This is a fairly common argument, but I
don't find it compelling.
CHAIRMAN KASS: I'll give you one
more round briefly. You see the incorrigibility of this. One more
DR.GÓMEZ-LOBO: I'll follow the
rules. A heart is a part of an organism. It's not a complete
organism. And what matters, really, is the entity through time of the
complete organism, it seems to me.
CHAIRMAN KASS: Michael Sandel, Bill May,
and then Rebecca is what I have.
PROF.SANDEL: I liked your paper
very much. I was just going to offer a brief reply that you might
offer to Leon, but while I'm at it, I could also offer you a brief
reply to Alfonso.
DR. LAURITZEN: That would be great.
PROF.SANDEL: That would be that
it's also true that every oak tree was once an acorn, but it
doesn't follow that acorns are oak trees or that we should regard
the loss of an oak tree as the same as the loss of an acorn.
The reply to Leon, do you want to hear
DR. LAURITZEN: Absolutely, and anybody
PROF.SANDEL: The reply to Leon
might be that the reason that commerce in the body is objectionable in
a way that is independent from the giving, as in your surrogacy case,
the reason there may be a difference is that to support your intuition
that there is something objectionable to commercial surrogacy that
might not be the case with gifted surrogacy, say, of a sister, for
example, that the ground for that intuition might be that the body
isn't private property, open to any use that we may desire or
devise, but, instead, is a gift with a certain telos. This should
appeal to Leon, in fact, a natural telos, which means that it's not
open to use for other lesser purposes, like making money.
So that in the case of commercial
surrogacy, this would be a case of using the body or selling oocytes,
for example. This would be a case of using the body for a purpose at
odds with its telos, namely making money.
But to donate or to gift without any
commercial transaction for one's sister, say, to carry her child
wouldn't be objectionable in the same way. It would still be in
accord with the natural telos of the body.
CHAIRMAN KASS: I won't say more than
it's an odd natural telos to say that one woman's uterus is to
carry the child of someone else, even out of love. I mean, that's
a new kind of natural teleology. We would have to argue about it.
PROF.SANDEL: But you would agree,
wouldn't you, that it's in line with the natural purpose in a
way that selling it to make money clearly isn't?
CHAIRMAN KASS: No. It's a nice
try. But I think that if there weren't something disquieting about
the thing itself, the fact that money changed hands wouldn't even
occur. The same thing is true about prostitution. The same thing is
true about a whole range of things.
I am not saying it is wrong, but we are
not, most of us are not, upset with the fact that people sell their
labor. And the money changes hands. And it may distort human
relations profoundly, but we don't regard that somehow as a deep
violation in the same way as a lot of people seem to regard the selling
of body parts as a violation. And that must mean it has something to
do with the alienation of one's body from one's self to begin
PROF.SANDEL: It's use, rather
than alienation. The intuition at odds with this is kidney fails, a
lot of people that object to a market in kidneys who wouldn't
necessarily consider that our position requires you to say that there
is something objectionable to a kidney transplant as such.
CHAIRMAN KASS: I said,
"disquieting." I didn't say, "objectionable."
PROF.SANDEL: Well, even
CHAIRMAN KASS: There is. There is
something to begin with disquieting about taking an organ from one body
and putting it in another. I think it's terrific that we do it.
It's not a question of an objection. But it's odd.
I'm sorry. I'm not on trial
here. It is Bill May.
DR. MAY: I hadn't planned to say
anything on surrogacy, but it seems to me not simply the question of
the telos of the body, but it's different. Gestating is different
from manufacturing, where you can distinguish the process from the
product. But in gestation, there is a kind of bonding to what is
within you. And the releasing of that child to another because
it's a bond ought not simply to be based on commerce.
The early court case on this said they
tried to distinguish process from product, you know. And merely buying
the process misses what is going on for the woman and bonding and why
it should not be an enforceable contract. It can only be a gift
because a kind of bonding has gone on.
I was interested in another issue, and I
will take advantage of my opportunity here to say you and Dan Callahan
have brought up front the issue of access to benefits in a way that it
seems to me we have not as frontally discussed that topic. It has come
up from time to time, but it really hasn't been as openly discussed
across a couple of sessions. And I wanted to deal with that issue.
There might be a way of talking about the
status of the embryo but relate that issue to the import for access to
product. Some of us in this group did not agree with the idea of a
total ban on cloning for research purposes. We talked about the
intermediate status of the embryo, that it is not fully there with the
claim of the human. And, therefore, we were not ready to talk about a
On the other hand, it is not nothing. It is not yard-lot materials.
It has a kind of intermediate status. And that has implications.
Most of our time was spent on the issue of how you do the research
and respect for this pre-implanted embryo. Most of the discussion
was in that area.
But it seems to me if you use the pre-implanted embryo in research,
one has to talk about regulations that not only constrain how you
conduct that research, let's say the 14 days before the neural
streak an all of that, but if you are using this human source and
you are removing it from life, you are not removing it from the
circle of human indebtedness.
And that is a consideration that is not
simply individualism. It's that you are conducting research on
something that doesn't have the full claim of urgent human needs of
extant human beings.
But, on the other hand—and I would not
want to use the word "resource." I would call it
"source," a human source. And if you are conducting this
research and removing it from life, you are not removing it from the
circle of human indebtedness. And that has consequences not only in
how you conduct the research, but you structure the results in such a
way that all of those who are in need have access to the benefits of
Otherwise one creates I think a lack of
respect for what one has used. And that doesn't mean you don't
pay researchers and so forth, but you think through the problem of the
health care system.
I think Dan this morning talked about and
you yourself talked about expanding the issues. We're concerned to
talk about are we going to produce a lot of products that would be
available only to the few and not to all of those in need.
And it may be the status of the embryo,
this intermediate status, is not simply individualistic reflection but
forces us to think about the communal significance of what we have done
and the necessity of honoring it in such a way to make sure that it
reaches not just the few privileged but the many.
CHAIRMAN KASS: Gil, do you want—
PROF. MEILAENDER: Yes, just really
quickly. Bill, this is a question for you. We're letting Paul off
the hook. I know you have made this argument before. And I am sort of
afraid I may be asking the kind of question where I am just asking you
to repeat yourself, but I really don't understand that argument;
that is to say, the "circle of indebtedness" language.
So that if we use some embryos and
distribute the knowledge gained unequally, we have somehow not honored
those embryos that we used; whereas, if we distribute the knowledge
equally, we have honored them.
Now, I just don't understand. I am
prepared to grant that it would be better to distribute the knowledge
equally than unequally. I just don't see what in the world this
has got to do with whether we have honored the embryo as a human
source. Can you help me?
DR. MAY: I'm not sure that I can do
it in a form that doesn't realize your fears. It just seems to me
that in making use of this to produce this benefit, one has to insist
that it reach the many. And that is not simply some principle out
there separate from, indeed, what has been done.
PROF. MEILAENDER: May I try once
CHAIRMAN KASS: Briefly, yes.
PROF. MEILAENDER: So we honor the
slave better if we distribute the cotton garments equally than if we
distribute them unequally.
DR. MAY: Well, you have assumed that I have equated the
pre-implanted embryo with an extant human being.
PROF. MEILAENDER: Well, it was a
human source. That's all.
DR. MAY: That sets me up for an equation that I am not
prepared to assert. I already began with the notion of the intermediate
status. And the slave does not have an intermediate status.
CHAIRMAN KASS: Mr. Lauritzen, do you
want to respond to the original comment?
DR. LAURITZEN: I was hoping Michael
would do that for me, but let me say just a couple of things. In the
past, I have tried to weigh out a position that tries to avoid
understanding the early embryo as a person with a full set of rights
and to use language that is common and controversial about respecting
this as a source or whatever precise language we use and that one way
to do that would be, in fact, to do the research on adult stem cell
first, see what we can learn there as a last resort and perhaps
invoking fairly explicitly just war theory to do this deterrence of
using embryonic research if we hit dead ends.
There are some issues about scientifically whether that is a viable
strategy, I understand. But over time, I have come to be a little
concerned that—and this is I think reflected to some degree in
the report. I have become somewhat suspicious of the language of
respecting the early embryo. And this I think partly goes to Gil's
point, while, nevertheless, destroying itregularly, et cetera.
Perhaps the better way to proceed here would be to talk about
a slightly different frame for thinking about this, the way in which
we have increasingly kind of instrumentalized everything about our
world. I mentioned before the instrumentalization of non-human
animals so that they're simply now artifacts that we create
with different traits without any concern for their value as independent
And I think we see the same dynamic with
in vitro fertilization, frankly, with regard to embryos.
Whatever we happen to think about their status, I think there is little
question that in vitro fertilization has led to the kind of
instrumentalization of embryos that ought to give us real pause so that
we get some new idea about how to create an embryo. Somebody dreams up
ICSI. Oh, I know. We can do that this week. And we don't
So I think the danger here is a danger
that is difficult to appreciate when you throw it into a certain
context where the frame of the debate is largely about protecting
individual rights and individual autonomy.
So a John Robertson is going to say,
"Who is harmed?" Well, unless you give some account of the
early embryo as capable of experiencing harm, there doesn't seem to
be a good answer, at least in terms of the objects or subjects
But it may be that we are harmed when we
so approach the world around us as something that we ought to be
utterly controlling in every aspect so that everything turns into a
human artifact, including humans.
So that's a very different tact on
the issue that to some degree could remain agnostic about embryo
status, I think.
CHAIRMAN KASS: Let's see. Rebecca?
PROF. DRESSER: I liked the way that
you are trying to bring in other issues because I do think this is a
complicated area. And I think, especially when we are talking about a
topic that has public policy implications in a pluralistic country like
ours, we should think more broadly.
So I wanted to mention a couple of other
points that maybe you might want to think about that I have talked
about and that bother me about the stem cell debate.
One is the area of what I would call truth-telling and the way
that both adult and embryonic stem and all other kinds of stem cell
research is being discussed in terms of the exaggeration I think
of promise. I don't know about exaggeration of promise but
exaggeration of speed with which this is likely to develop into
therapies, the likely success of any therapies, degree and percentage
of people it is likely to help, all of those kinds of things.
I think in bioethics, we started with informed consent and we
went along with a focus on truth-telling to patients about a serious
prognosis and terminal prognosis. And now in the United States,
at least, there is a strong belief that physicians should be honest
with patients about a prognosis that may not be very optimistic.
So I think that we need to talk about research of all sorts in those
terms. And I really see a violation of that in this area. So that
is something that I think might be worth mentioning.
The other is, is it worthwhile to think
about an ethical value of deliberation, accommodation, and compromise
when we are talking about issues like this that, as I said, have public
And knowing that we live in this nation
where people have very strong beliefs on different sides, how should we
think about the problem and the activity of coming together to try to
work out policies, of course, in different areas? But should we give
ethical weight to the idea that perhaps I will give a little on my
favorite outcome in order to reach an accommodation that might be
acceptable to more people?
And, again, that's something I have
personally felt in working with this issue and something that might be
worth separating out and talking about on its own terms.
CHAIRMAN KASS: Thank you.
Shall we collect a few or do you want to
DR. LAURITZEN: That's fine.
CHAIRMAN KASS: Let me collect a couple
of others and see. I have Bill Hurlbut and then Mary Ann.
DR. HURLBUT: I want to return to the
idea of commodification. I think it's very helpful to what you
said earlier about reflecting back on the embryo in light of these
other categories of consideration.
When I think about the issue of
commodification, I am naturally drawn to thinking about, well, what is
it that you are commodifying or selling, commercializing even.
And when I think about the body parts or
associated body realities that could be commercialized, I think of
people selling their hair for people to make wigs. That doesn't
bother me very much at all, maybe none.
Blood, that's a little more something
there, but that seems okay to me. Sperm or ova, that troubles me a
little. There's more going on there, and maybe troubles me a lot.
Selling a kidney definitely bothers me.
And then selling your whole life really
bothers me if you know what I mean; in other words, "I'll give
up my life. I'll sell you my life." Okay? Somebody might
sell their life so that their children got money, for example, to
survive. That bothers me a lot.
So there is a spectrum going on there.
On the one hand, something seems simple, trivial, and okay. On the
other, it requires highly significant justification to even give up
your life or to give up a significant part of it.
What is it that bothers me at the far end
of that spectrum? What is the key here? I think it has to do with
something that you would call integrated organismal integrity,
identity, or continuity that we can give up something that doesn't
challenge those three, but if we give up something that does, we have
to have a really good moral reason for doing it. So commodification of
an expendable part is completely different than commodification of a
whole human life.
And then when I reflect on it, what
bothers me about sperm, for example, is not just that it's giving
up a part of the being. In this case when you give it up, it
doesn't hurt the static reality of the organism. It's that
you're giving up a part of what you might say is the dynamic of an
integrated identity and continuity. You're giving up a relational
dimension of being.
There is no significant disruption of a
relationship to sell hair, but selling a sperm or a womb, use of a
womb, is not just part of the static being but parts of dynamic
So it seems to me that the key here is
that the moral meaning is in identity with the integrated organismal
integrity and the integrated of dynamic process or continuity or
This brings me back to the point that
Michael Sandel and I think it was William May and Leon were in a few
minutes ago. What is the difference between selling and giving? Well,
it seems to me that giving can sometimes be justified, even at the loss
of something, integrity, identity, and continuity, because it is an
adult form of voluntariness.
You are doing something that is a very
high order act of hopefully consciousness, which preserves the fullness
of being of the individual as a moral entity. This, in turn, brings me
back downstream to your comments that these larger issues of
commodification and so forth can inform our understanding, not just of
the absolute total landscape but can actually focus back down on the
status of the embryo.
For me, as I read your paper, I thought
yes, yes as I went all along. And I got to the end. And I thought,
every one of these categories makes me more concerned about the moral
status of the embryo.
Obviously commodification of the embryo violates the things I
have been talking about; whereas, selling or giving a body part,
let's say giving, is a high order of self-donation. Relegating
an embryo to research is exactly at the opposite end. It really
is commodification. It doesn't have the voluntariness of giving
in it at all. It's a violation of something that is fundamentally
human in the process.
So what seems to me is going on here, at
least from my perspective as I looked at all of this, is all of your
categories, commodification or, worse, at the level of the embryo,
justice, giving something its due, is worse at the level of the embryo
because it's not taking something from anything that has a choice.
The idea of natural embodiment, the embryo, everything we are is
deeply, inextricably in continuity with that embryo.
The erosion of species boundaries raises
a specialized dilemma here, violation of integrity, which is at the
concern of that ethical consideration. And, finally, the implications
for personal identity and a deeply rooted thing that it is.
So I don't know if this at all makes
the point, but what I would like to say is that I think these issues
are of one piece and that organismal integrity and identity and
continuity seem to focus all of your higher concerns right back down
again, I mean, both directions, of course, but there is a whole package
here that is inextricably related.
CHAIRMAN KASS: Do you want to take both
of these together? I mean Rebecca Dresser's earlier comment.
Please respond if you wish.
DR. LAURITZEN: Well, let me just respond to the last part.
CHAIRMAN KASS: Okay.
DR. LAURITZEN: Then I can go back to Rebecca's. It
just suggested some friendly directions in which it might be pursued.
I actually think that is a very interesting observation. And I
want to think fairly carefully about that because I think that you
may be right about this.
It may provide some language for actually
teasing out some of the concerns I want to articulate about adult stem
cell research and then rethink their implications for embryonic stem
I forget the exact language you used.
What did you say, the organismal integrity? I wonder if that isn't
threatened in some significant ways, not by selling parts of our bodies
but purchasing new possibilities for our bodies in a way that might
fundamentally change who we are.
I have thought about this a little bit.
I got married when I was 24 and have been faithfully married to my wife
now for quite a few years. And at 24, I promised to be faithful until
death do us part, but that was a commitment of about 50 years. And if
we doubled the life span, I am making that commitment for 100 years or
something. What would that commitment look like and whether it would
fundamentally change how we thought about an institution like marriage
and things of that sort?
I think it would have implications for
personal identity and responsibility over a very extended period of
time. So there would be questions about purchasing as well as selling.
My initial reaction, going back to the
embryo, is mixed. On the one hand, I want to think more carefully
about this notion of eroding the sense of a kind of natural trajectory
because if there isn't that kind of natural trajectory, then I
don't think what is threatened with the embryo early on is that
unity that you describe because it has got multiple possible
trajectories depending on the environment, the interaction, et cetera.
But I want to think about that more because I think it is a very
DR. HURLBUT: One little brief follow-up on that. I think that,
actually, what you said has a power to it, but I see it at the other
end of life. I think the embryo is not as contingent as the full
human being who has a sense of real opened determinacy and contingency.
I mean, sure, environment is going to
affect things a lot for sure, the final trajectory. I think it is more
determined early and less determined later. And so if the criterion of
expendability is in determinacy, it wouldn't be the embryo. It
would be the up and breathing, bubbling human beings.
CHAIRMAN KASS: Mary Ann? We will break
in about three minutes.
PROF.GLENDON: I'm going to
follow Dan Foster's illustrious example except just to say that Dr.
Lauritzen I think has responded in his last remarks to the concern I
was going to raise that what I think we're getting at when we use
terms like "instrumentalization," "commodification"
is really a deep concern about what kind of people we are becoming when
we make certain decisions. And so I think this has been a really
CHAIRMAN KASS: Yes. I would like to
take at least one minute to add one thing to underline something that I
thought was fairly good in the paper. It ties in with things that we
didn't talk very much about in Dan Callahan's presentation. I
found the two papers very nicely complementary.
That really has to do with the questions
of the goal of stem cell research, combining both the embryonic and the
adult and thinking through the purposes for which these are used,
purposes which I think all of us at first glance will simply endorse
what we endorse for generative medicine.
But the question about the limits of that
and whether or not that really isn't also using things at the
beginning of life to transform not just the trajectory but also the
question of whether there really ought to be an end or a completion I
think is a very important issue here.
I've got sort of half-baked notes for an essay called "The
Old Man and the Embryo," in which it's at least paradoxical
that one comes to look upon these cells, which are in some ways
part of the seed of the next generation, to come to see them as
the salvation for those of us who are getting close to the end.
And if you want to present yourself with
a kind of parable in stock terms, imagine Abraham, the biblical
Abraham, and Sarah in a desolate world except for an IVF clinic. And
they manage themselves. I guess I've got to make two embryos.
They manage a couple of embryos. And the question is whether the
embryo ought to be Isaac or ought to be the cure for Abraham's
Parkinson's disease. Then you take that and universalize the
matter, and I think you see something of the difficulty here.
This is not an objection to stem cell
research. I want to underscore that. But there is something going on
here about the way in which we think about the things at the beginning
of life in relation to things at the end of life. And they're
becoming somewhat unmoored.
I think your paper I think highlights the
importance of thinking about those things and the powers, what
we're going to use these powers for, as well as the questions of
the ethics and the means upon which we for the most part so exercised
ourselves. So I'm in your debt for that and for much else as well.
CHAIRMAN KASS: Council members, show up at five of. Thank
you very much.
(Whereupon, at 12:25 p.m., the foregoing matter was recessed
for lunch, to reconvene at 2:00 p.m. the same day.)
SESSION 3: STEM CELL RESEARCH: RECENT
SCIENTIFIC AND CLINICAL DEVELOPMENTS
CHAIRMAN KASS: Could we come to order,
please? The third session of this meeting is on "Stem Cell
Research: Recent Scientific and Clinical Developments." The most
challenging aspect of trying to fulfill our charge of monitoring stem
cell research is the monitoring of the scientific research itself.
There is so much of it, it's very diverse with many sources and
types of stem cells, and many types of research. Things are changing
amazingly rapidly, and we are trying to monitor a moving target. The
material is highly technical and hard, even for scientists outside of
the field, let alone a layman, to evaluate carefully.
"The Isolation of Human Embryonic
Stem Cells," and, "Human Embryonic Germinal Cells," by
James Thomson and John Gearhart respectively was reported only five
years ago. The obvious promise of these cells both for gaining
knowledge of development, both normal and abnormal, and eventually for
regenerative therapies with hundreds of thousands of patients with
degenerative diseases or injuries has produced great excitement, much
fine work, and to be frank, more than a little hype.
At the same time, reports of previously
unknown and unexpected multipotent or stem cells in various tissues of
children and adults has produced enormous interest also in so-called
adult stem cells, with similar promise, and to be frank, also more than
a little hype.
By almost all accounts we stand today in
the infancy, not to say embryonic, stage of these researches, and it is
surely too early to answer the questions that the layman wants
answered. How soon, for which of our diseases, from what sort of
cells, at what cost, and at what risk will the cure be available?
Yet it is not too early to learn where we are in fact in this
rapidly growing field, to try to separate fact from fiction, true
promise from hype. And to do this we have gone to the experts,
commissioning review essays, essays that would review for us the
published literature over the past two years since the August 2001
decision, covering work in five areas according to the origin of
the cells. "Human Embryonic Stem Cells," a paper by Tenneille
Ludwig and James Thomson, "Human Embryonic Germinal Cells,"
a paper from John Gearhart, a paper on cloned embryonic stem cells,
a paper by Rudolph Jaenisch, a review of the adult stem cell research,
a paper from David Prentice, and an update on the work with her
own multipotent adult progenitor cells from Catherine Verfaillie.
The papers have been sent out with the briefing books, and I assume
that they've been read. We are thinking about another paper
on mesenchymal stem cells.
We're very fortunate and grateful to have with us this afternoon
three of the authors, Dr. John Gearhart, Dr. Rudolph Jaenisch, and
Dr. David Prentice, who will, in brief presentations, highlight
their own papers, after which we will have questions and discussion.
I would remind Council members that the
purpose of this session is wholly scientific. We want to learn as much
as we can about the current and projected state of this research. This
isn't the time for ongoing ethical arguments about the moral status
of the embryo, the research imperative, or equal access for the current
funding policy, important though these issues are. And I will simply
say I'll use the authority of the Chair to see to it that we try to
stay on the topic.
Dr. Gearhart has kindly agreed, by the
way, to field questions pertinent to the review essay submitted by Drs.
Ludwig and Thomson. Gentlemen, welcome to you all. Thank you for your
papers, your presence, and in advance for your presentation and
participation. And we will proceed in alphabetical order with John
DR. GEARHART: Well, I can't say
I'm delighted to be back, but I'm happy to be back. And to not
really dwell on the research that's going on specifically in our
laboratory, but to give you a bit of a general overview of where the
work is in this field, and I think there will be ample opportunity from
some of the things that I say that you can ask questions about it.
I think the first question, and judging
from some of the morning topics, that I would like to address is the
one before you now, which is, why study these cells? And what we have
heard most frequently are the issues, well, this is going to be the
most versatile source of cells for promised cell-based interventions
for various therapies.
But I came at this at a different angle. I am an embryologist
by training. I've been a student of human embryology for 28
years. And I'm extremely interested in knowing how we are put
together. What are the events, what are the mechanisms that lead
to the formation of the human being?
And over time, as you can imagine, we've studied fruit flies, we've
studied mice, we've studied rhesus monkeys. And I think one
of the major, and perhaps the most important bit of information
that we're going to get out of embryonic stem cells are going
to be the issue of how we are formed. And this is going to involve
cell biology, genetics, on and on and on. But this is what is going
to enable us. And I think with this information, which at the moment
is under the heading of Fundamental Science, or Fundamental Discovery
in Basic Science, this, I think, is going to be the lasting contribution
of studies from embryonic stem cells.
They're going to have applications,
obviously, with that information, and the sources of cells. And
we're going to apply those to birth defects. We're going to
apply it to injuries and disease, because many of the processes are
similar. And we're going to be able to draw on that information in
trying to correct diseases and injuries.
True, I think out of this we're going
to get sources of cells which, in the short term, are going to be used
directly for the cell-based interventions. And I think through the use
of these cells, we're going to discover other important things
about these cells, and some in our research we've learned, which we
can apply in therapies.
But I want to emphasize one point, and
this is my belief, that this period of time that we're going
through in studying embryonic stem cells is going to be transient. And
I want to emphasize that I believe it's the information we're
going to get out of these cells that are going to be used in the longer
term to restore function, to regenerate tissues within the bodies of
patients, without the use of these cells. And that to me, as I look
downstream, is going to be the most important outcome of this research.
Now I realize that this quote is taken
out of context for these essays that were written, and what was being
questioned here. But I want to make some comments which are important
when we consider the use of human embryonic stem cells directly. And
that is, we are finding enormous differences between mouse embryonic
stem cells and human embryonic stem cells, not only in practical issues
within the laboratory from the standpoint of cell cycle times, et
cetera, but also, as we begin to differentiate these cells in a dish,
we find some very subtle and some very not so subtle differences
between the mouse cells and the human cells to get us to the
differentiated functional tissue that we need.
So I do believe it's time that we
work directly on the human embryonic stem cells if we want to gain this
information on embryogenesis, and if we want to move forward with
developing cell-based interventions.
So, the sources that we're going to
talk about in general deal with this very early stage here derived from
the IVF-donated embryos, and from tissues collected within the early
stage of fetal development, the germ cells. These cells have many
things in common, and we've published on this. You've seen
this, probably. And so we look at them as a group.
There's a third member of this group,
which is embryonal carcinoma cell, depicted here on the right, which
has very similar properties to these two other cell types. In fact,
it's the only cell type from which any cell has been derived
that's being used in a pre-clinical trial. And this is on stroke
patients at the University of Pittsburgh.
I want to spend time now, or my brief time, on three slides to
give you an indication of where the human work is on this class
of cells. What are the questions that are being asked, where are
we on some of this stuff, et cetera?
So here now are issues around human embryonic stem cells, or embryonic
germ cells. One of the first questions that's being asked about
the stem cell itself is what is meant by "stemness"?
And obviously this, at the molecular level, gets us into genomics,
proteomics. And so there is a major effort around the world at
trying to determine the genetic basis of a stem cell. And the human
cells are being used extensively for this purpose. How many genes
are involved, what genes are involved, what signaling pathways,
on and on and on. So stemness is an important issue within this
Now, it's a comparative thing. We
can do it also with mouse cells. We can do it with adult cells as
well, trying to find commonality. What is it that makes a cell a stem
cell? That information will be vital, I believe, in the future, in
converting virtually any cell to a stem cell, if we want to go that
The second major issue currently are
characterizations of existing lines. As you may know, there's no
standardization within the field as to what constitutes a human
embryonic stem cell. We talk about developmental potential. We talk
about molecular markers, biochemical/antigenic markers, this is now
being taken up by an international committee under the auspices of the
MRC in London to try to get an agreement on these issues from stem
cells around the world, human embryonic stem cells around the world.
There's also the issue now of whether
or not we should be deriving new stem cell lines. And in many
countries, this is indeed happening. There are a number of new cell
lines coming online. And what is the importance of this? Now, many of
you have heard at least from what the Europeans refer to as the
presidential cell lines, those that are eligible for funding in this
country. Should we have cells that are only grown on human feeder
layers? Most of the cell lines that have been derived are on mouse
feeder layers, and there is a concern about infectious agents passing
into the human cells.
I think there's a misconception out
there that these lines will be ineligible for any kind of therapeutic
use. I think the FDA has made it very clear that they're certainly
willing to consider those grown on mouse feeder layers if they meet
certain criteria to also be eligible for use in the clinic.
But there are a number of lines now that
have been derived on human feeder layers, and there are lines being
derived that are feeder layer independent, which means it makes it much
easier to work with in the laboratory. You don't have to worry
about these other cells that are present in your cultures.
And there's an attempt now being made
to derive these lines in defined media, which means there are no other
animal products, no serum, that you can control very carefully the
differentiation of these cells by adding specific growth factors in a
The most important element to this,
though, is this top line here. Many of you may not realize it, but
when we say that routinely three or four different mouse embryonic stem
cell lines have been used for the last 20-some years, what's the
problem here, why can't we use just a few of the human. Those
lines have been selected from a hundred and some cell lines that were
made as to being the best cell lines to use for those purposes. And so
I think we're still in this phase of trying to determine what are
really the good cell lines, human embryonic stem cell lines that are
available. And thus the issue of generating more.
For the use of these lines, emphasis in the lab now is in the
following area. We're trying to work up high-efficiency differentiation
protocols that result in homogenous cell populations of functional
cell types. That is, can we in the laboratory come up with protocols,
growth conditions, that are going to get us 10 million dopaminergic
neurons, and only dopaminergic neurons? Most of the protocols we
have now result in a mixture of cell types within a dish, and we
go in and select out the ones we want.
So there's concern about the
heterogeneity of the cells, and the fact that we can't at this
point have a high efficiency in getting the cell types we need. We
manipulate the growth environments, and we manipulate the cells
genetically to accomplish this goal.
Once we differentiate these cells, and
we've had some success in certain pathways which we can talk about,
we are very concerned about what we refer to as the authenticity of the
derived cells. That is, is the dopaminergic neuron you've formed,
the insulin-producing cell you've formed, the cholinergic neuron,
the cardiac muscle, are these actually functional cells that are the
equivalent of those that you normally find in the adult?
So a great deal of effort, both in the
dish, in vitro, is being made in different parameters to measure
whether or not these are authentic cells. There are many protocols, as
you can imagine, that lead to cells that look like something, but
they're not functional. And this is a major concern. The other
side of this is, the golden test is can you transplant these cells into
an animal model of some kind and see that they assume the function that
you're hoping that they would.
But again, these are human cells going
into rodents, primarily. Do we have every reason to believe that
they're going to function appropriately? We don't know that
yet. We're also putting cells into non-human primates to get that
kind of a measure as well.
We are in the laboratory contrasting and
comparing among various sources of stem cells. In our laboratory, we
work on human ES, human EG, umbilical cord blood, et cetera. And the
importance of this is that you are able to compare and contrast in the
same paradigms the sources of these cells to see which ones are going
to be appropriate for which tasks. And I think this is extremely
We're also very concerned, as you
know, if these cells are going to be continuously grown in the
laboratory, there's a finite possibility that you're going to
get genetic mutations. We're interested in the frequencies of
this, and the types of the mutations that occur in these cells.
It's a safety issue. But with our genomic and proteomic studies,
we can get a good handle on this at this point in time.
When we get into the grafting issues,
which is obviously a desirable endpoint, both in the basic science
side, to say you have a functional cell, and then transitioning into
any use of these cells in cell-based therapy, we have a number of
The first, and I think you have to
realize this. There is virtually no appropriate animal model for any
human condition. That's the fact. We approximate it. We do the
best we can. But under those limitations, we do the best we can. And
you have to be aware of this. There's a concern about what animal
models you're using for what test.
The issue of what stage of cell
differentiation in any of these cells do you use for a specific graft?
We are finding that many things within the central nervous system, you
want to use something that is fairly undifferentiated so that the cells
can interestingly migrate to where they're supposed to go, set up
the appropriate connectivity. And so if you are working with a motor
neuron, you'd like to use a motor neuron precursor. If you put in
a fully differentiated motor neuron, nothing works. I mean, when you
think about the nervous system, it's not surprising.
With insulin-producing cells, we find
that you want the terminal cell, at least in the experiments that we
are doing. But for each of the cell types you're working with,
we've got to determine this, as well as how do you want to deliver
it to those animal models.
The last two are extremely important.
What are the fates of these cells that you've grown in a dish,
selected for in a dish, once you graft it into an animal paradigm? We
know these cells like to migrate. Do they differentiate
appropriately? Do they form tumors? I remember a few years ago when I
was all puffed up that our cells were working so wonderfully, and I
went to the FDA for this meeting I thought was going to be one-on-one
with members of that group. And it turned out that there were 40 of
them and one of me. All their questions were about safety issues. We
now spend as much time on these safety issues as we do at looking at
differentiations of these cells in a dish.
Why? Well, what have we found? Indeed,
in the early mouse work with embryonic stem cells the rates of tumors
were extremely high. Formation of teratocarcinomas, mixed germ cell
tumors. We have at this point, though, grafted well over 3,000 animals
with our human cells, and we haven't seen a tumor yet. And maybe
we're just lucky, maybe there's a difference between mouse and
human cells. We don't know that.
But these experiments are extremely
expensive because you've got to serial section through the whole
central nervous system if you're putting cells in there.
You're putting them in IP, et cetera. It's a lot of work. The
FDA, ideally, would like to know if you're putting 300,000 cells
into an animal, they want to know where all 300,000 cells went. This
has gotten us into extremely expensive experiments in labeling cells,
developing labels for cells that you could follow for a year or more
later. You could go back and find those cells. So we've employed
radiologists, and chemists, et cetera, to help us with these kinds of
things. So it is a major issue. And in all of our experiments, we
look at this.
The last issue, on immune response graft
rejection, is obviously to some extent the Achilles' heel of this
work. If we can't provide tissue that's going to be accepted
in a graft, then all this work has gone for naught. So there are
issues of active experiments now going on in tolerance, in genetic
alterations of cells, the consideration of cell banks, how many
different stem cell lines would you need to cover certain populations
of people, and something you'll hear about probably from Rudy on
nuclear and cell reprogramming, so-called therapeutic cloning. Is this
one of the avenues that we can approach? So all of these are very
active research elements going on with respect to the human embryonic
germ cells and stem cells. We can't divorce them.
Now, in this cartoon, what I've
depicted here is one of the more difficult scientific aspects of the
research. And that is that you have in a dish—now this is a bit of a
repeat, but it's important to mention—you have in a dish these
cells that are capable of forming any cell type that's present in
the body. The major problem here is how do you get them only to form
hepatocytes, dopaminergic neurons, heart muscle, blood cells,
pancreatic islet cells, solely. How do you do that? This is where the
real issues are within the laboratory.
And we try to recapitulate, as I showed
you this before—oh, and finally, the issue of—I put this little
thing down here to remind me. Some of you have seen this report
earlier this year from Hans Schuler's lab at Penn, that he's
been able to find oocytes within embryonic stem cells derived from the
mouse. Now, he did not—now keep this in mind, he did not
purposefully differentiate these cells into oocytes. He came up with a
neat little trick of identifying them once they were present in the
plate. Okay, so it's not that he's worked up a condition to
differentiate them only to oocytes, it's that they're there.
You can use that technology to pull the cells out, and then further try
to mature them, see if they are actually functional oocytes, et cetera.
So we rely in the lab on trying to
recapitulate what has occurred to some extent in the embryo by
providing growth factors that these cells normally see to get them to
enhance, or try to direct their differentiation into the product that
We use selection techniques in the
laboratory after getting these mixtures of cell types by different
avenues in the dish. We then come back using genetically selected
markers, different growth media, cell sorting, which is a fancy way of
sending cells through a beam of light, and if they have a certain
antigen on the surface, you tag it in a way that will put them into
different pots. And this works fairly effectively for a number of cell
types. But it's highly inefficient, and we've got to improve
So what have we done? What have we been
able to do? We've been able to identify many, many different cell
types in a dish. We've been able to expand many different cell
types, whether they're insulin-producing cells, dopaminergic
neurons, heart muscle cells, smooth muscle cells, hepatocytes,
we're able to do that. Human. And we've been able, in many
cases, to show that they are functional within the parameters that we
like. And in a few cases we've studied extensively we've been
able to graft them into animal models to show that they will work, and
can ameliorate a condition in the animal, whether it's, to some
degree, whether it's a diabetic animal, or one with motor neuron
loss, mouse models of Parkinson's disease, we can do that at this
To reiterate, we are concerned about
safety issues. They go hand in hand with all that we do in the
laboratory. It adds, again, expense and time, but we want to make sure
we get it right.
Here's another issue of safety. We
find that in many of these cell lines, if you're not careful—now
human embryonic stem cells are much more difficult to grow in the
laboratory than mouse, and if you're not careful, this can
overwhelm your cultures very quickly. This is an example of a
tetrasomy 12p, and also of a trisomy 17, which appear to be fairly
common coming out of the human cell lines for whatever reason. We
don't know. But you have to constantly monitor these cell lines
to make sure that they are remaining normal as far as the karyotype is
concerned. Not an unusual circumstance.
Rudy, I'm sure, will deal with this.
But we got highly involved with the issue of somatic cell nuclear
transfer, mainly coming in from the desire to have matched tissue for a
patient. But I want to point out two other issues here that I think,
in my way of thinking, are perhaps more important. Rudy will probably
Number two on this list, to increase the
diversity of stem cell lines. Number three, to facilitate the study of
inherited genetic diseases and somatic mutations. Now, there's
been a lot of talk about, with the justice issues, of diversity of cell
lines. We now know how many cell lines we need to cover the population
of the United States. How are we going to get these lines? We're
not going to get them, if we wanted them, by going out and matching up
people to get embryos, okay, or even assaying embryos in banks. The
easiest way to do it is you identify a person that has the haplotypes
of class I and class II genes, and take a nucleus out of their cell.
And generate stem cells through somatic cell nuclear transfer. No
question about it, easiest fast way of doing it.
The issue of the studying of inherited
genetic mutations and somatic mutations. It means that we can take
cells from a patient with a disease, some of them not expressing very
much from the standpoint of the pathogenesis of the disease, to others
that are full-blown, to try to figure out why some patients have one
form of the disease, another has the mild form of the disease. We can
take this directly, and generate stem cells for those studies. Somatic
mutations, breast cancer mutations. We can generate cell lines—it's the only way we can do it—through somatic cell nuclear
And then the issue of being able to
determine mechanisms of nuclear reprogramming. We would hope that they
would approach normalcy from the standpoint that we may be able to use
that information to convert somatic cells into stem cells at some point
downstream. This is why I think somatic cell nuclear transfer into a
human are reasons that are quite important.
Well, I think with the issue of the human
embryonic stem cells, I think they have uniqueness in certain areas,
and I think that what we're going to learn out of these studies is
going to be extremely important in the future, not only for deriving
cell-based therapies, but in getting information that we're going
to be able to begin to instruct our own genes.
And this is something which hasn't been paid a lot of attention,
but I think even within this Council, it may be a good idea, that
we're on the verge, I believe, of being able to instruct our
own cells. And I think the ramifications of this are enormous.
I mean, talk about enhancement. One could go on the Internet and
get a kit for enhancing any part of your body to a certain degree.
And this is all going to be done, I think, from information that
we get out of learning about cell differentiation, how these cells
function. So I think we've got to keep our eye on this for
the future as well.
Just in closing, the greatest impetus
that I can think of for making advancement in this field is funding
through the National Institutes of Health. This is the only
information that I could get my hands on. It's available.
It's for the fiscal year 2002. You see how much money is being
spent on stem cell research in toto, how much on human adult stem cell
research, how much on animal adult. And up to this point, $11
million. On the human embryonic stem cell research, I think this year
it's going to be more, and we would hope in the future, as the
bottleneck for cell lines and more applications come in to the NIH,
that these numbers will become robust.
And I think this will be the key to the
dreams that we have, anyway, of learning more about how humans are
built, and cell differentiation of human cells on their way to
therapy. So I hope I've given you enough to think about. Thanks.
CHAIRMAN KASS: Thank you very much. Why don't we simply
proceed in order. Dr. Jaenisch.
DR. JAENISCH: Well, thank you very much for inviting me
here. And I will right away get to the cont roversy. I'm not
going to agree with much you said.
So I want to try to develop two arguments. One is reproductive
cloning faces principle biological problems that may not be solvable
for the foreseeable future. And the other one is therapeutic cloning
poses no principle biological obstacles, only technical problems.
And this, I think, in my opinion has implications for the status
of the fertilized and the cloned embryo.
So you need one piece of data. When we
do nuclear transfer, then it's clear that the donor cell, the donor
matters. So if we use a somatic donor nucleus, cumulus cells,
fibroblasts, Sertoli cells, the result to get cloned adults is really
low, a few percent. If you use B or T cells, or neurons, it is very
low. Only with tricks we were able to get animals. However, when one
uses embryonic stem cells as donors, it's an order of magnitude
more efficient. So the conclusion is an embryonic cell is easier to
reprogram to support life than a somatic one. I will come back to this
later when I make an argument.
So, let me first come to cloned animals.
If you have an animal born, if you looked at this carefully, you find
that approximately four to five percent of all genes, as done in
percentile, are not correctly expressed. Still, the animal develops to
birth. If you look at imprinted genes, it's even worse. Thirty to
fifty percent are not correctly expressed, regardless what the donor
cell nucleus is. So from this we would argue that it's amazing
that these defective embryos can develop to birth and beyond. But you
pay for that. You pay with abnormalities.
So my argument would be, and I will
develop this more, that there may be no normal clones. Of course, we
have the problem to define what we mean with "normal". But
let me then say that faulty reprogramming seems to me is a biological
barrier that may preclude the generation of normal cloned individuals,
at least for the foreseeable future.
Let me come to therapeutic cloning. So,
as we heard, cloning would involve taking from a patient a somatic
nucleus and derive an isogenic embryonic stem cell by nuclear
transfer. This could be used, then, to correct the genetic defect if
it was present. One has to differentiate these cells in vitro,
and then transplant it back into the individual and see whether it
could improve the condition.
So we have made such an experiment. I
just want to briefly outline the steps we went through. As a patient
we used a mouse, which was totally immune-incompetent. Due to the Rag2
defect, it did not have any B and T cells. So that was our patient.
From this, skin cells were removed from
this animal. They were transferred. A blastocyst was derived. And
from this blastocyst, an embryonic stem cell, which of course is
mutant, as the donor. And then we used just simple homologous
recombination to repair one or two alleles to make a functional Rag2
gene, and then differentiate these cells which had problems into
hematopoietic stem cells, put them back into the animal, and the result
was that these cells could colonize the embryo and repair, in part, the
So some have argued that this experiment
really didn't work. It really only showed that when you have—I
think Dr. Prentice argued that it only showed that one has to use a
cloned newborn as a source. And this, of course, is not therapeutic
cloning. I think that is a misrepresentation of those data.
I would argue that from this experiment
we know that somatic nuclear transfer and therapeutic cloning will work
because it has worked in the mouse. So only technical, not principle,
barriers exist to adapt it to human use, although these technical ones
may be daunting. Technical, in contrast to principle ones, which we
see in reproductive cloning.
So, if I look at the two ways we can
think about cell therapy, then we have the nuclear cloning approach as
I just outlined, which in the mouse we know works, at least for
hematopoietic cells, and I believe will work for other cells. The
alternative is somatic adult stem cells. We'll hear later from
And I believe here there are many, many
question marks. It is a very young field, very interesting, but we
really don't understand how to really handle these stem cells, how
to propagate those. And there's really, with the exception of bone
marrow stem cells, not really any proof of therapeutic potential at
this point. So I think we need much more to learn here, but this we
know will work.
So I want to come to really two key
questions. One is can reproductive cloning be made as safe as in
vitro fertilization? And the other one: Does faulty reprogramming
after nuclear transfer, does it pose a problem for the therapeutic
application of this technology? I think these are the key questions in
So, can reproductive cloning be made safe? I believe in addition
to the technical problems, which are solvable, there are serious
biological barriers. And the main one is this one. The two parental
genomes in all of our cells are differentially modified depending
on where the genome came through the egg or through the sperm.
They're epigenetically distinct in the adult. If you want to
recreate that situation, you would have to physically separate the
two genomes and treat them independently in an oocyte- or sperm-specific
So let me point that out in this very complicated-appearing diagram,
but it's very simple. So let me just go through briefly what's
happening during normal fertilization. In normal fertilization,
the egg genome and the oocyte genome are combined. And they are
differentially modified during gametogenesis. And this is what
these lollipops here show. So they're different in the zygote.
But now something very curious happens. Within hours of fertilization,
the sperm genome is stripped of all methylation. The oocyte is
resistant to this not-well-understood demethylation activity because
the oocyte genome has been, of course, together with this activity
So then cleavage proceeds. And the point
I'm making now is that the cells of the genomes in the adult are
different, different because of their history. It's not only for
imprinted genes, but also for non-imprinted genes. Now what happens in
cloning? In cloning, one removes, of course, the egg nucleus and
replaces it now with one of the somatic nuclei.
Now, both of these genomes are now
exposed to the egg cytoplasm. So both become really—they're in
identical chromatin state. So they'll be both modified, and the
difference will be equalized. So the difference you see in a normal
adult cell will be equalized, tends to be equalized in cloning. I
think that is a problem among those which we call epigenetic problems.
So in order to solve that, I think one
would have to separate the two genomes physically and treat one in an
egg-specific appropriate manner, and the other one in a sperm-specific
manner. I think if we could do that, then I think we would have a way
to solve that problem.
So the phenotypes of clones, I would
argue, is a continuum without defined stages. So we know the most
important stages are implantation and birth, and indeed, most clones
are lost at implantation, and then at birth again many are lost. You
end up with very few which develop to late age. And we know from most
experiments, even animals which are one year of age, 80 percent of
those die very early with major problems. These experiments could only
be done so far in the mouse because the mouse is the only organism we
have old cloned animals.
So I think the problem here is, yes, you
might get—because our criteria are not very good here—you might get
quasi-normal or maybe a normal individual with a certain frequency.
It's very difficult in animals to test, really, because our tests
are limited. But we cannot predict ever at any of these stages who
will be among those outliers, and who will not be. There's no way
to select good healthy from non-healthy clones. I think that's
very important to emphasize. There's no way we can think of to do
that. So there's no predictability whatsoever. So from my point
of view, this doesn't matter, really, whether one or two percent of
potentially normal animals which survive for a long time. You
can't predict who this will be.
So, therapeutic cloning. So, as I said,
cloned animals are abnormal due to faulty reprogramming. Why is
normalcy of differentiated cells derived from ES cells not affected by
this problem? There are two reasons. One is that we don't involve
a generation of a fetus. And the other one is that the embryonic stem
cells lose what I'm going to call epigenetic memory of the nucleus
they came from. So let me develop these two ideas.
So first, it's simple. In contrast to reproductive cloning,
there's no embryogenesis required to derive functional cells
in vitro. So it's totally irrelevant, for example, whether
imprinted genes are reprogrammed or not. Imprinted genes have a
function only during fetal development, not in the adult. So it
doesn't matter. There is one or two exceptions, and those would
have to look at.
Very importantly is the cells themselves
select themselves in vitro for the cell type you are selecting
for. There's no selection possible in vivo after
implantation in a cloned animal. And then we know that cloned ES cells
form normal chimeras, as do any other ES cells. So biologically there
is no difference.
Let me come to the memory question on
this slide here. So we know we can make blastocysts from a zygote from
a fertilized egg, or by nuclear transfer from these various donor
cells. Now I would argue the blastocyst remembers exactly where it
came from. And we know that because we implant this blastocyst,
derived from a zygote, into the uterus, it will with a high efficiency
develop to birth, and will make a normal animal.
If you derive—take a blastocyst derived
from an ES cell, and implant it, it will develop with a high efficiency
to the newborn stage, but it will make an abnormal animal. If it came
from a cumulus cell, it would be very low efficiency—I showed you
this on the second slide—low efficiency to the newborn stage. It
will be abnormal. If the nucleus comes from B-, T-cells, or neurons,
it will be very low. And it will be, of course, abnormal, if you get
So these blastocysts know exactly where
they came from. And we know this, actually, when we look at gene
expression patterns in clones derived from ES cells, or from human
cells, they're different. So they remember at birth where they
came from. That's why cloning doesn't work. That's why
these cloned ones develop abnormally, too, in the great majority.
So what about ES cells? In ES cells,
it's a very different thing. I would argue you erase the
epigenetic memory of your donor nucleus. And the argument is the
following. We know that if you take such a blastocyst, the ES cells
are derived from the inner cell mast cells. These inner cell mast
cells express certain set of genes, one of those called the Oct-4 gene,
one of the key genes, but another 70. You put this blastocyst in
culture. All these genes, all these cells array—silence, Oct-4.
This has been published. And they don't divide. They sit there.
But over the next days or week or so, some of these cells, one
or the other, begins to re-express Oct-4 and another set of 70 genes.
And these are the cells which would proliferate. And we call them
ES cells. It's a total tissue culture artifact of those cells
which can survive under the harsh tissue culture conditions. So
I would argue ES cells have no counterpart in the normal animal
model. They are a real tissue culture artifact, although a very
Now the same occurs, of course, with
these blastocysts. The efficiency is lower. But once you go to the
selection for the survivors, they're exactly—I think in order to
survive, they have to express the set of 70 genes which we call the
embryonic genes, which are important for the early developmental
stages. So the point of this slide is really that this selection
process, which selects just for the fastest growing cell, erases the
memory to where the ES cell came from. And indeed, when you transplant
these cells derived from a B- or T-cell or from a neuron or from a
zygote, they have identical properties. They form normal chimeras, and
they in vitro differentiate indistinguishably.
I want to summarize this. An ES cell
derivation selects for survivors. And I would argue survival depends
on an ES default epigenetic state which needs these Oct-4 like genes
being on. Selection process erases the epigenetic memory of the donor
nucleus, and the cloned and the fertilized cells form normal chimeras.
So the potential of ES cells derived from an in vitro fertilized
embryo and from a cloned embryo is identical by all measures we can do.
So I would conclude, then, it's
unlikely, if not impossible, to create a normal individual by nuclear
cloning. The problem of reprogramming may not be solvable for the
foreseeable future because of these principle barriers, but ES cells
derived from clone embryos have the same potential for tissue repair as
those from the fertilized embryo.
So I think one of the key concerns I can
see of this committee is that the derivation of embryonic stem cells by
nuclear cloning necessitates the destruction of potential human life.
I think that's a major concern. And if I just compare now, to my
opinion, the difference between a fertilized and a cloned embryo. The
fertilized embryo is created by conception. It's genetically
unique. There's a high potential it will develop to a normal
baby. The cloned embryo of course has no conception, no new genetic
combination. It is really the product of a laboratory-assisted
technique. Sloppily, we could say it's a laboratory artifact. But
most importantly, it has little or no potential to ever develop to a
So I think the embryo, the cloned embryo,
lacks essential qualities of the normal embryo, which on this sort of
maybe summarizing my thoughts is on this slide where I think there are
really three possible fates for a cloned or for fertilized embryo. We
fertilize one of these leftover embryos, hundreds of thousands in the
clinics. They can be disposed of, they can be implanted to form a
normal baby with a high probability, or they can generate normal ES
cells. The cloned embryo, three fates. It can be disposed of. It can
make normal ES cells, as I have argued, but it cannot make with any
acceptability efficiency a baby, not even a normal one.
So if this is accepted, instead of
disposing these leftover embryos and use them for normal ES cells,
which could be used for research, as we heard. This, of course, to my
opinion generates an ethical problem because you destroy potential
human life. I think this—so if this is acceptable to some, I think
it should be ethically less problematic, because in this case I think
you don't have the potential to form, within acceptable
possibility, a normal baby.
So from the biological point of view, I
think the derivation of embryonic stem cells by nuclear cloning
develops the structure of an embryo that lacks the potential to develop
into a normal being with any acceptable efficiency or predictability.
I was asked—and I want to close with my
final slide, which really follows what John said—what are the
potential applications of cloned embryonic stem cells derived from a
cloned embryo. I think we talked about therapy. Clearly, I don't
have to dwell on this. I'm not sure whether this will be really
generally available technology. It maybe too expensive. I don't
know. And I don't know how fast we could solve the technical
problems of adapting this to human medicine.
However, I think this is the more
important point, which I think John emphasized. I think it allows us
to derive genetically identical cells from patients with multigenic
diseases, such as Parkinson's, Alzheimer's, ALS, diabetes. And
we can now use this system in vitro to validate the cellular
defects of these complex diseases. So compare ES cells derived from a
healthy individual with those from such a patient. I think there's
enormous potential here if we find a difference, to find out why that
is so, and is it a screen for potential therapeutics, just in the
culture dish. And as John emphasized, such diseases cannot be studied
in animal models, because there are no animal models for those
diseases. But you can really make those in the culture if you just use
a cell of the patients.
So I think this is a very important,
maybe the most important driving issue, to my opinion, to use this
technology. Thank you.
CHAIRMAN KASS: Thank you very much. Dr.
Prentice. While we're waiting, Dr. Jaenisch, would you mind just
taking one question of just factual information so that we don't
lose a lot of time. This last point about the models for multigenetic
diseases. If someone were to say the same kind of models might be
available through, for example, the multipotent progenitor cells that
Dr. Verfaillie has, where you could go into the patient and get out
progenitor cells. You might not get all the tissues, but if those
cells could reliably be differentiated into islet cells, couldn't
you do the studies on the pathogenesis of—in other words,
couldn't one, if one had stable and reliable adult stem cell
populations, wouldn't you have the same access to the cells from
the multigenetic diseases?
DR. JAENISCH: Yes. I think if this
would work, if this would efficiently work, I think absolutely I agree
with you. I think the problem as I see it now is that, indeed, working
with adult stem cells is very difficult. And the major problem is that
we lack the ability in most cases to, for example, propagate them in
the undifferentiated state. For example, with bone marrow stem cells,
although they're known for 30 years, this has not been
accomplished. They are very useful for therapeutic applications
because they select themselves in the patient, but not easily for this
type of research, what you want to do.
So I think there might, at some point, if
we learn that in this young field, I agree with you. Then I think
these cells would, if you could differentiate them to dopaminergic
neurons in a way that we can do for now from ES cells, as Ron McKay has
shown, yes I think that would be useful.
CHAIRMAN KASS: Thank you. Dr. Prentice,
you're all right?
DR. PRENTICE: Yes.
CHAIRMAN KASS: Good.
DR. PRENTICE: I think we're ready to
roll. Thank you, Mr. Chairman. I apologize for the delay up here. I
was fighting off a fever from a respiratory virus, so I probably was in
a time warp.
One of the main goals of stem cell
research, as you're all aware, is the idea of regenerative medicine
with stem cells, the idea that you might be able to take a stem cell
from some source, for example here from bone marrow, inject that into
an area of damaged tissue in the patient and regenerate or replace the
Now, the interesting, confusing thing
about adult stem cells has been that it defies what for years we have
thought of as the normal developmental paradigm, that as we develop
from the blastocyst stage here, that cells follow one of these main
developmental trees. And as a cell would become more and more
developed and more and more differentiated, they would end up out here
on the tip of a branch and not be able to back away from that
particular tip; not be able to back down and take a separate branch,
whether it were a nearby branch or one of these main branches.
A lot of evidence now suggests, however,
that adult stem cells, at least some of them, can actually move from
branch to branch. Now exactly how they're doing that, the
mechanism involved in these types of differentiation or different
branches of tissues, is still unknown.
There's several questions related to
adult stem cells, and in fact many of these have to do with the same
questions related to embryonic cells. What is their actual identity?
How could you identify a particular adult stem cell? What is their
actual tissue source? How do they form these other cell and tissue
types? Do they form actual functional cell and tissue types, as we
look at these organs and tissues? And what's the specific
mechanism of differentiation?
They do seem to have some unique
characteristics, such as a homing phenomenon, where they tend to home
in on damaged tissue. And most of the results that have been seen in
terms of an adult stem cell differentiating into another cell type or
tissue type seem to be tied primarily with injury to a tissue or
organ. Usually you do not see these types of changes in the
experiments taking place unless there is some sort of damage. The
other thing would be what type of cellular interactions and signalling
within the target tissue might trigger some of these differentiative
Now, one way to try and identify a stem
cell is with various markers, and I discuss this at some length in the
paper. Typically what people have tried to do is eliminate what are
termed "lineage markers" for particular blood cells. Some
people pick a particular marker called CD34, which has been associated
with bone marrow. But others tend to eschew that type of marker. And
I mentioned other markers in the paper that might indicate that an
adult cell is a stem cell. The CD133 marker, or the c-kit marker.
Several people have begun to undertake
studies of the gene expression within adult stem cells, and compare
them to embryonic cells to see if there is a commonality in terms of
all of the various genes that might be expressed that identify a cell
as a stem cell. One of the problems that's been faced, though, is
that these markers tend to change over time. This has been seen in
several studies where actually a marker such as CD34, that might have
been a chosen marker to identify a stem cell, actually might not be
expressed at a later time with that cell. And then expression of that
gene would re-occur, even within the same cell.
So it may be difficult to actually
identify one particular stem cell based on some of these markers,
simply because of changes in gene expressions as the cells undergo
changes in environment, as they may undergo changes in their isolation
conditions, and what Theise and Krause simply have called the
uncertainty principle, equivalent to the Heisenberg uncertainty
principle. You might at one point be able to isolate a cell with a
particular set of markers or milieu of gene expression and say this is
a stem cell, but then as you would try to put it into different
conditions, or isolate it from different tissues, those particular
markers might change, or might be different.
So it may actually be very difficult with
adult stem cells to particularly isolate a particular cell and say,
yes, this is an adult stem cell. It may be more a matter of the
particular context of the cell: the tissue they're derived from,
the isolation conditions used, or the tissues that they're put back
into that may determine their functionality.
In terms of differentiation mechanisms,
cell fusion appears to be one particular mechanism by which an adult
stem cell may change into another tissue type. Now there were some
in vitro experiments done approximately a year and a half ago
that indicated this possibility, but the in vitro experiments
were unable to verify whether this was actually a particular mechanism
that might be used by an adult stem cell. More recently, two papers
have verified in mouse systems that bone marrow stem cells, at least in
these experiments, did fuse with hepatocytes and take on that
differentiated morphology and function, even in terms of repairing
liver damage. So this is obviously one possible mechanism with some
Another possibility might be that a cell
would de-differentiate, actually back down one of those branches and go
up another branch. This would involve changes in gene expression to an
earlier state, or more primitive type of cell, and then re-expressing
specific genes particular to the tissue into which the cell was
placed. Another possibility is what's termed
"trans-differentiation" in which the cell apparently is not
backing down a branch, but instead simply changing its gene expression
so that it now conforms to whatever tissue or cell population that
In terms of sources of adult stem cells,
not just tissues, but how did they get there? How did an adult stem
cell get into bone marrow, or brain, or liver? One theory is that some
of these cells may be leftover primitive stem cells, perhaps embryonic
stem cells, a few that are kept around, maintained in a state so that
then they can differentiate into various types of tissues.
Another proposal is that there may be a
universal stem cell, an adult stem cell, not a primitive cell, but one
more geared towards maintenance and repair functions in the adult
body. It may arise in one or more tissues, and then may disperse into
Other possibilities are that there are
particular tissue stem cells, multipotent, not able to perhaps form all
tissues of the adult body, but a limited subset, and that they would be
resident within a few of these tissues.
And then I mentioned here transient stem
cells, cells that are just sort of passing through. And there is the
possibility that, especially if we're looking at this idea of a
universal stem cell, or even a tissue stem cell that can migrate in
some cases, that it may end up passing through a tissue, so you will
isolate what appears to be a stem cell from a particular tissue. But
it didn't arise there. It just happened to be passing through via
the circulatory system.
I might mention, too, that some of the
other challenges for adult stem cells are very similar to some of the
challenges for embryonic cells. For example, standardization. There
essentially is no standardization in terms of adult stem cell
isolation, propagation, differentiation into other tissues at this
point. Long term culture, with a few exceptions, has not been
attained. Catherine Verfaillie's MAPC cells from bone marrow do
appear capable of long-term proliferation in culture. And there are a
few other examples, very limited, that I point out in the paper. But
being able to keep these cells growing in culture for a long period of
time has been difficult up to this point.
The idea of safety, of course, is always
an issue when we're going to be dealing with patients. Do these
cells form tumors? Do they differentiate abnormally so that you
don't get the correct differentiation in the place, in the time, in
the tissue that you need? So all of these need to be faced.
Now this idea of a potential universal or
at least tissue stem cell that can migrate primarily has been put forth
by Helen Blau of Stanford, the idea being that perhaps the cell is in
the bone marrow, but then can go into the circulation and then exit the
circulation into another tissue. Again, most of the studies have seen
this type of phenomenon in response to an injury, not in response to
the normal physiological systems.
How would we then define a stem cell,
especially an adult stem cell, if we have all of this problem with
changeability of markers, and lack of standardization? Moore and
Quesenberry have proposed a couple of simple guidelines. Now
obviously, any stem cell has the ability to continue to replicate and
maintain a population of cells. And then in response to some signal,
to differentiate into one or more potential tissue types.
An initial first cut at how to identify a
stem cell in the adult would be, can it take on a different morphology
in a tissue in which you place it? Can it take on some of the
differentiated cell markers that you would see in that tissue? Now
this is a bare minimum, and it doesn't really mean necessarily that
the cell is functional, that it can participate in tissue repair, or
perhaps even that it has truly differentiated into that specific cell
Supplementing that, if you could
demonstrate functional activity, and actual integration into a tissue,
this would be a much better marker of a cell as a stem cell. And
certainly, if in an injury situation, in animal model or even in human,
you could demonstrate a physiological improvement. That would be a
good indication that you were seeing this sort of stem cell
differentiation and repair.
Now, the next set of slides, what
I've tried to do is just condense from that rather difficult mass
to read of all of these various tissue sources, and cell types that
they can turn into, and so on. I won't spend a great deal of time
on these. I'll just try and point out some particular points on
With mesenchymal or stromal stem cells
from the bone marrow, we need to keep in mind that bone marrow is a
mixed population. We've known about hematopoietic stem cells from
bone marrow since the 1960s. These are well-studied and used
clinically. The hematopoietic stem cell is differentiating primarily,
at least, into blood cells.
Another stem cell that's in the bone
marrow is this mesenchymal, or stromal, cell. As I mentioned in the
paper, one way that this type of cell is actually isolated is perhaps
first by markers, but then also simply by its ability to form attached
adherent layers in the culture dish, once you're putting them into
the dish in the lab.
Now, there have been various studies, and
I've just tried to collect a number of them here, showing potential
differentiation into different tissue types, either in the lab dish, or
in the animal. Again, the way they're following this in the animal
is primarily to use a genetic or a fluorescent marker, follow the cell,
see what tissue it ends up in, and look at its morphology, and then
also potentially try to analyze functionality and integration into the
In various disease models, some of these
cells have been used. For example, in models of stroke. And I want to
point out again what Dr. Gearhart said. Animal models are only an
approximation. This does not tell us the actual situation that we
might encounter in human beings. But at this point, it's the best
we can do. We can see if these cells might participate in cell and
tissue repair. Using rat or human cells, there has been some
therapeutic benefit in some of these disease models in stroke with
animals. With demyelinated spinal cord.
Intravenous injection, interestingly
enough, of mesenchymal stem cells in the mouse has shown some
remyelinization in spinal cord injury. Adult stem cells are not alone
in terms of this ability. Other cell types have shown this. And this
does not necessarily mean that you've totally corrected the
condition. It simply means that you're able to provide some sort
of functional recovering of a bare nerve.
Another interesting point about this
particular study was that they did not see a large incorporation of
these cells into the spinal cord tissue. So what benefit they did see
did not appear to be due primarily to the adult stem cells actually
differentiating into the myelinating cells here. Instead, what
appeared to be happening was the presence of those cells caused a
signal for the endogenous cells to start to re-grow and repair the
In fact, Dr. Gearhart's lab just
recently published a paper showing that embryonic germ cells showed in
a particular mouse model the same type of repair phenomena. The mice
did show therapeutic benefit. But what they found was that the cells
did not, to a large extent, integrate in and participate in the
repair. Instead, it seemed to be a signalling phenomenon. And
I'll point this out in a couple of other examples along the way.
There has been one clinical trial that I could find in the literature
where 11 patients were treated for Hurler syndrome, or metachromatic
leukodystrophy using allogeneic, and not from the original patient,
but from donor mesenchymal cells. Now, the study noted that four
out of those eleven patients showed a small increase in nerve conductance.
One of the problems with these diseases is a decrease in nerve conductance.
There are other neurological effects, and so on. So small increase.
And in terms of loss of bone mass, all 11
patients seemed to maintain, at least for a certain time. But in terms
of any of the other symptoms in these patients, there was no effect of
the adult stem cells. Very early study.
Using mixed population of bone marrow
stem cells. So in this case, and again, this lack of identifiability
for a particular adult stem cell. What many people have done is simply
take raw bone marrow and either in culture try to get various
differentiations, or putting back into the animal in various disease
models. And they've been tried in quite a number of disease models
showing some therapeutic benefit. In this particular case, again in
stroke, intravenous injection of this mixed population of cells.
Again, no attempt to purify the cells, or identify the particular cell
that's being used for the treatment of the animal model. But the
cells in this case did home in on the damage. Again, this interesting
phenomenon that we've seen.
Various other conditions. There was an
interesting study relating to cardiac damage, where cells from mice
were actually put into rats. And what they noticed was over a fairly
extended period of time there did not appear to be immune rejection of
these transplanted cells, even though they were even from a different
Now, it's only one study. Does that
mean that these particular cells might be immune privileged and not
subject to rejection? Only more experiments will tell. Recent study
indicated that with diabetes, in a mouse model again, where the
pancreas was damaged to induce loss of insulin secretion, bone marrow
stem cells injected into the animal could regenerate insulin-secreting
cells. As in the other example I mentioned before, there was very low
incorporation of the actual bone marrow stem cells identified as
forming insulin-secreting cells. Instead, what they seemed to be doing
in this instance was again secreting particular growth or stimulatory
factors to stimulate the endogenous cells to re-form insulin-secreting
And there have been several clinical
trials and publications, peer reviewed publications, from those trials,
primarily with cardiac damage. There have been several groups in
Germany and a group in Japan that have published their results. Again,
very, very limited numbers of patients, we must keep in mind. And what
they're seeing, though, is some physiological improvement in the
ejection fraction from the heart, and when they actually examine some
of the damage that seems to be being repaired. One Japanese group has
reported growth of blood vessels in limbs that were threatened to be
lost by gangrene.
Peripheral blood. Probably we should
just skip this category, in a sense, because they seem to be very
similar to the bone marrow stem cells. And it makes a lot of sense
that bone marrow stem cells could actually enter the circulation. The
interesting thing is that two groups recently have isolated peripheral
blood stem cells from human blood. One group in particular noticed
that the cells that they isolated showed high levels of Oct-4
expression, this gene that's associated with pluripotent status of
a stem cell.
In a couple of animal disease models for
stroke and cardiac damage, and I put this under peripheral blood
because what the workers did was not remove adult stem cells and then
re-implant them in the animal. They injected growth factors to
stimulate mobilization of the stem cells, most likely from bone
marrow. And these cells appeared to provide a therapeutic benefit in
these conditions. And we'll come back and talk a little bit more
about mobilization later.
Neural stem cells. I certainly was
taught in graduate school that you start with as many brain cells as
you're ever going to have and it's downhill from there. And on
my campus, it's downhill even faster on a good Friday or Saturday
night. But within the last decade or so, the discovery that there are
these stem cells within neural tissue that can at least regenerate all
three main neuronal types, and perhaps some other tissue types as
Interestingly enough, they have been used
in some animal disease models to show some therapeutic benefit. And
there have been some clinical trials, very early. There is one
Parkinson's patient who was treated with his own neuronal stem
cells. The cells were removed, grown in culture for awhile, and placed
back just into one side of the brain. He did see a benefit. He did
In terms of spinal cord injury, there are
no peer reviewed publications in terms of actual human treatment. But
there have been reports that at least one group in Portugal are
beginning these types of treatments on patients for spinal cord
Dr. Gearhart mentioned the embryonic
carcinoma cells. And there's one group of this cell termed usually
"hNT" that you might say has been tamed in culture. This
particular line that they've come across primarily forms
neuronal-type cells in culture, and, as he mentioned, it's being
used in a beginning clinical trial on stroke.
Muscle stem cell can regenerate itself.
It has its own stem cell, primarily dedicated to forming more muscle.
But there's indication that it does have, perhaps, another stem
cell present in that population. Debate as to whether those cells can
actually form blood, or if that was one of these so-called transient
cells moving through. The potential though, perhaps, to form bone from
this type of cell, and these muscle stem cells have been used in some
disease models, primarily directed back towards muscle. Very
interesting one that I came across was to re-form bladder muscle, or at
least reinforce bladder muscle, in a rat model of incontinence. And
there's been one published paper regarding a clinical trial using
muscle stem cells, one patient, in France, where the patient did seem
to receive some therapeutic benefit from the muscle stem cells.
Liver stem cells and pancreatic stem
cells. Pancreas and the liver derive from the same embryonic
primordia. And so it might not be surprising that you tend to see
liver able to form pancreas, or pancreas able to form liver. The
interesting thing here is that genetically engineered liver stem cells,
simply by adding and activating a gene, have helped an animal model
induce diabetes in these animals. The pancreatic stem cells, likewise,
have shown the similar ability.
Corneal limbal stem cells are a very
limited subset. And what we might in one sense call a unipotent stem
cell, at least for the most part, other than one or two little reports,
so that they would re-form only the tissue in which they're
located. They have been used, however, in corneal transplants in a
number of countries. And there are several published reports on this.
In vitro, one group was able to get them to form neuronal cells
in culture, or what looked like neuronal cells.
Cartilage, again, a very limited sort of
application, but clinical trials for articular cartilage transplants.
And one group has used them in an attempt to treat children with
Umbilical cord blood, not a great deal of
research has been done, but there are a growing number of
publications. The interesting thing here is, in terms of the disease
models, stroke, spinal cord injury, and one particular model of ALS,
the cells are delivered intravenously. So again, this potential to
home in on areas of damage.
And then just a list of a number of other
tissues here where some type of adult stem cell has been identified, or
potentially identified. And I want to point out the adipose, or
fat-derived stem cells. And I use "derived" because it's
very likely this is one of those transient stem cells moving through
via the circulatory system. Interestingly enough, though, it provides
a reliable, readily available source, you might say, from liposuction
fat. And one group has been able to see neuronal differentiation in
the lab; not in any animal models yet.
Now, in terms of activation and
mobilizing these adult stem cells, this may be actually one of the best
directions to go in terms of potential clinical treatments. Simply
because it may not be the stem cells themselves that participate in the
repair of the damage. And in that case, maybe what we need to do is
simply activate the cells so that they can deliver the signal to the
damaged tissue. And again, there may be various states within the bone
marrow as an example of a tissue where you might activate, where the
cell could be activated and then mobilized into the circulatory system,
and then reach the particular tissue to differentiate.
Again, there were two animal models that
had been used, one for cardiac damage, and one for stroke, where there
was an indication that this might be a potential avenue of research.
Rather than removing the cells, having to culture them, isolate them,
identify them, put them back, simply being able to mobilize the cells
within the body.
Another possibility is genetic
engineering. And in terms of actual animal models of disease,
genetically engineered adult stem cells have been used in a few
examples in the publications. In lung, that one particular reference
indicated that there was a large contribution of the adult cells to
lung tissue. Again, a damaged tissue system.
Clinical trials, not directly, you might say, repairing a damaged
tissue. But in Severe Combined Immuno-Deficiency Syndrome, bubble
boy syndrome, several infants have been treated using genetically
modified bone marrow stem cells from the patient. They seem to
have been, quote, "cured," and I use that word advisedly,
of the disease. There have been reports that at least two, and
potentially a third infant, has come down with leukemia as a result
of that treatment, most likely due to the viral vector that was
used to insert the gene into those cells. Because the gene is not
targeted in those instances. Instead, it may go into an area where
it can activate oncogenic genes within the cells.
In terms of delivering the signal, this
might be an even better use of genetic engineering in adult stem
cells. And there have been a few published examples, potentially for
use in animal models with tumor therapy, to alleviate some of the
symptoms in the model of Niemann-Pick disease for increasing bone
healing, and in a Parkinson's model, where the cells were not
participating to any great extent in repair of the tissue. Instead,
they're delivering a signal to the endogenous cells there, and
And in terms of that then, perhaps the
best avenue eventually to pursue might be trying to isolate what these
factors are, so that no stem cells would be needed at all. Instead, if
you can identify those factors to stimulate regeneration within the
tissue, they could be delivered directly.
And there are a few published examples of
this, one in which there was some axon regrowth, some, in a rat spinal
cord injury model by injecting a couple of different factors. One
mouse Parkinson's model study infused directly a factor into the
brain of the mouse model and saw a therapeutic benefit. Another
publication lists a different factor in terms of a model of chronic
kidney damage. And one clinical trial where five patients, five
Parkinson's patients were treated with infusion of this
glial-derived neurotrophic factor, they did see some improvement. Not
a cure, and it may be that that's not the sole signal that's
needed, or the correct signal. But it did seem to stimulate some
physiological improvement in the patients.
CHAIRMAN KASS: For a young field,
there's a lot going on. And we have also talked our way late into
the hour. Let me make a suggestion, if I might. Technically, this
session was to run till 3:30, with the next to start at a quarter of
4:00. I'm going to take the liberty of suggesting we spend a half
an hour here at least with our visitors to get some of our questions
asked. And if Lori Andrews will forgive us, we'll be pushing back
the start of the next session, just so we can get the questions asked.
Michael Sandel, then Jim Wilson.
DR. SANDEL: I learned a great deal from
all of these presentations, as I suspect we all did. I was especially
struck by one feature of Dr. Jaenisch's presentation, and I'd
like to put this as an observation which actually will end with a
The subtitle of the paper and of the
talk, Dr. Jaenisch, and my Council colleagues will appreciate this
perhaps more than our visitors. The subtitle could well have been,
"The Vindication of Paul McHugh." Because when we were
discussing the biology of cloning, almost everyone here shared an
assumption, regardless of the positions that we took on the ethical
issues. Almost everyone took it for granted that biologically the
fertilized embryos and cloned embryos were essentially the same, and
the moral argument proceeded from that assumption. With the exception
of one person, Paul McHugh.
And he introduced a distinction, a
distinction, as he put it, between a zygote and a "clonote",
by which he meant the cloned embryo, the product of cloning. And for
insisting on this distinction, poor Paul suffered heaps of ridicule and
abuse, and, at best, a kind of bemused chuckling, by those of us around
the table. And he argued that there's a difference, a biological
difference, with a possible ethical significance between a zygote and a
clonote, between a fertilized embryo and an artifact created in the
lab. And he was told that this is an eccentric position. He was told
that this is an off the wall distinction, that it had no basis in
biology or science.
And in a memorable exchange with our
colleague Charles, who unfortunately isn't here for the benefit of
this discussion, he was asked, "Well, but what if a cloned embryo
actually came to term? Isn't Dolly a sheep?" And Paul's
answer was, "Well, a sick sheep."
And then we read, Dr. Jaenisch, in your
paper that a cloned human embryo would have little, if any, potential
to develop into a normal human being, that it lacks essential
attributes that characterize the beginning of normal human life. And
you explained that it has to do with faulty reprogramming after nuclear
Now, I don't know whether that's
true, whether it's generally accepted, or controversial in the
scientific community. But whatever the case, it seems that what we
regarded here as an eccentric, off the wall suggestion, that there is a
biologically significant difference between a fertilized embryo and a
cloned embryo, now, if I understand you correctly and here's my
question, now, you're telling us that far from being eccentric or
off the wall, Paul's position may be true.
DR. JAENISCH: Well, I think that was the
whole purpose of going through these arguments for me. To argue from a
biological point of view, it is a continuum. We have to struggle with
that. And we have, for the early, most abnormal stage, we have good
markers. Death is a terrific marker. Then we have molecular markers
after birth, or we have aging as another marker.
So these are concrete markers, and we know these animals are not
normal. So when it is claimed that cows on the field are normal,
which has been published by ACT. They looked at their one- to four-year-old
cows sit on the fields and eat and give milk. They argued, well,
they must be normal. So they checked that. And they checked it
by checking if it had a heart. Yes, it had a heart. A liver, yes
they had a liver, and that serum, even. So they concluded they
must be normal and publish this in "Science".
Now, this of course is a very superficial
way of looking at it. And very interesting. Once this paper came out,
six months later, two of these healthy cows, one got multiple tumors,
the other one generalized seizures. Now this is not normal. You wait,
and these things come out.
The point I was trying to make is that
these are stochastic problems. There is not a key master gene which,
if this is right then the embryo's right. No. The whole genome is
stochastically, correctly reprogrammed or not. And what's amazing
to me is that mammalian development is so regulative that it can
tolerate so much gene disregulation and still get an animal to birth
and beyond. But you pay for that. You pay with subtle or less subtle,
more or less subtle problems.
And of course, because it's
stochastic, you will arrive at the end at some animals which live a
normal life span. And by all our available tests they might be normal,
or you might not see it. If you look at the primate, or in the human,
we might see this because we could look at some much more subtle
So I think the point I was trying to make
is if you want to use this as a technique to generate human beings,
there's no predictability. You cannot do this. And for me, it
doesn't matter with one percent or two maybe something normal,
because you can't predict it before.
So I totally agree with what your thought
CHAIRMAN KASS: Jim Wilson.
PROF. WILSON: Michael asked the same
question I was going to ask using virtually the same words. I guess
it's the Harvard affliction.
But I want to just press a bit more. An
oocyte is not potential human life because it's an unfertilized
egg. You can enucleate it and put in a new nucleus, and now it is a
clone. But according to your account, a cloned embryo has little, if
any, potential to ever develop into a normal human being.
If you would step back, then, from your
biological role and adopt a somewhat more philosophical role, would you
say that a clone, therefore, is not potential human life?
DR. JAENISCH: I would argue it's not
potential normal human life.
PROF. WILSON: Thank you.
DR. JAENISCH: I think that's the
only thing I can say.
CHAIRMAN KASS: And Dolly still is a
DR. JAENISCH: Still was a sick sheep, was a very sick
sheep, and which died, of course, predictably very early.
CHAIRMAN KASS: Janet Rowley.
DR. ROWLEY: Well, I, too, learned a
great deal this afternoon. I want to make two comments, and then I
have a question for Rudy.
The first comment is that I think it is
most unfortunate that we're prevented from asking our experts, and
particularly John Gearhart, about the status of funding that supports
this very critical area of science.
The second comment is also directed to
John. And I was struck by the specific chromosome abnormalities that
you identified in your human embryonic cells, because you probably know
that an isochromosome for 12p is the most common abnormality in human
So it's astonishing that this is the
abnormality that you see in these cells, and I'm sure it is
The question that I have for Rudy—I
was surprised when you said that imprinted genes are only important in
embryogenesis, because clearly there are a number of human conditions.
Now, you could say, well, human condition
and the malformations occur because of embryogenesis, but there is also
this whole question of imprinting and its relationship to
carcinogenesis. So I'd like you to expand on that.
DR. JAENISCH: This is a very important
point you're bringing up, so I was probably a little bit
generalized. So I think most imprinting, as we know, have—so that
could be among these things that could be the most interesting, because
it's IGF-2, which is a loose cannon.
IGF-2 is a tumor, an oncogene
essentially, so this would be available for cloning, because IGF-2 is
very easily dysregulated. And I would worry if you have both copies
active, because that's pretumor status. So you want to screen for
But the other genes—for all of the
other genes, for example, an Angelman Syndrome probably really is—there are really problems of fetal development. So these genes and
fetal development—I could go further into this, because it's
really growth of the fetus, where these genes appear to play the most
And there's really no evidence, with
the exception of IGF-2, maybe KIP-257, which is a tumor suppressor
gene, those are the ones you would worry about. So I think we know
only two of those, and those you would test for I think.
So I agree, which makes this a little bit
more restrictive when I say it.
DR. ROWLEY: Right. And there probably
are others that we don't know about, but—
DR. JAENISCH: There might be others
which we don't know—
DR. ROWLEY: —you're saying that
DR. JAENISCH: Yes.
DR. ROWLEY: —just all be tested for.
DR. JAENISCH: Those two we know for
sure, but others we know they don't play a role.
CHAIRMAN KASS: I have myself next, if I
might. A question for Dr. Prentice, and then for the group as a
whole. In Dr. Gearhart's presentation, he gave a great deal of
emphasis to the importance of the characterization of these cells, the
reproducibility, all of these various things.
You had to cover an enormous amount of
material in the number of papers, and you also in your presentation
alluded to the problem of characterization, though I gather many of
these studies seem to be one-shot efforts of throwing some things in
and trying to see what their clinical effect might be.
And as I've read the debates, a lot
of people wonder, are these really stem cells? How well characterized
are they? So could you say something about what criteria should be
used for these stem cell preparations?
What criteria would they have to meet
before you could satisfy the critics that these are, in fact, fit to be
called human stem cells, and fit, therefore, for controlled studies on
the kinds of things that you're talking about here?
And kind of a subordinate question,
what's the best characterized of, and the most versatile of, these
adult stem cell preparations? Are there any that at the moment meet
the criteria that you yourself would advance?
DR. PRENTICE: In answer to your first
question, it's difficult, obviously, because as you point out many
of these studies have been sort of one-shot, especially if you look at
the mixed bone marrow population studies where they are simply taking a
preparation, putting it back into a diseased animal or a diseased
model, and trying to come up with some therapeutic benefit.
You know, obviously, what you'd like
to be able to do is to isolate the cell or the population, keeping in
mind that caveat that the population dynamics may be an important facet
But let's say there's one
particular stem cell that you're after. Supposedly, if you saw
that sort of therapeutic benefit from the mixed population, you should
be able to go in and simply take cuts and eventually isolate that one
cell, and then be able to grow it in culture.
In terms of the overall markers,
that's been very difficult, and there have been a few studies
looking at the gene expression common to neural stem cells, bone marrow
stem cells, embryonic stem cells. And there are a subset of those
genes that are common to all of those cells.
Now, what you would hope to be able to
do, then, is to go look at each of those genes and start using those as
guides to come up with a marker for any stem cell that would be
targeted for the types of differentiation models that we'd like to
see, and eventually clinical applications.
CHAIRMAN KASS: And with respect to the
second question, what is the best characterized and most versatile
adult stem cell preparation at the moment? I mean, can you—is there—
DR. PRENTICE: Probably Dr.
Verfaillie's MAPC cells, and I can't speak for her, but those
do show many of these characteristics that ideally you would like—long-term growth in culture, clonogenic growth, and then
differentiation. They've been used in a couple of different animal
models of disease to see some sort of benefit.
One of the mesenchymal cell—stem cell
lines, if I remember correctly—and there are a lot of things to sort
back through there—had been kept in culture, I believe, for about
two years. There was another cell line that—I think it was also a
bone marrow derived cell line, but it had been genetically engineered
to contain telomerase or additional telomerase gene. And that had been
kept in long-term culture.
I believe also one of the neural stem
cell lines has been kept in long-term culture, and actually Dr.
Gearhart might be able to comment more on that.
CHAIRMAN KASS: Okay. Thank you.
And I have a general question to all of
you, if I might. Since we sent you some general questions that we were
hoping to get some help on, to go from where we are now to actually
having reliable tissue grafting therapeutic applications in humans,
since there's a fair amount of speculation out there—and, Dr.
Gearhart, you did emphasize how early we are in the process and the
emphasis, really, on learning of the basic biology.
But the public out there is more—much
more interested in, you know, where are the cures? Could you address
that particular question of the various sort of stages, and where we
are, and what kind of—how one should talk about these things
responsibly in relation to the widespread hopes for remedies for which
the patient groups are, quite understandably, clamoring?
DR. GEARHART: The answer to that
question is a very complex one for me. I could run through a number of
cell lineages with respect to the human embryonic and stem cell and
germ cell lines, where we are in the process, but it's the other
end that I want to address.
The most difficult talks that I give
anymore are those before patient-based groups where the hopes are
high. They come with expectations that far exceed, I think, where we
are. And this is the result that I think that early on in the field,
as you mentioned, the hype was there when circumspection should have
been there. And I don't think circumspection is a retreat from
The reality is when you get into the
laboratory, and you are working on cell lines, it seems the more
progress you make, the further away the goal is as we learn. And we
can show I think remarkable things in our animal models of putting in
cells, and these are almost—they bear some resemblance to the adult
stem cell story where you try a lot of things empirically, you get a
response of some kind, and you're trying to figure out what it is,
But when you superimpose on top of the
biology issues of trying to control these cells in a dish, and trying
to expand them in a dish to characterize them, to show that they're
authentic, that they do work, the issues of safety, which I think we
all are in agreement have to be foremost in this, that the time frame
is years away before I think any of this will be realized in a clinic.
I think there's misunderstanding,
that if all of a sudden you have an insulin-producing cell in a
laboratory, which we do, and we're—as other labs have as well—that most people think this is the answer. You just put
insulin-producing cells into a diabetic. And as you know, this
doesn't solve the underlying problem.
We can—so I don't know how to
answer the question that you ask. I mean, I'm certainly
optimistic. I think it's going to be a direct function, and
I'll come back to Janet's question that she can't ask or
isn't supposed to ask, and that is that obviously more funding into
this area—and I know that this isn't a congressional committee
of any kind, where we're seeking funding, but obviously the
progress is directly proportional to the number of good investigators
you have working on projects.
And in this field, we've had a
bottleneck, first from the number of lines that could be used, now the
NIH funding I'm sure is going to be more robust over time, but this
remains not only I think a financial issue but also almost a
psychological one—for students getting involved, for post-docs
getting involved, for young faculty getting involved in the field,
where we don't know what the future will be, to be honest with you,
in this country.
We see our colleagues around the world in
different laboratories I think making really substantial progress
here. And so I'll get off this part of it, but I think this is an
important issue, at least with the embryonic and fetal sources of
cells. And I hope we'd get over that.
CHAIRMAN KASS: Thank you.
I have Gil Meilaender, Bill Hurlbut,
PROF. MEILAENDER: Yes. Dr. Jaenisch, I
want to come back to where Michael Sandel started us, because I'm
just not certain that I'm clear on something. And what I want to
know is, you know, it's always hard to know when one's speaking
as a scientist and when one's speaking as something else.
But as a scientist, there are various
kinds of chromosomal or genetic defects that a fetus might have, the
result of which would be that it might die immediately after birth or
very soon after that. How would you scientifically describe those
fetuses? Would you say that they have—that they also do not have
the potential to be a normal human being?
I'm trying to get away from the stem
cell issue for a moment. Would the same characterization be the
appropriate one there?
DR. JAENISCH: This a really a question
which is not a scientific question, then, right? An embryo which has a
trisomy number, whatever, large chromosomes will die very early, maybe
before implantation. So that has this embryo which is afflicted with
this genetic alteration.
Has that a normal potential development
to a human being? No.
PROF. MEILAENDER: So it falls into the
same—so, in other words, this is a rather large category of embryos
and fetuses that—about which we would say this. We're not only
talking about cloned embryos.
DR. JAENISCH: Well, I think that—
PROF. MEILAENDER: The same
DR. JAENISCH: Yes, I—
PROF. MEILAENDER: —would fit.
DR. JAENISCH: I think the difference,
from my point of view, if a chromosomal abnormality occurs after normal
fertilization, something which is totally unpredictable and is
assessed, that is what fate is to genetic game. With cloning, I think
it's predictable, and that's the difference. It is predictable
to a large extent, so I think that would make the difference.
One is spontaneous, unpredictable,
it's a risk of normal reproduction. The other one is predictable.
Otherwise, I really can't—I think this for me is a major
difference. You predictably generate a human being which has no chance
to become normal with any acceptable efficiency.
PROF. MEILAENDER: I think I'll stop
CHAIRMAN KASS: Bill Hurlbut, and then
DR. HURLBUT: Did I hear you correctly
say you find destruction of IVF embryos morally troubling, but cloned
embryos for embryonic stem cell use less troubling?
DR. JAENISCH: No. Well, I said that if
you accept that instead of throwing away an in vitro fertilized
embryo which cannot be implanted because nobody wants it, instead of
throwing this embryo away generating to an embryonic stem cell, I mean,
people accept this. I find this acceptable. But it does pose an
ethical problem, because you do destroy potential normal human life.
There's no talking around it.
So if you accept that, then I would argue
that a cloned embryo is less of an ethical problem. That's all
that I want to say. So the potential is not there.
DR. HURLBUT: And from hearing you and
talking with you at lunch, I had the sense that you feel like nuclear
transfer actually offers us more versatility and more promise than
using IVF embryos, because we can use the genotypes we want and control
various things. Is this fair?
DR. JAENISCH: Yes, I would think so.
DR. HURLBUT: So I have to admit I'm
troubled by your comment, and not convinced by Michael Sandel's
comment. As much as I like my colleague Paul McHugh, I'm not—I'm troubled by the notion that what you called not potentially
normal human life does not have a moral standing.
And the reason I'm troubled by that
is—was just alluded to by Gil, that I would not say that a
potentially abnormal trajectory of embryogenesis is not a human life
Now, I have a handicapped child myself,
and she does not have a problem of development, but she had brain
damage at birth. But she's not what you would call a normal human
life in that specifically all-healthy sense. But she's very human,
as human as I am.
I'll let somebody make the joke on
that one, if you want.
But the question is this. I feel for
what you're saying. I feel for what Michael said, and I feel—have been with Paul to some extent on this all along.
But if we say that natural—the natural
meaning of the definition of a human life is not normal, but some
meaningful process of integrated—of integration of identity, of
continuity, then it seems to me that the clones that have been produced
at least with animal studies have to qualify as entities of their
So even though, as you said to me even a
year ago, a cow standing on a green hill chewing its cud isn't—doesn't make it a normal cow. I agree. But I think it's still
And likewise, the human trajectory of
whatever the clone could be is troublingly human-like. I personally
wouldn't feel comfortable saying, for example, as was implied by
John Gearhart in his talk, that we could use it to harvest out later
tissues for more difficult differentiations.
Well, let me back that up. All of my
colleagues, and my own reading on this, confirms to me that going from
embryonic stem cells to useful cells, tissues, and organs, is a long
journey, maybe short for Parkinson's Disease, but longer for more
complex tissues, and very long for—what we really want is organs and—for transplant, like kidneys, and so forth.
I think there will be a temptation in our
civilization to move the trajectory of something that's designated
non-human on to further stages of gestation. Now maybe not gestation
in a human womb. Maybe it'll be in an artificial endometrium or
something that can coax it just 30, 60 days longer for good use. It
starts to be troubling, even if you accept your premises.
Let me back it up, then. I think in
principle what you're saying has something to it, and Paul and I
have been trying to talk about this, and I've had dialogues with my
colleagues on this.
I put forward in my personal statement on
the President's Council Report on Cloning what I called a
speculative proposal, where I suggested that—drawing on what Paul
had said, that this is an artifact, not a human being, a clonal
Why don't we go to the bottom of the
problem? Why don't we say that something that does not have a
human potential in any meaningful way, not an abnormal human potential,
but no meaningful human potential, might supply us with the essential
way to get around the moral problem, at least to get us to stem cells?
And we can deal with the next issues later.
And I want to stay two things before I
conclude. One is in making this proposal, I was very aware that the
first issue of what you might call the inviolability of the human life
is only the beginning of the questions about the moral use of human
process or human tissues or anything.
But what I had in mind was this—that
just as we've come to see that a cell does not define the locus of
human dignity, nor does a gene, of course—let's start at the
smallest. A gene—a human gene can be put into a bacterium, grown,
used to make insulin. A cell—we do blood cell transplants. Tissues—we do skin transplants. Organs—we do transplants and even organ
systems. None of those are the locus of human dignity, human moral
Likewise, in this age of developmental
biology, we will learn that partial generative potentials are not the
locus of human moral standing. We will harness these partial
generative potentials in such a way that we can do wonderful things
with them without violating the integrity, identity, and continuity of
So this is my question to you. Could we
find a scientific way to meet the challenge of our President and our
nation and the imperative of our civilization to go forward with the
science? Could we define the danger as we never want to interrupt a
normal human life in process, or even one that is remotely normal?
Could we meet that moral objection while
at the same time opening the positive future of our science? And here
the suggestion I would have is using something so fundamental, like
short, interfering RNA, to preclude the very possibility of anything
but the most minimal and genetic mammalian process to the blastocysts
from which we could then take embryonic stem cells.
What do you think?
DR. JAENISCH: Yes. I think we talked
about this before. I think it's a really interesting possibility.
So what we need to—for a human being to develop two major lineages,
which is a trophoblast lineage and the epiblast lineage. The
trophoblast lineage will support the embryo from the placenta.
So certainly there are genes which are
only needed, as far as we know from experiments, that are only needed
for placental development. They are not needed for the epiblast
lineage or for the embryo. So one would modify a donor cell—let's say a skin cell that you want to transplant—with
inactivating such a gene—I can give you examples of those—and
expressing, for example, using the SI RNA technology, which now really
becomes—seems to become a routine procedure to inactive genes.
And, indeed, an embryo—a cloned embryo derived from such a nucleus
would not be able to form a trophoblast lineage which would be functional.
So, therefore, if this embryo would be implanted, it would definitely
fail. You could predict it would fail much earlier than this continuum,
which I outlined for the cloned embryos which are not modified.
So I think, in principle, this is a
doable—potentially doable manipulation which would prevent what you
are interested in and what you are raising, prevent the development
very far in utero.
DR. HURLBUT: In your opinion, could we
reasonably call that not in any sense a human life in process, abnormal
or normal, but call it a clonal artifact, a laboratory production for
the procurement of cells with a potential for something, but not what
we would have to call embryonic cells?
DR. JAENISCH: Yes, because you would
argue this embryo—I mean, the definition of an early embryonic cell,
like a two-cell or a four-cell embryo, the blastomere, is totipotent.
These cells can make the placental lineage and the epiblast lineage.
This embryo would not be able to make the
trophoblast lineage, so, therefore, it would not be totipotent. So I
think you could argue this would be a real biological difference.
CHAIRMAN KASS: We do want to go to the
next session shortly, but I've got Janet and Elizabeth, and then
I'm going to call a halt for this session.
DR. ROWLEY: I come back to John
Gearhart. And, first, I want to take you to task for comments at the
very end of your talk, and then I have a question. And what I want to
take you to task for are your comments, all related to enhancement and
how easy it's going to be to just get genetic enhancement of all
sorts of features.
And I think—well, you could expand on
that or explain what you meant by that. But this has been such a
critical issue for this particular Council—the likelihood of
enhancement—that I think that it shouldn't just be left
And the question that I have is, with
regard to characterization of current lines, you indicated that
that's under the auspices of the MRC in London. And I'm just
curious, are they looking at both so-called presidential lines as well
as lines available elsewhere? Or are they only lines available
elsewhere? And what kinds of characterization are they proceeding
DR. GEARHART: Let me answer the
non-controversial question first. This is a relatively—this panel—there has been, over the last nine months or so, an international
consortium that has been meeting on human embryonic stem cells.
The outcome of this was the appointment
of a panel headed by Peter Andrews at Sheffield University, who will be—that panel will be setting up the standardizations, if you will, or
the criteria for the embryonic stem cell lines.
They will—I think some of this work
will be done in the equivalent of what's the FDA in the United
Kingdom. But they will take any cell line that's submitted to
them, whether it's a presidential one or one from anywhere else.
They are not a—they are not distributing cells. They are just
testing them for these different parameters.
And, obviously, there will be a number of
transcription factors, a number of surface antigens. This kind of
thing will be in that mix.
DR. ROWLEY: Will they do karyotypes?
DR. GEARHART: Oh, yes, karyotype is—yes, it's absolutely essential to have a normal karyotype, and one
that's stable over a number of cell passages is critical.
The comment I made about enhancements, I
just—it may have been out of order here, but I am concerned, I mean,
as a biologist I'm concerned. I'm concerned about a number of
issues. It makes it sound as if most of the time that scientists
aren't concerned, that we're just going along in a fashion
that, you know, science for science sake.
And I only have to remind you over the
last few months to see the use of human embryonic stem cells in mouse
chimeras, the use of chimeric human embryos that has been done, that
you say there's no reason that these things should have been done.
I mean, there's no scientific basis for this.
And we have to have some degree—and
I'm not going to call it regulation, I don't like that term,
obviously, but there has to be some consensus as to what should be
permitted and shouldn't be permitted in almost a global way. And I
realize that this is very, very difficult.
I've been to two G-6/G-7 meetings in
which we have tried to get some kind of consensus even on human cloning
among countries. I mean, let alone the use of embryos for research,
and things like this. And as you can imagine, nothing much happens.
Everyone has their own opinions, and we go away.
When we have the capability—if this
work is successful—I'll be frank with you. If this work is
successful, and by success that we are learning mechanisms around
differentiation and the development of cell types, we are going to have
an awful power that we can instruct ourselves.
Now, we're not necessarily going to
be talking about germ line cells or germ line modifications. Maybe.
Because, obviously, if we can grow oocytes from these cells—there
are reports that we can grow spermatogonia and sperm cells out of these—maybe the possibility exists for that at this point.
But I'm just hoping that people are
thinking ahead a bit, that, you know, this is something that's
going to be on the table in a number of years, and that we should give
it some thought—where we're going to go with this. That's
And so I made a comment about, you know,
getting it off the internet or something to do it. Maybe that's an
overstatement. Maybe that's just crying wolf, and I apologize for
But I think it's something that we
have to be aware is out there. It's going to be out there. Not
out there now, but will be out there, and we should be thinking ahead.
So I apologize to the Council for making that kind of a comment.
DR. ROWLEY: Well, I don't think an
apology is necessary. I think what I'm trying to say is—my own
personal view is that the Council should be especially concerned about
things that are relatively near term. And by "near term," in
such a rapidly-moving field I think a few years is near term. And if
you're saying, well, in 10 years' time we'll be able to do
this, we can't see that far ahead.
DR. GEARHART: Right. Right.
DR. ROWLEY: And so that—so what kind
of terms are you talking about in terms of time?
DR. GEARHART: Oh, I'm talking not
about 10 years. I'm talking about a shorter time interval.
DR. ROWLEY: Okay.
DR. GEARHART: You know, Janet, I think
to be honest with you, the number of federal Blue Ribbon Panels that
have been set up, at the NIH level, the National Academy, to discuss
issues that seem to be 10 years away, recommendations were made by our
leading scientists, our leading scholars, only to be ignored. And
then, we find ourselves in a pot once these things happen.
And it's just, I mean, frustrating as
a scientist. It's frustrating almost as a citizen to do this,
where it seems that the scientific community, to a certain degree, is
marginalized when it comes to making recommendations as to how we
And we are left, then, every time
something comes up in this area everything is thrown up in the area as
to where we're going, etcetera. So that's the nature of the
comment. Or, I'm sorry, that's the basis of the comment that I
CHAIRMAN KASS: Last comment. Elizabeth,
if you—did you still want to say something? You were on the queue.
PROF.BLACKBURN: I'll return to the
science, and I don't know who would like to answer this question.
But it was picking up on the point that I think Leon did raise about
asking about the sources of adult stem cells. And you mentioned that
there's really only one good one, or the best one, is that right.
Dr. Verfaillie's. And—
DR. PRENTICE: I think Dr.
Verfaillie's is the best characterized—
PROF.BLACKBURN: Yes, best
DR. PRENTICE: —in terms of all of
these various traits.
PROF.BLACKBURN: Yes. So, you know,
we're struck—and I think Leon pointed this out, too—by the
fact that there's a great deal of research that's been ongoing
in the last, you know, couple of years—
DR. PRENTICE: Yes.
PROF.BLACKBURN: —on adults. And yet
it seems to me there's a real problem. And, you know, what's
the problem? Why is there so little known? To put it bluntly.
You know, here's 192 publications
that you cite, and why is it so difficult? Are these just inherently
really difficult things to work with? Is this what it comes down to,
that people who work with adult stem cells don't really like to say
that, or—sorry to cut to the point, but I know time is of the
DR. PRENTICE: I think one of the reasons
comes back to this difficulty in identifying which one is actually the
stem cell, how to actually purify it, isolate it. Some of the cells
seem rather easy to isolate. Certainly, peripheral blood is quite
easier, or the adipose-derived cells would be easy to isolate.
But then, how do you really know that one
is the stem cell? And, again, most of the results—the best results
seem to come primarily from these mixed populations of the bone marrow
stem cells, where they have not intentionally in many cases isolated
the particular stem cell. Instead, they've been geared towards
some sort of physiological endpoint.
My assumption would be, then, working
back from that, once they could achieve that end point, then they might
be able to derive the particular cell.
But I think it also brings up a point I
tried to raise before in that it may not be possible, or it may not be
preferable, to try to get a particular cell. It may be the context of
these cells with the population and their interactions, exchanging
growth factors, altering their own gene expression, and then—in the
tissue milieu—that really gives them this ability to somehow cause
And I use that term because, again, I
think in many of the instances the research is showing that it's
not direct integration and taking on the function. It's somehow
stimulating endogenous cells.
PROF.BLACKBURN: So it may—are you
hinting that it might be qualitatively different from what is going on
with embryonic stem cells, when those were tried to be used?
DR. PRENTICE: Well, I—
PROF.BLACKBURN: I don't want to get
too much into this, but I'm just trying to understand the science
DR. PRENTICE: Yes, I think that might be
a good way to put it. It may be qualitatively different. You know,
it's interesting Dr. Jaenisch mentioned that embryonic stem cells,
in a sense, are a tissue culture artifact. He might just as well, by
the same definition, call Dr. Verfaillie's MAPC cells a tissue
And it may be that putting these cells
into culture, now changing their context, gives them some of these
characteristics that are so sought after. Our target might be better
put in terms of, what is the physiological endpoint that we want? Not
a particular starting cell, but how do we achieve the repair of the
And, again, as I mentioned in the talk
and in the paper, it may be that it's not a particular cell that we
really need. Short term, cellular regeneration may be our best goal.
But long term, figuring out the particular molecular and cellular
signals—and, again, it may be a context-type signal—cell-cell
context or cell-matrix context—that actually can give us that
physiological endpoint, and so eventually going to a non-cell-based
system, but a signal-based system if you will.
CHAIRMAN KASS: Paul McHugh insists on a
very brief comment, and then we're—
DR. McHUGH: I have just two—
CHAIRMAN KASS: —going to break.
DR. McHUGH: —little tiny scientific
questions, but because they are important science that we're
discussed here. The first one really relates to Dr. Jaenisch, and that
is, I wanted to know, sir, now whether you could say that the genetic
alterations and the problematic genetic status of the fully cloned
animal, whether those genetic abnormalities would then pass on to their
offspring, and so, therefore, be a contaminant to the whole human
genome legacy from then on? That's the one question.
DR. JAENISCH: Let me first clarify there
are no genetic alterations which are important. They are all
DR. McHUGH: Right, yes.
DR. JAENISCH: So the experiment has been done. You can
take two animals afflicted with large offspring syndrome and mate
them. The offspring will be all (risk?) normal, because you send
the genome through the process of gametogenesis, which reprograms
everything in a normal way, everything is reset.
Of course, there might be some genetic
alterations which are acquired during somatic life.
DR. McHUGH: Right.
DR. JAENISCH: Those would not be—they
cannot explain the phenotype. They would be recessive, and so they
haven't shown up yet.
DR. McHUGH: Right.
DR. JAENISCH: So we don't know if
they would show up.
DR. McHUGH: They might show up later.
DR. JAENISCH: Right.
DR. McHUGH: And secondly, to John
Gearhart—John, you whine a lot about how troublesome it is to be a
scientist nowadays. I just want to know this. The President made a
very good Solomonic decision and produced the cell lines for you
scientists to work, putting the ball in your court.
Are you saying to us now you've used
up all of the potential in those cell lines, and now, because of the
President's decision, are restricted in your progress?
CHAIRMAN KASS: You don't have to
answer, and he's over time. But if you'd like to—
DR. GEARHART: I have to answer Paul.
CHAIRMAN KASS: —15 seconds.
DR. GEARHART: Being a scientist is the
greatest thing in the world, and I wouldn't trade it for anything,
Paul. And so I don't—
DR. McHUGH: I know that, John. Me, too.
DR. GEARHART: Okay. And I'm not
here to whine. The funding issues are improving, and they are
improving nicely here. Okay? And, clearly, we can learn a lot through
the lines that are approved.
CHAIRMAN KASS: Gentlemen, thank you very
Look, we have a guest we've kept
waiting for quite a long time. Would the Council, please, 10 minutes.
Thank you all very much.
(Whereupon, the proceedings in the foregoing matter went off
the record at 4:10 p.m. and went back on the record at 4:23 p.m.)
SESSION 4: STEM CELL RESEARCH: CURRENT
LAW AND POLICY WITH EMPHASIS ON THE STATES
CHAIRMAN KASS: The last session of the day, also on stem
cell research, recent developments in law and policy, with emphasis
on the states. Federal policy governing human stem cell research
is well known to the Council.
It has been formed basically of two elements — a legislative
prohibition on the use of federal funds for destructive embryo research,
and President Bush's funding decision to support work on the
already-existing human ES lines, with some 70 lines eligible but
only 11 lines available for use.
Funding for research on adult human stem cells is unrestricted,
as is research on human embryonic stem cells in the private sector.
The Europeans, who have similar national policies, don't understand
either American federalism or the traditional distinction over here
between public and privately funded activities. And they are surprised
to learn, say, the difference between what California and Louisiana
are doing in these matters. But to Americans, the separate laboratories
of the several states are nothing new.
And to help us monitor developments in
this area we've commissioned a paper by Lori Andrews, Professor of
Law at the Chicago-Kent College of Law, Director of the Institute of
Science, Law, and Technology at IIT, who is the country's leading
authority on this subject and a prolific writer also in the area of law
and bioethics, especially in relation to ART.
It's a very great pleasure to welcome
Lori Andrews for this presentation to the Council. We thank you for
your paper. We look forward to the presentation and the discussion.
Thank you for coming, and thank you for indulging us this extra time.
MS. ANDREWS: When you were having your
earlier discussion this morning about commodities and body tissue, it
made me think of a newspaper article I had read growing up saying the
chemicals in the body were worth 89 cents.
Well, obviously, with the tens of
thousands of dollars being paid for eggs and a human gene, like the
erythropoietin gene being worth a billion dollars a year, we've
entered an age of a market in human tissue.
And coming after the scientific panel,
talking about the many, many uses, you can see that market could be
burgeoning around embryo stem cells. Immediately after the potential
for these cells was announced in 1998, every NIH institute put on their
website what they planned with those cells.
The Heart, Blood, and Lung Institute said
it would repair failing hearts and grow new heart chambers. General
Medicine said it wanted to grow artificial skin. And even the
Environmental Sciences Group wanted to get in the act, proposing to use
embryo stem cells to "test the toxic effects of biological
chemicals and drugs."
Now, obviously, this is not without
controversy, and both pro choice and pro life advocates have
particularly centered on some of the commercial aspects of this. About
a week after the announcement in '98, I got a call from an in
vitro fertilization clinic, and the head of the clinic said to me,
"We have about 300 embryos that nobody has asked about recently.
Can we sell them to a biotech company?"
And I think this kind of goes against Dr.
Kass' idea that the people who aren't the individuals but who
are making the profits out of it have mixed their labor into it. Since
obviously this in vitro clinic had charged people to do the
in vitro, were charging them for storing it, and so they would
just clear a sheer profit on it.
But imagine the heartache of a couple who
later showed up wanting their embryo for a second child and learned
that it had been sold, and what if—you know, even if a couple had
checked "research" on their in vitro form, they may
have had in mind at the time research dealing with fertility and not
something that would turn their embryo into a set of nerve cells that
was sold to the highest bidder.
And we've also seen instances where
the couples now disagree about the fate of the embryo. In one case,
there was a divorce. The woman wanted to use the embryo for creation
of a child. Her husband did not. But they had checked
"research" on their form, so after seven years of litigation
the court agreed that research could be done.
And as we've heard from Dr. Gearhart,
there's no guarantee necessarily that these stem cell lines will be
used to cure serious diseases. It might turn out that the cardiac
cells would be used not only to repair damaged heart chambers, but to
enhance athletic ability. Geron Corporation touts the artificial skin
it's developing as a treatment not just for burn victims but for
people with sun damage and other age-related conditions.
And, indeed, one older Senator might have
let slip his real interest in embryo stem cells when he referred to
them as "a veritable fountain of youth."
So what perspective is the law,
particularly state law, taking on all of this? I've been asked to
address how existing laws apply and affect this work, what kind of
legal research might be permissible, who should oversee it, and who, if
anyone, should own rights to the processes and the products of embryo
stem cell research.
I'll just briefly go through several
approaches, and then the meat of the laws themselves.
Now, one approach that we could take, and
some states do take it, is to ban embryo stem cell research altogether
and focus more effort on the exploration of the potential of adult stem
cells. We saw from the budget put up by Dr. Gearhart that more money
is being distributed in the adult area.
A second approach — the opposite extreme could be to allow
any type of stem cell research. There have been bills proposed
on that, including the creation of embryos for research purposes,
as was done at the Jones Institute where they paid an egg donor
and a sperm donor and created an embryo for research purposes, or
at Advanced Cell Technologies, creating that six-cell embryo through
In China, such research is also proceeding, with a study of .
apparently transferring a human cell, nuclei from a seven year-old
boy into a rabbit egg.
A third approach might be to use excess
in vitro fertilization embryos. There are, as the papers show,
over 400,000 such frozen embryos, and studies show that 10 to 30
percent of them are . could be made available based on couples
interested in participating in research.
Again, though, there's a question
about whether there actually ever is such a thing as an excess embryo,
if there are couples willing to adopt such embryos, and also, you know,
given, you know, other, you know, concerns about the couples'
Now, the states as well as the Federal
Government have a role in setting policy in this area, and 26 states
have laws that govern research on fetuses and embryos. They are
enormously different, and they vary widely on things such as whether
they only apply in situations where there's been an abortion. For
example, 12 of the states only apply if the research subject was the
subject of a planned abortion.
So there's more leeway in those
states to do research on a miscarried fetus, but there are medical
reasons to think that might be less than optimal, since most stem cell
research will not take place on miscarried conceptuses but on in
In that situation, we currently have nine
states that banned research on IVF embryos altogether. And what that
means, though, is that it doesn't really get to the heart of the
activity. For example, if Dr. Gearhart found that a certain type of
destructive embryo research produced a safe and effective therapy, once
it passed the experimental stage it could be done in those states. It
only applies when the activity is at the research stage.
And it has created a kind of funny
situation across time where . for example, one of those laws is in
Massachusetts, and so researchers at Harvard couldn't do certain
research on embryos and fetuses, like chorionic villae sampling
research in the early stages. They had to wait until their colleagues
at Yale in Connecticut, which doesn't have such a law, got it to
the stage where it was clinical and then it would be okay to do it in
Massachusetts as well.
There are also, at least in one state, in
California, a law that permits human embryonic and adult stem cell
research from any source, including somatic cell nuclear transfer.
Now, in that state, there's only a
little bit of regulation on this being done. The research has to go
through an institutional review board, and the research can't be
undertaken unless there's a written informed consent of the embryo
Now, I'm intrigued because they
don't say donors, you know, and an embryo, of course, has a male
and female, you know, part to its creation. And so it would appear
that the female patient of infertility services, the woman, and not her
husband, is the sole source of consent under the California law.
Now, if it goes forward in California, I
think they need lots more attention to issues around informed consent
for some of the reasons I mentioned earlier. Some couples who would
consent to research generally may not feel comfortable with that
And I've seen that in another area
that I work where there are people who are willing to participate in
certain types of genetics research, but for religious or other reasons
oppose gene patents, and so are troubled with that application.
In addition, neither the California law
or any of the proposed laws give any attention to the recipient and the
level of informed consent you might need from someone who would use a
therapy based on human embryonic stem cells. Some people may not want
treatment that uses cells derived from human embryos, just as
Jehovah's Witnesses will turn down treatment involving blood
And it won't always be necessarily clear. I mean, there was
an issue in Germany, for example, where there was a product called
Lyrodura, which people used, and it wasn't explained to them
it was made out of human brain matter—dura. And so not only did
they not understand that, but they weren't prepared for the
medical problems that happened when some of them started having
negative effects from infections passed on by it.
And I think there are other issues around
informed consent and CGD which have to do with what you tell the person
you're going to do in terms of the screening. I mean, you
generally asked about the characterization of these lines. Okay.
And so if my embryo is used for research purposes, and I'm
not told that they're going to do infectious disease screening
and karyotyping and a lot of things that might have implications
for my future health insurance, or even my future liability- I recall
when Jose Cibelli was first using purportedly a cheek scraping to
create an embryo at U. Mass.
It went through their institutional review board, and the IRB
said, "Oh, of course it doesn't apply to researchers who
do scientific studies on themselves," without thinking about
what happens if he creates a heart cell line that has some defect
in it. He'd be open to a products liability case for— potentially
for that. And so there are ways in which the donor needs information
about what's going to be done.
So Dr. Kass had mentioned that this is an area that I've studied
for a long time. In fact, the past 25 years — 25 years ago
this week I took the bar exam on the day that Louise Brown, the
first in vitro child was born, and so I've looked at,
you know, what has happened in state legislatures around embryo
research, around in vitro around fetal tissue transfer, around
germ line gene therapy, all of these things.
And I see something different emerging
now. I mean, one thing that I see emerging is this real inflated hype
in kind of both directions, in the preambles to these bills, and so
forth, either promising the moon, you know, we can do all of these
treatments now, we're going to cure every disease, to be skeptical
of, or this is all really horrible and a kind of misstatement of the
science that I point out in my paper.
I'm a little . and then, another
difference I see is that in the earlier generations of laws dealing
with embryo research, the issue was only, is it permissible, or not?
Now, though, what I'm seeing is that both states that want to
discourage and states that want to encourage put forth all of these
provisions about what also applies to contracts and liability.
You know, for example, states that
don't like cloning sometimes have in their laws liability
provisions that say if anything's wrong with the clone, they can
sue, you know, their parents, the doctor, everybody else. And states
that like embryo stem cell research actually already have liability
provisions being suggested and in place that would make it harder for
someone who does have a real problem with the stem cell research to
So in terms of the restrictions that are
in place . that are being proposed as opposed to the ones that are in
place, 22 states have bills currently being considered that would ban
therapeutic cloning, and nine states have bills that would allow it.
And some of those bills that would allow it . I mentioned Kentucky in
You know, you just give $50 to register
that you're doing this, and kind of that's the oversight as
opposed to some sort of regulatory structure that might deal with the
safety of it.
In addition, four states have bills that
would prohibit acts where the human fetus or embryo is destroyed or
subject to injury. So a parallel to the federal law and would ban
embryo stem cell research as a subset of that.
Ten states have bills that would allow
embryo stem cell research from any source, and they often say human
embryonic stem cells, human embryonic germ cells, human adult stem
cells, somatic cell nuclear transplantation. And those that want to
encourage it, there's a small subset of about five that have
thought through at least a few of the issues.
How would this work kind of on an
industry-wide basis? And they have proposed provisions in these bills
that talk about what the responsibilities of physicians are to inform
couples in in vitro clinics of this possibility.
Some have . five states talk about
institutional review board approval. One would have all proposed
research assessed by a state committee. And 11 states have bills that
really are more study bills. They would establish a subcommittee to
think about these issues much as you're doing at this moment.
Now, my paper also points out that not
all of these laws are necessarily constitutional, if you ended up going
to court as a scientist or other individual who was limited. And
remember the state laws that are in place, like the nine states that
ban embryo research, apply no matter what the source of funding is. So
it's very different than the federal law hinging on
And some of these laws have been
challenged. In Arizona, Illinois, Louisiana, and Utah, there used to
be embryo research bans that got knocked out. And why did they get
knocked out? Because they are criminal laws, and under criminal law
you have a right to notice . a sufficient notice about what behaviors
you're supposed to avoid.
And something that just says it's a
crime to do embryo research doesn't give sufficient notice. I
mean, think about it. If I'm an obstetrician and I'm treating
a pregnant woman for asthma, and I don't know the impact on her
fetus, that could be viewed as, you know, criminal experimentation on a
Or if I'm an in vitro
physician, and I use a different medium in the petri dish, that could
be research on the embryo. So it's just too vague.
Now, you can get around that in some of
the new generation of bills that are being proposed that specifically
say you cannot do somatic cell nuclear transfer to create a human
organism and use it for stem cell purposes.
Now, policy obviously can tremendously
affect what science is taking place, the scope of research, access to
research results, and the rights of the participants. And I think the
law can play an important role in this area in terms of creating a
sense of trust in people, no matter what your decision is. And I
don't see that any of the proposed laws going either way have the
ability to do that.
And I think of all the in vitro
physicians who have said to me across time, "Oh, I'm so glad
I'm not in the United Kingdom, because they have all those horrible
rules about review, and they have that Human Fertilisation and
Embryology Authority, and it's just too cumbersome and
But then, what happened was that I think
that system in place created a sense of trust where when the embryo
stem cell research issue came along there was more of a willingness to
go forward, because the public at large there didn't feel it was,
you know, in such a state of laissez-faire as in the in vitro
situation in the United States.
So we're hearing this brain drain to
actually a culture where science is more restricted, but I think has
created a sense that at least someone is watching over it. And I
don't see that any of the proposed bills are sufficiently detailed
in either direction to give that, you know, sense of trust.
So I'll open it up for questions.
CHAIRMAN KASS: Thank you very much. The
floor is open for discussion. Michael Sandel.
PROF. SANDEL: Well, this is a question
for our speaker as well as the other lawyers in the room. Would a
federal ban on cloning—put aside even the debate about reproductive
versus therapeutic cloning, but a federal ban on reproductive cloning
even, would that be constitutional? Is that a federal function?
MS. ANDREWS: I think it is, and I would
say that when . I'd say 10 years ago there would be more hesitation
to my answer. But looking at how courts are ruling on things like the
Americans With Disabilities Act, and whether it applies . and natural
law, whether it applies, for example, to a dentist who only practices
in his own state, and so potentially there's no interstate commerce
And in decisions like that, the federal
courts have said, you know, if you're in an area where it's .
it deals with people coming from other states to get the services, it
deals with doctors who go to seminars in other parts of the country or
are trained in other parts of the country, there's enough of an
interstate commerce issue to make it an area of federal reach.
Then, the second question would be: does
it interfere with reproductive liberty if you ban my right to clone
myself? And I would argue that reproductive liberty does not cover it,
much as the argument was made by Dr. Kass earlier that it's hard to
think of natural law covering carrying someone else's child.
But even if it did cover it, and
certainly in California right now there's someone who wants to
challenge the California ban on reproductive cloning on the idea that
it interferes with his reproductive liberty, you can nonetheless still
sustain a ban if you show that it furthers the compelling state
interests in the least restrictive manner possible. And I think the
dangers physically are high enough that you would meet that, so I see
no problem with a federal ban.
PROF. SANDEL: I wasn't thinking of
the reproductive liberty issue, which I agree could be raised.
But strictly on federalism grounds, Mary
Ann, Rebecca, do you agree with that, that it wouldn't be a
controversial constitutionally . no, I mean, it wouldn't be a live
PROF. GLENDON: That's a different
question, whether there would be a case, whether it would be
controversial. But I think Lori's analysis is correct.
MS. ANDREWS: You know, the same way the
Food and Drug Administration can regulate . I mean, if you look at some
of those decisions, and lots of times drug makers in individual states
try to challenge it, and they say, "We only have used things from
within our state."
And the court decisions say,
"Listen, you know, you're using a glass vial or the adhesive
on the back of your label comes from another state," and so in
that sense I think you could regulate.
CHAIRMAN KASS: Mary Ann Glendon.
PROF. GLENDON: On the vagueness
argument, the constitutional argument based on vagueness, were those
old statutes that were struck down in those four states? And are there
examples of statutes banning certain kinds of embryonic research that
are drafted so as to resist that kind of challenge?
MS. ANDREWS: They are exactly the same
language that was struck down as exists currently in the nine states
that banned embryo research, you know, because they basically . those
statutes just talk about it in those terms—embryo or fetal
So these are states where it hasn't
been challenged. And where it has been challenged they were— it was
struck down as too vague. I think if you described more what process
you choose to ban, as some of the states do with the reproductive
cloning bans, one of the problems with that, though, is you sometimes
get too narrow, that people can invent around it.
You know, so like the statutes that say,
oh, you can't put, you know, somatic nuclear material into a human
egg, then if someone comes along and puts it into another mammalian
egg, it—the law doesn't apply.
CHAIRMAN KASS: I have Gil, Rebecca, and
Frank, in that order. Gil Meilaender.
PROF. MEILAENDER: Lori, can you say a
little bit about what you think the significance of these proposed laws
might be? And at least one thing I mean by that is this: if we look
at your chart, in relatively few cases are there laws actually that
have been enacted. Mostly what we have are laws that are proposed.
It wouldn't be that—it's not
that hard to propose a law. In a way, that can happen, and it can have
no chance of going anywhere in one or another state legislature.
So do you—I mean, do you sense any
trends, for instance? Is there anything that you would conclude from
what you've put on the chart, other than that, you know, quite a
few states are—in quite a few states there is at least somebody who
is interested in the question.
You know, I don't know quite what we
should conclude from this, and probably nobody can know for sure. But
anything you could say about it I would be interested in hearing.
MS. ANDREWS: Yes. I mean, I think the
more interesting things are just to assess what the motivations might
be behind these laws. And, you know, if we're concerned about an
ultimately important interesting legal outcome, how to deal with those
motivations. And I think that, you know, there are a number of states
that are just saying, "We want to be a biotech haven."
And so unless you take on straight away,
you know, kind of what fundamentally do we want out of our
technologies, and so forth, you're just going to see a sort of
crazy quilt of proposals that are saying, "Biotech, come to
You know, on the other hand, on the other
side, there are laws being proposed that are, you know, part of a
packet of a pro life agenda. And so it's really—it's about
that, and it's really not so much about this particular technology—embryo stem cell research.
I mean, I see the same thing going on at
an international level. When I'm in other countries, you know,
like France they'll say, "Oh, we hate, you know, what
you're doing in the United States, and we think you're getting
us down to the least common ethical denominator about gene patents and
stem cells, because of the GATT treaty."
At the same time, these same people are,
you know, wanting not to lose any chance for the biotech dollar.
CHAIRMAN KASS: Rebecca.
PROF. DRESSER: Two questions. One is, I
wonder if any of the bills that are in California—I looked for this
a little bit, the law that was passed that wants to permit research
cloning, if any of them have anything in there about the oocyte
providers, and who is going to be deciding how that should be arranged,
and the payment issue, and so forth.
And the second question was: have you
seen any groups or individuals trying to work on, say, a model statute
approach with alternatives? You know, if you like X, don't like Y,
here's what you could do, similar to what I think it was the ABA
did with surrogacy.
MS. ANDREWS: I haven't seen that
approach in model laws, although I've seen it a lot with
reproductive technologies. And maybe if I go back over those, I'll—I think all they say about research is giving people the choice to
donate to research or to have their embryos terminated or to give them
to another couple.
There is a lot of law on the banning of
payments to the egg donors or providers of embryonic or fetal tissue.
There is less concern for quality of consent or monitoring. You know,
if you made a market in this, monitoring the effects of Lupron or other
fertility drugs, and so forth, and I think that that's an
intriguing problem, even at the federal level with the Food and Drug
Once it gets into this therapeutic model,
this whole area of embryonic stem cell and embryonic tissue is treated
as if these were drugs. So the whole focus is kind of on the safety of
the recipient, if you look at proposed FDA guidelines. Are infectious
diseases going to be passed on? And so forth.
There's very little attention paid to
safety issues around the donor, or even disclosure issues, and so
forth. So I think that's a big—perhaps because we're
uncomfortable with the human source of it, you know, we're just
pretending this is like any other pharmaceutical product, without
looking at, you know, the implications on the donor.
CHAIRMAN KASS: Frank Fukuyama. I'll
follow you, Frank.
PROF. FUKUYAMA: Professor Andrews, could
you say something about the ability of the FDA to accomplish what the
state laws are trying to do, given its existing statutory authority?
Because we've heard from a number of fairly authoritative sources
that, in fact, the existing statute would allow them to do that.
For example, although they typically
don't regulate procedures, they do regulate medical products, and
there's no IVF clinic in the world that doesn't use medical
products of various sorts. And so if they interpreted their statute in
a certain way, they could in fact, you know, extend those regulatory
powers. And the primary reason they don't is just a prudential
political judgment that the country doesn't want them to do that.
But, you know, in terms of their legal
authority, that's—you know, that would be perfectly possible.
MS. ANDREWS: Well, one of the
difficulties is that their focus is on safety and efficacy, so they
have pretty—you know, they have a really broad range. I mean, they
could use—do more with the authority they have under certain of the
public health laws.
You know, but certainly this is an area
where people have concerns far beyond safety and efficacy, and
that's where the FDA is not going to provide guidance either by its
temperament in having talked to people there, you know, and asked, you
know, for guidance, and also by their mandate.
And so to the extent that society wants
to make a decision that says, you know, we don't potentially think
the benefits of this particular—you know, some aspect of this
technology are worth running roughshod over other values, it's not
going to be the FDA that can say that. They can just tell us, you
know, if you go ahead, what would the implications be for human health.
PROF. FUKUYAMA: If I could just follow
up. But if they wanted to, for example, ban reproductive cloning in
effect on safety grounds, I mean, wouldn't they be able to do that?
MS. ANDREWS: In part it depends whether
a medical organization, like the American Society of Reproductive
Medicine, argued that it was a procedure. You know, they can't
regulate medical procedures, and so a lot of unsafe surgery is going
on, and sometimes for years on end. But the FDA can't step in.
And so that has been part of the
problem. I mean, in fact, when the FDA first said, "Oh, we have
the power to regulate human cloning because it could be—you know,
there could be genetic problems in the offspring, and, you know,
there's this manipulation at the lab," everybody said,
"Well, why haven't you been regulating IVF," which has
those same problems.
And there was considerable, you know,
concern that this exception for medical practice, which they can't
regulate, could be used in a way to swallow it up. So, I mean, I think
they have more power than they've traditionally exercised, but
that's where the conflict would come up.
CHAIRMAN KASS: We've given you a
narrower assignment than you could manage. That is to say, we've
asked you to talk about the legislation on stem cell research, and, of
course, it is in some cases tied up with cloning, both for producing
children and for biomedical research.
And to tie this in with the Council's
own inquiry, which we will visit again tomorrow, on the aspects of
oversight monitoring and regulation and the whole area of the
confluence of ART and the growing genomic knowledge, we've in a way
been trying to think about this area as a whole rather than piecemeal,
cloning here, stem cells there, though it looks like in most of the
state laws that we have either on the books or proposed they are
responses to the latest threat that's perceived by somebody either
to their interest in going forward with the research or to the
embryonic life that they seek to protect.
And I guess one question is: is it at
all feasible to think that the states might be laboratories for more
comprehensive treatment of what the people are now starting to call
reprogenetics? Or this whole area of which stem cell research is but a
piece, ART is a piece, PGD is a piece, and things of that sort. Or is
that something which, if to be considered at all, is something to be
considered federally? That would be one question.
And the other—and I think we can
figure out why the current new state laws—people being frustrated at
the prospects of enacting something federally are going into those
states where they have the best chance of winning and pushing through
either Louisiana or California, or everything in between.
So it might very well be that these are
the kinds of issues, precisely because of the issue of the embryo in
the middle, that are not easily amenable to compromise. You don't
balance if one side holds something as a matter of inviolate principle
and right. It doesn't enter into a balance.
On the other hand, comments that you made
about you don't see any place where the people interested in
protecting human dignity, and the people interested in having the
research go forward, sit down together in some state and try to work
out some kind of a package that is the best possible arrangement here
in Kansas, or some other place, do you think that because of the
intractability of the embryo question it's out of—it's
unlikely to try to develop some kind of collaborative efforts in which
industry and the people who are worried about where this is going could
collaborate on some kind of state regulatory activity? Or is that just
a pipedream? That was really two questions, rather long-winded.
MS. ANDREWS: No. I think that is a
possibility, because I do think there is more consensus if you start,
you know, in some other area. Even if you start from a question like,
what do you do in a divorce with frozen embryos, and, you know,
something that hasn't been as—you know, where sides have built
up the sort of animosity that they have around the abortion question.
And I think that there are some states—and I'm trying to think—maybe Virginia, Florida—on
reproductive technologies generally where they've created more
detailed laws. They've tried to think about all of the different,
you know, possibilities of, you know, diagnostics and of different
combinations of parents, and kind of work it out a little bit in
One of the problems at the state level,
though, is that even well-meaning lawmakers who have gone into that
sort of approach find out this is unlike, you know, regulating the
roads or insurance, because everybody has an opinion about how the next
generation should come into the world.
And there's no political gain from
ever taking a position on this. So I think that's, you know, one
observation of legislation-watching for a long time on these issues.
The other observation is that it takes
some huge public event to really push an issue. For example, there are
lots of states that had really interesting, very comprehensive
surrogate motherhood legislation working through the pipeline before
the Baby M case. But nothing got adopted, and then, you know, this
case came to the fore of a surrogate changing her mind, and then
quickly states adopted laws that just dealt with that situation.
So when other situations came up where
nobody wanted the baby, instead of everybody, they didn't have
anything to cover it. And so I really think—and I fear for our
biomedical policy in that sense, because I know that the policy we get
on, say, you know, certain gene therapies is going to be based on
whether we have some horrible case in the media or some wonderful case
in the media. And that's not really the way to think these things
But, I mean, I do think that the part we
have—I guess what we've talked about is a bioethics fire drill.
A new technology comes around, and we all run around and try to deal
with it, rather than thinking through the various possibilities and
trying to do this collaborative effort to deal with it.
CHAIRMAN KASS: Could I follow on just
briefly? As I listened to your answer, it makes me think that it's
even more unreasonable to expect such collaborative and far-sighted and
thoughtful effort in the states.
MS. ANDREWS: I think—
CHAIRMAN KASS: What's the incentive
there for people in the states to sit down and figure out, you know,
what the state policy overall in reprogenetics ought to be? Aren't
they likely to react only when something like this happens? Think some
kind of piecemeal—
MS. ANDREWS: It's hard. They
don't have the staff—staffing available. But that's the
perfect situation for the sort of —
CHAIRMAN KASS: The models.
MS. ANDREWS: —model—
CHAIRMAN KASS: Yes.
MS. ANDREWS: —law to come along to
say, okay, we've thought about all of these things. And I
certainly think in the overall issue of different biotechnologies that
are on the table, there is getting to be a growing interaction between
people who have previously identified themselves as pro life and pro
choice, who are waking up and saying, you know, let's put abortion
off the table, because we're going to lose a lot of ground with
human dignity and human life if we just let the people who are
commercially benefitting make all the laws, while we're busy, you
know, shooting across the barricades on this other issue. So I see big
CHAIRMAN KASS: Janet Rowley.
DR. ROWLEY: It's my impression that
you were on one of the panels, if that's the proper term, at NIH
over the past decade that was looking at the issues about embryo
research. Is that—
MS. ANDREWS: No, I was on one dealing
with the Human Genome Project, actually.
DR. ROWLEY: Okay. Because what I was—the question—and it's been alluded to—that we are trying to
figure out where to go next on this issue. And there are some of us
who feel that—I think everybody agrees that there needs to be some
sort of oversight body in addition to the IRBs.
And then, the struggle is, would this
body be best housed, say, at NIH? Should it be a higher level Health
and Human Services issue? Or is this the kind of thing that you need a
Presidential commission looking at?
And so I was just wondering whether in
your experience in considering some of these issues whether you have
any advice for us.
MS. ANDREWS: My advice would be not to
put it at NIH, you know, just because of the potential conflict of
interest when you've got sort of every institute there saying,
"Well, we'd like to, you know, do all of these techniques.
You know, we'd like to do gene therapy. We'd like to do embryo
stem cell research." There shouldn't be any constraints on
what we do.
I mean, it is sort of, you know, the fox
guarding the chicken coop, so I would suggest that, you know, at either
at the higher level, at the Secretary's office. And it is an
important, you know, issue, much as we were talking about with the Food
and Drug Administration. You've got these regulations that apply
to federally-funded research that specifically say that IRBs are not to
consider the long-range effect of the research.
And so you do need some other body
potentially saying, you know, is germ line genetic engineering on
embryos, is sex selection of embryos appropriate or not, because
that's precluded from consideration in part under the existing—you know, from consideration by institutional review boards.
DR. ROWLEY: Can I follow up on that?
Because some of us, myself included, have thought that the Recombinant
Advisory Committee, the RAC, was a potential model, and that's an
NIH committee. So you're saying that isn't the model that you
think might be wise to—
MS. ANDREWS: You know, I don't think so—I mean, the RAC
occurred before NIH itself started adopting, you know, based on
the 1980 laws that said NIH researchers can patent their findings
and make an additional $150,000 a year based on their patents, and
they could form biotech companies, and so forth.
So there are ways in which the NIH itself—you know, unlike in the early days when the RAC was formed, now our—you know, have some of the same commercial motivations in a way.
DR. ROWLEY: Well, but I was thinking
that though the—such an oversight body might be within the purview of
NIH, I wasn't thinking that any NIH members would actually be part
of that. It would be more, as the RAC is, external scientists and
lawyers, ethicists, etcetera.
MS. ANDREWS: In part, it just I think
makes sense as an institutional structure to make sure it's, you
know, staffed elsewhere, though. You know, if you staff it by NIH
people, you know, volunteers that meet once a month or, you know, so
forth, I mean, they ultimately, you know, may not have the last, you
know, say in it if the day-to-day recommendations, and so forth, come
out of an entity that really wants to go—you know, would not like to
be encumbered by problematic regulations. But that's just my
DR. ROWLEY: Okay.
MS. ANDREWS: —from my own, you know,
experience at NIH.
CHAIRMAN KASS: Comments? Questions? I
want to ask—some of us attended a meeting a week ago, a seminar that
Frank Fukuyama is running on this whole area, and the professor of law
at a local university was in fact—the question was: what are the
constitutional obstacles to regulation in this area?
I'm going to revisit the question
that Michael Sandel asked you earlier, where he was dealing with the
question of Congress's power to enact legislation, not so much the
constitutional protections that such legislation might violate.
You alluded to the possible claims in
reproductive rights. This lawyer, who was practicing creative legal
thinking to see what might be done, suggested that there might be, in
an expansive understanding of the protection of freedom of speech,
understood as expression and understood as fatly as you'd like,
some kind of claim that scientists might bring under the First
Amendment a complaint that laws restricting research in any area, for
whatever reason, was a violation of what?
MS. ANDREWS: Of the First Amendment.
CHAIRMAN KASS: Yes, the First Amendment.
MS. ANDREWS: Sure.
CHAIRMAN KASS: Very broadly conceived.
MS. ANDREWS: Yes. I can comment on
CHAIRMAN KASS: I don't want to
encourage such thinking, but do you have an opinion?
MS. ANDREWS: Yes. You know, we are
under the First Amendment, freedom of speech, there is the idea that it
not only protects speech itself, but the precursors of speech, so the
funding, you know, of—and the gathering of news, whether you go into
prisons, or whether you—you know, that sort of thing, or campaign
funding, and so forth.
So you could make the argument that doing
science is a precursor to having a marketplace of ideas. How can we
talk about things if we don't generate the research to do it? And
there are some cases that talk about it.
The most prominent one has to do with
whether the Kinsey Institute at Indiana University can—researchers
there can look at pornography, you know, things that are considered
obscene, or whatever, or does that interfere with their right to
And it was held that they could, you
know, look at this, because, you know, and so there's some—there's even some low-level case law in addition to the theory.
Now, people have tried that argument with
respect to fetal research, for example, and courts have, you know, sort
of slapped them down in terms of saying, you know, freedom of research
is one thing, but there's also the need to protect the subjects of
research. And so, you know, virtually any regulation that you can come
up with that promotes safety, for example, would not run afoul of
freedom of research.
CHAIRMAN KASS: Okay.
MS. ANDREWS: And so it's basically
been interpreted to be allowing people access to existing materials,
and so forth, not cutting off what's there, but in terms of
generating new knowledge in a way that might be risky, it doesn't
CHAIRMAN KASS: All right. Anyone else?
MS. ANDREWS: May I add another legal
comment that we haven't—
CHAIRMAN KASS: Please.
MS. ANDREWS: —addressed? And this has
to do with the sort of fruits of the research in the sense of the issue
of patenting. And I think that is going to play an important role
ultimately in what happens in the embryo stem cell area and touch on
all of the issues you were dealing with this morning, in terms of
access, and so forth.
The approach of the President of allowing
access to existing stem cell lines obviously has an impact on
accessibility in terms of the fact that most of those stem cell lines
are owned and patented, and so forth, by particular entities.
And even though there has been access
allowed to some of them for, you know, not horrendously high fees,
there are still these intellectual property reach-through rights. So
what's happening is that, okay, I'm percolating along, maybe
I'm a scientist who is, you know, trying to develop, you know,
And I might come up with something
really, really fabulous. But the owner of the—you know, depending on
the reach-through agreement, that original owner can then say,
"Well, you have no right to make it; we kind of own what
you've ultimately done." And I think that's problematic.
I think there's not only the issue of
sort of taxpayers paying, you know, what some have estimated as, you
know, 40 percent of the costs for the intellectual property rights to
use stem cell lines, that's a cost that you wouldn't have if
people could generate new ones.
But, you know, there's also a real
issue—and it resounds with me, because I'm seeing it play out in
the gene patent area, where you're not supposed to be able to have
patents on products of nature or formulas, and a genetic code seems to
And now we're seeing researchers
being prevented from looking at a gene sequence because some other
company or institution owns that gene sequence, or people being
detoured entirely from going into a field because the idea is, why
should I spend all of this time when I'm not secure that I—you
know, when an ultimate pharmaceutical product, which clearly should be
covered by a patent, comes out, you know, it's unclear I'll
have rights to it.
So I would say significant problems are
developing in the gene patent area in terms of access to diagnostics
and in terms of research. I would—you know, you're a little
earlier on in the embryo stem cell area, but I would alert you to
those. I mean, that's a legal issue that will have an enormous,
CHAIRMAN KASS: Thank you.
Frank, and then I think we'll
probably wind up.
PROF. FUKUYAMA: Well, okay. I just want
to go back to Leon's earlier question and follow up. It's not—the lawyer in question was Steve Goldberg at Georgetown who was
talking about these constitutional issues. I don't think that he
was so much advocating that you could declare, you know, that there was
this constitutional issue, he was just trying to—he's like a
lawyer. He's trying to make the best legal case you could.
But one thing that he said on the other
side is that the interest of the people—you know, the power of the
interest of the people that are trying to ban cloning, in this case the
House bill, also has to be taken in account.
And the law was written in a very narrow
way, such that the primary objection was essentially a moral objection
rather than the health of, you know, a child or, you know, other kinds
of—or safety or efficacy, other kinds of issues that they could have
picked. And that the trend in court decisions—and he thought that
this recent Texas—you know, the striking down of the law, the Texas
sodomy—homosexual sodomy law, was important in that regard.
And I guess Justice Kennedy has played a
big role in this, is in saying that although we take seriously moral
claims, you know, these purely moral claims made in the community, that
those by themselves, you know, cannot be written into these laws.
And that was the reason—and he thought
that this is a broader trend in I guess a kind of enshrining of a
certain kind of moral relativism, you know, into American
constitutional law. And that given that, if that's the only basis
on which the law is being enacted, then that's not a very powerful
counterweight to whatever potential, you know, constitutional claims,
First Amendment claims are being made on the other side.
Could you comment on that?
MS. ANDREWS: Sure. Well, you have two
things going on. I mean, first, unless you're protected by some
fundamental right, and so that would occur if you're dealing with a
particular category we protect, a category based on race or religion,
and so forth, or a particular sort of activity we protect—speech, you
know, reproductive liberty, and so forth—and I don't really see
an indication there's enough court cases that don't find
scientific inquiry to be one of those that probably wouldn't find
human reproductive cloning to be one of those.
You know, and if you don't—if
you're not in one of those fundamental categories, then states can
enact laws even if it just is for a moral, you know, reason, or they
can enact zoning laws that say I can't paint my mailbox purple or,
you know, whatever.
And so you'd have to make—you'd
have to first get in that category. I think you're right, once
you're in that category, if we had societal accord, and we had a
Supreme Court who might say reproductive cloning is a fundamental
right, then if we got to the stage that—where you didn't have the
physical or psychological problems—and it doesn't matter if the
law itself said it, because lots of time legislatures, when they get
into constitutional fights, say, "Oh, we really meant this to do
this for protective purposes."
So it doesn't have to be on the face
of the law. You know, if you got to that—that stage where it was a
fundamental right, maybe we all became infertile, it was the only way
to, you know, carry on, and it was all of a sudden safe, really safe,
then moral arguments wouldn't be enough. So once you're
protected, you know, you're right.
Thank you all for letting me attend.
CHAIRMAN KASS: Thank you very much.
Thanks very much, Lori, for your work on the presentation and the
Tomorrow morning we will meet at 8:30.
We have two sessions tomorrow, and then a public session. We should
wind up not long after 12:00.
We're adjourned. Thank you very much.
(Whereupon, at 5:17 p.m., the proceedings in the foregoing
matter were adjourned, to reconvene at 8:30 a.m., the following