1400 M Street, NW
Washington, D.C. 20005
COUNCIL MEMBERS PRESENT
R. Kass, M.D., Ph.D., Chairman
American Enterprise Institute
S. Dresser, J.D.
Washington University School of Law
W. Foster, M.D.
University of Texas, Southwestern Medical
Johns Hopkins University
Michael S. Gazzaniga, Ph.D.
P. George, D.Phil., J.D.
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.
D. Rowley, M.D., D.Sc.
The University of Chicago
J. Sandel, D.Phil.
Q. Wilson, Ph.D.
University of California, Los Angeles
WELCOME AND OPENING
CHAIRMAN KASS: Good morning, everyone. Welcome to the
members of the President's Counsel on Bioethics to this, our 11th
A very special welcome to Jim Wilson who rejoins us after
successfully completing several months of medical treatment. He has
escaped from the leeches in better shape than before.
CHAIRMAN KASS: Welcome, too, to the members
of the public.
I note the presence of Dean Clancy, the Designated Federal
Officer, in whose presence this is a legal meeting.
Jim has asked for a moment to address the Council.
PROF. WILSON: I simply wanted to apologize for my long
absence. I did not realize during my absence that Leon, in the spirit
of kindness to which he is so disposed, had not revealed the reason,
but I had to be at home for 90 consecutive days.
Ninety consecutive days are over. I'm fine, and I'm back
to join you as mean-spirited as ever.
CHAIRMAN KASS: That's why I have him close.
The agenda for this meeting, as you know, the bulk of this
meeting will be devoted to biotechnology and public policy and our
project to assess the current state of regulation of the technologies
that touch the beginnings of human life with panels this afternoon from
a variety of stakeholders and their representatives and tomorrow
morning with a discussion of the discussion document that the council
commissioned the staff to prepare.
The first session this morning is separate and is a
continuation of our efforts to fulfill the charge to monitor stem cell
research. The topic of stem cell research will be the heart of the
July meeting. We have commissioned five or six scientific review
papers from leading researchers to review the work in stem cell
research, embryonic and adult, that has taken place since August of
We also have commissioned an ethics review paper and a
paper that will review relevant legislation, federal and state, that
has been enacted since that time.
Today, in advance of that meeting, we are trying to inform
ourselves about one crucial challenge to the possible therapeutic uses
of stem cells and their derivatives, the problem of immune rejection.
This, as many of you know, is an area of intense research activity, not
just of stem cells but across the board in transplantation of solid
And we are very fortunate to have with us as our guest this
morning Dr. Sylviu Itescu, who is Associate Professor of Medicine in
the Cardiology Division at the Columbia University College of
Physicians and Surgeons and also the Director of Transplantation
immunology at Columbia Presbyterian hospital of the College of
Physicians and Surgeons.
Dr. Itescu's curriculum vitae is at your place, and the
paper that he has submitted, I think, was delivered to you at your
hotel rooms, and it is, as he acknowledges, a technical paper, but one
I think that will, in addition to the discussion that he's now
going to lead us through, will help us a lot, I think, in thinking
through this particular crucial problem in the area of stem cell
research and regenerative medicine.
Dr. Itescu, thank you very much for your paper, for your
presence, and we look forward to hearing from you.
SESSION 1: STEM CELLS AND REGENERATIVE MEDICINE: OVERCOMING IMMUNE REJECTION
PROF. ITESCU: Dr. Kass and council members, I want to
thank you very much for having me at this session.
I would again like to apologize for the technical nature of
the paper, but please I would really appreciate if anybody has any
questions as we go through even from my slide presentation, just feel
free to interrupt and ask questions freely, and I'll be delighted
to explain in more detail.
The objectives, I think, are twofold. Firstly, what
I'd like to do is to give you an overview of the current state of
knowledge and clinical practice in terms of the basic immunobiology of
organ transplantation and methods by which we currently immunosuppress
patients and prevent organ transplant rejection.
And secondly, I think the objective is to gain an
understanding of those issues as they may relate to the subsequent use
of stem cells for organ regeneration or for tissue regeneration, and so
that you understand the fundamental issues that will be faced by
physicians trying to manipulate or to use stem cells for those type of
But I think of even more interest, towards the end of the
presentation by understanding the obstacles to accepting a foreign
organ, there are some interesting new concepts and data that have
arisen regarding the use of stem cells to alleviate some of these
issues that I would like to really open up for discussion at the end of
I'm not sure how to switch the projector on actually.
It may require a — okay.
What this slide shows is that despite the fact that the
number of patients on our transplant waiting lists continue to
exponentially grow year by year by year, what you can see is that there
continues to be a major limitation in the supply of organs.
In yellow you see the living related donors have remained
minimally pretty much the same over the years and, more important, the
cadaveric donors have remained the same. So we have a real problem in
terms of shortage of donors.
And it is the same for the previous levels for renal
transplantation, and this slide shows the same for heart
transplantation. Significantly increased numbers of patients were on
the transplant waiting lists.
And what this results in is a significant increase or
significant rate of mortality of patients who otherwise could be saved
if they had an appropriate organ donor.
And what you see for kidney transplant patients who are on
the waiting list, the mortality now is fairly low, five percent,
despite a very long waiting time, and that is because we have dialysis
as a modality to keep patients alive.
In contrast, until the last couple of years, you can see
that for the heart transplant patients on that waiting list, mortality
was as high as 30 to 31 percent, and that is because we didn't have
until very recently any way of keeping patients alive who were waiting
for a heart transplant.
More recently, over the past couple of years, there's
been quite a significant new development, and that is the development
of left ventricular resist devices. You can see these type of
artificial devices that are essentially the equivalent for a patient on
a heart transplant waiting list to what is dialysis for a kidney
This is an artificial pump that takes over the function of
the left ventricle and keeps the patient alive while we find an organ
donor for the patient. And this has now brought the mortality rate on
the transplant waiting list back down to almost zero, quite a major
Nevertheless, there are few ways by which we can increase
the ability to have donors. One is the use of live donor organs. The
pros of using live donor organs are that they are superior in terms of
outcome to cadaveric. The costs are much less than cadaveric, and
there are psychological benefits in terms of donor/recipient issues.
The risks. There are some small risks to the donor in terms of morbidity
and mortality, inconvenience, and obviously the overall decision
is a voluntary one for the donor.
The short and long-term risks of a living, related or
unrelated and living donor donation for a kidney, there's a very
small risk of death primarily related to pulmonary emboli. There are
some major complications that could be seen primarily related to the
surgical procedure. Approximately one to two percent of donors will
have some degree of clinical complication.
The long-term risk is pretty low to the donor. However,
the survival of a living related organ transplant is significantly
superior to a cadaveric organ donor. You can see that in a kidney
transplant, the living related organ significantly survives for a
significantly greater period than cadaveric organ.
And interestingly, even a living unrelated donor, in blue,
has a better outcome than a cadaveric donor, and what I wanted to
emphasize here is that a living unrelated donor is typically a spouse,
where genetically completely disparate between the husband and wife.
Nevertheless, the outcome is almost the same as a partially matched
sibling related graft donor.
The reason for this probably is the fact that you can
prepare the spouse well in advance. The whole procedure is done in a
convenient way, timed appropriately, with minimal risk to the donor.
But the outcome is significantly superior to cadaveric. That's
really the point of this.
And what you can see, there's a change in distribution
in the U.S. in terms of living donors, particularly in terms of spouses
who are now providing organs to their spouse in need, as well as
actually unrelated donors who are now donating organs to unrelated
In contrast to that, you can see that family related
donation has pretty much remained unchanged of these.
Okay. I'd like to move on to some of the immunologic
issues that primarily a cadaveric or unrelated donor recipient pair
will undergo when an organ is transplanted. The primary difference
between individuals is at the level of a certain complex called the HLA
complex or the MHC complex. We're talking about genes that
incurred a protein on the surface of all of our cells that are called
HLA genes or HLA molecules, two types, Class I and Class
II, and these Class I and Class II molecules you can see in blue are
two-chained molecules that serve to present a foreign protein or
antigen to our own T cells so that they can be recognized as foreign
and rejected or removed from the circulation.
This is the fundamental basis of how our immune system will
recognize bacteria or viruses and eliminate them from our circulation,
and typically what happens is that if this a virus — consider this to
be a virus — taken up by these cells which are called antigen
presenting cells, but otherwise known as macrophages, the virus is
taken up in a vesicle. It's then broken down into little pieces or
little peptides, and the peptide in yellow is then assembled in the
cytoplasm of the cell together with an HLA molecule in blue, and the
complex of a piece of the virus plus the HLA molecule is then shuttled
up to the cell's surface, and as a complex is presented to this
structure over here, which is called the T cell receptor on the surface
of the T cell.
Typically this is a CD-4 helper T cell, but the key issue
is that this T cell receptor structure recognizes a three dimensional
structure between the peptide antigen and the HLA molecule, and the
whole thing activates a whole pathway in the T cell that then results
in removal of the whole invading antigen or invading virus or
And this is a typical immune recognition reaction that
occurs throughout life, throughout our blood systems and, you know,
our immune organs. You can imagine, therefore, if this now becomes a
foreign organ, the HLA molecule on the surface of this foreign cell
will be viewed as totally different from all of the HLA molecules of a
given individual by our own T cell receptor. It will no longer. It
will no longer be seen as a non-molecule. It will be seen as foreign.
And the fact that the HLA molecules on a foreign cell, this
structure itself is different from the HLA molecules of a given
individual always will trigger a reaction as though this whole
structure was a foreign structure.
What I have just outlined to you is actually a very complex
immunological phenomenon. So if anyone has any questions, I'm sure
this is not a straightforward issue to understand, but please, just
feel free to ask.
Can we just focus that a little bit?
Okay. So with the notion that if this is now the —
consider this to be the foreign cell from the foreign organ that has
been transplanted. Understanding that the MHC or the HLA molecule on
the surface of this cell is totally foreign to the recipient, it can
trigger two types of an immune response. It can trigger what's
called a direct immune response and an indirect immune response.
The direct immune response is when the foreign HLA molecule
as a total structure is seen as foreign by the T cell receptor of the
recipient T cell. So under normal circumstances, as I've mentioned
to you, the T cell receptor will recognize a little peptide that should
be here, not the HLA, just the peptide.
In this scenario, the T cell receptor recognizes the whole
HLA as a foreign piece, and so this is called direct recognition, and
it allows the immune system to be activated and attack this cell
A second process of immune recognition, the indirect
process, is one where this HLA molecule is internalized in the cell of
origin, and a little piece is secreted, and you see there is the little
piece of the foreign HLA molecule, and it's just this little piece
that then comes up.
And this cell now is the recipient cell, if you can
imagine. It's the recipient antigen presenting cell. And so this
little yellow piece, which is a component of the original foreign HLA,
is now presented as an antigen by our own HLA molecule.
And so this recognition is the more classic form of immune recognition
the same as you would recognize a virus or a bacterium. You not
only recognize a little piece of this entire structure, and this
is called an indirect allorecognition. But it's two different
types of recognition directed at the foreign HLA molecule of the
donor. Both of them drive the immune response against the donor
This is the basis actually of an immune assay called tissue
typing or mixed lymphocyte reaction, which allows us to test how
different the HLA molecules of one donor are in terms of recognition by
the HLA molecules of the recipient.
And so what we typically do is take cells from a potential,
let's say, kidney allograft donor, and this really is done in terms
of selecting a potential living related donor. We want to know really
how different is the potential donor to the potential recipient in
terms of those HLA molecules.
So we'll take cells, blood cells, from a potential
donor. We'll know the typical type of HLA molecules on the
surface. We mix them with the HLA molecules or with the cells of the
potential recipient, and we look for the type of reaction. We look to
see whether the recipient cells proliferate and become activated or
don't proliferate and don't become activated.
And essentially the degree of proliferation and activation
is a measure of the difference between the HLA types on the surface of
the donor and on the surface of the recipient, and what you don't
want to be doing is transplanting a potential donor whose cells
stimulate very vigorously a proliferative response in the recipient
Okay. Now, in terms of once you have selected your donor
for living related, for example, based on as good a matching as you can
get at the HLA locus or for a cadaveric kidney transplant we also do
HLA typing. We try to minimize the differences in HLA molecules
between donor recipient.
For cardiac transplant actually we don't have the time
to do that. In fact, for cardiac transplant recipients there is no HLA
matching. We take whatever comes because of the severe shortage of
But essentially once you've actually bitten the bullet
and you've accepted a particular donor, there's a variety of
types of rejections that can occur, and those are defined based on both
the immunobiology of the type of reaction and the time taken to
induce the rejection process.
And there are at least four types of rejection processes
that I'd like to talk about. One is called hyperacute. One is
accelerated. One is acute, and one is chronic, and as indicated,
hyperacute happens within minutes to hours, and the fundamental issue
here is that unbeknownst hopefully to the transplant physician, the
recipient had what we call pre-formed anti-donor antibodies in his
circulation, and as soon as the organ gets put in these, if you've
got this type of a serum, you will reject the organ immediately, within
minutes. It is a horrendous outcome.
So we always try to exclude the possibility that a given
recipient has antibodies that might destroy the organ, and we do
what's called a donor specific antibody cross-match prior to any
organ being transplanted. This is both for kidneys, hearts, and lungs.
Assuming that this doesn't occur, and I'll show you an
example of this in a minute, but assuming that this doesn't
occur because you've been diligent and have excluded this risk,
the typical type of rejection that would occur in the absence of
immunosuppression is an accelerated or an acute process which happens
within the first six to seven days primarily.
And this is a result of either reactivation of T cells that have
previously been activated by some type of similar HLA, such as blood
transfusion or primary activation of T cells, that the natural process
by how the T cells will recognize the foreign HLA, and it will
take them about seven days to recognize them, and you will get an
acute rejection process.
And we understand that, and this is what we have tried
always to prevent by treating with a number of immunosuppressive drugs
at the same time.
In addition to this, and while the patient always remains
at risk of recurrent episodes of acute rejection, there is another
process called chronic rejection of the graft which happens within
months to years, and we'll talk about that in more detail, that
causes a very complex and unclear, but this really is the major
limitation of long-term survival of the graft at this point in time.
Just an example of what I was talking about in terms of the hyper
acute form of rejection. If an individual has pre-formed antibodies
against the HLA of that particular donor, as soon as the blood comes
into contact with the foreign allograft or the foreign organ, those
antibodies will bind to the surface of the organ. They'll recognize
the foreign HLA immediately and activate a whole complex that results
in a clot formation in the blood vessel and occlusion of the blood
vessels to the organ.
This is what it looks like. This is a classic hyperacute
rejection of the heart, where you can see swelling of the heart,
hemorrhage, and then within minutes the heart goes black and you've
lost the organ and the patient really is in extremis, and often dies in
So in this day and age, it's very rare to see that type
of hyperacute rejection, and we try to minimize the risk of that by
screening and doing a variety of assays.
Assuming that you've gone through that first couple of
days, what happens is through those two processes I talked about,
indirect; so direct recognition of the foreign HLA and the indirect of
the HLA, the CD4 T cell, helper T cell is the orchestrator of the
immune response, is activated by the foreign HLA molecules. The CD4
cells start to divide and proliferate, and they then help these cells
called CD8, or cytotoxic T cells, to become activated. These are the
effectors of the rejection process.
They also help B cells make antibodies, and the antibodies provide
a second barrage, second attack against the graft. So these are
the two effector arms that cause the rejection process, particular
CD8 cytotoxic cells. But the CD4 cells are the primary cells that
recognize the foreign HLA and orchestrate the whole process.
And you might recall that CD4 cells, which are the primary
orchestrators of all immune responses, are also the targets of the HIV
This slide is a little complex, but just to show you that
the cytotoxic CD8 cells that I mentioned ultimately destroy the graft
by secreting a variety of factors that punch holes in the graft and
cause it to leak and explode pretty much.
We'll just keep going.
Okay. So that complexity in terms of cellular activation
has defined multiple targets for immunosuppression. You can inhibit
the ability of the CD4 T cell to recognize the HLA molecule directly.
You can inhibit T cell activation and secretion of cytokines, and
we'll talk about that in a minute.
The most important cytokine here is IL-2 because IL-2
activates the whole downstream pathway of CD8 cells and other T cells
that are important in the rejection process. You can then try to
suppress activation of other T cells and B cells, and then we have
drugs at all of these points that synergistically will inhibit the
The axioms of immunosuppression, three major things to
think about. You want to have an immunosuppressive effect of the drug
that you're giving. You want to minimize the immunodeficient
complications obviously, and you want to minimize the non-immune
And the best way to do these, to maximize the
immunosuppressive effect and minimize these two other issues is by
combining drugs that work at different sites of the immune response.
And so you see, for example, if we only treat with one
agent, and cyclosporin is our example here, we have a fairly minimal,
specific immunomodulatory effect, and a fairly high range of
nonspecific or immunosuppressive effects.
But if we now add two drugs working at two different sites
of action, we maximize or optimize our immunosuppressive effect at a
selective level, while minimizing our undesirable side effects, and
that's the rationale for combining immunosuppressive therapies.
In addition to that, you want to use drugs that act on
different arms of the immune response and at different time points in a
synergistic fashion. So all patients are routinely treated with
glucocorticosteroids, which are essentially nonspecific inhibitors of
most arms of the immune response, and they act very early to switch
Now, what you don't want is to continue to have to be
using high doses of steroids because they're associated with lots
of side effects, most notably global immunosuppression. So you want to
use steroids early on and be able to switch the steroid usage off.
We also now use cyclosporin or FK506. These are related
agents. These have made probably the biggest difference in the
transplant survival over the past 20 years by acting directly on T cell
activation to prevent IL2 and other cytokine production.
And then there's a bunch of other drugs that alone or
in combination are used to prevent the second stage of immune
activation, other cells, the recruitment of other cells, the
differentiation of other cells, and the prototype of this is
azathioprine. Now the most commonly used drug in this group is MMF, or
mycophenolate mofetil. And then there's a bunch of other
experimental approaches to prevent other aspects of the immune
What this slide shows you is the impact of cyclosporin on
allograft survival here in kidney transplant. You can see that prior
to the early '80s — actually cyclosporine was introduced, I think,
around 1978, and you can see the difference in survival of kidney
allografts. This is graft survival as opposed to patient.
Patient survival is not the issue. If the graft is
rejected, it dies, and the patient goes back on dialysis. So what you
see here is in the late '70s, early '80s, our one-year graft
survival was as low as about 50 percent for kidney allograft. It's
now much higher than this actually. It's about 95 percent one year
survival, and it's the same for cardiac allografts.
So this drug, when this drug came in, it revolutionized the
treatment of solid organ allografts, and the way it works, let me just
go very quickly.
Cyclosporine binds a calcium activation factor in the
cytoplasm called calcineurin and turns on a whole cascade of events
that in the DNA and in the nucleus of the activated T cell inhibits the
ability to activate various genes of cytokine production, such as IL-2
and interferon gamma, which regulate immune cell divisions.
If you don't make these cytokines, you do not get
immune cell division. That seems to be a critical component of
However, despite the fact that we understand this process
of immune activation and were able to prophylactically treat patients
and prevent acute episodes of rejection, we clearly have improved
short-term allograft survival.
Despite all of that, there is a second process that kicks
in some time during the course of the recipient's life span, and
what you see is that, for example, with cardiac transplants over time,
over a five-year course, there's a cumulative loss of as much as 40
percent of the allografts in heart transplant patients.
And with kidney transplants, this curve is pushed forward,
but you still have about a 50 percent loss of allografts at ten years.
So the question is: if we're able to reduce the
incidence of acute rejections, why are we still getting a limited
long-term survival of the graft itself?
And the reason is this pathologic, unusual lesion that
happens in actually just about every graft that's put in whether
the heart or the kidney or the lungs. You get a lesion like this in
the blood vessels of the allograft. It's very unusual. It's
proliferating the lesion where you can see that the lumen of the blood
vessel is almost occluded by these proliferating cells.
And this is in the heart. This is called accelerative
transplant related vasculopathy. In the kidney, this is, again, a
And the cause of this is not clear, but it probably is due
to — much of that, as I suggested, is due to an ongoing immune
response against the foreign HLA antigens, which are expressed here on
the luminal side of the blood vessel.
And even though the patient is not experiencing major acute
episodes of cellular rejection, there is an ongoing subclinical level
of rejection process going on that damages and causes these vessels to
The causes of this process really is multi-factorial, but
HLA, attack against the HLA of the donor continues to be the number one
cause of this.
And you can see that chronic rejection — this is in our cardiac
transplant population at Columbia — chronic rejection accompanies
those patients who had many more episodes of acute rejection. So
for every hit that you have, for every acute rejection episode that
you have, you'll destroy a little bit more of your heart, and
you're more likely to go on to get chronic rejection as opposed
to those individuals in blue who have less episodes of acute rejection.
So fulminant episodes of acute rejection, even though you survive
them and your graft continues to work well and we can reverse them
will predispose to chronic rejection and even in the absence of
fulminant episodes of acute rejection, ongoing immune reactivity
against the donor HLA will also predispose you to chronic rejection.
As you can see in this slide, these are patients who
actually have not had episodes of acute rejection over a number of
years, but make antibodies against the foreign HLA. In yellow are the
kidney patients or heart patients. Antibodies against the HLA
antibodies, in yellow the HLA of the donor, have a poorer outcome in
terms of developing graft failure.
So even in the absence of acute episodes of rejection, an
immune response that results in anti-HLA reactivity causes graft loss,
and this shows the same.
So what that means is that we need to be vigilant. We need
to monitor the patients very closely. We can't just expect that a
combination immunosuppressive regimen that is used initially is going
to keep all patients in check and all patients quiet.
We have an active immunologic monitoring of particularly
our cardiac transplant recipients who are much more prone to having
rejection episodes, and we actively on a weekly basis measure
antibodies, T cell function. We identify patients who are at high risk
of cellular rejection. We have a whole algorithm that allows us to
study these patients on a weekly basis, and you can see that this
algorithm allows us to be very flexible and change the type of
therapies that we use so that if at a particular time point certain
test number one plus test number two in terms of immune activation
become positive, we know that we need to change our immunotherapy.
In contrast, if these assays remain negative or perhaps
revert from a positive to a negative, we can reduce the type of
biopsies that we do. Instead of doing a biopsy every 30 to 60 days, we
may reduce our biopsy frequency to every 90 days.
And this is the type of dynamic approach that we use to
monitor our patients and to modify the type of immunosuppression
that's required. It's not a static process.
And I think what I'm trying to emphasize is that the
recipient's immune response continues to be a major obstacle in
terms of accepting and long-term survival of the graft. And so since
these issues are so complex and so difficult, the Holy Grail really of
transplant immunobiologists has always been to try to induce a state of
transplantation tolerance, in other words, a permanent acceptance of
the graft that can allow the recipient ideally actually to not require
any type of immunosuppression.
And the definition or criteria of transplantation tolerance
are outlined here: specific immunologic unresponsiveness to
alloantigens, otherwise known as HLA antigens, of the donor, of the
graft, in the absence, total absence of continuous immunosuppression;
prevention of acute rejection and promulgation of graft survival;
acceptance of a second test graft on the same original donor strain —
this is for experimental tolerance in animals — and the specificity is
then confirmed because the recipient will reject a third party graft.
In other words, tolerance is defined as being absolutely
tolerant only to the organ that you've received or that you've
seen, but not tolerant to an unrelated donor. This type of tolerance
has been extremely difficult, if at all possible, to detect or to
attain in humans, although many studies have suggested that perhaps a
term called microchimerism or chimerism may actually reflect a state of
tolerance in organ transplant recipients.
And what chimerism relates to is the presence in your
circulating blood of at least five percent of your circulating cells
being of donor origin. Whether that, in fact, really does induce
tolerance is really not clear, but the concept is that if five to ten
percent of your circulating blood pool comes from the donor,
essentially what's happened is that the passenger cells from the
graft that was placed into the recipient, the passenger cells left the
graft, circulated to the lymphoid organs, particularly the bone marrow
and the thymus, engrafted in the bone marrow and the thymus, and then
have maintained their own essentially self-renewal capability, and
continue to be shed and secreted into the circulation to essentially
make the recipient think that cells of that HLA type are the same as
Again, in experimental models, you need to attain at least
five to ten percent of your circulating cells being of donor origin in
order to have a so-called chimeric state that may reflect tolerance.
And so what are the mechanisms by which tolerance might be
attained? And again, all of this we're talking about now has not
been defined in humans, but is based on experimental models in both
small animals and larger primates.
The mechanism includes clonal deletion, clonal anergy, and
perhaps development of regulatory cells that change the type of
cytokines that are produced.
Clonal deletion refers to the ability of the thymus to
regulate the type of T cells that we produce that reject the organ. In
other words, if we know that CD4 T cells in our blood recognize the HLA
of the donor, why are they not deleted or why are they not removed by
mechanisms in our body that can actually do that to our own T cells
that attack our own grafts?
And so the function of the thymus is to actually remove
self-reactive T cells that we all have at various time points, and if
our thymus can remove our own autoreactive T cells, could we perhaps
induce our thymus to remove those T cells that are reactive to the
And so this process of clonal deletion or how do you induce
clonal deletion is one mechanism by which tolerance might be attained.
Clonal anergy does not involve the thymus. Clonal anergy
is the same sort of concept: can you remove those deleterious clones,
but this happens in the periphery, in lymph nodes, similar mechanisms
but in a different location.
Regulatory cells that change your cytokine profile — let
me just go to the next slide — it's well known that the type of
cytokines that induce an acute rejection process, Interleukin 2 and
interferon gamma, and I've already mentioned that cyclosporin
primarily inhibits the production of these cytokines, but these
cytokines are made by certain types of T cells called TH-1 cells. It
has been shown that if you can prevent the development of these TH-1
cells and instead skew the immune reactivity towards what's called
a TH-2 type of T cell that produces a totally different repertoire of
cytokines, this type of T cell preponderance and this type of cytokine
preponderance appears to switch off the immune response and allow
engraftment and allow a tolerogenic state.
And this switching between a TH-1 and a TH-2 phenotype of
cells can be attained, again, by a variety of experimental approaches,
but if we can drive to this preponderance of cells, we might be able to
prevent allograft rejection.
Other novel experimental approaches include inhibition of
co-stimulatory molecules on the surface of the graft. We know that HLA
was — well, HLA is the primary antigen that drives the T cell immune
response. There are other molecules on the graft that help
deactivation of the T cell, and these are called CD28 and CD40 ligand
at least. There are many others as well.
If you don't have molecules on the surface of the
graft, an HLA, foreign HLA molecule by itself may not necessarily
activate the T cell. So there are ways of perhaps altering the graft
so that it doesn't express these co-stimulatory molecules, that may
induce a tolerogenic state.
Other approaches include the use of MHC or HLA peptides
that can mimic the foreign HLA and bind to the T cell and switch it
off, and perhaps also induction of death, artificial induction of death
of the T cell that mediates rejection.
Another molecule that's important in this pathway is
called Fas ligand that could be over expressed, again, by genetically
altering the organ, over expression of Fas ligand to kill the T cell
that recognizes Fas ligand instead of allowing it to become activated.
These are all experimental approaches, none of which have
yet been proven in men.
Let me just keep going.
This is one approach that I would like to just touch on
very briefly. Amongst the co-stimulatory molecules is the IL-2
receptor, IL-2 to IL-2 receptor, and you can see that if you don't
express a functional IL-1 receptor on your T cell, the T cell is not
able to then proliferate and become activated.
So we said that cyclosporin is a very active drug by virtue
of the fact that IL-2 is inhibited. However, how about if we can
inhibit the IL-2 receptor rather than inhibiting IL-2?
And that has led to a strategy from a number of the large
pharmaceutical companies that have developed anti-IL-2 receptor
monoclonal antibodies, and here's an example of one where in
conjunction with other immunosuppressive agents you can see that it
delays the onset of kidney allograft rejection.
However, what's interesting here is that as soon as the
antibody treatment is stopped at around day 180, you can see that the
rejection process starts to come together again.
In other words, what this tells you is that this type of an
approach of an antibody to block a surface receptor that may be
considered important for the immune response does not lead to a
tolerogenic state. It simply leads to an inhibition of the immune
Because when you stop that treatment, you should continue
to have an inability to reject the organ. Because these rejection
rates come together, it means you have an induced tolerance.
And so we get back to what I was just talking about, which
is can we artificially allow the thymus to delete cells that would
otherwise be alloreactive. And the way we can do this experimentally
is to use a drug called cyclophosphamide. It is yet another
immunosuppressive drug, but what this essentially does is it activates
a pathway in the thymus that causes T cells that would reject the organ
to explode or die through a process called apoptosis.
And what you see here is that if we actually treat — this
is now in patients — if we treat patients with cyclophosphamide to
induce apoptosis in the thymus of alloreactive T cells, we inhibit the
rejection process very significantly relative to patients who are
treated with another combination of drugs.
And so this is a major clue to the fact that the thymus can
be manipulated to enable a tolerogenic state to occur.
And that leads to this. This is really my last slide.
This leads to understanding a phenomenon that was described quite a
number of years ago in kidney transplant recipients where blood
transfusion that preceded the kidney allograft, and this is blood
transfusion of the same donor type infused peripherally prior to
actually putting the kidney transplant in, significantly prevented the
rejection of the organ.
And this phenomenon has now been known for many years,
although it has been poorly explained. Many variations of this have
now taken place in clinical practice, trying to define the cells that
most likely prevent allograft rejection.
And we have moved from using whole blood because it's
very difficult to know exactly how many cells. If you actually give
too many cells, you can actually induce an immune response. You can
induce an accelerated rejection process.
It seems to be very critically linked to how many blood
cells are actually transfused, which means that if we don't
understand which cells are doing this effect, you really haven't
got a handle on the process.
So now people are looking at other subpopulations, and
since the whole field of stem cell transplants and bone marrow
transplants have moved along pretty dramatically over the past few
years, people have tried to now look at whether cells in the adult bone
marrow, particularly stem cells in the adult bone marrow, may have this
effect when transfused prior to an organ transplant.
And what I'd like to just quickly do is to sort of
shift — that is my last slide — but I'd like to just quickly
shift into some aspects of my paper, which I think addressed the
current state of knowledge in terms of how cells from the bone marrow
or from other sources might actually do this sort of thing, induce a
tolerogenic state and prevent organ rejection.
In order to — if we could just switch off the - thank
In order to understand the type of tolerance that we're
talking about, we need to understand a little bit about the
characteristics, particularly the immunogenic characteristics of stem
cells, both embryonic and adult stem cells.
Embryonic stem cells have been known for a number of years
in murine models and recently in human cell lines, but adult stem
cells, a population of adult stem cells has recently been described to
be present in the adult bone marrow that has many features and many
characteristics that seem to be shared with embryonic stem cells.
So I'd like to sort of combine the discussion in terms
of the characteristic of both these cell types because they're
Both embryonic and adult mesenchymal type stem cells do not
express HLA Class I and Class II molecules and demonstrate reduced
surface expression of co-stimulatory molecules required for T cell
When one transplants either embryonic stem cells or
mesenchymal stem cells from the adult, one finds long-term graft
survival of the cells despite the fact that these cells to acquire HLA
Class II antigens after in vivo differentiation.
A striking recent observation of the mesenchymal stem cell
population has recently been noted that they broadly inhibit T cell
proliferation and activation by various types of antigenic stimuli,
including those from HLA of foreign donors. Mesenchymal stem cells
have been shown to inhibit both naive and memory T cell responses, to
affect cell proliferation, and to reduce the number of interferon gamma
And we actually know more about mesenchymal stem cells,
their ability to escape immune surveillance, than we do about embryonic
stem cells at this point in time, but nevertheless, there's some
information that both when they're transplanted are able to escape
Extending the observations of donor derived blood
transfusions to induce a tolerogenic state. Several groups have tried
to reproduce this type of an approach using embryonic derived stem
cells or mesenchymal stem cells.
The two underlying mechanisms by which creation of a mixed
chimeric host results in tolerance as I've mentioned are, one,
thymic deletion of potentially donor specific alloreactive T cells and,
two, non-thymic peripheral mechanisms as we've mentioned.
The theoretical advantages of either of these cell types is
that because they don't express HLA Class I or Class II, they might
be able to migrate to the thymus, might be able to reeducate the thymus
so that the thymus then thinks that these cells are part of its own
normal repertoire, and the thymus will then eliminate potentially those
type of T cells that could reject these type of cells.
And, in fact, in experiments where either embryonic or mesenchymal
stem cells from the adult have been injected intravenously, we know
that long-term acceptance of these cells has been accompanied by
the presence of large numbers of these cells in the recipient thymus.
And in a particularly interesting study using rat embryonic stem cells
recently, it was demonstrated that intravenous injection of rat
embryonic stem cells in the absence of any type of immunosuppression
resulted in long-term engraftment, as well as the thymus, and resulted
secondarily in the recipient rat being able to accept a cardiac
allograft of the exact same HLA type as the embryonic stem cells,
but not a cardiac allograft of an unrelated donor, which meets all
of the criteria of tolerance induction.
In the only study to date using mesenchymal adult derived
stem cells, what we have been able to see is that a similar type of
long-term engraftment in the bone marrow in the thymus can be achieved
with adult mesenchymal stem cells, and I think it's reasonable to
anticipate that a similar experiment would likely also demonstrate,
although obviously it still has to be done, that the engraftment in the
thymus might lead to long-term tolerance and acceptance of a graft of
the same HLA type.
So I think those type of experiments are very exciting and
raise the possibility that stem cells might have, by virtue of the fact
that they do not express high levels of HLA, and even when they are
induced to express HLA molecules, might have very special
characteristics that allow them to evade immune surveillance and, even
more importantly, might actually allow them to re-educate the host to
accept a different type of donor tissue.
And perhaps the hope would be the induction of tolerance
might actually obviate the need for all of the stuff that I just told
you about this morning, all of those complexities in terms of
And I think I'll stop there.
CHAIRMAN KASS: Thank you very much.
Since my guess is that for at least the non-medical,
non-scientific members of the house, this was complicated. Let me see
if I could try to formulate something of the nub of this and ask you to
I think the large part, the preliminary part of the talk
indicates the enormous complexity of the immune system and the
difficulties of getting especially long-term graft survival and also
the need for long-term immunosuppressants, which have risks and harms
of their own.
And the strategies for inducing tolerance have up until
this point tried to attack various parts of the host response,
But if I understand the most exciting part of this, the
last part of this discussion, the suggestion seems to be that the use
of stem cells, mesenchymal or embryonic - this is now the concept and
not the data — that such cells, first of all, to begin with lack the
HLA provocative antigens so that they are not themselves immediately
Second, that they can apparently take up residence in the
thymus and, if given from the same donor, if given from the individual
who is then to serve as the donor of a particular organ, that increases
the survival of a solid tissue donation from that person.
Is that correct so far?
PROF. ITESCU: That would be one potential use of such
CHAIRMAN KASS: And let me draw out an implication for
regenerative medicine using stem cells or their derivatives. Again,
just the concept now, not the evidence.
The concept would be that because these are immunologically
unprovocative materials, original stem cells introduced into a patient
which presumably would take up residence in the thymus and perhaps, as
you suggest, re-educate the immune response even after the HLA antigens
appear in those cells; re-educate the immune response to no longer
regard those cells as foreign; might make the host now receptive to
even the introduction of differentiated cells derived from those stem
cell lines. One could put in heart cells taken from these stem cell
lines and have them not seen as foreign.
Am I understanding the concept correctly?
PROF. ITESCU: Yes, I think that's actually correct.
In fact, it's almost a beneficial aspect. The stem cell that is
initially infused does not express HLA, takes residence in the thymus
in the absence of HLA expression, and then is induced to express HLA at
that site because it's the actual expression of the HLA molecule
that allows a re-education process and tolerance induction to that HLA.
So that if it didn't express HLA at all, at any time
point, you would not develop tolerance to that HLA molecule. So it
doesn't get rejected in the first instance because it doesn't
express HLA. It enables engraftment in the thymus long enough to
up-regulate its HLA molecule, and then it re-educates the thymus to
accept that HLA molecule.
So you can then come along with a differentiated tissue or organ
which now does express that same HLA and it will be de-rejected
it from the outset. That's right.
DR. KRAUTHAMMER: So it essentially causes a change in the
immunological identity of the recipient.
PROF. ITESCU: And that's the concept of chimerism.
CHAIRMAN KASS: Right. So it's a magic bullet if it
works. Would be.
PROF. ITESCU: It would be, yeah.
CHAIRMAN KASS: Paul McHugh.
DR. McHUGH: That was a splendid presentation with very
exciting prospects in the future, and of course, the most exciting
prospect to any of us who have followed the transplantation business
from the time when — I was an intern at the Brigham in the 1950s. So
I was there in the beginning - is the possibility and the prayer of
But you know all about that. Will this bring to bear the
possibility that we'll be able to use animal tissues ultimately for
transplantation of these vital organs and the use of animal stem cells
and, therefore, animal organs will spare us not only this problem you
have here of people in need and the lack of donors, but also much of
the ethical problems related to stem cells?
PROF. ITESCU: Well, my laboratory actually was very
heavily involved in trying to understand the rejection processes of
disparate xenografts, and we have tried to develop a variety of
immunologic strategies to try to overcome that.
At this point in time I actually am much more hopeful that
regenerative medicine using adult stem cells is much closer to reality
than xenotransplantation for a number of reasons.
Most importantly, I think, is the fact that the differences
between animals and humans is a wide array of antigens. HLA is just
one antigen, and the fact that we're all so closely related as
humans is simply the fact that the only thing that differentiates us is
the HLA structure from individual to individual.
However, between species not only is HLA different, but
there are many other structural genes, and I, frankly, am fairly
pessimistic actually that those differences are likely to be overcome
So I would emphasize actually the human stem cell
regenerative possibilities rather than xenotransplantation.
CHAIRMAN KASS: Rebecca Dresser.
PROF. DRESSER: Two questions. I was wondering how long it
takes for this re-education process of the immune system after the
first inducing of the stem cells.
And the other question was exactly where is this in terms
of laboratory data theory, human data, animal data. How much of this
is hope and how much of this is demonstrated?
PROF. ITESCU: Sure. The chimerism concept all comes from
human data. In other words, for many years people have looked at
whether donor cells continue to circulate in the recipient's blood
stream or organs, months, years, many years after a transplant.
And so this concept that the recipients who do better are
those who have the higher percentage of donor cells circulating has
been around for many years, and it is data from humans.
In terms of proving that that has anything to do with
tolerance, you have to go back now to the animal models. The
experiments that I've outlined to you are actually recent
experiments in the last 12 months primarily using embryonic derived
stem cells where those embryonic cells were able to be engrafted from
one rat to another rat type, induced chimerism, induced tolerance to
those cells, and subsequently were able to induce a state of
nonresponsiveness to a heart transplant of the same donor.
Now, the experiments with adult mesenchymal stem cells are
also within the past 12 to 24 months, and what we know about adult
mesenchymal stem cells is that if they're injected at a time of
in utero - the experiments that I was referring to where these
cells were injected in utero in developing fetuses — and those
cells can then engraft and survive for at least one to two years after
birth. This is human cells actually in an animal model, and those
cells survive, are not rejected. They're found in multiple organ
types, including the thymus.
What we also have learned in the last 12 months is that
these same adult mesenchymal stem cells which do engraft in
vitro are able to actually inhibit immune responses from other
human T cells against themselves and also inhibit the immune responses
of other T cells against other antigens, including HLA antigens.
So we have a lot of information in vitro that
mesenchymal adult stem cells are functional. We know in vivo
they're able to engraft in a similar way to the way that the
embryonic stem cells can engraft and not get rejected.
And so the only experiment that's missing is that same
other experiment that has been done with the fetal cells, and that is
can actually induce a tolerogenic state to allow a solid organ graft to
be put in.
PROF. DRESSER: And how long does it take to induce that
PROF. ITESCU: In small animal models, we are talking about
probably weeks. To translate that to man, you know, is a guess, but I
would think weeks to months would be the objective.
CHAIRMAN KASS: Bill May.
DR. MAY: You said that adult stem cells from the bone
marrow may significantly reduce organ rejection, and later you said
adult stem cells have many characteristics shared with embryonic stem
I'm interested in the policy implications of this. Do
you feel that we should simply follow out, play out the line of
exploration with adult stem cells and delay explorations with embryonic
stem cells, or should we be following both tracks at the same time?
PROF. ITESCU: I think what we know at this point in time
about both cell populations, and again, what one calls a stem cell in
the bone marrow differs from experimental group to experimental group.
There are many types of stem cells in the adult bone marrow.
But there are a number of well defined stem cells, and
I'd talk about mesenchymal stem cells. There's another group
of perhaps an even earlier progenitor cell type to the mesenchymal stem
cell, but what I think most people will agree on is that the stem cells
defined in the adult bone marrow have many features that are similar to
true embryonic stem cells in terms of surface markers and in terms of
the way they behave, but there are some differences as well.
So, in particular, what we know is that at this point in
time I think the adult stem cells probably do not have the same range
of differentiation capability that an embryonic stem cell does in terms
of their ability to become almost any organ in terms of
Nonetheless, the differentiation capability of adult stem
cells at this point is quite remarkable.
Secondly, the self-regenerating capacity, meaning how many
times can the cell continue to divide before it stops dividing, and
that's one of the fundamental features of any stem cell. The more
division it can undergo, the more likely it is to then differentiate
and become a useful clinical entity.
The self-renewal capacity of most of the adult stem cells
that have been defined to date probably it's fair to say are not
quite to the same degree as great as the self-renewal capability of an
embryonic stem cell.
I would say at this point in time it remains an open
question as to whether these differences are at a clinical level, and I
think I would support continued research in both cell types to
understand (a) whether these differences are relevant; (b) whether the
diverse functional capability and range of differentiation exhibited by
the adult stem cell is sufficient in many cases.
In the work that we're doing with respect to the
cardiovascular system and the heart, we have found that so far there
are certain stem cells that are terrific in terms of their ability to
improve cardiac function.
So I would view these fields as overlapping and say that at
this point it's far too early to decide which field is going to be
the right way to go for every type of regeneration strategy that one is
But I think that there's enough hope in the adult stem
cell area that it may be sufficient to go down that path. I would at
this point continue research in both areas.
CHAIRMAN KASS: Dan Foster.
DR. FOSTER: I have two questions in regard to possible
downstream effects that might be difficult, and the first question, I
presume that the injection of the stem cell of one sort or the other to
protect against the donor's solid organ transplantation would be
that the immune inhibition there would be, the tolerance there would be
restricted to the donor. It would not, in other words, in your view
interfere with immune responses to infectious agents or anything else.
I presume that's correct, right?
PROF. ITESCU: The hope would be twofold. To
call this tolerance, it would have to be a tolerogenic state induced
only against the inducing cell and antigen and a continued responsiveness
to any other antigen. That would be the hope of the whole process.
Otherwise you would have global immunosuppression. That's right.
DR. FOSTER: The second question is probably unimportant to
somebody who needs a heart or something of that sort, but if you're
look in simple terms at the immune system, it does two things. It
fights off invaders, as you say, viruses and bacteria and so forth, and
it surveys for cancer. I mean, so that in one sense anybody who gets a
cancer has had in some way a failure of the immune system to see the
oncogenic antigens and as a consequence not to delete it.
I mean, a lot of people think that all of us are forming
cancers all the time, and that the failure is the immune system.
I presume that there is at least a theoretical possibility
that since even donor tissues or other tissues might get a malignancy
that that might be impaired with the tolerant state that was there so
that you might be at risk for malignancy, even early malignancy.
I mean in some ways tumor suppressor genes, you may get
very early things. I think if I needed a heart I wouldn't worry
about that, but just in theory that might be something that we would
have to worry about even if there was not a defect against the one wing
of the immune system that fights off against infection, but might make
us vulnerable to the other thing that's devastating.
PROF. ITESCU: No, I think that's actually an excellent
point, and that's right. So in other words, if a cell is so
primordial and so early that it confers some type of protection against
itself being rejected, it's also that same cell type that is so
plastic that it has the ability to differentiate into so many different
lineages that it also has a high rate of becoming cancerous.
Typically the embryonic stem cells obviously have the high
risk potential for teratoma formation. Again, if you then think about
the adult mesenchymal stem cell versus the embryonic stem cell,
there's a tradeoff between these two. So the embryonic stem cell
is the most pluripotent, has the highest rate of proliferation and cell
divisions. The mesenchymal stem cell has a slightly more
differentiated, let's say, than the embryonic stem cell. So it has
a less likelihood of — it has less cell divisions left and maybe a
little bit more of a restricted differentiation pattern.
But if you then take these two cell types and if they are
both able to induce a state of immune nonresponsiveness, the one
that's less likely to induce a neoplastic transformation, I think,
would be the adult mesenchymal stem cell.
So from that point of view there would be a preference to
that versus the former.
CHAIRMAN KASS: Could I ask just a technical question?
This so-called re-education process that stem cells might induce in the
host thymus, could that process persist even if the mesenchymal cells
In other words, if the adult cells are not
self-perpetuating and, therefore, die out as a population, could a
short term residence in the thymus be sufficient to confer a long-term
tolerance for a subsequent graft?
PROF. ITESCU: Yes, I think so. And examples of that are
many experiments in transplant immunobiology where people have directly
injected HLA molecules into the thymus using specific HLA molecules of
the subsequent donor organ to induce a state of immune
The organ is then transplanted and long-term tolerance has
been achieved. Presumably the injection of the HLA molecules resulted
only in a transient expression in the thymus.
CHAIRMAN KASS: Thank you.
Janet and then Michael Gazzaniga.
DR. ROWLEY: I wanted to ask several questions. Going back
to the mesenchymal stem cells, I assume that they are a related type to
those that we heard about earlier from Catherine Verfaillie. They may
not be quite as primitive as the ones she's been able to identify,
but it is the same lineage.
PROF. ITESCU: That's right.
DR. ROWLEY: Now, going on into the real world, and
let's say it's a kidney transplant, you would then get bone
marrow mesenchymal cells from the donor. So it would be cultured to
identify the stem cells. Those would be injected into the potential
recipient, and then at some point later you would take the kidney from
the donor and hope that you had induced tolerance.
PROF. ITESCU: Yes. I think that's about right. Now,
to be fair, you know, to try to do that in the setting of an acute
process, such as, for example, when we have a cardiac transplant donor,
we are talking about hours from the moment of identification to actual
To be fair, I think in that type of scenario it would be
extremely difficult to then isolate bone marrow stem cells, purify,
inject, and hope to achieve tolerance all in the same space of time.
I think this type of a strategy and approach is much more
amenable to living related transplants and would really increase the
survival and success of those type of transplants.
DR. ROWLEY: Part of the reason for pursuing this is to
show that this may be potentially useful in a subset of patients, but
as you just said, for cardiac transplants this approach is limited and
maybe not even be feasible.
PROF. ITESCU: Well, let me extend the thought. If you
needed to use — at this point in time, I think, with known technology
of how to immunoselect and how to get hold of these cells, I think it
would be a little bit impractical in the situation of a cardiac
I think there is the possibility that you could potentially
use mesenchymal stem cells of an unrelated donor that could potentially
enhance the ability of the thymus to be nonresponsive at the time that
a graft was implanted and induce tolerance to that graft through
mechanisms other than simply the HLA molecules that the stem cell
Do you see what I'm saying?
DR. ROWLEY: Okay. What occurs to me is why don't you
then get hyperactive response to those rather than suppression.
PROF. ITESCU: Well, for reasons that are unclear at this
point, stem cells do not seem to induce an active immune response to
themselves. They seem to down-regulate immune responses to —
DR. ROWLEY: In general.
PROF. ITESCU: In general.
DR. ROWLEY: Right.
PROF. ITESCU: So there may be a possibility of the
potential of using unrelated stem cells plus a third party graft and
you induce tolerance to that particular graft, but not to another graft
because the immune system has seen only that graft in conjunction with
the stem cells that were infused.
DR. ROWLEY: Okay. Now, but following on with this, I
guess in terms of the use of embryonic stem cells, unless it's in
this same context of a neutral or an unrelated stem cell affecting, in
a sense, general immune unresponsiveness, you're not going to take
an organ from the embryonic stem cells and transplant it into a donor
as you would with the adult stem cell scenario that we just pursued.
So I guess I'm a little bit confused as to how you
foresee embryonic stem cells in the sense of organ transplantation or
is it in the example you just gave?
PROF. ITESCU: Yes. The ideal scenario would be to have
mesenchymal stem cells obtained from the same donor where the organ is
coming from. So I think in that type of combination, the embryonic
stem cells would have no role. I think a second scenario would be
where stem cells of whatever source you want could potentially be used
as a local immunosuppressive agent for that particular organ that's
used at that time point.
And, again, we're talking about a tolerogenic induction
to the HLA of that organ.
A third possible use of stem cells in this way might be,
again, irrespective of whether you're talking about adult stem
cells or embryonic stem cells, to induce a state of tolerance by
injection of the cells followed by a more differentiated set of cells
for organ regeneration.
So as a strategy to prevent rejection of stem cell derived tissue
regeneration. So, for example, if we wanted to improve cardiac
function using adult stem cells and we would take, let's say,
adult mesenchymal stem cells, differentiate them in vitro
into cardiomyocytes, we would be concerned that if we took those
cardiomyocytes now and injected them directly into the heart they
might get rejected.
So what we might want to do then is take our source of
mesenchymal stem cells from a given individual with heart failure,
let's say; take those mesenchymal stem cells, set aside a number of
them and try to differentiate into cardiomyocytes, take the first batch
of mesenchymal stem cells from the same patient, infuse them back,
allow that patient to develop a tolerogenic state, and we're
talking about mesenchymal cells from a different donor, not from
obviously the same, where we're able to have a larger bank of cells
to provide back to the first recipient.
DR. ROWLEY: Okay, and my final question is: do you have
to worry in this situation about graft versus host disease?
PROF. ITESCU: That's a very good point. In fact,
that's, again, an advantage of using stem cells for this process.
Whereas whole bone marrow transplantation or whole bone marrow used to
try to induce tolerance runs a risk of graft versus host disease.
As you probably know, bone marrow transplants, I think, in general,
allogeneic transplants keep something like 20, 25 percent incidence
of graft versus host disease. The animal treatments with to date
only embryonic stem cells that has been published has not resulted
in any type of GVHD, as you would anticipate that you wouldn't
get if these cells, in fact, inhibit rather than activate immune
DR. FOSTER: But in fairness, in the bone marrow
transplantation, a low level of graft versus host disease proves to be
advantageous, I think.
DR. ROWLEY: Well, that's true if you're doing it
with leukemia because then you get a graft versus leukemia.
DR. FOSTER: I'm talking specifically leukemia, yes.
PROF. ITESCU: But we don't want it to happen if
we're trying to induce tolerance.
CHAIRMAN KASS: Michael Gazzaniga.
DR. GAZZANIGA: I should remember the answer to this, but
is there an interesting variation in tolerance to grafts? In other
words, there's a subpopulation that seems to just take it and all
of the tricks in the medical bag don't seem to be that necessary?
PROF. ITESCU: There's no question there are some
patients who do wonderfully well with minimal immunosuppression for
many, many, many years, and absolutely I would be the first to say that
we have no idea why some people accept the graft so well.
So that clearly a mechanism of tolerance induction in some individuals
works beautifully. I would suspect that it's the same type
of mechanisms we're talking about today that take for whatever
reason in some individuals better than others, but it will be the
same mechanism. It won't be different mechanisms, I think.
DR. GAZZANIGA: Is there any way that you could predict
PROF. ITESCU: Yeah, and what I was alluding to earlier,
the type of chimerism approaches. What people do is using genetic
probes or genetic markers, you can look for the amount of donor cells
or donor tissue in the blood or in the ingrafted in various organisms,
the lymph nodes or bone marrow.
You can do these kind of fancy tests, and you can certainly
predict that if there's a high percentage of donor cells that
continue to be present two, three years out, actually two or three
years — if the patient has already gone two or three years, you know
it has done well, but let's say in the first three to six months
which is the highest risk of rejection.
If you see a high rate of persistence of donor cells, you
can predict that this patient is going to do better.
DR. GAZZANIGA: So could you use that as information in
maybe jumping the patient ahead on the transplant list because you
think there's going to be a —
PROF. ITESCU: Well, you don't know that until the
patient has already been transplanted.
DR. GAZZANIGA: I was asking if there were predictors.
PROF. ITESCU: No, there are no predictors prior to a
transplant as to who's going to accept the particular donor at a
given point in time. There are no global — what I was trying to
emphasize is that the exquisite response, the exquisite specificity of
the immune system here dictates that there's going to be a very,
very close and tight response between the donor's immune system and
the particular genetics of the host.
And those two are so specific that they cannot be predicted
globally, and that forms the basis for why we actually monitor each one
of our patients very closely and we tailor our therapy on an individual
basis. You just cannot make global decisions like that.
DR. GAZZANIGA: And one final thing. Maybe it was on your first
graph, but I didn't catch it. If you were to say what the survival
rate, transplantation survival rate in 2003 versus ten years ago
was, how much has it changed with all of the new technologies?
PROF. ITESCU: The most dramatic leap was probably about 20
years ago, as I mentioned, with cyclosporin coming in from 50 percent
one year survival to about 80 percent. We've now gone from about
80 percent ten years ago to I would say 95 to 100 percent one year
survival for kidneys and for hearts.
You can't get any better than that at this point in
time. The biggest problem right now still is that five and ten-year
survival rates, and those are the issues that I was getting at. I
think still donor-recipient immune activity is the problem, that we
cannot induce tolerance.
CHAIRMAN KASS: Janet.
DR. ROWLEY: I'm not sure whether people have questions
along this line because mine is a different question.
So coming back to the first slide where you show the great
disparity between the number of people who need kidney transplants and
the number of potential donors and cadaveric donors, and your data on
cadaveric donors would suggest that that's not necessarily an
avenue to pursue actively because the results are so much poorer in
terms of response.
The question I have, and that we've had minimal
discussion on this, is whether we should change the strategy of
obtaining donors, and I'm interested in your view on whether there
should be a program for paying donors for their organs.
It has been pointed out to us that everybody in the system
makes money except for the donor, and the donor is the essential
individual in this whole chain of events, and I'm curious as to
your perspective on this.
PROF. ITESCU: Okay. I think that it's clear that
we're not increasing the donor pool. I would disagree. I think
outcome with cadaveric transplants is excellent. My only point, that
was with living related is even better, but there's nothing wrong
with our current outcomes with cadaveric donors.
And I wish that we would be able to increase our cadaveric
donor pool. So if question number one is should the families of
cadaveric donors be appropriately looked after, I think the answer
should be yes. I think that the families need to be involved in this
In terms of the living related and whether there should be
issues with reimbursement, I would strongly oppose that.
CHAIRMAN KASS: We've got time just for a couple of
questions. Michael Sandel, Bill Hurlbut.
PROF. SANDEL: Why do the cadaveric organs not work as well
as living ones?
PROF. ITESCU: For a number of reasons. First of all,
because the living ones you've got more time to select on the basis
of how well the donor-recipient are matched, number one. I mean,
that's the objective. You find the best match, and that's the
one that's going to be the best in your family pool.
And you're already starting out with related
individuals who are at least going to be 50 percent identical, you
know, because you inherit 50 percent from your mother and 50 percent
from your father. So you will share at least 50 percent of your genes
with siblings, et cetera.
So we're starting out with a closer pool, and then
you're looking for a perfect match. That's the number one
But interestingly, as I mentioned, spousal related grafts
which are HLA completely unrelated generally also do better than
cadaveric. So the answer is more complex than that.
It's also probably because if you can perfectly plan
and coordinate the surgery so that everything goes according to
schedule, you've minimized all of the potential risk factors, et
cetera. That obviously impacts on the outcome. You can, you know,
organize your timing and the spouse will be there exactly on time and
provide the organ, et cetera.
CHAIRMAN KASS: There's no chimerism there.
PROF. ITESCU: You know, that's a very interesting
question. It may very well be some other interesting immunologic
issues that may also explain this.
CHAIRMAN KASS: Yeah. Bill Hurlbut.
DR. HURLBUT: Two parts to my question. First, can you
make some comment about the effect of mixing of peoples from diverse
geographic regions and how it may be making more complex the search for
a compatible donor and increasing the reshuffling of HLA types?
I assume that in a specific population there would have
been a greater match. Whether that's making it more difficult, but
softening the immune rejection because people are mushing towards the
middle, if you will or if it's diversifying a complex mismatch
problem. That's the first question.
Second, if, in fact, it's possible for the marrow cells, mesenchymal
stem cells or the ES cells, to induce a kind of generalized inhibitory
response or lack of response that makes tolerance of a completely
different third party organ donor, then would it be reasonable to
say that it might turn out that you only needed one or a few lines
of these, let's say, ES cells for the moment, these ES cells
or would you need many that would be a better match for the situation?
Do you get what I'm getting at?
PROF. ITESCU: Yes, I know.
DR. HURLBUT: Because the argument will be made that the
few stem cell lines that are currently available either might be
adequate to that task or that we need many more.
PROF. ITESCU: No. So let me address the question number
one first. I think clearly that as you're getting mixing of
populations, it's making local identification of appropriate donors
much harder. Actually there's much more diversity.
It's not going to make inhibition of rejection easier
because the type of exposure to antigens, that takes generations. What
you're talking about essentially from a practical point of view, it
makes selection and identification of a matched donor much harder.
More homogeneous populations have a much easier time of finding matched
DR. HURLBUT: So we're heading for a worse problem with
PROF. ITESCU: Absolutely, yeah.
And in terms of your second question, if we're talking
about an unrelated stem cell inducing tolerance to an organ transplant,
it's essentially, I think, pretty much irrelevant what the HLA type
of the stem cell is.
And so rather than needing a wider pool of stem cells, you
probably can get away with a more narrow stem cell population because
you're not specifically trying to induce tolerance to HLA antigens
that that stem cell expresses.
It's the ability of that stem cell to switch off the
immune response to HLA antigens on the organ that is seen at the same
time as the stem cell is present. So you potentially would not need
many cell lines, whether we're talking about embryonic or whether
we're talking about adult stem cells.
DR. HURLBUT: So just to clarify, if, in fact,
there are stem cell lines not grown on mouse feeder cells, even
just a few of them, that might turn out to be the central resource
to effect these ends.
PROF. ITESCU: Potentially.
CHAIRMAN KASS: Before we close, I
want to be somewhat flat-footed here so that as we hear the presentations
in July I know what I'm supposed to think about the immunological
aspects or prospects of stem cells for regenerative medicine.
You seem to be suggesting the following, and this was, in
fact, the reason for the invitation, to learn what we could from
experience with immunological problems in the transplantation of solid
organs to anticipate the possible obstacles to the uses of stem cells
in regenerative medicine.
We've heard something surprising here in a way, that
stem cells, both embryonic and adult might actually hold some promise
for making the immunological obstacles to the solid organ
transplantation less than they now are. That would be the first point.
And that second, if this matter of education of recipient T
cells by some kind of chimerism works, there may not be as large a
problem in the use of stem cells for regenerative medicine as has been
anticipated, and in fact, just to make a footnote, it might not be
necessary as some people have argued that only by cloning can one get
immunologically compatible stem cells for therapy. Is that correct?
PROF. ITESCU: I think that would be the natural extension
of the argument, although I think at this point in time far too few
data are available to be able to make those kind of conclusions, but I
think that's right. The surprising evidence to date, I think, is
that even when stem cells of either source are enabled to differentiate
sufficiently to up-regulate their HLA molecules, they still seem to be
able to engraft, and they still seem to be able to regulate immune
responses in a downward fashion.
So potentially what that does suggest is that these cells
may be less immunogenic than other cells in our body and might produce
to requirement for cloning even when used therapeutically, yeah.
CHAIRMAN KASS: Thank you very much.
DR. ROWLEY: Can I just interject though? You said in your
presentation that the data all come from experimental animals, and so
this last exchange, in fact, we don't know whether the data from
the animals are applicable to the human system.
PROF. ITESCU: Absolutely. I agree entirely with that,
CHAIRMAN KASS: Thank you very much, Dr. Itescu, for an
interesting and enlightening presentation and discussion.
We'll take a break for 15 minutes. Come back at ten
minutes of 11.
(Whereupon, the foregoing matter went off the record at 10:36
a.m. and went back on the record at 10:54 a.m.)
SESSION 2: MEDICALIZATION: ITS NATURE, CAUSES, AND CONSEQUENCES
CHAIRMAN KASS: All right. In this session we
move from the scientific and medical to the sociological and philosophic,
the question of so-called medicalization, making medical some aspects
of human behavior not previously regarded as medical, and the question
before us is what is medicalization and why might it be important
to our enterprise as the President's Council on Bioethics.
And I'm going to make some semi-coherent, I hope, at
least semi-coherent remarks to introduce this, just to indicate why
we're talking about it.
We have touched on this topic implicitly in many of our
discussions of beyond therapy, whether using biomedical technologies to
satisfy personal desires or to achieve some form of behavior control,
and we have sometimes tried to get at that question by distinguishing
the medical from the nonmedical, say, and the distinction between
therapy and enhancement of the use of medical means for nontherapeutic
or nonmedical purposes.
The topic also came up in the last meeting in the
discussion with Steven Pinker, where the issue was not so much the uses
of biomedical technologies as the question of the assignment of guilt
and responsibility in a world in which behavior is understood largely
Some observers of the work of the council have concluded, I think
falsely, from random remarks made in these discussions that the
council has doubts about the existence of genuine mental illness,
such as schizophrenia, depression, bipolar disorder, or that it
means by raising these kinds of questions to object to the treatment
of these disorders under a medical model using psychotropic drugs.
I think that is a misreading of what we have been doing.
But rather than shy away from this subject, it seems to me
that we would do well to try to clarify this matter of medicalization
by actually treating it thematically rather than as an adjunct to other
matters, to see what it is, what causes it, and whether and why it
might be important.
And one of the reasons for doing so is it provides us with
at least one look at the larger social, cultural context that shapes
almost all of the bioethical issues that we have examined or might
examine. For example, ethical issues raised by preimplantation genetic
diagnosis or even prenatal diagnosis are really unintelligible save
when seen in the context of the fact that pregnancy and childbirth have
already been pretty much completely medicalized, or the ethical issues
that would be raised by the uses of psychotropic drugs in children
would be unintelligible except if we recognize the degree to which
behavioral problems have been medicalized and taken out of the moral
realm and brought into the therapeutic, or even any discussion of the
regulation of the use of biomedical technologies must begin with the
fact that uses of approved remedies are, by and large, left to the
practice of medicine and the standards of care.
Now, medicalization is a sociological concept that's
been around for some 30, 35 years, and it has been a matter of interest
and concern to sociologists for some time, and its scope is much
broader than questions just of behavior control or mental diseases.
The background paper written by Peter Conrad that we
circulated is a review essay by a person who is one of the first to
write on this subject, and he discusses the concept of medicalization
and shows how widespread is its reach, beginning with discussions of
the medicalization of deviant behavior from alcoholism to compulsive
gambling, to child abuse, to the medicalization of natural life
processes of childbirth, child development, and the end of life, and
going on to women's issues, from eating disorders, birth control,
premenstrual syndrome, menopause; children's issues of learning
disabilities, behavior problems.
And as this little clip at your place from the Wall
Street Journal from yesterday indicates, now shortness of stature
is about to become a medical problem, to old people's issues of,
alas, forgetfulness and growing kinds of weaknesses.
And I think that Conrad's essay points out, I think,
quite nicely how these are matters partly of conceptualization, partly
matters of institutional rearrangements, and also when the doctors are
actually involved of direct medical implications for the human
relations whenever people bring these matters to the physicians.
And he also points out how the development of effective
technologies to intervene in a whole range of areas also increases the
tendency to make more and more aspects of human life matters of medical
concept and medical approach. And this is meant to be said simply
descriptively. You know, there's no prejudgment, although some
people talk about medicalization with a negative connotation. We
simply mean it at least at this point to be descriptive.
Three things I would like to in my own name sort of put
before us that seem to me to be of special significance before
introducing the materials that Paul McHugh has especially prepared for
First, the matter of surveillance and how many, many more
things are now coming under the medical gaze, where the medical view of
this, that or the other is now kind of commonplace. The medical view
of marriage and its benefits for health, a recent bit of discussion.
And this medical surveillance, I think, now is something
that should concern us especially with the coming of the powers of
genetic screening which will, I think, soon be a major issue in which
not only will child birth be under the medical gaze, but so, too, the
necessary conditions for thinking about what are the criteria
sufficient to warrant entry into life.
So the whole question of surveillance is one of the things
Second, there are economic questions that I think are worthy of
our attention, and he points out very nicely, Conrad does, that
if the only way to get reimbursement for gaining help with life's
problems is through medical insurance, there is a high premium on
having all kinds of things declared medical in order to get the
help that you need.
And the corollary of that is this, of course, drives up
medical costs and places enormous burdens on the health care system as
more and more things, whether medical in the narrow sense or in the
broad sense, now come to the doors of hospitals and clinics.
Finally, in a most abstract way, this question of
medicalization bears really even on the business of bioethics because
it finally bears on what constitutes a medical or biological phenomenon
and what is an ethical one, as our friend Michael Gazzaniga will be
quick to tell us, especially if and when we come to begin to think
about ethical sensibilities in terms of their underlying biological
basis and substratum.
So that even the very activity that we're engaged in is
affected by the rise of the medical and biological model for thinking
about behavior, including even ethicizing.
Now, with this as a background and presupposing the Conrad
material as read, I want us to turn to the material especially prepared
for this meeting. Although the areas of human life that have been
medicalized are many, the area of behavior is, in fact, of special
interest, especially as behavior at least as we've always
understood it has some kind of biological or natural substrate, but
also a human and moral meaning.
And staff has asked Paul to help us think about this larger
topic by reflecting on the phenomenon of medicalization in the domain
of psychiatry, a subject that has been one of his professional
interests really for decades.
And I think before we start that one should simply declare
for the record that there should be no mistake about this. Neither
Paul nor I nor the council means in any way to cast doubts on the
existence of these mental illnesses or the urgency of caring for the
thousands who suffer from them or the families who are also devastated
by these illnesses.
There is no hidden agenda here. We're simply trying to
understand this phenomenon and what it might mean for the work of this
Paul chose to develop his thoughts in epistolary form, and
we decided that it was less work to synthesize his two letters as if
they were a seamless document than to allow the things to appear
actually as the conversation went between us, and we put those
materials before you for discussion.
Paul, do you want to say anything by way of start?
DR. McHUGH: No, Leon. I'm very grateful
to you for having this epistolary discussion with me. I enjoyed
I would like to — I think the stuff rather speaks for itself.
There is a subtext, I'm sure you see, that is, that Leon asked me
to do a little something about medicalization and psychiatry. I
wrote the first letter, disappointing him. He wrote—
DR. McHUGH: — a letter reminding me that
I could do better, and I tried harder the second time, and I want
you all to know that I'm aware of that subtext and want you
to be as well.
CHAIRMAN KASS: If others would like to begin, please do
so. If not, I would in a way put a question to you, Paul, as away of
continuing the conversation.
I'm very excited, as you know, by your attempt to go
beyond the merely symptomatic classification of human troubles, to
provide what you call the reference classes of diseases, of aberrant
behaviors, of what you sometimes call dispositions and sometimes you
call — I've lost the other term for it — and then finally the
sort of life experiences problems.
And the first of the three is the only class that you see as being
somehow on the model of ordinary somatic disease, but all of them
legitimately come to the healer of the soul for help.
And I guess the question is: why isn't that part and
parcel, in fact, of the growing medicalization, in fact, of all of
those other things even if our approach to them is not exactly the
Maybe you could elaborate on the value of these kinds of
categories for leaving the things to Caesar that are Caesar's and
the things to God that are God's.
DR. McHUGH: Well, it's a long story at one level, and
I'll try to make it brief. What it amounts to is that psychiatry
is a discipline of medicine. It is a medical discipline, but people
come into your office just like they come into any doctor's office
with complaints and with plenty of psychiatric complaints. The
conditions from which they spring don't necessarily seem directly
medical, and a psychiatrist has to decide where they belong.
Prior to DSM-III, the dominant approach to dealing with
people's complaints was to try to fit them into an ideological
scheme. In America the dominant one was, of course, Freudian thought
and a subdominant one in plenty of institutions was the Skinnerian
The great advantage that the classifications developed by
DSM-III were that patients' complaints were subgrouped according to
which complaints the patient brought forth and which symptoms could be
recognized out of an examination.
The problem with that though is that by classifying things
by symptoms and complaints, psychiatry was condemned really to stay at
the level that 19th Century medicine was when we classified people
according to the fever charts and the characteristics of their pain.
And no director of a department, such as I was, that hoped
to achieve a coherent discourse with his group, direct research, and at
the same time care for patients could be satisfied with simply that
And so what I have been writing about and I have been
proposing for a long time is to see different reference classes of
patients just as medicine does. After all, medicine talks about
infectious disorders, neoplastic disorders, congenital disorders,
genetic disorders, and the time has come in psychiatry to move towards
that kind of classification.
But when you think about psychiatry, it's quite clear
that there are plenty of conditions that go beyond because of human
kind and the particular features that the human brain brings into play
that give other reference classes for disorders.
And so I was interested in my department and in my work to
separate the things which are diseases, where everyone could see that
these are a breakdown of cerebral faculties, straightforward losses of
the capacity to think, to perceive, to remember, to emote
appropriately, to have executive control from a second group of classes
that are the abnormal behaviors in which what are the rhythms of our
ordinary behaviors fall awry sometimes because of injury to the brain,
sometimes because of conditioned experiences, the behavior disorders,
in other words.
The dimensional disorders in which our psychological
characteristics are dimensions of human variations just as our physical
characteristics are, and so some people can be in distress not because
they have anything broken like a disease would imply, but simply
because they are at some extreme along a dimension of human variation,
the most obvious one being mental retardation, but others being
excessive neuroticism, excessive extroversion or introversion.
And then finally, the conditions or the complaints people
bring me or any psychiatrist that fundamentally come out of their life
experience, what they've encountered in life and what assumptions
they're making about that.
These four reference classes, what I refer to in my books
as the four perspectives of psychiatry, obviously interrelate. They
all, of course, depend upon a brain. You can't have any of this
without a brain, but the brain, the human brain does all kinds of
interesting things, and a psychiatrist in interacting with such people
does different things.
He tries to cure diseases. He tries to interrupt behaviors, to
guide the individuals that are often some extreme in human variation.
He tries to help, essentially rescript assumptions that lead people
into encounters with life that will distress anybody.
And when you ask me about how to think about psychiatry in
these terms, those were the things; that was my natural place to go.
I think the question that you could ask is: well, by doing
this kind of an approach and, by the way, then generating — let me
just spell out briefly that this would mean that any department of
psychiatry would have in it individuals, for example, who are skilled
at brain imaging and the recognition of certain breakdowns of faculties
out of the generation of molecular abnormalities, genetic abnormalities
and physiological abnormalities.
The disease model that is clear in medicine should be found
in psychiatry departments and representatives of that would be there,
but also psychiatry departments should have people who are very
interested in the life story of individuals, the narrative and how the
narrative reveals sometimes the natural wellsprings of disorder.
And such a broad psychiatry department would be open then
not only to the medical departments that surround it in any university,
but it would also be open to the public at large that wonders and wants
to find not only help for, but some kinds of understandings that could
make sense out of current problems, current sets of assumptions and the
Your question that started me off on this little preamble
was, well, does this make medical everything. Well, no. In my
opinion, although a psychiatrist is often the person that people come
to now at first with a concern, like feeling sad or feeling disrupted
in their plans of life or disappointed in what they had hoped for, he
or she might come to a psychiatrist first to make sure that the
psychiatrist in evaluating the person didn't find something else
more fundamental wrong, but the psychiatrist at the end might well say,
"Look. This complaint that you have, this demoralized state, this
state of discouragement or depression is, in fact, something that
derives from who you are and what you're thinking and lots of
people besides me can help you with that, and I want you to be able to
turn to those other people to think about what you want to do."
In that way, you see, I feel I would like to move
psychiatry where medicine or surgery is today, namely, to the point
where the patient can be really on all fours with me in discussing the
implications of not only the symptoms that they have, but the treatment
that they might accept.
Prior to this or often with simply a categorical diagnostic
system, the patient comes to a psychiatrist and then has to say,
"Well, you're a person with all of this experience. You must
know better than I do about what counts and the way I ought to live and
all of that because you know the secrets."
And this way you'd say, "No, I don't know the
secrets. I think you belong in this kind of problem. Let's find
out who might know better and who might open you and me, by the way, to
a better understanding of what you've encountered and how that
encounter has shaped your reaction."
I can assure you right now that the problem here is not
that you've got some twisted neuron or a twisted molecule. I'm
good at that. I want to open you to the idea that maybe you have a
twisted thought that somebody else as well as me might help you with.
And that's a long answer to your brief question. I
have to say that it has been the story of my life, trying to make this
clear to as many people who will be willing to listen.
CHAIRMAN KASS: Do you want to follow up on this, Frank?
Because I had Gil and then — Gil, then go ahead. Sorry.
PROF. MEILAENDER: Yeah, I mean, I am following up on this
if that's okay with you.
CHAIRMAN KASS: Well, sure. Yeah.
PROF. MEILAENDER: I just want to try to figure out, Paul,
and I have to sort of direct it to you though someone else may have
insight. What difference this really makes, the kind of distinction
that you're trying to make. All right?
And I have in mind a sentence that comes on page 9 of your
now published correspondence where you say near the top, "But the
claim that alcoholism, narcissistic personality, and stage fright are
sicknesses of the same kind as schizophrenia cannot be sustained just
because these people walk into our office and we help them."
Okay? Now, it's evidently okay with you that they
continue to walk into your office, people who have stage fright or
these obnoxious narcissists. It's okay that they come in, and you
think that on a number of occasions you are able to do something or
other that helps them. It might be pharmacological in some cases. It
might just be conversation on other occasions.
So that in terms of the points that Leon raised before,
these can still come under medical surveillance, and they can still
find ways to be reimbursed through insurance and so forth for the costs
So what difference does it make that some of these things
don't fall into the category of brain disease, but they fall into
one of the other categories?
I mean, I understand that, and it certainly makes some
difference just in the sense of conceptual clarity, but in terms of the
practice of medicine, it doesn't seem to make much difference other
than, I guess, the person with the brain disease. You wouldn't
say, "Go talk to your friends about this," but with the
narcissist you might say there are some other people, too.
But, you know, it's appropriate that they come into
your office. There are things within your armamentarium that you can
use to help them. So what's the difference finally?
DR. McHUGH: Well, let me say, first of all, Gil, that
nobody comes into any doctor's office usually with a diagnosis
attached to him. He doesn't come in and say, "Guess what I
have. An aortic aneurism, and it's causing me pain."
DR. McHUGH: He doesn't do that. He comes in and says,
"Listen. I've got belly pain, and I don't know."
Of course, it could be nowadays when you read the magazines
that you could do that, and occasionally I can tell you in psychiatry
people come in and tell me they've got adult ADHD and I'm to
give them Ritalin and let's get on with it.
But for the most part people don't come in to a
doctor's office with that. They come in with complaints and
wonder, appropriately, whether the doctor can help them.
And the difference that we're making here amongst them
is to say that there are different sources of these complaints, and
psychiatrists have greater or lesser capacities to help them, and by
making these differentiations and differentiating things according to
their essential differences, I think, not only do we serve that patient
well, but we ultimately serve the public well who want to ask us
appropriately who and whether the patient should get help from you or
from other people, and ask us exactly how we give them help.
So first of all, the differentiation is very helpful to the
public, in my opinion, by enhancing the differential, enhancing the
discourse on the differences in natures about conditions that cause
people to suffer.
Yes, I think that I often tell people with stage fright who
come into me and say, "Dr. McHugh, I have stage fright, and guess
what. I saw at the Super Bowl that Paxil is very good for this and
you're to give it to me."
And I tell them, "No, I'm not going to give you
that. I don't think we have to go that route. Why don't you
find another way to practice and then come back and tell me whether by
helping you practice will help you do better? Okay?"
So I will ask them to go back to their teachers. I mean, I
get this question of stage fright from high school students, you know,
who are working, and I'm telling them, "No, I'm not going
to give you a medicine now."
It may well be that when I see a person who has more
difficulty, for example, a violinist who has problems with trembling in
their hands, I might and I often do recommend, as a lot of people do,
Propanolol to help them from those trembles, help them with the
physical condition, but I will debate with all of them what they're
And by showing them the nature of what they're asking,
I think I enhance their understanding, my understanding, and the
public's understanding of my role. Okay? Which is not to be the
only arbiter of how life should be led.
CHAIRMAN KASS: Gil, do you want to follow or not?
PROF. MEILAENDER: Well, no one else is champing at the
CHAIRMAN KASS: No. Well, I mean, if —
PROF. MEILAENDER: I'll wait. I'll wait.
CHAIRMAN KASS: Okay. I have Frank and Robby George and
PROF. FUKUYAMA: Well, I enjoyed the exchange
of letters between you and Leon. I think we ought to do all of
our reports henceforth in epistolary form. I have a question about
the underlying biology, which maybe you could help me with it, Michael
Gazzaniga or other scientists.
Now, in somatic medicine, as I understand it, there's a
fairly clear, you know, model for what a disease should look like.
There's a clear etiology. There's a causative agent. So we
have this thing calls SARS. We believe that there is actually
something that you've going to find, a virus or whatever that will,
you know, cause it.
Now, in the world of psychiatry, I assume that there are
diseases in that somatic disease sense, but actually the vast majority
of the phenomenon that you deal with is this very large category of
things called disorders, all of which have biological correlates. I
mean even the most fleeting thought or emotion is going to have some
biological correlate, but that there are degrees of biological
causation, and there are certain disorders where the biological
determinants, you know, are relatively more important.
I guess what I'm getting at is that it seems to me
within this category of disorders what makes it so squishy is that a
very large number of them are basically, you know, normally distributed
behaviors, and that what you're classifying as a disorder is simply
something that's out in the tail of the distribution.
And so the question is: if your project is to try to move
your discipline towards a more, you know, biologically grounded
categorization of these different things, you know, your four
categories, what are the prospects of doing this in terms of the
For example, is it clear in all cases which of these are
simply points on a distribution as opposed to, you know, things that
will have a different kind of biological, you know, correlate?
And what are the prospects of, you know, moving the field
towards a system of classification that is grounded, you know, more
firmly in the underlying biology?
DR. McHUGH: Well, first of all, my aim was not simply to
move the field into a more biologically based classification, although
I support biologically based opinions about certain disorders.
My effort was to say which ones in which I thought a broken
part played the major role, that is, the classical disease concept in
which an etiology, a pathology lied underneath an expressed clinical
I also wanted to say, as everyone would, that you can't
have anything in mental life without a brain. We're not angels.
We all do that.
On the other hand, I also want to acknowledge that there
are things about the human brain which are at least to all of us
mysterious as to how the brain itself as mechanism causes the problems
that the patients bring.
For example, the issue of jealousy. You can find jealousy
as a symptom of a disease, that is, a disease like schizophrenia or
manic depressive disorder or Huntington's disease or
Alzheimer's disease. All of those conditions have been described
in some of its classical forms as presenting with a jealousy.
On the other hand, much jealousy comes out of dispositional
characteristics of an individual in relationship to a life circumstance
that they find themselves in, and that their assumptions coming out of
their dispositions and the interactions with that environment produce a
I want to be sure that people who want to talk about
psychiatry would want to differentiate those and appreciate the place
of other forms of therapy than a strictly biological form of therapy
for that. Okay?
And, please, press on.
PROF. FUKUYAMA: I mean, if I can just follow-up.
DR. McHUGH: Yeah.
PROF. FUKUYAMA: I mean, I'm not asking to make these
distinctions so that we can then discard everything that doesn't
have a very strict biological, you know, cause. That's not my
DR. McHUGH: No, that's right. No, that's right.
PROF. FUKUYAMA: I accept fully that you also want to treat
that vast realm of things where the cause is squishier.
But it does seem to me that — and in a way, this gets to
Gil's point about why these differences are important, you know.
If something is simply caused by a virus, you don't expect anybody
to do anything about that other than, you know, get treatment for it,
DR. McHUGH: Right.
PROF. FUKUYAMA: On the other hand, there's a whole
range of behavioral and mental phenomena where, you know, there may be
a biological component to that behavior, but the other component is
what we traditionally think of as kind of moral behavior that is the
result of self-discipline, education, you know, thinking things through
and so forth.
And I think that the thing that troubles me and probably a
lot of other people about the progressive medicalization or this
expansion of the domain of the therapeutic is that it tries to move
things that are within this traditional moral realm into a realm of,
you know, biological causation where, you know, you're basically
telling the patient, well, you can't do anything about it. So you
know, you just have to take your medicine and the like.
And so even if you can get money for being treated for
that, you know, what used to be treated by the priests and counselors
and so forth, it's still a helpful distinction to be able to say,
"Well, look. This thing is, you know, 90 percent biological. You
can't do anything about it," whereas another category of
disorders actually does have this very large component where individual
responsibility and, you know, so forth plays a large role.
And so I guess the question is: does the state of the
science give you any help in trying to make that distinction?
DR. McHUGH: Well, I think it does, and I think the
advantage of having separate reference classes or separate perspectives
of disorder is to see that with each separate class there is a separate
understanding of what constitutes disorder within this class, and I
think the science does help us a tremendous amount in this.
Well, let me just talk about, for example, what the
science, essentially epidemiological science, did to help us understand
psychotherapy, and in this case we're talking about the
psychotherapy of people that come to us with things like ordinary
grief, demoralization, jealousy.
The epidemiology showed us that in contrast to what was
expected at the time of the Freudian dominance, that all of these
patients would have similar sources of their problems, namely in their
libidinal conflicts. It turned out that these people had very
different sources of their problems.
What was common to the psychotherapy patients is that they
all felt over mastered by something in life and were discouraged about
being over mastered by that rather than that they had a common sources
for their problems.
And so that immediately opened up psychotherapy and psychotherapists
tomore individual understanding of lives rather than trying to dig
deeper for some problem in infantile or early childhood life in
relation to their libidinal problems.
But as well it said, well, since the problem here is
feeling over mastered, a psychiatrist can help you maybe, but
they're going to help you in the same way as other counselors,
friends, people of that sort, priests, and the like have previously
helped people and open the door to that.
Now, when you bring in, as you did, as Gil did and you did,
this idea that we want to be paid for it, I just want to be paid not
necessarily for my treatment. I just want to be paid, I think, for my
time like other people, and I want to be sure that I am offering some
kind of help.
Sometimes the help is not therapeutic in the sense of
actually correcting a disorder, but it is reassuring to people and
things of that sort, the same things that other professional people
like lawyers do.
And at some level the work is of that sort. But just to come
back to the main point, to express my reference classes could from
one point of view be seen as extending medicine out beyond its boundaries.
On another way of looking at it, it could be, and the way I look
at it, it would be by defining these reference classes. People
could look at what places — the medical doctor would be primary
in the care, and in such classes lots of other people would be able
to be on equal standing in that care, and that, I think, would advance
us in all kinds of ways, including, by the way, being able to give
parity to the mentally ill for the conditions which are most like
medical conditions and not clamor for parity for individuals for
whom some aspects of their condition, their over mastery, could
be helped by others.
CHAIRMAN KASS: To this? Mary Ann Glendon.
PROF. GLENDON: I just need a little help understanding the
distinction between your Class I and Class II, and maybe I'm just
wrong in what I've read in the popular literature, but is there not
some scientific support for the idea that, say, alcoholism — that
there are some people who are more prone to that through brain
characteristics than others?
So that your boundary between one and two doesn't seem
to me to be quite clear.
DR. McHUGH: Well, the boundary only relates to what leads
to the course, not that there — by the way, again, there are going to
be brain things behind everything, including, by the way, behind
Your question is a frequently asked question, namely,
don't you see that certain people, perhaps because of their
make-up, have more temptations to sustain a behavior like alcoholism
For example, oriental people often are sickened by alcohol
because of an Antabuse-like reaction that they have. This is very
protective for them from taking up this conditions and carrying it
It's also probably true that some people get more
aroused by a glass of alcohol than other people do and, therefore, find
it more rewarding.
Both of those things are true, but in contrast to a disease
like Huntington's disease, you will advance in that condition
steadily forward regardless of whether you are able to move about or
not. You cannot advance in alcoholism unless you choose to drink, and
that choice is, after all, a matter of deciding one way or the other.
That there is a vulnerability behind that choice does not change the
fact that it's still a choice, and ultimately the Alcoholics
Anonymous that wants to clamor for the concept of disease here as
though it was a broken part ultimately does say that, you know,
you have to choose to live a different life and acknowledge.
You know, it doesn't matter whether you acknowledge
that Huntington's disease has a power over you or not. It will
carry itself through, but it does make a difference if you acknowledge
that you are powerless against alcohol and, therefore, avoid it.
And since there are those elements to it, the therapies
change. The responsibilities change, and ultimately the outcome.
Just as a final thing, I might have mentioned this to you
before, Mary Ann. About once a year I get someone coming to my office
and saying to me, "Dr. McHugh, I want you to come to court with me
because I've been arrested for driving while intoxicated, and I
want you to tell the judge that, of course, I'm an alcoholic and,
therefore, should get off."
And I always tell them, "No. I want you to go and be
punished for driving while intoxicated because my friends and my
children and everybody else are driving, and I don't want that to
happen. After you are punished, I might be able to help you with this
conditions, but I might not be able to help you either, depending upon
what you're after. It seems to me today that what you're after
is some license and not the appropriate contrition."
CHAIRMAN KASS: I have Robby George.
PROF. GEORGE: Paul, I have two questions. I think
they're only remotely related, and the first one you may have gone
far toward answering, but it would just help me to get a little firmer
grip on it.
I want to sort of follow up. What I took Gil's
question to be, which is really about when are you as a psychiatrist in
and when are you out.
Now, from what you've said in response to Gil and Frank
and now Mary Ann, I take it that the situation is a little like the
separation of powers, if I can use an analogy from my own field.
There's an old line that says we don't have so much a
separation of powers in our government as having separate institutions
sharing powers, and I take it from what you're saying what we have
when it comes to treatment of certain sorts of things that are
problems, but they're not like Huntington's disease, we have a
kind of sharing of authority, sharing of roles where the psychiatrist,
the priest, the dad, all might be dealing with the same problem, and
you wouldn't want to carve things up such that you would have
strict boundaries where you say, "Ah, this counts as the
psychiatric problem. This counts as the spiritual problem. This
counts as the moral problem."
Am I right so far?
Okay. But that leaves us where I think we were left after
Gil's question. There must be some criteria by which you as a
psychiatrist and others in the field decide, look, this just isn't
appropriate for me to deal with. If I did that I would be practicing
priestcraft without a license.
Let me just try and example or two. I mean, if a corporate
CEO comes to see you and says, "Look. I've got a great
career. I'm making a ton of money. My business is going well.
Everything is great, but you know, I find myself getting involved with
the secretaries romantically, and this could wreck everything. Doc, I
want you to help me."
Would that be the kind of case in which if you didn't
detect some pathology, what you detected is a guy who's prone to
this kind of —
DR. McHUGH: Fall in sin, yeah, right.
PROF. GEORGE: Would you say, "Look. You've got
the wrong place. I mean this is not something that I as a psychiatrist
am qualified to deal with"?
DR. McHUGH: We certainly recognize incontinent behavior
and call it just that and say, "You don't have a disease,
pal. You have become incontinent in your sexual behavior, and I can
tell you what I think about it, and I can tell you some of the things
that might help you stop it, but you need lots of other forms of help
in the process."
Because they often come with this and say, you know,
"I just can't help it, Doc."
And I say, "Can't means won't, and you
won't help it," and I begin to talk about drawing in these
other people to help them.
PROF. GEORGE: Well, now he said, "Well, Doc, look.
Don't get me wrong. I'm an enlightened guy. I don't have
any moral problems about what I'm doing. I just don't want my
career — I know that the world is such that my career and my company
and my business is at risk here. I just want a fix so I won't do
this. You know, I'm not religious. There's no clergyman I can
go to. If I told my pals that this was a particular problem I had,
they wouldn't consider that to be a problem. I need you to fix
Now, do you now because you're the only game in town,
you're the only person he can go to, do you now say, "Well,
look. This isn't psychiatry. I'm now functioning as some sort
of counselor to you, but I'm going to stick with you and see if we
can save your professional life"?
DR. McHUGH: Always the beginning of building up a
hypothetical case, you gradually get to the point where you might be
imagining pigs with wings, you know, and what are you going to do with
this flying pig.
But look. In my opinion, the kind of case you're drawing,
Robby, is not at all unusual for many psychiatrists to say, and
they, at least as far as I know have not given up on the idea that
this kind of behavior is destructive to the milieu in which the
person is living, as well sa the character of the person who is
Some of them will use the word "sin" and
"adultery." Others will say this is corruption and the like,
and begin from that position, not from the position that your patient
that you've imagined said, that is, "Listen, Doc. You and I
are guys together, you know. Aren't we having fun? And I just am
afraid that his having so much fun is going to get me into
If someone said that — no one has ever said such a thing
to me — but if they said that, I would say, "No, we aren't
guys together. We are people in this society, and there are certain
things not only which are against the law, but which are against our
ethical posture towards this."
Now, this is to take in some situations a judgmental
stance. Okay? And, by the way, in my opinion, because psychiatry is
the kind of discipline it is and it moves up through these reference
classes or up a hierarchy, ultimately we do make judgments and
acknowledge that those judgments are derived from the world in which we
DR. KRAUTHAMMER: If I could just say, Robby, we had a
recent case of that, and the attempted intervention was not psychiatry,
CHAIRMAN KASS: I have Michael Sandel and then Jim Wilson.
PROF. SANDEL: The question that occurs to me
in this discussion, and, Paul, I'm constrained to more general
territory and the general question of medicalization, is why we
worry about it or if we should worry about it.
Why should we have an impulse to try to limit the scope of
the medical? But what is the source of that impulse and is it
And in listening to the discussion, it seems to me there are two different
kinds of reasons to worry about the expansion of the medical. One
of them, the one we tend to focus on for the most part is a worry
that the biological will colonize the ethical and crowd it out;
that the therapeutic will displace the moral. That's the worry
that comes to the fore when we worry about diminishing the responsibility
people have for their own conditions if they come to see those conditions
as subject to remedy by a pill or by surgery or some kind of medical
And so we wrestle with cases like narcissism or child abuse
or the drunkenness of the driver or the squirminess of the child in the
class, and realizing those kinds of things will crowd out or diminish
moral responsibility for one's conduct. So that seems to be one
set of reasons to worry about medicalization.
But it seems to me there's a different set of
considerations that have nothing to do with whit worry about the
biological displacing the ethical, but instead have to do with the
range of cases, Leon, that you mentioned at the beginning having to do
with medicalizing shortness or the kind of medicalization that
accompanies more and more cosmetic surgery.
And this worry has nothing to do with disputing the biological
character of these conditions. No one disputes that shortness is
a biological condition. No one says, "Well, if we medicalize
shortness, then people will no longer take moral responsibility
for being so short," as in the other cases.
Or if we medicalize the question of someone who has a
prominent nose and wants to have cosmetic surgery, we don't say,
"No, that's troubling because we want people to pull
themselves up by their bootstraps and deal with this themselves, not to
pretend that it's just a medical problem that needs to be taken
So it's not that issue at all. Here it's not the
worry about the displacement of moral responsibility, and yet there is
still a worry about medicalization in this other domain, and it comes
closer to the enhancement cases we were discussing.
And then I think it has to do with another feature of the
medical, the reason we want to cabin or confine the medical, and that
has to do not with its concern with the biological, but instead with
its orientation to fixing rather than accepting.
And so because it's a feature of the medical that it attends
to disease. The telos of medicine, traditionally understood at
least, is to attend to disease, which is to say to attend to things
in need of fixing.
And so we worry here in this second domain that we will
redescribe conditions like shortness or like having a prominent nose as
diseases when they're not properly regarded as diseases, and one
way of expressing this worry is to say that medicalizing these kinds of
things will stigmatize people who are short, let's say such that
beforehand we might not have noticed it as much, but now that it
becomes something that's routinely subject to a medical cure we
notice and worry more when people are short or when they have prominent
noses or when they have teeth that aren't perfectly white and
aligned or whatever the case may be.
So it's the fixing part of medicine here that wants us
to rein in the scope of application of the medical lest we consider
more and more conditions as things to be fixed rather than as things to
be accepted or, for that matter even appreciated.
I don't know if that's a helpful distinction. The
one final thought about the second category is we could deal with that
problem, the problem of medicalizing conditions like shortness and so
on in one of two ways. We could say, "Well, all right. We will
expand, as implicitly we must, what counts as a disease to include
that, but that seems bothersome."
Anther way of dealing with it would be to say, "Well, maybe
medicine should be detached from that. Maybe we need to enlarge
the telos of the medical so that we no longer regard it as concerned
with curing disease."
What do we call the people who do cosmetic surgery for a
living? Well, they're engaged, we would say, or are they, in a
medical practice. Well, here let's talk about just purely
elective, or would we say we should detach the medical from the notion
of curing disease so that at least we don't taint all sorts of
conditions with disease and just say, "Well, maybe medicine
isn't solely about curing diseases. Maybe it can be for fixing
things that people simply want to fix, even if there is no
But that seems also to carry a certain kind of cost or at
least there seemed to be reasons. I think a lot of people would
resist. So enlarging the medical by detaching it from curing or
attending to disease, but it seems to me in any case that these are two
very different reasons to worry about medicalization.
CHAIRMAN KASS: Does someone want to join in on this before
we move on?
DR. KRAUTHAMMER: Yes, I would. I would like to add a
third reason, I think, and it might actually be the reason why society
decides that it's going to have to act on it, and that is the
economic cost, that apart from the moral cost of expanding the medical,
the economic cost would be huge.
There is a sense that we have, and I think it's
correct, that if you suffer from a medical condition, society has a
kind of obligation to help you in coping, and that if you're poor,
you shouldn't have to suffer in a way that a rich person would not,
and that's why we have this idea of Medicare-Medicaid and expanding
It's inexorable. In Europe, of course, it's
universal. Here it's expanding.
Now, as you expand what is legitimately considered medical
you will expand the realm in which society is seen as required to
contribute to your assistance, and as that area expands, it's going
to create a huge social cost, and I think that in the end may be the
reason why there are attempts to contract it.
We see the argument acutely in whether or not a psychiatric
illness, mental conditions should get the same kind of coverage as
so-called physical illnesses. That's the most obvious and acute
example of this, but I think it's going to expand as the range of
the medical expands as well.
PROF. SANDEL: Could I give a quick reply to that? I
don't think that the economic reason is a third reason independent
of these two. To the contrary, I think it's parasitic on one or
the other of these two for the following reason.
If it were just a matter — if worries about medicalization
were just a matter of society having to bear too great a financial
cost, it can't just be that because the reason — suppose the
reason that things became very expensive is simply because we got very
good at transplants, and so people in need of hearts and kidneys on a
much larger scale were able maybe because the immune problem were
overcome to have them.
We wouldn't regard that — it would be an economic
challenge, but it wouldn't be a challenge of the kind that we worry
about when we object to medicalization because it's not
controversial that a heart or a kidney transplant is a medical
DR. KRAUTHAMMER: What about orthodontics?
PROF. SANDEL: What's that?
DR. KRAUTHAMMER: What about orthodontics?
PROF. SANDEL: Well, the reason that becomes controversial
is it falls into one of the two reasons we have for questioning the
scope of the application of the medical.
So the economic issue only arises against the background
assumption that we as a society agree that genuinely properly medical
needs are covered, and so we worry about medicalization under these two
other headings — maybe there are others — because in both of those
cases we have reason for questioning whether the scope of the medical
isn't being expanded in ways that are objectionable, whether
because it crowds out the moral or whether because it tries to fix what
should be accepted.
CHAIRMAN KASS: Gil, did you want a small thing on this,
PROF. MEILAENDER: Yeah. I think that finally there's
not such a large distinction between your two categories, Michael. I
mean there is an obvious on the face of it distinction between your
accepting moral responsibility and what medicine ought to do.
But as you yourself recognize, if it turns out that there
are some things that people want and that we can do, but that don't
seem to constitute fixing in the sense that medicine traditionally
fixed things, then we have a couple alternatives.
We could expand the realm of medicine and say doctors
didn't used to do this, but now doctors do it, or we could say,
"Well, but people still want it done. So proctors should do it.
Yo u know, they've got a lot of the same skills that doctors do and
they should do it."
And if you want to resist that, whether you want to resist
the expansion of medicine or you want to resist the notion that kind of
somebody else should do this, what you're going to have to say is
this is something that should be accepted, that should not just be
And we're beginning now to do talk that though granted
it grew out of a different issue is rather like the moral
responsibility talk. So I don't think that there is finally quite
as wide a gap between them, though I agree that the second kind of case
you raise grows out of the question of what really constitutes health
and what really constitutes disease or medicine, but it finally drives
us back to assert what we do or do not take responsibility for.
CHAIRMAN KASS: Briefly Michael and then .-
PROF. SANDEL: They're both normative question I agree,
but they're different normative questions. One has to do with what
should people be held morally responsible for, and the other has to do
with what do we consider should be accepted rather than fixed.
I agree they're both normative.
PROF. MEILAENDER: Well, people perhaps should be held
morally responsible for learning to accept certain things about life.
CHAIRMAN KASS: Jim Wilson will now make trouble.
PROF. WILSON: I think the problem that Paul has addressed
under the concept of medicalization is much broader than the problem as
he sees it in psychiatry, and my views on this are, in part, an effort
to answer Gil's question what difference it makes.
Medicalization to me as a non-real scientist, but a fake
political scientist is a synonym for causation. Now, all behavior is
causes, and there is an effort in not only our society, but most
societies around the world to extend the concept of cause so that
everything is caused in a way that crowds out the moral, as Michael
Let me give you the case from criminal justice, if Mary Ann
Glendon will overlook the many mistakes I will make in this brief
Somebody shoots another person by firing a gun. The person
is brought to trial, and there are a variety of arguments a person can
use. One is that he is a victim of epilepsy. Admiring a gun that is
part of his collection, he had a seizure and his finger squeezed the
trigger and fired a bullet at somebody else.
The next level is he's insane or, to put it bluntly, he
is crazy. He doesn't know the difference between right and wrong
and thinks the voices of Satan are directing him to do it.
The next level is duress. Someone pressed a gun to his
temple and said, "If you don't shoot this bullet through this
window and hit this person, I will blow your brains out."
The next level up is diminished capacity, which is kind of
an adolescent version of insanity. They're kids. They're not
quite sure what they're doing. They're 14 years old.
On the next level up is prior abuse or neglect of the sort
pled by those two wealthy, young Beverly Hills men who pumped 12 rounds
of 00 buckshot into their parents and watched them die because, as
their lawyer later claimed, they had been the victim of abuse when they
were ten years younger.
And then the next level up are life experiences generally,
in which you could put alcoholism.
And then finally at the highest level — I'm skipping
several — is pure choice.
Now, defense lawyers will go into court and try to push
the argument back toward causation, and prosecutors will go into the
court and try to push the argument back towards pure choice.
Now, in this case, there is a solution to the problem.
That is to say a judge and a jury must make a decision that is either a
yes or no decision. The person is guilty or innocent or possibly not
guilty by reason of insanity.
And in making their judgments, they asked the question: to
what extent was the person able to control his behavior? And the
control judged by a contemporary social scientist may not be very
large, but though they would probably excuse epilepsy and insanity and
perhaps duress from diminished capacity all the way up to pure choice,
they tend to collapse it into the category of pure choice.
Now, what evidence do they have to back it up? I think the
evidence they have, which the judges sometime state and sometimes not,
is that we can think of people who had the same prior abuse, prior
neglect, diminished capacity, alcoholism, et cetera, who didn't
shoot anybody, and since people with these conditions can avoid
shooting other people, the fact that you chose to shoot somebody else
means that whatever your circumstances may be, you made a choice that
you didn't have to make.
Now, this is not the problem that society faces because
society does not have a judge or a jury, and society increasingly, in
my view, over the last half century has begun to say that social
controls, society's effort to judge somebody as innocent or guilty,
have been profoundly weakened because to judge somebody as guilty,
society must use such things as shame or stigma, and increasingly we
are told that shame and stigma are a bad idea.
And, indeed, the people who go to Paul and say,
"I've got stage fright," or, "I am sexually
incontinent," or the other will hear from him a response that
says, "This isn't a medical condition. You should be ashamed
And what they're going to do is drop Paul as their
psychiatrist and go to somebody else, and they will find other people
who will say, "Yes, we certainly mustn't use the word
'shame' and 'stigma.'"
Society does not want to be judgmental. Being
nonjudgmental is a good thing. So I think the problem that the
exchange between Leon and Paul raises should not be limited to the
definition of what is medical in the eyes of a medical professional,
but rather should be viewed as the general social problem of how we
define personal responsibility and the fact that in my opinion, which
could be wrong, we have changed profoundly the extent to which we judge
people as acting improperly, and we are reluctant to impose social
rewards and punishments to induce them to act properly.
PROF. GEORGE: Leon, could I ask a question of Jim?
CHAIRMAN KASS: Please.
PROF. GEORGE: Jim, I followed that, I think, completely,
and it certainly sounded right to me, but I just wondered about a
statement you made very early on in the presentation and its
compatibility with what followed, and that was the statement that all
human behavior is caused, unless you mean by that simply that there are
empirical conditions of all human behavior, including choices that
constrain the options for effective choice.
PROF. WILSON: Yes.
PROF. GEORGE: Is that all that that meant?
PROF. WILSON: Yes, I probably shouldn't have used the
phrase, but behavior is caused in the sense that some combination of
biological imperatives, cultural traditions, personal choice, and the
nature of immediate circumstances leads persons to exercise Option A
rather than Option B.
I mean nothing more profound than that, and you can strike
the word "cause" if that seems to become a motive.
PROF. GEORGE: No, in philosophy there's a big
literature about the distinction between reasons and causes.
PROF. WILSON: I understand.
PROF. GEORGE: And I was just wondering whether you were
rejecting the idea that there could be reasons that are something
independent of the causes.
PROF. WILSON: No, no.
PROF. GEORGE: And I take it you —
PROF. WILSON: I am not rejecting the notion that all
behavior is caused and part of the causes are the reasons people
developed to make a point.
PROF. GEORGE: Yeah.
DR. McHUGH: And if I could just enter, too, into this very
interesting comment you've made, Jim, and it's this issue of
stigma. And it is often said that psychiatrists and doctors and all of
us should give up on stigma, and that is certainly true for the
diseases in psychiatry. We want to give up on stigma. In epilepsy we
want to give up the stigma on bipolar disorder.
But everyone knows that no one is giving up the stigma on
certain behaviors. Smoking behavior is the most stigmatized behavior
right now in our country. It's stigmatized and not tolerated.
In point of fact, your other statement that if I did
stigmatize this to a person — again, we have to remember that we made
a pig with wings here with Robby — that he would run away.
In point of fact, that's not my experience. People who
come in with the concern that, gee, my behavior is liable to get me
into trouble and hear from me that, yes, it will get you into trouble
and it should if you continue it would then ask me and do ask me not
only how they can avoid it, but how they might look at it in a
different way, stigmatizing it appropriately and thinking about it in
its relationship to its effect on others.
And, by the way, most of them stay with me and say,
"You know, I never thought of that before," when they give as
their cause that they're doing this because their feelings matter
and their feelings are driving them, and their feelings are the cause,
and they hear from me and from other psychiatrists that, you know, when
you grow up your feelings don't matter to most people. It's
just your behavior that does.
And they always say, "That's a very remarkable
statement to hear," and stay with me as their behavior gets
PROF. WILSON: People keep coming back to you, Paul,
because you have such an engaging personality.
PROF. WILSON: You can stigmatize them without using the
DR. McHUGH: Well, that's —
PROF. WILSON: But I would be willing to bet you that the
search for non-stigmatic relief is more widespread than your own office
experience would be.
CHAIRMAN KASS: Alfonso and then Bill May and then Janet
and then Bill.
DR. GÓMEZ-LOBO: This is going to be a very brief and
perhaps minor remark. I'm just trying to think for my own benefit
about the more general context, and I tend to think that this is a
really particular case of something much deeper and much more pervasive
in Western culture and Western history.
What I have in mind is something like this. I would bet
that 30 years ago most people made financial decisions on their own,
you know, whether they were going to buy stocks or bonds, et cetera.
Nowadays, I think most people would deeply hesitate to do
this before consulting an advisor, financial advisor, or I found this
out some time ago. People who are going to send their kids to college
now can go to a college choice counselor.
Now, what does this mean? It means that socially we have
tended to parcel reality and to assume that there are people that
within a domain have something close to an algorithm to make the
The reason why we go to a physician is because we trust
that the physician is going to have symptoms, et cetera, in front of
her and then come to the conclusion, oh, you have pneumonia, and then
the solution is going to come.
So I'm not surprised at all about the medicalization,
this tendency to reduce things to treatment that can be controlled
because this tendency in our culture is a tendency to find areas of
control, and naturally enough to displace the prudential approach to
those fields, which I think is what Paul is alluding to, and also the
moral deliberation, the moral reasoning about those fields.
If a field is dominated by a specialist, of course, we can
withdraw and say, "Well, that's where the responsibility
So what I'm just suggesting is that we really immerse
in a much broader thrust of our culture to control certain areas of
behavior by handing them over to people who would know how to decide.
CHAIRMAN KASS: Bill May.
DR. MAY: Well, it's very interesting hearing you,
Alfonso, talk like Ivan Ilyich, the broader professionalization of life
in all aspects.
DR. GÓMEZ-LOBO: My source is actually Aristotle.
DR. MAY: Yeah. Well, the pathology, however, is a very
large and growing, modern one. You know, professionals hang out a
shingle, and in doing that it specifies a little further and you invite
certain strangers in to deal with, but at the same time, of course, off
the streets comes an awful lot of things that are unbidden and not
And now you end up. You've got a moral alternative
there as a professional. You can preserve the purity of your
specialization and say, "But I don't deal with that," and
therefore refrain from medicalizing everything or lawyers legalizing
everything and so forth across the board in the professionals.
But on the other hand, at the same time, you happen to be
neighbor to the problem because they've come in and you're
nearest to that problem, a little bit like 19th Century doctors who
became aware of the problem of sanitation even though they were not
Of course, in that case you saw the social remedy, and that
led to important improvements in health care that were not available
directly through the efforts of the professional, but you are neighbor
to the problem, and it may be a rather privileged moment for that
She can't talk to her husband. The relation is frozen
in all sorts of ways. They've moved at least once every five
years. Other forms of help and larger family and so forth are quite
distant, and so forth. And he or she has come to you with a problem.
Now, have you medicalized everything by not simply turning
attentive ear? It's a moment that may pass, and you have further
responsibilities. It seems to me that you may not be fully paid for if
you stick simply to treating disorders, but in your ascending scale
interrupting behaviors, guiding dispositions, and reframing life
stories, you're moving farther away from the medical, but humanly
you have certain responsibilities.
And how can we sort this out in such a way that one does
not escape ones responsibilities as human being in order to preserve
the purity of professional identity?
High school teachers or junior high teachers maybe even
more than senior high are in a position of privileged neighbor when
things aren't working out well with mother and father and so forth,
and that's not what they teach, but they have a privileged position
close to that problem.
Now, we have — and this is where Leon's economic
issue, concern here. It's easier to get compensation for this kind
of time expended in life if one can define it as medical, and so we end
up medicalizing an awful lot through the economic pressure here, but we
don't want excessively to shrink responsibility simply in order to
avoid medicalizing problems.
DR. McHUGH: And I think, Bill, if you look at the history
of some of the great advances in psychiatry over the last several
decades, it has been just exactly this being neighbor to a certain
problem and then helping the society, the culture, the school and the
like to enhance what it's doing for the betterment not just of this
particular patient, but for people in general.
I mean, much of the advances, for example, in child
psychiatry have been in relationship to speaking to the schools,
offering a wide spectrum of opportunities for children to succeed in.
Once it was recognized that it helped children to become adults if they
had had some kind of success earlier in life that came out of first
looking at the individual patients, but ultimately it spoke to the
public at large as to how a school should have a variety of things,
from athletics out to scholarly work, to give more people a chance to
And I think that the place, it is a very privileged place
to be close or neighbor to it. I think that's a wonderful metaphor
you draw there because it does speak to many of our situations to which
we become responsive by calling attention to the patient and to the
society that this is the place where they could work together.
DR. KRAUTHAMMER: Could I make just one interjection on
CHAIRMAN KASS: Yes.
DR. KRAUTHAMMER: Bill, you brought up an interesting
example of the person who comes into you and you feel a responsibility
to respond humanly, even though it may not be a medical problem.
The complication here is that she came into you because you
hung a shingle and you are a doctor. She didn't go to the
bartender or the man on the street.
And I felt this acutely. I quit psychiatry exactly 25
years ago this month, an anniversary that I celebrate every year. One
of the reasons is that I always felt that uneasiness, a sense to
respond humanly, but I was doing it because of her illusion that as a
psychiatrist or as a doctor I had a special insight or wisdom or
secret, as paul phrased it.
And I found that by actually using that misconception on
her part, I could actually do good, essentially produce a placebo
effect, but it was under a false premise. I knew that there wasn't
a secret, and it was in a sense a Wizard of Oz operation.
So you've got an obligation as a human to respond, but
given the context, you're doing it under the rubric of having
special medical powers, and that creates a real complication and a
contradiction in some sense.
DR. MAY: Yes, although the way Paul has described his work
as a psychiatrist, he takes advantage of that in order to clarify
instead of remain behind the vail.
DR. KRAUTHAMMER: Well, he gives it up in the first half
DR. MAY: Yes.
DR. KRAUTHAMMER: I found out if you didn't you could
actually get a real placebo effect, and that would actually help the
patient, particularly in changing behaviors like smoking or excessive
I mean, hypnosis essentially, which is one of the things I
practice, is essentially a way of using that aura as a way to achieve
the results, and it actually does work remarkably.
CHAIRMAN KASS: Janet Rowley.
DR. ROWLEY: Well, first I have to express my
surprise when I was reading this interchange of letters to note
the comments about a lecture that I gave at Hopkins, and I certainly
want to thank Paul for his very generous comments.
I'd like to take a different track, and Paul McHHugh also
mentioned the analogy of psychiatry being in the 19th Century as
compared to many aspects of medicine. One could certainly see now
that we've moved to yet another century that it's in the
20th Century and not in the 21st.
And I think that psychiatry, as well as many areas of
medicine are both a moving target and clearly even better defined
diseases are very heterogeneous.
I guess the concern I have about this discussion is to what
extent are we mixing medicalization with increasing scientific
understanding of the biological basis for behavior, and certainly in
many aspects of understanding brain function and interneuronal
connections and the importance of that, we're only on the
threshold, and this increasing understanding of a very complex system
is certainly going to change both our understanding of behavior, but
also a possibility of modifying behavior.
Now, certainly one modification of behavior can just be
learning to take advantage of other aspects of the nervous system so
you control unwanted behavior, but again, in a heterogeneous situation
where there are tails of behavior, it may well be that some additional
form of treatment might be helpful.
But I think that it is very important that we keep
understanding that we're pretty ignorant about behavior. We just
had a lecture on the immune system and the complexity of the
interaction of cells, B cells, T cells, antigen presenting cells, and
antigen. The nervous system has been likened to the immune system in
that there are these multiple cellular interactions, which we are very,
very ignorant of.
And just as cells communicate by releasing substances which
tell other cells to do other things, this is certainly true in the
nervous system as well, and we're early on in, say, understanding
homosexuality. Some of this is almost certainly going to be due to the
lack of receptors on critical cells or the lack of ligands so that the
kind of behavior that we accept as normal does not occur in these
individuals because of these biological differences.
And we will some time in the next several decades be able
to sort this out. So as I say, I have concerns about worrying about
some of these things.
Amongst the things that are listed as being medicalized are
childbirth. I think that it's pretty clear as you look at the
statistics for maternal deaths and fetal deaths in the black population
that their lack of health care emphasizes that childbirth is not just
something that you can go off in the corn field and everything goes
And I think we also have to recognize that very soon
obesity is going to become a very serious medical problem which will
have many complex aspects of it, genetics as well as the total change
in life style, our lack of exercise, our exposure to foods that are not
good for us. All of these things are going to be important.
But we have to then look at a very complicated response to
this major health problem, and one response may well be some aspect of
involving medicine or drugs at the same time as we also try to help
people understand how they can change other things so that we don't
have this problem, which leads to very serious, fatal medical
So this is a long winded expression of concern that we look
at this in a broader context and are sort of cautious as to coming back
to Michael Sandel, is this a problem or why is it a problem or what
problem might we as a council be able to provide advice and guidance
CHAIRMAN KASS: Okay. We are late in the hour. I have
just — Frank, did you want a very quick thing? Bill is in queue.
PROF. FUKUYAMA: I mean, Janet, it seems to me
that that doesn't really — it fails to recognize how politicized
a lot of this is, and homosexuality is a perfect example of that.
As I understand it, homosexuality used to be classified as
a psychiatric disorder, came out of the DSM at about the same time
that ADHD went in. All right? We know about both of those
conditions. Actually fairly similar. They had biological correlates.
Over time there's been growing understanding of the biological
bases of both of those disorders, but you know, the only way that you
can actually understand the actual outcome, I think, is in terms of the
politics and the sociology of the way the society, you know, constructs
one as a disease and the other as not.
So I think that is is true that we are .- I mean it would
be nice if there were this correlation between our understanding of the
biological causes and the way we classify these things, but there's
a huge element of social construction, I think, in the way we
understand these psychiatric disorders.
CHAIRMAN KASS: Bill —
DR. ROWLEY: Well, all I'm saying is I think
it's very important that we first understand that it's heterogeneous,
and that we be very cautious in how we as a council, separate from
society and politics, how we think about the broader issues.
CHAIRMAN KASS: Bill.
DR. HURLBUT: It's interesting Janet because as I
ponder the emergence of scientific knowledge as you say, I feel what
you mentioned, the possibility of interventions at various levels and
the possibility that things that we attribute to some kind of
construction of personal identity as being, in fact, driven by
But what impresses me even more is that our notion of cause
is changing. We've talked here about how medicalization is really
a shift in the notion of causation, but what I would add to it is also
a shift in our sense of what is appropriate by way of cure, if you
will, for a given condition.
When I ponder what science is teaching me as I see the underlying
processes by which the person emerges, if anything cause is becoming
more complex and instead of labeling something biological versus
whatever you call it, moral or personal character, it's beginning
to seem more and more, as it should obviously, that the emergence
of the person within the phylogenetic process was, in fact, a biological
phenomenon with significance. In other words, if you look at all
of phylogeny, you see the steady assent from physicochemical determinism
up to an increasing sense of genuine freedom, distancing from determinism.
So that the person actually makes a difference, has a
meaning, and allows a specificity of response that you can't get
with a chemical, and I think Paul's early letter actually had a lot
of good things about this with psychiatric treatment, is that it's
often directed at symptoms. Symptoms are very broad, and the drugs
lack the specificity of actually remediating an individual person.
And Charles' comment about the placebo effect and so
forth is an interesting one because at least the placebo effect engages
the reality of the person.
The problem, it seems to me, is that a simple, materialistic cause deletes
the complexity of the cause and also the sense of solving something
with a chemical erodes the engagement of the full human person and
the manning of the human process. So that it actually operates
too low in the chain of causation. Therefore, it's not specific
enough. It doesn't operate at the real level of what is causing
things, which is both chemical and at the same time the convergence
of chemistry with ideas, attitudes, memories, beliefs, and in other
words, chemistry and the underlying chemistry and the overarching
cognition that's actually part of human existence, and the proper
approach to a real human problem, not a problem that has a genuine
underlying medical or physical cause that probably is properly treated
by medicine, but the problem is that medicalization is delivering
into the medical hand and the medical gaze and the sense of where
the cure should come from, those things which are actually humanizing
in their way of being dealt with properly.
In other words, what I'm saying is that in a sense those fullest
extensions of human nature, what you might call a mental spiritual
psyche are actually extensions of more fundamental biological agencies
so that what really makes a person a full person and a more effective
person is not just physical, but what you might call the realm of
philosophy and faith, a true integrated personal identity operating
within a cosmology, which is at once deeply humanizing. It both
upholds the person and the process of the person alike.
I mean, in the final end what's going to happen with
this medicalization is we're going to medicalize morality itself so
that we think that there isn't really any free agency. There is
And this is what is the most corrosive quality of
evolutionary psychology. It essentially deletes the higher order
meaning of human consciousness. It actually converts ultimately
everything to a simplistic medical explanation, deletes human fullness,
and in the process converts everything into what you were calling
earlier a libidinal problem just driven by unconscious drives and
desires over which we have no agency.
In the final end then all of criminal behavior, all of
behavior will be simply medical problems deleting the person and the
meaning of life itself.
CHAIRMAN KASS: Thank you.
We are at 12:30. We have guests coming at two
o'clock. The hour is late. I'll spare you a summary.
Please be prompt for our guests.
(Whereupon, at 12:29 p.m., the meeting was recessed
for lunch, to reconvene at 2:00 p.m., the same day.)
CHAIRMAN KASS: This afternoon we turn our attention to
biotechnology and public policy, the regulation of the uses of
biotechnology, the domain of activities touching the beginnings of
Although we will be at this topic for the next four
sessions, I would like at least to set the stage with some general
remarks so that council members will be reminded of what we're
about and that our guests might understand also perhaps more clearly
than they would have beforehand what's going on here.
The council at its very first meeting signaled an interest
in exploring how, if at all, the existing regulatory mechanisms in the
United States addressed the ethical, moral and social issues that arise
from advances in biomedical science and technology.
Some members of the council suggested that perhaps new
regulatory institutions might need to be devised. Others were
skeptical, especially in the absence of knowledge of how well the
current arrangements worked; in fact, first of all, what they were and
then how well they worked, and also which principles should guide any
such new activities.
In the council's 2002 report, "Human Cloning and
Human Dignity," a suggestion emerged for pursuing this interest
regarding regulation in the context of a specific domain larger than
cloning itself. Members observed that for the activities at the
intersection of assisted reproduction, pre-implantation, genetic
diagnosis, and human embryo research, and I quote the report:
"We lack comprehensive knowledge about what is being
done, with what success, at what risk, under what ethical guidelines,
respecting which moral boundaries, subject to what oversight and
regulation, and with what sanctions for misconduct or abuse. If we are
to have wise public policy regarding these scientifically and medically
promising but morally challenging activities, we need careful study and
sustained public moral discourse on this general subject and not only
on the narrowly defined pieces of the field, i.e., cloning."
And not long after the release of the report, the council
members agreed to undertake a thoroughgoing inquiry into the current
regulation of those biotechnologies that touch the beginnings of human
life simply to inform ourselves of what the current situation is on the
And the staff has been preparing materials on this, and
tomorrow council members will be discussing the discussion document
that comes out of, is in response to the council's charge.
In the process of doing this work, we thought it absolutely
imperative that various stakeholders and their representatives in this
field, which ethical principles and which human goods were important to
them and deserved to be either promoted or protected in this activity
sine, after all, one cannot devise regulatory activities, and one
certainly can't evaluate them if one doesn't know what it is
one is seeking either to advance or to safeguard.
And we thought that our work would be incomplete and
improper if we didn't actually hear from the various people who had
an interest in this, whether scientists and physicians or patients and
their advocates, or public policy people or bioethicists and the like.
And we requested submissions, and we received quite a
number, and from that group of submissions, we have invited a group of
people to join us here today, and on behalf of the entire council I
want to thank all of you here for your written submissions and for your
willingness to come and join us today.
The two major questions on which, as you know, we want your
help on are: what are the human goods and values that should antimate
monitoring the regulatory activities in this area or things that should
be promoted or protected?
And then, secondarily, how well do you think current
practices are succeeding in promoting and protecting these goods and
In short, what do and should we care about in this domain
and how are we doing and, implicitly, what might we do to do it better?
The two sessions this afternoon, although they have no
absolute division and people are free to say whatever it is that
they're prepared to talk about, we have more or less tried to
organize them so that the first panel will be to discuss more of the
reproductive side of this activity, that is to say the assisted
activities that help people produce children augmented by — and I want
to emphasize this — augmented by the growing powers of genetic
screening and selection.
That's really in a way what's new, the major new
thing in the area of assisted reproduction.
And in the second session we will attend more to the
research side, including also the commercial aspects of this activity.
A couple of words of explanation because I know that when
people talk about regulation everybody gets nervous. We should make
quite clear what we are not doing. We are not here with any
preconceived plan that anything beyond the status quo is necessary or
desirable, and we do not constitute ourselves a body to design new
regulatory activities. That's not our mandate.
At the moment, we are interested in getting information and
some diagnosis with some evaluation of the status quo. What you see is
what you've got. There are no hidden agendas.
People say that in Washington. In this case it's true.
Second, the council staff has prepared a discussion
document which we have withheld from you, from the presenters, partly
because we didn't want you to react to what it was that we had
found, but we waned to hear your presentations fresh as you see it.
The document will be available tomorrow here, posted on our
Web site, I think Monday at the latest, perhaps even tomorrow
afternoon. It is not a council report. It is a discussion document
prepared by staff for the council members, and we certainly hope to
have your reaction to this document in addition to the benefits of your
SESSION 3: BIOTECHNOLOGY AND PUBLIC POLICY: ASSISTED REPRODUCTION AND REPRODUCTIVE GENETICS
CHAIRMAN KASS: The procedure this afternoon, although many
of you have submitted things which are longer than what could be read
in five minutes, we will stick to the five-minute allotment of
presentation. We will then have the presentations, all five in order.
Council members have seen and read your submitted statements. So you
can presume them as part of our understanding, and then we will have
And the order is slightly different. We listed you in
alphabetical order, but we'd like to go in the following order, and
let me introduce people so that you all know who's here, and then
we'll just proceed.
First, welcome Pamela Madsen, who is the Executive Director
of the American Infertility Association, to my left.
Mary Mahowald, who is Professor Emeritus of the Department
of Obstetrics and Gynecology, McLean Center for Clinical Medical Ethics
and the Committee on Genetics at the University of Chicago.
Dr. Robert Brzyski, President of the Society for Assisted
Kathy Hudson, who is the Director of the Genetics and
Public Policy Center at Johns Hopkins University.
And David Smith, the Professor of Religious Studies and
Director of the Pointer Center at Indiana University.
Welcome to you all. Thank you in advance, and we look
forward to hearing from you, and we'll start with Ms. Madsen,
MS. MADSEN: I was third, but that's okay.
Well, good afternoon, Dr. Kass, and —
CHAIRMAN KASS: Excuse me. Might I ask you to move the
microphone a little closer or else have someone to amplify this a bit
MS. MADSEN: There we go.
CHAIRMAN KASS: Yeah.
MS. MADSEN: All right. Good afternoon, ladies and
gentlemen, Dr. Kass. I'm honored to speak on behalf of the
estimated six million Americans whose lives are compromised and
sometimes devastated by infertility.
As the Executive Director of the American Infertility Association,
one of the nation's leading patient advocacy organizations and
a personal veteran of the infertility wars, I can assure you that
our vast community is deeply concerned about the issues raised by
What is at stake here is nothing less than the quality of
our lives and for those of generations to come. This is why any policy
discussion of bioethics and regulation of assisted reproductive
medicine must have at its core the welfare of the people most
affected: the patients, our children, and the children that we all
hope to have.
As a group, we are educated, reasonable, and well informed,
and we are persistent, determined to overcome the cruel twists of fate
that leave us unable to reproduce without medical intervention.
We would prefer to have what is usually a private matter
between consenting adults remain a private decision. It's our
believe that no governmental or religious body should control these
uniquely individual decisions.
In my case, it was a leap of faith that gave my husband and me
two boys, both IVF babies conceived through assisted reproductive
technology when it was in its early years. Our 14 year old was
made the new old-fashioned way, with Mommy's egg, Daddy's
sperm, no micromanipulation, and a fresh embryo transfer.
Our ten-year-old grew from a cryopreserved embryo, held over from
one of our previous cycles at a time when freezing and thawing were
considered newer technologies. It was an informed choice, and we
knew the success rates at that time were not very encouraging.
Our tenacity paid off with a healthy baby boy who hit is
first home run last week in Little League.
We have our family precisely because my husband and I were
able to make that most private choice unencumbered by any government,
social, and research policy. The science was sprinting. This country
had taken the lead in finding new ways to outwit, if not vanquish, the
disease of infertility.
The technology was available. It cost, but it was there
for us to use, and for that we are eternally grateful.
The freedom to avail ourselves of progressive techniques is what
we need. For those afflicted with infertility, assisted reproduction
transcends ideology or electorial politics. It is about the opportunity
to realize the possibility of family.
Yet to our dismay we have been drawn into battles far from
our own immediate struggle, and it is the belief of the American
Infertility Association that productive medicine is being dragged most
unwillingly into abortion politics.
Why? Because our treatment results in the creation of an embryo.
However, we all must remember that these embryos are a part
of our medical treatment to combat our infertility. We take issue with
the presumption that others can lay claim to what is rightfully ours.
We are incensed that we become the lightning rod of often vicious
political debate around what some refer to as, I quote, "excess
Medical investigators want them for stem cell, DNA,
research, disease cure research. Anti-abortionists want our embryos to
be donated to others who want to experience pregnancy.
And those are all perfectly reasonable options, but they
are options that belong to us, the individuals who created those
embryos. Every decision about their disposition is emotionally
fraught, even the choice to do nothing. To keep them suspended in
liquid nitrogen is hard. Trust me. I have four. They're
sitting. It's hard.
Those of us who have gone through the unimaginable, life-altering
experience of assisted reproduction have and should have the right
to determine the fate of those three or five cells because their
fate is bound with ours.
Unfortunately, we must depend on the intellectual and
scientific creativity of researchers and clinical practitioners to
develop the technologies that we need. We expect our elected and
appointed officials to help insure a hospitable environment for
research and clinical practice of integrity.
We expect our government to take an enlightened approach to
the science and encourage it, not impede it.
And we expect those who are weighing in on the most
intimate part of our lives to please respect the intimate nature of the
Further, we demand unimpeachable ethical behavior from all because there's
nothing on our agenda but children, healthy, normal children, regular
boys and girls who make it into this world because we can pursue
and should have equal access to a constantly evolving and expanding
array of therapies.
To date, more than one million IVF children have been born,
and they, for all intents and purposes, are indistinguishable from
everyone else, and that is what we want.
You will find few others as keenly aware of the ethical
ambiguities of assisted reproductive technology than the infertile. We
struggle with the large and the small philosophical, religious, and
moral implications of treatment even before we walk in the door.
We analyze and carefully weigh the risks we knowingly
assume before undergoing sometimes still experimental procedures.
How we resolve these dilemmas is as personal and singular as DNA.
We, the infertile, object to the manner in which our disease and
the outcome of our treatments are increasingly depersonalized, treated
as commodities, as things apart (from) who we are.
Even the language to us is really troublesome. We hear
about patentable human goods when what is really under discussion are
We hear about embryo adoption as if it was an acceptable
legal term, when what really is under discussion is embryo donation.
We worry about the government impinging on individual liberties, our
religious and cultural beliefs, by determining for us what hundreds of
years of philosophical and scientific debates have not when life
And once again, the infertile have no wish to be roped into
that particular debate.
Certainly the infertile community — I'm wrapping up —
the infertile community welcomes the help of a compassionate
government. We would deeply appreciate a government commitment to
health coverage for infertility treatment for all that need it.
We believe federal funding for research is essential to
safely expedite the process and defray the financial burden that now
falls squarely on mostly uninsured patients.
And we need solid, long-term studies of the welfare of
infertile couples, the impact of the disease on parenting after ART
that track the health and development of our children, that yield
dependable data from large samples, and still protect privacy. That is
how the government can protect the general good.
We advocate the rigorous oversight of the development and
application of assisted reproductive technologies. Indeed, we have
paid richly for the regulation already in place.
However, it has yet to be determined that heaping on more
regulations would improve the ethical landscape. Rather, we believe
that government participation in a joint committee of physicians,
psychologists, theologians, lawyers, as well as other professionals,
and patients, we can strengthen existing mechanisms.
Let us have standardized informed consent and institutional
review boards for all institutions involved with experimental
infertility protocols. Let's strive for transparency and openness,
and hold people accountable.
We are not naive.
CHAIRMAN KASS: Ms. Madsen.
MS. MADSEN: Infertility patients —
CHAIRMAN KASS: I'm going to have to stop you.
MS. MADSEN: Just my last two sentences.
We know that there are no guarantees. We adamantly oppose
additional regulation without a concomitant throw of federal funds to
underwrite research and support access to care.
We don't want you to slam the doors on all of those who are
happy, wanting to have children, and I apologize for speaking too
CHAIRMAN KASS: Thank you very much.
Professor Mahowald, please.
PROF. MAHOWALD: First of all, thank you for inviting me.
I really have looked forward to meeting some people that I've known
a while and admire a great deal and meeting a few others whose work
I've admired but not have had the pleasure of meeting.
In the E-mail inviting me to this, Dean Clancy articulated
a little differently than you did, Dr. Kass, but I think the same
questions that you began this session with. He said: what values and
principles currently do and which ideally should guide the regulation
of assisted reproduction in the United States?
Now, this is, in fact, two questions, one mainly applicable
to the self-regulation that prevails — that's a descriptive
question, I think — and the other applicable to government regulation
which would presumably have the force of law.
Now, I was asked to bring to the discussion, and I'm
quoting again from Dean Clancy, the perspective of someone who's
concerned about the ethical duties owed to women and children to be in
the context of assisted reproduction.
So with these concerns in mind, my answers to the questions
posed can be put very succinctly. The principle that guides current
practice is the right to have a biologically related child, and the
principle that should ideally guide regulation is the principle of
Now, in the longer piece that was distributed to you, I
talked about these themes a lot more, although I would not say
adequately in less than 3,000 words, but today I just want to highlight
some of what I wrote there, and also on the outline that I think you
have, I've identified some areas that deserve more regulation than
currently exists, and I hope we can discuss some of these later.
In her presentation to the council, Sandra Carson
identified three values as central to professional self-regulation:
safety, efficacy, and privacy. Now, these are necessarily addressed
through the basic bioethical principles of respect for autonomy,
non-maleficence, beneficence, and the right to have a biologically
related child is attributed to potential parents on grounds of the
first of those, respect for their autonomy.
Justice, the fourth basic principle of bioethics, serves a
mediating or balancing function when other principles or values cannot
simultaneously be upheld.
Now, regarding my first answer, the right to have a
biologically related child, this is a relative and negative right.
It's relative or contingent rather than absolute because its
exercise depends not only on the cooperation of others, but also on
factors that may prevent its expression even then.
It's a negative right rather than positive because it
only obliges others not to interfere with its expression. It does not
oblige them to positively assist or facilitate its exercise.
The right to have a biologically related child is usually
asserted with a crucial caveat that the child be healthy, and in her
presentation to the council, Dr. Carson made it clear that the
potential child's health is a goal of infertility treatment.
But the right to biological progeny doesn't necessarily
entail the right to healthy progeny. Some patients give priority to
health by undergoing preimplantation or prenatal diagnosis to avoid
having children who are unhealthy or disabled.
For the potential child it's seldom, if ever, better
not to be than to be unhealthy, if these are the only alternative.
Regarding my second answer, even a minimalist approach to
government regulation should be based on some conception of justice.
The conception that I would propose draws on the work of Nobel Laureate
Amartya Sen. This view eschews a policy of political correctness that
ignores differences, insisting instead on attention to differences that
provide advantages to some while disadvantaging others.
It starts from the premise that people are of equal value
despite our differences, and it calls for efforts to reduce inequities
that are often associated with the differences among us.
Differences that need to be examined to develop just
regulation of assisted reproduction include those based on gender,
class, age, marital status, sexuality, ability, ethnicity, and moral
beliefs. I won't bother trying to give you examples of all of
these, but regarding gender, for example, women obviously incur risky,
invasive, and uncomfortable or painful procedures that men don't
experience even when the treatment is for male infertility.
Accordingly, women's decisions should generally have
priority over those of their male partners if these are at odds, and it
should not be assumed without question that the priorities of both
members of a couple are always the same.
Regarding class, economically disadvantaged women and
couples often don't have access to medical treatment for
infertility or they only have access to suboptimal treatment. The
recent cases of octuplet and septuplet births are probable examples of
If the right to have a biologically related child is
fundamental, then justice demands that infertility treatment not be
individuals solely on grounds of their ability to pay for it.
Regarding age, the right to have a biologically related child
is more compelling for those who are in their reproductive years,
than for naturally and healthy post-menopausal women. Moreover,
if as a society we regard all children as of equal value, a recommendation
that supports the right to have a biologically related child should
be articulated in the context of a broader and more basic right
of children to be parented.
On grounds of justice, the right to have a child already
born, regardless of whether the child is biologically related, is more
compelling than the right to have a biologically related child who has
not yet been conceived.
In a pluralistic society such as ours, justice demands attention to
moral differences, and with regard to infertility treatment, many
of these stem, as you said, from different positions on the moral
status of the embryo.
But U.S. law is clear that a woman has a right to abortion
which entails destruction of embryos at least until fetal viability.
If moral differences ought to be respected, clinicians may be, I think,
required to offer alternatives consistent with their patient's
moral beliefs, and researchers should be encouraged to develop more of
In sum, and to repeat my answer to the question I was
asked, the right to have a biologically related child is the main guide
to current treatment of infertility, and the principle of justice is
the ideal guide for regulation.
Both principles should be supported, I think, in the
council's recommendations. In cases of conflict though, justice
should have priority.
CHAIRMAN KASS: Thank you very much.
DR. BRZYSKI: Dr. Kass, members and guests, I appreciate
the opportunity to speak on behalf of the Society for Assisted
Reproductive Technology regarding the regulation of ART.
By way of introduction, let me provide some background
about the society, SART, as we refer to it.
The idea for SART began in 1985 with a group of
professionals who convened an effort to foster development of the field
and communication within the field.
One of their first efforts and priorities was to publish an
annual report of IVF technology to foster that communication
In 1988, the society was founded formally, and that first
annual report was published as it has been every year since then by the
Today there are approximately 370 member programs of SART
that are responsible for the vast majority of the 100,000 cycles of ART
and 35,000 babies that are born annually in the United States.
SART's mission is to promote and advance the standards
for the practice of assisted reproductive technology for the benefit of
our patients, our members, and society at large. I would state that
the explicit benefit we seek for our patients is healthy children.
To meet this mission, SART's activities comprise
several varied efforts. First, the registry oversees the collection of
annual clinic-specific data for publication by the Centers for Disease
Control, and in fact, the registry was responsible for the development
of the current data collection software program that is the basis of
SART provides the validation process which reviews the data
quality and accuracy submitted by the programs. Not just SART members,
but any IVF program is required to submit data annually, and that
validation occurs by state visits of peers to the programs with chart
reviews and reviews of the medical records and laboratory data.
Quality assurance efforts by SART provides a process for
assessment and promotion of member performance through consultative
services provided by SART members. The Practice Committee continually
develops and reviews guidelines and all aspects of ART, and all members
are expected to abide by those guidelines, which include ethical
guidelines as developed in conjunction with the American Society for
I have reviewed the current regulatory landscape as I see
it in my invited written comments to the council in April. This slide
shows a summary. Here I will just emphasize again that today as we
meet that there are a variety of regulatory processes operating at the
federal, state, and professional level.
In the short time I have, I'd like to point out some
characteristics of professional regulations as I see them and provide
some observations on the principles that I believe should inform
First, I would argue that the peer dialogue that is the
basis of professional regulation promotes engagement and investment in
the issues at hand by all of the parties involved. Attitude and
environment for professionalism fosters commitment to professional
Second, in contrast to legislative mechanisms of
regulation, professional regulation and professional regulatory
mechanisms support timely engagement of new issues. This is important
in fields such as assisted reproduction when progress is so rapid.
A final comment I would make is that associating
professional performance with economic consequences creates, I believe,
an opportunity to influence behavior. For example, tying participation
in a large insurance program by an IVF practice to board certification
or professional society membership provides leverage to those boards
and those societies to regulate and influence professional behavior.
That being said, I'll just make a few comments
regarding principles of regulation which I touched upon, again, in more
detail in my written comments in April.
First, I think beneficence considerations obligate an
analysis of the cost and benefits of any regulatory schema because in
the current environment, patients are the primary bearers of the cost
of care. These costs entail terrible burdens to patients and prevent
many from ever receiving the necessary care.
Justice considerations require that regulation not
discriminate against individuals based on their inability to reproduce
without assistance. Given the vital importance of reproduction and
human life, justice and regulatory objectives are both served by
promoting expanded insurance coverage for ART.
Likewise justice and beneficence would be served and a
significant regulatory infrastructure would be brought to bear if
federal support for ART research were promoted.
Finally, the principle of autonomy requires that
reproduction be recognized as fundamentally private, and that this most
intimate relationship between couples should not be unduly scrutinized
or compromised by regulatory interventions.
As to the future, SART will continue to foster and promote
collaborations with various professional organizations, government, and
bureaucratic organizations, such as collaboration with the Centers for
Disease Control for data collection, collaboration with the Food and
Drug Administration regarding guidelines to inform their oversight
efforts, a collaboration with the Joint Commission for Hospital Review
and their efforts to oversee laboratory regulation in the IVF field,
and collaboration with our patient advocacy groups with whom we have
had a rich and successful history.
The final comment I would make is I want to thank the
council for bringing this social dialogue to the forefront. I think
that's probably the most important effort that you could pursue,
and it's the fundamental basis to make ethical judgments that we
understand the social environment, that voices are heard, and that
information is collected so that informed decisions can be made.
I thank you again, and I look forward to further progress
in the field.
CHAIRMAN KASS: Thank you very much.
DR. HUDSON: Dr. Kass, members of the council, thank you
very much for the invitation to speak before you today.
I'm Kathy Hudson, the Director of the Genetics and
Public Policy Center at Johns Hopkins University.
The center is a little bit over a year old, and we were
created to build tools and resources to help policy makers and the
public address issues emerging from advances in human genetics.
Our first project is on reproductive genetics, funded by
the Pew Charitable Trusts. As this committee knows and has discussed,
the fusion of advances in genetic science and advances in human
reproductive medicine have brought forth new technologies that give
parents unprecedented new powers to identify, select, and perhaps in
the future to modify the genetic characteristics of their children.
The specific aims of our attention to reproductive genetics
are listed here. We want to understand what the public is thinking
about reproductive genetics. We want to engage them in a conversation
about reproductive genetics.
We would like to create objective, comprehensive, and
hopefully comprehensible information resources, and ultimately to
develop a set of policy options that can be considered by the public
and its representatives.
We will not be creating individual recommendations, but
rather, an array of options with robust underlying analysis that can be
used by others in making decisions.
Dr. Kass, in the center's written comments, we
responded to the council's request for information about the
current regulatory and legal landscape. This morning I would like to
make two points.
The first is that I think it's quite clear that
safeguarding and improving human health is the key motivation and key
principle that guides genetics not only in the research laboratory, but
in the clinical context, and similarly reproductive medicine research
and its practice. And yet I believe there are weaknesses in the
Second, I'd like to point out that public participation
must be a core principle that guides policy development, process, and
So of the core values or principles that should guide
reproductive genetics policy, safeguarding human health is perhaps the
easiest to identify, to understand, and ostensibly to address, and yet
there are weaknesses in the current system of policy, and I use the
term "policy" quite broadly to include research policy, that
have significant implications for human health.
As Pam addressed, as did Robert, there are now over a
million babies that have been born worldwide through assisted
reproductive technologies. And yet in the United States, we do not
have an effective system to monitor the health and developmental
outcomes of these children.
There have been a number of studies that have produced
sometimes confusing, sometimes contradictory, and often incomplete
information about the health status and developmental outcomes of these
To make sense of this information, the center this week
convened a panel co-sponsored by the American Academy of Pediatrics and
the American Society for Reproductive Medicine to evaluate the current
medical knowledge and to make recommendations for future research to
resolve uncertainties and fill gaps in our knowledge.
The second example of a weakness in the current
reproductive genetics policy is the absence of a well paved and clearly
marked road that genetic tests must traverse in moving from the
research laboratory into widespread clinical use. While the accuracy,
reliability, and interpretability is important for all genetic tests,
it is particularly critical in the reproductive genetic testing
There are now over 900 genetic tests that are available
clinically or that are in development, and it's possible to do
genetic testing at virtually every point in the human reproductive
cycle. We can test parents. We can select gametes based on the
presence of sex chromosomes. We can test embryos, fetuses, and
In the reproductive context, it is often the genetics test
alone that is the sole clinical information available for making
important decisions. Attempting a pregnancy or not, implanting an
embryo or not, continuing a pregnancy or not, these are profoundly
important decisions, and thus we need to have the very highest degree
of confidence that the genetic test results and their interpretation
So I believe there are weaknesses in the current system of
oversight and policy that result in an inadequate understanding of the
health risks of these technologies and an inadequate assurance of the
health and safety of their use.
Briefly, on the second point, I would like to propose that
a fundamental core principle that should govern the process by which
policy decisions about reproductive genetics are made in the United
States, and that principle is the public's participation. The
public should have a voice in public policies about reproductive
The goods and values that are advanced and embodied by
policies governing reproductive genetics should be the goods and values
that are held most dear by the citizens in this democracy, and yet we
have only the faintest glimpse of what our citizens hope for and fear
in this new realm.
We don't know largely because we haven't asked. As
you have heard from other speakers during the course of your
deliberations, other nations when trying to develop a regulatory
framework for these issues have turned to its citizens. Both Canada
and the United Kingdom consulted with tens of thousands of citizens in
their consideration of human genetics policies.
The Genetics and Public Policy Center is engaged in a
modest effort to understand and listen to the voices of the public. We
took an initial pulse through a survey last fall. We recently
completed 21 focus groups with Americans in five cities around the
country, and we're now conducting over 200 interviews with
individuals who have special experience, expertise, or perspective.
The themes and hypotheses emerging from this work will be
validated and tested in a very large survey of citizens this fall, and
in addition, this winter we will be engaging groups of citizens to
learn about genetics, to learn about reproductive medicine, to learn
about governance, and then provide to us their ideas and input about
how we should move forward.
The center will use this input along with our extensive
policy analysis to construct an array of options that can be considered
as society grapples with the development and use of these technologies.
In closing, I'd like to quote Thomas Jefferson, who certainly had
some interesting perceptions of genetics and the nature of families,
and he said, "I know no safe depository of the ultimate powers
of society but the people themselves, and if we think them not enlightened
enough to exercise their control with wholesome discretion, the
remedy is not to take it from them, but to inform their discretion
Thank you for your attention.
CHAIRMAN KASS: Thank you very much.
DR. SMITH: It's an honor to be asked to be here, and
I'll promise nothing but brevity, and I'll be rather
I'm going to talk very briefly about two things. One
is parenting and the importance of children, and the other is embryonic
life, which I think are issues the council has obviously addressed, but
seem to me to be central.
I'm going to say four things about parenting and the
importance of children. The first is I think it's correct to say
that having biological children is a good fortune, a gift, or a
blessing rather than a right.
Secondly, I think adoption is an option that should always
be presented to and be considered by parents seeking fertility
Thirdly, techniques, such as prenatal genetic diagnosis
that select among gametes or embryos, may, I think, appropriately be
used so long as they're proven safe and respectful of embryonic
Fourthly, my intuition is to support regulation by interdisciplinary
boards with a professional as well as a lay component, whether they
be local or regional. More general regulations seems to me to be
very likely to get things wrong.
With reference to embryonic life, I take the view
theologically that it's a kind of vestigial image of God. It's
not to be created to be sacrificed, but unlike those of us sitting
around the table, it's usable for research when there's no
prospect of implantation or development. They are, as others have
said, potential people, but not possible people.
And I'll stop there and make up for some other time.
CHAIRMAN KASS: Thank you very much.
Let me start. I think there are lots of people around the
table with questions of their own. Let me put a couple of questions
This one, I guess start with Dr. Brzyski, if I might.
I'm interested in how the professional standards,
especially the professional ethical guidelines established by the
society and by SART are forced. I mean it in the broadest sense. As I
understand it, these guidelines are mostly hortatory, but it's not
obligatory that people who are members in good standing, in fact, obey
An instance known to both of us, at least one member of the
society that advertises publicly that they, in fact, engage in PGD for
nonmedically related sex choice. And yet this is an activity
discouraged in the society's own guidelines.
I don't want to argue through that particular case, but
if one wanted to trust to professional self-regulation and that there
were certain kinds of values or concerns that the profession itself
had, how does the profession see to it that its own recommendations are
effective or does it and what can it do and what might it do better?
DR. BRZYSKI: Well, I think that I touched upon a thought,
an idea briefly in my oral presentation that I think might need to be
explored more, and that's the issue of professionalism and the
attitude of professionalism that promotes an environment where
individuals are sort of exhorted to participate and to achieve the
expectations of their professional colleagues, and that's a rather
vague way of accomplishing something, but I think it's something
that can't be ignored; that the dismissal of an attitude of being
part of a profession as opposed to having a job or having a business; I
think that those values and attitudes that go along with the membership
in a profession need to be emphasized and form more of a basic attitude
and principle with which to deal with each other.
CHAIRMAN KASS: Well, let me pursue this a little bit. I
mean the American College of Surgeons, the American College of
Physicians have certain kinds of norms and guidelines that people who
accept membership agree to uphold, and at least in some cases, although
it doesn't happen that often, people who sort of flaunt those
recommendations, given several opportunities to reform their practice,
but since fellowship is a privilege and not a right, the colleges are
certainly free to say, "Look. I'm sorry. We recommend, for
example, that ICSI is a new, relatively unstudied procedure for use in
male infertility, but we find it odd that there are some clinics now
using it at, say, 85 or 90 percent of cases not related, and that we
think that's unreasonable. Either show cause for doing it, change
your practice, or we might have to reconsider your membership in the
And the other professional societies, while being
collegial, nevertheless exercise more than "please do this,"
and I wonder whether — I mean, you're a young society relative to
those others, and the guidelines are being developed as the field
grows, but certainly the coming of preimplantation genetic diagnosis
and the uses of those things beyond just reasons of the health and
prevention of serious diseases, and sex selection is just the
forerunner of this.
It does seem to me that there are things in which the whole society
has a stake. If it is to leave the regulation of this in the hands
of the professionals, it wants at least to have some sense that
the professionals will see to it that those kinds of norms are,
in fact, observed.
If that sounded too much like a lawyer's brief, I
apologize, but I'm trying to sort of push the question about what
are the limits of professional self-regulation here, not in those cases
where, you know, it's certainly obvious that those things should be
followed, but in cases where some fellows think, look, the parents want
to have a girl child now. Why not?
Or they say, "Look. We want to increase our batting
average here. So we'll use ICSI rather than something else or
we're going to start doing this kind of practice though it's
relatively untested," and the couples don't mind and
they've been properly informed of the risk.
Those are the general areas for sort of professional
self-regulation and, generally speaking, enforcement or adherence.
DR. BRZYSKI: Well, I would say that I would agree that
this society is young, and part of the process that we go through as a
society is to plot a course of development that will cement our
recognition as setting the standards in ART as we have put as our
And I think there's a growing collaboration that's
developing over time among several aspects of the ART field. When it
becomes important economically, as I mentioned, for members to be
members of the society, then that's one way to leverage behavior,
and there are cases now where as I mentioned, insurance programs
require that if you're a patient and you're going to seek
assisted reproductive technology services, that those be provided by a
member of SART.
That's I would say a minority of individuals that are
covered by those sorts of benefits, but if that became more widespread,
then that would provide some impetus for individuals to maintain
I would say that the society believes at this point that to
try and maintain a communication with members and maintain a membership
that could be potentially influenced in the future would be more
important than taking a strong stance and depleting the membership
based on those stances which have no potential impact on behavior.
DR. FOSTER: Can I just ask a question in follow-up to
CHAIRMAN KASS: Dan Foster.
DR. FOSTER: Has ever anybody, since this is a young
society, has ever anybody who is a member of the society where peers
believe that there has been a practice that's not in accord with
the standards, been in any sense counseled or dismissed?
As an aside, as I know you know, the residency programs in
this country are controlled by the ACGME, and in internal medicine
where I work, for example, there were strong standards about what you
had to do to train residents, and so forth, and for years the programs
that were recognized as being absolutely disastrous were never closed
because of the fears, some of the fears that you just expressed, either
lawsuits or that there would be a fallout.
So I think there is some concern on my part that regulation
by societies — I mean, what happened is that the professors of
medicine, the chairs of medicine, in essence, forced the RRCs to begin
to close programs that did not actually meet the standards that were
required of everybody. I mean, we had the situation for a great
academic program was put on probation, and at the same time a program
in, let's say, Philadelphia or Dallas or somewhere that everybody
knew was absolutely no good was not disciplined at all because of fear.
And so the question is twofold. One, has anybody ever been
called, in essence, to account for their practice in the two or three
years that you've existed?
And secondly, do you have confidence that without some sort
of discipline that might require somebody to lose their accreditation,
the absence of that would be effective?
These are just two questions that I wanted to — I got the
sense that you thought that the fact that the membership itself was
enough to be sure that everybody followed the programs that you have
DR. BRZYSKI: Well, one example that I can point to is that
there are advertising guidelines that the membership adhere to, and
when there are variations from those practice guidelines that are
brought to the attention of the society, then there is an educational
effort that's carried out with those memberships, and there are
cases where — and the typical response of the member is to modify
their advertising behavior just in response to those educational
Another case involved sort of the combination of
advertising and practice, was utilization of experimental procedures in
a clinical setting without documentation or support or evidence that
the patients were being cared for in a clinical trial in a research
setting with appropriate controls.
So a practice has instituted what professionals in the organization
recognized as experimental, as accepted clinical practice, and offered
that as a service to their patients, and that membership, after
a long discussion back and forth, efforts led to the termination
of that membership or that program.
CHAIRMAN KASS: Michael Sandel.
PROF. SANDEL: I had two questions, and I'd be
interested to hear anybody respond to them who would like to, but I
would like to address them initially to Professor Mahowald because the
question arises from a distinction that you drew between two rights,
the right to have a biologically related child and the right of an
already existing child to have a parent.
And you said that the first was implicit in the current
regulatory practice, but you suggested that the second was morally more
important, if I understood you correctly.
And in your paper you said thinking about government
regulation that policies that encourage and facilitate adoption are
more morally incumbent on regulators than policies that facilitate
infertility treatments, which reflects the priority you would give to
the right of already existing children to have parents over the right
to have a biologically.
If some limited funding were available in this area, you
would say, would you, that given the choice between funding infertility
treatment and funding adoption programs, we should do the second before
Did I understand you correctly?
PROF. MAHOWALD: Substantially, that is what I said.
Basically the right to be parented, the right to be nurtured, the right
to be given what one needs to grow, I think, takes precedence over the
right of parents to have a not yet existent child.
PROF. SANDEL: Is there anyone on the panel who disagrees
MS. MADSEN: I'll chime in in a slightly different
way. I don't know necessarily that infertile people are the only
people to adopt children. Fertile people can adopt children, and
putting us together as, well, if you can't have a biological child
we'll help you adopt one is our solution.
Children need to be adopted, and people want to have
PROF. SANDEL: Well, that addresses a different —
MS. MADSEN: And they're separate. And they're
PROF. SANDEL: That addresses my second question, which I
don't think answers the first. My second question was going to be
that. Is there any reason to think that the obligation to fulfill the
right of children, already existing children, to have a parent should
fall more heavily on those who are infertile than on those who are not?
You've said no. The answer to that is no. Is there
anyone who —
PROF. MAHOWALD: No.
PROF. SANDEL: You would agree.
PROF. MAHOWALD: Yes.
PROF. SANDEL: But those are two separate issues,
Though everyone here might agree that the answer to that
question is no, that there's no special obligation to fulfill the
right of children to have parents that falls upon those who are
infertile. It doesn't equally fall upon those who are capable of
conceiving naturally. So that's one issue.
But to answer that question in the negative still isn't
to disagree with the first claim, namely, that the right to have a
biologically related child is morally less important than the right of
a child to have a parent.
That's why I was trying to separate those two questions
and see whether people —
MS. MADSEN: I think it's very, very difficult when you
put lots of different groups with tremendous needs and pain and ask
them to compete against each other. Children deserve homes. Children
need to be adopted, deserve wonderful adoptive families.
People who have a disease deserve treatment, and I hate to
be in a society where we can constantly make disease groups and people
with special needs. Real needs that are all legitimate, compete
against each other and make us decide who should be cared for.
CHAIRMAN KASS: I have Gil, Rebecca, Robby George.
PROF. MEILAENDER: Yeah, this follows in a way on
Michael's question, and I think I'm going to address it, Mary,
to you, but I'd be happy to hear from others because I think at
some level there is disagreement among the panel on issues.
What I want to think about is what you mean in terms of the right
to have a biologically related child or perhaps the right to have
a healthy biologically related child, what that language means exactly.
And I realize that in a certain sense at that point in the materials
that you submitted to us and in your talk you were speaking descriptively,
and so you're not necessarily arguing your own view, but nevertheless,
you may be able to kind of think it through with us.
And it goes in some sense to the question about
private/public, and how much of this is a private matter and how much
is a public matter, in which there was some difference at least at the
linguistic level among the panelists.
One of the things is what it means to have a biologically
related child. There are lots of ways to produce them, and the
question is whether they all amount to doing the same thing, to having
a biologically related child, and to take the example at one extreme,
and I believe as I recall you do mention it, to use cloning, to produce
a clone of myself might be said to be a means of having a biologically
Now, are you saying that descriptively at the level of our
practice right now, whatever you may happen to think normatively,
descriptively that I do have a right to have a biologically related
child by that means?
PROF. MAHOWALD: I think people who have argued in support
of reproductive cloning use exactly that argument.
PROF. MEILAENDER: I guess let me follow it up, if I may,
and invite others.
Does the fact that some sizable number of people have moral
reservations about cloning to produce children suggest that the
language of a right to have biologically related children is too broad
and needs greater narrowing and precision?
PROF. MAHOWALD: Yes.
CHAIRMAN KASS: Please.
DR. BRZYSKI: I would just comment that I'm
not aware of any professional organization or patient advocacy group
that's in favor of reproductive cloning to produce children,
and I would contend that there are practically no scientists that
would equate a clone with a child.
So I would make that distinction. So the argument that
cloning is a way to have children, I think fundamentally is a
misconception that practically all professionals that work in
reproduction would argue.
CHAIRMAN KASS: I think if I understand the force of
Gil's question, and it certainly is one of the things that springs
from this discussion, granted that reproduction is a private matter in
the first instance and an intimate matter in the first instance, and we
generally believe that government has no business interfering, and some
people even think government has an obligation to help where there are
obstacles to realizing these private goals.
The question is whether the presumption of privacy and the
rights to be exercised in that private realm are unqualified and
embrace also having a child by whatever means, having a healthy child,
which is very different from the right to have a child, and having a
child with certain desirable characteristics.
Look. If it weren't for the coming of the new genomic
knowledge, I doubt that we would be having this conversation really. I
mean there are questions to be raised about the adequacy really, the
concerns for the well-being of the child-to-be who is produced here,
who is also a patient of this procedure, but invisible to the eye and
merely hoped for when you get started, though that being is the patient
of the operation and that person's well-being and safety was an
uppermost consideration not always regarded in advance.
But I don't think we would be having this conversation
were it not for the fact that new kinds of choices now begin to enter
into the right to have a child or the privacy here where the society
might have an interest.
I mean, look. You've got other nations where they
practice sex selection not by PGD, but by sonography and abortion, and
the sex ratio at birth approaches 120 males to 100 females.
Those are aggregated private choice with enormous social
consequences, and the society can't be indifferent to whether that
goes on and how it's practiced.
So here is an instance where one wonders whether or not the
language of rights, the language of privacy, given what's coming
before us, is going to be adequate to deal with the implications of
And that's partly why, while I share your starting
point, I wonder whether from the social point of view all of the things
that are of interest to us and that we all care about are adequately
simply handled in terms of the language of rights.
And I think Gil's question is meant to probe the limits
of that concern.
I'm sorry for jumping the queue, but I think it
that's where we're —
PROF. MEILAENDER: Thank you for the assistance.
CHAIRMAN KASS: Yeah.
CHAIRMAN KASS: I have Rebecca and then Robby, then Bill
May. I'm sorry.
PROF. DRESSER: One of the major concerns in this area is
when the prospective parents who, of course, are very much interested
in trying to have children might have preferences that conflict with
the well-being, particularly physical well-being, but also other kinds
of well-being of our future.
So Leon just mentioned that this future child can be
considered a patient. So I was interested in whether you all agree
with that. Do you think that the to-be child or hoped for child is
considered a patient, and if so, what safeguards should be in place
professionally and perhaps in an oversight capacity from the government
to handle situations when there is a conflict of interest between the
prospective parents and the child to be?
And I guess the easiest thing to talk about would be a
physical threat, and so let's look at ICSI. That's a procedure
which some people still have some questions about in terms of whether
it's producing healthy kids, and it's not being studied in a
very rigorous way.
And this would certainly be a case where many prospective
parents might say, "Well, if it raises my chance of having a
child, I want it, and don't make me go into a clinical trial or
don't make me wait for the clinical trials and the data. I want it
And, you know, that's perfectly understandable, but
should there be any kind of oversight there? What should the role of
the physician be in that situation?
CHAIRMAN KASS: Is that addressed to someone in particular?
PROF. DRESSER: No. I just wondered if anyone in the group
had views on this.
DR. BRZYSKI: Well, my microphone is on. So I guess I
First let me make a comment about ICSI. there have been
some recent articles about the safety of ICSI, but I think I would
emphasize that there are also studies that suggest or don't
suggest, that show that the health of the vast majority of ICSI
children, who may be several years old now, is equivalent to that of
And here I would emphasize again scientifically the issue
that the easy way to look at outcomes is to compare ICSI babies or ART
babies, IVF babies to the general population, and that may not be the
best group to compare because there may be underlying problems that
infertile individuals have that may be associated with their
infertility that manifest themselves in ill health or disease in their
So although SART and ASRM are concerned about the safety of
ICSI and believe very strongly that it needs to be examined carefully,
the evidence that we have seen indicates that the vast majority of
those children are healthy.
As far as the issue of conflicts between parents and the
potential child, I think I'm going to pass on the discussion of the
potential child. Maybe Dr. Smith could.
DR. SMITH: Well, I'm not going to talk about that, but
I do just want to make two remarks. First, I think it is obvious we
have to distinguish rights from desires. I mean, we can't assume
that everything people desire they desire it with their whole heart.
For very good reason is, therefore, a right.
And at the end of the day, I come down on the side that
says that having one's own biological child is not a right.
On the other hand, I have to say that I'm very
uncomfortable with that because parenting was for me and has been for
two of my three children a life transforming experience, and in my
case, I'm lucky that it has been biological parenting.
So that it's a difficult one, and the possibility of
adoption — actually I think Mary had some of this just exactly right
— the possibility of adoption is a very relevant fact.
CHAIRMAN KASS: Please.
DR. BRZYSKI: I'm sorry. I wanted to get to the
initial issue that you raised about the conflicts between the parents
and the potential child, and I guess I would go back to the concern I
have about discrimination.
For instance, we know that there's a certain risk of
transmission of HIV to offspring when HIV infected parents conceive,
and I guess I'm concerned about having a different level or a
different category of regulation or intervention for a couple that is
able to conceive naturally, spontaneously in that regard versus a
couple seeking medical care for other conditions where they happen to
be HIV positive, and there's a judgment that has to be made there
about is participation in health care delivery contributing or
compromising the health of the child versus not meeting the needs of
the patients there, the actual patients that are in front of you versus
the potential patient that you might create.
And I think that's an issue that's been raised in
discussions with the ASRM Ethics Committee, that it's difficult to
isolate, segregate infertile couples and to somehow modify, you know,
what to do to them versus what we allow us to do to individuals who
CHAIRMAN KASS: Please, Mary.
PROF. MAHOWALD: I guess Gil was right that that
descriptive claim wouldn't be the one that I myself would make
prescriptive, and as a matter of fact, I agree with David and would
avoid the language of rights in my own arguments along this.
A word that I feel comfortable with for any parent by any
means is that having a child is a privilege, and it ought to be viewed
as such by anyone who becomes or hopes to become a parent.
But your question, Rebecca, really does nonetheless go to
this notion of a right, and if there is any right to have a child,
there surely is a right to have an unhealthy one.
PROF. DRESSER: I guess I would wonder if there's a
difference though. Certainly if someone is a carrier of a genetic
disease, the idea that we would somehow as a society say you're not
allowed to reproduce is offensive to just about everyone.
But once the medical profession is involved and sometimes
insurance and social resources and so forth, I think there are
questions of responsibility and what is appropriate for the profession
and the society to help.
I mean this is assisted reproduction. So I guess I'm
trying to get at your ideas about and back to this question of when
prospective parents may prefer something that is perhaps not in the
best interests of a future child.
MS. MADSEN: This whole notion of children being a gift,
life is a gift; we use this language an awful lot. Good health is a
gift, but when we do not have good health, we don't say, "Gee,
I didn't get the gift. I'm going to sit here and be really
sick because I didn't get the gift. I'm not going to see a
doctor because, you know, God didn't give me the gift of good
So I didn't get the gift of fertility, but I was able
to have the gift of a doctor who was able to help me have this
wonderful basic human life activity, that I was able now to engage in
and give birth to a child who at 14 understands that he's an IVF
child, and who thanked me for the gift of being here and being a part
of the family and couldn't wait to have his picture taken with
Professor Edwards who had the first IVF child. He was an embryologist.
He said, "I want to stand next to this man and have my
picture taken because without him I wouldn't be here."
So there's lots of gifts, and I think that we should
just be really clear about that.
And my children who are older now, ten and 14, they
didn't get to vote that they were conceived. It's true, but
neither did I. They're really happy to be here.
CHAIRMAN KASS: I have Robby George, Bill May, Frank, and
then we'll probably stop.
PROF. GEORGE: Thank you, Leon.
I was going to follow up a little bit on the very
interesting line of questioning that Gil opened and Leon then very
helpfully advanced, and I wanted to take it a little bit further and
raise a different fundamental question, I think, that flows from it.
I take it that at least in the case of Ms. Madsen and Dr.
Brzyski, the position is that ART is an area that's appropriate for
government funding to support research and to advance the science in
the area in order to make this technology more widely available and
Am I right about that?
MS. MADSEN: Yes.
PROF. GEORGE: Now, the point was made by a couple of
members of the panel that we live in a morally pluralistic society, and
in this particular area we're touching very intimate and inherently
Is that also something you agree with?
These are areas in which people hold very different moral
views and the moral views of different people ought to be respected.
Everybody seems to agree with that.
But then, if we're talking about an area that is
fundamentally private and intimate, it's not like a public
function, provision of a police force or national defense, where people
might have moral objections to it, but we've always held as a
society that people's moral objections to it notwithstanding,
we're going to carry out this public function and even tax people
to pay for it.
But if you take the position that everyone's moral
views ought to be respected, that people have different moral views
about ART, you want your views to be respected; you're saying their
views should be respected, and this is an inherently private area, not
like the military or provision of police forces, what justification can
you offer for compelling using the course of the power of the state to
tax people who don't share your view on ART to contribute, to
implicate themselves in fundamentally private behavior?
MS. MADSEN: This is health care, and we're
not talking about anything other than health care here, and you
do not have to seek treatment. No one is telling a couple that
they have to seek treatment. That's a private decision with
the couple, and that's the same in any other disease group.
Patients make private decisions, whether it's breast
cancer or prostate cancer or infertility. In this country we provide
health care for these kinds of treatments, and whether or not you
participate in that is your right.
I'm not going to ever tell a couple what they should
do. I will tell a couple what options are available for them.
PROF. GEORGE: But the reason I think that response
doesn't get you off the hook of the question is that to treat the
creation of embryos to solve infertility problems as health care is
already to make a controversial moral judgment.
Certainly, the infertility is a health care issue, but
whether we're dealing with medicine strictly speaking in the
creation of embryos, and certainly you yourself concede that the
question of the morality of creating embryos by this method or dealing
with fertility by this method is more fundamentally controversial than
whether to treat breast cancer, whether to treat kidney failure.
MS. MADSEN: I actually didn't say it was more
fundamentally controversial. I don't believe that it —
PROF. GEORGE: So you believe that it's not
controversial, that ART is not morally controversial?
PROF. SANDEL: The issue, Robby, isn't whether it's
controversial. The issue is whether you can provide a compelling
reason publicly by ART is so morally objectionable that it
shouldn't be included in health care.
PROF. GEORGE: Oh, sure.
PROF. SANDEL: So the burden is on you. It's not on
her to say whether it's controversial or not.
PROF. GEORGE: Oh, no, no, not at all, Michael. I'm
afraid the burden is on you or on her because we know as a matter of
fact on the ground that it's morally controversial, that people
have different moral views.
The premise for the argument for privacy here is that where
we have different competing moral views, those moral views ought to be
respected and nobody ought to be imposed upon.
PROF. SANDEL: But if the controversy isn't based on an
objection that's well founded, we shouldn't take any notice of
it. So you —
PROF. GEORGE: So people who believe other people's
moral views are not well founded can simply disrespect those views. So
the principle that we ought to respect diverse moral views only depends
on an assumption that the other person's moral views are morally
defensible; is that right? Is that your view?
CHAIRMAN KASS: Gentlemen.
PROF. SANDEL: No. You can be a conscientious objector to
the tax if you can show you've got a good reason to subtract it.
CHAIRMAN KASS: Without settling the dispute between these
gentlemen, and I'll even resist an opportunity to advance the ball
on the discussion, let me call on Bill May.
DR. MAY: I would like to address a question to you, David
Smith, on the whole question of regulation and discretion and building
up case by case something that you say resembles the common law
On the subject of embryos, you say, "Under these
circumstances I think we will be best served by a flexible and
case-by-case regulatory system with teeth."
Apparently a flexible system also can have teeth.
That's interesting because that's not the way that that term is
usually used, but it is interesting that you do put them together.
DR. SMITH: Well, I grade papers.
DR. MAY: Yeah.
DR. MAY: "We should be regulating all uses of embryos
whether in the public or private sector, but our regulatory process
should be modeled on common law, on incremental and something like
case-by-case decision making within a very few, broad parameters."
Now, I guess I wonder who is the decision maker, the courts
or professionals and potential patients. Is the law simply permissive,
turning over such decisions in the setting of which some kind of
quasi-common law tradition would develop within a profession maybe or
are the parameters really regulative?
You haven't seen a document that we will be discussing
later, but there's a sentence I noticed. "Most governmental
authorities simply lack the expertise to provide meaningful oversight
of professional activity, and medicine is a profession where crucial
judgments must be made on a case-by-case basis by a practitioner
familiar with the details and circumstances involved. The law tends to
give physicians ample latitude to make such judgments."
So when you're talking about parameters and so forth,
are you talking about parameters with some kind of content and then
within which professionals operate and make the decisions or within the
setting of which one further elaborates case by case the common law
tradition in which case the courts are making decisions?
DR. SMITH: (a) I think these are very good questions.
(b) I think my instinct is to say that just — that's
the first thing. Secondly, my instinct is, in fact, to trust
professional discretion, but I was not encouraged by the report that we
heard a few minutes ago about the Fertility Society's
community's history of self-regulation.
I do strongly sense — I really think that circumstances
alter cases, and I want people on the ground making those decisions as
much as possible, but if, in fact, there's a history of loss of
teeth, of de facto no regulation and entirely permissive practice, then
something else has to be set up.
I don't know if the IRB system in which you've got
a combination of professionals and nonprofessionals serves as a useful
model. I do know one example that isn't good for my point. When
the U.K. altered its abortion law in the '60s, they opted for a
regulatory system that was essentially local or, in the case of less
populated areas, regional boards that would decide on a somewhat
case-by-case basis if the stakes in individual cases were high enough
to justify abortion, and I thought that made great sense.
De facto, however, it failed or it has failed because what
it evolved to is total permission or evolved, in effect, to no
I still haven't given up on the idea, and I think this
is an area where sweeping prohibitions or just blanket permission
strike me as wrong.
I don't know. That's not a very good answer.
CHAIRMAN KASS: Frank Fukuyama.
PROF. FUKUYAMA: Well, it turns out this question actually
follows on the last one, but it's actually directed to Kathy
I agree with you, Kathy, completely that, you know, one of
the basic principles ought to be participation by, you know, a fairly
broad community, and I wonder whether you have given any thought to,
and I'm very glad that you're doing these polls and focus
Have you given any thought to how you institutionalize
participation as you go down the road in the future?
You know, in a constitutional democracy, the basic
guarantee of participation is elections, and you know, you elect people
to Congress, and you can lobby them, and so forth. When you get into
biomedical regulation because it is so technical, democracies then tend
to delegate regulatory authority through an epistemic community that
has the knowledge and specialization, you know, to deal with that set
of issues, which then tends to insulate, you know, that group from
broader public participation.
Congress can always intervene, but you know, it is not
encouraged and so forth.
Now, do you think that the current situation where as we go
down the road to these kinds of more controversial technologies like
PGD and, you know, some day germline and other things, the current
system where that delegation to the professional community with
occasional focus groups and polling and the existing, you know, comment
and, you know, posting regulations and opening them up for public
comment; is that going to be adequate or do we need something else to
get on an ongoing basis the views of a broader public other than, you
know, the people that are professionally engaged in the practice of
DR. HUDSON: I'm not sure I'm going to be able to
satisfactorily answer the question because I don't know how this is
all going to turn out. I think there is an appropriate role for the
public's voice or some representative sample of the public to
provide their reflected opinion, not just their knee-jerk reactions.
That can provide sort of the framework, the bounds within
which the professionals can then say in order to achieve that vision of
the way we want the world to be, in order to uphold those goods and
reflect those values, you know, we know what our course is, and now
we'll do the tinkering to construct the regulatory framework that
can best achieve that. Looking in our policy toolbox, what tools can
we apply to do that, to accomplish that?
I think that there can then be a disconnect because you are
speaking different languages at some point. Whether or not that
process of public participation can be institutionalized I'm not
sure exactly how to do that.
Engaging the public beyond just asking them five questions
in a telephone survey is a very difficult and very expensive
undertaking. So in some ways it's a privilege for us to be able to
have the opportunity to do this.
CHAIRMAN KASS: The last question to Mary Ann Glendon, and
then I'll have a comment and we'll break.
PROF. GLENDON: I'd really like to know something about
the kind of conversation that you have with a woman who's
considering IVF. I assume that your organization has guidelines for
clinics about what subjects should be brought up, and I'm wondering
in particular about two things.
One is whether in any more than a cursory way the subject
of adoption is brought up, the exploration of alternatives.
And, secondly, whether in addition to discussing the known
risks of the procedure for the woman, there is any discussion of the
potential long term health consequences. It's a relatively new
procedure, and you know, we found out some unpleasant things about
diethylstilbestrol used to prevent miscarriages back in the 1950s.
Is there a conversation about those long-term risks
incorporated into this preliminary counseling?
DR. BRZYSKI: Well, I would say that the principles of
informed consent, regardless of the therapeutic intervention that's
proposed, incorporates a discussion always of alternatives and risks.
Specifically in the case of assisted reproduction, whether
the discussion of adoption is more than cursory or not I think would be
hard to say. Most patients who come to the decision to do IVF,
it's a process that they go through. So it's not something —
like a typical patient I see will come. They're infertile. They
don't know why they can't have children. They go through a
diagnostic process. We try some therapeutic interventions perhaps, and
over the course of time, maybe even at the first consultation we'll
say, "Well, I'll take fertility drugs, but I'd never do
IVF, you know."
And then three years later as they've learned more
about their condition, about their options for treatments, the
expiration of the possibility of adoption, which practically all
patients discuss with me over the course of that time, there's a
consensus among the physician and the patient to pursue the IVF
So it's not like you just sit down and say,
"Okay. Now we're going to talk about this consent form,"
because practically it's a process that stretches over a long
period of time.
But during that time the issue of long-term risk has certainly been
brought to our attention or concerns about that has been brought
to our attention, and again, practically the example of whether
fertility drugs cause ovarian cancer is sort of open the door to
that line of discussion with patients, you know.
Whether or not that's true or not, it provides an
example to patients that they can understand regarding other possible
risks to their children and to themselves.
So I would say that professionals are used to discussing
and are comfortable discussing with patients.
CHAIRMAN KASS: Thank you very much.
Let me make a request. First, thank all five of you very
much for being here, for clear presentations, for very thoughtful and
I would like to take the liberty of being able to write to
you, have the council staff write to you to follow up on some kinds of
questions that have emerged here.
In particular, I would flag the question that Rebecca
Dresser asked. To what extent is the child to be, in fact, regarded as
a patient in this process?
And also more thought on the meaning of the fusion of
assisted reproduction with the coming genomic knowledge. We barely
touched on that, and whether or not — this is for you, especially,
Kathy — whether there are lessons that we might have learned as a
result of genetic testing in the adult context that ought to prepare us
for the kinds of questions to worry about here, as this is now coming
On that subject, by the way, let me call council
members' attention to a paper by a person who couldn't be here
to present today, Tonya Simoncelli, who has a paper that you have seen
a presentation on PGD, regarded in her view as sort of the gate opening
or the wedge technology toward a new kind of eugenic future and those
kinds of concerns haven't yet really been discussed here, but the
council members should notice that.
We'll take a break. Let's make it ten minutes this time.
Our guests are waiting, and we don't want to keep them too long.
Ten minutes we'll reconvene.
Thank you all.
(Whereupon, the proceedings went off the record at 3:39 p.m.
and resumed at 3:56 p.m.)
SESSION 4: BIOTECHNOLOGY AND PUBLIC POLICY: EMBRYO AND RELATED RESEARCH
CHAIRMAN KASS: I think we should get started.
This is the second of our panels with public presenters trying to help
the Council understand the current state of regulation of
biotechnologies touching the beginnings of human life.
Since I had long introduction of the first panel, which I won't
repeat, I'll simply say that the Council is at the moment simply
trying to understand the status quo and, in particular, to understand
what human goods and what values now govern whatever regulatory
activities we have; also, some suggestion as to what human goods and
values ought to govern here, and how well we are doing in promoting and
The last panel was selected with the view that they would largely talk
about the actual reproductive uses of these technologies. This panel
was selected expecting that most of you might be more comfortable
addressing the research questions and also the commercial questions.
But you are free to say whatever you want on whichever aspect of this
topic strikes you as important.
We thank you for your submissions, in advance. You should know that
the Council has prepared its own staff document, instructed by the
Council to take a look at the status quo.
We didn't distribute it to you in advance because we wanted you not
to react to what the staff had done, but to have your own input, and we
have your original submissions that were under consideration when the
draft document was done.
Our document will be available tomorrow here and also on our Web site
by the latest, I think, on Monday, and we would certainly welcome your
comments on what the staff has done.
Let me welcome then in order of presentation Michael Manganiello, who
is the President of the Coalition for the Advancement of Medical
Richard Doerflinger, who is the Deputy director of the Secretariat for
pro-life Activities at the United States Catholic Bishops Conference;
Maxine Singer, who is the Chairman of the Committee on Science,
Engineering, and Public Policy at the National Academies of Sciences;
Michael Werner, who is the Vice President for Bioethics at the
Biotechnology Industry Organization;
Andrew Kimbrell, who is the Executive Director of the International
Center for Technology Assessment;
And William Kristol, who is the Chairman of the Bioethics Project.
We are going to ask you to try to hold as best you can to five
minutes. We will take you seriatim, hold our questions and discussion
to the end.
We thank you for your presence. We look forward to your comments.
Please. I think you have to press - maybe it would be best if you
could get it a little closer to you.
MR. MANGANIELLO: How's that?
CHAIRMAN KASS: Is that all right? Can you hear from the back?
Please. Thank you.
MR. MANGANIELLO: Good afternoon, Chairman Kass and members of the
The Coalition for the Advancement of Medical Research, CAMR, values the
opportunity to offer remarks on the regulation of technologies and
practices relating to embryonic stem cell research. Although CAMR is
honored to testify today, the coalition feels the voices and strong
beliefs of the patients in this country suffering from disease and
disability should have been considered in the formulation of this
commission and in the conclusions you came to last year.
The coalition is comprised of more than 75 patient organizations,
universities, scientific societies and foundations advocating for the
advancement of breakthrough research and technologies in regenerative
medicine in order to cure disease and alleviate suffering.
It is disappointing that the voices of so many organizations dedicated
to medical and scientific research were not considered in establishing
a policy that affects over 100 million Americans suffering from
presently incurable diseases and disabilities.
CAMR strongly supports the freedom to conduct ethical research and
explore biomedical science in the hope of finding potential treatments
and cures for society.
Furthermore, we strongly support federal regulation of research to
insure that it is safely and responsibly executed. By stalling the
advancement of regenerative medicine, we are sending a message to
researchers and young academics, in particular, that scientific inquiry
For example, it should be noted that over two- thirds of the U.S. population
supports somatic cell nuclear transfer research to produce stem
However, your commission's recommendations for a moratorium will
delay and deny hope to millions of Americans.
The field of biomedical research, biomedical science adheres to
regulations set by state and federal regulatory systems. As you know,
Congress has failed to regulate cloning, but scientific discovery
continues in this field without a ban on reproductive cloning and no
regulations on SCNT for research.
CAMR concurs with the report issued by the National Academies of
Science in June of 2002. The National Academy of Science, the
nation's most august scientific group, concluded that while the
science of reproductive cloning must not be pursued, SCNT is likely to
be the best technology to cure deadly and crippling diseases.
SCNT can also be used to understand the genesis of disease and provide
an opportunity to advance the understanding and biological and cellular
All Americans will suffer from the restrictive environment in our
scientific community which has indefinitely delayed the development of
stem cell therapies. The President's policy limits federal funded
research to a homogeneous group of human embryonic stem cell lines.
Since some diseases are gender, race, and ethnicity specific, it is
vital to have a genetically diverse group of lines to study.
A greater number of stem cell lines available for a study would provide
statistically significant results. Our scientists are being driven
into a sequential form of research rather than research done on
In addition, as was stressed recently by Dr. Ron McKay and Dr.
John Kessler in recent Senate testimony, "The history of the
cells or the way they are derived may change their behavior."
The President's policy means, as Dr. Kessler said, "We will
perhaps be developing cells the one way that is not the optimal way, so
we need to expand our ways of trying to develop the cells."
Additionally, the President's policy not only severely restricts
the work of stem cell researchers, but encourages the exportation of a
very promising field in the biotech industry. Scientists in many
countries of Europe and Asia do not face the constraints in place in
the United States. These nations are making embryonic stem cell
research the cornerstone of their biotechnology industry.
America is losing its preeminence in medical research. Rather than
sitting on the sidelines, we should be supporting America's
ingenuity and experience by promoting and regulating the expertise of
CAMR has strong reservations about the President's decision that
was announced August 9th, 2001, regarding funding human embryonic
stem cell lines. This broad public policy was grounded in political
Dr. Zerhouni, the Director of NIH, has publicly admitted that there are
only 11 stem cell lines available at this time, not 64, and they are
simply not enough.
The American Society of Reproductive Medicine recently established that
there are over 14,000 embryos in the U.S. that would be donated for
stem cell research by the couples that created them. If that research
is not permitted, those 14,000 frozen embryos are set to be discarded
It makes no sense to forfeit the knowledge that our scientists would
gain from the stem cell lines that could be derived from these embryos.
The field of stem cell biology should move ahead on all fronts. It
would be devastating to proceed in only limited fields of research and
discover the science is flawed.
Our scientists should receive federal funding to conduct research using
stem cells from any source: adult, embryonic, and those created by
Working independently, with limited funding, scientists in the private
sector and the laboratories of our universities have already achieved
breakthroughs that clearly demonstrate the promise of stem cells, but
without a reversal of the administration's policy, their efforts
may go unrealized.
Congress and the administration should support SCNT, ban reproductive
cloning, and allow broader federal funding of stem cell research to
provide hope for better treatments - I repeat hope for better
treatments - and cures for our fellow citizens; maintain America's
dominance in the biotech industry; and pro-actively regulate new
The 75-plus members of the coalition, the National Academies of
Science, the 40 Nobel laureates who sent a letter to President Bush,
Senator Orrin Hatch, former First Lady Nancy Reagan, the State of
California, England, Israel, Sweden, Singapore, and China, among
countless groups, states and countries have given serious thought and
attention to this matter, and they have spoken.
Promising medical research must proceed. These are our neighbors, our
friends, our allies, just as moral and as ethical as anyone sitting in
this room. Who are we to ignore them?
CHAIRMAN KASS: Mr. Doerflinger.
MR. DOERFLINGER: Thank you, Mr. Chairman, and the
Bishops' Conference is grateful for this opportunity.
I have a longer statement and appendix that I've distributed
to the council.
I was asked to comment on the principles and values that are at
stake on these issues, and that is the aspect of the issue that
we feel most comfortable talking about.
There has been a substantial, though certainly not a unanimous,
consensus on certain key values and principles that are relevant
here. Tragically, even when those key values and principles have
sometimes been stated by advisory boards to the government dealing
with this issue, they have then been neglected when the time came
to use them as a basis for public policy.
The first norm I'd like to talk about is simply the importance
of ethics itself— that medical research can and should always
be guided by fundamental ethical norms. I say "guided by"
rather than "balanced against,"because one of the ways
in which the principles of declarations like the Nuremberg code,
the Declaration of Helsinki and other instruments have been somewhat
eroded in recent years is with the claim, sometimes written into
proposed legislation, that ethical and scientific considerations
must be balanced against each other in promoting research.
But if they have to be balanced, that means that even when you
know something is unethical, you can go ahead and do it anyway as
long as the medical benefit is, or is thought to be, great enough.
And that is what the Nuremberg code and so many other instruments
in our history stand against. CAMR, for example, says it supports
ethical research, but that is exactly what we're here for.
They say we have to give greater weight to the demands of patients
— I am one of those who thinks that the demands being made
by the patient groups are not at all, on embryo research, coordinate
with the actual needs of patients.
But to say that that has to be weighed in the equation is to turn
this into a cost-benefit calculus. If ethics matters, then it has
to matter when it keeps you from doing something that you very much
wanted to do. If the only things ethics keeps you from doing are
things that were useless anyway, it doesn't have much weight.
It doesn't have any weight.
And that's what has happened in some of the government advisory
panels that dealt with this issue. The Human Embryo Research Panel
actually endorsed the ethical theory of its ethics co-chair, Ronald
Green, who set up what he called a Copernican revolution in our
thinking about the ethics of research.
Essentially the Copernican revolution is to turn the Nuremberg
code on its head, and instead of saying that ethical norms form
an ultimate barrier to potentially useful research that ignores
the interest of the human subject, that medical benefit simply can
cause one to redefine that subject as not being due any respect.
That brings me to the second norm, which is respect for developing
human life, even at the embryonic stage. It is commonly thought
that this argument is about when life begins. The astonishing thing
is that all the government advisory panels that have dealt with
this issue —the Ethics Advisory Board in 1979; the Human Embryo
Research Panel in 1994; NBAC, the predecessor to this commission
in 1999; and the National Academy of Sciences — all describe
the early embryo as a developing human, in the case of the NAS,
or as a developing human life that deserves respect.
Respect is a very important term. It means a kind of inviolability.
It means someone who should be respected as an end in him- or herself
not only as a means to something else. And that means that when
we have avenues of research presenting themselves, each of possible
benefit — at the very least NBAC did recognize this —
it means that we should pursue and exhaust the avenues that do not
contravene that respect before we consider doing something that
would violate that respect, even as a last resort.
That burden has not been met in the case of embryo research.
For instance one could make a very good case that it is far less
promising for the full range of diseases represented in CAMR than
many avenues that present no moral problem.
The third norm that I think is important here, and it relates
to the reproductive technologies, is the dignity of procreation
of marriage and family. There are aspects to some of the reproductive
technologies, cloning being the most obvious, in which we very much
endanger dehumanizing or denaturing our very notion of the relationship
between parents and children.
That's most obvious in cloning when the entire procedure is
reduced to a manufacturing process to preset specifications. But
some of those problems arise in the other reproductive technologies
Setting aside the fact that parents who resort to IVF can be very
loving parents, the procedure by its nature is the kind of procedure
that tends to invite abuses like seeing this embryo as an object
for experimentation, particularly among those who actually practice
it in the laboratory.
Finally, in terms of specific recommendations, we propose a series
of those at the end of our prepared text. We support, of course,
a complete ban on cloning for research or reproduction. We support
a ban on federal funding of human embryo research, and we would
invite the council to look at laws in Louisiana and South Dakota
that try to embody the principle of respect for embryonic life in
the research context.
We also are very interested in what this council may have to say
about the regulation of reproductive technologies, such as IVF.
But we would also caution against any regulatory approach that assumes
that one has to fund or actively support that industry in its basic
form in order to prevent abuses, particularly since in our analysis
it is the very nature of the IVF procedure that has led to and invited
I have much more to say, including contradictions of much of what
Mr. Manganiello said, but maybe we will get into those in the discussion.
CHAIRMAN KASS: Thank you.
DR. SINGER: Chairman Kass, thank you for the opportunity to come.
I'm going to try and answer the questions that were posed from the
point of view of at least one member of the scientific community, and
I'd like to say that although I am the Chair of COSEPP, my remarks
today do not represent the views of COSEPP or the academy's.
So the education of scientists actually builds on two historically
validated values: first, to increase knowledge and understanding, in
particular, about the natural world; and, second, to apply that
knowledge for the benefit of human beings.
Physician scientists have additional values, including the commitment
to do no harm, and it is these values together with intense curiosity
that drive most scientists to ask and try to answer technically and
intellectually challenging questions.
In all fields of science the application of knowledge means, first of
all, sharing it with non-scientists, but application of new knowledge
also has more material effects, and people have for millennia used
scientific insights from various fields for new materials, for new
tools, for new agriculture.
Starting perhaps from Jenner and his cowpox vaccinations in the early
19th Century, biology began to impact people's lives more directly
At the same time, some research itself and most of the material
benefits of research can be associated with new kinds of problems.
Some research is dangerous for the researchers and the general public,
and examples would include work with pathogenic organisms. Scientists
welcome and even initiate regulation and restriction of such research.
In a pluralistic nation like ours, scientists are also respectful of
restrictions based not on possible hazards, but on other kinds of
societal concerns that are sufficiently widely held to justify
Current examples would include the rules and laws governing clinical
research with patients and human subjects, the humane treatment of
animals, and even the planting of genetically engineered crops.
But it is essential to keep in mind that regulation, restrictions,
and controls are not the same as an outright ban on research. Contemplation
of such bans is only appropriate under particularly compelling situations.
Well, what I've just described is the context in which many, if not
most, biological scientists see the Council's current agenda.
Thus, as far as we know, most scientists, but in fact not all, agree
with this Council's conclusion that human reproductive cloning
should now be outlawed, and as you all know, several reports from the
National Academies agreed with that.
This conclusion is based on compelling scientific evidence from
research on other mammals that reproductive cloning is both dangerous
and likely to fail.
The situation for other avenues of research with human embryos is quite
different. First of all, no hazards to researchers or the general
public have been identified.
Second, as evidenced by testimony to NBAC, to Congress, and to this
Council, there is no common view among the public about how to balance
concerns expressed by some segments of the general public against the
possible knowledge and applications that can follow from the research.
And in this I clearly agree with Mr. Doerflinger about the need to
So the conclusion is that a moratorium on such research is not justified.
But restrictions and cautionary practices are another matter, and thus,
according to the policy enunciated by President George Bush on August
9, 2001, federally supported U.S. scientists can use for research
certain lines of embryonic stem cells that were established prior to
that date from spare embryos made for reproductive purposes, provided
that there is informed consent by the donors and no financial
The NIH has taken a variety of steps to assure the availability of such
cells and their use under appropriate conditions, and this has allowed
important research to proceed.
Nevertheless, these few cell lines - at last count 11 were available -
cannot for a variety of reasons permit the full program of important
research that scientists envision.
Additional cell lines from diverse populations and developed under
different protocols will be essential. Moreover, to realize the full
potential of the research, it will be important to work with embryonic
stem cell lines derived from the transplantation of a somatic cell
nucleus into an enucleated egg.
Here, too, there is evidence that societal concerns about the
research do not reflect a broad consensus. The Congress is stalemated
over the issue of allowing this research with the unfortunate consequence
of providing no moratorium on reproductive cloning.
It would be appropriate now to outlaw the implantation of a blastocyst
made by somatic cell nuclear transplantation, into a uterus because
that's a bright line. While research with such cells can be
done by a single scientist in a laboratory, implantation requires
several people, and this is unlikely to be done surreptitiously
if the penalties are severe because the more people involved, the
more unlikely it is that they would conspire successfully to break
So rather than a slippery slope, it seems to me this is more like the
edge of a steep cliff.
The views in our country about the nature of a fertilized egg cell and
a blastocyst are so opposing as to appear to be unreconcilable at
the present time. And we have dealt with the situation in the messy
ways that a democracy does deal with such a situation.
So we find that reproductive cloning remains legal. Research
on developing eggs, blastocysta, and embryos also remains legal
even if they're made by SCNT so long as it is not carried out
with federal funds, in which case it is perfectly legal and possible.
Most of the nation's scientists depend on federal funding,
and thus are similarly barred from developing new cell lines by
nuclear transfer, and from carrying out research with fertilized
eggs in a dish or blastocyst.
At the same time, research with such materials can, as I said, proceed
with private resources and is not subject to any governmental oversight
Various states have passed, and others are considering legislation, and
those laws are really all over the map. Some of them encourage the
research. Some of them prohibit it, and so we have a patchwork.
That patchwork may have advantages for a few people, but it can
encourage undesirable procedures and exploitation for personal gain at
the same time that it prohibits our best scientists from undertaking
this important research.
CHAIRMAN KASS: Thank you.
Mr. Werner, please.
MR. WERNER: Good afternoon, Mr. Chairman, members of this
distinguished Council. My name is Michael Werner. I'm Vice
President for Bioethics for the Biotechnology Industry Organization,
Thank you for the opportunity to speak today about the values
underlying appropriate regulation of biotechnology and biomedical
BIO members conduct genetic, cellular, and protein research and develop
health care, agricultural, industrial, and environmental biotechnology
products that are used by billions of people worldwide to identify an
unmet medical need, improve the quality of the food supply, and broaden
The biotechnology industry is a remarkable success story. There are
currently 157 FDA-approved products on the market that have helped more
than 325 million people worldwide. These people suffer from illnesses
such as Hepatitis B and C, arthritis, cystic fibrosis, multiple
sclerosis, many forms of cancer, and on and on.
Our industry has achieved these accomplishments in part because the
state and federal regulatory system that governs the development and
use of our products works very well. Our nation's regulatory
system assures patients and their physicians that they can rely on the
safety and efficacy of our products.
Biotechnology companies have always worked with and within this
regulatory system to ethically bring safe and effective products to
market, and we're proud that our scientists have been able to
sustain aggressive lines of inquiry while complying with a robust and
diverse regulatory system, including oversight from agencies such as
the U.S. Food and Drug Administration, the National Institutes of
Health, and others.
We believe that knowledge and understanding progresses not only through
scientific research, but also through dialogue and discussion.
Throughout its history BIO has been actively involved in bioethics
education and discussion inside the industry at all levels and branches
of government and with the public.
Many years ago, BIO formed a bioethics committee chaired by a member of
our board of directors to discuss bioethics issues, and our board has
adopted a statement of ethical principles that details ethical uses of
biotechnology, and we're proud that the previous chair of our
committee served on the National Bioethics Advisory Commission, the
group that preceded you.
The existing regulatory and ethical framework within which
biotechnology companies operate has successfully protected patients
while allowing critical research to advance. Appropriately, current
regulations embody values, such as autonomy, such as whether to
participate in a clinical trial, beneficence, and social justice.
These values should remain the basis of any regulatory system, and in
addition, personal autonomy and privacy as well as academic freedom
should be a crucial part of the discourse for further understanding the
use of what you refer to as new technologies and practices in assisted
reproduction, embryo research and human genetics.
The American legal system is grounded in the fundamental right of individuals
to define their own existence through personal and shared decision
- making. BIO members share the belief inherent in American civil
rights laws that our lives are not preordained by our genetics,
but are often the result of choices that individuals make, choices
that parents make for their children, and the opportunities available
in our communities and our physical environment.
Choices such as whom to marry, whether to have children, how to raise
those children, whether to accept or refuse medical care have all been
protected by the Constitution, and the individual has the right to make
these decisions whether or not biotechnology products or an
understanding of genetics is involved.
Individuals' freedom of self-determination extends to parental
rights. American law and societal norms have historically respected
the family's rights to autonomy and have long recognized
patients' rights and responsibilities to make decisions that affect
their children's future.
These rights and duties should be read to include responsible use of
genetic information, as well as other medical, social, and personal
information about a child.
BIO strongly supports education about biotechnology and genetics and
the freedom to explore their potential uses for the benefit of
humankind. State and federal regulatory systems must support and
promote freedom of responsible inquiry which is at the heart of First
Amendment protected academic freedom.
These values animate our members' research and their development of
products that licensed practitioners use to provide services that may
be elected for themselves and their children. Such products and
services allow millions of people to pursue their own destinies as they
choose to live productive and healthy lives.
So, in conclusion, appropriate regulation of biotechnology is solidly
rooted in values such as autonomy, privacy, beneficence, social
justice, and intellectual freedom. BIO supports responsible and
ethical testing of new technologies and believes that decisions
regarding whether and how to use medical products and technologies
always must be made with profound respect for the rights of patients.
We cannot condone regulations that unjustifiably curtail intellectual
freedom of researchers to think and dream in the pursuit of greater
understanding which could lead to a better life for all of us.
Patients and their families are counting on our companies to develop
products to meet unmet medical and health care needs.
Thank you very much.
CHAIRMAN KASS: Thank you.
MR. KIMBRELL: Thank you, Mr. Chairman. I thank the Council for
inviting me here. This is a fascinating and important subject that so
many of us around this table have grown gray dealing with over all of
these many years.
We have submitted a paper on pre-implantation genetic diagnosis, and I
will be here during the public comment period tomorrow and maybe we can
talk about some of the issues there that we thought were important for
the Council to think about, Mr. Chairman.
CHAIRMAN KASS: Thank you.
MR. KIMBRELL: In the brief time that I've been given, I want to
try and make three points, which is probably hubris in itself.
The first one really comes from that long history that so many of us
have on this issue and I've had as an attorney on this issue
for almost 20 years. We often approach these issues, it seems to
me, with kind of a technological amnesia as if we were looking at
these issues for the very first time, and of course we're not.
I remember at least two instances of where we were looking at a miracle
cure du jour, which unfortunately means that we had to trample some of
our most important ethical norms, and this is really the third one that
I've been looking at. I'd like to bring you back through that
By the way I'd probably just like to start by saying that Dr.
Michael West of ACT went before the Senate almost two years ago and
said within six months that he would not only have isolated stem cells
from cloned human embryos, but that they would have been differentiated
sufficiently so that he could cure several major diseases.
He told Senator Harkin, who was chairing that committee hearing, that
even a six-month moratorium would cost millions of lives, at which
Senator Harkin said, "Thank God we have some real numbers to look
at in this debate."
So the subject of this little session is hyperbole versus healing.
I remember very well doing a lot of litigation in the fetal tissue
controversy of the middle '80s. I remember The New York Timeseditorial
that warned, "To interfere with these fetal tissue experiments
is to interfere with the progress that could save countless lives."
You may have already heard some of that from this panel. I'm sure
you've heard it from a number of other panels.
We brought up several important issues that needed to be looked at.
Should these fetal organs, should the fetuses themselves be for sale?
Should there be some limit on their use? Could you use them for
cosmetics, or in one case in England, for earrings, freeze-dried
embryos, or should you only use them for serious diseases? Should you
use them for all?
What about changing the method and manner of abortion in order to get
fetal tissue that was more valuable or could be more valuable?
What about informed consent? What does informed consent mean when
something isn't dying of itself? It's a chosen death. What
does the concept of informed consent mean?
The Reagan administration, based on many of these concerns, correctly,
I believe, declared a moratorium. One of the first acts of the
Clinton administration was to lift this moratorium, without asking
a single one of these questions, under the rubric we need to save
Well, let's look back now 15 years, 200 million federal dollars
spent on fetal tissue research. I don't know how much private. I
don't have those figures, but well over 200 million. How many
lives have been saved? Zero.
And with 15 percent of these patients that I don't think ever
should have gotten this fetal tissue, what happened? Well, let's
quote the guy, Dr. Paul Green, who is at Columbia University College of
Physicians and Surgeons who actually was the lead researcher in the
federally funded study, and he described his patients - because what
happens, when they put the fetal tissue in their brains, they cannot
control the amount of chemicals they put out. And so he described
these patients writhing, twisting, jerking their heads, flinging their
arms about, spasms so severe they could no longer eat, needing feeding
tubes. This is 15 percent of the patients.
For others, spasms made their speech completely unintelligible.
Despite these effects, Dr. Green says there's no way to remove the
transplanted fetal cells to stop them from creating these impacts on
the patients. "It's tragic, catastrophic," Dr. Green
explained. "It's a real nightmare, and we can't
selectively turn it off."
As for the near future, Green said, "No more fetal transplants.
We are absolutely and adamantly convinced there should be research
Countless lives? We don't have regulations right now. We have
basically open sale of fetal tissue. We gave the HHS some very vague
guidelines which they've never enforced by their own admission.
All of those important ethical questions trampled over, no regulations
because, oh, goodness, we don't want to get in the way of something
that might save countless lives.
So who are the victims? The very patient groups that have been talked
about. They are the ones who are the victims of this, and of course,
again, our ethical norms.
Let's look at another one, gene therapy. I filed the first lawsuit
against the Recombinant DNA Advisory Committee. Dr. Singer may
remember some of this history. We successfully sued them because they
didn't have an open process for deciding who would get gene therapy
and who wouldn't. All right?
We talked about the incredibly important questions about once we start
changing genetic make-up of human beings, shouldn't we wait?
Shouldn't we look at this?
No, we need to save countless lives. French Anderson and others were
called genetic wizards, miracle cures. Fifteen years later, hundreds
of millions of dollars later, how many people have been cured in
the United States with gene therapy? Zero.
First we heard about one death. Then we heard of another death of a
patient. Now they're looking at over 1,000 serious adverse events,
and from one of the purported cures in France, we get a report that
this retroviral vector they used, which many of us knew and I wrote
about in my book in the early 1990s, has caused a rare and unknown form
of leukemia in two of the young patients.
So now we have another miracle cure du jour, which is a very naive sort
of American view of how to cure disease anyway. Disease is obviously
very complex. It has environmental, genetic ideas, and once again
we're asked to trample over these.
So we have been here before, and I think to approach this issue
in a kind of, again, technological amnesia, does not reflect both
the suffering of those who have been misused in this process for
venture capital and other reasons and the failure of Congress, and
the failure of our regulatory agencies to take these ethical issues
seriously and to be railroaded by these false hyperbolic claims.
And I hope this Council and I hope, as well, members of Congress will
no longer be subject to that kind of blackmail, particularly with this
The second point I'd like to make is that we shouldn't
substitute regulation for ethics. All right? Richard Weaver said we
should never substitute arguments of consequence for arguments of
definition. If we believe something definitionally shouldn't
happen, it shouldn't happen.
In both of those cases we gave HHS guidelines saying, "Hey, you
look at the ethics of fetal tissue and you go out there and make sure
that whatever ethics you decide on, HHS" - well, we haven't
We had the Recombinant DNA Advisory Committee looking at all of these
gene therapy experiments. Of those 1,000 serious adverse instances I
talked about, researchers only reported 37 of the 1,000. It took
independent investigators to come in to find the rest of them.
So let's not substitute regulation for ethics and make sure if we
have something to say ethically we say it. It's said by our policy
makers and not give it over to the agencies because it just doesn't
happen there, and as an administrative law attorney, I can tell you if
you're looking at enforcement these days, it's a very, very
The third thing I would like to say very, very quickly is I would
like to recommend that this Council take a look at a very important
legal precedence that is developing that might create a kind of
a consensus that Dr. Singer was talking about, that Doerflinger
was talking about, and that's the Tennessee Supreme Court case,
Davis v. Davis. They came up with this idea of a special
entity, the idea that an embryo is neither property nor a full adult
person, but is perhaps a special entity because of its in potentia,
human life in potentia. It has a trajectory that could make it
a full human being.
As such it is due respect. As such it is due protection. In this way
we cannot remain deadlocked in this ideological divide between it has
the legal status of a person, it's murder, or it's no more
important than a toenail, or it can be used as a medical device and be
And I'm hoping that perhaps by looking at a consensus around either
a special entity and that combining with other ethics - I'm not
suggesting that it be a fundamental that we can all agree with, but as
a policy given our current legal precedent, as a policy context that
that special - that we look at the embryo as legally a special object
that needs certain respect, and in that sense I hope we would do at
least three things.
Say if it is a human life in potential, no sale, no patenting, and it
should never be created solely for its own economic exploitation or
CHAIRMAN KASS: Thank you very much.
MR. KRISTOL: Thank you, Dr. Kass.
Maybe I should say a word about how I came to be particularly
interested in these sets of issues. I had studied and taught political
science and political philosophy for a few years and then served in
government for a few years and then have edited a magazine for a few
And in all of these, as someone who, therefore, believes in a vigorous
debate in a whole bunch of areas of public life, I was struck in 1999
and 2000 how little serious public debate there was beyond specialists
and beyond experts in this whole range, about this whole range of
questions in the field of bioethics, the so-called "Brave New
World" issues of where we were going with the biogenetic
I remember writing an editorial on the eve of election day 2000 saying
that I was really shocked. I think historians reflect that these
pretty fundamental issues about shaping our nation's future and
even the future of the human race had not even been considered during
the election campaign or at all or barely in our public life. Dolly
was cloned and there was a flurry of interest, and it quickly subsided.
There were occasional similar flurries of interest. They quickly
subsided. I actually was heartened in 2001 when we started the
Bioethics Project to try to foster this debate and with a certain point
of view of skepticism about or at least a point of view that there
needed to be some countervailing force to the huge dominance of the
avatars of progress, untrammeled scientific and genetic progress in
We started the Bioethics Project. We were heartened actually by the
debate in early 2001 about embryonic stem cell funding. It was a
serious debate actually and raised important issues.
The President made his decision on August 9 and then September 11
happened. It's hard to know whether the short-circuiting of the
debate might not have occurred, I suppose, if everyone hadn't moved
on to an awfully important threat and how to deal with it after
September 11, but I think it is fair to say that since then I don't
think we've had a particularly enlightened or enlightening - really
with the exception of the efforts of this Council - public political
debate about these issues.
I find that depressing. I find it something of a scandal really since
these are awfully important decisions that are being made about our
future with no debate comparable to the debate I think that takes
place in all kinds of other areas: foreign policy, economic policy,
you name it really, but in this one area there's not much debate.
People are intimidated, of course, because of the scientific expertise
that's required or that's claimed to be required. Those who
were dominant in this field that were driving policy, as is always the
case with dominant interest groups, have no particular reason to
welcome debate. If you're in the driver's seat, there's no
reason to encourage a big public debate, and I think that has been
actually the behavior of the scientists, of the business types who have
been getting their way with rather little regulation, as has been
pointed out, in a fairly untrammeled way.
There's a tendency to sort of caricature the opponents and beat
back the efforts of modest legislation and regulation and then move
on. The values, so to speak, that are embodied by scientific progress,
by health, by business, if you put those three together - science,
health and business, and they basically do come together in this area
- against any serious curbs, ban, or even regulation, those are
awfully hard to fight, especially when there's no, as I remember
from my days in political science, when there's no equally
organized interest group with real interests on the other side.
There are certain people with strong views on the other side, some of
whom are somewhat well organized, but that's not really enough,
ultimately, to stand up to the assault by the entire scientific
establishment, much of the medical establishment, those who claim to
speak on behalf of patients and on behalf of health, and those who
claim to speak on behalf of scientific progress and large chunks of the
business community, which is powerful in a commercial republic like
And so I think the state of debate, if I can address just that little
part of what you asked us to address, what do we think of the state of
debate on these issues is, with the exception of the work of this
Council, something of a scandal; and an awful lot of disingenuousness
is gotten away with. There's an awful lot of talk about respecting
nascent human life; and respecting the embryo, though it doesn't
deserve full protection, it deserves respect.
It never turns out that any embryo should actually ever be protected
from any procedure as a result of this vague respect, but this is
simply a way of throwing a bone to those who are discomfited, and then
moving right along with whatever. People who run IVF clinics or
scientists who want to do embryonic research, who want to do - we
slide down a path from assisted reproduction, to selective
reproduction, to enhanced reproduction, and again, at each stage these
steps are incremental. They're small, and sometimes the scientific
and medical establishment will acknowledge that at some point there
probably should be a ban on something, but it should always be the
something that is over the horizon, and indeed we've seen this, of
course, very clearly with stem cells and cloning where many advocates
of government funding for embryonic stem cell research strongly made
the point that, "Well, there are these spare embryos; it's
ridiculous not to use them to advance human health."
But, of course, that's a very different thing from creating
embryos de novo and then destroying them and then, as soon
as that became scientifically desirable, of course, the limitation
that had been expressed quite powerfully, actually just months or
very few years before, was forgotten and anyone who stood in the
way of so-called research on cloning or experimental cloning was
then standing in the way of scientific progress.
So I have no recommendation, except this: that I think the debate is
important, and I think the debate, to be serious, must be not just
public but political, and I think the political debate, to be serious,
must at some point call on participants in it to be honest about what
they would permit and what they would not permit.
And it is not in my view sufficient to sort of pocket everything
that has happened up till now, put all of that out of bounds, one
is not allowed to question anything about the status quo. And I
would just ask this of all the very powerful, well - financed groups
that represent patients' groups, physicians, scientists: Is there
anything about the status quo that discomfits them? Is there anything
they would like to change or bend? Is the status quo of IVF clinics
- 400,000 spare embryos, no ban on creating embryos for the sake
of destroying them - is that just fine? Is there anything that
should be limited that currently is permitted?
So, first of all, I think to be serious one has to talk about
limitations and restrictions at some point, and I'm curious whether
people think there's anything that now exists that shouldn't
exist and anything that is now permitted that shouldn't be
And, secondly, as I say, looking forward, I think it shouldn't be
acceptable to sort of claim to be for debate, for thoughtfulness, for
respect for everyone's opinion, but then it just turns out that in
every single possible concrete choice that has to be made, well, in
this particular case, the ostensible claims of health and science and
progress trump whatever ban or limitation or moratorium those who are
more skeptical are suggesting.
CHAIRMAN KASS: Thank you all, and let me start to see if I can pull
together some threads and actually where Bill Kristol left off is one
of the two kind of general questions I would like to put to the panel.
I would hope that this not turn into a specific argument on the status
of the embryo. We could be here all day. We know that our group is
divided on that. The panel before us is divided.
I would like to try to generalize from that to certain larger
It seems to me that we have heard from three of our panelists a strong
defense of the values of the growth of knowledge and understanding,
translating that for the benefit of humankind, especially the benefits
of health and the cure of disease, and the sort of betterment of
human prospects through science based technological application.
Those speakers acknowledge the importance of doing this ethically. In
some cases the ethical norms that were operative were given some
specification as in, for example, avoid doing harm, the question of
danger and safety, one that's congenial to everybody and we need
not argue about it.
But beyond that question, respect for the human subject of research so
that we adhere to certain kinds of guidelines and research. Maxine
Singer mentioned even some concern for animal welfare, although the
respect question there is again one of these difficult questions that
And in Michael Werner's presentation, a listing of autonomy,
beneficence, social justice, intellectual freedom, that was sort of one
family of concerns.
Richard Doerflinger suggests, first of all, the importance of
ethics not as something to be balanced, but as something to guide
or to regulate, and then goes on to emphasize respect - questions
of respect and questions of dignity which are not exactly the same
as the questions of rights, privacy and autonomy, and that's
at least one of the areas where we've got some kind of disagreement,
and then some kind of concern really for truthfulness and not taking
advantage, in fact, of the people in whose name we speak. And the
importance also, as Bill Kristol suggests, that up at least until
this point we have had a more or less laissez-faire attitude with
respect to these innovations, but given that the stakes appear,
at least to some people, to be much higher, and that these technologies
serve not merely human health, but goals beyond health, and that
the means to attain that technology is also threatening to trample
values that some people hold dear, the importance at least of lifting
up to public debate and actual public scrutiny and political argument
the questions of where we are going, how fast, and under what kind
I think that summarizes reasonably well, if I say so myself, the things
that I heard to bring it down.
Now, it seems to me that two kinds of challenges might be raised to the
different parts of the panel. I would be interested to know from,
let's call it the science/research/technology/patient side of the
panel, what kinds of goods or values you yourself might see justifying
limitations on the freedom to conduct research, even beneficial
research in this area or that might get in the way of business as usual
In other words, assuming that the government left you alone, but
you were simply trying to think through how you might deal with
the concerns of the other people in this discussion, who, by the
way, I would think we would say are defending things that if you
don't hold dear, you ought to hold dear.
The question is: What are the kinds of moral boundaries apart from
questions of safety or letting the patients have what they want?
And I could give you some lurid cases to try things out, but I'll
leave the question general at first.
Whereas it seems to me Richard Doerflinger or Bill Kristol or Andrew
Kimbrell, the question might be put in a different way. We now have a
very awkward situation where this whole area of reprogenetics has not
really been subjected to federal scrutiny or regulation except
indirectly through safety and efficacy criteria of the FDA or IRBs that
govern research proposals involving human subjects.
We don't have it, in part, because at least some of the values that
are of importance to people suggest that to suggest that this practice
be regulated is to countenance it in the first place, and that we
refuse to do.
So it does seem to me that for the first group of people who are
regulation-shy, the question is: in the absence of regulation - I
guess let me make it two questions.
What kinds of moral boundaries would you impose upon yourself or your
scientific colleagues or your industrial colleagues, and are you
prepared to enter into a discussion with people outside your community
to seriously discuss what those boundaries might be and actually live
by them as a result of the political process?
Because if I might correct Mr. Werner, this isn't just wishing and
dreaming, thinking and dreaming or inquiring. There are deeds here.
There are deeds involving human materials and human subjects, which
means that you're in the realm of action and not just thought.
And for the other side, what's the cost of doing nothing in this
area and leaving this area completely unregulated, the sole benefit of
which is you do not expend public funds and do not give public sanction
to an area of research that you regard as deeply morally questionable?
It seems to me both sides here - I would like to lean on both sides in
this discussion as the Council tries to think about our regulatory
difficulty and see what you might have to offer.
If you wouldn't mind, if I could address the first question to the
scientists, the BIO people, and then the other question to the other
three of you.
Maxine Singer, please.
DR. SINGER: I'd like to make two points, Leon.
First of all, I don't think it's appropriate to describe the
current situation as being without any limits. It is impossible to
carry out research with embryos or with fertilized eggs in dishes or
with blastocysts with federal funding, and that means that most of the
research that could be done cannot be done because most scientists in
the United States are dependent on federal funds. So that's a
CHAIRMAN KASS: But that research can go on in the private sector.
DR. SINGER: Exactly.
CHAIRMAN KASS: And it does.
DR. SINGER: It can go on in the private sector, and it goes on now
without any restrictions or controls as I think I've pointed out,
and I believe, and I think that there's good evidence for this,
that most people who thought about this in the scientific community
understand that there ought to be controls on this kind of work.
But at the present time we have no controls, and most of the scientists
in the country can't do their research, and therefore, they're
not interested in discussing how they might do it or regulations or
controls because they can't do it anyway. So that's -
CHAIRMAN KASS: But let me put it the other way, Maxine. I mean, it
seems to me the argument seems to be, give us the money and then
we'll figure out what regulations -
DR. SINGER: No.
CHAIRMAN KASS: Whereas -
DR. SINGER: Not at all.
CHAIRMAN KASS: But I'm simply asking you,
quite apart from whether the money is there, so that I understand
when we start to fund this research that there might be certain
kinds of boundaries that the scientific community wants to respect
here even if they're not forced to.
DR. SINGER: First of all, I think it's incorrect to assume that
there aren't considerations about the kinds of controls that you
might put on this work. There are.
There are people thinking about it. There are people thinking about it
at the NIH. People have thought about it before. We, in fact, have
guidelines that were prepared, but are not operative.
I don't think it's true that no one is thinking about it or
willing to think about it. I think they are. But they will think more
urgently if they imagined that they could possibly carry out the
research, and I think that's quite normal.
And with respect to the second point that you raised, I tried to say
that I thought that putting aside questions of safety and so forth,
scientists are willing to reflect societal values in restrictions and
control on research, so long as the societal values are very widely
held and there's wide agreement about that.
And I think one of the problems in the current situation is that we
don't have that kind of wide agreement. And I gave the Congress,
just as an example, one piece of evidence for the fact that we're
stymied over what appeared to be irreconcilable views.
CHAIRMAN KASS: Well, thank you.
Michael Werner, please.
MR. WERNER: Well, I think a couple of things.
First of all, I do think that, by the way, protecting human subjects
in research in many ways is about dignity, and I think — so
I wouldn't make quite the dichotomy you made.
I do think that's an important thing, and it is about the dignity
of patients and about people involved in research.
And then as to the other part of your question, our companies have
essentially in various contexts called for ethical review of our work.
The one I'm thinking about actually has to do with protecting human
subjects, which is - It came about in the debate about HIPAA and
privacy regulation, where our industry essentially took the position
that even research that was not covered by Institutional Review Board
review, which is, of course, at least in part an ethical review of a
protocol, should, in fact, be overseen.
So I think that's one issue, one time. Also, there's a moratorium
on germline gene therapy, genetic modification of the germline in
the scientific community now which is something we certainly support.
We certainly support other legislation and regulations that have to do
with use and disclosure, for example, of genetic information and, of
course, a ban on reproductive cloning.
So I think there are situations where we've either accepted
oversight or accepted limits on how far research should go or how it
should be conducted to ensure that it's done ethically.
CHAIRMAN KASS: Would you like to comment?
MR. MANGANIELLO: You know, I'm neither an economist, to talk about
goods and services, nor am I a scientist, nor am I a regulatory
lawyer. I'm just an advocate for patients.
But I was raised with a certain set of values by my parents, who were
raised with a set of values by their parents, and I think our
scientists in many ways - if you're asking in lieu of anything in
terms of self-regulation, I think that we aren't a nation of mad
scientists. I think we're a nation of people like Maxine Singer.
I attended the ISSCR meetings that are happening here in the city right
now. Probably 500 of the most brilliant stem cell researchers in the
world are gathered here in the city right now, and in lieu of a
regulation, they had an ethics panel with great thinkers and religious
leaders, and the order given to the scientists was: We need to start
So I have all confidence that in lieu of regulation, which we look for
and are hoping is going to happen through the federal government, that
our good scientists will hopefully regulate themselves.
CHAIRMAN KASS: Let me follow up just one on this side.
There are a couple of areas in the area of sort of reprogenetics
that - let me just be hypothetical. Questions about prolonging
the gestation of human embryos ex vivo or chimeras involving
human and nonhuman embryonic material, are these kinds of questions
that you think deserve public decision? Should scientists simply
be free to go ahead and do these things on their own?
I mean, I'm trying to pick certain kinds of things which are out
there which are being explored. The public doesn't even know yet
that they ought to have an opinion about these matters, and we're
going to wake up one day if the profession doesn't somehow say to
itself, "Look. You know, these things are coming. Maybe we
should watch our step here," and as in the case of germline
modification where I think the objections are at the moment primarily
those of safety at least to begin with. There is, it seems to me, for
the time being agreement.
But could you take it one step further if I offered those sorts of
things? Are there people talking about that as opposed to certain
kinds of large things like respect of human autonomy? But to dig in
really in this area and say, "Here are things that are coming
along the way. We're not going to do it until we bring this
question to the larger public and find out what the public wants done
DR. SINGER: I'll make a comment about that. As I think you and I
have talked about this before, I don't think that anyone knows that
you can clone, do reproductive cloning, on a human.
CHAIRMAN KASS: Right.
DR. SINGER: The latest information has to do with a description of at
least one of the explanations why attempts to clone non-human primates
has not worked, and it's a complicated biological explanation.
So we don't, in fact, know. We know that our nearest neighbors so
far have not been amenable to the techniques that gave rise to Dolly
and other cloned animals. So we don't know whether that would
So for scientists involved in that kind of research to be worrying
about the modification of such cloned blastocysts or whatever you want
to call them, when they don't even know that the whole thing will
work, it's just not likely, and I don't think it's because
they would shy away from it. They haven't shied away from a lot of
But my colleagues are very much here and now, and we worry about what's
here now, and that's very far- fetched. It's a bit like
science fiction at the present time. So nobody is likely to be
worrying about it a lot, but they will worry about the other kinds
of things that we talked about.
MR. WERNER: Yeah, if I could echo that. It's similar to what I
was going to say, and I think there's also a little bit of a
chronology question, which is, you know, are you suggesting, sort of,
things don't happen until there's a public vetting and some
kind of societal, maybe, consensus or are we saying that sort of as
things progress and as research moves forward and if these things
become more real, then there should be some public discussion about
I think, speaking for our scientists, I think they would agree with
what Dr. Singer said. And also having said that, I think, you know,
public discussion, public awareness about ethical issues as research
goes forward, I think is important and I think our industry does, too,
and so we certainly wouldn't hesitate to participate in discussions
about the ethics of certain research.
But I think for some of the things that you mentioned and things like
that that are so far out there, for a lot of our members it does
have a little bit of a, you know, science fiction quality which
is, you know, it's way out there. Is that happening in - Where
is that happening? How many people are doing it? Is that something
CHAIRMAN KASS: Okay. Let me turn to the other - Janet, sorry.
DR. ROWLEY: Let me just intervene here because I'm concerned about
both some of the questions and also some of the comments. I think
it's extraordinarily important to emphasize, firstly, in the report
of the National Academy of Science published in September 2001, and I
quote, the academy said, "The panel stresses that a broad ethical
debate must be encouraged so that the public can be prepared to make
decisions about these issues."
So to say that scientists have been trying to cut off debate is, I
think, not a fair statement of the situation.
And I again emphasize that it was the scientists who recognize
the potential problems with recombinant DNA technology and who themselves
declared a moratorium in 1973 and developed what became the Recombinant
DNA Advisory Committee, the RAC.
I think both the academy and all of the scientific reports that have
taken place have all said that this must take place in the context of
appropriate, careful review for the science as well as the safety and
the ethical issues of any kind of research that went forward.
So, again, to say that scientists are running away from and trying to
avoid regulation is not a correct statement of the facts.
CHAIRMAN KASS: Could I turn the other question around to see if I
could get the response before we leave the scientist side of it?
Could I get a response on the other side? And then Michael will follow
up. Richard Doerflinger, Bill Kristol, Andrew Kimbrell, a question to
Right now we have nothing, relatively speaking. We have certain
restraint having to do with the absence of funding, but otherwise
things proceed as people wish, and I'm not suggesting that there
are mad scientists or rogues, but there are things that are proceeding
that affect all of us, and they proceed in private places, and
that's partly because people don't want to countenance this
activity sufficiently to see it brought under regulation.
Is that a problem?
MR. DOERFLINGER: Well, I think you might be understating
what's happening in policy circles, because certainly regulation
of privately funded research has generally been a matter for the
states. The federal government has in the past gotten into it mainly
by way of federal funding.
And in the states a number of things are happening — some
new laws against research in which embryos are destroyed; some new
bans on cloning. The bans that have been passing in the past year
or so are chiefly complete bans on cloning in Iowa, Arkansas, North
Dakota, and so on.
I think the area for even federal regulation is fairly broad,
and I think of the restrictions that could be placed by the federal
Patent and Trademark Office on patenting human organisms. Can we
I believe I've seen a letter from BIO to a member of Congress
saying that BIO is against patenting human embryos. A point of
There are opportunities for the FDA and other federal agencies
to use the interstate commerce clause to look at th interstate trafficking
engaged in by the fertility industry. The ways in which success
rates are hyped to couples, the ways in which first women are superovulated,
then multiple embryos produced, many frozen without informed consent
from the parents, many parents left wondering after the fact, "why
didn't I think about this beforehand, about the fact that I
now have five or ten or fifteen frozen embryos?"
There are regulations in Louisiana based on respect for the life
of the embryo that limit some of these practices.
There are laws in Europe that limit, for example, embryo freezing.
There is a move towards freezing unfertilized eggs instead of the
already conceived embryo, which somewhat reduces the ethical problem
there. They are limiting the number of embryos that could be produced
at one time or placed in the womb at one time. There are limits
on using embryos for experimentation or on creating only for experimentation.
These are all things I think can be done at the state level, but
also things that the federal government may have a hand in, and
I think that the federal government has a role in looking into those
things even without funding any of this. I think the new documentation
on increased birth defects from IVF is a cause for federal agencies
to look at IVF, and see whether it is being oversold unnecessarily
to couples who may benefit from far less radical procedures that
don't pose these risks of increased birth defects.
But I think the range of possible regulation is available. I
think that any road into that regulation that starts by saying the
first thing we have to do is contradict the longstanding congressional
judgment from 1996 against federally funding research that destroys
embryos, is going to be a nonstarter. I don't think that's
the way to show your moral high ground to start regulating the industry.
CHAIRMAN KASS: Either of the two of you want to comment on this?
MR. KIMBRELL: It's a very important question, and a difficult
one. I do have to just spend 30 seconds saying some of the examples
you were giving as far as patented embryos or human fetal organs in
animals, these are happening. They're not science fiction.
They're science facts.
So you were actually not bringing up a hypothetical, as you probably
know, but actual facts, and scientists are working with those, and to
my knowledge haven't questioned the ethics of those in any
published journal I've seen.
It's very instructive if you go back to 1987. A firm called Hana
Biologics out of Alameda, California decided to try and get FDA
approval for fetal organs as medical devices. Which allowed them not
only, of course, to patent these devices, but to sell them.
That was a fascinating moment actually in sort of reductionism, and
particularly giving a legal definition of fetal organism as medical
devices. So we filed a petition with Dr. Otis Bowen, who was running
HHS for the Reagan administration, and believe it or not, the HHS even
in that administration said, "We actually think that they really
should be regulated as medical devices, and that that's
We were concerned with that and threatened them with litigation,
and they kind of retreated on that. And then we went to Senator
Gordon Humphrey, and we had exactly the kind of conundrum you're
talking about, Mr. Chairman, which is that Senator Humphrey, in
light of his pro-life constituents, said, "Wait a minute.
If we say," which is what we were asking him to do, "if
we add fetal tissue to the Organ Transplant Act saying you can't
sell it, then a lot of our constituents are going to say that doesn't
make it right because we don't think it should be used at all
because we're pro-life. We don't think that should be something
we should use, aborted fetuses for transplantation."
We went to Senator Kennedy's office, and he said, "Are
you kidding me? If we elevate fetal tissue to the level of other
human tissue protected from sale under the Organ Transplant Act,
couldn't that be the beginning of the diminishment of Roe
And I said, "Now, wait a minute. If both of you guys succeed,
we're going to have an open sale of fetuses in the United States
where economically disenfranchised women are going to be selling
fetuses to the highest bidder," and it wasn't a hypothetical
because that was during the middle of the surrogate motherhood issue,
and we were representing some of these surrogate mothers where they
were doing that with babies. They are actually...So this wasn't,
Finally, actually I'll give Vincent Ventimiglia as a
wonderful activist on the Hill and who was working with Senator Gordon
Humphrey then. He got all of the sides to agree that you have to give
up on this position if you're going to have adequate regulation.
If we're not going to have the sale, everyone is going to have to
give a little.
And everyone did give a little, and that was passed in 1988. So
there's an example of where it can work.
And in this regard, again, the Davis v. Davis case, and again,
I'm speaking now not as an ethicist. I mean, was it Thomas Aquinas
who said that abortion isn't murder; it's frustration of
These are very difficult questions, which an administrative law lawyer
has very little grasp on. I find them fascinating, but a little
knowledge is a very dangerous thing.
But the one thing I do know a little bit about is public policy, and I
know that in this current context, for example, in cloning we are at a
deadlock exactly for that reason, and I could dispute what Dr. Singer
was saying about, you know, the regulatory aspect of that. We can save
that for another time.
But I do think that the Davis v. Davis case should be of
interest. I'm not saying this is something I personally agree
with, but I think it might be important as a context here.
The Davis v. Davis case was an argument about the disposition in
a divorce case of embryos. Right? They had frozen embryos. During a
divorce does Mom get them or does Dad get them? This is the fight,
And they went to the lower court. It was a pro-life judge, and he said
these embryos have the legal status of people. We can't treat them
as property in a divorce settlement.
The husband appealed because that wouldn't have worked for his
side, and then the appellate court said the opinion is completely
invalid. It violates Roe v. Wade, and these embryos are merely
property. They're not different than hair, semen, blood, any other
Well, the wife appealed and it went to the Supreme Court of Tennessee,
and they came up with sort of a Solomonic thing, which again I suggest
would be of interest to this Council, which is they said, and I'm
quoting now, "Pre-embryos are not, strictly speaking, either
persons or property, but occupy an interim category that entitles
them to special respect."
And this has been called a special entity. By the way, the State
Supreme Court of Massachusetts and others now have followed this.
And the idea of the special entity that they talked about is that this
is, again, a human life in potential, an adult human life in potential
with a trajectory that, therefore, differs from hair, differs from
blood, because this could become a human life. That is something
absolutely different from any other biological product. It should be
distinguished from those products and given respect.
Now, that's the context for discussion, Mr. Chairman. It's not
the answer to what you then do with that context. I suggested in my
remarks that I think some of the things you need to do is if this is
human life in potential, this special entity certainly shouldn't be
sold. It shouldn't be patented, and I think it certainly deserves
respect and should never be created solely for its own economic
exploitation and destruction like some other product.
I think those would be minimal things that this special entity status
would grant it.
But perhaps that special entity status is a way of bringing some of
the ethical norms into this, not in a way that many of us would
morally agree with on one side or the other, but to provide a context
to break some of the ideological deadlock that I think you correctly
talked about and that certainly is currently blocking our legislation
on cloning from passing.
CHAIRMAN KASS: William.
MR. KRISTOL: The ideological deadlock in cloning hasn't got much
to do with funding or regulation really. I just think there are
legitimate arguments about bans, moratoria, regulatory structures.
There are legitimate arguments about funding mechanisms as a matter of
public policy, whether the federal government or state governments, I
suppose, should or shouldn't fund various medical research. Those
are debated every day, week, month and year in Congress. They're
not necessarily hinged together.
We regulate. We legislate against, and have huge regulatory structures
to govern industries that do not get federal funding or don't
directly get federal funding, and conversely, we fund things that we
then regulate extremely lightly, you know, just to make sure that the
money is used for whatever it's supposed to be used for, but with
very little substantive regulation. You know, college student loans
would be an example of that.
So I don't think there's much to be gained frankly from sort of
a complicated, alleged tradeoff of funding and regulation, though I
mean if someone wants to make a precise argument about what we're
talking about, I guess I'd be interested in it, but it's not
the issue on cloning.
And if you look, it seems to me maybe it would help just a second to
separate two things. There are two, it seems to me, sets of issues
that have come up in our discussion here in this panel. There is the
current situation and whether legislation should reform, restrict,
change the current practices that go on. We have right now, as I
understand it, selective reduction of embryos in IVF clinics that is
entirely legal and unregulated. Is that a good thing or not?
This is not a "Brave New World" issue. It is not a
scientific progress issue. It is a current practice and one's
judgment on it, I suppose will depend on one's judgment about how
much respect one wants to give nascent life or the embryos.
So you can't avoid an embryo debate on a lot of these issues
because what is being debated is how much weight to give the embryo.
It's that simple.
So that debate should be had. One could then raise constitutional
issues if one tried, for example, to ban this, but that could be argued
out like any other piece of legislation before the court.
So there's sort of the current situation, which I think does
largely depend on how much status one has to give the embryo. The fact
that the society disagrees on that doesn't mean it shouldn't be
debated. We disagree on all kinds of things, and that's why we
We didn't agree on civil rights in 1957 or '60 or '64, and
we didn't agree on the war, and we debate all of these things.
The second set of issues is different, which I think germline
modification, as Dr. Singer suggested, is perhaps a good embodiment of
that, but there it seems to me actually from the point of view of
democratic theory or democratic practice, frankly, aren't
acceptable that any group no matter how well meaning, well educated,
and public spirited, through self - I'm not saying that Dr. Singer
was suggesting this, but if this were to be the model for the future -
through self-regulation or voluntary regulation would resolve an issue
of this magnitude, I'm not even sure what I think about - I'm
not so sure I think all germline modification should be banned.
But in any case, if we don't as a society not only get to decide on
this, but have to decide on this, then what are we? Then we're
leaving to professional groups the most fundamental decisions about the
future of the human race?
I can't choose to delegate certain things as we often do to
professional groups under some general legislative guidance.
So there are the kind of current issues, which I think are legitimate
issues for debate. Are we morally behaving as well as we should?
And I think there I'm not happy with the status quo, but others can
defend it and we can argue that out. Many of those do depend on the
status of the embryo.
And then there's the sort of future genetic revolution sorts of
issues, but there I think you absolutely need to have public policy,
and I don't think anything there hinges on funding. That's
just a question of what we're going to permit and what we're
going to encourage, and what we're not.
CHAIRMAN KASS: Thank you.
Michael Sandel and then Gil.
PROF. SANDEL: I'd like to pursue and push and sharpen Leon's
question, and to do so, first of all, I think Bill is right. We should
put the issue of funding to one side for the moment. I understand, and
I'd like to direct the question to Mr. Doerflinger.
I understand you don't want to regulate practices you object to at
the price of federal funding. So let's put that issue aside.
What I'd like to explore and I think was the spirit of Leon's
question was not the tradeoff between regulation and funding, but an
ethical dilemma about regulating a morally objectionable practice.
There's no federal regulation on ART in this country or on embryo
research or on reproductive cloning, federal regulation restriction,
and one of the reasons for that is not just because the libertarians
and the free marketeers and the scientists and the patient advocates
are so effective.
One of the reasons is that those who object in principle to those
practices hesitate to support regulation out of a concern that to favor
regulations of those practices would be implicitly to condone them, to
confer legitimacy on them.
So it's not funding, but it's that feature of the hesitancy
that I want to explore.
So the question is: Is it ever justified, do you think, to regulate a
practice that you consider to be morally objectionable, or does that
carry the moral taint of complicity, that you become complicit in the
So, for example, would you favor a federal regulation banning the use
of PGD for non-therapeutic sex selection, or would you not favor that
out of concern that you consider PGD morally objectionable to begin
with, and to ban that particular application of it, though it would
prevent some wrong, would implicitly condone underlying wrong?
Now, I can imagine one possible reply might be, no, we wouldn't
want to ban that because we consider it so wrong any more than we would
want to participate in regulating slavery, regulating the worst abuses
of slavery, because that very regulation would implicitly accept and
make us complicit in the underlying practice, the evil of slavery
Yes, we might be able to eliminate some suffering, but at the cost of
endorsing implicitly the practice.
So is it more like slavery or is it more like another case? Consider
prostitution. Where one might consider prostitution morally
objectionable, but in a case of an epidemic of sexually transmitted
disease, the question might arise: would you favor regulating
prostitution for its health effects to alleviate the epidemic even
though that might implicate you morally in condoning a practice by
recognizing it publicly?
We're not talking about federal funding of prostitution.
We're just talking about the price you pay of a certain implicit -
So the question is: are these -
CHAIRMAN KASS: Go ahead.
PROF. SANDEL: So with those two, with the slavery case, is it more
like slavery or is it more like prostitution? And here's the case
I'd like you to address:
German federal law limits the number of embryos that can be created in
IVF. Would you favor federal regulation to restrict the number of
embryos that can be created in any given cycle in IVF? Would that be
more like slavery or more like prostitution?
MR. DOERFLINGER: I might surprise some members of
the council by saying even if it is like slavery, one could morally
seek to regulate it if that's the best we could do. That's
what Abraham Lincoln did, and his whole campaign theme was "I
want to keep slavery from spreading to the territories. Leave it
where it is. Don't expand it."
And of course, the abolitionists were very distrustful of him
because of his middle position.
Let me answer your question in two ways. One is that I think
there's a discussion of this very point on page 15 of our prepared
statement, which goes into this and provides some sources.
I like the word "hesitation" that you used, for this
reason. It's not immoral, if it is the best that one can do,
to regulate against the most egregious abuses of an industry, even
if the industry itself is morally objectionable.
A single example for the Catholic Church would be that we have
supported clinic regulations at abortion clinics, to at least limit
the damage done by that industry. Sometimes those laws only limit
the damage that might be done to women and not to the unborn, but
it is still worthwhile to prevent damage to the woman, and I don't
think that those regulations and informed consent requirements,
waiting period, parental consent requirements, and so on, condone
the underlying practice.
There are some pro-life groups who disagree with us on that, but
Catholic teaching is pretty firm in saying that if it is the best
that can be achieved, you may limit the worst and most reachable
abuses and then build for a more just society in the future.
The reason why there is hesitation is not that it's immoral
to support such laws, but because one has to support them in a certain
context. Otherwise one creates scandal by leading people to think,
even if it's a misimpression, that that is one's ultimate
goal or that is one's ideal. That is one reason why, having
raised some particular points and particular deficiencies in current
law at the end of our document, the Bishops, Conference says, "We'll
be very interested to see what you produce that we can react to,"
to see what range of regulation and law the Bishop,s Conference
can support, now that it has been offered and is the best that there
is a consensus can be done.
Does that make —
PROF. SANDEL: Yes. Just a quick follow-up.
Would you extend that line of reasoning to support a law that banned
reproductive cloning by outlawing implantation of the product of SCNT?
MR. DOERFLINGER: That is very different, because we
actually don't think that implantation in a womb is or should
be a crime. It's actually what embryos have been doing for
many centuries, which is why any of us are here.
It is a completely misdirected law in our view. What it does
is, it allows the cloning procedure — which I know I'm
not supposed to call "cloning," I'm supposed to call
it SCNT whenever people want to do it, but it's cloning. It's
the cloning procedure. You know, those whom the gods of science
would destroy they first call by an acronym, but SCNT is cloning.
So you do the cloning procedure, without meaningful limit, and
then you regulate the consequences, in a sense, of that wrong procedure
by doing a second wrong, which is to make it illegal for that embryo
So in our view that's two wrongs claiming to make a right.
It's worse than no law at all, and that's why the impasse.
If that were simply a partial law that regulates against the worst
evils, we could in principle support it. But we don't think
the birth of a baby is an evil. We think the cloning is the evil.
CHAIRMAN KASS: Gil Meilaender.
Just so that people know where we are, we started a little late. You
took some extra time for food, and people want to get in here. Ten
minutes and we'll break. We'll run five minutes over here.
Gil Meilaender and then Robby.
PROF. MEILAENDER: Well, there are so many things by now actually that
one might want to talk about, but I want to say a word about something
that Dr. Singer first brought up, the National Academy's report on
cloning, and then Janet quoted from it, because I don't think
enough was said about it by you, Dr. Singer, to sort of get to all of
Let me say what I think the "more" is, and you may wish to
react. As you point out, the Academy report supported a prohibition of
what it called reproductive cloning, and it said that on safety
grounds, given the results in animal studies, that prohibition was
warranted, but that even if at some point those studies became more
promising, there should be a wide public debate on the moral and
ethical questions before proceeding with what it called reproductive
In the case of what it called nuclear transfer to produce stem cells,
but which we can just call research cloning here, it was prepared to
support going ahead because there weren't safety questions of the
same sort. We understand that. If you're not going to implant the
embryo certain kinds of safety questions can't arise.
But it did not say - and this is the thing that you left out
— it did not say that a wide public debate on the moral and
ethical questions should take place first.
And it seems to me it's important to ask why not. If in the case
of what's called in the report reproductive cloning, even were
it safe, a wide ethical debate in the public should take place before
proceeding. Why in the case of what we'll call research cloning,
even if it doesn't raise certain sorts of safety questions,
should that same public debate not take place before we simply assume
that we may proceed with it?
It seems to me that that's the question that needs answering and
that you didn't get to, and I'd be glad to hear you comment on
DR. SINGER: So I can't resist just saying that I'm going to
talk about nuclear transfer. I think that abrogation of the word
"cloning" in general has been a big problem. It used to have
a completely different meaning for those of us in biology, and so I
don't talk about "research cloning," but I understand you
when you do, for sure.
So I think that one reason why that wasn't said in connection with
nuclear transfer is that there was not a sense in that panel that that
raised any ethical or moral issues that would be debated.
PROF. MEILAENDER: Don't you need to broaden your horizons at that
point? I mean, if the burden of your testimony to us has been that
scientists are interested in these questions, that they don't want
to short circuit such debate, that they're interested in having it
take place, I mean, how could one suppose that this was not a live
DR. SINGER: Well, it's very clear that the question about
reproductive cloning raises issues that are moral and ethical issues.
But I would need to turn it around and ask you to define for me what
you think the moral and ethical issues are for nuclear transfer when we
have no idea in transferring a human somatic cell nucleus into an
enucleated egg whether there's even the potential for this to
become an organism.
PROF. MEILAENDER: If I even embarked on that, the Chairman would want
me to stop, but I don't think it's crucial for me to try to
sort out those things right now, but simply to say that I simply report
that I have a hard time taking seriously the report that scientists
want to engage in widespread discussion of the ethical issues if
you're telling me that you don't even find here a moral
I just have to report that to you.
DR. SINGER: Well, unfortunately I think that tells us something about
just how difficult these disagreements are and why they are so
difficult to resolve.
Dr. Rowley rehearsed for you various steps that the scientific
community has taken over many years, and there are many more examples
where scientists have certainly been willing and have, indeed, taken
the initiative to face issues where there were clearly issues among
which even scientists disagree because they are people like everyone
But I think in this particular instance, certainly speaking for me
personally, I don't understand what the issue is.
CHAIRMAN KASS: Dr. Singer, I just point out that the Council report
with one exception, however people came down finally on whether to
favor cloning for biomedical research or not, all members but one
thought that there was a moral issue and that the other side had
something to defend, and I commend Chapter 6 of our report to you and
your colleagues, a chapter which was approved by everybody.
DR. SINGER: So, again, I'm speaking just for myself.
CHAIRMAN KASS: Of course.
DR. SINGER: I have read the report. I did not understand those
CHAIRMAN KASS: Come to dinner. We'll work it out.
DR. SINGER: Every time I have dinner with you, I get in more trouble.
CHAIRMAN KASS: We won't tell anybody.
Let's me see. Robby.
DR. GÓMEZ-LOBO: One sentence.
CHAIRMAN KASS: Yeah, please.
DR. GÓMEZ-LOBO: Let me try in one sentence to explain the moral
Dolly was created by, generated by somatic cell nuclear transfer, and
she was a sheep. A human being generated by somatic cell nuclear
transfer would be human.
DR. SINGER: Well, I don't disagree with that if you make a whole
organism, but we don't know that you can make an organism, and
moreover, I've made it very clear that both personally and in terms
of the COSEPP report, we believe that trying to do that should be
banned. No question.
DR. GÓMEZ-LOBO: No, I was referring to the embryo. You get a human
embryo through somatic cell nuclear transfer with a human ovum and the
whole set of 46 chromosomes.
DR. SINGER: And that's where we part.
DR. GÓMEZ-LOBO: I'm sorry?
DR. SINGER: And that's where we part.
DR. GÓMEZ-LOBO: Well, that's what generates the moral problem. I
mean, even before our ways part, that's where the problem lies.
CHAIRMAN KASS: We at least see where the discussion has to go.
Robby George has the last question and then we will break, please,
and let's try to keep it modest.
PROF. GEORGE: Okay. I'm going to try to set a -
CHAIRMAN KASS: Just no 30-minute cross-examinations.
PROF. GEORGE: Okay. Before turning to it, just to make sure I
understand, and I won't argue with you, Dr. Singer.
PROF. SANDEL: You did understand.
PROF. GEORGE: Just to make sure.
Are you arguing that it's unclear whether we have an organism at
the blastocyst stage when that blastocyst came into existence by
nuclear transfer, although we would be clear that we have an organism
at the blastocyst stage if that organism came into existence by gamete
Is it the nuclear transfer that generates the doubt about whether we
actually have an organism or is the position indifferent as to whether
the means is nuclear transfer or gamete union?
DR. SINGER: So for any normal gamete union we don't know if we
have an organism?
PROF. GEORGE: That's what I'm wondering.
DR. SINGER: There's a certain probability that we have an
organism, and we don't actually have as good numbers as we would
like about what percentage of fertilized eggs, eggs fertilized in
vivo in a normal way, what percentage of those actually make it.
We know that it's probably not more than 50 percent. Okay. So
PROF. GEORGE: Yeah, but my only question, just for clarification is -
DR. SINGER: Well, you called a blastocyst an organism, which I would
PROF. GEORGE: Whether it's gamete union or nuclear transfer.
DR. SINGER: Right.
PROF. GEORGE: That's all I wanted to know. So either way it's
DR. SINGER: So either way -
PROF. GEORGE: It doesn't have to do with it being nuclear
transfer. It's just however it came into existence, you're not
going to call that an organism.
DR. SINGER: Either way, either way you don't know for any given
blastocyst what the probability is that it will become or has the
potential to become a full organism.
PROF. GEORGE: Okay.
DR. SINGER: And what we do know is that those that are made with other
mammals other than humans, the probability of becoming a complete
organism when it's done by nuclear transfer is very low, and for
many mammals we have very hard data.
PROF. GEORGE: Okay. I think I understand the position. Thank you.
A question for the two Michaels. It's something that Bill Kristol
raised, and I'm grateful for the opportunity to raise it with you,
and I really would appreciate your candid reply to it.
Again, I won't argue with you. I just want to know sort of where
you stand on this.
Mr. Kristol raised the issue about a kind of moving of the goal
posts that went on. Bill Hurlbut has raised it in the Council before.
In the run up to the President's stem cell decision of August
2001, there were a number of people both in the political field
and among scientists - now everyone is just speaking for himself,
I'm not accusing anybody for speaking for any organization -
who advocated, who defended the change in the law to permit funding
of embryonic stem cell research and who at the same time said that,
of course, they would not be in favor of creating embryos by whatever
method for research involving their destruction, but they wanted
to use embryos that would otherwise be wasted, as they would characterize
Well, then it was months later when some of these same people changed
their position in favor of creating embryos for research.
Is it, therefore, fair - isn't it fair - for those of us who are
critical of the position that you've adopted here to at least ask
and get an answer to the question: What is the limit of what is being
Is it not fair to ask: Are you saying that you're in favor of
embryo research and funding on embryo research ought to be permitted to
the blastocyst stage, to the 14-day limit, implantation?
Is it possible for you to take a firm position on exactly where you
would limit funding for embryo research? What degree of development of
nascent human life would constitute the point at which you would say,
you would agree, well, no more research then, no implantation, for
example, for purposes of research?
MR. WERNER: I have an answer. First of all, there was a debate in
Congress, as you probably know, in 1998, I guess, also about whatever
we want to call it, therapeutic cloning, cloning for research,
whatever, and during that debate my organization took the position
we've taken subsequently, which is that, you know, we thought the
research should go forward.
So I guess in terms of the first part of your question I feel like we
were clear, you know, pre-isolation of the human embryonic stem cell
and the debate within the Bush administration and all of that that, you
know, therapeutic cloning was something that we thought should be
allowed to continue.
So I feel like we've been on record about that for a while. So I
don't think we were one of the organizations that you referred to
which said what we were saying, this was okay and then, oops, we've
moved the goal posts now a little bit; now X.
You know, we've been clear all along that we thought this research
would go forward.
And then in terms of the limits, I mean, you know, I think the 14 days
is the one that we feel comfortable with.
PROF. GEORGE: Is that the position of BIO?
MR. WERNER: Well, I'll put it this way. We were supportive of the
legislation that contains that provision. So I can't tell you that
we've sat around and said, "Gee, should we allow federal
funding for 14 days or 20 days?" You know, I haven't had that
kind of conversation.
But I do know that when we have talked about it, we have talked with
our researchers in our companies, and we have talked about the various
proposals, and especially we have a lot of our folks who are operating
in the U.K., and we are comfortable with the 14 days, and as that as a
PROF. GEORGE: So if there were promising lines of research that would
require implantation, you would not be in favor of pursuing those lines
MR. WERNER: Yes, that's correct.
Having said that, I will be fair and say I think that - No, I think
that it's fair to say that, you know, science advances, ethical
thinking advances. We constantly are reexamining our views and our
principles. I think it's okay for us to say we've said it
throughout history with new technology. It's okay to say, you
know, this is something that's troubling, but now, you know,
umpteen years later we for some reason feel like, you know, we can
reexplore whether that's an appropriate limit.
I will tell you that I have no view that, sure, we're going to
move the goal post. I would say our view is 14 days because the
primitive streak seems like an appropriate boundary, and that's
where we are.
PROF. GEORGE: So for you that's a principal
CHAIRMAN KASS: For the time being.
MR. WERNER: Yeah.
PROF. GEORGE: Well, that's the question.
MR. WERNER: Now. That's correct. No, look. And you know, for
what it's worth, I understand that that's frustrating, and
that's why I sort of hesitated to say it, but I do think that
that's where we are, and I don't know that it's appropriate
to say that limits on scientific research should stay static over the
course of decades as things change.
PROF. GEORGE: But isn't the status of the
embryo something one has got to have a principal position on at
some point? The status of developing human life, there's got
to be some point at which you say as a matter of principle we're
not going to experiment on human beings at this developmental stage.
PARTICIPANT: I thought you promised not to interrogate.
PROF. GEORGE: Oh, sorry.
CHAIRMAN KASS: Yes. Do you want to comment?
Look, thank you for a really wonderful panel, spirited and frank and
Council members, we start tomorrow 8:30. Please review the discussion
document and you have at your place the information regarding
The meeting is adjourned.
(Whereupon, at 5:41 p.m., the meeting was adjourned, to reconvene
at 8:30 a.m., Friday, June 12, 2003.)