UNITED STATES OF AMERICA

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THE PRESIDENT\'S COUNCIL ON BIOETHICS

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THIRD MEETING

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Thursday,

April 25, 2002

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The Council met at 8:30 a.m., in the Dewey Rooms of the Hilton Crystal
City, 2399 Jefferson Davis Highway, Arlington, Virginia, Dr. Leon Kass,
Chairman, presiding.

PRESENT:

LEON R. KASS, M.D., PH.D., Chairman

ELIZABETH H. BLACKBURN, Ph.D., Member

REBECCA S. DRESSER, J.D., Member

DANIEL W. FOSTER, M.D., Member

FRANCIS FUKUYAMA, Ph.D., Member

MICHAEL S. GAZZANIGA, Ph.D., Member

ROBERT P. GEORGE, DPhil, J.D., Member

MARY ANN GLENDON, J.D., Member

ALFONSO GOMEZ-LOBO, J.D., Member

WILLIAM B. HURLBUT, M.D., Member

CHARLES KRAUTHAMMER, M.D., Member

PAUL MCHUGH, M.D., Member

GILBERT C. MEILAENDER, JR., Ph.D., Member

JANET D. ROWLEY, M.D., D.Sc., Member

MICHAEL J. SANDEL, D.Phil, Member

JAMES Q. WILSON, Ph.D., Member

C-O-N-T-E-N-T-S

Session 1: Stem Cells 1: Medical Promise

of Embryonic Stem Cell Research

(Present and Projected)

Dr. John Gearhart 10

Session 2: Stem Cells 2: Medical Promise

of Adult Stem Cell Research

(Present and Projected)

Dr. Catherine Verfaillie 88

Session 3: Stem Cells 3: Ethics of Human

Stem Cell Research

Dr. Gene Outka 171

Session 4: Human Cloning 10: Ethics of

Cloning for Biomedical Research 247

Adjournment 315

P-R-O-C-E-E-D-I-N-G-S

(8:43 a.m.)

CHAIRMAN KASS: Well, I would like to ask Dean Clancy to officially open
the meeting, please.

MR. CLANCY: This meeting is lawful.

DR. KASS: Thank you very much. Apologies to our guests and to members of
the audience for the late start. Council Members had to take an oath of
office, which should have been administered to us before our very first
meeting.

That has been done and we are now legal in every respect. Welcome to
this, the third meeting of the President\'s Council on Bioethics. We are
expecting colleagues Krauthammer and George today, and Stephen Carter
will not be with us, and Bill May will join us tomorrow.

I would like to introduce a new member of our staff, Judy Crawford, who
comes to us as the office manager. Judy, would you please rise so that
the council members can know you. We are very delighted to have Judy
with us.

We reconvene as the debate about the cloning legislation heats up around
us, a debate that we did not begin and do not control. We are in the
midst of our own careful and thorough investigation of the ethical,
social, and policy implications of human cloning seen in its larger
scientific, medical, and human contexts.

We have chosen to proceed in a deliberate, collegial, wisdom-seeking,
mode in keeping with our charge to inquire fundamentally into the human
and moral significance of developments in biomedical science and
technology.

The most challenging aspect of our inquiry to date has been the moral
significance of cloning for biomedical research, a topic discussed for
the first time at our last meeting, and to which we return later today
in the hope of making progress and clarifying the contested moral issues
at stake, and in articulating the best possible moral arguments for and
again the conduct of such research.

On behalf of the council, I would like to thank the staff for its superb
work in advancing our inquiry, and on behalf of the staff, I would like
to thank council members for their thoughtful comments and responses. We
are in your debt.

The agenda for this meeting brings us into some new, but not altogether
unrelated, areas of inquiry. Stem cell research, a topic of our first
three sessions today.

Second, the question of therapy versus enhancement as a goal for the
uses of biomedical technology, and third, possible regulation of
biomedical technology. These topics have been selected with a view to
initiating one of our obligatory future projects, stem cell research,
and exploring two possible future projects for the council for the rest
of our two year charter.

As everyone knows, in his speech announcing the creation of this
council, President Bush charged us with monitoring stem cell research,
embryonic and non-embryonic, human and animal, in order to assess their
progress in gaining knowledge and beneficial therapies, and in due
course to offer guidelines and regulations for the conduct of such
research.

As I indicated at our first meeting, we have begun to collect data that
will enable us to describe, assess, and compare the successes achieved
with both embryonic and non-embryonic stem cells.

As we are doing this, however, it seemed desirable for council members
to learn firsthand, and from some leading researchers in the field,
about the scientific and therapeutic promise of stem cell research
present and projected; embryonic and non-embryonic.

And it also seemed desirable to explicitly begin a disciplined
conversation about the ethical issues of embryonic stem cell research.
Our first three sessions today constitute the official thematic
beginning of our project on stem cell research.

We have of course already been deliberating about some of these matters
in our discussion of human cloning for biomedical research, a topic that
first arose for us as a crucial side question of the larger subject of
human cloning to produce children,

what to think about it, and what to do about it.

This is therefore a useful juncture at which to indicate the
distinction, as well as the connection between these two topics. Many
members of the public, including many of our elected officials who are
in the process of making policy in this area, as well as some members of
the media, have conflated the issue of stem cell research and the issue
of cloning.

The issue of cloning comes first to attention as an issue of the ethics
of producing children by novel technological means, and the issue of
cloning, insofar as it has captured the public attention, is primarily
about what to think about the asexual production of new human beings who
are going to be genetically virtually identical to already existing
individuals.

And the issues there are in the first instance the questions of the
ethics of, crudely speaking, baby-making. That is quite different from
the question of the ethics of embryo research.

Virtually all embryonic stem cell research now under way, both in humans
and in animals, involve cell lines developed from embryos, whether
inner-cell mass, or from the gonadal ridge of donated fetuses, that
originate from the sexual union of egg and sperm, and very often in the
human case using excess embryos produced in in vitro clinics and in all
cases from material not produced for the sake of the research. The
question of Federal funding of this research that President Bush
resolved last summer, this was the question that was resolved last
summer, and the research in this area proceeds not only with Federal
funding under the guidelines that the President established, but also in
the private sector.

The two topics, however, intersect and overlap because cloning to
produce children necessarily proceeds through the production of cloned
blastocysts, which offer special opportunities for embryonic stem cell
and other research.

Some proposals to curtail cloning for providing children would do so by
curtailing the initial steps, thus interfering with the possibility of
using cloned embryos for research.

And this has given rise to arguments for and against cloning for
biomedical research proper. This is where the intersection can be made
explicit, and that is where we now are.

In order for us in the other project to continue to make progress, and
therefore in order to see what value added might derive from working
with embryonic stem cells extracted from *cloned* blastocysts, one needs
to know something about what it would be added to. That is to say, to
work on ordinary embryonic stem cells. And in order to see more clearly
what the ethical issues are that might come from the question of
producing cloned embryos for biomedical research, it would be helpful
for us to know something of the ethical issues of experimenting on human
embryos of sexual and not clonal origin, and of using extra embryonic
\-- using the extra embryos or fetuses not created for experimental
purposes so we can see what different questions arise here.

To help us with our scientific and medical education, we are very
fortunate to have as our guests and presenters this morning two
distinguished researchers, one who is a pioneer in isolating and
characterizing human pluripotent stem cells, Dr. John Gearhart, the C.
Michael Armstrong Professor of Medicine at Johns Hopkins University, and
the Director of the Institute of Cell Engineering.

And second a person who is a pioneer in work with human multipotent
adult progenitor cells, Dr. Catherine Verfaillie, a Professor of
Medicine and Director of the Stem Cell Institute at the University of
Minnesota.

Each of our guests in separate sessions will make formal presentations,
roughly 30 to 35 minutes, after which time we will have a chance to ask
questions about the scientific, technological, and clinical aspects of
these areas of research.

This is our chance to learn about the wonderful prospects of these
investigations. However, let me say that because our guests are here not
only as scientists, but also as our neighbors, in a morally aspiring
human community, we will perhaps try toward the end to elicit from them
their own thoughts about the ethical issues in their own work.

But the purpose of these sessions is primarily our own education about
the scientific and medical aspects. With that I would like to turn the
meeting over to Dr. Gearhart, and to thank him very much for joining us
this morning.

DR. GEARHART: I am certainly grateful to have this opportunity to share
with the President\'s Council my knowledge in a very tiny area of
biomedical research, and it is currently quite tiny, but if you read and
believe the press, it is obviously going to expand enormously.

Much has been written and much has been said about stem cells, and it
seems every morning in the paper there is some article relating to it
and continuing the debate.

In the scientific literature, we see virtually in every issue of leading
journals a paper dealing with stem cells. An age old dream I think of
mankind or humankind has been to replace damaged or diseased tissues
with functional ones, new ones, and wouldn\'t it be nice to be able if
you had a damaged liver or kidney to take one off the shelf if you know
what I mean.

And this dream I think is going to become a reality, and with some of
the advances in biomedical research, and one of the ones that we are
going to talk about today, I think this will provide the starting
material that will lead to this reality.

The concept behind cell-based therapies \-- and this is what we are
talking about here initially \-- is a very simple one, and I think that
that makes it attractive, and it makes it understandable to the public.

And that is that if there is a tissue deficit, why not just replace the
tissue. Now, it is easy to say, and it will be difficult to do, but the
concept is an easy one.

Cell-based therapy has also been called regenerative medicine, and there
are many rubrics for this today. The power of this technology is derived
from information inherent in our genes and in our cells, and the recent
isolation of these embryonic type stem cells I believe is going to
provide the enabling material as I mentioned for this to go forward.

Stem cells are going to serve several purposes, the first of which could
be as a direct source in transplantation therapies. That means specific
cell types will be grown in culture, such as heart muscles, nerves, et
cetera, and transplanted to patients for function.

Or they will be genetically engineered to do exactly what we want them
to do and transplant it to patients; or they will be used by our tissue
engineer colleagues to construct tissues and parts of organs, which
would then be transplanted to patients.

Stem cells will also be used as a source of information, basic science,
and this is really where we are at currently. That could be applied to a
patient\'s own cells, such that we could remove cells from a patient and
alter them in some fashion to produce the cell types that we want, and
then transplant them.

Or ultimately I feel that what we are going to be able to do from the
information that we are going to learn on stem cells is that we will be
able to work in vitro with patient cells to get them to perform in a
manner that we want without taking them out and putting them in culture.

This, I believe, is the future. The scientific challenges to attain our
goal of producing safe and effective therapies are formidable. It will
take the efforts of many scientists and clinicians, in a variety of
disciplines, to bring this endeavor to fruition.

Now, the stem cells that I am going to talk about today interestingly
really do not exist naturally. That is, they don\'t exist in embryos or
fetuses. They are artifacts of culture.

But we take tissues from embryos and fetuses and they undergo a type of
transformation in culture to provide these stem cells. And this source
obviously brings with it a number of ethical concerns.

I, as an investigator, who has had to cross this bridge 9 or 10 years
ago when I began this work, believe that the ethical issues are
manageable.

I also believe that it is the responsibility of scientists to candidly
and in a timely fashion present the social implications of their
research and its technological applications; to provide assessments on
reliability, and to participate in the establishment of ethical
guidelines and to work within those guidelines.

For the past 9 years at Hopkins, we have been in compliance with all
institutional, State, and Federal policies in dealing with the cells
that we work with.

It has not been easy because the landscape has changed in 9 years, and
every year there have been new concerns raised, and new issues that had
to be addressed, and I think we are keeping up with it.

I should tell you also up to this point in time that no Federal monies,
no public monies, have gone into our research effort. Now that Federal
policy has changed, we do have applications pending before the National
Institutes of Health.

I also want to point out something that may be surprising to most of
you; that in our laboratory at Hopkins that we just are not
concentrating on an embryonic or fetal source of stem cells.

We are studying stem cells from adult sources, umbilical sources, et
cetera. This is the only way that we feel that you can have a scientific
advance, and that is to be able to compare and contrast the different
sources of stem cells.

So side by side, in the laboratory, in experimental paradigms, we are
using stem cells from a variety of sources, and this is what I think has
to happen to assess which of these sources are going to prove the most
effective for any specific type of therapy.

Another thing that I want to point out to you is that the work on the
human cells, I do have the questions that came from your committee in-
hand, and many of them are asking what is the status of certain types of
work.

I just want to point out that this work has been ongoing for a period of
2-to-2-1/2 years, and although we feel that we are making progress, we
certainly are going to come up with, well, I don\'t know as answer to
some of your questions.

I just want to let you know that we don\'t have all the answers to this,
and we are very, very early in all studies of stem cells, be they from
the embryonic or adult sources.

I would tell you though that to date the work in our lab and others on
embryonic stem cells and the results of that work is certainly
consistent with the idea that this is going to prove to be a productive
line of research.

Well, it is interesting that very few people know you and what you are
about, and I think it is important to point out something. My interests,
or my research interests for decades, have been in the area of
developmental genetics and development biology.

I have been labeled as a human embryologist, and my interests certainly
are in the area of how an embryo goes from a single cell to a
multi-cellular integrated organism.

And this is where our research has been in the past 25 years, and I have
carried this a step further. We are very interested in congenital
malformations and birth defects.

I have had a program project through the NIH for many, many years
dealing with Down\'s Syndrome, and we are very interested in trying to
determine what the mechanism is that underlies many of the unusual
anatomical neurobiological consequences of this extra chromosome in
human beings.

And this is essentially how I got into this work. We wanted to have in
the laboratory a source of cells in addition that we could study at the
site or level of the impact of these extra genes.

And this obviously is a goal, along with a number of other genetic-based
diseases and malformations in the human being. So this is what led to
our getting into this area of research.

Now, I have to say up front that we are now required by our university
to reveal where our monies come from, and these are the sponsors of our
research, and there is one sitting in the middle there that I also have
to show to you that I am conflicted.

And which means that to the sponsorship of this private company, we have
received money for research, for which licenses have been negotiated
between Hopkins and Geron, and that I am a stockholder, albeit a few
hundred shares of something that is trading now at \-- and I hate to
think about it.

It is not in our possession as you know. It is held in escrow. But
nonetheless we do have this arrangement with this company. So I would
tell you that this is not the motivation, this connection.

Without the sponsorship of this research, this work would not have gone
forward over the past seven years. We are not in this business as
individuals to make money.

Well, having said all of that, let\'s talk about stem cells. The first
thing I want to give you is a little bit of a primer on stem cells so
that we are talking the same language, and you have an understanding of
where I am coming from.

Well, what is a stem cell, and basically a stem cell is a cell that has
two properties. It has a property in that it has a capacity for
self-renewal, which means that the cell can divide and produce more
cells like itself.

And it has some type or some degree of differentiative capability, which
means that it can go on to specialize into a single cell type, or it can
specialize into a number of cell types.

And in a developmental sense, if we over time at what our research has
told us about stem cells, they fall into a number of categories. Early
on in developmental practices, we have a cell that is totipotent.

It can renew, and it can form virtually every cell type that is present
in an embryo. As development proceeds, its developmental capabilities
become more restricted until we get into different lineages, specific
lineages, and its ability to divide also becomes more diminished over
time.

This has been the classical picture of development. Now, what has
happened over the past couple of years interestingly is we find that
these restrictions in developmental capability are much more plastic
than we had thought.

So out here where we thought that these cells are highly restricted,
perhaps they aren\'t so, and when you remove them from the organism and
culture them, they have capabilities of forming other cell types, and
Catherine will be talking to you about some of these issues.

Well, we are going to be talking about embryonic stem cells, and what is
it about them. Well, interestingly, we know that these cells are capable
of producing virtually every cell type that is present in an embryo, a
fetus, or an adult, except one.

And that one happens to be the trophoblast cell, which I will tell you
about in a moment. So we consider these cells to be totipotent.

They don\'t have the ability in and of themselves to form an embryo or
an individual, okay? They have this other property of self-renewal,
which basically with respect to embryonic stem cells means that they
will expand indefinitely, and grow indefinitely, and this is a very
important property.

It means that within the laboratory from a very few cells that you could
grow a roomful of these cells very easily. But there is an issue here
that we don\'t know much about, and that is obviously there is a finite
probability that at every cell division that a genetic mutation will
appear.

And there was a paper published recently that indicated that indeed this
is the case, and the types of mutation, although the mutation frequency
and the mutation rate is greatly \-- by several folds lower than in
normal somatic cells, mutations do occur in these cells, and they are of
the nature of making these cells susceptible to formation of tumors.

The uniparental disomy appears and it is a condition about which we
should be concerned. And up until this point, in the mouse where these
cells were first isolated, and for that work the person who did this,
Martin Evans, was awarded the Lasker Award last year.

We know that these lines forming whole animals, which is what they have
been used for up to this point, in genetic mutations is getting
genetically defined strains of mice.

That there comes a time when these cells are no longer productive in
doing this and that they lose some quality. So we know that there is
going to be a half-life to the use of these cell lines for whatever
reason.

I just want to point that out, although they do have this replicative
ability. Well, where do these totipotent cells come from, and two major
sources. The first is this pre-implantation stage which we are going to
talk about, and the second are from specific cells within the fetus.

I also have on this slide, and by the way, I have given you two
handouts. One is the slides in the presentation, and another in a fairly
recent [Nature]{.underline} review of this material, that you can refer
to.

I want to point out another source of a cell that is very similar to
these two that we have isolated, and that comes as a stem cell for a
specific type of tumor called in the old days teratocarcinoma, and now
called mixed cell carcinomas.

These stem cells, referred to as embryonal carcinoma cells, were first
isolated back in the 1970s when I worked on this, and we thought that
these would be the answer to finding cells that would produce a variety
of cell types that we could work with within the human.

And I should tell you that at this point in time that there is a
clinical trial going on at the University of Pittsburgh using embryonal
carcinoma cells that have been selected for a neural lineage, and so
that in culture you can derive neural cells and that these have been
placed in the brains of 12 stroke patients.

It is a cell that is very, very similar to the two that I am going to
talk about. Well, the first source that you are aware of comes from
these structures here, which are pre-implantation stage human embryos,
and I am sure you are familiar with this.

And where that structure consists of two groups of cells; this outer
layer called trophectoderm, and an ectopically placed inner group of
cells called the inner-cell mass. It is from this group of cells here
that the embryo proper is derived, and it is connected ultimately to
this outer layer, which develops in the placental tissue by connecting
stock in an umbilical cord.

These cells may number only 15 or 20 in an embryo that may consist of
perhaps several hundred cells. And in work in the mouse, and
subsequently done in humans, first by Jamie Thomson, was that these
cells were isolated, placed in a culture condition, which then permits
their growth and their conversion into an embryonic stem cell.

This process of conversion can be highly inefficient, meaning that you
would need a large number of blastocyst and inner cell mass cells to
derive a few cell lines.

In some people\'s hands, it can be more efficient, but there is an issue
with that. A second source of cells with the same features was
identified in the early 1990s, first by Peter Donovan at NCI.

And what they were attempting to do were to culture long term cells that
are called primordial germ cells. These are diploid cells that are
present in an early embryo that eventually give rise to egg and sperm.

And they isolated, and this is superimposed upon a human fetus, they
isolated from the gonads, the gonadal ridges, these large cells, which
at the time of isolation in humans are about 20,000 of them present in a
gonad, and placed them in culture and essentially ended up with the same
type of cell.

This is what a human EG culture looks like, this clustering of cells and
I want to point out that there are cells in the background here which
are the so-called feeder layers.

All of these cell lines are derived on feeder layers, and all the lines
that were approved by Mr. Bush, and all the lines that we have, are
derived on a mouse feeder layer, and this is a point of contention,
meaning that we are concerned now about the fact of any endogenous
viruses being transferred from other animal tissues into the human
cells.

And the FDA must deal with this at this point in time, but we do not
have permission on the use of Federal funds to derive new lines,
avoiding this issue of other animal products.

But they are grown on feeder layers. They are established and grown on
feeder layers of other species. If we compare different properties of
these cell types, and I bring this up \-- some of these are of no value
to you immediately, but these are the criteria that one must use to say
whether or not you have a cell line.

It is very important, and of the 80 some lines that are now purported to
be available, I can guarantee you in talking to many investigators from
around the world that only a handful of these are bona fide cell lines,
and/or available to investigators.

Now, this may beg the point and that that may be enough to serve the
purposes in the immediate future. But really the majority, the vast
majority of so-called lines available do not meet the criteria that are
now used to say whether a line is a line.

Now, how do we \-- we are very interested then in two things here. One
is the basic science aspect of this, and of course what is driving all
of this is the hope for some type of transplantation therapy.

Let\'s talk a minute about the basic science. What we have in the
laboratory now are cultures of cells in the plate that can form any cell
type in a human body.

Now, the argument is have we demonstrated that you can get out of these
all 200 and some cell types? No. You only find what you are looking for.

What we have found though are a large number of cell types that are
present in the human body within these dishes. The problem at the moment
is getting homogenous population of pancreatic islet cells or blood
cells, or muscle cells.

This is the real part of the scientific struggle here, and coming up
with the paradigms to say can we take a cell that can form any cell
type, and get it to form but one cell type.

And to do this we have to rely upon our knowledge coming out of
molecular embryology as to the genetics and what not involved in any
type of cell specialization.

And this is really the limiting issue at this point in time, getting
these purified populations of cells on demand. There are strategies that
are used that we do pretty good at, and we will take the initial
populations of cells, and we can change feeder layers, and we can change
growth factors, and we can put them in different types of cultures and
force them then to begin to specialize.

But they are mixed cultures, and within the same dish you are going to
find neurons and muscle, et cetera. And we must then go another step and
begin to sort out either through procedures called flow sorting based on
what is on cell surfaces to get then pure populations of hematopoietic
stem cells, muscle cells, or neuro cells.

And this works fairly well. We can get cultures of dopanergic neurons
that are 80 percent pure, and we can get cardiac muscle that is 97
percent pure, et cetera.

But we are a long way from isolating in a homogeneous fashion the
various types of cells that we would like to get. Some of them were
doing well at and others were not.

And it is going to require an extensive amount of research to achieve
this. Now in going to transplantation therapy \-- we are going to jump a
little bit ahead here, and if we start, this could be ES.

If we start with this population, we do not transplant into anybody, or
into an animal at this point, one of the stem cells. You don\'t do it.
The reason that you don\'t do it is this.

These stem cells are capable of forming a variety of tissues, and they
will form tumors, and these tumors are these mixed germ cell tumors that
contain a variety of cell types.

They are called teratomas in the old literature. Monster. I mean, they
are contained in a mixed array, and you can see teeth, sebaceous glands,
hair, bone, parts of the gut, et cetera.

So what you have to do to make this work is you want to at least get
cells that you have treated somehow in a dish into some of these more
defined lineages that are away from this capacity to form tumors.

So that we then begin to select tissues downstream, all right? Part of
the problem, and you will read this in the literature, is how good your
selection is, is also indicated by whether or not when you take
myocardiocytes that you say, oh, these are all 100 percent
myocardiocytes, you transplant them into the wall of the heart, and you
end up with a teratoma.

This happens, and we are into the central nervous system, and you end up
with a teratoma within the brain. So getting rid of those initial stem
cells are essential, and we have ways of doing this genetically, but I
just want to point out that this is an issue.

To say nothing about the fact that we do not know whether any cell
downstream here has the capacity to revert. We know very little about
that at this point in time.

So let me give you an example. There are many of these coming out in a
number of laboratories, most of them in the mouse in which lines have
been derived in different lineages, and they have been transplanted into
animals to show proof of concept, and that you can isolate a specific
cell type, and you can transplant it, and it will function within the
transplant.

I would like to give you now an example from our work at Hopkins. It is
an unpublished work, and it is now under review, but I think it is
important because it really illustrates several points that are critical
here.

We have taken our human cells and grown them under culture conditions
that would select for specific types of lineages, and whether it is
neural, or whether it is muscle, et cetera. And now we have, I believe,
in our laboratory over a hundred a hundred lines like this, of the human
lines.

And in the one example that I want to present to you, which was done
with members of our department of neurology, and in collaboration with
our lab, is a model, using these cells in an animal model of the motor
neuron disease.

And in this study, these animals are treated with a virus that destroys
lower motor neutrons, so that animals become paralyzed, and they are
paralyzed because they lose the big nerve muscles that in your spinal
cord hook your muscles up to the central nervous system.

So that in a period of 10 days following the injection of the virus into
the brain, the animals become paralyzed, and we have gone to great
lengths to show that it is really the ventral roots that are involved.

You wipe out these neurons and these animals never recover. They never
recover. So what we have done is to take our human neural cells out of
this and infuse it into the spinal cords of these rats, and to look then
for the recovery of motor activity.

This is a rat out for a mid-morning stroll, and this animal is infected
with the virus, and it is a virus that really leads to an
encephalomyelitis, and within a period of 10 days the animal is
paralyzed.

We can document exactly what this paralysis is about. The virus is
cleared, and shortly thereafter we will put a cannula into the lumbar
region of the animal, and infuse 300,000 cells into the cerebrospinal
fluid, and these cells will float all the way up to the hind-brain.

And then we monitor the motor activity of these animals, and within a
period of a few months, we begin to see animals that can now place their
limbs underneath them, and that can draw them up, support some weight,
and begin to push off.

And at the high end, within a several month period, we can have animals
that are now walking. And the issue is why are they walking. And what we
have learned, although it is not as you can see a normal gait, et
cetera, and we have really documented this as well, they are walking.

And why are they walking? Well, initially what we felt was this. This is
a panel showing cells within the ventral horn of those animals and I
want you to look at this cell here.

This cell, based on its marker, and based on its physical
characteristics, and molecular characteristics, is a human motor neutron
cell that has been specialized out of these neural precursor cells, that
has sent an axon out into the periphery at least two centimeters.

And we have been able to cut the sciatic nerve out on the limb of this
animal, place a dye at that site, and that dye is picked up by that
axon, and brought back to the cell body that extended the axon.

And it comes back, and this is the green stuff here, and it comes back
then into the cell body of the human motor neuron. We have gone on to
document how many human cells are present, and what they are as far as
the phenotype is concerned, to see \-- you know, yes, they are forming
glia, and they are forming a variety of cell types within the ventral
horn of that animal.

Interestingly, and one of the safety issues that we find is that 50
percent of the cells don\'t do anything. And we are a little bit
concerned about that.

I mean, is it good to have all these cells in there that aren\'t doing
anything, but this is an issue that we have got to resolve. Well, it
turns out that this is only part of the answer. It turns out that the
human cells at the same time are producing growth factors that rescue
and enhance the regeneration of the animal\'s own cells within the
ventral horn.

And so this has led us then to set up experiments to try to figure or
try to determine what growth factors it is that is causing the growth of
axons in those mice and in rats in the ventral horn, and it may be that
eventually we can use just the combination of those growth factors to
elicit this response. We don\'t know.

So these cells are serving in a dual capacity, which is somewhat
exciting. We have taken the human cells and we now have grafted them
into monkeys. They were in monkeys for over a year.

This was a safety study to in fact show that we are not getting tumors
formed. I think you can appreciate one of the major issues here that we
are going to be faced with, with this type of approach, is animal
experiments are of a very short duration. Mice and rats are for periods
of several months.

Monkeys we can go much longer. How much data is going to be needed to
convince the FDA that this is a safe approach, and this is something
that is being debated now within the FDA and it is a difficult issue.

But here we show human cells, and that is these blue ones that have been
in this monkey, and in this case for 180 days, but we are now out a
year, and we can show that these cells are forming specialized
structures and they are non-tumorigenic.

The next phase is to look at a graph model here that is functional.

DR. KASS: Can I just ask a question?

DR. GEARHART: Sure.

DR. KASS: What has been injected here?

DR. GEARHART: Oh, I\'m sorry. These are the same \-- what has been
injected into this monkey are the same cells that were injected into the
rat. The same cells. They were human cells \--

DR. KASS: Neural precursors?

DR. GEARHART: Neural precursor cells. The same cells, the same culture
cells. A major issue that we must discuss and that we are concerned
about is graft rejection. Obviously, anything that you grow up, unless
it matches the patient, is going to be subjected to that, and now we get
into an area which Dr. Kass has mentioned earlier.

But what are our options here? What are the options of being able to
grow these cells into any of these lineages and then to transplant them
and not have rejection?

Well, there is a long list, and it starts with, well, maybe what we
ought to do is derive hundreds of ES and EG cell lines, and then you
would have a best match for a patient. Not very practical.

Can we use the patients own cells, and you will hear about some of this
shortly. Should we use immunosuppressive therapies. We would like to get
away from that.

Can we use what the tissue engineers are referring to as sequestering
grafts, and what this is, is you can take grafted cells and put around
them matrices that will not permit other cells to touch them, but yet
they can produce products, or they can function in a graft.

So you are trying to hide them from the host immune cells. How effective
that is going to be, we don\'t know.

Can we perhaps come in and genetically modify, which is easy to do in
these cells with the histo-compatibility genes, so we can make them more
like a patient that is going to receive these cells.

Or is it possible that we may end up being able to produce cells that
may be universal donors. Again, we are trying this, and at the moment it
is speculation.

Clearly the one thing that has worked is the issue of nuclear transfer
therapy, the so-called therapeutic cloning, in which as you know the
argument is to take a cell from a patient, and fuse it to an enucleated
egg, derive a blastocyst, recover the inner cell mass, culture it out,
and then these embryonic stem cells would match the genome of the
patient.

Is this a pipe dream? The answer is no, and I will give you an example
of that in a moment. To get around some of the issues with the human
cloning, embryonic cloning in humans, you have seen reports in the Wall
Street Journal and other places which I can confirm are real, in which
there are attempts now to take human cells, human nuclei, place them for
example into rabbit eggs, enucleated rabbit eggs, and grow up a
blastocyst, and generate stem cells that have human nuclei and rabbit
mitochondria.

And the argument has been made here that, well, these cells would be
perfectly fine for an autograft, and this isn\'t accurate. We know that
mitochondria produced polypeptides that are integrated into the cell
membrane, and are actually considered to be minor histocompatibility
antigens, and will be recognized and rejected by the host from which the
nucleus came from.

So this really is not getting around the issue of the graft stuff at all
using other animals, and we are a little bit concerned about how this is
being handled.

So, let me give you an example, and one which you should read these
papers if you haven\'t from Rudy Jaenisch and George Daley at MIT, using
the nuclear transfer therapy, or the therapeutic cloning, to do two
things.

What they did was to take a mouse that had a genetic mutation in genes
that are important as far as the immune response is concerned. And they
took cells from this mouse, took the nucleus out of the cell, and placed
that nucleus into an enucleated egg to produce a blastocyst from a
cloned embryo.

They took the inner-cell mass cells out of that, and generated embryonic
stem cells, that then are the same genome type as this animal, and then
went in and repaired genetically the mutation within those cells.

And then differentiated these cells into the hematopoietic stem cell
component, transferred them back into this animal that had the mutation,
and the transplant took, completing the whole hematopoietic system, and
in rescuing that animal.

So this is a proof of concept kind of experiment, and I urge you to read
it. It is an extremely powerful illustration, not only of the
therapeutic cloning end of things, but also the ability then to come
along and correct the genetic mutation and the reference was given to
you.

Another argument has been made that we should be using perhaps just eggs
that have been stimulated to form embryos, and these are parthenotes.

And the argument here has been that we can then use these directly into
the female from which the eggs were taken. I just want to point out that
in my opinion that this is going to have very low usage.

You are going to have to recover embryos or eggs from patients,
post-pubertal, and pre-menopause. The window is going to be fairly
short, I think, for many of the therapies that you would want to effect.

And the other issue is that we don\'t know much about cells that are
derived this way, and how viable, and how functional they are going to
be. But this has been used or promoted also as a source, and this is an
illustration of where you take those cells.

All of this type of technology, I just want to let you know, and I know
that you are grappling with this, but even within the field of the
scientists are beginning to argue about what is an embryo and what
isn\'t an embryo.

So any arguments that you have within your council on this, I will tell
you is also being held among biologists. I think that my own personal
feeling is that anything that you construct at this point in time that
has the properties of those structures to me is an embryo, and we should
not be changing vocabulary at this point in time. It doesn\'t change
some of the ethical issues involved.

What are some of the problems here, and I will summarize this a little
bit. Current research. Well, we have to come up with better ways of
having high efficiency differentiation protocols resulting in
homogeneous cell populations.

We are dealing with growth environments, and genetic manipulations, and
we are trying to define stages of cell differentiation within our
cultures.

And assessing whether or not the differentiated cells that we are
getting out are normal and completely functional. And this is in a dish.

And let me tell you that there are examples of where you can spend all
of an effort studying something in a dish, only to find that if you pop
it in an animal that it doesn\'t behave how you think it is going to
behave. We have a lot to learn here.

I think you can imagine that what is going on in a dish is not exactly
what is going on in a site where you transplant. The whole issue of
grafting, and how you put it in, and the safety issues, and that cells
migrate away, and they differentiate, and will they form tumors, and
then the issue of the immune response.

These are all, you know, formidable obstacles that lie ahead. I
mentioned to you that we can use cells individually, and have been used
in a variety of paradigms in our collaborators of single cells, and the
tissue engineers are now taking these different cell types and seeing if
they can reconstruct or construct organal aids or tissues to do
in-grafting, and thee has been some success with this at this point.

Finally, to me, the future is going to be that the basic science coming
out of this is the most important element, and that from that
information we are going to be able, I think, to take patient cells,
where appropriate, and I say where appropriate because if you have
autoimmune disease, or in cases where you have an injury, spinal cord
injury, or stroke, or heart attack, and you don\'t have time to take
that patient\'s cells, you are going to have to come up with different
paradigms.

But I think we are going to be able to eventually coax a patient\'s own
cells to behave in a manner that we want to, but we are going to learn
this I think through the study of stem cells.

The last thing I will say is I know that you want to ask, well, what is
the future going to bring, and I am concerned about predicting the
future. I can\'t even do this on a three year NIH grant and this is what
is expected of us.

You know, what is going to happen here. I certainly think that
everything that has happened up to this point is consistent with success
in this area, and I could get into more predictions in a moment.

But we are always asked when is this going to happen, and it is going to
be I think based on specific cell types, and on, and on, and on. But the
predictive thing is very, very difficult.

Well, I thank you for your attention, and I hope that this was enough of
a primer to add more meat to your discussions. Thank you.

DR. KASS: Thank you very much.

(Applause.)

DR. KASS: We were only physically in the dark, but we are grateful for
your enlightenment, Dr. Gearhart, and the floor is open for questions,
and comment, and discussion. Don\'t forget that you have to turn your
microphones on to be heard. Jim, go ahead.

PROFESSOR WILSON: Dr. Gearhart, do you foresee that it will ever make a
difference whether cells that are transferred for human cell
regeneration come from cloned eggs, or from the retrieval from IVF eggs?
Does it make a difference what the source is?

DR. GEARHART: Well, I think in the short term that it will. I think the
only way we have around the immune rejection story at this point is from
cloned embryos.

For a patient in which you can predict ahead of time is going to need
stem cell therapy and you have the time and money available to do the
cloned approach.

I would like to think that this is going to be a transitionary period,
and that we will not have to rely upon this in the long term, and that
we will be able to take for any specific disease a stem cell, or a
derivative of a stem cell that may come from the adult source, the
umbilical source, the fetal source, or embryonic source.

I mean, whichever presents, and that we will have ways of dealing with
this graft rejection story other than through the cloning of human
embryos.

PROFESSOR WILSON: If I could just supplement my question with a related
one to which you referred. What is your current assessment of the value
of adult stem cells, as opposed to embryonic ones, as a source of organ
regeneration currently?

DR. GEARHART: Oh, I think it is a very viable option and I think NIH
should fund it. I think that from what we see in the work, and Catherine
will present a nice overview of this, that this is going to be a good
source of stem cells.

They have some issues that they have to overcome, issues of
expandability, and plasticity, that we feel are \-- that have not been
demonstrated as well as embryonic stem cells, but I think that
eventually we will be able to overcome this.

But I think part of the knowledge of overcoming it is going to be coming
from our studies of cells that have those capabilities, and being able
to transfer that information to those other cells.

So I think we are going to come up with \-- I believe that in the stem
cells, cell-based therapies, that we are going to identify certain adult
sources that are going to be good for some diseases, some injuries, and
embryonic sources for others.

So I think we are going to mutually proceed on this and benefit from it.

DR. KASS: Please, Elizabeth.

PROFESSOR BLACKBURN: Dr. Gearhart, you can give us I think a unique
perspective on the comparison between adult, and embryonic, and fetal
stem cells.

And in particular many of us read the recent papers, the scientific
peer-reviewed papers that came out with respect to the adult stem cells,
and the interpretation of their plasticity being cast in some
considerable doubt by the observation that there was cellular fusion of
those cells which had led to in these particular cases examined a
mistake in interpretation of their plasticity.

And I wondered if you could give us your perspective on that aspect,
which extends Jim\'s question somewhat.

DR. GEARHART: I will do so in the face of Catherine sitting back here,
who is \--

PROFESSOR BLACKBURN: Yes, I am going to ask her, of course, about this,
too.

DR. GEARHART: \-- actually done those experiments. Clearly the most
difficult experiments that we have had to address and interpret are
those utilizing adult stem cells that have been placed into the
blastocyst of mice to create chimeras.

And in those chimeras, we see that the descendants of those adult cells
gave rise to many, many lineages within the embryo, and this was really
the issue. How did we explain this.

And from the studies of Austin Smith and others that you are referring
to, the implication was that when those cells were transplanted into
that blastocyst to generate the chimeras, that a subset of these cells
fused with the hosts own cells and it was those fusion products then
that gave rise to the variety of lineages.

At the moment that is an implication, and that has not been demonstrated
in the embryo. It has been demonstrated in the dish that they had that
capacity.

So we are now waiting and putting pressure on Catherine, and Freizen,
and others to look into those animals to see if they can recover those
specialized cells that were derived from or that had the adult phenotype
if you know what I mean, the marker, to say are you truly of the adult
stem cell lineage, or do you have other markers present, other
chromosomes present, that come from host cells.

So until we see that data \-- you know, I will wait. That is something
that can be looked at scientifically, and that is as far as I would go
with you, Elizabeth, at this point.

It is an interesting observation, and we will see if it actually is the
answer.

PROFESSOR BLACKBURN: And just to extend on what you said, I think what
it does now do is to demand that the onus be put on the researcher to
show that there has been a plasticity or transdifferentiation, and there
are other set of criteria, which would be karyotype and multiple
micro-satellite, polymorphisms \-- sorry to get overly technical \-- and
other genetic markers.

There are clearly tools in hand, and so it seems as if every experiment
can in fact be subjected to those sets of analyses now.

DR. GEARHART: Right.

PROFESSOR BLACKBURN: And will need to be before we can get a good view
of this.

DR. GEARHART: Right.

DR. KASS: Rebecca.

PROFESSOR DRESSER: I have four questions, and maybe if I say them all it
will be possible to answer some of them together. One, I was wondering
if the rats are being given immunosuppressants in this study.

And then you said a problem with the rabbit eggs is that the
mitochondrial DNA might cause rejection, and so I wondered if that would
happen with a cloned human embryo as well if the egg came from another
person, and if you are trying to do a therapy that is compatible with a
patient.

And let\'s see. The feeder layers, I was wondering if they have
available feeder layers that do not come from animals or what the state
of that development is.

And then finally what about the fact that if you are creating a
blastocyst from a patient\'s cell, and if the patient, let\'s say, has
cancer or some condition that could be related to genetics, would the
stem cells somehow perhaps be risky?

DR. GEARHART: There is no question in my mind that the possibility
exists that if you are doing an egg donor, and nuclear transfer into an
egg, that there possibly exists that that cell \-- that the embryonic
stem cells derived from that could be rejected. Absolutely.

Now, how do you test this? I mean, where do you test it. This almost
comes under the same criteria that I have for anyone coming to \-- if I
was on an IRB and they wanted to clone a human reproductivity, what data
do you present before you permit it to go.

To me, it is one of these things where you need perfection before
experimentation, or without experimentation, which is something in
science is anathema.

PROFESSOR DRESSER: Well, you could test that in an animal, right? I
mean, you could at least see \--

DR. GEARHART: Well, you can, and we could set it up in an animal, but
the issue is \-- I mean, where you are very defined and to demonstrate
it by doing it into a different strain of mouse. There is no question
about it.

But whether or not that would carry over in polymorphisms that exist in
human, again you are still faced with human versus rodent.

The feeder layer issue. It is one that is being taken on, and there is
no banning of this type of work with private money, and clearly there
are a number of investigators, laboratories, working on establishing
feeder layers from human tissue that could be used, and I think that
this is very important.

So those studies are certainly under way. We have used a variety of
different human tissues as well to look at in our studies. Oh, the very
first question that you asked. I\'m sorry, it was again?

PROFESSOR DRESSER: For the rats \--

DR. GEARHART: Oh, sorry. We did animals that were immunosuppressed and
animals that were not immunosuppressed. And we did not find a great deal
of difference in the short term, although \-- I mean, as far as any type
of destruction of cells and things like that, although clearly in the
animals that were not immunosuppressed that you could see reactive cells
present.

So clearly in the monkeys immunosuppressed, absolutely, and so we have
done them both. And then the blastocyst question?

PROFESSOR DRESSER: If it comes from a patient with a particular disease.

DR. GEARHART: Yes. Clearly where there is a genetic basis of any type of
a disease, you would be concerned about reintroducing the same cells
that were subjected to whatever the disease process was.

And I think that this carries over also into, for example, the diabetes
work, where if you have an attack on insulin itself, you know, is this
going to be a viable alternative, and there are some evidence now that
you can alter the insulin molecule to make it not recognized by some of
the autoimmune antibodies.

I should say that there are a number of laboratories \-- and this is one
area that is being emphasized in the use of human cells, including our
own, with Mike Shamblott, where we have lines that are \-- human lines
that are insulin producing that you can pop them into animals, and
demonstrate that they can produce human insulin.

And we are very encouraged by some of these early results. But I would
still contend that we have a long way to go to carry that into some type
of clinical application. We have a lot of questions to answer.

DR. KASS: Janet.

DR. ROWLEY: Well, I, too, have multiple questions and I want to thank
you for a very lucid presentation. That helps a great deal. I would like
to first \-- and I think I will do these one at a time.

It is a substantial question as to what value the embryos that are left
over from IVF can play in this whole process as compared with embryos
that you develop for either a particular purpose, or just straight off.

And my understanding was that maybe some of the embryos were
sufficiently mature so that maybe the cells derived from IVF would not
be useful in developing, say, cells lines or things. And I would like
your comments.

DR. GEARHART: One of my hats at Hopkins when I moved there in the late
\'70s was to develop the IVF program. So we are very well tuned into the
issues of IVF, and clearly in an IVF procedure the best embryos obtained
are those that are used first in first transfers.

So that generally those that are left over are of the ones \-- we don\'t
want to call it a lesser quality, but at least as far as our eye is
concerned, and how we judge grades of embryos, based mainly on
morphology to be honest, and more currently we are looking at
biochemical parameters that we can measure in the media in which these
cells are growing that something has been secreted to have some kind of
a measure.

And that clearly those that are the spare embryos generally are those of
\-- let\'s say, what we deem, and knowing what that means, of lesser
quality.

So what does that mean? In most cases, they have not developed far
enough along, which means that if they are left over that you take them
back out of the freezer, and you try in your culture conditions to get
them up to this blastocyst point.

If you can\'t get them to a blastocyst stage, you can\'t derive the
cells. If there is no inner cell mass, you can\'t do it. And you find
that you are compromised there, and that generally these are not very
good embryos.

So one could argue that overall that you would expect to have a low
efficiency yield with respect to taking in embryo and deriving a line
from spare embryos in an IVF program. That is in general.

DR. ROWLEY: Okay. You mentioned modifying the histocompatibility locus,
and I would have thought that there is still so much that we don\'t know
about the MAC that that would \-- I mean, obviously anything can be done
in the future with time, but do you look on this as practical?

DR. GEARHART: Well, back in the ancient days, in the early \'80s it
seems in this field, Oliver Smithies and others did do knockouts of
Class I and Class II genes, in an effort to determine whether or not
this could prolong grafts into animals without those.

And that depending on the tissue or the organ, there was evidence that
this indeed could be the case, and not that it was an indeterminate
thing, but just by days, or weeks, or months, that this was the case.

What they didn\'t know about at that time were NK killer cells, and
those kinds of things, and the importance of other determinants which
must be on cells. They wiped everything out.

So some labs are now taking a look at this to see if it is possible then
to rebuild back some of these markets. But it is a matter of speculation
at this point whether or not this could occur.

Now, what we can talk about I think is it possible to take using the act
of transgenesis and things like this, where we could move big pieces of
DNA; of taking part of a patient\'s chromosome-6, you know, and cloning
that into a stem cell after knocking out some of it, and we may get some
degree closer.

But that says nothing about the myriad of other loci that could be
involved as minor histocompatibility problems. So, some of it is
speculation, but I think it is also testable at this point in time.

DR. ROWLEY: And my last question is coming back to the 80 plus cell
lines, and you raised concerns, which many of us have, as to how useful
some of those are going to be.

DR. GEARHART: Right.

DR. ROWLEY: Could you expand a little bit, in terms of whether you think
they are really not going to be long term cell lines, and that is your
concern, or whether there are other aspects.

DR. GEARHART: Well, I have many concerns, and I hope that I can get them
all in. I mean, look, we were all thrilled when Mr. Bush made the
decision to move forward with this and establish cell lines to permit
the work to go forward. There is no question about it.

But as we looked into \-- and by looking into, it was a practical
matter. Many investigators around the world, and I have close contacts
with colleagues in Germany, and in France, and in England, and Japan,
and Australia, and on and on, as we compare notes all the time on our
results of research, as well as on practical things like this, and on
political issues.

I mean, there is no question that we have to keep abreast, and what
happened, particularly from the German investigators, which is
significant, as you know, in Germany, they are not permitted to derive
cell lines.

And for a while they were not permitted to use those that were even
derived, and recently their parliament voted to permit the use of
existing cell lines as of January 2002.

But what happened was that when these investigators set about to import
cell lines, and contacted the registry list at the NIH, which continues
to grow each day, and more lines are added to it as you know, it turned
out that many of the lines were not defined.

Someone just reported that they had a clump of cells growing in a dish,
and they didn\'t have any of these parameters or very few of them done.

And this reduced the list substantially, quite substantially, down to
\-- we are talking about, say, a dozen. And then the issue came up as
to, well, are these \-- can they be imported without a stringent
material transfer agreement, and with a reach through clause that would
say that anything that you would do with those lines belongs to the
person giving you the line.

And this reduced the line substantially. And then other lines are not
available because if you needed to get them, you needed NIH funding, and
only NIH funding. You could not use private funding with them, and on
and on.

And so it drastically reduced down the number of lines that are
practically available. Now, whether or not this will have a major
impact, clearly the NIH is receiving grants, and we have been reviewing
grants, and using the existing approved lines, the few that one can get.

And the work will go forward, and whether or not that will be
sufficient, and we recognize that there is going to be a half-life to
these lines for various reasons, and that there will come a time if it
proves effective in the basic science part of this to move forward, that
we should be looking at being able to generate new lines.

And the issue of the feeder cells is a major issue as well, and to begin
to establish lines on human cells so that we are not faced with that
anything that we derive from this now, and it is important to consider,
has to be considered as a xenograft.

Although it is a human line, the FDA requires that if it has seen these
other products, it has to be considered a xenograft, which sets up a
whole new set of criteria for moving this into the clinical
applications.

So I think there are reasons why we should eventually be permitted to
derive new lines. Well, I\'m sorry. We can do it now on private money,
but anything that is derived cannot receive Federal money for support.

DR. KASS: There are people waiting in line, but can I get a
clarification on this question that came up in your answer to Janet
about the durability and longevity of the lines, and on the one hand,
one says that the embryonic stem cell lines, their great virtue is that
they can be self-renewed indefinitely.

On the other hand, they have a half-life, perhaps because of accumulated
mutations. Could you say a little more? I mean, some people claim these
are eternal lines.

DR. GEARHART: Right.

DR. KASS: And could you say something about the possible differences
between human and mouse with respect to renewability, because I think it
is an important factor.

DR. GEARHART: Well, the issue is maybe they are eternal, but can you
still use them. They can still divide indefinitely, but they may not \--

DR. KASS: But they are no longer the same.

DR. GEARHART: Yes, they are no longer the same, and they may not give
you the biologic properties that you need. Strangely enough, Leon, there
have been very few publications up to this point, and up to this point
there is one that I can cite for you, and I have it in answer to some of
your questions by Joe Stanbrook at \-- Peter Stanbrook, at the
University of Cincinnati, in which he looked \-- these were mouse lines.

And he looked at the frequency and rate of mutation within several mouse
lines, and contrasted those with several schematic cell lines that were
in the lab as well.

And he found that indeed the mutation rates \-- and what you do is you
pick certain genes to look at changes, and to look at chromosome lost or
gain.

This paper was published in [PNAS]{.underline} in the March 19th issue
for those who are interested, and what he found was that the frequency
and rates of mutation were orders of magnitude less in the embryonic
stem cell line than in the schematic cell line.

And you are looking at a rate of generally 10 to the minus 6 frequency
within any mammalian cell as it is divided. But what he did find, and
that was a bit troublesome, was that the type of mutation that appeared
in the embryonic stem cell one led to what is called uniparental disomy,
which is a situation where you end up with homozygosity across a region,
or across chromosomes or regions of chromosomes, that gets rid of really
the dominant tumor suppressor genes, which then raises the issue that
these cells may be more susceptible to tumorigenesis than others.

Now, that is the only report, and I will tell you that in several
laboratories what is being done now with the human lines, and that is
using express sequence tags, for example, and you can use 10,000 of
them, they are looking at mutation rates at 10,000 loci, if you know
what I mean, over time in culture passage, after passage, after passage.

So we will get information on this parameter, and how significant it is
going to be, I don\'t know, but one would predict that clearly there is
going to be an accumulation of mutations within these cells.

DR. KASS: Okay. Thank you. I have Michael \-- well, also, was that on
this point?

PROFESSOR BLACKBURN: Just a very brief clarification. Did the absolute
frequency of uniparental disomy go up? Was it an absolute frequency
increase, or simply did it relatively increase as you looked at the
whole spectrum of mutations in the mouse embryonic stem cells?

Do you see the difference that I am trying to get at?

DR. GEARHART: Yes.

PROFESSOR BLACKBURN: That if it were an absolute increase, that is a
reason for concern, much more than if it were simply a relative increase
in a number that has already gone down by \--

DR. GEARHART: These numbers are rates, and so I believe it is an actual
number. In other words, it was a real \--

PROFESSOR BLACKBURN: An absolute increase?

DR. GEARHART: Yes, an absolute increase.

PROFESSOR BLACKBURN: So I just wanted to make sure that I understood the
numbers here.

DR. KASS: Michael Sandel, and then Frank.

PROFESSOR SANDEL: I would like to go back to the adult stem cell versus
embryonic stem cell question, and ask it in a slightly different, and
maybe more pointed, form.

As you know, there are some people who regard embryonic stem cell
research as morally objectionable. I am not asking you or trying to drag
you into that debate. But I would like to know your view on the
following scientific question.

If adult stem cell research in the best case scenario redeems its
promise, what would we lose medically and scientifically if we ban
embryonic stem cell research, or imposed a moratorium on it for a period
of time, until we could assess what adult stem cell research could
achieve?

DR. GEARHART: I personally think it would be a tragedy, and for the
following reason, if this was to happen. I think the length of time that
it is going to take to assess whether the adult stem cell avenue is
going to provide the potential therapies that we are thinking about, is
going to be years.

And I think for us to deny at this point any avenue that has the
potential of the embryonic stem cell story is a tragedy to those people
who need or who will need these cures.

And I think that it is a time element. If this could be done in a year,
I would maybe listen to that argument. But it is going to take years to
really assess any of these approaches.

And I really think they should move forward together. I think we are
going to learn in both directions how to utilize information coming out
of these studies that would benefit, for example, or enable us to
understand more about the adult sources if this is going to be the
emphasis, and to really make them effective in their use.

So I think that it wouldn\'t be wise to put a ban on the embryonic
source at this point, and wait until another avenue is assessed. The
length of time is going to be too long.

PROFESSOR SANDEL: Can you be more specific? Are there certain types of
research avenues that you would associate more with embryonic stem cell
research, as against adult stem cell research?

Is it likely that success is in particular areas, or is it just that you
feel that as a general matter it is better to have more avenues rather
than fewer?

DR. GEARHART: Well, I think that one of the messages that I hope that I
can get across, and maybe Catherine will, too, is that we are in very
early stages in all of stem cell research, no matter what the origin of
the cells are.

And to make a judgment as to which of these is already more advanced
than the other, it would be a tenuous one at this point, because you
have got to remember that there are very few investigators actually
working on embryonic stem cells at this point.

The list on the adult side obviously is larger. I mean, as far as
investigators are concerned. And I don\'t think that any of us are
really showing dramatic \-- you know, utilization in the sense that we
can say we are going to go to any clinical use of this.

It is going to take years for this to occur. We are in the very early
stages and so I would be really hesitant to say that anything is
demonstrating anything better.

All I would say about embryonic stem cells at this point in a very
positive way is that we know that at this point that out of these cells
we can virtually generate any cell type we want in dish and in large
numbers.

That is the advantage of this approach. Now, whether this will be
surmounted by other discoveries in adult stem cells to do the same kinds
of things, I don\'t want to predict. I hope that it happens.

You know, our \-- and I also want to emphasize that we \-- and although
we are associated with the embryonic form, we are studying other forms
as well. We are not foolish.

As a scientist, you know, you are not going to put all your eggs in one
basket here. And so we are trying to move forward on a broad front, and
I think that this would be the more rational way to proceed in this
arena.

DR. KASS: Frank.

PROFESSOR FUKUYAMA: Dr. Gearhart, did I understand you correctly that in
the experiment that you headed up with the mouse that it lost the motor
function in its rear legs, that you were injecting human stem cells?

DR. GEARHART: Yes. Well, if I could correct you a moment. It was a rat,
first of all.

PROFESSOR FUKUYAMA: Okay. A rat.

DR. GEARHART: Rat, too, but the issue is please don\'t say that you are
injecting stem cells. These are derivatives of stem cells. I mean, just
so that we know, but they are out of the stem cell line, okay?

PROFESSOR FUKUYAMA: Okay. Fine. But what was the resulting tissue? It
was a mixture then of rat and human neurons, or do you think it was
simply the stimulation of these other factors that was causing the rat
neurons?

DR. GEARHART: Right. That is a good question. We still don\'t know \-- I
mean, to be honest with you \-- what the mechanism of recovery here is.
We know that sitting in the ventral horns of these animals, and where
these big neutrons reside, you now have a mosaic population of host
cells, of neurons, inner-neutrons.

I mean, we all \-- I mean, human and rat, or human and mouse, depending
on which one we did. We don\'t know the relative contributions. We can
count cells, but really what is the functional basis of what occurred
there.

We know that the human cells are also rescuing the other, but to what
degree. This is where the hard work comes in. What was the mechanism,
and what really went on or is going on in that ventral horn.

I can tell you in work that John McDonald has done at Wash U, in which
they generate a contusion injury in the spinal cord of a mouse or a rat,
and then infuse in mouse embryonic stem cell derivatives, and that he is
faced with the same issue. He can see that these animals recover to a
certain degree, but the mechanism of what is it, of what has really
occurred there, is not known.

And I think what we are going to find is a demand that we come up with
mechanism in some of these animal models so that we can completely
understand what that therapy is going to be if you take it to a human.

And this is going to require a lot of work. Now, some of it you could
argue is that you could do it all within animal studies. You know, mouse
embryonic stem cells, and you don\'t have to put the human in.

But I think we are finding enough differences between species that it
would warrant at least the study also of the human derived cells in the
same paradigms to ask those questions.

PROFESSOR FUKUYAMA: But I am just curious. Are you getting actual
tissues in which you have cells from different species that are growing
simultaneously?

DR. GEARHART: Oh, yes, absolutely. Yes, sitting in the same \-- well,
you can see in the section here that might be 15 or 20 microns across,
you see a mixture of the rat cells or mouse cells, and human cells,
functioning.

You know \-- I mean, this isn\'t uncommon. We do interspecific grafts a
lot in experimental things, and the question is when you do it, and we
see, you know, human cells growing in animals very nicely. I mean, as
long as there is immunosuppression and things like this occurring.

PROFESSOR FUKUYAMA: But could you go the other way, also injecting stem
cells from other species into human beings?

DR. GEARHART: Oh, yes. I mean, this is one of the issues with
xenografts. You know, is this something \-- well, there is a report
recently about chicken embryonic stem cells, and the fact that people
who had derived these were promoting the use in humans.

Pig stem cells, you know, et cetera, and so it can be done, but a couple
of issues, and one of them is the issue of the xenograft itself, of
bringing in endogenous viruses, and is this a wise thing to do.

And the other thing that I would ask you, and I won\'t be flippant about
it, is to say that if you \-- and one of the concerns that we have that
maybe this council and others would take up, is long term in a
neurologic sense.

If you are putting stem cells in, and you are putting them in between
different human beings, what are you doing to that individual. And I
would say to you that if you have a stroke, and someone comes along and
says, well, we have pig, cow, mouse, human, take your pick, what would
you select.

I am not being flippant about it, but I am just saying that I think that
we know that human would be preferable at this point in time.

DR. KASS: Could I ask a question, and just for clarification again also
on your own experiment that you showed us. You said that some of the
rats were immunosuppressed and some were not. Is that correct?

DR. GEARHART: Yes.

DR. KASS: And were there functional differences in the results between
those two groups, and would that bear upon the question of whether or
not the major effect was owing to the action of the human cells, or a
stipulation of the endogenous cells?

And lastly, if these animals had come to post-mortem was there a
difference? Was there rejection in the non-immunosuppressed animals of
the human cells?

DR. GEARHART: It is important to keep in mind the time frame that these
experiments are done in. They are of very short duration relatively
speaking, in a period of several months maximum.

In experiments that have been done in our laboratory, principally by
Mike Shamblott, in taking human cells and grafting, and these are
insulin-producing cells, and we have done it in a variety of tissues
into rodents, you always see reactive cells, which means that you are
eliciting an immune response.

Again, they are short term, and whether you are getting destruction, we
see cellular debris, and we see this kind of stuff at these sites. I
should tell you a little bit that may be enlightening.

When you do grafts like this, if we say we are putting in 300,000 cells
or we are microinjecting in a lot of these cells, many of these cells
will die at the time of injection, simply because you have taken them
out of one environment and you put them into another, and you see a
tremendous amount of cell death.

Very few of these populations of cells continue to divide. In other
words, it may undergo one more round of division, and they sit there.

You do see when you come in finally to look at where is the human versus
where is the rodent, and you use your human markers. You invariably find
a group of cells that you can\'t phenotype, if you know what I mean, and
to say what has happened here, and clearly there are cells being
destroyed.

DR. KASS: Fused?

DR. GEARHART: Well, we don\'t know that. And one of the arguments for
many years has been that the central nervous system is an immune
privileged site. I don\'t think anymore that this is something that is
believed or subscribed to, and if you have the option of
immunosuppression, or of getting around that, that that would be
preferred.

And particularly when you are talking about a graft going into a human
being that may be there for 20 years, as opposed to a matter of a few
months. So I think that this is going to remain a major issue, and there
is no question about it.

DR. KASS: Thank you very much. Bill Hurlbut and then Paul McHugh.

DR. HURLBUT: John, I hear you saying that we should pursue all lines of
research, but I want to weigh the different options here and pursue the
question of if the lines were restricted what would be gained or lost.

Specifically, I have several questions that hinge each on the other.
First of all, the cells that were implanted or tested for their
tumorigenicity effect that you spoke of in your paper were the so-called
EBDs.

Were those derived only from embryonic germ cells; is that what is
implied there?

DR. GEARHART: Yes. In our paper, we took the stem cell itself and plated
it out in a variety of culture conditions, some of which are designed to
enhance or select for certain types of differentiation.

And we referred to these as embryoid body-derived cells. They came out
of this little cluster, and in our field it is essential that we take
the stem cell off the dish, and let it form into a little ball, and
which is just a multi-cellular structure, called an embryoid body.

Now, this was an unfortunate name that was given to it by a French
pathologist back in the \'30s, but as you can imagine, when someone in a
political sense talks about an embryoid body, they conjure up embryos
here.

But these are little clusters of cells, and within those or within that
cluster, the beginning of differentiation begins. These cell-cell
interactions are essential for this. We have not been able to mimic this
in a sheep yet.

So what happens is you get within that ball a variety of cell types
being formed, and all that you want to do is to disassociate that ball
after a period of time, and select out only those that are going in the
direction that you want them to go in.

So this is what we did in that experiment, and so we have now these EBD
lines, and in these lines, in these human lines, and these lines have
been placed in a large number of animals, in the grafts that we have
used, we have never seen a tumor up to this point.

And it may be unique to humans, because human primary cultures are easy
to establish and mouse aren\'t. I mean, there is an issue here that we
don\'t know that you can\'t do the same experiment in the mouse.

So with our experience with the EBDs, we have never seen a tumor. Our
experience in the mouse and using what we thought were equivalent lines,
we have seen too many tumors with respect to grafts into the central
nervous system.

DR. HURLBUT: Just parenthetically haven\'t I been reading all along that
embryoid bodies are also formed from ES cells?

DR. GEARHART: Oh, yes, absolutely.

DR. HURLBUT: But the point is that your particular lines don\'t produce
tumors, and the ones derived from the primordial germ cells don\'t seem
to produce tumors; whereas, the embryonic stem cell lines do?

DR. GEARHART: Well, the only comparison that we have at this point are
mouse ES lines, in which we have derived different types of precursors
under different conditions, have been compared to human EG lines that
have been derived, or which precursors have been derived in a slightly
different manner.

You can\'t derive them both in the same way. We have seen nothing up to
this point on human ES derived lines transplanted. We just have not seen
any data on that.

So I don\'t want to make it clear that there is a difference between the
derivation either from a germ cell derived, or an inner-cell mass
derived line. Does that make sense? That comparison is not there yet.

DR. HURLBUT: Well, obviously what I have been getting at here is if in
fact your cell lines are less likely to cause tumors, then does that
imply that there might be some advantage to using your cell lines, and
if so, would it in fact be the greatest advantage if a patient\'s own
cell line could be derived from primordial germ cells?

DR. GEARHART: Oh, boy, this committee would \-- well, wow. Now, think
what this means. It means that you would be generating an embryo, and
having it implanted. Now, what you don\'t know is that our fetal tissue
comes from 5-to-9 weeks post-fertilization. These are therapeutic
abortions.

And which means now that you are way beyond \-- I mean, the point of
where a blastocyst is, and obviously way beyond I think anyone
subscribing to that approach.

DR. HURLBUT: You told us that in your paper.

DR. GEARHART: Okay.

DR. HURLBUT: But is it true that maybe there would be some great
advantage if we could find a legitimate way to harvest tissues generated
from a specific patient at a later date?

DR. GEARHART: Right. Well, I think it would be terribly risky. We have
been asked this question a lot though; is it possible to do a biopsy on
a developing embryo, and to remove just a few germ cells.

I think at the stage that we are using these embryos are a matter of \--
or fetuses are a matter of maybe 6 or 7 millimeters in length, and to do
the surgery on this I think would just be impossible without causing
harm.

The other issue that I would contend is do you think it would be okay to
go in and remove the germ cells from an embryo and let that individual
go on and say, well, we have taken your germ cells. Now, we have another
therapy for you.

And so I don\'t think it is a very good thing to do.

DR. HURLBUT: And that is my final point, and I wanted to ask you
personally in working with these cells, do you see 14 days as some kind
of magic marker moment?

Do you see something crucial about implantation? And you spoke of
keeping all options open.

DR. GEARHART: Right.

DR. HURLBUT: Why in fact do we allow abortion fairly late in term, and
yet now we are speaking as 14 days as the sacred moment? I know that I
am opening a very difficult issue here.

But in fact wouldn\'t we gain a lot scientifically from extending that
14 day limit potentially if we could find a culture median that could
sustain the embryo, or wouldn\'t we gain a lot from implanting, even
gestating and harvesting?

And why do we feel that we shouldn\'t do those things? And I would also
be interested in your personal response to these ethical issues.

DR. GEARHART: Wow, you have asked a lot. As you know, stem cells have
been obtained from many stages of human fetal development, and have been
found to be useful in generating various cell types in culture.

And if we look at a variety of studies, you can find it in the published
literature. We have had a number of requests for fetal tissue at
different stages, and I think legitimate requests of investigators
willing to investigate cell lineages, et cetera, within the embryo.

So people have been thinking about it. I mean, there is no question
about that. We have found it difficult enough to be fortunate enough to
obtain the fetal tissue that we work with.

I mean, there is a consenting process and we have nothing really to do
with other than to make sure that it complies with institutional,
Federal, and State law.

To obtain viable tissue from abortuses of any kind is a major concern.
When we started our studies, we looked into using spontaneously aborted
material, which occurs across the board, but mainly in the early stages.

And we thought that this would be a good source. As it turned out, by
the time that we were notified \-- and this occurs in outlying
hospitals, and not at major medical centers, where investigators are \--
you know, a patient presents with a miscarriage, and it is taken care of
in the ER.

And it turned out that it was very ineffective, number one. And, number
two, and then I will get back to your question, we found that most of
the material that did come to us had chromosomal abnormalities that made
it less desirable for use.

Now, the issue of the 14 days, and what does it mean. Well, this was
something that really came into play in the United Kingdom when they
were trying to deal with this issue.

And it was decided at that point that at that stage the embryo still
does not have a central nervous system. It can feel no pain, et cetera.
And this was why basically that period of time was set to be able to
grow them in culture, or to remove tissue.

We, as embryologists, argue the point all the time as to what is going
on in these early stages, and we were always asked these questions. When
do you believe personhood occurs and when is it established, and things
like this.

To me that is not a biologic question. We don\'t have a means of probing
that. So I think that is why the 14 days was selected, and that\'s why
it is sort of adhered to in a sense.

Do I adhere to that? Well, to a certain degree, no. We take material
that is later on, and it is cadaveric fetal tissue. I think that we
should be able to utilize any tissue that comes out of abortion if the
alternative is that it is just going to be disposed of, which is what
happens.

The pathologist takes a look at it to make sure that all of the parts
are accounted for, and there is an issue about being concerned about
what is left in the uterus.

That is my personal opinion on that. But I don\'t think that we should
be going and establishing pregnancies, and to downstream then utilize
that tissue.

I mean, to then stop the pregnancy and then to recover it. I mean, that
is my personal opinion. I don\'t think we should be doing that. As you
know, years ago, President Reagan was faced with this, I believe, when
he heard that families were establishing pregnancies so that regions of
the brain could be harvested to treat Parkinson\'s disease in the
family.

And clearly we don\'t subscribe to that in any fashion.

DR. KASS: Thank you. We are coming up to the break and I have Paul
McHugh, Mike Gazzaniga, and we are running a little late because we
started a little late. We will take a break shortly. Paul and then Mike.

DR. MCHUGH: My point is very brief, John, because you have touched upon
it in several places. But first of all, I want to thank you very much
for that coherent presentation, and I especially thank you for showing
us experimental data.

And that is what of course generates better questions to ask you. And it
is really out of that experimental work that I did have a question. And
that is what you showed us was fundamentally a xenograftic experiment
using human tissue, human cells, in rats.

And the results were very interesting, and not only was there growth of
cells, but you told us that there were trophic factors that were
probably acting in this way.

And I then wondered, and you can answer this, why was it necessary to
use human cells to demonstrate this phenomenon in a rat, and why
weren\'t you using rat cells to do rat experiments.

And if that is true, that you could do rat cells to do rat things and
the like, the development of the question is would it not be wise of us
to ask you all to go back and work with your rats and your mice, and
your cats and your sheep, and keep going at it, and come back and tell
us why you need human stuff to do this stuff, okay?

DR. GEARHART: Okay. We did it first with mouse cells. We don\'t have rat
embryonic stem cells. We did it first with the mouse and it worked.

And in our exuberance, saying, well, would the human cells work, and
they did. There is no question that I think that the mouse cells worked
better, and the mouse cells were from these neural precursors that we
had obtained that I had mentioned that we had this concern about tumors.

But they did work, and so the only two cell types that we have found at
this point that work have very similar origins if you know what I mean.

Clearly the paradigm has to be extended to other sources of stem cells,
adult and umbilical, and this is planned to say in this particular
paradigm will it work.

So, Paul, the answer is that we did it first with the rodent cells, and
we could pursue that. I mean, as far as looking for the growth factors
and what not.

But we have changed almost completely to the human cells for trying to
determine what those growth factors were that were secreted, but we
could do that again with the mouse, absolutely.

DR. KASS: Mike.

DR. GAZZANIGA: Just briefly, thank you again for a wonderful
presentation. This moves to another level, and that is how big is the
American biomedical engine.

And I ask that from the sense of having just taken a trip to China and
Japan, and England, and you read that Sweden and Singapore, and India,
and so forth, are going ahead.

If America dropped out of this for legal reasons that are on the
horizon, how big an impact would that have on the overall resolution and
development of these therapies?

In other words, if you just look across molecular genetics and
microbiology now, and prior to this issue arising, what is the size and
importance of the American effort?

DR. GEARHART: Well, I don\'t think that there is any question that the
investigators funded through the National Institutes of Health, and our
academic establishments here, are the engine that drives biologic
research, biomedical research, in the world.

There is no question about it. I mean, the volume, the sheer volume of
this, is enormous. And if you look at this compared to even in our
country to what the biomedical industry, or I mean the private industry
is putting into this, it is dwarfed by the Federal funding.

And this is really what is enabling and this is why I think the U.S. has
been so far ahead. So it is essential I think to have Federal funding
into this area really to reach our goals as quickly as possible.

There is one last thing or one thing that I would like to say to the
committee, and it is understandable, but when you are in and start in a
business like this, you don\'t know the impact of it.

The thousands of communications that we have received from patients, and
patient-based groups, about our work and about moving the work along,
not only is it emotional, it is unbelievable. I mean, from the
standpoint of just pure numbers, sheer numbers.

It doesn\'t just extend within the United States, but throughout the
world. In 1998 when we published our paper, within a few days we had
10,000 e-mails alone about it.

And every day I still get hundreds of e-mails relating to this. It
extends not only to bona fide \-- you know, many people don\'t
understand what this work is about.

They are contacting you for a brain, or a uterus, or from some countries
we have had requests, hundreds of requests for penises, for example. And
you are trying to figure out why \-- you know, what is the issue here.

We need education and we need informing to say that we are dealing
really with cells and tissues at this point. That is what we are really
about. It is going to be years away before it goes beyond that.

And so what I am trying to say is that there are requests throughout the
world. So that is one issue. I mean, the pressure is enormous, and also
people offering you large sums of money to provide them with cells
outside of the arena that it should be done in. Do you know what I mean?

There is desperation, and you see this, and it is tragic, and as a
researcher this is new to you. This is something that you are not
accustomed to and never will be accustomed to handling.

So I just wanted to let you know what that pressure is like. It is
enormous. I have boxes full of these things. I don\'t know what I am
going to do with them, but you try to respond.

There has been an issue with brain drain. We know that there has been
one investigator from the University of California system that went to
the U.K. and received one-and-a-half million pounds to pursue this work
in the U.K.

Well, this happened here. I will tell you that \-- and I am talking to
students in our own group, you know, go to Europe for your post-doc, and
go to England for your post-doc if you want to continue in this thing.

And I think you will see more of this, and whether major investigators
will leave, I don\'t think so. I think we will get through this, and I
hope that we will get through this period in this country.

There are many, many investigators, many investigators, and I can\'t
tell you what it is like not to be able to give a cell to the person
next door to you because of a policy.

I mean, this is just an incredible situation. I think we will get
through it, and I think we will be okay. But I am still concerned about
it. Sorry for the editorial, but I think it is important.

DR. KASS: Charles, did you want a quick word?

DR. KRAUTHAMMER: If I could just ask a very quick question. You said
that you would oppose and you supported the opposition of creating a
fetus for, say, harvesting the brain cells, and you talked about the
example in the Reagan years.

On the other hand, there is no difficulty, at least in your estimation,
of using tissue from a discarded fetus already aborted, and tissue which
would otherwise be thrown away.

Would you apply that same distinction to the embryonic stage? In other
words, you now use \-- you develop embryonic stem cells from discarded
embryos from IVF clinics, and would you be equally opposed to the
creation of embryos specifically for their use as sources of embryos
using that same analogy?

DR. GEARHART: No, I would not be opposed to that. I don\'t give the same
moral status to that entity.

DR. KASS: Well, we have \-- let me just make mention of one matter.
Janet Rowley has submitted in writing, and I would endorse, these
questions if we had enough time.

We would like your comments on what kind of regulation you think might
be or should be developed for this area, and what is the status of
government support for what kind of research, and what are the
limitations that are counterproductive.

If we could invite \-- if you would be willing, and these are hard
questions and they are big questions, but if you would be willing to
respond if we put these set of questions to you, and perhaps some others
to you in a letter?

DR. GEARHART: Absolutely.

DR. KASS: I think the committee would be very grateful for your help in
thinking through the regulatory questions, which are at the moment not
what we have here.

DR. GEARHART: Absolutely.

DR. KASS: I just want to thank you very, very much, for an instructive
morning, and also for the wonderful spirit in which you presented your
remarks and engaged the questions. I am very grateful to you for coming.

We are running about 15 minutes behind, and we will reconvene at a
quarter-of. We have an hour-and-a-half for the second session this
morning as originally planned.

(Whereupon, at 10:33 a.m., the council was recessed and resumed at 10:49
a.m.)

DR. KASS: Would the members please rejoin the meeting. While we are
waiting in the hope that our straggling colleagues will arrive, a couple
of matters of business.

If anyone has not turned in a request for a box lunch, please do so now,
and that should be in front of you. We will have lunch in the room just
down the hall where we gathered before.

The photographer who has been around here is doing individual
photographs for the commission and he will want to take individual
photos of members, and we can do that in connection with lunch.

And you will also have in front of you in addition to the materials that
Dr. Gearhart provided us, which by the way is \-- and the lights were
out and so you couldn\'t see, but one could recapitulate his talk with
the help of the figures here, as well as checking his article in
[Nature]{.underline}.

But you also have in front of you a revised version of Bill Hurlbut\'s
memorandum. This has been updated and corrected, and he would like us to
substitute it for the one that was sent around earlier this week. Is
that correct, Bill?

DR. HURLBUT: Yes.

DR. KASS: All right. Well, again, it is a great pleasure to welcome Dr.
Catherine Verfaillie, from the University of Minnesota. You have her
curriculum vitae in the briefing book, which you can consult.

I won\'t waste any more of her time by reading from it, and just simply
allow her to help educate us on the prospects of present and projected
of adult stem cells for regenerative medicine.

DR. VERFAILLIE: Good morning. I would also like to start out and thank
Dr. Kass and the council to allow me to present this information on new
findings in adult stem cell biology which have been received with great
excitement, and correctly so. If they are, and they are actually set
upside down, the classical paradigms of biology, and so to be able to do
that you have to have full proof to actually be

able to be in a position like that.

If they are, and they are actually set upside down, the classical
paradigms of biology, and so to be able to do that you have to have full
proof to actually be able to be in a position like that.

As Dr. Gearhart already gave in his previous eloquent description of
what stem cells are and what they can do, and we will get back to that
to some extent at the end, although we are far away from actually being
able to use adult stem cells for clinical applications.

But what I would like to do is give you an overview of the greater
potential of adult stem cells, which has always been termed adult stem
cell plasticity, and what we do know and what we don\'t know.

And where this may actually lead us. Dr. Gearhart also indicated that
embryonic stem cells in humans are fairly or very much in their infancy,
the same as we are for adult stem cell biology, too, and so I don\'t
think we are anywhere close to be able to come up with new therapies at
this point in time.

I would also like to reiterate that even though my laboratory and our
group works on adult stem cells, we have actually actively pursued
investigators in embryonic stem cell research, human embryonic stem
cells, just so that within the same institution we would have
laboratories that have one cell, and other laboratories that have the
other cell, so we would be in a position to compare and contrast the
potential of the different cell populations, and I think that is very
important.

With that, I will actually start my presentation, and I will point out
that the work was mainly funded through the NIH, since it is all adult
stems that we are working on, and not embryonic stems. And also a number
of foundations and one pharmaceutical company.

Dr. Gearhart already gave you an overview of where embryonic stem cells
come from, and where primordial germ cells or stems come from. And I am
going to reiterate that for you.

I just put up this cartoon that Dr. Weissman published two years ago in
[Science]{.underline} to point out a couple of things. During
development, cells in the inner cell mass make sequential decisions, and
each of these decisions is actually accompanied with gain of function,
but also loss of function.

The gain of function is that the cells learn how to become a more
specified cell type; and on the other hand, actually lose the potential
to become other cell types.

And so the decision to be made is somatic or germ cell, and within the
somatic lineage doing something that is called gastrulation, cells
decide to become the different parts of our body, whether it is
endoderm, which is the internal organs, mesoderm, which are limbs and
soft tissue, and ectoderm, which really comprise the skin, the central
and peripheral nervous system.

And within each of these groups cells again make decisions and learn how
to become stem cells for specific organs. And the stem cells for
specific organs that has been most well studied is actually the
hematopoietic stem cell, which is currently extensively being used in
clinical applications for bone marrow transplantations or peripheral
blood stem cell transplantations, or cord blood transplantations.

And so that actually has set the paradigm on how we decide what stem
cells are. Aside from hematopoietic stem cells or blood stem cells, we
have a number of investigators who have identified tissue-specific stem
cells in a number of different organs, including for instance the brain,
which we until about 10 or 20 years ago thought was a final product when
we were born.

But it is now clear that there are stem cells in the brain that can
recreate neurons and other components. There is also stem cells in the
liver, and stem cells in the gut, and there is stem cells in the skin,
and so forth.

The reason why I put this slide up is actually to point out that these
arrows have always gone down, and so we have always thought that each
time a cell decided to learn something new that it lost the capability
of doing something else.

And so if we envisioned beforehand that the arrows would be reversed, we
thought that was possible, but we associated that with classical
transformation, or actually cancer-forming cells.

So what do we know about hematopoietic stem cells and that is really the
paradigm to which I am going to try to talk through the whole field of
adult stem cells.

In hematopoietic stem cells, we can actually take a single mouse bone
marrow cell that we characterize by proteins on the cell surface, and
take that single cell, and for instance you can take it from a mouse
that is engineered to fluoresce green under a specific light, and put
that in a regular mouse, and ask whether they can reconstitute the blood
elements of that animal.

And a number of investigators have actually been able to do that. You
can take a single cell, and give it to a mouse that was lethally
irradiated so it has no blood, and this cell can recreate the red cells,
the white cells, platelets, lymphocytes, for the lifetime of that
animal.

And that is really the proof that you have a stem cell that can
self-renew, and a single cell can make multiple different things, and it
can repopulate functionally the organ that it needs to repopulate.

And so that is really the criteria that we have to hold ourselves to, to
actually talk about stem cells, and if you talk about plasticity, you
will have to hold us on the same criteria and showing that a single cell
can now make two tissues, and that this cell can make two tissues from a
single cell, and that these new cells can repopulate a tissue
functionally in vitro.

Now, over the last 5 or 6 years, there has been an enormous number \--
well, not an enormous number, but probably 40 or 50 papers now that have
come out in the scientific publications that have used the word adult
stem cell plasticity.

And what is meant by that is that you take a cell that was supposed to
be a one cell type. For instance, you take a bone marrow cell, or you
take cells that are enriched for hematopoietic stem cells.

And it appears that some of these cells may acquire characteristics of
cells outside of the organ where they came from. And so it has been
shown for bone marrow cells, or cells enriched for hematopoietic cells,
that if you transplant these into an animal that was irradiated, and you
look in tissues outside of the blood, that you can actually find, for
instance, skeletal-muscle cells, heart muscle cells, or endothelial
cells, that are now derived from this donor hematopoietic cell.

There is also papers that have shown that if you take muscle from an
animal and mix it up in the laboratory, and culture it for a few days,
and then use the muscle tissue to give back to an animal, that you could
reconstitute the blood system in that animal.

Now, if you think in anatomical terms, this is still within one of the
three categories that I gave you at the beginning; mesoderm, endoderm,
and ectoderm, and all of this is still within the mesoderm. So this is
maybe not so hard to understand.

However, there is also papers that two different cells from bone marrow,
hematopoietic cells, and zymogenic cells, which are cells that make bone
and cartilage, can give rise to cells that appear to have neuronal
characteristics, both neurons and glial cells, that support the
structure of the brain.

And there is a number of studies that have shown that bone marrow cells
can contribute to liver, skin, lung, gut, and so forth, and so you can
pretty much put arrows in whichever way you want.

You know, people have published data that suggests that indeed this may
be possible. So obviously this goes against our paradigms and this would
say that either something strange is going on, and just something in the
last few years is something that we have actually identified.

Now, if we want to talk about blastocyst, I started out with the
paradigm of stem cells, and so there is multiple different possibilities
here.

Either the bone marrow, which seems to be the organ that harbors the
most of these cells, harbors many, many different stem cells, and it
harbors the hematopoietic stem cells, but it also harbors the neuro stem
cell, and the liver stem cell, and so forth.

And which that would not be bad, but that truly would not be a single
stem cell that could be expanded and used to actually transplant
patients with all kinds of different organ diseases.

A second possibility is that somehow the cell can be
\"de-differentiated\" and redifferentiated, depending on the environment
that it is put in, and that the hematopoietic stem cell can learn how to
become a liver if you put it in the liver, or it can learn how to become
a brain if you put it in the brain.

Or it could be that it is a remnant of embryonic stem cells or the
primordial germ cells that you heard about from Dr. Gearhart that are
left around in the body, and that under specific circumstances can be
reactivated and contribute to tissues.

And the issue of fusion has been brought up because of the two papers
recently in [Nature]{.underline}, and the possibility is in theory that
what we see is actually that.

For instance, a hematopoietic stem cell fuses with a liver cell, and now
you actually have something that is a hybrid, but it has actually liver
characteristics.

The other questions that I am going to try to address, and I don\'t have
all the answers for this, is this actually clinically relevant? You
know, if you transplant bone marrow into a patient and you find two
liver cells that are derived from the patient, from the donor, it
doesn\'t necessarily mean that that is going to help anybody down the
line.

So the graft has to be robust and persistent, and there has to really be
proved that we don\'t just see cells that look like a tissue that they
end up in, but they also have to function like a tissue that they end up
in.

And then the question that I will bring back up at the end, the first
question, what is plasticity, and will that matter from a clinical
standpoint?

And so we started out in this field \-- I am a hematologist, and I do
bone marrow transplantation as my clinical profession, and I have been
interested in hematopoietic stems in the bone marrow.

And about six years ago somebody in our group asked me whether we could
grow mesenchymal stem cells, which are cells that may grow on cartilage,
to treat children with a specific genetic disease called Hurler\'s
disease.

And when we did this, mesenchymal stems we happened to find, and we went
about trying to create these to be in compliance with GMP
qualifications, meaning we were trying to remove all sera out of the
system, and yet we were trying to use very well defined culture systems.

And so while we were doing this, we came up with a cell that you have
heard Dr. Kass refer to as a multi-potent adult progenitor cell, because
we don\'t have a much better word for it.

And it will be appreciated as MAPC, and which appears to have a much
greater possibilities than the mesenchymal stem cell possibilities. So
we take these cells from bone marrow from humans, and we can also take
them from mice and from rats.

And you place these in a culture system that is very well defined, and
ingredients, and growth factors, and no serum, and low density, and we
expand the cells as much as we can by splitting the cultures on a
regular basis.

And if we do this, we have actually found that these cells appear to
have an enormous growth potential. And so here on the left-hand side
would be bone marrow from an individual, and we start with about 10cc\'s
or a spoon of bone marrow, deplete all the blood elements from the bone
marrow, and put it in a culture dish, and then grow the cells for long
periods of time.

Classical adult cells would actually not expand much more than 50 times
or 60 cell population doublings, just because we have a clock inside the
cell that actually causes the cells to become senescent or old once they
go beyond a certain number of cell divisions.

And so in the human system, as well as in the mouse and the rat system,
we have been able to show that we can create or grow cells that do not
seem to conform to this internal aging clock.

And the cells can go beyond that and the human cells are now close to a
hundred population doublings, and in mouse and rat, over 150 population
doublings.

If you look at the aging clock itself, which are the telomeres, the
telomeres are long and they do not seem to shorten in culture, which
goes again with the idea that the cells do not senesce in culture.

So in this respect, they have characteristics that are similar to what
you would find in embryonic stem cells, but also this internal clock is
actually not working.

The phenotype of the cell is strange, and it doesn\'t really fit
anything in particular, but there is definitely no characteristics in
these cells.

These cells are blood hematopoietic stem cells, and I am not going to go
through all the details here, but if you do an extensive phenotype
characterization of the cells, they don\'t look like blood.

They have some characteristics of embryonic stem cells, but there are a
lot of other ones that they do not have. So they have some genes that
are turned on that are present also in embryonic stem cells, which are
the top two here, and then they have on the cell surface antigens that
you really only find on embryonic stem cells, or primordial germ cells.

So in some respects again these cells have some features of embryonic
stem cells, even though we got these from the bone marrow of humans,
mice, and rats.

We then started trying to test initially all in culture dishes what
these cells could do, and we asked whether they could differentiate in
multiple different cell types.

And because our initial charge was actually to try to grow mesenchymal
cells and make bone and cartilage, that is what we did first. And so
what we showed in the culture dish is that if we switch the culture
conditions around, and actually use ingredients that are no longer
supported for maintaining the stem cells in an undifferentiated state,
by actually switch them such that we hope that we can turn on the
genetic programs to make bone or cartilage, and so forth, we could
indeed do this.

And this is no different than the classical mesenchymal stems that have
been described. So we can induce the cells to become bone, and if we say
that they differentiated into bone tissue, it is actually a calcified
tissue at the bottom of a dish.

We can induce the cells to become cartilage that looks like articular
cartilage, even though it isn\'t very well organized. And you can induce
the cells to become lipid-laden lipocytes, and we can induce them to
become skeletal muscle cells.

And these cells can actually fuse and make long muscle tubes almost, and
we can induce the cells to express a number of muscle markers for the
heart, even though we haven\'t really seen beating cells.

And so we don\'t really know whether these cells are heart muscle cells.
So this is still not that strange, because there is this cell in the
bone marrow that has been identified that can do this.

Now, we found three other lineages that are completely outside of the
mesenchymal lineage, and some of this has been published, and most of it
is actually in press currently.

One of the things that we found is that these cells can differentiate
into cells that line blood vessels, which we call endothelial cells. And
we have been able to show that these cells differentiate into cells that
look like endothelial cells, but also function as endothelial cells.

And as shown in this picture here is actually a blood vessel from an
animal that had a tumor underneath the skin, and we actually infused
human endothelial cells derived from human MAPCs in this animal, and
showed that these endothelial cells seek out the tumor and actually help
create new blood vessels in the tumor, which the tumor needs otherwise
it can\'t grow.

And so this proves that these cells that are in the bone marrow can
differentiate into cells that can make endothelium. More surprisingly is
that the cells can differentiate into cells that look like neutrons,
look like astrocytes, and support themselves in the brain, and to some
extent function like these cells in the brain.

And so we show here that they differentiated into cells that look like
neurons and have electrophysiological characteristics like neurons.

And so this is the second major layer of the embryo, and then we also
have been able to show that we can make these cells differentiate into
cells that look like liver cells, and actually function like liver cells
in a culture dish.

And so this would mean that this cell population, these MAPC cells, can
actually differentiate into all of the major components of a human
being, even though we only show a few cell lineages here.

I am not going to go through this in too much detail because it is
highly technical, but essentially we have not been able to use genetic
marking to prove that this could all be derived from a single cell, and
we don\'t depend on population of cells.

So this fulfills two of the criteria of a stem cell. A single cell can
differentiate and grow for long periods of time, and can differentiate
into multiple different tissue cells.

Two more sets of experiments were done to try to gauge the potential of
these cells. The first one was done in an chimeric animal model, in
which we took the adult cells, and injected even a single adult cell
into the blastocyst of a mouse and asked what would happen in this
mouse, and whether we would see contribution to some tissues, no
tissues, or all tissues.

So we injected a single cell or we injected 10 to 12 cells, and shown
here are two animals. The top one is obviously and the donor cells here
have a gene that if you stain it correctly the cells turn blue.

So what we did is we let the animals get born, and we looked at the
animals by genetic tools to try to figure out if there were donor cells
in multiple different organs.

And we also then took the mouse and actually cut a thin slice through
the middle of the animal and asked which organs would have blue cells
contributing to the mouse.

The top mouse is an animal that if you looked in the tail by genetic
tools that we couldn\'t find any donor cells, and the bottom mouse here,
this is its head, and over here would be his tail, and you can see the
spine, and the brain, and all the internal organs.

And you can see that the majority of all the tissues of this animal
actually appear to be derived from a single blue adult cell that we have
put into the blastocyst.

The efficiency isn\'t a hundred percent, and this is shown on the bottom
here, and so if you look over here, and if you put in one cell per
blastocyst, 60 percent of the animals will not be chimeric, but 30
percent or 40 percent of the animals will be chimeric to varying
degrees.

If you increase the cell number the chimericism goes up. So this is
probably not quite as good as embryonic stem cells, but it is a fairly
significant degree of chimericism, and actually the frequency appears to
be one in three cells.

So this would suggest that the cells can probably make under the right
circumstances more cell types than we have be able to prove in a culture
dish.

We can also ask if we now take these stem cells and give them to a mouse
that is born, and we give here again cells from the donors\' mouse,
which again are blue, and we gave these to an animal that was either not
irradiated or irradiated with a small amount of radiation therapy in the
hope that maybe that would help the cells engraft.

We used an immune-deficient recipient mouse, just because we were
worried that the new genes that are in the blue mouse might actually be
a basis for rejection. So we don\'t know what would happen in a
non-immumodeficient mouse.

If we do this, what we found is that we do find engraftment in some
tissues, but not all. So, for instance, in the top panel, we see that
there is engraftment between 3 and 9 percent in the hematopoietic system
of this mouse, and we can find the cells, and the blood we can find in
the bone marrow, and we can bind them in the spleen.

And if we look in these animals, we can also find over here, and what we
did is we actually \-- the blue color, we used an antibody that is now
green, and co-labeled it with a red stain that stains the specific
tissue.

And you can see in the liver that there is areas in the liver where
donor cells appear to be present. And there is areas in the guts, in the
villae of the gut, where donor cells appear to be present.

And there is areas in the lung where donor cells appear to be present.
The presence of these cells can be seen anywhere from four weeks after
transplantation, all the way to 24 weeks, which is about six months, and
the unfortunate thing with the mouse model that we use is that these
mice usually die from lymphomas at an early age because of the
deficiency that they have.

So we really have not been able to extend the cultures or have the mouse
experiments beyond 6 months, and so we are actually trying to go
further.

We transplant the cells in an animal that is 6 to 8 weeks old, and so it
is not a very young mouse, and it is also not an old mouse. What we
showed is that if you damage certain tissues like the hematopoietic
system, and the gut system, that you have increased engraftment, which
is consistent with the fact that these cells go to places where the
repair might be needed.

However, we did not see in this mouse model engraftment in a number of
other tissues, and mind you that we gave these cells IV to an intact
mouse, which actually was not damaged in any way, shape, or form.

And we don\'t see engraftment in the heart, skeletal muscle, or brain,
and these tissues do not proliferate. We also don\'t see engraftment in
the skin and the kidney, and so these organs we didn\'t really see very
much engraftment.

However, if you infused the cells directly in the muscle, which causes
damage, and actually done the cells in response to the local cues within
the muscle, appear to be able to differentiate into muscle cells.

So it appears that these cells have the ability and blastocyst
experiment to give rise to many, many different tissue types, if given
post-natally, and we gave them as stem cells, not as differentiated
cells.

They appear to be able to respond at least in some respects to cues that
are present in certain organs to differentiate into the cell type that
is specific for that organ.

We have looked carefully at the cells in culture and we do not see a
significant number of gross genetic abnormalities. We have not looked
with a very fine-toothed comb through whether there might be some minor
genetic abnormalities over time and culture, and these studies are
ongoing.

If we infused the MAPCs in animals, we really do not see any tumors, and
so far we have not seen that there are tumors that Dr. Gearhart talked
about, and we also have not seen any other tumors.

Obviously if these cells come from bone marrow there is lots of
precedent on bone marrow transplantations, where actually if you do
this, actually you do not cause tumors in patients.

So MAPC that we have identified in our laboratory seems to be a cell
that is not senescing and that can be found in adult tissues of humans,
as well as mouse and rats, and they seem to be capable of giving rise to
cells from the three germ layers, and it can engraft in vitro in a
limited number of tissues.

Now, what I cannot tell is whether these cells actually exist as such in
a person, in a mouse, or in a rat, or whether our culture condition is
actually such that it, quote, reprograms or dedifferentiates the cells
that we take out of the animal, and that then acquire this much more
greater potential, and I will come back to that in just one second.

So we now go back to my initial definition of what is plasticity, which
is really at the bottom of all of the adult stem cell excitement. I
mentioned initially that we would have to show that this is a single
cell of a rat, and I think the majority of papers so far published have
actually really not been able to prove that a single cell could, for
instance, give rise to blood and muscle.

In vitro, we have evidence for that, and in the blastocyst injection, we
took a single cell and actually found multiple different tissues. You
could ask, well, does it matter?

Does it matter if there are multiple different cell types in the bone
marrow, and I think ultimately from an FDA or regulatory standpoint, it
will matter, and we will have to be able to say exactly what cells that
we are using to be able to acquire a certain function in vitro, and so I
think that will be important.

The second question is, is the differentiation or is the remnant ES, and
again you could say, well, it probably doesn\'t matter. But I think at
this point in time, I don\'t think anybody in this field knows whether
these are left-over early stem cells like ES cells, or whether these
cells are cells that can be reprogrammed, and redifferentiated, and
dedifferentiated under certain circumstances.

Now, does it matter? Well, you heard from Dr. Gearhart that embryonic
stem cells as such, and not necessarily the differentiated progeny, but
the ES cells themselves can cause teratomas, and even though nobody in
the adult stem cell plasticity era has actually shown teratomas, it
doesn\'t mean that it might not happen.

If it is dedifferentiation, it means that you reprogram or you change
the genetic material in a cell. But if you do that, currently we have no
proof that we actually change something and actually cause an oncogene
or something like that to be activated, but that is definitely within
the possibilities, and that definitely needs to be looked at carefully.

Is it fusion? All the in vitro work that has been published, including
the data that I have shown to you today, I couldn\'t prove beyond any
doubt that that is not based on fusion.

Our in vitro data, we have never co-cultured things with anything. So we
have single cells that are deployed that can do multiple different
things, and so we can\'t really ascribe that to fusion.

However, in vitro, I couldn\'t prove it to you today, and we are doing
studies to try to address this. I think that fusion might be the reason
why some studies in which a lot of pressure has been put on to the
system, which is essentially what those two papers had to do in vitro.

So we have a lot of pressure exerted to have that one cell survive after
it fuses, and that is a possibility. Also, single cells that are found,
rather than whole colonies, may also be the result of fusion, more so
than experiments where you see huge colonies arise in an in vivo model.

And so I think we currently cannot exclude the possibility that some of
the data is as a result of fusion. Some would say does it matter, and I
think it matters a whole lot, even though some investigators say, well,
if you fuse the cells and it functions properly, it probably doesn\'t
matter.

But I think ultimately that we do need to make sure that we understand
the whole mechanism underlying everything. And is all this plasticity
clinically relevant?

And so the majority of studies published to date have actually shown the
very low numbers of tissue differentiated cells can be found in multiple
different tissues.

A number of papers have been published, two in particular. The paper by
Lagasse, et al., where they show that they could rescue an animal with
liver failure by bone marrow transplantation, but they have significant
degrees of engraftment.

So that definitely was up to 80 or 90 percent of the liver could be
replaced by bone marrow cells. And a paper by Don Orlic showing that if
they injected stem cells into the heart that was infarcted that a
significant amount of donor cells would be found in the heart.

And in the data that I have shown you, that we have up to 5 to 9 percent
of the differentiated tissue that seems to be derived from the graft.

However, the majority of studies again haven\'t really addressed the
other question in plasticity, meaning is it in vitro functional
differentiation?

And there is really only a single study that has been able to show that,
and it is again the same study by Lagasse, et al., who showed that if
you did bone marrow transplantation in an animal that had a failing
liver, you could rescue the animal and take it off the drugs that kept
it alive.

Some studies have shown that there is functional improvement, although
the mechanism for the functional improvement isn\'t completely known,
and that is to some extent similar to what you heard from Dr. Gearhart.

And so there is a number of studies who have injected cells in adults in
organs and have shown, for instance, that there was improvement in the
neuronal function, and that there was improvement in heart function,
although there is no proof that the cells, per se, were actually
responsible for doing this.

And the question will be is this acceptable from a clinical standpoint,
and if you show only functional improvement without knowing the
mechanism for knowing why we see functional improvement, and in the long
term, again, that is not a tenable situation, and we really have to dig
into this much further.

So what can adult stem cells be used for? Well, I think like embryonic
stem cells, or primordial germ cells as you heard from Dr. Gearhart, the
cells are good tools to study five basic principles in biology.

And we can study self-renewal, and we can study differentiation and
redifferentiation if that is indeed the case, and learn what the
implications for that are.

And actually try to understand how organs are being created, and what
the genetic programs are that you need to turn on. The cells, like other
stem cell populations, could be used for drug discovery, for drug
toxicity screening.

Adult stem cells could be used as systemic therapies, and currently
systemic therapies are done with adult stem cells. Bone marrow
transplantation is done every day in many, many institutions around the
world, and so we can infuse these cells if we do not think that they
make tumors.

So since adult stem cells don\'t seem to have that as their side effect,
theoretically, we could genetically correct cells for patients who have
deficiencies of certain enzymes. And the disease, and Hurler\'s disease
would be one example, and a second possibility would be, for instance,
in hemophilia, where you need to have a cell that produces clotting
factors.

Or other congenital diseases, like Alpha-1-Antitrypsin deficiency, or it
could be used for systemic cell therapy, which you would have to treat
in many, many different places in the human being. For instance,
muscular dystrophy.

So if you had a stem cell that was able to engraft in most muscles, and
you could genetically correct it, you could correct that disease in
patients with that disease.

Systemic cell therapy may be more complicated with cells that have the
inherent capability of making teratomas just because you would always
run the risk that teratomas might show up.

And then again if this field progresses further, the same diseases that
has been quoted for embryonic stem cell therapies would also be on the
list here, and if indeed the cells can differentiate into functional
neuron cells, they could be used to treat Parkinson\'s disease and many
other ones.

And since the cells can appear to be able to differentiate into
functional liver cells, they could be used either in vivo to replace the
liver, but also would be very useful to make bioartificial livers, for
instance.

We have shown, and others have shown, that cells from bone marrow can
contribute to new blood vessels, and so this could be harnessed to
create new blood vessels in vivo, or actually the opposite; lower these
cells with anti-cancer agents, and actually use them in a
anti-angiogenesis approach for treatment of cancer, and then many other
diseases.

Again, we are not anywhere close to being able to do this in any way,
shape, or form, and a lot of basic research still needs to go on.

So the first point that was on my previous slide, we really need to
spend a lot of time in trying to understand what these cells are and
aren\'t.

And at the same time, start thinking about how we might be able to scale
these up under GMP conditions that conform with regulatory agencies, and
we will have to ask the question, as with any other stem cell
population, whether we will use the cells as stem cells, or as more
mature cells that have been educated to some extent to become the final
product are totally mature cells.

And then again perform large scale culture systems or develop large
scale culture systems. And then the last question is whether we should
use these cells in an autologous setting or in an allogeneic setting.

Obviously adult stem cells for a number of diseases could be used in an
autologous setting. However, if they were to be capable of repairing
hearts, and you have a heart infarct today, we would not have adult stem
cells sitting around instead of your own to treat you at that moment in
time.

So I think there are some issues, and Dr. Gearhart also brought up the
idea that with diabetes, for instance, in Type-1, is an immune problem,
and again autologous transplantation may not be the way to go.

I think that for adult stem cells, the initial trials may well be
autologous, but that in the long term, to make it more cost effective
and more available to many patients with certain frequent diseases, that
it might have to be an allogeneic therapy, and then we are actually
faced with the same questions that investigators that work with ES
cells, and primordial germ cells are faced with. I think I will stop
there. Thank you.

(Applause.)

DR. KASS: Thank you very much, Dr. Verfaillie, for a clear, lucid,
orderly presentation, and it is very helpful to us. The floor is open
for questions, comments, discussion. Elizabeth Blackburn, please.

PROFESSOR BLACKBURN: Thank you. Could I just ask a couple of quick
clarifications. Dr. Gearhart mentioned in response to Bill Hurlbut\'s
question the difference between fetally derived human cells and mouse
embryonic stem cells with respect to their teratoma producing
properties.

And I could not quite gather whether it is human embryonic stem cells
that are also known to have any teratoma producing properties. Could you
clarify that for me, because you also had mentioned this, and I wasn\'t
sure if you were referring to the mouse embryonic stem cell work or the
human.

DR. VERFAILLIE: If you use either mouse or human embryonic stem cells
without predifferentiating them into a committed progenitor cell, and
you use the stem cells as such, they will form teratomas, because it is
one of the tools that investigators use that an embryonic stem cell has
that capability. So they will form teratomas.

PROFESSOR BLACKBURN: And then post-differentiation?

DR. VERFAILLIE: I think there is very little data on the human embryonic
stem cells, post-differentiation in vivo, and whether there is still the
tendency for these cells to make teratomas.

PROFESSOR BLACKBURN: And the second question, since I promised that I
would ask you about, is the fusion issue, and which of course you have
raised in your talk as well, but again a question of clarification for
me, and maybe expanding on your point that you said, well, fusions are
going to be problematic.

I mean, the thing that immediately occurred to me was that these
fusions, as reported from the in vitro culture, and I believe from
engraftment into mice, that they showed aneuploidy, which of course
anybody being a hallmark of tumor cells.

So I wondered if those issues and perhaps others were things you could
tell us a bit more about when you mentioned that you had concerns about
the fusions.

DR. VERFAILLIE: Well, I think it is something that because of the papers
that were published that elegantly showed that if you took a somatic
cell, an adult hematopoietic stem cell or brain stem cell, and
co-cultured it with embryonic stem cells, and then put quite a bit of
selectable pressure on the system in the culture dish, they proved that
an embryonic stem cell quality could be transferred to the blood brain
stem cell.

And initially they interpreted this as being reprogramming of the cell.
But then it turned out that there were four sets of chromosomes, and
that the cells fused.

And they took these fused cells and gave them to \-- injected them into
a blastocyst as hyperdiploid as cells with four sets of chromosomes. One
group was not able to create chimeric animals, and the second group,
under the direction of Dr. Austin Smith, were able to create chimeras in
the mice that were what he calls unbalanced, meaning that he saw a
contribution to tissues, and that four sets of chromosomes are actually
tolerated.

For instance, the liver, where at least 50 percent of the cells,
actually half, have two nuclei. So I think that currently no
investigator who has worked with adult stem cells has set up the right
experiment to actually be able to disprove that it isn\'t fusion.

I would argue that the data that I showed today in vitro, where single
cells make three layers of the embryo, and these were euploid cells,
meaning that they had a normal set of chromosomes, and which done in
human, mouse, and rat, at the single cell level, we can make the three
major layers of the embryo.

So that would go against the argument that at least in vitro, that all
of it is caused by fusion. In vivo, in our blastocyst experiments, 1 in
3 cells could do it, which is much higher than the one in a million
cells that were quoted in the two papers that were in
[Nature]{.underline}, but which indicated that one bone marrow cell out
of a million could actually make a fused cell population.

And I think one in 50,000 neural stem cells could actually cause fusion.
So that was a very rare event; whereas, our events are higher. We are in
the process of actually going back to these animals \-- that we have
cryopreserved, to try to identify that since some of the transplants
were done female into male, we should be able to prove that we do not
find the y chromosome in the engrafted areas and in the chimeric areas,
which would get at the question whether it is caused by fusion.

And so I think we really need to set up experiments where we have
generic markers on both sides, meaning the donor and the recipient, so
that we can prove beyond any doubt that the in vivo results would be the
results from a fusion.

PROFESSOR BLACKBURN: Yes, I totally agreement with that. I think the in
vitro, and I am very impressed by the in vitro results, and as you said,
there are questions in vivo.

I think in-part my question was addressing this issue, and I was asking
about the tumor forming ability or otherwise, because it was not exactly
4N. It was the median number of chromosomes was different from simply
4N, suggesting that there was aneuploidy, and for example, one might not
find Y chromosomes, for example, because those had been selectively
lost.

So one would probably have to do much more extensive genome-wide
analysis of both of those to be sure that there wasn\'t some genetic
contribution from the recipient cells.

But I certainly am very impressed as you say with the in vitro results,
and they seem quite unequivocal, and I guess which is the question that
you are addressing, and we will find out as the in vitro \--

DR. VERFAILLIE: Yes, and I think we need to set up the experiments where
we have on multiple chromosomes genetic markers. You know, sequences
that we can distinguish the donor and recipient between. So these
experiments need to be repeated.

DR. KASS: Questions? Janet Rowley, please.

DR. ROWLEY: Well, I would like to ask a question that will include both
Elizabeth, as well as Catherine, because I was struck in the data that
you presented on your human cell lines that you had passed for more than
a hundred generations, that telomerase was still active.

And I just am curious about that, because many of us do believe that
that is, if you will, the internal clock that limits the number of
doublings that those particular cells can undergo.

And you derive these from adults, presumably young adults in human, but
at least adults, and I am curious as to what you thought about the
mechanism of preserving the telomerase activity, and maybe if Liz would
have any further comments on that, because again one of the critical
features and potential limitations of adult stem cells is the fact that
they would have potentially fewer doublings than would those derived
from embryos.

DR. KASS: Could I ask as a favor to the non-scientists in the group if
someone would just give an ABCs on the telomerase matter, and just very,
very briefly, so that everybody can understand what the discussion is
about. Elizabeth, or Dr. Verfaillie, if you could just give the barest
\--

PROFESSOR BLACKBURN: I am the worst person, because I will fall into
expert jargonese and so I will try not to. So, telomerase keeps the DNA
at the ends of chromosomes replenished, and such replenishment is
necessary, because each time one of our cells divides, the DNA at the
end of the chromosome is a little bit whittled away.

So, telomerase keeps putting back a little extra DNA on to the ends of
the chromosomes each time on average a cell divides. So the issue that
Catherine pointed out in her talk was that if you don\'t have telomerase
after a number of cell multiplications, that whittling away process
would have gone too far, and that sends a signal to cells to cease
dividing.

And so many, many normal cells in culture are characterized by the
inability to keep on multiplying. Did that clarify the question? So many
cells do not keep multiplying because they turn the cells' telomerase
off as part of their natural differentiated state.

Cancer cells, on the other hand, have telomerase, almost in a great
majority of the cases, and very up-regulated, and cells of the
hematopoietic system \-- and I will defer to Catherine on this \-- have
an interesting intermediate situation, where they have regulated
telomerase activity that is turned on in a natural and regulated way as
the cells multiply in response to signals in the body. Is that fair to
say?

DR. ROWLEY: Yes.

PROFESSOR BLACKBURN: So I think it is a very interesting question of why
telomerases is turned on in those cells that are multiplying so well in
culture, and has there been a selective event that has allowed those
cells, that for some reason have turned their telomerases on in the
culture conditions.

But those are the cells that are outgrowing perhaps others in the
population, and perhaps that question might be answered by what is the
clonal efficiency with which you get these lines growing out. You may
already know this.

DR. ROWLEY: But can I intervene, because you assured that it was often
turned on, and maybe these cells are identified because they never
turned telomerases off.

PROFESSOR BLACKBURN: Yes, and I don\'t know if that is the typical
situation when one puts cells into culture, and I thought that they more
often would turn off and an earlier subset would keep multiplying, and
again I want you to correct me on that cell growth phenomenon.

DR. KASS: Thank you.

DR. VERFAILLIE: So currently we do not know whether it is often turned
back on in culture. If we look at the cultures, for the first 40
population doublings, the cells appear to grow slightly faster.

And then a second wave of cells grows out and it grows slightly slower.
So initially we thought that maybe the more classical senescing cells
were disappearing, and that those were the cells that were growing
faster, and the you then select for the cell that has inherent \-- you
know, has the system turned on to not be subject to the clock of aging.

The frequency with which we can grow out the cells from human bone
marrow is we believe one in a million bone marrow cells. So it is a very
rare event, and so it will be quite difficult to actually specifically
ask whether it is turned on and then back off, or turned off and then
back on, unless we can actually do some genetic trapping experiments to
try to ask the question.

PROFESSOR BLACKBURN: I\'m thinking of David Beaches\' experiments in
which he was able to show that cells would spontaneously, if you keep
them in culture, turn their telomerases back on, because that gives them
some selective advantage.

DR. VERFAILLIE: Right.

PROFESSOR BLACKBURN: And so I was wondering if such selected advantages
occur in your situation?

DR. VERFAILLIE: It could well be, and so the culture conditions are very
particular, and so I didn\'t go into too much detail.

But if you do anything wrong to the culture conditions, we cannot create
the cell lines, and so it might well be that it is what we call in my
lab a cultural artifact what we see, which would mean that these cells
may not exist really as such, but actually are induced to become this
long-term proliferating cell by the culture conditions that we put them
under.

PROFESSOR BLACKBURN: Thank you.

DR. KASS: Janet, again, please.

DR. ROWLEY: I have two more questions. One is a follow-up of a question
that I asked you about a year-and-a-half ago, on whether out of your
MAPC cells you can get hematopoietic tissue.

DR. VERFAILLIE: Well, I think I showed you in vivo that if you infuse
the cells into mice that were either not irradiated or sub-irradiated,
that the cells appear to be able to differentiate into hematopoietic
elements that have red cell, and granulocytic markers.

In vitro, we have had more difficulty to try to do that, even though it
appears now that we can at least get for people who don\'t understand
this, but what would be yolk sac hematopoiesis, even though we haven\'t
really seen hematopoiesis that would occur in the embryo proper.

But we can find cells that look like the cells that have been created at
the earlier stages of development, where the initial one is made, which
is in the yolk sac.

DR. ROWLEY: And the other question is more a more practical question. I
don\'t know precisely how many cells would be required to treat an adult
patient with a particular disease, and are the number of cells required,
or what kind of limitations, using your system, would be faced if you
have not one patient, but hundreds or thousands of patients that could
benefit from a particular therapy?

Is this really going to be an applicable strategy?

DR. VERFAILLIE: I think it is a bit too early currently to really be
able to answer that question. We have been able to take cell populations
and have them undergo 80 to a hundred population doublings, which is
really if you were able to do that and not throw cells away along the
way, it is 10 to the 50th cells or something like that.

So it is an enormous number of cells that you can in theory create. What
I didn\'t go into too much detail on is that the way that we have to
grow these cells is under very low density conditions, meaning that the
cells have to be far away from one another, or otherwise they do not
maintain their undifferentiated state.

Which is quite different from embryonic stem cells, which tend to grow
in tight clusters. From a bioengineering standpoint, meaning scaling it
up to making hundreds of millions of cells, will be a major
bioengineering question of how we can actually adjust the system to be
able to do that.

But on theoretical grounds, you know, if you could overcome all the
bioengineering problems, you should be able to create enough cells to
treat multiple individuals, rather than a single individual at a time.

DR. KASS: Question. Robert and then Mike.

PROFESSOR GEORGE: Just a very quick question of clarification in
response to Janet\'s first point. On this question of whether they were
\-- whether the teleomerases were turned off and then turned back on in
the culture.

If it is not that, and if that\'s not what is happening, the other
possibility is that they were never off to begin with?

DR. VERFAILLIE: Correct.

DR. KASS: Mike Gazzaniga.

DR. GAZZANIGA: Again, thank you for a very excellent talk and a cautious
talk I thought. I thought it would be helpful for us to understand the
new pressures of a biologist like yourself, which are the following.

Here you have this fantastically interesting finding, and up until 5 or
10 years ago, the normal way that such things would be treated is you
publish the work in peer review, and then you make the stuff, whether it
is reagents, or whether it is cell lines available to others for
reproducibility.

And that is a normal sequence of events that we are all familiar with.
And now we have the bio-med inserting itself into these laboratories,
where all of a sudden it becomes proprietary goods from this work.

When the original media picked up on your story, and I guess it was [The
New Scientist]{.underline}, there was this cryptic little paragraph in
there about how they had seen the patent on some of this work, which is
a very complete description, and how does that \-- what is going on
here?

How can \-- and this is where I would like to go obviously, and
obviously it is good for everybody here to get these cell lines that you
have out to other labs, and reproducibility, and then the process goes
forward.

Are you constrained in some way, and has life been made complicated
because you didn\'t have full public funding and you had to use this
other money, or was that your own? What is going on?

DR. VERFAILLIE: So the work was really done at the university with NIH
funds and university funds, and so there was really no private funds,
except for the small amount from the company that was listed in the
beginning, has gone into the work that we have done.

And because of the possible importance of the observation, the
university, as well as myself, thought we should get some kind of
protection, even though I am not sure that you can truly patent stem
cells, because all of us have them.

But just such that we would be in a position to work with biotech
companies to be able to produce large-scale numbers of cells and things
like that, which is hard to be funded to known private funds.

So there is patents pending on the cell population. Currently, that
really has not precluded us of collaborating with other institutions, or
investigators within the same institution.

So they have collaborations with 10 or 15 different groups within the
U.S., or outside of the U.S., depending upon the expertise that we need,
to try to recreate the cells in other laboratories, and actually use
their expertise, since I am a hematologist, and not a liver physician or
a neuro scientist.

And to actually be able to use expertise in other people\'s laboratories
to move the research forward. So there are some minimal ties attached to
working with the cells, but I think it isn\'t overcomeable, and it
really has not been an issue with other academic investigators to
collaborate with them.

And teaching people from those labs to come and to grow the cells, and
at least start working with the cells. But it is a very complicated and
it is a \-- and I have had myself a lot of problems in trying to find
the right patent between potential biotech interests and academic
interests.

DR. GAZZANIGA: Right, and you are not alone in that dilemma. So are
there other MPAC lines at other institutions now that behave like yours,
or is yours still the Golden Grail here?

DR. VERFAILLIE: We have given out the mouse, and to some extent, human
MAPC lines to other investigators who are now setting the lines back up.
We are also explaining and teaching people how to create them from
beginning bone marrow.

And I know that there is one group in Japan who I think pretty much as
the system set back up from human bone marrow. You know, they still need
to do some additional studies to prove that it is really MAPCs, but we
trained a person from there for 3 or 4 months in my lab, and they went
back to Japan, and were able to it appears to recreate them.

DR. KASS: Could I ask a couple of sort of semi-scientific and
semi-practical questions? How hard is it \-- I mean, you have just
indicated that not many people have already been able to do this, but
how hard is it to find these cells?

And by which I mean two pieces, and in how many individuals in which you
look for them can you find them? And how hard is it to find \-- how rare
are they, and how hard is it to find in any particular individual?

Both of these questions bear upon at least a preliminary assessment of
how useful this might be clinically speaking down the road, although
things could change where you might be able to enhance the yield.

But could you give us a preliminary sense of this?

DR. VERFAILLIE: I think we have studied now between 70 and 80 normal
humans to try to identify the cells. The age range, the youngest donor
was two, and the oldest donor was 55. The majority are young adults who
want some money to donate bone marrow at the universities.

DR. KASS: The two-year old?

DR. VERFAILLIE: No, the 20 year olds. The 2 year old actually did a bone
marrow donation for a sibling who needed a bone marrow transplantation.
So we have been able to create the cells I would say in about 70 percent
of the individuals that we have looked at.

Whether that means that the other 30 percent didn\'t have it, or there
was some technical issue that came about, and we were not able to create
them, we start out with 10 milliliters of bone marrow, and we would
usually find a few clones that can actually grow out.

And so really the frequency is quite low, and it is one in a million,
and that is at least the estimate that we have right now. But there is
lots of bone marrow and so one in a million isn\'t an impossible task to
do it.

DR. KASS: And could I also follow up on the question of these cells and
their promise, assuming the best, and the embryonic stem cells, assuming
their best.

This is not a question of whether one should prefer one line of research
or another, or whether we should now go ahead with them. But is there
anything specific that you could imagine could not be done
therapeutically with these MAPC cells that you would then need cells
derived from embryonic tissue to do?

Or is this in the rosiest division, is this really a substitute, and one
that might even have the rejection problem solved if I am dreaming?

And this is not a question about whether the other research should go
forward, but really what is the best promise of this research so that at
least we can think about it?

DR. VERFAILLIE: Well, I think that the data that we have in vitro
suggests that we can create cells of the three germ layers of the
embryo, and so theoretically, you could envision that you might be able
to make more than we have done so far.

We have made liver-like cells, and brain-like cells, and epithelial
cells, and we have not tried all the other ones. In vivo, the blastocyst
experiment, unless that is a fusion event, and if it isn\'t a fusion
event, would indicate that the cells hold the inherent promise of making
all the different cell types that make up the tissues, the somatic
tissues of an animal.

So again that would suggest that is under \-- that if we changed culture
conditions further that we might be able to, for instance, create
insulin-producing beta cells, which we haven\'t done, or create two
heart muscle cells that function like heart muscle cells, and don\'t
just look like it.

So if all these promises hold true, and if we continue the cultures and
they can be expanded even further into 80 or 90 population doublings,
and so there are lots of ifs here, they may be able to be used to treat
a large number of diseases.

The problem at this point in time is that there is so many ifs that it
is a very difficult question to specifically answer.

DR. KASS: Of course, and I appreciate that, and on the question of the
longlivedness, or the half-life of these things, you have gone through
\-- in vitro is what? It is what?

DR. VERFAILLIE: From 80 to 100 population doublings.

DR. KASS: And it is obviously too early to say how much longer, and
whether those conditions are matched in vivo. But when the people say
that the promise in terms of longevity for cells derived from the adults
is really much less, is there anything to be said on that question of
the basis of knowledge now had?

DR. VERFAILLIE: Human embryonic stem cells have been kept in culture now
for 350 or 400 population doublings. So that is 3 or 4 times as long as
the adult cells. So we are striving to go there, but we just need time
to do that.

Are these cells going to be able to do that? As far as we can tell,
after 80 population doublings, there is no shortening of telomeres, and
so that means that there is at least another 50 or 60 left.

If for some reason telomerase is shut off along the way for reasons that
we currently don\'t know why that might be, then the longevity would be
less than what has been shown for embryonic stem cells.

Now, for classical adult stem cells, if you take hematopoietic stem
cells that make blood, but not something else, they would not go for 80
population doublings.

So there is something special about these cells, that they can overcome
this senescent block at 60 or 70 population doublings, which is actually
long for any other adult stem cell.

DR. KASS: Thank you very much. Questions or comments? Janet again,
please.

DR. ROWLEY: Coming back again to partly the real world in this iffy
situation, and it is a question of the practicality for treatment for
particular individuals.

It seems to me that the notion that you might be able to derive these
MAPC cells from an individual who had some medical problem might have
some limitations because it probably takes 3 to 6 months, or so to get
enough cells to then be able to use them therapeutically in that
individual, and that is always assuming that the individual has some
kind of a somatic disease, and not the basic underlying genetic problem.

So then the way to get around that if it really is 3 to 6 months, and
you don\'t have that window of time, would be to do somatic cell nuclear
transplant. Now, have you ever tried that in your MAPC cells?

DR. VERFAILLIE: In collaboration with Dr. Jaenisch, and two weeks from
now we will try the mouse MAPC cells in mouse eggs, and ask whether the
efficiency of nuclear transfer would be closer to what you would see
with embryonic stem cells, and where the efficiency is much, much, much
higher than if you use a classical adult cell.

And that might improve efficiency of making cloned embryonic stem cells.

DR. ROWLEY: But I am thinking of the other experiment. You have a
patient who is desperately ill, and so you would have cells from that
patient, and you would want to use the nucleus of the patient\'s cells
into your MAPC cells, and so that is a different thing.

You have got these cell lines, and how can you make them more compatible
with the patient, and agreeing that you can\'t get rid of the
mitochondrial problem unless you do additional manipulations and
strategies.

But have you ever tried to replace the nucleus in your MAPC cell with a
nucleus from an adult somatic cell?

DR. VERFAILLIE: No, we have not yet.

DR. ROWLEY: Do you plan to?

DR. VERFAILLIE: We might.

DR. KASS: We could always get everyone at the age of 15 to put away a
little bit of marrow for the time that we might need it.

DR. ROWLEY: Another reason to save cord blood.

DR. KASS: This is your chance, council members. This is a wonderful
opportunity. Questions?

DR. ROWLEY: Well, I would just be interested from Catherine\'s point of
view on her answers to some of the questions, to the two questions that
I posed at the end to John Gearhart, and again give her the option to do
this as a written response rather than a direct response, but I think it
may be easier to \-- and the second question, which may be very simple
to answer in terms of the kinds of restrictions that you find now in
funding.

And I would assume since you are dealing with adult cells that there
aren\'t any, but I would be interested in your perspective on the
funding, in both government and other agencies.

DR. VERFAILLIE: Well, currently for the work that is ongoing in my
group, which works with adult stem cells, actually the amount of funding
that has become available through the NIH has increased dramatically
over the last few years to support this kind of research.

So that has not been a problem. I have wanted to compare these cells
carefully with embryonic stem cells, and so we are in a position
currently to do this in a mouse, but mice aren\'t humans.

And so we have really not been able to do that until earlier this year
when human embryonic stem cell research was allowed in academic
institutions under NIH funding.

And as I mentioned, we had actually gone out and tried to recruit an
investigator with that kind of expertise to be in a position to try to
address some of the questions that have come up here, and are these
cells going to be equipotent.

And I think to date, even though they are exciting and they seem to be
quite potent, I can\'t really say whether that is the case. And so
ultimately we won\'t be able to answer this question until we can truly
compare them and not across country borders, but actually within the
same institution, where people can look at the two cell populations at
the same time.

And so in that respect, I think that the lack of funding for embryonic
stem cell research in humans has made it impossible up until just
recently to be able to do that.

DR. KASS: Michael Sandel.

PROFESSOR SANDEL: I wonder if I could put to you the same question I put
to the previous speaker. Given that some people regard embryonic stem
cell research as morally problematic, what would you think of the idea
of imposing a moratorium on embryonic stem cell research until we could
assess what might be achieved by adult stem cell research?

DR. VERFAILLIE: I think that my answer is very much in line with what
you heard from Dr. Gearhart. I think that the main reason why we \-- to
investigate in the field of embryonic stem cell \-- human embryonic stem
cell research is to be able to compare and contrast the two cell
populations at the same time.

I also think that what we did in our culture dishes to try to
differentiate these MAPCs into liver-like cells or neuronal-like cells
is really based on what has been learned from mainly the mouse embryonic
stem cell field, where investigators have been able to take these cells
and drive them in vitro to become certain cell types, even though that
is not a hundred percent fool-proof, and it is not completely figured
out how you should do that.

So I think if you have a number of different cell populations at the
same time, we try to test all these different questions. What we learned
in adult cells might be applicable to embryonic stem cells if they are
the cells that ultimately will be the suitable source for our clinical
applications or the other way around.

And so I think stopping research in one field actually will slow down
research in the other field, and it would be either way. In other words,
if you stop our research in adult cells, or embryonic stems, as I think
what can be learned in the two systems should be translatable in the
other system.

And so I think if you were to ban all embryonic stem cell research, it
would really slow down the insight that could be gained in adult stem
cell research.

DR. KASS: Rebecca Dresser.

PROFESSOR DRESSER: This is unfair, but I am wondering if you had any
ideas about the cost of such a procedure? I mean, just based on what you
have done in mice, and you mentioned at the very end that to be cost
effective that you would probably would have to just have a number of
cell lines and not rely on the patient cell.

Is this going to be a very, very expensive technology, and where we have
to worry about \-- well, if all these ifs work out, will we have to
worry about who has access, or will it be comparable to the stem cell
transplants that we do now with bone marrow now? Or what do you think?

DR. VERFAILLIE: Well, I think it will be relatively expensive if you do
it on a single person basis, and you will have to create the cell lines
from the beginning, rather than go going to a frozen stock of cells,
where you have a very well-qualified product to start with and where you
expand cells.

And so you might even have already committed cells frozen as well, and
so the cost to get to that point would have to be incurred once rather
than doing this over, and over, and over again.

The costs I think \-- well, it is hard to say, because I am not sure how
much of the regulatory issues we have actually complied by at this point
in time to actually truly gauge how much it would cost.

But I think that by the time that you do all the quality control tests
for infectious agents and things like that, that amounts to quite a bit
of money for each cell line that you try to establish.

And in the long term I think it would probably be more cost effective if
you would have a therapy for heart infarcts that you could go to a
limited number of cell lines. And to put numbers of them, I don\'t
really know.

It would probably be in the range of a bone marrow transplantation
currently, which is quite expensive. So it is anywhere between \$50,000
and \$200,000 per patient.

If you had qualified cells that were frozen, and then you could expand
them for a short period of time and do a limited number of tests at the
end, the amount of cost incurred would really be all up-front, and then
there would be a relatively small amount per patient.

PROFESSOR DRESSER: I guess the other thing is that bone marrow
transplants work fairly well with some illnesses and not with others,
and would you expect to see those kinds of results with these kinds of
therapies?

DR. VERFAILLIE: I think that would highly depend on the type of disease
that you tried to treat. You know, you are all well aware of the
treatments that have been used for Parkinson\'s disease, which the
trials that were done in Sweden have made little complications.

But when this was extended in multiple hospitals in the West, there were
a lot more complications if it was done on a larger scale. So I think
that depending on the disease that you go after that it may work better
or worse, and it is really way to early to be able to comment on that.

DR. KASS: Bill, do you have a question?

DR. HURLBUT: Well, if we have time, I would like to ask a couple of
scientific questions if that is all right.

DR. KASS: Please.

DR. HURLBUT: Do I understand this correctly that you are saying that
your MAPC is put into the blastocyst to perform more cell lines than do
other adult stem cells?

I thought that adult stem cells generally formed lines in a blastocyst?

DR. VERFAILLIE: There are 3 or 4 papers published on adult stem cells
into blastocyst experiments. There is one paper published by a German
group, where they took purified hematopoietic stem cells, and injected
them into the blastocyst, and what they were able to show was that the
cells gave rise to some hematopoietic elements, and that they actually
recapitulated the developmental behavior of hemoglobins, which switched
at different stages of development during embryos, fetuses, and then
adults.

They did not see any contribution outside of the hematopoietic system.
The second paper is a paper from a Swedish group, where they had taken
neural stem cells that have been cultured, and introduced them in the
blastocyst, and as far as I know, they have never had animals been born
alive.

And they saw a contribution to a few tissues, but not all tissues of the
mouse fetus. And in the last papers, we did a paper by Austin Smith, the
one that reported on fusion, where they had taken defused cells and
given them to a blastocyst again, and it showed a contribution in one
animal that was born, and that was really only a single animal, to the
liver and a few other tissues.

But it was not quite the amount of contribution that I showed in the
picture here, where every single tissue of the mouse appeared to be
having a fraction of the single MAPC cell.

DR. HURLBUT: That is very, very exciting. Another question that I think
might be of good general interest to our council, but he question of
whether transdifferentiation is occurring, or even the process of
embryonic stem cells just differentiating, it is always clouded by the
question of how do you know when there is actual differentiation taking
place?

In other words, just because you follow one or two gene expressions, you
don\'t know, and one of the problems with embryonic stem cell therapies
will be to get the target tissues up to speed, like beta cells producing
enough insulin.

I know that there are advances being made on this, but can you just give
us a general description of how you identify when you are satisfied that
a tissue has in fact been produced?

And maybe tell us a little bit about the \-- maybe we need a little
education on messenger RNA assays.

DR. VERFAILLIE: Okay. The criteria to say that you produced tissue I
think needs to include that you turned on the genetic program that is
compatible with the tissue that you want to produce.

You find therefore proteins from the genetic program in the cells, and
the cells have morphological changes consistent with the cells that you
are looking for, and the cells have functional characteristics of the
tissue that you are looking for.

So what happens in a cell is that in an undifferentiated state a number
of gene programs are shut down, meaning there is no transcription to the
messenger RNA, and you will find no protein, and therefore no function.

During a differentiation process, you come in with a growth factor or a
cytokine, or a stimulus from the outside, and you trigger a certain set
of signals that then open up a new genetic program and the first thing
that happens is that you transcribe messenger RNA, that then gets
translated into proteins and/or sugars, that then supposedly give a new
function to the cell.

So what we have been looking for in vitro, and that is where most of our
work has been done initially, is actually taking an undifferentiated
cell and showing that a certain genetic program isn\'t turned on,
meaning that you don\'t find mRNA, and you don\'t find protein, and you
don\'t find function.

We then switch the culture conditions and add triggers by trial and
error, to a large extent to try to activate certain genetic programs.
And if we do that, we look for protein and mRNA first.

So we look to prove that the genes are turned on, and then we look to
prove that these gene products actually give rise to proteins. We have
gone to the next step also and actually tried to then take the cells
that we believe that are like brain or like liver, and started asking
questions.

If it is a liver cell, it should secrete certain things. It should have
the machinery to detoxify blood and things like that. So we have been
able to show that in the liver lineage, for instance, that we do turn on
the programs to make albumin, which is one of the major proteins that is
being secreted in the liver and is present in the blood.

These cells have, for instance, cytochrome p450, which is a massive
machinery in the liver that helps detoxify the blood components. And we
can show that it is there, and it responds in the correct ways as liver
cells would do.

So that is what you do in vitro, and in vivo, it is a bit more
complicated, and you really need to use animal models where there is a
disease. So you would have to show that the cells ingraft and you can
find the donor cells.

You would have to show that they turn on RNA and protein, and therefore
have this genetic program turned on. And then function, which means that
if you take an animal that has a failing liver, and you give the liver
cells to this animal, the animal will now live without having drugs that
keeps it alive.

And so that would prove that the cells that you put in have actually
acquired the ability to function like a liver cell. And so for adult
stem cell research, very little proof of the latter is actually present.

For embryonic stem cell research in mice, there is a lot of evidence,
and in the human embryonic stem cells, that evidence is just starting to
become available, just like it is with adult stem cells.

DR. HURLBUT: Could I ask one last little question? How many genes are we
talking about here; like hundreds, or thousands, and how many do you
monitor in fact?

DR. VERFAILLIE: Well, we usually monitor between \-- well, there is
probably hundreds of thousands that get turned on, and so using the new
technologies, the array technology, and the proteomics technology, that
is one of the things that we are looking at, because it will give us a
much better insight in the whole programs that are being turned on.

We just pick and choose the ones that we think are known to be important
at certain stages of the differentiation. So, for instance, if you go
from a stem cell to a liver cell, we know that you have to turn on X
number of genes that happen to be known to be turned on.

So we look at 2 or 3 that are early, and 2 or 3 that are in the middle,
and then 5 or 6 at the end. We have not exhaustively looked at all of
them yet.

But I think with the human genome being sequenced, we now have the tools
in hand to now take cells created from stem cells and look at the whole
program of genes that is present, and what we created in a culture dish,
compared to what is actually present in real life in vivo, and get a
feel of how closely we actually are getting to the real cell.

DR. HURLBUT: Thank you.

DR. KASS: Could I \-- Robby, did you have a question? Why don\'t you go
first, because I have a couple of things as well. Please.

PROFESSOR GEORGE: Actually, I just wanted to follow up the question that
Dr. Kass asked earlier just for clarification, and I recognize that
there is a great deal of uncertainty as to what the future holds in your
area for research, as well as in embryonic stem cell research.

And estimating or evaluating what the prospects are therapeutically is a
speculative business, but having all of that in mind \-- and I was not
clear in responding to Dr. Kass whether you identified some areas in
which knowing what we do know now about the differences between
embryonic stem cells and the MAPC cells, it is possible to identify some
areas where we just know that whatever the prospects are for MAPC cells
that they won\'t be able to do, or our therapies won\'t be able to be
developed based on them to do certain things.

And that there is at least a prospect of embryonic stem cells being used
to do.

DR. VERFAILLIE: It is so very hard for me to answer that question, just
because embryonic stem cells have been worked with for so much longer,
and so investigators have been able to, for instance, make cells that
secrete insulin to some extent on demand, which has not been
accomplished with adult stem cells.

There is a little bit of evidence from pancreatic tissue itself that
there might be precursors that can do that, but from MAPCs, for
instance, we have not been able to do this yet.

It doesn\'t mean that we can\'t. I don\'t know that answer. So there is
a lot more experience with embryonic stem cells and there is a lot more
\-- at least in the mouse system, there is a lot more known on how to
try to trigger certain differentiation programs and whether the MAPCs
will respond to the same extent and to the same degree.

And I think that currently I can\'t really answer that question.

PROFESSOR GEORGE: But asking if you look at it and not asking what do we
know MAPC cells will be able to enable us to do, and have a prospect of
doing, that embryonic stem cells have a prospect of doing.

But if we simply ask the question as do we know just on the basis of the
facts of what we know about the differences, and that there are in fact
some things that MAPC cells, no matter what, won\'t be able to do. Or is
the answer that we just don\'t know?

DR. VERFAILLIE: I think we don\'t know currently, and I can\'t really
answer that question, because we just don\'t know at this point in time.

DR. FOSTER: I just want to interrupt with this one point. Those
questions are really hard to answer, but there is another whole area
that is going to impact what you are going to use cellular based therapy
for.

And that has to do with good vectors, retroviral gene therapy, and that
you are going to accomplish with other diseases that you don\'t have to
use cells for at all.

I mean, the most recent thing in severe combined immunodeficiencies in
humans, is you put a retrovirus in, and you put the common gamma chain
in for about five cytokines, you know, for these kids. It was just in
the [New England Journal]{.underline} a couple of weeks ago, or three
weeks ago, or something like that.

And they are now two years out, and so there are going to be a whole lot
of diseases that you are not going to have to use regenerative therapy
or cell therapy. You can\'t predict those things either at this point.

So I think if you try to jump way ahead of what the basic science is
doing, then you are prone to error, and I know everybody wants to know
whether an adult cell is better than an embryonic stem cell, or
something like that.

And I don\'t think you can answer those questions, and one of the things
that we have heard from both the investigators this morning is that they
cross-fertilized with each other.

And so \-- I mean, that you could not have done what you are doing in
the adult cells without what had already been done with the embryonic
cells.

So I just would argue against trying to push investigators to say
whether an adult stem cell can do this or do that at this point, because
we have not even taken into consideration many other approaches to human
disease.

I don\'t mean to be fussy, but I do think that that is an important
thing.

PROFESSOR GEORGE: But I was actually asking \-- well, I think the
question I asked was that it really is about what we know now. The
question is do we know now that there are certain differences, that as a
result of which the prospects for the one area are different from the
prospects of the other. And I got my answer. Thank you.

DR. KASS: Let me take the privilege of the Chair to expand in a way Dan
Foster\'s comment in a direction that he might not have intended.

DR. FOSTER: That does not surprise me.

DR. KASS: Well, I mean, you are a genial sort, and I think you won\'t
\-- I mean, one of the things that one has to remember in this
conversation is that wonderful as the stem cell approach is from
whatever source to the treatment of these diseases, that is not the
whole area here also.

And that the gene therapy is not the whole story as well, and there are
preventive measures, and there are all kinds of other things. I mean,
the conversation, because we are taking it up, gives it a certain type
of dramatic focus and concentration.

But for the people who work in clinical medicine, they know that this is
\-- that there are lots of ways to try to skin this cat. But I wanted to
ask a couple of \-- to make a comment, and then ask a couple of
questions.

You have talked understandably and very welcomely to us about your own
very exciting work. There is a great deal of skepticism about many of
the published works in using adult stem cells.

And unfortunately, for better and for worse, these reports are caught up
in the political controversy that now surrounds us, with people on both
sides having a stake in either making the results on one line of work
seem better than the other, precisely because they are wed to an
either/or choice.

Can you, abstracting from all the political considerations, and the
various axes that various people are grinding on these poor cells, can
you say anything at all generally about the kinds of initial reports of
a clinical sort that we have had with alleged adult stem cells?

Because at least according to some accounts, these have been very
exciting, and yet there is a great deal of skepticism about whether
these are in fact stem cells that are producing the results.

Can you tell the council anything at all about how we should at the
moment regard the news that is coming out to us in this area? How should
we receive it?

DR. VERFAILLIE: There have been several publications that came out over
the last 1 or 2 years now, where investigators or clinicians have looked
at individuals who were transplanted with classical bone marrow
transplantations, and looked in tissues outside of the hematopoietic
system to ask whether bone marrow derived of donor-derived cells could
be found in different tissues.

And the reports that have come out have indicated fairly significant
levels of contribution to certain tissues, meaning they have found cells
in the heart, and they have found cells in skin, gut, liver, and so
forth.

And we really have not looked in the same situation to see whether we
can confirm these data or not. I know that some clinical groups have put
in doubt to some extent the degree of contribution that has been
reported, and it is not quite clear whether the 5, 10, or 20 percent
that has been quoted in some papers is indeed actually going to hold up
over time.

I think there is some contribution, and the question in my mind still is
how clinically important is it what investigators have seen or what
clinicians have seen currently.

If you go strictly by the term of stem cell plasticity, none of these
studies really show that it was a single cell, or it was a blood cell
that gave rise to these tissues, and it might still be that some
contaminating cells were contributing to that.

And really none of these studies have shown that this has had any
clinical impact on what was going on in these patients. And so they
didn\'t really show that you restored function of the organ that the
cells were found in.

DR. KASS: I was thinking of a recent report on the Parkinson\'s cases.

DR. VERFAILLIE: Correct. So the Parkinson\'s cases were \-- and that is
with fetal brain tissues, and are those the reports that you are
referring to?

DR. KASS: Yes.

DR. VERFAILLIE: And so there has been a series of patients transplanted
in Sweden with Parkinson\'s disease, where one team of investigators in
a non-controlled study, shows that implantation of the fetal tissue
brain \-- fetal brain tissue into the brain of patients with
Parkinson\'s disease could rescue patients, and could actually correct
the Parkinsonism.

And actually have now done so for some patients for more than 10 years.
Now, these were highly selected patients, and done by a single group of
investigators.

The same was done in the west in 3 or 4 institutions, and some patients
got better and some patients did not get better. But I think that gets
to the proof of concept that if you have the right cells, and if you can
create the right cells, and if it is from embryonic stem cells, or adult
stem cells, or from tissues itself, that there might be a way of
correcting Parkinson\'s disease.

But there is again \-- and I think it would behoove us to really look
carefully at exactly what single cell or fused cells that we have to put
into the brains of patients with Parkinson\'s disease to try to correct
the disease, and not over correct it as it was done in some of the
patients in the U.S., where they had more side effects from the therapy
than they initially had from their Parkinson\'s disease.

And so even though there is an enormous amount of pressure on all of us
with stem cell research to try to come up with therapies yesterday, I
have been very, very cautious in telling people that do the clinical
work that you can\'t just go around and take stem cells and put them in
places in the hope that they will work.

Because we will get into situations like the gene therapy field, where a
couple of awful problems have popped up, and have actually halted the
clinical potential of these cells enormously.

DR. KASS: Could I follow that up, because if there had been more time, I
would have asked Dr. Gearhart this question as well, and you are a
clinician who deals with patients that are also \-- now thanks to your
new results, and I am sure that you are getting lots of calls as well.

There is an ethical dimension to this area that worries not so much
about where you get the cells from, but how we deal with the desperately
sick patients looking for any sort of hope.

And let me say flat out that in-part to fend off the opponents, the
people in the scientific community and medical community, has to some
extent not been adverse to shall I say hyping the benefits here and
possibly even taking rather cruel advantage of these hopes.

And from what I hear from you, and from what I hear from Dr. Gearhart,
these therapies, there are lots of problems to be solved before these
things will be made available.

And that is not to say that there isn\'t this enormous promise, but what
can you tell us, or what advice would you give us about we could
responsibly speak about this promise without behaving, let me say,
unethically in dealing with the very patients who are coming to us for
help?

And I think that\'s something that you have probably faced directly, and
whatever help you could give us on that would be welcome.

DR. VERFAILLIE: Well, like Dr. Gearhart, my e-mail and phone have a lot
of messages on them from patients locally, around the country, and
around the world who want to bring a child or a parent with a certain
disease, and want us to treat whatever disease you can come up with.

And we have to speak the truth, and even though we are excited about the
work that we have, and for the work that people do in embryonic stem
cells, at this point it is a promise, and I don\'t think there is any
data to say that in the next 1 or 2 years we will actually be in
clinical trials with any of this.

So we really have to tell patients, families, and whomever, that
currently we are trying to cure mice, but a lot of mice have been cured
with a lot of different things, and that doesn\'t necessarily mean that
it will translate into humans.

And so we need to do the regular science that needs to be done to come
up with a therapy that is both potentially useful and for certain not
dangerous.

And so that the last part of that whole thing is really where everything
sits. And so we could go ahead and do things now, but then run into
major, major complication issues which would make patients way worse off
than they started out.

You could argue that bone marrow transplantation, there was not a whole
lot known when the first bone marrow transplants were done, and that is
before I started in bone marrow transplantation, and probably some
patients didn\'t fare that well either in the beginning.

But people ultimately still have to learn by doing it in humans, but we
have to learn as much as we can in culture dishes, mice, rats, and
larger animals before we proceed with therapies for things that are not
immediately legal.

And so it is not because you are diagnosed with Parkinson\'s today that
four months from now that you will die from your disease, which is
different if you have a acute leukemia, where there is really no other
solutions.

And so I also think it will have to be graded depending on the type of
disease that you start treating.

DR. KASS: And I have one last question, and I don\'t think we will have
another opportunity in this discussion, but this comes to Rebecca
Dresser\'s question about the costs, and how to think about this. And
also about the applicability.

There was recently a meeting of the major biotech companies in
Princeton, and our scientific director, Dick Roblin, was there, and they
were discussing among other things the question of the solution of the
immune rejection problem from all these various things.

And all of the ones that were present there are putting their research
money not into somatic cell nuclear transfer to deal with the rejection
problem, but into other means, for a reason that would have never have
occurred to me until it came back from this meeting, which is to say
that if you have highly individualized treatments, case by case, that at
least under present regulatory systems, if you call these things
products, each one of them has to be approved independently by the FDA
before it can be used.

And so the question is whether or not \-- and in partly thinking about
the cost and the scalability, and the things that might make things
universally applicable, doesn\'t it make sense more to be thinking more
in terms of cell lines, whether embryonic or adult, and that could be
made universally applicable, rather than trying to continue to think
each person, his or her own replacement, given these practical problems
of scale and product approval?

I am not sure that the question was clearly put, but it bears upon the
efficacy of this in terms of long term clinical use, and the questions
of cost.

DR. VERFAILLIE: Ideally, it would be personalized therapy, and so you
would create cells that are completely compatible with the person that
you need to treat, except again in situations where there is an
autoimmunity issue, which makes it complicated.

And if it is an autoimmune problem starting out, then cell therapy is
probably not the best way to go about doing this. For instance, Type-1
diabetes would come to mind, where there is really a rejection of your
own islet cells.

I think the costs \-- and I spoke to that just a little bit before \--
of creating everybody\'s own cell line will in the long term will be
extremely high, and it will not be a therapy that is suitable for acute
events.

So if you have an acute stroke, or if you have an acute heart infarct,
and you try to correct that, there is no way that you can clone ESLs to
correct that, or you could create MAPCs to correct that within the next
one or two weeks.

It just takes too much time to try to do this. Then you could argue,
well, I will store our own MAPC cell lines or own ESL lines just in case
we need it, which definitely I don\'t think is financially tenable.

So even though the ideal situation would be to be able to make
everybody\'s own cells, and I think in the long term if the cell
therapies are proven to be, for instance, very useful in patients who
have a severe MI that you can actually correct them almost immediately
after the MI has occurred, or within the next few weeks after it has
occurred, it almost has to be done on an allogeneic basis.

And in that case, trying to come up with wise ways of making the cells
acceptable to the vast majority of patients, whether it is multiple cell
lines and a minimum amount of immunosuppression, or establishing partial
chimerism by creating both blood cells and heart muscle cells from the
same cell lines, for instance, would be one way to get around that.

DR. KASS: Thank you very much. Thank you very much for a wonderful
presentation, and a very generous and full response to our questions. If
we might take the liberty of just contacting you with some other things.

I know that your e-mail is full, and we will try to add very little, but
as we go along, we might have some additional things.

DR. VERFAILLIE: That would be great. Thanks.

DR. KASS: Thank you very much. Members are asked to go immediately from
here to the other room, where they want a group photo, and the four or
five of us who have not yet posed for our individual mug shots, are
asked to stay. I think lunch will be served there.

We will reconvene here shortly after 1:30, and let\'s say about 1:35 or
1:40.

(Whereupon, at 12:28 p.m., a luncheon recess was taken.)

A-F-T-E-R-N-O-O-N S-E-S-S-I-O-N

(1:41 p.m.)

DR. KASS: Well, if I sing a song, or make some announcements, maybe we
will get the full numbers, but this is the third of our three sessions
on stem cell research, having spent the morning hearing two
presentations on the science.

And we now turn in this session to ethical questions in stem cell
research, and we are very fortunate to have as our guest Professor Gene
Outka, who is the Dwight Professor of Philosophy and Christian Ethics at
Yale University.

And for a long time one of our most careful students of the ethics of
biology and medicine among many other things.

Apart from our interest in the merits of the case, a paper written on a
subject of concern to us, I have confessed in the chairman\'s cover
letter, in a sentence which has a missing word, that I have an
additional purpose in mind here, namely as just as those of us who are
not experienced in science, need practice in grasping the concepts and
methods of scientific analysis, so those of us who are not experienced
in ethics would need some practice in working with the concepts and ways
of ethical analysis. And Professor Outka\'s work is nothing if not
careful, analytical and disciplined, and we are very thankful that he
could be with us to discuss his paper.

All of us have had a chance to read it, and I exhorted you to read it
more than once, and there is a lot packed in it. And Professor Outka is
going to lead off with a few remarks, after which I have asked Michael
Sandel to make comment that would open our discussion. Thanks very much,
Gene.

DR. OUTKA: Well, it is a great honor for me to be here, and I enjoyed
sitting in enormously in the morning sessions, and noted that although
the focus was on scientific matters, moral matters also arose from time
to time, as when Dr. Gearhart told us that he doesn\'t give the same
moral status to the embryonic entity as he does to the fetus.

And I think that illustrates one of the claims that I actually make in
the paper, which is that on this subject, whether we like it or not, we
all have to be moralists in one way or another; that certain moral
determinations are unavoidable.

And in-part that is because the moral positions that we take have such
direct and sometimes colliding implications for the policy and political
recommendations that we make.

And I contrast that with certain other cases where you could have some
theoretical debates and disagreements might abound on that level, but
you could when you turned to practical and political matters, you could
come to some [modus vivendi]{.underline} or something of the sort, where
the theoretical disagreements don\'t translate into necessarily
practical political disputes.

That is not the case with this subject I contend, and so we all have to
be inclined to engage in moral reflection, and although moral reflection
has its own esoteric features in the hands of at least some, I think
that this session may be more egalitarian in a way, because I, like
Samuel Johnson\'s dictum, that we are perpetually moralists, but we are
geometricians only by chance.

And by that I take him to mean that moral matters, that there is a
fundamental equality about our reflection on moral matters, and it does
not require a special talent in the same way.

So that then leads me to say a few things about this paper, which we are
going to discuss. I tried to do several different things in it, and I
tried to give some kind of an account of some of the major points of
disagreement, and I have a spectrum of views from the right to the
center, to the left.

And I myself then plum for a particular region of the center, and along
the way though I do try to show how debates about abortion and debates
about stem cell research converge and diverge.

And finally I propose a nothing is lost principle, and let me say a
little more about that, but I think probably the most economical way to
proceed is simply to indicate for you some of the normative conclusions
that I put forward in the paper.

And not tarry over the questions about whether I do justice to those
either more conservative than I am, or more liberal than I am.
Spokespersons for both positions can speak for themselves later on.

So let me just then lay out some of the claims that I make, and that
will get us started at least. I make some claims about the status of
human life from conception forward, and I argue that once conceived each
entity is a form of primordial human life that should exert a claim upon
us to be regarded as an end and not a mere means only.

And I say that it is one thing to allow that we need not yet ascribe
full moral standing or equal protectibility to embryos. That is to say,
I deny that abortion and embryonic stem cell research are morally
indistinguishable from murder.

But I claim on the other hand that it is another thing to
instrumentalize embryos through and through when what we intend in the
actions we perform exhaustively concerns benefits to third-parties.

And I take that to be one indication of sheer instrumentalization, where
the actions that we perform we can only justify, and justify
exhaustively by virtue of benefits to third-parties.

That is to say that I deny that abortion and embryonic stem cell
research are morally indifferent actions in themselves to be evaluated
wholly by the benefits that they bring to others.

I then go on to conclude that to conduct research on embryos that
creates them in order to destroy them clashes directly with the judgment
that entities conceived have irreducible value.

So that is on the one hand. I want to say that the case for sheer
instrumentalization is to be resisted, but on the other hand, I also
think that we don\'t confront a single either/or as some conservatives
and some liberals suppose, to the effect that we should forbid all
embryonic stem cell research, or we should permit it all.

I consider instead a more nuanced possibility, or at least I think it is
more nuanced, where we may distinguish creating for research and only
employing for research.

And the latter of employing for research allows us to consider in vitro
fertilization as a practice in our culture, and employing for research
connects with the datum of discarded embryos, where I want to say that
the original creation of embryos has a non-instrumentalist rationale,
namely the promotion of fertility.

So that what we intend does not exhaustively concern benefits to third
parties. But yet the aftermath allows us to pursue benefits to third
parties when we may do so without from the start creating in order to
disaggregate.

And the way that I try to speculate about the pros and cons of this
conclusion is to invoke the nothing is lost principle, which I think
illuminates a morally significant distinction between creation for
research and employment for research.

The nothing is lost principle says that we may \-- that although it
takes the prohibition against murder seriously, it allows two exempting
conditions. The first is that the innocent \-- that some innocent will
die in any case, and the second exempting condition is that other
innocent life will be saved.

And applying that to the matter at hand, I say that we cannot choose
whom we save in the case of discarded embryos. They will die if we do
nothing.

And we cannot save them by killing others or letting others die. Yet, we
may save others by virtue of the research. And yet on the other hand,
and why this remains incurably in the middle, while the nothing is lost
principle permits attention to the possible benefits to third parties
from research on discarded embryos, it does not permit the concern about
the status of embryos to recede to a platitude.

And where such concern never has efficacy and can always be trumped, and
that is one of my tests about saying that a commitment to in this case
embryonic life is serious only if it trumps something whenever there is
a conflict.

It does not have to trump on all occasions, but it has to trump on some
occasions. And where I want to say it trumps is where it disallows the
creation of embryos only and exclusively for the sake of, and in order
to, disaggregate them.

I speculate on some of the difficulties that this position generates and
trying to face those I hope honestly. Some of the difficulties I regard
as more demanding than others, but I do rehearse some of them.

But I think it would take us too far a field to review those now. So let
me just content myself with having summarized that part of the case.

DR. KASS: Thank you very much. Michael Sandel will lead us off with some
prepared comments. Thank you.

PROFESSOR SANDEL: Well, let me first of all add my thanks for really a
fine paper that has so many virtues of the best work in moral
philosophy, and its close reasoning, and its careful reasoning, and in
it directing our attention to some really central moral questions.

And it also has, the paper does, and the proposal of the appeal of
staking out a middle ground, of trying to find an alternative to
either/or positions, that it exudes the spirit of compromise, which is
appealing in and of itself.

And more than that, the kind of compromise that it offers has a certain
kind of intuitive appeal, which is faced with these hard moral questions
about the status of embryos, it is on the other hand the goods to be had
from research and possibly curing disease.

And the intuitive appeal is to say, well, the spares, the excess embryos
left over from IVF clinics, they are going to die anyhow, and so we may
as well get some good use out of them and do some good.

But we shouldn\'t therefore consider it morally permissible to create
for the sake of the research or curing of diseases new embryos. We
should just use the spare ones and that is the nothing is lost
principle.

There is something very appealing about that compromise and intuitively
persuasive. But since I don\'t find it persuasive, I want to see if I
can press a little bit and offer a concrete case to illustrate why I
don\'t think the principle works, or is persuasive.

The first thing to notice \-- and this struck me I think only maybe in
my second reading of the paper \-- is that the distinction, the crucial
distinction is not as we might think from our common discourse about
these subjects, between fertilized eggs left over from the \-- well, the
distinction isn\'t between the IVF fertilized eggs, or embryos, on the
one hand, and cloned ones on the other.

To the contrary, the morally relevant distinction here cuts across the
distinction that we are familiar with between the ones that come from
the IVF clinics, and the ones that are created as clones.

Because the crucial distinction is why the embryo was created. So if we
imagine an embryo, a cloned embryo, created for reproductive purposes,
and then we consider it spares in that process, it would be all right to
do research on those cloned ones, provided that they were created for
the sake of reproduction.

But it wouldn\'t be all right to use cloned embryos created for the sake
of research. Likewise, it would be all right to use embryos created with
sperm fertilizing an egg in an IVF clinic, provided that it was created
for the sake of reproduction.

But it wouldn\'t be all right to use an embryo created when a sperm is
brought together with an egg in sexual reproduction in a clinic if the
purpose of the clinic bringing the egg and sperm together was to create
an embryo for research.

So the key here, and what is carrying the moral weight, is not how the
embryo was created, but why. Scientists may use excess embryos, however
created, provided that they were created for the sake of reproduction.
But scientists may not use embryos created for the purpose of research
or curing diseases.

Then the question arises why or the reason, or the motive for creating
the embryo determines whether it is permissible to use them for research
into diseases.

Now that is the heart of the question; why the motive matters, and why
the motive for the creation makes a moral difference. And the way to
explore this question would be to put aside cloning altogether.

Let\'s imagine two cases; of traditional sexual creation of an embryo,
or in a clinic, or in a lab. In case one, a woman comes to an
infertility center and donates some eggs because she wants to help
infertile couples have a genetically related child.

And the clinic brings together her eggs with donor sperm and creates
some embryos, some of which are implanted, and some of which wind up
being spares.

In case two, a woman goes to a clinic or to a lab, and donates eggs for
a different reason. She donates them because she wants to support stem
cell research to cure Alzheimer\'s and Parkinson\'s.

Her eggs are brought together with donor sperm, and made available to
scientists who are engaged in this research.

In both cases, the motive of the woman who contributes or who donates
the eggs is to advance a worthy end; helping an infertile couple have a
genetically related child in the first case, and advancing scientific
research in the other.

And in both cases, she contributes knowing that at least some of the
embryos created from her eggs will be sacrificed, will be discarded or
destroyed.

Now, according to the nothing is lost principle, what do we say about
the availability of these two embryos, or sets, or batches of embryos
for research?

Well, the nothing is lost principle in the paper tells us that it is
okay for scientists to extract stem cells from the first batch, but not
from the second. And the question that I have is why.

The answer that the paper seems to give is, well, in the first case,
they are spares. They are excess embryos. But then it is not so clear to
me what counts as spare.

Well, strictly speaking, a spare is an embryo not needed for
reproduction that is going to die anyhow. So we may as well use it for
some good. But by that definition of a spare, both batches of embryos
are spares.

Once they exist, they both meet the nothing is lost principle. It is
true that both batches of embryos that we have here are going to die
otherwise, and we might as well get some good use out of it.

So that can\'t be \-- well, maybe that is too limited of an account of
what you mean here by spare embryos, because by that definition they
would both be spares, both batches.

So maybe there is a further condition of an embryo being a spare embryo;
namely, that it had been created in the first place for the sake of
reproduction. That would limit us to batch one.

But then the question is whether that condition adds any moral relevance
or interest. The idea must be that the intention of the donor confers
some morally relevant difference.

Moreover, a morally relevant difference that somehow filters all the way
down to govern what a scientist may morally do. Well, what could that
difference be?

How could the motive, the different motives in these that led to the
creation of these two batches of fertilized eggs, or of embryos, how
might that work? Why would the motive make a moral difference?

Well, there are at least two possibilities that I see from the paper.
Maybe the motive makes a difference in the moral status of the embryos
that result. Maybe it makes a difference therefore in the respect that
the embryos are due. But why would that be?

How does the different motive in the two cases confer different moral
status on the embryos in batch one than in batch two, such that the ones
in batch one are properly open to use, to be sacrificed for a worthy
scientific end, but not the ones in batch two?

There doesn't seem anything different in the moral status of the embryos
in batch one and batch two. Well, maybe the difference then isn't in the
moral status of the embryos that result from these different motives.

Maybe the difference is in the way that the scientist who would do the
research is complicit in the destruction of the embryos that is a
necessary feature of the research. But how does the motive that the
donor had in creating the two batches change the degree of complicity of
the scientist?

And here I am drawn to our Footnote 12, which cites our colleague, Gil,
in a question that he put, which I think is a perfectly relevant
question here if you are trying to work out some difference in the
complicity.

Just because there are some embryos that somebody else has decided to
destroy or to discard, why does that remove the complicity of the
scientist who does the killing, and Gil's example, who is cited in the
paper, seems to me to be a very good one.

If the Nazis decided to gather people in the concentration camps and had
determined that they be killed, it wouldn\'t \-- that fact that they
were going to die anyhow, wouldn\'t justify a doctor coming and yanking
out their organs to save some innocent people.

He would not be less complicit or she, that doctor, in doing or in
yanking out their organs to do a good thing simply because somebody else
had decided that those people would already be killed, regardless of how
you regard the moral status of the embryo.

It seems to me the degree of complicity isn\'t affected by the motive of
the person who created the embryo in the first place. Well, the only
other possible answer that I can think to the question why does the
motive of the donor confer some morally relevant difference on these two
batches, is \-- well, maybe to recur to the underlying intuition of the
paper, which is that embryos should be treated as ends, and not only as
means.

And therefore to sacrifice excess or spare embryos in connection with
IVF is morally permissible, because the donor didn\'t know which of the
embryos created would be sacrificed, i.e., treated as a means, even
though the donor knew that some would be.

But even if that marks out a morally relevant difference for the donor,
and the donor\'s willingness to sacrifice embryos for the sake of
various ends, it is not clear how this makes the embryo that results
more open to use by the scientist.

So my question is going back to these two scenarios, these two batches,
created for different motives, to test my motive matters, is what moral
difference does the motive make.

DR. KASS: We have to decide on a procedure it seems after a wonderfully
rich comment like that. The only fair thing to do is to ask Gene if he
would like to respond now or later.

DR. OUTKA: Well, I think it was a wonderfully rich comment, and probably
since it was a rather complicated one, it might be best at least to
maximize the chances that I will forget less of it if I go ahead and
respond now rather than wait, because there are a number of points that
come up.

And I thank you very much for your care in putting these questions to
me. I guess I don\'t really want to use as you suggest \-- and I don\'t
use I think the language of motive. There is a wide question about why
the embryo is created, but I don\'t think that is satisfactorily
accommodated by calling it a motive.

What I wanted to do was two things. I wanted to take seriously the
notion of the injunction that comes to us in religious traditions, but
also in some philosophical ones, above all, Kantian ones, that treating
people as ends and not merely as means.

And I wanted to say that that generates a certain case for
inviolability, and so I connected that injunction to the ethics of
killing. So the first thing that we are talking about I think is more
the morality of actions, rather than the morality simply of motives.

And I want to say that certain actions may be licit if one can say that
the rationale for

\-- let\'s say in the case of IVF clinics, being in the mess that we are
in with respect to them doesn\'t have to do with actions that we
ourselves perform.

We are actually dealing with the after effects of an entire industry,
and so that would already distinguish the status of what we are
contemplating there from the status of contemplating a direct action
ourselves when we do X in order to do Y.

And I want to say that a prime case for treating an entity as
instrumental through and through is when we do X in order to destroy
them for the sake of the benefits that destruction will bring to third
parties.

I want to say that that is an instrumentalist action through and
through. So I would prefer to use the language of ends and means, and
the morality of actions, and specifically the prohibition against
killing, rather than I think the language of motives.

And which does not seem to me to quite capture those points. Now, in
regard to your very interesting example, of case one and case two, it
would be the case that if a woman donates eggs for reproduction, she
there is donating her eggs for an end that isn\'t menial.

I mean, there she is donating her eggs for the sake of a couple who want
a child, and so nothing that the couple contemplates, or nothing that
she does contributes to a case for creating in order to destroy.

Whereas, if she gives her eggs to support stem cell research \-- and
that is her only reason, so that she is giving her eggs in order to do
that \-- there it seems to me that she runs the risk of violating the
thing that I am objecting to, which is creation in order to destroy.

So the relevant fact is not simply that they are both spares. The
relevant fact has to do with the morality of the two different kinds of
actions.

And where the ends have to then be also distinguished, and you say that
both ends are worthy. One is to help a couple, and one is to promote
research. But I am precisely objecting to the second kind of so-called
worthy end if it means that you may directly create a life in order to
destroy it.

That seems to me to be a trumping action; that is to say, the objections
against a trump, the good aim of promoting research. Whereas, nothing
about helping a couple involves a creation in order to destroy. So it is
not subject to the same kind of objections.

Now, you also then list some possibilities about how these different
cases might be distinct. I think the batch one and batch two \-- I hope
that I have given a different account of why I make a distinction
between those two cases.

Your reference to Gil Meilaender is a very important objection to me in
correspondence about whether or not nothing is lost allows to much or
permits too much.

I strain there, and I grant that I strain, but what I want to argue is
that in the case of embryos slated for destruction, and who are frozen
in perpetuity, or eventually to be discarded, we have a peculiar
condition of perpetual potentiality.

And that distinguishes them from some of the other possible uses of
nothing is lost, which I disallow. So there the argument would be that
they are the peculiar features of entities that are characterized as
having perpetual potentiality that distinguishes them.

That is not certainly an adequate reply, but that would be the shape I
think of my general response.

DR. KASS: Michael, please come back and maybe one more round would help,
and other people would like to get in on this.

PROFESSOR SANDEL: Well, there are two issues here. The last point was an
attempt to show that in the first case the woman who donated an egg to
help a childless couple, that her act was morally permissible.

Whereas, the second woman\'s act was not morally permissible because it
instrumentalized the embryo in a way that the first one didn\'t. Now,
that is one issue, and I would like to come back to that issue maybe
later.

But even if you are right about that, it still would be true that the
nothing is lost principle, from the standpoint of the scientist, must
regard both batches of embryos as spares in the relevant sense that they
are going to be discarded or destroyed anyhow, and why not derive some
good from them.

So even if you made out the first distinction between the acts of the
woman donor, and there are questions about that, but independent of
that, still how does that limit or change the scope of the scientist\'s
responsibility, such that \-- there are certain eggs or the eggs in
batch one, because they were not conceived instrumentally, are open to
use.

Whereas, the eggs in batch two, the embryos in batch two, because they
were conceived instrumentally, are not open to use. Why is that?

DR. OUTKA: Well, the key thing there I think I think is that I was
talking about the rationale of in vitro fertilization clinics by and
large, and rightly or wrongly, characterize that rationale as being able
to sort of claim that.

Their dominant aim was to address the problem of infertility, and not to
provide embryos for research. That is the overall generalization, and I
know that there are a lot of questions to be raised about that, and at
the very end of the paper, in the last version of the paper, I raise
some of those questions myself.

But nonetheless I would stick to that. So I would think that your second
case, your second batch, would not come up very much. I mean, I am
obliged to you for thinking that it might. I guess I was talking about
in vitro fertilization with that overall rationale.

You are talking about women who would donate their eggs simply to
support stem cell research, and they would do that independently of
whatever the scientist did.

And I would agree that in such a \-- and I think they are pretty rare
cases though, that scientists would not be complicit.

PROFESSOR SANDEL: They are rare only because IVF happened to get going
sooner, and it has generated a hundred-thousand of them. But once stem
cells get going, there is no reason to think that there won\'t be a
hundred-thousand of those out there.

DR. OUTKA: I doubt it very much. I mean, there are lots of questions
actually about the pressure placed on women to donate eggs, and the
morality of egg donation is actually I think a really important subject
that has not been discussed by ethicists.

But the important point here is that since you don\'t have such a class,
what I am objecting to are researchers, scientists, who become complicit
because they themselves do the creating.

PROFESSOR SANDEL: Through cloning, but morally speaking, what do you say
about the case where a lab takes or invites women to donate eggs,
whether it pays them or asks them to donate them for the purpose of stem
cell research?

DR. OUTKA: If it is inviting them, I would have to look at that. To the
extent that it takes initiative, to that same extent it becomes more
complicit, and therefore more subject to the objection that I am
raising.

PROFESSOR SANDEL: But you would agree that from the scientist\'s point
of view how it got there, whether it was from someone who gave it for
reproductive purposes, or from someone who gave it for stem cell
research purposes, from the scientist\'s point of view, do you think
that makes a moral difference?

DR. OUTKA: Well, I do if they are inviting a woman to donate eggs so
that they may take those eggs and fertilize them in order to destroy
them for the sake of, and so yes, then they are complicit.

PROFESSOR SANDEL: Well, the lab. I am assuming the lab does and then the
scientist goes and gets the \-- whether the scientist, or whether she
goes to the lab and says give me some of your spares from reproductive
donations, or says give me some of your spares from people who actually
wanted their eggs to go to this purpose, do you think it is worse in the
second case for the scientist to do that?

DR. OUTKA: I think it is worse whenever there is an active role played
in an action which I regard as disallowed for reasons given. Now, there
are a lot of nuances here, and I know that there are a lot of
conservatives who think as I say in the paper, there will be some
colluding going on between people who run in vitro fertilization
clinics, and scientists who want spare embryos.

And I agree that there is a kind of performative problem there, and I
tried to discuss that. So I am not saying that there aren\'t shades
here, but the spirit of the paper is this.

That we do have an action where we are creating in order to destroy
something, and that does seem to me that it should give us pause. It is
not the same, and it won\'t simply be justified by saying, well, look at
all of the third parties who are going to benefit.

If that is what we are saying about it, and we are creating in order to
destroy for that reason, then let\'s say it very clearly. But let\'s say
that we are then treating some entities totally instrumentally, and make
no bones about it.

That is the first part of the spirit of the paper. The second part is to
say, all right, it is the case that there are enormous benefits to be
derived from embryonic stem cell research.

Let\'s see whether or not we can mount a consistent moral argument that
will allow us to draw on some of those, but to keep some limits, so that
we are not simply tolerating anything, or losing all of our criteria for
distinguishing.

That is the spirit of the paper. Now, some of these cases will involve
as I say gray areas, but I don\'t think that those gray areas by
themselves will invalidate that two-fold part of the case as such.

PROFESSOR SANDEL: Just a brief reply. If doing something to help a
third-party is instrumentalizing, then all of the embryos in batch one
are also morally impermissible because we are imagining a case where the
woman goes to the infertility clinic to donate her egg for the sake of a
third-party, for the sake of another couple having a child.

So that is doing a good thing for a third-party, and so that is
instrumentalizing isn\'t it in just the same way as the second case?

DR. OUTKA: But there is no killing involved. She is donating her eggs in
order that they may take those eggs and fertilize. That is life
enhancing. This is as I said \--

PROFESSOR SANDEL: Provided that there are no spares that are destroyed.

DR. OUTKA: No.

PROFESSOR SANDEL: The issue arises only because \-- if it were a one for
one, if there were no spares, no excess, then the issue wouldn\'t arise.
We are talking about the woman making the donation to help the
third-party have a genetically related child, knowing that there will be
some fertilized egg, some embryos, that will be sacrificed, discarded,
as a consequence of her doing that.

DR. OUTKA: But you know how long, and perhaps too long in the paper,
that I agonized about precisely that recognition. That that is a case
where we foresee under present circumstances that more embryos will have
to be created for promoting this end of conception, and fertilization,
than we would like.

But we say that we foresee that, but we don\'t directly intend it, and
there is still a claim that I think needs to be \-- I would still want
to try to make, which is that there is a morally relevant difference
between foreseeing the inevitability of excess embryos, and lamenting
that, and wanting it over as soon as we can, et cetera.

And creating again in order to kill, or to destroy, and I still think
that there will be a difference there.

DR. KASS: There is a long queue that is prompted either by the paper or
the comments. I have Jim Wilson, Mary Ann Glendon, Alfonso Gomez-Lobo.

PROFESSOR WILSON: Let me begin with the language of motive, because
though he may not have intended it, I think Professor Outka has in fact
used the language of motive on page 24, where he talks about creating an
embryo exclusively for research, the motive of the person.

Or creating it exclusively for fertility, the motive of the actor; and
then again on page 35, creating for research, motive, and creating for
baby creation, motive.

I think it is well to get the word motive out of our language. I hope
that Mary Ann Glendon will forgive me if I use an inept legal analogy,
but in the criminal law, we don\'t ordinarily determine guilt or
innocence on the basis of the motive.

The man lies in wait to kill a woman, and shoots her from a distance,
and approaches closely to make sure that she is dead, and finishes her
off with several bullets to the head.

We don\'t ask in the court whether he did it to collect her insurance or
to prevent her from carrying on her experiments in dogs, since she
happens to be a biologist at a local university laboratory.

We might take motive into account in the sentencing decision, but that
would be up to the probation officer. It seems to me that to modify the
circumstance that Michael laid out for you and with which we have been
struggling, suppose now the woman donates eggs in an IVF clinic, and
they are all fertilized.

And suppose before picking the egg she wishes, she does what I think is
in fact not impossible, and may indeed be commonplace, she has each
fertilized egg tested for its likely hair color, or intelligence, or
sex, or whatever of the embryo that will be produced.

And having selected the egg she wants and has it in place, she looks at
the other people and says kill the rest. In fact, particularly kill
those two. One is going to have Down\'s Syndrome, and the other one is
going to have cerebral palsy.

Doesn\'t that put the IVF eggs in exactly the same position as the eggs
created by a woman who has done it solely for the purpose of creating
somatic cell nuclear transfer for the purposes of biomedical research?

In fact, does it make it worse, because now not only are the eggs that
she has picked out with the doctor\'s consent going to be destroyed,
they will not be destroyed in a way that will help anyone else.

So that to me the leftover egg solution to this problem doesn\'t work.
The leftover egg solution doesn\'t solve the moral difficulty.

DR. OUTKA: Shall I try to respond to each of these as I \--

DR. KASS: Well, I think that these are all solid, and \--

DR. OUTKA: Oh, yeah, very solid. I am indebted to you all, and let me
say though that I think the statements that you read really are
precisely about motive.

Let\'s maybe use the language that is closer to what I actually use in
the paper, which is intention rather than motive. Now, I have always
been drawn to an old assumption about the doctrine of double effect.

I am not sure that it is going to work, but I have always been
fascinated with this claim, and I think there are some cases where it
worked, but it doesn\'t always work.

And that is that certain action descriptions entail certain intention
descriptions. Now, that is much closer to the timbre of my argument than
the language of motive, because what I want to say is that an action,
where you actually create in order to destroy, if you describe that
action, it is hard to avoid identifying one intention.

And that intention is to destroy, and so I don\'t \-- I am going to
continue to try to resist of saddling me with the language of motives
here, and I don\'t think the statements that were cited really do that.

Let\'s think about intentions with respect to actions more than about
general motives. With respect to your case, Professor Wilson, of all of
the eggs fertilized. That it seems to me is \-- I have gotten a little
bit of a bee in my bonnet about this.

The suppose this or suppose that, as a kind of test for measuring the
adequacy of an argument, this hypothetical case that you cite is I think
not at the moment within the realm of possibility.

So I am not sure that I have \-- that I am obliged to respond to it in
precisely the terms that you have set it out. The fact of the matter is
that we do have a situation where one of these embryos is going to be
chosen to be implanted and brought to term, and the others will not be.

That is the datum that we are dealing with in trying to make moral sense
of, and I would have to stick with that one, rather than speculate on
all of the eggs being fertilized, and then if she chooses only one,
rather than all of them, she is guilty for what she does to the other.

I think that changes the terms of the example so far that it is not any
longer precisely comparable as a test of what at least I want to argue.

DR. MCHUGH: Leon, I have to interrupt just for a second. I just don\'t
understand when you say the intention, or any intention, is in order to
destroy. Nothing is being made here in order to destroy.

Will you explain that a bit further? I just got stuck on that. In none
of these cases is anybody creating anything in order to destroy.

DR. OUTKA: That is a very important point and thank you for mentioning
it.

DR. MCHUGH: Sorry to interrupt.

DR. OUTKA: No, no, no, I\'m glad you did. If I am wrong about this one,
then a lot of things go by the board, and I could be wrong about this
one. I actually had wrung my hands about it quite often.

It involves a description of what is done that does include my importing
a kind of conclusion about what is in effect going on that researchers
might not immediately consent to.

But it does seem to me that if you ask a researcher why are you creating
this entity, and the answer is, well, I want to do something to it,
which will certainly kill it, but I am doing it for the sake of
third-parties.

Then that seems to me to be an instance of instrumentalizing it. So the
in order to destroy, or in order to disaggregate, is internal to the
description of the act I want to argue. Now, one might try to get at the
position by challenging that, but it is hard for me \--

DR. MCHUGH: You just used the word intention, that it was intention in
order to destroy. I mean, you had several intentions.

Perhaps, and I might accept that, but there were several intentions
involved here. But you put it all on the basis of in order to.

DR. KASS: Could I lend a hand on this? I mean, had you not raised the
question, I would have at some point.

DR. MCHUGH: I am sure that you would have.

DR. KASS: But I think I can \-- if I am right, Gene, let me have a try.
I think the proper way to state the intention is we create these embryos
\-- and by the way, I don\'t think this paper is primarily \-- I don\'t
think it is at all about somatic cell nuclear transfer.

I think the question really should be taken up universally, regardless
of how the embryos come to be. I think that Michael is right about that,
and this paper was written without even a reference to it.

But the researchers \-- and there have been people who have come forward
to \-- well, people have come forward to donate their eggs and embryos
for the sake of research. And the researchers who go to work on that
wouldn\'t say that we want these embryos in order to destroy them.

We want these embryos because we want to use their stem cells for
understanding or for treatment. But it is the unavoidable and
inescapable entailment of that intention that the embryo be destroyed in
the process.

If there was some way in fact to get the stem cells without destroying
the embryo, people would be delighted I assume. And it seems to me that
you can make the same case as follows.

This is not to say that the embryo is the human being, but if you were
to say that you too, out my heart in order to save my friend, Wilson,
here who needed a transplant.

And that you weren\'t taking out my heart in order to destroy me. All
you were really trying to do was to save him, but if there was no way to
do that without destroying me, then that material fact of your intent
becomes embraced in the overall act with great clarity.

So I think that I myself would not describe this as saying to create it
in order to destroy it. I would create it in order to do something else,
but the necessary and inescapable entailment of which is the
destruction, and therefore you embrace that intrinsic aspect of the act.

I think that is a better way to do it and it doesn\'t try to gain
mileage, if you don\'t mind, from a more lurid expression that implies
that the people are in the destruction business because they like
destruction. I don\'t think that is the flavor or the intent.

DR. OUTKA: No, I take that as \-- I will regard that as a friendly
amendment, and certainly agree with it. I think the reason that I used
that language was simply to underscore that it is unavoidable that we
can\'t ignore this as part of a full characterization of the act.

DR. KASS: Sorry to have intruded. I want \--

DR. OUTKA: That was very helpful. Thank you.

DR. KASS: I have Mary Ann.

PROFESSOR GLENDON: Well, doctor, you were very kind when you started out
to adopt an egalitarian approach, and suggest that we are all on a equal
footing with respect to the moral dimensions of these very difficult
problems.

I must say that I feel a little backward maybe because I am a lawyer,
but I am still \-- from the very beginning, from my very first meeting,
I have been struggling with a problem that maybe you can help me with.

I am having a hard time seeing the difference between what is done \--
forget about motive and intention, but what is done in in vitro
fertilization, and what is done in creating an embryo for research
purposes, and let me explain why.

I think that in both cases the procedure is done with full knowledge
that embryos will be destroyed. Now, many people, and not just at this
meeting, but at previous meetings, many people have said that the
difference is that in vitro fertilization is done for a worthy end.

And I think you or Professor Sandel said to help couples with
infertility. Well, we all know that that is not quite right. That very
often it is not couples. I don\'t know whether couples are predominantly
the ones, but certainly a large proportion.

But leaving that aside, there are a number of factors that I can think
of that to my mind call into question a casual assumption that what we
are dealing with here is such a worthy end that it would justify the
destruction of embryos.

I will name some of them. One is \-- and I am naming these as a
constellation, and not that each factor would be decisive in and of
itself. But it is an extraordinarily expensive procedure.

It is highly uncertain in outcome. It has unknown long term health
effects for women who are subjected to massive doses of hormone
injections, and the evidence coming out now is suggesting that children
born from this procedure may have an unusual proportion of defects and
disabilities.

And then finally as I said, it involves creating an embryo with the
certain knowledge \-- or creating embryos with the certain knowledge
that some of them will be destroyed.

So I guess that my problem is that not only that I wonder how that can
be easily said to be a worthy end, and then I guess more seriously, if
we accept the creation of embryos with the certain knowledge that they
will be destroyed for purposes of in vitro fertilization, doesn\'t it
become or haven\'t we gone very far down the road indeed toward
justifying the creation of embryos for research purposes?

DR. OUTKA: Well, I thank you very much for that question and I think it
is forceful and important. And my perhaps only flagellations at the end
of the paper suggest that I feel its force.

But for better or for worse, let me at least sketch the lines of a
reply, even though I don\'t think this addresses all the things that
need to be addressed in your important set of objections. One is that I
do think that there are two things in conflict here. One is infertility,
and the other is excess embryos, and we welcome neither. I think that is
where we have to begin.

But I indicate that the datum leaves me deeply disquieted, and I don\'t
easily assume that it is simply a good. I agree with you that it is
expensive and uncertain.

It nonetheless is something, and I have talked to a few people who have
been through it, and who have actually \-- it has resulted for them in
children, or grandchildren, and they are nonetheless very thankful for
it.

But I suppose the spirit again of my approach is to say, look, this is a
practice about which there are many, many questions. But I am a little
uneasy with the grand \-- now that a lot of people are beginning to
realize this, and are quickly denouncing it, they often use the language
of we.

That we are responsible for this, and this isn\'t like a contingent
disaster. This is something that we have created by our own hands, and I
would register a slight disquiet with that, too, because I don\'t think
that we did it.

I think that most folks who have the gift of fertility don\'t worry very
much about this. And so this was developed \-- and I agree that we
didn\'t object to it, or resist it, but it was developed by people with
vested interest in it, both the infertile and those would were prepared
to create these industries in order to address that problem.

And now it is time it seems to me to air whether or not the current
arrangements can be justified, where you have 10,000 new spare embryos
being created every month, et cetera. I mean, there are a lot of
questions that have to be asked.

But I would also say that in the case of nothing is lost, I do observe
that nothing is lost sometimes can be justified even in response to an
evil practice.

I mean, there are some interesting cases. For instance, in Jewish
rabbinic literature, about acquiescing to the demands of the tyrant
under certain circumstances. So you can invoke that nothing is lost even
when you don\'t think that the situation that got you to here is
admirable, or free from a certain amount of evil.

And I think that it is in that spirit that I will want to say that
however we got here, and whatever we should do from now on, we do have
this datum of a hundred-thousand embryos frozen in perpetuity, or slated
for destruction, and we do have to reflect about that.

I am not sure that is a very satisfactory reply, but it is to evidence a
good deal of sympathy with your reservations, without I think ignoring
that one datum.

DR. KASS: Gil Meilaender.

PROFESSOR MEILAENDER: Gene, as you know, I think it is a very nice
paper, and as you also know, that doesn\'t mean that I have no questions
about it.

And there are several things that I wanted to ask about, but I want to
stick with the nothing more is lost, because it is central to your case,
and which I take it to mean \-- I mean, if we were thinking about what
other kind of language would we use to describe that, it means with
respect to the particular human subject, human entity, that we are
talking about, that there is nothing that we can do that would further
diminish its life prospects. I mean, that is just by the nature of the
case.

DR. OUTKA: And also nothing much we can do to help its life prospects.

PROFESSOR MEILAENDER: Yes. And there are a number of analogies that we
might think of. I want to come around to one of them in particular, but
there are a whole number; the condemned person, whose last appeal has
been lost; the irretrievably dying person, who has only days to live;
the permanently unconscious person; the fetus in the process of
abortion, or after a decision for abortion has been irrevocably made.

I mean, there are a whole number of such, but let\'s take the
anencephalic infant. I take it that there is nothing that you can do to
further diminish its life prospects.

I don\'t know whether you are prepared to think that under those
circumstances that it may be instrumentalized for various research
purposes, but I would like to sort of hear you reflect on it, since in a
certain way it almost seems to me that the case might be stronger for
that than for the spare embryo.

The spare embryo is sitting around waiting to be instrumentalized
because we made some choices. The anencephalic infant is just there. I
mean, it is not any choice of ours that got it there, and it almost
seems to me that the argument would be stronger.

So I would just like to hear you reflect on that, and see how you would
think about that in relation to the kind of argument that you make.

DR. OUTKA: I know that is a first-rate question, Gil, and since the
anencephalic infant case came up in connection with that suggested in
your correspondence to me, I should have been more careful probably in
how I used it.

My unsatisfactory response to this is that I see the logic of saying
that in some ways, since we didn\'t have a role in bringing this about,
there might be greater warrant for using it.

But I guess the context of my discussion of that, of pairing them, was
the context only of saying that we are unable to do anything for them.
That there is a kind of cessation of the injunction to treat them as
ends rather than means. We are limited in what we can do.

Our love can\'t affect very much, and I really only wanted to make the
comparison in that connection. I didn\'t want to sort of suggest that in
such cases that it would be quite all right to go ahead then and use
anencephalic infants for research purposes.

But I think that you are right in suggesting that that would have to be
a loophole that I would have to close. I mean, I am worried about this
datum of the hundred-thousand spare embryos.

I mean, there is a kind of overwhelming fact to go back to the earlier
question that I think we need to say something about. Is there anything
that we are doing that is preferable morally by freezing them in
perpetuity.

And my one place where I do not understand the conservative concern
about them is that I don\'t know what people who don\'t want to destroy
think they are saving that is significantly different \--

PROFESSOR MEILAENDER: Gene, can I just make one suggestion?

DR. OUTKA: Yes.

PROFESSOR MEILAENDER: We are not embracing their death as our aim.

DR. OUTKA: Right.

PROFESSOR MEILAENDER: I mean, just as a hypothesis, might that not be
what someone would reply?

DR. OUTKA: They certainly could reply, but the result of that is this
peculiar situation of perpetual potentiality, and so the witness looks
very marginal to me. It almost looks like it doesn\'t have very much to
do with them.

It simply has to do with a refusal to do something that would bear on
them, but at that point \-- and I would agree that my application of
nothing is lost, and it might have a slightly consequential sound to it
there.

But I would be willing to risk speculating about consequential steps
there if there was something to be done that might do some third-parties
good.

But in any case, back to your excellent example. Yes, I would have to
say that I would have to be careful, and if the logic of the position
involved my saying that there would be some even stronger case for doing
something before the infant died, then I would have to address that and
modify the position so that that consequence was not allowed.

How I would do that is a nice question, but I think I probably could
devise a way to do it that would not be unlike these other ways that I
have tried to devise of saying, look, this is a very special case, this
class of perpetual potentiality types.

And it is not to be generalized from to allow nothing is lost to
generally be invoked to harvest organs from the living, or from those
whom the government has condemned as criminals, or whatever.

I do accept that there is a whole range of those cases that I don\'t
want to allow in, in my use of the nothing is lost principle for the
sake of talking about embryos discarded.

DR. KRAUTHAMMER: Could I interject?

DR. KASS: On this point?

DR. KRAUTHAMMER: Yes, on this point, and a suggestion for an answer. And
that would be that there is a fundamental moral difference in the status
of an embryo and of an anencephalic child.

The child is a full human being, and anencephalic or not, a comatose
person is a full human being, comatose or not, and we don\'t tear them
apart for their parts.

They are inviolable, and so I don\'t think it is a terribly strong
objection. An embryo has an intermediate, if you like, moral status, but
certainly is not the moral equivalent of a child or an adult who is in a
coma.

So I don\'t think that you open yourself up under your argument,
professor, to tearing up people who are in comas or who are
anencephalics.

DR. OUTKA: I will accept that as another friendly amendment. Thank you.

DR. KASS: I have Alfonso next.

DR. GOMEZ-LOBO: I\'m afraid that I am going to disagree with Charles
here, but he knows that. Going to Michael Sandel\'s point. I would put
it in very simple terms.

Namely, if you go into a lab and you have an embryo in a dish there, and
you would not be able to tell whether it was created for research or for
reproductive purposes. There is nothing in the being itself.

And what I am trying to do is this, is turn the discussion back to what
I think is the key point, namely what kind of being we are dealing with
here. There were parts of the paper where you, Professor Outka, seemed
to be treating embryos and fetuses as if they were different entities.

And I think at a given moment you would talk about these entities and
these other entities. And it seems to me pretty common sensical that we
are talking about stages. Every fetus was previously an embryo, and an
embryo developing naturally will become a fetus.

These are names that have been coined for certain periods in the live of
what, of a human being, if we are talking about human embryos. Just the
fact that we can talk about ovine embryos shows that the world embryo
doesn\'t tell us what sort of thing it is. We need the word human there.

Now, if that is the case, then of course the big problem is if we have
one human being, and you agree that from conception onwards that we have
a human being, then why this \"diminution of value\" in one stage, and
then from then onwards \-- I don\'t know, is there an increasing value?

You seem to take implantation as the breaking point, and I have heard
that before. Of course, you are familiar with the work of Tom Shannon, I
assume, right? You quote him.

DR. OUTKA: I cite him in a footnote.

DR. GOMEZ-LOBO: Sure. Sure. Now, the real critical question is this. Are
Shannon\'s arguments convincing? Is it the case that there is such a
decisive break there that we may \-- I think you would be more
consistent totally to disregard the value of the embryo, or to say,
well, it is part of a human being, and therefore it is equally valuable
as that same human being at a different point.

Now, I don\'t know if we want to get into the discussion of potentiality
in the individuation.

But those would be the key points it seems to me, because if a human
being starts its conception, if we have there the basic genetic
information that is going to carry this organism through the phase in
which we find ourselves, then of course I see no reason to think that
there might be less value at that point than at another point.

In a way, it seems to me that people like Robertson are a lot more
consistent at times, and say, well, let\'s respect \-- or Mary Ann
Warren for that matter, but let\'s respect them after they are three
years old, after they are rationale, or something along those lines.

So the point that I am trying to focus in is why or on what grounds
establish this magic break point at 14 days?

DR. OUTKA: Well, thank you for that question. I actually think your
characterization of the position \-- well, I would want to offer the
following amendments to it, but then let me talk about whether I think I
have given anything like adequate arguments for the positions that I
take.

But the great or the only bright light that I see in this range of
possibilities is conception. So, conception is the point at which
someone becomes a kind of primordial part of the human race, and an
embryo has the genetic wherewithal to become a person just like the rest
of us given the right opportunities.

So conception is the first and the brightest line for me. Implantation
is none of the other subsequent discriminations that I also defend are
anything more approximate, but they are approximate.

So I don\'t actually make as much of the 14 day period as Shannon does.
I don\'t have this big commitment to individuation versus the other. I
stay with conception.

But I do say that there is approximate discrimination at the point where
implantation occurs, because now we can describe this entity as a power
under way, a self-developing power under way. You can\'t say that about
the embryo.

DR. GOMEZ-LOBO: Why?

DR. OUTKA: Because it is not implanted. It isn\'t yet a self-developing
\--

DR. GOMEZ-LOBO: That\'s a circular response.

DR. OUTKA: No, it\'s not. A self-developing power under way means that
if left to its own devices will, and if not interfered with, come to
term.

No embryo is going to do that prior to implantation. It won\'t. I mean,
that is not circular. With respect, I don\'t think so.

DR. GOMEZ-LOBO: A fetus left to its own devices won\'t survive either.

DR. OUTKA: In one way it will, in the sense that it certainly depends
upon the woman, and I have tried to argue that the one person in all the
world for at least the first 20 weeks, and that makes the circumstances
of pregnancy [sui generis]{.underline} in my view.

It is a satisfactory analogy that are entirely satisfactory elude us.
But nonetheless, there is now a natural process where if the woman
doesn\'t do anything but live normally, that entity will come to term.

And that is not a generalization that you can make about the embryo. You
can only make it about the fetus. So I do think that there is
nonetheless a difference.

PROFESSOR MEILAENDER: Leon, may I just ask one question of Gene with
respect to his response to Alfonso. Given what you have said, why did
you accept Charles Krauthammer\'s comment as a friendly amendment since
you have just \-- it seems to me \-- committed yourself to a very high
estimate of the embryo, if not from conception, at least from the time
of implantation?

DR. OUTKA: Well, then it is no longer an embryo. It is a fetus. There is
a \--

PROFESSOR MEILAENDER: Well, his distinction was at birth, and that was
the friendly amendment that you \--

DR. OUTKA: Well, I know that it was, but the embryo, though it has
irreducible value, I want to argue still \-- that until it becomes a
fetus, it has moral standing, but not the same moral standing that a
fetus has.

DR. KASS: By fetus, you mean simply implanted?

DR. OUTKA: I mean implanted. So there is a irreducible value, but not
the same kind of moral standing that a fetus has. I try to lay this out.
Whereas, equally protectable value, only occurs when it is viable.

DR. KASS: Could I intrude myself in this just because I think that we
spent most of the time here on the nothing is lost point, and the
distinction between using the spare and creating for.

But it seems to me, and I am intuiting from the silence of some of our
colleagues, whose manner of making a living I am aware of and you are
not, but that we might like some help from you on something else in this
paper, which actually has to do with the question of the evaluation of
the status of the pre-implantation embryo, which is after all central to
our business, whether we are talking about cloning for biomedical
research, or down the road to embryonic stem cells.

So central to your \-- I mean, I think if I understood the paper, you
make a lot out of \-- the reason that you do not regard either abortion
or the destruction of embryos as murder, though you regard the embryonic
life as having irreducible, but not necessarily, therefore, equal value
if I am not misunderstanding.

And that turns on some notion of potentiality, which you develop richly,
and there are people in this room from previous discussion who have used
the term embracing it, and others use it dismissively.

You would, I think, make a contribution to our ongoing discussion if you
could say a little bit more about that notion, and to do it in a way in
which it might be persuasive, and not to the moral theologians in the
room, but to those of us who studied some science.

Can you help? How does the notion of potentiality, how does it help us
think about this thing that we have before us created in vitro if it is
not a full person, which if I understand your paper, you don\'t claim
that it is?

That seems to be the core of your teaching to us about its value, and if
we don\'t understand that, I think we may miss this. So can you help?

DR. OUTKA: Well, I can try, but I\'m afraid that I will probably
reiterate what is already on the pages. But maybe to refresh our
memories, I say that potentiality applies to embryos and fetuses.

And I take fetuses first, and I say that potentiality refers to what
they are not yet, and also what they are. And I try to keep fairly low
flying here, in terms of trying to offer a descriptively accurate
characterization of them.

They are not yet an equally protectable life because by virtue of this
dependence on one person in all the world, and I do make quite a bit of
this, and that pregnancy does have this very special feature.

Only the woman can help in a certain way. She is strictly
non-transferable. There is no one else in the world that can help if she
doesn\'t. Now, in a way that is a natural fact about us, but it is also
a very peculiar natural fact, though it is very common.

It is kind of numerically common and yet it is striking in that there
aren\'t precise analogies to it. And I want to argue then that during
this early period she is allowed special discretion by virtue of this
absolute dependence that one entity in the universe has on her, and only
her.

But potentiality also refers to what the fetus already is, and what the
fetus already is, is this power under way, which I realize has not
convinced all of you of its accuracy.

But nonetheless the fetus is very connected to the woman, and still
totally dependent upon it, but nonetheless again if she lives a normal
life, there is a self-developing quality to the fetus, which if simply
left alone will result finally in an entity just like the rest of us.

That is also a natural fact about it, and it is this peculiar
combination of what the fetus is not yet, and yet is, that represents
its peculiar status in the world.

And so I want to say that to kill it causes it incomprehensible harm,
and that is what makes abortion and infanticide so serious, because
there is nothing that we can ever do to compensate, or make amends for
that action to the entity.

But I also then want to argue that embryos are like fetuses with respect
to having this reducible value. They have the genetic wherewithal, but
they are not yet a power under way.

Now, I take it that given the overall assignment that you all have as a
council, you want to see whether or not, and especially your scientific
colleagues, or members of the council have any reactions to that with
respect to its scientific adequacy, because that is part of your
assignment, is to get clearer on that.

So I would ask any of you who care to, to comment on whether you think
that is a useful description, or wildly inaccurate, or somewhere in
between.

DR. KASS: Does someone want to join on that? I mean, there are people
still on the queue, and I jumped slightly. The question of potentiality
came up here, and I know that it would be a shame if you left without
our having a chance to address that, because it seems to be part of the
case for the moral work that we had here. Paul.

DR. MCHUGH: Well, just a moment on your question of potentiality. I want
again to underline something that the professor said. He said that this
has the potential if left alone.

Well, that of course doesn\'t apply to, for example, the human
development from somatic cell nuclear transplant. You have to do even
more to it than just produce it to get it to be human.

And I just wanted to make the point that sometimes potentials depend
upon further human actions. And the council knows why I am fussing about
this, but I want to be sure that I heard you correctly when you said the
potential here is if left alone, this entity will follow a course with
\--

DR. OUTKA: Well, you are perfectly right, but that applies to fetuses.

DR. MCHUGH: Yes.

DR. OUTKA: It does not apply to embryos. I mean, that is the difference
between the two as far as I can see. If you don\'t do something in
addition to an embryo, i.e., implant it, it will never be a power under
way.

DR. KASS: Bill Hurlbut, and then \-- well, are you going to speak to
this particular point about the science?

DR. HURLBUT: Yes. The first thing is that I think we need to come to the
point of using the same terms. Scientifically speaking, at least in
current literature, the term embryo is used for the first eight weeks of
development.

But I sense that you are using it pre-implantation and then \--

DR. OUTKA: Yes, I am. But I think that has almost become in a way a [de
facto]{.underline} use. Do you have a sense of that as well?

DR. HURLBUT: They are not using a term \-- people are using a term, and
Elizabeth suggested that we use this in various contexts,
pre-implantation embryo, or pre-embryo, but that actually has its
historical derivation from the term pre-implantation embryo.

And scientifically speaking, an embryo is from conception until 8 weeks.
There has been a little fuzzing over the history of it. But basically
the distinction that is trying to be put in place there scientifically
is that approximately 8 to 10 weeks the organization is set, and it is
not just getting bigger after that, but it is much more like that.

The early development of form and organization are taking place. One
little scientific comment and then I want to ask you a question. I
personally don\'t understand why you feel that in a natural setting at
least the pre-implantation embryo has a different moral status than the
implanted embryo.

The fact is that the pre-implantation embryo is drawing nourishment from
its mother, and as is evident from the varied result that you get from
putting it into a different medium for a while \-- larger offspring, for
example, and more twinning, or example.

And so I can\'t quite see why that really makes a difference. But that
might be the wrong point to address. What I would really like to know
\-- and this is a very vexing question to me. I have sat in this council
now for \-- this is the third meeting, and every meeting the issue of
potential versus actual, and accrued, or accumulated status keeps coming
up.

And I feel the good intentions of those who bring it up, and I got in a
little discussion with Mike Gazzaniga about this the first week. I felt
the weight of it when Janet Rowley said it several times.

I keep wanting to know, and wanting to ask of other people why they
assign a particular characteristic of accrual as being the moment of
implicit dignity; and why the various sides of this equation can\'t find
some meeting point.

So I would really like \-- I would personally very much value an
exchange between you and somebody at least on this panel, or on this
council, who is taking a position of accumulated or accrued personhood,
or something of that nature. Do you understand what I am getting at?

DR. OUTKA: Well, I think so, but let\'s be sure I do. I mean, my
position is \-- well, I hope nuanced, but it is hard to pin down,
because I both want to attribute irreducible value to any entity after
conception, and still make as you say some distinction between the
embryo and the fetus.

And I accept by the way your pervasion that by embryo I mean
pre-implantation entity, and that\'s what I mean. And if there is an
acceptable way to refer to that and that makes for clarity, I would
happily accept it.

And you may be right that the embryo is dependent upon the woman, too,
in a way that I ma not fully doing justice to. It is perhaps significant
that I am thinking of embryos as potentially in a state of limbo by
virtue of in vitro fertilization clinics.

I mean, that has made me more aware of implantation as a kind of stage
that is discrete in some ways. So I may be overdoing that. You are
certainly right that unless we are talking about embryos created that
way, or conceived that way rather, we are not talking about an entity
that is not also dependent like a fetus is on the woman.

But now let\'s go to your basic concern, and maybe you had better repeat
that for me, because I am not sure that I do have it clearly, and it is
clearly an important point to you and to some others, and I want to
promote whatever I can by way of clarity about your ongoing discussions.

DR. HURLBUT: Well, I would really, really like personally to hear a good
deep discussion on the issue of the moral significance of potential.

And I don\'t know if it is too much to ask for specifically from one of
my colleagues. For example, if Mike Gazzaniga would actually jump in
here and engage this, because a lot hinges on this subject.

And a few of us are deeply enough trained philosophically to know the
real or the deep thoughts on what this term so factual and potential
actually mean.

DR. OUTKA: Well, I don\'t think that even the philosophers, however
deeply trained they are, have come to any agreement. This is why in a
way I felt more emboldened just to say, look, whatever position you take
on this status of the embryo and the fetus are going to have major
implications for a position that you take on stem cell research.

But there is so much disagreement all the way down the line, and yet
those disagreements matter so much, I am going to tell you what my own
views are.

Now, I don\'t defend them altogether, and that goes back to something
that came up earlier. There is a booklet in which I talk about abortion,
where I defend them a bit more.

But some of that defense is still to come, but nonetheless I think I am
clear now on the general lines of the argument, even though I haven\'t
fully justified all the parts of it.

DR. KASS: Let me say \-- and because there are people in the queue, and
we are moving toward the end of this session, I want to let the people
who have asked to speak, to give them a chance.

Could I simply say that this question of either absolute or [prima
facie]{.underline}, were tied to something actual or potential, it is
not going to go away. And that we had better put it on the agenda for
ourselves.

Lots of people had a stake in this discussion, and I think Professor
Outka has in fact, if we revisited those 3 or 4 pages of the paper. He
has given us something to chew on, but I suggest that we perhaps bracket
it for now.

I just wanted to highlight it as important, and unless someone really
wants to join in on and solve this one, let me suggest that we take the
people who are waiting.

And let\'s try to do this in about 10 minutes, and then break. I have
Robby, Frank, Janet, Michael, and Rebecca. That is rather long for the
time that we have, but let me ask for a certain concision if I might.
Who was the first? Robby? Please.

PROFESSOR GEORGE: Thanks, Leon. Well, I will then lay aside the
discussion and I was going to go right into the questions that Bill and
Alfonso raised, but let me lay those aside right now, because I have
another set of questions that will take us back to Michael\'s original
comment and the exchange with Gene.

And perhaps I will write to Gene with my own two cents about this
question about the status of the embryo. But back to the set of
distinctions that Michael was calling into question, Michael Sandel.

I take it that our position is that once there exists an embryo, who
will not be implanted, and whose life will soon end one way or another,
then it is either \-- and you can tell me which, and I don\'t know
whether it matters.

It is either not instrumentalization to disaggregate the embryo for good
reasons, or if it is an instrumentalization, it is not a wrongful
instrumentalization.

I don\'t think you have declared yourself on that, and I don\'t think
that much turns on it, but do you want to say which way you will look at
it?

DR. OUTKA: it is probably closer to it. I think that is a fine question,
and I haven\'t really thought about it, but I think it is probably
closer to not a problematical instrumentalization. I think that is
probably what I would say.

PROFESSOR GEORGE: Okay. I take it then, if I were going to try to defend
a position given that point against my point, I wonder if you would
accept this way of defending it.

I have to confess in the end that I don\'t think it can be defended, but
I am just trying to see how far it can be defended against Michael\'s
particular critique.

Then I think you would have to say that the morally bad thing is in \--
and I am sorry to use this language, but I think it is in the spirit of
what you have been saying. I am not going to talk about motivation.

But the morally bad thing is in the intention to create the embryo as an
object. That is to say, to create the embryo as a means only. Is that
right?

DR. OUTKA: Yes.

PROFESSOR GEORGE: So that in way you have distinguished creation by
whatever means, and Michael has to be right that the means don\'t
matter, but the creation of the embryo for reproductive purposes from
the creation of the embryo again by whatever means for research that
would involve its destruction. Yes? Okay.

PROFESSOR GEORGE: Then I think what has to be defended to make that out
would be the idea that embryos created for purposes of reproduction are
not created as means or objects, but are created as ends in themselves,
even if we know that some of the embryos that are created will in fact
not be implanted, and therefore will be subject to licit disaggregation.
Right?

DR. OUTKA: Yes. That is okay. Licit disaggregation is probably all
right, but note the somber quality of this, of accepting all of this.
This is mournful stuff. I mean, I mean I am not happy about it.

PROFESSOR GEORGE: No, I understand.

DR. OUTKA: It is not licit in a kind of pure moral sense at all. It is
like we have this aftermath, and what do we do with it.

PROFESSOR GEORGE: That it is permissible and that is the key. We may be
unhappy about the whole thing, and regret how it came about. Okay. Then
the question becomes can we distinguish the treatment of the spares
created, again by whatever method, in such a way as to make sense of the
idea that despite the fact that they are going to be discarded, and
therefore subjected licitly to disaggregation as ins in themselves.

And how does that argument go? Does that argument have something to do
with the idea that each has a chance of being the one implanted? Does it
have to be an equal chance, and that gets us into Jim Wilson\'s problem
about embryo screening?

DR. OUTKA: I don\'t think I have fully worked out what I want to say
about that. In part, it is because I see the moral calculations that I
am trying to defend as working in response to decisions made by others,
which I don\'t necessarily either rejoice over, or even approve, but
where I am nonetheless forced to now deal with them.

And what it is maybe licit to do to them. I mean, there the status of
fetal cadavers would be a sort of \-- well, the use of fetuses
terminated in abortion decisions would have a similar kind of status for
me, where I am deliberating about things where I am not wholly happy
about this data, but I am going to have to now confront it and make some
determinations with respect to it.

And I am trying to offer a moral case for doing that. But I think that
sometimes the force of some of these questions implies that one is more
of an actor with respect to what is being decided about than one is.

And I would want to be wary about that, and I think the way that you put
that almost hints at that, and I would want to resist it.

PROFESSOR GEORGE: Oh, I am willing to grant you that, but it seems to me
that then on the other side, by the same terms, we have got Michael\'s
scientist.

You know, he was not involved in any of this, and he is just facing a
batch, or at least one embryo that is now in the condition that
objectively from your vantage point renders it legitimate for
disaggregation.

And he is willing to do it and doesn\'t see any moral reason not to,
because it seems to pass the test that you set out.

DR. OUTKA: I said that there were gray areas.

DR. KASS: Let me just remind you of the \-- I mean, I would still like
to get other people on the queue, and so if you could \--

PROFESSOR GEORGE: I\'m sorry, I will \--

DR. KASS: Well, I mean, could we ask the following? This sounds like a
nice dialectic. Would you be willing to put in writing, and Gene, would
you be willing to respond, and we share this exchange?

PROFESSOR GEORGE: I would be intending to write to Gene about the status
of the embryo issue anyway, and we can \--

DR. OUTKA: That\'s excellent, but these are very important questions.

PROFESSOR GEORGE: Just a final point on where we would go and why I
think it is relevant. I mean, I am just wondering if at the end of the
day what you have got left to say to Michael as a scientist is really a
practical or prudential matter; that simply if you go ahead and
experiment or use it to disaggregate these embryos, you will be
encouraging other people to do.

DR. OUTKA: I am not sure \-- I am going to try to assimilate Michael\'s
scientist\'s case into the general case that I want to make about the
appropriate use of discarded embryos. That is what I am going to do with
it.

I am not going to allow it some kind of independent status that derails
the basic distinction that I want to make.

DR. KASS: Frank.

PROFESSOR FUKUYAMA: Well, I apologize, but I am going to have to leave
as soon as you respond to my question, as I have one last class to teach
this afternoon.

DR. OUTKA: I won\'t misinterpret your departure then.

PROFESSOR FUKUYAMA: This is in a way a devil\'s advocate kind of
question. But I am struck in these discussions of bioethics often that
you begin with a moral rule or principle, and then as we have done, have
a very subtle discussion about the application of it.

But there is no prior agreement on that principle, and the one here is
the Kantian distinction between a means and ends, which we have all been
\-- I mean, nobody has questioned that basic framework.

Now, I personally would much prefer that you be a Kantian than a
utilitarian, and so I am not hostile to Kantianism, but it has got a lot
of problems.

I mean, for one thing, pure Kantianism presupposes a dualistic ontology
that I think no natural scientist sitting around this table would be
willing to accept.

I mean, noumena do not obey the laws of physics. You know, laws of
natural causation. But I think also Kantian ethics is a big mess,
because if is ethics of intentionality.

I mean, I don\'t really see under Kantian ethics how you can fight a
\"just\" war. I mean, when Douglas MacArthur was a division commander in
France, he once said I will give a thousand men to take that hill.

I mean, if that is not pure instrumentalization, and every military
commander that has ever lived has had to make a decision like that, and
if that is not instrumentalization, I don\'t know what is.

And this came up \-- I think Mike Gazzaniga brought this question up in
kind of our e-mail discussion prior to this meeting, that making the
distinction between treating human beings as means and ends just begs a
lot of questions as to where you make that distinction.

I have heard, for example, people argue that since Kant believed that
the noumenal quality had to do with our ability to reason that it is
actually only fully adult human beings that deserve that kind of
protection.

Which means actually that you could experiment on infants, and a lot of
other people by those rules. So I just would like to hear you defend why
we should start from a Kantian premise rather than some other kind of
premise.

DR. OUTKA: Well, I mean, my reasons are actually much lower flying than
you might fear. For one, it did come up in the literature that I was
reviewing.

Doerflinger mentioned it. In his case, and in mine, too, there is a kind
of Christian \-- but I think you could have some more generally
religious. I think you could have some specifically Jewish or other
kinds of formulations, too.

So it is set in a larger framework, and that is point one. It was handy
because it had already been cited, and I was desperate to try to find
some ways to tie into what I had already presented for reasons of space.

But I don\'t think that it commits. I don\'t want to be committed to
Kantianism, per se. I want to be committed to the second formulation of
the categorical imperative is one potentially felicitous way to identify
some things we should continue to care about.

But I will sort of reserve the right to interpret it in my own ways, and
also stress its importance for our purposes only with reference to
illuminating this, the problematical character of doing something to X
in order to, or with Leon\'s friendly amendment, and as part of our plan
to create in order to destroy, or some variant of that.

That seems to me to be objectionable, and this was one way to try to
make that point. So low flying acceptance, your cautions are very well
taken.

DR. KASS: Very briefly, Janet, and then Rebecca.

DR. ROWLEY: Actually, one of these is a response to Jim Wilson, who
unfortunately has stepped out. But I think it is not correct to say that
the mother to be walks in and looks at a petri dish and says that I want
that egg, and that one, and not the others.

My impression is that is not how it happens, and there is no way at the
present time for us to suggest or to screen for hair color or
intelligence, or any other features.

We can screen for sex, and we can screen for known genetic abnormalities
that might actually be relevant based on family history. The other issue
that keeps coming up again is we are preserving these eggs in
perpetuity.

And for me perpetuity is hundreds and thousands of years, and I think
that is not what the IVF embryos \-- their fate and future is. One
question that I personally am sorry that I didn\'t get a chance to talk
to, or ask to John Gearhart, is how long can you really keep frozen
embryos and expect them to be viable when you thaw them out.

Now, I suspect it is some number of years, but I don\'t know precisely
if these embryos are kept in liquid nitrogen, which is very expensive,
and you have to keep replenishing it in the tanks at major costs to
someone or some institution.

It is also clear that he said that at least in his experience that one
does look at the embryos that are developing as a result of a particular
in vitro fertilization for a family, and selects those that appear to be
the best.

And he didn\'t define exactly best, but presumably either are growing
somewhat larger, or have more cells, or whatever features are used.

And the leftover ones are not as good, and that they have a much lower
efficiency or viability than do the ones that are selected for
implantation.

So I think for us to say that every single embryo left over from IVF has
the potential to go on and develop into a robust embryo fetus and child
is probably totally incorrect.

And I think that we ought to be a little more careful in how we frame
some of these things, because I think we are not taking into account
some of the other issues.

DR. OUTKA: If you all ever find out that question about perpetuity, and
how long that actually is, I would be very pleased to know.

DR. ROWLEY: Well, what do you think, Liz?

PROFESSOR BLACKBURN: Well, enzyme solutions, which are much, much more
biologically simple than \-- not only cells, but blastocysts, or stages
around them, and enzyme solutions will go \"off\" as you store then for
a couple of years, even with care and liquid nitrogen.

So there must be some sort of half-life, and so it is maybe a few years.
I honestly don\'t know from IVF clients how that is going to be an
assist, but just based on the precedent of even less biologically
delicate material, I would be surprised if it was more than a few years.

DR. OUTKA: That is a very important question. The United Kingdom, I
think, discards them more decisively doesn\'t it?

PROFESSOR BLACKBURN: My accent is Australian.

DR. OUTKA: Sorry.

DR. KASS: It is no longer that united.

PROFESSOR BLACKBURN: I am jumping ahead to your inference. I don\'t
know. I don\'t know what the policy is. So I am just speaking from my
very direct laboratory experience of delicate biological material, which
is much less delicate than these.

DR. KASS: Look, we need to break. I want to give Rebecca the last word
if I might.

PROFESSOR DRESSER: I didn\'t try very hard, but I was trying to find out
the answer to this question, and I did see last year that there was a
report of a healthy live birth from an embryo that was stored \-- I
believe it was 9 years, and they presented it as if this was the longest
duration that they were aware of.

But obviously it is difficult on how you do the research to find out the
answer. I was interested in the fourth point that you mentioned at the
beginning, where you were going to focus on four points, and the fourth
point was this issue of political and legal context.

And you mentioned this issue of whether there should be a different
policy for private funding and public funding. And I know that is not
really your specialty, but I wondered if you had any thoughts for us on
that fourth point?

DR. OUTKA: Well, nothing really interestingly beyond what is on those
pages. I mean, I am distressed at the amount of liberality out there in
the private sector, where it really is just taken as a matter of course
that a thousand research flowers may properly bloom out there.

And I think that really is making too many decisions by default, but
that doesn\'t help us very much. And I did remark though that I think
that a number of people have come to the conclusion that if you try to
impose some overall governmental criteria, you are going to get
conclusions that certain people regard as too conservative and
constraining.

And so it is better to leave it alone, and I am not myself prepared to
just accept that without further adieu. But much more work would need to
be done on that.

PROFESSOR DRESSER: But you wouldn\'t take the step that, well, that your
position should be the position that should be our public policy?

DR. OUTKA: No, I would not necessarily presume to that, but I am a great
admirer actually of Canadian ways of managing their health care. I just
have to confess that.

And I do note in the last version of this paper that the position I take
is actually closer to the recently announced Canadian one than it is
either to the more restrictive policies that the United States has, or
the more liberal permissive policies that the U.K. has.

So on this, or on Canada\'s attitude towards reproductive technology,
and all of that, it seems to me that they have been more responsible
than we have.

DR. KASS: I want to thank Professor Outka for an excellent paper, and
for a very forthcoming and lively discussion, and for all of you for
actually sitting patiently through what is a long and for many of us an
intellectually challenging and stretching session.

Thank you very much for being with us, and we will take a break for 15
minutes, and then have our last session.

(Applause.)

(Whereupon, the meeting went off the record for a break at 3:15 p.m.)

DR. KASS: Could we come to order? Why don\'t we begin? I think a few of
our members have had to leave either for class or had a conflict for
this last session. I think we\'re just missing Dan Foster at the moment
and maybe he \-- ah, perfect. Good, thank you.

This is a session in which we return to the topic of our last meeting
and revisit our project on cloning. The specific questions are the
ethical issues of cloning for biomedical research and I would simply
remind us of the approach that we have adopted in full recognition that
not that we have failed to reach agreement, but we never expected to
reach agreement because this is a vexed, moral question where reasonable
people put the moral weight in different places, and that our effort is
to explore these differences with no expectations that they\'re going to
be overcome, but rather that they can be clarified.

The aspiration in this discussion and, if you will, on this part of what
we eventually produce, a common document owned by us all in the sense
that we agree that this is, in fact, a good representation of the state
of the question, while preserving and even sharpening our differences so
that no position held by any member of council or by some person not in
council that deserves to be represented in council isn\'t given its
fullest and fairest expression.

We have been proceeding as colleagues, as fallible human beings with a
certain, I don\'t like the term, but it\'s been used, with a certain
kind of epistemic modesty about our own claims, I mean, to encounter
thoughtful people who ought to know better than not to agree with us,
ought to give us somehow pause and make us a little more humble about
where we stand and that we are interested, maybe when we leave this
room, we\'re interested in victory, but at least for the sake of our
meetings, we are adopting the pretense we are interested in clarity and
wisdom and not simply beating the other side down.

I would suggest and so far, I think with some perhaps exceptions, we
have tried to recognize that the people with whom we disagree have
something vital to defend and if I might be so bold, vital to defend
even for us whether we know it or not, and therefore it behooves us to
make sure that we don\'t shortchange ourselves. And one formulation
would be to say that it would be \-- nobody would want to see us callous
to the needs of suffering humanity. Nobody would want to see us cavalier
regarding the treatment of nascent life at some stage or other and no
one ought to be indifferent to the effects on a society of doing A
rather than B, or B rather than A, or C or none of the above.

So I want to tell you where I think we stand in this discussion to see
whether I\'m right in where we stand and then continue to have \-- to
advance the discussion. The question of the vexed status of this entity,
the cloned embryo, we\'re now back to the cloning topic. It\'s related,
but not identical, with the status of the embryo created by IVF, which
will be, I think, central to the question.

I want to remind us of something that we\'ve gotten from Stephen Carter
in a message to us about the importance of upholding the distinction
between what\'s legal and what\'s moral, between the realm of what is
permissible legally and what is either good or bad, better or worse,
noble or base, right or wrong.

All too often and perhaps for understandable reasons, the question of
permission or ban hovers over the moral conversation, but it\'s
certainly possible that someone might conclude that this activity is
morally dubious, but ought to be permitted and there are all other kinds
of possibilities. So I would like us, as best we can, to have this
conversation still on the moral plane which is where we\'ve had it
before.

I would also make an observation and this has come also in some of the
conversations, that some of us have been adopting the language of
competing goods to describe the present situation before us. And I would
at least like to put before us that that might be a way of putting the
question that is congenial to some, but that there is another way of
formulating what\'s here and might help us understand why this is so
intractable.

In moral philosophy there is a distinction made between the right and
the good in which the good is an object of desire. There are multiple
goods. They don\'t have any kind of absolute standing for us and you can
compromise them to get more of one for the sake of less of the other,
whereas claims of right or of justice are things which lay down a kind
of marker and at least there\'s a prima facie claim that they should not
be violated, that the burden of proof is on someone to show why they
should \-- why they can\'t be violated. And I have the sense, at least
in some of the previous discussions, that for those people who regard
the embryo as either one amongst us or enough like us to be entitled to
some kind of irreducible respect, that is not being treated as a
category of a good to be preserved, but as a matter of right. And
therefore, arguments of that sort are less likely to

\-- people who hold that view are less likely to want to put that into a
pan balance of competing goods, but who want to insist that this is one
of those markers like \"thou shalt not\" because there\'s something
inviolable here.

I don\'t want to shape the discussion, but I at least want to introduce
that distinction as possibly being helpful to us and seeing what might
seem to be simply a matter if we talk long enough, we can find the right
balance, when in fact, for some people this is not a balancing operation
at all, but two different kinds of moral discourse.

I think that\'s \-- there are other things to be said, but I want to
really open the discussion with the following observation. We have tried
in staff conversations and in conversations with you all to stake out
several moral positions with respect to cloning for biomedical research
and while two of them seem to have come to the fore and have commanded
at least some support, I suspect that the two might indeed be enlarged
to four. And let me state them and see where we are.

It seems to me there are two possible grounds for approving or finding
morally acceptable cloning for biomedical research and two possible
grounds for disapproving. One would be to approve and to let\'s say
approve with eagerness and without qualification because one does not
believe that any harm is being done. This would be a view that held that
the embryo in question was beneath the status of having any moral worth
and I don\'t want to get into the language of person and things. I\'m
not sure that\'s helpful, but it is not the sort of thing that ought to
restrain us from use when good might come of it. Let\'s call it the
position of "approve with zeal" or "approve without qualification."

The second would be to recognize that there is something in the
embryonic life here that one is at least agnostic about it or one thinks
it has some kind of standing, but that one engages in a balancing
operation and it approves with humility and is willing to accept some
kind of restrictions or restraint on what can be done, recognizes that
there is a harm being done to the embryo, but does not regard that as a
moral wrong, that is to say, a violation of some stricture of right.
This has been put into a balancing operation.

A parallel on the side of the disapprove, it seems to me I\'m going
upwards in scale. You\'d have a position that one could call disapprove
with regret or has been said, with tears. I\'m sorry, the tears belong
on the other side. Approve with tears and here, disapprove but with
regret, recognizing that there might be certain kinds of benefits had,
but making calculations on prudential grounds or on certain kinds of
moral considerations about where this might lead, that one decides, on
balance, that the goods to be had are not worth the cost of the
balancing operation. And there could be the position that would
disapprove as a matter of principle and without qualification because it
is immoral to treat even the earliest of human embryos as anything but
one amongst us, no matter how much good might come from it.

I take it those are four positions that have been heard around the
table, not necessarily articulated in those ways. In the intermediate
conversations between the last meeting and this one, we\'ve been mostly
working in the middle, that is to say, we have \-- I\'m not exactly sure
about that, but we\'ve had expressions of views that look like
disapprove with regret and positions that argue for approve, but with
humility and the willingness to accept some kind of restraint.

I think from some of the correspondence that there are at least some
amongst us who believe that their view of this matter is not adequately
represented and I think it turns on the question of whether we haven\'t
made all too much fuss about these little 7-day old embryos.

Let me see if I have correctly stated analytically where we are and if
so, then the question is where we can go to make sure that these
viewpoints are properly developed before we actually either try to
persuade one another to move from where we now are to some other place
or we finally have to choose and come down with what we really think
about this.

I think I\'ve said both too much and too little, but let that be \-- to
prime the state of our own discussion. I remind you, cloning for
biomedical research, the arguments of course overlap with the question
of the embryos used for research, but we\'re back on our more narrow
topic and the larger one is still in the offing though perhaps informed
by some of the things we\'ve just been talking about.

Comments, questions, arguments, corrections?

Gil, please.

PROFESSOR MEILAENDER: Just very briefly, I just want to note that it\'s
not necessarily a question of whether someone thinks his or her position
has been kind of adequately represented in that focus on the middle. For
instance, as I recall, one of Frank Fukuyama\'s comments that he sent in
was really questioning whether the approve with humility position was
the right representation of the going argument in a way and I, myself,
had questioned whether it was really the strongest form of the argument.
So it\'s not \-- I think it\'s not just a question of whether one thinks
one\'s own position is represented, but just where the balance of the
argument should lie.

DR. KASS: Mike, do you want to get in on this, please?

DR. GAZZANIGA: I\'ll take the bait. I think we should do everything we
do with great humility. You realize how often in life you\'re wrong,
it\'s a good model. But someone with I guess my particular view would
not see the need for the preceding two hours of torturous debate of
trying to shoehorn into this problem all of the issues that are trying
to be shoehorned into us. So I view the embryo by which we mean the
blastocyst, either formed by IVF or through somatic nuclear cell
transfer as a thing that deserves human respect like all human tissue,
but provides me with absolutely no moral dilemma to proceed into
biomedical research on it.

DR. KASS: Does someone join on that? This is, in fact, I suspect, a not
uncommon position. It might even be more common in this body than simply
Michael, so could we have some discussion?

DR. GAZZANIGA: I guess what I was \-- I don\'t know what other people
think and it\'s up to them to say. But I do like what you\'ve done here
which is to broaden the spectrum of response to the question at hand.

DR. KASS: Right.

DR. GAZZANIGA: And I think that was an important gesture.

DR. KASS: Right. Rebecca, please?

PROFESSOR DRESSER: This isn\'t exactly in response to what you were
saying, but in thinking and reading about this, it seems to me that
people in both 1 and 2 categories, the approval categories are affected
by some notion of duty to rescue or duty to be a good Samaritan and that
it\'s not just some judgment about the value of the embryo or the
viability of the embryo, but it\'s a moral \-- a strong moral feeling
that this is what we ought to do to help people who are very ill. And I
just wondered if that is a concept worthy of exploring with these two
positions, that is, you know the moral philosophy on duty to rescue and
when do we have one and what are the considerations that ought to go
into determining whether people have a duty not just to refrain from
harming, but to actually act to rescue people who are in dire
circumstances. So I\'ll just throw that in.

DR. KASS: Let me add one further thing. As you know from the start we
have been trying to place our limited moral arguments in the larger
context. In the case of cloning for producing children, we tried to put
it in the context of human procreation and with the help of some
comments from Michael Sandel and others, it\'s clear that human
procreation also means relations between parents and children. It\'s not
just the procreative act. We\'re trying to put these things \-- the
right context for this is not just what\'s the status of the embryo, but
the right context for this is what is the vocation of healing and what
is, in fact, the mission of biomedical research and these are not simply
technical activities. These are activities informed by deep moral
commitment and principles and the question is whether these duties are
absolute or relative and so on is, of course, for discussion. But I
think it\'s absolutely welcome. We can\'t simply hash this out over the
status of these 100 cells. We also have to think really about the moral
principles that guide us here. So that\'s, I think, very welcome.

Elizabeth, please.

PROFESSOR BLACKBURN: I\'ve been grappling with this and I think that
I\'m in position 2, as you\'ve outlined it, approval, but thinking
seriously about it and for me a helpful metaphor was thinking about,
well, if one were, let\'s say, there with a blastocyst and you had to do
something to keep it alive and then you saw a child drowning, who would
you save, if it was a matter of you being in one or the other place and
you knew that if you went and helped the child drowning, and I\'m using
a dramatic example, but if you helped the child drowning, you would have
to let the blastocyst die because you couldn\'t carry out whatever next
thing you had to do to keep it alive. So to me, then the choice \-- it
very much comes down to choosing between two things and making a choice
as to what is the more morally imperative, so equating research with its
goal of therapy isn\'t therapeutic benefit and other medical advantages
to the idea of saving an existing life in some way that is a fully
formed life. So to me, it sort of came down to an either/or. Which one
does one weight. So I think your category 2 seems to be fitted by that
metaphor.

DR. KASS: Please, Alfonso?

DR. GOMEZ-LOBO: I think that was a very nice illustration, actually, and
very helpful, although since both are duties of care, I don\'t think
that there is any really serious and deep moral conflict. I think that
it\'s perfectly legitimate to care more for one than the other, if you
can\'t save both. In fact, I would like to take up the \-- perhaps the
challenge sketched by Rebecca and I think it\'s a general way of
clarifying things or trying to clarify things. I think we do have duties
of care, moral duties of care, duties to take action to preserve the
goods or to promote them and doubtless, our duties involved in health
care are usually of that nature. I mean we make all sorts of effort to
say bring our child to the emergency room when the child is sick,
etcetera. And of course, that\'s a very, very important aspect of our
moral life.

On the other hand, we have duties of respect and we have duties not to
harm. Physicians of the older generation perhaps were quite familiar
with this, the \"first, do no harm\" principle. And now these duties
have to do with the impermissibility of taking action intentionally that
will deprive someone of a good. So in a way it\'s symmetrical with the
other one and the first case we have a duty to promote, protect a good,
otherwise would go unprotected and that would make it a moral
obligation.

Now what happens when there\'s a conflict between the two because
that\'s what we\'re talking about. If there were no conflict we
wouldn\'t have much of a problem. Now I don\'t \-- I do agree that some
things we have duties of care, but duties of care are usually not that
dramatic because if something goes wrong with one of the options, we\'re
really not 100 percent responsible for it as in the case of letting the
blastocyst die.

Now what happens when we have, I\'m sorry, did you want to interrupt?
Okay. What happens when we have a conflict of care and we have a
conflict between care and respect? If I understand it correctly, the
tradition of moral philosophy tends to say well, if the duty of respect
is such that if you act intentionally, you would be producing an
important harm to human good, then that should take precedence over the
care.

Let me give you an example, perhaps a trivial one, but one which appears
in ethics books very often. You have a bandit who has kidnapped 20
hostages, an American college woman goes by and this man says look, if
you kill one, I\'ll let the other 19 go and of course, that is perceived
as a conflict because of course this woman has a duty of care,
apparently, to save 19 people. But in order to achieve that goal she has
to harm, that is, intentionally kill one person. Since that is the
primary action in which she is engaging, it follows that the agent in
this case should morally refuse to do it.

Now I\'m sketching this argument because for me \--

PROFESSOR SANDEL: Excuse me, would you say that even assuming that you
know for sure that the villain will kill the 19 of the 20 if you don\'t?

DR. GOMEZ-LOBO: Yes. Well, first of all, you never know for sure because
there\'s another agent making another decision there. I mean we\'re not
as predictable. Bandits are particularly unpredictable and in most
ethics books the bandit is called \"Pedro\".

(Laughter.)

That says something.

PROFESSOR SANDEL: The reason I asked is if that condition did apply,
then we would have the nothing is lost principle to argue for killing
the one.

DR. GOMEZ-LOBO: Sure. Well, I don\'t subscribe to the nothing is lost
principle by all means.

PROFESSOR SANDEL: Nor do I.

DR. GOMEZ-LOBO: Don\'t sign me on on that one. Plus, I don\'t think
there was a good application of the principle of double effect in our
previous discussion. So I\'m torn. I\'m definitely in group 3 here
because from the marvelous exposition this morning, I see that, well, we
had heard that from Dr. Weissman already. I see how promising all of
this is and I see that there are these duties of care, but if \-- I know
many of you will not concede the \"if\" clauses of the following
sentences, but if embryos are human beings at an early stage of the
development, and if we should not intentionally kill innocent human
beings, it follows for me that I should not violate the harm principle
in this case and that\'s why I\'m on level 3. I do think that this is a
morally impermissible action, but I regret it and that\'s why my
question is going to be whether the scientist can\'t figure out a way of
harvesting the stem cells without doing harm and the reply,
unfortunately, was no.

DR. KASS: Gil Meilaender and then Paul.

PROFESSOR MEILAENDER: Well, you\'re in charge.

DR. KASS: No, go ahead. My rudeness and his gentlemanliness give you the
floor.

PROFESSOR MEILAENDER: Well, a couple of things. I just want to note with
respect to the example that Elizabeth gives, I mean I agree with what
Alfonso says in the sense that it really brings us back to your comments
kicking off this session. Elizabeth\'s original way of formulating it
was a way of thinking about several goods, clearly in competition since
you could only save one. Alfonso\'s way of reformulating it has to do
with how he changed it into the question of respect and care, but it\'s
really \-- that\'s a form of the right and the good, in a way. And it\'s
worth noting that there might be other factors that would enter in. I
don\'t know what you\'d say to this, but even thinking of it just in
terms of the competing goods model, suppose the blastocyst is mine and
the drowning child or whatever it was, is somebody else\'s? Does that
count? I mean there are all sorts of factors that enter in here, in
fact.

So the notion that we\'ve only got one kind of thing, namely stages of
development that makes a difference, when we weigh competing goods is
not the case, in fact. It\'s considerably more complicated.

We have obligations to try to do good as much as we can, but that means
within certain kinds of limits and it means taking account of a whole
range of factors, and so it\'s just worth noting that it\'s there.

Then the other thing I wanted to comment on was just to come back to
Michael\'s comment that basically what he was saying was he falls into
category 1, as you outlined, that there\'s not really a moral problem
here, but that doesn\'t get us very far to say that because we want to
know then what will give us a moral problem. If the early embryo
doesn\'t, at what point would we have a moral problem and why? In order
to think about how persuaded we are by that, we need some kind of
characteristics or criteria or something that will help us think about
it. Otherwise, we only have a position and we don\'t yet have a kind of
a piece of reasoning that we can go to work on. We just need more to do
something with it there.

DR. KASS: Michael has in previous meetings, in fact, in the very first
meeting if I\'m not misremembering, articulated what might be the
criteria for moral standing and they were pretty much neurological, but
I wouldn\'t speak for him. Could we draw you out on this because it
would be welcome.

DR. GAZZANIGA: Sure. One hates to try to answer impossible questions,
but you can certainly take approximations. And the approximation that is
safe for all concerned who are concerned about your question is that by
14 days the British line in the sand, we\'re dealing with a system that
is brainless and has no capacity for sentience. The brain cells aren\'t
even born and that\'s pretty raw, elementary biology to \-- for me to
draw the line at the 14th day and then people come back and give you the
potentiality argument and I also said something about that which \-- so
yes, I\'m willing to draw for \-- where are we, 2002, that a 14-day line
in the sand is a pretty comfortable, keeps you free from thornier issues
and I\'m going to let someone else draw the next line.

DR. KASS: I\'m sorry?

DR. GAZZANIGA: I\'m going to let someone else draw the next line.

PROFESSOR MEILAENDER: Can we have 20 days maybe?

DR. KRAUTHAMMER: Michael, could I pursue that? Michael, I just want to
ask you, forget about the legal issue here. At what point, clearly,
you\'re not at all morally disturbed by working on a blastocyst. At what
point in the development of this entity are you personally morally
disturbed?

DR. GAZZANIGA: Well, you know, let\'s see how she goes. One step at a
time. What\'s before us in terms of what the scientists are saying we
can provide untold remedies, hopefully they can be provided. For the
time being, they would be happy and everybody would be happy with the
line that I\'ve drawn. The line that I\'ve drawn \-- a line. So in 10,
15, 20 years, if they come back to the meeting and say look, we need to
move that line, how much \-- how good their argument is, what people
think about it is for another time to be considered. I don\'t think we
have to think that far into the future. I think can we make a
comfortable decision in 2002 and I think we can.

DR. KRAUTHAMMER: But clearly, what you think about when this organism
deserves some respect has to have some influence on your thinking on
this, I would assume that you believe a newborn child deserves
protection.

DR. GAZZANIGA: Of course.

DR. KRAUTHAMMER: And I understand that what you\'re saying of the
7-day-old blastocyst is just a piece of tissue, clearly there\'s a point
at which if you were asked to do the research on this organism, you
would say no, and I\'m just curious to know what that \-- you certainly
have thought about this.

DR. GAZZANIGA: Well, I don\'t know if I have.

DR. KRAUTHAMMER: Perhaps you could give it a try.

DR. GAZZANIGA: I mean the obvious, from the neurologic base, the obvious
fact on the ground is that the organ that is responsible for everything
going on in this room is the brain. And the discussions of the issues of
human dignity, of human concern, piety, sympathies, those are all
constructs of the human mind and so that means you need a brain around
to enable those concepts to be used. So one could say that you at least
needed the presence of a nervous system and a nervous system doesn\'t
start forming for 4 or 5 weeks and that nervous system, as you know, is
impoverished, it\'s not ready to do the kinds of things we\'re doing
now. And then you start getting into all these unanswerable questions
and I just would rather set those aside because I don\'t have those
problems at 14 days.

DR. KASS: Do you want to continue?

First of all, Michael is very good natured and he\'s not shy, if I may
speak for him. And I think that this, if we\'re here, let\'s pursue this
a little bit further and see if we can get some clarity on this, if
people don\'t mind. I\'m taking advantage of your good nature.

DR. GAZZANIGA: We\'ll see how good natured I remain.

DR. ROWLEY: Have you checked with his wife?

(Laughter.)

DR. GAZZANIGA: Sure, go ahead, push me, push me.

DR. KASS: Did you want to go further?

DR. KRAUTHAMMER: Well, I don\'t, as a former psychiatrist, I\'m guessing
here, but I don\'t think I\'m going to succeed. The position I\'ve taken
which cut down a lot of trees to publish in [The New
Republic]{.underline} this week, is based on basically a slippery slope
argument. It begins by trying to not assume any intrinsic worth to the
7-day blastocyst, but asking were we to pursue this research,
particularly in cloning where you create for the purpose of using the
blastocyst and destroying it, what will we become? So I think it is
relevant. If you think that it becomes wrong to do the research at a
fairly near point after that, and as I understand what you\'re saying,
Michael, it would be at the point where there\'s beginning of neural
development. But you seem to also be saying that you want to draw the
line at two weeks, so the slope here, I don\'t know how slippery it is,
but it isn\'t a big slope between 1 week and 2 weeks.

DR. GAZZANIGA: This is where I am in over my head. I like to call up
philosophers I know and say can you help me with this slippery slope
thing.

(Laughter.)

And they say oh, that\'s been written about and there\'s a pro side and
a con side. And I say okay.

(Laughter.)

I\'ll take the con side and we hang up. You can get a driver\'s license
when you\'re 16, right? Now someone said well, what about 15 years, 11
months, 30 days, is that really different than 16? Nah, it\'s not really
different. Well, about 15 years, 11 months, and 29 days. Pretty soon
with the slippery slope argument you can get down to where babies could
be getting driver\'s license. And of course, that\'s nonsensical. So
what we develop as a species is a capacity for form categories,
categories of action, what is generally acceptable. And all I\'m
suggesting is that we have a category here that we can make a clear
decision about and in that way get around the slippery slope analogy
which I think can find you in some pretty slippery situations.

DR. KASS: Bill?

DR. HURLBUT: Here\'s what it seems to me to come down to. Some people
would say that what you\'re talking about here is not a license to
drive, but a license to kill. Now I\'m not a lawyer and unfortunately,
as I look around the room, it seems to me there aren\'t any left.

Oh, good, right, okay. Rebecca, you\'re here. But my understanding of
the law concerning abortion is that it was not fundamentally a right to
take a life. That was a circumstantial secondary effect. The woman had a
right of privacy to evacuate her womb of this alien presence that was
not, she did not have an obligation to have. Okay? Maybe you can correct
me in a second, but let me keep going. So now we have \-- you say we
have this capacity to form categories. And I want to say
parenthetically, I have a lot of trouble figuring this out too, so I\'m
not trying to attack in saying this, but I\'d like clarification on it.
You say we have this capacity for categories. Well, one of our major
categories is this distinction between a life present or in process and
its right to continue or whatever you want to call it. I don\'t even
want to use the language of rights, but this is a major category, this
position that you should never take an innocent life in process.

Now here\'s what troubles me about all this from the slippery slope side
of the argument. I\'m also troubled by the potential argument, but
let\'s put that one aside for the moment and here, Mike, I want to ask
you a specific question.

So if you really go down and you talk to people about stem cell
technology as I\'ve tried to do and by amazing circumstances I know
quite a few of the major figures in this field, my assessment of it is,
yes, we might be able to find the reagents and bathe the culture in them
and get the proper cells we want, but that in fact, we\'re more likely
to get what we want if we were to gestate it for a while, either [in
utero]{.underline} or artificially of some kind of ectogenesis could be
generated.

So now what I want to ask you \--

PROFESSOR WILSON: Mike, what was that? What could be generated? I
didn\'t hear you.

DR. KASS: Growth outside, ectogenesis. It grows outside the womb.

DR. HURLBUT: It turns out that a lot of what happens in the development
process is highly circumstantial. So people working with stem cells are
beginning to appreciate how there are these other little micro
environments, that if surrounded in a semicircle by one kind of cell
which are sending a diffusible agent in in a particular way, then
another agent coming from the other side will cause the differentiation,
but you can\'t just bathe it in the reagents.

The point is that it seems more logical to me that you reasonably could
produce more useful therapeutic tissues by allowing gestation or some
kind of artificial gestation to go for a while.

So I want to take the opposition position for a moment and say why not
go beyond 14 days and why restrict ourselves to 14 days now if brain
criteria \-- I think even now my assessment is we could learn a lot and
progress faster with the science if we didn\'t draw that boundary. So I
really feel as though that boundary is really just shifting the question
of not taking an innocent life to 14 days instead of point of origin.

DR. GAZZANIGA: Are you in a position 1, we\'re haggling price here?

DR. HURLBUT: No, because I said I\'m prescinding from the question of
potential for the moment. So just on your principles, I want to know why
we would draw the line at 14 days. And why now?

DR. GAZZANIGA: I just told you. It is a line that is comfortable for me
to draw. It is a line that would allow the research to go forward. I
won\'t keep repeating myself.

DR. HURLBUT: But you said a minute ago that you are comfortable with the
fact that until there\'s a neurologic system which you said was 4 to 5
weeks, that you didn\'t think there was any increased moral standing, so
why would you not set that boundary for the moment at 4 to 5 weeks which
would make science progress much faster.

DR. GAZZANIGA: I don\'t know enough to know whether you\'re right or
wrong. I leave it to the adjudicating regulatory panels might inform us
on that. I don\'t see this as a crucial point whether it\'s 14 days or
whatever. I\'m comfortable with 14 days and I\'m simply stating my
position of 14 days.

DR. HURLBUT: I\'d also like to comment on \-- I\'m sorry Mary Ann is not
here. Her summation of the last which is relevant here that she seems to
be moving towards a conservative position on this issue because of the
failure of \-- to see any demonstrable products or line of research that
are coming out of various stem cell efforts.

DR. GAZZANIGA: There\'s a wonderful article in [Science]{.underline} a
couple of weeks ago entitled \"Some History Should be Repeated.\" And
they review the claims and concerns of people about the recombinant DNA
research in 1976 where there was a group of people from Cambridge,
Massachusetts where a lot of this was going to go on at MIT that felt
funny little organisms were going to ooze out of the MIT labs and
envelop Cambridge and people were going to die of these horrible things,
yadda, yadda, yadda.

And in a similar meeting held in 1970, the late 1970s, they set up this
regulatory agency and as a result of now going ahead with recombinant
DNA research, none of which was immediately envisioned at the time, we
now have, according to this article, 11 major drugs that are used in
diabetes, hepatitis, acute myocardial infarction, rheumatoid arthritis,
stroke serving and saving the lives of millions and millions of people.

So the notion that I think some people not scientifically trained don\'t
quite understand is that let the scientists roll. They\'ll figure it
out. They\'ll figure it out and they\'re the most conservative people in
this room.

DR. GAZZANIGA: They beat each other up on a daily basis as to whether
what they\'re saying is correct or wrong. But you can\'t project into
the future what they\'ll find out. You have to just understand the
competencies that they\'re currently arguing for and then let them go to
work.

DR. KASS: Dan.

DR. FOSTER: I just want to interrupt for one second.

DR. KASS: Please.

DR. FOSTER: I want to say something a little bit later, but I want to
respond to Bill in one sense. We, ourselves, as a council, tend to have
different views. We can sort of sense what, as Leon said, and he\'s come
a long way to try to get us into thinking about these things. I think
it\'s critically important in terms of, as Charles would say, building a
fence, that we not try to expand what has already been done already when
\-- outside. I think it\'s critically important. I myself would be
perfectly happy to draw the line at the blastocyst level because I think
all the initial basic science can be worked out there and to start
moving beyond to the 20 days and so forth. Maybe that would speed up the
science. I don\'t know about that at all. We may find something from the
blastocyst in terms of mutation rates and all sorts of things, going to
pass away.

My own view is I\'m starting to get \-- but I think it would just be
crazy from a practical standpoint to try to say the council wants to
come up and extend what we can\'t even agree on here ourselves. So
that\'s not a moral \-- the only reason I\'m hesitating to say this,
it\'s not a moral issue, but sooner or later, we have to get off of the
high standards of moral things and talk about practical things as well.
I think we\'re starting to talk about very practical things this
afternoon. I maybe want to come back to that a little bit, my comments
about that a little bit later, but I sure would \-- Gil, I always learn
things from what you say and write and send me, but I think this time,
you\'re wrong. I think it\'s wrong to try to expand this thing out, both
practically and in terms of trying to get a consensus on some views, our
views here in the council.

DR. KASS: Let me say I think I understand. I don\'t want to pretend to
have mind reading capacities. But I\'ve been in a number of these
discussions and I begin to get to know who\'s talking. I think what\'s
at issue in this conversation, let me see if I\'ve got it right. Mike
Gazzaniga sees no moral difficulty with using blastocysts because he
does not regard them as being things of moral worth.

He was asked by several people to say well, all right, and he also
enunciates a powerful moral principle for going forward, namely, we\'re
going to learn good things and important things and people will benefit
from it.

So no harm, and great good. What\'s the problem?

Then people want to know well, is there a place where you would have a
problem so that if we want to join you we want to know where this train
is going and where the limits are which is partly why Charles wants to
know, why Gil first of all wants to know what\'s the ground of this,
where is there going to be moral standing and then he gives the argument
of nervous system and then the question is well, is the 14 days merely a
prudential calculation because that\'s all we need right now and he\'s
willing 15 years down the road to go some place else. I think that\'s
what, in effect, Michael was saying. But there are people who are
nervous and who want to hear the principled defense because what they
hear here is something like the duty to care and cure being treated as
an unqualified imperative beneath which everything else has to submit.
And so part of the question for those of us who would care about
something, about not doing harm or not violating that which should not
be violated, they want to know is there a place.

Now other people have used the 14-day marker not as a merely time saving
place for the time being, but who really think that 14 days is a
transitional point, whether it be implantation \-- I don\'t mean by that
just transfer into the woman, but actual physical implantation into the
wall of the uterus where you actually have the beginning of a pregnancy,
until that time, you don\'t \-- or who want to talk about the primitive
streak or who want to talk about the absence of twinning and who try to
provide some kind of biological foundation for saying ah, there\'s
something here now not fully one of us, but that\'s a biologically-based
boundary, not in a nervous system, but something else that might count
for the discussion.

So for some of the people in the conversation who want to know, is there
something in the nature of things that would give us a guide if the
blastocyst is not it yet? I think that\'s part of the conversation.

And the other part of the conversation seems to be to test out what
actually is the limit of the moral imperative on the side of going
forward or are we simply going to say there are sick people out there
who need these things and until you come to newborn infants, which I
think was the implication of Charles\' question, it\'s ultimately fair
game because we can\'t really, I think, and this is not my \-- this was
an attempt to summarize what I thought was going on in the conversation.
I would add a position of my own. Yes, we are faced with a certain
practical decision here and now, but we have to think about the meaning
of the kinds of decisions we take here and now for what it legitimates
in the future. Yeah, and therefore, we should try and find a good moral
foundation as well as being prudential and practically sensible here in
trying to reach this and to see whether we can find a place to rest our
head, if we can. If not, I think we\'re in danger of reaching an
unprincipled kind of compromise which offers no guidance to those who
are going to come after and who might look to this body which was
invited to think about this with a view to where this is going,
admittedly with uncertain knowledge, but with some power to predict some
of the things that might be coming ahead.

DR. FOSTER: Leon, I always seem to start these long speeches that I was
not speaking to the issue that you posed before us about the moral
things. I was talking about a very practical thing and I didn\'t want to
divert off into some other thing. I want to get back to this. I was not
making any moral argument at all. I think it\'s perfectly legitimate to
do that. So if you were lecturing me, I was not attempting to make a
moral argument.

DR. KASS: Excuse me, it wasn\'t a lecture to you.

DR. FOSTER: Well, it sounded like it.

DR. KASS: No, sorry, Dan. It was heading off what I thought were going
to be people pouncing on you.

DR. FOSTER: I\'m so delighted that you\'re going to take care of me just
like the fetus, you have to take care of me, right? Okay, I\'m just
kidding.

DR. HURLBUT: Can I respond, Leon, just to that because I have a very
salient point to respond to that.

DR. KASS: Okay.

DR. HURLBUT: And it ties to what you\'re saying.

DR. KASS: Okay.

DR. HURLBUT: Dan, we were told this morning that fetal primordial neural
cells may be useful in Parkinson\'s disease, right? Okay.

DR. FOSTER: Some people believe that.

DR. HURLBUT: But let\'s assume it\'s right for the moment. Now it\'s not
abstract and it\'s not way off in the future. It\'s here and now. So why
then would we say, on what principle will we say that a person should
not clone himself, gestate or hire somebody or gestate for themselves
the embryo up to the age to harvest out those particular very useful
cells? This is right here, right now. And yet, the question \-- and
look, let me make two other points. I am a physician. I really want to
see the science go forward very, very, very much. I feel the weight of
this. I dream it actually, but I think if we define our principles, we
will allow the science to go forward because then we will, for example,
if we say, full, generative potential is not acceptable to violate, then
we\'ve got the possibility of creating partial generative potential,
perhaps, and going around it, the moral problem in a moral way.

If we define our larger principles well, it will allow the science to go
forward. Otherwise, it\'s going to get stuck in this morass of conflict.
So what I see myself as saying here is something positive to try and set
the future in an open way.

Moral reality is a fragile reality in any given society and it\'s
something we have to contend with. We can\'t just ignore it. I think
it\'s harder to set a moral tone of cooperation in a society than it is
to make scientific progress. But hopefully, they can go forward
together.

DR. KASS: Paul McHugh. Thanks for your patience, Paul.

DR. McHUGH: Well, I\'m going to distract us, I think, from that kind of
conversation, but only to reiterate what has been and to emphasize what
has been the subject of the conversation between you and me in our
epistolary debate in the e-mails.

I feel that we will totally submerge into arguments of opinion over
actions if we don\'t agree or come to hear that the somatic cell nuclear
transfer clonote is different than the zygote. With Michael, I can
partially agree that the clonote should have \-- be the subject of study
because I think of it as an artifact and I think it different from a
zygote. Where I disagree with Michael is that dealing with a zygotic
natural program is equally okay. In fact, I wanted to make a point about
Mary Ann Glendon. I think she would say her argument was not
conservative, but liberal in the sense of wanting to encompass more
people under the umbrella of our protection, but the issue of the
science here in what we\'re talking about is an effort to bring science
forward in the best way.

I want to emphasize what I said in those notes, that is, that the lived
experience of scientists making somatic cell nuclear transplants is not
that they are creating a new individual, that they are then going to
destroy. They are thinking that they are producing tissue that has a
particular program and that they\'re going to use that tissue at some
time for the benefit of everyone and I\'m approving of that and I want
to support that. In fact, I do support it. I believe that the artifact
can then be misused if brought on into reproductive cloning, but the
fact of it as a different kind of thing permits different kinds of
actions towards it.

DR. KASS: Do you want to answer publicly one question on this?

DR. McHUGH: Yes.

DR. KASS: You believe that the clonote is an artifact different in kind
because it\'s different in origin from a zygote, correct?

DR. McHUGH: Different in its origins and in its constitution.

DR. KASS: And in its constitution. And should that cloned \-- should
that become cloned at the blastocyst stage and should it be implanted
for reproductive purposes and should a child emerge, would that be a
human child or would that be an artifact?

DR. McHUGH: Well, first of all, those actions should not be done.

DR. KASS: But \--

DR. McHUGH: That human person would be a different person, although you
would extend to him because he was tragically created, natural rights to
him, but you would see him as a person mistreated and never to have been
created.

DR. KASS: But not a member of our species?

DR. McHUGH: Not quite a member of our species in the same way, yeah.

DR. KASS: Even if capable of reproducing with another member of our
species to produce more members of our species?

DR. McHUGH: He would be different.

DR. KRAUTHAMMER: Is Dolly not a sheep?

DR. McHUGH: Dolly is a sick sheep.

DR. KRAUTHAMMER: But Dolly is \--

DR. McHUGH: But this would be a sick person and we would have to take
care of him.

DR. KRAUTHAMMER: But Dolly is a sheep, sick or not, she\'s a sheep. I
think she\'s a sheep, right?

DR. KASS: The question has been joined. I don\'t know if we can sort it
out.

DR. McHUGH: The point of saying that the clonote has these potentials,
that if they are illegally and I would believe that this would be as
illegal as slavery or as genocide, that because it has those potentials,
that therefore it should be treated as though only those potentials
characterize it or that it should be conceived of as only characterized
by potential would be an error, an error of logic and an error that
would hold back the advancement of science.

DR. KASS: Instead of arguing, let me see if I can put you on the map of
positions, the moral positions on this question so we know what homework
we have to do.

If I now understand you, you do not regard cloning for biomedical
research to be a moral problem because the thing that is produced isn\'t
on the human moral scale and therefore \--

DR. McHUGH: I found it problematic to take your spectrum because I was
looking at where I would place myself.

DR. KASS: You\'re in a fifth position.

DR. McHUGH: To some extent I hold myself in the place where \-- between
1 and 2, okay? I don\'t think any harm is being done by creating a
clonote. I think something good is being done by creating a clonote. But
because it is a special kind of new, a kind of biology, I would
therefore not permit it to be implanted in a uterus, so maybe therefore
I\'m treating \-- approving with humility in some way because I\'m
putting limits around what I would do with it.

DR. KASS: Okay.

DR. McHUGH: You see, if you take the point that the clonote is something
different, it\'s something manufactured rather than begotten, then you
would want to study, use its best potentials for human kind and not let
its potentials for error and slavery appear, okay?

DR. KASS: I owe you a 5-page e-mail.

DR. McHUGH: Yes.

DR. KASS: You\'ll get it. Dan, please?

DR. FOSTER: I don\'t want any e-mail. I never write e-mails in these
things and the one that I sent I said don\'t circulate. I\'d rather talk
personally, but that\'s okay.

Let me make a preliminary remark. Leon said a moment ago in passing, he
used a phrase that I think Adam Seligman popularized called
epistemological modesty that in the philosophy of studying knowledge
that you looked at limits and so forth. I think epistemological modesty
means that you believe certain things, but you\'re modest about these
claims and you can be a believer and yet say I\'m not really sure. And
that\'s sort of a fundamental fault line here in the discussion.

I take seriously and I\'ve been influenced by the people who occupy
position 3 here and I\'m not willing to agree with Paul that this is
just an artifact. I think there\'s serious issues here that make me
nervous.

But if you live in what Alfred Shutz called paramount reality, that is
being wide awake in the every day world, that\'s what paramount reality
is, it seems to me that common sense shows that a 100-cell human embryo
with a potential to ultimately, if everything goes right, becomes a
human, has to be taken as serious, as being serious. But it seems to me
from this wide awake view that it\'s different and it doesn\'t have the
same demands for protection and respect as let\'s say something a little
bit later. But I don\'t know that for sure. And that\'s why I think one
has to occupy what I think I and what I know I occupy which will be
position 2.

It seems \-- I don\'t \-- I\'m not comfortable with Rebecca\'s view that
there\'s some messianic demand to rescue people. I think there are great
virtues in suffering and death that come to humanity. I think none of
the things that are great in humanity would occur without threat and
suffering in the world. If there were not pain, there wouldn\'t be any
need for mercy. If there were not fearful things, there would be no room
for courage. One could go through the whole litany of what makes humans
different and great or the consequences of risk and suffering in the
world. That does not mean that when we\'re given these brains that we
should not try to make the world better. I\'m distressed enormously by
the fact that the slope of evolution in science appears to be steadily
upward and that the slope of evolution for human kindness and
beneficence and morality seems almost not to have moved at all.

And therefore, I think there\'s an obligation for those of us who live
in this world and want it to be better to try to make wherever we can
the world better and if you take \-- I may be the only one in the room
that really actively takes care of patients and \--

DR. McHUGH: Hold on.

DR. FOSTER: I\'m sorry, Paul. He\'s retired, but he still takes care of
them. Okay, forgive me for that.

But it is a daunting thing to deal with death. I just lost my long-term
colleague. We did 30 years of science together. We did good science
together and from a glioblastoma multi-form and there are papers,
somebody read the [PNAS]{.underline} paper last year where you can mark,
you can put human glioblastomas in and then just infuse adult neural
stem cells in the peripheral blood targets, the glioblastoma, you can
take the mass out, but they infiltrate, you can just see pictures. There
are two new articles in [Nature]{.underline} and [Medicine]{.underline}
just showing them infiltrating. But these adult cells clamp on to them
and you modified them so that you can give a small drug and convert it
into a chemotherapeutic agent across the blood-brain barrier. I mean we
tried to see if we could do anything for humans like that.

So myself, for myself, it\'s perfectly clear that we ought to try to do
better in terms of medicine and the relief of suffering and I don\'t
think the worry, although I\'m very worried about it is sufficient to
stop that.

Here\'s another point that I think I made

\--

DR. McHUGH: Can I ask you a question then about that, Dan?

DR. FOSTER: yes.

DR. McHUGH: Can I ask you would you take a blastocyst that was naturally
formed, taking it out of a uterus, a natural blastocyst and use it in
the way you want to use the clonote?

DR. FOSTER: No.

DR. McHUGH: Why wouldn\'t you?

DR. FOSTER: Because then I would clearly be interrupting a progression,
unless nature took it away.

DR. McHUGH: Well \--

DR. FOSTER: Let me answer it another way. Everybody talks about if you
use this, you\'re going to destroy it. Well, I don\'t know what the
figure is, but 30 to 70 percent of the embryos that form normally are
deleted by nature. So what do we say that God is destroying these \--

DR. McHUGH: Would you put a filter in a uterus and pick up those and
then use them the way you want?

DR. FOSTER: I would not.

DR. McHUGH: I\'m coming back to my artifact which you wish to use as an
artifact, but deny. That\'s what I\'m saying here.

DR. FOSTER: Well, I guess \--

DR. McHUGH: You are saying that things which occur naturally you
wouldn\'t use, but things which come out by cloning you would use and I
believe that that\'s because you see an artifactual nature to the
clonote.

DR. FOSTER: Well, I don\'t think that\'s what I believe \--

DR. McHUGH: Well, would you use a naturally occurring blastocyst formed
\--

DR. FOSTER: You mean while it\'s in the uterus?

DR. McHUGH: Yes, when it falls out of the uterus.

DR. FOSTER: You mean if you take it out of the uterus?

DR. McHUGH: yes.

DR. FOSTER: No, I wouldn\'t. I don\'t want to get into \--

PROFESSOR SANDEL: that\'s not the only possibility.

DR. McHUGH: No, that\'s not the only possibility.

DR. FOSTER: I don\'t want to get into one of these long e-mail exchanges
that you and Leon try to do. I\'m just trying to make a simple, succinct
point and then I\'m going to stop right here in just a second, but I do
think that we \-- that I feel a strong obligation not to stop this and
the only thing I was going to say and I argued this with Charles a
moment ago, I think if we allowed this to go forward, that is biomedical
research, if it turns out that it doesn\'t work, I agree with Mike, the
scientists would be the first to quit and so will biotechnology
companies because if it doesn\'t work, if it\'s got mutations in it
we\'ll end it. Or, if there are better ways to do this as I think there
may well be, it will be abandoned quickly. We\'ve seen that all over in
medicine that we abandon things when they go through. So my view is,
let\'s try to learn from this and keep it very limited and I\'ll pay the
price of tears, if that\'s what it is, if it turns out that in some
sense that the universe thinks I\'ve killed a child, which I hope we get
rid of that murdering and killing things. I mean there\'s some sort of
an implication that scientists are unethical or immoral or less ethical
or less moral than people who are not scientists and I want to try to
get away from that. But if that\'s wrong, then I\'ll try to tell the
universe sometime, I\'m sorry, I made a bad mistake. But on the other
hand, in the meantime I want to try to see if we can\'t help a whole lot
of humanity with what to me seems to be a different sort of moral
problem than the idea of beyond ending a life that\'s not neurons and
other organs and things of that sort.

I didn\'t mean to talk so long. I just was really trying to say that
I\'m in the position of with a lot of concern as to whether I\'m right
or not about that.

DR. KASS: Charles?

DR. KRAUTHAMMER: I\'m a 3 and I\'m there for prudential reasons. Mike
says and I think if I have the quote correctly, those not trained in
science don\'t understand that what we need to do is let science roll.

Well, we let science roll in the 20th century. We got eugenics. We got
the Tuskegee experiment. We had such horrors in mid-century that we
needed the Nuremburg Code. Humanity hadn\'t had to write it before, but
it had to write it after. So I\'m a little skeptical about letting
science roll. Scientists are one of the great resources in any society.
They do the science, but they don\'t own the science. And the reason
that we\'re here is because we don\'t have a guild system in this
society, we have a democracy. We don\'t say to auto makers you know how
to make cars, therefore you will determine what safety standards will be
in cars. No, it\'s the nonexperts, it\'s the lawyers and the Congress
who decide what are going to be the safety requirements in cars and that
is imposed on the experts who make the cars and that\'s how we do it in
a democracy and that\'s why we have this council to advise the President
and the country on what restrictions might or might not be applied on
what is undoubtedly a wonderful enterprise.

But we don\'t have a guild system in which all the rules are made
internally, not in a democracy.

The reason I\'m against research cloning is not because of the reasons
underlying position 4 which is somehow attributing a worth to the
blastocyst equal or at least comparable to that of a human, but out of a
prudential consideration as to what happens if we don\'t.

The first slippery slope and I think an argument that in and of itself
would be enough for a person to oppose research of cloning is that I
think there can\'t be any doubt that if we sanction an industry \-- and
it will become an industry \-- for the creation of cloned embryos, it is
absolutely inevitable that we will begin to see those embryos implanted
and we will have the moral horror of having a cloned embryo in gestation
which under penalty of law would have to be destroyed and that is a
moral certainty that I think is intolerable. But as I wrote in my piece
in [The New Republic,]{.underline} that is a little bit too easy. I
think it would be reason enough to prudentially oppose research cloning,
but let\'s assume, put it aside. I think there are other reasons and the
reasons are that once you start on this, once you start rolling along
this road, it will lead us to places where I think that we don\'t want
to go. I may be wrong, obviously nobody knows exactly how we will end up
or where this will take us, but I think a prudent society needs to make
choices based on past history and some understanding of human nature.

The problem, Daniel, is not that the research might fail. The danger is
that it might succeed wonderfully and we will then have scientists say
as we just heard, give me three more weeks with this embryo. Why not
have a fetus where the organs are developed and use them for
transplantation rather than have a Rube Goldberg system of growing it
into a blastocyst, teasing out stem cells, tweaking them into developing
into cell lines. Why not let nature produce with that wonderful machine
a fetus and let\'s strip it apart for its parts? Most of us would say
today that is unconscionable. Well, I suspect that if we live in a
society where we do this kind of stuff at an earlier level, for a decade
or two or three, it will be less unconscionable.

In the end, I think the major issue here is that we are crossing a new
barrier with research cloning and that is the creation of embryos solely
for their use and I\'m afraid that once you do that and we create an
industry in which this will be the business of that industry, embryo
creation, that we will so desensitize ourselves to the use or misuse of
this entity that we will end up doing things that we don\'t want to do
and don\'t want a society to do.

I think that prudential argument is one on which we can argue about
well, what are the likelihoods of these things happening, but I think we
ought to be realistic, that once you start on that road, we will be, as
a society, far less able to resist the temptations that today seem
obvious that we ought to resist, but tomorrow, probably won\'t.

DR. KASS: Jim Wilson?

PROFESSOR WILSON: I\'ve listened for years to Charles and read Charles
for years without, I think, disagreeing with a single word he\'s uttered
until today. And my problem is with the slippery slope argument. The
slippery slope argument which we hear much of in the literature although
it\'s rarely defined, is kind of a warning sign that\'s put up on a
highway, don\'t go any further or unknown bad things will happen to you.
But rarely is it carried out to show that if you walk past that sign,
these unknown, soon-to-be-named bad things will, in fact, happen to you.
The slippery slope argument here does have a name as what\'s going to
happen to us if we permit the use of somatic cell transfer for the
purposes of creating clones for biomedical research. It is inevitable
that we will soon have cloning to make babies and perhaps cloning to
produce from fetal organs parts to be used by human beings and after
that God knows, perhaps organs taken from babies.

That\'s an argument that can be used against every advance in medical
science that has been made that I can think of. We must not invent
surgery because the use of the scalpel to take out an appendix will
inevitably, on the slippery slope, lead to organ harvesting and the
selling of kidneys and livers on the public market. We must not allow
neurosurgery, even to cure a terrible tumor because it will lead
inevitably to lobotomy. Now, in fact, lobotomies have occurred. And in
fact, some instances of organ harvesting have occurred, but the
public\'s horror and the government\'s horror at these things has
quickly shut down those enterprises and penalized, often severely, the
people who did it. Or perhaps we shouldn\'t have automobiles because we
will have fatalities. Well, we do have fatalities, but then we balance
the value of the automobiles with the value of the fatalities. Or we
shouldn\'t \-- you can make an argument about any human innovation and
say we must not adopt it because we\'ll be on the slippery slope and it
is, in fact, a Luddite argument, unless you\'re able to show that
sliding down that slope is inevitable.

Now you might be able to say that sliding down that slope is inevitable
in the case of cloning because there will be such a huge financial
demand for the benefits of cloning that any form of cloning, however
benign in original intention, will lead to the worse forms of cloning to
satisfy that demand. But from all the scientific testimony I\'ve heard
so far, there isn\'t this huge financial demand and there isn\'t because
nobody has found yet the exact techniques that competent, but ordinary
physicians can use to cure these diseases, so that I want us to back
away from the prudential or this particular prudential argument because
I don\'t think it\'s correct unless Charles is in a position to show
that the slope is so slippery, so covered with banana oil, that one step
past the warning line we have now drawn on the pavement will bring us
down into chaos.

DR. KRAUTHAMMER: Well, let me give you a recent and empirical example of
that slope. The country had a debate on stem cells about a year ago and
the major argument by the proponents of stem cell research \-- and I was
one of them \-- was that we are using discarded embryos, everybody
understood that, and we were going to bring a benefit from something
that would otherwise bring no good. The understanding was, in fact,
Senator Frist made the presentation on the floor of the Senate and he
established conditions under which he would support stem cell research,
the regulations that we ought to institute in support of that research
and among them he listed very emphatically that the research would not
be done with embryos created for the purpose of using for stem cells.
That was what he said.

Now and here we are a year later and we\'re arguing over a technique of
cloning which can only be done in a manner in which an embryo is created
in order to destroy. So within a year, what we have is the ground
shifting on this debate on precisely a point that a year ago we had been
assured would be excluded by regulation and by law.

PROFESSOR WILSON: The Senator Frist example is a good one, a
particularly good illustration of the proposition that Congress doesn\'t
often mean what it says. You could use an even better example with the
1964 Civil Rights Act and Senator Humphrey\'s assertion to the Senate at
large that it would never be used to establish quotas or goals. These
things do happen. But the fact that a year later, a year ago or two
years ago, whenever Senator Frist spoke, we now find ourselves
discussing this subject. It\'s very different from saying that the
subject, once having been discussed and some authorization once having
been past, we have now slipped down the slope to the point where we are
creating clones for the making of babies and harvesting organs from
fetuses.

DR. KASS: Janet, did you want to comment? Please.

DR. ROWLEY: Well, let me first just respond to Charles because I think
though Senator First may have made some comments, I\'m sure that anyone
in the field of cloning and embryonic stem cells would not have
supported his point of view. So it isn\'t as though we started and
we\'re downslope. I believe that individuals in embryonic stem cell
research had already envisioned that, so we haven\'t \-- that position
has not been changed of the people who are involved in it.

I would like to respond to the discussion that Leon framed as we began
this session and my points of view are certainly influenced
substantially by my view that we are really, we have the potential of
being on the threshold of some major biological discoveries that will be
of enormous importance, but I qualify that with the same statement I
made when we began this discussion in January, that this is a hope and
at the present time we have no idea as to how much that hope will
actually be successful and that was reiterated and confirmed again by
both speakers this morning, that these are very, very, very early days
and the promise that many of us see in this kind of research may \-- I
think it\'s not fair to say that the promise will not be realized, but I
think that it is fair to say that the promise may take a very long time.
And I just want to point out that we began the war on cancer in 1970
with the notion that it was all going to be over in 10 or 20 years and
we\'re far from it. We\'re far from it because we\'re dealing with very
complex systems in cells about which we are woefully ignorant, but I
think the part of the research that will be permitted by going ahead
with cloning and some of the aspects of experiments with somatic nuclear
cell transfer will enlighten us so much that we\'ll be able to see
better how to expand on these in the future. And I would only echo our
morning speakers by saying that I think that to ban this kind of
research which has the potential for therapy would be a great tragedy.

DR. KASS: Michael Sandel?

PROFESSOR SANDEL: I just wanted to pick up on the last small
uncharacteristic slip of Charles where he slipped back into the
polemical action description to use Professor Outka\'s phrase of what
cloning for biomedical research is. I thought following Paul\'s and
Leon\'s corrective which Outka accepted, we agreed that there are two
possible action descriptions for both of these practices. By both, I
mean creation of embryos for reproductive purposes and creation of
embryos for purposes of medical research, a charitable description and
an uncharitable one. The charitable description in each case describes
the action in terms of the end it\'s aimed at. So in the case of embryos
created for reproduction we point by the description to the end.
Likewise, in the case of cloning for biomedical research, the end there
is the creation of an embryo for the sake of promoting the curing of
disease. There is an uncharitable description available equally to both
and if we want to compare them, compare the moral status of these
practices, we should use either the charitable descriptions of each or
the uncharitable descriptions of each. The uncharitable descriptions in
each case doesn\'t refer to the end being aimed at, but instead to the
foreseeable, though undesirable effect.

So it would be fair to say that with Charles and with Outka\'s paper
that in the case of creating an embryo for the sake of biomedical
research to describe that as creating an embryo in order to destroy it,
but only in the same sense that we should describe creation of embryos
for reproduction purposes as the creation of embryos in order to discard
the inevitable extras that will accompany the practice of IVF. So both
activities admit of charitable and uncharitable descriptions and if
we\'re going to compare their moral status, we should compare them
either under one description, the things they aim at or under the other
description, the foreseeable, but undesirable side effects that
accompany both.

DR. KRAUTHAMMER: Michael, I\'m surprised that you also made an
uncharacteristic slip when you said the inevitable destruction of the
embryos in IVF because you know, as I know, we could, in principle,
establish an IVF clinic tomorrow in which you assign only a single
embryo to a woman. So you would thereby have a process of IVF where you
have no inevitable, indeed, indeed no discarded embryos.

On the other hand, in cloning, it is absolutely inevitable that that
embryo, because it will be disassembled, will be destroyed.

PROFESSOR SANDEL: Well, if the practice of creating embryos for
reproductive purposes involved no spares, no extras, then it would have
a different moral status and character from the practice we currently
have.

DR. KASS: Elizabeth?

PROFESSOR BLACKBURN: It would be different from natural which, in fact,
if anything the majority of embryos naturally are lost and destroyed \--

DR. KRAUTHAMMER: We\'d be improving on God.

PROFESSOR BLACKBURN: That\'s good.

PROFESSOR SANDEL: What the natural case Elizabeth raises is the \--
there\'s also an uncharitable description of natural procreation which
would be very odd, which is you\'re engaging in the inevitable creation
of spare embryos that will be sacrificed for the sake of having one that
works.

PROFESSOR BLACKBURN: Well \--

PROFESSOR SANDEL: And there\'s no more warrant for that description than
for the contentious version of the description in the cloning for
medical research case.

PROFESSOR BLACKBURN: Well, I think it might be helpful to return to
somewhat more the homely and something Gil said that he said to me,
well, would you say the blastocyst, if it were yours versus the child
and I think I wouldn\'t be able to look the parents of the child in the
face if I hadn\'t made an attempt to save the child. And I think that
also addresses the issue of should we be trying to do cures, even though
we know that they\'re not inevitably going to work tomorrow, next year,
10 years or 20 years. I think we have to try and so I think this
question of the fact that we don\'t have successful answers right now
for whether embryonic stem cells or somatic cell nuclear cloning is
going to work, I don\'t think that absolves us from the necessity to try
when we see real human disease and suffering that we should try to act
on, even though we know we may not be necessarily successful in every
attempt.

DR. KASS: Gil, and I then I think I would like to put my oar in and
I\'ll give rebuttals, but we should probably wind up. We need a nap
before we drink, right?

Gil, do you want to comment?

PROFESSOR MEILAENDER: Well, just a couple of things quickly. To pick up
Elizabeth\'s point again. The hypothesis was and I think it\'s worth
thinking about, the hypothesis was that you could only save one of the
two entities, so that I don\'t know how we set up this case the way the
philosophers do it, but there\'s a fire and you can go up one stair to
save the newborn in the crib who\'s not yours or you can go up the other
stairs to save the blastocyst in vitro that is yours. Okay?

DR. KASS: That\'s a copy of your dead child, if you want to make it \--

PROFESSOR MEILAENDER: Whatever. It\'s not \-- it\'s not immediately
apparent, kind of, that one choice must be made and that suggests that
there are other considerations and it\'s not just stage of development.
The other thing I just wanted to say in response to what Michael \--
just \-- I mean Gene Outka can sort of take care of himself, but as a
matter of interpretation, I think he didn\'t quite grant what you
described him as granting. I think he granted that creating in order to
destroy was a tendentious description. He did not grant that the two
situations were the same where he had recourse or double effect line
which because he did still think that in the description of the one act,
the killing was inextricably involved and I take that\'s really what
Charles was getting at. So it isn\'t in terms of what he was granting, I
want to be clear.

DR. KASS: Okay, I\'m winding up to \-- I want to say a couple of
substantive things, but come to a procedural suggestion for what we
should do next. First, since Jim Wilson began by being surprised that he
could disagree with Charles, I\'m surprised that I have to disagree with
Jim Wilson with whom I\'ve disagreed only once before and he since told
me that I\'ve persuaded him, but I\'m not going to do it again.

PROFESSOR WILSON: Not this time.

DR. KASS: The slippery slope, to call something a slippery slope
argument is already to put it in a category where you can abstract it
and then say you like those arguments or you don\'t. Rather, it seems to
me, it\'s worth thinking about, not in general in the light of other
examples, but to think about it in the context of the particular thing
we are talking about.

I think I might have said once before that the reason that arguments
about continuity of action are so appropriate in the area that we are
here talking about is because development is itself a continuum and the
value of the thing being developed, never mind morally, but
biologically, increases with development and if it should turn out that
tissues down the road are really more valuable for the treatment of the
same patients we now want, the argument that\'s now being made for doing
it will be very hard to resist.

The real essence of the slippery slope argument is not a prediction, an
empirical prediction. It is a question of the logic of justification and
it\'s very important how you somehow justify what you\'re doing here
because if, as in this area, the continuity of development and the
continuity of research offers such great promise, you might, without
even knowing it, be countenancing the next sort of stages and in the end
you will wind up as Bertrand Russell said about pragmatism. It\'s like a
warm bath. It warms up so imperceptibly you don\'t know when to scream.
Eventually, we will get to some place that none of us would want to be
and we therefore have to be very careful. It\'s not a prediction of a
certain kind of certainty, although we have seen, I mean five years ago
[The Washington Post]{.underline} editorialized on this question. No
creation of embryos, especially for research \-- use these others. The
newspapers are no better than the Senators on this and times change and
there were no stem cells five years ago. The benefits to be had were
less.

I think it\'s very important that we, instead of calling this a slippery
slope argument, talk about the question of prudence and if we put it in
those terms, then the question is: Is it really prudent to head down
this road and I don\'t think you have to believe that the embryo is a
full human person, at least to be worried, not just about what\'s \--
the destruction question. It may be a terrible thing to say in public,
but I worry much less about the destruction of the embryos as I worry
about the exploitive mentality on the part of not just the scientists,
scientists are trying to do good, but of a community that comes to
accept as routine, the instrumentalization of nascent life and in which
we become sort of desensitized to this. This is not a question about the
ontological status of the embryo, but about how we come to regard those
earlier stages of our own being. I don\'t know what they are, but that
they\'re somehow part of a continuity with what we are. Of that, as a
biologist and not as a religious figure, I mean I see the continuity.

Two other things, just for your thought. I don\'t want to harangue much
longer. The IVF case has been around a number of times, but let me
suggest one thing. The fact that there are a lot of embryos lost in
normal sexual procreation doesn\'t settle anything. It doesn\'t really
settle anything. And it seems to me one could say something like this
with respect to that in the IVF clinics. When a couple now undertakes to
procreate by ordinary sexual means, if they\'ve learned the facts about
this, they know that they are saying yes to the sad fact that there will
be a lot of loss.

That\'s just the way things are and without going Charles\' route about
improving God\'s way, when a couple now goes to the IVF clinic even with
the extra embryos, they are saying yes in advance to the sad necessity
that some of these embryos are going to be frozen in perpetuity or put
to some kind of use. They\'re simply compressing into one month or into
one visible time what in ordinary biology might take months. Well,
situations are fairly comparable. I think it is a matter, somewhat
different when you undertake to produce the embryos for the purpose of
exploiting them for use in which the destruction is \-- I won\'t say a
minor thing, but it is the deliberate exploitive disposition is what
bothers me.

Lastly, to Elizabeth, if I might, the lurid cases are wonderful for
focusing the mind and the examples, both of the business about the child
and the exchange we had last time between Michael Sandel and Robby
George about dismembering one\'s 2-year-old child for the organs and
dismembering a blastocyst for the cells spoke, it seems to me, volumes.
It seems like for my own sake a knockout case.

On the other hand, I\'ll give you another knockout case and we can
wander away and ponder it. Let\'s imagine that you\'ve got the last
couple on earth and a couple of embryos and he has Alzheimer\'s disease.
And the question is, do you sacrifice the embryos for the sake of the
cure of the living or do you allow them to be what they in fact are,
biologically speaking, the seed of the next generation? We can force
ourselves not to look at that because there are so many extra seeds, but
if you somehow focus the question and ask, then the merely instrumental
use of this seed, even though it doesn\'t have a nervous system somehow
begins to look rather different.

There\'s a lot there to be quarreled with and I probably abuse the
privilege of the chair, but there were a number of things floating
around here that only make the subject for me more complicated.

What we\'ll sort out finally is we have to move forward on this. I think
if I understand the discussion here and Paul, you and I will have to
work out a way to find room for your so far eccentric, that doesn\'t
mean wrong, but unique position in this conversation, whether you want
to have a separate \--

DR. McHUGH: I\'m glad you say it doesn\'t mean wrong. One could be \--

DR. KASS: On this point we agreed last time that we don\'t want to
simply decide on the basis of the wisdom of the vote of the majority to
silence any arguments sincerely held and properly defended. It might
very well be that an argument made and held by one person is the best
argument and we would deprive our readers of the benefit of having to
weigh that.

I\'m serious about that.

DR. McHUGH: I appreciate that.

DR. KASS: And it goes across the board. I think we have to tidy up our
work on the ethics of this and move on to the policy questions by the
next time we gather.

I would like to ask everybody here, if they haven\'t already, if things
that haven\'t been passed before you don\'t already speak for you and
there are some people who we haven\'t properly, I think, taken care of.
If you would write from 3 to 5 pages and if it turns out that the
argument is shorter, less, a statement of your view not on the question
of ban or no ban, the policy question, but on the question of the
morality of cloning for biomedical research and let\'s have it in two
weeks and then we can put this particular part of our discussion in a
form that can be circulated for everyone\'s approval. I hope that\'s not
too onerous. If there\'s anybody who\'s writing another paper for
another course, I\'ll give you an extension, but tomorrow morning we
meet at 8:30 to take up the enhancement discussion and then the
regulatory discussion. Thank you for your endurance, your patience, your
good will and we\'re adjourned.

(Whereupon, at 5:33 p.m., the meeting was adjourned.)