FRIDAY, December 3, 2004
CHAIRMAN KASS: In this last session before the session for
public comment, the council returns to the subject of embryonic stem
cell research, not to continue to argue about the moral issues or
to discuss the wisdom of the current federal funding policy, but to
explore two very interesting proposals demanding public attention
that suggest means of deriving embryonic stem cells that would get
around the morally charged necessity of doing so
Session 6: Seeking Morally Unproblematic Sources of Human
Embryonic Stem Cells
Howard A. Zucker, Department of Pediatrics, College of Physicians
and Surgeons, Columbia University
Donald W. Landry, Professor of Medicine, College of Physicians
and Surgeons, Columbia University
Council Member William Hurlbut
This council, I think, has distinguished itself in the discussion
of these questions, notwithstanding our sharp differences of opinion
about the conclusion, in recognizing that all parties to the existing
debate, in fact, have something vital to defend — not just
for themselves, but for all of us. We have recognized the importance
of the scientific research and the medical benefits to which it
will lead. We recognize the supreme and important value of respecting
human life, indeed in all of its stages. People may differ about
how much respect and at which stage, but these are important human
goods and it would be very exciting if ways could be found in which
these two goods did not have to be pitted against one another, but,
in fact, could be embraced by all people whichever way they pitch
the balance amongst them. And therefore it's, I think, of great
interest to this council that we have for presentation today two
such proposals: one presented by Howard Zucker and Don Landry, both
from the College of Physicians and Surgeons at Columbia University,
Howard Zucker from the Department of Pediatrics, Don Landry from
the Department of Medicine. And their proposal, which we will have
had occasion to read, talks about the possibility of deriving human
embryonic stem cells from no-longer-living, not merely just non-viable,
not merely doomed-to-destruction, but actually no-longer-living
embryos. And our own colleague, Bill Hurlbut, has a proposal for
deriving — that would enable people to derive human embryonic
stem cells from embryoid-like bodie,s but which are not in the strict
sense embryos proper. We look forward to the presentations.
I should say, so that there won't be any misunderstanding,
these are not at the moment presented as council proposals. The
council is simply eager to hear about this and we will see in the
discussion afterwards what council members think about these things.
But first, we have to inform ourselves about them both with respect
for the question of the ethical issues and of the scientific feasibilities.
So Howard Zucker and Don Landry, welcome to you and the floor is
first yours and then we'll proceed to Bill.
DR. ZUCKER: Thank you, Dr. Kass, and Don and I would like
to thank the entire Bioethics Council for giving us the opportunity
to present before this illustrious panel. We recognize that the
stem cell controversy has resulted in a very polarized and heated
debate but it is our personal opinions that there is a common ground
for medicine, for law, science, and ethics that can be reached,
and we published this view in the Journal of Clinical Investigation
last month which you all have a copy of.
Scientists cannot go anywhere without a laptop and visuals and
so, in the interest of efficiency, Don will present our paper, after
which we will be happy to answer any questions that you have for
us, thank you.
DR. LANDRY: I also thank you for the opportunity to present
our ideas to you. Let me say also that I'm Director of the
Division of Experimental Therapeutics in the Department of Medicine
at Columbia. I don't engage in stem cell research, so I don't
have a vested interest in this beyond that of a concerned citizen.
I do take care of critically ill patients in a small private practice
and I think it's the context of seeing death in a close and
personal way and seeing the issues of organ donation that informs
to some extent the ideas we're going to present today.
I'm going to present some things that are painfully obvious
to you but I think are important just to state the premises upon
which the proposal was based. The creation of human embryonic stem
cells involves the destruction of an embryo, well known to you.
What that means to an individual depends on how they answer certain
questions. When it's formulated in the most general sense,
when does life begin, it doesn't make very much sense to me
but these are my answers to these questions. Life begins two billion
years ago, human life begins 200,000 years ago. A new human life,
a new human being, a genetically unique entity begins at conception.
A human person, however, is not a question — the origin of
a human person is not a question that science alone can answer.
And so this tension between human being and human person results
in a conflict. We have on the one hand a requirement for respect,
for human dignity, to treat humans as subjects and not objects,
pitted against the drive to relieve human suffering.
And there is no easy compromise. This is not an economic matter.
The differences cannot be split. And so between, on the one hand,
persuasion, which is difficult to achieve, and imposition of will,
which is unseemly, there's a third way, a search for a common
ground, which I think is one of the central activities of this committee.
Our general notion is that death is such a common ground because
the death of the human being subsumes the death of the human person
and so whatever the disagreements about the origin of a new person,
with the death of a new human being that issue of person is also
Some background from the death of a developed human person can
inform our thoughts on the death of the developing human person,
and so just a quick review of some recent history and our notions
of death for developed individuals. Prior to the 1960s going back
for thousands of years, irreversible cessation of cardiopulmonary
function was the definition of death and improvement in respiratory
technology led to a crisis. It was possible to maintain ostensibly
dead individuals for extended periods of time and this crisis was
addressed by an ad hoc committee of the Harvard Medical School with
a definition of irreversible coma that becomes the basis of our
modern notion of brain death.
And in that context of a definition of brain death, not driven
by it but in the context of it, cadaveric organ donation went from
speculation to standard of care and so I would abstract from this
slide the idea that the availability of material, if obtained in
an ethically reasonable fashion, can actually drive research and
Some comments also about the legal definition of death. First
of all, it's a specific question of fact, not a question of
law, and so it's determined by physicians. And yet there are
legislative attempts to codify it. Originally, there were two separate
definitions of death contingent on the desire to harvest organs,
clearly a problematic issue. This was resolved by Capron and Kass
in 1972 articulating a single concept of death, but application
of a particular criterion would depend on the circumstances, the
circumstances of machinery maintaining a dead individual that makes
the application of one or another criteria particularly difficult
or facile. A variety of laws follow, tend not to precede some consensus
on the issue and we conclude with the Omnibus Reconciliation Act
of 1986 that, at brain death, the removal of vital organs for transplant
is legally and ethically permitted.
We have criteria for brain death. Our notion is an irreversible
action critical in brain stem function that gets translated through
observational studies, when does someone no longer wake up, finally
to diagnostic tests, unresponsiveness to pain, inability to breathe
off ventilators, certain eye movements upon putting cold water in
the ear canal, a flat EG and the absence of conditions that might
otherwise suppress EG activity.
Embedded in all of this is the concept of organismic death, the
human — the adult or developed human that has died is not
thoroughly dead. Organs are alive, they're available for transplant.
The tissues that make up those organs, the cells that make up those
tissues are alive, and so we like to extend this idea to the developing
human. The developing human, just as for the developed human, is
more than the sum of the lives of constituent cells, and so just
as the nervous system integrates tissues and organs in the developed
human, so too there's a system of chemical communication and
surface recognition that integrates cells in the developing human.
Deprived of the necessary internal signals, an irreversible arrested
cell division can occur.
Our specific proposal, then, is a new definition of death for
the human organism, an organism in development, and that is the
irreversible arrest of cell division.
Now, what are the prospects for producing normal cells from dead
embryos? Just as a backdrop to this consideration, consider for
a moment that 60 percent of IVF embryos fail to meet criteria for
viability. Non-viability is one of those vague terms. It's
an incapacity to develop to live birth and so it contains a number
of categories embedded in it, but there is a morphologic criterion,
abnormal appearances of one sort or another, also a functional criterion,
failure to cleave at 24 hours. Important to note, non-viability
does not mean dead but the functional criterion, cleavage arrest,
likely correlates. Now, cleavage arrest most often reflects various
genetic abnormalities and this might seem to eliminate any prospect
for some useful development occurring from these considerations,
not that the considerations are invalid but that nothing good would
come of them.
But there are several studies, two that I include in the binder,
and summarize very briefly here, that suggest some prospect for
producing normal cells from dead embryos. So Laverge et al observed
mosaicism and, briefly, from 166 frozen embryos that were thawed,
78 remained arrested at 24 hours, 71, no further sign of cleavage
at 48 hours, and fluorescence in situ hybridization, which allowed
examinations of chromosomes X, Y and 1, on all blastomeres of 63
arrested embryos, was performed. Eighty percent showed chromosomal
abnormalities. Aneuploidy, severe aneuploidy was common but mosaics
were present with normal diploid blastomeres embedded in this sea
of abnormality. Voullaire et al also observed mosaicism, 63 blastomeres
from 12 unselected embryos thawed after five years of cryopreservation,
two out of 12 were in cleavage arrest, partial arrest was observed
In this case, they used comparative genomic hybridization, a powerful
technique that's able to look at all chromosomes with the exception
of several that overlap, 17, 19, 20, 22. Again, they noted marked
aneuploidy, very common but also the eggs were identified —
PROF. WILSON: Excuse me.
DR. LANDRY: — with no diploid blastomeres in five
of 12 embryos.
PROF. WILSON: Could you define aneuploidy, please?
DR. LANDRY: Aneuploidy is multiple copies of chromosomes,
and so, instead of the normal diploid, we can have tetra and beyond,
sometimes five full sets of chromosomes, and this is a marked abnormality
that does not bode well.
Now, if one could obtain live cells from dead embryos, are they
truly normal, what is their developmental potential? I've presented
human data till now. This is the one bit of animal data that I'm
going to mention but it's so marked that — and understanding
limitations in animal data, it's still worth mentioning here.
In one experiment, cloned tadpole embryos showed 99 percent irreversible
arrest, 95 percent early on, 99 percent overall.
Now, cells from arrested blastocysts were aggregated and an individual
cell is injected into a normal tadpole blastocyst. Twenty-five
percent resumed division and were stably incorporated into differentiated
tissues, becoming muscle, for example. And so blastomeres from
an arrested embryo can be reprogrammed for differentiation and growth
if placed in the proper environment. And this is a natural environment,
but in principle it could be an artificial environment made up of
cell surface proteins and various chemical mediators.
Back to human data, an experiment by Alikani and Willadsen, 107
"non-viable" human IVF embryos were disaggregated. Two
hundred forty-seven intact cells were isolated and they were combined
in 36 aggregates, approximately six to seven cells per aggregate.
Thirty-three percent of these went on to develop and form normally
organized blastocysts with defined inner cell masses, again indicating
that a new environment can re-establish growth and development.
So a summary; we're proposing a new definition for human death,
irreversible arrest of cell division. The criteria for determining
irreversibility would begin with the natural history study of cleavage
arrest and progress to biochemical markers for irreversibility.
Many embryos generated for IVF are organismically dead. Aneuploidy
is present but, due to mosaicism, normal cells are found and it's
at least arguable that they could have normal developmental potential.
The signals required for transforming blastomeres into stem cells
without recourse to the formation and destruction of human blastocysts
is an area of current research. Interest in this area would increase
markedly if, in fact, there were material to pursue this work.
And we propose an ethical framework for investigating embryonic
cells from organismically dead embryos, and this framework would
parallel the cadaveric donation of central organs with consent of
next of kin, in particular organs donated from children with the
consent of parents.
So, in conclusion, application of the ethical framework for central
organ donation to the harvesting of human embryonic cells from organismically
dead embryos maintains respect for human dignity and can advance
biomedical research. Now, two corollaries that do not appear in
the paper but I would be interesting in hearing your thoughts on:
with a clear and clean recognition of embryonic death also comes
the recognition of embryonic life in extremis. And one can apply
the ethical norms for research on a patient in extremis, which are
different from the average patient, to the embryo in extremis.
And so, for example, the extraction of a single blastomere from
an embryo in extremis would not seem to be an enterprise that would
have severe ethical or moral problems. And I've engaged in
research on adults in extremis with the approval of our IRB, engaging
in interventions that would not be permissible with someone not
in the last few hours of life.
This is not an idle consideration with respect to the embryo.
Consider on the one hand organs harvested from an executed prisoner,
mesenchyme from an aborted fetus, versus cells obtained from an
IVF embryo that died despite best efforts for its life. It would
seem that there's a very bright line separating these. What
if cells from a cryo-preserved embryo that is thawed after five
years of storage and allowed to succumb, some may feel this is all
right, some may feel it's problematic but certainly an embryo
in that position is in extremis, and harvesting a single cell a
potential risk but not a lethal, unnecessarily lethal event, might
be considered morally acceptable. And that concludes my remarks,
and Howard and I are available to answer questions as best we can.
CHAIRMAN KASS: I think that — let me suggest that
we discuss each of the presentations briefly rather than have them
both together and to raise any kind of technical question. The
presentation was luminously clear as is the paper. I mean, I think
everybody understands what this is about, so there might be people
who have either technical questions about the scientific feasibility
or what we might know about the likelihood of this, but let's
take at least a few minutes to make sure that everybody understands
what they need to and get ideas clarified. Then we'll have
Bill's presentation and then we can discuss the two things together.
So the floor is open to Doctors Landry and Zucker.
Now, Paul McHugh?
DR. McHUGH: Just one question; you told us you could take
a cell out of an embryo that you had demonstrated aneuploidy in
the embryo and then those cells would reproduce when placed —
this, I guess, was the tadpole work. Aneuploidy cells can reproduce
and they produce cancer. How will we be sure that this method won't
technically lead to the implantation and the use of cells that will
have cancerous potential?
DR. LANDRY: You can simply screen for that. The cells
you isolate, you know, are grown. You can take one of those cells
having now grown and analyze it, so I don't think there would
be any risk of cancer in that circumstance.
DR. McHUGH: Even after you've transplanted them?
I just need to understand the technology a little bit. You have
this embryo. You say you find aneuploidy in it in various cells.
You find 33 percent of them will grow later in the tadpole. Were
those 33 percent of cells you grew in the tadpole demonstrated to
lack aneuploidy in every one of them?
DR. LANDRY: No, and remember that we're not suggesting
that this be used for reproductive purposes. This is meant for
in vitro use and as such, while it's always possible that there
could be unforeseen events, one gets to observe these cells for
extended periods of time. I mean, after all, the ultimate objective
of stem cells, stem cells are indefinitely reproducing ideally by
definition, and so it's possible to go and at any point now
having produced this cell, to examine it and one would seek to eliminate,
for instance abnormalities such as marked aneuploidy and —
DR. McHUGH: Let me just continue on this because I just
want to be sure I've got it. And sticking with the tadpole
experiment, the cells that were later put into the tadpole from
frog embryos that were known to be non-viable for a variety of reasons
including aneuploidy, that those cells had gone through a sufficient
phase themselves to know that they did not carry an aneuploidy potential
and a cancer potential.
DR. LANDRY: The experiment on tadpoles involved arrested
embryos. They were not examined for aneuploidy.
CHAIRMAN KASS: Gil Meilaender?
PROF. MEILAENDER: What is luminously clear to our Chairman
is not necessarily so clear to me. So can you just explain to me
or help me be sure I'm clear, cleavage arrest correlates with
death of the embryo according to your proposed definition. And
that's the — so that's the test that you'd use
to determine whether an embryo was available for use in this way,
and would you therefore be using some embryos which were dead and
some which were conceivably still living according to your definition?
That's what I don't understand in terms of the correlation
DR. ZUCKER: They would be dead — if they're
at 24 hours, they are not cleaving and 48 hours they're not
cleaving, those are dead. They wouldn't be — that's
the concept that they would be organismically dead at that point.
It wouldn't be that we would take cells that were then dividing
further and try to redefine that as being dead.
DR. LANDRY: And the precise moment, also is something
that's open to a natural history study and observation. So
the precise moment when, you know, a group of disinterested observers
would reasonably conclude that death has occurred is — and
to devise a definition for death, would occur as a result of observation
by analogy to observations of, you know, comatose patients.
DR. ZUCKER: And as Don mentioned in the presentation also
that we would be able to find specific markers to match up with
CHAIRMAN KASS: What begins as phenomenological account
of the natural history of this would then be supported by the discovery
of various kinds of biological markers that would give one confidence
that cleavage not only hasn't occurred, but isn't going
to occur. I think that's the —
PROF. MEILAENDER: So it was luminously clear to you and
it was luminously clear to you and not to me.
CHAIRMAN KASS: It was not luminously clear to you. Other
— yes, Robby George.
PROF. GEORGE: Thank you. I'm trying to see if I understand
what is new in what you're proposing and what is not new. It
sounds to me — and please correct me if I've misunderstood
you — it sounds to me as though you're not proposing a
new criterion of death or a different criterion of death. It sounds
as though the criterion of death you're proposing is what we
might now call the standard one of the complete and irreversible
loss of integrated or integral organic functioning. Is that right?
DR. LANDRY: I would call that the concept.
PROF. GEORGE: It's the concept of death.
DR. LANDRY: And then the criterion is what you take down
from that concept.
PROF. GEORGE: So the concept of death is the same whether
we're talking about, you know, an 80-year old person or we're
talking about an embryo.
DR. ZUCKER: Correct.
PROF. GEORGE: And so now what you're looking for is
what is the reliable evidence and I guess this you would then call
a criterion? All right, what is the reliable evidence of the complete
and irreversible loss of integrated organic functioning.
DR. LANDRY: Correct, so we would define it as arrested
cleavage and then the criteria for defining that arrested cleavage
would come down from that, a certain amount of time, the absence
of Oct4, you know, a series of biochemical markers in its fullest
PROF. GEORGE: Okay, so just again to be very clear, there's
no proposal here for a new concept of death —
DR. LANDRY: No.
PROF. GEORGE: — in order to accommodate the harvesting
of stem cells from embryos.
DR. LANDRY: No.
PROF. GEORGE: Okay, a second point, just a minor point
of clarification, I was interested in what you were saying about
the legitimacy of interventions on patients, and let's again
consider say an 80-year old person in extremis, that you were saying
there were circumstances in which it's ethically legitimate
to do certain things to patients in extremis that you couldn't
do to patients who were not in extremis. And I wonder if —
what the norms are governing those interventions. Are such interventions
legitimate but only when the purpose is to benefit or attempt to
benefit the patient himself, or is it sometimes permissible to do
some things to patients in extremis that you couldn't legitimately
do to patients not in extremis, not for the benefit of those patients
but for the benefit of others?
DR. ZUCKER: I guess one of those, you can use the analogy
of a chid who is critically ill lying there in an intensive care
unit and needs to be placed on let's say extracorporeal membrane
oxygenation or life support, and one may say at that point that
that person, you're doing a procedure on somebody and providing
a new therapy obviously through an IRB that you wouldn't routinely
do on other patients that weren't at that teetering on the edge,
and in the same way, we would feel that — as Don mentioned
before with the embryos in extremis, you could make that analogy.
PROF. GEORGE: Perhaps I'm being obtuse here, but —
DR. LANDRY: Since I've actually done this, maybe I
PROF. GEORGE: Go ahead.
DR. LANDRY: Maybe I can just —
PROF. GEORGE: Please.
DR. LANDRY: Okay, we're dealing with patients in extremis
and by definition the intervention we're engaged in is not going
to benefit that patient. It is not anticipated that a patient in
the last few hours of life is going to be pulled from that moment
by the intervention. With the approval of the IRB, with the assent
of next of kin, it's possible to, for instance, provide experimental
drugs to observe their physiologic effect, understanding that it's
not a therapeutic effect.
PROF. GEORGE: I see. So it would be to benefit others
and it would be considered legitimate. But it wouldn't be considered
legitimate to do precisely the same thing if a patient were not
DR. LANDRY: Exactly.
PROF. GEORGE: And this is an accepted norm of medicine.
DR. LANDRY: Right, accepted norm.
CHAIRMAN KASS: Gil, I think, wants in on this subject.
PROF. MEILAENDER: Yeah, just the very same thing; you
wouldn't extract the organs of that infant, though, right?
DR. LANDRY: No, no, we're not talking about activities
that would kill or that would immediately hasten death, but activities
that might entail some risk and yet you would argue that, in the
last few hours of life, that risk is less than incremental to that
person at that time. Of course, if they're looking at the next
80 years of their life, then perhaps this is not a risk that should
be undertaken on their behalf. And so removing a cell from an embryo
that's about to expire, that activity not killing the embryo
necessarily although entailing a risk to that embryo if we wanted
to implant that embryo, we could take direct analogy from that activity
and the activity of experimentation in developed humans.
CHAIRMAN KASS: This really — this matter if I understand,
what you would be talking about would be the equivalent of single
blastomere biopsy that's used say in PGD which, though we haven't
had the studies to give us absolute confidence in this, there are
lots of children who have been born perfectly, apparently perfectly
normally, so that the removal of a biopsy or the removal of a cell
is already practiced in that case, I suppose you could say for the
benefit of that particular individual. Here you would not be adding
any extra risk and the act would be no more dangerous to that embryo
in extremis than that act is to an embryo that's headed for
implantation in the diagnostic procedure at PGD.
DR. LANDRY: Yes.
CHAIRMAN KASS: Is that —
DR. LANDRY: That's correct.
CHAIRMAN KASS: Now Gil.
PROF. MEILAENDER: But these are two different sorts of
justifications that you're thinking through. Am I right about
that? That is to say one sort of justification is if we have an
embryo that in terms of the criteria you've developed is dead,
we may use it in these ways. The other sort of justification is
that the rules for what we may do experimentally with a human organism
change when the organism though not dead is in extremis. That's
a different kind of justification. Am I correct on that?
DR. LANDRY: That's why I included it after the conclusion.
PROF. MEILAENDER: Yeah, and that general issue there's
actually a long history of discussion and argument about and I would
be more inclined to worry about — I would want to think that
one through considerably more. It gets to do with the issue about
whether equal treatment must involve identical treatment, whether
you can wrong someone without harming them and various kinds of
questions like that and there is a long history of discussion about
that. So I just want to be clear, these are two different sorts
of justifications, and one might be persuaded by one but not the
other, for instance.
CHAIRMAN KASS: I want to turn to Bill, but only if there
aren't any questions to simply clarify what this proposal is
so that everybody should understand what Doctors Zucker and Landry
are proposing here. Alfonso and Jim Wilson, I think, have technical
questions rather than argumentative ones.
DR. GÓMEZ-LOBO: Yeah, this is, I think, a clarification
question. Of course, from a moral point of view, it seems to me
the idea of using cadaveric tissue for instance, should be less
problematic but I think we shouldn't forget that there's
going to be questions about the cause of the death or what led to
the death. I'm thinking out loud about the circumstance in
which say, a child or an older person is about to die, the death
is expected, in order to extract organs in circumstances, say, where
a rescue could have been possible. So I'm just leaving that
question open, because it is going to be ultimately of importance
for the moral judgment on the whole project.
CHAIRMAN KASS: Jim Wilson.
PROF. WILSON: Should your techniques prove with further
scientific inquiry to be valuable and the removal of non-viable
embryos can become a routine medical —
DR. LANDRY: Don't use the word "non-viable".
PROF. WILSON: I understand. What would you like? I like
DR. LANDRY: Organismically dead.
PROF. WILSON: Organismically dead, thank you. But at
one point in their history, they were —
DR. LANDRY: They were alive?
PROF. WILSON: Yes.
DR. LANDRY: If they were classified as non-viable, they
may have been dead, dying or doomed but we would restrict, you know,
our inquiry to those that are organismically dead.
PROF. WILSON: Organismically dead, fine. My question is,
should this procedure become widespread, what would be the source,
the principal source of these organismically dead entities?
DR. ZUCKER: The IVF embryos that are presently frozen
that then would be thawed for the purpose of creating life.
PROF. WILSON: And they would go through the test you've
DR. ZUCKER: Correct.
PROF. WILSON: Thank you.
CHAIRMAN KASS: Bill.
DR. HURLBUT: Can I ask you what stage of development you
anticipate most of these cells would come from?
DR. LANDRY: Eight to 12 cells.
DR. HURLBUT: It's my understanding that nobody's
ever seen a single eight-cell embryo lose seven of its blastomeres
as often happens after freezing and thawing, but is it absolutely
clear that a single cell from an eight-cell embryo cannot form a
DR. LANDRY: That's our understanding. And if evidence
came to the contrary, then we would move to 12 cells but the idea
is to avoid any question that that cell could by itself go on.
The loss of aggregate cytoplasm when you're dealing with a single
cell out of eight, would seem to preclude it.
DR. HURLBUT: Yeah.
CHAIRMAN KASS: Let's just stop on this and invite
Bill to make a presentation of his proposal and then we'll follow
the same procedure and we'll still have some time to discuss
both of these together and what we think about it.
DR. HURLBUT: Thank you. So what I want to say has some
similarity to the previous proposal. Death is the loss of potential
for future life through the disintegration of organismal life.
What we propose is the creation of entities that never rise to the
level of integrated organismal existence essential to be designated
human life with potential. I want to present some ideas that seem
worthy of discussion and possibly preliminary scientific investigation.
Those of us who have been working on these ideas have already explored
some of the philosophical and technical dimensions but there are
important theoretical and practical issues that need further consideration.
We offer these ideas not as an assertion of certitude but as a
promising avenue of inquiry, one that might move us beyond our current
conflict over the procurement of embryonic stem cells by providing
a third option, a technological solution to our moral impasse.
In the broadest sense, we propose a creative exploration of a full
range of scientific approaches. More specifically, we raise the
possibility that, using the technique of nuclear transfer, it may
be possible to produce embryonic stem cells within a limited cellular
system that is biologically and morally akin to a complex tissue
culture and thereby bypass moral concerns about the creation and
distruction of human embryos.
I want to make two points very clear from the beginning. What
is proposed here is a concept, an approach to a problem. The specific
examples, which may or may not be morally acceptable or scientifically
feasible, are offered only to make clear the larger concept as a
starting point for discussion. Second, we are at the stage of a
constructive dialogue; if these ideas are deemed feasible, extensive
studies with animal models must follow. We do not propose any projects
involving human cells until we can be certain that embryos are not
created by these methods.
The present conflict over the moral status of the human embryo
reflects deep differences in our basic convictions and is unlikely
to be resolved through deliberation or debate. May Americans oppose
embryo destruction for the procurement of embryonic stem cells,
believing that there is an implicit dignity and inviolability in
the individual continuity of a human life from fertilization to
Many others, however, believe that the benefits of advances in
biomedical science outweigh these moral concerns. A purely political
solution will leave our country bitterly divided, eroding the social
support and sense of noble purpose that is essential for the public
funding of biomedical science. While there are currently no federal
legislative constraints on the use of private funds for this research,
there is a consensus opinion in the scientific community that, without
NIH support for newly created embryonic stem cell lines, progress
in this important realm of research will be severely constrained.
Notwithstanding this apparently irresolvable impasse, we believe
there may be morally uncontroversial ways to obtain embryonic stem
cells. Drawing on our increasing understanding and control of developmental
biology, the techniques of altered nuclear transfer may allow us
to generate embryonic stem cells even apart from the organismal
system that is their natural origin. In order to evaluate the potential
solutions and allow forward progress within moral consensus, we
have to understand the perspectives and address the concerns of
those who believe that life begins at conception. By this view,
the most fundamental principle on which all other moral principles
are built is the intrinsic dignity and inviolability of human life
across all of its stages.
In both constitution and conduct, the zygote and all subsequent
embryonic stages differ from any other cell or tissues of the body.
They contain within themselves the organizing principle for the
self-development and self-maintenance of the full human organism.
The activation of an egg by the penetration of a sperm or the equivalent
events in nuclear transfer cloning procedures, triggers the transition
to active organismal existence with the potential to develop into
an adult human. But without all of the essential elements, the
necessary complement of chromosomes, proper chromatin configuration,
the cytoplasmic factors for gene expression, et cetera, there can
be no living whole, no organism and no human embryo. Recent scientific
evidence suggests incomplete combinations of the necessary elements,
failures of fertilization, are the fate of many, perhaps most early
natural initiations in reproduction. Altered nuclear transfer proposes
the artificial construction of such a cellular system mimicking
these natural examples, a system that lacks the essential elements
for embryological development but contains a partial developmental
potential capable of generating embryonic stem cells.
It is important to realize that many of these naturally occurring
failures of fertilization may still proceed along partial trajectories
of organic growth without being actual organisms. For example,
grossly abnormal karyotypes such as trisomies of Chromosome Number
1, the largest chromosome with the most genes, you may know that
chromosomes are named by the largest to the smallest. These grossly
abnormal karyotypes will still form a blastocyst but will not implant.
Even an egg without a nucleus when artificially activated, has the
developmental potential to divide to the eight-cell stage; yet,
clearly is not an embryo or even an organism.
The messenger RNA in these activated enucleated cells has the
protein already in it, the protein synthesis that drives the early
cell divisions, it's generated during the maturation of the
egg and then activated after fertilization. Like a spinning top,
the cells contain a certain biological momentum that propels a partial
trajectory of development but unlike a normal embryo, they are unable
to bootstrap themselves into becoming an integrated and self-regulating
Some of these aberrant products of fertilization that lack the
qualities and characteristics of an organism appear to be capable
of generating embryonic stem cells or their functional equivalent.
Mature teratomas are neoplasms that generate all three primary embryonic
germ cell types as well as more advanced cells and tissues including
partial limb and organ primordia and sometimes hair, fingernails
and even fully formed teeth. If you look at the radiograph there,
the little bright white areas to the left of the spinal chord are
teeth, fully formed teeth.
Yet these chaotic disorganized and non-functional masses lack
entirely the structural and dynamic character of organisms. These
benign ovarian tumors are is some cases derived by spontaneous and
disorganized development of activated eggs. They generally have
a complete karyotype, 46 XX, and they produce a diversity of cell
and tissue types that suggest that they may proceed through a developmental
process similar enough to natural embryogenesis to produce pluripotent
stem cells. In fact, through intentional parthenogenic activation
of monkey eggs, which mimics teratoma formation, one private US
company was able to coax them to a blastocyst-like stage and harvest
ES cells. Serious scholars and scientists including the geneticist
and Dominican priest, Nicanor Austriaco, have made serious moral
arguments supporting such a source of human ES cells. Furthermore,
there may soon be patent applications for such a procedure.
The disorganized character of teratomas appears to arise not from
changes in the DNA sequence but from genetic imprinting and epigenetic
modification that affects gene expression, keeping some genes turned
off and others on. In natural reproduction the sperm and egg have
different but complementary patterns of imprinting, allowing a coordinated
control of embryological development. When an egg is activated
without a sperm, the trophectoderm and its lineages fail to develop
properly and the differentiation of the trophectoderm and the inner
cell mass which forms the ES cells is considered to be the first
globally coordinated divergence into distinct cell lineages, so
it's an important indicator of organismal integrity and it lays
the pattern for the whole future of that organism. Nonetheless,
in this entity it fails to generate.
The trophectoderm is necessary for the cross-inductions that are
the foundation for all further coordinated and organismal growth
of the embryo. Later it contributes to the formation of the extra-embryonic
membranes, but early in development it is crucial for both embryo
structural integrity and for the development, continued development
at least, of a normal inner cell mass.
In the absence of the complementary genetic contribution of the
male, the activated egg is simply inadequately constituted to direct
the integrated development characteristic of human embryo genetic
process. Interestingly, an inverse failure of formation characterizes
development driven only by genetic elements from the male where
the complementary contribution of the female is missing. In hydatidiform
moles, an egg missing its nucleus is fertilized by one or more sperm
but this time, lacking the maternal genetic contribution with its
complementary imprinted genes, there is an over-growth of trophectoderm
with no apparent inner cell mass or embryonic stem cell-like cells
and little or nothing in the way of fetal parts.
Recent evidence suggests that in their development both of these
disorganized growths may proceed to the blastocyst stage. They
may appear on visual inspection to be growing normally but they
carry an intrinsic insufficiency, making them incapable of the essential
formation of body axis and infrastructure characteristic of human
embryogenesis. The cause of the aberrant and disordered growth
of these failures of formation is not fully understood, but studies
with parthenogenic mice provide a remarkable window into the organizing
or disorganizing role of a single genetic alteration.
Employing a form of altered nuclear transfer, Japanese scientists
produced a fully formed mouse using only female chromosomes but
with a single modification of an imprinted region to simulate the
necessary male contributions. They produced something that absolutely
can't happen in nature, just by modifying a single gene. With
— actually, it wasn't even a gene; it was a promoter region
expressing a gene — with this one change in genetic regulation,
directly affecting expression of just two genes downstream, instead
of disordered growth, normal offspring were produced and then to
everyone's amazement, the simple restoration of the male/female
complementarity of gene expression resulted in changes further downstream
of gene expression of over 1,000 other genes. This striking example
of our increasing power to intervene and alter natural processes
points to a coming era of challenging ethical dilemmas through advances
in developmental biology.
With new tools from cytology to synthetic biology, we are gaining
control of not just component parts and their partial trajectories
of growth but the very principles and dynamics of organismal systems.
Beyond highlighting our strange and challenging new powers over
developmental biology, the parthenogenic mouse points to another
level of advance in our understanding, our new appreciation of systems
biology in which we see how even a small change of one gene can
affect the entire balance of an enormous network of biochemical
processes within a cell. What's going on here? That's
too bad not to see that one [referring to a slide that did not project
Systems biology offers us the view of an organism as a living
whole, a dynamic network of inter-dependent and integrated parts.
If severed from the whole, these partial sub-systems may temporarily
proceed forward in development but, without the larger environment
of their organismal system, they will ultimately become merely disorganized
cellular growth. Altered nuclear transfer proposes that small but
precisely selected genetic alterations will allow the harnessing
of these sub-systems of partial development apart from their full
natural organismal context in order to produce embryonic stem cells.
Eventually, we will understand the biochemical factors that can
transform a somatic cell to a pluripotent state. But while the
ultimate goal for the generation of embryonic stem cells is the
direct nuclear reprogramming of an adult nucleus, it may be many
years before our scientific knowledge and control of cellular factors
will make this approach feasible. More immediately, we may be able
to use the techniques of nuclear transfer but with an intentional
alteration of the nucleus before transfer to the cytoplasm to construct
a biological entity that by design and from its very beginning lacks
the attributes and capacities of a human embryo.
Studies with mice already provide evidence that this altered nuclear
transfer may be able to generate functional embryonic stem cells
from a system that is not an embryo but possesses the limited organic
potential of a tissue or cell culture. For the sake of specifics
in this discussion, let me propose one particular example of how
this could be accomplished. This may not be an acceptable ultimate
solution but it will allow us to consider the necessary criteria
for scientific success and moral acceptability.
As well demonstrated in the work of Dr. Janet Rossant at Mount
Sinai Hospital in Canada, the gene cdx2 is essential for embryogenesis.
This gene is expressed immediately after compaction around the 16
to 32-cell stage and is crucial for the differentiation of the trophectoderm,
the outer layer of cells that seals the embryo and controls the
flow of water and ions into the inner cavity of the cell. Without
this, there's just an open space and the cell just can't
form its own integrity of an inside and an outside. Although the
trophectoderm is ultimately the source of embryonic membranes, it
is more properly considered part of the embryo as it plays a central
part in the interactive cell inductions that generate all subsequent
embryonic development. Studies confirm that a functional trophectoderm
is absolutely essential in embryogenesis. In experiments with mouse
models when cdx2 is not expressed, there is only a partial and disorganized
developmental process resulting in a visibly abnormal blastocyst.
Nonetheless, there is the formation of an inner cell mass from
which functional embryonic stem cells have been harvested as reported
in the May 2004 Proceedings of the National Academy of Sciences.
For the purposes of altered nuclear transfer, cxd2 might be deleted
from the somatic cell nucleus before transfer. Once the partial
embryonic stem cells have been generated, the gene in these cells
could then be reinstalled to allow fully potent embryonic stem cells.
This technologically created limited cellular subsystem from which
the embryonic stem cells would be obtained would fail to establish
even the most basic features of human organismal infrastructure.
A deficiency at the first differentiation of cell type, the formation
of the trophectoderm, means the absence of the most fundamental
order. According to Dr. Maureen Condic, a developmental biologist
at the University of Utah, she says, "When the trophoblast,"
which is immediately after the trophectoderm, "when the trophoblast
does not form, subsequent development follows a chaotic pattern
suggesting that organismal development has not been disrupted in
the absence of the trophoblast but rather that an organism never
existed in the first place."
The resulting cells would have no inherent principle of unity
— that is, the entity produced, not the embryonic stem cells,
but the entity produced would have no inherent principle of unity,
no coherent drive in the direction of the mature human form and
no claim on the moral status due to a developing human life. Rather,
such a partial disorganized organic potential would more readily
be designated a biological artifact, a term I owe to my colleague,
Paul McHugh, when talking about early discussions of cloning. This
entity would be more rightly designated a biological artifact,
a human creation for human ends. The fact that some part of such
a constructed entity will carry a certain momentum of development
is morally analogous to the fact that we can grow skin in a tissue
culture and may one day grow whole organs or limbs in isolation.
Lacking crucial elements of its fundamental constitution, such an
entity would never rise to the level of a living being.
The scientific prospects for altered nuclear transfer remain largely
unexplored but, as stated by Rudolf Jaenisch in testimony to this
council, they are already within the reach of our current technology.
Unlike other proposals, ANT — I'm calling this alternate
nuclear transfer ANT — ANT would allow a uniquely flexible
approach by providing a wide range of embryonic stem cell types
that would have the full normal complement of human chromosomes,
would be of specific genetic types for tissue-compatible transplantation
and would not carry the danger of contamination from animal components.
In addition, this technique would offer a far wider range of scientific
and medical possibilities than embryonic stem cell lines derived
from leftover IVF embryos, including generation of diverse and predesigned
embryonic stem cell lineages for disease modeling and pharmaceutical
Indeed, in allowing controlled and reproducible experiments, altered
nuclear transfer might serve as a temporary bridge to transcendent
technologies such as direct nuclear reprogramming. Furthermore,
in establishing a morally acceptable means for the procurement of
embryonic stem cells, this important realm of scientific investigation
would be open to federal funding and have the advantage of both
broad public support and cooperative research collaboration on a
Altered nuclear transfer would also unburden ES cell research
from the additional ethical concerns of the leftover IVF embryos
including the attendant clinical and legal complexities in a realm
of great personal and social sensitivity. The one remaining link
with in vitro fertilization, the procurement of oocytes is the subject
of intense scientific research and there appear to be several prospects
for obtaining eggs without the morally dubious and expensive superovulation
of female patients, the specifics of which we can discuss later
if you want.
The crucial principle of any technological variation of altered
nuclear transfer, however, must be the pre-emptive nature of the
intervention. This process does not involve the creation of an
embryo that is then altered to transform it into a non-embryonic
entity. Rather the proposed genetic alteration is accomplished
ab initio, the entity is brought into existence with a genetic structure
insufficient to generate a human embryo. From the beginning and
at every point along its development, it cannot be designated a
living being. If such a limited biological entity were accorded
a certain cautionary respect, as with all human tissues, this project
would not compromise any fundamental moral principle. Moreover,
such techniques could be developed using animal models and confidently
extended to work with human cells without engaging in research that
involves the destruction of human embryos. The moral distinctions
essential to discern and define the categories of organism, embryo
and human being will inevitably be vital as we go forward with scientific
research involving human embryonic stem cells, chimeras and laboratory
studies of fertilization and early embryogenesis. Advances in developmental
biology will depend on clarifying these categories and defining
the moral boundaries in a way that at once defends human dignity
while clearing the path for scientific progress.
At this early stage in our technological control of developing
life, we have an opportunity to break the impasse over stem cell
research and provide moral guidance for the biotechnology of the
future. This may require a constructive refinement of some aspects
of moral philosophy together with creative exploration of scientific
possibilities, but any postponement of this process will only deepen
the dilemma as we proceed into realms of technological advance unguided
by forethought. We must initiate the cooperative dialogue that
is essential to frame moral principles that can, at once, defend
human dignity and promote the fullest prospects for scientific progress
and its medical applications. Thank you.
CHAIRMAN KASS: Thank you very much, Bill. As before,
we'll just direct questions to Bill for technical clarification
but also certain moral questions. I'm sure some people might
have some. Jim Wilson, please.
PROF. WILSON: Bill, thank you very much. Could you describe
for us now the scientific procedure you or someone else would follow
and the entities on which they would work that would test the viability
of this theory?
DR. HURLBUT: Well, we already know that you can take,
at least in this example I gave, that you can take an entity which
— from which you can get disorganized growth and yet functional
embryonic stem cells. What we would have to do is — I think
the first thing that would happen is, there should be a very thorough
discussion about what the criteria to meet both the moral concerns
and functional scientific goals would be. Once those were decided,
you would have to see if you could do it. And the way to do this
would be, and I have scientists including Evan Snyder at the Burham
Institute in San Diego who are interested in working on this and
enthusiastic about the idea. You would have to start with mice,
probably — they're the easiest and quickest to work with
— and just go through the genes that might be of interest
and they could probably do this fairly easily because you can use
— for the initial research, you can use techniques called
short interfering RNA, which are very easy to apply and do a first
scan to see what genes might serve the functional purposes that
we want. Doing it fully and officially with human cells, you might
want to knock out the gene, a technique that I've checked out
with my colleagues, Ron Davis, who's head of the Human Genome
Technology Center at Stanford and Andy Fire, who basically invented
RNA interference, these scientists both confirm that to be finally
and ultimately sure the best way to do this is likely to be the
knockout and then replacement of the gene, but the preliminary studies
could be done with short interfering RNA. You could scan through
many, many possible genes, and by the way, gene combinations to
double and complementarily assure your success and refine your technique.
Then I think it would have to — once you identified something
that worked in mice, you'd have to move on to primates which
has already been done, as I mentioned, harvesting of embryonic stem
cells but you'd have to do the knockout and then the harvesting
to see if it worked and the thinking is among all the developmental
biologists I've spoken with, that there is such a conservation
of biology of these developmental genes and developmental processes
that we could, with assurance, go forward with human cells without
the fear of creating a human embryo.
PROF. WILSON: Which human cells would you use?
DR. HURLBUT: That is probably going to be dictated by
which human cells most effectively go forward with nuclear transfer.
It appears that some cells are better than others. Cumulus cells
are what they used in South Korea. They're the cells around
the egg during its development. We would have to use a cell, if
we were going to knock out the gene, a cell that multiplied through
numerous cycles in vitro because you want to be sure you've
got the gene knocked out, but I think that's just a technical
problem and it wouldn't be that hard to do and there's great
advance going on constantly in this technique of nuclear transfer.
CHAIRMAN KASS: Questions of clarification on the technical
side first so that we — I want to make sure that everybody
here understands precisely what it is that Bill is proposing. Gil
and then Paul.
PROF. MEILAENDER: Bill, I'm just trying to think this
through, and let's just suppose hypothetically that you could,
through some technique, produce an entity which had the capacity
to implant but would absolutely not develop beyond eight weeks something
like that, how would that procedure — and I realize that may
never — perhaps that would never be technically possible,
but just suppose you could produce an entity which from the start
is characterized that way, how would that differ from what you're
DR. HURLBUT: Well, that's an important question and
I might add that one — what I think one of the positive dimensions
of my proposal is that for the concerns that these techniques might
lead to implantation of human embryos perfected through this technique
and surreptitiously implanted without the genetic alterations, it's
important to note that these cells produce, if it's done with
a gene knockout and replacement, would carry a bar code that would
identify them as having undergone this transformation, but to get
to your central issue — in other words, it would not lead
to human reproductive cloning in the sense of child-producing.
To get to your fundamental question, you're saying will this
not lead us to push the process forward and say well, this wasn't
an organized human entity and so forth. That's a very challenging
question. What level of organization defines an organism? I've
gone back to what is considered the primary tissue differentiation
of the organism and by the way, these would be abnormal from the
beginning as are also all nuclear transfer cells. Some of them
are abnormal to the extent they can right themselves.
As we saw in the paper that, as presented earlier, nuclear transfer
greatly disrupts the gene expression patterns. But we would have
to be certain that this was to the very most primary level of disrupted
organismal organization. And I think there is some scientific thinking
to be done, but I think we should turn to scientists to help us
with that. I think we have to be very careful that the principle
we set up does not allow it to be pushed forward to regions that
are — that evoke our natural moral sentiments and to the most
minimal possibility. What's being said is we want embryonic
CHAIRMAN KASS: You follow, Gil.
PROF. MEILAENDER: Yes, I'm still just trying to think
through the description, kind of. You're talking about producing
an entity that appears — I mean, the kind of language you
use — and I might not get this quite adequately translated,
but it's about an entity that appears to be growing normally but
really lacks the capacity to continue that development beyond a
certain point. And again, I'm just thinking analogously. Could
I use that same sentence about a child born with Tay-Sachs disease?
I'm not trying — I'm just trying to think —
could we say of that same child — of that child that it appears
to be growing normally but lacks the capacity for continued development
beyond a certain point? I'm just trying to think through where
that kind of language goes and I may not have the language technically
sophisticated enough and you know, that may be part of what you
want to say to me but what — how would you answer that?
DR. HURLBUT: I mean, that's a very important question
but to — I think to think clearly about that question you
have to have some sense of how the organismal process unfolds.
There is a — as I said earlier, there is a certain momentum
of substance in the egg. There's a certain kind of primordial
automaticity to the way things happen initially. Without the coordinated
interaction of subsystems as I tried to show in the systems biology,
you just simply can't go there. I think it's a difference,
an ontological difference between something that never organizes
itself in what is meaningfully called an organism and I don't
mean meaningfully like they say in Marin County in California.
I mean rightly by scientific criteria not organizing itself in the
minimal constructions. And what those would actually be would
have to be clearly and carefully worked out by both scientists and
moral philosophers but I would include at the very least one or
maybe several of these entities and I would think at least it should
not be able to form the infrastructure and body plan of a human
That's — I think that's too far. I would go back
to the most primary lineage differentiation and I don't think
that's analogous to a fully formed self-evidently human entity.
I mean, there's been a big debate about whether an anencephalic
baby is a human person. I think it's self-evident. If not
a human person in the full sense of what it is, it has a radiance
of respect due to it just by its humanness somehow, its human likeness.
And I don't — those are very difficult definitional terrains,
but let me say again, we are heading into this terrain inevitably
whether this proposal goes forward or not. We're creating hybrid
human animal creatures. We're going to generate human parts
apart from the whole. We're going to have to start doing the
hard work of defining what is the minimal construction of a moral
entity called a human being.
CHAIRMAN KASS: Look, can I intervene? It seems to me
this — I don't want to dissent from what Bill has just
said, but on the limited question that you asked, I don't think
you need to go in that full theoretical direction to say —
he's given you a couple of examples here of things that grow
on their own, teratomas and hydatidiforms cysts which are developing
but are not organisms. And I think anything that you would say
that gets to develop to be a fetus at eight weeks with the human
form is not a mole and it's not a cyst. But Bill, I think
what we want to say is what we're talking about here is not
an organism and not a being, in the same way as a cyst or a mole
is not a being. It's not just that it will not develop further.
It's not a developing thing. It's a thing — there
is growth that takes place here but it is not an organism, growth
in the sense of increase but there isn't somehow a pre-given
form that is being developed in the way an eight-week old embryo
would and I don't think you need — and I think that's
sort of descriptively accurate without having to get into ontological
questions. You don't really have a being here, in the same
way as those moles and things —
DR. HURLBUT: Let me show you something interesting on
this slide. This is — on the top is a normal human embryo
forming. On the bottom is an embryonic stem cell in a culture forming
a so-called embryoid body. I mean, it's not identical but
what I use this for is to show that there are biological qualities
within just the chemistry, the cell that will organize to some degree.
And so organization, per se, is not — is not indicative of
organism in the meaningful sense of the word. There's —
biology has a certain self-organizing power. So —
PROF. MEILAENDER: And what is indicative of organism?
It's not just growth but it's also not organization?
DR. HURLBUT: It is organization but it's organization
of the species- typical kind.
PROF. MEILAENDER: Okay.
CHAIRMAN KASS: Paul McHugh and then Mike Gazzaniga.
DR. McHUGH: Well, Bill has talked with me several times
before about this. It's nice to hear the whole thing laid out,
and I still have some technical questions. I don't want to
talk about the ethical issues right at the moment, because they
are deep and important, but I do, with Gil, want to follow along
on this terminological business because at one level this procedure
that you propose to us, and we've talked about before, is really
to build a weird genetic hybrid that in its next steps of development,
call it what you will, that next steps of development, would lack
the features that would render it ultimately viable as an independent
organism. Isn't — first of all, is that right?
This is a strange genetic hybrid that you've made but it —
and it's going to go through a process, a process of embryonic-like
development built in as it is —
DR. HURLBUT: Partial.
DR. McHUGH: — and you don't want to call that
an embryo because you said it doesn't have the potential for
full independent —
DR. HURLBUT: Well, it doesn't have the actual at any
level that is embryo-like. It's different.
DR. McHUGH: Well, it's very embryo-like. I mean,
that's the whole thing about these hydatidiform moles for that
matter, is that they are embryo-like.
DR. HURLBUT: Well, okay, embryo-like but embryo truly?
DR. McHUGH: No, and now we're back right at square
one again. Do you want to call everything that follows along this
developmental process an embryo or not, and the real issue with
SCNT right from the start as we've discussed before, and that
Rudy Jaaenisch tended to emphasize was that, in point of fact, it
differed from in vitro fertilization in that its origins were not
through fertilization but through this remarkably different process
so that no new creature had appeared and, as well, it lacked the
potential at least in the primate form of ever getting through the
pregnancy and therefore, perhaps by your definition, it also cannot
be called an embryo, and if it cannot be called an embryo, but rather
a source for embryonic stem cells, is it listed?
That gets us into the ethical problem. I just want to be sure
I understand that the process that you are proposing here is fundamentally
to interfere with the nucleus, with the genome, really, of these
things so that you have made a genetic hybrid. Now to come to the
ethical problem, we have just heard our Canadian friends tell us
that you cannot make, under their laws, a chimera or a hybrid with
in vitro fertilization or other kinds of things, and they reject
This would seem to be making a deadly hybrid and therefore, might
be saluted in this purpose but it would be an opening to make —
to propose or make — the process of making a new model chimera
or hybrid which would be super-human in some kind of way and therefore,
enter a domain that — I haven't finished my thoughts on
this because this is so important what you're telling us, Bill,
this is very, very important stuff but at the same time, I begin
to get — a few red flags begin to come up for me over what
we have done and or what we're thinking of doing here and what
it might mean.
DR. HURLBUT: Well, Paul, let me make one comment about
that. I'm not suggesting you create a deadly hybrid. To be
— to use that term, you'd have to say that the thing was
alive first. The point is, you do this ab initio. You never —
you create an entity that never rises to the level of what can properly
be called a living being.
DR. McHUGH: That brings us back to the point I made about
our friends here. It brings us back to our friends here. They
are very — they want to use what you want to use, the organismically
integrated organism and are very fearful of the use of the word
"non-viable" unless by their definition non-viable means
dead, dying or doomed. Those are a rattle of Ds that I thought
were very helpful to me in thinking about this process. Well, what
you have done is made a doomed hybrid, doomed.
DR. HURLBUT: Not doomed. Only doomed if it's alive
DR. McHUGH: Well, it's doomed in the sense that it
will never get out.
DR. HURLBUT: Well —
DR. McHUGH: Develop.
DR. HURLBUT: — you mean somebody with only potential,
like any chemicals mixed together.
DR. McHUGH: No, no, that these are cells — they
want to make the point that non-viable means, as I understand it,
I'd refer back to Dr. Landry and Dr. Zucker, who brilliantly
presented their views on the concept of death and discussed it nicely
with Robby. They want to make the — they want to use your
point of organismically integrated as being the issue of —
the concept of death but they want to not use the word non-viable
because the cells they want are, of course, viable. They want to
use those cells, at least as I've understood the conversation
this morning in relationship to life processes and life organization
and systems. But as I say, I'm still groping here.
CHAIRMAN KASS: Paul, can I try to help, Bill? Look, Doctors
Landry and Zucker don't like the language of non-viable here
because there are things which are non-viable which are still alive
and to use them might be to kill them. They want an embryo —
they want to develop criteria for embryonic death that would make
this exactly analogous to the determination of death in a developed
being. But the reason that they insist on those criteria is because
they know perfectly well that what they're starting with is,
in fact, a being of a human sort and alive, which will be first
doomed by somebody's decision, and then, if they can develop
the criteria, can be pronounced dead.
That doesn't apply to the way Bill is speaking because what
Bill is talking about doesn't yet rise to being a living human
being. The cells are of human origin and that says they're
human. But no more than is a hydatidiform mole a human being would
Bill's re-engineered entity be an organism. It would simulate
certain organic activities, in the sense that there would be cell
division, but it would have been engineered in such a way that you
couldn't — if you understood what you were doing and what
you have done, you could not call it a living human embryo. It
would be embryo-like only in the sense that it went through certain
stages of cell division but it would not be embryonic in the sense
that it had no — it was incapable ab initio of being embryonic
in the sense that it is pointed toward and developing — it
is not a being to begin with, with that kind of future.
And I think for me the question is, can you make such things.
It seems to me it's a technical question less than it is a philosophical
one if I have understood what he has told us.
PROF. GEORGE: You mean more than it is.
CHAIRMAN KASS: I'm sorry.
PROF. GEORGE: More than it is. A technical question more
than a philosophical one. In other words, you're saying it's
not really a philosophical question, it's a technical.
CHAIRMAN KASS: Yeah, exactly. Yeah, I'm sorry. Mike
DR. GAZZANIGA: Well, we're not capable of —
first of all, thanks, Bill. I appreciate what you're trying
to do and I think it's admirable. In many ways, I'd just
like to make a couple of observations, it does say to us that we
do need more stem cell lines and —
DR. HURLBUT: More what?
DR. GAZZANIGA: More stem cell lines. We need more lines
if we're going to get this job done. Why else would we be torturing
ourselves with this proposal. The — I do take exception and
I just want to bring a little clarity to those of us who don't
have this deep moral dilemma with using a 14-day old blastocyst
to harvest stem cells and therefore the need for this bio-engineering
project. And the other point I want to make, is that what we're
trying to do here, it seems to me, is, normally, we generate a word
to describe a biologic phenomenon and here we seem to be tinkering
with biologic phenomenon to have it fit the meaning of a word, and
that's not what you do.
So this rests a little bit back to Paul's point of two years
ago and basically the question underlying now is you are building
something here and we're going to have to call it something.
And it's not an embryo, it's something else if you want
to have it play out this way. And finally, I would just say, I
— because of my position on the moral status of a 14-day old
blastocyst, that has no brain, so we don't have to worry about
brain dead and all that sort of stuff — I forgot what I was
going to say. What was I going to say? Oh, that — excuse
me, I'm sorry, that the money and investment and time and trying
to develop a science of this, postpones, if we were doing it serially,
what we now know how to do, what I gather will be going forward
in the State of California and many other nations that — that's
right, well, many of them not as big as California, that it has
the risk, and I'm sure you've thought about this, of delaying
the important advances that could come from the sort of research
to alleviating pain and suffering and people who surely would like
DR. HURLBUT: Mike, I don't even understand how you
make laws. I start all my classes at Stanford by saying, "We're
going to not really talk about laws in this class. We're going
to talk about ideals, what we should do if we could", and
I quote that saying, "Never ask what goes into sausages and
laws". I truly do not raise this issue with a political agenda.
I raise it with the desire to see our society go forward, in both
forward progress in science, and forward progress in our moral thinking.
You say we need new embryonic stem cell lines. I think with —
if the scientific goals are the ones we're after, I agree with
that. As far as I've been able to understand from my colleagues,
I'm not a stem cell biologist, but I think it was obvious that
when the President put forward his policy, we would seek moral ways
to get new embryonic stem cell lines. So I don't think any
reasonably educated person in science is going to contend with that,
but at the same time we also need to confirm and solidify those
moral principles that will help us go forward into increasingly
complex terrains with development biology and if you could say that
progress walks forward on two legs, one technical and one moral,
we need to solve this — in my opinion we need to solve this
in a way that we can, as human beings, as a collective, cooperative
society in a way that creatively and intelligently recognizes that
neither side in this debate is — nobody is a fool in this
debate. Both sides are upholding important human goods and the
amazing thing is there might be ways to do this so that we could
both be confirmed in the positive things we're trying to defend.
CHAIRMAN KASS: Okay, Dan, and after Dan, I want to suggest
that we be thinking about the general conversation while we consider
both of these proposals and I would like to know what the council
thinks of either or both of this general direction. We can't
settle that today, but Dan, please, first.
DR. FOSTER: Yeah, I only want to make a brief statement
and I'm one of the minority, you know, in the original thing
but it seems to me that one of the fundamental principles that we
started off in this discussion about the bioethical concern was
that you had a series — you had two sets of goods. You had
two sets of goods, and one of them has to be dominant and the other
one did not in the 10 to 7 vote, but the principle that I think
that Bill is working on here and others is that this may be a way
to accomplish both of these goods without violating either of the
issues which are there, so I think it's a — and I'm
not worried about the cost because I believe that scientists always
learn things if you're working with one of these, what, "new
creations" or whatever you want to call it. We're going
to learn things that are also powerfully important.
I don't think you're going to have any dearth of scientists
that want — that would not want to explore this. Whether
it's going to work, I mean, the whole issue, I mean, from Dolly
on, as we were talking about, you know, I mean, it's really
hard to get — you know, to do this sort of stuff. I mean,
it took 270, 280 attempts to do it. The Koreans took — you
know, so there are many technical problems but that's what science
is all about. So I would say, to me, this is a very attractive
way to remove the issues that were of major concern about destroying
human life and at the same time, extending the stem cell things
where we can get diseased molecules and things of that sort, so
I'm adding my side in contrast to some of the view, in very
strong support, not of any technical aspects of this, but the principle
that one might be able to accomplish both of these goods with some
model like Bill or the Columbia people have put forward.
CHAIRMAN KASS: If I might, I would be interested in hearing
from especially the people we haven't heard from what you think
about this, Diana, Peter, Alfonso, Robby, Mary Ann, Jim Wilson.
DR. LAWLER: Let me ask Bill, what's your objection
to the other proposal which is basically to work with dead embryos?
DR. HURLBUT: Well, it's not really an objection.
In fact, by the way, if you can get embryonic stem cells out of
eight-cell morula, my project is a snap. I'm not sure you can.
I know Verlinski claims to have done that but the stem cell biologists
I've talked to say that at least at this point we don't
know how to coax them up and that they are more primordial cells
still, but maybe that's true. You know, the one thing we just
have to stop doing is being so narrow in our view of what science
can accomplish. I mean, science is a wonderfully creative process
and can yield for us all sorts of new ways to do things that we
have concerns about one direction, get them another way. I basically
think this is wonderful thinking at the heart of this proposal and
by the way, I'd be perfectly happy if my proposal was bypassed
by other easier, more practical ones and I think that eventually
Every stem cell biologist I talked to has told me that they think
it's just a little period here we have to get through eventually
to understand all of this well enough to create these entities with
no moral concerns at all. Is that what you asked me?
DR. LAWLER: Well, right, so the answer would be the question
is, which is more possible then.
DR. HURLBUT: Which is more possible?
DR. LAWLER: Yeah, which proposal can —
DR. HURLBUT: I mean, that's anybody's call but
we don't have any markers for the death of these things and
when you say that at 24 hours of rest, 10 percent still go onto
48 hours, that is a little bit of a problemmatic moral question.
You've in a way endorsed in vitro fertilization in the first
place. That would be a problem for some people. You've got
a limited number of cell types you can work with. You've got
the question that Paul put forward and it's not a trivial question,
whether even a mosaic, a normal appearing karyotype from a mosaic
cell may still have something in the constitutional cell that provoked
the aneuploidy in the first place.
There's some evidence that aneuploidy is promoted by certain
factors in the developmental powers of the cell themselves, although
it may just be pushing the growth too fast. But these are all really
fundamental questions... but again, they're technical questions.
The moral principles that were put forward before me I think make
sense. If something is not integrated, if it does not have the
principle of life in it, that's what we're trying to defend.
We're not trying to defend parts of things. We have to find
the locus of our concern. In the twentieth century, we came to
terms with the fact — I'm sorry — we came to terms
with the fact that cells like in transfusions were not the moral
locus of the person, although some cultures still believe that.
We came to terms with the idea that genes were not the locus. We
put human genes into bacteria. We learned that organ transplants
I was at Stanford Medical School when the first heart transplant
was done and some people were saying, "Well, that's just
too much of the person, or that's the person". It took
a few months and we figured that that wasn't the — in
this area of developmental biology, we're going to learn that
seemingly alive, partial trojectories of organic growth without
the full integrated principle of life organizing unity of their
organismal context, are not — even if they're human I'm
speaking of, without that principle of life, they are not moral
CHAIRMAN KASS: Look there are people who have to make
a plane and we also have a public comment session, so I really want
— if anybody wants to — we're not forced here to
choose between these things. The question is, does the concept
appear to the council, knowing that the technical questions are
not in our hands to determine, and I don't think — I'd
rather not have arguments for the proposal as much as I would like
to hear, from the people who haven't spoken, what they think
DR. LAWLER: I completely agree with what Dan said on this,
it's a promising area to explore, bound to benefit us and resolve
a question that might not be resolved any other way.
CHAIRMAN KASS: Diana?
DR. SCHAUB: Yeah, it seems to me almost too good to be
true that scientific advance — well, that scientific advance
itself would solve these moral dilemmas, and if — I mean,
I guess I am persuaded that you are not creating an embryo and therefore,
it doesn't trigger my concern about the equality principle.
I guess the only question I would have, I think it does not trigger
that concern about equal treatment of all human beings because you're
not creating a human being. Is there any concern that you were
doing something even more radical than that, namely, that you're
tampering with the organizing principle of, I don't know of
life itself. I mean, is there —
DR. HURLBUT: I think that principle is only of moral concern
only when it's instantiated in a living human being. What I'm
trying to do here is define more clearly the boundaries of our moral
concern and that's what I'm saying, it's the integrated
G.K. Chesterton has a beautiful little metaphor, little boys are
playing soccer on a field but right at the edge of a field there
are cliffs that go down 2,000 feet to the crashing waves on the
rocks below, so where are they playing soccer, in the middle 20
yards of the field. And then somebody comes and draws a clear line
at the borders, puts up a fence and they can play to the field.
Right now, and even more in the future, if we don't define
these moral boundaries clearly, we're going to impede forward
progress in science or many people are going to feel like moral
purposes are being violated, moral goods are being violated. We
need to do that hard work of defining these boundaries, but I think
the meaningful boundary is the integrated human organism at all
of its stages, and just make one sentence more: I, as everybody
in this council knows, have stood very strongly for the principle
that human life is present from conception. When I looked at the
scientific facts — and I didn't come in like some rubber
stamp agent of this counsel to do what somebody told me to do —
I looked as plainly as I could and I simply could not think —
could not agree that the early embryo was, as some scientists are
saying, an inchoate clump of cells. It's a living whole human
CHAIRMAN KASS: Bill, look, I think we've had your
elaboration on this and I really do want to get people who have
to leave, their comments on the record, so if you'd hold back
until we've heard from Jim and Mary Ann and Alfonso and I want
to have a word, too. Jim.
PROF. WILSON: I support this venture for all the reasons
that have been indicated. I do agree with Mike that you have to
find a name for this. It's extremely important. We can't
go around saying we're producing ANTs because the ant lovers
— the name is already used and widely admired by some close
friends of mine. But we have to find a name for it. Being a gardener,
I would call what we're doing as producing weed, not an animal
and not a desirable plant but I certainly support the venture.
CHAIRMAN KASS: It's not weed in the California sense.
CHAIRMAN KASS: Mary Ann. Jim, thank you.
PROF. GLENDON: Well, I think that this may turn out to
be one of the most fruitful meetings that the council has had and
I'm very grateful to both of — all three of the presenters.
I think a problem for some of us is we don't want to get over-excited
about these indications that there may be a path through the thicket
of technical and moral problems that we've been struggling with
for so long but I think you've all been so careful and nuanced
and at least as clear to us lay people as it's probably possible
to be although I — with Gil I can't pretend that I followed
everything, but I do think that this may be the beginning of very,
very significant turn in our history. So thank you very much.
CHAIRMAN KASS: Alfonso.
DR. GÓMEZ-LOBO: At present, my thinking is still
hypothetical on both proposals. On the Columbia University proposal,
if I may call it like that, of course, if indeed the extraction
of the cells proceeds from a dead organism, I would say that's
morally viable and extremely interesting. I'm sure there has
to be a lot of refinement in terms of the concept of death of the
criteria and the actual tests, I mean, the empirical evidence.
With regard to Bill's proposal, we've talked a lot about
it and I'm very close to the affirmation of the conditional
hypothetical question, but of course, there has to be a lot more
elaboration in the sense of making it very clear to the public that
we're not talking here about mutilation, because that's,
I think, what is lurking in the back of many people, whether what's
going on here may be the moral equivalent of generating a human
embryo but you just knock some genes so that it becomes non-viable,
which was Rudolph Jaenisch's position. I remember discussing
it with him and I insisted that we had to distinguish between genetic
modification that makes an organism non-viable from a genetic modification
that made it non-human and I think that's very important. Now,
your argument, Bill, is an argument fortiori at present.
DR. HURLBUT: A what?
DR. GÓMEZ-LOBO: A fortiori —
DR. HURLBUT: Yes, I get it.
DR. GÓMEZ-LOBO: — in the sense that since
it's not an organism, therefore, it cannot be a human organism.
It seems to me that that concept has to be refined in terms of what
would be necessary and sufficient conditions for the organism to
be human. I know that that's a major, major enterprise, but
I think both proposals are very, very interesting, worth pursuing.
CHAIRMAN KASS: Robby George.
PROF. GEORGE: Thank you, Leon. Bill, it's always
seemed critical to me in this debate that the embryo is a whole
living member of the species homo sapiens at the earliest stage
of his or her natural development. It's also always seemed
clear to me and I've seen no one here or elsewhere dispute this,
that a hydatidiform mole or a teratoma is not a whole living member
of the species of the homosapiens at any developmental stage.
So it seems to me that the whole ball game as far as your proposal
is concerned is the question whether an entity created by the altered
nuclear transfer process would be the equivalent of a hydatidiform
mole or teratoma or would be a severely damaged embryo or an embryo
programmed for an early death and I think this goes to the heart
of what Gil raised originally. Now, when I ask myself why are we
so sure that a teratoma is not a whole living member of the species
homosapiens, why are we so sure we can distinguish the teratoma
from an embryo, my conclusion is that the teratoma, unlike the embryo,
lacks, you know, from the start and always, the active disposition
for self-organization and self-directed development in the direction
of human maturity.
There may be additional things we can say about that but it seems
that we begin by saying at least that much.
Now, is it critical to you that we not go forward with your proposal,
at least with ANT, at least in humans, until we've reached moral
certainty that in fact, the product would be analogous to a hydatidiform
mole or teratoma rather than to an embryo? Is that critical to
DR. HURLBUT: Yes, it is.
PROF. GEORGE: So you, yourself, would not want to see
the proposal go forward unless it could be shown that in the human
case, we would not be creating an embryo.
DR. HURLBUT: Yeah, that would violate the very principle
we're trying to defend.
PROF. GEORGE: Right. Animal experimentation then would
be critical to determining whether, in fact, the entities created
are non-embryonic —
DR. HURLBUT: Yes.
PROF. GEORGE: — truly non-embryonic in which case,
I think then you're saying that all you're proposing to
us is animal experimentation to determine whether when we examine
the products of ANT we have on the basis of our, you know, biochemical
and molecular examination entities that are truly analogous to teratomas
or hydatidiform moles and therefore, are non-embryonic, no more
than that, right?
DR. HURLBUT: Yes, that's right.
PROF. GEORGE: So you're not proposing that we do this
in human beings now. That proposal has gone on the table.
DR. HURLBUT: Absolutely no.
PROF. GEORGE: Okay, one other very brief line of questions;
you have used as an example of a method of ANT the switching off
of the cdx2 gene which would then be switched on later when the
stem cells are derived. That possible method was described in an
article in The Boston Globe by the science writer Gareth
Cook recently. And my own e-mail tells me that a lot of people
interpreted what was said in that article to imply that ANT just
is the method involving switching off cdx2. But I thought I heard
you say today, and you can correct me if I'm wrong, I thought
I heard you say today that that method is simply one of perhaps
any of a number of possible methods of altered nuclear transfer
which you, yourself, think has some promise but may turn out to
be inadequate to the task of creating a truly non-embryonic entity
in which case you would look to another method.
DR. HURLBUT: Yes, or a combination of methods with great
surety. See, it doesn't have to be just one thing. SiRNA,
you can put several in at once. You can knock several genes out
if you have to, just maybe a little more complicated, but you know,
the idea is that we've beginning to understand the biology of
development enough to determine to some degree what is going on
with teratomas. And if we biologically could artificially mimic
that or some equivalent of it that was ontologically equivalent,
that would be what I would be after.
PROF. GEORGE: So the method involving the switching off
of cdx2 could prove in the animal experimentation to be inadequate
to the project of producing a truly non-embryonic entity, in which
case you would abandon that as a morally legitimate method of ANT
if used in humans.
DR. HURLBUT: Oh, yes, I didn't put the one project
forward with the specific gene as anything but an example of how
amazing it is that you can get a fully normal functional embryonic
stem cell out of an entity that is grossly abnormal, with a trophectoderm
not forming in that entity, the thing doesn't even hold together
— the inner cell mass over-grows the center of the blastoseal,
the cavity of the blastocyst — and yet, you still get functional
cells out of it. That was why I used that example, but I specifically
am not tied to any one gene or any suggestion at this point. I'm
proposing an exploration of this.
PROF. GEORGE: Thank you.
CHAIRMAN KASS: We are just about at the end and want to
have the public comment session. Let me put my own thoughts on
the record and also make a proposal to the residual of the council.
I know people have had to go to catch planes, but if you —
the Communist party's slogan was to come to the meeting early
and stay late and those of us who stay till the end can actually
approve the next procedures, but I think these are two extremely
interesting, extremely interesting, very creative proposals, absolutely
worth not only our consideration but much more public consideration.
Bill has been working on this for two years and has consulted enormously
widely with moral leaders and religious leaders and with scientists
and there has been a tremendous amount of encouragement.
And I was a foot-dragger on this, not so much on moral but aesthetic
grounds, not altogether unrelated to the point raised by Diana,
and I'm not sure that the aesthetic objection turns on whether
or not this thing is or is not the organismic entity. But that
objection, I think has been overcome by the sense of the real promise
of this, and I, myself, am prepared at least in principle to endorse
it and eager to see the details worked out scientifically.
This other proposal, which has also been a long time in gestation,
and very, very carefully thought out and very subtly now refined
and clear conceptually also strikes me as extremely exciting. It
should not be too hard to do this kind of research, starting in
the mice or starting in various kinds of things, and to begin to
look for these criteria. And it seems to me that for this council
and the public generally what would be most encouraging, is if,
in the course of the next several months, we could begin to receive
some kind of information on some specific suggestions on where the
science might be or some kind of protocols or suggestions for where
the science could go, so that if we indeed mean to endorse this
as a morally fruitful possibility for the nation to go, we could
also back it up with some kind of practical information on that:
"this is not just a nice idea, but might be feasible, if the
following kinds of steps are taken." I think both of you are
prepared to do this and have the information. It didn't —
since this was the first airing in this gathering, it wasn't
probably the time to get all that scientific detail out there.
By the way, just accidentally, although one doesn't generally
regard the New Scientist or BBC News as a scientific
publication, there is this report that human eggs have now been
developed parthenogenetically, with the expectation that we will
get to the blastocyst stage, using just an enzyme derived from sperm,
in which the whole process goes on along. There are no male chromosomes
in this thing and there's an almost certainty that this will
not go on — could not go on — to develop into a child,
and this might be yet another route, another morally non-problematic
route to getting the kinds of — to getting us to the point
of getting new embryonic stem cell lines.
So I want to thank the three of you for — not just for the
presentations today but for the enormously serious and careful and
thoughtful work that has gone into bringing these proposals forward,
the consultations that you've taken and the evolution of these
two separate projects which I've known about really since almost
the beginning. And I think the council and the nation are really
in your debt for trying to find a way forward that does not involve
the — if successful, would not require anybody who's party
to this debate to sacrifice anything of great importance. So thank
you very, very much.
Gentlemen, you may be excused but you're also free to sit
here. We have two people who want to make public comment and they
might, in fact, be on this, so if you have five to 10 minutes, we
have a public comment from Jaydee Hanson of the International Center
for Technology Assessment, followed by Richard Doerflinger of the
United States Conference of Catholic Bishops. Do you want to take
the microphone there?
SESSION 7: PUBLIC COMMENTS
MR. HANSON: Well, thank you for the opportunity to comment
today. The Executive Director of the Center wanted me to extend
his personal greetings to you, Dr. Kass. So greetings from Andrew
Kimbrell. I want to say my comments are going to be on the altered
nuclear transfer technique and I want to begin by offering my personal
words to Bill and how much I appreciate his thoughtful thinking.
But, we're told that this procedure is intended as a means
of avoiding the destruction of embryos in producing embryonic stem
cells, but we think this notion is mistaken in that we believe that
the technique actually does produce embryos albeit defective ones
through a combination of cloning and human germline and genetic
engineering. We think if the proposed experiment were to be conducted
on human embryos, it would confront us with an ethical question
about whether we produce any human life solely for its commercial
We also think there's a second ethical watershed that would
be crossed. This would be in effect, the first human germline,
genetic engineering experiment. For the first time, we would be
engineering human life at its earliest stages. In fact, it seems
to require two engineerings. We do not believe that society should
cross these boundaries without a very full public debate. We urge
the council to support an immediate moratorium on all such experiments
with human embryos until a robust public debate has occurred and
there is wide public consensus that we have in place safeguards
to prevent abuse of this potential technology.
We go on and list some other concerns we have but those are out
two main concerns and I thank you for your time.
CHAIRMAN KASS: Thank you very much and hold it just a
second. If there is a longer statement either now or soon, I think
this would be welcome and we'll see that it's circulated
to everybody here. The genetic modification aspect of this is an
issue that so far hasn't been discussed today and whether or
not this is or is not an organism or an embryo, there are people
who have reason to be concerned about such genetic engineering close
to the human and I think the point — it's something we
will want to talk about.
MR. HANSON: We also, just to briefly summarize the longer
point, we also have some concerns that this — even if the
proponents don't consider this an embryo, they may well want
to patent it. The patent office might consider in embryo-like enough
to use it as a precedent. So we have other concerns as well.
CHAIRMAN KASS: Thank you very much.
MR. HANSON: I do have copies of the statement I'll
leave with whoever.
CHAIRMAN KASS: If you'd just leave it with Diane Gianelli,
she'll see that all of us get sent this. Thank you very much.
MR. HANSON: Thank you very much.
CHAIRMAN KASS: Richard Doerflinger.
MR. DOERFLINGER: I also want to talk about altered nuclear
transfer. I have — as many on the council know — have
been skeptical and remain skeptical of many claims for the unique
benefits of embryonic stem cells, including those derived from nuclear
transfer. That being said, I know many scientists believe in those
unique benefits, and some of them share my moral convictions against
destroying human life at any stage.
If, and this is a big if, a procedure can be found to provide
embryonic stem cells without creating or destroying embryos, that
would address the Catholic Church's most fundamental moral objection
to embryonic stem cell research as now pursued. Clearly, such a
procedure would not be prohibited by the cloning bans the Catholic
bishops have supported at the state or federal level, which routinely
exempt the use of nuclear transfer or any other cloning procedure
to produce tissues, organs or cells other than human embryos.
I, therefore, see no moral reason at this time to oppose the further
exploration of this theory in an animal model so its feasibility
can better be assessed. This would give scientists an opportunity
to show their real commitment is to scientific progress, not to
the exploitation of embryos, and gives organizations like mine an
opportunity to show that our concern is respect for life, not a
fear of scientific research or scientific progress.
Regarding one particular technique for pursuing this, the deletion
of the cdx2 gene, I for one am not convinced it fulfills my criterion
for saying the resulting entity is never an embryo. Surely, it
is not enough to say the genetic defect preventing organismal development
was introduced into the genome from the very beginning. Any adult
who develops Huntington's disease at the age of 40 had the genetic
defect ab initio. But it also matters what development has taken
place in the meantime.
If that gene is expressed only after the 16 to 32-cell stage,
it seems to me this would be an embryo that undergoes normal development
as a human organism to a certain point and then dies. Surely the
entity has to depart from organic human development from the beginning
to fulfill what I would see as the correct goal for altered nuclear
If no procedure can be found that truly produces embryonic stem
cells but not an embryo, my objections would certainly be equal
to some of those raised by Mr. Hanson.
Finally, the problem of using human eggs and the potential of exploiting
women for their eggs will ultimately have to be addressed once this
is attempted in humans. Perhaps animal eggs will turn out to be
sufficient. Those have proved very disappointing to researchers
trying to use cloning to make normal human embryos using animal
eggs, but here we are not trying to make normal human embryos.
Perhaps very few eggs of any kind will be needed, because this
technique will be used chiefly to make a few cell lines as disease
models or for drug testing. Increasingly, proponents of cloning
for research are admitting that large scale use of nuclear transfer
to make cells for direct therapeutic use in patients is doomed to
practical and economic failure. I would only note that it would
have been nice for them to admit that before they managed to convince
the voters of California to approve the $3 billion give-away for
cloning last month. Or perhaps other ways to achieve complete or
partial reprogramming of a body cell nucleus without using an egg
will be further refined and replace the use of eggs for this technique.
I do simply want to offer the caveat that this problem ultimately
must be addressed as well, the problem of use of human eggs, if
this approach is to achieve moral consensus. But at this time, I
certainly appreciate the conceptual model that Dr. Hurlbut has presented,
and I think exploration in animal models is well worth at least
pursuing at this time. Thank you.
CHAIRMAN KASS: Since you have the floor and since you
are really one of the most meticulous and thoughtful and careful
people about such things and even though you didn't come prepared
to speak about it, do you have any reaction to the other proposal
of developing criteria for death in embryos follow — only
following which would the removal of embryos be attempted? Does
that strike you as morally acceptable, questionable? Do you have
— or would you rather think about it and let me know privately?
MR. DOERFLINGER: I would rather think about it. I came
in late and was not here for the presentation and have not read
the materials, and I will certainly study that as well. Anything
that achieves the promised scientific benefits without exploiting
or destroying human life is something that the Church wants to have
an open mind to, so I will certainly study that as well.
CHAIRMAN KASS: Thank you very much. I think we've
done everything that we hoped to do at this meeting and more. I
thank our guests especially. Thanks to council members. Thanks
to the members of the public and the meeting is adjourned.
(Whereupon, at 12:13 p.m. the above entitled