FRIDAY, MARCH 4, 2005

Session 5: Alternative Sources of Human Pluripotent Stem Cells

Council Discussion of Draft White Paper

CHAIRMAN KASS:  This fifth session of this 20th meeting is devoted to a draft white paper of the President's Council on Bioethics entitled "Alternative Sources of Human Pluripotent Stem Cells."

Just to remind everybody and also to put this on the public record, this white paper, a reworked draft of an earlier staff working paper, grew out of discussions that we had at the last Council meeting where we had two presentations, one from Drs. Landry and Zucker, Columbia; one from Bill Hurlbut of our own Council, on alternative ways of deriving pluripotent human stem cells that would not require the destruction of human embryos.

Subsequent to that meeting, staff, in researching the literature, also discovered two other kinds of proposals, one the attempt to derive stem cells by biopsying living embryos, analogous to the biopsy of living embryos used in prenatal genetic diagnosis; and also, activities in the realm of attempts to find ever more de-differentiated or undifferentiated stem cells taken from children and adults, encouraged by the findings now of, I think, three different groups in addition to Catherine Verfaillie's group of multipotent cells found in the bone marrow, some of them bearing markers normally associated with embryonic stem cells.

And the Council prepared a paper reviewing all four of these proposals, first of all, explaining what they are, then conducting an analysis to ask whether each of these proposals were ethically sound, whether they seem to be scientifically sound, whether it was realistic even to consider these matters, and that meant whether these were likely, if successful, to be met with scientific approval, whether they might secondarily be eligible for federal funding.

We did not take up the question of whether these things should be recommended for federal funding.  That was a prudential judgment that rested upon answers to the ethical questions and also the next question of how much resources should be invested in these kinds of, for the time being, still speculative proposals.

The major emphasis in this document, since this is an ethics council, has been on the ethical analysis, and the thought was that we are convened here like a body that's conducting a preliminary hearing.  The question is:  do these proposals pass minimum ethical muster and, second, are they of sufficient possible scientific interest that we could recommend them for further public consideration?  That has been the spirit here.

And I want to say a couple of things about why we are doing this.  You'll recall that this is a council which is charged, indeed, with upholding certain ethical norms and at least venting all of the important ethical questions connected with biomedical advance.  We have been involved in issues that concern embryo research, and early on in our cloning report we prided ourselves, I think rightly, and all of us signed onto this particular part of that cloning report, that we recognize that all parties to the debate about embryo research had something vital to defend, not just for them, but for everybody.

Also, this Council distinguished itself, in my opinion, in our finding common ground in the Reproduction and Responsibility report, notwithstanding the remaining large differences amongst on the moral status of early human embryos, and it seemed to me, and I think this was the sense of the group the last time, that this was a wonderful opportunity for this Council to demonstrate once again the desirability and the possibility of trying to find common ground and also of seriously considering ways that science might advance in ethically uncontroversial ways, in which neither side would have to compromise.  And it seemed to me a public bioethics body that could help in attaining such goals would have more than justified its existence.

There have been people who have looked at our discussions, and our discussions have gotten a lot of press, and there are also papers being published about these things even as we speak.  There are people who have been cynically saying that all of this is an attempt to distract the country and to divert attention from the need to pursue embryonic stem cell research by the conventional means and that this is a disingenuous conversation.

I reject that in the name of all of us.  If there are any of you who are speaking disingenuously, you're free to confess, but I've been in conversation with everybody here, and it has not been my sense that that is the motive of anybody who has been participating in this discussion.

That's a cynical charge which to my mind ranks really with those who say the people who support embryonic stem cell research over adult stem cell research are really motivated by the desire to kill embryos or to defeat their pro life opponents.  That's a canard.  I reject that, and similarly, I think we should reject those who would caricature what we're trying to do here as somehow disingenuous and an attempt to deflect research.

I think everybody ought to be interested in finding morally uncontroversial ways for science to proceed if we can and ways that would respect the seriously held ethical opinions of our fellow citizens whether we agree with them or not.  Whether these proposals finally pass ethical muster on their own terms is, I think, the question we want to consider.  These are serious proposals advanced by morally serious people who are, in fact, committed to scientific progress, and so are we all.

With that as a kind of preface, this is a session in which all of you have had a chance to see the draft white paper.  This has been reworked in the light of your comments made on an initial draft, in the light of comments made by three outside researchers whose expertise bears upon the feasibility of these proposals.

I want to thank especially Adam Schulman and Dick Roblin who worked heroically to put together what I think is really a quite remarkably thorough and clear document at least in terms of the analysis.

I think most of our time probably should be spent on the question of the conclusion and what we want to say by way of conclusion, but before doing so, let me see if, on the sort of more general questions, in terms of the ethical analysis and the document as a whole, whether people find this a fair and balanced document, whether it presents a sober and sufficient analysis of the issues, before we take up the particular questions of the conclusion.

Are there any comments about everything up to the sort of conclusion just in terms of the analysis that's offered?  I don't mean line editing, but more serious reservations, serious omissions, questions of balance.

Bill Hurlbut.

DR. HURLBUT:  Well, it's a small comment, but I think we should take the issue of parthenogenesis a little more seriously than we have because there are some serious scholars and scientists interested in that subject, and notwithstanding its mention in the Dickey amendment, I'm not sure that it has been properly analyzed ethically.

I'm not committed to one view or another on the outcome of that ethical deliberation, but I just think that since we know that there has been successful procurement of embryonic stem cells from parthenogenic primates and now apparently from human productions, I think we ought to recognize it as already having practical import and, therefore, ethical worthiness to at least be discussed more thoroughly rather than dismiss it.

CHAIRMAN KASS:  On this very point, anyone else?

PARTICIPANT:  Is there a page you could give us reference to or is this just a general omission?

DR. HURLBUT:  It's on page 21.

CHAIRMAN KASS:  At the center of this is this thought:  is a parthenogenetic blastocyst-like entity an embryo?  That's, in a way, the conundrum here.

Most people will say this is not an embryo because it cannot, in fact, by your own criteria, Bill, cannot really develop and become an organism.  There's really only one experiment, I suppose, that could prove that definitively.  You would have to presume the innocence, I think, of that experiment, I think, to try it, and in the absence of this proof, there is a kind of doubt both on scientific and moral grounds about just what this thing is.

And I'm not sure.  Maybe there's more to be said on that subject, but I thought we tried succinctly to say what the conundrum is and why that conundrum is probably not going to go away.  And at the very least, as a practical matter, there is a certain bar even to investigating this further, at least in this country.

Now, the Dickey amendment wasn't written at Sinai, and even the things that are written at Sinai are under review, but I'm not sure what more one would want to say here, but we will certainly consider it, and if you have some specific suggestions for enriching that discussion, I think we would be glad to have them afterwards.

DR. ROWLEY:  Can I?  Just for a point of clarification as to how you plan this morning's discussion, it seems from the way it has begun that we will consider the ethical issues and then at a later time this morning go back and discuss some of the scientific bases for some of these?  I wasn't clear.

CHAIRMAN KASS:  No.  Thank you, Janet.

No, I thought that at least from the mail received before the meeting that most of the discussion that people wanted to have was — well, in fact, it stems really from Michael's comment on the current draft that you have, namely, here we have this extensive ethical analysis, and then it looked to Michael as if it were sort of a cop-out to say, "Well, you know, some of us like this and some of us like that," without our having actually had that discussion.

So it was Michael's suggestion, and I concurred, that we try to see where we are on a limited ethical question and it's also a provisional judgment because some of these ethical judgments depend, indeed, on certain empirical questions.  I mean whether some of these biological artifacts are or are not embryos might be discernable from the animal research.

So I thought I would save the bulk of the time for the discussion of the conclusions, and I'll cut this off if it gets too long because the conclusions, I think, are the most important thing.  But if there are major difficulties with things prior to the conclusions, this would be a good time to at least mention them.

And so if there are things earlier, Janet, this would be good.

DR. ROWLEY:  Well, I think I indicated some of my concerns at least in my first response to receiving a copy of the draft of the white paper, and I do think that there are some serious issues, and I will talk basically only about the Landry proposal and about Bill's.  And I think I was particularly troubled that we have ourselves in what I find a quite unusual situation.

And on page 7 in the middle, under Item 3, "yet is important to note that under the Landry-Zucker proposal embryos that divide normally upon thawing but are allowed to die by a human decision, that is, not to transfer them into a woman's uterus, would not be eligible for donation."

So viable embryos are going to die at the same time one would take those embryos that don't divide and, therefore, appear dead for scientists then to be able to see if there's any way to find within the few cells in those dead embryos something that might then go on to be used for an embryonic stem cell line.

And I think that for me this is a strange way of solving an ethical dilemma, that you let something that is useful die and then try strenuously to rescue cells from a dead embryo.

So I think that in the apparently dead embryo it's clear, and it's pointed out here in this discussion, they may have chromosome abnormalities that would prevent their ever developing, certainly not normally, and many of these chromosome abnormalities lead to cell death.

So getting long-term embryonic cell lines out of these would be difficult.

I think with regard to Bill's proposal — and I realize all of this is couched in the terms of this as at present a thought experiment that has no basis in actual experiments — but I think we do have to be very cognizant of the fact that this proposal is based on using oocytes obtained from women, and it does include the possibility that the women would be paid for it, though that's going to be controversial and that's not central.  So that it says they can be donated.  Women can be paid for them, but the feeling of many individuals in the country and I think the proposal of the National Academy of Sciences that is currently working on guidelines will be that there be no payment for the donation of oocytes.

But I want to just point out what this really potentially means in the real world, and we don't have very good evidence, but based on the paper of Dr. Hwang from South Korea that was published in Science in 2004, they used 176 oocytes for SCNT, somatic cell nuclear transfer, and they got one stable cell line and that's using a donor nucleus actually from the same individual who provided the oocyte and under the best possible conditions.

And to say that you're going to go through a series of experiments to identify a gene that will disable a human embryo or a human cell such that it can't develop into an embryo, but it is otherwise functioning, and to figure out which of several or probably quite a number of genes might fulfill that requiremen, is going to take many, many, many human oocytes, and I find that an extremely troubling process.

Moreover, once you get the embryo with this defective gene, you're then going to do manipulations, presumably homologous recombination, but there are several possible strategies, to rescue that defective gene later in the course of the development of this cell line.  That, too, is fraught with a lot of problems.

So you're going to have enormous wastage all the way along the line, and each wastage is the use of an oocyte donated by a woman, and I think this is not a line of research that I at least am prepared to support.

CHAIRMAN KASS:  Let us move to the conclusions.  I know a couple of people have to leave early, and anyway, Janet has already begun on the conclusions. 

I can't, Janet, refrain from commenting just to the side that ordinary SCNT, which a considerable number of members of this Council were fairly enthusiastic and remain enthusiastic about, also involves a rather large number of human oocytes as you began by indicating.

DR. ROWLEY:  I don't deny that, but at least you're giving them the best possible chance of developing into a usable cell line.  This takes that thing — and that's why I pointed out the statistics from South Korea — one line from 176 oocytes under the very best circumstances.  We're going to talk about one line probably out of 1,000 oocytes.

CHAIRMAN KASS:  Bill, do you want to speak to that just briefly?

DR. HURLBUT:  You know, Janet, I really welcome your well-expressed concern about your oocytes.  Coming from a prominent scientist in our nation, to have such a serious concern about oocytes put forward in plain English is very, very positive, I think.

I, too, share that concern, and in raising the prospect of altered nuclear transfer, I am trying to draw on the best possible scientific possibilities, while being sensitive to the moral concerns.  And one of the moral concerns I truly am concerned about is the procurement of eggs.

I think if my project ends up inducing the superovulation of a single woman to produce eggs, I will be disappointed.  Now, there are other possible ways to get eggs.  There are leftover eggs from the IVF clinics.  There's talk of in vitro maturation of eggs after ovaries are removed surgically or from cadavers.  There's talk of putting ovaries from such sources into animals, and because of the conservation of the hormonal systems, there may be ways to induce the formation of eggs.

All of that is science in rapid transition, and I think my project would depend on morally acceptable ways to procure eggs.  I completely agree with you.  The egg issue is a very, very serious issue, and yet at the same time, the scientific community has promoted the important possibilities of SCNT, has said that it's a far superior technology to harvesting ES cells from IVF lines which cannot be designed by genotype to serve as disease models, and so forth.

So the reason I put forward my proposal is because it seemed to offer the greatest spectrum of possibilities while preserving the moral notion.  But I completely agree with you about the eggs.

So if that's a preemption for my project, it might also be for all of SCNT, and then we're back to the starting block, but I put forward my proposal in the spirit of defending both the science and the ethics.

CHAIRMAN KASS:  Let's proceed in the spirit of Michael's suggestion that we see where we are on the individual proposals.

I'm going to say in advance that depending on how this discussion goes, we would either modify the conclusion to express the sense of the Council on these various proposals or go back to the more wishy-washy formulation suitably modified to meet various people's approval.  I don't want to prejudge the wisest course until we hear where people are in the discussion.

Charles.

DR. KRAUTHAMMER:  Well, perhaps I can just start it off by saying where I stand on the proposals.

First of all, I endorse the effort.  I read Mike Gazzaniga's objection that it is a distraction.  I don't think he meant it as a disingenuous distraction, but a distraction from science, and I think he's missing the point that we have a deep difference in the country among large numbers of people over the ethics of these procedures, and if we can find what's essentially a technical fix, which is kind of a magical solution to an ethical issue, we ought to pursue it, not to the exclusion of other research, but we ought to pursue it.

So I think what you're proposing Leon is that at least we look at the four proposals as extremely useful.

I'm rather inclined to support the first and the fourth, Landry-Zucker and the de-differentiation.  The last one is very obvious because it's rather simple.  It raises no ethical dilemmas, the de-differentiation to the point of pluripotency, but not totipotency.  So I think that one is pretty obvious, and I'm sure there will be consensus on that.

I'm intrigued by Landry-Zucker simply because it gets us around the problem of destruction of embryos.  If there are cells in what we might call clinically dead embryos that can be used reliably, there are tens of thousands of these embryos left over.  It solves our problem, and it would allow people who are not troubled by the ethics of this to pursue traditional use of discarded embryos, live embryos if they wish, perhaps without federal support, and those who are troubled, to use the cells of the deal embryos.

And I say this as someone who has spoken here publicly and written that I support the use of discarded embryos, living discarded embryos in IVF clinics in stem cell research.  I disagree with where the President drew the line in his August 9th speech, 2001, although I respect the reasoning behind it.

But even though I support the use of discarded embryos, I think we ought to look seriously at whether or not Landry-Zucker could work.  If it does, it would allow us to pursue it in a way that would be ethically untroubling to large numbers of Americans, and I think that would be a great advance.

Oh, I might say on the others, too, that I'm a little bit troubled by the biopsy notion, and also by the proposal that my friend, Dr. Hurlbut, has proposed about the creation of what are essentially teratomas.  I find that troubling ethically. 

I agree also with Janet's objection that, just on practical grounds, it would involve the use of very large numbers of eggs, but I think my objection is more that I'm not sure we ought to be creating these bizarre organisms as a way to harvest stem cells.

But anyway, I'll stop there.  Thank you.

CHAIRMAN KASS:  Someone want to respond or go next?  Michael.

PROF. SANDEL:  I agree with what Charles has just said, and I think we should follow that suggestion.

I want to, having raised a question about a portion of the conclusion, I want to say something about the analysis in the document prior to the conclusion.  I think it's superb and thoughtful and carefully done.  And I'm speaking here especially about the ethical analysis.  I'm less equipped to judge the scientific analysis, but I think the ethical analysis of these four proposals in the white paper is very powerful and extremely well argued, I would say the best and most carefully and, to my mind, persuasively argued of the documents that we've put out.  So I think that's something we can be proud of.

My objection was to the conclusion and to the lack of fit between the ethical analysis presented in the white paper and the last paragraph of the conclusion.

And what I would propose, and this is consistent with Charles's suggestion just now — I would also want to draw attention, by the way, to Leon's memo where he summarized as a point of departure for our discussion the ethical evaluation of the four, and I think that's a perfectly reasonable statement of the ethical position.

I'm referring here to Leon's memo, and I would much prefer that we substitute for the last paragraph of the conclusion something that captures Leon's summary of our ethical analysis in the memo, and I actually have specific language drawn from the two to suggest if it's of use, and it would embody, I think, the view that Charles has just stated.

If we go to the last paragraph, the thing I objected to was simply saying "where ethically appropriate," as if we were agnostic on that question as a bioethics body, and I think that problem is corrected precisely by Leon's memo.

So what I would suggest is that we amend the conclusion, beginning in the second sentence, the one that begins "because the Council is wholeheartedly committed to both the advancement of science for the betterment of humankind and to the defense of human freedom, dignity, and the value of life," comma, and then I would say, "We encourage public discussion of any proposal to achieve these ends," period, and then say, "Of the proposals we consider in this paper, we endorse scientific exploration of Proposals 1 and 4," in line with what Charles has suggested, and then drawing on what Leon has summarized in the memo something like the following:

For reasons stated in the ethical analysis, we consider Proposals 2 and 3 ethically unacceptable in humans at least for now.

CHAIRMAN KASS:  Robby.

PROF. GEORGE:  Yes.  I'd like to say a word on behalf of the altered nuclear transfer proposal that Bill has put before us.  I think it's important to understand what that proposal is, as Bill described it to us in the last meeting of this Council.

It is not a proposal to go forward at this point with the use of human cells.  Rather, it is a proposal to conduct animal experimentation precisely with a view to determining to a high degree of certainty that we can create non-embryonic entities that are capable of generating embryonic type, pluripotent stem cells.

Bill also said then what he has reiterated this morning in response to Janet, that he would not like to see his proposal go forward if it did involve having to obtain eggs by subjecting women to superovulation.

Now, I think what that means is that in endorsing Bill's proposal, we are simply endorsing going forward with that basic animal research to take things to the next step while at the same time hoping, as those who support SCNT no doubt hope, that we will be able to come up with ways to meet the need for eggs that don't involve subjecting women to dangers and exploitations.

So I think with that understanding of Bill's proposal in mind, we can add to what Michael has just said, an endorsement of the continued discussion of Bill Hurlbut's proposal or continued investigation of Bill Hurlbut's proposal as well.

CHAIRMAN KASS:  In animals.

PROF. GEORGE:  Yes, precisely in animals.  I would reiterate what Bill said last time on this score, that the only way that the proposal is being put forward only on the assumption or in the hope that what will be created, the teratoma-type entities that would be created, are truly non-embryonic entities.

Bill himself said very clearly on the record that he would not want the proposal to go forward.  He would not want this to be practiced if it turned out that what was being created was merely a defective embryo or an embryo that's pre-programmed for an early death.  It would have to be a distinct non-embryonic creature for Bill to — not "creature," but an embryonic entity — for Bill to endorse it, and that would certainly be true for me and I suspect for other members of the Council who share our view.

DR. KRAUTHAMMER:  I'm afraid it was that slip that really troubles me about this proposal.

CHAIRMAN KASS:  Charles, would you speak up?

DR. KRAUTHAMMER:  I'm afraid it was that slip of the tongue which troubles me about this proposal.  You call it an "entity."  I see it as a "creature," and I think that's a fundamental difference, and that's why I'm repelled by it in principle, apart from all of the issue of obtaining oocytes.

PROF. GEORGE:  Could I ask Charles a question?

DR. KRAUTHAMMER:  Yeah.

PROF. GEORGE:  Yeah, just to be clear, do you consider teratomas and complete hydatidiform moles created in nature to be creatures as well?

DR. KRAUTHAMMER:  I think it was a targeted missile that went wrong.  It was perhaps — look.  It's philosophical here.  It's on point —  it was an attempt at a human that didn't go right.  I'm not sure we ought to want to reproduce that.

I mean there are other ways to deal with our problem of obtaining stem cells without killing embryos, and this one I find is simply the most troubling.

It could be what Leon calls sort of the wisdom of revulsion, and I haven't, you know, done an extensive philosophical analysis, but if you've seen a teratoma or you think about development, I'm not sure we want to be in that business.

PROF. GEORGE:  Well, let me just point out in response to Charles that I think that there are two distinct questions here.  One is:  do we, in fact, have a creature or was my slip of the tongue telling?

And I think the answer to that is, frankly, no.  We don't have a creature here precisely in the same sense we do not have a creature in the case of a teratoma or complete hydatidiform mole.

The second question is the one I think actually bothers you.  It's not the question of a creature.  It's the question of:  is it ethically acceptable to create something that even in nature is repugnant and weird. 

Now, I don't share your principled ethical objection to that, although I understand —

DR. KRAUTHAMMER:  Repugnant, weird and somewhat human.  If it's just repugnant and weird, it's just an aesthetic issue.  If it's somewhat human, it's a moral issue.

PROF. GEORGE:  Somewhat human in the sense of possessing a human genome?

DR. KRAUTHAMMER:  Yes, and is an aborted attempt to produce a human essentially.  I mean, it is an attempt to produce a human that went wrong.

CHAIRMAN KASS:  Just procedurally, because I think we have probably started the discussion that is the one most to be sustained, let me see if I can get agreement.  Let's see if the Council agrees on the other three things so that we can spend all of our time on this and see where we are.

The provisional formulation which Michael has at least endorsed on one, two, and four is as follows.  And, by the way, I would like to modify slightly that we don't recommend for scientific exploration.  That is not finally the judgment.  Ethically acceptable for investigation —

PROF. GEORGE:  Yes.

CHAIRMAN KASS:   — that's kind of a minimal threshold I think we should say. 

The rest is the matter of prudential judgment of resources and the like, which I don't think we're in the position here to do.

DR. KRAUTHAMMER:  But couldn't we say that we encourage this research in the name of finding some ethically consensually accepted way of obtaining stem cells?

CHAIRMAN KASS:  I think that's what —

DR. KRAUTHAMMER:  It's implicit.  So why not say it?

CHAIRMAN KASS:  It's implicit partly because I think this was a question raised by Janet already in the comments on the last draft.  Resources are going to be put into this.

DR. KRAUTHAMMER:  But it would be stronger if we were explicit in what is obviously implicit here, that this ought to be looked at without giving it a dollar figure.

CHAIRMAN KASS:  We now have a new question for deliberation.  Let me put that one last, but —

PROF. GEORGE:  Leon, could I finish one remaining thread with Charles just very quickly?

CHAIRMAN KASS:  It won't be quick, but go on.

PROF. GEORGE:  No, no, it will.

Charles, just to —

DR. KRAUTHAMMER:  It's not fair.  He was thinking on this while you were talking.

(Laughter.)

PROF. GEORGE:  On the objection to the creation of the entities, just to be clear, your objection is precisely to creating such entities.  It's not the objection that I and others have to the use of embryos in this regard where the objection is to killing the embryos.

You're not objecting to killing teratoma-type creatures.  Your moral objection is to creating them.  So they're on a different plane.

DR. KRAUTHAMMER:  The answer is yes.

CHAIRMAN KASS:  The first proposal, cells from organismically dead embryos, it's ethically acceptable for investigation in humans, but with the IRB-type caution about the need for observing the stringent guidelines, Janet, we will deal with you directly on that other question that you have raised about the way the text reads at that particular point.

DR. ROWLEY:  Yes, but I emphasize that because that's exactly what's going to happen.  So I think to be honest, you have to say that perfectly normal, viable embryos, at least as determined at the four-cell stage, will die, whereas you will then spend vast efforts to try to rescue some cells, potentially normal, but potentially abnormal, from these dead embryos.

I just raise the question:  is this an ethically appropriate way to proceed?

CHAIRMAN KASS:  Okay.  The somatic cell de-differentiation studies, ethically unproblematic.  Is there anybody who would disagree with the conclusion on the second proposal, the blastomere extraction from living embryos, ethically unacceptable in humans at least for now owing to the reasons given in the unethical analysis?

Most especially, we should not impose risks on living embryos destined to become children for the sake of getting stem cells for research, not even for their eventual speculative benefit to the donor child.  Okay to study this in animals.

Is there anybody who would dissent from those sort of provisional conclusions?

Janet?

DR. ROWLEY:  I don't want to dissent, but I think that one should omit the last phrase because it's much more effective to get cells that could be potentially useful to the child if they were needed by that child in the future from cord blood, and this is done as a standard procedure everywhere.

So to take a blastomere to set up a cell line that may be useful for the child is not something I think that the Council should be considering or endorsing because saving cord blood is much better and safer.

CHAIRMAN KASS:  Thank you very much, and that will be added.  That's an important omission.

Are we okay on the others?  Bill.

DR. HURLBUT:  I'm not quite clear what we're doing here.  Are we — you sent the note at the last minute about evaluation of each of the proposals individually.  Are we now talking about including that somehow in our white paper, adding it on as something, or are we just discussing how we feel about things?

Because from a practical perspective, I think we're making summary statements that are at this point in our deliberation on this, whether we intend to go forward in it or not, we are not prepared to make, and I would cite even just one and four, which have been given a nice endorsement thus far.  I personally think that many of the same concerns that Charles has raised could be raised reasonably about one and four.

I mean, take four, for example.  De-differentiation; at first glance we use a certain understanding of what's going on biologically to say, "Oh, that's nice.  We add a few chemicals and it becomes pluripotent."

That's not at all clear what it would involve, de-differentiation, that is.  We don't know if there's a sequential patterning like the building up of a building that's necessary for establishing pluripotency.  That is very likely, as *embryogenesis is a process.

We don't know whether we would need eggs, for example, to do it because cytoplasmic factors from oocytes are probably the chemicals you need to do that.  So it might involve huge numbers of eggs to do de-differentiation.

The objection that is sometimes raised about my proposal is that it's very close to human, although indeed it would not be human by the understanding that Robby and I share.  Well, if you take de-differentiation, you take it down to within one molecule of being totipotent, then is that not close to human?  Just because you came from above?

I think, in fact, the little dialogue that went on there a few minutes ago points to the difficulty of all of these discussions, and just to step back for a moment to proposal number one, if you read Janet Rossant's comments, she's not clear about the moral meaning of proposal number one either.  She says that the scientific definition of the word "organism" is not at all clear.

Besides that, there are interesting and important ethical questions about the practicality of actually knowing if a single cell is either totipotent or if, when taken out of the culture and placed into a womb, it might actually grow.  If you talk to the people who work in IVF clinics, which I've done extensively, they say it's pretty hard to predict.  As Janet Rossant clearly says, they've been searching for this marker of lethality or no longer viability of the embryo and they haven't found it yet.

That's not to say that's not an empirical study, but it also involves a deeper ethical analysis than we've done here.

My understanding of our whole project was not that we were going to do the natural process of a serious ethical Council like ours, which would involve hearing proposals, taking testimony, doing serious deliberation and then comprehensive moral analysis.  We surely have not done that yet for any of these proposals.

What we have done is a pretrial hearing to say whether there's a case that merits serious consideration.  I think we should say that all four of these proposals do merit serious consideration, and at this stage, nothing more for any of them really, except maybe observing embryos; nothing in the way of humanly involved engagement because we're not quite there yet.

If we end up by adding summary statements about individual views of each of these proposals, we will be jumping way ahead of ourselves as a serious ethics council into statements that will be taken by the public and the press as being conclusions, and we're not ready to make judgments.

We've done the pretrial hearing.  We say there's something worth investigating.  To stop at this point would be to stop halfway through the trial when we only have sort of hearsay and a few comments, not cross examination, not cross-testimony.

I think many of the things that have been raised about my proposal I think I can easily answer, but I've not had a chance to do so, and that might change people's point of view.  After all, the whole point of this difficult debate is that we talk it through, not just politically posture.

CHAIRMAN KASS:  Jim Wilson.

PROF. WILSON:  Would it be helpful if instead of revising the last paragraph of our conclusions we cut it very short by ending it with the first sentence?  So that we would say, "Despite these differences among us, and we recognize there are differences, the Council shares the view that the proposals here discussed and others like them that they may stimulate deserve careful and serious consideration," period.  Go no further.

CHAIRMAN KASS:  Does someone want to speak directly to — no, wait.  It's Jim's point in response to Bill's concern.

PROF. FUKUYAMA:  Well, I guess it kind of depends on what you then expect to do afterwards.  I mean, is this a prelude then to another council meeting or two in which we actually do, you know, what Bill suggests and do a much deeper analysis of each of the four, or do we just throw it out there and say, well, someone — because I do have some sympathy for the point that Michael made that if we don't do this analysis, who's going to do it.  I mean, it does seem to be that that's kind of our charge here.

PROF. WILSON:  Well, Michael, I believe, has said that, given the present state of our knowledge, the ethical analysis of these four proposals is, I believe he said, sharp, clear.  I forget the exact adjective, but it was quite positive.  To do more than that requires a substantial advance in scientific knowledge so that we know what we're talking about.

We can't even adequately describe these things.  We're inventing names as we go along, and unless there is more research, we can't have a trial.  We are saying that there's probable cause to go forward and look at these matters, but we don't know whether any of them will pass the test of useful beyond a reasonable doubt.  And that can only come about when science has advanced much further than it is.

So I'm saying all we can do at present, even if we spent another ten days on this, is essentially the analysis we have because that's based on all we know, and therefore, we should simply say these matters deserve careful and serious consideration.

Now, at some point the Council should continue its existence, may gather more information and you can come back and take a closer look, if not us, then other bodies.  But I don't imagine this is going to happen for some time because the research is going to be time-consuming.

DR. KRAUTHAMMER:  May I just interject here, Leon?

But to be completely agnostic here, I think, is a little bit disingenuous.  In the absence of new scientific evidence, would we not here unanimously agree that the removal of a blastomere from a living embryo in order to produce these stem cells would be unethical.  I mean, do we need a lot of evidence on that one? 

Is that number three or number two?

CHAIRMAN KASS:  Two.

DR. KRAUTHAMMER:  Number two.  I mean, what's the scientific evidence that's lacking that prevents an ethical decision here?

CHAIRMAN KASS:  Gil.

PROF. MEILAENDER:  It may just be that I'm sloppy, but I think we've done a good bit actually.  We haven't done everything you might want, Bill, but it's not as if we haven't done a decent amount.

And I think, therefore, that I agree with Michael's general point that we should not simply punt at the end, but we should reach some conclusion. 

I actually think — I mean, as you know, I'm not ordinarily one who cares whether we reach consensus or not, but I think we're not that far from a kind of consensus here.  I don't have a problem with language something like the language Michael suggested that we're prepared to endorse two or three in humans right now.

I'd be happy to say something more positive about three with respect to animal studies rather than just let it go as an assumption, say, you know, it would be good to do the animal work in order to try to determine what actually is happening.

So it seems to me that, whatever reservations different ones of us may have with respect to one or four, those are not reservations that lead us to say science should not conceivably go forward investigating these more.  I mean, after all, our mantra has generally been that science proceeds on as many fronts as are ethically acceptable, and we're trying to figure out whether there are insuperable ethical objections here.

And it seems to me that, whatever differences we have with respect to, well, three in particular, I can't see that there are insuperable objections to our saying something positive about doing animal research in connection with it while regarding it as for now unacceptable in human beings.

So that, granting that there is more that could be done on discussing any of these, I do work with the assumption that we have actually done a good bit, that we've not done nothing, and that we're not that far from conclusions which almost all of us could share even with slightly different intonations about, you know, how we feel about them.

CHAIRMAN KASS:  Jim wants a brief response.

PROF. WILSON:  Thank you, Gil.

I very much share your general view.  Perhaps my effort to reach a conclusion by getting rid of language led me to get rid of too much of it.   Perhaps we could take that first sentence in the last paragraph and say that the Council shares the view that Proposals 1, 3 and 4 here discussed and others like them that they may stimulate deserve careful and serious consideration, and then perhaps add, if you wish, an explicit reference to animal studies.

If you all feel now that two is ethically dubious, I don't believe three at the present stage is ethically dubious from the point of view of further research.  Two from my most elementary scientific knowledge could fall on the other side of the line.

CHAIRMAN KASS:  Dan Foster.

DR. FOSTER:  Well, you know, I think we can have some statement about animal research, but you know, the world of science, if it's perceived that any of these ideas have potential, it will be explored.  I think Bill and a colleague are already planning studies.  I think I read it in some press.  So those studies are going to go on whether we say it or not if there's thought to be scientific viability.

I don't mind mentioning it as a guardian thing, but I don't think that that is a big deal because that's what scientists do, I mean, and this stuff, you know, has been in the papers and so forth.  So I think it's sort of automatic that that will go on whatever we say.

I mean, if it is thought that somebody can do that whether they have moral inhibitions or not, you know, they might go ahead and do that.  So —

PROF. WILSON:  The science may go ahead, but our job is not to direct science.  Our job is to direct policy makers and the attitudes they should have about science.

DR. FOSTER:  I understand that, Jim, but I mean, you and others have brought up about the fact that we need to encourage or we should encourage scientific experiments in animals to see where these things are going.

When altered nuclear transfer came up at the last meeting, I was tremendously enthusiastic about it, and I still really admire Bill's thought about it.  The more I've thought about it and read about it, I've somehow come a little more towards the view that Charles has expressed.

And I wonder if in terms of the conclusion one might alter it a little differently along what Michael has said, that with our current understanding that we believe that one in four have no immediate ethical restraints for potential use in humans; that the issue on three is such that it may well move into this category, but because of the number of questions that have arisen, some in my mind, some are worried about making something that's — in a way, I sort of thought that even though one understands why we use the term "teratoma" and so forth, it might not have been the best analogy to what we're trying to do, I mean, it seems to me.

So I would myself be in favor of the proposal that has come from Michael and Charles to say that, at this state in our knowledge, one and four appear to us to be ethically acceptable and that the potential for three may well move into that category, but at this point we are not willing to do that.

I think I'm in that stage, even though I probably was more verbally supportive of Bill's idea, or somehow it has begun to bother me a little bit.  So I just raise that possibility.

CHAIRMAN KASS:  Peter and then Paul.

DR. LAWLER:  I like the image of the pretrial hearing, that we really don't know enough to make a judgment about any of these, and the more we move towards definite judgments, the more I back away.

I'm not sure I would segregate Bill's proposal, enough though I have objections to it or concerns, and not so different from the ones Dan has, and two big ones that have been mentioned.  I wonder about the prudence of engineering a third category that's not life or non-life but kind of a near-life experience.  This may not be deeply morally problematic, but I wonder about the prudence of doing that.

And I also wonder about using reproductive materials for reasons having nothing to do with their natural purpose, which I think Bill's proposal suggests he would do.

Having said this, this proposal still has promise.  It merits research in animals, and it merits Bill's persuasive work.  He hasn't persuaded us yet, but he's an energetic guy.  He will continue to try to persuade us.

From my point of view, it passes the pretrial hearing test.  It's ready to go to trial, and it's going to be a long trial, a difficult trial, I hope a nationally televised trial.

(Laughter.)

DR. LAWLER:  And I think all of the other proposals finally are in that category, too.  We don't endorse Bill's proposal in terms of experiments on humans now, but he's not asking for that.  It's not like it's something he wants.

With respect to the dead embryos one, that demands investigation, I mean, observation of human embryos.

Number four seems to me in such early stages of development we don't know what we're talking about.  Nonetheless, we can't help ourselves, and number two, the ethical objection raised by Charles and others, I think, is obvious for now, but that, too, can change through further scientific development.

DR. FOSTER:  Well, in terms of four, let me just interrupt there.  There are at least three and maybe four papers that I know about that with small molecules you can at least with myotubules move back to make a myotubule, you know, make fat and bone and so forth.  So I don't think that we're devoid of evidence that that might work.  I don't know about the issue of pluri- to totipotential cells.  I mean, I don't know, but I do think that there is enough evidence on four that you could say that that's potentially a useful thing.

CHAIRMAN KASS:  Excuse me.  Paul is next in the queue, but Charles I know has to leave.  Are you watching the time?  Do you want a last comment before you go?

DR. KRAUTHAMMER:  I'm going to stay another 15 minutes and then go.  I'll wait a little bit longer then.

CHAIRMAN KASS:  Thank you.

Paul.

DR. McHUGH:  Well, I want to come back really into the discussion that Michael gave and make the issue of this product more personal.  I read it and thought it was a wonderful document, very clear, very coherent.  It included all of my concerns in relationship to all of these, and I was so pleased with what it had done, Michael, that I simply read the last paragraph as your sentence, Jim.

And then I think Michael made a wonderful pickup, in other words, in a kind of editorial pickup that we would have, if it were sent out the way we had originally, we would have been marked by other people, and we might well have woken the next day and said, "How did we forget that?"

And so I'm very interested in going beyond Jim's sentence to express what Michael has proposed, and I think Charles and Michael and I are seeing commonly these clear themes as being easily expressed in terms that are the charge of this Council; that these are clearly things — at the present time if new knowledge came around, we might well change our mind in relationship to it, but one and four seemed ethically coherent at the moment.

Two seems to me unless — two is on life supports.  As far as I'm concerned, in order to have two, you'd have to do something very radical to save it.

And three, Bill's suggestion, I think, has sufficiently problematic issues, sufficient red lights, as I put it before, to make us say that has to be something that will go forward in animal research to find out, just as Janet said, that no scientist — for example, I share Charles's view about these things as being creatures.  I share the idea that it's also a kind of pollution of the human genome that I have a yuk factor towards, and I am equally concerned that fundamentally it has — since I think the SCNT normally without fooling around with it also won't become human — I think this is painting the lily, and I think scientists will soon learn that.

On the other hand, I think Bill has made a persuasive argument to do more research.  I come back fundamentally to supporting what Michael said.  The combination of what we did added to the thoughts that Leon's memo had would be a very appropriate final product for this session to achieve.

CHAIRMAN KASS:  Bill, do you want a quick response?  Yes.

DR. HURLBUT:  You know, first of all, I want to say plainly that in raising my proposal, I'm trying to defend the important goods being defended by both sides of this issue and differently expressed by all of us in this Council.

I personally believe that a decent society does not build the foundations of its biomedical science on the intentional creation and destruction of human embryos.  That's a fundamental starting point for me personally, but as a person trained in science, as a physician, as a father of a handicapped child, as a person who has seen the possibilities of the science, I also want to try to open the science.

I think some of you are raising prudential concerns, and you have to put into the balance of the prudential concerns about my proposal the tremendous possibilities and positive goods that could come from it.

Now, I know that, getting down to the crux, I resonate with what Charles is saying and what you're saying.  Red flags go up in my mind, too, but as Leon expressed, some concepts of manipulation of human life are unbeautiful.

Disease is also very unbeautiful, and we do things in medicine that are strange and unintuitive.  We give people a dose of disease for vaccination.  We send in reengineered cells like targeted toxins.  We grow great sheets of skin from cells harvested from foreskins.  We cut the body.  We do things that are not easily and intuitively aesthetically pleasing for the very purpose of a higher good, which is healing.

I, on the other hand, would never favor the creation of something I thought was a living human being for its destruction, but the very point of this difficult dialogue, and I think it was characterized in this exchange here, is we have not as a society nor even as a Council actually contended seriously with the question.  We have not reached a consensus conclusion, nor really even properly deliberated on what is the definition of an organism, an embryo and the moral thing we're trying to defend.

We are in a transition time.  We are at the beginning.  We've gone from genomics to proteomics, the genes, the proteins they produce.  We are at the beginning of the era of developmental biology.  From here on out, those questions, what is an organism, are crucial questions.  I think it's going to be evident in our next session.  What are the boundaries of humanity with regard to chimeras?  What are parthenotes?  What are you going to do with the products that you produce with embryonic stem cell research?  Once you differentiate them, are you going to reaggregate them?  Are you going to grow human parts apart from bodies?  Are we going to have factories of kidneys?  Are we going to grow brains in vats?  It's just simply challenging conceptual issues here that we have not yet contended with.

And just one final point.  Paul, you yourself have argued  and, you know, with a certain sympathy from my side, that what we call cloning for biomedical research, or SCNT, is not really a reproductive process.  It's a lab process.  It's not really the production of a new human being, you've said.  It's an extension of bodily being of the individual.

I have some sympathy with your perspective on that, but am uncomfortable because it's clear that Dolly, if she was a sheep, Dolly was once an embryo.

So I agree it's a proposal called altered nuclear transfer.  In fact, in July 2003, Rudy Jaenisch came to our Council and explained that all cloning for biomedical research, all SCNT, in fact, involves altered biology, and I've got the quote from you here, and these are the words of Michael Sandel, who says, referring to Jaenisch's comments and how your attitude had all along been right, and that, in fact, this produces an entity that is not capable of becoming a human being and, therefore, is moral.

Michael speaks of the vindication of Paul McHugh's attitudes.  Remember?  And then he goes on to say of Rudy Jaenisch's comments, "And he argued that there is a difference."  He's affirming now that this entity produced by cloning is not a human being.  "And he argued that there is a difference, a biological difference, with a possible ethical significance between a zygote and a clonote, between a fertilized embryo and an artifact created in the lab, and he was told that this is an eccentric position," namely, you were told that it was eccentric.

Well, you argued this.  Rudy Jaenisch confirmed it, and all I'm trying to do is really confirm it biologically.

Janet Rossant has —

DR. McHUGH:  Let me just say, maybe just finish that point.  That's a very good point, and my point is this then becomes making an ANT; it becomes painting the lily, and no scientist will bother to do it for all of the reasons that Janet has said, that is, that it will consume eggs.  It will ultimately — you know, it is my opinion the SCNT does produce, in the primate, a nonviable organism.

Other people disagree with me on that, but I don't think that the step to then poison  it  further .-

DR. HURLBUT:  Poison it?

DR. McHUGH:  — is even necessary.

DR. HURLBUT:  What are you talking about?  It has already got five percent of its genome improperly expressed even in the newborn form of clones.  There's a massive reorganization of the epigenetic factors.  This is just adding a sure confirmation of it.

DR. McHUGH:  Okay.  Well, I mean, there is our distinction.  I don't think you need to do more than is already damaged in it.

CHAIRMAN KASS:  I'm going to try to hold a bit of order.

DR. KRAUTHAMMER:  I'm sorry, but may I make just a final statement because I'm going to need to go, if I could just respond?  I don't mean to interrupt.

CHAIRMAN KASS:  Your final statement, not everybody else's.

DR. KRAUTHAMMER:  Yes, I did mean mine.  I wasn't speaking on behalf of the Council.

CHAIRMAN KASS:  No, thank you.

DR. KRAUTHAMMER:  Look.  I'm sympathetic to Bill's seriousness and his attempt to bridge the difference between our ethical concerns, our scientific concerns, and I happen to share the principle that you enunciated, that we ought never create human embryos in order to destroy them, which is why I support the use of discarded embryos in IVF clinics, because I consider that a different category, and why I oppose research cloning.

But I believe that a teratoma is a tragedy, and we ought not be creating tragedies deliberately.  That's just a shorthand.

Given that that view at least has some support here on the Council, I'd suggest that we not be entirely agnostic; that we speak, if we have a consensus, as I think we do on numbers one and four, express it explicitly.  I think it's an advance.  It will help to encourage that research and legitimize it.

I would also add the word "encourage."  I think you want to discuss that a little bit later, Leon, but I don't see any reason why that ought to be only implicit.

We ought to explicitly rule out number two, which I think we have a consensus on, and of course, when we preface all of this by saying that the science is shifting, and if the science evolves in a way that causes reconsideration, we're open to reconsider all of these numbers one through four and perhaps end up with three.

I happen to oppose it in principle, but I'm speaking only personally, but perhaps we could state consensually that there are some ethical issues still unresolved, and we would, therefore, perhaps permit it in animals and not in humans, although I would oppose — I mean, I would not oppose, but I would be a little bit troubled by pursuing it in principle.

But I would offer that as a way to perhaps bridge our differences, have a statement that would be strong, and would launch an area of thinking in research that I think would be extremely useful and beneficial.

And I apologize for leaving in the middle of a brawl.  It's always interesting and enjoyable, but see you next time.

Thank you very much.

CHAIRMAN KASS:  Thanks, Charles.

I have Ben Carson, Diana, Janet, Gil, Michael, Frank.  I want to hear from everybody.  That means Rebecca and Alfonso, too, before we break.

What did I say?  Ben.

DR. CARSON:  Okay.  First of all, I thought the white paper was well done.  It was a good overview and very easily understood.  I think that's very important.

I would like to say that, you know, three years ago many of the things that we're discussing in terms of these four proposals would not have been on the table, and yet there was a raging debate going on about stem cell research and its potential for good.

I think we need as a Council to make sure that we do ferret out those things in these proposals that we agree with unanimously because we want to maintain our relevancy, and we don't want to be so tentative that nothing we say means anything.

But I think at the same time we need to recognize that there are more than just these four proposals.  There are going to be a lot more than just these four proposals, and we don't want to give anybody the impression that these are the only things that are being looked at and considered.

CHAIRMAN KASS:  Thank you very much.

Diana.

DR. SCHAUB:  Yeah, it seems that there are a number of suggestions on the table about how to slice these, and some want to put one and four in one category and two and three in another category, a yes category and a no category.  Others would slice it differently and put one, three, and four in the yes category and two in the no category.

I guess it seems to me that the way it's stated in Leon's memo is pretty good.  I would be in favor of not trying to lump them into categories, but discussing each one separately.

And I think the statement that's given here is maybe pretty accurate about what the consensus is.  I would be in favor of somewhat strengthening the endorsement of number three.  I mean, the three elements in there should remain that we think it's as of now ethically unacceptable in humans, but despite the serious ethical concerns that some folks have about the proposal, we do think it's worthy of being pursued in animals.

I mean, I guess I'd sort of like to know is there a consensus about that, about pursuing it in animals, and if there is, then that could be stated somewhat more strongly in the assessment of number three.

CHAIRMAN KASS:  Thank you.

It is how to find the right balance that this discussion is supposed to give guidance, and that was a very useful suggestion.

I have Janet, Gil, Michael.  Michael, do you want a last word before you go, too?

PROF. SANDEL:  I apologize that I have to leave early.

First, two comments.  First, on the moral arguments, I think it's very difficult to read the pages 16 through 19, the ethical analysis contained in the white paper unless one has, as Bill may feel he has, persuasive arguments to each of those four ethical objections and not to regard proposal number three as morally dubious.

Those are devastating arguments, I think.  I'm talking now about the ethical analysis in Proposal 3 on pages 16 to 19, not about the conclusion.

And different of us weigh those, find those arguments some more persuasive than others, but the one that I find most persuasive, just to go to the moral merits for a moment, I think that regardless of our other disagreement about the moral status of the embryo, there were some of us who have an equal moral status view and others who had an intermediate status view, and we had long arguments about that.

But it seems to me that even on the intermediate moral status view, on that view to do the stem cell research and to destroy the blastocyst does carry a certain moral burden that requires that the use be restricted to lifesaving and morally weighty purposes so that it couldn't be used, for example, to develop a new line of cosmetics.  That's the intermediate moral status view.

Even on that view, there is something, and here I speak just for myself, something morally creepy about genetically engineering a mutant embryo-like being and then saying with that being you remove even the moral weight of justification that this must be used only for especially important lifesaving purposes.

And so I think that's captured in Charles's invocation of the kind of saying it's weird.  If it's somewhat human, it's weird.

Number three, objection number three doesn't depend on any scientific discovery.  Number three, it's the third ethical objection laid out worries about it, regardless of what the creature or the being or the thing created, the artifact.

So I just wanted at least to state why even — well, I don't think it depends what moral status one attributes to the embryo; that it's still possible to make sense and be moved by some among the four moral objections laid out in the white paper.

CHAIRMAN KASS:  Thank you.

On that point, I'm going to keep Bill from responding on this. 

DR. HURLBUT: Please.

CHAIRMAN KASS:  Very briefly, but I really want to keep — there are people waiting to get in on this.

DR. HURLBUT:  Michael, you're saying that the slight difference between what I'm proposing and what Paul called the gilding of the lily; you're saying that that is more of a mutant human being in some sense, those loaded words?  You're saying it's more than what you've called for publicly, the endorsement of SCNT?

And second —

PROF. SANDEL:  Yes.

DR. HURLBUT:  — I want to ask you.  I assume you've read my comments that I made for the President's Council's first report.  Have you, in fact, read through them carefully?

PROF. SANDEL:  Yes.

DR. HURLBUT:  And you don't find any of those — can you cite back for me my arguments perhaps?

CHAIRMAN KASS:  Bill, I think —

DR. HURLBUT:  I mean, it's like I don't think you've read them, frankly.  I don't get the sense of —

PROF. GEORGE:  Bill.

CHAIRMAN KASS:  Bill, I'm going to intervene, and let me say that I think Michael has pointed to the place in the analysis where there are ethical objections to ANT itself, not depending on slippery slope, not depending on the egg question, not depending upon the question of whether answering this question which can only be empirically or at least partly empirically answered.  Is this artifact really a defective embryo or something else?

There are people who have these kinds of concerns.  Here is the place where I think the document has been one-sided, and if Bill has answers to these objections, as he says he does, then that document has to be corrected so that those particular objections can be countered.  I think that's simply only fair.

We've made the slippery slope arguments and then finished by remarking that, look, slippery slope arguments always presuppose that people cannot find the means of finding some boundary where you can hold the line between what's acceptable and what's objectionable, and I think we ought to balance this up and similarly add something on the egg question.

But I think, look, everybody has to acknowledge — Bill has to acknowledge, and I think Michael is speaking for himself and perhaps others — that there are some people who do find this particular kind of practice aesthetically or morally troublesome to the point of dubious and in some cases unacceptable, and that's a difference of ethical perspective on this which we simply have to acknowledge.

Now, there are other people in the room who have already spoken, who notwithstanding their worries about this are prepared to say with you that we do lots of peculiar and aesthetically problematic things in medicine, some of them even morally complicated, and that doesn't necessarily rule them out, especially if the animal research shows great human promise, and I think there's a way of fixing this document to make sure that this particular kind of — Michael reads that, and he says it's sort of devastating, and it's partly devastating because the other side has not been presented in that particular paragraph, and I think if Bill can give us a response to that, that fills out this document and improves it.

I'm simply going to go to the queue.

DR. HURLBUT:  May I —

CHAIRMAN KASS:  No.

DR. HURLBUT:  I'd like to withdraw my last comment to Michael.

CHAIRMAN KASS:  No.

DR. HURLBUT:  May I withdraw my last comment?

Michael, I'm sorry.  I didn't meant to imply you hadn't read my statement, but I do think that I have serious arguments that have not been discussed properly.

CHAIRMAN KASS:  Okay.  I have Janet, Gil, Rebecca and who else has been hiding out?  Frank and Alfonso, and I'd better say something, too, at the end.

So, Janet, please.

DR. ROWLEY:  All right.  Well, I'd like to deal with the issue raised on page 19 under the rubric of is it scientifically sound because I think Charles and several others in the text of this part of the document talk about teratomas.

Teratomas are chromosomally very abnormal, and that's not what we're talking about here.  So I think the analogy with teratomas is potentially an unfortunate one because the ultimate goal of this research, of all stem cell research or most of it, is to think about ways that stem cells can be used to treat very devastating human disease.

And the proposal here is going to take a nucleus before it is introduced into an oocyte or an oocyte-like cell.  It's going to change, potentially change only one gene that then prevents that cell from developing into an embryo, but the critical thing, as pointed out on page 19, is that this has to be fully reversible without residual abnormalities in the derived cell.

So you want to make the smallest possible genetic change to prevent the cells from forming an embryo and a change which will be fully reversible so that the cells that you finally give to a patient to treat a disease are, in fact, functional cells.

Now, that's like saying that an embryo that has a defect, say, in the disease of hemophilia, for example, the embryo has 29,999 genes, all normal human, all going to lead to a normal developing human with brain function and things of that sort, but one gene is abnormal.  The proposal to work has to be that a single gene that is essential for developing an embryo is disarmed, if you will, before the nucleus is inserted into the oocyte, but then is fully reversible afterwards.

And I don't see how one can look on the developing cell with essentially all normal genes except one as any different from an embryo carrying a defect that leads to hemophilia, that leads to muscular dystrophy or something else.

So it's a fully human embryo with one gene defect, and for me that's the equivalent of a human embryo.

CHAIRMAN KASS:  Let me continue in the queue.  Gil and then Rebecca.

PROF. MEILAENDER:  As far as I can tell, everyone or almost everyone agrees that the basic structure and analysis of this paper is very good.  I mean, everybody thinks it's well done.

And I've been trying to figure out sort of how to describe what exactly it is that we're arguing about.  I think in some ways we're actually arguing about some old questions and not about the question that's here.

I haven't heard any proponents of or any of those who are favorable toward alternative three argue that  it should for now be done in human beings.  I have not heard that.

I have not heard any of those who have reservations about it argue that it would somehow be morally wrong to proceed to do it in animals, though even if those studies proved to be promising, they might still have the yuk factor and have a moral objection to proceeding in human beings, but I haven't heard arguments that it shouldn't be done in animals.

If that's right and, you know, subject to correction from anybody who thinks differently, whether they're favorable or unfavorable toward alternative three, it doesn't seem to me that we have a deep disagreement.  We may have a difference in tone about how many exclamation marks we want behind the sentence that says it would be fine to proceed with this in animals, but that's about what it amounts to.

The only thing that would be disingenuous would be somehow to say, while we normally say that science should attempt to proceed on every ethically acceptable front, we know in advance that this is not an ethically acceptable front.  I mean, that, I think, would be a mistake.

But if you say do the basic work in animals, see what happens with however many exclamation marks we together want at the end of the sentence, I don't think that we have a deep disagreement about that.

So to me that's where it seems we are, and it doesn't seem to me to be a bad place to find ourselves.

CHAIRMAN KASS:  Why don't you hold off, Bill?  Okay.

DR. HURLBUT:  My one comment to Gil is I agree with you, but I think that equally applies to all four proposals.

Until you are clear about what four is producing you certainly can't say it's ready for human use, and in a way that's true also of one.  Until you're absolutely clear that the single cell from an eight cell embryo is not totipotent, for example, you can't say that you can go proceed with human use of this technique.

All four proposals, with maybe the exception of two, offer promising prospects, but also are at the stage of being investigated.

CHAIRMAN KASS:  I think I know how one could write such a conclusion that makes it perfectly clear that these are provisional findings of a preliminary hearing, and that this is not the end of the ethical analysis or the ethical discussion.  "On the other hand. . . ."

There's a way to write this that begins from where Diana is and where Gil is and takes into account your precautionary concern that this ethical conversation, even about the ones that seem to us relatively innocent, may turn out not to be so innocent on further reflection, but that they pass a certain kind of minimal ethical threshold to say these are things worth considering talking about, and the Council is not just punting, having done this analysis.

I think there is a way to do this and find a kind of general acceptance around the table, and I certainly welcome the chance to try to produce such language, not here on the spot today, but in short order, and the troops in the office know how to do this very well.

Rebecca, you've been very quiet.

PROF. DRESSER:  Well, I don't have deep disagreement with much of what I've heard.  I don't have an objection to saying it's permissible to go forward with these investigations in animals.

I think we should acknowledge that science is always or often very surprising, and it's not clear that any of these things will develop to the point where people are seeing clinical applications.

If certainly three — and, of course, I share the concern about two and the risk to any children who might be born from any procedure — but for some of these others, especially three because it requires eggs, if the science does go forward and prove to be promising and then the question comes, well, should we try these in humans, I think there will be very serious ethical considerations, just as there will be and are with SCNT in the fact that you have to use the human eggs.

So I would go along with the trend of your proposal in terms of no ethical objections to looking at this in animals.  There could be some serious issues, depending on how the science turns out, if the step toward humans occurs.

CHAIRMAN KASS:  Thank you.

Alfonso.

DR. GÓMEZ-LOBO:  My apologies for coming in late today.

My overall inclination is to endorse the document.  I find it very good, very clear, and ultimately solid.  But my main reason for endorsing it is because, contrary to an E-mail circulated by Michael Sandel, I don't think we're in a position of making any definitive moral judgments, but I know that by now we have a consensus on that.

Let me just mention this.  Of course, there are questions of the development of the science.  If some of these proposals simply don't work from a scientific point of view, of course, it's going to be moot and, thank God, we're not going to have to worry about it.

But we need time not only for the science, but also for the ethics because I think that these are quite new ethical problems, and we need time to consider externalities, if you will, or other aspects that are not considered here.

Let me just give one example.  I have very serious problems with Proposal 2 because of the reasons just mentioned.  It's a case of battery really to go into the body of a human being and extract cells.

But number one also has its problems because there are important disanalogies between the practice of extraction of organs for transplantation, say, after an accident and the circumstances of the waiting for the death of an embryo in order to extract the organs.

I think that one can imagine several scenarios that would make it morally very problematic.  Up to now in transplantation ethics, one of the key demands is that there be a drastic separation between the physicians dealing with the person who has died and the team of transplantation surgeons that move in to extract the organs, whereas here we'd have practically the same team as if around the deathbed of someone waiting for that embryo to die in order to extract the cells.

Now, that's just one example which occurred to me is the kind of problem that needs time.  There may be others, or they may be resolvable.

So basically, you know, I praise the document, and there may be need to include some responses from Bill and then to modify the last paragraph.

Thank you.

CHAIRMAN KASS:  Thank you.

Frank.

PROF. FUKUYAMA:  Well, I don't know.  I guess I'm not so sure I'm happy with the document just from listening to this discussion today, and I'm not quite clear, Leon, what you think the procedure from here is, that if we endorse the document, you're just going to get some language from Bill to strengthen, you know, his objections.

Because as I'm listening to this discussion, I'm even more confused about what I think about this issue because there's a huge difference between creating something that looks like a teratoma and creating something like what Janet suggested, which is basically a complete embryo with just a kind of minimal, you know, number of genes changed.

And I would think that it's also something where the scientist creating this entity could actually use some ethical guidance because I presume that there's a certain, you know, range of variation in exactly how many genes they could change that would make it look, on the one hand, more like a teratoma and, on the other hand, more like a real human being.

So I don't think it's simply enough to say, well, we can't say anything more ethically about this until the science goes ahead and, you know, does a proof of possibility study in animals.  I'm just not at all certain that we've really explored this whole set of issues adequately.

Second, just a brief comment I'd like to make.  I know this is an ethics council, and we're not supposed to deal with politics more broadly, but the political landscape on this really has changed since we first started discussing stem cells at the beginning of this Council because this proposal back then was a way to break this logjam at the federal level where the funding was blocked.

Now we're in a very different landscape where it looks like, I mean, first of all Proposition 71 has opened the floodgates to stem cell research in a much more straightforward way.  Every state is reacting to that.  The university that three of us, you know, teach for is under big threat because all of the postdocs now are going to be heading out to a university in California to get, you know, some of this, and some of the senior researchers may be departing Maryland as well.

And what we're heading towards is actually — Gil and I were discussing this yesterday  off line — but a kind of blue state/red state federalism in which different types of scientific research under different ethical guidelines are going to appear in different parts of the country because of the blockage and the inability to get a federal policy.

And so it's something to bear in mind that, you know, I'm not quite sure who we think we're giving guidelines to because, in fact, the nature of the political landscape in this country is such that we're actually going to have about 50 different, you know, state policies on this issue.

And it does weigh a little bit in the ethical considerations because if you think that stem cell research in a much more straightforward way is going to be lavishly funded on a state level, then this as a solution, you know, Bill's proposal, number three, as a solution to the blockage, you know, it becomes a little bit less salient because there is really an alternative way to get to the same, you know, body of scientific knowledge.  You just have to move jurisdictions a little bit.

CHAIRMAN KASS:  Thank you.  Peter, I think, and I will have a comment, and then we'll take a break.

Peter.

DR. LAWLER:  In light of what Frank just said, it's perfectly true, right, that every thing we're doing today presupposes this.  It would be a good thing if we could acquire embryonic stem cells without destroying embryos.  That would be an improvement in our present situation.

CHAIRMAN KASS:  Pluripotent, not embryonic.

DR. LAWLER:  Sure.

CHAIRMAN KASS:  Okay.

DR. LAWLER:  Pluripotent.  It would be better if we could do that.  That would be an improvement on our situation.  For some, that improvement would be merely prudential.  You could get funding.  That may be becoming irrelevant.  I admit that.

But it may be good simply because the moral division in the country, which is tragic in a certain sense because there are well- intentioned people on both sides, would come to an end.  It might be a good thing; I think it would be a good thing if there could be a technical solution to our moral problem, and it's reasonable to hope there could be a technical solution to our moral problem simply because the moral problem exists, it would seem, at a certain level of technology.

So there's a reason to hope that technology will cause us to be able to overcome or surpass this problem, but we also have to admit, I think, that none of these four possibilities are anywhere close to being acceptable at this point.  It remains to be seen.  It remains to be proven, and from that point of view I agree with many of the criticisms or reservations expressed about Bill's proposal.

I'm not so clear it should be treated differently finally from number one and number four because I think they're fairly problematic in different ways, too.  So I would encourage further research in one, three, and four, with the acknowledgement that none of this has been proven useful in terms of overcoming the moral problem we have now.  I mean it really is, to repeat, a pretrial investigation.  I think one, three, and four do give us probable cause and we should go forward.

CHAIRMAN KASS:  You want a comment and then I'm going to wind up.

DR. HURLBUT:  I just want to make it clear I never proposed making teratomas.  Teratomas I drew as an example of how nature produces an entity that is not in my mind a living being.  I would not as a physician have any problem doing a therapeutic preemption of that process.

I just used it as an analogy.  What we're talking about is something that is more like an inner cell mass.  Janet Rossant in her comments to us said, and I quote, "Each cell has its own course of action and will continue to divide and differentiate even if isolated from other cells."

It should be possible with a small change that has a very dramatic effect on the coordinated coherence of the integrated unity of the process of its organization to preempt the organismal nature of what's created.

We do not know yet how pluripotent cells or embryonic stem cells are actually formed.  Is it just a matter of having  the cytoplasm in the cell and then just waiting until it grows like Janet Rossant implies, that each cell has its own trajectory, or does it need the perfect and synchronized interaction of the entire organism?

That's an empirical question, however, one that can go below our argument about whether or when the embryo had moral status to whether or not it is an organism at all.

It's the idea that is to get below our problem.  This is a transition time in the history of science.  In the end of the 19th Century, we overthrew a simplistic vitalism in favor of studying biochemistry.  It's a little harder for us to understand and to intuitively grasp with our natural moral sentiments that developing trajectories, too, can be separated off from the totality of the organism.

But we will learn that in our era of developmental biology, if we're going to go forward at all in developmental biology, we're going to have to do the same thing they did in biochemistry, that is, break the parts apart from the whole so that we're not violating human dignity while we have a tool to study it all.

I admit that my proposal, as with all of the other proposals, raises interesting and important questions.  My proposal also offers a tremendous breadth of flexibility and could provide much or most or all of what the scientists hope and I hope we can proceed forward investigating.

It raises important questions.  Our role as a Council, given to us by the President, was to engage and educate the public.  This document does that in that it initiates an important conversation.  It was never intended to be a comprehensive analysis.  If that were true, we would be at fault for having done an inadequate job, never hearing testimony, never really having a proper deliberation.

But, in fact, what we've done is we've produced an initial cursory view that raised some questions like little red flags for sure, as does all of SCNT, as does all of harvesting of IVF embryos that are left over, all these things, but just saying that in the deadlock of our country, the serious question could be perhaps solved by a third option that we hadn't really thought through carefully enough yet, and wouldn't that be instead of red state medicine and blue state medicine, instead of people having to come into the hospital 20 years from now and checking a box and saying, "I don't want anything developed in California," wouldn't it be better if we found a way to go forward in a coordinated, collaborative research on a national level, funded by the NIH with proper peer review, proper ethical overview?  Wouldn't that truly be a triumph for humanity?

If that's true, then it makes it worthwhile doing the hard work that we have initiated in this Council that should be taking place on a broader level in our society, the hard work of thinking through these serious proposals.

CHAIRMAN KASS:  I'll try to be brief.  I think I concur with — well, let me say this.  I think we should try to find a way that the conclusion does a little more than what it does in this particular draft where it says some of us this and some of us that, et cetera, but do so in a way that indicates the strict preliminary character of these judgments, since there's a great danger that what is going to be written in the conclusion, especially in this town, will be treated as dictum, and everything else, the analysis, just disappears, and it will look like the Council recommends thus-and-such.

That I don't think we are exactly in a position to do for the reasons that have been so both well expressed and well reflected in the comments.  I think there is a way to go partly from this second memorandum to the Council, to introduce certain kinds of greater ethical cautions about the proposals that we think pass the minimum test, to revise the way in which the discussion of the biological artifacts — when you indicate that there are these serious concerns, but to adopt something like Diana's approach so that what's written at the end really reflects the diversity of opinion here, the tentative character of the opinion here. 

I think no one has answered Gil's challenge.  No one here has really said that Bill's proposal should not now be investigated in animals, that we think that there's an ethical bar to doing that, which was all that that proposal was in the beginning.

And I think if the Council is willing to trust me and the staff to produce a revision of the conclusion for your consideration, we could do the rest of this by mail.  Is that an agreeable thing?

And of course, line edits and things of that sort are welcome, but we had better have them soon.

Frank.

PROF. FUKUYAMA:  Okay, but then do we just drop the subject after that?  What happens subsequently?

CHAIRMAN KASS:  Well, it seems to me let us undertake — let's step back from what we've done here, think about it a while and see where one wants to go next on this matter.

None of these individual proposals may pan out.  Landry and Zucker, by the way, have submitted their proposal for IRB approval at Columbia and they are, I think, planning to go ahead with this.  I know that Bill is in collaboration with some scientists who meet already to try to do some of his work in animals.

And to my astonishment, the various kinds of findings of these multipotent cells now in multiple places has just not gotten the kind of attention that I think it deserves simply from a scientific point of view to try to understand why is it so easy to find these multipotent cells in bone marrow, in addition to the mesenchymal cells, in addition to the hemopoietic cells, and what do they mean?

But the interesting thing is, in fact, to suggest that there really might be room for creative thinking, that these proposals might, indeed, stimulate other ones, and no one is saying that we're not going to continue to perhaps have our disagreements about embryonic stem cell research.  There will continue to be political battles over it, I'm sure, in this session of Congress.  The states will do as they will.

Some of them will produce bans and other ones will, you know, produce a windfall, and that's the way we are, but we do have an audience here.  We have monitored stem cell research.  Here is something that contributes to that discussion, and I think we do a service if we put out this document suitably concluded, suitably corrected, and then think further down the road what would come next.

Let's take a break.  We're 20 minutes over, but I think it was important that everybody get their views expressed.

Could we make this break short?  I know people have to leave early.  Let's come back in 12 minutes or so, and we have a session on chimeras.

(Whereupon, the foregoing matter went off the record at 10:20 a.m. and went back on the record at 10:34 a.m.)