PCBE: Transcripts (February 13, 2002)

CHAIRMAN KASS: Could we get started, please? I would like to call on Dean Clancy to open the second meeting of the President's Council on Bioethics.

MR. CLANCY: Good morning and welcome back to Washington. You are good to go for this meeting. It is all legal.

One quick announcement. Members and staff are required to receive an ethics training at least once a year. An ethics attorney from the Administration will be available at 5:00 o'clock to discuss the ethics rule. Until then, please bear in mind that as federal employees you may not take part in a discussion of a particular matter that is likely to have a direct and predictable effect on your own financial interests or the financial interests of your immediate family or employer. When it doubt, refrain from weighing in the particular matter under discussion.

CHAIRMAN KASS: Thank you. I would first like to welcome Alfonso Gómez-Lobo , Professor of Metaphysics and Moral Philosophy at Georgetown.

It's nice to have you with us, Alfonso, and glad to see you looking so well.

DR. GÓMEZ-LOBO: Thank you.

CHAIRMAN KASS: I would also like to welcome our special guest, Dr. Irv Weissman, the Karel and Avice Beekhuis Professor of Cancer Biology, and Professor of Pathology and Developmental Biology at Stanford, and the Chair of the National Academies Panel on Scientific and Medical Aspects of Human Cloning, the topic of our discussion later in the morning.

I would like to announce to all members that our web site, a rather spartan one for the time being, is now functional. You can find us at www.bioethics.gov. You will find the transcripts, unedited, posted there, as well as Working Papers and other additional matters.

Lunch for council members will be in the Club Room where the continental breakfast was. The evening for members is free.

If you have logistical questions, please see Emily Jones, who is, I think, standing. There is Emily in the back.

Would you raise your hand?

And people with media questions should see Diane Gianelli, our communications director, in the back.

As Dean said, we will have a lawyer with us at 5:00 this afternoon to deal with any questions we might have.

You have all received the announcement of the subsequent meeting dates. Please hold all of them for the rest of the calendar year. We will not use them all. There will be no March meeting. We are missing four members and, quite frankly, it is something of a rush to get these things set up. We would have to have the next meeting planned by two weeks. So between this meeting and the meeting on April 25-26 will be the time to collect comments from all of you and for our staff to begin to prepare drafts of documents for discussion at that time.

I want to begin with some remarks which will then make a transition into the topic of the first session.

I want to remind us of the charge that was given to this Council: "To advise the President on bioethical issues that may emerge as a consequence of advances in biomedical science and technology."

To offer sensible advice for action, we must first seek clarity in thought. We must examine carefully and critically the specific ethical and policy questions related to biomedical advances. Yet this modest way of describing the work of public bioethics belies the weightiness of our subject. Many of the ethical and policy challenges we shall increasingly face arise because of new and foreseeable powers to intervene in the human body and mind in unprecedented ways and, in some cases, for indeterminate ends.

Though these powers are being acquired as part of the project to cure disease and relieve suffering, their acquisition often raises serious moral questions and their possible uses go beyond the goals of therapy for which they are first sought. Everyone understands, even if only dimly, that how we use these powers could make a very big difference for what it means to be a human being, for us and especially for future generations.

Precisely for this reason, the ethical issues we face necessarily go beyond the utilitarian concerns of ordinary technology assessment, which confines itself largely to questions of "Will it work? Is it safe? And how much will it cost?" They even go beyond the traditional questions of medical ethics or even the ethics governing research on human subjects, with its reliance on informed consent or its application of the abstract principles of "beneficence, respect for autonomy and justice."

To develop a bioethics that does justice to the subject, we need to develop a view that is broader and deeper. We must, to begin with, take pains to locate the new biomedical developments, both with their promise and their peril, within the larger context of human life. We must not merely reactively respond to the potential consequences of this or that particular technological innovation. We must rather prospectively try to articulate the human goods, activities, relationships, and institutions that we wish to defend in advance. Developing the ideas, questions and approaches for a "truly human" bioethics is one of the prime goals of this Council, one that we shall pursue both thematically and, I hope, by example, as we tackle our particular topics.

At our first meeting, we spent roughly half our time explicitly reflecting on how we should conceive and approach our subject. Using Hawthorne's story, "The Birthmark", we considered the meaning of a one-sided pursuit of the otherwise noble struggle against what Bill May called "the un-elected marks that go with our birth," which include -- whether we know it or not -- disease, decay, and death itself.

And we struggled with the question of the extent to which this aspiration is or is not part of the aspiration of modern science and the culture that celebrates it.

With the help of Gil Meilaender's paper, we took up some of the essential themes of a bioethics true to the character of human life: Questions about freedom and its limits; questions about the relationships between the generations, the nexus of connection that we owe to the fact that as finite beings, we beget and we belong in families; questions about the project to relieve suffering and its moral standing among other human goods, as well as questions about what means we may morally use to attain this worthy goal.

In the discussions that followed, people spoke about human equality and human dignity, though with little specification given, as well as about the dangers of trying to subdue the mysteries of life or to seek to exchange our position in the world as "imperfect recipients of a gift" for one of "flawed manufacturers, controllers and designers." We have much more to do on these matters and we shall in future meetings schedule time to consider them explicitly.

For this meeting, however, we shall spend all our time on human cloning, our first short-term project. It is my hope -- nay, my expectation -- that the way that we shall proceed with our exploration of human cloning will show signs of our striving for the richest possible treatment. This means concretely thinking about cloning in the context primarily of human procreation: What it means to have a child; the meaning of "origins" for one's identity and sense of self; what it means to regard the child as a project or a product rather than as a gift given; the difference between "begetting and making"; the balance between what Bill May called "accepting love" and "transforming love" of children; the relation between the freedom to have a child and the great limitation of freedom implicit in the duty to protect, nurture and educate the child; and other comparable matters.

It also means thinking about cloning in the context of the progress of biomedical science, as well as the growing technological powers to assist and control human reproduction, and to influence human genetic endowments.

These considerations reminds us that we are taking up the cloning question not only because it is timely and a matter of intense public discussion to which we have been asked to contribute. Indeed, we can contribute most fruitfully to that discussion especially as what we say keeps these larger contexts in mind. We are mindful that cloning intends not only to produce a child but a child of a particular and approved genetic endowment; in this sense cloning is discontinuous with IVF and stands as a possible forerunner of future efforts at genetic design and even eugenics.

We recognize that the argument about what to do about cloning is, in fact, also about who should bear the burden of persuasion or of proof regarding the introduction of such radical new technological alterations of human life. It also makes explicit the complicated relation between science and society, as freedom of inquiry, innovation, and medical research may be threatened or limited, rightly or wrongly, by public strictures. A broad view makes clear that there is more at stake in the cloning discussion than cloning itself.

The logic of our meeting begins with questions of terminology, moves to the scientific and medical aspects, continues with the ethical issues connected to reproductive and research users of cloning, and concludes with a discussion of the policy issues tomorrow.

Turning now to the theme of this first session, I want to make just a couple more remarks. The first task of any serious and thoughtful inquiry is a self-conscious consideration of how the topic should be described. Terminology matters. The answers one gets are no better than the questions one poses and the questions are shaped by what one chooses to call the matter in question.

Human speech is necessarily precarious and contestable. The word is not the thing. Always there are dangers of mischief and misunderstanding. There is risk of imprecision, euphemism and the ever present temptation to win a moral argument by choosing focus group tested soothing usages.

In our area of bioethics there is an additional and crucial danger of terminological distortion. What are fundamentally human activities are frequently described in merely technical terms and the choices presented are described medically and technologically rather than humanly and ethically. This is especially likely to happen where bioethics proceeds reactively in the face of a new technology, rather than prospectively from the vantage point of human activities involved.

For example, in considering the ethical issues of assisted reproduction, it will be one thing to frame the questions in human terms of having and bearing children and quite another thing to frame it in the scientized (sic) and medicalized (sic) language of reproductive technique and medical risk alone.

As it happens, there is a great deal of confusion about the terms used in discussing human cloning. There is honest disagreement about what names should be used, and there are also attempts to select and use terms in order to gain advantage for a particular moral or policy position. It is terribly important to try to be accurate and fair in the matter of language. Efforts to win the moral argument by Orwellian use of speech must be resisted. This is not just a matter of semantics; it is a matter of trying hard to call things by their right names; of trying to fit speech to fact as best one can.

We should not only stipulate the meanings we intend by our use of terms -- that we must do -- but we should also try to choose terms that most accurately convey the descriptive reality of the matter at hand. If this is well done, the moral argument can then proceed on the merits without distortion by linguistic sloppiness or chicanery.

It is for this reason and for the reason that this question came up so frequently in our discussions last time that we begin our meeting this time with a discussion of terminology. The basis for that discussion is Working Paper 5, a rather detailed analysis of the difference between the what, the why and the how of these activities. We have also had e-mail comments from Gil Meilaender that are included in your briefing book and a late submission came yesterday from Stephen Carter, which is before you in the packet.

I should say, by the way, that you have other materials before you. Some of them provided by the National Academies of Science, and they will be relevant for Dr. Weissman's presentation.

The goal, I think, for this session is simply to discuss the terminologic question as that has been prompted by the Working Paper. The end of the Working Paper has -- offers a certain conclusion as to what it seems proper to mean by human cloning, distinguishing the what, the how and the why. Refer to page 6 of the Working Paper. It then goes on to describe reproductive and research therapeutic cloning in terms of that discussion. And it concludes with a question posed for us: Having done this linguistic analysis, so what? I mean, do we simply make clear how we are using these terms, appending to it this analysis or some corrected version of it so that everybody at least knows what we mean or shall we creatively try to find some other way of speaking about these matters that might not fall prey to the difficulties inherent in any choice that we make?

But, first, I think we should discuss the questions raised by the Working Paper and whether that description is adequate, and then try to figure out what, if anything, we should do to -- what terms we would like to adopt.

With that, I would open the meeting for discussion of the Working Papers and this topic.

Michael, please.

SESSION 1: HUMAN CLONING 4: PROPER USE OF LANGUAGE

WORKING PAPER #5: ON TERMINOLOGY

DR. GAZZANIGA: In the spirit of reducing linguistic sloppiness, speech as fact, if you look at the two definitions there, which basically are what are at stake here in terms of us trying to determine what we mean by those, the reproductive cloning, as stated there, is creating a living cloned human embryo. We stopped there because that is how each definition is launched. I think the case could be made that using the word "creating" is loaded; "living" is redundant; and "embryo" is flat out wrong.

So, in fact, if you think about what is going on is that we are synthesizing a totipotent cell for...and then the rest of the definition is fine. But what is going -- "embryo" is defined in biologic terms as "a fertilized egg, which is two haploid cells coming together, to grow into the organism in question," whether it be an animal or human being. So it is an incorrect use of the word.

I do not think it is a slide point or an irrelevant point. I think it almost focuses our attention on the fact that what a strange thing this is and what we are talking about but what we are actually doing is synthesizing a totipotent cell for the production of a blastocyst in the therapeutic cloning idea for the production of stem cells and for the production of an organism in the other definition but that is what is going on.

CHAIRMAN KASS: Well, this substitute suggestion has got multiple parts that we could investigate.

I am not sure that synthesize -- well, I guess, by "synthesize" you mean, quite literally, to place together. Right?

DR. GAZZANIGA: Coming together of two different chemical elements to produce something else, which is what is happening. You are reprogramming the totipotent cell or the somatic cell to become a totipotent cell and you need the oocyte to do that at this point in our knowledge.

CHAIRMAN KASS: Now, why isn't a cell, which is -- will on its own proceed to divide and develop to the blastocyst stage -- I think there is a certain place earlier in the discussion where it describes this product. It is a cell but it is not an ordinary cell. It is a cell that resembles and can be made to act like a fertilized egg. It not only has the full complement of chromosomes but, unlike a somatic cell, it is capable of developing into a new organism. In other words, it is a zygote or a zygote-like being. Is that --

DR. GAZZANIGA: It is not a zygote.

CHAIRMAN KASS: It is a zygote or a zygote-like being. Do you think that is wrong?

DR. GAZZANIGA: Well, it is a totipotent cell that is being reprogrammed is what it is. A zygote means two gametes have come together to form.

CHAIRMAN KASS: Yes, but what you mean by "totipotent."

DR. GAZZANIGA: Well, totipotent is just the description of the first few cells in a division of a fertilized embryo that have all the potential to become a full human being and that is what miraculously happens when you put a somatic cell in a nucleated oocyte that as far as my understanding is -- actually there is not a lot of understanding on how that actually works. It works. We know it works but that is the -- I mean, embryo -- if you just take the word "embryo," embryo actually is used after -- after the egg or the entity is impregnated so it is actually incorrect -- it would be an incorrect use of the word given you did not -- we did not want to make these distinctions for the therapeutic case because the therapeutic case wants to stop the whole process at the blastocyst stage.

CHAIRMAN KASS: Let me -- I do not want to monopolize the discussion, others want to get in, but let me try to clarify. The brunt of the analysis was to distinguish the lot of the act from the purpose for which it is done. So to do whatever we are doing for the purpose of reproduction or to do whatever we are doing for the purpose of investigation or harvesting stem cells --

DR. GAZZANIGA: That is fine.

CHAIRMAN KASS: -- those are separate.

DR. GAZZANIGA: Yes, that is fine.

CHAIRMAN KASS: What we are trying to discuss now is what actually is the act.

DR. GAZZANIGA: Right. But what is the best biologic definition and I am making a suggestion here. There are many biologists here who can raze me and correct me but that is my thinking of the terminology and maybe we could hold this in abeyance until this afternoon or later on this morning when we have the pros tell us.

CHAIRMAN KASS: Other comments? Let's proceed. Rebecca, please?

PROF. DRESSER: This is somewhat related. On page 5, the first two paragraphs or second two paragraphs, there is a lot of discussion about this as a cell that could become, I mean, implicitly a baby and, I guess, this is somewhat related. It struck me that we do not really know that. I mean, it is -- we do not know whether it is a potential human life. Based on other animal work it might be but they have been having a lot of problems trying to do this with other primates so in a way it is almost saying underlying argument is, well, we should not find out whether it is potential human life, that is whether it could become a child because -- in part, because it is potential human life.

Whether this, whatever it is, this totipotent cell can become a human being, I do not -- you know, science has not investigated that and we are sort of deciding whether it ought to be able to. So that just struck me as a little odd.

CHAIRMAN KASS: Well, Gil, is that a hand? Go ahead.

PROF. MEILAENDER: Yes. This is really to come back to Michael's point. I just wanted to ask in connection with his what -- Michael, what would the difference in the capacities be between the synthesized totipotent cell and a fertilized egg?

DR. GAZZANIGA: Well, the idea, of course, is that one would have the diploid representation of the contributing adult only and the fertilized eggs, of course, would share hereditary information from the man and the woman but maybe connotatively what you are suggesting, to pick up on Rebecca's point, is that we do not know yet how that will pan out, how that totipotent cell will work where there are lots of problems for the human. There are lots of problems in current animal research but that is separate. The distinct difference is, as you know, the genetic make up of the two.

PROF. MEILAENDER: Well, I understand that.

DR. GAZZANIGA: Yes.

PROF. MEILAENDER: But if I take your point, either -- you know, if there is no difference between the capacities, either I do not see why you are concerned about the terminology of the Working Paper or it seems to me one could never talk about reproductive cloning right now. I mean, if we take your point that we simply do not know in the case of the synthesized totipotent cell whether reproduction can take place.

DR. GAZZANIGA: I do not see the problem. Synthesizing a totipotent cell for the purposes of developing a blastocyst is an accurate description of what is going on.

CHAIRMAN KASS: Yes, but look --

DR. GAZZANIGA: And it is not an embryo in the sense of how embryo is defined in the medical and scientific literature.

PROF. MEILAENDER: But it could not be for the proximate purpose of reproduction in your view.

DR. GAZZANIGA: No.

CHAIRMAN KASS: Look, we have got to separate the question of the purpose from the deed.

DR. GAZZANIGA: Right.

CHAIRMAN KASS: And, look, totipotency is a description. It means to describe the powers of this cell. To call it a totipotent cell is to speak about what that cell can turn into. Correct? I think Gil Meilaender's question rephrased is wouldn't you want to say that a fertilized egg is a totipotent cell? That is whatever it means to be a fertilized egg it is a totipotent cell, i.e. it has the capacity to turn into an entire organism.

DR. GAZZANIGA: Absolutely.

CHAIRMAN KASS: So the question Gil Meilaender asks is put again from the point of view of potency, from the point of view of capacity, what is the difference between the zygote produced by fertilization and this synthesized cell produced by somatic cell nuclear transfer, are they not totipotent in the same way? Let's not call them embryos. What is the difference?

DR. GAZZANIGA: Well, they are both totipotent, yes.

CHAIRMAN KASS: They are both totipotent?

DR. GAZZANIGA: Yes.

CHAIRMAN KASS: And in the same way?

DR. GAZZANIGA: No, well, not in the same way because they are made up of a different genetic composition but they are totipotent as defined by the ability to grow into a full organism. Yes, if you want to limit the -- yes, sure, that is it.

CHAIRMAN KASS: That, it seems to me, is the point.

DR. GAZZANIGA: Yes.

CHAIRMAN KASS: And I think that whether -- that the -- the textbook biological definition of embryo as from fertilization to -- I have forgotten, is it two months or eight weeks when they start calling it a fetus? There is something arbitrary about that and it seems to me that what you mean humanly speaking when you are synthesizing this is do you or do you not have that which can turn into an adult? Does it have the potency if it works? Now Rebecca's point is still here but, if it works, is not the product of somatic cell nuclear transfer identical to the product of fertilization in this respect, mainly both of them, if things go well are capable of producing an adult of that species? And, therefore, to call one a totipotent cell and to call the other one an embryo or a zygote might be technically correct but it would be to substitute a certain technical meaning for the human import. The human important is if they are totipotent they are both the same.

DR. GAZZANIGA: Well, I hear you but creating a living cloned human embryo is loaded connotatively and everything else, and to say synthesizing a totipotent cell is the accurate way of describing it -- now the interpretations and ethics of that event are all subsequent to getting the initial definition correct.

CHAIRMAN KASS: Okay. Let's scrap "created for synthesized." Living --

DR. GAZZANIGA: Well, you do not -- that is redundant because you have "potent."

CHAIRMAN KASS: I am sorry.

DR. GAZZANIGA: I think "living" is redundant.

CHAIRMAN KASS: No, let's --

DR. GAZZANIGA: Cloned means in this context --

CHAIRMAN KASS: Cloned refers to the genetic relation to --

DR. GAZZANIGA: Right.

CHAIRMAN KASS: Right. And then the question is what to call the product.

DR. GAZZANIGA: It is not an embryo.

CHAIRMAN KASS: What is it?

DR. GAZZANIGA: It is a totipotent cell.

CHAIRMAN KASS: What does that mean?

DR. GAZZANIGA: The -- what you are suggesting is that we abandon the current medical definition of an embryo. Now maybe you want to do that but that is a new usage and by use of the usage it takes on it will be entered into subsequent dictionaries but right now an embryo refers to a fertilized zygote.

CHAIRMAN KASS: Alfonso?

DR. GÓMEZ-LOBO: What you are saying I do not doubt for a minute but the problem is this, that all language is invention. I mean, all language is a matter of agreement, of an agreement of sorts. In some cases language is developed naturally and for some strange reason there are people who called doors "puertas," right? But in medicine it is usually an agreement probably made, you know, as the profession developed, et cetera.

Now it is true that the way the term -- the word "embryo" is used now it does not cover clones but the reason for that is that it had not been necessary until this point. So I really do not see a problem. I mean, as long as we are clear that there is a parallelism going on there, I do not see the problem with calling "embryo" the organism that develops from a cloned cell.

In fact, I think it is interesting to do this, to imagine for a second Dolly. Let's imagine Molly being a normally conceived sheep and we would have to ask ourselves, well, what happened in one case, what happened in the other case? And there is going to be a phase called the "embryonic phase" I suppose, which took place in both of them.

So if Molly got to be the adult Molly and Dolly got to be the adult Dolly, I just do not see that there is a decisive difference there.

Thank you.

CHAIRMAN KASS: Irv, do you want to get in on this?

DR. WEISSMAN: Sure. So, I think I have to agree with part of what Michael says that, in fact, it is a totipotent cell in the terms of embryology. That is it can give rise to both the embryo and the surrounding membranes that allow implantation. I suppose the important part of this would be is if you could create such a thing by some genetic trick or other trick which could not give rise to say the trophoblast, then it would not be officially a totipotent cell or, therefore, capable of being an embryo because it could not implant.

So I think it is important to try to have very clean language that is free of even convention because I would wager that if we all sat down here and I asked you to draw an embryo and pass it in to Leon -- I am not going to ask you to do that -- but I am willing to bet you that there would be a wide diversity of drawings of what an embryo is with lots of confusions about what a fetus is and so on and so on. And because these are images that are in the minds of people who have to make decisions, for example, in Congress or in the Executive Branch, it is really important to get this part clean if you can.

So I am very worried again about language and I will talk about the second definition when we get to it.

CHAIRMAN KASS: Please, Paul, go ahead.

DR. MCHUGH: I just want to support Michael in what he is saying because I am concerned that we have already made decisions when we begin these definitions and I would reword the classification here in answer to Gil to say that using the term "totipotent" is to fundamentally discuss a genus and distinguishing a zygote from a clone is to talk about a species of cell.

So all species belong to the genus totipotent. They are distinct as zygote and clone in the way they came about and in their essence fundamentally and that from those essences different ways of handling are going to -- different ways of managing is going to occur.

CHAIRMAN KASS: Gil?

PROF. MEILAENDER: If you could keep that synthesized totipotent cell that is a clone alive for four weeks, what would you call it?

DR. MCHUGH: That is an interesting question. I had not thought about what I would call it but I might call it a synthesized embryo.

PROF. MEILAENDER: If you could keep it alive for nine months, what would you call it?

DR. MCHUGH: Well, that is the issue that comes with the eventual use of these products.

PROF. MEILAENDER: No.

DR. MCHUGH: For which we are eventually going to want to speak.

PROF. MEILAENDER: No, it is the issue about what capacities it has from the start.

CHAIRMAN KASS: I think that is absolutely crucial. The uses to which it is put do not determine, do not alone decide what it is and what its capacities are. I think it is important. I mean, I understand. I understand the concern that if you ask lots of people to describe an embryo they think of a baby. Okay. That is a problem. On the other hand, if you talk about totipotent cells, people think that this has no capacity to become a baby and I think the force of the questions that Gil and I are raising is -- there is no -- there was no intent in the paper to try to find language that would carry the moral argument in advance. The point of the paper was to try to find terms which one could then go on and have the moral analysis about.

DR. MCHUGH: I accept that motivation. I am just saying that maybe enhancing the distinction between genus and species here might help us ultimately in our decision. I absolutely agree that the thing was written in an effort to not preclude a particular position but perhaps it has inadvertently and we should talk about that.

CHAIRMAN KASS: Other comments? Charles?

DR. KRAUTHAMMER: Could I jump to where we would end up in our discussion here about what we would call the two kinds of cloning because I think that is the issue that we are trying to face? We agree calling one :reproductive cloning," the question is what do we call the other? I noticed -- and I would like to endorse the spirit of what Stephen Carter had in his e-mail in which he said, "We ought to search for the most neutral possible term."

I think that would enable us all to agree and I think it might also be a contribution in the sense that if we were to issue a paper whose title were this formulation that might actually have an effect on what terminology is used in the future. We may or may not succeed if we invent new terminology but we will be read and we will have something that will be in the public eye and we might actually have an influence over the terminology.

My problem with Stephen's suggestion is that Type 1 and Type 2, I suspect, simply would not take. What I would like to offer as an alternative would be one of the four terms used actually in the National Academies paper. They listed four possible words. They chose one. They listed "nonreproductive therapeutic research," and the fourth was "somatic cell nuclear transfer," which they then adopted.

I would offer as one that I think might be able to command consensus, "nonreproductive." It avoids a lot of the connotations that we would be arguing about. It is simply descriptive and by simply being a negative of the one on which we agree, I think it would allow a neutral way to express what we are talking about in the same way that when we talk about history and we have no idea what to call a period, we call it a post. Post-war or post Cold War because that is all we know is what happened before and we will decide later what it really is when the era has achieved an identity.

So I would say that at this stage of our discussion it might be useful to adopt "nonreproductive." The reason I would be hesitant to adopt "therapeutic" is because I think it would meet some resistance and I would offer two reasons why. (A) we are not sure that in the end it would be therapeutic. It is only hypothetically so. And, secondly, it is not therapeutic for the organism of which we are speaking.

If my brother decides he wants to offer me a kidney, I am lacking all of mine, he decides he will offer me one of his kidneys and he undergoes a nephrectomy, I am not sure -- I think it would seem odd if we called it a therapeutic nephrectomy. It is not. If he had a renal cell carcinoma and had a nephrectomy it would be a therapeutic nephrectomy but if he is a donor it is not going to help him in any way but it is going to help me, I think it would be an odd usage.

So I think if we adopt "therapeutic" we would either have to it with quotation marks or without. In either case we would have dissent on the panel so I would throw out as a suggestion that we use "nonreproductive" as a way to square the circle.

CHAIRMAN KASS: Charles, are you going to solve the problem that Michael has left us with? You see Stephen Carter in his memo still uses this contested word "embryo." Where is it? I just gave it away. I have it here. "Type 1 cloning would be creation of a human embryo for the purpose of medical research or treatment. Type 2 cloning would be creation of human embryo for the purpose of creating a postnatal child."

We would still be in the position of having to say what we mean by both of these things. The cloning simply refers to the relation between the product and the progenitor. That is not hard. That is -- and then the question is how to describe what this means.

DR. KRAUTHAMMER: I am not sure the use or nonuse of the word "embryo" is at the heart of the issue here. I think where the debate has been and where the debate is prejudiced is by what we call the second type of cloning. I think that is what we saw in our last meeting. There was some dissention about the use of quotation marks and the need for the quotation marks was a way of saying that there is fundamental disagreement over the appropriateness of this work.

So I would opt for Stephen Carter's solution, although with a different set of terms.

CHAIRMAN KASS: Stephen, do you want to respond, please?

PROF. CARTER: Well, a couple of things about what we have heard so far. We have two different problems about nomenclature that we are discussing as one. We have a problem of a noun and a problem of an adjective, and they are not at all the same problem, although they are related problems. We are trying to find a noun to describe things that some people think are the same and some people think are different and the difference that the people think they are different is based on is based on not the noun but the adjective that is attached to them.

I should make clear that in my note I am not tied to the term "embryo" in any sense nor am I tied to the terms "Type 1 and Type 2." That was more of an example. But I am concerned a little bit that we do need to have an actual resolution. We cannot talk about this for a while and go on to the next thing because we will not be able to have a conversation, much less produce a written report, if every few minutes we have to begin our comments by saying, "Now, of course, I do not endorse your use of the term this and this and this, and so on."

Now, why are we having such trouble? Well, why do we have trouble with the noun? We have trouble with the noun because I do believe that although some of the nouns that are posed are proposed as being the scientific language and some of the nouns that are proposed for other reasons that behind the proposals for various nouns are substantive positions about what it is that we ought to be doing. And so I think that for those who find all forms of cloning troubling, the natural urge is to reach for a noun that somehow is of better touchy-feely human significance. For those who find the forms of cloning quite different there is a natural tendency to say that the term is less important or rather that the terminology is crucial and that what we really have to do is find the correct scientific name because, after all, no one in the general public is going to know what we are talking about in either of these terms, I suspect, anyway.

In the case of the adjective, we have a very similar problem that we have -- we are still engaged in exactly what you, Leon, warned us against but I do not know how we escape it that we are trying to find adjectives and yet each of us recognize -- I confess this as freely as anyone -- that the adjective we choose will help shape the substantive position.

So the reason -- now let me make clear. I am at this point quite indifferent as to what noun we choose. The noun does not interest me that much and other people feel the noun is crucial. The noun is not that important to me because, I think, whatever noun we choose at least we will have one and we will know what we are talking about, I hope, the same thing, whether the noun is colorful and touchy-feely or whether it is more dry and detached and scientific.

The adjective is very important. The adjective is very important. It is important to a lot of people around the table and the reason, Charles, that I think the "nonreproductive" does not solve the problem is that there were two different kinds of objectives last time, and I want to review what they were.

One objection was to the quotation marks. The objection to the quotation marks was phrased as a concern that if we use quotation marks around these words like "reproductive or therapeutic or nonreproductive," whatever we are going to call it, we are suggesting in some way we do not really think they are the right words and others would say if we do not use the quotation marks it would suggest that we do think that they are the right words.

And, Leon, you suggested, well, you think the staff just chose the quotation marks to show there was a controversy, and I respect that but there is a deeper controversy about the nouns. And that is that remember last time there were people around the table who expressed the view quite forcefully that simply by choosing the adjective -- the two different adjectives we are suggesting a moral distinction that might not exist.

What I was trying to do with words that are taken from -- that have no relation to the debate at all, like Type 1 and Type 2, is avoid that dispute over on the one hand quotation marks versus non-quotation marks, and on the other hand whether we are suggesting through the adjectives we choose a distinction that some wish to challenge. I am not tied to Type 1. I am not tied to Type 2.

I was simply trying to suggest the possibility that we try to find adjectives that do not seek to describe the division. Let the description occur in the definition so that we can have the conversation without having to use words that, whatever word we choose, some people will think it loaded and not wish to use it. That was really my only goal and I want to make clear that I am tied to any of the words I chose. It was a kind of late at night off the cuff memo and yet I think it is important to think about proceeding this way.

The last point: One of the reasons it is important, I chaired a committee at Yale Law School a few years ago, which had nothing to do with abortion but someone raised an abortion analogy and said, "For example, in abortion, we do this and this and this." And the committee fell apart into a discussion of abortion terminology. I mean, just do you use "pro-choice"? Do you use "pro-life"? What is the thing you are talking about? And the committee was not even about abortion. The committee work had nothing to do with abortion, science, civil liberties, anything. It was about some internal procedure and this was an analogy someone had raised but the nomenclature debate there made it impossible to get back to the other point.

I guess I was trying to find a way to allay the nomenclature debate but it may be that what I am being told is that is not possible and if it is not then I would certainly yield to wiser heads.

CHAIRMAN KASS: Gil?

PROF. MEILAENDER: Yes, I was actually -- I mean, I liked the suggestion you made. They are just sort of placeholders which you then defined in a way but our problem is that now our discussion has moved in a direction that it is not clear we could agree on how to define the placeholders. I mean, that is whatever neutral terms we arrive at so I am not sure that that will solve it.

I wanted to say a word about Charles' suggestion and then just ask a question. I do not think, Charles, that what you suggest is going to solve the disagreements because, I mean, what you can do with a thing depends on what it is and how you name it is a way of saying something about what it is, and the real issue is what you can do with these things, whatever they are.

CHAIRMAN KASS: Can I just make a small comment on that? As one who thinks that the right name for this product is "embryo" in the sense that it is a kind of totipotent cell, that it has in a way the same meaning as totipotent cell but it has the human understanding of it and capable of becoming an adult organism. I do not think that that settles the moral question one way or the other. I am perfectly prepared to say that it is an embryo and it does not determine what you do with it. I would, in fact, rather call it that so that I do not deceive myself by sanitizing the name that I am doing something to something that is nothing at all.

PROF. MEILAENDER: Well, maybe the word "determine" was too strong. Obviously, once you know what something is, you can still have a discussion about what it is or is not appropriate to do with it.

CHAIRMAN KASS: Yes.

PROF. MEILAENDER: But deciding what it is will be a crucial matter in arriving at that decision. That is all I meant to say but I just had a question. This is just a question and I do not know the answer. Would it be scientifically inappropriate to call a synthesized totipotent cell an organism and would it be scientifically inappropriate to call a fertilized egg an organism?

CHAIRMAN KASS: Irv, do you want to --

DR. WEISSMAN: I will finish that. Of course, it is not yet an organism until it is an organism. Potential and real are different so if we just leave that. I am worried about the way the discussion is going and I do not want to differ too much with you, Stephen, but what this group is trying to do now is without going into the science of the matter and, therefore, the subtle distinctions in the science, it is trying to make a definition that it could make in a couple of hours, I think, much more easily so I am going to give you the tiniest example without giving my talk.

"Therapeutic cloning" is not at all an accurate term of what is going on and I will talk about it but therapeutic cloning is an invention of commercial enterprises to get you to think that what you are using that for only, and you talked about uses before, is to transplant back into humans for a means of therapy. That is not at all what this is about and I will talk about what it is about but I would argue that you should -- sorry, Stephen -- put it in abeyance, try to talk about what you are talking about as you describe it even though there is going to be quotes and so on, and then maybe later, maybe by noon or so, come back to the question of what Type 1 should be called.

CHAIRMAN KASS: Comments? Bill, Michael, Bill Hurlbut?

DR. HURLBUT: It seems to me looking at the various definitions, and I have them in front of me, from different documents that have been produced that define the embryo, it repeatedly puts the emphasis on the developing organism. What in the working notes has been called "the coordinated process into the governance of an imminent plan for such development encoded in the cell's genetic material." In other words, the cell is an organism in its germinal stage and its activities are those of an integrated and self-developing whole.

When I look at these definitions there are two sides of it. One is how it got to be formed, namely the fertilization. And the second is this concept of a developing organismal process.

Now, admittedly, in the current scientific situation there is a different origin of formation but it seems to me to deny the second part.

And I am a little curious, Irv, how you used the word "organism" a second ago because these definitions include it from the time of the single cell. You implied it was a later development.

In any case the definitions generally put it from fertilization. Organism, if you think of "organism" -- I guess it is from the Greek for tool, is that right? -- the cell itself already has compartmentalized tools so to speak and the emphasis there is on varied things producing concerted action towards an end.

In that sense, whether the thing is formed by fertilization or by nuclear transfer, it initiates the same process. Otherwise, what would be the point of doing it to obtain these cells?

So, in that sense, I do not object to the use of the word "embryo" if we could acknowledge, and I think we all know already that it is a technologically -- it is an embryo with a technologically different origin but it is still an embryo in the strong sense of what we want to define the embryo as.

And every one of the Working Papers that I have read, and I have read them all, uses the term in that sense. I mean here we have listened to three of them.

In the stem cell and future -- and the future of regenerative medicine defines: "Embryo: In humans the developing organism from the time of fertilization until the end of the eighth week of gestation when it becomes a fetus."

In NBAC's report it said, "Embryo: The developing organism from the time of fertilization until significant differentiation."

And the same went on with even Irv's report where he used the term in that way. Let me see if I can find it here.

The point is in any case that we had -- if we are going to balance the objections, Robby is not here but last week he objected to the use of nonreproductive cloning because he said all cloning is reproductive if you take it as the initiation of the human process or human organism.

So I know this is cumbersome and I am not really making this with strong conviction but what if you did allow the word "embryo" to be retained but put the -- so that you had that humanness that Robby wanted present, that potential humanness, if not actual, and put some term like "nonreproductive embryonic cloning" or "research embryonic cloning" so that it is a compromise of all purposes wrapped into it.

CHAIRMAN KASS: Stephen and then Gil?

PROF. CARTER: I think there was somebody next.

CHAIRMAN KASS: Was there? Did I miss somebody?

PROF. CARTER: Well, let me -- one possible way to get around a little bit of this in keeping with what Irv said, as well as what Bill just said, maybe we could do the following: Perhaps what we should do is first adopt a definition of cloning, which could be very much along the lines of the NAS report. Even though it is talking about human cloning, we can take -- we can take elements of the definition there up to the point where it begins to talk about implantation and just stop there.

And then we can draw our distinction, as I suggested in my notes, based not on the claim or denial of a moral difference but rather on the intention of the person doing the act. So, in other words, we first say cloning is this. All right. And then whatever you want to call one type of cloning is that when it is intended for this purpose and whatever you want to call the other cloning is that when it is intended for this second purpose so that we will simply be defining the term "cloning" and then distinguishing two things to talk about based on the purpose for which it is done without making any claim about the what, which is a lot of -- whether there is a distinction in the what's that are created based on the purpose.

And the definition I had in mind, which is not inconsistent I should add with the twin definitions on page 6 of the Working Paper, if you look at the NAS report on page 22, the first paragraph, "Cloning of Somatic Cell Nuclear Transfer," you could stop either after the fifth line or the sixth line. "The egg is then stimulated and in some cases it starts to divide." Or after the next line, "Leads to formation of a blastocyst," period. You could stop there and then make our further distinctions based on the basis of the intention of the actor.

The reason I focus on intention is to avoid for definitional purposes the questions we have yet to confront which we have already spent a lot of time on about moral significance. Otherwise, I am worried that every effort to define it is going to collapse into the very discussion that we are here in order to have and that we have quite sensibly said it is going to take a very long time to work out so that is my suggestion.

CHAIRMAN KASS: Michael?

DR. GAZZANIGA: I was just -- sorry.

CHAIRMAN KASS: Please.

DR. GAZZANIGA: Mr. Chairman, you should be approached in this formal way because it strikes me that why don't we be inventive here and, in fact, let Dr. Weissman give his talk now and we return to this after the talk since there are going to be -- these issues are so much a part of his comments that we just sort of change the order here a little bit.

CHAIRMAN KASS: I am open to that. I am half open to that because his talk is going to be --

DR. __________: Half his talk then.

(Laughter.)

CHAIRMAN KASS: Well, I mean, because the purpose of the next session was really to allow us to ask questions about the whole of the report of which the terminological point is but a small part and I guess if I might -- I mean, here is one of those occasions where it might be true for the sake of getting on with our business that we find a kind of least common denominator, least controversial way of finding terms that enable us to talk and if it comes to that I will settle for it but remember I have given us the kind of charge that we should strive, in fact, to speak about these things in their human significance and not just simply in technical terms.

And one of the things, if I may say in advance -- and the Working Paper was written not with the Academies report in mind -- but one of the things that the analysis of the Working Paper shows is that nuclear transplantation for producing stem cells, okay, the first describes the technique, the how. The last describes the purpose but what the thing actually does immediately is missing. And it seems to me -- maybe the word "embryo" is not the right word.

I am not sure that we can find another one but I think in the light of the question that Gil posed earlier to Paul and in light of the comments that Bill Hurlbut has made, namely that the product, the immediate product of nuclear transfer, is in this limited sense an organism. I do not say it is a person. I do not say it is a human being. I do not say it has rights. I do not even say it has dignity but it is a self-developing whole dividing as a unit and it could conceivably -- it can certainly get to be five or six days old in the animals if they develop these various placental supports that we have been reading about. It could go further.

The ACT people have implanted those clones and harvested primordial kidney cells from it so you can take those things further. That means that whether it is technically an embryo the way the biologists speak about it, it has the same characteristics from the point of view of potency that a fertilized egg does and that is its human importance, whether you use it for stem cells, whether you use it later for producing organs by implanting things in uteri in animals or whether you use it to grow a child.

I think we should not hide from ourselves that fact about what the result of this is and that is not ignorance of biology, that is to treat the biological entity in terms of what it can turn into and what it can turn into not because we want to turn it into that but because that is what its powers are once we have created it. That I think is -- it is a philosophical biological point. It might not be a technical one but I think it is absolutely crucial to understand the meaning of what is being done without arguing the moral questions. That is partly why I think that this cannot simply be done on the basis of the technique.

CHAIRMAN KASS: Gil, and then Paul, and then Irving, I think, wants -- and Rebecca, sorry.

PROF. MEILAENDER: Well, the reason I had asked my question about organisms before was because I -- precisely I was searching for a different term that might somehow encompass the several purposes but I just wanted to note that the Academies report itself -- I mean, I do not know if this is just a case of Homer nodding or what but on page 26, the first sentence of the first full paragraph reads, "The experimental procedures required to produce stem cells through nuclear transplantation would consist of the transfer of a somatic cell nucleus from a patient into an enucleated egg, the in vitro culture of the embryo to the blastocyst stage, and the derivation of a pluripotent ES cell line from the inner cell mass of this blastocyst."

CHAIRMAN KASS: Right.

PROF. MEILAENDER: I mean, it is a natural way of talking about what is going on.

DR. GAZZANIGA: Maybe we should put the quotes around "embryo."

(Laughter.)

CHAIRMAN KASS: Perfectly all right with me. Perfectly all right with me. Who was it? It was Paul, Rebecca and Irv.

DR. MCHUGH: I mean, we ought to put it on the table. What we are wondering about and worrying about is the distinction between words like "stem cell-zygote-clone and embryo-fetus-baby-person." And if given that we have deep concerns of the human significance as you said, the reason I wanted to second what Michael was saying is that I would like to use the word "clone" and in the definition of the word "clone" I am happy to use the word "totipotential cells" and say that is a genus of cell and the species of cell includes zygote, clone, stem cell, which is that is also a totipotent cell, and then we can come eventually to discuss what we mean by the use of these cells to produce embryos, fetuses, babies, persons, and decide how it goes.

It allows us, I think, to get to the purposes with which we are using these issues without already defining the problem.

CHAIRMAN KASS: Thank you.

Rebecca and then Irv?

PROF. DRESSER: I guess, I am just hung up on this. If the genus is totipotent cell then we know that the natural forming embryo can become a person so that kind of totipotent cell can turn into a baby and we do not know whether this other kind of totipotent cell can. I guess part of the question is, well, what kind of evidence do you need to say that there is enough of a chance that it can and that we should put this other kind of totipotent cell into the same category.

CHAIRMAN KASS: Well, we know that in animals.

PROF. DRESSER: So we know in animals.

DR. KRAUTHAMMER: If it were a sheep, would you put it in that same category?

PROF. DRESSER: Excuse me.

DR. KRAUTHAMMER: If it were a sheep, would you put it in the same category?

PROF. DRESSER: Yes, it has been demonstrated. But, I guess -- I mean, as a nonscientist, it seems to me there are so many questions about even different species and also, you know, reprogramming and all these things imprinting. We do not know whether you can create a baby even if -- and we might be able to but I guess it is just -- it is a different kind of level of potential than a naturally occurring embryo.

CHAIRMAN KASS: Let me -- in calling on Irv Weissman to make his own comment, would you address Rebecca's question as well? And with this qualification: If it should turn out that the product of nuclear transfer could grow up to be a blastocyst from which stem cells could be taken, would that perhaps imply even before the thing is tried that it might also be potent to produce a baby if that was intelligible?

DR. WEISSMAN: Sure.

CHAIRMAN KASS: Thanks.

DR. WEISSMAN: So the extensive studies in the animal literature that the National Academies of Sciences reviewed and heard in workshops and discussed and criticized says that in many but not all species tried so far, one can by nuclear transplantation into an enucleated egg, followed by activation, get with a certain probability a one, two cell, four cell, eight cell blastocyst stage of development without doubt.

The probability of a blastocyst in an animal species implanted -- first, I will just say none of them without implantation can give rise to a living organism. That should be clear.

Now once you implant it correctly in the prepared uterus, meaning that it is capable of receiving and implanting, and that is not in every female at any stage, it has to be prepared, once it is implanted the IVF, that is sperm-egg fusion, leads to a viable birth with a pretty high probability. The probability in all animal species where you get success of nuclear transplantation to give rise to a blastocyst that gives rise to a live birth averages about 0.8 percent and, of course, all the way, and that is the reason when I talk about it, you get fetal loss and even maternal loss all the way -- do I feel like I just got censored?

(Laughter.)

DR. WEISSMAN: All of the way. So there is no doubt, Leon, that some blastocysts created by nuclear transplantation will give rise to a full organism that has different probabilities even of life thereafter but clearly it is an organism. So that is not what we are talking about.

I do believe that the popular conceptions of the two words "clone and embryo" are so far from being complete or being even true in most people's minds are such that you ought to reconsider in the purpose not for the purposes of taking away or adding human or human sensibility to it but in the purposes of clarity this body after due consideration could do everybody a favor if you came up with the right terminology and watch even yourself because all of us come in with bias. When I read, you know, in the Working Paper that you have a "being" I understand something different than you might about what a "being" is, including personhood and so on.

So I think that all of us should leave our prejudices at the door and try to get through soon the discussion about what we are describing. I do not think we can do it ahead of time, it is my view. Certainly if you try to move on and say "therapeutic or research cloning" I will just say you better just stop and do as Mike says. Let's have the talk. Let's go through what the science really is and then come back to that issue.

CHAIRMAN KASS: Rebecca, go ahead.

PROF. DRESSER: Well, I had a couple other points but if you would like -- if it is on the same point.

CHAIRMAN KASS: Do you want to respond to this? Please, yes.

DR. HURLBUT: Irv, we have talked about the three components that you would like to put into a definition, the how, the what and why. Was that what they were? So what would you put in? I mean, do you want some reference to biological process, organismal process? I understand why you do not want cloning in. It has a science fiction overextended implication. I understand embryo is a weighted word. Your suggestion, which was not just somatic cell nuclear transfer but nuclear transplantation to produce stem cells, strikes me as describing the why, not quite the what, and it also seems to me that is not the only uses that you could put nuclear transfer to.

So what -- could you tell us what your -- you would like to see included in a definition even if you do not have the words for it?

DR. WEISSMAN: Can I respond now?

CHAIRMAN KASS: Please.

DR. WEISSMAN: After our discussion, what is described when you say "nuclear transplantation to produce stem cells"? Is the general purpose animal or human? Now if you wanted to be absolutely precise about what it is, you would say "nuclear transplantation to produce human pluripotent stem cells." So it is not multipotent or tissue specific stem cells. It is not to produce totipotent cells because that certainly is gone by the time you get to the blastocyst. You do not have that.

The insistence of trying to say, "Well, it is an embryo," certainly it has all of the features of an embryo if it made it that far but it does not help you or hurt you to go on with what actually is going on and it is nuclear transplantation to produce human, if you like, perfectly fine because that is the real process. That is the point of discussion. Pluripotent stem cells. It is -- now, if you want some other purpose, like cloning a human being, that is different than this definition.

DR. HURLBUT: Can I follow up?

CHAIRMAN KASS: Please.

DR. HURLBUT: First of all, the point is there would be many other uses of this nuclear transfer. For example, it could be nuclear transfer for the purposes of studying reprogramming or for the purposes of studying imprinting. So to tie stem cells to it is just one of the possible avenues of use but it seems to me that what is going on here is you are -- in making the definition, the only reason we are here discussing this is not because there is a little lab manipulation going on that goes on all the time in a multitude of permutations and combinations, the reason we are here is because in nucleated this cell with an external nucleus we do not want to enucleate its moral meaning.

So how do you preserve the moral meaning of it, Irv?

I guess that gets down to the question of how much moral meaning does it have but maybe we need to do it backwards then but we do not want to enucleate at least its potential moral meaning with our definition.

DR. WEISSMAN: May I respond?

CHAIRMAN KASS: Do you want to respond?

DR. WEISSMAN: I will just say briefly that we have not even gotten on to the discussion and certainly my panel never discussed the question of whether a nucleus of an egg has moral meaning. This is a pluralistic society. I think there is going to be a lot of different definitions that will come from that and I do not want to get into that discussion.

I agree with you that the science on the way to make it work, nuclear transplantation, to produce human pluripotent stem cells will have a lot of scientific components to it, including reprogramming and understanding what it really would mean if it is possible but I will say again what I have told you is an accurate description at all stages of what happens.

DR. KRAUTHAMMER: Could I ask just one quick question, Leon?

CHAIRMAN KASS: Please.

DR. KRAUTHAMMER: I'm sorry. If I could just ask you assuming you have got a lab that engages in somatic -- in nuclear transplantation for the purpose of producing pluripotent human stem cells, right, and has got a bunch of blastocysts all around the lab, and one night somebody breaks in, he steals a bunch and he implants them in prepared uteri of women, and one miraculously becomes a child. What do you call that?

DR. WEISSMAN: You are going through a lot of steps that we took great care to deal with and I certainly will deal with it in the context of the whole discussion.

DR. KRAUTHAMMER: Are you saying that, in principle, it is impossible.

DR. WEISSMAN: I promise you, I will deal with that issue but to take that away from the whole discussion, I think, is interesting but it is not going to help us out today but we will get there, I promise you. I will answer your question fully.

DR. KRAUTHAMMER: All right.

CHAIRMAN KASS: Charles, do you want to continue?

DR. KRAUTHAMMER: Well, I just do not understand how can you -- how you can define a process by one specific application when we know that there are others that can be applied so it seems to me a definition that on its face is inadequate. If you cannot answer that question that means that we have a definition that does not accurately describe what is happening.

CHAIRMAN KASS: Dan?

DR. FOSTER: I do not want to be judged as wanting to cut off the conversation, though I am in favor of switching the talk, but the late nobelist Medowar (?) said that the only important questions were the questions children asked and one follows from that by saying that in one sense the only important answers are the answers that come to what children ask.

My concern in the conversation this morning, highly technical, begs the point that we have to address the ordinary population consisting of people who have babies and Congresspersons and so forth. And some highly technical discussion of the difference between a zygote and by in vitro fertilization and so forth is likely to lose everything of importance.

I understand that to say "reproductive cloning" and "therapeutic cloning" has nuances that we have discussed today that are very important but my conversations with ordinary people, this is not scientific at all, is that they clearly understand the difference between the common usage that is in the newspapers every day of reproductive cloning and therapeutic cloning.

And what they understand is that one thing that they find, to use a term that is tossed around, repugnant is the idea to make human beings for enhancement and all sorts of things. They understand that, that one is trying to take, whether it is a blastocyst or whatever, to full human capacity and have that human born.

And they also are very concerned with the great hope that stem cells in one form or the other may deal with human disease and they are interested in the scientist dealing with human disease.

Now, there are doubtless moral questions. I, myself, am open. One of my concerns about some of the working papers also is that they imply a conclusion before we ever have the discussion but I think that ordinary people understand what we are talking about and I think they are very interested in that. And I do not want us to get so bogged down either in a written report or in our discussion here that we do not communicate with all the people that count. I mean, we are so worried about whether we are going to convey that we are against all cloning or for all cloning or so forth that we are missing the whole point.

So I would simply say that I would like for us to keep before us the Medowarian principle that we ought to speak accurately but in terms that ordinary people understand. When a baby, when a mother, when a child asks a mother where babies come from, you do not have to go into the precise description of sexual intercourse. You can simply say that this is where they come from. So it is only a plea. It is not for -- it is not to stop the conversation, although I would like to hear what Dr. Weissman says before we use these definitions.

CHAIRMAN KASS: Stephen?

PROF. CARTER: Well, I have no particular attachment to any particular agenda order, however I think that in Dr. Weissman's last comment he made a point that I think is really very important about the pluralism of our society and, indeed, the pluralism is in some ways reflected around the table. We are seeing a number of different views about these issues.

Part of the problem we are facing with definitions, and it is also a problem that we are facing with the debate about the agenda order, is that it is not obvious to everyone around the table that the fact that there is a particular scientific way of addressing the issue means that that is clearly the most accurate way of addressing the issue.

This, in a sense, is what I took to be the burden of Bill Hurlbut's comment a moment ago that to the extent that one believes the point that was very eloquently made by, among others, Robby George last time, to the extent that one believes that moral meaning attaches a contested point but a point that is alive in the country and alive around the table then the definition becomes very heavily freighted.

And to suggested even for the purpose of further conversation or let's move on that we talk as though it does not will then, I think, to a lot of people not merely confuse the issue but belie a very important issue that is one of the reasons that we sit here.

On the other hand, as I said before, it is also true the other way around that if we find a way of talking about it that does suggest moral meaning. Others will say, "Well, but now you are concluding already before we have had the conversation."

And that is why, Leon, despite your heroic efforts and the fact that no one else seems to think this is a good idea. I cling to my original -- not original but my previous suggestion that we define the scientific act (a) and then (b) distinguish according to the intent of the person performing the scientific act and go no further than that in our definitions.

CHAIRMAN KASS: A couple of comments and then we will wind up this session and, in fact, do as everybody wants.

(Laughter.)

CHAIRMAN KASS: Charles, Paul. Charles, was that your hand up?

DR. KRAUTHAMMER: Yes, I did. I would just like to entirely endorse that and I took that to be the spirit of your e-mail that you wrote late that night. It seems to me that we ought not be having our debate on the moral aspects of cloning in this session and try and trying to find a definition. The whole idea of trying to find a definition is a way to enable us to then have our debate in which our terms are agreed upon so I think we ought to go for the lowest common denominator and to find an adjective and a noun that work.

And I would suggest, and I am not sure I would -- I mean, I am not sure how it would work but I had suggested "nonreproductive cloning" as the second type and it is just a way of indicating what kind we are -- what activity that we are talking about without having passed judgment. I mean, there may be judgment read into it but I think it is as neutral a term as we could adopt and it would allow us to have a debate over whether it ought to be allowed or not, which is what we are here to decide or at least to discuss.

CHAIRMAN KASS: Since you have the floor, do you want to say something about the noun? What is cloning, Mr. Krauthammer?

DR. KRAUTHAMMER: I would argue for using the word simply because that is what the public policy debate is about. If we were to adopt some other word I think we would be in some ways dodging our responsibility.

CHAIRMAN KASS: Okay.

DR. KRAUTHAMMER: The bill that the House voted on was a cloning bill. The bill that the Senate is going to have is a cloning bill. If we want to invent a new word that would be heroic but we are not here to do heroism. We are here to do public policy and to discuss the implications of it. Cloning is on the table.

I think both of these activities are a form of cloning and what we want to distinguish is the intent. It seems to me a fairly simple issue. I am not -- perhaps I am missing all the depth here and complexities but the definition ought to be fairly simple and one that we can agree on and proceed to have a debate about whether it ought to be done or not.

CHAIRMAN KASS: Two final comments. Paul, and then Alfonso, and then we will break.

DR. MCHUGH: I really do not need to add much to what Charles and Steve have said. I, also, think that the word "clone" is perfectly fine. I like the breaking down of its definition into encompassing it within its genus and the major reason, and I suppose this is going to ultimately speak to the issues of pluralism and prejudice. I believe that rights are fixed and duties are demanded at some level to embryos, fetuses, babies and persons. And I want to avoid getting to those things, those prejudices or pluralism. I mean, pluralism, you know, is limited. We are a pluralistic society but, by God, we are limited about certain things like slavery and I would like to have our definition at this moment for the use of the word "clone" avoid that.

CHAIRMAN KASS: Alfonso, and then we will take a break.

DR. GÓMEZ-LOBO: Okay. I want to contribute to the consensus at this moment, referring to Stephen and Charles. I think by now in my mind it is clear that we are trying to name three things. Cloning, the activity as such, and then what is intended by researchers, and that can be either reproductive or nonreproductive. So it is really three things and by now I think we pretty much have a denotation for those three things.

Thank you.

CHAIRMAN KASS: All right. Let me see if I understand where we are on this. We are, of course, in the middle and, you know, we start in the middle and we stay in the middle. Hopefully, with a little clarity about where the shore is and what we need to do to get there, invitation number one of many. We have a long time between this meeting and the next. That means that there is a lot of work that has to be done by staff but also I would hope by members. Comments solicited, please, from as many of you as would like on this terminological matter. Creative accounts of the noun and of the adjective. I think Dan Foster's comments also should be kept in mind. We can do our own internal analysis but it is not clear to me that we are simply free to abandon the terminology which is in popular use, though we have been warned that cloning has connotations and embryo has connotations.

I do think that it would be good if in choosing certain terms we do not simply stipulate them but maybe have some discussion about the complexities of these terms for anybody who is interested to be so informed. That, too, is a contribution to the public discussion as it goes on.

So we will hear from Irv Weissman after the break. He will make a beginning presentation. We have questions. I have duplicated and put at your place the questions that were sent to Irv. You might have other ones. And part of what he has to say will, I am sure, influence how we continue to think about the terminological matter but we will bracket it for now and hear about the science and medical aspects, scientific and medical aspects of human cloning. And then this afternoon actually get into the moral arguments without appearing to be doing so surreptitiously.

Fifteen minutes. We will be reconvened at 10:15.

(Whereupon, at 10:01 a.m., a break was taken.)

CHAIRMAN KASS: All right. I have been asked by our audio technician to tell people that they should -- when they speak, they should speak a little bit further back from the mic but still speak into the general direction. It should pick up very well.

We come to the second session of the meeting devoted to a discussion of the report by the National Academies of Science's Panel on Scientific and Medical Aspects of Human Reproductive Cloning. And we are delighted that Irv Weissman, who is the Chair of that panel, is here to discuss the report with us.

We want to do three things. I mean, Irv is going to make a beginning presentation. Council members will have an opportunity to discuss the findings of the report and then take up certain questions of either assumptions or questions of the reasoning. I am not sure that these distinctions are going to be able to be kept from one another. And, finally, we would like to have at least some discussion about Irv's view on the relation between what the Academies has done and what remains for us here in the consideration of these issues.

I would also, if I may, before we start, like to welcome and introduce Dr. Maxine Singer, who is the President of the Carnegie Institution of Washington, Distinguished Scientist at the National Cancer Institute and the Chairman of the Academies CSEPP Committee who oversaw and worked on this report.

Nice to have you with us, Maxine.

DR. SINGER: Thank you.

CHAIRMAN KASS: Irv, would you like to begin, please?

DR. WEISSMAN: Sure.

SESSION 2: HUMAN CLONING 5: NATIONAL ACADEMIES' REPORT
"SCIENTIFIC AND MEDICAL ASPECTS OF HUMAN REPRODUCTIVE CLONING"

IRVING L. WEISSMAN, M.D.

So let me introduce myself first because I think it is important to know where I come from. So my name is Irv Weissman and I am a professor of cancer biology, pathology, developmental biology and biology at Stanford. It just means that the field I am in is a new field and, therefore, it crosses into many disciplines and it has uses in many disciplines.

I work, especially in the last 20 years, on adult stem cells and it happens that we were the first to identify and isolate adult stem cells from any tissue from any organism and you should know that in the course of the research that began with mice in my laboratory I helped co-found two companies. One called Systemics, Incorporated. Another called Stem Cells, Incorporated. And at those companies I was a director or am a director, have an equity position or had an equity position, got consultant fees. Just so you know that there might be unconscious biases or not but you know that.

Now, I should say that none of my companies that I have been associated with, and no current plan of the companies, involves embryonic stem cell research. In fact, if there were an analyst in the crowd he would say, or she would say, what I am going to talk to you about, the permission of nuclear transplantation to produce stem cell lines, if it worked in the narrow sense of the term "therapeutic cloning," would create competition for any commercial effort I am in. So I have been advised of that, too, by people in the company.

So is that all clear so far? Adult stem cells, that is my expertise, it is what I work on but I certainly have worked hard on trying to understand embryonic stem cells.

Now, I am Chair of the panel, as you know, of the National Academies Human Reproductive Cloning Panel and Report. And, I think, the most important thing to say first about that report, both by the charge, by the way we carried out the investigations which were extensive and over a long period of time, and in the report we published we did not look at ethical issues or moral issues or religious issues or political issues. We never discussed them.

Our charge was to look at the scientific and medical, and if medical practice were to be involved, the use of human subjects or human participants in research issues only. Our objective was to try to report to society-at-large what are the facts about either human reproductive cloning or nuclear transplantation to produce human pluripotent stem cells to give you and Congress and others in society that data so that you would be informed about the debate.

Now I should say, since you mentioned that Congress has passed a bill, they passed a bill without the benefit of scientific or medical information. I am sure if you look back at the debate, it did not include what the two Academies' reports are. The first one headed by Burt Vogelstein on stem cells; the second headed by me on human reproductive cloning.

Now you will know if you look carefully at the report that we examined and heard testimony about all of the many animal experiments to produce reproductive clones; that is to produce whole organisms to be born. And what we learned is that in every animal species, whether it is the beginning of the trial or experiments done even most recently, that using nuclear transplantation to give rise to a blastocyst that is implanted in the uterus with the intention of making a living newborn or a living organism that that failed at virtually every step of the way.

Now, you also know that both by IVF and by natural reproduction that there are miscarriages that occur and usually they occur in the first trimester. These failed with a high rate throughout the pregnancy and the consequences of a failure late in the pregnancy did have some morbidity and mortality for the mother that carried it.

There were also defects in placentation, making of the placenta, and also large offspring that developed from it and each of these had morbidity and mortality. Of the blastocysts implanted, on average, 8/10ths to 9/10ths of a percent of them made it to parturition, birth. And even then, many of the newborns died because they lacked the ability to breathe or carry out other functions and those that lived for a long time are coming down with defects that may or may not be attributable to the nuclear transplantation method.

So given that what we learned in many species is likely to occur in man, we decided that that was not ready for prime time. So now I will read just the recommendation itself, not all the preamble.

"Human reproductive cloning should not now be practiced. It is dangerous and likely to fail. The panel, therefore, unanimously supports the proposal that there should be a legally enforceable ban on the practice of human reproductive cloning.

"The scientific and medical considerations related to this ban should be reviewed within five years."

Now, go back. "Scientific and medical."

"The ban itself should be reconsidered only if at least two conditions are met: (1) a new scientific and medical review indicates that the procedures are likely to be safe and effective and (2)..." which we did not do "...a broad national dialogue on the societal, religious, and ethical issues suggests that a reconsideration of the ban is warranted."

We did not recommend that if it was safe and effective that it should be instituted, that is unfortunately, as I see some of the questions, a misconception and maybe it is our miscommunication but I am going to clarify it here.

Next: "Finally..." this is still part of the recommendation. "...the scientific and medical considerations that justify a ban on human reproductive cloning at this time are not applicable to nuclear transplantation to produce stem cells. Because of the considerable potential for developing new medical therapies for life-threatening diseases and advancing fundamental knowledge, the panel supports the conclusion of a recent National Academies report..." that's the Stem Cell Report, the Vogelstein Committee "...that recommended that biomedical research using nuclear transplantation to produce stem cells be permitted. A broad national dialogue on the societal, religious and ethical issues is encouraged on this matter." And I should say, this also was unanimously approved -- this recommendation approved by the committee.

Now I want to, therefore, say that from our point of view, we want -- we recommend a legally enforceable ban, and that is really important because, like many laws, we expect the ban will have an effect on society and those who would attempt to break the ban, rogue scientists you might call them or rogue clinicians or other groups that want to do it, that they would face whatever penalties a legally enforceable ban no matter where they are. So we wanted to make sure that we were not limited to those people who were under the purview of federal funding or under the purview of the FDA. We wanted it to be in the United States and to be clean. It was the line in the sand.

I do not believe we could have moved on to the next recommendation if we did not draw that line in the sand.

Now, for me to get into the terminology issue, I want to get it a little bit into the science, and I am going to apologize. I am going to get up like a professor and show you a figure and talk you through it, and you do not have that figure in front of you but Debbie Stein has assured me that by this afternoon you will have a copy of that figure.

Right, Debbie? You do not have that figure?

DR. STEIN: It is very close.

DR. WEISSMAN: It is close but I want to use this to explain what is going on.

It is like Figure 2 but it is not the same. You could write in the notes what I am going to tell you.

Okay. This was Figure 1. So just so you know, and I am sure you know it better than I even by now that if you enucleate a human egg or in the animal circumstance an animal egg, so you move the chromosomal material, you can transplant into it a whole somatic cell or the nucleus from a somatic cell from some part of the body. And in some frequency when you electrically stimulate that egg, some of them go on to form the blastocyst stage of embryo development, the pre-implantation embryo.

Of course, the fertilized egg is an embryo. The two cell stage, the four cell stage. And if you implant that in the prepared human uterus, which is a complicated procedure to prepare the female who will be the recipient requiring medical treatment and medical personnel, in an operating room setting -- and you will see why I am going to get there in a minute -- if it implants, it can go forward.

At about the time organs begin to form in a very vague way definitionally, it transitions from an embryo to a fetus. The common perception, I will just say to you, and you know it, when you ask somebody in society to draw what an embryo is, they usually draw a fetus, not a single cell or a two cell or a four cell. So that is just a problem that we all have to deal with is that the popular conception of what an embryo is, is not necessarily even close to the facts that are at least defined by embryologists.

So now let's talk about the nuclear transplantation technology. So here now the nucleus can be from any somatic cell. Let me back up just for one second. President Bush's recommendation, edict, whatever you want to call it, on stem cell, embryonic stem cell research has given to the scientific community the possibility to do research on as many as 64 embryonic stem cell lines derived from blastocysts, over there, from spermate fusion, excess blastocysts in in vitro fertilization clinics. That does not represent genetic diversity of humans and if one is going to do even research based on this you would want wider participation by all elements of society, humans genetically so you would understand.

So, one reason to do nuclear transplantation into an enucleated egg to create the blastocyst stage of development from which you derive inner cell mass cells that grow as pluripotent stem cells is to have a broad representation of cells to understand normal human cellular decision making as you go from a pluripotent stem cell, which can make any tissue in the body but does not have the capacity to make a whole placenta or trophoblasts that are involved in the placenta. So this is the only totipotent cell that can make both placenta and embryo, placenta and the developing embryo but after you get this stage. It cannot do it on its own and so it is a pluripotent cells. It can give rise to germ line and to somatic line.

Now, we know next to nothing about the processes that a pluripotent stem cell will turn into say a blood forming stem cell or a nerve stem cell or a muscle stem cell or so on. So it is a legitimate avenue of research to understand those processes with human cells that you could get analogies in animal cells but in the very end to understand the real decision making ourselves, which are crucial to understanding a number of developmental defects that could occur, would be to use a broad diversity of human cells.

Now, if -- and this is a very important point for at least the discussion. The nucleus could come from a normal person or the nucleus could come from somebody with a heritable disease. Everybody in this room, me included, contains genes which give a certain predilection for a human disease, and they are common diseases. Cancers, cardiovascular diseases, neurodegenerative diseases, both kinds of diabetes have a genetic component, and so on, Lou Gehrig's disease.

Now, the particular mutation that anybody found first, say for Lou Gehrig's disease, it is an enzyme called superoxide dismutase, when you have a defect in that, many, if not most people who have the disease, have that defect but not everybody who has a defect in that particular gene gets that disease. So if you want to have a real understanding of that particular disease or the other diseases I talked about, you would need to know all of the heritable components that come together to give rise to that disease.

Now in the human that has that disease, the components came together. So having a body nucleus cell would allow you to make pluripotent stem cell lines to study that disease process.

Some diseases, almost certainly all cancers, have something that goes beyond what you inherit. You have what is called "somatic mutations." Janet Riley is famous for finding somatic mutations that cause human leukemia or at least are involved in an important process. We also studied that in animal models and I can tell you that there are many successive mutations that have to occur. Only in that disease cell, only in that patient do you have the life history that led to that disease. There is no animal model close to this. And understanding how that nucleus, making a pluripotent stem cell line, could lead to the differentiation of cells, for example breast cancer, colon cancer and so on, would be a boon for science. There is no doubt about that.

Now, once these kinds of cells are allowed to differentiate, in many cases you can transplant them into a mouse and show in the context of normal development what goes right or what goes wrong. So the full uses, therefore, of nuclear transplantation for this kind of biomedical research includes normal subjects, heritable disease body cells and the nucleus of the disease cell itself.

If that is permitted, I can tell you that many, many of the best and the brightest will want to study that because it gets you closer to the truth of what is going on rather than the other reductive processes that one uses to try to get at the truth of what is going on. It allows you to look directly rather than by correlation.

Now, since these cells can be made and shown to be made in the tissue culture, many people, and of course companies, say that nucleus coming from that person has the same genetic material and, therefore, could be transplanted to repair defective, degenerated tissues. That is called "therapeutic cloning." That is the only place that therapeutic cloning, the word, fits in. That is why even though I agree completely with you about the popular sense of this, we need to come to the right terms because after a while what this group does, what the government does, what the national societies do to change the terminology will lead to a terminology that will be learned by the popular group but to say this is the only use is to, I think, skew the understanding of the broad importance of this kind of science if it is permitted. Okay.

And I should say even if these cells were here tomorrow, a lot of research would need to be done to make them transplantable entities. And in the -- for full disclosure, I should say that when you put the nucleus in from a somatic cell, the mitochondria still come from the host.

Mitochondria in every species so far are genetically diverse so that between two individuals, Janet's, for example, a particular enzyme like cytochrome C will have maybe one or two different amino acids by mutations that are still functional but our immune system, especially the so-called T cell components of our immune system, look -- scan those small peptides as they are presented on the surface of a cell to make an immune response.

And in mouse studies it is clear that those genetic differences can lead to a mild but certainly effective transplant rejection and so immunosuppression, mild though it is, will be required for that.

So, I think I have given you all the provisos that science can put in and I want you to know that if a ban or a moratorium occurs that blocks the fundamental research in understanding human disease development or therapeutic cloning, clearly promising avenues of medical research will be closed down. And, although I will get to it again in a couple of minutes, this group has a unique responsibility.

On the one hand, as you say, this might be a blastocyst with a tenth percent probability. Right? And that you are judging for various reasons whether that should retain the capacity to stay alive if it was created or in that case when it was naturally created or by in vitro fertilization. So you have a responsibility there. One that my committee did not even address but there is another responsibility that all physicians have taken an oath, and that is to try to be able to treat their patients.

And so I want to say that I believe, and I will give you an argument in a minute, that this is an equal awesome responsibility. Those who make the judgment that this research is banned take the responsibility of whatever medical treatments could have derived from it. There is no escaping this. All of us have that same responsibility. Just so we are all on the same page for that.

I will just take another minute to finish.

So what will be lost if there is a ban? I am going to use only one example, which was a hotly debated example in the '70s, as my precedent and you will find your own precedents. As you know, in the '70s the ability to put two pieces of DNA together became possible. Recombinant DNA. And it was hotly debated for many of the same reasons and, in fact, by many of the same people that this was creating life. It was creating a life form that had never existed before and the kinds of issues, I am sure, you are dealing with came up then.

The scientific community, notably Maxine Singer and Paul Berg, had a conference in Asilomar in 1975, I believe it was, I was there, where the scientific community said, "Let's wait for a minute and let's look at the possibility that something bad could happen from this at least that we could assess directly."

And from that a regulatory agency, the Recombinant Advisory Committee, was developed that looked at and regulated and, in fact, passed on all the plans to do recombinant DNA research.

There is probably not a person in this room who does not know somebody whose life has been made better or saved by the products of that recombinant DNA research. Erythropoietin, all kinds of cancer patients, dialysis patients, GCSF, the way to make stem cells come out of the bone marrow into the blood and do transplants which inarguably have saved lives by prospective analysis and clinical trials, the interferons, the antibody Herceptin for breast cancer, retuximab, and so on.

So I do not think it is arguable that if there had been a ban on recombination DNA research that there would not have been a loss of lives and many of them that could have been saved. Now I know that is going to be on my committee but I am just trying to say to you these are the facts. These are what you must know because the responsibility you are going to take to block a line of research could have that outcome and, of course, it can and probably will go forward in other countries. And then physicians here and the government here will be placed in a very unusual situation of what do you do when a cure comes from that kind of research and they want to import the cure to Americans?

What do you do as a physician, as a practicing physician? Would you deny your patient that treatment? I think you are going to have to consider that. I am not going to come down on it other than what seems to be apparent.

Now, many times the issue has come up that if you make the blastocyst in a research laboratory, what is to stop a rogue scientist from secretly putting it in the uterus of a woman?

That is what you said to me, Charles.

So I am going to try to deal with that issue. It was the reason that we needed to have a legally enforceable ban to stop that because we recognized we had testimony from three groups, two or three of which were going to go ahead no matter what we said and that was a fear.

So let me just say for those who have not participated in the isolation of eggs, the implantation of the blastocyst into a woman, this is not a single person's job. So for the safety of the person who is going to receive the eggs, of course, the -- I mean, the blastocysts, the blastocyst has to be grown in a sterile environment. The transplantation involves a medical team. It involves a woman who has to have been prepared hormonally for it. It is a surgical procedure to put it into the place that will go into the uterus and it involves anesthesiologists, nurses, doctors and so on. It is not something that a single rogue scientist can do in hiding.

Now, to the extent that one is governed by law, there are a lot of people and a lot of places that would then fall under the jurisdiction. It would be a hospital or a clinic or whatever. It would be very difficult, I would say, to do this and, I still say from my point of view, if you have covered it by law, you have covered it. We could argue, and you will argue long after I am gone, what about that rare rogue one who will just go all the way?

So that is my prepared remarks or actually unprepared remarks of my reflections of what the committee did. If you would like, I could go to some of the questions you have or we could just stop here and have open questions and then come back to the questions that you have written.

CHAIRMAN KASS: Let's -- Michael Sandel and Jim, let me make the suggestion -- I mean, Irv has -- you do not mind my saying have gone beyond the findings to speak about additional things towards the end, so even a way maybe to provoke comments about that as well. But I think if at least the beginning part of the discussion we could try to get some help such as we need it about the findings of the report proper and then move on to other things but I do not want to prevent people from going with it like Michael I saw and then Jim Wilson if I am not mistaken.

PROF. SANDEL: I have a scientific question and then a terminological one. The scientific question is could you tell us, based on what is currently known in the scientific community, what are the advantages of embryonic stem cell research as against adult stem cell research and how do those compare with this technique that was written up recently in the paper where an egg has been made to divide with our fertilization such that it might generate stem cells but does not have the potential for life?

DR. WEISSMAN: So let me go to what is known. And here I am going to try to adhere to a standard that journalists have recently, not all but many have crossed the line. Usually when scientists want to evaluate something scientific to know whether it is true there are two preconditions. One, of course, is that it is published in a peer reviewed journal so that other scientists can look at it with different viewpoints and look for holes in it and look for different interpretations and so on so that it has really gone through the wars before it gets published.

And then I still do not believe it, and most scientists do not believe it, until it has been independently verified by at least another laboratory as being something true.

Given those, we have nothing that adult stem cells, human or otherwise, would match the requirements here and I know that New Scientist magazine, not a scientific journal, reported unpublished results from a laboratory in Minnesota that would give all of us great hope that you might be able to get cells for therapeutic cloning. I will just say, first, it is not published yet.

CHAIRMAN KASS: You do not mean therapeutic cloning?

DR. WEISSMAN: Not cloning. Excuse me.

CHAIRMAN KASS: Yes, for therapy.

DR. WEISSMAN: Therapeutic outcomes -- I am sorry -- from adult cells. Thank you very much for the correction. All right. See what happens when you shut off, just all the natural words come by and then -- I will try not to shut off the brain while I talk.

So anyway -- and just to make sure, even though it was not published, I asked the inventor, the scientist, whether it would do everything that we described here. And I have a letter, which I do not know if it is published, she sent it to three senators say that it would not -- and I could read it to you if you like but what I am trying to say is that --

PROF. SANDEL: What are you referring to here?

DR. WEISSMAN: That there is no -- as yet, no fully pluripotent human cell taken from adults that will allow you to study normal development, heritable disease development, somatic mutation disease development or perhaps even therapeutic intent of transplantation. It might happen and it might come out, that part of it, but the scientist said, "You cannot fulfill all of these research objectives with that kind of a cell line."

So, I know every day you read in the media, you know, does umbilical cord do this, do placental cells do this, and are hematopoietic stem cells, the guys I study, can they do everything? And the answer is it is not there. It may come out to be there and all of us would be happy if we could do that but it is not there and so one should not make policy on the basis of those kinds of reported findings or unpublished findings.

PROF. SANDEL: And what about the other one, the parthenogenesis one, the unfertilized that has been --

DR. WEISSMAN: Sure. The parthenogenesis will only give rise to cells, of course, from that genetic origin, the mother. So, quite clearly, it will not cover any of those research objectives that I told you and it would limit the therapeutic intent to that mother. So if you needed to have it, you do not have a chance from that. You cannot do parthenogenesis. Okay.

CHAIRMAN KASS: Jim Wilson?

DR. WILSON: Thank you very much, Dr. Weissman. I would like you to clarify for me, a complete nonscientist, some aspects of your report. To be precise, these: You have spoken about nuclear transplantation and described it on your second chart here. Cell -- adult stem cells can also be derived, as I understand it, from fertilized eggs in in vitro fertilization clinics. In your judgment, are there important medical differences or are there likely to be in the future important medical differences between cells produced by nuclear transplantation and cells derived from fertilized eggs in IVF clinics?

DR. WEISSMAN: Yes. And part of this I probably did not explain it clearly enough first. The IVF clinics have people who come there for fertility problems. It is a very limited part of human genetic diversity. There are not nuclei there that I could go to and say if I want to study Lou Gehrig's disease or cardiovascular disease where you get a heart attack from the result of particular genetic defects, that is not there. So in a very important way those cell lines are only really able to tell you about the normal development from those cells and they will not allow you to do any of the other research objectives. And, of course, if you believed in the therapeutic transplantation, they would only be useful by having the same genotype as nobody who exists.

CHAIRMAN KASS: Stephen Carter and then Frank and Rebecca.

PROF. CARTER: Well, first, I want to thank you for what I think has been a very informative and in certain respects a very enlightening presentation. I am -- I have a question about -- I just want to make sure I understand something clearly about the presentation. I have a question -- I hope this, Mr. Chairman, is in order -- about the recommendation of the panel. Is that something I can ask now?

CHAIRMAN KASS: Sure.

PROF. CARTER: I just want to be absolutely clear that although I recognize the reasons for the different terminology that you chose for the processes you are talking about that up to the blastocyst stage these are identical processes; is that correct? This is the same process.

DR. WEISSMAN: Oh, you mean between this and this?

PROF. CARTER: Yes, this is the same process up to that point.

DR. WEISSMAN: Without a doubt.

PROF. CARTER: There is nothing -- nothing is different up to that point.

DR. WEISSMAN: Nothing is different.

PROF. CARTER: All right. I just wanted to clarify --

DR. WEISSMAN: Except perhaps the choice of the nuclei but there is nothing different between nuclear transplantation with the intent to create a blastocyst to be implanted from nuclear transplantation to create a blastocyst from which you get pluripotent human stem cells.

PROF. CARTER: Okay. Now, I have a question also about the recommendation. In the recommendation the panel unanimously proposed a total ban, a legal ban on what you called human reproductive cloning. It should be -- in five years we should reconsider the medical, that is the scientific basis for the ban. If the scientific evidence tells us at that point the process is likely to be safe and effective, then we should reconsider the ban itself only if there has been a dialogue, a national dialogue that also points to the same direction on the societal, religious and ethical issues.

DR. WEISSMAN: Exactly. A body like this.

PROF. CARTER: Now -- so the point is the ban itself is not based on those issues. You did not consider them. The ban itself is based on the question of whether it is -- the technique is safe and effective. It is not based in any way on these other issues that should also be considered. And so even if it becomes safe and effective, the ban should continue in place in your recommendation until such time as this dialogue has taken place. Is that -- I do not want to misstate it. I want to make sure this is correct.

DR. WEISSMAN: Yes, and I will look around for Maxine or Debbie. That is exactly my reading of our recommendation.

PROF. CARTER: So would it then also be the case that one could plausibly say that a ban on the second form of technology should remain in place until such time as the societal, religious and ethical issues have been addressed since in the first instance even if it is safe and effective medically you still think there ought to be time for a conversation about these other issues. Is that also the case with respect to nuclear transfer that is not intended to create a born human being?

DR. WEISSMAN: Here is where I will differ with you in words but not in the outcome. Since we did not recommend a ban for nuclear transplantation to produce pluripotent stem cells, there is no recommendation for a ban to be in place. Nevertheless, we said clearly, and I think it is the last sentence, a broad national dialogue on societal, religious and ethical issues is encouraged on this matter.

So what we are reporting to you is that human reproductive cloning is dangerous. It is a dangerous medical practice. It contravenes the Nuremberg Code clearly. It contravenes everything that we gave our oath as physicians but there is no such evidence for a nuclear transplantation to produce these cells but as we are scientists and medical, people were not going to impose our personal opinion, which we do not even know. We never polled the panel what their personal opinions were. What we said is we are reporting to you, we are reporting to Congress, we are reporting to NIH, and we hope that this is going to be useful information in your dialogue.

PROF. CARTER: Let me -- I do not want to press much more. I guess, the point -- the question I was trying to ask another way is this: That with respect to human reproductive cloning, the way I read the recommendation of the panel, the question of safety and effectiveness does not conclude the matter.

DR. WEISSMAN: That is true.

PROF. CARTER: Okay. Thank you.

CHAIRMAN KASS: I have Frank --

DR. WEISSMAN: Or of responsibility for those who make the decisions.

PROF. CARTER: Yes, of course.

CHAIRMAN KASS: I have Frank, Rebecca, Gil and Robby at the moment.

PROF. FUKUYAMA: Thank you very much. That was quite helpful. I have two questions. The first is my understanding is that by either of these processes once you get to the blastocyst stage, in a certain sense, strictly speaking, is actually not cloning because the mitochondrial DNA always inherits from the mother's side and you mentioned that that might in some cases lead to the immune system rejection.

Are there other implications of that at further developmental stages? I mean, what --

DR. WEISSMAN: You mean in terms of the transplantation study in the animal models and in vitro ?

PROF. FUKUYAMA: Either. Or in terms of reproductive cloning. I mean, will the difference in the mitochondrial DNA lead to different outcomes in terms of --

DR. WEISSMAN: Well, we discussed the issues about normal embryos are born that have a fit between the nuclear gene products and the mitochondrial gene products, and in some experimental systems there are implications.

PROF. FUKUYAMA: Right.

DR. WEISSMAN: But these are by no means, at least from a scientific point of view, the major cause in reproductive cloning in animal systems that cause the demise of the animals. Many other -- and really not understood -- genetic changes in expression are probably involved in that.

PROF. FUKUYAMA: The second question is I am a little unclear as to what kind of research will happen after the somatic cell nuclear transfer produces the blastocyst and you say you want to study various disease models and then normal development and so forth.

DR. WEISSMAN: Sure.

PROF. FUKUYAMA: Does that invariably involve just harvesting the stem cells from the blastocyst and then doing things with them or does it involve actually allowing the blastocyst to develop, you know, to further stages?

DR. WEISSMAN: Right, right. In my view, and I believe in the panel's view, you are only harvesting the cells from the inner cell mass of the blastocyst. We would be pleased if it were so efficient that you could harvest one cell from the inner cell mass of the blastocyst. That is not here today.

There is no research that has been proposed by members of the panel or that I think are out in society to implant that into a woman that has been prepared for the purposes of harvesting cells or tissues. In my own personal view that would require -- that would also be medical research and would have risks not just for the embryo or fetus that develops from it but for the woman who went through the procedure.

So that is my personal view but certainly everything I have told you here is only done with the pre-implantation blastocyst.

PROF. FUKUYAMA: Would it be possible to develop a blastocyst, you know, outside of a womb?

DR. WEISSMAN: I have heard people say that that is an object for research. I have not myself, and I -- if anybody else has any information -- I have not myself seen an extrauterine development of a complex organism like a vertebrate or a primate beyond the blastocyst stage, although I could conceive it could happen but I think -- our report, by the way, did not go into enforcement that you might want, regulations that you would want.

The California report did and, I think, you ought to look at that report and other people's reports because I firmly believe that the Recombinant DNA example tells us how that should go forward through strict regulation but it was not part of our report.

CHAIRMAN KASS: There are several people, I think, who want in on this point.

Janet, were you going to go somewhere else or do you want on this point?

DR. ROWLEY: It will not be this direct point.

CHAIRMAN KASS: