FRIDAY, MARCH 4, 2005

Session 6: Human-Animal Chimeras

Council Discussion

CHAIRMAN KASS:  The last regular session before the session for public comments is on human-animal chimeras or hybrids, this time in the context of basic research in developmental biology.

I remind you that the Council last discussed this topic in connection with our recommendations in the reproduction and responsibility report.  You'll recall that we all agreed that there should be restrictions on fertilizing human eggs by animal sperm and vice versa, and on placing human embryos into the bodies of animals.

The question of producing chimeras by introducing human stem cells or their derivatives, for example, neurons into animals or animal embryos came up for discussion, but it wasn't fully treated.

There has been a fair amount of recent journalistic attention to this topic, as well as presentations on chimeras at a workshop of the National Academies of Science's Committee on Guidelines for Stem Cell Research last October and an anticipated report from the academies, I think to be released fairly soon, if I'm not mistaken.

Janet would be able to tell us since she is a member.

We'll probably speak to this subject, and therefore, I thought it was reasonable that we should have another look.

In preparation for this meeting, I should have suggested that you do likewise.  I went back and read the transcript of our meeting in October of 2003, where it was on the plane of whole animals and humanzees, but we didn't get down to the kinds of questions which are of immediate research interest, but it turned out to be for a first pass really one of the very rich and interesting conversations, and I'm looking forward to the conversation that we have today to see if we can make some progress on basically two questions.

If people say mixing the human and the animal, the general public responds with some, to say the least, with some kind of unease or disquiet, and the question is:  what, if any, is the reasonable basis of any unease over or objection to such kind of mixing?  And let's be clear:  even at the very beginning of life in this kind of developmental research.

And second, could one develop and articulate reasonable boundaries between what would be acceptable and what would be objectionable; what would be the acceptable and what the objectionable kinds and degrees of mixing in this research.

To get the conversation started, we've asked several people to open up with some comments, and first Diana and then Alfonso, which I assume will be more on the first of these questions rather than on the second.

So, Diana, please.

DR. SCHAUB:  Leon asked me if I would make a few opening remarks for this session in which we're considering human-animal mixing and developmental research.  In trying to figure out a way into this topic, the standard approach seems to be to focus on human dignity, the boundaries of the human and possible transgressions of those boundaries.

But I want to start less anthropocentrically.  Whenever human dignity is involved, some humans at least get mighty concerned.  They get on their high horse about it.  So I wanted to ease our way into figuring out our unease or possible unease by reflecting a bit first about animal-animal mixtures.

We should remember that the original mythological chimera was altogether beastly, a she-goal with a head of lion and the tail of a serpent.  There were, of course, mythological human-animal mixtures as well, like the Minotaur and the Manticore.  But let's take the chimera first, especially since she now gives her name to these new biotech possibilities.

I did look back at the Council's earlier discussion from October 2003 when this topic was first broached, and the humanzee, our version of the Minotaur, was much talked of, but the geep, the combination of a goat and a sheep that is our rather less indominatable version of the chimera, was not much mentioned.  No one seemed too bothered by the geep.

So let me just say that geeps do make me uneasy and uncertain.  I can state my confusion in the form of a somewhat tongue-in-cheek question.  When and if a geep behaves like an old goat, is he sheepish about it?

(Laughter.)

DR. SCHAUB:  In other words, does he feel sheepish about his goatish behavior?

What I mean to suggest is that species' integrity can be thought of not just genetically, but characterologically.  We know of the identity struggles and dilemmas of transgender persons.  I suspect certain transgenic creatures would also feel themselves displaced or find themselves displaced, uncertain of what form of animal happiness to pursue.  Maybe mules are mulish for good reason.  Maybe they aren't happy about their betwixt and between lot in life.

The hybrid I know the most about is the wolf-dog hybrid, and from what I know, I would say that one does the animal no favor by mixing the wild and the domesticated.

So of the readings for this session, I very much appreciated the Midgley (phonetic) article for its sensitivity to the species specific character of animal flourishing and for its warning about the consequences of a wanton disregard of that character.  Feeding sheep's brains to cows is as much a violation of species integrity as breeding sheep to goats.

There is an ethics of animal husbandry which ought to be a part of bioethics.

By contrast, I found the Cohen article much too facile in its dismissal of the species argument.  The authors want to take human dignity seriously, but I don't see how you can make an argument about human dignity without some fundamental understanding of what it is to be a human being and what it is to be some other kind of being.

Nonetheless, I think I agree with the policy position laid out in the Cohen article.  I don't like the geep because it confounds two creatures that make perfect sense in their own right, but as far as I can figure out right now, I don't object to the creation of human/non-human chimeras in neural stem cell research so long as adult human stem cells are used.

The reason I don't object is that they aren't, strictly speaking, chimeras.  They are pseudo chimeras or, more accurately, they're chimeras at the cellular level, but not at the level of function or temperament.

According to the Kennedy Institute paper, and I am trusting here that its authors are correct, the mixing that is being done so far, introducing small numbers of dissociated human stem cells into non-human animals or embryos, has not resulted in the emergence of altered human-like features or functions in the non-human.

And interestingly, the reason why the new material has not produced a new compound creature seems to be that species are to a certain extent at least fairly impervious to tampering.  Monsters aren't so easy to create.

According to the paper, the overall architecture of the host animal's brain would not be affected by the presence of these cells.  It did make me wonder how informative these experiments are if, quote, the non-human host governs the way that these cells function, end quote, and because of things like host mediated recruitment, the human cells become, quote, the practical equivalent of mouse or monkey cells, end quote.

And it seemed to me that the authors admit the limitations of these experiments when they say that the human stem cell chimeras are not so much a test of human neural characteristic development as a proof of principle that human cells can contribute to a non-human animal's development.

So transplanting human neural stem cells into a mouse no more transforms the mouse than transplanting a pig heart valve into a person transforms the person.  All of the rules that the authors recommend seems to me sensible, and although they don't acknowledge it, those rules are based on preserving species integrity.  Transfer the smallest number of cells necessary; use dissociated human stem cells rather than larger tissue transplants; and select host animals carefully, preferring distant relations over our nearer primate cousins.

The Council has already spoken out forcefully in opposition to any attempt to create a true human-animal chimera, like a humanzee.  It might be worth remembering that the Minotaur, that murderous half man/half bull, was the offspring of Pasiphaë, the Queen of Crete, and a beautiful bull.  In other words, the Minotaur was the monstrous issue of an act of bestiality.

In calling for a prohibition on the production of a hybrid human-animal embryo by fertilization of human egg by animal sperm or of animal egg by human sperm, the Council was simply calling for a ban on high tech bestiality.  One hopes that is one tabu still intact.

I do have a question.  I had hoped that Mike Gazzaniga would be here, but there may be other scientists present who can answer it.

In the Council's earlier discussion, Mike suggested that one should view the mouse as simply a big, interesting, and better tissue culture system, but if I understand the Cohen article correctly, it sounds that this medium is an unusual medium in that it is not neutral.  The animal host is said to govern or rule the interaction and to rule in its own favor, co-opting the human cells.

My question is:  is that a help or a hindrance to learning what we want to learn about human neurons?

And if it's a hindrance, will there be pressure to relax the kinds of regulations recommended by Cohen so that the operation of the human cells is given larger scope within the animal most.

In other words, would these regulations and limitations that they recommend be readily accepted and observed or not?

CHAIRMAN KASS:  Thank you very much.

Are there people who want immediately to put questions either of clarification or comment on Diana's or shall we have Alfonso's presentation and then proceed?

It looks to be the latter.  Alfonso, please.

DR. GÓMEZ-LOBO:  Thank you.

I guess there will be considerable overlap with what Diana has presented, but my exposition is geared more towards the second question, the aim to articulate reasonable boundaries, and this is just a first attempt at it.

In thinking about ethical perplexities involving human-animal chimeras, it is useful, I think, to start with the distinction between two symmetrical cases:  (a) the transplantation of animal stem cells into human embryos and (b) the introduction of human cells into animal embryos, and I'm leaving aside those other cases that we have commented on right now.

The ethical concern about modifying a human embryo by inserting into its cells from another species falls within the domain of the ethics of embryo experimentation.  It is one more experimental procedure that must be judged in accordance with the principles that should govern what is done to human embryos.

What principles apply will depend, of course, on the ontology of human embryonic life, that is, on what a human embryo is taken to be, and here, of course, the waters part.  We know of three positions here on the Council.

One, anyone who holds that an embryo is a kind of being that does not deserve respect will be inclined to hold that to produce a chimera presents on special difficulty, providing that such an embryo not be implanted nor be allowed to develop to later stages of fetal life.

Then there's number two.  For those who admit that a human embryo is a human organism at an early stage of her life and hence that she deserves respect, the introduction of foreign cells for experimental purposes represents a serious violation of ethical norms, in my view.  It is analogous, again, to battery, to the violation of the physical integrity of a person without her consent.

And number three, for those who hold the intermediate status of human embryos and the thesis of special respect, I honestly do not know what follows because of the indeterminacy of the position.  I suspect that many upholders of this position will give in to utilitarian pressure and admit that this form of xenotransplantation may be done for good reasons.  Acceptable reasons will surely include some reference to expected therapeutic results for a large number of people.

In the alternatives, just examined, what I had in mind were instances in which the human embryo would remain basically what it is and would receive dissociated animal cells that would be incorporated into a human life.  The resulting organism would still be human, though modified to a lesser or greater degree.

I find this morally troubling because I think that human embryos deserve respect.  In other words, as you know, I uphold position two above; and that an invasion of the body of this sort is, indeed, a violation of respect.

But more troubling is the possibility of introducing undissociated animal stem cells that replace the inner cell mass of the human embryo so that they take over the whole organism, and  Diana addressed this.  This would amount to a loss of identity, a loss of identity of the host organism.  That organism would cease to be human and become animal, an animal of the kind to which the donor of the cells belongs.

It seems to me that intentionally transforming a human being into an animal in this way would be an extreme instance of reducing humanity to a mere thing that can be obliterated at will.  Indeed, it seems to me that this would violate even the weakest form of the special respect claim.

Now, I move to Case B.  The ethical considerations for the second case, that is, transplanting human cells into animal hosts, do not follow so neatly from the diversity of opinion concerning early human life, and the reason for this is that the key moral features of the action do not depend on the host organism, but on the manner and type of transplantation of the human cells.

Let me start with the most extreme and highly unlikely case.  Suppose human neurological stem cells are transplanted into a primate so that the animal acquired some key human features.  It seems to me that this would be morally troublesome in spite of the often heard argument that there's nothing wrong with enhancing the capabilities of an animal.

In my opinion, this procedure should be viewed the other way around.  It is not that an animal is thereby enhanced, but rather that what is essentially human is really debased.  It is closer to the production of a human being in the wrong body.

And I often imagine what it would be like to wake up one day only to realize that I have the body of a chimpanzee.  Luckily, we're told that this is virtually impossible because the human body as we know it seems to be absolutely necessary for the development of the human mind, and I'm thinking about size of the brain, the cranial space, et cetera.

The insertion of human cells in a host animal does not produce specifically human capabilities, but works in the manner of a genetic magnification.  If by xenotransplantation pigs are made to have human blood flowing through their arteries and veins, I do not see an equivalent moral problem.

If such chimeras are generated not arbitrarily, but with a clear goal of benefitting human beings, for instance, by providing a source of blood transfusions, they would be one more instance of putting animals at the service of mankind.

Our dominion over animals, however, is not without moral boundaries.  If our stewardship of nature becomes a form of tyranny, we'll not only be turning against our own humanity.  We'll probably risk initiating partial ecological disasters as well.

Even if there's uncertainty about the notion and status of biological species — I'm making a little concession to the Cohen paper here — even if one grants that, it seems reasonable to respect species as they are, as we know them, because we know too well that there are myriads of checks and balances in living organisms that we do not quite understand.  Upsetting those balances often brings about undesirable consequences.

The generation of Chimeric animals by transplantation into them of human cellular material with the aim of putting some of their tissues and organs at the service of human health then seems to me to be in principle morally correct.  This includes the use in research that should precede the therapeutic applications.

However, again, we also have a moral obligation to be cautious and to bound ourselves to certain limits.  Among them I would mention the following.  For instance, I think that the number of Chimeric animals to be generated should be as few as possible, as few as possible and, secondly, should be kept under strict surveillance and, third, they should not be released into the environment.

Moreover, they should not be subject to avoidable pain.  Their use in experiments should be carefully scrutinized to determine whether there might not be alternative research avenues, et cetera.  In other words, many of these boundaries would overlap with standard principles for use of animals in research.

Mixing of animals from different species, on the other hand, with no specific human good in sight, such as, for example, the production of the geep, seems to me, as far as I'm informed, seems to me arbitrary and really morally unjustifiable.

Maiming or deforming animals just to show that we can do it seems to me deeply disturbing.  It is simply an exercise in arrogance and lack of respect for other living beings.

In sum, it seems to me that any Chimeric mixing in which human organisms are made partly animal while retaining human identity or are transformed into animals, losing their identity is objectionable.

The same holds, I submit for animal chimeras that run the risk of acquiring human capabilities.  On the other hand, the generation of animals with tissues and organs that through early transplantation of adult human stem cells makes them of service for human cures seem to me to be acceptable.

Finally, the Chimeric mutilation of animals when no human good is in sight can hardly be justified in my opinion.

Thank you.

CHAIRMAN KASS:  thank you very much.

Let me just open the floor for comments on either of the presentations or an elaboration of some of the arguments.

Robby and then Frank.

PROF. GEORGE:  I want to begin by thanking both of our colleagues for those splendid presentations.  Very informative and thoughtful.

I have a question that I think is mainly for Diana, though I'd be very happy to hear Alfonso's response or any reflections that it generates in Alfonso, from Alfonso as well.

It's this, Diana.  It goes to the question of species integrity as a moral concern or principle.  There is a conception of morality, one that I happen to share, which is broadly speaking humanistic.  Under that conception, what moral norms do is specify the integral directiveness of principles that, in turn, direct our action toward things that are intrinsically worthwhile for human beings and away from whatever is a contradiction or violation or whatever damages things that are basic forms of human flourishing because they're intrinsically good for us as humans.

Now, Alfonso, when he gets to the point in the analysis where he's talking about species mixing in geeps and so forth, resolves it in a way that does not go beyond that humanistic conception of ethics.  At the end of the day, the points that Alfonso adduces against the mixing, where he thinks there are problems with the mixing, have to do with the violation of human goods.

But I think you were different.  I think your analysis is one which holds before us the possibility that precisely something beyond the humanistic concern is at stake here, is that species integrity is itself the stuff at least of a moral principle, if not a moral principle itself, because it gives us a reason for action or a restraint quite independently of the impact on the human good; that there's just something about species mixing itself that is troubling even if moral goods are not at stake there.

I'm not suggesting at all that that's idiosyncratic.  I mean, there's a strong tradition that's contrary to my own that says that the humanistic principle isn't the uniquely correct touchstone of ethics.

But I wonder if you could say a word about why you would embrace that, what argument you would give for treating species integrity, if I've read you correctly, for treating species integrity quit apart from any impact on human goods as providing something that will morally constrain our actions.

DR. SCHAUB:  Yeah, I don't know that I can give you an argument.  I mean, I think you're right that I am making a slightly different argument than Alfonso.  I think there's such a thing as animal happiness and particular modes of animal flourishing, and that we should come to understand and respect those modes.

PROF. GEORGE:  For our sake or for theirs?

DR. SCHAUB:  For both probably.

PROF. GEORGE:  Is it because there's a sense in which our fate is bound up with theirs?  Do we have some kind of solidarity or communion with them that is at least analogous to that which we have with each other, which provides the foundation?

Dan Callaghan and I were getting into this a little bit yesterday, the foundation for principles of justice and charity that govern human relations.

DR. SCHAUB:  Yeah, I mean, I suppose if you began from a kind of stewardship argument.  I mean, that's why I mentioned about animal husbandry being part of bioethics.  That would be beginning from what our responsibilities are toward the rest of creation.

PROF. GEORGE:  I wonder if Alfonso would have a word on this.

DR. GÓMEZ-LOBO:  Well, as my argument showed, I share your basic humanistic approach, although I'm willing to argue that a case can be made for the entirety of nature in terms of something, for instance, like the internal tuteology (phonetic) that makes it questionable that we should, for instance, mutilate animals in a way that they would not acquire their usual flourishing.

But in this discussion, I prefer to keep it within these boundaries and the reason is this:  is that many people who have completely divergent positions in ethics would totally reject that view.  Many people view nature simply as a big repository of genes or whatever, where you can do whatever you want.

So I prefer to — but those people would accept, say, liberal principles of respect for persons, and that's where I would like to meet the challenge.

CHAIRMAN KASS:  Frank.

PROF. FUKUYAMA:  I would just like to say on that last question if you're going to defend species integrity, then you're going to have to take on the whole agro-biotech  industry because they're already doing things like inserting jellyfish genes into corn plants and so forth, but that wasn't the main point I wanted to make.

It does seem to me — I appreciated the two presentations — it does seem to me that it's really not possible to take on this issue systematically unless we revisit a question that we never really came to closure on in the first term of the Council, which was the whole question of what we mean by human dignity, and that, of course, is a criticism that was made, you know, of various reports that the Council issued without really defining, you know, what the term meant.

And it's important in this respect, because, you know, that's what's under threat by mixing human and animal, and there are several things that can be said to it.

It is historically and culturally, I think, a byproduct of Western Christian civilization.  I mean, that's the historical origin of the concept of dignity.  If you look at most Eastern religions, that boundary simply does not exist, the boundary between this bright line between human and non-human, and it has a lot of interesting ethical implications for how they think about human rights and also the rights of non-human nature, but that's a separate discussion.

And what I think that we really need to have is a discussion about what we mean by human dignity, and particularly those of us that do not want to root it, you know, in Christian doctrine.  I believe that it is possible, you know, to retain a concept of human dignity.

In my mind, a non-religious version of this would be that human dignity is in some sense an emergent property of higher creatures, the highest of whom is a human being that cannot be explained in terms of, you know, any kind of reductive reference to the biological substrate, you know, that produces the animal.

So simply understanding, you know, the biology of the human brain does not explain the origins of human consciousness, and I think that then if you define human dignity in those sorts of terms, it gives you some moral guidance because it could entirely be the case that neurons, whether animal or human, are simply wires.  You know, that's all they are.  They're just wires, and so if you had a human brain built out of mouse neurons but organized as a human brain, that you would get the same emergent properties of consciousness and, you know, human emotion and experience.

We simply empirically don't know whether that's the case or not, but it seems to me that's quite possible, and if you define human dignity in those terms, then you know, you would actually have no objection to a medical procedure that tried to use, let's say, mouse stem cells to produce, you know, damaged human neurons to replace, you know, some neurological disorder.

On the other hand, it may turn out that, you know, the material substrate affects the emergent properties in ways we simply do not understand, and so that's an area that, you know, we'll just have to await further research.

But as I said, I really don't think that unless we come to some kind of a further discussion  of what it is, what we mean by human dignity that we're trying to protect in these discussions, that you can have any kind of systematic approach to this whole question of  mixing human and animal.

CHAIRMAN KASS:  Let me just see if I can get another couple of sentences from you.  The paper that was distributed from the soon to be published Kennedy Institute of Ethics journal, and our thanks to the authors for permission to circulate this prior to publication.

They, in fact, do try to articulate something of what's to be meant by human dignity, giving it a somewhat functional definition.  Most of the functions connected with things of the intellect and consciousness and the like, and tend to short circuit or at least to put down things that would be matters of species.

I think Diana alluded to that in her comment, however pointing out at a certain point that  — let me see if I can find the page — it's very doubtful that a human brain could be developed outside of the human body, which suggests that the human body is not simply a contemptible vessel in which a human brain and, therefore, personhood resides, but that something like the totality of the human being given not in terms simply of these functions that especially brainy people seem to elevate above all other things would be the measure of human dignity.

So are you committed when you introduce that?  I mean is your intuition that we need an account in terms of the distinctive functions that are somehow dignified, or would you go with Diana who seemed to be suggesting that there is a kind of species being in which the human body and the possibility of the embrace, as well as the ability to write the B Minor Mass counts.

PROF. FUKUYAMA:  Well, my instinct is always to assume that these things are much more complicated than we ever imagine, and so any simple functional list I am sure, you know, those functions will actually depend on all sorts of things that we simply do not really comprehend, including, you  know, many aspects of the body that may not seem immediately relevant.

So, yes, so I think that there probably is a certain thing like species integrity, although, you know, species do evolve and you can imagine the same kinds of functions being maintained under very different kinds of somatic characteristics, and so I think you have to be open to that also.

CHAIRMAN KASS:  Thank you.

I have Jim and then Gil and Ben and then Peter.

PROF. WILSON:  I think Frank is right that we have to come to grips with the concept of human dignity.  The animal world is filled with if not geeps, then deliberately arranged mergers.  Horses and donkeys produce mules, and mules are very different from both horses and donkeys.  If you have ridden them, you know, what the differences are.

In zoos we have ligers and tions, and I'm not aware that an important moral principle has been violated by these combinations, though the one that occurs in nature, the production of mules, is different from what occurs in zoos since what occurs in zoos would not occur in nature, as Hertz Meyers pointed out.

In this paper they talk about humanity from a Kantian perspective.  That is to say they are moral agents whose actions can be imputed to them.  People, human beings have the ability to act on principles, not simply on instincts, impressions, social pressures or the like.

And I think that's a very good place, and it is hardly a functional argument.  It is a profound argument to begin.  There are, of course, other religious arguments that one could make.

What I find troubling about the paper from the Kennedy Institute is that when it tries to defend human dignity, however defined, the definition I prefer or one that one of you prefer, it tends to fall apart.

For example, on page 23, it says we can at least envision that some investigators might attempt to transplant a whole adult human brain into a non-human animal in order to study certain important neurological questions.

But then on page 30 it says the rule for Chimeric experiments should be to limit to the smallest number necessary the number of human brain cells that are required to reach a reliable scientific conclusion.

Now, if they reject the idea of putting a human brain in a non-human animal, it seems to me they have already rejected the principle they state as the conclusion of their argument.  So that though I agree with their that human agency and human dignity are the crucial principle, I don't think this paper does a very good job of supporting it.

CHAIRMAN KASS:  Thank you.

Gil and then Ben and then Peter.

PROF. MEILAENDER:  Well, I originally got on the list to say something about the exchange between Robby and Diana, and I still want to say a word about that, though first may be just a word about Frank's comment.

However one ends up characterizing human dignity, as emergent property or whatever, one does with it, I think it's going to be important to keep in mind that there I'll just say may be — I think is — a significant distinction between whatever the distinguishing characteristics or capacities are that constitute this property of dignity which we ascribe to human beings, to the species.  There's a distinction between those characteristic capacities and the criteria for membership in the species which is so dignified.

That's going to be a crucial distinction because otherwise a large number of members of the species will lack the quality of human dignity.  So, I mean, if we're going to sort that notion out, that's an important distinction to keep in mind from the start.

Now, of course, everything is arguable, but it would be an important issue to keep in mind.

Now, just a word on the  Robby-Diana exchange because my own intuition is that actually it may not be sufficient to just count on the dignity language to handle the chimera problem, and we may need to get at the other kinds of arguments that the paper that we had took up only to dismiss, although I thought not always very persuasively.

In terms of your humanistic approach, as you called it, Robby, the animals are the other animals.  They're not just the animals.  They're the other animals because whatever else we are, we clearly are animals as well.

And maybe you're going to think this is just a round about way of bringing some human good in finally, but one might argue that it is in some way degrading for the human animal to fail to appreciate the bios, you know, the biological life of those other animals.

And it's not that there's any particular human good that's at stake there so much as it is imply that we don't act in a way fully in accord with the fullness of our own nature, which is animal as well.

I don't know.  You know, I don't have that argument all sorted out yet, and there would be more to say about it, but that's the route I'd want to try to take if I were going to try to tie into the suggestions Diana made.  It seems to me that there's something there worth trying to develop more fully, though I may not be able to do it that well right now.

CHAIRMAN KASS:  Ben Carson.

DR. CARSON:  Well, first of all, as a brain surgeon, let me say we don't have to worry about transplanting human brains into other animals because we're already dealing with billions and billions of neurons and hundreds of billions of interconnections, and it's not going to happen.

Now, you know, in terms of, you know, the integrity of the different species and why we should have respect for them, I think we have to look at environmental factors.  You know, when you look at environmental stability, obviously it has a great deal to do with how the various species interact, and when we begin to tamper with them, we'd better know what we're doing in terms of what's going to happen subsequently downstream.

I think in terms of let's say we got rid of all the snakes because we all hate snakes.  Well, we'd be overrun by rodents, and that's just, you know, one small example of that.  So we obviously need to be extremely cognizant of what happens when we interfere with natural environmental factors.

Now, is there, in fact, something different about human species versus animals?  And I guess some of that depends on where you think humans came from.  Obviously if we evolved as a matter of some promiscuous biochemicals from a slime pit a long time ago and just gradually changed until we reached the stage where we are, then perhaps there is not a great deal of difference between a human species and other animals.

If there is more to us than just our physical being and our mental being, if in fact there is a spiritual being as well, which in fact does allow us to compose the B Minor Mass and do a number of other things, then maybe that is the thing that distinguishes us.

Why is it that if we're dealing strictly with physical beings like animals, why is it that a human being going through a forest seeing another human being that they don't know drowning will jump into that river and try to save that person?  That would make no sense from a natural selection point of view.

So is there something different about us and other animals?  And I'm not sure that you can totally divorce that from a religious or spiritual aspect.

CHAIRMAN KASS:  Someone want to join this directly?  Peter, please.

DR. LAWLER:  First let me say something about animal happiness, which to my shame I had never thought about before.  Pardon?

Plant happiness which I'm not going to think about even now.

(Laughter.)

DR. LAWLER:  I think Diana is onto something here, although it is of no public policy consequence whatsoever.  There are animals which are dependent on us psychologically, like dogs.  The happiness of the dog is obviously arguably not purely physical, and we do some moral violence to our nature and the nature of dogs when we  treat dogs as something other than dogs.  If we treat dogs as less than dogs, that is being torture and utterly slave to our whims, and we do some violence to dogs when we treat dogs as more than dogs, if we treat them too anthropomorphically, if we have pet cemeteries and all of this.

So we are in a certain respect responsible for dog happiness.  We do a certain violence to our nature, although I'm not endorsing a law that would punish people who somehow did violence to their natures by sinning against dog happiness, but I think she's right in some way.

But with respect to human beings, what Ben was just talking about, the point that has been made and needs to be made again is we have no idea what a human brain would be like apart from a human body.  It's unthinkable.  The human brain and the human body are an undifferentiated whole, and it's the whole, right?  The brain and body that make possible what is distinctive about human beings and what arguably has dignity because, in fact, at the end of the day, being human is an all or nothing affair.  We can't imagine what it would be to be semi-human.

Human beings are the beings with language, who are as a result open to the truth about all things.  Either you're human in a certain way or you're not.

And so from this point of view, the difference between a human being an a dolphin is infinitely greater than the difference between a dolphin and an ant.  And so we know what it means to be human, a being with language and so all of the characteristics Ben was talking about.  This is observable.  It doesn't require really just faith really.

So if a human being had an animal body and nonetheless was a being with language open to the truth about all things, then that being would, in fact, be human.  It wouldn't be a human giraffe or whatever or some combination word, but it would be a human being.

And so the idea of designing a being that's partly human and partly not is not really given to us.  That designer point of view implies that you're not an animal at all, that you're standing outside natural life as Midgley points out, and so it's beyond our imagination even to conceive what the function of this designer being would be.

But if we could do it, here's something that we would know.  the thing that we would  create would be the most dangerous thing we could do to the environment imaginable because the truth of the matter is if it weren't for human beings, there would be no ecological crisis.  Nature would be fine.  If we were to disappear, we're the beings that can do war against nature or the technological beings, we're the beings who could kill for no good reason, dot, dot, dot, and so we have all of these adverse qualities which we have to try hard to keep under control.

Imagine what a being would be like that had a being with language and a body that was not fit for that.  Imagine the discontent of this being.  Imagine the perversity of this being.  This being would wreck havoc on nature.  This would be the ultimate ecological catastrophe.

So we shouldn't do this, but fortunately, as Ben points out, we can't do this.

CHAIRMAN KASS:  I want to shift the gears slightly.  The conversation has been sort of up here at a very high, talking about mixing organisms that would run around and also talking about, I think quite rightly, to try to give some sense of what are the principles or the grounds of the disquiet and the importance of trying to articulate some notion of human dignity or the species integrity or their relation.

But I'd like to spend the rest of the time on the concrete activities on which the science is now proposing to proceed, which is not to produce things that run around, but is to use the possibility of creating certain kinds of Chimeric organisms at early stage of development for the purpose of understanding certain things about development or transplanting, say, human cells into the developing brains of mice to learn something about — and then you can fill this out.

I mean, this is, I think, where the practical subject is, and I don't know, Janet, whether it's appropriate to ask you for comment on this since I know that the academy has had testimony on sort of chimeras in relation to stem cell research.

Could you say something about how you as a scientist, and not necessarily speaking on behalf of that committee, but how you would begin to think about this question of limitations between what would be perfectly appropriate, what becomes worrisome, and where the boundaries would be in this kind of research?

DR. ROWLEY:  Well, I'm hesitant to say too much.  As Leon has indicated, and this is not secret, the National Academy of Sciences currently has a group that is preparing guidelines for the conduct of human embryonic stem cell research.  These, of course, would be strictly voluntary, but it is hoped that if there were a thoughtful set of guidelines available for people who are embarking on this research, it might help to both set the bases for individual institutions setting their own guidelines, and if the guidelines were acceptable to institutions, they could be accepted as a whole.

The issue of chimeras has been discussed.  It is clearly, along with SCNT, one of the very thorny issues as to what should and shouldn't be allowed.  I think it's recognized by all members of the workshop that this is an area that science has to proceed very cautiously because some of these procedures are going to raise substantial concerns in the broader community in which we live.

We realize that the greatest areas of concern — and that clearly is reflected in the paper from Cynthia Cohen and her colleagues, is the area of the brain and mixing human and animal neurons and also any experiments that would allow human gametes to be produced by or mingled with gametes of animals.

So those are really the two most serious concerns, and the provision is made that any experiments that would be proposed in these areas would be reviewed very, very carefully by committees at the institution, and actually it's proposed that there be a special committee that would be developed at individual institutions, particularly those having a very active program in human embryonic stem cells, such that this would be a committee composed of individuals who were knowledgeable in the area, as well as ethicists and the public.

So the point is that individual research in this area is going to be scrutinized from the standpoint of is it necessary.  Are we going to learn something important?  Is there another way to do it that would not involve the use of human embryonic stem cells or stem cells differentiated down the neuronal pathway, and that slow is better in this particular regard, at least as regards to research that involves either neurons or the potential for gamete mixing.

CHAIRMAN KASS:  Not to press too much further on this, and it may be premature to day more, but you've identified certain areas of greater caution, neuronal and things having to do with gametes.  You set, therefore, a certain higher bar of scientific necessity before one considers these matters.

But then with respect to the ethical judgments, these are then to be left to the individual IRBs to sort through, or are there certain kinds of provisional, for the time being guidelines that one would say — because, I mean, Cynthia Cohen's paper, it's also partly — you know, it should be more of this.  I don't have the — it's a similar kind of quantitative rather than qualitative kinds of boundaries, leaving room for judgment as to what is too much and the like.

Is that the general spirit of the inquiry?

DR. ROWLEY:  I think that's the general spirit right now, in part because we are so ignorant, and there is the balance between in a rapidly moving field that is changing so constantly.  To be very precise means either that you allow things that you ought not to or you prevent things that would turn out to have some merit.

So at this stage at least it is left to each individual IRB to consider and try to come to the best judgment that that particular group comes to.  You are absolutely correct, and we say this specifically in the report, at least in its current state.  It's still under review and will be modified, but the report does say we're setting a much higher bar than is normally set for research by a standard IRB.

So that's stated explicitly early on in the report, and I think that to some extent it's going to be quantitative.  All of us are aware of the concern that we're going to have a human brain in a mouse with a person saying, "Let me out."  And that clearly is not a state that we want to get into.

At the same time, there are individuals who feel that we could learn a great deal by having human neurons within the brains of experimental animals, and these would depend on the different experiments, in trying to see how those neurons may function or may respond to certain drugs, to certain hormones, to certain growth factors. 

What would normal cells do in the brain of a mouse that has amyloid deposits?  Might it change the level, the position, et cetera?

So there are experiments that do have to take place in living tissue, distinct from at least some of the papers here saying that everything can be done in vitro.  That's absolutely not the case.  You really have to have the interaction of living cells in the environment because there is so much that we don't understand about the communication between cells, which is extraordinarily important in governing the behavior of those cells.

They respond to signals outside,a nd most of those signals are unknown to us at the present time.  So they think this is a balance, and I think we've tried in our considerations to recognize the concerns and to try to set fairly conservative limits at least in the beginning on how we think this research should proceed.

CHAIRMAN KASS:  Gil.

PROF. MEILAENDER:  Yes, just a question of clarification on this.  In the paper from Cohen and the others, the three guidelines that are given.

CHAIRMAN KASS:  Page 30.

PROF. MEILAENDER:  On page 30.  The third of them is about dissociated stem cells having to be used, and this may just be ignorance on my part, but would you characterize that as a quantitative rather than a qualitative guideline?

I would have thought that that was — whatever exactly those terms mean, that was closer to a qualitative than a quantitative guideline, unlike, say, the Guideline No. 1 about limiting the number of cells to the smallest number, but maybe I'm just misunderstanding something.

CHAIRMAN KASS:  No, I take your point.  Yeah, I think that is, if I understand it, as written, that looks to be different.  It seems to say that for the time being one should not use anything other than the introduction of dissociated separate cells rather than integrated tissues, not that the transfer integrated tissues is necessarily going to integrate into the new host, which is a point that Ben, I think, has already made powerfully.

PROF. MEILAENDER:  Right, but it would be a little stronger, these guidelines, what everyone thinks of the whole argument and so forth, is a little stronger than just recommending some quantitative restrictions.  That was just what I was trying to get clear on.

CHAIRMAN KASS:  There was a hand.  Bill.

DR. HURLBUT:  I want to underscore what Janet has said about this scientific significance offered by these possibilities.  I think that we should take that very seriously and recognize it because of the conservation of biology across phylogeny.  You get useful systems that can be in some ways compared or studied with parts of human capacities, even partial trajectories of human development in animal models could teach us a great deal without in any way violating the integrity of human moral standing that we would want to assign to a natural human being.

But I would also like to add another element of caution.  Janet has, I think, rightly identified the danger implicit in early mixing of ES cells, and can develop very much into human characteristics.

I think we also have to be attentive to this concern with regard to later what I sometimes call the architectural changes.  It is possible using certain technologies to transplant whole modules of developing portions of the embryo from one species to another.  This has been done by Le Dourian and Balabon, where they actually transplanted a portion of the developing brain, early neurologic system at that stage, and got the crowing capacities of a quail put into a chick.

And so he actually transplanted a unit of behavior.  Just to draw that a little farther, I think we should also be careful to not do that with elements of human form.  In other words, it isn't just a matter of cognition that we're concerned about.  The categories of our world, the conceptual categories that organize our world provide an intelligible world to us.  These are not to be taken lightly.

The way we understand our world is by the separations within the world.  For very serious purposes we might mix those, but I think we should be careful not just to see that as a matter of inner psychological or cognitive functions, but we need to preserve the human form, the dignity of the human form.

So I would say as at least an additional principle that we've been discussing, that later stage transplantation of human embryonic stem cell derived tissues, cells or organs, or any other way of deriving these things would be allowable until they manifest evocation of defining human dimensions of function or form also.  No unique human neurological capacities, but also no human faces, larynx, hands, or genitals, no characteristic body plans, postures, gaits should be produced by such a project.

Now, in order to prove something is too human-like even if we didn't assign it full human moral meaning, and certainly we don't want any of those kinds of elements of animals placed onto the human form either, no tails or antlers, for example.

I say that jokingly, because we wouldn't do it, but we need to take seriously the notions of where our natural boundaries sustain our understandable world, our intelligible world. 

So it isn't just a matter of function.  It also involves a matter of preserving human dignity by preserving the uniqueness of human form.

CHAIRMAN KASS:  Diana.

DR. SCHAUB:  Yes, can I ask Bill a question about that?

CHAIRMAN KASS:  Yes.

DR. SCHAUB:  I thought that some of that had already been done.  I thought I read something about, you know, a human ear on the back of a mouse, and I also wondered what it would mean for these possibilities that were distributed yesterday about growing human kidneys within animals and then being able to transplant them.

I mean, what counts as form?  Is the form the human kidney or the respect in the way that the — if one of our ears is worthy of respect.

DR. HURLBUT:  You know, that's a terrific question.  This morning earlier when we were talking about altered nuclear transfer, I was thinking about how we're uncomfortable with anything that's growing and seems to be alive.  Is it a being?

I personally feel a certain queasiness about factories growing kidneys, but nonetheless, I would think that it has such a good possibility if we could do it, I think we probably ought to.

But growing human organs inside of animals, if we could do it, does not strike me as the same as growing human forms in animals.  I mean, if you had a sheep with a human face or an animal that had human hands of a very identifiable sort, I think you'd be doing something that would involve violence.

The mouse with a human ear, I think everybody kind of understood they put a — isn't the way they did that, they put a form and the tissue grew around it?  It wasn't really a human ear exactly.

I agree there was a weirdness to it, but I'm talking about something a little bit more serious than that, I think.

DR. SCHAUB:  But why would the hand be different than the kidney?

DR. HURLBUT:  Because the kidney does not evoke for us the natural moral sentiments that preserve the intelligibility of our world.  It's a functional agent, an internal organ.  I think our external manifestations — let me extend this to robots, too. 

I don't think we should produce robots that are so indistinguishable from human beings that they confuse our categories.  That I think is actually a serious issue, and so it doesn't even have to be biological.  I think we have to preserve the meaning of the human form.  And that's largely a visual phenomena.

The very word "species" is related to the word "to look" and the appearance of a thing.  And I think we have to take these species separations seriously.

CHAIRMAN KASS:  Could I?  I think we should wind up and go to public session fairly soon, in fact, in a couple of minutes.

But I want to come back to these currently proposed developmental studies rather than producing things that are sort of visible grotesque and strange and raise those kinds of questions.

And I'm sorry Charles isn't here because Charles had a kind of intuition about what it means to be creating what he there called certain monsters or creating teratomas.  And I suppose for people who don't think an early embryo is much of anything — and Alfonso's comment, I think, prepared the ground for this — something which is not much of anything into which you incorporate an animal cell doesn't seem to be grotesque or weird if you sort of guarantee that you're not going to sort of face it grown up.

And similarly, since we probably rightly or wrongly care less for mice than we do for ourselves, putting a few human stem cells into a mouse blastocyst, especially if you think it's not going anywhere, one could sort of say, "Well, that's not really very much of anything either."

But leaving aside the vexed question of what really is the ontology and moral standing of the earliest stages of life, whether human or animal, and even allowing that this research could be beneficial, are there no people here who have some sense that we're engaged in something strange and weird, even going in the direction of a few human cells into the animal?

Now, Janet in her comment says we have to proceed cautiously because — and I listened pretty carefully — it was not necessarily because the people proposing to do these experiments themselves had qualms, but that the public at large wouldn't somehow understand this or would be nervous about it.

We are not altogether immune from being members of the public at large, and the question is:  is there some kind of — leaving aside the gross things that we've been talking about, but just staying with this very it looks like modest research, I mean, do people like Charles or Dan or Paul or Peter who have expressed some kinds of disquiet over creating teratomas or teratoma-like things which are not organisms had any kind of disquiet about creating these kinds of mixed species?  And is that disquiet articulable in some way?  And does it make any sense?

I think if we could have a minute or two on that, that I think is the practical question that we face at the moment and worth some attention.

Ben, do you want to say at least something?

DR. CARSON:  Yeah, just briefly.  I think it's very important as a Council that we make sure that  we distinguish between using human or animal parts across species, such as, you know, insulin, heart valves, things of that nature, and mixing the genetic material that has, you know, proliferative capacity.

I mean, there's a huge difference between those two things.  We need to make sure that the public understands that we are distinguishing between those two things.

CHAIRMAN KASS:  Well, thank you.

And I think in our last report we were very clear about that, and I think as the conversation proceeded, we should absolutely be clear about that.

Gil, do you want to have a comment?

PROF. MEILAENDER:  I was just going to say, I mean, I think what gives one pause, even if it doesn't finally lead you to object to say the sort of thing that this paper we read talks about, is that the sense that we are on our way to thinking about the human being as much a collection of interchangeable parts or species as just collections of interchangeable parts.

Now, I realize that once you start to press that, you can ask questions about organ transplantation and so forth, too.   Here we're thinking mainly about much lower levels of organization, but it's sort of the unity and integrity of the human person that's really the issue there.

Yeah, I mean, I think that it's the sense that having set foot on that path, it's not clear where there would be an exit ramp that is troubling in a way.

And that is actually why I asked the question about whether that one guideline was qualitative.  I mean, I'd be more interested in qualitative than quantitative guidelines because that would suggest that there was some ability still to make important distinctions.

CHAIRMAN KASS:  Last comment.  Alfonso and then we should stop.

DR. HURLBUT:  I completely agree with that, Gil, but that's why we have to do the hard moral work of defining what we're trying to protect because otherwise we're going to close off great human goods with scientific investigation.

You didn't say we would close it off, but it seems to me that we need to figure out what is it.  What combination of fundamental moral principle and natural moral sentiments, those things which we're trying to preserve, what analysis can help us define this?

That's why this whole arena with developmental biology requires that somebody do that hard work of figuring out what is the locus of human moral standing and human dignity.  It's not a simple matter.  It's the challenge of our era.

CHAIRMAN KASS:  But it seems to me Diana's paper was very, very useful because she didn't simply want to allow us to rest with the concern about the human, and that there is a certain posture with respect to the natural world, and at least raised the question beginning with the geep.

And I don't think — I mean, there are, in fact, people interested in proposing legislation that might seek to stop the creation of chimeras in which animal cells are added to human embryos rather than the reverse.  There are people worried about that.

But Diana at least has raised the question:  what does it actually mean to start down the road to producing these admittedly merely embryonic hybrids?  Is it sufficient that we know that that they're not going to grow up to somehow make the moral question sort of disappear, or is there a certain posture toward either species integrity or what is somehow owed to the animals in our relation to them?

That may not be the moral question of greatest interest to Robby or to Alfonso, but it is, I think, part of what's a concern for, quote, unquote, creating monsters, meaning something simply the crossing between two different kinds.

I don't want to sweep that particular question away.

Frank and then Alfonso and then we'll stop.

PROF. FUKUYAMA:  I would just like to point out that we eat all of these animals.  So I'm not quite sure what interest of the animals we're protecting by this.

CHAIRMAN KASS:  I think that's one question that leaving aside the alternative that rejects the eating of animals, there are respectful and disrespectful ways to treat the creatures who we exploit, and Diana.

DR. SCHAUB:  Yeah, this is not an example of a chimera, but I think it says something to it.  Yeah, we eat pork or some of us eat pork, but pigs should not be raised in a way that they gain weight at such a rate and to such an extent that they all become lame, and apparently for a while in the industry that's what was happening.  You had just, you  know, all of these lame animals.

So that, you know, pigs should enjoy a kind of pig happiness before the point at which we slaughter and eat them.

PROF. MEILAENDER:  I just wanted to remind Frank that we would be remiss if we did not call to his attention that, you know, he could read the Hungry Soul and think about these matters.

(Laughter.)

PROF. MEILAENDER:  Or read some of the reviews of the Hungry Soul that we produced back when the Hungry Soul was  public.

CHAIRMAN KASS:  Alfonso, the last word on this.

DR. GÓMEZ-LOBO:  Yes.  Just a question of conceptual clarification or for any other reason for my own mind.  I think that from what I read about chimeras there's a sense in which there are no real chimeras, that there is an incorporation of something coming from a different species into the life of whatever organism that is.

In other words, the geep, strictly speaking, is a goat, is a goat.  Now, this may prove to be useful in trying to draw boundary lines, and as Ben just said, for instance, just using pig valves clearly does not threaten the identity of the host.

So the real question is here what kinds of mixers are such that the identity of the host is being threatened.

But that brings us back, of course to the need to identify in humans what is that core.