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.
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.