## 1. Introduction




In classical Greek and Egyptian myth, chimeras are depicted as having
parts with the morphological characteristics typical of different
species. The chimera of Greek mythology, for example, has the head of
a lion, the body of a goat, and the tail of a serpent. Not all
chimeras are mythical, however. In fact, each one of us is most likely
a chimera, according to the modern scientific definition of a chimera
as a single organism composed of cells with different embryonic
origins (Nagy and Rossant 2001). As we interact with other organisms
over the years, their cells become incorporated into our bodies, not only
through a process of consumption and digestion, but also through processes
that leave the cells intact. For example, pregnant women acquire cells
from their fetuses and mosquitoes transfer blood between their
successive victims. More exotic natural chimeras occur when
early-stage human embryos fuse in utero, resulting in a child with two
distinct genotypes. Laboratory-created chimeras include the geep, an
intraspecies chimera made by fusing a sheep embryo with a goat embryo
or by transplanting cells from one embryo into another (Fehilly,
Willadsen, and Tucker 1984; Polzin *et al*. 1987). Like the
chimeras of myth, the geep exhibits morphological traits of multiple
species, with wool on some parts of its body and hair on
others. Researchers have also created quail/chick chimeras by
transferring parts of the neural tube (the precursor of the central
nervous system) from a quail embryo into a Leghorn embryo, resulting
in the transfer of vocalizations typical of a quail into the Leghorn
chick (Couly, Coltey, and Le Douarin 1992). Intraspecies mice/mice
chimeras, the most common of the laboratory-created chimeras, are
typically created by genetically engineering embryonic stem cells
derived from one mouse embryo and inserting them into another mouse
embryo at the blastocyst stage. The modified embryos are then
implanted into surrogate mice and brought to term. If the gametes
(sperm or eggs) of the resulting chimeric mice are descendants of the
genetically engineered cells, they can then be bred with each other to
produce nonchimeric offspring carrying the genetic alteration in all
of their cells.




The early discussion of ethical issues raised by chimeras occurred
under the heading of xenotransplantation, the use of non-human animals
as a source of cells, tissues, or organs for transplantation into
humans (Institute of Medicine 1996). The moral argument in favor of
xenotransplantation was one of beneficence: the shortage of human
organs available for transplant and the inadequacy of alternatives
meant that if non-human animals could serve as a source of organs,
hundreds of thousands of human lives could be saved or improved each
year (*ibid*., 14). The main ethical problems included the
health risks for the transplant recipient (e.g., a substantial risk of
hyperacute rejection and graft-versus-host disease), traditional
animal ethics issues, concerns about informed consent (complicated by
empirical uncertainties and the possibility of legally mandated
life-long health surveillance), fair allocation of health care
resources, and the public health issue that xenotransplantation would
allow viruses to jump the species barrier into humans.




For the purposes of this entry, however, the term
"chimera" will be restricted to chimeras formed by the
introduction of human pluripotent stem cells (hPSCs) or their more
specialized derivatives into non-human animals. Pluripotent cells are
capable of turning into any kind of tissue, and stem cells are capable
of renewing themselves indefinitely. So hPSCs theoretically provide an
indefinitely renewable source of any kind of human tissue, thus
offering tremendous potential for basic research, drug development,
and regenerative medicine (NIH 2001, 5-21). The first sources of hPSCs
were human embryos, and are thus referred to as human embryonic stem
cells (hESCs). These were established by James Thomson and colleagues
at the University of Wisconsin, Madison, in 1998 (Thomson et al. 1998)
and their availability has expanded the range of human/non-human
chimeras that scientists are capable of making. For example:


* The gold standard for ascertaining whether non-human cells are
pluripotent involves injecting them into blastocyst-stage embryos. The
resulting chimeras are then bred and the offspring examined to see if
all of their cells are progeny of the inserted cells. If so, then the
inserted cells were pluripotent, as evidenced by the fact that they
could give rise to germ cells and, consequently, to an entire
individual. In the case of hESCs, such a procedure would involve the
creation of human offspring as a means for testing cell potency, not
an ethically viable procedure. Instead, the standard method for
ascertaining whether putative hESCs are truly pluripotent is to inject
them into postnatal, immune-deficient mice, and see whether they give
rise to teratomas (tumors that consist of disorganized tissue growth
of the three embryonic germ layers, endoderm, mesoderm, and
ectoderm).
* Su-Chun Zhang, a researcher at the University of Wisconsin,
Madison, discovered how to direct undifferentiated hESCs into neural
precursors. To begin exploring whether these cells could serve as a
source of cells for possible nervous system repair, he transplanted
them into neonatal mice. The cells "were incorporated into a
variety of brain regions, where they differentiated into both neurons
and astrocytes" (Zhang et al. 2001, 1129).
* Undifferentiated hESCs have been transplanted into
blastocyst-stage chick embryos to determine whether "the chick
embryo could be used as an in vivo system for the study of human ES
cell differentiation" (Goldstein et al. 2002, 80).
* Transplants of hESCs into blastocyst-stage mouse embryos have been
performed to see if the chimeras could provide "an accessible
platform for studying the emergence of many human cell types; and with
the expansion of available hESCs to include genetically diseased
lines, mouse/human chimeras may allow us to elucidate the bases of
disease by examining the behavior of such hESC lines in live animal
models" (James et al. 2006, 100).
* As mentioned, xenotransplantation was traditionally conceived
of transplanting animal organs into human beings. Such interspecies
transplants, though, impose even greater risks than
allotransplantation (human-to-human transplants) on the organ
recipient because animal organs tend to induce a much more extreme
immune response than do human organs. Recent research attempts to
genetically engineer the animals to remove the most immunogenic
components. But some researchers are exploring the possibility of
going further by genetically engineering the animal so that it cannot
produce the desired organ on its own. This creates an unoccupied niche
in the animals. Human pluripotent stem cells are then inserted into
the animal to occupy that niche, with the result that the relevant
organ is made entirely of human cells (Waltz 2017.)




Chimera research inherits the ethical issues associated with
traditional animal ethics and, when using hPSCs derived from embryos,
with hESC research in general, but one striking feature of the chimera
debate is the existence of several advisory bodies that exhibit a
cautious reaction to certain kinds of chimeric research even though
they maintain that non-human animal research and embryo research are
generally permissible. For example, the Human Embryo Research Panel of
the National Institutes of Health (NIH) issued a general endorsement
of a wide range of embryo research (including hESC research) and
research on non-human animals. Nonetheless, the panel expressed
concern about the "extensive mixing" that would occur in
some chimera research and unanimously opposed, "on ethical and
scientific grounds, the creation of heterologous, or human-nonhuman
chimeras, with or without transfer [into a uterus]" (NIH 1994,
80). Similar statements have been made by the Ethics Advisory Board of
Geron, the private biotechnology company that financed Thomson's
original derivations (Geron Ethics Advisory Board 1999, 34), the
University of Wisconsin's Biotechnology Advisory Committee, which
provided guidance to UW on hESC research policy (University of
Wisconsin Biotechnology Advisory Committee 2001), the Committee on
Guidelines for Human Stem Cell Research created by the National
Academies' Institute of Medicine and the National Research Council
(National Academy of Sciences 2005), and the International Society for
Stem Cell Research (International Society for Stem Cell Research 2006,
7). This suggests that chimera research raises some ethical concerns
that are distinct from the traditional issues discussed about the use
of non-human animals or human embryos in research.


## 2. The Unnaturalness Argument




The argument against chimeras most often discussed is the
Unnaturalness Argument. It is also the argument against chimeras most
often rejected. Taken in its most basic form, the Unnaturalness
Argument alleges that because the creation of chimeras is unnatural it
is therefore wrong. The source of the alleged unnaturalness lies in the
fact that creating chimeras involves violating the natural species
boundaries between humans and non-humans.




Some criticisms of the Unnaturalness Argument focus on the
difficulties of defining "species." As Jason Robert and
Francoise Baylis (2003) note, although species can be defined
in terms of reproductive isolation, genetic isolation, shared
ancestry, or homeostatic property clusters, none of these definitions
takes precedence over the others. Rather, "Biologists typically
make do with a plurality of species concepts, invoking one or the
other depending on the particular explanatory or investigative
context" (Robert and Baylis 2003, 3).




Definitional difficulties, though, do not in and of themselves
provide reasons for thinking that a concept is morally irrelevant.
There are, after all, intractable disagreements about how to delineate
many key concepts relevant to ethics, including: killing and letting
die, life and death, consciousness, rationality, equality, justice,
respect, rights, and goodness.




Other criticisms focus on the permeability and fluidity of the alleged
"boundary" between species. Over long spans of time,
species undergo fusion and fission and although wide-crosses (breeding
between individuals of different species) are rare, they can occur
without human intervention. Moreover, bacteria and viruses frequently
transfer genes between organisms without any human intervention in a
process called "horizontal gene transfer."




This criticism is certainly probative against those who believe that
the boundary between species is morally relevant because they hold a
"biblical or Aristotelian view of species as fixed and immutable
rather than being slices of a dynamic, ever-changing process"
(Rollin 2003, 15), but the proponent of the Unnaturalness Argument
need not hold such a view. For example, the groups constituting one's
family and one's fellow citizens change over time, and yet we owe
special duties to our compatriots and to our kin in virtue of our
special relationships to them. So, fixed boundaries are not necessary
for moral relevance. And the mere fact that bacteria naturally
transfer genes across species boundaries does not mean that the
activity is natural when it is performed by humans.




A better objection to the Unnaturalness Argument challenges the
alleged link between unnaturalness and wrongfulness. Indeed, if
crossing species boundaries is sufficient for unnaturalness, and if
unnaturalness is sufficient for wrongfulness, then the creation of
mules and all other cross-species hybrids, even hybrid lilies, would
be wrong. On those definitions of "unnatural" that make
human intervention sufficient for unnaturalness, the view that
unnaturalness is sufficient for wrongfulness would entail the even
more outlandish conclusion that everything humans do is wrong. If the
Unnaturalness Argument is to be at all plausible, it must avoid such
implications.




The alleged link between unnaturalness and wrongness can be
supported in two ways, depending on whether the Unnaturalness Argument
is intended to be a so-called intrinsic objection or an extrinsic
objection. An intrinsic objection alleges that an act is wrong because
of its intrinsic properties, whereas an extrinsic objection alleges
that an act is wrong because of its consequences. A person who claims
that it is unethical to feed a certain diet to an animal because the
diet is unnatural is presumably making an extrinsic objection: because
the diet is unnatural, it will not meet the nutritional requirements of
the animal and therefore it will have unacceptable consequences for the
animal's health. A person who claims that the unnaturalness of
bestiality makes it unethical, even when it does not cause any harm or
pain, is presumably making an intrinsic objection.




If the Unnaturalness Argument is intended to be an extrinsic
objection, the link between unnaturalness and wrongness will most
likely be supported by pointing to possible adverse consequences for
the environment, public health, or the animal subject itself. Adverse
environmental consequences have not received much discussion, probably
because they are presumed to be adequately managed through standard
guidelines and regulations regarding the use of animals in laboratory
research. The possibility of a public health crisis arising from a
transmissible infection crossing species boundaries, a significant
concern with xenotransplantation, is greatly reduced when the source
of the biological material is human and the recipient a non-human
animal confined to a laboratory. (It should be noted, though, that
transmission of a porcine virus to human cells in a human/porcine
chimera has already been demonstrated (Ogle *et al*. 2004).)
Adverse consequences for the animal are important to address, but
their implications will depend on the moral status of the animal, an
issue addressed by the Borderline-Personhood Argument. On any of these
bases of support, the proponent of an extrinsic unnaturalness argument
would not be committed to the conclusion that everything unnatural is
unethical, since unnaturalness is not necessarily connected with these
kinds of bad consequences, and even when it is connected with bad
consequences, the act may be justified on other grounds. 




The Unnaturalness Argument is more commonly interpreted as being an
intrinsic objection. Even as an intrinsic objection, though, it still
might take a direct or an indirect form. A person who thinks that
promise-breaking is intrinsically wrong might think that
promise-breaking itself is the wrong-making property, or they might
believe that promise-breaking is intrinsically wrong because it is the
betraying of an induced expectation (Scanlon 1998; Pratt, 2001), which
itself is the wrong-making property. On the latter view,
promise-breaking is still intrinsically wrong because the betraying of
an induced expectation is not a consequence of a prior and distinct act
of breaking a promise; rather, in those circumstances, the breaking of
a promise is identical to the betraying of an induced expectation. The
ontological relationship between the two acts is not analogous to that
between pulling the trigger and a person's death but rather to that
between pulling the trigger and firing the gun. Similarly, those who
believe that it is wrong to create chimeras because doing so is
unnatural might claim that the intrinsic wrongness of these acts stems
directly from their unnaturalness or they might think that the link
between unnaturalness and wrongness is mediated by another property. As
John Stuart Mill observed, concerns about unnaturalness are, for many,
derived from concerns about offense to God:



> 
> 
> 
> The consciousness that whatever man does to improve his condition is
> in so much a censure and a thwarting of the spontaneous order of
> Nature, has in all ages caused new and unprecedented attempts at
> improvement to be generally at first under a shade of religious
> suspicion; as being in any case uncomplimentary, and very probably
> offensive to the powerful beings (or, when polytheism gave place to
> monotheism, to the all-powerful Being) supposed to govern the various
> phenomena of the universe, and of whose will the course of nature was
> conceived to be the expression. (Mill 1958 [1847], 14)
> 
> 
> 




The content of God's will with regard to the manipulation of nature,
though, is subject to speculation on both sides. Gary Comstock, for
example, defends the use of recombinant DNA techniques against the
objection that it constitutes playing God:



> 
> 
> 
> If humans are made in the divine image, and if God desires that we
> exercise the spark of divinity within us, then it should be no surprise
> that inquisitiveness in science is part of our nature. . .. It is
> unclear why the desire to investigate and manipulate the chemical bases
> of life should not be considered as much a manifestation of our
> God-like nature as the writing of poetry and the playing of sonatas
> should be. (Comstock 2000, 185)
> 
> 
> 




No matter whether the proponent of an intrinsic unnaturalness argument
believes that the link is direct or mediated, she will still not be
committed to thinking that all unnatural acts are wrong. Even if the
wrongness stems directly from the unnaturalness, this leaves open the
possibility that something unnatural could be justified by
sufficiently strong countervailing considerations, such as those
provided by medical benefit or scientific knowledge. The same holds if
the link is mediated, with the additional caveat that unnaturalness
may not be invariably correlated with the actual wrong-making
property. As Mill noted, the proponent of the Unnaturalness Argument
need only object to attempts "to exercise power over
nature *beyond a certain degree and a certain admitted
range*" (1958 [1847], 15, emphasis added). There is also the
possibility that the moral relevance of properties, unnaturalness
included, can vary from context to context (See Dancy 1993). In short,
it could be true that creating chimeras is wrong because it is
unnatural even though not everything unnatural is wrong.




Conceding that unnaturalness is not sufficient for wrongness, however,
opens the proponent of the Unnaturalness Argument to a further
challenge, that of providing principled grounds for distinguishing
between those cases in which an act is wrong because it is unnatural
and those cases in which an act is unnatural but not wrong, and of
showing that creating chimeras falls into the former category. If the
Unnaturalness Argument is intended as an extrinsic objection, there
are several detailed frameworks available for addressing risks to
public health, the environment, or the non-human animal research
subject. Any extrinsic Unnaturalness Argument is free to apply those
frameworks to chimeras, but will be incomplete until it actually does
so. If the Unnaturalness Argument is intended as an intrinsic
objection, then Paul Thompson's observation regarding intrinsic
objections to the use of recombinant DNA techniques states the problem
succinctly: "no one has succeeded in articulating a principled way of
stating why the unnaturalness associated with the manipulation of DNA
is unethical, while ordinary plant and animal breeding, computers and
modern transport are not" (Thompson 2000, 9).




At this stage in the dialectic, the Unnaturalness Argument can be
supplemented by considerations of the "yuck factor."
Proponents of the yuck factor argue that the reaction some people
experience in contemplating certain acts sometimes suffices for
knowing that the act is wrong, even in the absence of satisfactory
justification for the reaction (Kass 1998, 687). So proponents of an
intrinsic unnaturalness argument can insist that in spite of not being
able to provide principled grounds for distinguishing between the two
kinds of cases, they still know that creating chimeras is
wrong. Again, this conclusion is potentially supported by the
literature on moral particularism, which allows that a property's
moral relevance can vary not only from context to context, but also in
a way not capturable by a general theory (Dancy 1993).




Some have argued that the yuck factor has been discredited because it
has been used to rationalize discrimination (Thompson 2000). Racists
claimed to "know simply by looking" that interracial
marriages were wrong. But the fact that an argument has been used
inappropriately in some areas does not mean that it is inappropriate
in other areas. Paternalistic arguments were used to rationalize
unjust treatment of women and racial minorities, but that does not mean
that they are inappropriate when applied to toddlers.




Even opponents of the yuck factor must concede that, sometimes, we
know that an action is wrong merely on the basis of our reaction to it,
even if we cannot satisfactorily justify that reaction. We know it is
wrong to kill a healthy person so that his organs can be transplanted
to save five lives, even though we presently lack any theoretically
satisfactory way of distinguishing that case from the various trolley
cases prominent in the killing/letting-die literature. (See Kamm (2006)
for recent discussion.)




So appealing to the yuck factor can insulate an intrinsic
Unnaturalness Argument from the most common objections. It does so,
however, at significant cost. By conceding that unnaturalness is not
sufficient for wrongfulness while failing to provide any positive
argument for thinking that unnaturalness in the particular case of
chimeras makes them wrong, the proponent of an intrinsic Unnaturalness
Argument is reduced to the bald assertion that chimeras are wrong
because they are unnatural. This fails to provide any reasons
whatsoever to those who do not already share that view. The many
people, then, who think that the unnaturalness of a chimera does not
make it unethical to create them are in no way epistemically
irresponsible in simply rejecting the argument out of hand. Moreover,
the intrinsic Unnaturalness Argument differs from the killing/letting
die example given above in a significant way: although it is true that
we presently lack any theoretically satisfactory way of distinguishing
between the organ transplantation case and the various trolley cases,
we can nonetheless go a long way towards explaining why it is wrong to
kill a healthy person so that their organs can be transplanted. We can
talk about the harm of death, the frustration of future interests, the
loss of valuable opportunities, the right not to be killed, and so on.
But why think that the mere fact that an activity is unnatural makes
it intrinsically wrong, or even provides any reason whatsoever for
thinking so? It is hard to even begin to make the case, at least in
secular terms. Although some maintain that certain patterns of
inference from an "is" to an "ought" are valid
(see Thomson 1990, 1-33, for discussion), inferring that
something is even prima facie intrinsically wrong from the particular
fact that it is not natural certainly seems fallacious. An intrinsic
Unnaturalness Argument, therefore, is in a much weaker epistemic
position than an argument for the conclusion that it is wrong to kill
a healthy person for his or her organs.


## 3. The Moral Confusion Argument




In the first journal article focusing on the ethics of chimeras,
Jason Scott Robert and Francoise Baylis (2003) puzzle over
the negative reaction exhibited by the public to human/non-human chimeras.
Some people think that the public's reaction is explained by a widely
held belief in fixed and well-defined boundaries between species, or at
least between the human species and non-human species, but in fact "no
extant species concept justifies the erection of the fixed boundaries
between human beings and nonhumans that are required to make breaching
those boundaries morally problematic" (*ibid*., 6). Others think
that what people find objectionable is that crossing species boundaries
constitutes playing God, but many people do not believe in God and
others believe that God not only licenses, but enjoins the kind of
creative research involved in chimeras. Others think that people react
to the prospect of chimeras with repugnance, but such reactions are not
themselves sufficient grounds for concluding that an activity is
immoral. Nor do people's beliefs in its being taboo to blur sharp and
significant conceptual boundaries explain their negative reaction,
because the conceptual boundary between humans and non-humans is not
sharp.




So what does explain the public's negative reaction? Baylis and
Robert speculate that people object to chimeras because
they accept the Moral Confusion Argument, according to which it is
wrong to create chimeras because of the moral confusion that would be
generated by the existence of individuals that cannot be definitively
classified as human or as non-human (*ibid*., 9). This moral
confusion would arise because people employ two distinct frameworks for
understanding moral status: if an individual is a human being, then it
has full moral status, and it has that status independently of anyone
else's attitudes or intentions regarding it, but if an individual is a
non-human animal, then it does not have full moral status, and,
further, the moral status it does have and the nature of the
obligations we have towards it are contingent upon the attitudes and
intentions of their human creators or overseers. For a borderline
human/non-human chimera, it would not be clear which framework to employ
and, consequently, it would not be clear what our moral obligations to
this entity would be. Would it be appropriate to kill it for
food, or would that be murder? Which set of biomedical research
protections would apply, the relatively weak constraints on animal
research or the comparatively strong constraints on human subjects
research?




A real-life example that illustrates the possibility that chimera
research might disrupt a useful social practice is the attempt in 1998
by Stuart Newman (a professor of cell biology and anatomy) and Jeremy
Rifkin (an anti-biotechnology activist) to patent a broad range of
chimeras resulting from the mixing of human and nonhuman embryonic
cells (Heathcotte and Robert 2006; Rabin 2006). In 1987, then-United
States Commissioner of Patent and Trademarks, Donald Quigg had
announced that although human beings were not patentable,
multicellular living organisms, including animals, were. Newman and
Rifkin submitted their patent application in the hopes that either (a)
the patent would be issued, thus giving them the legal right to
prevent people from creating such chimeras, or (b) the patent would
not be issued, forcing the United States Patent Office to clarify the
dividing line between human beings and nonhuman animals. In the end,
the patent application was rejected, both on technical grounds as well
as the grounds that it encompassed human beings, which were not
patentable (Weiss 2005). The Patent Office, however, declined to offer any precise
details as to how to evaluate whether a chimera counted as a human
being or not. But what if, a proponent of the Moral Confusion Argument
might ask, the Patent Office had instead decided to revise their view
and allow patents on human beings or to reject all patents on
animals. Either decision would have entailed significant changes in
the social practice of patenting with, arguably, significant
costs.


Moreover, the existence of a borderline human/non-human chimera
would generate confusion regarding our existing relationships as we
were forced to revisit the general question of whether being a human
being really is necessary and sufficient for full moral status. Such
confusion, Robert and Baylis say, "threatens the social fabric in
untold ways; countless social institutions, structures, and practices
depend upon the moral distinction drawn between human and nonhuman
animals" (2003, 10). In these ways, then, "the creation of
novel beings that are part human and part nonhuman is sufficiently
threatening to the social order that for many this is sufficient reason
to prohibit any crossing of species boundaries involving human beings"
(*ibid*., 10).




There appears to be no empirical evidence to support the
sociological claim that the Moral Confusion Argument explains the
public's negative reaction. Among the voluminous social science
research on public attitudes towards biotechnology, the U.S. Office of
Technology Assessment's (OTA) report on public perceptions of
biotechnology remains the most comprehensive study of its kind in many
ways. It found that consequentialist concerns were cited by only a
meager 1% (for environmental concerns) to 8% (for "unforeseen
consequences") of the respondents who believed that creating
cross-species plants or animals was morally wrong (Office of Technology
Assessment 1987). Concerns about playing God and tampering with nature
were much more prevalent. And even if these concerns are unfounded, as
Baylis and Robert contend, it is surely fallacious to conclude that
they are not motivating the public's negative reaction. Conversely,
even if the threat of moral confusion is a serious one, that does not
alter the fact that it apparently did not even merit explicit mention by
the OTA.




Setting aside the sociological claim that the public's acceptance of
the Moral Confusion Argument explains its reaction to chimeras, what
about the Moral Confusion Argument itself? (Robert and Baylis
explicitly refuse to endorse or reject the argument, but they do invite
bioethicists to begin assessing its moral weight.)




Claims that the social fabric will be threatened by the latest
scientific research are usually vague and ill-defined enough so as to
resist conclusive refutation, but two things seem clear about
the Moral Confusion Argument. First, it seems highly unlikely that
chimera research would cause significant confusion along the lines
described. Second, even if chimeras were to cause confusion, that would
not provide much, if any, moral reason against creating them.




As to the first point, chimeras that are truly difficult to
definitively classify as human or non-human are purely hypothetical.
Even the chimeras involving the most extensive mixing to date
(Goldstein et al. 2002; Muotri et al. 2005; James et al. 2006) resulted
only in individuals easily classified as non-human animals. Such easily
categorized individuals pose no more threat to our views about moral status
than does a human being with a pig heart valve, that is, no threat
whatsoever. Hence, the idea that such confusion is threatened by
"*any* crossing of species boundaries involving human beings"
(Robert and Baylis 2003, 10; emphasis added) is surely mistaken. And
even if researchers were to create chimeras that were truly on the
border between human and non-human, it still would not follow that
there would be significant confusion as to the proper moral framework
for their treatment. If the chimeras were clearly persons (by
exhibiting a high degree of autonomy, rationality, self-awareness,
etc.), then it would be clear to most people that they have full moral
status, even if it would not be clear what species they were. As Andrew
Siegel (2003, 33) notes, most people hold the belief that "species
doesn't matter where one possesses other traits that confer moral
standing." Those who do mistakenly believe that being a human being is
necessary for full moral status might simply correct their mistaken
belief when confronted with an actual example of a non-human or
borderline-human that was clearly a person. Only the remaining people
who retain that belief would be confused.




Potentially more confusing would be an individual that was clearly a
non-person but who had just enough human material that they could not
be definitively classified as human or as non-human; for example, a
blastocyst-stage chimpanzee embryo which has had half of its inner
cell mass replaced with hESCs. But even in this extreme case, those
who believe that a fully-human conceptus has no moral status prior to
the onset of consciousness will simply conclude that a
blastocyst-stage chimeric conceptus has no moral status either. Those
who believe that a fully human conceptus has full moral status from
conception would need to decide how to classify such a chimera and may
be confused by the situation. But it is unclear why Robert and Baylis
think that someone's being confused about the specific case of the
chimera would also make them revisit their general belief that being a
human being is sufficient for full moral status. If the clear lack of
personhood of a human embryo or fetus does not cause such people to
revisit the general issue, why would the clear lack of personhood of a
chimeric embryo, which would seem to have even less going for it from
this perspective, cause them to revisit it? Indeed, it is not clear
why borderline cases pose any challenge to a general belief about
necessary and sufficient conditions. Someone who believes that being a
male sibling is necessary and sufficient for being a brother will not
be led to doubt that biconditional by the existence of an intersex
person who is on the border between being male and being female. To
the extent that it is vague whether the individual is male, it is also
vague whether the individual is a brother.




So confusion would really only arise for certain subgroups of people
with specific beliefs and with respect to chimeras that are, at the
present time, purely hypothetical.




As to the second point, even supposing that chimeric research did
cause society to revisit its views about the comparative moral worth
of humans and nonhumans, it still remains that this would provide
little reason not to create chimeras. Indeed, it seems more plausible
that this would provide, on balance, a reason to create
them. Returning to the example of Stuart and Rifkin's patent
application for chimeras, although the United States Patent Office
declined to offer guidance on distinguishing humans from nonhumans for
the purpose of patent law, legal scholars have begun to address this
issue (Stankovic 2005; Zylstra 2012). Of course, it is logically
possible that their scholarly efforts will result in changes to patent
law that will be for the worse, but that bare possibility is clearly
insufficient to justify an ethical condemnation of the scientists who
created chimeras that led to Newman and Rifkin's patent application
which in turn led to scholarly efforts that might in turn lead to
negative changes in patent law. As another, more urgent example,
consider that our willingness to place the gustatory interests of
humans ahead of the interests of non-human animals in avoiding pain,
suffering, and death has been one of the greatest causes of
unnecessary suffering in history (Scully 2002). In the United States
alone, there are approximately 9.5 billion agricultural animals
slaughtered each year, even though a vegetarian diet could easily
satisfy most Americans' nutritional needs (Humane Society of the
United States 2009). (This count excludes marine animals, which could
easily triple the total, and for whom death almost inevitably comes
from either suffocation or being crushed.) Revisiting the moral views
that are invoked to support this situation is probably essential to
improving this social institution. Thus, to prevent scientific
research on the grounds that it would force people to reexamine our
views about moral status would be to prevent not only scientific
progress but urgently needed moral progress as well.


## 4. The Borderline-Personhood Argument




Most groups that have issued an opinion on chimeras acknowledge the
existence of traditional animal ethics issues, but are content to
assert without argument that the use of non-human animals in chimeric research is
justified because of its scientific and, ultimately, clinical
importance. On the one hand, this attitude seriously underestimates the
difficulties, abundantly articulated in the animal ethics literature,
of justifying the use of non-human animals along these lines without either (a)
implying false and morally odious conclusions about research on
cognitively disabled humans or (b) taking an uncharitable view of the
cognitive capacities of non-human animals that is inconsistent with current
research on animal psychology. On the other hand, this attitude
probably reflects a realistic assessment of the limited willingness of
these groups' audiences (primarily scientists and research oversight
bodies) to seriously consider the possibility that most animal research
is ethically unjustifiable. The earliest evaluation of chimeras in terms of traditional animal ethics considerations is by David DeGrazia,
who has argued that the psychological characteristics of great apes
(chimpanzees, bonobos, gorillas, and orangutans) makes them "borderline
persons." Borderline persons have full, or near-full moral status,
which makes it unethical to use borderline persons in what DeGrazia
calls "neural chimeric research," research intended to lead to the
growth of human neurons in the subjects' brains (DeGrazia 2007,
325).




What is it to be a person? Being a human being (viz., being a member
of the species *Homo sapiens*) is neither necessary nor
sufficient for being a person: newborns are human beings but are not
yet persons, and members of other advanced, now-extinct hominid
species were persons but were not human beings. Rather, DeGrazia says,
to be a person is to have the capacity for sufficiently complex forms
of consciousness (*ibid*., 319). More specifically, albeit
still vaguely, to be a person is to have "enough" of the
following properties to a "high enough" degree: autonomy,
rationality, self-awareness, linguistic competence, sociability, moral
agency, and intentionality in action (*ibid*., 320).




Great apes deliberate, plan, and reason, thus displaying rationality
and the capacity for intentional action. They exhibit bodily
self-awareness, as evidenced through imitations of bodily gestures and
their reactions to mirrors. They also exhibit social self-awareness, as
evidenced by their knowledge of their position within their group's
social hierarchies. Their social self-awareness also, ipso facto,
demonstrates their sociability, which is also implied by the cultural
transmission of accumulated knowledge in primate communities. The
existence of a limited degree of moral agency is also supported by
apparently altruistic actions for which no conditioning or instinctual
explanation seems plausible.




Although great apes exhibit such forms of consciousness, DeGrazia also
notes that primarily because of their lack of linguistic competence
(itself important to personhood and also relevant because it limits
the cognitive capacities available), non-linguistically trained great
apes "are not so well endowed with [personhood-relevant] traits
that they clearly qualify as persons" (*ibid*.,
321). They do not even fare well compared to normal human children,
who "are clearly capable of introspective awareness ...,
robustly competent in language, and more likely to show signs of
autonomy" (*ibid*., 322). Despite his use of the adverb
"clearly" which suggests that this is an epistemic claim,
the conclusion is metaphysical: "It's not that we don't know
enough about them to say whether they are persons. Rather, they exist
in the gray area between paradigm persons and the vast majority of
animals who definitely are not persons" (*ibid*.,
322).




So what moral status do borderline persons have? On some views,
moral status is a binary property; an individual either has moral
status or it does not. Given that all sentient animals have at least
some moral status, it would follow on such a view that all sentient
animals have full moral status. A fortiori, borderline persons, being
sentient, would have full moral status.




On other views, moral status comes in degrees and while paradigmatic
persons (individuals that fully satisfy the criteria for personhood)
have full moral status, merely sentient animals (animals that are
sentient but that are clearly not persons) have a lower degree of moral
status. DeGrazia distinguishes between two views of what such a
difference in moral status consists in, the Unequal Consideration Model
and the Unequal Interests Model. On the Unequal Consideration Model,
this difference consists in its being the case that the interests of
paradigmatic persons matter more, in and of themselves, than the equal
interests of merely sentient animals. For example, causing a harm of a
certain magnitude to a paradigmatic person is morally worse than
causing a harm of the same magnitude to a merely sentient animal, even
setting aside the fact that the harm to the paradigmatic person might
well cause additional negative effects not caused by inflicting the
same harm on a merely sentient animal (Harman 2003).




According to the Unequal Interests Model, the difference in moral
status between paradigmatic persons and merely sentient animals
consists in the fact that paradigmatic person have interests of
significantly greater weight than the interests of merely sentient
animals. These weightier interests mean that killing a paradigmatic
person and thereby frustrating those interests will generally be
morally worse in and of itself than killing a merely sentient animal.
Moreover, harms that appear comparable at first glance, say, causing a
certain kind of injury, are generally morally worse in and of
themselves, when inflicted upon a paradigmatic person than on a merely
sentient animal. This is because the same kind of injury is likely to
impair the interests of the paradigmatic person more severely than it
would the interests of a merely sentient animal.




It should be noted that the Unequal Consideration Model is compatible
with assigning moral significance to the difference in interests cited
by the Unequal Interest Model. A proponent of the Unequal
Consideration Model could, for example, agree that being confined in a
cage generally causes a much greater harm to a paradigmatic person
than to a merely sentient animal. Differences between the two
frameworks arise when the harms to the interests of the individuals
are not merely similarly describable (e.g., "being
confined"), but are in fact of equal magnitude: the Unequal
Interests Model is committed to the conclusion that such harms are
equally morally problematic in and of themselves while the Unequal
Consideration Model is compatible with the conclusion that the harm to
the paradigmatic person is more morally problematic in and of itself
than the equal harm to the merely sentient animal.




According to these two models, what moral status do borderline
persons have? DeGrazia's argument continues: personhood-relevant
properties come in degrees, and so on the Unequal Consideration Model,
it is plausible to say that the amount of consideration an individual
is due is proportional to its "cognitive, emotional, and social
complexity" (DeGrazia 2007, 323). Depending on how fine-grained the
account is, borderline persons would therefore either have the same
moral status as a paradigmatic person (viz., full moral status) or, at
most, be due only slightly less consideration than paradigmatic
persons.




According to the Unequal Interest Model, the difference between
paradigmatic persons and borderline persons consists in their different
interests. But, here again, DeGrazia maintains, the differences between
paradigmatic persons and borderline persons are relatively slight, and
so on this account of moral status, borderline persons will either have
full moral status or, at most, have a moral status very near full moral
status.




On any reasonable view of moral status, then, there will not be a
large difference between the consideration due a borderline person and
the consideration due a paradigmatic person, and a borderline person
should therefore be viewed as analogous to a child: "not as
substantially autonomous or as having full-fledged moral agency but as
deserving moral protections of full strength" (*ibid*.,
323).




Such an individual, with full or near-full moral status, should not be
used in research unless (a) the research is more or less compatible
with the individual's best interests, (b) poses no more than minimal
risk, except where greater risks are justified by therapeutic
potential to the individual, and (c) the individual has not
meaningfully dissented, unless participation is of pressing
therapeutic urgency for the individual (*ibid*., 323). But
neural chimeric research does not come close to satisfying those
standards. The research is more than minimal risk, is not intended for
any therapeutic benefit for the animal, and at this experimental
stage, could not reasonably be intended as such. To take an extreme,
albeit hypothetical, example, the idea of a human/chimp neural chimera
in which the human and chimp phenotypic traits are thoroughly mixed is a chilling
one. All great apes are social creatures, and such an individual might
well be rejected by both species, evoking the tragic plight of
Frankenstein's monster. DeGrazia's argument, however, does not only
apply to such science fiction scenarios. Although he does not draw
this conclusion, if great apes have full or near-full moral status,
then it is probably impermissible to use them in any kind of chimeric
research in which scientists are currently interested.




Defenders of research on non-human animals typically object that
arguments against such research are overbroad. Where a defender of
animal research would locate the main problem with the
Borderline-Personhood Argument depends on whether moral status is a
binary property or whether it admits of degrees. If moral status is a
binary property, then, given that even merely sentient animals have
some moral status, it follows that even merely sentient animals have
full moral status. The Borderline-Personhood Argument then implies
that any research on any sentient animal is subject to conditions
(a)-(c). Given that all vertebrates are sentient, this would
prohibit the use of any vertebrates, even guppies, in any
non-therapeutic research that was more than minimal risk, irrespective
of how large the benefit for other individuals might be. Although some
animal rights theorists would accept this conclusion, defenders of
animal research will take it as a reductio of the Borderline-Person
Argument, maintaining that if full moral status really is as
ubiquitous as that, then DeGrazia's claim about the research
protections owed individuals with full or near-full moral status is
overly strict.




If moral status admits of degrees, then the defender of animal
research would locate the main problem with the Borderline-Personhood
Argument in its claim that there are only slight differences in
personhood-relevant properties between borderline persons and
paradigmatic persons. In fact, the differences between even a
language-trained chimpanzee and a normal adult human are quite large.
As DeGrazia himself argues elsewhere, for example, only normal adult
humans are capable of what he calls "full-fledged moral
agency" (1996, 199-210). Now, the Borderline-Personhood
Argument only requires that borderline personhood be sufficient, not
necessary, for full or near-full moral status, but both the Unequal
Consideration Model and the Unequal Interests Model quite generally
relate moral status to personhood-relevant properties. The question
therefore arises as to why these vast differences in
personhood-relevant properties do not underwrite a large difference in
moral status and a concomitant difference in the research protections
owed to individuals of the two groups.




DeGrazia could respond that, were they to do so, it would follow
that *human* borderline persons (he gives the example of an 18
month toddler) would also have significantly reduced moral status,
which is false (*ibid*., 322). But there are two problems with
this reply. First, it begs the question of why, on his view, there
*isn't* a large difference in moral status between human borderline
persons and human paradigmatic persons. The fact that large variations
in personhood-relevant properties do not seem to affect the moral
status of humans might support a very coarse-grained or threshold view
of moral status, but it might instead indicate that personhood-relevant
properties are not as central to moral status as the Unequal
Consideration Model and the Unequal Interest Model posit (Kittay 2005).
Second, if, as this response presupposes, the lack of
personhood-relevant properties of a non-human reduces its moral status
only if the same lack of personhood-relevant properties would reduce to
the same degree the moral status of a human, then the range of
non-humans with full or near-full moral status is much larger than
DeGrazia seems willing to concede. After all, despite the near complete
absence of personhood-relevant properties of a healthy but premature
infant or an elderly person in the late stages of dementia, such
individuals have full or near-full moral status and are owed
significant protections against being harmed in research (even though
their cognitive capacities might affect what kinds of treatments are
harms). Extending full or near-full moral status to all non-humans who
satisfied such a minimal threshold would have implications comparable
to those of the view that moral status is a binary property, and
defenders of animal research would find them equally implausible.




It should be noted that the U.S. National Institutes of Health has
ceased funding biomedical research with chimpanzees, and many private
companies have followed suit (Collins 2015; Human Society of the
United States n.d.). With Gabon being the only remaining country that
has a captive research population of chimpanzees (Nature 2011), the
question remains as to how applicable DeGrazia's arguments are to
other great apes and other non-human primates.


More recent evaluations of chimeras in traditional animal ethics
terms include work by Shaw, Dondorp, & de Wort (2014), who apply a
three R's framework (focusing on reduction, refinement, and
replacement) to argue for a generally favorable conclusion regarding
the use of chimeric non-human primates as a source of organs for
xenotransplantation. (For a critical response, see Palacios-Gonzales
(2016)).


## 5. The Human Dignity Argument




Although an evaluation of chimeric research in terms of human
dignity was first put forward by Josephine Johnston and Christopher
Eliot (2003), since then Philip Karpowicz, Cynthia Cohen, and Derek van
der Kooy (2004, 2005, Cohen 2007) have been the main proponents of this
view, and I will follow them here.




An approach to chimeric research in terms of human dignity needs to
provide an account of (a) what human dignity is, (b) what kinds of
individuals have human dignity, (c) what moral implications human
dignity has, in terms of generating moral prohibitions, requirements,
or presumptions, and (d) what constraints those moral implications
place on chimeric research.




Human dignity is a kind of "unconditioned and incomparable
worth" (Karpowicz et al. 2005, 119) and individuals with dignity
are therefore "uniquely valuable and worthy of respect"
(*ibid*., 120). Human dignity, understood in this rarefied way,
is distinct from the common kind of dignity manifested by someone who
responds to difficult circumstances in a dignified manner. Although a
person can be stripped of this common kind of dignity by being placed
in degrading circumstances such treatment would be said to violate,
not eliminate or diminish, human dignity in the rarefied sense; thus
the two concepts are distinct. Indeed, the individual's dignity in the
rarefied sense is often alleged to explain what is problematic about
eliminating this common kind of dignity.




Human dignity is grounded in the possession of certain morally
valuable cognitive and emotive capacities, and it is because these
capacities are valuable that individuals with human dignity are
themselves valuable. Accounts of which capacities are relevant vary,
but typically include the following: reasoning, autonomous choice,
complex communication, participation in social relations, sympathy, and
empathy. Those who possess such dignity-grounding capacities have human
dignity.




What kind of moral implications does human dignity have? Although it
is common to invoke human dignity in condemning a wide range of
nefarious and odious practices, proponents of human dignity are
notoriously vague both on the general principles generated by human
dignity and on how those principles tell against the activities in
question (Macklin 2003). Part of the vagueness lies in the fact that
proponents of human dignity frequently use language that implies that
human dignity itself is the subject of the wrong (e.g.: "torture
undermines human dignity", "human cloning denigrates human
dignity"), but if we instead understand such language as
shorthand for saying that an individual with human dignity is wronged,
and is wronged in a way relating to that individual's
dignity-grounding capacities, then the following moral implications
seem plausible. If an individual with human dignity is uniquely
valuable and worthy of respect because she possesses morally valuable
dignity-grounding capacities, then there would be a presumption
against interfering with the development, maintenance, or exercise of
her dignity-grounding capacities. More strongly, there might even be a
positive duty to support the development, maintenance, and exercise of
her dignity-grounding capacities. The proponent of human dignity is
also likely to hold that dignity-grounding capacities and the
individuals that possess them have a kind of moral value not
susceptible to utilitarian or, more broadly, consequentialist
trade-offs. Hence, these presumptions will not be rebuttable merely by
appeals to increased utility or value. This does not, of course,
commit the proponent of human dignity to the claim that the
presumptions are absolute, but it does mean that the presumptions will
probably correspond to rights with a relatively high degree of
stringency.




How, then, do considerations of human dignity give rise to an
objection to certain kinds of chimeric research? Karpowicz et al. say
the following:



> 
> 
> 
> By giving nonhumans some of the physical components necessary for
> development of the capacities associated with human dignity, and
> encasing these components in a nonhuman body where they would either
> not be able to function at all or function only to a highly diminished
> degree, those who would create human-nonhuman chimeras would denigrate
> human dignity. The torturer or the enslaver of human beings denies them
> the option of exercising the capacities associated with human dignity.
> The creator of the human-nonhuman chimera would do even
> worse--he or she knowingly would diminish or eliminate the
> very capacities associated with human dignity. (*ibid*.,
> 120-121)
> 
> 
> 




So, human dignity generates not only a moral prohibition on denying
people with human dignity the option of exercising the capacities
associated with human dignity, it also generates a moral prohibition
on diminishing or eliminating those capacities themselves. Chimeric
research, especially the introduction of an undissociated mass of
human stem cells into an animal blastocyst-stage embryo
(*ibid*., 126), has the potential to run afoul of this second
moral prohibition because such a transplant raises the possibility of
conferring upon an individual some of the physical components
necessary (presumably, biologically necessary) for the development of
dignity-grounding capacities, but without enabling the individual to
significantly exercise those capacities. Such research, Karpowicz et
al., maintain, therefore diminishes or eliminates those capacities,
and is therefore unethical. As an admittedly fantastical example of
research that would run afoul of the prohibition, Karpowicz et
al. consider transplanting an entire human brain into a nonhuman
primate: "the decision to manufacture a nonhuman research
subject with a human brain and, at most, diminished capacities for
various forms of human-like cognition and action would violate human
dignity" (*ibid*., 123).




There are two main problems with the Human Dignity Argument.




To see the first problem, notice that despite the terminology of
*human* dignity, whether some non-human animals have the
capacities that ground human dignity and whether some humans lack the
capacities that ground human dignity are empirical questions. As to
the former, Karpowicz et al. maintain that "[t]he family of
capacities associated with human dignity seem to belong uniquely to
human beings" (*ibid*., 122); as to the latter, they
maintain that "those who are human and yet display a limited
subset of these capacities, say, the newborn infant or the person with
severe disabilities, still have human dignity" (*ibid*.,
121). These answers are inconsistent. If the dignity-grounding
capacities of a human infant are sufficient to give it human dignity,
then the many non-human animals with the same or greater degree of
dignity-grounding capacities have human dignity as
well. Alternatively, if a chimpanzee's lack of dignity-grounding
capacities is sufficient to imply that it does not have human dignity,
then the even more meager dignity-grounding capacities of a human
infant are also sufficient to imply that *it* does not have
human dignity.




It is worth noting that this objection does not presuppose any
particular amount of dignity-grounding capacities as being necessary or
sufficient for human dignity. Given the fact that some non-human
animals possess the kind of cognitive and emotive capacities cited by
Karpowicz et al. to a greater degree than some humans, it cannot be the
case that (a) those capacities determine whether an individual has
human dignity, (b) that all humans have human dignity, and (c) that no
non-human has human dignity. This is true no matter how strict or
lenient one wishes to be regarding how many of the dignity-grounding
capacities an individual must possess to have human dignity.




The second problem for the Human Dignity Argument lies in its claim
that dignity-grounding capacities have been diminished or eliminated
whenever (a) we give an individual some of the physical components
biologically necessary for the development of dignity-grounding
capacities and (b) we do not give it significant opportunity to
exercise those capacities. Consider that having adequate blood pressure
is a physical component biologically necessary for dignity-grounding
capacities. Stitching a wound on a mouse so that it regains adequate
blood pressure, then, counts as giving it some of the physical
components biologically necessary for the dignity-grounding capacities,
but it fails to provide the mouse with a body sufficient for the
significant exercise of those capacities. It is clearly false to
maintain that such a medical procedure diminishes or eliminates those
capacities or, more generally, that such a procedure violates human
dignity in any way. Or, consider again DeGrazia's views about the
capacities of great apes. If he is right about those capacities,
whenever we provide for the biological needs of a great ape while
failing to provide them with intensive linguistic training, then we
provide them components necessary for dignity-grounding capacities
without the opportunity for exercising them. It is implausible that
such an activity is unethical, as implied by the Human Dignity
Argument, but even if it were, considerations of human dignity seem
irrelevant here.




Later, Karpowicz *et al*. mention not the physical components
"necessary" for the dignity-grounding capacities, but
rather those "especially associated" or "closely
connected" with the dignity-grounding capacities. This raises
the possibility that the physical capacities at issue are those
sufficient for the possession of the dignity-grounding capacities. But
research that confers the physical capacities sufficient for the
possession of the dignity-grounding capacities ipso facto confers the
dignity-grounding capacities themselves, in which case the research
has not diminished or eliminated the dignity-grounding capacities of
the animal research subject. Quite the opposite, the research secured
those capacities for the subject (Palacios-Gonzalez 2015, 493). More
generally, the proponents of the human dignity argument face a dilemma
that limits their argument's relevance. On the one hand, if the
introduction of human stem cells into a non-human confers
dignity-grounding capacities onto an animal that would otherwise not
have them, then the charge that such research diminishes or eliminates
those capacities is false. On the other hand, if the introduction
does *not* confer dignity-grounding capacities, then the charge
that such research diminishes or eliminates those capacities is also
false, as the capacities were never there to begin with.




Considerations of human dignity could ground an objection to research
in which the subject possesses the dignity-grounding capacities at the
start of the research, but then has them eliminated or diminished
during the course of the research. Such research would certainly be
objectionable, but this cannot be the objection that Karpowicz et
al. have in mind since they believe that non-humans do not have human
dignity at the start of the research. Finally, considerations of human
dignity could ground an objection to research in which, although the
subject does not possess the dignity-grounded capacities at the start,
the research brings it about that the subject comes to possess those
capacities but also prevents it from having the significant
opportunity to exercise those capacities. The problem in such a case
is not, pace Karpowicz et al., the elimination or diminution of those
capacities, but is rather the treatment of the subject after those
capacities have been acquired. This objection overlaps with the
objection implied by the Moral Status Framework, discussed in the next
section. The difficulty for the human dignity version of this
objection is to explain why the problematic feature of such research
is best understood in terms of human dignity as opposed to moral
status, autonomy, rights, and interests (Macklin 2003, DeGrazia
2007).


Considerations of human dignity occupy a central place within
German law: Germany's Basic Law says that "Human dignity shall
be inviolable." For extensive discussion of chimeras within the
German legal context, see the German Ethics Council report,
"Human-Animal Mixtures in Research" (Deutscher Ethikrat,
2013 [2011]). 


## 6. The Moral Status Framework




According to the Moral Status Framework (Streiffer 2005), what is
distinctively problematic about chimera research is the possibility
that the introduction of human material would enhance an animal's
moral status to the level of a normal human adult without respecting
the moral obligations entailed by that status. That is, such research
might cause an animal, which would have had a comparatively low moral
status, to instead have the moral status of a normal human adult, and
yet the animal might continue to be treated in ways typical of animal
research subjects and which would be profoundly unethical given its
new moral status.




Let us say that an individual's moral status is enhanced if it is
raised from a (significantly) lower degree of moral status to the
moral status of a normal adult human. The Moral Status Framework
raises two general questions about chimeric research. First, under
what circumstances is it permissible to perform research in which an
animal's moral status is enhanced? (If animals already have the same
moral status as a normal human adult, then the Moral Status Framework
becomes otiose, except as a possible sociological explanation of why
some people who believe that animals normally have a significantly
lower moral status than humans might object to some kinds of chimeric
research.) Second, under what circumstances would the introduction of
human material actually enhance an animal's moral status?




The moral permissibility of research in which an animal's moral status
is enhanced can be evaluated both from the perspective of the research
subject and from the perspective of others. From the perspective of
the subject, there would seem to be the following main
possibilities. First, an enhancement in moral status might always be
an unequivocal good. Any deleterious effects an enhancement might have
on other factors that are relevant from the subject's perspective are
always outweighed by the enhancement itself. This can be labeled the
Millian View, since it echoes Mill's remark that it is better to be
Socrates unsatisfied than a pig satisfied. (If one links moral status
to the Kantian good will, it also echoes Kant's remark that the good
will, "regarded in itself, is to be valued incomparably higher
than all that could merely be brought about by it in favor of some
inclination and indeed, if you will, of the sum of all
inclination" (*Groundwork*, AK 4: 394). 




Second, there is the opposite of the Millian View, the No-Enhancing
View, which holds that conferring an enhanced moral status on an
individual is always objectionable from the individual's
perspective.




Intermediate between these extreme views are various Instrumentalist
Views, according to which the evaluation of an enhancement from the
individual's perspective depends (at least in large part) on how the
individual's life compares, in terms of other independently relevant
factors, to the life that it either would have had (the Instrumentalist
View with the Non-Moral Baseline) or to the life to which it is
entitled, given its enhanced moral status (the Instrumentalist View
with the Moral Baseline). The two Instrumentalist Views disagree on the
evaluation of research in which an enhanced individual's life is better
than it would have been had its status not been enhanced, but given its
new moral status, it deserves to have its life be even better.




Both of the extreme views are implausible. Imagine conferring an
enhanced moral status on an individual, and then ensuring that it
lives a life in which it receives much better treatment than it would
have gotten otherwise and in which it is given everything it is owed
in virtue of that enhanced moral status. It is hard to see how this
outcome could be objectionable from the individual's perspective, as
implied by the No-Enhancing View. Nor does such research seem
objectionable from the perspective of others. It might be objected,
for example, that bringing new individuals into existence that have
the (previously) distinctive moral status of normal human adults
somehow lessens the value of that status for extant humans, as
expanding membership in an exclusive club might lessen its value to
its already existing members. That objection, however, is belied by
the fact that every time people reproduce, they engage in just such an
activity, and they produce far more individuals with human moral
status than would ever be produced by chimeric research. Another
objection might be that the extension of human moral status to
"lesser animals" somehow diminishes the value of that
status for humans, as extending a university diploma to those who do
not deserve it lessens the value of that diploma for those who do. If,
however, a transplant truly has enhanced the moral status of the
chimeric research subject, then in whatever sense we humans
"deserve" our special status, it now does as well, and so
the value placed on human moral status will not be lessened.




The Millian View is also implausible: what kind of life an
individual with an enhanced status will lead surely matters. My life is
better than the life of even a *very* satisfied pig, but if my
life were filled with enough pain and misery, and with extremely
limited prospects, it arguably would be worse. Indeed, the Millian view
is even too extreme for Mill, who agrees that some people's lives are
filled with "unhappiness so extreme" that they would be better off
exchanging "their lot for almost any other, however undesirable in
their own eyes" (1979 [1861], 9).




This leaves the Instrumentalist Views. If one of the Instrumentalist
Views is correct, then the question arises as to whether the moral
baseline or the non-moral baseline is relevant. To decide between these
two options, consider an example from the literature on exploitation in
which a transaction provides someone with a benefit, but with far less
benefit than they deserve: an employer who pays an employee a wage that
is beneficial compared to the alternatives, but is still substantially
less than what justice requires. In such cases, the relevant baseline
for the evaluation of the work is the moral baseline: given that the
employee deserves more, it is no defense of the employer's behavior to
say that the employee is better off than he would have been without the
job (see Wertheimer (1996, 289-291) for extended discussion of the
analogous case of an exploitative marriage). Similarly, the relevant
question for evaluating status-enhancing research is surely whether the
subject's new entitlements are respected.




Because the relevant baseline is the moral baseline, research in which
a non-human animal's moral status is enhanced to that of a normal
human adult raises the following problem. The view institutionalized
by animal research oversight committees is that almost any valid
research objective justifies sacrificing even the most fundamental
interests of non-human animals (Francione 1995). In contrast, the view
institutionalized by human subjects research oversight committees is
that humans have a moral status which provides them with substantial
moral protections, including a very stringent prohibition on harmful
research without informed consent. So long as experiments that involve
the transplantation of human stem cells into non-human animals are
overseen by animal research oversight committees, or by human subjects
committees attentive only to concerns of those who provided the
gametes or embryos from which the stem cells were derived, the wrong
set of moral protections is likely to be afforded to status-enhanced
chimeric research subjects. If the relevant baseline were the
non-moral baseline, then transplants that enhanced moral status
probably would be no more problematic than other kinds of biomedical
research on animals. But because the relevant baseline is the moral
baseline, sacrificing the fundamental interests of the chimeric
research subject as they would have been sacrificed in any other
animal research is the moral equivalent of sacrificing the fundamental
interests of a fully functional adult human being. In status-enhancing
research, what would have been animal confinement, pain, suffering,
and death, becomes the moral equivalent of--and, on an
anthropocentric view, also becomes--human confinement, pain,
suffering, and death. On all but the most extreme animal rights views,
this makes status-enhancing chimeric research much worse than other
biomedical research on animals, and on any plausible view, makes it
absolutely unacceptable.




Alternatively, if researchers adequately respected the chimeric
research subject's newly enhanced status, then this objection would
not apply to the research. But respecting the subject's newly enhanced
status would most likely frustrate the researcher's aims since most
biomedical research on non-human animals is done on non-humans
precisely because it involves procedures that plainly would be
unethical if performed on individuals with the moral status of a
normal human adult. And even if the researchers were willing to try to
respect the subject's newly enhanced status, it is hard to imagine
that they could come close to succeeding: what kind of life are they
proposing to provide for this individual they have created and who is
now under their care? Moreover, even if the research in question would
be compatible with the protections due to an individual with the moral
status of a normal human adult, another objection would then apply, at
least when the research is intended to provide human-relevant
information. Regular, non-chimeric humans will typically provide a
better model in which to learn about human development and in which to
test possible therapies intended for human beings. Thus, it would be
scientifically preferable to perform the research procedures on
regular human beings rather than on chimeras. To insist on performing
such research on enhanced human/non-human chimeras when they could
ethically be performed on human beings, then, would be scientifically
unjustified and would arguably constitute unethical exploitation of
the chimera for the benefit of others.




If almost any status-enhancing research would be unethical, then it is
important to know what kinds of transplants could enhance an animal's
moral status. Progress on this question can be made by asking why
normal adult humans possess their comparatively high moral status. On
cognitive capacity views of moral status, an individual's cognitive
capacities give them their moral status, and the high-level cognitive
capacities that normal human adults have is what gives them their
relatively high moral status (VanDeVeer 1979). Given that high-level
cognitive capacities are intimately related to the individual's brain,
this view obviously justifies focusing on transplants that could
affect the brain in a way that enhances cognitive capacities.
However, there are many constraints on the ability of human stem cells
to significantly enhance an animal's cognitive capacities. In some
cases, the subject will be terminated before the development of the
relevant cognitive capacities, thus side-stepping the entire
problem. In many cases, cognitive enhancements would likely be
prevented by the animal's smaller skull size and shorter gestation
period, as well as by the surrounding non-human cellular environment
that would provide developmental cues to transplanted cells (Karpowicz
*et al*. 2005, 124-126). In 2015, the National Institutes
of Health hosted a workshop on research with animals containing human
cells. Janet Rossant, chair of the workshop and a leading figure in
chimera research, summarized several of presentations from current
researches as follows:



> 
> 
> The state of the art today from all the contributors we heard was that
> you can do these experiments, if you make the cells perhaps a bit more
> naive then you can get cells into the blastocyst, but the
> contributions that you see in post-implantation fetuses are very
> low. They're not necessarily in all tissues, and the contributions are
> quite dispersed. So nobody showed us a very extensive contribution of
> human cells into an interspecies chimera (National Institutes of
> Health 2015).
> 
> 
> 



For the kinds of research currently underway, it seems highly
implausible that human cells could have significant effects on
cognitive capacities. There are, however, a few caveats that should be
noted.



First, following Rossant' summary, the scientists present had
extensive discussion about strategies for improving the rates of
chimerism. Considered purely as a scientific problem, there seems to
be significant interest in overcoming the current limitations which
prevent human cells from having much of an impact. Moreover,
exceptions to Rossant's generalization were mentioned later in the
workshop, including research in which human neural progenitor cells
proliferated "extensively" when injected into the adult mouse brain,
research in which some cell lineages continued to act like the
donor-species cell regardless of the surrounding animal environment,
and research in which human-derived glial progenitor cells outcompeted
the corresponding mouse glial, "ultimately dominating the brain".


 Second, some researchers might be interested in designing experiments
that intentionally seek to overcome existing limitations on cognitive
development in non-human animals. Some might want to do basic research
on the neurological development involved in language acquisition,
mathematical concept acquisition, moral development, or any number of
other cognitive capacities that are now limited to normally
functioning human beings. Other researchers might be interested in creating chimeras
in which the limitations on animal's cognition are overcome so that
they can be used as models to study diseases or injuries that impair
high-level cognitive functions in humans. As noted by the NAS
Committee,



> 
> 
> 
> [T]he idea that human neuronal cells might participate in
> "higher-order" brain functions in a nonhuman animal,
> however unlikely that may be, raises concerns that need to be
> considered. Indeed, if such cells are to be used in therapeutic
> interventions, one needs to know whether they could participate in
> that way in the context of a treatment. (NAS 2005, 33)
> 
> 
> 




Status-enhancing research performed for such ends, were it ever to
become more than science fiction, would be deemed impermissible by the
Moral Status Framework.




Second, it is not yet clear what kinds of cognitive enhancements might
be possible even within a constrained environment. For example, it is
possible to use genetic engineering to enhance the learning and memory
of mice without modifying skull size or gestational period (Tang et
al. 1999). Further, the incorporation of human glia and astrocytes
into the brains of neonatal mice was found to "sharply enhance" their
learning (Han et al. 2013, Cossins 2013, Cole 2013). More extremely,
if large quantities of hESCs are introduced during the early stages of
embryonic development, it is possible that the cells themselves could
induce changes that would eliminate some of the constraints mentioned
above. Although some of the experiments cited above do involve the
introduction of hES and neural progenitor cells early in development,
experience in this area is limited. As the NAS Committee
concluded,



> 
> 
> 
> This approach [the introduction of human ES cells into a non-human
> blastocyst] is an obvious extension of techniques widely used in
> research with [mouse ES] cells--namely, aggregation of
> morulas from two mice or injection of mES cells into mouse blastocysts.
> In both cases, the cells can contribute extensively to any mouse that
> arises from implantation of such a chimeric blastocyst. Clearly, an
> animal (e.g., mouse) blastocyst into which human cells are transplanted
> raises other issues because potentially the inner cell mass, the
> progenitor of the fetus, would consist of a mixture of human and mouse
> cells. It is not now possible to predict the extent of human
> contribution to such chimeras. (NAS 2005, 34; for further discussion
> see Streiffer (2005, 355-357, 363-364).)
> 
> 
> 




It therefore seems premature to place much confidence in our ability
to draw a precise line between transplants during the embryonic stages
of development that will, and those that will not, enhance an animal's
cognitive capacities. Moreover, even among those who favor a
cognitive-capacities view of moral status, it is contentious just what
level of cognitive capacities is needed to attain full moral
status.




On anthropocentric views of moral status, normal human adults have
the moral status they do simply because they are human beings, that is,
because they are members of the species *Homo sapiens* (Noonan
1970; Devine 1978; Schwarz 1990). As has often been noted,
anthropocentric views seem to suffer from an explanatory gap: it is
hard to see how being a member of a certain species could give an
individual its moral status (Regan 1978; Feinberg 1980; DeGrazia 1996,
56-61). Nonetheless proponents of these views argue
that they provide the only way to adequately explain the equal moral
status of all human beings, even human beings who lack high-level
cognitive capacities, and thereby to avoid the so-called "marginal
cases" that afflict cognitive capacity views.




Anthropocentric views raise difficult questions about how much human
material an individual needs in order to be a human being. Since normal
human embryos are both human and organisms, they are human beings,
albeit ones at the earliest stages of development (Feinberg 1980,
288-291). But when faced with an organism that has
some human cells and some non-human cells, how is one to decide whether
the organism is human, and hence, whether it is a human being? It is
overly narrow to focus on transplants that affect neural tissue, since
it is not plausible to suppose that an individual must have a human
brain to be a human being: an anencephalic infant is a human being and
would possess human moral status on an anthropocentric view.
Presumably, replacing the entire inner cell mass of an animal
blastocyst with hESCs would suffice to make the resulting
individual a human being since, in normal human development, the inner
cell mass is what goes on to form the fetus. In such cases, one could,
at least in principle, end up with a human being surrounded by a
non-human trophectoderm (the layer of cells surrounding the embryo
which goes on to form the placental structures). If an anthropocentric
view of moral status is correct then the Moral Status Framework would
clearly condemn such research. On the other hand, having only a few
non-human cells in the final individual would not suffice since a human
with a porcine heart valve is still a human being. But where to draw
the line is unclear, similar to the situation with objects that have
vague identity conditions (Parfit 1984, 231-243;
Thomson 1987; Thomson 1997; Piotrowska 2014).




In sum, then, although the Moral Status Framework appears to provide
a sound objection to status-enhancing research, its application is
nonetheless hampered by the empirical uncertainties regarding the
effects that various kinds of hESC transplants would have and the moral
uncertainties regarding which effects would be status-enhancing.


## 7. Conclusion




The Unnaturalness Argument raises concerns about the unnaturalness
of crossing species boundaries, and while it is sufficiently inchoate
that it may perhaps resist conclusive refutation, it is nonetheless a
very weak objection and it fails to provide any reasons for those who
do not object to chimeric research to change their minds. The Moral
Confusion Argument has been alleged to be at the heart of the public
controversy, but this allegation is not supported by the extensive
social science research on public attitudes towards modern
biotechnology. Moreover, the consequences posited by the argument as
being morally problematic seem unlikely to occur, and were they to
occur, would probably be beneficial in the long run, even at the cost
of some short-term social disruption. The Borderline-Personhood
Argument focuses on the personhood-relevant properties of great apes
and concludes that their borderline status as persons confers a high
enough degree of moral status to make most, if not all, chimeric
research on them impermissible. Like other traditional animal ethics
arguments, though, the argument depends upon controversial claims about
the sufficient conditions for full, or near-full, moral status. The
Human Dignity Argument attempts to explain why partial humanization of
a certain sort is morally wrong, but mistakenly assumes that such
research would eliminate or diminish an individual's dignity-grounding
capacities. The Moral Status Framework maintains that status-enhancing
chimeric research is permissible only if reasonable assurances are in
place that the individual's enhanced moral status will be adequately
respected. There are, however, several empirical and ethical
uncertainties as to which chimeric research, if any, would enhance a non-human
animal's moral status.




The foregoing has focused on the ethics of creating chimeras, but much
of the ethics discussion has either attempted to infer public policy
conclusions straightaway or has taken place within discussions
about what public policy should be. The recommendations of the
National Academies guidelines prohibit the introduction of hESCs into
nonhuman primate blastocysts (NAS 2006, 41), citing concerns about the
potential human contribution of such cells. The International Society
for Stem Cell Research guidelines prohibit research that involves
introduction embryos into which hESCs have been introduced into any
human or nonhuman primate uterus (ISSCR 2006). Although the ISSCR
guidelines do not provide a rationale for this prohibition, the only
potentially relevant rationale articulated in the accompanying
commentary cites a concern for the creation of "humanized cognition,
awareness, or other mental attributes" (Hyun *et al.* 2007,
162). Both groups appear to intend their recommendation to apply to
all institutions carrying out hESC research, including public
institutions. President Obama's National Institutes of Health
regulations prohibit federal funds for research in which hESCs are
introduced into nonhuman primate blastocysts (National Institutes of
Health 2009). And, of course, proponents of stem cell research
typically do not argue only that the research is permissible but also
that the research should be eligible for federal funding.




It should be noted, however, that caution is warranted when inferring
public policy conclusions from conclusions about substantive,
first-order ethics about biotechnology (Streiffer and Hedemann
2007). 




Public policy should take into account public opinion and comply with
norms of transparency (Baylis 2009). With regard to public opinion,
the UK Human Fertilisation and Embryology Authority (HFEA) conducted a
12-week public consultation in 2007 on chimeras and hybrids, providing
background materials on the current state of science, law, and ethics
and then soliciting people's opinions on a variety of ethical and
policy questions (Human Fertilisation and Embryology Authority
2007a). Although the consultation did not focus on human/animal
chimeras as defined in this entry, it did find significance opposition
to creating human/non-human hybrids, inserting animal cells into human
embryos, and inserting mitochondrial DNA from animals into human
embryos. In terms of transparency, a review by Baylis (*ibid*.)
of the consultation process found it to be "an exercise in strategic
public relations" in many respects (*ibid*., 47) in which the
HFEA's preexisting policy preference led to bias in the presentation
and discussion of options as well as their interpretation and
reporting of the results (*ibid*.). 




A deeper concern about legitimacy also applies to chimera
research. Legal moralism, the view that the fact that an act is
morally wrong provides a legitimate reason for the state to ban it, is
incompatible with very plausible views about the requirement that
legitimate public policy be based on considerations that are neutral
on certain kinds of issues. For example, even on the assumption that
the Unnaturalness argument, interpreted as a religious objection
against interfering with God's plans, is sound, it still would not
provide legitimate grounds for a public policy restriction on
chimeras. Similarly, proponents of chimera research cannot
legitimately argue that it should be funded, or even just that it
should be legally permitted, because it represents humanity's partial
fulfillment of a divine imperative to acquire knowledge and improve
the human condition. Chimera research raises issues about
unnaturalness, God's plan, human dignity, and the moral status of
animals and humans at all stages of development. To evaluate these
issues in the context of chimera research, some scholars are beginning
to develop faith-based frameworks as well as Aristotelian-Thomistic
frameworks (DiSilvestro 2004; Degeling, Irvine, and Kerridge 2013;
Eberl and Ballard 2009). In such discussions, many considerations that
are viewed as carrying moral weight should not be viewed as providing
legitimate reasons for public policy (Basl 2010; Streiffer
2010). Groups advocating, making, or implementing public policy
regarding chimera research should therefore be sensitive to the
distinction between sound ethics and legitimate public policy.