Above: A four-week-old pig embryo containing human cells. Scientists at the Salk Institute in La Jolla, California grew this chimera in 2017. (U.S. Salk Institute/Xinhua/Alamy)
Researchers from the United States and China announced in April that they had created the first ever human–primate chimeras. Mixing human stem cells with macaque monkey embryos, the scientists produced creatures with cells from both species.
The creation of such beings is deeply troubling, and raises questions about why it was done and where it might lead. What is the point of this research? Will we have monkeys with human features running around the nation’s laboratories? Who is making the decisions about where to draw the line between research we should want and research we shouldn’t?
We may be inclined to trust that the biotech industry will regulate itself — that it will set and follow ethical standards that respect human life, or at least try in good faith to take account of public concerns. That has been the approach in the past. But today, we know enough about the industry’s track record that we should no longer expect it to police itself.
Experiments producing chimeras that combine human and animal organisms are not new. For years, scientists have grafted human cells and organs — often from aborted fetuses — into mice. Such “humanized” mice have specific human features, such as human blood or immune system cells. The general aim of such experiments is to gain a better understanding of human development or disease than is possible just from studying mice.
But this recent experiment with monkeys goes further. The researchers injected human pluripotent stem cells into an early macaque embryo. This procedure can, in principle, lead to the growth of human organs and tissues across the entire organism. Scientists believe that by making the right genetic tweaks to both the animal embryos and the human stem cells, they can produce chimeras that contain specific human organs or tissues. These chimeras could then serve as experimental subjects for studying human development and disease or for testing drugs. They could even be used to grow human organs for transplantation.
So why monkeys? Scientists have had trouble getting human stem cells to contribute much to the embryos of distantly related animals like pigs, so these researchers turned to a more closely related species instead. Their immediate purpose in experimenting with human–monkey chimeras was not to create organisms that are part human and part monkey. The researchers note in their paper and in interviews with the media that they never allowed these chimeric embryos to be gestated, and destroyed them before they had a chance to develop past a certain stage. Rather, the purpose was to refine chimera-making techniques in order to better understand how to make chimeras “in species more evolutionarily distant that for various reasons, including social, economic, and ethical, might be more appropriate” for potential therapies. In other words, the scientists acknowledge the potentially troubling implications of their work.
On the one hand, chimeras are promising because they could be enough like humans to be useful — capable of growing human organs, or of serving as accurate models of some aspect of human biology. On the other hand, chimeras are promising because they could be enough unlike humans not to raise ethical red flags about using them this way, as one could argue that they are essentially just animals. So chimeras could offer researchers not just a technical means of increasing the supply of human organs, but a moral justification for harvesting them — namely, that while the organs are human, the animals of which they are a part are not.
It is just what makes chimera research so promising, then, that also makes it so troubling. We want the scientists to make a pig that is human enough that the organs we take from it will work for our bodies, without being so human that we will need to worry about what taking those organs will do to our souls.
Advocates would have us believe that this kind of research is justified because the chimeras only contain human cells or organs, and this does not make them human persons. What does this really mean?
When we create chimeras by adding pluripotent stem cells to an early embryo, human cells grow and develop alongside the cells of the animal embryo “host” in a unified way. These human cells always belong to some actual person — whether a human embryo that has been destroyed to create embryonic stem cells, or a still-living donor whose skin cells have been reprogrammed into a stem cell line. The human cells will retain that person’s human genetic identity throughout the chimera’s life. But they will be working and growing alongside genetically distinct animal cells, exchanging metabolites, sending and receiving signals, binding together to form organized tissues and carry out the needs of this curious, admixed creature. In all this, the cells remain human, and they will remain the cells of the particular human person from which they were taken. How can that person then relate to the chimera in which his or her own flesh and blood lives alongside the flesh and blood of an animal, in a creature that will be experimented on and probably killed, perhaps to provide that very person with a life-saving organ?
We could dismiss these concerns outright by positing a strict dualism between the mind and the body — insisting that the body and its components are merely incidental to the mental capacities that make a human a person whose life is worth respecting. But while this stance might seem like a reasonable way to justify our intuition that a pig that happens to contain a human kidney is pretty much just a pig, and is nothing like a human being, we should not forget our other intuition, that the presence of the human body, even in part, should command our respect. As the ethicist Paul Ramsey observed in The Patient as Person (1970), there is “no life that is not embodied life; no man whose life is not … the soul (the subject) of his body, and the body of his soul.”
In place of this commitment to respecting the embodied life of the human being, chimera research aims to blur the boundary not only between animal and human, but also between the body and the person. It disassembles and admixes the living human body, to treat it as an object for exploitation, rather than the physical presence of the person, the seat of the soul.
In the United States, the only regulations governing this kind of research are policies about what the federal government will and will not fund. So the only potential regulatory hurdle for researchers is getting funding from sources other than the government. The hurdle is not enough to prevent American scientists from conducting chimera research — indeed, half of the human–primate research team was American, working at the Salk Institute in California. The federal government has for years maintained a policy of not funding research involving the creation of human–primate chimeras with human stem cells. A 2015 moratorium banning federal funding is still in place. But in the wake of this recent experiment, there is renewed pressure on the government to rescind this moratorium to permit funding for just this kind of study.
According to reporting in the Wall Street Journal, the National Institutes of Health are waiting to make a policy decision until the International Society for Stem Cell Research (ISSCR) updates its policy guidelines in May.* The ISSCR is essentially a stem cell lobbying group, whose current recommendations on human–animal chimera research offer only vague procedural advice on the review process that research institutions should follow. The organization does not offer actual ethical guidance, and public statements from the organization and the members of its ethics committee, such as Insoo Hyun, downplayed ethical concerns about the recent experiment: “I don’t see this type of research being ethically problematic. It’s aimed at lofty humanitarian goals,” Hyun told NPR in April.
The scientists, for their part, justified their experiments by noting in their paper that they were “focused entirely on ex vivo chimeric embryos” — meaning the embryos were never implanted — and that they limited their work to “early-stage chimeric embryo development.” In other words, they diligently killed the embryonic human–animal chimeras before they could grow into anything like a “monster,” as one of the researchers put it in an interview.
How much faith should we put in researchers and in groups like the ISSCR to establish sound moral principles for regulating this type of research? On the one hand, this is a complicated area of science, and there are many important technical details that scientific experts and ethicists with a deep familiarity with the science will be well-positioned to understand. On the other hand, precisely because this is such a scientifically and morally complex subject, involving the blurring of ethical boundaries, we will need to put a great deal of trust in whoever is making these kinds of decisions.
Researchers will always face the temptation to go a little bit too far, and to conceal or misrepresent the moral significance of any given experiment in a haze of obscure technical jargon. But a group like the ISSCR, which exists to represent the interests of scientists, could fall into the temptation to simply adopt and ratify the ethical principles of its members.
For example, one rule that would follow from the ethical reasoning of the scientists who created these human–monkey chimeras — a rule that the ISSCR could very well adopt — would be to destroy any potentially controversial chimeras before they reach some specified stage of development. Such a rule would prevent the appearance of troubling, human-like creatures coming out of scientific laboratories. But rather than prohibiting their creation, it would mandate their destruction. The rule would serve the interests of the scientific community by merely placating the concerns of the public without honestly responding to them.
To get a better sense of why the scientific and ethical experts don’t deserve to be trusted with the responsibility of self-regulation, we can consider an earlier episode in the history of human embryo research.
There is a long-standing norm of growing human embryos in the lab for only fourteen days after fertilization. The rule was established in the late 1970s and early 1980s in response to the new practice of in vitro fertilization, and has become law in some countries, such as the United Kingdom, whereas in the United States it has functioned as a voluntary guideline.
Why fourteen days? Two weeks is a nice round number, but it is also associated with the formation of the “primitive streak” in the early embryo, an event that marks the beginning of the embryo’s differentiation into the body’s basic cell types. As Patrick Lee and Robert P. George have argued in these pages (“The First Fourteen Days of Human Life,” Summer 2006), dating the beginning of a human life to the formation of the primitive streak is arbitrary and incoherent compared to acknowledging that each human life begins at conception. Thus the 14-day rule has little sound basis in any morally relevant biological facts.
The 14-day rule was not proposed by political leaders accountable to the public. It was the product of the deliberations of blue-ribbon bioethics commissions, where experts in science, law, theology, and ethics discussed the technical and moral issues and released hefty reports on their findings that went on to influence the guidelines promulgated by professional associations like the ISSCR. Writing in Nature in 2016, three ethicists make clear that the rule should be understood not as a way to limit what scientists should do, but as a way to limit public outrage at what they are doing:
The 14-day rule was never intended to be a bright line denoting the onset of moral status in human embryos. Rather, it is a public-policy tool designed to carve out a space for scientific inquiry and simultaneously show respect for the diverse views on human-embryo research.
In other words, these ethicists argue, the rule was always a flexible and pragmatic one, not a moral principle.
Indeed the 14-day is so flexible that, according to a March report in MIT Technology Review, researchers now intend to drop it. Why? Because in recent years, they have developed techniques to keep human embryos alive in the lab for longer than 14 days, and so the rule now poses a serious impediment to their research.
Let us not miss the gall of all this: For decades, the 14-day rule has been the way that human embryo researchers have publicly demonstrated they are placing ethical constraints on their research. In reality, the rule is arbitrary, is based on no meaningful ethical principle, has been acknowledged by ethicists as just a public-relations tool, and never placed any constraint on researchers at all. And now that it might constrain them, they’re discarding it. As if to make sure we don’t miss the point, the new version of the ISSCR guidelines that are expected to propose greater permissiveness on chimera research are the same guidelines that will drop the 14-day rule.**
If ethical rules for research are this flexible, what will happen when researchers decide that the advantages of fully grown human–monkey chimeras are too great to pass up? A human–monkey chimera with extensive human neural tissue, and endowed with superior memory and cognitive abilities, would be extremely troubling. But it would surely also be a better model of poorly understood neurological diseases like Alzheimer’s than the mice and rats scientists currently rely on. Developing cures for Alzheimer’s would be just the kind of “lofty humanitarian goal” that Insoo Hyun referred to, and that ethicists might use to justify experimenting on a monkey with a more human-like mind.
Once such an experiment is technically feasible, why would the experts who created the rules limiting this research not then go on to describe those rules as not a “bright line” but a “public-policy tool” that can easily be adjusted as the scientific stakes change?
Our trust in scientists to responsibly regulate themselves should be low. But there is another way of achieving compromise between competing public views on embryo research. Consider President George W. Bush’s policy on stem cell research, which limited federal funding to be used for studying a small number of existing cell lines. Bush was not trying to accommodate the views of people who were concerned about embryonic stem cell research, he was instead representing their views with political actions.
The policy was not an especially strict limitation on human stem cell research, since it did allow funding for research on existing cell lines while barring funding for research on new ones. Its aim was to reduce the incentive to destroy embryos for research. This compromise was meant to allow for the most promising work to continue, while at the same time channeling research in less ethically problematic directions. Nonetheless, the policy was highly controversial. It was used as a wedge issue by Democrats throughout Bush’s two terms, and it proved so unpopular that subsequent Republican presidential candidates have not sought to return to it. Suffice to say, it was not an effective tool for managing public opinion.
But, in no small part because the policy was made as a genuine attempt to represent a particular moral position — that embryo-destructive research is wrong — it did make a difference. It actually set limits, albeit modest ones, on how research was conducted. Those limits changed the incentives for scientists working on human stem cells. Because the limits on funding were a real inconvenience, and not just a symbolic measure meant to accommodate the views of aggrieved groups, they forced scientists to take ethical arguments seriously that they might otherwise have ignored.
Though the policy was abandoned under the Obama administration, while it was in place it helped to nudge the scientific community toward developing a morally acceptable alternative to embryonic stem cells — what are called induced pluripotent stem cells, derived from adults. That alternative has helped to change how research in this field is conducted to this day.
In his 1970 book on reproductive technologies, Fabricated Man, Paul Ramsey wrote:
We need to raise the ethical questions with a serious and not a frivolous conscience. A man of frivolous conscience announces that there are ethical quandaries ahead that we must urgently consider before the future catches up with us. By this he often means that we need to devise a new ethics that will provide the rationalization for doing in the future what men are bound to do because of new actions and interventions science will have made possible. In contrast, a man of serious conscience means to say in raising urgent ethical questions that there may be some things that men should never do. The good things that men do can be made complete only by the things they refuse to do.
In the half-century since Ramsey wrote those words, we have witnessed much frivolity of conscience from those charged with the responsibility of thinking through and governing our growing power over nature — from surrogacy to pre-implantation genetic diagnosis to embryo research to cloning, and now human–primate chimeras. The scientific community and its bioethical enablers now offer the same kind of rationalization that they have engaged in for decades: brushing aside the inconvenient or controversial human beings they create by killing them before anyone can notice.
But if we have the courage to act, the will to face the ethical questions of our time with a serious conscience, we ought to say that there are things that we should never do.
* UPDATE: On May 26, after this article went to press, the ISSCR published its updated guidelines, which offered recommendations for how researchers can proceed with the creation of human–animal chimeras, including chimeras with cells from humans and non-human primates. The new guidelines emphasize the need to “proceed incrementally, stopping at well-defined timepoints” in the development of human–animal chimeras — in other words, that researchers should be careful to kill the human–animal chimeric embryos that they create.
** UPDATE: As expected, the May update to the ISSCR guidelines effectively dropped the 14-day rule.
Just Say No to Human–Monkey Chimeras