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Bioethics Forum Essay

Public Comment: Should NIH Fund Research on Human-Animal Chimeras?

On August 4, the National Institutes of Health called for public comment on proposed changes to its guidelines governing the funding eligibility of research involving human-nonhuman chimeras. Although the term chimera has a broad interpretation, the NIH proposal addresses a particular kind of chimera: nonhuman vertebrates (excluding rodents) into which human stem cells or tissues have been introduced at an early stage of embryonic or fetal development.

The policy change proposes to end a one-year moratorium on funding this kind of research.

The NIH expects these chimeric animals to solve a huge problem facing health sciences research. For decades, evidence has been mounting that nonhuman animals are poor models for many human pathologies. By aiming to manipulate nonhuman animals to develop human tissues, organs, and other traits, the NIH expects that these chimeras will ultimately serve as improved models.

But this research brings its own challenges. The chimera test subjects need to be humanized enough to serve as effective models for human health research – that is, as more accurate, predictive, and thus effective tools for developing medical interventions in humans. However, if the chimeras are too similar to humans (what we refer to as “substantively humanized”), they raise a host of ethical concerns for society at large.

It seems to us that the NIH’s objective with this proposal is to address these specific challenges by threading a path that reaches the desirable goal of humanizing chimeras while avoiding the undesirable outcome of substantive humanization. Although what would count as substantive humanization to the NIH remains unclear (for reasons we discuss), examples might include human-looking faces or hands, or humanlike mental processes. There are some early findings suggesting the plausibility of some of these concerns in mice and macaques. As far as we can see, the NIH’s objective is to prevent the creation of beings that would have morally significant traits such that it would be morally reprehensible to perform nonconsensual invasive research on them. The NIH is particularly concerned with avoiding this possibility with respect to nonhuman primates, for whom specific restrictions are stipulated.

However, the NIH’s proposal is not sufficient to address these, or other, concerns raised by human-nonhuman chimera research.

Loosening the restrictions on chimera research promises to reverse international trends (mirrored in the U.S.) that are moving toward minimizing the use of nonhuman primates that demonstrably possess many of the capacities that we take to be morally significant in humans. The primary motivation for these efforts is that many primate species share psychological similarities, leading many to question the status quo that seems to arbitrarily assign nonhuman primates lower moral status than humans. Thus, any sharp line between “humanized” and “substantively humanized” ignores growing recognition that psychological capacities carry greater moral significance than species identity, and it also ignores the scientific fact that species boundaries are not distinct. But if the “‘human” versus “substantively human” distinction is murky with unmodified organisms, it gets even murkier with chimeras.

One of the objectives of the NIH is to encourage research that impacts the brains of nonhuman mammals. Yet even NIH officials acknowledge that scientists don’t know how this sort of manipulation will affect a chimerical creature’s experience of the world or general well-being. What’s more, since the welfare of nonhuman test subjects is ordinarily evaluated in terms of species-typical functioning, it’s not clear how the NIH will be able to evaluate the welfare of chimeras. This pressing issue has not been substantively addressed.

Moreover, much of the discussion at the 2015 NIH Workshop that culminated in the recommendation that the moratorium be overturned hinged upon the concept of necessity. Chimera-based research, it was argued, is necessary to advance scientific knowledge of human disease and to help solve pressing problems, such as the shortage of organs for transplantation.

We contend that the NIH’s position on the necessity of human-nonhuman chimera research is unlikely to withstand scrutiny because it sidesteps several crucial issues. First, there might be viable alternatives to the creation of chimeras for the advancement of scientific and medical knowledge. Second, there are epistemic problems with the knowledge produced via chimera-based research, especially if the research addresses behavior and psychology, because it is unclear how relevant this research would be to humans. Third, there are likely better ways to address some of the problems under consideration (e.g., organ shortages) by nonmedical means (e.g., legal reform, education, political strategizing). Finally, we question whether the NIH has sufficiently considered the possibility that some types of scientific investigation shouldn’t be done at all because of the severity of the harms to the research subjects (e.g., arguably, Harry Harlow’s deprivation experiments).

We conclude that it is unreasonable for the NIH to end its moratorium on funding human-nonhuman chimera research when so many serious issues clearly remain unaddressed. In our view, there is an urgent need for further deliberation – perhaps by the Presidential Commission for the Study of Bioethical Issues or its successor – to more fully examine the ethical issues and challenges raised by this research.

If you have concerns, you can submit comments here. The deadline is September 6.

G.K.D. Crozier is an associate professor of philosophy and a Canada Research Chair in Environment, Culture and Values at Laurentian University. Andrew Fenton is an assistant professor of philosophy at Dalhousie University in Canada and Fresno State University in California. Lori Marino is a neuroscientist formerly on the faculty of Emory University and currently executive director of The Kimmela Center for Animal Advocacy. Letitia Meynell is an associate professor of philosophy at Dalhousie University. David M. Peña-Guzmán is a Hecht-Levi postdoctoral fellow in the Berman Institute of Bioethics at Johns Hopkins University.

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Hastings Bioethics Forum essays are the opinions of the authors, not of The Hastings Center.

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