La Chimère by Gustave Moreau (1867)
Lamassu, sphinx, Ganesha, qilin, centaurs, griffins: amalgams of human-animal species have been mythologized, depicted and deified throughout the history of human civilization. These hybrid species, known collectively as chimeras from the eponymous ancient Greek myth of a lion-goat hybrid, arose from the wellspring of human imagination and creativity. With modern advancements in biotechnology, however, chimeras of a sort are less a myth and more of a reality.
Genetically-engineered human pluripotent stem cells (hPSCs) implanted into an evolutionarily-related, nonhuman animal embryo can be considered modern day, corporal chimeras. The concept of chimeras has transcended myth and is now emerging as a tangible, biological spectacle that has been touted to solve the organ transplant shortage and bridge the gap between in vivo animal testing and human clinical research models.
Such powerful research does not come without objections, though. Many arguments against developing chimeras span the gamut of moral ideologies and engage medical ethics. In order for future physicians to grapple with thorny bioethical dilemmas surrounding concepts like chimera research, we need not only understand their biochemical and clinical mechanisms, but we must also delve into the philosophy and art surrounding these issues. Analyzing the histories of chimera art and mythology alongside moral philosophies can aid in comprehending the full context of said debate before forging our own opinions.
Chimeras, like hPSCs, have much potential in enhancing human health, and they are already becoming a possibility in the early stages of research (the first human-pig chimeras were created successfully early in 2017). One group has even successfully grown healthy mouse-derived pancreases in rats, which were then harvested and transplanted into diabetic mice. They successfully secreted insulin and thereby reversed the diabetes of the mice.
Given such sparks of success, chimera technology has seen a dramatic rise in popularity — and dissent. In 2015, the National Institutes of Health (NIH) issued a funding moratorium on chimera research until the bioethics were better resolved. In August of 2016, the NIH lifted this same moratorium from chimera research under the stipulation that an ethics oversight committee would monitor the research. However, legislation is continually being drafted to prevent such research, and the opposition present in the literature is even more deafening.
What forms the basis of this formerly-banned and now-restricted research? We can look along diverse philosophical veins to see where the discomfort in chimera research originates. One such vein is the “Unnaturalness Argument,” which was supported by a prominent 20th-century philosopher of biology, Hans Jonas. Deeming chimeras as “unnatural” and thus wrong, Jonas claims an inherent disgust evoked by moral intuition that “produce[s] an involuntary shudder” — colloquially dubbed the ‘yuck factor.’ The underlying thesis of the Unnaturalness Argument is that chimeras transgress some natural divide between humans and nonhumans, and that issues them with a moral prohibition. To Jonas, the very “interchange of genetic material between animals and man” would summon “ancient, forgotten terms such as ‘sacrilege’ and ‘abomination.’”
Still, the aversive reflexes evoked from the concept of the “admixture” of an animal and human could be considered an over-inflated concern by some. In discussing gene therapy technologies, contemporary philosopher and biophysicist, Henri Atlan, paints the Unnaturalness Argument as “irrational fears which derive from misunderstandings in biology, and are compounded by the effects of popular creations of fiction, such as Frankenstein’s monster.” In that same report, Atlan recognizes that, perhaps that it is not simply unjustified fear or “merely a fear of the unknown that engenders caution, but also a recognition that the ability to modify the genetic endowment of human beings…in touching the gene, therefore is touching the essence of life.”
Here, Atlan conceives of the implicit “playing god” phobia — or “master of the hereditary model,” as Jonas refers to it. Importantly, Atlan points out that the “essence of life” is a “wooly” or vague notion, one that biomedical ethics must eschew from and adopt a more “pragmatic” analysis of each instance of bioethical debate by “[analyzing] the specific potentially dangerous or undesirable effects.”
One example of such a “pragmatic” analysis lies in the most-feared scenario of chimeric organisms: the situation in which hPSCs tread off the genetic lineage intended by researchers and into a neural fate, where hPSCs either form a mosaic of human-animal neural tissue or completely pervade the nervous system of the host organism. Today, despite significant progress in (epi)genetic knowledge, the issue with chimeras is that scientists have still not elucidated how hPSCs precisely migrate in utero. Therefore, it has been postulated that hPSCs implanted into animals could diverge from their original coaxing to instead take hold in the areas that are destined to become embryonic neural tissue. Assuming this (e.g. human-pig) chimera was brought to full term, what would hypothetically result is a newborn pig with a genetically-human central nervous system.
Questions pour forth: does the chimeric animal achieve a sort of moral status? Does the chimera have the same rights that a human would? Can the animal cognize as a human would, and would experimentation/organ harvesting on the animal thus be considered unethical due to the sensations and suffering it would undergo? The existence of borderline human-nonhuman chimeras could generate moral and ontological confusion. But consider how the modern surgical procedure of xenotransplanting a porcine heart valve is morally acceptable for many patients (save for patients of religious backgrounds that prohibit the consumption of porcine food products, namely Islam and Judaism). Perhaps it is the possession of a specifically human central nervous system, which provides sensation and cognition, by a nonhuman animal that truly enlivens the ‘grotesque’ reaction to chimeras in some.
When discussing chimeras in scientific research, it is rare that we consider our very selves to be chimeras, too, just shaped by the different mechanism of natural selection. According to endosymbiotic theory, our own mitochondria derive from an oxidative prokaryote that was engulfed by a larger prokaryotic host cell, essentially forming a symbiotic chimera of sorts that ultimately evolved to power complex, multicellular organisms like Homo sapiens. As ‘natural’ chimeras ourselves, selected over time to think and create and debate, we are responsible for directing the course of synthetic chimera research and its potential use in the future of biomedicine.
Blaise Pascal once proclaimed in his Pensées, “What a chimera then is man! What a novelty! What a monster, what a chaos, what a contradiction, what a prodigy!” Just as Pascal invokes the clashing qualities of humankind’s essence as chimeric, so too are scientists and bioethicists as divided on chimera research today. Certainly, the incomprehensibility about what constitutes life and what factors make humans human is grounds for some to hold an instinctive aversion to promoting chimera research. But the utilitarian benefits that could spring from chimera biomedical research must not be ignored either. As biotechnology progresses rapidly, future physicians will have to trod the murky path of new bioethical dilemmas with both the medical humanities and scientific medicine as our guiding lights.
Image credit: La Chimère by Gustave Moreau (1867) in the public domain.