From Bench to Bedside via… The Island of Dr Moreau?

Jason Scott Robert suggests that the creation of part-human animals in stem cell biology may generate scientific confusion.

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Shipwrecked in the South Pacific, Edward Prendick is rescued and transported to a remote island owned by a fellow expat, Dr. Moreau. His host is an exiled physiologist from London, chased away due to public outcry over his cruel commitment to vivisection. Most of the island’s inhabitants are hybrid beast folk created by Moreau. Such is the premise of H.G. Wells’ classic science-fiction novel, The Island of Dr Moreau. Published in 1896, it retains its appeal today – despite some terrible film adaptations.

One reason for the continued salience of the story is that, like all good science fiction from Mary Shelley’s Frankenstein onward, it taps into cultural insecurities about what it means to be human, epistemic worries about forbidding knowledge, and ethical concerns about the moral limits of science. Another reason is that it foreshadows developments in science and technology that could only have been dreamt of by their authors. Of course, except for organ transplantation (and face transplantation, and maybe, eventually, head transplantation), clinician-scientists aren’t literally stitching together cadaveric body parts; and, except for genome-editing for de-extinction, researchers aren’t attempting to breathe new life into long-dead creatures; and, except for synthetic human embryos, bioengineers aren’t galvanizing novel forms of human life ‘to-order’ by re-purposing skin cells; and, of course, except for transferring human induced pluripotent stem cells into pig blastocysts and then transferring them into pig uteruses, no scientists nowadays are actively creating part-human animals like old Dr. Moreau. Right? Oh snap… Science fiction can indeed become science fact.

It’s been 15 years since Françoise Baylis and I started the conversation about scientific and moral dimensions of creating part-human animals in stem cell biology. Our paper was widely and wildly misinterpreted. We aimed to highlight the possibility that part-human animals are potentially morally confusing – which is neither good nor bad and speaks neither for nor against their creation. We suggested that those who morally object to creating part-human animals should explore the terrain of moral confusion for fertile arguments. Here I take another path: the creation of part-human animals in stem cell biology may generate scientific confusion.

Image Credit: “The Island of Dr. Moreau” by Tom Simpson.
Image Description: Side profile of 3 heads. The first, a white image with red eyes is human; the second, a grey image with red eyes is a human-looking face with fangs; and the third, a place head with red eyes, is a non-human animal with fangs. The image of the three heads has been placed above the silhouette of an island.

The attempt to create part-human animals as a strategy in translational medicine may generate genuine epistemic confusion by introducing myriad confounding variables. Scientists want to study human pluripotent stem cells in a permissive developmental environment (such as an early human embryo). This research is largely restricted, however, either by stem cell research guidelines forbidding the injection of human pluripotent stem cells into human embryos, or by proscriptions on human embryo research. By contrast, scientists are relatively free to inject non-human pluripotent stem cells from non-human animals (such as mice) into animals of the same or other non-human species (mice, rats, pigs, cows, non-human primates).

The difficulty with this strategy for learning about human pluripotent stem cells is that these cells are interestingly unlike pluripotent stem cells from other animals. Cell-cell signaling varies between species, as does developmental timing. Anatomically, physiologically, genetically, and otherwise, species vary, as do members within species. Recognizing this, scientists (mostly) appreciate that it will be impossible to translate one-to-one from mouse to human. For this reason, scientists have tried to “humanize” their experimental model organisms (mouse, rat, pig, cow, non-human primate). With the advent of CRISPR-CAS9, the prospects for humanization have increased considerably.

To bridge the gap between (impermissible) human studies and (permissible) mouse studies, scientists have undertaken a wide range of interspecies chimera studies, most recently in mammals. With part-human chimeras, one ambition is to transfer human pluripotent stem cells into non-human embryos to assess the potential for cellular functional integration. The goal might be to infer from this research what would happen were the same cells, or their derivatives, transferred into a human embryo (or a more developed human) for medical benefit. Another goal might be to create a chimeric animal into which the same cells, or their derivatives, could be transferred as a stepping stone to inferring what would happen were the same cells, or their derivatives, transferred into a human embryo (or a more developed human) for medical benefit.

But herein lies the challenge, and the potential scientific confusion. Insofar as even a part-human chimera is part-human, it is sui generis and not actually human. Accordingly, scientists may discover interesting facts about part-human chimeras and nothing about how to make the science work in actual humans. Instead of bridging the interspecies gap, creating interspecies chimeras may generate new inferential gaps. These may be gaps between humans and part-human chimeras, and gaps between part-human chimeras and the non-humans. Moreover, any further attempts to bridge these gaps may create ever more gaps. (Elsewhere, I call this “Xenopus’ Paradox”.) Interspecies chimeras – however technically cool – may then turn out to be little more than remote islands, an archipelago in the middle of nowhere. Perhaps in the South Pacific…

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Jason Scott Robert holds the Lincoln Chair in Ethics and serves as Director of Arizona State University’s Lincoln Center for Applied Ethics and Dean’s Distinguished (Associate) Professor in the Life Sciences.