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Chimeric animals: Bioethically questionable but scientifically informative?

Recent news reports have drawn attention to a new study published in Cell that demonstrates the potential of donated embryonic stem cells to proliferate throughout a living primate and to essentially ‘mix in’ with the primate’s own cellular DNA.

In the words of the study’s authors, the experiment revealed that ‘mammalian pluripotent stem cells possess preimplantation embryonic cell-like (naive) pluripotency.’

Pluripotent cells are cells that have the potential to differentiate into cells of any type within the body: they can become brain cells, heart cells, lung cells, and so on. Stem cells are cells that can regenerate (self-renew) and reproduce on their own through mitotic division (mitosis). Pluripotent stem cells are self-regenerating cells that can differentiate from one cell type to another.

There are also different kinds of pluripotent stem cells. So-called naive cells are those that function like cells at the earliest stages of development (as if they are from an embryo at the pre-implantation stage) and are more easily incorporated into an organism. By contrast, ‘primed’ pluripotent stem cells are more mature cells that cannot be incorporated into developed organisms.

As the summary notes, the finding is really about the potential of mammalian embryonic stem cells (ESCs) to differentiate into cells of different kinds within a mammalian organism. However, what appears to have caught the attention of the news media is the fact that this experiment generated a so-called chimeric animal — that is, an animal that represents a combination of two lines of cellular DNA from two separate embryonic stem cell lines.

In a nutshell, the monkey’s embryonic development has been subject to what is called ‘complementation’: the ordinary development of the monkey’s embryo was complemented or subject to the addition of a ‘donated’ line of other homologous embryonic stem cells derived from another genetic origin. The monkey, in short, has developed from a blastocyst that is a compound of two embryonic stem cell lines.

Unsurprisingly, the news stories have been focusing on an eye-grabbing and perhaps rather disturbing aspect of the experiment: that is, that the monkey in question exhibits fluorescent green fingers and eyes.

But the reason for these features is not because the monkey is a mutant — not in any unforeseen way, anyway. Instead, it is because the researchers used green fluorescent protein (GFP) to ‘label’ the embryonic stem cells (ESCs) that were incorporated into the host embryo at the blastocyst stage.

The monkey also had fluorescent green fingers.
See Cao et al, ‘Live birth of chimeric monkey with high contribution from embryonic stem cells’ (2023) 186(23) Cell 4996-5014 <https://doi.org/10.1016/j.cell.2023.10.005>.

The green fingers and eyes are visual evidence that the homologous embryonic stem cells that have been ‘complemented’ successfully into the blastocyst of the host monkey. Indeed, the images show how the cells have moved and survived throughout the primate’s body. The images show a proliferation of the cells in the brain and ileum (small intestine), among other organs.

The ethical aspects of the experiment are quite confronting. Not only is it quite disturbing, albeit not at all unprecedented, to imagine organisms being engineered as ‘combination’ animals like this; it is also unfortunate and bioethically problematic to note that the monkey died after only 10 days of life. At the same time, it should be added that this is still the longest period of time for which such a chimeric organism has lived before.

As the ‘Highlights’ section of the article points out, the characterisation (or analysis) of the embryonic stem cells in the body of the monkey revealed that they remained in a pluripotent state. In other words, not only have the ESCs been shown to be able to differentiate into the different kinds of cellular categories (glial (brain) cells, heart cells (myocytes), lung cells (epithelial cells) but they also appear to remain pluripotent. They remained capable of changing cell type for as long the monkey remained alive.

In a story published on news.com.au, I am quoted as saying the following:

Sydney University lecturer in health law Dr Christopher Rudge told new.com.au the medical experiment had been on the cards for a long time.

“This is another step along the journey,” he said.

“The advancement here is that scientists have never been able to show such a prolific survival / proliferation of donated (or ‘complemented’) embryonic cells through a single organism.

“You’ve got more of these donated or secondary cells throughout the organism in a mammal.”

But he cautioned whether it would lead to anything substantive.

“Regenerative medicine has been hyped since the late 1990s,” he said. “Unfortunately it has not borne fruit.”

See https://www.news.com.au/technology/science/stunning-monkey-born-with-glowing-eyes-and-fingers/news-story/27d84700628476da1579968e76cbda5d

It is true that regenerative medicine has been a source of hope and hype since the late 1990s — especially stem cell medicine. This has led to not only optimistic speculation, but many instanced of medical malpractice. These episodes have typically involved medical practitioners promising that an infusion of stem cells into a patient’s body could restore and regenerate a pathogenic organ or limb.

This study, however, is far from the practice of medicine on humans. Still, it demonstrates that certain new protocols and techniques can be adopted to expand the capacity of scientists to create living chimeras in mammals. Of course, the point of the study is not to create chimera, but to investigate the mechanisms by which embryos develop and the manner through which embryonic stem cells might be used as a tool of biomedicine.

Scientists have long had the capacity to infuse mouse and rat blastocysts with pluripotent stem cells to generate live chimeric animals that feature this high proliferation of homologous cells. What is new here is that this capacity now extends to non-human primates — a species of animal much closer, in evolutionary terms, to humans. It could be understood as another step along the way to discover the ability of stem cells to be used as a viable source of medical intervention.

Whether an experiment of this nature would be approved in Australia is an interesting and troubling question. If nothing else, however, this study indicates the extent to which stem cell medicine and science continues apace, albeit without much practical application as of yet.

Much has been written in recent years about the potential for monkey embryos to be complemented with human embryonic stem cells. Indeed, this appears to be a source of more serious and considered bioethical analysis than questions arising about these monkey-monkey chimeras. Whether that is as it should be, however, is open to debate. In one unfortunate sense, it could be that the monkey who was subject to this experiment did not live for long enough for the bioethical questions relating to its identity and about suffering to arise.


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