CHIMERAS

Is a Pig With a Human Brain Still a Pig?

Using gene editing, scientists hope to use pigs to grow human pancreases and, potentially, other organs. What happens when a pig has a human brain?

Human organs grown inside of pigs are the stuff of science fiction. Pigs with human brains would be more at home in a horror movie. As it turns out, researchers may have to risk the latter to obtain the former.

As the BBC reported Monday, animal scientist Dr. Pablo Ross and other researchers at University of California, Davis have been injecting human stem cells into pig embryos in order to create genetic mixtures known as chimeras. Using gene editing, the team hopes to produce pigs that have human pancreases but are otherwise, well, pigs.

This outcome requires careful gene editing. First, the researchers must delete the portion of pig DNA responsible for the pancreas from a new pig embryo. Then, they inject human stem cells into the embryo to replace the deleted DNA. Finally, they implant the chimeric embryo into a sow and harvest its tissue after 28 days.

If successful, the research could be a revolutionary development in the ongoing organ shortage crisis. A non-human source of immunocompatible human organs would be lifesaving for those on the waiting list. But the experiment is not without its risks, chief among them the remote possibility that the injected human DNA could do more than just grow a pancreas—it could put a human-like brain in a pig’s body.

As Dr. Ross told the BBC, “We think there is very low potential for a human brain to grow but this is something we will be investigating.”

The entire project presents a uniquely 21st-century ethical quandary. Dr. Jeffrey Kahn, the Levi Professor of Bioethics and Public Policy at the Johns Hopkins Berman Institute of Bioethics, told The Daily Beast that this controversial line of research addresses the organ shortage but also poses philosophical questions about the nature of humanity.

For instance, few would argue that a pig with a human pancreas is still just a pig. But, as Kahn puts it: “What if it has a human pancreas, a human kidney, a human liver, and a human heart?” The question’s going to arise eventually: When does it become a human in a pig’s body?”

Kahn compared the question to the legend of the Ship of Theseus, a Greek vessel that was completely replaced, piece by piece and plank by plank, over the course of a voyage. Was it a different ship when it returned? Or was it still the same ship?

There is no doubt, Kahn says, that using animals to grow personalized organs for dying humans is “an easier case to make than using the animals for food.” But the ethical conversations around human-animal chimera research are still ongoing, and still need time to develop.

Human-animal chimera research is not banned in the United States, despite a 2005 attempt by then-Senator Samuel Brownback, now the Republican governor of Kansas, to pass prohibitive legislation.

But there is a wide gap between being illegal and being openly endorsed. The National Institutes of Health (NIH), for example, reiterated last September that “it will not fund research in which human [stem] cells are introduced into non-human vertebrate animal … embryos.” That stance is subject change in the future.

In a statement to The Daily Beast, an NIH spokesperson said that the biomedical research agency is “in the midst of a deliberative process” to review human-animal chimera research and determine whether “new policies and procedures are needed to ensure [it] can progress responsibly.” By conducting the review early on, the agency hopes to be able to develop a “sound policy framework” before the research becomes mainstream.

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“We are doing this now because we are not yet funding this research, but are aware that the science is moving in this direction,” the spokesperson noted.

But the NIH still considers research like the UC Davis experiment “an area of some concern, given the possibility of human cell contribution to multiple organs and tissues.”

“A significant contribution of human cells in an animal, if that were to occur, may raise concerns for the welfare of the animal, particularly if there are significant alterations of the animal’s cognitive state,” the spokesperson wrote.

It’s a fear ripped straight from the pages of Kafka’s Metamorphosis, in which a man wakes up in a large insect’s body, capable of thought but not speech. But while that fear is vivid, it is not especially likely from a scientific perspective.

A 2015 review of the ethical issues surrounding this research published in the Journal of Medical Ethics acknowledged that the animals in these experiments could potentially develop “human physical or mental features such as human limb development or neuronal development.”

“Fortunately,” the review continued, “the chances of this happening are remote. Even if human neurons were present in a pig brain, it is likely that they would act like pig neurons, being influenced by their environment rather than their genomic makeup.”

The ethicists also noted in their review that researchers could mitigate the risk by preemptively deleting the portions of the human stem cells responsible for neuronal development before injecting them into animal embryos.

Ultimately, the ethicists wrote, there are more pressing problems to address in this emerging field than the hypothetical pig with human brain. For one, the research raises the question of how much animal sacrifice is justified in the name of saving human lives. But, as the authors noted, even if every human donated their organs upon death, there would still be an organ shortage crisis.

And there is still one more troubling possibility: Theoretically, human-animal chimera research could result in the creation of an animal virus that infects humans, known as a zoonosis. The risk of zoonosis can be carefully controlled in a laboratory setting but it is still a risk nonetheless.

“A deadly zoonosis could theoretically kill millions of people, and one might question whether the benefits of creating a new source of organs is worth outweighing the potential harms following from even a small risk of zoonosis,” the authors wrote.

Human-animal chimera research has the potential to be miraculous. Eventually, it could save thousands of people from death every year. But the nightmare scenarios, however unlikely, are still possible.