More than 120,000 Americans are currently on waiting lists for lifesaving organ transplants. Every day some 22 of them die before they can receive a transplant. Wouldn't it be great if organs precisely matched to their recipients could be grown inside domesticated animals, such as pigs or sheep?
Scientists are trying to achieve just this goal, but some ethicists are opposed to the research.
At Stanford University, stem cell researcher Hiromitsu Nakauchi has made some significant steps toward growing human organs inside of animals. As a proof of principle experiment, he grew a rat pancreas in a mouse. He did this by disabling the gene for generating a pancreas in a mouse embryo, then injecting the embryo with stem cells from rats. The rat stem cells took up this vacated "organ niche" and differentiated into fully functioning pancreases.
Such cross-species mixtures are called chimeras, after the creature from Greek mythology that was part lion, part goat, and part serpent. Nakauchi also successfully used this method to grow a functioning pancreas in a pig using stem cells from a genetically different pig.
Nakauchi is now working with Pablo Ross, a developmental biologist at the University of California, Davis, to create human-pig and human-sheep embryos to see if the technique can produce human organs. The genes for generating specific organs are disabled and human induced pluripotent stem cells (iPSCs) are injected into pig and sheep embryos. Induced pluripotent stem cells are adult cells that have been genetically reprogramed to an embryonic stem-cell-like state. Once reprogrammed, iPSCs can grow into different types of cells and tissues. For example, reprogrammed skin cells would be able to differentiate into liver cells or heart cells.
Once the human-pig and human-sheep chimeric embryos are created, they are installed in the wombs of pigs and sheep, where they are allowed to gestate for 28 days before being removed for examination. Normal gestation is 114 days and 152 for pigs and sheep respectively. For now, they stop short of full gestation in an effort to avoid ethical controversy.
Last year, the National Institutes of Health imposed a moratorium on funding any research in which human pluripotent cells are introduced into non-human animal embryos. But why would anyone object to this potentially lifesaving research?
"You're getting into unsettling ground that I think is damaging to our sense of humanity," the New York Medical College biologist Stuart Newman told NPR this week. Sufficiently unsettling, in fact, that some U.S. senators tried to outlaw human-animal chimera research back in 2009. In the same NPR report, Jason Robert, a bioethicist at Arizona State University, said, "One of the concerns that a lot of people have is that there's something sacrosanct about what it means to be human expressed in our DNA." He added that some people might consider that inserting human DNA into "other animals and giving those other animals potentially some of the capacities of humans that this could be a kind of violation—a kind of, maybe, even a playing God."
One issue that worries folks like Newman and Robert is the possibility that human stem cells, instead of growing into transplantable hearts, kidneys or livers, might migrate to the brains of animals or to their reproductive organs. Would human neurons in the brains of pigs generate something like human consciousness? It is worth noting that mice, into which glial cells obtained from donated human fetuses were injected into their brains when they were pups, learned much faster to fear a sound associated with a mild electric shock than did their normal confreres. But while the human brain cells boosted the efficiency of mouse neural networks, they did not confer any specifically human qualities on the mice.
When worrying about the migration of human stem cells into the brains of animal embryos, it is also important to keep in mind that pig brains are only about an eighth the size of humans and those of sheep about a tenth the size. (As for other animals, I should note that the National Academy of Sciences issued guidelines in 2010 urging researchers not to inject human stem cells into nonhuman primates at any stage of embryonic or postnatal development.)
Another concern: If human stem cells grew into ovaries and testes, it might be possible for human-pig chimeras to mate and possibly give birth to a human child. The simplest way to avoid this problem would be to make sure that any such chimeras never get close enough to one another to breed.
Ultimately, concerns about humanizing animal brains or reproductive organs will be precluded if Nakauchi's hypothesis is further confirmed that human stem cells confine themselves to occupying and proliferating only in organ niches made vacant by experimenters. Other researchers note it is possible to avoid the issue entirely by disabling genes in human stem cells that could give rise to neurons or reproductive cells.
Are such experiments really somehow inherently "damaging to our sense of humanity" or in violation of "something sacrosanct"? Nonsense. To make such claims is to confuse human organs and human DNA with human beings. A heart or liver is not a person, whether or not it is grown in a pig. And Human DNA is just the instructions on how to make a human body; it isn't a human body or brain.
To people worried that growing human organs animals somehow violates human dignity, bioethicist David Shaw asked the right question: "Is it dignified to let people suffer and die when we could use this new biotechnology to provide them with organs that will let them live long and happy lives?"