In 2003, a South Korean company called Maria Biotech announced its newest success: it had created mouse embryos with human cells in them.
The idea is that the mice could be born with human cells in all their tissues, and this would make them more accurate animal models for research. The problem came when a reporter asked whether there would truly be human cells in every tissue. (Yes.) Does that include human cells in ovaries and testes? (Presumably, yes.) So what happens if two of these mice get together, and a human sperm meets a human egg in the Fallopian tube of a mouse?
“That ended the project,” says Kevin FitzGerald, a bioethicist at Georgetown University. The scenario described by the reporter was almost certainly impossible, but the incident represents some of the ethical questions around transplanting organs between species, or xenotransplantation.
There’s a big organ shortage, and xenotransplantation has long been floated around as a possible solution. Once, attempts at xenotransplantation meant putting chimpanzee kidneys in humans, which usually wasn’t successful. The big problem with transplantation of any kind is that the immune system can reject the donated organ, even if it’s human. Now imagine how bad the rejection would be for an animal organ. Additionally, animals contain viruses that are harmful to humans, and a number of dangerous diseases (including HIV, SARS, and MERS) have all jumped from animals to humans, causing concern that xenotransplantation “might save one person’s life and cause a plague that kills 10,000 others,” as FitzGerald puts it.
But we might be able to get around some of these issues with advances in genome editing. Just a few months ago, scientists debuted the world’s first human-pig chimeras, or pig embryos injected with human stem cells. The pigs, which weren’t allowed to develop past the fetal stage, started to grow organs with human cells in them. They set the stage for a world where we could grow human organs in other animals. One day, we may even be able to use stem cells to grow our own organs in other animals. But all of this comes with ethical questions.
Xenotransplantation has a long history, with some pointing out that the procedure is mentioned in Greek mythology — specifically, when Icarus and Dedalus attached bird wings to their arms to try to fly. (As the author of one history of xenotransplantation put it: though Icarus died, “Daedalus successfully made the journey, providing this pair with an enviable 50 percent success rate.”)
In the early 20th century, Nobel Prize-winning surgeon Alexis Carrel developed a method of connecting blood vessels, which made xenotransplantation possible for the first time. It also made horrific experiments possible: by the 1920s, a doctor named Serge Voronoff decided that the best way to revive men’s “zest for life” (read: sex drive) was by transplanting monkey testicles into human men. It wasn’t a full transplant. Rather, he sliced up the monkey testicle and then inserted slices into the human testicle. Despite the seeming horror of this approach, it became rather popular, and at least several hundred operations were performed. Later, the American “doctor” John Brinkley (he had no degree) did the same thing with goat testicles for the low, low price of what would be $9,000 today. He became rich, famous, and was probably responsible for many deaths.
More medically sound transplants came in the 1960s, with chimpanzee kidneys transplanted into 13 patients, one of whom lived for almost nine months. The decade also brought an attempt at transplanting a monkey heart, but the patient died immediately. More optimistically, one patient survived for 70 days after he received a baboon liver in 1992.
In the 1980s, things began to heat up. Danish scientist Steen Willadsen, a pioneer of cloning, combined portions of both sheep and goat embryos to made chimeras — animals that were half sheep and half goat, colloquially called “geep.”
“That was the breakthrough insight that mammals may be a bit more compatible than we thought,” says FitzGerald. “If you could put goat and sheep together, what else could you do?” Maybe you could get past the immune rejection problem if you created something that was part animal and part human because the immune system would then develop seeing both sides as itself, he continues. Interest grew even more after Dolly the sheep was successfully cloned in the ‘90s.
Today, the bellwether for tracking further developments isn’t necessarily academic research or federal policy, but rather, business. These developments tend to be driven much more by a practical analysis of just how market-friendly a technology is, and how much investment it can get, says FitzGerald. And each advancement raises questions.
The first question is always, where does the needle stop? Is this an ethical use of animals? If we’re putting animal organs into humans, at what point do we start asking if this changes what it means to be a human being? “Do we really want to say human beings are reducible to the brain? Because that’s not necessarily a good way to go ethically either,” says FitzGerald, “and that would require a lot of thought and reviews.”
Even if growing full organs in animals were successful, questions of money and scale remain. “We can grow pigs in large numbers for food, but the necessary housing and development for organ transplant pigs would be much more expensive than for regular pigs,” says FitzGerald. How many organs would be available, and how much would they cost, and who would pay? “Xenotransplantation is fascinating in so many ways scientifically, but it could be that it’s not really the solution to the organ shortage problem,” he adds.
Ultimately, though, FitzGerald thinks that xenotransplantation doesn’t have to be an end in itself. “I don’t think people should wrestle with this as sort of ‘this is the solution or it isn’t’ situation,” he says. This type of technology could lead the way to other solutions — like growing organs successfully in labs — with fewer ethical complications. “My guess would be that this is just merely another step along the way and merely an intermediate step to try to get where we want to be.”