After Centuries, We Still Can’t Perform Animal-to-Human Transplants

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In January, a team from the University of Maryland in Baltimore transplanted a genetically modified pig heart into a 57-year-old man with end-stage heart failure. David Bennett died on March 9, but it was recently revealed that Bennett had been infected with a pig virus, possibly contributing to his death. “It doesn’t really scare us for the future of the field,” Bennett’s surgeon told The New York Times. “It’s just a learning point. Knowing it was there, we can probably avoid it in the future.

This optimistic assessment embodies a broader enthusiasm for the promise of “xenotransplantation,” or the transfer of organs, tissues and cells from one species to another. If fully realized, xenotransplantation could solve the country’s organ shortage crisis – with one new person added to the waiting list every nine minutes and 17 people dying every day. Xenotransplantation has long captivated humans searching for ways to circumvent death, and with Bennett’s operation, it promises once again to reshape the way we think about human longevity.

This promise is born out of a long history of cultural fascination with hybridity. The famous transplant surgeon Keith Reemtsma considers the myth of Icarus to be one of the first examples of xenotransplantation: the inventor Daedalus and his unfortunate son escaped imprisonment in Crete by grafting bird wings onto their bodies. Ancient Egyptian and Indian pantheons alike featured deities with animal heads on their human bodies, from the jackal god Anubis to the monkey god Hanuman. In Christian tradition, Satan is often depicted with cloven hooves and horns, while Dante’s “Inferno” depicts him as having the wings of a bat.

In 1667, French physician Jean-Baptiste Denys performed the first documented human blood transfusion by giving a teenager 12 ounces of lamb’s blood. After all, Jesus was the Lamb of God, so animal blood, Dionysius thought, would be “less full of impurities than that of men because debauchery and irregularity in eating and drinking are not so common among them. “. While Denys’ first and second attempts went well, his third and fourth patients died, leading the Parliament of Paris and the Catholic Church to ban all blood transfusions.

In the centuries that followed, xenotransplantations of skin, cornea and testicles – to restore men’s “taste for life” – were attempted, but the first cardiac xenotransplantation was not performed until 1964. In fact, it was the first human heart transplant in history, with University of Mississippi surgeon James Hardy transferring a heart from chimp Bino to 68-year-old Boyd Rush. The glimmers of hope were shattered by desperation as it was almost immediately apparent that the little chimpanzee heart wasn’t strong enough to withstand Rush. He survived for 90 minutes. Following this pioneering operation, Hardy became a medical pariah, with the public outraged and his clinical integrity questioned by his colleagues.

The dream of circumventing death and prolonging life, however, persisted. Indeed, the most famous attempt at heart xenotransplantation took place 20 years later, in 1984. Baby Fae was a 12-day-old infant with a congenital heart defect, doomed to die. Without first seeking a human donor, Loma Linda University surgeon Leonard Bailey transplanted a walnut-sized baboon heart into Baby Fae. “We are optimistic that within three months she will be able to return home,” Bailey projected. And initially, Baby Fae seemed to be doing well. “Except for the gauze-covered wound that ran nearly the length of her torso,” Time noted, “the little dark-haired girl could have been any baby.” She stretched out her skinny arms, swallowed her formula, and hungrily sucked on her pacifier.

But Baby Fae died 21 days after the operation, sparking national controversy with widespread protests. Animal rights activists have argued that Bailey should be tried for manslaughter, while bioethicists have called his work a “bestial business”. Other medical professionals called Bailey delusional, believing that the biological barriers between animal and human were too difficult to overcome.

Despite more than half a century of setbacks, xenotransplantation has remained “a biomedical project, an individual aspiration, a public policy challenge, and a societal goal,” according to Sharon Kaufman, the former chair of the Department of Anthropology, of history and social medicine at the University of California, San Francisco. “Potential carries with it the cultural meaning of open living.”

At the heart of this dream of xenotransplantation are dreams of immortality. We age and eventually die as our cells, tissues and organs begin to lose their function over time. What if they could just be replaced as needed?

This aspiration should not surprise us. The enterprise of modern medicine has long led us to question our relationship to nature. Patients may be stuck in persistent vegetative states, but life support (ventilation, dialysis, etc.) rekindles hope that one day they might wake up. But xenotransplantation is also about biological issues, rather than just mechanical ones. “How can we make humans live longer when parts wear out? What are the options?” Kaufmann asked. “Using hardware or animals.”

Medical advances are now allowing biological investigations to take on new forms of sophistication and precision. To carry out Bennett’s pig heart surgery, the CRISPR-Cas9 genetic engineering tool was used to create a special line of pigs with six human genes inserted and four pig genes knocked out. These pig-human hybrids were then raised in complete isolation in a high-security facility to ensure they were pathogen-free. Bennett, however, was infected with porcine cytomegalovirus anyway and died soon after.

When life is on the line, whatever is on the table, Kaufman said, “becomes ethically appropriate, necessary, and standard,” however experimental, however fantastic, even if it works. Our understanding of the natural world is constantly being remade; what was once unique becomes perversely normalized through clinical manipulation. Hardy and Bailey were the early martyrs of this cultural transformation, but now xenotransplantation sparks hope and longing rather than outrage.

“Before, there was no potential. Now everything is potential,” Kaufman said. “That’s what has changed in medicine over the last 50 to 60 years.”

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