Zap! The coffee juice turned into a black mass. Transplant surgery is all about timing, says Dr. Brandon Guenthart, a cardiothoracic surgeon at Stanford University School of Medicine. Anesthesiologists put the patient to sleep after the recovery team confirms that the donor heart is fine. Two surgeons begin operating an hour before the donor heart arrives at the hospital. They don’t start cutting the patient’s heart until the donor heart has landed safely at the local airport. And if the plane crashes? “Knock on wood,” Guenthart says. Unfortunately there is no wood in the operating room. I was at Stanford Hospital attending this heart transplant because of my interest in David Bennett, a 57-year-old man who had died in March. On January 7, 2022, at the University of Maryland Medical Center, Bennett had received a major heart transplant from an unusual donor: a genetically modified pig. Surgeon Muhammad M Mohiuddin leads a team placing a genetically modified pig heart into a storage device at the Xenotransplant lab before transplanting into David Bennett on January 7. Photo: UMSOM/Reuters In 2021, 41,354 human-to-human organ transplants were performed, but over 100,000 Americans are still stuck on the transplant list. Every day, 17 people die waiting because there simply aren’t enough organs to go around. Xenotransplantation – or the transfer of cells, tissues and organs between species – promises to solve this shortcoming and reshape the way we think about human longevity. Lost in this limitless potential, however, is the significance of the human-animal divide. People walking around with pig organs fused to their bodies – human-animal cyborgs – might seem dystopian. And as the zoonotic Sars-CoV-2 has killed more than 6 million people, breaching the human-animal interface may just promise more destruction. This labyrinthine relationship is nothing new, but it’s often sanitized and hidden from view—think smiling cows on milk cartons and secret animal research shelters. Left open are a host of questions, starting with the most complex of all: what does it mean to be human? Humans are animals. But animals are not people. And yet, our history is full of a cultural fantasy of hybridity. The ancient Egyptian god of the sky, Horus, was depicted with the head of a falcon and the goddess of war, Sekhmet, that of a lioness. Similarly, the Hindu god Ganesha was beheaded and then resurrected with an elephant’s head grafted onto his body. In ancient Greece, fantastical creatures roamed the fables, from the bull-headed Minotaur to the serpent-haired Medusa. Amidst this wealth of choices, the International Xenotransplantation Association chose a more obscure mascot: Lamassu, an Assyrian deity with the body of a bull, the wings of a bird and the head of a man – a wisdom of grounding. Xenotransplantation, as a research field, started with only cells and tissues. In 17th century France and England, animal blood was transfused into humans to treat a whole range of medical conditions. The spiritual meaning was infused into practice: “Since Christ is the lamb of God,” wrote one recipient in a letter to the Royal Society, “the blood of a sheep possesses[es] a symbolic relationship with [his] blood”. One patient’s violent fever was supposedly cured, as was another patient’s paralysis, but at least two others died soon after these “xenotransfusions”. The ancient Egyptian goddess of war, Sekhmet. Photo: Smith Collection/Gado/Getty Images Other early xenografts would follow, including those with bone, cornea, and skin. Perhaps most infamously, French surgeon Serge Voronoff transplanted slices of chimpanzee and baboon testicles into men, and monkey ovaries into women, to revive his patients’ “appetite for life.” Thousands of these operations were performed around the world, but any reported benefit, such as reduced fatigue or increased sex drive, was probably just the placebo effect and quickly disappeared. While cell and tissue xenografts have been performed for centuries, whole organ transplants have been more difficult to understand. Sewing all the blood vessels together is a difficult task. You need to put two disks together “mouth to mouth”, tying them tightly enough that the patient does not bleed, but gently enough that there is no significant clotting either. This was a Nobel prize-winning problem that French surgeon Alexis Carrel solved with a small embroidery needle and fine silk suture and was recognized in 1912. He is sometimes known as the father of surgical transplantation. Half a century later, in 1964, University of Mississippi surgeon James Hardy attempted the world’s first heart transplant, transplanting the heart of chimpanzee Bino into the rapidly deteriorating chest of 68-year-old Boyd Rush. Rush only survived for 90 minutes, with the chimpanzee’s heart providing insufficient support and rejection rapidly shutting down his body. It was Baby Fae who really raised the stakes for xenotransplantation. He was a 12-day-old infant with hypoplastic left heart syndrome, a congenital abnormality where the left side of the heart is a fragment of its full form. The condition was the death penalty. So in 1984, surgeons at Loma Linda University in California transplanted a walnut-sized baboon heart into Baby Fae’s chest. The conditions were almost perfect. The heart was a good size, the Baby Fae’s immune system was immature (and sympathetic), and the immunosuppressant drug cyclosporine could suppress the baboon’s heart attacks. After the operation, Baby Fae seemed to be doing well. Resting in her cot with a gauze-covered scar piercing her chest, she was “just getting her formula out” and crying out a “lustrous scream,” according to the hospital spokeswoman. The hospital also released photos of Baby Fae “talking” to her mother, the phone receiver larger than her entire torso. She died 21 days after her operation, her immune system refusing to accept the new infant-baboon hybrid. Outrage from doctors and the public soon followed, with animal rights activists protesting and bioethicists publishing articles such as “Baby Fae: The ‘Anything Goes’ School of Human Experimentation”. Xenotransplantation died with the Baby Fae, if only for a little while. “During surgery, when the drapes are in place, it’s not really a person,” Guenthart said. “It’s a duty.” From a technical point of view, a heart transplant is quite easy. It takes only five incisions to cut out the failing heart and only five connections to place the new one. Cautery in one hand, scissors in the other, you usually cut the superior vena cava first – the vessel that brings blood back to the heart from the head, neck, arms and chest – because it’s the most accessible structure. Next is the inferior vena cava, which brings blood back from the south, but is a bit difficult to access. So you cut out a part of the right chamber of the heart where this vessel drains. Then follow the aorta and pulmonary arteries in fairly simple, direct cuts. More difficult are the pulmonary veins, because they are four delicate vessels that are almost impossible to reconnect. The way around this is to lift the heart up and cut a lip of left heart tissue underneath. “You create a pool or a small crater,” Guenthart said. Stop it. “I’m just giving a description. They don’t actually call it a pool.” Regardless of whether you are transplanting a human heart or a pig heart into someone, the steps are essentially the same. “If you asked 99 out of 100 doctors, they couldn’t tell you if they were looking at a human breast or a pig breast,” Guenthart said. Pigs are dirty animals, as the conventional wisdom says. Judaism and Islam forbid the consumption of pork and other unclean meat. The “cops are pigs” insult definitely has teeth. And in the Odyssey, the witch Circe transforms Odysseus’ gluttonous men into pigs. Pigs stand in a barn at the Badersfeld Peat Test Farm in Oberschleissheim, Germany. Photo: Lukas Barth/Reuters Pigs are also highly intelligent animals, capable of showing emotions. About 11,000 years ago, wild pigs may have been domesticated, recognizing a benefit from an alliance with humans. They love to play fetch, are adept at navigating mazes, and can outwit dogs and chimpanzees, according to their IQ tests. After the Baby Fae experiment, primates fell out of favor for xenotransplantation, and pigs became the new model organism for researchers to develop. If you ask xenotransplantation experts today, they’ll give you a list of reasons why pigs are better than baboons: they’re easier to genetically manipulate, they can be raised in a sterile environment to reduce infections, and they can be grown to provide organs . of whatever size is required. It’s a nicely packaged narrative, but Dr. Brad Bollman, a historian of science at the University of Chicago, argues that sheep, goats, or some other animal could qualify. At first, Bolman said, “it wasn’t obvious that pigs were the right replacement for nonhuman primates.” But when pigs were chosen, scientific ideals were retroactively constructed to seem like the clear choice all along. Bolman says pigs were chosen because it was socially and economically convenient. They produce large litters quickly, with piglets reaching adult human size in six months. There is also an almost unlimited supply of them – 700 million worldwide – and as…
