Bursts of electricity burned through Mr. P’s flesh. Layers and layers of subcutaneous fat sloughed off, filling the operating room with a pungent, metallic smell, like charred hair at the neighborhood barbecue. Within minutes, the pearly white bone of the sternum was protruding before a vein opened, filling the operative field with blood.
Zap! The garnet juice turned into a crusty black mass.
Transplant surgery is all about time, 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 looks fine. Two surgeons begin operating an hour before the donor heart arrives at the hospital. They do not begin removing the patient’s heart until the donor heart has landed safely at the local airport.
What if the plane crashes? “Knock on wood,” says Guenthart. Unfortunately there is no wood in the operating room.
I was at Stanford Hospital looking at 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 received a landmark heart transplant from an unusual donor: a genetically modified pig.
In 2021, a record 41,354 person-to-person organ transplants were performed, but more than 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 shortage, and change the way we think about human longevity.
Lost in this limitless potential, however, is the meaning of the divide between humans and animals. People who walk around with pig organs fused to their bodies, a kind of human-animal cyborgs, can seem dystopian. And given that the zoonotic virus Sars-CoV-2 has killed more than 6 million people, breaching the human-animal interface may promise more catastrophes.
This devious relationship is nothing new, but it’s often sanitized and hidden from view: think of smiling cows on milk cartons and secret bunkers for animal research. A whole series of questions remains open, beginning with the most complex of all: what does it mean to be human?
We humans are animals. But animals are not human. And yet our history is plagued by a cultural imagination of hybrids. The ancient Egyptian god of the sky, Horus, was depicted with a falcon’s head and the war goddess, 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 myths, from the bull-headed Minotaur to the snake-haired Medusa.
Within this myriad of options, the International Xenotransplantation Association chose a darker mascot: Lamassu, an Assyrian deity with the body of a bull, the wings of a bird, and the head of a man: a fundamental wisdom.
Xenotransplantation, as a field of research, started with just cells and tissues. In 17th-century France and England, animal blood was transfused into humans to cure a host of medical conditions. Spiritual meaning was imbued in the act: “Since Christ is the Lamb of God,” one recipient wrote in a letter to the Royal Society, “sheep’s blood bears a symbolic relation to [su] blood”. One patient’s violent fever was supposedly cured, as was another patient’s paralysis, but at least two others died shortly after these “xenotransfusions”.
Other early xenotransplantation would follow, including those of bone, cornea, and skin. Perhaps most infamously, French surgeon Serge Voronoff transplanted slices of chimpanzee and baboon testicles into men, and ape ovaries into women, to rejuvenate the “zest for life” of his patients. Thousands of these operations have been performed around the world, but any reported benefit, such as reduced fatigue or increased sexual desire, was probably just the placebo effect and quickly faded.
While cell and tissue xenotransplantation has been done for centuries, whole organ transplants have been more difficult to crack. Stitching all the blood vessels together is a tricky business. You have to join two flexible tubes “mouth to mouth”, tying them tight enough so that the patient does not bleed out, but delicate enough so that the patient does not have a 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 referred to as the father of transplant surgery.
Half a century later, in 1964, University of Mississippi surgeon James Hardy attempted the world’s first heart transplant, transferring the heart of the chimpanzee Bino into the rapidly deteriorating 68-year-old Boyd Rush’s chest. Rush survived for only 90 minutes, with the chimp’s heart offering insufficient support and rejection quickly shutting down his body.
It was Baby Fae who really placed the bets for xenotransplantation. She was a 12-day-old baby with hypoplastic left heart syndrome, a congenital anomaly in which the left side of the heart is a portion of her entire shape. The condition was a death sentence.
So, in 1984, surgeons at Loma Linda University, California, transplanted a walnut-sized baboon heart into Baby Fae’s chest. Conditions were almost perfect. The heart was a good size, Baby Fae’s immune system was immature (and sympathetic), and the immunosuppressant drug cyclosporin could suppress the baboon’s heart attacks.
After the operation, Baby Fae seemed to be fine. Resting in her crib with a gauze-covered scar across her chest, she was “just swallowing her formula” and crying a “lustful cry,” 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.
He died 21 days after his operation, his immune system refusing to accept the new baby-baboon hybrid. He soon followed outrage from doctors and the public, with animal rights activists protesting and bioethicists publishing articles such as “Baby Fae: The ‘Anything Goes’ School of Human Experimentation.”
The xenotransplant died with Baby Fae, if only for a little while.
“During surgery, when the curtains are up, it’s not really a person,” Guenthart said. “It’s a homework”.
Technically speaking, a heart transplant is quite easy. Only five incisions are needed to remove the defective heart and only five connections to place the new one. Electrocautery in one hand, scissors in the other, the superior vena cava, the vessel that carries blood to the heart from the head, neck, arms, and chest, is usually cut first because it is the most accessible structure.
Then there’s the inferior vena cava, which brings blood from the south but is a bit difficult to reach. So, you cut out a part of the right chamber of the heart where this vessel drains.
Next comes the aorta and pulmonary arteries in fairly simple and direct incisions. 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 an edge of tissue from the left heart from below. “A pool or a small crater is created,” Guenthart said. He paused. “It’s just me 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 doctors out of 100, they couldn’t tell you if they were looking at a human chest or a pig chest,” Guenthart said.