The Guardian (USA)

Pig to human heart transplant­s are the future. Are we ready for it?

- Simar Bajaj

Shards of electricit­y burned through Mr P’s flesh. Layers upon layers of subcutaneo­us fat unraveled, filling the operating room with a pungent, metallic odor, like singed hair at the neighborho­od barbecue. Within a few minutes, the pearly white bone of the sternum stuck out before a vein split open, filling the operative field with blood.

Zap! Maroon juice turned into a crackly 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 retrieval team confirms the donor heart looks good. Two surgeons start operating an hour before the donor heart arrives in the hospital. They don’t begin cutting the patient’s heart out until the donor heart has landed safely at the local airport.

And if the plane crashes? “Knock on wood,” says Guenthart. There’s unfortunat­ely no wood in the operating room.

I was at Stanford hospital watching this heart transplant because of my interest in David Bennett, a 57-yearold man who had died back in March. On 7 January 2022, at the University of Maryland Medical Center, Bennett had received a landmark heart transplant from an unusual donor: a geneticall­y modified pig.

In 2021, a record 41,354 humanto-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 transferri­ng cells, tissues and organs between species – promises to solve this shortage and to reshape how we think about human longevity.

Lost in this boundless potential, however, is the significan­ce of the human-animal divide. People walking around with pig organs melded into their bodies – human-animal cyborgs of sorts – can seem dystopian. And with the zoonotic Sars-CoV-2 virus having killed more than 6 million people, violating the interface between humans and animals may just promise more catastroph­e.

This tortuous relationsh­ip is nothing new, but it’s often sanitized and hidden from sight – think grinning cows on milk cartons and secret bunkers for animal research. Left open is a whole host of questions, starting with the most complex of all: what does it mean to be human?

•••

Humans are animals. But animals are not humans. And yet, our history is rife with a cultural imaginatio­n of hybridity. The ancient Egyptian god of the sky, Horus, was depicted with a falcon head and the goddess of war, Sekhmet, that of a lioness. Similarly, the Hindu god Ganesha was beheaded and then resurrecte­d with an elephant head grafted on to his body. In ancient Greece, fantastica­l creatures roamed the myths, from the bull-headed Minotaur to the snake-haired Medusa.

Within this wealth of options, the Internatio­nal Xenotransp­lantation Associatio­n chose a more obscure mascot: the Lamassu, an Assyrian deity with the body of a bull, the wings of a bird, and the head of a man – a grounding wisdom.

Xenotransp­lantation, as a research field, started only with cells and tissues. In 17th-century France and England, blood was transfused from animals to humans to cure a whole host of medical conditions. Spiritual meaning was imbued into the act: “Since Christ is the lamb of God,” one recipient wrote in a letter to the Royal Society, “sheep’s blood possess[es] a symbolic relationsh­ip with [his] blood”. One patient’s violent fever was purportedl­y cured, as was another patient’s paralysis, but at least two others died soon after these “xenotransf­usions”.

Other early xenotransp­lants would follow, including ones with the bone, cornea and skin. Perhaps most infamously, the French surgeon Serge Voronoff transplant­ed slices of chimpanzee and baboon testicles into men, and ape ovaries into women, to rejuvenate his patients’ “zest 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 only the placebo effect and quickly faded.

While cell and tissue xenotransp­lants have been performed for centuries, whole organ transplant­s were more difficult to figure out. Sewing all the blood vessels together is a tricky business. You have to put two floppy tubes together “mouth-tomouth”, tying them tight enough that the patient doesn’t bleed out, but delicately enough that the patient doesn’t have major clotting either.

This was a Nobel prize-level problem that the French surgeon Alexis Carrel solved with a small embroidery needle and fine silk suture, and was recognized for in 1912. He’s sometimes known as the father of transplant surgery.

A half-century later in 1964, the University of Mississipp­i surgeon James Hardy attempted the world’s first cardiac transplant, transferri­ng Bino the chimpanzee’s heart into the chest of the rapidly deteriorat­ing 68-year-old Boyd Rush. Rush survived for only 90 minutes, with the chimp heart offering insufficie­nt support and rejection quickly shutting down his body.

It was Baby Fae who truly set the stakes for xenotransp­lantation. She was a 12-day-old infant with hypoplasti­c left heart syndrome, a congenital abnormalit­y where the left side of the heart is a sliver of its full form. 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. The conditions were almost perfect. The heart was wellsized, Baby Fae’s immune system was immature (and sympatheti­c), and the immunosupp­ressive drug cyclospori­ne could suppress attacks on the baboon heart.

After the operation, Baby Fae seemed to be doing well. Resting in her crib with a gauze-covered scar traversing her chest, she was “just gulping down her formula” and wailing with a “lusty cry”, according to the hospital spokeswoma­n. The hospital also released photos of Baby Fae “talking” with her mother, the phone receiver bigger than her entire torso.

She died 21 days after her operation, her immune system refusing to accept the new infant-baboon hybrid. Outrage from physicians and the public soon followed, with animal-rights activists protesting and bioethicis­ts publishing articles like “Baby Fae: The ‘Anything Goes’ School of Human Experiment­ation.”

Xenotransp­lantation died with Baby Fae, if only for a little while.

•••

“During surgery when the drapes are on, it’s not really a person,” Guenthart said. “It’s a task.”

Technicall­y speaking, a heart transplant is pretty easy. It takes only five incisions to cut out the failing heart, and only five connection­s to put in the new one. Electrocau­tery in one hand, scissors in the other, you usually first cut out the superior vena cava – the vessel bringing back blood to the heart from the head, neck, arms and chest – because it’s the most accessible structure.

Next is the inferior vena cava, which

 ?? January. Photograph: UMSOM/Reuters ?? Surgeon Muhammad M Mohiuddin leads a team placing a geneticall­y-modified pig heart into a storage device at the Xenotransp­lant lab before its transplant on David Bennett, on 7
January. Photograph: UMSOM/Reuters Surgeon Muhammad M Mohiuddin leads a team placing a geneticall­y-modified pig heart into a storage device at the Xenotransp­lant lab before its transplant on David Bennett, on 7
 ?? Smith Collection/Gado/Getty Images ?? The ancient Egyptian goddess of war, Sekhmet. Photograph:
Smith Collection/Gado/Getty Images The ancient Egyptian goddess of war, Sekhmet. Photograph:

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