Donated bodies are powering gene-edited organ research

This article first appeared in The Checkup, MIT Technology Review’s weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here.

Hooked up to a ventilation machine, a person can be dead in the eyes of the law, medical professionals, and loved ones, yet still alive enough to be useful for medical research. Such brain-dead people are often used for organ donation, but they are also of increasing importance to the biotech world.

This week, we reported how surgeons at the University of Pennsylvania connected a pig liver to a brain-dead person in an experiment that lasted for three days.

The point was to determine whether the organ—which was mounted inside a special pumping device—could still do its job of cleaning up toxins from the body, and possibly lead to a new approach for helping patients with acute liver failure.

Using entire bodies in this way—as an experimental “decedent model”—remains highly unusual. But there’s been an upsurge in requests for bodies as more companies start testing animal-to-human organ transplants using tissues from specially gene-edited pigs.

“In order to get to humans, you have to go through steps. You can’t say ‘I am going to try it tomorrow,’ as you did 50 years ago,” says Abraham Shaked, the surgeon at Penn who directed the experiment.

To learn how common it is to use bodies as experimental models, I checked in with Richard Hasz, CEO of Gift of Life Donor Program, a nonprofit that arranges for organ donation in Pennsylvania, New Jersey and Delaware, and which provided Penn with the body used in the liver experiment.

“It’s definitely a new model. But sometimes we repeat things that have happened before. We have been around 50 years, and this is the second time it’s been requested,” says Hasz.

The previous time was in the 1980s, when researchers at Temple University sought out brain-dead bodies as a “no risk” way to test an early artificial heart made from plastic and metal. They wanted to see how it fit in a chest and test surgical techniques before trying the mechanical heart in a living patient.

Starting in 2021, though, donation organizations again started hearing from surgeons who needed brain-dead people, sometimes called “beating-heart cadavers.” That was because several companies had developed gene-edited pigs and doctors were ready to start trying their organs.

According to a tally from the biotech company eGenesis, of the 10 pig-to-human transplant experiments that have taken place in the US since 2021, two have been in living people, but the other eight have involved brain-dead bodies.

The main use of such bodies is as organ donors. Although most people don’t realize it, says Hasz, only that relatively rare 1% to 2% of people who experience brain death while under medical care can have their organs collected.

“It’s a big misconception that anyone who has died in a car accident or outside the hospital can be an organ donor. You have to have died in the ICU from a devastating neurological injury to your brain,” he says.

It’s that brain-dead but beating-heart state that provides the time—sometimes a day or two—to move the body to a central location, find a suitable recipient, and allow surgeons to remove the organs.

Organizations like Hasz’s are the ones that approach families, transport the bodies, and help match organs to recipients. Last year Gift of Life helped arrange for 1,734 transplants of organs taken from 693 donors.

The family of the patient in this case—really, the “decedent,” since he’d been declared brain dead—wanted to see his organs donated. But there weren’t any takers; sometimes factors like cancer, age, or infections make organs less desirable.

So Hasz approached the family about another option. Would they agree to let his body be used in an experiment with a pig liver? The whole concept was new to them, but they quickly agreed, he says.

“Our team tried to shepherd this family to understand all the ins and outs of what that would mean—the length of time, the goals, the fact that it would be an extracorporeal support—and provide them with all that information,” he says.

This time the experiment lasted only 72 hours, as that’s about how long a pig liver would be needed to support a real patient. Hasz says other families might be comfortable with longer experiments, but probably not anything indefinite: “We can maintain a body with mechanical support once they are declared medically and legally dead, but families have a desire for closure, funeral services, and depending on the family, they may limit it to one day or one month.”

Hasz says his team will be looking for more body donors to support further experiments with pig livers. And he expects many will agree. “We depend every day in organ transplant on the kindness of strangers who are at their worst possible moment, but they can set that aside and think of others,” he says. “Having talked to many families over the years, I am always surprised and humbled by their willingness to say yes.”

Around the web

A lab in China reported experiments with a coronavirus that is 100% fatal to mice and could harm humans. It caused brain damage and turned their eyes white. Some scientists condemned the risky research as “madness.” (New York Post)

Perverse incentives, no real negotiation, and profiteering middlemen. Those are among the five key reasons drug prices in the US are nearly twice those in some European countries. (New York Times)

No one can resist a cute animal story—I think that’s why efforts to test anti-aging drugs in pets get so much media attention. But now people are howling about the $7-million-a-year Dog Aging Project, whose organizers say they’re about to lose their government funding. The project has been testing the life-span effects on dogs of a drug called rapamycin. (Science)