How scientists are reviving cells in the organs of dead pigs

The pigs had been lying dead in the lab for an hour – their bodies had no blood circulation, their hearts were still, their brain waves were flat. A team of Yale scientists then injected a specially prepared solution into the bodies of dead pigs using a device similar to a heart-lung machine.

What happens next raises questions about what constitutes the wall between science and death. Although the pigs were not considered conscious anyway, their seemingly dead cells were reanimated. As the solution, which scientists call OrganEx, circulates in veins and arteries, their hearts begin to beat. Cells in their organs, including the heart, liver, kidneys and brain, began to function again, and the animals never froze like normal dead pigs.

The other pigs, which had been dead for an hour, were treated with ECMO, a machine that pumps blood into their bodies. He was confused, his organs were swollen and injured, blood vessels collapsed, and purple spots of blood pooled on his back.

The team reported their findings Wednesday in the journal Nature.

The researchers say their goal is to one day increase the supply of human organs for transplants and allow doctors to harvest viable organs long after death. They say they hope their technology could be used to prevent severe damage to the heart after a heart attack or to the brain after a massive stroke.

But the findings are just the first step, said Stephen Latham, a bioethicist at Yale University who worked closely with the group. He notes that the technology is “very far from being used in humans.”

A group led by Dr. Nenad Sestan, a professor of neurology, comparative medicine, genetics and psychiatry at Yale School of Medicine, was amazed by the ability to revive cells.

“We didn’t know what to expect,” said Dr. David Andrievich, also a neuroscientist at Yale, is a co-author of the paper. “Everything we’ve recovered has been incredible for us.”

Others unrelated to the case were similarly surprised.

“It’s incredible, mind-boggling,” said Nita Farahani, a Duke law professor who studies the ethical, legal and social implications of emerging technologies.

And, Dr. Farahani added that the work raises questions about the definition of death.

“We think of death as something, a state of being,” he said. “Are there reversible forms of death?” Or not?”

The work began a few years ago, when a group conducted a similar experiment with the brains of dead pigs in a slaughterhouse. Four hours after the pigs died, the team injected an OrganEx-like solution they called BrainEx and saw that brain cells that should have died could come back to life.

This led them to question whether they could revive the whole body, said Dr. Zvonimir Vrselja, another member of the Yale team.

The OrganEx solution contains nutrients, anti-inflammatory drugs, drugs that prevent cell death, nerve blockers — substances that slow down the activity of neurons and prevent the pigs from regaining consciousness — and artificial hemoglobin mixed with each animal’s blood.

When they treated the dead pigs, the investigators took precautions to prevent the animals from suffering. Pigs were anesthetized by cardiac arrest prior to killing, and deep anesthesia continued throughout the experiment. In addition, the nerve blockers in the OrganEx solution stop nerve activity to keep the brain functioning. The researchers also chilled the animals to slow down the chemical reactions. Individual brain cells were alive, but there was no sign of any organized global neural activity in the brain.

One surprising discovery was that pigs treated with organEx nodded their heads while researchers injected an iodine contrast solution to take pictures. Dr. Although the cause of the movement is unknown, Latham emphasized that the brain is not involved.

Yale applied for a patent on the technology. The next step, Dr. According to Sestan, he will check whether the organs are functioning properly and can be successfully transplanted. Over time, the researchers hope to test whether this technique can repair damaged hearts or brains.

The journal Nature asked two independent experts to comment on the study. Inone, Dr. Robert Porte, a transplant surgeon at the University of Groningen in the Netherlands, discussed the system’s potential to expand the pool of organs available for transplant.

In a phone interview, he explained that OrganEx could be used in the future in patients with brain injuries rather than brain death.

In most countries Dr. Port said there is a five-minute “no touch” policy after the respirator is turned off and before the transplant surgeons remove the organs. But, he says, “extra minutes pass before you rush to the OR,” and by then organs can be useless.

Sometimes patients do not die immediately when life is stopped, but their hearts beat too weakly to keep their organs healthy.

“In most countries, transplant teams wait two hours for patients to die,” said Dr. mail And he, if the patient is not dead, they do not try to take the organs.

As a result, 50-60 percent of patients who died after life support was stopped and whose families wanted to donate their organs could not become donors.

If OrganEx can revive these organs, Dr. The effect, Port said, “would be huge” — an increase in the number of organs available for transplant.

Another comment was made by lawyer and ethicist Brendan Parent, director of transplant ethics and policy research at New York University’s Grossman School of Medicine.

In a phone interview, he discussed what he said were “difficult questions around life and death” raised by OrganEx.

“According to the accepted medical and legal definition of death, these pigs are dead,” said M. Parents said. But, he added, “the critical question is: Which function and what function will change things?”

If the group hadn’t used nerve blockers in their solution and their brains had reactivated, would the pigs still have died? If the goal was to save organs for transplantation and the pigs somehow regained consciousness during the process, this would pose ethical problems.

But restoring brain function may be the goal if a patient suffers a severe stroke or drowns.

“If we’re going to get this technology to the point where it can help people, we need to see what happens in the brain without nerve blockers,” he said. Parents said.

He believes that this approach should be applied to people who may eventually benefit, such as those who have suffered a stroke or drowned. But this requires a lot of thinking by ethicists, neurologists and neuroscientists.

“The critical question becomes how do we get there,” Mr. Parents said. “When will the data we have justify this leap?”

Another issue is the effect of OrganEx on the definition of death.

If OrganEx continues to show that the length of time that cells can’t recover from a lack of blood and oxygen is much longer than previously thought, then there should be a change in how long a person is considered dead.

“It’s interesting, but it’s no different than what we experienced with the development of the ventilator,” he said. Parents said.

“In another age, there’s a whole population of people who could be called dead,” he said.

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