How scientists are reviving cells in dead pig organs

How scientists are reviving cells in dead pig organs

The pigs had been lying dead in the lab for an hour – no blood was circulating in their bodies, their hearts were quiet, their brain waves flat. Then a group of Yale scientists pumped a custom-made solution into the bodies of dead pigs with a device similar to a heart and lung machine.

What happened next raises questions about what science considers the wall between life and death. Although the pigs were not considered conscious in any way, their apparently dead cells were revived. Their hearts began to beat as the solution, which the scientists called OrganEx, circulated in their veins and arteries. The cells in their organs, including the heart, liver, kidneys and brain, were functioning again, and the animals never stiffened like a typical dead pig.

Other pigs, dead for an hour, were treated with ECMO, a machine that pumped blood through their bodies. They stiffened, their organs were swollen and damaged, their blood vessels collapsed, and they had purple spots on their backs where blood pooled.

The group reported its results Wednesday in Nature.

The researchers say their goals are to one day increase the supply of human organs for transplant, allowing doctors to obtain viable organs long after death. And, they say, they hope their technology can also be used to prevent severe damage to the heart after a devastating heart attack or the brain after a major stroke.

But the findings are just a first step, said Stephen Latham, a bioethicist at Yale University who has worked closely with the group. The technology, he pointed out, is “a long way from being used in humans”.

The group, led by Dr. Nenad Sestan, professor of neuroscience, comparative medicine, genetics and psychiatry at Yale School of Medicine, was amazed by its ability to revive cells.

“We didn’t know what to expect,” said Dr. David Andrijevic, also a neuroscientist at Yale and one of the authors of the paper. “Everything we restored was incredible to us.”

Others not connected to the work were equally astounded.

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

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

“We assume that death is a thing, it’s a state of being,” she said. “Are there forms of death that are reversible? Or not?”

The work began a few years ago when the group did a similar experiment with the brains of dead pigs from a slaughterhouse. Four hours after the pigs died, the group injected an OrganEx-like solution they called BrainEx and saw that brain cells that should have died could be revived.

This led them to wonder if they could revive an entire body, said Dr. Zvonimir Vrselja, another member of the Yale team.

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

When handling the dead pigs, investigators took precautions to ensure the animals did not suffer. The pigs were anesthetized before they were killed by stopping their hearts, and deep anesthesia continued throughout the experiment. In addition, the nerve blockers in the OrganEx solution stop the firing of the nerves to ensure that the brain was not active. The researchers also chilled the animals to slow down the chemical reactions. Individual brain cells were alive, but there was no indication of any organized global neural activity in the brain.

There was one surprising finding: Pigs treated with OrganEx nodded when researchers injected an iodine contrast solution for imaging. Dr. Latham stressed that while the reason for the movement was unknown, there was no indication of any brain involvement.

Yale has filed a patent on the technology. The next step, said Dr. Sestan, it remains to be seen if the organs work properly and if they can be successfully transplanted. Sometime after that, the researchers hope to test whether the method can repair damaged hearts or brains.

The journal Nature asked two independent experts to write reviews about the study. In one, Dr. Robert Porte, a transplant surgeon at the University of Groningen in the Netherlands, discussed the potential use of the system to expand the pool of organs available for transplant.

In a telephone interview, he explained that OrganEx could in the future be used in situations in which patients are not brain dead, but brain injured to the extent that life support is futile.

In most countries, said Dr. Porte, there is a five-minute “no touch” policy after the ventilator is turned off and before the transplant surgeons remove the organs. But, he said, “before you rush to the OR, additional minutes will pass,” and by then organs may be so damaged as to be unusable.

And sometimes patients don’t die immediately when life support is stopped, but their hearts beat too weakly for their organs to remain healthy.

“In most countries, transplant teams wait two hours” for patients to die, Dr. Ports. Then, he said, if the patient isn’t dead yet, they don’t try to harvest the organs.

As a result, 50 to 60 percent of patients who died after life support was withdrawn and whose families wanted to donate their organs are unable to be donors.

If OrganEx could revive those organs, said Dr. Porte, the effect “would be huge” – a huge increase in the number of organs available for transplant.

The next comment was from Brendan Parent, a lawyer and ethicist who is director of transplant ethics and policy research at New York University’s Grossman School of Medicine.

In a telephone interview, he discussed what he said were “complicated questions about life and death” that OrganEx raises.

“By the accepted medical and legal definition of death, these pigs were dead,” Mr Parent said. But, he added, “a critical question is: Which function and what kind of function would change things?”

Would the pigs still be dead if the group didn’t use nerve blockers in their solution and their brains would work again? This would create ethical problems if the goal was to preserve organs for transplantation and the pigs regained some degree of consciousness in the process.

But restoring brain functions may be the goal if the patient had suffered a severe stroke or was a drowning victim.

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

In his view, the method would eventually need to be tried in people who could benefit, such as stroke or drowning victims. But this would require much discussion by ethicists, neurologists and neuroscientists.

“How we get there will be a critical question,” Mr. Parent said. “When does the data we have justify this leap?”

Another issue is the implications that OrganEx may have for the definition of death.

If OrganEx continues to show that the length of time after a lack of blood and oxygen before cells cannot recover is much longer than previously thought, then there should be a change in when a person is determined to be dead.

“It’s strange, but not unlike what we went through with ventilator development,” Mr. Parent said.

“There’s a whole population of people who in another era could be called dead,” he said.

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