How scientists revive cells in the organs of dead pigs

How scientists revive cells in the organs of dead pigs

The pigs had been dead in the lab for an hour—no blood circulating in their bodies, their hearts were still, their brainwaves flat. Then a group of Yale scientists pumped a custom-made solution into the bodies of the dead pigs using a device resembling a heart-lung machine.

What happened next adds questions to what science considers the wall between life and death. Although the pigs were in no way believed to be conscious, their apparently dead cells were revived. Their hearts started beating as the solution, which the scientists dubbed OrganEx, circulated in veins and arteries. Cells in their organs, including the heart, liver, kidneys, and brain, functioned again, and the animals never went rigid like a typical dead pig.

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

The group reported their findings in Nature on Wednesday.

The researchers say their goal is to one day increase the supply of human organs available for transplant by allowing doctors to preserve viable organs long after death. And they hope their technology could also be used to prevent serious damage to the heart after a devastating heart attack or to the brain after a major stroke.

But the results are just a first step, said Stephen Latham, a bioethicist at Yale University who has worked closely with the group. The technology, he stressed, is “very far removed from human use.”

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

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

Others unrelated to work were similarly amazed.

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

And, added Dr. Farahany added that 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 conducted a similar experiment using the brains of dead pigs from a slaughterhouse. Four hours after the pigs died, the group infused an OrganEx-like solution they dubbed BrainEx and saw that brain cells that were supposed to be dead could be revived.

That led them to wonder if they could resuscitate a whole 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 dampen the activity of neurons and prevent the pigs from any chance of regaining consciousness — and an artificial hemoglobin mixed with each animal’s own blood became.

When treating the dead pigs, investigators took precautions to ensure the animals did not suffer. The pigs were stunned before being killed by stopping their hearts and deep stunning was continued throughout the experiment. In addition, the nerve blockers in the OrganEx solution prevent nerves from firing to ensure the brain is not active. The researchers also refrigerated the animals to slow down chemical reactions. Individual brain cells were alive, but there was no evidence of organized global neural activity in the brain.

There was a surprising finding: The pigs treated with OrganEx jerked their heads when the researchers injected an iodine contrast solution for imaging. dr Latham stressed that while the reason for the movement is not known, there is no evidence of brain involvement.

Yale has applied for a patent on the technology. The next step, said Dr. Sestan, will be there to see if the organs are functioning properly and can be transplanted successfully. Some time later, the researchers want to test whether the method can repair damaged hearts or brains.

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

In a telephone interview, he explained that in the future OrganEx could be used in situations where patients are not brain dead but are brain damaged beyond the point of survival.

In most countries, said Dr. Porte, there is a five-minute “no touch” policy after the ventilator is turned off and before transplant surgeons harvest organs. But, he said, “it will be a few more minutes before you rush to the OR,” and by then organs can be so damaged they are unusable.

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

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

As a result, 50 to 60 percent of patients who died off life support and whose families chose to donate their organs cannot be donors.

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

The other comment comes from Brendan Parent, an attorney and ethicist who is the director of transplant ethics and policy research at New York University’s Grossman School of Medicine.

In a phone interview, he spoke about “tough questions of life and death” that OrganEx raises.

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

Would the pigs still be dead if the group didn’t use nerve blocks in their solution and got their brains working again? This would raise ethical issues if the goal was to obtain organs for transplantation and the pigs regained some level of consciousness during the process.

But restoring brain function could be the goal if the patient had a major stroke or was a drowning victim.

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

In his opinion, the method should eventually be tried on people who could benefit from it, such as stroke or drowning victims. But that would require much thought from ethicists, neurologists and neuroscientists.

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

Another issue is the impact OrganEx could have on the definition of death.

If OrganEx continues to show that the length of time after blood and oxygen deprivation before which cells cannot recover is much longer than previously thought, then the point at which a person is determined to be dead must change.

“It’s weird, but no different than what we went through developing the ventilator,” Mr. Parent said.

“There’s a whole demographic of people who would have been pronounced dead in another time,” he said.

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