The pigs had been dead in the lab for an hour: no blood circulating in their bodies, their hearts were still, their brain waves flat. A group of Yale scientists then injected a custom-made solution into the bodies of the dead pigs with a device similar to an extracorporeal circulation machine.
What happened next adds questions to what science considers to be the wall between life and death. Although the pigs were not considered conscious in any way, their apparently dead cells revived. Their hearts began to beat as the solution, which the scientists called OrganEx, circulated through their veins and arteries. The cells of their organs, including the heart, liver, kidneys, and brain, returned to function 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 became swollen and damaged, their blood vessels collapsed, and they had purple spots on their backs where blood collected.
The group reported their results Wednesday in Nature.
The researchers say their goals are to one day increase the supply of human organs for transplant by allowing doctors to obtain viable organs long after death. And they say they hope their technology could also be used to prevent serious damage to hearts after a devastating heart attack or to the brain after a major stroke.
But the findings are just a first step, said Stephen Latham, a Yale University bioethicist who worked closely with the group. The technology, he emphasized, is “a long way from being used in humans.”
The group, led by Dr. Nenad Sestan, a professor of neuroscience, comparative medicine, genetics, and psychiatry at Yale School of Medicine, was stunned by its ability to revive cells.
“We didn’t know what to expect,” said Dr. David Andrijevic, also a Yale neuroscientist and one of the paper’s authors. “Everything we restored was amazing for us.”
Others not associated with the work were equally amazed.
“It’s unbelievable, 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 is a state of being,” he 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 on the brains of dead pigs from a slaughterhouse. Four hours after the pigs died, the group infused an OrganEx-like solution they called BrainEx and found that brain cells that should have been dead could be revived.
That led them to ask 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 dampen the activity of neurons and prevent any chance of the pigs regaining consciousness), and an artificial hemoglobin mixed with each pig’s own blood. animal.
When treating the dead pigs, the researchers took precautions to make sure the animals didn’t suffer. Pigs were anesthetized prior to sacrifice by stopping their hearts, and deep anesthesia continued throughout the experiment. Additionally, the nerve blockers in the OrganEx solution prevent the nerves from firing to ensure the brain is not active. The researchers also chilled the animals to slow chemical reactions. Individual brain cells were alive, but there was no evidence of any organized global nervous activity in the brain.
There was a surprising finding: OrganEx-treated pigs shook their heads when the researchers injected an iodine contrast solution for imaging. Dr. Latham stressed that while the reason for the movement was unknown, there was no indication that the brain was involved.
Yale has applied for a patent on the technology. The next step, Dr. Sestan said, will be to see if the organs function properly and can be successfully transplanted. Some time later, the researchers hope to test whether the method can repair damaged hearts or brains.
The journal Nature asked two independent experts to comment on 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 phone interview, he explained that OrganEx could be used in the future in situations where patients are not brain dead but brain injured to the point that life support is useless.
In most countries, Dr. Porte said, there is a five-minute “no touch” policy after the ventilator is turned off and before organs are removed by transplant surgeons. But, he said, “before you rush to the operating room, there will be additional minutes,” at which point the organs may be so damaged that they are no longer usable.
And sometimes patients don’t die immediately when life support is stopped, but their hearts beat too weakly for their organs to stay healthy.
“In most countries, transplant teams wait two hours” for patients to die, Dr. Porte said. So, he said, if the patient isn’t dead yet, they don’t try to retrieve the organs.
As a result, 50 to 60 percent of patients who died after life support ceased and whose families wanted to donate their organs cannot be donors.
If OrganEx could bring those organs back to life, Dr. Porte said, the effect “would be huge” — a huge increase in the number of organs available for transplant.
The other comment was from Brendan Parent, an attorney and ethicist who is director of transplant ethics and policy research at New York University Grossman School of Medicine.
In a phone interview, he discussed what he said were “tough questions about life and death” that OrganEx raises.
“By the accepted medical and legal definition of death, these pigs were dead,” Parent said. But, he added, “a critical question is: What role and what kind of role 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? That would create ethical problems if the goal was to preserve organs for transplantation and the pigs regain some degree of consciousness during the process.
But restoring brain functions might be the goal if the patient has had a serious stroke or drowned.
“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,” Parent said.
In his opinion, the method would eventually have to be tested in people who could benefit, such as victims of strokes or drowning. But that would require a lot of deliberation on the part of ethicists, neurologists, and neuroscientists.
“How we get there is going to be a critical question,” Parent said. “When does the data we have justify taking this leap?”
Another problem is the implications that OrganEx could have for the definition of death.
If OrganEx continues to show that the period of time after blood and oxygen deprivation before which cells cannot recover is much longer than previously thought, then there has to be a change in the timing of determining that a person is dead.
“It’s weird, but not unlike what we went through with ventilator development,” Parent said.
“There is a whole population of people who in a different era might have been called dead,” he said.