How scientists revive cells in organs of dead pigs

The pigs had been dead in the lab for an hour — no blood circulating in their bodies, their hearts were silent, their brain waves were flat. Then a group of Yale scientists pumped a custom solution into the dead pigs’ bodies with a device that resembles 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 considered conscious, their apparently dead cells came back to life. Their hearts started beating when the solution, which the scientists called OrganEx, circulated in veins and arteries. Cells in their organs, including the heart, liver, kidneys and brain, functioned again, and the animals never became as stiff as a typical dead pig.

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

The group reported the results Wednesday in Nature.

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

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

The group, led by Dr. Nenad Sestan, a professor of neuroscience, comparative medicine, genetics and psychiatry at the Yale School of Medicine, was stunned by her 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 article. “Everything we recovered was incredible for us.”

Others not involved in the work were similarly amazed.

“It’s unbelievable, amazing,” said Nita Farahany, a Duke law professor who studies ethical, legal and social implications of emerging technologies.

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

“We assume 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 brains from dead pigs from a slaughterhouse. Four hours after the pigs died, the group injected a solution similar to OrganEx that they called BrainEx and saw that brain cells that should be dead can be brought back to life.

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 neuron activity and any possibility of the pigs regaining consciousness — and an artificial hemoglobin mixed with each animal’s own blood.

When they treated the dead pigs, the researchers took precautions to make sure the animals didn’t suffer. The pigs were anesthetized before being killed by stopping their hearts, and the deep anesthesia continued throughout the experiment. In addition, the nerve blockers in the OrganEx solution keep the nerves from firing to ensure that the brain was not active. The researchers also cooled the animals to slow down chemical reactions. Individual brain cells were alive, but there was no indication of any organized global nervous activity in the brain.

There was one surprising finding: The OrganEx-treated pigs jerked their heads when the researchers injected an iodine contrast solution for imaging. dr. Latham emphasized that while the reason for the movement was unknown, there was no indication of any brain involvement.

Yale has applied for a patent on the technology. The next step, said Dr. Sestan, will be to see if the organs are functioning properly and can be successfully transplanted. Some time 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 comments 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 collection of organs available for transplantation.

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

In most countries, said Dr. Porte, there is a “no touch” policy of five minutes after the ventilator is turned off and before transplant surgeons remove organs. But, he said, “before you rush to the OR, extra minutes will pass,” by which time organs may be so damaged that they are useless.

And sometimes patients don’t die immediately when life support 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. Porte. Then, he said, if the patient isn’t dead yet, they don’t try to retrieve organs.

As a result, 50 to 60 percent of patients who died after life support was discontinued and whose families wanted to donate their organs cannot 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 transplantation.

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

In a phone interview, he discussed what he believes to be “tough questions about life and death” raised by OrganEx.

“By the accepted medical and legal definition of dead, these pigs were dead,” said Mr Parent. But, he added, “a crucial 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 the solution and their brains work again? That would pose ethical problems if the goal was to preserve organs for transplantation and the pigs regained some consciousness in the process.

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

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

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

“How we get there is going to be a crucial question,” said Mr Parent. “When does the data we have justify making this leap?”

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

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

“It’s weird, but no different from what we’ve been through with the development of the fan,” said Mr. parent.

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

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