How scientists are reviving cells in the organs of dead pigs

The pigs had been lying dead in the lab for an hour – no blood circulating in their bodies, their hearts still, their brain waves flat. Then, a team of scientists at Yale injected a custom solution into the carcasses of dead pigs with a device similar to a heart-lung machine.

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

The other pigs, which had been dead for an hour, were treated with ECMO, a type of pump that pumps blood through their bodies. They become stiff, their organs swell and become damaged, their blood vessels collapse, and they have purple spots on their backs where blood collects.

The group report its results Wednesday in Nature.

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

But the discovery is just the first step, says Stephen Latham, a bioethicist at Yale University who has worked closely with the team. The technology is “far from being used by humans,” he stressed.

The team, led by Dr. Nenad Sestan, a professor of neuroscience, comparative medicine, genetics, and psychiatry at Yale Medical School, was astounded by its ability to revive cells.

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

Others unrelated to the work were similarly surprised.

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

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

“We think death is something, it’s a state of being,” she said. “Are there any reversible forms of death? Or not?”

Work started a few years ago when the team worked a similar experiment with brains from pigs that died from a slaughterhouse. Four hours after the pig died, the team infused a solution similar to OrganEx, which they called BrainEx, and found that brain cells that should have died can be revived.

Zvonimir Vrselja, another member of the Yale team, said it made them question whether they could revive the whole body.

OrganEx solution contains nutrients, anti-inflammatory drugs, cell death inhibitors, nerve blockers – substances that decrease nerve cell activity and prevent any ability of the pig to wake up – and an artificial hemoglobin mixed with the blood of each animal.

When they handled the dead pigs, investigators took precautions to make sure the animals weren’t in pain. The pigs were anesthetized before being killed by cardiac arrest, and deep anesthesia continued throughout the experiment. In addition, the nerve blockers in the OrganEx solution prevent the nerves from working to ensure that the brain does not function. The researchers also chilled the animals to slow down the chemical reaction. The individual brain cells were still alive, but there was no sign of any organized global neural activity in the brain.

There was a startling discovery: Pigs treated with OrganEx were startled when the researchers injected an iodinated contrast medium to take pictures. Dr Latham emphasized that while the reason for the movement is not known, there is no indication of any brain involvement.

Yale has applied for a patent on this technology. The next step will be to see if the organs are functioning properly and can be successfully transplanted, Dr. Sestan said. 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 oneDr. Robert Porte, a transplant surgeon at the University of Groningen in the Netherlands, discussed the possibility of using this system to expand the source of organs available for transplantation.

In a phone interview, he explained that in the future, OrganEx could be used in cases where patients are not brain dead but have brain injuries to the point of being useless.

Dr. Porte said that, in most countries, there is a “no touch” policy for 5 minutes after the respirator is removed and before the transplant surgeons remove the organ. However, he says, “before you rush to the OR, a few more minutes will pass,” and by which time organs can be damaged beyond use.

And sometimes patients don’t die immediately when life support is stopped, but their heart beats too weakly for their organs to stay healthy.

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

As a result, 50-60% of patients die after life support is stopped, and the family who wants to donate their organs cannot be a donor.

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

The Other comments is by Brendan Parent, an attorney and ethicist, 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 are the “conundrums around life and death” that OrganEx raises.

Mr Parent said: “According to the accepted medical and legal definition of death, these pigs have died. However, he added, “an important question is: What function and what kind of function will change things?”

Would the pigs die if the team didn’t use the nerve blocker in their solution and their brains work again? That would create ethical issues if the aim was to preserve organs for transplantation and the pigs had regained some degree of consciousness in the process.

However, restoring brain function may be the goal if the patient has had a major stroke or is 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 the neuro-blocking drugs,” said Parent.

In his opinion, the method will eventually have to be tried on people who might benefit, like stroke or drowning victims. But that would require a lot of deliberation by ethologists, neuroscientists, and neuroscientists.

“How we get there will be an important question,” Mr. Parent said. “When will the data we have to support making this jump?”

Another issue is OrganEx’s impact on the definition of death.

If OrganEx continues to show that the period after a lack of blood and oxygen before which cells cannot recover is much longer than previously thought, then a change in the time it takes to determine that a person dead.

“It’s weird, but it’s no different from what we’ve been through in the development of ventilators,” Parent said.

“There are many people from another era who could have been called dead,” he said.

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