US scientists have used a new procedure to restore many biological functions in pigs that had been dead for more than an hour, raising profound questions about the boundary between life and death.
The project at Yale University extends a groundbreaking experiment that restored some brain functions to decapitated pigs three years ago. In the latest development, the team has restored blood circulation and cellular activity to the bodies of whole animals that were anaesthetised and then killed through an induced heart attack.
The researchers, who used about 100 pigs in the latest project, said the technique could eventually extend the health of human organs during surgery and expand availability of donor organs.
The procedure, called OrganEx, involved pumping a restorative fluid containing a blend of 13 compounds that promote cellular health and suppress inflammation, through the dead pigs. Biological activity resumed in many organs including the liver, kidneys, brain and heart, whose cells retained the ability to contract.
“We were also able to restore circulation throughout the body, which amazed us,” said Nenad Sestan, the project leader. Results were published in the journal Nature on Wednesday.
Sam Parnia, director of critical care and resuscitation research at New York University medical school, said the study was “truly remarkable and incredibly significant”.
“It demonstrates that after death, cells in mammalian organs including humans, such as the brain, do not die for many hours,” said Parnia, who was not involved in the research. He also pointed to the far-reaching implications of the study.
“This study demonstrates that our social convention regarding death, as an absolute black and white end, is not scientifically valid,” said Parnia. “By contrast, scientifically death is a biological process that remains treatable and reversible for hours after it has occurred.”
When the heart stops beating, the body enters a state of ischemia in which organs start to swell and blood vessels collapse. Yet tissues in the dead pigs appeared to be functional after OrganEx treatment — unlike those in control animals that received a more conventional procedure called Ecmo, pumping their own blood and fresh oxygen around the body.
“Under the microscope, it was difficult to tell the difference between a healthy organ and one which had been treated with OrganEx technology after death,” said Zvonimir Vrselja, another member of the Yale team.
As in the 2019 experiment with pigs’ heads, researchers found that cellular activity in some areas of the brain had been restored, although they detected no organised electrical activity that would indicate consciousness.
However, Sestan said his team of scientists was surprised to observe involuntary and spontaneous muscular movements in the head and neck areas of the treated animals, which remained deeply anaesthetised throughout the experiment. These movements indicated the preservation of some motor functions, he added.
The experiment was designed in consultation with the university’s animal care committee and external ethics advisers. One condition was that the OrganEx perfusion should stop after six hours. It means the scientists do not know how long the procedure might have maintained signs of life in the dead pigs if it had continued indefinitely.
The Yale researchers believe the first applications of OrganEx in people will be to preserve individual organs in good condition for transplantation rather than keeping whole human bodies alive.
“There are numerous potential applications of this exciting new technology,” said Stephen Latham, director of the Yale Interdisciplinary Center for Bioethics. “However, we need to maintain careful oversight of all future studies, particularly any that include perfusion of the brain.”
Sestan said the team was consulting its advisers over the next steps — likely to involve more experiments with pigs to evaluate more closely whether their organs functioned well enough after OrganEx treatment to be used in transplant operations.
“We are far away from a human use of this whole body kind of experiment,” said Latham. “There’s a lot more work to be done, a lot more precision needed, before we would launch anything in that direction.”
The project was funded by US National Institutes of Health and Schmidt Futures.
