The pigs had been lying dead in the lab for an hour – there was no blood circulating in their bodies, their hearts were still, and their brain waves were flat. Then a group of Yale University scientists injected a custom-made solution into the dead pigs’ bodies with a device similar to a heart-lung machine.
What happened next adds questions to what science considers the wall between life and death. Although the pigs weren’t conscious in any way, their cells that seemed dead came back to life. Their hearts began to beat as a solution, which scientists called OrganEx, and it spread to veins and arteries. The cells in their organs, including the heart, liver, kidney and brain, were working again, and the animals didn’t stiffen like normal pigs.
The other pigs, who had been dead for an hour, were treated with ECMO, a device that pumps blood into their bodies. They became stiff, their organs swollen and damaged, their blood vessels collapsed, and they had purple spots on their backs where blood pooled.
The group announced its findings Wednesday in the journal Nature.
The researchers say their goals are to one day increase the supply of human organs for transplantation by allowing doctors to obtain viable organs long after death. They say they hope their technology can also be used to prevent serious damage to hearts after a devastating heart attack or to the brain after a major stroke.
The findings are only a first step, said Stephen Latham, a bioethicist at Yale University who has worked closely with the group. He stressed that the technology is “a long way from being used in humans.”
The group, led by Dr. Nenad Sestan, professor of neurology and comparative medicine, genetics and psychiatry at Yale University School of Medicine, stunned its ability to revive cells.
“We didn’t know what to expect,” said Dr. David Andrejevic, also a neuroscientist at Yale University and one of the paper’s authors. “Everything we recovered has been amazing for us.”
Others unrelated to work were similarly surprised.
“It’s incredible, mind-blowing,” said Nita Farahani, a professor of law at Duke University who studies the ethical, legal and social implications of emerging technologies.
Dr. Farhani added that 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 can be reversed. Or not?”
The work began a few years ago when the team conducted a similar experiment on the brains of dead pigs from a slaughterhouse. Four hours after the pigs died, the group injected a solution similar to OrganEx they called BrainEx and saw that brain cells that should have been dead could be revived.
This prompted them to wonder if they could fully revive the body, said Dr. Zvonimir Vrsilia, another member of the Yale University team.
OrganEx lotion contains nutrients, anti-inflammatory drugs, drugs to prevent cell death, nerve blockers – substances that suppress the activity of nerve cells and prevent any possibility of pigs regaining consciousness – and synthetic hemoglobin mixed with each animal’s blood.
When they treated the dead pigs, the investigators took precautions to ensure that the animals were not harmed. Pigs were anesthetized before they were killed by stopping their hearts, and deep anesthesia was continued throughout the experiment. In addition, the nerve blockers in the OrganEx solution prevent nerves from being stimulated to ensure that the brain is not active. The researchers also cooled the animals to slow chemical reactions. Individual brain cells were alive, but there was no indication of any global regulated neural activity in the brain.
There was one startling discovery: pigs treated with OrganEx shook their heads when the researchers injected an iodine solution for imaging. Dr. Latham emphasized that while the cause of the movement was unknown, there was no indication of any brain involvement.
Yale applied for a patent on the technology. Dr Sestan said the next step would be to see if the organs were working properly and could be successfully transplanted. After some time, the researchers hope to test whether the method is able to repair damaged hearts or brains.
Nature asked two independent experts to write comments about the study. In one, Dr. Robert Porte, a transplant surgeon at the University of Groningen in the Netherlands, discussed the possibility of using the system to expand the range of organs available for transplantation.
In a phone interview, he explained that OrganEx might be used in the future in situations where patients are not brain-dead but have brain injury to the point where life support is futile.
Dr. Porte said that in most countries, there is a “no touch” policy for five minutes after the respirator is turned off and before surgeons remove the organs. But, he said, “before you rush into the operating room, extra minutes will pass,” by which time organs can be so damaged that they are unusable.
Sometimes patients don’t die right away when life support stops, but their hearts beat so weakly that their organs can’t keep them healthy.
“In most countries, transplant teams wait two hours” for patients to die, Dr. Porte said. Then he said, if the patient is not yet dead, they don’t try to get his organs back.
As a result, 50 to 60 percent of patients who died after life support was discontinued and whose families wanted to donate their organs could not be donors.
Dr. Porte said that if OrganEx could revive those organs, the effect would be “enormous” – a huge increase in the number of organs available for transplant.
Another comment was by Brendan Barnett, attorney, ethics expert and 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 were the “tricky questions about life and death” that OrganEx raises.
“By the accepted medical and legal definition of death, these pigs died,” said Mr. Barnett. But he added, “The crucial question is: What job and what kind of job would change things?”
Would the pigs remain dead if the group did not use the nerve blockers in their solution and their brains worked again? This would create ethical problems if the goal was to preserve organs for transplant and the pigs regained a certain degree of consciousness during the procedure.
But restoring brain function can be the goal if the patient has had a severe stroke or is a drowning victim.
“If we want to take 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,” said Mr. Barnett.
In his opinion, the method should eventually be tried on people who could benefit, such as stroke or drowning victims. But this will require a lot of deliberation by ethicists, neuroscientists, and neuroscientists.
“How we get there is going to be an important question,” Mr. Barnett said. “When does the data we have justify making that leap?
Another issue is the effects that OrganEx may have on the definition of death.
If OrganEx continues to show that the period of time after blood and oxygen deprivation before which cells are unable to recover is much longer than previously thought, there must be a change in when a person’s death is determined.
“It’s strange but not unlike what we went through with the development of the ventilator,” said Mr. Parent.
“There is a whole group of people who might have been described as dead in a different era,” he said.