While the scientists warn that the findings are not clinically evident, they also say that the fact that the definition of death should be redefined from the research has emerged. Pigs that received a blood solution from a system called OrganEx showed activity in their hearts, livers and kidneys after death.

Pig Organs Reanimated in Dead Animals

While the scientists warn that the findings are not clinically evident, they also say the fact that the definition of death should be redefined from the research has emerged.

The researchers revived circulation and cellular activity in the pigs' vital organs, such as the heart and brain, in an hour after the animals died. The research challenges the notion that cardiac death, which occurs when circulation and oxygenation ceases, is irreversible and this raises ethical questions about the definition of death as a result. The study questions the idea that brain death is final, following 2019 experiments in which the same scientists regenerated detached brains of pigs four hours after the animals died.

Nita Farahany, a neuroethicist at Duke University in Durham, North Carolina, says the latest experiments are "stunning." She says that although this study is preliminary, it suggests that some of the perceived limitations of the human body may be overcome over time.

In the study, published August 3, 2022 in Nature, researchers connected pigs that had been dead for an hour to a system called OrganEx, which pumps blood substitutes into the animals' bodies. Containing the blood of animals and 13 compounds such as anticoagulants (blood thinners), the solution slowed the decomposition of the bodies and quickly restored some organ functions, such as heart contraction and activity in the liver and kidneys. Although OrganEx helps preserve the integrity of some brain tissues, the researchers did not observe any coordinated brain activity that would indicate that the animals had regained any consciousness or sensitivity.

As with the 2019 article, the study is likely to rekindle a debate about the definition of death and the ethics of postmortem organ donation. Medical authorities warn that these results do not indicate some form of resuscitation of pigs after death, particularly in the absence of electrical activity in the brain. "We made the cells do something they couldn't do," says team member Zvonimir Vrselja, a neuroscientist at Yale University in New Haven, Connecticut, when the animals died. "We're not saying it's clinically relevant, but studies are moving in the right direction."

Circulation restarts

Nenad Sestan, a Yale neuroscientist and member of the team, predicted that these experiments could work in light of the 2019 pig-brain study, as the brain is the most sensitive organ to oxygen deprivation. “If you can perform one function in a dead pig brain, you can do it in other organs,” he says.

To find this out, he and his co-authors modified the BrainEx solution and the technique used for this study. “BrainEx was specifically designed for a particular organ, but with OrganEx we needed to find a common denominator that worked for all organs,” Vrselja says. In the OrganEx solution, the researchers included compounds that would suppress blood clotting and the immune system that is more active elsewhere in the body than the brain.

The images on the left show liver (upper panel) and kidney (lower panel) cells from control pigs; the images on the right show cells from OrganEx-treated pigs that have restored some tissue integrity and certain cellular functions. Photo : David Andrijevic, Zvonimir Vrselja, Taras Lysyy, Shupei Zhang; Sestan Laboratory; Yale School of Medicine

Six hours later, the researchers noticed that the pigs who received the OrganEx solution restarted circulation much more effectively than those who received ECMO (extracorporeal life support) or did not receive the treatment. Oxygen had begun to flow to tissues throughout the organs of the OrganEx animals, and the heart scan detected some electrical activity and contraction. However, team member David Andrijevic, a neuroscientist at Yale, says the heart isn't fully working again, and it's unclear what exactly it does in these animals.

The researchers also noticed that the livers of OrganEx pigs produced much more of a protein called albumin than the livers of pigs in other groups. And cells in each of the OrganEx pigs' vital organs were much more responsive to glucose than animals in the other groups, suggesting that the treatment kickstarted the metabolism.

The findings are striking, Vrselja says, considering how quickly decomposition begins after death. “A few minutes after the heart stops, the body is deprived of oxygen and enzymes begin to digest the cell membranes, causing the organs to rapidly lose their structural integrity.”

The researchers also found that more genes responsible for cellular function and repair were active in all major organs in the OrganEx group compared to the ECMO or no treatment groups.

Involuntary movements

Interestingly, only OrganEx pigs began to involuntarily shake their heads, necks, and trunks after the treatment received an injection of a contrast dye that helped scientists visualize the animals' brains. The researchers did not have a good explanation for the movements, noting that impulses are unlikely to arise in the brain given the lack of electrical activity. They say the movements may have originated in the spinal cord, which can control some motor functions independently of the brain.

If the findings of cellular restoration can be replicated in animals and eventually humans, the effects on human lifespan could be as "profound" as the advent of CPR (heart massage) and ventilators (cryogenic respiration equipment), Farahany says. This is because the technique could one day be used to preserve organs for an undersupplied organ transplant or even resuscitation.

ECMO is currently used to preserve the organs of some dead people for donation or to try to resurrect people who have had a heart attack. For these purposes, physicians often need to begin ECMO soon after a heart attack or death — and success rates can be low depending on the severity of the injury, says Sam Shemie, MD, a critical care physician at McGill University Health Center in Montreal, Canada.

Given the difference in how pigs' organs work with OrganEx compared to ECMO, “This is a potential "landmark" study that could significantly increase the number of organs that can be saved for transplant," says transplant surgeon Gabriel Oniscu. Edinburgh Royal Hospital, UK.

Shemie says that before that happens, further research to assess the viability of salvaged organs will be crucial.

Ethical challenges

Ethical challenges arise with these potential consequences, especially if this technique could restore brain activity one day after death, Farahany says.

The researchers note that electrical activity in the pigs' brains may not exist because the pumped solution is at 28 ºC (colder than normal body temperature) or because it contains anesthetic compounds and neuronal blockers that can suppress such signals. Farahany says it will be important for future researchers to test for any restoration of brain activity, especially in light of the neck concussions observed during the experiment.

Arthur Caplan, a bioethicist at New York University, says the study also emphasizes that death is a process, not a moment, making it difficult to find a uniform way to declare a person dead. This means that as medicine continues to advance, the legal definition of death will continue to adapt to these developments, he adds. “People tend to focus on brain death, but there isn't much consensus on when cardiac death occurs,” he says. "This article brings important clarity to this issue."

Levent Aslan

Quoted from Nature