A Question of Life and Death: Yale Scientists Bring Pig Organs Back to Life

Research scientists from Yale University have found a way to restore organ and cellular function in pigs an hour after death. If replicated in humans, this technology could prolong organ health during major surgeries and improve the availability of donor organs.

Shortly after death, the heart stops beating and blood flow is cut off. Deprived of oxygen and other crucial nutrients, cells and tissues in the body undergo a complex chain of biochemical reactions, causing organs to malfunction, and ultimately resulting in their slow deterioration. 

However, using a novel perfusion device to deliver an experimental but cell-protective fluid, Yale scientists have been able to restore important cellular functions to many different pig organs, even when they intervened an hour after death. 

The data, published last week in Nature, showed that after six hours of treatment, cellular activity return to the liver, heart and kidneys. The heart, in particular, displayed signs of electrical activity and was able to contract, effectively restoring blood circulation.

“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,” Zvonimir Vrselja, a researcher involved in the study, said in a statement. Vrselja, the Harvey and Kate Cushing Professor of Neuroscience at Yale and the study’s senior author, worked under Nenad Sestan.

OrganEx is the perfusion device that the team developed to deliver cytoprotective fluid. Similar to a heart-lung machine used during bypass procedures, OrganEx was used to pump the experimental fluid into anesthetized pigs in whom cardiac arrest had been induced. The solution itself was formulated to contain factors and compounds that suppress systemic inflammation and promote cellular health. 

The technology for OrganEx was first established in 2019, when Sestan’s lab used a perfusion-based system, which they dubbed BrainEx at the time, to restore brain activity in pigs that had already been killed for their meat. The basic idea is the same: to restore and support its function, BrainEx pumped a hemoglobin-based, cell-protective, and non-coagulative solution directly into the pigs’ brains, which had been removed from the skull and placed in a special chamber.

They were successful then, too. BrainEx saw the return of brain cellular function in 32 pigs, an effect that lasted for up to six hours after treatment.

“If we were able to restore certain cellular functions in the dead brain, an organ known to be most susceptible to ischemia, we hypothesized that something similar could also be achieved in other vital transplantable organs,” Sestan said.

Aside from restoring blood flow and organ function, the OrganEx approach also induced involuntary muscle movements in the pigs’ head and neck area, which the researchers took as a sign that their intervention could also restore motor function. 

Still, the researchers are quick to point out that many more studies are needed before OrganEx and BrainEx hit the clinic. Not least of these are those that look at the ethical ramifications of these technologies, especially as they cross over into human studies.

On one hand, OrganEx and BrainEx could vastly expand the pool of viable organs up for transplantation, leading to thousands more lives saved yearly. Delaying organ deterioration could also yield unique medical insights regarding the underlying cause of diseases, in turn paving the way for better, more effective medicines.

On the other hand, however, such technologies pose a serious challenge, not only to some deeply ingrained cultural beliefs, but also to laws. In many countries, after all, death is defined as the point when the brain, heart or lungs cease to work. This in itself is already a shaky premise, as medical interventions that can prolong life beyond brain death already exist. And OrganEx, BrainEx and other similar advancements could force governments to reassess the legal definition of death altogether.