Pig brains partially revived hours after death—what it means for people
Scientists have restored cellular function in 32 pig brains that had been dead for hours, opening up a new avenue in treating brain disease—and shaking our definition of brain death to its core. Announced on Wednesday in the journal Nature, researchers at the Yale University School of Medicine devised a system roughly analogous to a dialysis machine, called BrainEx, that restores circulation and oxygen flow to a dead brain.
The researchers did not kill any animals for the purposes of the experiment; they acquired pig heads from a food processing plant near New Haven, Connecticut, after the pigs had already been killed for their meat. And technically, the pig brains remained dead—by design, the treated brains did not show any signs of the organized electrical neural activity required for awareness or consciousness.
“Clinically defined, this is not a living brain,” says study coauthor Nenad Sestan, a neuroscientist at the Yale University School of Medicine.
The new system instead kept the brains in far better shape than brains left to decompose on their own, restoring functions such as the ability to take in glucose and oxygen for up to six hours at a time. Researchers say that the technique could give a major boost to studies of human health by providing a rich testbed for studying brain disorders and diseases.
“We're really excited about this as a platform that could help us better understand how to treat people who have had heart attacks and have lost normal blood flow to the brain,” adds Khara Ramos, director of the Neuroethics Program at the U.S. National Institute of Neurological Disorders and Stroke. “It really enhances our ability to study cells as they exist in connection with each other, in that three-dimensional, large, complicated way.”
Even so, the finding opens up considerable ethical questions, a conversation that the researchers themselves welcome.
“This is an extraordinary and very promising breakthrough for neuroscience. It immediately offers a much better model for studying the human brain, which is extraordinarily important, given the vast amount of human suffering from diseases of the mind [and] brain,” says Nita Farahany, a bioethicist at the Duke University School of Law who wrote a commentary about the study for Nature.
“It [also] challenges a lot of the fundamental assumptions that we had in neuroscience, like that once there is a loss of oxygen to the brain, it’s an irreversible march toward organismal death,” she adds. “That turns out not to be true—and because that’s not true, there's some pretty profound ethical and legal issues that are raised as a result.”
Defining death
Death is final, but the number of truly irreversible medical outcomes has shrunk over time. For millennia, people were considered dead when they stopped breathing and their hearts ceased to beat. But then modern medicine intervened. The invention of mechanical ventilators allowed failing bodies to be kept alive for longer, and decades of improvements to heart surgery and transplants mean that even a stopped heart might not necessarily be the end.
But the brain remains a finicky patient. Mammal brains such as ours are high-performance machines; they demand a constant stream of oxygen-rich blood to work to their fullest. If blood flow is cut off, we lose consciousness after just a few seconds. Within five minutes, the brain's stores of vital molecules such as glucose and ATP—the body's universal currency for chemical energy—run out.
The brain then enters a death spiral that, up to now, scientists considered irreversible: Nerve cells' delicate chemistries get thrown out of whack, a buildup of carbon dioxide makes the brain's blood more acidic, and leaks of a powerful neurotransmitter called glutamate quickly become toxic. Soon, enzymes that break down nerve tissue come online, and the brain's smaller structures and blood vessels rupture and break.
The more researchers understood this process, the more they incorporated it into the definition of death itself. In 1968, a committee of doctors assembled by Harvard University put forth a landmark definition of “irreversible coma,” what we now call “brain death”: a total lack of responsiveness, the inability to breathe on one's own, a total lack of reflexes, and no signs of large-scale electrical activity in the brain. Now, the American Academy of Neurology maintains a checklist that clinicians use to judge brain death in patients.
But there have been hints of greater brain resilience. Some parts of brain cells, such as the mitochondria that process chemical energy, still work up to 10 hours after death. In cats and macaques, researchers have successfully made brains recover after a full hour cut off from blood by carefully restoring circulation. And in humans, some medical case studies point to a brain that can bounce back. In 2007, researchers reported that a woman suffering from acute hypothermia—with a body temperature less than 65 degrees Fahrenheit—made a full neurological recovery.