The pigs whose brains were used in the study had been killed at a slaughterhouse for meat.Credit: Chaiwat Subprasom/Reuters

In a challenge to the idea that brain death is final, researchers have revived the disembodied brains of pigs four hours after the animals were slaughtered. Although the experiments stopped short of restoring consciousness, they raise questions about the ethics of the approach — and, more fundamentally, about the nature of death itself. The current legal and medical definitions of death guide protocols for resuscitating people and for transplanting organs.

Details of the pig-brain experiments appear in a paper1 published on 17 April in Nature. Researchers at Yale University in New Haven, Connecticut, hooked the organs to a system that pumped in a blood substitute. The technique restored some crucial functions, such as the ability of cells to produce energy and remove waste, and helped to maintain the brains’ internal structures.

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“For most of human history, death was very simple,” says Christof Koch, president and chief scientist of the Allen Institute for Brain Science in Seattle, Washington. ”Now, we have to question what is irreversible.”

In most countries, a person is considered to be legally dead when brain activity ceases or when the heart and lungs stop working. The brain requires an immense amount of blood, oxygen and energy, and going even a few minutes without these vital support systems is thought to cause irreversible damage.

Disembodied pig brains revived: Your questions answered

Since the early twentieth century, scientists have conducted experiments that keep animals’ brains alive from the moment the heart stops, by cooling the brains and pumping in blood or a substitute. But how well the organs functioned afterwards is unclear2. Other studies have shown that cells taken from brains long after death can perform normal activities, such as making proteins3. This made Yale neuroscientist Nenad Sestan wonder: could a whole brain be revived hours after death?

Sestan decided to find out — using severed heads from 32 pigs that had been killed for meat at a slaughterhouse near his lab. His team removed each brain from its skull and placed it into a special chamber before fitting the organ with a catheter. Four hours after death, the researchers began pumping a warm preservative solution into the brain’s veins and arteries.

The system, which the researchers call BrainEx, mimics blood flow by delivering nutrients and oxygen to brain cells. The preservative solution the team used also contained chemicals that stop neurons from firing, to protect them from damage and to prevent electrical brain activity from restarting. Despite this, the scientists monitored the brains’ electrical activity throughout the experiment and were prepared to administer anaesthetics if they saw signs that the organ might be regaining consciousness.

Time trial

The researchers tested how well the brains fared during a six-hour period. They found that neurons and other brain cells had restarted normal metabolic functions, such as consuming sugar and producing carbon dioxide, and that the brains’ immune systems seemed to be working. The structures of individual cells and sections of the brain were preserved — whereas cells in control brains, which did not receive the nutrient- and oxygen-rich solution, collapsed. And when the scientists applied electricity to tissue samples from the treated brains, they found that individual neurons could still carry a signal.

Pig experiment challenges assumptions around brain damage in people

But the team never saw coordinated electrical patterns across the entire brain, which would indicate sophisticated brain activity or even consciousness. The researchers say that restarting brain activity might require an electrical shock, or preserving the brain in solution for extended periods to allow cells to recover from any damage they sustained while deprived of oxygen.

Sestan, whose team has used its technique to keep pig brains alive for up to 36 hours, has no immediate plans to try to restore electrical activity in a disembodied organ. Instead, his priority is to find out how long his team can maintain a brain’s metabolic and physiological functions outside the body. “It is conceivable we are just preventing the inevitable, and the brain won’t be able to recover,” Sestan says. “We just flew a few hundred metres, but can we really fly?”

The BrainEx system is far from ready for use in people, he adds, not least because it is difficult to use without first removing the brain from the skull.

Questions multiply

Nevertheless, the development of technology with the potential to support sentient, disembodied organs has broad ethical implications for the welfare of animals and people. “There isn’t really an oversight mechanism in place for worrying about the possible ethical consequences of creating consciousness in something that isn’t a living animal,” says Stephen Latham, a bioethicist at Yale who worked with Sestan’s team. He says that doing so might be ethically justifiable in some cases — for instance, if it enable scientists to test drugs for degenerative brain diseases on the organs, rather than people.

G﻿auging awareness in a brain outside a body would probably be difficult, given that the organ’s surroundings would differ so radically from its natural environment. “We could imagine that brain could be capable of consciousness,” says George Mashour, a neuroscientist at the University of Michigan in Ann Arbor who studies near-death experiences. “But it’s very interesting to think about what kind of consciousness, in the absence of organs and peripheral stimulation.”

T﻿he latest study also raises questions about whether brain damage and death are permanent. Lance Becker, an emergency-medicine specialist at the Feinstein Institute for Medical Research in Manhasset, New York, says that many physicians assume that even minutes without oxygen can cause irreversible harm. But the pig experiments suggest that the brain might stay viable for much longer than previously thought, even without outside support. “This paper throws a hand grenade into the middle of what the common beliefs are,” says Becker. “We may have vastly underestimated the ability of the brain to recover.”

Part-revived pig brains raise slew of ethical quandaries

That could have practical and ethical consequences for organ donation. In some European countries, emergency responders who cannot resuscitate a person after a heart attack will sometimes use a system that preserves organs for transplantation by pumping oxygenated blood through the body — but not the brain. If a technology such as BrainEx becomes widely available, the ability to extend the window for resuscitation could shrink the pool of eligible organ donors, says Stuart Youngner, a bioethicist at Case Western Reserve University in Cleveland, Ohio.

“There’s a potential conflict here between the interests of potential donors — who might not even be donors — and people who are waiting for organs,” he adds.

Far to go

In the meantime, scientists and governments are left to confront the legal and ethical quandaries related to the possibility of creating a conscious brain without a body. “This really is a no-man’s land,” says Koch. “The law will probably have to evolve to keep up.”

Koch wants a broader ethical discussion to take place before any researcher tries to induce awareness in a disembodied brain. “It is a big, big step,” he says. “And once we do it, it’s impossible to reverse it.”

Read more: N﻿ature reporter Sara Reardon answers reader questions about the pig study.