Pig brains kept alive outside the body for hours after death

In a challenge to the idea that brain death is definitive, the researchers reinstated the disembodied brains of pigs four hours after the slaughter of the animals. Although the experiments did not restore consciousness, they raise questions about the ethics of the approach and, more fundamentally, about the very nature of death. Current legal and medical definitions of death protocols for resuscitation of patients and organ transplantation.

The details of the experiments on the pork brain are contained in a document1 published on April 17 in Nature. Researchers at Yale University in New Haven, Connecticut, connected the organs to a system that injected a blood substitute. This technique has restored some crucial functions, such as the ability of cells to produce energy and eliminate waste, and to preserve the internal structures of the brain.

"Most men have experienced death very simply," said Christof Koch, chairman 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 legally dead when brain activity stops or when the heart and lungs stop working. The brain requires a huge amount of blood, oxygen and energy, and it is badumed that spending only a few minutes without these vital support systems would cause irreversible damage.

Since the early twentieth century, scientists have conducted experiments to keep animals' brains alive as soon as the heart stops, cooling the brain and injecting blood or a substitute. But it is not yet known whether organs have worked well2. Other studies have shown that cells extracted from the brain long after death can perform normal activities, such as protein manufacture3. This prompted Yale's neuroscientist, Nenad Sestan, to marvel: could an entire brain be resuscitated hours after death?

Sestan decided to find out by using the severed head of 32 pigs slaughtered for meat in a slaughterhouse near his laboratory. His team removed each brain from his skull and placed it in a special chamber before providing the organ with a catheter. Four hours after the death, the researchers started injecting a warm preservation solution into the veins and arteries of the brain.

The system, which researchers call BrainEx, mimics blood flow by providing nutrients and oxygen to brain cells. The team's preservation solution also contained chemicals that prevent neurons from firing, protect them from damage, and prevent the electrical activity of the brain from resuming. Despite this, scientists monitored the electrical activity of the brain throughout the experiment and were willing to administer anesthetics if they saw signs that the organ could regain consciousness.

Against the watch

The researchers tested brain behavior during a six-hour period. They discovered that neurons and other brain cells had restarted normal metabolic functions, such as sugar consumption and carbon dioxide production, and that the brain's immune system seemed to work. The structures of the individual cells and sections of the brain were preserved – while the control brain cells, which did not receive the nutrient and oxygen rich solution, collapsed. And when scientists applied electricity to treated brain tissue samples, they discovered that individual neurons could still transmit a signal.

But the team has never seen coordinated electrical patterns throughout the brain, which would indicate sophisticated brain activity or even consciousness. The researchers say that restarting brain activity may require electrical shock or brain conservation in solution for a prolonged period of time to allow the cells to recover from damage when they are deprived of their ability to function. oxygen.

Sestan, whose team used his technique to keep pork brains alive until 36 hours, does not plan for the moment to attempt to restore electrical activity in an organ disembodied. Instead, his priority is knowing how long his team can maintain the metabolic and physiological functions of the brain outside the body. "It is conceivable that we simply avoid the inevitable, and the brain will not be able to recover," says Sestan. "We have just gone a few hundred meters, but can we really fly?"

The BrainEx system is far from ready for use in humans, he adds, particularly because it is difficult to use without first removing the brain from the skull.

Questions multiply

Nevertheless, the development of technologies with the potential to support sensitive and disembodied organs has broad ethical implications for the welfare of animals and humans. "There is not really a monitoring mechanism to worry about the possible ethical consequences of becoming aware of something that is not a living animal," says Stephen Latham, a bioethicist at Yale who worked with Sestan team. He says that this could be ethically justifiable in some cases – for example, if it allowed scientists to test drugs for degenerative brain diseases on organs rather than on humans.

It would probably be difficult to be aware of the brain outside the body, since the environment of the organ would be so different from its natural environment. "We could imagine that the brain is capable of consciousness," says George Mashour, a neuroscientist at the University of Michigan at Ann Arbor, who studies near-death experiences. "But it is very interesting to think 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, a specialist in emergency medicine at the Feinstein Institute for Medical Research in Manhbadet, NY, says many doctors badume that even a minute without oxygen can cause irreversible lesions. But experiments on pigs suggest that the brain could remain viable much longer than expected, even without outside support. "This document throws a hand grenade at the center of what people believe," says Becker. "We may have grossly underestimated the brain's ability to recover."

This could have practical and ethical consequences on the donation of organs. In some European countries, emergency responders who can not resuscitate a person after a heart attack sometimes use a system that preserves organs to transplant by pumping oxygenated blood into the body, but not into the brain. If a technology such as BrainEx becomes widely available, the possibility of expanding the resuscitation window could reduce the number of eligible organ donors, says Stuart Youngner, a bioethicist at Case Western Reserve University in Cleveland, USA. # 39; Ohio.

"There is a potential conflict between the interests of potential donors – who may not even be donors – and those who are waiting for organs," he adds.

Far from going

Meanwhile, scientists and governments face legal and ethical dilemmas related to the possibility of creating a bodyless conscious brain. "It's really a no-man's land," says Koch. "The law will probably have to evolve to keep pace."

Koch wants a broader ethical discussion before a researcher attempts to sensitize a disembodied brain. "It's a big step forward," he says. "And once we do it, it's impossible to reverse it."