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TThe pigs came directly from the slaughterhouse, where workers had sliced their jugular vein and carotid artery and then decapitated them. But from four hours after the animals' brains stabilized and for the next six hours, the brain became … well, a little less dead, University scientists reported Wednesday. Yale.
By attaching the brains to a specially constructed device and circulating artificial blood, the researchers claimed that they were able to restore certain molecular and cellular functions of the brain, including spontaneous electrical activity in the neurons and functions metabolic characteristics such as consumption. oxygen and glucose.
Although pork brains showed no organized electrical activity throughout the cortex associated with consciousness, sensory perception, pain, distress or other functions of the order Higher, the experience challenges a long-standing medical dogma and is likely to revive a heated debate on the subject. What is brain death, especially for the purpose of giving organs? Less controversial, the restoration system, called BrainEx, promises to give neuroscientists a better way to study brain wiring and function.
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Scientists not involved in the study, who had heard the principal investigator present his preliminary results at closed meetings in 2017 and 2018, have described it with almost astonished terms, calling him " incredible "," very impressive "and" extremely significant ". Yale's team "has shown that, at least at the cellular and molecular level, things are not so irreversible [after the brain is deprived of blood and oxygen] as we thought, said neurologist James Bernat of Dartmouth College. "I think it's remarkable: they were able to restore some of the brain activity a few hours after the death and cessation of the disease. [blood] circulation, which was supposed to cause irreversible damage and loss of function. "
Like all scientists aware of the study, Bernat quickly added that "there is a major difference between the restoration of cellular and molecular activity in the brain and the resuscitation of overall brain function , what they were not able to achieve ". Or as a neuroscientist at Yale Dr. Nenad Sestan, who led the study, told reporters at a teleconference: "This is not a living brain. It is a brain active on the cellular level.
Nevertheless, Andrea Beckel-Mitchener of the National Institute of Mental Health has described technology as a "breakthrough for brain research". The restoration of cell function "has never been done before" in a mammalian brain brain supposedly dead, she said. Keeping the cells alive and active, she added, the system will promise scientists to study the complex circuit connections "and the functions that are lost when the samples are preserved from another way". Neither isolated brain cells cultured in culture, nor slices of brain tissue post mortem for example, say much about the neural circuits and the activity that underlies the thought.
The further development of BrainEx may one day support "neuroresuscitation", reversing the damage caused by stroke and other brain damage. "If the system proves safe on a living person, there is a potential for improvement in the recovery of brain function," Bernat said.
Beyond any scientific or medical application, the work raises profound philosophical questions. In an essay accompanying the article, published in Nature, three bioethicists wrote that it "challenges long-standing assumptions about what makes an animal – or a human – alive." ".
For their experience, Sestan and his colleagues bought nearly 300 pork heads at a slaughterhouse near the New Haven Campus, Yale, for nearly 10 years while working on the BrainEx optimization. ex "means ex vivo, or" on the team. Eventually, the team connected 32 brains of pigs to the system – a blur of software, mixers, fluid holders, pumps, heaters, filters, and so on. for Rube Goldberg, whose function was to mimic pulsed blood flow using a special artificial filter. blood – via the carotid artery four hours after the killing of animals. They kept the brains connected for six hours and at normal temperatures, not cryogenic.
Other brains were connected to BrainEx but did not receive the infusion solution, or were not connected at all. In comparison, brains connected to BrainEx and infused showed "dramatic differences," said Sestan. Brain cells metabolized oxygen and glucose in the same way as living cells. Neurons have triggered electrical gusts carrying information, called action potentials, both spontaneously and in response to an electrical stimulus, as do living brains. The blood vessels have dilated in response to the drugs that cause this reaction in living brains. Glia, the brain's immune cells, caused a realistic inflammatory reaction when it was provoked. Mitochondria, which provide energy to cells, were intact inside neurons, as was myelin, the fatty sheath that insulates neurons so that they can conduct electrical signals.
Overall, many more cells remained alive, the circulatory system functioned, and the size, shape and disposition of neurons and other cells were normal compared to brains that did not receive BrainEx treatment.
In a scientific underestimation model, the authors write that the brains of large mammals have "an underestimated ability to restore microcirculation and the molecular and cellular activity after a prolonged post-mortem interval". In other words, in some cases, a brain death can be either. permanent or irreversible.
"We never imagined we would get to that point, … restaurant cells at this level" of functionality, said Sestan. Neurological dogma has long held that brain cells die irreversibly and minutes after the blood ceases to circulate, as do pigs. "But we were able to restore some cellular and molecular functions" after four hours of oxygen loss, he said. "We were really surprised."
Although he insisted that the lack of electrical activity on the brain scale meant that the pig brain had not regained consciousness and so could not feeling pain or distress, it was not won in advance. Scientists were sufficiently concerned about this possibility that they were ready to administer anesthesia to the brain or to cool it down drastically to stop such activity.
"It's the elephant in the room: the consciousness," said philosopher Jonathan Moreno of the University of Pennsylvania, who reviewed the document for Nature and heard Sestan describe his findings as "the most important thing in the world." last year at a meeting at the National Institutes of Health, whose BRAIN initiative was partially funded. the research. "Neuroscience is competing a lot to understand what people mean by conscience and what criteria should be used. Is [electrical activity in the dead pig brains] a small piece of consciousness? A small degree of consciousness?
To complicate the question of whether consciousness can be restored in a dead brain, BrainEx liquid contains a chemical that inhibits neuronal activity. Without this, could the brains of pigs have shown the type of brain electrical activity associated with consciousness? "They could have," said Moreno. "This must make you ask, what would be the moral status" of a brain once dead but (partly) "restored"?
Beyond the philosophical and ethical concerns, BrainEx could complicate the already charged debate on brain death and organ donation, experts said.
By questioning the hypothesis that the brains of large mammals would irretrievably lose their neuronal activity and consciousness within minutes of stopping blood flow, the results point to "the possibility that researchers will better recover a person's brain even after the heart and lungs have stopped working, "bioethicists Stuart Youngner and Insoo Hyun of Case Western Reserve University wrote in a commentary on the study. If the results continue, they "could exacerbate the tension between efforts to save the lives of individuals and those aimed at getting organs to give to others. As the science of brain resuscitation progresses, some efforts to save or restore people's brains might seem more and more reasonable – and some decisions to forgo such attempts in favor of the brain. Obtaining organs for transplantation might seem less and less. "
The significance of brain death is controversial enough for ethicists, transplant surgeons, other doctors and emergency responders to wonder whether to abandon efforts to save someone's life. but rather to preserve the organ donation. Most of the organs to be transplanted come from people who have been declared brain dead. But if BrainEx is improved and effective on human brains, people who have been declared brain dead may be eligible for brain resuscitation, not organ donation.
The study "further specifies that the brain is actually dead under certain circumstances," said Dr. Kathleen Fenton, a bioethicist and pediatric cardiologist surgeon in Maryland. "It should enlighten the discussion around brain death, [since it] shows that some loss of life and cellular functions that we all thought were irreversible do not seem irreversible. It's important. "
In another comment, Nita Farahany, an ethicist at Duke University, and two co-authors stated in a commentary: a phrase from the 1987 film "The Princess Bride" indicates that "there is a big difference between most dead and all the dead. Especially dead is slightly alive. "
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