Scientists Restore Some Function In The Brains Of Dead Pigs

Enlarge this image toggle caption Stefano G. Daniele and Zvonimir Vrselja, Sestan Laboratory, Yale School of Medicine Stefano G. Daniele and Zvonimir Vrselja, Sestan Laboratory, Yale School of Medicine

The brains of dead pigs have been somewhat revived by scientists hours after the animals were killed in a slaughterhouse.

The Yale University research team is careful to say that none of the brains regained the kind of organized electrical activity associated with consciousness or awareness. Still, the experiment described Wednesday in the journal Nature showed that a surprising amount of cellular function was either preserved or restored.

The implications of this study have staggered ethicists, as they contemplate how this research should move forward and how it fits into the current understanding of what separates the living from the dead.

"It was mind-blowing," says Nita Farahany, who studies the ethics of emerging technologies at Duke Law School. "My initial reaction was pretty shocked. It's a groundbreaking discovery, but it also really fundamentally changes a lot of what the existing beliefs are in neuroscience about the irreversible loss of brain function once there is deprivation of oxygen to the brain."

The brain is extremely sensitive to a lack of oxygen and shuts down quickly. But researchers have long known that viable cells can be removed from post-mortem brains hours after death, says Nenad Sestan, a neuroscientist at the Yale School of Medicine in New Haven, Conn.

Such cells can be studied in a lab dish, Sestan says, "but the problem is, once you do that, you are losing the 3D organization of the brain."

He and some colleagues wondered whether it might be possible to study brain cells while leaving them in an intact organ. Doing so meant somehow supplying them with oxygen, nutrients and various other cell-protective chemicals.

The scientists have spent the past six years developing a technique to do that, testing their methods on around 300 pig heads they obtained from a local pork processing center.

"This really was a shot-in-the-dark project," says team member Stefano Daniele. "We had no preconceived notion of whether or not this could work."

After deciding on the final version of their technology, which they call BrainEx, they did a detailed study using 32 pig heads. Daniele says that while at the slaughterhouse, he and fellow researcher Zvonimir Vrselja flushed the brains to clear out residual blood and to cool down the tissue.

Back at the lab, they removed the brains from the pigs' heads and placed the isolated brains in an experimental chamber. The researchers hooked key blood vessels up to a device that pumped in a specially formulated chemical cocktail for six hours, starting about four hours after the pigs had been killed.

These brains ended up looking dramatically different from pig brains that were left alone to deteriorate. "We found that tissue and cellular structure is preserved and cell death is reduced. In addition, some molecular and cellular functions were restored," Sestan says. "This is not a living brain, but it is a cellularly active brain."

The researchers' approach offers a new way to study brain diseases or injuries in the lab and to explore the basic biology of the brain. "We could actually answer questions that we can't now," Vrselja says.

"This is a real breakthrough for brain research. It's a new tool that bridges the gap between basic neuroscience and clinical research," agrees Andrea Beckel-Mitchener of the National Institute of Mental Health who works with the BRAIN Initiative. The BRAIN Initiative, which started in 2013 to accelerate neuroscience research, provided funding for the work.

The researchers emphasize that the goal was definitely not to restore consciousness in these pig brains. "It was something that the researchers were actively worried about," says Stephen Latham, a Yale bioethicist who worked with the team.

The scientists constantly monitored the pig brains' electrical activity, Latham says. If they had seen any evidence that signals associated with consciousness had emerged, they would have used anesthesia and cooling to shut that down immediately.

"And the reason is that they didn't want to do an experiment that raises the ethical questions that would be raised if consciousness were being evoked in this brain," Latham says, "without first getting some kind of serious ethical guidance."

The special solution pumped into the brains included the anti-seizure drug lamotrigine, which is known to block or dampen neuronal activity. That's because "the researchers thought that brain cells might be better preserved and their function might be better restored if they were not active," Latham says.

But tests done on single cells taken from the pig brains, which involved washing off the solution, showed that individual cells were capable of electrochemical responses. So it's unclear whether the team would have seen global electrical activity linked to consciousness in the pig brains if the neuronal-activity blocker had been left out of the treatment or if the blocker had been removed after cells had partly revived.

"That's a very important question, and one that we have discussed at length," Daniele says. "We cannot speak with any scientific certainty to that point since we did not run those experiments."

The potential ethical questions raised by this research range from how to protect animal welfare to how it might affect organ donation from people declared brain-dead.

"The science is so new that we all need to work together to think proactively about its ethical implications so that we can responsibly shape how this science moves forward," says Khara Ramos, director of the neuroethics program at the National Institute of Neurological Disorders and Stroke.

A few years ago, the Yale researchers consulted with a neuroethics working group convened by the National Institutes of Health's BRAIN Initiative. That's how Farahany learned of the research. She says these results need to be replicated in other labs to see whether they hold up.

But if they do, the findings challenge a lot of assumptions that underlie legal and ethical controls on experiments.

"If it's a dead animal, it's not subject to any research protections because you wouldn't expect that it would suffer from any pain or distress or need to be thought about in terms of humane care," Farahany says. But if that animal's brain can be even partially revived, she asks, then "what do we need to do immediately, today, in order to ensure that there's adequate protections in place for animal research subjects?"

What's more, she adds, "immediately people are going to recognize the potential of this research. If, in fact, it is possible to restore cellular activity to brain tissue that we thought was irreversibly lost in the past, of course people are going to want to apply this eventually in humans."

While there are protections in place for human research subjects, that's not so much the case for dead human tissue, says Christine Grady, chief of the department of bioethics at the NIH Clinical Center.

"Once a human dies and their tissue is in a laboratory, there are many fewer restrictions on what can be done," Grady says. "It is interesting to think about this issue in light of this experiment."

In a commentary that accompanied the research paper in Nature, Farahany and her colleagues Henry Greely and Charles Giattino say the work reminds them of a line from the 1987 movie The Princess Bride: "There's a big difference between mostly dead and all dead. Mostly dead is slightly alive."

Research like this could complicate the effort to secure organs for transplant from people who have been declared brain-dead, according to another commentary written by Case Western Reserve University bioethicists Stuart Youngner and Insoo Hyun.

If people who are declared brain-dead could become candidates for attempts at brain resuscitation, they write, "it could become harder for physicians or family members to be convinced that further medical intervention is futile."</s>Scientists restored some activity within the brains of pigs that had been slaughtered hours before, raising hopes for some medical advances and questions about the definition of death.

The brains could not think or sense anything, researchers stressed. By medical standards “this is not a living brain,” said Nenad Sestan of the Yale School of Medicine, one of the researchers reporting the results Wednesday in the journal Nature.

But the work revealed a surprising degree of resilience among cells within a brain that has lost its supply of blood and oxygen, he said.

“Cell death in the brain occurs across a longer time window than we previously thought,” Sestan said.

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Such research might lead to new therapies for stroke and other conditions, as well as provide a new way to study the brain and how drugs work in it, researchers said. They said they had no current plans to try their technique on human brains.

The study was financed mostly by the National Institutes of Health. The 32 brains came from pigs killed for food at a local slaughterhouse. Scientists put the brains into an apparatus in their lab. Four hours after the animals died, scientists began pumping a specially designed blood substitute through the organs.

The brains showed no large-scale electrical activity that would indicate awareness. Restoring consciousness was not a goal of the study, which was aimed instead at exploring whether particular functions might be restored long after death.</s>A bizarre Frankenstein-style experiment has breathed life into the brains of pigs four hours after death.

Scientists in the US restored circulation and cellular activity in 32 pig brains obtained from a meat-packing plant.

While there was no evidence of re-awakening awareness or consciousness, the re-vitalised brains were said to be “cellularly active”.



The study has huge implications that challenge long-held assumptions about the finality of death, and opens up a new frontier in brain research.

Lead scientist Professor Nenad Sestan, from Yale University, said: “The intact brain of a large mammal retains a previously under-appreciated capacity for restoration of circulation and certain molecular and cellular activities multiple hours after circulatory arrest.”

Cellular brain death is usually considered to be swift and irreversible.

Once the supply of oxygen and blood are cut off, the brain’s electrical activity and signs of awareness vanish within seconds.

A cascade of destruction then occurs leading to widespread degeneration from which there is no turning back.

However Professor Sestan and his team noticed that small brain tissue samples routinely showed signs of cellular life returning, even when harvested hours after death.

To investigate further, they turned their attention to whole, intact brains from pigs processed for food production.

In a ground-breaking experiment, a specially designed “chemical blood” preservative was circulated through the brains of dead animals that had been slaughtered four hours earlier.

The solution, warmed to normal body temperature, was perfused through the brains’ blood vessels for six hours.

During this time the scientists observed a reduction in cell death and the restored functionality of certain nerve, blood vessel and glial cells.

Glial cells are important brain “support cells” that hold neurons in place, feed them with nutrients and oxygen, provide insulation, and clean up the carcasses of dead cells.

The revived activity even included some synaptic function, the transmission of signals between neurons.

Details of the study are published in the latest issue of Nature journal.

Co-author Dr Zvonimir Vrselja, also from Yale, said: “At no point did we observe the kind of organised electrical activity associated with perception, awareness, or consciousness.

“Clinically defined, this is not a living brain, but it is a cellularly active brain.”

Lessons learned from the study could in future help doctors find ways to salvage brain function in stroke patients, or test the effectiveness of treatments designed to aid cellular recovery after injury, say the scientists.

The “BrainEx” system developed at Yale could also provide a powerful research tool.

Andrea Beckel-Mitchener, from the US National Institute of of Mental Health, which co-funded the research, said: “This line of research holds hope for advancing understanding and treatment of brain disorders and could lead to a whole new way of studying the post-mortem human brain.”

Any future studies involving human tissue or the possible revival of global electrical activity in “dead” animal brains would have to undergo strict ethical supervision, the team stressed.

However it was unclear that the technique would work in a recently deceased human brain.

The chemical solution lacked many components found naturally in human blood, such as immune system cells.

Dr Stephen Latham, director of Yale University’s Interdisciplinary Center for Bioethics, said: “Restoration of consciousness was never a goal of this research.

“The researchers were prepared to intervene with the use of anaesthetics and temperature-reduction to stop organised global electrical activity if it were to emerge.

“Everyone agreed in advance that experiments involving revived global activity couldn’t go forward without clear ethical standards and institutional oversight mechanisms.”

In Mary Shelley’s famous gothic novel, Dr Victor Frankenstein instils life into a monster created from dead body parts obtained from grave yards and butchers.

British expert Professor Derek Hill, from University College London, said: “This research raises some fascinating questions. Firstly, was this somehow a chance finding, or can it be reliably replicated?

“Secondly, could brains maintained by BrainEx help scientists discover new treatments for brain diseases like Alzheimer’s and Parkinson’s disease, which are proving really hard to treat?

“And thirdly, what are the ethical implications for the way we treat animals after slaughter, and humans after accidents?

“This ingenious experimental work provides challenges and opportunities both to brain scientists and for science policy makers.”</s>The pigs came straight from the slaughterhouse, where workers had severed their jugular vein and carotid artery and then decapitated them. But starting four hours after the animals’ brains had flat-lined and for the next six hours, the brains became … well, a little less dead, scientists at Yale University reported on Wednesday.

By attaching the brains to a specially constructed device and running souped-up artificial blood through them, the researchers said they were able to restore some of the brains’ molecular and cellular functions, including spontaneous electrical activity in neurons and such signature metabolic functions as consuming oxygen and glucose.

Although the pig brains showed none of the organized, cortex-wide electrical activity associated with consciousness, sensory perception, pain, distress, or other higher-order functions, the experiment challenges long-held medical dogma and is likely to reignite an impassioned debate about what constitutes brain death, especially for the purpose of organ donation. Less controversially, the restoration system, called BrainEx, promises to give neuroscientists a better way to study brain wiring and function.

Scientists not involved in the study, who had heard the lead researcher present preliminary results at closed-door meetings in 2017 and 2018, described it in almost awestruck terms, calling it “incredible,” “very impressive,” and “extremely significant.”

The Yale team “showed that, at least at the cellular and molecular level, things are not as irreversible [after the brain is deprived of blood and oxygen] as we thought,” said neurologist Dr. James Bernat of Dartmouth College. “I think it’s remarkable: They were able to restore some brain activity hours after death and the cessation of [blood] circulation, which was previously thought to cause irreversible damage and loss of function.”

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Like every scientist familiar with the study, Bernat quickly added that “there is a major difference between the restoration of cellular and molecular activity in a brain and the resuscitation of overall brain function, which they were not able to achieve.” Or as Yale neuroscientist Dr. Nenad Sestan, who led the study, told reporters on a conference call, “This is not a living brain. This is a cellularly active brain.”

Still, Andrea Beckel-Mitchener of the National Institute of Mental Health called the technology “a real breakthrough for brain research.” Restoring any cell function “has never been done before” in a large, supposedly dead, mammalian brain, she said.

By keeping cells alive and working, she added, the system promises to let scientists study complex circuit connections “and functions that are lost when specimens are preserved in other ways.” Neither isolated brain cells grown in culture nor slices of post-mortem brain tissue reveal much about the neural circuitry and activity that underlies thinking, for instance.

Further development of BrainEx might one day support “neuroresuscitation,” reversing the damage cause by strokes and other brain injuries. “If the system is found to be safe in a living person, there is the potential for improvements in the recovery of brain function,” Bernat said.

Beyond any eventual scientific or medical applications, however, the work raises profound philosophical questions. In an essay accompanying the paper, published in Nature, three bioethicists wrote that it “throws into question long-standing assumptions about what makes an animal — or a human — alive.”

For their experiment, Sestan and his colleagues obtained some 300 pig heads from an abattoir near Yale’s New Haven, Conn., campus, over nearly 10 years as they worked to optimize BrainEx — the “ex” stands for ex vivo, or “out of the living.” Eventually the team connected 32 pig brains to the system — a Rube Goldberg-esque blur of software, blenders, fluid holders, pumps, heaters, filters, and more, whose function was to mimic pulsating blood flow using a special artificial blood — via the carotid artery four hours after the animals had been killed. They kept the brains connected for six hours and at normal temperatures, not cryogenic ones.

Other brains were hooked up to BrainEx but did not get the perfusion solution, or were not hooked up at all. By comparison, the brains connected to BrainEx and perfused showed “dramatic differences,” Sestan said. Brain cells metabolized oxygen and glucose much like living cells. Neurons fired information-carrying electrical bursts called action potentials both spontaneously and in response to an electrical stimulus, as those in living brains do. Blood vessels dilated in response to drugs that cause that response in living brains. Glia, the brain’s immune cells, revved up a lifelike inflammatory response when provoked. Mitochondria, which supply energy to cells, were intact inside neurons, as was myelin, the fatty sheath that provides insulation to neurons so they can conduct electrical signals.

Overall, many more cells remained alive, the circulatory system worked, and the size, shape, and arrangement of neurons and other cells looked normal compared to brains that didn’t get the BrainEx treatment.

In a model of scientific understatement, the authors write that large mammalian brains have “an underappreciated capacity for restoration of microcirculation and molecular and cellular activity after a prolonged post-mortem interval.” In other words, in some cases a brain’s death may be neither permanent nor irreversible.

“We never imagined we would get to this point, … restoring cells to this level” of functionality, Sestan said. Neurological dogma has long held that brain cells die irreversibly and within minutes after blood stops circulating, as the pigs’ did. “But we were able to restore some cellular and molecular function” after four hours of oxygen loss, he said. “We were really surprised.”

Although he was emphatic that the absence of brain-wide electrical activity meant the pig brains had not regained awareness and therefore could not feel pain or distress, that was not a foregone conclusion. The scientists were concerned enough about that possibility that they were prepared to administer anesthesia to the brains, or drastically cool them, to shut off any such activity.

“That’s the elephant in the room: consciousness,” said philosopher Jonathan Moreno of the University of Pennsylvania, who reviewed the paper for Nature and heard Sestan describe his findings last year at a meeting at the National Institutes of Health, whose BRAIN Initiative partly funded the research. “There is a huge fight in neuroscience about what people mean by consciousness and what criteria should be used. Is this [electrical activity in the dead pig brains] a little piece of consciousness? A small degree of consciousness?”

Complicating the question of whether consciousness can be restored to a dead brain is that the BrainEx fluid included a chemical that suppresses neuronal activity. Without that, might the pig brains have shown the sort of brain-wide electrical activity associated with consciousness? “They might have,” Moreno said. “That has to make you ask, what would be the moral status” of a once-dead but (partly) “restored” brain?

Beyond raising such philosophical and ethical concerns, BrainEx could complicate the already-fraught debate over brain death and organ donation, experts said.

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By challenging the assumption that large mammalian brains irretrievably lose neural activity and consciousness within minutes of when blood flow stops, the findings raise “the possibility that researchers could get better at salvaging a person’s brain even after the heart and lungs stop working,” bioethicists Stuart Youngner and Insoo Hyun of Case Western Reserve University wrote in a commentary on the study. If the results hold up, they “could exacerbate tensions between efforts to save the lives of individuals and attempts to obtain organs to donate to others. As the science of brain resuscitation progresses, some efforts to save or restore people’s brains might seem increasingly reasonable — and some decisions to forego such attempts in favor of procuring organs for transplantation might seem less so.”

The meaning of brain death is sufficiently controversial that ethicists, transplant surgeons, other physicians, and emergency responders wrestle with when to abandon efforts to save someone’s life and instead try to save their organs for donation. Most organs for transplant come from people who are declared brain dead. But if BrainEx is improved and shown to work on human brains, people who are declared brain dead could qualify for brain resuscitation, not organ donation.

Asked if the United Network for Organ Sharing, the private group that manages organ donations in the U.S., had any comment on the study, a spokeswoman said, “We do not. This is way removed from organ donation.”

Experts disagreed. The study “makes it even less clear that the brain is actually dead under certain circumstances,” said Dr. Kathleen Fenton, a bioethicist and pediatric heart surgeon in Maryland. “It should inform the discussion surrounding brain death, [since it] shows that some cellular life and function loss that we have all thought was irreversible appears to not be irreversible. That’s important.”

Or as Duke University ethicist Nita Farahany and two co-authors said in another commentary, a line from the 1987 film “The Princess Bride” notes that “there’s a big difference between mostly dead and all dead. Mostly dead is slightly alive.”

This article is reproduced with permission from STAT. It was first published on April 17, 2019. Find the original story here.</s>Yale University scientists have succeeded in restoring basic cellular activity in pigs’ brains hours after their deaths in a finding that may one day lead to advances in treating human stroke and brain injuries, researchers reported Wednesday.

The scientists emphasized that their work did not even come close to reawakening consciousness in the disembodied pig brains. In fact the experiment was specifically designed to avoid such an outcome, however improbable.

Still, the study raises a host of bioethical issues, including questions about the very definition of brain death and potential consequences for protocols related to organ donation.

The research grew out of efforts to enhance the study of brain development, disorders and evolution. The main practical application is the prospect of allowing scientists to analyze whole brain specimens of large mammals in three dimensions, rather than through studies confined to small tissue samples, Yale said.

The study, backed by the National Institutes of Health, offers no immediate clinical breakthrough for humans, according to the authors.

Results of the experiment, to be published Thursday in the journal Nature, run contrary to long-accepted principles of brain death, which hold that vital cellular activity ceases irreversibly seconds or minutes after oxygen and blood flow are cut off.

The limited rejuvenation of circulatory function and cellular metabolism in pig brains, which were harvested from animals slaughtered at a meat-packing plant, was achieved four hours after death by infusing the brains with a special chemical solution designed to preserve the tissue.

“The intact brain of a large mammal retains a previously underappreciated capacity for restoration of circulation and certain molecular and cellular activities multiple hours after circulatory arrest,” lead researcher Nenad Sestan said in a Yale press release issued ahead of the study.

It was in the lab run by Sestan, a Yale professor of neuroscience, comparative medicine, genetics and psychiatry, that researchers developed the so-called BrainEx system used to pump artificial nutrients into the pig brains’ vascular network.

Scientists stressed, however, that the treated brains still lacked any detectable signs of organized electrical activity associated with perception, awareness or consciousness.

“Clinically defined, this is not a living brain, but it is a cellularly active brain,” wrote study co-author Zvonimir Vrselja, associate researcher in neuroscience.

The BrainEx preservative included substances to block nerve signals. Researchers also were ready to halt any electrical activity that might have emerged through anesthetics and temperature reduction, according to Yale.

While the study offers no immediate therapeutic benefits for humans, it creates a new research platform that may ultimately help doctors find ways to revive brain function in stroke patients or to test new treatments for restoring brain cells damaged by injury, the authors said.

In the meantime, the research could spark new quandaries surrounding the determination of death itself, widely defined by one measure as the irreversible loss of all brain function. The blurring of that line has implications in turn for deciding when doctors are ethically bound to go from preserving a patient’s life to preserving their organs.

“For most of human history, death was very simple,” Christof Koch, president and chief scientist of the Allen Institute for Brain Science in Seattle, said in a Nature article accompanying publication of the Yale study.</s>Scientists restored partial cellular function in brains removed from pigs hours after slaughter, according to the new study published in the journal Nature. The achievement raises ethical and philosophical questions about death and how we define it.

A person is considered legally deceased when the brain stops functioning or when the heart and lungs are too compromised to supply enough blood to the oxygen-hungry organ, as Sara Reardon explains for Nature News.

But the veil between life and death is perhaps thinner than many have supposed. Since the early part of last century, researchers have tried to keep animal brains alive soon after death by cooling them and keeping them supplied with blood, but with inconclusive results. Other recent studies have shown that genes in some organs remain active well after death. That’s something Yale neuroscientist Nenad Sestan, one of the study’s authors, had noticed as well. Small tissue samples he worked with showed signs of cellular viability, even if the tissue had been harvested hours before.

He began to wonder if it was possible to awaken an entire brain after death. To find out, he and his team obtained the severed heads of 32 pigs from a meatpacking plant. They removed the brains from their skulls and placed the brains in a system they call BrainEx, in which the circulatory system of the organ is pumped full of a nutrient and preservative. It also contains a chemical that prevents neurons from firing, stopping any electrical activity from restarting in the brain.

The team found that neurons and other cells resumed normal metabolic function when hooked up to BrainEx. The team was able to keep one brain functional for 36 hours. In control brains without the synthetic blood, the cells began to collapse.

But that doesn’t meant they “revived” the brains. “At no point did we observe the kind of organized electrical activity associated with perception, awareness, or consciousness,” co-first author Zvonimir Vrselja of Yale says in a press release. “Clinically defined, this is not a living brain, but it is a cellularly active brain.”

Ed Yong at The Atlantic reports that the team showed that neurons in the brains could still fire, but they never sparked back to life. Just in case one of their porcine patients did resume consciousness inside its glass sphere, they had anesthetic on hand to stop the process. But that was not necessary. “The pigs were brain-dead when their brains came in the door, and by the end of the experiment, they were still brain-dead,” Stephen Latham, the Yale ethicist that advised the team says.

So is science on the edge of a world where we can preserve brains in jars after death or shuffle them from one body to another? Not really. Michael Greshko at National Geographic reports that the study shows that brains can be kept intact and working longer than we thought, but not conscious or aware.

That means, instead of ushering in an era of sci-fi body-swaps, the study is more likely to allow researchers to better study 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,” Khara Ramos, director of the neuroethics program at the United States National Institute of Neurological Disorders and Stroke tells Greshko. “It really enhances our ability to study cells as they exist in connection with each other, in that three-dimensional, large, complicated way.”

The researchers say they have no intention of bringing brains back to consciousness and are taking pains to make sure that does not happen. Instead, they hope to continue working with the BrainEx system to extend the longevity of these brains.

Still, the entire concept is raising legal and ethical questions for many, and brings the long held concept of brain death under the microscope. “We had clear lines between ‘this is alive’ and ‘this is dead,’” bioethicist Nita A. Farahany at Duke University tells Gina Kolata at The New York Times. “How do we now think about this middle category of ‘partly alive’? We didn’t think it could exist.”

In an accompanying commentary to the paper, Farahany and her colleagues suggest that this study necessitates the establishment of immediate new guidelines, like using neural blockers and keeping anesthetic handy during this type of research. They also suggest transparency be at the top of the list and that a committee should be established to draw up guidelines and discuss ethical issues as neuroscience pushes the limits of what we thought was possible.</s>In a study that raises questions about the line between life and death, researchers have restored some cellular activity to brains removed from slaughtered pigs.

The brains did not regain anything resembling consciousness: There were no signs indicating coordinated electrical signaling, necessary for higher functions like awareness and intelligence.

But in an experimental treatment, blood vessels in the pigs’ brains began functioning, flowing with a blood substitute, and certain brain cells regained metabolic activity, even responding to drugs. When the researchers tested slices of treated brain tissue, they discovered electrical activity in some neurons.

The work is very preliminary and has no immediate implications for treatment of brain injuries in humans.

“We had clear lines between ‘this is alive’ and ‘this is dead,’ ” said Nita A. Farahany, a bioethicist and law professor at Duke University. “How do we now think about this middle category of ‘partly alive’? We didn’t think it could exist.”

The new research confirms how little we know about the injured brain and so-called brain death. Bioethicists like Farahany were stunned and intrigued by the findings, published Wednesday in the journal Nature.

Until now, it has been assumed that the brain declines quickly when its blood supply is cut off. Cells deteriorate, and the connections between neurons crumble. Scientists have believed those changes are irreversible unless blood is quickly restored.

Researchers at Yale University acquired the heads of 32 pigs killed for their meat. The scientists sawed into the skulls and removed the brains. By the time the experiment started, the brains had been without blood and at room temperature for four hours.

The team has developed a system called BrainEx that pumps an experimental solution into the intact brain. The scientists hope the technology will help point the way to new treatments for strokes, traumatic brain injuries and diseases like Alzheimer’s.

The scientists pumped the solution into the pigs’ brains for six hours. It brought oxygen to the tissue and contained chemicals that allowed the scientists to track its flow with ultrasound.

The solution also contained chemicals intended to block nerve signals.

In addition to the brains that got the BrainEx solution, the scientists also examined brains that did not receive infusions and those receiving infusions of a dummy substance. Brains in both groups showed no signs of activity, and their cells deteriorated.</s>It’s a cliché image from bad science fiction—the living “brain in a jar.” Now scientists at Yale University say they have actually done it.

Pig heads: A team led by Nenad Sestan report in Nature today how they have been picking up severed pig heads from a New Haven slaughterhouse and trying to restore circulation to them a few hours after death.

The experiments were successful in keeping many of the cells inside the brains alive and functioning for more than a day. MIT Technology Review first reported the pig brain experiments in April 2018.

Not conscious: Sestan says while the brain cells lived, the team did not detect organized electrical signaling from neurons. That would have suggested the disembodied brains had regained consciousness.

An ethicist involved in the study said during a conference call with reporters that if there had been evidence of consciousness, the studies would have had to be stopped. Sestan insists the brains are “not alive.”

High-tech jar: The researchers employed a device they built and called BrainEx, which reestablishes circulation of oxygen carrying fluid to the brains, including their small blood vessels, using a series of pumps, filters, and surgical connections.

Death in question: Doctors can declare a person deceased a few minutes after the heart stops—sometimes quickly harvesting the heart and kidneys for others. But this technology could blur the definition of death.

“If technologies similar to BrainEx are improved and developed for use in humans, people who are declared brain dead … could become candidates for brain resuscitation rather than organ donation,” write Stuart Youngner and Insoo Hyun, bioethicists at Case Western University.</s>Scientists spur some activity in brains of slaughtered pigs

NEW YORK (AP) — Scientists restored some activity within the brains of pigs that had been slaughtered hours before, raising hopes for some medical advances and questions about the definition of death.

The brains could not think or sense anything. By medical standards, they'd been dead for four hours by the time scientists began pumping a special artificial blood through them in their lab.

Yale University researchers reported Wednesday in the journal Nature that they were able to restore activity in some brain cells. Further work might lead to new therapies for stroke and other conditions, as well as a new tool for studying the brain.</s>A bizarre Frankenstein-style experiment has breathed life into the brains of pigs four hours after death.

Scientists in the US restored circulation and cellular activity in 32 pig brains obtained from a meat-packing plant.

While there was no evidence of reawakening awareness or consciousness, the revitalised brains were said to be "cellularly active".

The study has huge implications that challenge long-held assumptions about the finality of death, and opens up a new frontier in brain research.

Lead scientist Professor Nenad Sestan, from Yale University, said: "The intact brain of a large mammal retains a previously under-appreciated capacity for restoration of circulation and certain molecular and cellular activities multiple hours after circulatory arrest."

Cellular brain death is usually considered to be swift and irreversible.

Once the supply of oxygen and blood are cut off, the brain's electrical activity and signs of awareness vanish within seconds.

A cascade of destruction then occurs leading to widespread degeneration from which there is no turning back.

However, Professor Sestan and his team noticed that small brain tissue samples routinely showed signs of cellular life returning, even when harvested hours after death.

To investigate further, they turned their attention to whole, intact brains from pigs processed for food production.

In a ground-breaking experiment, a specially designed "chemical blood" preservative was circulated through the brains of dead animals that had been slaughtered four hours earlier.

The solution, warmed to normal body temperature, was perfused through the brains' blood vessels for six hours.

During this time the scientists observed a reduction in cell death and the restored functionality of certain nerve, blood vessel and glial cells.

Glial cells are important brain "support cells" that hold neurons in place, feed them with nutrients and oxygen, provide insulation, and clean up the carcasses of dead cells.

The revived activity even included some synaptic function, the transmission of signals between neurons.

Details of the study are published in the latest issue of Nature journal.

Lessons learned from the study could in future help doctors find ways to salvage brain function in stroke patients, or test the effectiveness of treatments designed to aid cellular recovery after injury, say the scientists.

The "BrainEx" system developed at Yale could also provide a powerful research tool.

Any future studies involving human tissue or the possible revival of global electrical activity in "dead" animal brains would have to undergo strict ethical supervision, the team stressed.

However, it was unclear that the technique would work in a recently deceased human brain.

The chemical solution lacked many components found naturally in human blood, such as immune system cells.

In Mary Shelley's famous gothic novel, Dr Victor Frankenstein instils life into a monster created from dead body parts obtained from grave yards and butchers.

British expert Professor Derek Hill, from University College London, said: "This research raises some fascinating questions. Firstly, was this somehow a chance finding, or can it be reliably replicated?

"Secondly, could brains maintained by BrainEx help scientists discover new treatments for brain diseases like Alzheimer's and Parkinson's disease, which are proving really hard to treat?

"And thirdly, what are the ethical implications for the way we treat animals after slaughter, and humans after accidents?

"This ingenious experimental work provides challenges and opportunities both to brain scientists and for science policy makers."
Yale University researchers led by professor Nenad Sestan announce, through the Nature journal, that they successfully partly revived the brains of deceased pigs, four hours after death occurred. However, there were no signals from the brains that would indicate awareness or consciousness.