The brains of killed pigs have been partly revived hours after death. Here’s everything you need to know about the experiment and what it means for those of us with a human brain. What happened to the pig brains? The brains were removed from pigs four hours after they had been decapitated and were then hooked up to an artificial supply of blood-like fluid, in a device called BrainEx, for six hours. Surprisingly, this seemed to reduce the amount of brain cell damage that normally happens after bodily death, and it also seemed to restore brain cells’ ability to perform some functions such as using glucose and oxygen. Could the dead brains have been aware of what was happening? The fluid contained drugs that stop nerve cells from firing – partly to help the cells recover, but also to avoid any chance of the brains experiencing some form of awareness. But when some nerve cells were removed and tested separately in a dish without these drugs, they were found to still be capable of sending electrical signals. Advertisement Does this mean we can bring people’s brains back to life after they’ve died? Not at all. There were only limited signs of individual brain cells surviving and functioning – not the coordinated activity of all the brain cells and structures needed to achieve perception or awareness. It would be a massive leap to assume such higher functions are possible. “This is not a living brain, it’s a cellularly active brain,” says Nenad Sestan of Yale School of Medicine, who was part of the team that did the work. Are we sure the drugs will have blocked any brain activity? Yes, because Sestan’s team also measured activity of the brains with electroencephalogram (EEG) recording while they were hooked up to the device. There were no brainwaves, which are necessary for any kind of awareness. “The organised electrical activity associated with consciousness was never detected,” says ethicist and team member Stephen Latham of Yale University. If there had been any brainwaves they would have stopped the experiment. How ethical was this experiment? The group used pigs that had been killed for food, so caused no extra deaths, and they got approval from all the relevant ethics committees. But some US laws on animal research only concern work done on creatures that are alive, so it’s unclear how they apply to brains in this novel state. The team want the regulations reviewed. To be on the safe side, any such brains should be dosed with a general anaesthetic in future, Nita Farahany of Duke University in North Carolina suggests in an accompanying commentary published in Nature. How does this change our understanding of the brain? Until now, we thought that just a few minutes of oxygen deprivation could lead to brain damage, triggering a cascade of irreversible cell death and degeneration. Now we know that at least some cell activities can be restored even four hours after death without any cooling. “Cell death happens across a longer time window than we thought,” says Sestan Could this affect organ donation after brain death? Not any time soon. Donor organs usually come from someone who has had a severe brain injury and no longer have a functioning brain stem, a part of the brain that is essential for life. With existing technology, no one recovers after tests have shown brain stem death, says John Dark of Newcastle University, UK. Are there any other implications? For a start, the experiment provides a new way to study brains in the lab. And in medicine, the artificial blood substitute could be useful for helping to protect the brain or other organs after damage caused by lack of oxygen, as happens after heart attacks. The fluid contains chemicals that protect nerve cells from damage, and unlike blood, has no immune cells, which may contribute to brain damage. “If this works for brain cells it will also work with some less sensitive organs with some tinkering,” says Latham. Journal reference: Nature, DOI: 10.1038/s41586-019-1099-1<doc-sep>Over the course of a six-hour treatment, the brains were infused with a cocktail of synthetic fluids designed to halt cellular degeneration and restore cellular functions, such as metabolic activity. It worked: The brains continued to consume oxygen and glucose. Many brain cells, including neurons, which send messages within the brain and to the rest of the body, ceased decaying and appear to have been revived in dramatic and detectable ways.<doc-sep>The brain is the hardest-working organ in the body with the most daunting tasks: controlling the rest of our internal organs, our voluntary and involuntary movement, and creating consciousness. It’s a huge amount of responsibility for a 3 lb (1.3 kg) grey blob, but it handles them expertly. For all its might, though, the brain has a molecular Achilles heel: an oxygen dependency. All organs need blood to routinely deliver oxygen to them. The brain, however, is the neediest. Within seconds of interrupted blood flow to the brain, the body will suspend consciousness in an effort to save energy. Ideally, gravity will then take over as the body goes horizontal, allowing blood to flow more freely towards the brain. If that doesn’t work, brain cells die within minutes, which could lead to catastrophic damage, or even a person’s death. However, brain-cell death as a result of oxygen depletion may not be as fast or as permanent as scientists previously thought. In a first, an international team led by scientists at Yale University showed it may be possible to reanimate brain cells after death, according to a paper published today in the Nature. The researchers worked on the brains of 32 pigs that had been killed and decapitated at a food-processing plant. Applying a system called BrainEx, the scientists were able to get cells in these brains to carry out some normal function for six hours. Although these brains never regained full working capacity or consciousness, the development opens doors for future treatments for events that acutely choke the brain of oxygen, like stroke. First, the brains and their blood vessels were carefully removed from the pigs’ bodies. Then, after raising the temperature of the brains to 37°C (98.6°F), the normal body temperature of pigs, scientists flushed them with a synthetic solution that works like blood. The brain cells took in oxygen and glucose and flushed out carbon dioxide, which suggests they were using energy. Some brain cells even started signaling one another. These functions are both typical in living brain cells. It appeared that the artificial system either revived some brain cells that had died, or postponed their death. However, the brain never regained its overarching electrical connections. In other words, the organ was never fully revived. “This is not a living brain,” Nenad Sestan, a neuroscientist at Yale who led the study, said in a press conference. “But it’s a cellularly active brain.” At the end of a six-hour period, the brains themselves had largely deteriorated, creating an automatic end to the experiment. There was no evidence that the brains here regained any kind of consciousness; in fact, the solution used to provide oxygen to cells contained a drug that inhibits neurons from fully functioning like they are alive. This is crucial, Stephen Latham, a bioethicist at Yale, explained in the press conference, because bringing consciousness back to an organ like a brain is still an ethically grey area. Before that kind of research can be done, he said, international scientists and ethicists will have to decide whether or not the ends of such experimentation justifies the potential suffering of the animal (or in this case, pain that could possibly by felt by the brain itself). In this particular experiment, the scientists were ready to administer anesthesia to and lower the temperature of the brains immediately to alleviate any pain and suffering should it become clear the brains were completely reanimated. “The main implication of this finding is that cell death in the brain occurs over a gradual time,” said Sestan. “Some of those processes can be postponed or even reversed.” This technology opens the doors for different modes of studying activity in the brain post-mortem, to try to understand what happens in the final days of diseases like Alzheimer’s or Parkinson’s. It could also lead to restoring the function to brain cells in people who have suffered a stroke or other trauma that deprived their cells of oxygen. But, the team says, the work is a long way from having any practical application in humans.<doc-sep>Such applications are a long way off, and even if they never materialize, “this is already an extraordinary breakthrough,” says Nita Farahany, a bioethicist at Duke University. Although neuroscientists can study lab-grown neurons or peer at thin slices of brain tissue, these capture nothing of the three-dimensional intricacy that makes the brain, the brain. By restoring some activity to postmortem pig brains, Sestan’s team has created a much better proxy for the real thing. The irony, of course, is that “the better the proxy, the sharper the ethical dilemmas,” Farahany says. Johnson adds that no animals died for the sake of the study: The team used brains from pigs that had been killed for food. “Thousands of sentient animals have been killed in studies searching for neuroprotective treatments that have not borne fruit,” she says. “Meanwhile, millions of animals are killed for food every year, and that’s a potentially rich source of experimental brains that would involve no additional harm.” The study still needs to be replicated by other independent teams. And before anyone takes the technique further, or even contemplates the possibility of human trials, there are several ethical issues to consider. For example, is the team really sure that the partly revived brains have no consciousness? Latham, the Yale ethicist, feels confident. Even people under anesthesia show signs of coordinated, brainwide electrical activity, he says, so the absence of such signals strongly suggests that “we don’t even have the possibility of consciousness showing up.” Read: A new genetic clue to how humans got such big brains But consciousness is still hard to define, much less measure. And no one has ever had to measure it in a brain that lacks a body. How would you assess awareness, pain, or suffering “in a brain that has restored circulation and neural function, but that’s disconnected from external sensation?” asks Steven Hyman, a neuroscientist at the Broad Institute of Harvard and MIT. “This is a very hard scientific problem and policy issue.” As Johnson says, “I think it’s very unlikely that consciousness or sentience could be restored in a several-hours-dead brain, but I’m also pretty sure that if it was, we wouldn’t know that it was.” It’s also unclear why the pig brains never regained coordinated activity. Is it because team members waited for four hours? Is it because they only treated the brains for six hours? Was it something about the way the pigs were killed? Or is it because they added chemicals that dampen neural activity to the fluid that they pumped through the brains? (They did this because excessive firing helps to kill neurons in oxygen-starved brains.) And if that’s the case, could isolated brains gain consciousness if the blockers were removed? Possibly, and that would certainly blur the line between living and dead. But that experiment is emphatically not in the cards. The team’s next and only step is to try BrainEx for longer periods of time. If that leads to signs of coordinated activity, “we’d have to close down the research for a while,” Latham says, “because there’s no institutional body for us to consult. We’d need to create one.” Current regulations on animal research exclude individuals that either were raised for food or have died. Nothing covers the gray area posed by an isolated brain with signs of cellular activity and that may or may not be conscious.<doc-sep>
A team of Yale University scientists were able to restore some function to a dead pig’s brain four hours after it’d been decapitated, a new study published in Nature on Wednesday said. While consciousness or awareness was not restored to the brains, many other parts of the organ and a lot of cellular function either came back or were preserved in the study, creating an ethical conundrum for bioethicists and scientists who are struggling to understand how this will change what separates the living and the dead, the research team told NPR News. “It was mind-blowing,” said Nita Farahany, who examines the ethics of emerging technology 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 scientists gathered around 300 pig heads from a local slaughterhouse, removed the brains, placed them in an experimental chamber and, using their developed technology “BrainEx“, pumped them with a special formula of chemicals for six hours, starting around four hours after the pigs died, NPR reported. “We found that tissue and cellular structure is preserved and cell death is reduced. In addition, some molecular and cellular functions were restored,” said Nenad Sestan, a neuroscientist at the Yale School of Medicine. “This is not a living brain, but it is a cellularly active brain.” However, the team was “actively worried about” it getting close to the activity of a living brain, Stephen Latham, a Yale bioethicist, told NPR. They even had a plan in place in case signs of consciousness did emerge — which would have been to use anesthesia and cooling to shut it down immediately. One of the chemicals pumped into the brain included lamotrigine, an anti-seizure drug that’s known to block or dampen neuronal activity. “The researchers thought that brain cells might be better preserved and their function might be better restored if they were not active,” Latham explained. see also Human brains could merge with technology sooner than we think A new study suggests that human brains could be merged... But it’s not clear if the researchers would’ve seen activity linked to consciousness had that chemical not been present. When tests were done on single cells taken from the brains after the chemicals had been washed off, the individual cells were capable of electrochemical responses, which makes a brain conscious. “That’s a very important question, and one that we have discussed at length,” one of the scientists, Stefano Daniele, said. “We cannot speak with any scientific certainty to that point since we did not run those experiments.” The team admitted the research project was a real “shot in the dark” and had no idea if it could work and it will need to be replicated in other labs to see if it can hold up. If they do, aside from the legal and ethical questions that will come, “people are going to recognize the potential of this research,” Farahany said. “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.”