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Research: “Boundary between life and death not as clear as we once thought”​

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Research: “Boundary between life and death not as clear as we once thought”​

Just as the birth certificate marks the moment we come into the world, the death certificate marks the moment we leave it. However, this practice only reflects traditional ideas of life and death – a binary concept. We are here until the switch is flipped – like a lamp – and we are no longer there. But even if this idea is omnipresent, there are increasing signs that it is an outdated social construct. Dying is actually a process in which there is no clear boundary from which there is no way back.

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Scientists and concerned physicians have already embraced this more nuanced understanding of death. If society follows suit, the impact on the living could be profound. “Many people could be resuscitated,” says Sam Parnia, director of critical care and resuscitation research at NYU Langone Health hospital.

For example, neuroscientists have discovered that the brain can survive surprising amounts of oxygen deprivation. This could one day extend the window of time available to doctors to reverse the dying process. Other organs also appear to be recoverable for much longer than current medical practice – which could expand the range of organ donations.

However, to achieve this we would have to rethink our ideas about life and death. Instead of viewing death as an event from which one cannot recover, we should view it as a temporary process of oxygen deprivation, says Parnia. It could become irreversible if it lasts too long or if medical measures fail. If we adopt this mindset, “suddenly everyone will say, ‘Let’s treat this person.'”

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Legal and biological definitions of death typically refer to the “irreversible cessation” of life-sustaining processes by the heart, lungs, and brain. The heart is the most common weak point. For most of human history, once it stops beating, it meant no turning back. That changed around 1960 with the invention of cardiopulmonary resuscitation (CPR). Until then, it was considered a miracle to make a heart beat again.

Now it was within reach of modern medicine. CPR forced the first major rethinking of death as a fundamental concept. The term “cardiac arrest” entered common usage, creating a clear semantic separation between the temporary loss of cardiac function and the permanent end of life.

Around the same time, mechanical positive pressure ventilators that could supply air to the lungs appeared. They enabled people with severe brain injuries – from a shot in the head, a severe stroke or a car accident – to continue breathing. However, in autopsies of such patients, researchers found that in some cases the brain was so damaged that the tissue began to liquefy. In such cases, the ventilators had essentially created a “carcass with a beating heart,” says Christof Koch, a neuroscientist at the Allen Institute in Seattle.

These observations then led to the concept of brain death and initiated a medical, ethical and legal debate about whether such patients could be declared dead before their hearts stopped beating. Many countries eventually adopted some form of this new definition. Regardless of whether it is called brain death or biological death, the scientific intricacies behind these processes are far from clear. “The better we can characterize the dying brain, the more questions we have,” says Charlotte Martial, a neuroscientist at the University of Liège in Belgium. “It’s a very, very complex phenomenon.”

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Until now, medicine has assumed that the brain is already damaged if it is cut off from oxygen for minutes. That’s still the common opinion, says Jimo Borjigin, a neuroscientist at the University of Michigan, but we have to ask ourselves “why our brains should be designed to be so vulnerable.”

Recent research suggests that may not be the case. In 2019, scientists reported in Nature magazine that they were able to restore a range of functions in the brains of 32 pigs whose heads had been severed at a slaughterhouse four hours earlier. The researchers restarted blood circulation and cell activity in the brains by infusing oxygen-rich artificial blood with a cocktail of protective drugs. They also administered drugs that stop neurons from firing, preventing the pigs’ brains from regaining consciousness. They kept the brains alive for up to 36 hours before ending the experiment. “Our work shows that much more of the damage caused by oxygen deficiency is probably reversible than previously thought,” says study co-author Stephen Latham, a bioethicist at Yale University.

In 2022, Latham and his colleagues published in another Nature paper that they had managed to restore many functions of various organs in pigs that had already been dead for an hour – including the brain and heart. They continued the experiment for six hours and the anesthetized, previously dead animals had blood circulation again and many important cellular functions were active. “These studies have shown that the line between life and death is not as clear as we once thought,” says lead author Nenad Sestan, a neuroscientist at Yale School of Medicine. Death “takes longer than we thought, and at least some of the processes can be stopped and reversed.”

A handful of human studies have also found that when the heart stops beating, the brain can cope better than expected with a lack of oxygen. “When the brain is deprived of oxygen, in some cases there seems to be a kind of paradoxical overvoltage,” says Koch. “For reasons we don’t understand, the brain is hyperactive, at least for a few minutes.” Parnia and his colleagues are collecting data on the oxygen levels and electrical activity of the brains of 85 cardiac arrest patients for a study published in Resuscitation. In most patients, brain activity on the EEG monitors initially stagnated – but in around 40 percent of them, almost normal electrical activity in the brain temporarily reappeared up to 60 minutes after their resuscitation. How can that be?

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