The biggest questions: What is death?

Just as birth certificates mark the moment we enter the world, death certificates mark the moment we leave it. This practice reflects traditional notions of life and death as binary. We are here until suddenly, like an extinguished light, we are gone.

But while this idea of ​​death is pervasive, evidence is building that it’s an outdated social construct that isn’t really grounded in biology. Death is really a process – a process with no clear point demarcating the threshold beyond which someone cannot come back.

Scientists and many doctors have already embraced this more nuanced understanding of death. As society catches up, the consequences for the living can be profound. “There is the potential for a lot of people to be resuscitated,” said Sam Parnia, director of critical care and resuscitation research at NYU Langone Health.

Neuroscientists, for example, are learning that the brain can survive surprising levels of oxygen deprivation. This means that the window of time that doctors have to reverse the death process may one day be extended. Other organs also appear to be recoverable for much longer than is reflected in current medical practice, opening opportunities to expand the availability of organ donation.

To do so, however, we need to rethink how we perceive and approach life and death. Rather than thinking of death as an event from which there is no recovery, Parnia says, we should instead see it as a transient process of oxygen deprivation that has the potential to become irreversible given enough time, or medical interventions fail. If we adopt this way of thinking about death, Parnia says, “then suddenly everyone will say, ‘Let’s deal with it.'”

Moving goalposts

Legal and biological definitions of death typically refer to the “irreversible cessation” of life-sustaining processes supported by the heart, lungs, and brain. The heart is the most common point of failure, and for the vast majority of human history, once it stopped, there was generally no way back.

That changed around 1960, with the invention of CPR. Until then, resuming a stopped heartbeat had been largely considered miracles; now it was within reach of modern medicine. CPR forced the first major rethinking of death as a concept. “Cardiac arrest” entered the lexicon and created a clear semantic separation between the temporary loss of cardiac function and the permanent cessation of life.

Around the same time, the advent of positive-pressure mechanical ventilators, which work by delivering puffs of air to the lungs, began to allow people who suffered a catastrophic brain injury—for example, from a gunshot to the head, a massive stroke, or a car accident— to continue breathing. In autopsies after the death of these patients, however, the researchers discovered that in some cases their brains had been so severely damaged that the tissue had begun to liquefy. In such cases, ventilators had essentially created “a beating cardiac cadaver,” says Christof Koch, a neuroscientist at the Allen Institute in Seattle.

These observations led to the concept of brain death and initiated medical, ethical and legal debate about the ability to declare such patients dead before their heart stops beating. Many countries eventually adopted some form of this new definition. Regardless of whether we are talking about brain death or biological death, the scientific intricacies behind these processes are far from established. “The more we 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.”

Brains on the edge

Traditionally, doctors have believed that the brain begins to suffer damage minutes after it is deprived of oxygen. Although that’s the conventional wisdom, says Jimo Borjigin, a neuroscientist at the University of Michigan, “you have to wonder, why would our brain be built in such a fragile way?”

Recent research suggests that it may not actually be. In 2019, researchers reported in Nature that they were able to restore a number of functions in the brains of 32 pigs that had been decapitated in a slaughterhouse four hours earlier. The researchers restarted circulation and cellular activity in the brain using an oxygen-rich artificial blood infused with a cocktail of protective drugs. They also included drugs that stopped neurons from firing, preventing any chance of the pig brains regaining consciousness. They kept the brains alive for up to 36 hours before ending the experiment. “Our work shows that there is probably a lot more damage from oxygen deprivation that is reversible than people thought before,” said co-author Stephen Latham, a bioethicist at Yale University.

In 2022, Latham and colleagues published another paper in Nature announcing that they had been able to restore many functions in multiple organs, including the brain and heart, in whole-body pigs that had been killed an hour earlier. They continued the experiment for six hours and confirmed that the anesthetized, previously dead animals had regained circulation and that several key cellular functions were active.

“What these studies have shown is that the line between life and death is not as clear as we once thought,” says Nenad Sestan, a neuroscientist at the Yale School of Medicine and senior author of both pig studies. 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 suggested that the brain is better than we thought at dealing with lack of oxygen after the heart stops beating. “When the brain is deprived of life-sustaining oxygen, in some cases there appears to be this paradoxical electrical surge,” says Koch. “For reasons we don’t understand, it’s hyperactive for at least a few minutes.”

In a study published in September in Resuscitation, Parnia and his colleagues collected data on brain oxygen and electrical activity from 85 patients who experienced cardiac arrest while in the hospital. Most of the patients’ brain activity was initially flat on EEG monitors, but for about 40% of them, near-normal electrical activity intermittently appeared in their brains up to 60 minutes after CPR.

Similarly, in a study published in the Proceedings of the National Academy of Sciences in May, Borjigin and her colleagues reported increases in brain activity in two comatose patients after their ventilators were removed. The EEG signatures occurred just before the patients died and had all the hallmarks of consciousness, says Bojigin. While many questions remain, such findings raise tantalizing questions about the death process and the mechanisms of consciousness.

Life after death

The more scientists can learn about the mechanisms behind the death process, the greater the chances of developing “more systematic rescue efforts,” Borjigin says. At best, she adds, this line of study could have “the potential to rewrite medical practice and save a lot of people.”

Of course, everyone must eventually die and will one day be impossible to save. But a more accurate understanding of the death process could enable doctors to save some previously healthy people who meet an unexpectedly early end and whose bodies are still relatively intact. Examples could include people suffering from heart attacks, succumbing to a fatal loss of blood, or suffocating or drowning. The fact that many of these people die and stay dead simply reflects “a lack of proper resource allocation, medical knowledge or sufficient progress to bring them back,” Parnia says.

Borjigin’s hope is to eventually understand the process of death “second by second.” Such discoveries could not only contribute to medical advances, she says, but also “revise and revolutionize our understanding of brain function.”

Sestan says he and his colleagues are also working on follow-up studies that seek to “perfect the technology” they’ve used to restore metabolic function in pig brains and other organs. This line of research could eventually lead to technologies capable of reversing damage—up to a point, of course—from lack of oxygen to the brain and other organs of people whose hearts have stopped. If successful, the method could also expand the pool of available organ donors, Sestan adds, by extending the time doctors have to recover organs from the permanently deceased.

If these breakthroughs come, Sestan emphasizes, they will require years of research. “It’s important that we don’t exaggerate and overpromise,” he says, “although that doesn’t mean we don’t have a vision.”

Meanwhile, ongoing research into the dying process will undoubtedly continue to challenge our notions of death, leading to sea changes in science and other areas of society, from the theological to the legal. As Parnia says, “Neuroscience does not own death. We all have a stake in it.”

Rachel Nuwer is a freelance science journalist who regularly contributes to the New York Times, Scientific American, Nature, and more. Her latest book is I Feel Love: MDMA and the Quest for Connection in a Fractured World. She lives in Brooklyn.