“Coming Back from the Dead” Is No Longer Science Fiction
Last year, there were widespread reports of a 53-year-old Frenchman who had suffered a cardiac arrest and "died," but was then resuscitated back to life 18 hours after his heart had stopped.
The once black-and-white line between life and death is now blurrier than ever.
This was thought to have been possible in part because his body had progressively cooled down naturally after his heart had stopped, through exposure to the outside cold. The medical team who revived him were reported as being "stupefied" that they had been able to bring him back to life, in particular since he had not even suffered brain damage.
Interestingly, this man represents one of a growing number of extraordinary cases in which people who would otherwise be declared dead have now been revived. It is a testament to the incredible impact of resuscitation science -- a science that is providing opportunities to literally reverse death, and in doing so, shedding light on the age-old question of what happens when we die.
Death: Past and Present
Throughout history, the boundary between life and death was marked by the moment a person's heart stopped, breathing ceased, and brain function shut down. A person became motionless, lifeless, and was deemed irreversibly dead. This is because once the heart stops beating, blood flow stops and oxygen is cut off from all the body's organs, including the brain. Consequently, within seconds, breathing stops and brain activity comes to a halt. Since the cessation of the heart literally occurs in a "moment," the philosophical notion of a specific point in time of "irreversible" death still pervades society today. The law, for example, relies on "time of death," which corresponds to when the heart stops beating.
The advent of cardiopulmonary resuscitation (CPR) in the 1960s was revolutionary, demonstrating that the heart could potentially be restarted after it had stopped, and what had been a clear black-and-white line was shown to be potentially reversible in some people. What was once called death—the ultimate end point— was now widely called cardiac arrest, and became a starting point.
From then on, it was only if somebody had requested not to be resuscitated or when CPR was deemed to have failed that people would be declared dead by "cardiopulmonary criteria." Biologically, cardiac arrest and death by cardiopulmonary criteria are the same process, albeit marked at different points in time depending on when a declaration of death is made.
The apparent irreversibility of death as we know it may not necessarily reflect true irretrievable cellular damage inside the body.
Clearly, contrary to many people's perceptions, cardiac arrest is not a heart attack; it is the final step in death irrespective of cause, whether it be a stroke, a heart attack, a car accident, an overwhelming infection or cancer. This is how roughly 95 percent of the population are declared dead.
The only exception is the small proportion of people who may have suffered catastrophic brain injuries, but whose hearts can be artificially kept beating for a period of time on life-support machines. These people can be legally declared dead based on brain death criteria before their hearts have stopped. This is because the brain can die either from oxygen starvation after cardiac arrest or from massive trauma and internal bleeding. Either way, the brain dies hours or possibly longer after these injuries have taken place and not just minutes.
A Profound Realization
What has become increasingly clear is that the apparent irreversibility of death as we know it may not necessarily reflect true irretrievable cellular damage inside the body. This is consistent with a mounting understanding: it is only after a person actually dies that the cells in the body start to undergo their own process of death. Intriguingly, this process is something that can now be manipulated through medical intervention. Being cold is one of the factors that slows down the rate of cellular decay. The 53-year-old Frenchman's case and the other recent cases of resuscitation after prolonged periods of time illustrate this new understanding.
Last week's earth-shattering announcement by neuroscientist Dr. Nenad Sestan and his team out of Yale, published in the prestigious scientific journal Nature, provides further evidence that a time gap exists between actual death and cellular death in cadavers. In this seminal study, these researchers were able to restore partial function in pig brains four hours after their heads were severed from their bodies. These results follow from the pioneering work in 2001 of geneticist Fred Gage and colleagues from the Salk Institute, also published in Nature, which demonstrated the possibility of growing human brain cells in the laboratory by taking brain biopsies from cadavers in the mortuary up to 21 hours post-mortem.
The once black-and-white line between life and death is now blurrier than ever. Some people may argue this means these humans and pigs weren't truly "dead." However, that is like saying the people who were guillotined during the French Revolution were also not dead. Clearly, that is not the case. They were all dead. The problem is not death; it's our reliance on an outdated philosophical, rather than biological, notion of death.
Death can no longer be considered an absolute moment but rather a process that can be reversed even many hours after it has taken place.
But the distinction between irreversibility from a medical perspective and biological irreversibility may not matter much from a pragmatic perspective today. If medical interventions do not exist at any given time or place, then of course death cannot be reversed.
However, it is crucial to distinguish between biologically and medically: When "irreversible" loss of function arises due to inadequate treatment, then a person could be potentially brought back in the future when an alternative therapy becomes available, or even today if he or she dies in a location where novel treatments can slow down the rate of cell death. However, when true irreversible loss of function arises from a biological perspective, then no treatment will ever be able to reverse the process, whether today, tomorrow, or in a hundred years.
Probing the "Grey Zone"
Today, thanks to modern resuscitation science, death can no longer be considered an absolute moment but rather a process that can be reversed even many hours after it has taken place. How many hours? We don't really know.
One of the wider implications of our medical advances is that we can now study what happens to the human mind and consciousness after people enter the "grey zone," which marks the time after the heart stops, but before irreversible and irretrievable cell damage occurs, and people are then brought back to life. Millions have been successfully revived and many have reported experiencing a unique, universal, and transformative mental state.
Were they "dead"? Yes, according to all the criteria we have ever used. But they were able to be brought back before their "dead" bodies had reached the point of permanent, irreversible cellular damage. This reflects the period of death for all of us. So rather than a "near-death experience," I prefer a new terminology to describe these cases -- "an actual-death experience." These survivors' unique experiences are providing eyewitness testimonies of what we will all be likely to experience when we die.
Such an experience reportedly includes seeing a warm light, the presence of a compassionate perfect individual, deceased relatives, a review of their lives, a judgment of their actions and intentions as they pertain to their humanity, and in some cases a sensation of seeing doctors and nurses working to resuscitate them.
Are these experiences compatible with hallucinations or illusions? No -- in part, because these people have described real, verifiable events, which, by definition are not hallucinations, and in part, because their experiences are not compatible with confused and delirious memories that characterize oxygen deprivation.
The challenge for us scientifically is understanding how this is possible at a time when all our science tells us the brain shuts down.
For instance, it is hard to classify a structured meaningful review of one's life and one's humanity as hallucinatory or illusory. Instead, these experiences represent a new understanding of the overall human experience of death. As an intensive care unit physician for more than 10 years, I have seen numerous cases where these reports have been corroborated by my colleagues. In short, these survivors have been known to come back with reports of full consciousness, with lucid, well-structured thought processes and memory formation.
The challenge for us scientifically is understanding how this is possible at a time when all our science tells us the brain shuts down. The fact that these experiences occur is a paradox and suggests the undiscovered entity we call the "self," "consciousness," or "psyche" – the thing that makes us who we are - may not become annihilated at the point of so-called death.
At New York University, the State University of New York, and across 20 hospitals in the U.S. and Europe, we have brought together a new multi-disciplinary team of experts across many specialties, including neurology, cardiology, and intensive care. Together, we hope to improve cardiac arrest prevention and treatment, as well as to address the impact of new scientific discoveries on our understanding of what happens at death.
One of our first studies, Awareness during Resuscitation (AWARE), published in the medical journal Resuscitation in 2014, confirmed that some cardiac arrest patients report a perception of awareness without recall; others report detailed memories and experiences; and a few report full auditory and visual awareness and consciousness of their experience, from a time when brain function would be expected to have ceased.
While you probably have some opinion or belief about this based upon your own philosophical, religious, or cultural background, you may not realize that exploring what happens when we die is now a subject that science is beginning to investigate.
There is no question more intriguing to humankind. And for the first time in our history, we may finally uncover some real answers.
Forty years ago, Joy Milne, a nurse from Perth, Scotland, noticed a musky odor coming from her husband, Les. At first, Milne thought the smell was a result of bad hygiene and badgered her husband to take longer showers. But when the smell persisted, Milne learned to live with it, not wanting to hurt her husband's feelings.
Twelve years after she first noticed the "woodsy" smell, Les was diagnosed at the age of 44 with Parkinson's Disease, a neurodegenerative condition characterized by lack of dopamine production and loss of movement. Parkinson's Disease currently affects more than 10 million people worldwide.
Milne spent the next several years believing the strange smell was exclusive to her husband. But to her surprise, at a local support group meeting in 2012, she caught the familiar scent once again, hanging over the group like a cloud. Stunned, Milne started to wonder if the smell was the result of Parkinson's Disease itself.
Milne's discovery led her to Dr. Tilo Kunath, a neurobiologist at the Centre for Regenerative Medicine at the University of Edinburgh. Together, Milne, Kunath, and a host of other scientists would use Milne's unusual sense of smell to develop a new diagnostic test, now in development and poised to revolutionize the treatment of Parkinson's Disease.
"Joy was in the audience during a talk I was giving on my work, which has to do with Parkinson's and stem cell biology," Kunath says. "During the patient engagement portion of the talk, she asked me if Parkinson's had a smell to it." Confused, Kunath said he had never heard of this – but for months after his talk he continued to turn the question over in his mind.
Kunath knew from his research that the skin's microbiome changes during different disease processes, releasing metabolites that can give off odors. In the medical literature, diseases like melanoma and Type 2 diabetes have been known to carry a specific scent – but no such connection had been made with Parkinson's. If people could smell Parkinson's, he thought, then it stood to reason that those metabolites could be isolated, identified, and used to potentially diagnose Parkinson's by their presence alone.
First, Kunath and his colleagues decided to test Milne's sense of smell. "I got in touch with Joy again and we designed a protocol to test her sense of smell without her having to be around patients," says Kunath, which could have affected the validity of the test. In his spare time, Kunath collected t-shirt samples from people diagnosed with Parkinson's and from others without the diagnosis and gave them to Milne to smell. In 100 percent of the samples, Milne was able to detect whether a person had Parkinson's based on smell alone. Amazingly, Milne was even able to detect the "Parkinson's scent" in a shirt from the control group – someone who did not have a Parkinson's diagnosis, but would go on to be diagnosed nine months later.
From the initial study, the team discovered that Parkinson's did have a smell, that Milne – inexplicably – could detect it, and that she could detect it long before diagnosis like she had with her husband, Les. But the experiments revealed other things that the team hadn't been expecting.
"One surprising thing we learned from that experiment was that the odor was always located in the back of the shirt – never in the armpit, where we expected the smell to be," Kunath says. "I had a chance meeting with a dermatologist and he said the smell was due to the patient's sebum, which are greasy secretions that are really dense on your upper back. We have sweat glands, instead of sebum, in our armpits." Patients with Parkinson's are also known to have increased sebum production.
With the knowledge that a patient's sebum was the source of the unusual smell, researchers could go on to investigate exactly what metabolites were in the sebum and in what amounts. Kunath, along with his associate, Dr. Perdita Barran, collected and analyzed sebum samples from 64 participants across the United Kingdom. Once the samples were collected, Barran and others analyzed it using a method called gas chromatography mass spectrometry, or GS-MC, which separated, weighed and helped identify the individual compounds present in each sebum sample.
Barran's team can now correctly identify Parkinson's in nine out of 10 patients – a much quicker and more accurate way to diagnose than what clinicians do now.
"The compounds we've identified in the sebum are not unique to people with Parkinson's, but they are differently expressed," says Barran, a professor of mass spectrometry at the University of Manchester. "So this test we're developing now is not a black-and-white, do-you-have-something kind of test, but rather how much of these compounds do you have compared to other people and other compounds." The team identified over a dozen compounds that were present in the sebum of Parkinson's patients in much larger amounts than the control group.
Using only the GC-MS and a sebum swab test, Barran's team can now correctly identify Parkinson's in nine out of 10 patients – a much quicker and more accurate way to diagnose than what clinicians do now.
"At the moment, a clinical diagnosis is based on the patient's physical symptoms," Barran says, and determining whether a patient has Parkinson's is often a long and drawn-out process of elimination. "Doctors might say that a group of symptoms looks like Parkinson's, but there are other reasons people might have those symptoms, and it might take another year before they're certain," Barran says. "Some of those symptoms are just signs of aging, and other symptoms like tremor are present in recovering alcoholics or people with other kinds of dementia." People under the age of 40 with Parkinson's symptoms, who present with stiff arms, are often misdiagnosed with carpal tunnel syndrome, she adds.
Additionally, by the time physical symptoms are present, Parkinson's patients have already lost a substantial amount of dopamine receptors – about sixty percent -- in the brain's basal ganglia. Getting a diagnosis before physical symptoms appear would mean earlier interventions that could prevent dopamine loss and preserve regular movement, Barran says.
"Early diagnosis is good if it means there's a chance of early intervention," says Barran. "It stops the process of dopamine loss, which means that motor symptoms potentially will not happen, or the onset of symptoms will be substantially delayed." Barran's team is in the processing of streamlining the sebum test so that definitive results will be ready in just two minutes.
"What we're doing right now will be a very inexpensive test, a rapid-screen test, and that will encourage people to self-sample and test at home," says Barran. In addition to diagnosing Parkinson's, she says, this test could also be potentially useful to determine if medications were at a therapeutic dose in people who have the disease, since the odor is strongest in people whose symptoms are least controlled by medication.
"When symptoms are under control, the odor is lower," Barran says. "Potentially this would allow patients and clinicians to see whether their symptoms are being managed properly with medication, or perhaps if they're being overmedicated." Hypothetically, patients could also use the test to determine if interventions like diet and exercise are effective at keeping Parkinson's controlled.
"We hope within the next two to five years we will have a test available."
Barran is now running another clinical trial – one that determines whether they can diagnose at an earlier stage and whether they can identify a difference in sebum samples between different forms of Parkinson's or diseases that have Parkinson's-like symptoms, such as Lewy Body Dementia.
"Within the next one to two years, we hope to be running a trial in the Manchester area for those people who do not have motor symptoms but are at risk for developing dementia due to symptoms like loss of smell and sleep difficulty," Barran had said in 2019. "If we can establish that, we can roll out a test that determines if you have Parkinson's or not with those first pre-motor symptoms, and then at what stage. We hope within the next two to five years we will have a test available."
In a 2022 study, published in the American Chemical Society, researchers used mass spectrometry to analyze sebum from skin swabs for the presence of the specific molecules. They found that some specific molecules are present only in people who have Parkinson’s. Now they hope that the same method can be used in regular diagnostic labs. The test, many years in the making, is inching its way to the clinic.
"We would likely first give this test to people who are at risk due to a genetic predisposition, or who are at risk based on prodomal symptoms, like people who suffer from a REM sleep disorder who have a 50 to 70 percent chance of developing Parkinson's within a ten year period," Barran says. "Those would be people who would benefit from early therapeutic intervention. For the normal population, it isn't beneficial at the moment to know until we have therapeutic interventions that can be useful."
Milne's husband, Les, passed away from complications of Parkinson's Disease in 2015. But thanks to him and the dedication of his wife, Joy, science may have found a way to someday prolong the lives of others with this devastating disease. Sometimes she can smell people who have Parkinson’s while in the supermarket or walking down the street but has been told by medical ethicists she cannot tell them, Milne said in an interview with the Guardian. But once the test becomes available in the clinics, it will do the job for her.
[Ed. Note: A older version of this hit article originally ran on September 3, 2019.]
Earlier this year, Harvard scientists reported that they used an anti-aging therapy to reverse blindness in elderly mice. Several other studies in the past decade have suggested that the aging process can be modified, at least in lab organisms. Considering mice and humans share virtually the same genetic makeup, what does the rodent-based study mean for the humans?
In truth, we don’t know. Maybe nothing.
What we do know, however, is that a growing number of people are dedicating themselves to defying the aging process, to turning back the clock – the biological clock, that is. Take Bryan Johnson, a man who is less mouse than human guinea pig. A very wealthy guinea pig.
The 45-year-old venture capitalist spends over $2 million per year reversing his biological clock. To do this, he employs a team of 30 medical doctors and other scientists. His goal is to eventually reset his biological clock to age 18, and “have all of his major organs — including his brain, liver, kidneys, teeth, skin, hair, penis and rectum — functioning as they were in his late teens,” according to a story earlier this year in the New York Post.
But his daily routine paints a picture that is far from appealing: for example, rigorously adhering to a sleep schedule of 8 p.m. to 5 a.m. and consuming more than 100 pills and precisely 1,977 calories daily. Considering all of Johnson’s sacrifices, one discovers a paradox:
To live forever, he must die a little every day until he reaches his goal - if he ever reaches his goal.
Less extreme examples seem more helpful for people interested in happy, healthy aging. Enter Chris Mirabile, a New Yorker who says on his website, SlowMyAge.com, that he successfully reversed his biological age by 13.6 years, from the chronological age of 37.2 to a biological age of 23.6. To put this achievement in perspective, Johnson, to date, has reversed his biological clock by 2.5 years.
Mirabile's habits and overall quest to turn back the clock trace back to a harrowing experience at age 16 during a school trip to Manhattan, when he woke up on the floor with his shirt soaked in blood.
Mirabile, who is now 38, supports his claim with blood tests that purport to measure biological age by assessing changes to a person’s epigenome, or the chemical marks that affect how genes are expressed. Mirabile’s tests have been run and verified independently by the same scientific lab that analyzes Johnson’s. (In an email to Leaps.org, the lab, TruDiagnostic, confirmed Mirabile’s claims about his test results.)
There is considerable uncertainty among scientists about the extent to which these tests can accurately measure biological age in individuals. Even so, Mirabile’s results are intriguing. They could reflect his smart lifestyle for healthy aging.
His habits and overall quest to turn back the clock trace back to a harrowing experience at age 16 during a school trip to Manhattan, when Mirabile woke up on the floor with his shirt soaked in blood. He’d severed his tongue after a seizure. He later learned it was caused by a tumor the size of a golf ball. As a result, “I found myself contemplating my life, what I had yet to experience, and mortality – a theme that stuck with me during my year of recovery and beyond,” Mirabile told me.
For the next 15 years, he researched health and biology, integrating his learnings into his lifestyle. Then, in his early 30s, he came across an article in the journal Cell, "The Hallmarks of Aging," that outlined nine mechanisms of the body that define the aging process. Although the paper says there are no known interventions to delay some of these mechanisms, others, such as inflammation, struck Mirabile as actionable. Reading the paper was his “moment of epiphany” when it came to the areas where he could assert control to maximize his longevity.
He also wanted “to create a resource that my family, friends, and community could benefit from in the short term,” he said. He turned this knowledge base into a company called NOVOS dedicated to extending lifespan.
His longevity advice is more accessible than Johnson’s multi-million dollar approach, as Mirabile spends a fraction of that amount. Mirabile takes one epigenetic test per year and has a gym membership at $45 per month. Unlike Johnson, who takes 100 pills per day, Mirabile takes 10, costing another $45 monthly, including a B-complex, fish oil, Vitamins D3 and K2, and two different multivitamin supplements.
Mirabile’s methods may be easier to apply in other ways as well, since they include activities that many people enjoy anyway. He’s passionate about outdoor activities, travels frequently, and has loving relationships with friends and family, including his girlfriend and collie.
Here are a few of daily routines that could, he thinks, contribute to his impressively young bio age:
After waking at 7:45 am, he immediately drinks 16 ounces of water, with 1/4 teaspoon of sodium and potassium to replenish electrolytes. He takes his morning vitamins, brushes and flosses his teeth, puts on a facial moisturizing sunblock and goes for a brisk, two-mile walk in the sun. At 8:30 am on Mondays, Wednesdays, and Fridays he lift weights, focusing on strength and power, especially in large muscle groups.
Tuesdays, Thursdays and Saturdays are intense cardio days. He runs 5-7 miles or bicycles for 60 minutes first thing in the morning at a brisk pace, listening to podcasts. Sunday morning cardio is more leisurely.
After working out each day, he’s back home at 9:20 am, where he makes black coffee, showers, then applies serum and moisturizing sunblock to his face. He works for about three hours on his laptop, then has a protein shake and fruit.
Mirabile is a dedicated intermittent faster, with a six hour eating window in between 18 hours fasts. At 3 pm, he has lunch. The Mediterranean lineup often features salmon, sardines, olive oil, pink Himalayan salt plus potassium salt for balance, and lots of dried herbs and spices. He almost always finishes with 1/3 to 1/2 bar of dark chocolate.
If you are what you eat, Mirabile is made of mostly plants and lean meats. He follows a Mediterranean diet full of vegetables, fruits, fatty fish and other meats full of protein and unsaturated fats. “These may cost more than a meal at an American fast-food joint, but then again, not by much,” he said. Each day, he spends $25 on all his meals combined.
At 6 pm, he takes the dog out for a two-mile walk, taking calls for work or from family members along the way. At 7 pm, he dines with his girlfriend. Like lunch, this meal is heavy on widely available ingredients, including fish, fresh garlic, and fermented food like kimchi. Mirabile finishes this meal with sweets, like coconut milk yogurt with cinnamon and clove, some stevia, a mix of fresh berries and cacao nibs.
If Mirabile's epigenetic tests are accurate, his young biological age could be thanks to his healthy lifestyle, or it could come from a stroke of luck if he inherited genes that protect against aging.
At 8 pm, he wraps up work duties and watches shows with his girlfriend, applies serum and moisturizer yet again, and then meditates with the lights off. This wind-down, he said, improves his sleep quality. Wearing a sleep mask and earplugs, he’s asleep by about 10:30.
“I’ve achieved stellar health outcomes, even after having had the physiological stressors of a brain tumor, without spending a fortune,” Mirabile said. “In fact, even during times when I wasn’t making much money as a startup founder with few savings, I still managed to live a very healthy, pro-longevity lifestyle on a modest budget.”
Mirabile said living a cleaner, healthier existence is a reality that many readers can achieve. It’s certainly true that many people live in food deserts and have limited time for exercise or no access to gyms, but James R. Doty, a clinical professor of neurosurgery at Stanford, thinks many can take more action to stack the odds that they’ll “be happy and live longer.” Many of his recommendations echo aspects of Mirabile’s lifestyle.
Each night, Doty said, it’s vital to get anywhere between 6-8 hours of good quality sleep. Those who sleep less than 6 hours per night are at an increased risk of developing a whole host of medical problems, including high blood pressure, type 2 diabetes, and stroke.
In addition, it’s critical to follow Mirabile’s prescription of exercise for about one hour each day, and intensity levels matter. Doty noted that, in 2017, researchers at Brigham Young University found that people who ran at a fast pace for 30-40 minutes five days per week were, on average, biologically younger by nine years, compared to those who subscribed to more moderate exercise programs, as well as those who rarely exercised.
When it comes to nutrition, one should consider fasting for 16 hours per day, Doty said. This is known as the 16/8 method, where one’s daily calories are consumed within an eight hour window, fasting for the remaining 16 hours, just like Mirabile. Intermittent fasting is associated with cellular repair and less inflammation, though it’s not for everyone, Doty added. Consult with a medical professional before trying a fasting regimen.
Finally, Doty advised to “avoid anger, avoid stress.” Easier said than done, but not impossible. “Between stimulus and response, there is a pause and within that pause lies your freedom,” Doty said. Mirabile’s daily meditation ritual could be key to lower stress for healthy aging. Research has linked regular, long-term meditation to having a lower epigenetic age, compared to control groups.
Many other factors could apply. Having a life purpose, as Mirabile does with his company, has also been associated with healthy aging and lower epigenetic age. Of course, Mirabile is just one person, so it’s hard to know how his experience will apply to others. If his tests are accurate, his young biological age could be thanks to his healthy lifestyle, or it could come from a stroke of luck if he inherited genes that protect against aging. Clearly, though, any such genes did not protect him from cancer at an early age.
The third and perhaps most likely explanation: Mirabile’s very young biological age results from a combination of these factors. Some research shows that genetics account for only 25 percent of longevity. That means environmental factors could be driving the other 75 percent, such as where you live, frequency of exercise, quality of nutrition and social support.
The middle-aged – even Brian Johnson – probably can’t ever be 18 again. But more modest goals are reasonable for many. Control what you can for a longer, healthier life.