“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.
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Stacey Khoury felt more fatigued and out of breath than she was used to from just walking up the steps to her job in retail jewelry sales in Nashville, Tennessee. By the time she got home, she was more exhausted than usual, too.
"I just thought I was working too hard and needed more exercise," recalls the native Nashvillian about those days in December 2010. "All of the usual excuses you make when you're not feeling 100%."
As a professional gemologist, being hospitalized during peak holiday sales season wasn't particularly convenient. There was no way around it though when her primary care physician advised Khoury to see a blood disorder oncologist because of her disturbing blood count numbers. As part of a routine medical exam, a complete blood count screens for a variety of diseases and conditions that affect blood cells, such as anemia, infection, inflammation, bleeding disorders and cancer.
"If approved, it will allow more patients to potentially receive a transplant than would have gotten one before."
While she was in the hospital, a bone marrow biopsy revealed that Khoury had acute myeloid leukemia, or AML, a high-risk blood cancer. After Khoury completed an intense first round of chemotherapy, her oncologist recommended a bone marrow transplant. The potentially curative treatment for blood-cancer patients requires them to first receive a high dose of chemotherapy. Next, an infusion of stem cells from a healthy donor's bone marrow helps form new blood cells to fight off the cancer long-term.
Each year, approximately 8,000 patients in the U.S. with AML and other blood cancers receive a bone marrow transplant from a donor, according to the Center for International Blood and Marrow Transplant Research. But Khoury wasn't so lucky. She ended up being among the estimated 40% of patients eligible for bone marrow transplants who don't receive one, usually because there's no matched donor available.
Khoury's oncologist told her about another option. She could enter a clinical trial for an investigational cell therapy called omidubicel, which is being developed by Israeli biotech company Gamida Cell. The company's cell therapy, which is still experimental, could up a new avenue of treatment for cancer patients who can't get a bone marrow transplant.
Omidubicel consists of stem cells from cord blood that have been expanded using Gamida's technology to ensure there are enough cells for a therapeutic dose. The company's technology allows the immature cord blood cells to multiply quickly in the lab. Like a bone marrow transplant, the goal of the therapy is to make sure the donor cells make their way to the bone marrow and begin producing healthy new cells — a process called engraftment.
"If approved, it will allow more patients to potentially receive a transplant than would have gotten one before, so there's something very novel and exciting about that," says Ronit Simantov, Gamida Cell's chief medical officer.
Khoury and her husband Rick packed up their car and headed to the closest trial site, the Duke University School of Medicine, roughly 500 miles away. There they met with Mitchell Horowitz, a stem cell transplant specialist at Duke and principal investigator for Gamida's omidubicel study in the U.S.
He told Khoury she was a perfect candidate for the trial, and she enrolled immediately. "When you have one of two decisions, and it's either do this or you're probably not going to be around, it was a pretty easy decision to make, and I am truly thankful for that," she says.
Khoury's treatment started at the end of March 2011, and she was home by July 4 that year. She say the therapy "worked the way the doctors wanted it to work." Khoury's blood counts were rising quicker than the people who had bone marrow matches, and she was discharged from Duke earlier than other patients were.
By expanding the number of cord blood cells — which are typically too few to treat an adult — omidubicel allows doctors to use cord blood for patients who require a transplant but don't have a donor match for bone marrow.
Patients receiving omidubicel first get a blood test to determine their human leukocyte antigen, or HLA, type. This protein is found on most cells in the body and is an important regulator of the immune system. HLA typing is used to match patients to bone marrow and cord blood donors, but cord blood doesn't require as close of a match.
Like bone marrow transplants, one potential complication of omidubicel is graft-versus-host disease, when the donated bone marrow or stem cells register the recipient's body as foreign and attack the body. Depending on the severity of the response, according to the Mayo Clinic, treatment includes medication to suppress the immune system, such as steroids. In clinical trials, the occurrence of graft-versus-host disease with omidubicel was comparable with traditional bone marrow transplants.
"Transplant doctors are working on improving that," Simantov says. "A number of new therapies that specifically address graft-versus-host disease will be making some headway in the coming months and years."
Gamida released the results of the Phase 3 study in February and continues to follow Khoury and the other study patients for their long-term outcomes. The large randomized trial evaluated the safety and efficacy of omidubicel compared to standard umbilical cord blood transplants in patients with blood cancer who didn't have a suitable bone marrow donor. Around 120 patients aged 12 to 65 across the U.S., Europe and Asia were included in the trial. The study found that omidubicel resulted in faster recovery, fewer bacterial and viral infections and fewer days in the hospital.
The company plans to seek FDA approval this year. Simantov anticipates the therapy will receive FDA approval by 2022.
"Opening up cord blood transplants is very important, especially for people of diverse ethnic backgrounds," says oncologist Gary Schiller, principal investigator at the David Geffen School of Medicine at UCLA for Gamida Cell's mid- and late-stage trials. "This expansion technology makes a big difference because it makes cord blood an available option for those who do not have another donor source."
As for Khoury, who proudly celebrated the anniversary of her first transplant in April—she remains cancer free and continues to work full-time as a gemologist. When she has a little free time, she enjoys gardening, sewing, or maybe traveling to national parks like Yellowstone or the Grand Canyon with her husband Rick.