“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.
Should You Bank Your Kid’s Teeth for Stem Cells?
When Karen Davis attended a presentation at a dental conference in 2013, she unexpectedly discovered a service that could help her daughter, Madeline: storing stem cells derived from her teeth that potentially could be used in the future to treat her Crohn's disease.
"Even though this isn't a viable option today, I know how rapidly things can change."
Throughout high school, Madeline suffered from the painful autoimmune disorder, which wreaks havoc on the gastrointestinal system and can lead to life-threatening complications.
"I leave no stone unturned when it comes to medical care and this resonated with me," says Davis, a Dallas-based dental hygienist who was encouraged by advances in stem cell research. Later that year, when Madeline got her wisdom teeth extracted, Davis shipped them off to the Store-A-Tooth company in Massachusetts, where they will be kept frozen until needed. "Even though this isn't a viable option today, I know how rapidly things can change," says Davis. "To me, this was a worthwhile investment—I didn't want to miss out on an opportunity that would provide a pathway to a cure."
Karen Davis pictured with her daughter Madeline.
(Courtesy of Karen Davis)
The process itself was straightforward. Madeline's newly extracted wisdom teeth--baby teeth can be saved, too—were bathed in a special solution, loaded into a Styrofoam container lined with cold packs and sent to the stem cell company. There, a team harvested the dental stem cells from the pulp, then grew them in culture and cryogenically preserved them. Store-A-Tooth charges $1500-1749 for tooth collection and $120 per year for storage, while other dental pulp stem cell tissue banks cost $500-$600 upfront and in the $120 range annually for storage.
The rationale here is that if you missed out on banking your baby's umbilical cord blood, this gives you another chance to harvest their stem cells. "If their child later develops an illness that could be managed or even cured with stem cell therapy, this is an insurance policy," says Amr Moursi, DDS, PhD, chair of the department of pediatric dentistry at New York University College of Dentistry.
But is there a genuine potential here for some effective treatments in the relatively near future—or is this just another trendy fad? Scientific opinion is decidedly mixed. Stem cells have been heralded as the next frontier in medicine because of their versatility: with a little chemical coaxing, they can be transformed into different cell types, such as heart, blood or brain cells, to create tissue that can mend damaged body parts. Because they're taken from your own body, there's little chance of rejection, which means patients don't have to take strong antirejection drugs that can have all sorts of unpleasant side effects for the rest of their lives.
However, while stem cells are immature cells found in different tissues, ranging from abdominal fat to bone marrow, there is a vast difference between the stem cells found in cord blood and in teeth. Cord blood, which is culled from the umbilical cord when a baby is born, contains what are called hematopoietic stem cells (HSCs), which can mature into other blood cells. These type of stem cells have already been approved by the U.S. Food and Drug Administration to treat patients—especially children--with blood cancers, such as leukemias and lymphomas, and certain blood disorders like sickle cell anemia.
In contrast, stem cells in teeth are called mesenchymal stem cells (MSCs), which are found in dental pulp, the tissue in the center of the tooth that's filled with nerves and blood vessels. MSCs are adult stem cells normally found in the bone marrow that can transform into bone, fat, and cartilage cells, and also aid in the formation of blood stem cells.
"Right now we just don't have rigorous evidence that they can be used in that fashion and have real benefit."
Small studies on lab animals suggest that MSCs secrete growth factors—hormonal steroids or proteins—that can nurture ailing cells, act as powerful anti-inflammatory agents that could tame autoimmune disorders like the one that plagues Karen Davis's daughter, and may even generate new nerve and muscle tissue. Preliminary research suggests they potentially could treat medical conditions as varied as heart disease, spinal cord injury and type 1 diabetes by generating new cells, which can replace damaged or dead cells.
But this is all very early research and there's a vast difference between how cells behave in the tightly controlled environment of a lab versus the real world in a diverse population of human patients. "Right now we just don't have rigorous evidence that they can be used in that fashion and have real benefit," says Pamela G. Robey, PhD, chief of the skeletal biology section at the National Institute of Dental and Craniofacial Research at the National Institutes of Health.
Robey should know—she headed the research team that discovered stem cells in human baby teeth and in wisdom teeth more than fifteen years ago. She believes prospects are better using these stem cells for tooth repair: research suggests they may be able to fix cracked teeth, repair bone defects caused by gum disease, or in root canal therapy, where they can be used to replace infected tissue with regenerated healthy pulp.
In the meantime, though, there are no clinical applications for MSCs. "These tooth banking companies aren't doing their own research," says Leigh Turner, a bioethicist at the University of Minnesota who monitors stem cell clinics. "They cobble together reports of early research in humans or from animal studies in an effort to provide a narrative to make it seem like it is evidence based."
Still, in all fairness, tooth banking companies aren't making the kind of extravagant claims made by stem cell clinics, which operate in a gray area of the law and purport to treat everything from chronic lung disease to Alzheimer's. "We don't know when therapies will be available using these cells because the pace of research is hard to predict," says Peter Verlander, PhD, a molecular geneticist and chief scientific officer of Provia Laboratories, the parent company of Store-A-Tooth. "But for parents who regretted not banking their child's cord blood, especially if they later develop a disease like diabetes, this is another opportunity."
But the jury is still out if this is truly a good investment. Moursi, a national spokesperson for the American Academy of Pediatric Dentistry who fields queries about this practice from a dozen or so families a year, concludes: "If you could afford it, and know the risks, benefits and current limitations, then it is something to consider."
The Death Predictor: A Helpful New Tool or an Ethical Morass?
Whenever Eric Karl Oermann has to tell a patient about a terrible prognosis, their first question is always: "how long do I have?" Oermann would like to offer a precise answer, to provide some certainty and help guide treatment. But although he's one of the country's foremost experts in medical artificial intelligence, Oermann is still dependent on a computer algorithm that's often wrong.
Doctors are notoriously terrible at guessing how long their patients will live.
Artificial intelligence, now often called deep learning or neural networks, has radically transformed language and image processing. It's allowed computers to play chess better than the world's grand masters and outwit the best Jeopardy players. But it still can't precisely tell a doctor how long a patient has left – or how to help that person live longer.
Someday, researchers predict, computers will be able to watch a video of a patient to determine their health status. Doctors will no longer have to spend hours inputting data into medical records. And computers will do a better job than specialists at identifying tiny tumors, impending crises, and, yes, figuring out how long the patient has to live. Oermann, a neurosurgeon at Mount Sinai, says all that technology will allow doctors to spend more time doing what they do best: talking with their patients. "I want to see more deep learning and computers in a clinical setting," he says, "so there can be more human interaction." But those days are still at least three to five years off, Oermann and other researchers say.
Doctors are notoriously terrible at guessing how long their patients will live, says Nigam Shah, an associate professor at Stanford University and assistant director of the school's Center for Biomedical Informatics Research. Doctors don't want to believe that their patient – whom they've come to like – will die. "Doctors over-estimate survival many-fold," Shah says. "How do you go into work, in say, oncology, and not be delusionally optimistic? You have to be."
But patients near the end of life will get better treatment – and even live longer – if they are overseen by hospice or palliative care, research shows. So, instead of relying on human bias to select those whose lives are nearing their end, Shah and his colleagues showed that they could use a deep learning algorithm based on medical records to flag incoming patients with a life expectancy of three months to a year. They use that data to indicate who might need palliative care. Then, the palliative care team can reach out to treating physicians proactively, instead of relying on their referrals or taking the time to read extensive medical charts.
But, although the system works well, Shah isn't yet sure if such indicators actually get the appropriate patients into palliative care. He's recently partnered with a palliative care doctor to run a gold-standard clinical trial to test whether patients who are flagged by this algorithm are indeed a better match for palliative care.
"What is effective from a health system perspective might not be effective from a treating physician's perspective and might not be effective from the patient's perspective," Shah notes. "I don't have a good way to guess everybody's reaction without actually studying it." Whether palliative care is appropriate, for instance, depends on more than just the patient's health status. "If the patient's not ready, the family's not ready and the doctor's not ready, then you're just banging your head against the wall," Shah says. "Given limited capacity, it's a waste of resources" to put that person in palliative care.
The algorithm isn't perfect, but "on balance, it leads to better decisions more often."
Alexander Smith and Sei Lee, both palliative care doctors, work together at the University of California, San Francisco, to develop predictions for patients who come to the hospital with a complicated prognosis or a history of decline. Their algorithm, they say, helps decide if this patient's problems – which might include diabetes, heart disease, a slow-growing cancer, and memory issues – make them eligible for hospice. The algorithm isn't perfect, they both agree, but "on balance, it leads to better decisions more often," Smith says.
Bethany Percha, an assistant professor at Mount Sinai, says that an algorithm may tell doctors that their patient is trending downward, but it doesn't do anything to change that trajectory. "Even if you can predict something, what can you do about it?" Algorithms may be able to offer treatment suggestions – but not what specific actions will alter a patient's future, says Percha, also the chief technology officer of Precise Health Enterprise, a product development group within Mount Sinai. And the algorithms remain challenging to develop. Electronic medical records may be great at her hospital, but if the patient dies at a different one, her system won't know. If she wants to be certain a patient has died, she has to merge social security records of death with her system's medical records – a time-consuming and cumbersome process.
An algorithm that learns from biased data will be biased, Shah says. Patients who are poor or African American historically have had worse health outcomes. If researchers train an algorithm on data that includes those biases, they get baked into the algorithms, which can then lead to a self-fulfilling prophesy. Smith and Lee say they've taken race out of their algorithms to avoid this bias.
Age is even trickier. There's no question that someone's risk of illness and death goes up with age. But an 85-year-old who breaks a hip running a marathon should probably be treated very differently than an 85-year-old who breaks a hip trying to get out of a chair in a dementia care unit. That's why the doctor can never be taken out of the equation, Shah says. Human judgment will always be required in medical care and an algorithm should never be followed blindly, he says.
Experts say that the flaws in artificial intelligence algorithms shouldn't prevent people from using them – carefully.
Researchers are also concerned that their algorithms will be used to ration care, or that insurance companies will use their data to justify a rate increase. If an algorithm predicts a patient is going to end up back in the hospital soon, "who's benefitting from knowing a patient is going to be readmitted? Probably the insurance company," Percha says.
Still, Percha and others say, the flaws in artificial intelligence algorithms shouldn't prevent people from using them – carefully. "These are new and exciting tools that have a lot of potential uses. We need to be conscious about how to use them going forward, but it doesn't mean we shouldn't go down this road," she says. "I think the potential benefits outweigh the risks, especially because we've barely scratched the surface of what big data can do right now."