“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.
Sarah Mancoll was 22 years old when she noticed a bald spot on the back of her head. A dermatologist confirmed that it was alopecia aerata, an autoimmune disorder that causes hair loss.
Of 213 new drugs approved from 2003 to 2012, only five percent included any data from pregnant women.
She successfully treated the condition with corticosteroid shots for nearly 10 years. Then Mancoll and her husband began thinking about starting a family. Would the shots be safe for her while pregnant? For the fetus? What about breastfeeding?
Mancoll consulted her primary care physician, her dermatologist, even a pediatrician. Without clinical data, no one could give her a definitive answer, so she stopped treatment to be "on the safe side." By the time her son was born, she'd lost at least half her hair. She returned to her Washington, D.C., public policy job two months later entirely bald—and without either eyebrows or eyelashes.
After having two more children in quick succession, Mancoll recently resumed the shots but didn't forget her experience. Today, she is an advocate for including more pregnant and lactating women in clinical studies so they can have more information about therapies than she did.
"I live a very privileged life, and I'll do just fine with or without hair, but it's not just about me," Mancoll said. "It's about a huge population of women who are being disenfranchised…They're invisible."
About 4 million women give birth each year in the United States, and many face medical conditions, from hypertension and diabetes to psychiatric disorders. A 2011 study showed that most women reported taking at least one medication while pregnant between 1976 and 2008. But for decades, pregnant and lactating women have been largely excluded from clinical drug studies that rigorously test medications for safety and effectiveness.
An estimated 98 percent of government-approved drug treatments between 2000 and 2010 had insufficient data to determine risk to the fetus, and close to 75 percent had no human pregnancy data at all. All told, of 213 new pharmaceuticals approved from 2003 to 2012, only five percent included any data from pregnant women.
But recent developments suggest that could be changing. Amid widespread concerns about increased maternal mortality rates, women's health advocates, physicians, and researchers are sensing and encouraging a cultural shift toward protecting women through responsible research instead of from research.
"The question is not whether to do research with pregnant women, but how," Anne Drapkin Lyerly, professor and associate director of the Center for Bioethics at the University of North Carolina at Chapel Hill, wrote last year in an op-ed. "These advances are essential. It is well past time—and it is morally imperative—for research to benefit pregnant women."
"In excluding pregnant women from drug trials to protect them from experimentation, we subject them to uncontrolled experimentation."
To that end, the American College of Obstetricians and Gynecologists' Committee on Ethics acknowledged that research trials need to be better designed so they don't "inappropriately constrain the reproductive choices of study participants or unnecessarily exclude pregnant women." A federal task force also called for significantly expanded research and the removal of regulatory barriers that make it difficult for pregnant and lactating women to participate in research.
Several months ago, a government change to a regulation known as the Common Rule took effect, removing pregnant women as a "vulnerable population" in need of special protections -- a designation that had made it more difficult to enroll them in clinical drug studies. And just last week, the U.S. Food and Drug Administration (FDA) issued new draft guidances for industry on when and how to include pregnant and lactating women in clinical trials.
Inclusion is better than the absence of data on their treatment, said Catherine Spong, former chair of the federal task force.
"It's a paradox," said Spong, professor of obstetrics and gynecology and chief of maternal fetal medicine at University of Texas Southwestern Medical Center. "There is a desire to protect women and fetuses from harm, which is translated to a reluctance to include them in research. By excluding them, the evidence for their care is limited."
Jacqueline Wolf, a professor of the history of medicine at Ohio University, agreed.
"In excluding pregnant women from drug trials to protect them from experimentation, we subject them to uncontrolled experimentation," she said. "We give them the medication without doing any research, and that's dangerous."
Women, of course, don't stop getting sick or having chronic medical conditions just because they are pregnant or breastfeeding, and conditions during pregnancy can affect a baby's health later in life. Evidence-based data is important for other reasons, too.
Pregnancy can dramatically change a woman's physiology, affecting how drugs act on her body and how her body acts or reacts to drugs. For instance, pregnant bodies can more quickly clear out medications such as glyburide, used during diabetes in pregnancy to stabilize high blood-sugar levels, which can be toxic to the fetus and harmful to women. That means a regular dose of the drug may not be enough to control blood sugar and prevent poor outcomes.
Pregnant patients also may be reluctant to take needed drugs for underlying conditions (and doctors may be hesitant to prescribe them), which in turn can cause more harm to the woman and fetus than had they been treated. For example, women who have severe asthma attacks while pregnant are at a higher risk of having low-birthweight babies, and pregnant women with uncontrolled diabetes in early pregnancy have more than four times the risk of birth defects.
Current clinical trials involving pregnant women are assessing treatments for obstructive sleep apnea, postpartum hemorrhage, lupus, and diabetes.
For Kate O'Brien, taking medication during her pregnancy was a matter of life and death. A freelance video producer who lives in New Jersey, O'Brien was diagnosed with tuberculosis in 2015 after she became pregnant with her second child, a boy. Even as she signed hospital consent forms, she had no idea if the treatment would harm him.
"It's a really awful experience," said O'Brien, who now is active with We are TB, an advocacy and support network. "All they had to tell me about the medication was just that women have been taking it for a really long time all over the world. That was the best they could do."
More and more doctors, researchers and women's health organizations and advocates are calling that unacceptable.
By indicating that filling current knowledge gaps is "a critical public health need," the FDA is signaling its support for advancing research with pregnant women, said Lyerly, also co-founder of the Second Wave Initiative, which promotes fair representation of the health interests of pregnant women in biomedical research and policies. "It's a very important shift."
Research with pregnant women can be done ethically, Lyerly said, whether by systematically collecting data from those already taking medications or enrolling pregnant women in studies of drugs or vaccines in development.
Current clinical trials involving pregnant women are assessing treatments for obstructive sleep apnea, postpartum hemorrhage, lupus, and diabetes. Notable trials in development target malaria and HIV prevention in pregnancy.
"It clearly is doable to do this research, and test trials are important to provide evidence for treatment," Spong said. "If we don't have that evidence, we aren't making the best educated decisions for women."
The news last November that a rogue Chinese scientist had genetically altered the embryos of a pair of Chinese twins shocked the world. But although this use of advanced technology to change the human gene pool was premature, it was a harbinger of how genetic science will alter our healthcare, the way we make babies, the nature of the babies we make, and, ultimately, our sense of who and what we are as a species.
The healthcare applications of the genetics revolution are merely stations along the way to the ultimate destination.
But while the genetics revolution has already begun, we aren't prepared to handle these Promethean technologies responsibly.
By identifying the structure of DNA in the 1950s, Watson, Crick, Wilkins, and Franklin showed that the book of life was written in the DNA double helix. When the human genome project was completed in 2003, we saw how this book of human life could be transcribed. Painstaking research paired with advanced computational algorithms then showed what increasing numbers of genes do and how the genetic book of life can be read.
Now, with the advent of precision gene editing tools like CRISPR, we are seeing that the book of life -- and all biology -- can be re-written. Biology is being recognized as another form of readable, writable, and hackable information technology with we humans as the coders.
The impact of this transformation is being first experienced in our healthcare. Gene therapies including those extracting, re-engineering, then reintroducing a person's own cells enhanced into cancer-fighting supercells are already performing miracles in clinical trials. Thousands of applications have already been submitted to regulators across the globe for trials using gene therapies to address a host of other diseases.
Recently, the first gene editing of cells inside a person's body was deployed to treat the genetically relatively simple metabolic disorder Hunter syndrome, with many more applications to come. These new approaches are only the very first steps in our shift from the current system of generalized medicine based on population averages to precision medicine based on each patient's individual biology to predictive medicine based on AI-generated estimations of a person's future health state.
Jamie Metzl's groundbreaking new book, Hacking Darwin: Genetic Engineering and the Future of Humanity, explores how the genetic revolution is transforming our healthcare, the way we make babies, and the nature of and babies we make, what this means for each of us, and what we must all do now to prepare for what's coming.
This shift in our healthcare will ensure that millions and then billions of people will have their genomes sequenced as the foundation of their treatment. Big data analytics will then be used to compare at scale people's genotypes (what their genes say) to their phenotypes (how those genes are expressed over the course of their lives).
These massive datasets of genetic and life information will then make it possible to go far beyond the simple genetic analysis of today and to understand far more complex human diseases and traits influenced by hundreds or thousands of genes. Our understanding of this complex genetic system within the vaster ecosystem of our bodies and the environment around us will transform healthcare for the better and help us cure terrible diseases that have plagued our ancestors for millennia.
But as revolutionary as this challenge will be for medicine, the healthcare applications of the genetics revolution are merely stations along the way to the ultimate destination – a deep and fundamental transformation of our evolutionary trajectory as a species.
A first inkling of where we are heading can be seen in the direct-to-consumer genetic testing industry. Many people around the world have now sent their cheek swabs to companies like 23andMe for analysis. The information that comes back can tell people a lot about relatively simple genetic traits like carrier status for single gene mutation diseases, eye color, or whether they hate the taste of cilantro, but the information about complex traits like athletic predisposition, intelligence, or personality style today being shared by some of these companies is wildly misleading.
This will not always be the case. As the genetic and health data pools grow, analysis of large numbers of sequenced genomes will make it possible to apply big data analytics to predict some very complex genetic disease risks and the genetic components of traits like height, IQ, temperament, and personality style with increasing accuracy. This process, called "polygenic scoring," is already being offered in beta stage by a few companies and will become an ever bigger part of our lives going forward.
The most profound application of all this will be in our baby-making. Before making a decision about which of the fertilized eggs to implant, women undergoing in vitro fertilization can today elect to have a small number of cells extracted from their pre-implanted embryos and sequenced. With current technology, this can be used to screen for single-gene mutation diseases and other relatively simple disorders. Polygenic scoring, however, will soon make it possible to screen these early stage pre-implanted embryos to assess their risk of complex genetic diseases and even to make predictions about the heritable parts of complex human traits. The most intimate elements of being human will start feeling like high-pressure choices needing to be made by parents.
The limit of our imagination will become the most significant barrier to our recasting biology.
Adult stem cell technologies will then likely make it possible to generate hundreds or thousands of a woman's own eggs from her blood sample or skin graft. This would blow open the doors of reproductive possibility and allow parents to choose embryos with exceptional potential capabilities from a much larger set of options.
The complexity of human biology will place some limits to the extent of possible gene edits that might be made to these embryos, but all of biology, including our own, is extremely flexible. How else could all the diversity of life have emerged from a single cell nearly four billion years ago? The limit of our imagination will become the most significant barrier to our recasting biology.
But while we humans are gaining the powers of the gods, we aren't at all ready to use them.
The same tools that will help cure our worst afflictions, save our children, help us live longer, healthier, more robust lives will also open the door to potential abuses. Prospective parents with the best of intentions or governments with lax regulatory structures or aggressive ideas of how population-wide genetic engineering might be used to enhance national competitiveness or achieve some other goal could propel us into a genetic arms race that could undermine our essential diversity, dangerously divide societies, lead to dangerous, destabilizing, and potentially even deadly conflicts between us, and threaten our very humanity.
But while the advance of genetic technologies is inevitable, how it plays out is anything but. If we don't want the genetic revolution to undermine our species or lead to grave conflicts between genetic haves and have nots or between societies opting in and those opting out, now is the time when we need to make smart decisions based on our individual and collective best values. Although the technology driving the genetic revolution is new, the value systems we will need to optimize the benefits and minimize the harms of this massive transformation are ones we have been developing for thousands of years.
And while some very smart and well-intentioned scientists have been meeting to explore what comes next, it won't be enough for a few of even our wisest prophets to make decisions about the future of our species that will impact everyone. We'll also need smart regulations on both the national and international levels.
Every country will need to have its own regulatory guidelines for human genetic engineering based on both international best practices and the country's unique traditions and values. Because we are all one species, however, we will also ultimately need to develop guidelines that can apply to all of us.
As a first step toward making this possible, we must urgently launch a global, species-wide education effort and inclusive dialogue on the future of human genetic engineering that can eventually inform global norms that will need to underpin international regulations. This process will not be easy, but the alternative of an unregulated genetic arms race would be far worse.
The overlapping genomics and AI revolutions may seem like distant science fiction but are closer than you think. Far sooner than most people recognize, the inherent benefits of these technologies and competition between us will spark rapid adoption. Before that spark ignites, we have a brief moment to come together as a species like we never have before to articulate and translate into action the future we jointly envision. The north star of our best shared values can help us navigate the almost unimaginable opportunities and very real challenges that lie ahead.