“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.
COVID Variants Are Like “a Thief Changing Clothes” – and Our Camera System Barely Exists
Whether it's "natural selection" as Darwin called it, or it's "mutating" as the X-Men called it, living organisms change over time, developing thumbs or more efficient protein spikes, depending on the organism and the demands of its environment. The coronavirus that causes COVID-19, SARS-CoV-2, is not an exception, and now, after the virus has infected millions of people around the globe for more than a year, scientists are beginning to see those changes.
The notorious variants that have popped up include B.1.1.7, sometimes called the UK variant, as well as P.1 and B.1.351, which seem to have emerged in Brazil and South Africa respectively. As vaccinations are picking up pace, officials are warning that now
is not the time to become complacent or relax restrictions because the variants aren't well understood.
Some appear to be more transmissible, and deadlier, while others can evade the immune system's defenses better than earlier versions of the virus, potentially undermining the effectiveness of vaccines to some degree. Genomic surveillance, the process of sequencing the genetic code of the virus widely to observe changes and patterns, is a critical way that scientists can keep track of its evolution and work to understand how the variants might affect humans.
"It's like a thief changing clothes"
It's important to note that viruses mutate all the time. If there were funding and personnel to sequence the genome of every sample of the virus, scientists would see thousands of mutations. Not every variant deserves our attention. The vast majority of mutations are not important at all, but recognizing those that are is a crucial tool in getting and staying ahead of the virus. The work of sequencing, analyzing, observing patterns, and using public health tools as necessary is complicated and confusing to those without years of specialized training.
Jeremy Kamil, associate professor of microbiology and immunology at LSU Health Shreveport, in Louisiana, says that the variants developing are like a thief changing clothes. The thief goes in your house, steals your stuff, then leaves and puts on a different shirt and a wig, in the hopes you won't recognize them. Genomic surveillance catches the "thief" even in those different clothes.
One of the tricky things about variants is recognizing the point at which they move from interesting, to concerning at a local level, to dangerous in a larger context.
Understanding variants, both the uninteresting ones and the potentially concerning ones, gives public health officials and researchers at different levels a useful set of tools. Locally, knowing which variants are circulating in the community helps leaders know whether mask mandates and similar measures should be implemented or discontinued, or whether businesses and schools can open relatively safely.
There's more to it than observing new variants
Analysis is complex, particularly when it comes to understanding which variants are of concern. "So the question is always if a mutation becomes common, is that a random occurrence?" says Phoebe Lostroh, associate professor of molecular biology at Colorado College. "Or is the variant the result of some kind of selection because the mutation changes some property about the virus that makes it reproduce more quickly than variants of the virus that don't have that mutation? For a virus, [mutations can affect outcomes like] how much it replicates inside a person's body, how much somebody breathes it out, whether the particles that somebody might breathe in get smaller and can lead to greater transmission."
Along with all of those factors, accurate and useful genomic surveillance requires an understanding of where variants are occurring, how they are related, and an examination of why they might be prevalent.
For example, if a potentially worrisome variant appears in a community and begins to spread very quickly, it's not time to raise a public health alarm until several important questions have been answered, such as whether the variant is spreading due to specific events, or if it's happening because the mutation has allowed the virus to infect people more efficiently. Kamil offered a hypothetical scenario to explain: Imagine that a member of a community became infected and the virus mutated. That person went to church and three more people were infected, but one of them went to a karaoke bar and while singing infected 100 other people. Examining the conditions under which the virus has spread is, therefore, an essential part of untangling whether a mutation itself made the virus more transmissible or if an infected person's behaviors contributed to a local outbreak.
One of the tricky things about variants is recognizing the point at which they move from interesting, to concerning at a local level, to dangerous in a larger context. Genomic sequencing can help with that, but only when it's coordinated. When the same mutation occurs frequently, but is localized to one region, it's a concern, but when the same mutation happens in different places at the same time, it's much more likely that the "virus is learning that's a good mutation," explains Kamil.
The process is called convergent evolution, and it was a fascinating topic long before COVID. Just as your heritage can be traced through DNA, so can that of viruses, and when separate lineages develop similar traits it's almost like scientists can see evolution happening in real time. A mutation to SARS-CoV-2 that happens in more than one place at once is a mutation that makes it easier in some way for the virus to survive and that is when it may become alarming. The widespread, documented variants P.1 and B.1.351 are examples of convergence because they share some of the same virulent mutations despite having developed thousands of miles apart.
However, even variants that are emerging in different places at the same time don't present the kind of threat SARS-CoV-2 did in 2019. "This is nature," says Kamil. "It just means that this virus will not easily be driven to extinction or complete elimination by vaccines." Although a person who has already had COVID-19 can be reinfected with a variant, "it is almost always much milder disease" than the original infection, Kamil adds. Rather than causing full-fledged disease, variants have the potiental to "penetrate herd immunity, spreading relatively quietly among people who have developed natural immunity or been vaccinated, until the virus finds someone who has no immunity yet, and that person would be at risk of hospitalization-grade severe disease or death."
Surveillance and predictions
According to Lostroh, genomic surveillance can help scientists predict what's going to happen. "With the British strain, for instance, that's more transmissible, you can measure how fast it's doubling in the population and you can sort of tell whether we should take more measures against this mutation. Should we shut things down a little longer because that mutation is present in the population? That could be really useful if you did enough sampling in the population that you knew where it was," says Lostroh. If, for example, the more transmissible strain was present in 50 percent of cases, but in another county or state it was barely present, it would allow for rolling lockdowns instead of sweeping measures.
Variants are also extremely important when it comes to the development, manufacture, and distribution of vaccines. "You're also looking at medical countermeasures, such as whether your vaccine is still effective, or if your antiviral needs to be updated," says Lane Warmbrod, a senior analyst and research associate at Johns Hopkins Center for Health Security.
Properly funded and extensive genomic surveillance could eventually help control endemic diseases, too, like the seasonal flu, or other common respiratory infections. Kamil says he envisions a future in which genomic surveillance allows for prediction of sickness just as the weather is predicted today. "It's a 51 for infection today at the San Francisco Airport. There's been detection of some respiratory viruses," he says, offering an example. He says that if you're a vulnerable person, if you're immune-suppressed for some reason, you may want to wear a mask based on the sickness report.
The U.S. has the ability, but lacks standards
The benefits of widespread genomic surveillance are clear, and the United States certainly has the necessary technology, equipment, and personnel to carry it out. But, it's not happening at the speed and extent it needs to for the country to gain the benefits.
"The numbers are improving," said Kamil. "We're probably still at less than half a percent of all the samples that have been taken have been sequenced since the beginning of the pandemic."
Although there's no consensus on how many sequences is ideal for a robust surveillance program, modeling performed by the company Illumina suggests about 5 percent of positive tests should be sequenced. The reasons the U.S. has lagged in implementing a sequencing program are complex and varied, but solvable.
Perhaps the most important element that is currently missing is leadership. In order to conduct an effective genomic surveillance program, there need to be standards. The Johns Hopkins Center for Health Security recently published a paper with recommendations as to what kinds of elements need to be standardized in order to make the best use of sequencing technology and analysis.
"Along with which bioinformatic pipelines you're going to use to do the analyses, which sequencing strategy protocol are you going to use, what's your sampling strategy going to be, how is the data is going to be reported, what data gets reported," says Warmbrod. Currently, there's no guidance from the CDC on any of those things. So, while scientists can collect and report information, they may be collecting and reporting different information that isn't comparable, making it less useful for public health measures and vaccine updates.
Globally, one of the most important tools in making the information from genomic surveillance useful is GISAID, a platform designed for scientists to share -- and, importantly, to be credited for -- their data regarding genetic sequences of influenza. Originally, it was launched as a database of bird flu sequences, but has evolved to become an essential tool used by the WHO to make flu vaccine virus recommendations each year. Scientists who share their credentials have free access to the database, and anyone who uses information from the database must credit the scientist who uploaded that information.
Safety, logistics, and funding matter
Scientists at university labs and other small organizations have been uploading sequences to GISAID almost from the beginning of the pandemic, but their funding is generally limited, and there are no standards regarding information collection or reporting. Private, for-profit labs haven't had motivation to set up sequencing programs, although many of them have the logistical capabilities and funding to do so. Public health departments are understaffed, underfunded, and overwhelmed.
University labs may also be limited by safety concerns. The SARS-CoV-2 virus is dangerous, and there's a question of how samples should be transported to labs for sequencing.
Larger, for-profit organizations often have the tools and distribution capabilities to safely collect and sequence samples, but there hasn't been a profit motive. Genomic sequencing is less expensive now than ever before, but even at $100 per sample, the cost adds up -- not to mention the cost of employing a scientist with the proper credentials to analyze the sequence.
The path forward
The recently passed COVID-19 relief bill does have some funding to address genomic sequencing. Specifically, the American Rescue Plan Act includes $1.75 billion in funding for the Centers for Disease Control and Prevention's Advanced Molecular Detection (AMD) program. In an interview last month, CDC Director Rochelle Walensky said that the additional funding will be "a dial. And we're going to need to dial it up." AMD has already announced a collaboration called the Sequencing for Public Health Emergency Response, Epidemiology, and Surveillance (SPHERES) Initiative that will bring together scientists from public health, academic, clinical, and non-profit laboratories across the country with the goal of accelerating sequencing.
Such a collaboration is a step toward following the recommendations in the paper Warmbrod coauthored. Building capacity now, creating a network of labs, and standardizing procedures will mean improved health in the future. "I want to be optimistic," she says. "The good news is there are a lot of passionate, smart, capable people who are continuing to work with government and work with different stakeholders." She cautions, however, that without a national strategy we won't succeed.
"If we maximize the potential and create that framework now, we can also use it for endemic diseases," she says. "It's a very helpful system for more than COVID if we're smart in how we plan it."
Since the beginning of life on Earth, plants have been naturally converting sunlight into energy. This photosynthesis process that's effortless for them has been anything but for scientists who have been trying to achieve artificial photosynthesis for the last half a century with the goal of creating a carbon-neutral fuel. Such a fuel could be a gamechanger — rather than putting CO2 back into the atmosphere like traditional fuels do, it would take CO2 out of the atmosphere and convert it into usable energy.
If given the option between a carbon-neutral fuel at the gas station and a fuel that produces carbon dioxide in spades -- and if costs and effectiveness were equal --who wouldn't choose the one best for the planet? That's the endgame scientists are after. A consumer switch to clean fuel could have a huge impact on our global CO2 emissions.
Up until this point, the methods used to make liquid fuel from atmospheric CO2 have been expensive, not efficient enough to really get off the ground, and often resulted in unwanted byproducts. But now, a new technology may be the key to unlocking the full potential of artificial photosynthesis. At the very least, it's a step forward and could help make a dent in atmospheric CO2 reduction.
"It's an important breakthrough in artificial photosynthesis," says Qian Wang, a researcher in the Department of Chemistry at Cambridge University and lead author on a recent study published in Nature about an innovation she calls "photosheets."
The latest version of the artificial leaf directly produces liquid fuel, which is easier to transport and use commercially.
These photosheets convert CO2, sunlight, and water into a carbon-neutral liquid fuel called formic acid without the aid of electricity. They're made of semiconductor powders that absorb sunlight. When in the presence of water and CO2, the electrons in the powders become excited and join with the CO2 and protons from the water molecules, reducing the CO2 in the process. The chemical reaction results in the production of formic acid, which can be used directly or converted to hydrogen, another clean energy fuel.
In the past, it's been difficult to reduce CO2 without creating a lot of unwanted byproducts. According to Wang, this new conversion process achieves the reduction and fuel creation with almost no byproducts.
The Cambridge team's new technology is a first and certainly momentous, but they're far from the only team to have produced fuel from CO2 using some form of artificial photosynthesis. More and more scientists are aiming to perfect the method in hopes of producing a truly sustainable, photosynthetic fuel capable of lowering carbon emissions.
Thanks to advancements in nanoscience, which has led to better control of materials, more successes are emerging. A team at the University of Illinois at Urbana-Champaign, for example, used gold nanoparticles as the photocatalysts in their process.
"My group demonstrated that you could actually use gold nanoparticles both as a light absorber and a catalyst in the process of converting carbon dioxide to hydrocarbons such as methane, ethane and propane fuels," says professor Prashant Jain, co-author of the study. Not only are gold nanoparticles great at absorbing light, they don't degrade as quickly as other metals, which makes them more sustainable.
That said, Jain's team, like every other research team working on artificial photosynthesis including the Cambridge team, is grappling with efficiency issues. Jain says that all parts of the process need to be optimized so the reaction can happen as quickly as possible.
"You can't just improve one [aspect], because that can lead to a decrease in performance in some other aspects," Jain explains.
The Cambridge team is currently experimenting with a range of catalysts to improve their device's stability and efficiency. Virgil Andrei, who is working on an artificial leaf design that was developed at Cambridge in 2019, was recently able to improve the performance and selectivity of the device. Now the leaf's solar-to-CO2 energy conversion efficiency is 0.2%, twice its previous efficiency.
The latest version also directly produces liquid fuel, which is easier to transport and use commercially.
In determining a method of fuel production's efficiency, one must consider how sustainable it is at every stage. That involves calculating whenever excess energy is needed to complete a step. According to Jain, in order to use CO2 for fuel production, you have to condense the CO2, which takes energy. And on the fuel production side, once the chemical reaction has created your byproducts, they need to be separated, which also takes energy.
To be truly sustainable, each part of the conversion system also needs to be durable. If parts need to be replaced often, or regularly maintained, that counts against it. Then you have to account for the system's reuse cycle. If you extract CO2 from the environment and convert it into fuel that's then put into a fuel cell, it's going to release CO2 at the other end. In order to create a fully green, carbon-neutral fuel source, that same amount of CO2 needs to be trapped and reintroduced back into the fuel conversion system.
"The cycle continues, and at each point, you will see a loss in efficiency, and depending on how much you [may also] see a loss in yield," says Jain. "And depending on what those efficiencies are at each one of those points will determine whether or not this process can be sustainable."
The science is at least a decade away from offering a competitive sustainable fuel option at scale. Streamlining a process to mimic what plants have perfected over billions of years is no small feat, but an ever-growing community of researchers using rapidly advancing technology is driving progress forward.