Brain Freeze

The idea of cryopreservation is simple and beautiful: When a person is beyond saving by modern methods, we can give them another lifeline. First, perfuse their bloodstream with antifreeze. Once administered, it’s possible to safely cool the body to incredibly low temperatures without ice forming inside organs and crushing delicate cells. Cold slows chemical reactions, all of them: According to the Arrhenius equation, every 10 °C decrease in temperature halves chemical reaction rates. A coolant like liquid nitrogen halves the ordinary rate of chemical reactions 22 times over. That stretches a single second of life into 48 days. 

Cryopreservation can commute a death sentence. The hope is that although we may not know how to cure a terminal illness today, someday, we might. After all, 48 days for every second buys a lot of time to discover a cure.

As you might expect, this simple idea turns out to be monstrously complicated and exacting in practice. The human body is much more finicky than the field’s founders in the 1960s had hoped. But the techniques exist. I’ve spent my life helping to develop them. The cryopreservation available today is far removed from the ideal — fussier, less elegant, and limited in what it can offer. There is much room for improvement and much work to be done. Still, it works, at least for a particular definition of working. We can’t yet warm up a frozen person and revive them, and it’s not certain we ever will. What we can do is reliably preserve memory in an information-theoretic sense. If our current understanding of neuroscience is correct, then we have the techniques to preserve all the information that makes a person who they are — albeit in a form that's impossible to extract with today's technology. 

Getting there has been a long journey, from the visionary days in the 1960s, to the fits and starts of the 1970s, the hard empirical lessons of the 1980s, to today. The field’s progress is a triumphant demonstration of what a small, dedicated, heterodox group of people can do — and an object lesson in what they can get wrong. 

Fertility research laid the groundwork for human cryopreservation. In 1949, English biologist Christopher Polge demonstrated that it was possible to freeze sperm cells under controlled conditions, thaw them, and return them to life. Three years later, Polge published results showing he had hatched the first chicks conceived from frozen sperm, proving that their cellular functions—including metabolism and the machinery for swimming—survived intact.

In 1964, a Michigan physics teacher named Robert Ettinger published The Prospect of Immortality. In it, he argued that human preservation, previously the realm of science fiction, might be as simple as freezing them. At a cellular level, the problem was demonstrably solved: Science had proven that individual cells — the building blocks of life — could be preserved and resuscitated using a simple preparation of one-and-a-half-molar glycerine as antifreeze and dry ice (-79°C) as coolant. Ettinger believed that from there, preserving tissues, organs, and even whole organisms was largely a matter of scale. He anticipated that his book would spark rapid institutional change — cryopreservation might be adopted as the universal standard for end-of-life care within the next five years, displacing a tremendous amount of suffering and death. Soon,  humanity might  have a fully reversible preservation protocol. Ettinger believed the damage done by simple freezing was probably recoverable. “It is not inconceivable,” he wrote, “that [in the future] huge surgeon-machines, working 24 hours a day for decades or even centuries, will tenderly restore the frozen brains, cell by cell, or even molecule by molecule in critical areas.”

Ettinger was too optimistic. There were no worldwide freezer programs instituted in the 1970s. Still, there were ripples of response. Scatterings of amateurs and lone researchers took up the mantle. And in 1967, three years after Ettinger published his book, an organization named the Cryonics Society of California performed the very first preservation of a human being on psychology professor James Bedford. That’s when things started to get complicated.

Because the earliest cryonics organizations were run by amateurs, they generally operated on shoestring budgets. Consequently, they all relied on next-of-kin to make ongoing payments to cover the costs of refrigeration. Grieving families would generally keep up payments for a year or two, then stop. In short order, CSC folded. And with no funds left to pay for refrigeration, their clients were left to thaw (except Bedford, who is still preserved).

Ettinger started his own cryonics organization, the Cryonics Society of Michigan, in 1967. A second generation of cryonics organizations appeared alongside it throughout the 1970s. These included Alcor, the largest of the three major cryonics organizations in operation today, founded in 1972. These companies learned from CSC’s bankruptcy and required upfront payment to fund the costs of refrigeration indefinitely. This is cheaper than it sounds — they adapted the endowment model commonly used to fund graveyard plots. In a common scenario, the cryonics patient would fund the up-front costs of cryopreservation by using a life insurance policy. Then, Alcor would use interest on that initial endowment to pay for refrigeration in perpetuity.

The basic process Alcor and other cryonics organizations use today is essentially the same one they developed in the early ‘70s. Once a patient signs up, Alcor sends them a medical ID bracelet with a specific end-of-life directive: “no autopsy or embalming.” Instead, cool the body down, inject a blood thinner to prevent clotting, perform chest compressions to keep blood circulating, and notify Alcor immediately.

When the Alcor team arrives, they hook up the body to a heart bypass machine. First, they cool the body to near freezing while replacing the patient's blood with a clear washout solution. This process averts postmortem blood clotting, which could gum up the vascular system and block cells, or even whole tissues, from absorbing the anti-freezing agent. In the second stage, cryoprotectant — a chemical cocktail which includes antifreeze — is slowly introduced, further slowing body temperature. Finally, they pack the body in dry ice and ship it to their facility in Scottsdale, AZ, where it is stored in a large thermos-like dewar, a vacuum container, and lowered to liquid nitrogen temperatures.

What about the next stage — reviving people who have been frozen? Let me be clear up front: It has never been done. Despite occasional urban legends, no complex living organism has undergone the full cryopreservation protocol and been revived. We don’t know how. Alcor’s hope, from the 60s to the present day, is that future technology will be able to repair the physical damage incurred en route to suspended time. There are reasons to be hopeful this works. But there are also many reasons for concern.

First, the technological leap from preserving individual cells to preserving tissues and organs proved harder than researchers thought. Although Polge’s pioneering work established that individual cells could survive freezing intact, delicate intercellular connections are another matter. Freeze and thaw a handful of single cells or a liter of blood and they’ll mostly work just fine. Do the same to a kidney and the thawed organ will fail, even as its individual cells survive largely intact. The intercellular connections are crushed and ripped by partial ice formation, like washing away the mortar between bricks in a building. 

Then there’s the fact that end-of-life interventions are messy. Even before death, people may have blood clots clogging their circulatory system. They commonly die late at night when no one is around, due to the biology of circadian rhythms. And they sometimes die slowly, slipping into an agonal coma and accumulating serious brain damage in the hours and weeks leading up to legal death. Death is also a distressing time. Relatives of the deceased don’t always make the phone call to Alcor, even supposing they remember — and support something as fringe as cryopreservation. Then the cryopreservation response teams, run by volunteers, have frequent logistical problems: dead batteries, delays, faulty equipment. Sometimes, it takes days for the call to be made. Sometimes people die alone and it takes much longer.

Just how much room for error is there? What is the window of time before brains are not salvageable? Minutes, hours, or days? How do brain injuries, circulation problems, or long periods of pre-death coma affect the outcome? 

Historically, the attitude of the cryonics community has been: “We don’t know how well our procedures work. But when it comes to matters of life and death, anything we can do is better than nothing. If you’ve asked us to preserve you, we will do it. In the end, we can hope that future technological developments can undo the imperfections of what we can achieve today.”

To their credit, this insistence on preserving their clients by all available means has required courage and tenacity. This position is admirable. It’s also insufficient. A harsh truth of cryonics is that “Anything we can do” is not always better than nothing — a brain that is preserved too late and whose fine intracellular structure is lost cannot, even theoretically, be revived. To succeed in their mission, cryonics organizations need to treat preservation with a scientific rigor. That was what my friend and colleague Mike Darwin did when he entered the scene in the late 1970s.

Towards the end of the 1970s, cryonics tended to attract a particular personality. By then, the community had weathered years of disappointment. Instead of embracing cryonics, as Ettinger anticipated, the scientific community rejected the field’s researchers as crackpots and hucksters preying on fears of death. They were mostly cut off from scientific attention and chronically lacked institutional expertise. The people drawn to cryonics anyway tended to be stubborn, idealistic, fiercely defensive, and contrarian.

All of these describe Darwin. Born in 1955, he presented a science fair project on cryopreservation at age 12. He also started exchanging letters with Saul Kent of the Cryonics Society of New York, which led to an invitation to their facilities in 1972, where at age seventeen, he saw cryonics first-hand. And even more intimately than he expected. During his visit, staff recruited him to assist with an emergency preservation. The case was an eye-opening failure. Hours of post-mortem time passed, the team had no written protocol, and necessary equipment was missing or untested, leaving Darwin with tools worse than the kit he'd assembled in his garage. All of these were typical failure modes for cryonics organizations at the time. Appalled by the quality of preservation achieved, Darwin took it upon himself to fix the field.

When it came time to choose a profession, Darwin trained as a dialysis tech, which by happy coincidence was very useful for his cryonics work. He co-founded his own cryonics organization, the Institute for Advanced Biological Study, in 1977, which merged with Alcor in 1982. In 1983, Darwin became president and research director of Alcor. Since his first preservation experience in 1972, he worked to establish a standard of care grounded in advance preparation, rigorous medical protocols, and supporting evidence from the best medical literature.

Darwin’s first mission was to improve the performance logistics of cryonics teams: establishing careful checklists, protocols for monitoring the procedure for problems such as air bubbles in tubing, and maintaining detailed records in the form of case reports to help them iterate on what they learned. His friend and like-minded collaborator Jerry Leaf, a technician with surgical experience, joined him on this effort. 

His second mission was assessing and improving the effectiveness of the cryopreservation procedure. The gold standard would be complete freezing and revival, of course, but no one to date knows how to achieve that. Without the ability to revive frozen organisms, how could they rigorously test whether they were making any progress toward their goal?

Darwin and Leaf produced proxy results through studies on dogs and cats. They found that dogs could be revived after an attenuated form of the cryopreservation protocol, which involves the blood washout stage, no cryoprotectant, and cooling to a temperature slightly above freezing but nowhere near the temperature of liquid nitrogen. This positive result was encouraging: consider that after complete cessation of heartbeat and brain activity, full washout of blood, and significant hypothermia, they resuscitated dogs that were then able to run around the laboratory. ¹  

At the same time, Darwin and Leaf tested the limits of cryopreservation.  They were especially alert to the problem of postmortem delays,  the timespan between when a person’s heart stops and when the preservation team arrives with their equipment. They wanted to understand quantitatively how big of a difference that delay makes.  The main physiological culprit here is ischemic damage, the rapid deterioration of tissue when it is starved of oxygen, which happens when breathing and heartbeat stops. To estimate the effect of ischemia, they simulated the waiting period in experiments with cats. They deliberately varied the time between when a cat's heartbeat stopped and the moment when they switched on the heart bypass machine. Then, they carefully inspected the brains under light and electron microscopes. While the former often appeared to show well-preserved tissue, the latter revealed the sobering truth: Cat brains perfused perfectly immediately after death, but a wait of even 30 minutes caused extensive damage at the synaptic level. 

Based on these proxy studies, Darwin intensely focused on a standby practice for human preservation at Alcor. Under this protocol, whenever a cryonics client was near death, Alcor dispatched a cryonics team to wait around the clock in the next room. They needed to work like a well-oiled machine to avoid losing even a few minutes.

The 1980s and 1990s marked a high point for cryonics. Besides improving preservation logistics and instituting the standby protocol, Darwin also made progress on the reflow problem: the tendency of blood to resist restoration of blood flow after stopping circulation. At around this time, his colleague (and my eventual mentor) Greg Fahy pioneered a technique called vitrification. Antifreeze only lowered the temperature at which ice crystals formed. At sufficiently high concentrations of antifreeze, however, water ceases to crystalize at any temperature and instead solidifies into a smooth, amorphous glass. Fewer ice crystals means ice won’t suck the moisture out of neighboring cells, shredding and crushing them. This didn’t allow for perfect preservation of complete organs, but it brought cryonics substantially closer to the goal. 

Unfortunately, a small team is easily disrupted, and Alcor’s heyday soon came to an end. In 1991, Darwin’s longtime collaborator Leaf died unexpectedly of a heart attack.  Darwin and Leaf, at the time, were building a kind of “cryonics school” at Alcor, where they hoped to train a new generation of practitioners who shared their devotion to medical rigor. But with Leaf gone, Darwin  could not establish the necessary momentum alone.  He increasingly clashed with the leadership of Alcor, and finally left cryonics in 2000.  

In my view, the central question of cryopreservation has always been how do you test if it’s working?  Ideally, we could resuscitate the person and ask. For now, that solution is out of reach.  What are our alternatives? During his tenure at Alcor, Darwin took one approach, called metabolic reversibility. We cannot resuscitate people who have undergone the full cryopreservation protocol, but we can apply attenuated cryopreservation protocols on dogs — washout solution only, no cryoprotectant, very moderate cooling — and draw provisional inferences from that. In this approach, a good preservation technique is one where you can see that as many steps as possible are non-fatal in isolation. They can each be applied and then reversed without killing the animal. 

In 2010, the neuroscientist Ken Hayworth proposed an alternative standard. Hayworth was different from Darwin and his generation of cryonicists. For one: he was a neuroscientist, then a postdoc at Harvard and later based at the Howard Hughes Medical Institute. His conception of cryonics was fundamentally different, too. His standard was based on brain imaging: Since memory and personality are stored in the brain’s delicate arrangement of intercellular synapses, he argued, a good preservation technique is one which looks good under a microscope — where every synaptic connection in a preserved brain appears as crisp and undisturbed as in a living brain. He called his approach the informational integrity standard of success.

In Hayworth’s view, only a cryopreservation technique that could provably, visibly, and reliably preserve all the synaptic connections in the brain deserved clinical use. Unlike Darwin, he argued that it doesn’t matter if mild versions of a preservation protocol can be reversed, if after applying the full protocol, you find that the brain’s synapses have been damaged. This is the key difference between the two styles of cryonics. Hayworth’s perspective, which I share, is grounded in information theory. Under this view, it  doesn’t matter if the cells stay “alive” as long as the information is retained. Traditional cryonics, in contrast, is grounded in biology, and its priority is maintaining the health of tissues. There are still groups working on biology-grounded preservation: 21st Century Medicine, the de facto research arm of Alcor, and Cradle, founded last year by Laura Deming. I’m glad people are doing this work. It has exciting potential, but the fact of the matter is that we don't have a biologically reversible protocol today. That’s what ultimately drew me to the information theoretic standard. (If we ever do get a reversible protocol, I anticipate a very interesting debate about what the best preservation option is!) 

Hayworth spanned two research worlds: the mainstream neuroscience community and the more peripheral cryonics community. Though these communities differed in their particulars, both were in the business of developing high-quality techniques to preserve, store, and image brain tissue. To this end, he co-founded the Brain Preservation Foundation, an impartial nonprofit for evaluating brain images, and established the Brain Preservation Prize. This prize would be awarded to the first research group to demonstrate a technique that could preserve the complete synaptic map of a brain — a connectome — in nanoscale detail.  

Around this time, I entered the cryonics scene. I spent my childhood dreaming about ways to keep people from dying and my teenage years reading up on scientific approaches to do so. Maybe artificial intelligence would be the answer, or anti-aging research, or maybe cryopreservation. I duly signed up for Alcor in my twenties. At the time, I didn’t know about the field’s dysfunctions. 

I learned about the Brain Preservation Foundation shortly after graduating from college. I found their neuroimaging goal compelling and grounded in science,  so I began to volunteer for them. I maintained their website, fundraised, and developed a series of one-minute explanatory videos. This work entailed doing a lot of reading about  state-of-the-art techniques, which ultimately gave me an idea for an approach that I might be able to use to win the prize. 

I wrote a proposal to 21st Century Medicine. They demurred at first, possibly because my information-integrity project was a departure from their usual reversibility experiments, possibly because I had no neuroscience degree, and possibly because I was fresh out of college. I explained that the project was crucial for humanity, that I would do excellent lab work, and that above all I would work for cheap. They accepted.

My research proposal was straightforward: Combine the best of traditional neuroscience and cryonics techniques. Mainstream neuroscientists like Hayworth routinely took flawless nanoscale pictures of the brain, the kind you see in textbooks and research journals. The procedure is  straightforward: Perfuse a mouse's body with a formaldehyde solution, which acts as a chemical fixative: a compound that binds to biomolecules, forming a tightly-woven lattice that quickly and permanently glues even the proteins in place. Then take a paper-thin slice of fixed brain tissue and soak it in heavy metal solutions, alcohols, and eventually liquid epoxy. Once the tissue hardens, use a diamond knife to further cut that paper-thin slice into segments no more than 90 nanometers thick. (For reference, this splits a typical nerve cell body into around 1,000 layers.) Then, snap a perfect still-life picture with an electron microscope. While this brain imaging procedure produces textbook-quality pictures, it is not ideal for human cryopreservation.

The first problem is that while fixative can hold everything in place, it does so at room temperature.  We can — and neuroscientists often do — refrigerate fixed specimens to extend their shelf life for a little while. But they can’t freeze their samples without damaging the delicate tissue. Inevitably, the fine molecular structure breaks down. Even when it’s freshly fixed, slicing a neuron into 1,000 pieces will tend to impair its function. 

I was inspired by cryopreservation methods as a way to solve these problems. First, I could perfuse the brain with fixative, just like the start of the traditional neuroscience procedure, but skip all the later parts of the neuroscience imaging protocol and instead treat it like a cryonics case. Slowly, I would add cryoprotectants to the fixed brain. Then, vitrify everything. Cryoprotectants and fixative together could make up for each others' drawbacks. Fixative could immediately stabilize the brain tissue. Cryoprotectants could enable long-term storage. And I could verify that the brain was preserved well by taking a paper-thin slice, removing the cryoprotectants, and then completing the neuroscience imaging protocol to view the preserved synapses.

Cryonicists had not previously used fixatives in their preservations because they knew of no way to undo the fixation stage of the process and bring an animal back to life.  But if the goal was to preserve the delicate nanostructure of the brain with textbook-quality detail, fixatives were a silver bullet.

I spent a year toiling on this idea. The result was  aldehyde-stabilized cryopreservation. In 2015, I published a paper with Fahy, demonstrating our technique. Our images were crisp, showing none of the ice damage, osmotic strain, or cellular dehydration that plagued the mainstay cryopreservation methods. I submitted preserved samples of  rabbit and pig brains to Hayworth. To my immense delight, I was awarded both the small and large mammal prizes. 

This experience marked my break from cryonics orthodoxy. Although most of the cryonics community shunned fixation methods, I had seen firsthand how useful they are at preserving what I thought really mattered — the fine molecular structure of the brain. And I had also seen what brains looked like without adequate fixation: dozens of experiments ruined by the inevitable warping, crumpling, and ice crystals.

One experience in particular stands out.  In 2016, weeks before I was awarded the brain preservation prize, one of my beloved academic mentors died. I got the call two hours after it happened. I knew that Alcor had awarded him a free-of-charge preservation, and I asked if anyone had notified them after his death. No one had thought of it. I remembered Darwin's experiments on the postmortem interval: Unless the heart bypass machine was switched on within the crucial window following death, the ischemic damage was too severe and the animals were unrecoverable. I immediately notified Alcor myself, even though he had been dead for two hours and counting.  Something is better than nothing, right? In the end, it took multiple days for Alcor to recover him, and he was straight-frozen. 

Around that time, as part of my research, I happened to be working with a human brain preserved via immersion fixation after a similar time delay. I wanted to see for myself how well the synapses were preserved, so I took samples from the outermost, best preserved tissue in that brain, which was likely to be an upper-bound for the quality of my mentor's preserved brain. 

Like Darwin's early work in cats, the preliminary results were encouraging: Using an ordinary light microscope, I could see all of the cells and nerve bundles, and there was no obvious physical damage.  But the important information in the brain is really in the microstructures between cells — the synapses. And these tiny details are too small to see under a light microscope. 

So I prepared a sample for an electron micrograph. What I saw devastated me. The brain was shredded. Not only were the synapses ruined, the entire structure was riddled with holes. That was what my professor's brain must look like. 

I was heartbroken. I took off my Alcor bracelet, and soon after, I cancelled my membership. Anything was not better than nothing. Hayworth had challenged the cryonics community to preserve a whole brain to the same meticulous level of detail that neuroscientists routinely achieve for their scientific figures.  I knew it could be done. The next step was to build a technique to achieve it.

I had a technique that worked on rabbits and pigs in the lab.  But there’s a big difference between inventing a technique for the idealized, highly-controlled world of the animal lab and adapting it into a workable, real-world application.

More research needed to be done: fieldwork, surgical technique, cadaver studies, additional animal models. I started a Y-Combinator-backed company, Nectome, to fund and organize this research.  

What would it take to adapt this technique? I expected that biological species would not be the sticking point — humans are remarkably similar to pigs on the inside. The law, on the other hand, posed a problem: In the lab I used a heart bypass machine to start delivering fixative while the animal was still alive and heavily sedated under anesthesia. This step averted the ischemic damage that would accumulate in the interval between when blood flow stops and the heart bypass machine is switched on. But for a human case, this precautionary measure would be illegal almost everywhere—in general, only a medical professional can hook someone up to a heart bypass machine, and only they can perfuse a patient with chemicals, and then only if those chemicals would arguably improve the patient’s health.  Starting the heart bypass machine before death was a dealbreaker, no matter how much it protected against ischemia.

Avoiding ischemic damage is the central practical problem for cryopreservation.  If the point of no return was within even hours of death (optimistic, given my animal experiments, but I thought it might be possible that humans had a longer viable ischemic window — then Alcor’s practice of waiting by the phone was unworkable.  

But there are still further complications. While the cessation of heartbeat and breath are the most visible signs of death, in reality, these signs mark the outward culmination of an ongoing process. The biology of the body begins collapsing piecemeal in the so-called agonal phase preceding total death. The brain, in particular, often sustains massive damage, as the acidity of the blood rises beyond what neurons can tolerate, and they begin dying off. This attrition can go on for a long time before the heart and lungs cease functioning. 

The agonal phase is predictably catastrophic for the mind of the person being preserved, and for their prospect of adequate cryopreservation. It is a brutal biological fact which makes even Alcor’s paradigmatic best-case scenario — highly trained experts waiting to descend seconds after legal death — is dubiously effective, and in many cases, far too late. My mentor suffered a coma for a week before he died, during which a whole hemisphere of his brain failed to perfuse with blood. By the time his heart stopped, large sections of his brain were already destroyed. The agonal phase requires a complete rethinking of how we approach end-of-life preservation.

We cannot do much about the biology of the agonal period. We can only get ahead of it. The blocker here is a matter of law, not chemistry. First of all, we are mandated to begin cryopreservation only after legal death.  Second, a person to be preserved  cannot choose the time of their death to avoid the agonal phase. There are many situations where — cryonics aside — I believe it would be merciful and dignified to let people choose to die quickly rather than slowly. We have known for years how to prepare a cocktail of drugs that will quickly and painlessly end someone’s life, causing unconsciousness within a couple minutes and death  within 10.  I think it is therefore a shame that in nearly all jurisdictions in the U.S., the only option granted to terminally ill people is that if they are hospitalized, they may choose to refuse food and water continually until they are dead.

There has been some progress on this front. Ten U.S. states have passed some form of Medical Aid in Dying legislation, including Oregon, where I now live. These laws permit people to request, and doctors to prescribe, a drug that will quickly and painlessly end their life, though often with heavy stipulations attached.  

So, my aldehyde-stabilized cryopreservation technique faced three major real-world constraints: the agonal phase before death, the ischemic cascade following death, and legislation.

I rented lab space in California and began experimenting with rats. Through these experiments, I learned that heparin, a blood thinner, was absolutely essential. I learned something else as well: In a series of experiments that drew on Darwin’s tests on dogs and cats in the 1980s, I pinned down the true limits of the ischemic window for my style of preservation. How much delay could the brain withstand between the moment of death and the moment perfusion started? Unlike Darwin, my success did not hinge on  whether I could return these animals to life. It depended on whether I could perfectly preserve the nanostructure of their brains, as proven by electron microscope images.

After hundreds of experiments on rats and mice, I found my answer: 12 minutes.  If you start perfusion within 12 minutes of death (and you’ve administered heparin as a blood thinner in advance), you can get textbook-quality brain preservation. Any longer, and the results fall off a cliff, as segments of the vascular system will totally fail to perfuse. Those cut-off segments receive no washout solution to clear out blood cells, no fixative to harden them against chemical stressors, and no cryoprotectant to prevent ice damage when chilled. The brain images in this case are a hodge-podge of crisp and perfect preservation next to islands of harrowed, dehydrated, ruined tissue. 

In 2020, I moved from California to Oregon. My goal was to design and prototype a mobile laboratory, a sort of ambulance which I could use to perform the cryopreservation procedure anywhere I could drive. I wanted to develop a procedure that would work quickly in pigs (and thus hopefully humans), and to test whether the 12-minute ischemic window for good preservation held  in both pigs and donated human bodies. 

With a former U-Haul van as my starting point, I installed bright surgical lights, a metal operating table, and trays for bone saws, scalpels, blood-vessel clamps. I installed a perfusion machine, blood filters, and meters of clear plastic tubing. I contacted a pig farm that supplied pigs for scientific research. ² I put out a call for a thoracic surgeon to perform our first pig experiment. 

Finally, on a cold morning in November 2021, I drove to the pig farm with my two lab assistants. We had two vehicles: the mobile lab, in which the operation would take place, and a reservoir truck packed wall to wall with enormous color-coded drums of cryoprotectant, fixative, washout solution, and other tools and chemicals.

The pig arrived. It took the help of several farmhands to wheel the massive, anesthetized animal up the ramp and onto the operating table.  As I do with all of my laboratory animals, I privately expressed my gratitude to the pig for contributing to this scientific enterprise. An attending veterinarian administered life-ending drugs, and shortly afterward, declared death. The thoracic surgeon I had hired worked quickly to begin perfusion.

According to my stopwatch, it took 22 frantic minutes for us to open up the pig, reach the heart, attach the tubing, and start up the bypass machine — well outside the 12 minute ischemic window in rats. There were dozens of little mistakes, unanticipated problems, and miscommunication. But that was expected. We wrote a long list of everything we could think of to fix for next time. I had hoped that perhaps pigs (and thus potentially humans) would have a more forgiving ischemic window than rats, but the images from that first pig were a disappointment. Whole sections of the brain failed to perfuse. 

Over the next several months, we returned to that farm five more times. Each time, we were faster, more in sync, more prepared. We redesigned the surgical technique, and I learned to do it myself on a succession of pig carcasses closer to home. A procedure that originally took 20 minutes now took between four to seven.  And when we looked at the electron micrographs showing the fine structure of the brain on later pigs, they looked good — good enough to win the brain preservation prize again, but this time under conditions that would work in human cases in the real world.

With everything we’ve learned, let me summarize the requirements for robust, state-of-the-art cryonics today: Effective human cryopreservation can only happen under very controlled circumstances. Advance preparation is an absolute requirement.  Just before death, the patient must be injected with heparin. They must then die a quick and controlled respiratory death, after which the expert team has 12 minutes to preserve the body. Only under these conditions can we get a properly perfused brain and crisply-preserved synapses rather than mush.

These conditions make cryopreservation impossible for most people: people who die unexpectedly, or people who die slowly in hospice care. Biology is too exacting — preserving people who died suddenly remains beyond our capabilities, at least for now.

If you want to be cryopreserved under these controlled circumstances in 2025, you must come to Oregon, where you must be prescribed death-with-dignity medication, which currently requires a terminal diagnosis with a prognosis of six months or less.  

Less than we dreamed, but nature could’ve made it a lot more difficult still. The work continues. Right now, I’m working on building a preservation hospice to welcome out-of-state visitors who plan to be cryopreserved.  In the lab, I’ve been developing new forms of high-throughput microscopy that will hopefully be able to scan and store an entire mouse brain at nanometer resolution, capturing those trillions of synaptic connections in a digital archive. There’s much more to do, but the field of cryonics is finally at a respectable starting point.