Cryonics

Time travel

We invented religion to deal with the prospect of oblivion. There is prescious little comfort in the ability to predict one's own death, hence the propensity to convince ourselves otherwise. The rise of science destroyed this mythology, though, in a faustian bargain where we traded the comfort of immortality for a method that allowed us to satisfy our overwhelming curiosity. It is ironic that our ability to make abstract predictions about the future is what gave rise to both our curious nature and the knowledge of the inevitability of death. Nevertheless, the deal was struck and we could not return; all we could do was turn to science and ask whether we could somehow escape.

Low temperatures provide a means of escaping oblivion by suspending the aging process. The processes by which our programmed obsolescence is carried out are chemical in nature, thus the rate at which these reactions occur can be slowed dramatically by lowering the temperature. The biological clocks that control living organisms from birth to death can actually be stopped and then started again at a later physical time as if no real time had passed at all. This is surely one of the most fascinating concepts that can be presented to a life form that is conscious of its own mortality. For who among us does not wonder what the future may bring long after our lives are over. It might be as simple as this were we not principally composed of liquid water. For when we lower the temperature, water freezes: and this makes all the difference.

In 1964, Robert Ettinger, a college physics teacher, published a book called The Prospect of Immortality where he suggested that the idea of an individual traveling to the future had become technologically feasible. Ettinger suggested that the newly deceased could be frozen to very low temperatures and stored in cryogenic suspension. In the future, when medical technology had advanced sufficiently to revive them, they could be thawed and reanimated. In essence, this was a program to preserve learned information rather than just genetic information. This idea came to be known as cryonics.

It was no accident that cryonics became part of the popular culture in the 60's. Fundamental advances in both cryobiology (the first successful cryopreservation of mammalian cells) and resuscitation technology from the 50's set the stage for the cryonic proposal. After all, if people who had been declared dead a decade before were now easily revivable, had they only been able to wait for the new technology, then who was to declare that the current declaration of death would not also be subject to continuing erosion? For Ettinger, a physician's declaration of death was merely an opinion that technology simply hadn't advanced enough to revive the patient. Since cryopreservation of mammalian tissue had been successfully demonstrated, to Ettinger there seemed no cogent argument against cryopreserving individual humans, soon after a physician had decided that current technology wasn't up to snuff, for later revival once technology caught up to the disease.

There remains no physical or biological argument against the feasibility of cryonics, other than the observation that a living human cannot be successfully cryopreserved at this time. Indeed, the science of cryobiology indicates that this probably will be possible in the future, though it will likely be a formidable engineering challenge. Despite these indications, cryobiologists are surprisingly hostile toward the prospect of cryonics. The cryonicist must have faith (a lot of faith, actually) in technology and the stability of their organizations. The scientist, too, must have faith (e.g. in the constancy of the laws of nature) but the practice of science is now well enough established to use the probability of succession to reduce that faith to managable levels. It was not always so, however, therefore the faith of the cryonicist should not invoke contempt on the part of the cryobiologist. The smell of money casts its stench over the practice of cryonics; after all, if taking candy from a baby is easy, taking money from dead people is even easier. Cryonics being an American pursuit, it's easy to view it as just another attempt at bilking money from the wealthy through promises that are easily made. However, cryobiologists are largely humanists, and would probably tend to support redistributing the wealth of rich people, especially stupid rich people. Perhaps the viewpoint that cryonics will only be attainable by the wealthy tends to put them off, but does anyone who dreams of cryopreserving a kidney really believe that the poor of Calcutta will be getting transplants? There certainly cannot be any derision toward unholy tampering of dead bodies, medical scientists having built their profession upon such practices. What, then, is the objection?

One argument is that cryonics is simply unethical. The current technology is so far from being able to cryopreserve a live human that any freezing process will cause too much irreversible damage to ever be repaired. Thus these experiments on dead people are unethical because the chance of success is too small. Perhaps this is an illogical extension of the ethics that cryobiologists must employ when doing experiments on live animals or humans, but the ethics that apply to dead people are certainly different. Another common argument is that cryonics detracts from the respectable science done by cryobiologists. The potential for swindling large amounts of money from gullible people is inevitably attached to cryonics, and it is obvious. Even if an enormous effort was put into building checks and balances that would make such swindling almost impossible, the spectre of charlatanism would always be raised by journalists looking for sensational headlines and cryobiologists would be tainted by association. Also, there is the belittling of good science that looks at minute areas of cryobiology. Science needs funding, usually from the public. Even though scientists generally pursue questions because they are curious, it has become standard practice to sell their funding proposals through the technology that might arise out of their work. If people believe that cryonics has become a reality, they are not very likely to support work that looks at conformational changes in a membrane protein with an arcane name that is only found in a snail that lives only in tidal pools on Hudsons Bay.

Whatever the reasons, the fact remains that cryobiologists, as a group, tend to ridicule, or at least dismiss, cryonicists ("body freezers", as they are popularly known). Those members of the Society for Cryobiology who are cryonics enthusiasts are respected for their scientific work in cryobiology, but their subscription to cryonic philosophy is regarded, at best, as a curious eccentricity (it must be said, however, that the Society is built of "characters", the eccentricity of being a cryonicist is probably as valuable as any other curious behavior in the currency of scientific personalities).

Subscription to philosophy is one thing, but actually doing work in cryonics appears to be specifically banned by the Society. The bylaws contain the following provision:

Upon a two-thirds vote of the Governors in office, the Board of Governors may refuse membership to applicants, or suspend or expel members (including both individual and institutional members), whose conduct is deemed detrimental to the Society, including applicants or members engaged in or who promote any practice or application which the Board of Governors deems incompatible with the ethical and scientific standards of the Society or as misrepresenting the science of cryobiology, including any practice or application of freezing deceased persons in the anticipation of their reanimation.

Resurrection (a leap of faith)

	You are frozen	You are not frozen
Cryonics Works	Live	Dead
Cryonics Doesn't Work	Dead	Dead

Of course, this is just an updated version of Pascal's bet (you may as well believe in God since you have very little to lose by doing so). In fact, even the most cursory examination will reveal that there is a great deal to lose (for both wagers). There is money, naturally. There may be a relegation to the lunatic fringe of society. There is probably a fear of what might happen to you upon successful thawing (humans, having an erstwhile tendency toward truly evil behavior, have been known to inflict tremendous cruelty on other humans; a readily available supply of people devoid of advocates might prove too tempting for some future slavers). Nevertheless, cryonics enthusiasts have an enduring faith that the future is worth visiting. First and foremost, however, is the cryonicist's simple faith in the unlimited potential of technology.

Historically, the field of medicine has been plagued by an overly conservative rejection of new ideas, resulting in a great loss of life (also, if one is fair, there are enough examples to claim that medicine has been plagued by embracing premature ideas that hadn't yet been proven, also resulting in incalculable human suffering and death). Cryonicists point especially to the example of artificial resuscitation to illustrate how workable ideas can resist acceptance by the medical profession, and also how our identification of the boundary between life and death is a moving target.

As far back as the 15^th century (and probably much further back than this), midwives had discovered that mouth-to-mouth resuscitation was often effective in restoring the "breath of life" into newborns who did not breathe spontaneously. In the 18^th century, it was discovered that the same technique could be used to resuscitate adults who had suffered an accident such as drowning, where breathing was lost. The Humane Society was quickly formed to spread the word that death was not always so final. In fact, they developed methods for intubation and bellows-driven respiration as well as a capacitive defibrillator.

Perhaps because of too much science (or too little), mouth-to-mouth resuscitation went out of favor when it was discovered that less oxygen came out of a person's lungs than went in (not enough to matter, but they didn't look at that, and evidence-based medicine was apparently not in favor at the time). Electric defibrillation was also condemned when electricity started to be put to all kinds of crackpot uses. It was not until the late 1950's (yes, 1950's) that these two most useful methods of resuscitation were again re-evaluated. At the same time, the idea of organ transplantation was also accepted by the medical community. These events forced people to start thinking seriously about the question, "what is death?". The question remains at the pinnacle of the pile of conundrums known as bioethics.

What is Death?

Today we could go to the morgue and open up one of the refrigerator doors to take out a corpse who has been unquestionably dead for a week. If we were to open up his knee joint and remove some articular cartilage, and then digest the cartilage matrix, we would find living chondrocytes. These cells would be alive by any reasonable definition of life. We must distinguish between the death of the organism, of the individual, with the death of the component organs, tissues, and cells. Very few deaths are due to the parallel failure of all critical organs, thus at the time of death, most of the individual is still alive. Indeed, the practice of organ transplantation depends on this very fact.

The question is further muddied by considering just what it is that makes the individual. A person who has been subjected to a pre-frontal lobotomy is a living organism, but they are no longer the same person. Someone in the final stages of Alzheimer's disease is alive, but is the individual that was "them" still there? We change from moment to moment, dying and growing a little in turn, but something persists that makes us ourselves. Our continuity comes from our memories and the way that our brain responds to external events. Thus it is the information in our brains that must be preserved in order for us to continue living as individual entities. This information is stored as structure in the brain; the neural connections encode us. Therefore have to define death as the state that occurs when our brain structure is certainly and irreversibly being lost. Obviously, the availability of medical technology affects the conditions under which this pronouncement can safely be made.

It cannot be argued that many people have been declared dead in the past (and they have gone on to become truly dead, i.e. decomposed) who would have lived longer had current medical technology been available at the time of their deaths. It is also a very safe bet that future medical technologies will be able to successfully resuscitate people from conditions that are currently lethal. Cryonicists take the further leap of faith that current cryopreservation technology (which isn't good enough) can be corrected by suitable rewarming and repair technology. For most structures in the body, this may be a reasonable proposition. For the crucial issue of preserving brain structure (and especially the enormous number of axonal connections that make us who we are), however, the odds have to be regarded as extremely low.

Will the Future Want Us?

The second issue of faith for the cryonicist is the social issue: who will thaw them out? There isn't much room on the planet right now, why would any society want to add to its population by thawing old, dead people who require serious medical care right from the outset? Surely any crisis that curtails population (global thermonuclear war, for example) will also disturb the delicate arrangements that have been made for keeping dead bodies in liquid nitrogen.

Perhaps the unlimited faith in technology that allows the cryonicist to believe that the technical problems will be overcome, also allow him to believe that technology will also solve our social problems. Medical procedures to resuscitate and reanimate frozen people will be cheap and plentiful in the future, as will the technology to rebuild human bodies (without having a head on the body since that would desparately complicate matters).

Apparently, however, it is not a faith in technology or the promise of human civilization that really gives a cryonicist peace of mind. Rather, it is the simple faith in the continuity and success of the cryonic organization that they belong to. This is a faith that is every inch a match for that of contemporary religions.

At any rate, we may be sure that historians will want to talk to these people, if at all possible, and that they will want a decent sample size to make sure nobody tries to pull a fast one on them. On the other hand, it seems entirely likely that these same historians may become overly anxious and attempt the thawing before perfecting the system. You pay your money and take your chances...

Current procedures

For 120,000 US dollars you can have your whole body frozen or for 50,000 US dollars you can have a team of experts cut your head off and freeze it. The cryonics company Alcor will perform the following procedures to this end (quoted from Alcor's literature):

The Team springs into action

Medications are administered to minimize any effects of the ischemic episode and the subsequent reperfusion injury which the patient will experience. These medications consist of a slow calcium channel blocker (such as nimodipine), an anticoagulant (like heparin), and a variety of free radical inhibitors, in addition to several other medications which reduce the damage associated with depressed cerebral blood flow. Concurrent with the administration of CPS and medications, external cooling of the patient is begun, through packing of the patient in water ice. Each drop in temperature of 10°C cuts the patient's metabolic demand in half, so external cooling is initiated immediately.

Once the patient has been transferred into Alcor's special life support system and stabilized with CPS, and the medications have been administered (generally, 10-15 minutes from the initiation of CPS), surgery is begun to access the femoral vessels in the groin. This enables the more sophisticated and effective support provided through the blood pump and membrane oxygenator. Using the patient's circulatory system for direct control of respiration and circulation also provides the team with a very efficient method to rapidly "core cool" the patient. Under optimum circumstances, the patient may be on blood pump support within as little as 45 minutes of declaration of legal death by a physician. Once this level of support is available, the patient may be cooled to a temperature of 5°C within 15 minutes, using the high efficiency heat exchanger.

Once the patient's temperature has been sufficiently lowered and the artificial circulatory support is in place, the patient will be transported to an Alcor facility for cryoprotective perfusion.

Cryoprotective perfusion, to minimize freezing injury, consists of introducing increasing concentrations of a special solution into the patient's tissue to reduce ice crystal formation during the subsequent cooling to liquid nitrogen temperature. The most effective way to achieve a uniform disbursement of the cryoprotective solution is to use the patient's circulatory system. Artificial circulation similar to that used in open heart surgery is employed. The breastbone is divided medially and cannulae (tubes) are placed in the upper right heart chamber or atrium and the aorta, the great vessel leading away from the heart which supplies oxygenated blood to the rest of the body.

The cannulae are then connected to a heart-lung machine very similar to (though more complex than) the one used during the initial transport procedures. When the device is connected, a solution containing an increasing concentration of the primary cryoprotective agent is introduced to the patient's system. The increase is slow and gradual, due to metabolic limitations that inhibit the rapid assimilation of this rather viscous fluid.

At the time of writing, the main cryoprotective agent used by Alcor is glycerol. Dissolved in water with mannitol and other ingredients, it forms the cryoprotective solution. In the course of perfusion the concentration of glycerol in the solution will increase, that of water will decrease, while that of the other ingredients will remain roughly the same. Cryoprotective perfusion generally requires two to four hours to complete (whole-body suspension taking longer than neurosuspension), and has resulted in replacement of 60% or more of the patient's body water with glycerol.

Throughout cryoprotective perfusion, the patient's condition and response to the procedure are assessed. The pressure of the solution, rate at which the patient's tissues are assimilating the cryoprotectant, and patient's temperature and biochemical status are all carefully monitored. Additionally, a small opening is made in the cranium through a scalp incision so the brain surface can be observed during perfusion, an important step since brain preservation is the highest priority. This allows assessment of the efficacy of the blood substitution, the adequacy of the cryoprotective perfusion, and the degree to which the brain swells or shrinks in response to the perfusion. Shrinkage of the brain is preferable, indicating good water removal and replacement in the tissues by glycerol and the other cryoprotective components. All the observations provide an indication of the overall efficacy of the perfusion, the safety of maintaining the perfusion rates, and whether the optimum cryoprotectant concentration is achievable. The procedure may be halted before achieving the desired concentration if complications arise, such as noticeable swelling of the brain through fluid accumulation (edema). Careful monitoring may also provide information about the condition of the patient at the time of suspension that could be of eventual use in repair and resuscitation.

Neurosuspension Procedure

Following cryoprotective perfusion, the patient's head is surgically separated from the body between the sixth and seventh cervical vertebrae. The head is then prepared for cooling in a manner nearly identical to that described below for whole-body patients.

Cooling Process

The patient is then removed from the operating table and placed into two plastic, liquid-proof bags for the next phase of cryonic suspension: deep cooling. Air is evacuated from the plastic to enable better heat transfer from the bath of cold silicone oil into which the patient is submerged. Through the careful addition of small amounts of dry ice to the bath at regular intervals, the temperature of the patient is gradually and evenly lowered. Cooling from the post-operative temperature of about 5°C to the dry ice target of -79°C takes about 36-48 hours, depending on the mass of the patient, concentration of cryoprotectant, etc.

A recent and notable improvement in Alcor's operational efficiency is a computerized control of temperature descent for neuropatients. Rather than adding dry ice directly to the oil bath, small amounts of pre-chilled oil are introduced through a pump system, which adapts automatically to a desired cooling profile. This eliminates the need to have personnel vigilantly adding ice by hand and maintaining constant watch over the cooling process.

Once the temperature has stabilized at -79°C, the patient is removed from the cooling bath, and the outer plastic wrap is removed. Two sleeping bags are then positioned near the dry ice cooling bath and pre-cooled with liquid nitrogen vapor. The patient is very quickly transferred into these sleeping bags, further secured inside a protective (and equally pre-cooled) aluminum pod, and lowered into a cooldown vessel for the final temperature descent to -196°C.

Cooling to liquid nitrogen temperature is achieved through the gradual and controlled introduction of cold nitrogen vapor into the cooling vessel. Over a period of approximately 5 days the patient's temperature is slowly reduced to very nearly that of liquid nitrogen, and the patient is then submerged.

Long-Term Storage

Fig. 15.1.1 Sleeping Bags?

What science exists?

Art gained considerable notoriety with cryonicists for this quote. In the Sci.Cryonics FAQ, someone drily answers that this premise is ridiculous since some vertebrates have been demonstrated to survive freezing but none have been demonstrated to survive grinding. True enough, the scientific case for cryonics is under no burden to prove that it will work, it merely has to demonstrate that there are no scientific experiments that rule out the possibility. If cryonicists wish to convince scientists that cryonics is also worth pursuing, then the case should probably be made that evidence exists showing that the odds of success are reasonable.

The current proposal of cryonics is to preserve enough of the structure of the brain to allow future repair technologies to reconstruct the individual. Thus, the scientific basis for cryonics is really a question of how much brain structure can be preserved with current techniques, and what sort of molecular repair techniques is the future likely to bring. Molecular machines are currently used by biological organisms for repair, reconstruction, and regeneration of biological tissues. It can be said with confidence that the technology required for molecular repair has been successfully demonstrated. The design and construction of these molecular machines by human intelligence, rather than genetic information, is really an engineering problem, though one of outstanding difficulty. Nevertheless, an existence proof has been provided so we will turn out attention to the cryobiological problems to see if there are any scientific objections to cryonics.

Freezing and thawing of animal cells leads to irreversible changes that result in the death of those cells upon warming. Successful cryopreservation requires steps to be taken so that those changes are avoided; generally through the addition of cryoprotective compounds and control of the cooling and warming protocols. Freezing of tissues and organs involve additional mechanisms for irreversible injury to occur. For many tissues, cryopreservation schemes have been developed to mitigate this injury based on the same premise that has been used to cryopreserve isolated cells. Additionally, the successful cryopreservation of tissues usually requires some biological repair, once the tissue is implanted in a host, for complete recovery of function. Though progress has been slow in extrapolating these techniques to whole organs, there is yet no clear indication that successful cryopreservation of organs will not be done. In fact, many cryobiologists firmly believe that organ cryopreservation will become a reality. In light of this, we may ask whether there are any phenomena associated with brains that differentiate them from other organs; or better, is there any experimental evidence from the cryopreservation of brain tissue that addresses these issues.

There are now many cases of severe hypothermia (from immersion in ice water) where human brains have been chilled to near freezing temperatures and breathing suspended for hours with complete mental recovery following resuscitation. Ground squirrels have taken this even further, allowing their brains to cool below the freezing point for up to six weeks at a time, with complete function upon rewarming. Clearly it is possible to slow the clock in the brain appreciably without any loss of function.

Recent studies of freeze-tolerant amphibians have shown that not only can animal brains recover from low temperatures, but they can also tolerate ice formation within the brain tissue. MRI scans have shown that ice clearly forms not just within the brain ventricles, but also within brain tissue itself during freezing from which the animal fully recovers. This demonstrates that the damage of ice formation within the brain, within certain limits (the frogs cannot withstand temperatures below -8°C), can be mitigated through cryoprotection.

Some work has been done with mammalian brains cryopreserved with glycerol. EEG activity has been demonstrated in cat brains, cryopreserved in glycerol at -20°C for one to several years, demonstrating that many neurons are able to survive freezing and thawing, within an intact brain, and also that many neural connections were preserved and continued to function after thawing. Similarly, histological examination of cryopreserved brains has shown ultrastructure comparable with non-cryopreserved (but perfused with cryoprotectant) brains. This finding indicates that brain structure is better preserved through cryopreservation than the tissue of most other organs (e.g. kidney).

Of course cryonicists must preserve enough of the brain for continuity of the "self", whatever intangibles make up the individual, for the procedure to be successful. Which regions of the brain, and how much recovery of cellular connections are necessary to meet this goal is anybody's guess at the moment. Some people have lost enormous sections of their cerebral cortex (cf. Phinaeus P. Gage) and continued to be themselves (although often with personality changes), so there might be enough redundancy in the brain to accomodate less than perfect technique. Given the enormous number of neural connections that exist in a human brain, and the crude evidence that exists regarding preservation of those connections, it must be declared that current cryonic techniques are almost certainly destroying many of the neural structures that are necessary for full recovery, probably irreversibly. This is not to say that cryonics will not work, just that the likelihood of current techniques providing adequate preservation is slim. There appears to be no compelling reason to abandon the search for better techniques, however. Indeed, the problem seems to be one that is well worth studying. At the end of the day, if it can be done, it will be done.

Matters Arising

Several dozen people were frozen in the late 60's and early 70's, unfortunately the money required to keep them frozen eventually ran dry. Some relatives stopped paying, some died without making provision for the funds to continue, some companies declared themselves penniless. By 1987, there were only three frozen bodies remaining in the U.S. Today, fully one third of all bodies (and heads) that have been frozen are no longer cold. The result of these events was the tarnishing of all cryonics companies with the spectre of scandal. It was obvious to everyone that there was money to be made in this game if ethical behavior was sidestepped, thus the suspicion that snake oil was being pedalled gained rapid acceptance.

Today, cryonicist's have set up foundations to protect their interests once they too join their frozen brethren on their journey to the future. The money has to be in place, enough money to provide a trust allowance in perpetuity, before any freezing takes place. These organizations are relatively small, with probably only a few hundred people signed up for eventual freezing so far. Cryonicists relate to their organization much as the devoutly religious relate to their church. Indeed, the benefit they receive from fellowship, hope, and adventure is probably enough to justify their existence regardless of the chance for success. If all they ask of society is the freedom to do experiments on dead people (who have given their consent to such experiments before dying), then what is the motivation behind stopping them? It is a curious phenomenon...

That being said, a couple of questions go begging:

• Why not simply fix one's brain chemically and store it in formalin? This would provide better protection of neural circuits, storage would be less expensive and more robust, and any future technology that is sufficient to repair freezing damage or build new bodies de novo will surely be good enough to read the information stored in brain connections. Nobody has ever recovered function after chemical fixation, but the leap of faith necessary for such a procedure seems to be comparable to that employed in the standard cryonics gambit.

• Why are cryonicists not freezing animals alongside themselves, using identical techniques, so that the thawing and repair technologies can be tested and verified before being used on themselves? Presumably, future people will still only get one shot at thawing these people out. Since the cryopreservation procedures are likely to change radically as more scientific information becomes available, why not buy some insurance; something that can be used to test the efficacy of revival from the exact protocol that was used to freeze them? If the resuscitive techniques aren't up to scratch, keep the person in storage until a better method is developed. It seems that cryonicists have more faith in future people than perhaps is warranted.