Medical Myopia and Brain Death

Recently someone sent me a number of papers that discussed the biophilosophical underpinnings of brain death. Medical doctors increasingly find themselves in the midst of heated debates about what constitutes death by neurological criteria. It is not hard to understand how controversies can occur in this area. Whenever a patient who satisfies the criteria for brain death shows signs of improvement or recovery, these criteria are called into question. Or, perhaps more troublesome, some people will simply not concede that a patient is dead because recovery can be envisioned. In such cases, the concept of death becomes more like a subjective “decision” than an objective property of the brain.

To someone sympathetic to cryonics these debates are mildly infuriating because it shows the reckless medical myopia with which matters of life and death are approached. When bioethicists debate what constitutes “permanent and irreversible loss of the capacity for consciousness and self-awareness” there is little recognition of the possibility that what looks hopeless and irreversible by contemporary medical technologies may be rather straightforward to repair or recover by future medical technologies. Would we abandon a patient if a cure would be available tomorrow? What about next month? Next year? 50 years?

The standard rejoinder to this position is that cryopreservation of the patient (cryonics) itself produces irreversible damage to the brain and is thus not suitable to stabilize the patient longterm until more advanced treatments are available. But how can we know what will be considered irreversible damage in the future? Should we simply pull the plug based on our guesswork about the limits of future technologies? Would it not be more prudent to let future doctors make that determination?

This does look a lot like saying that cryonics is just an argument in favor of prudence based on ignorance. A sophisticated way of saying, “well, you never know!” Not quite. If a healthy brain without damage gives rise to consciousness and identity, it follows that if the original state of the brain can be inferred from the damaged state, the capacity to restore consciousness and identity is preserved in principle. Ice formation undeniably alters the structure of the brain but it does not make the ultrastructure “disappear.” In fact, at cryogenic temperatures nothing “disappears,” a point that is not even sufficiently recognized by many cryonics advocates. Today we can do better than freezing, though, and use vitrification agents, which solidify into a glass upon cooling to cryogenic temperatures. While these vitrification agents exhibit some toxicity, at the ultrastructural level this expresses itself at most as alteration of cell membranes, protein denaturation, etc., not wholesale destruction.

Where does this leave us on the issue of brain death? For starters, looking at a monitor and concluding that the patient is dead because of the absence of organized electrical activity will tell us little about the ultrastructure of the brain (case in point, at 15 degrees Celsius even a healthy brain will show a flat EEG). It is true that in some cases of brain death absence of electrical activity corresponds to substantial decomposition of brain tissue but it is important to recognize that in many such cases the brain has been permitted to self-destruct at body temperature as a result of trauma and ischemia. When a hospital is faced with a traumatic event of such magnitude that profound cell death can be expected, the most prudent action is to quickly cool the patient and prevent “information-theoretic death.” If the capacity for consciousness and awareness resides in the neuroanatomy of the brain, the first mandate of medicine is to preserve this.

Originally published as a column (Quod incepimus conficiemus) in Cryonics magazine, March, 2015

I’m Not Dead Yet!

The prevailing view among cryonics advocates is that cryonics patients are not dead. This view is reflected in the cryonics custom of calling people who are cryopreserved “patients” instead of corpses. We feel quite strongly about this, but to what extent do our organization and practices actually reflect this perspective?

Let us consider an event in which a person had a traumatic accident and is in a coma. There is no evidence of severe brain damage but it is not known if and when the patient will regain consciousness again. In a sense this patient appears better off than a cryonics patient because contemporary technologies are at least sufficient to sustain the patient in his current state. On the other hand, unlike the coma patient, the cryonics patient is not in a race against time and will be in a stable condition until advanced resuscitation technologies are made available.

We would be surprised, if not outraged, if we learned that family members and friends started calling a patient in a stable coma a corpse and started closing his bank accounts, selling his assets, and removing his internet presence. But this is what often happens to cryonics patients. While some of this behavior can be attributed to the different legal status of coma patients and cryonics patients, in many cases we simply don’t make the effort. Despite our objection that our patients are “not dead” we do not always act consistently with this view. Why is this important?

Acting consistently with our perspective that our patients are not dead is of crucial importance because the most formidable obstacle for people to make actual cryonics arrangements (instead of just endorsing the practice) is fear of losing their family, friends, and assets in an unknown future. Alcor’s response should not be to simply assure them that everything will be fine but to offer constructive solutions to these concerns that makes potential members feel safer.

Making potential members feel safer, and even positively interested in surviving and reaching the future, should start by broadening our presentation of cryonics to include topics such as re-integration and asset preservation. Currently, these topics (if discussed at all) are delegated to a dark corner on the Alcor website as if such concerns are just afterthoughts. We need to think of better ways to integrate these topics in our presentation of cryonics to the general public.

When someone decides to become an Alcor member (s)he should be issued an Alcor email address with the assurance that this email address will remain functional during cryopreservation and that Alcor will keep updating technologies to let communication options evolve with the times. Alcor can also offer a secure space on the main website where personal data and memories can be stored. After cryopreservation of the patient, authorized family members, relatives and/or Alcor should be able to update this space as well.

An even more ambitious realization of this idea is for Alcor to appoint a reintegration staff member whose sole responsibility is to help members maintain a presence during cryopreservation by assisting the member in preservation of assets and execution of trusts. This person could also function as a liaison between family members / friends and the patient during cryopreservation.

I think moving in this direction could go some way towards reducing the fears that people have about alienation and loss in the future. It is interesting to reflect why such efforts have not received a more important place in the history of Alcor. I think the most obvious answer is that Alcor has a hard enough time keeping the organization running and making sure members get a good cryopreservation. But I suspect there is also another reason. The people who have shaped most of Alcor’s presentation and policies are invariably “hardcore” advocates of cryonics and combine a strong desire to survive with a strong confidence in the technical feasibility of the idea. It would be a mistake to base our presentation and implementation of cryonics on such an unconventional subset of the population. We need to keep calibrating our presentation and services until it all becomes hugely attractive, instead of a source of anxiety.

Originally published as a column (Quod incepimus conficiemus) in Cryonics magazine, July, 2014

Killing Yourself to Live

I recently observed a heated exchange on Facebook about cryonics. One person said something to the effect that cryonics lacks evidence and that chemical preservation (“chemopreservation”) is the preservation technology backed by real evidence. Such statements bother me for a number of reasons. The most important reason, and this cannot be reiterated enough, is that while evidence can be presented that strengthens the case for cryonics (i.e. makes it more plausible), cryonics as such cannot be proven yet because this would require that we have certain knowledge about the capabilities and limits of future medical science. But the whole premise upon which cryonics rests is that future medicine may be able to fix conditions that cannot be treated today (including additional damage done by the cryopreservation process itself). Cryonics is a form of decision making under uncertainty and demanding proof in advance for its success is asking for the impossible.

The other problem, which I have covered in more detail in my extensive treatment of chemical preservation called “Chemical Brain Preservation and Human Suspended Animation” (Cryonics Magazine, January 2013), is that the evidence in favor of chemical preservation is necessarily incomplete because functional tests are excluded. All preservation technologies that involve a form of chemical fixation produce one consistent outcome. They render the (brain) tissue “dead” by contemporary viability criteria. Now, one could argue that making such an argument is akin to what opponents of cryonics do when they claim that our patients are dead. But this is a misunderstanding of the aim of human cryopreservation.

Cryonics is not just about “preserving structure” or preventing information theoretic death. Cryonics as practiced by Alcor is about keeping the patient alive. It is only when we fail to meet this objective that we are obliged to argue that lack of viability does not mean irreversibility. We can examine the brain (or the whole body) in its damaged state to infer the original state and (eventually) revive the patient. So when we use concepts such as “preservation of structure” or “information-theoretic” death it is important to remember that these are conservative fallback options when our efforts to keep the patient alive by conventional medical criteria have failed. The possibility of inferring the original state from the damaged state should never be used as an excuse to permit more damage than necessary. And this is the problem with chemical preservation of the brain. To borrow a song title from the metal band Black Sabbath, such approaches to life extension are akin to “killing yourself to live.”

Why is all of this important? If we want cryonics to gain greater recognition we should conceptualize it as something that is an extension of contemporary medicine but smarter. Cryonics breaks with the prevailing practice of abandoning people simply because they cannot be successfully treated by today’s medical technologies. What may appear irreversible now may be treatable in the future. But we do want to place these patients in cryostasis in the most viable state. Ultimately our aim is widespread recognition for placing critically ill people in suspended animation until a cure for their disease is found. Instead of saying “look how good the structure of this patient’s brain looks” we should aim for a situation in which we can say “this patient is in the same condition as when (s)he was admitted to us but now we have hundreds of years to think about a medical cure.” Evidence of good ultrastructural preservation after vitrification constitutes a strong case for cryonics, but cryonics can do better than doing good electron microscopy.

Originally published as a column (Quod incepimus conficiemus) in Cryonics magazine, June, 2014

The Valley of the Shadow of Death

The “uncanny valley” is a theory described in 1970 by robotics professor Masahiro Mori which posits that as a robot’s appearance becomes more human-like, observer affinity towards it will increase until the likeness reaches a certain threshold, after which affinity will drop sharply into the negative—the uncanny valley—before rebounding again towards levels exhibited toward ordinary, healthy-appearing humans.[1] The theory has received more widespread exposure since the advent of 3-D animated films, where attempted realistic depictions of human characters have sometimes resulted in quite negative viewer reactions, citing “creepiness” of the characters, despite animators’ efforts to render them as close to life (and presumably not-creepy) as possible.

The phenomenon is not unique to humans—it has been observed in monkeys presented with photographs and 3-D rendered images of monkey faces of varying degrees of realism. Mate selection and pathogen avoidance have been suggested as possible evolutionary reasons why subtle deviation from appearance norms would evoke a stronger negative response than a more substantial deviation. However, one researcher, Roger K. Moore has come up with an explanation of the uncanny valley effect, using Bayesian models, that suggests that the effect applies to all conceptual categories (to some degree), not just human vs. non-human.[2]

According to Moore, “the uncanny valley effect is a particular manifestation of… [the] ‘perceptual magnet effect’, in which stimuli close to a category boundary are judged by observers to be more dissimilar than stimuli that are away from a category boundary”. Where membership in one category or the other is determined by reference to more than one perceptual cue, and these cues are in conflict with each other, the differential distortion that results at the class boundary will cause “a form of perceptual ‘tension’… [that] may be experienced as physical or emotional discomfort, e.g. feelings of eeriness or creepiness.”

Moore posits that the drop in affinity described by Mori is a function of (1) decreased familiarity near the class boundary between a ‘target’ perception (i.e. human) and a ‘background’ perception’ that does not overlap significantly with the target (i.e. non-human), and (2) perceptual tension arising from conflicting cues to category membership. Individual observers have varying sensitivities to perceptual conflict, so the depth of the valley will differ from observer to observer, but the feelings of creepiness/eeriness “may induce the observer to take action in such a way as to reduce its effect.” Moore suggests four possible behavioral responses: withdrawal, attack, willfully ignoring one or more conflicting cues (‘turning a blind eye’), or integrating the new information into the category schema (i.e. habituation). Which behavior results from a particular stimulus depends on the stimulus itself, and intrinsic properties of the observer. Moore’s model even accounts for the different curves Mori proposed for still human-like artifacts versus moving ones. However, Moore asserts that “the model derived here provides a more general mathematical explanation… for a range of real-world situations in which conflicting perceptual cues give rise to negative, fearful or even violent reactions.”

One piece that I believe is missing from Moore’s explanation of the uncanny valley is the role that observer category membership plays. I suspect that the sensitivity of an observer to particular perceptual tension, and the nature of the behavioral response exhibited, may depend in part on whether the target perception is a category the observer considers themself to be a member of. This would explain why the effect seems more pronounced when the target perception is ‘human’. It may be that the individual observer sensitivity Moore discusses is generally higher when the cue conflicts force introspection into why the observer themself is a member of the target category, which could result in feelings of insecurity as cues previously assumed to be sufficient for determining category membership need to be reconsidered. It may also be relevant whether the observer considers themself to be a core member of the target category, or on the fringe—or alternatively, a member of the background category.

Now, let us consider cryonics. Might the uncanny valley theory shed some light onto why cryonics has such a difficult time garnering public and mainstream scientific support? I think it can. Mike Darwin has written about the conflict between cryonicists and cryobiologists, pointing out that there was not always a “war” between them, and that “[s]everal cryobiologists who later became some of the most vocal critics of cryonics were not only not hostile, but actually demonstrated interest in and support of cryonics; particularly with an eye towards getting money to pursue cryobiological research.”[3] Several cryobiologists sat on the Science Advisory Council to the Cryonics Societies of America in those early years, and Arthur Rowe, who went on to become a prominent anti-cryonics cryobiologist, at one time even wished Robert Ettinger “continued success in [his] endeavors”, was consulted for his expertise in an early cryonics case… and obliged! Though the collapse of the Cryonics Society of California and tragic loss of the patients at Chatsworth no doubt contributed to rising anti-cryonics sentiment, it is interesting that the move to ban cryonicists from entry to the Society for Cryobiology appeared to occur in reaction to close exposure to “medicalized” cryonics in an impromptu presentation by Darwin at the Society’s meeting in 1981.

This negative reaction by cryobiologists to the arrival of cryonics as a serious scientific endeavor can be explained using the uncanny valley theory. The target category here is clear enough—cryonics aspires to be recognized as a medical procedure. But what is the background category causing perceptual tension? One option is quackery, and certainly many public comments from scientists superficially seem to support this. However, remembering back to Moore’s explanation of the uncanny valley, perceptual tension arises from conflicting cues to category membership near the boundary between categories with low overlap, whereas quackery and actual medicine share many perceptual cues in common (if they didn’t, the snake oil wouldn’t get sold). So while we might not expect scientists to provide ringing endorsements of a practice they perceived to sit near the boundary between quackery and medical procedure, we also would not expect a previously neutral (and in some instances positive) response to shift sharply into the negative as a result of that same practice transitioning towards operating on a more rigorously scientific basis.

I believe the background category causing the trouble is ritual burial practice. The tip-off is that the regulators that anti-cryonics agitators invariably prod to clamp down on “cadaver freezing” are state funeral boards—even though the supposed cause for governmental intervention is that “it won’t work,” a standard which would never be applied to beliefs associated with other burial practices. This approach is illogical: a better strategy against cryonics would be to push for its regulation within the medical establishment, and in particular any devices which fall under FDA’s authority over “medical devices.” This strategy would require cryonics to prove its efficacy, which of course, by presently accepted definitions, cannot be done. Instead, cryonics is shoved in the direction of regulators responsible for burial practices and other modes of disposition of human remains, where, of all places, it might actually have a chance of being protected on the basis of the practitioners’ beliefs. It is telling, too, how often negative responses by scientists to cryonics will ignore or distort well-established science, often from their own field. To me, this all points to the irrational/emotional nature of these responses—many of these researchers no doubt consider themselves members of the extended medical community, and are trying to put distance between themselves and something that looks like them and talks like them, but is nevertheless decidedly not them. Without necessarily realizing it, their instinctive reaction is to push cryonics back towards the background category causing the perceptual conflict.

Ritual burial practice and medical technology are far more dissimilar from each other than medicine and quackery, and thus Moore’s model would predict any cue conflict near the class boundary to cause perceptual tension. Here, cryonics is the perfect storm of conflicting cues: it is a procedure performed after the person is already declared dead, that looks at first like attempts to resuscitate, followed by surgery (possibly involving decapitation) and then preservation, with the ultimate objective of continued life in an as-yet-unknown form, on the basis of a theory that can never be absolutely disproven… so long as the person’s remains are left undisturbed. These perceptual cues are a complete and utter jumble, pointing 100% in both directions at the juncture of life and death.

And if that all weren’t confusing enough, what role might the category of ‘scientific research’ have in this? We utilize anatomical gift legislation to effect transfer of the body for the purpose of research, but then refer to our specimens as “patients” and wait for other research to produce the evidence and technology in order for this research to become a medical procedure. In my opinion, the ‘scientific research’ label is a red herring—it has obvious utility for us, but it is a loose foothold in the uncanny valley, given how candid we are about our objectives.

So, will any amount of R&D short of actually resuscitating someone increase our public approval, or will it just heighten perceptual tension and plunge us further into the valley? Moore’s model tells us that individual sensitivity to perceptual tension isn’t something we can directly control for, other than perhaps through desensitization, but that is hard to accomplish with a movement so small. Also, some of the conflicting perceptual cues are not ones we can change. If our objectives sound quasireligious to others, we can try to explain how we reject the ordinary definition(s) of death while still being rational people—but if they are not persuaded, there’s not much else we can do other than keep building up our evidence, brick by brick. However, we may be able to reduce cue conflict on other dimensions. We can accomplish this by continuing to emulate medicine in more positive ways, and also by de-emphasizing cues that pull the other direction (i.e. the trend away from the word “immortality” is a good one, at least for the public acceptance of cryonics).

The current legal definition of death is a source of perceptual conflict that we may not be able to do much about just yet, but in the interim, we can at least try to minimize its apparent importance to the procedure. Reliance on life insurance to fund cryonics arrangements seems to pull in the wrong direction, as we are opportunistically capitalizing on a definition of death we fundamentally disagree with, in order to afford an opportunity to disprove it— to our benefit. Of course, for many life insurance is the only real means of access available to them, but perhaps down the road, we could negotiate or design a new form of insurance specific to cryonics, formally triggered not by the patient’s legal death, but initiation of cryonics procedures. This is really just a rose by another name, but it would also finally put to rest that old worry that the insurers will come back for their money if the patient is resuscitated.

A feature of mainstream medicine which is conspicuously underdeveloped in cryonics are surrogate decision makers for patients post-cryopreservation. As it stands currently, cryonics organizations have complete or near-complete authority over their charges, and while this is for the good purpose of preventing interference by third parties, it does give the appearance that the patients are essentially the property of the care provider. Given the potential time frames we are looking at, recognizing something like a power of attorney for health care, in cryonics care, still might not stretch far enough, unless it contained a power to delegate the authority further, or was vested in a trusted organization instead of an individual. Due to the legal status of the patients, the cryonics organizations would have a lot of latitude in designing what exactly their obligations were to the patient’s representatives, postcryopreservation, keeping in mind the precarious and high stakes nature of the cryonics venture. However, one scenario which should be seriously considered, is under what circumstances a surrogate decision maker (or self-regulatory body, see below) could insist that the patient be moved.

Another aspect of medical practice which cryonics can and probably should emulate sooner or later is self-regulation. Mainstream medicine is of course regulated through a mix of government and professional self-regulation, and the cryonics organizations’ proactively developing shared standards and oversight mechanisms will give the public confidence that whatever the patients’ status is in law, they are being treated with due care and respect. In the same vein, self-regulation may help ward off the risk of inappropriate government regulation down the road.

These are only a few ideas of how to keep non-research, non-technical dimensions of cryonics progressing smoothly toward recognized medical practice, mitigating as much as possible any perceptual tension with the background category of ritual burials.

If the uncanny valley theory holds true, there’s a high mountain of public acceptance on the other side waiting. The question is, have we already reached the bottom?

References

[1]: Masahiro Mori, “The Uncanny Valley”, 7 Energy 4 (1970) 33-35. Available online (English): http://spectrum.ieee. org/automaton/robotics/humanoids/ the-uncanny-valley

[2]: Shawn A Steckenfinger & Asif A Ghazanfar, “Monkey visual behavior falls into the uncanny valley” 106 PNAS 43 (2009) 18362-18366. Available online: http://www.pnas.org/ content/106/43/18362.full

[3]: Roger K Moore, “A Bayesian explanation of the ‘Uncanny Valley’ effect and related psychological phenomena”. Scientific Reports 2, Article 864. Published online, November 16, 2012: http:// www.nature.com/srep/2012/121115/ srep00864/full/srep00864.html

[4]: Mike Darwin, “Cold War: The Conflict Between Cryonicists and Cryobiologists”. Cryonics, June, July, August 1991. Available online: http://www.alcor.org/Library/ html/coldwar.html

First published as a regular column called In Perpetuity in Cryonics Magazine, June 2013.

Reintegration, Personalized

The latter half of therapeutic cryopreservation involves three “R”s: resuscitation, rehabilitation, and reintegration. Of the three, reintegration receives the least attention as to its content, so permit me to deconstruct it a bit before diving straight in. First off, it’s re-integration, so like re-resuscitation and re-habilitation, we are talking about some present state or condition that we want to return to – in this case, a state of integration, of being part of a larger whole. By identifying a need for something called reintegration, we are predicting that being awakened from a cryonic slumber, even with every memory intact and in perfect health, is not going to be the same as going to sleep one night and waking up the next morning. The world around us will have changed – possibly quite dramatically – and all that we were prior to cryopreservation may not be enough to immediately begin operating as part of the larger whole as we did before. However, none of us is integrated into all subsystems and sub-communities of the larger human social organism at the same time, and to the same degree. So when we talk about reintegrating revived cryonics patients, are we talking about bare, functional integration into the community immediately around the cryonics facility, or something more than that? And either way, how will we measure success of reintegration? According to the norms at the time of revival, or somehow relative to the individual’s first integration?

I think it is problematic to think of reintegration as a general, one-size-fits all process that will not require extensive, non-medical background knowledge of the individual patients. Reintegration is as much about how to fit resuscitated patients back into tomorrow, as it is about how they already fit into today. By leaving the reintegration problem entirely to our friends in the future, we may be allowing data about the patients which would greatly assist with reintegration slip through our fingers to be lost in the sands of time.

But there is another problem that is closely related to the reintegration problem, and that is fear of dis-integration, which is really combination of two things: fear of separation from features of one’s present integration, especially family, friends, but also wealth and possessions; and fear of not having a “place” in the future, of not having a reason to get up in the morning, or as the Japanese call it, ikigai. This problem was very well encapsulated in a recent segment on cryonics on the television show “The Doctors,” when one of the panelists was asked if she would want to be cryopreserved. After her resolute “No,” she was asked why not, so she quickly elaborated, “Well, everybody else you love is not there. Why would you want to be around without people you love?” In reply, one of the more openminded panelists suggested, “Well, freeze everyone then!” There is a certain logic to this, but social inertia being what it is, it is not a very persuasive argument to someone on the fence (or the other side of it) today.

Nor is such fear soothed by simply telling people that we (or our successors) will figure out how to tackle the reintegration problem closer to the relevant time. And by not addressing people’s fear of disintegration more effectively by making tangible efforts today to assist reintegration tomorrow, we may be hampering our own growth, potentially hindering the pace of development and thus prolonging revival for all patients – making the task of their eventual reintegration all the more difficult.

Personhood

It probably goes without saying that reintegration has legal components to it. The one which has received the most attention thus far is asset preservation, but this and most other legal aspects of reintegration rely on the threshold issue of personhood. Legal personality is quite fundamental to our current integration, as is the continuity of that legal personality over time, based on various identifying data like our names, unique appearance, date of birth, etc. Maybe some of us wouldn’t mind fresh starts, but for the sake of exploration I’m going to assume that, given the choice, most cryonicists will want to be recognized as continuations of who they are today, same as we would for any other lapse of consciousness. But for all the good of waking up feeling like we are the same person we were prior to cryopreservation, and expressing that feeling, how do we prove that is what we are? We wouldn’t expect to have much of a problem in an idealized (and impossible) revival scenario that just involved thawing the patient, waking them up with a sharp pinch, and going about curing the disease that caused their initial legal death – but clearly more is going to have to be done  for today’s patients than that. So the question is, how much deviation from that fictional ideal will the legal system of the day be able to tolerate before concluding that the resuscitated patient is not a continuation of the previous person – or maybe not a person at all! Those who are setting up trusts for their resuscitation may be able to work around the issue of continuity of legal personality by dictating that their cryonics organization and trust advisors are responsible for “recognizing”’ them, but without legal personality, the resuscitated patient may have rather a difficult time using those saved resources, not having recourse against those who might try to take them away, or even being able to enter into simple contracts.

Law is highly contextual, and particularly sensitive to place and time. We can only make predictions about what the legal result will be of certain facts tomorrow or the next day because we can predict with a reasonably high degree of certainty what the governing rules will be tomorrow or the next day. This gets a lot harder when we are talking about some decades in the future, though we can certainly try to make reasonable guesses about the larger context to which the system will have already had time to react and adapt. For example, it seems improbable that a cryonics organization would attempt an uploading method of resuscitation without it being previously established that apparently self-aware, conscious, intelligent beings can exist on substrates other than biological brains. Thus, the political and legal organs of the day should have already had opportunity to develop a rule on whether such beings are “persons,” and rules governing the effect of copying and transferring them, etc. But is it reasonable to assume that the rules arrived at will be the ones we want, when and where we want them? We can think ahead to all sorts of good arguments supporting our positions on the matter, but we can’t argue them unless and until we actually get there. It seems more practical to advocate for greater recognition and protection of cryonics patients now, through public awareness campaigns, lobbying and legal efforts.

Our Living Family

Some of the more logistical aspects of reintegration are equally ripe for present action. Practically speaking, the closest analogues to revived cryonics patients today are survivors of very long comas. However, only the longest of long comas are remotely comparable to the scale of temporal displacement cryonics patients are looking at, and survivors of such long comas are very rare. As such, good evidence for successful reintegration strategies is unfortunately lacking. However, one shared feature of several of the cases I found was extraordinary commitment of the patients’ families and/or spouses.[1] In fact, this is usually cited as the reason the patient recovered at all – and to some extent that may be true, given that long-term coma patients without such persistent advocates and caregivers might not be expected to receive the same quality of care, and thus survive long enough to reawaken. But surely reintegration, too, is facilitated by involvement of family, just as it is during our first integration in childhood. This got me thinking about whether my family (and friends) would remain connected to me and my care, if I were cryopreserved tomorrow. Would they scan the science headlines for relevant advancements? Would they check in periodically on the health of my cryonics organization? And even if they did at first, how long would their interest last? Would I have any connection to the people at my bedside upon resuscitation?

Well, maybe I would, because I am fairly integrated with the cryonics movement itself – but that is not going to be the case for everyone, and by leaving it entirely up to the patients’ families and friends to remain engaged… well, results may vary. Here, we have a real opportunity to personalize integration. What if cryonics organizations were to track their patients’ family trees, periodically reaching out to new members of the family (once they are old enough to understand) to inform them that they have a relative being cared for in cryostasis? Sadly, there are probably many cryonicists today whose immediate family are resistant or indifferent to their wishes, but perhaps the next generation will find the novelty intriguing. Ongoing family engagement could potentially benefit the patients’ cryonics organizations in the form of donations, and even new members. The real payoff, though, would be to have relatives of the patients on hand to greet them upon resuscitation, and hopefully assist with the reintegration process – maybe even hosting them with some financial assistance from the Patient Care Trust (and/or personal resuscitation trusts, where existing). Even if average human lifespan does not increase significantly in the decades ahead, the older living relatives of revived patients may not be very many generations removed from them.

Right now, the familial data collected by Alcor and CI as part of the sign-up process is significantly less than what most people can rattle off the top of their heads in the way of names of grandparents, aunts, uncles, and cousins. While a cryonics organization may have some ability to obtain this kind of information via medical records after the patient’s legal death, it would certainly be much easier to get it while they are alive. And that still only gets us part of the way. Where I live, at least, vital statistics information on births, marriages and deaths is not made publicly available for genealogical research until many decades after they occur. Part of keeping the family engaged with the patient would involve asking for their assistance in filling in our picture of the patient’s family tree as it grows new branches. This information may also be obtainable by scouring the web and social media, but the point is not to passively track the patient’s living genealogy in the most efficient manner possible – it is about the cryonics organization maintaining an active relationship with the family, keeping the connection between patient and family alive.

Arguably, this is a lot of work to identify relatives who might be tracked down with the aid of genetic data closer to the day, but I think the power of this idea is more than just the possibility of having patient relatives at bedside for resuscitation, but rather in the effort we make in keeping the family informed, and if they’re willing, engaged. It’s about what we can say we are doing, to the person who expresses to us that, in effect, their fear of being revived permanently separated from their families and loved ones is greater than their fear of death.

These are only some of multiple aspects of reintegration that I think can be constructively brainstormed and worked on today. I will be exploring more at the upcoming Symposium on Resuscitation and Reintegration of Cryonics Patients, hosted by the Institute for Evidence Based Cryonics in Portland, Oregon on May 12, 2013.

Endnotes

[1] Annie Shapiro, 30 years. Jan Grzebski, 19 years. Terry Wallis, 19 years. (Wallis was actually in a minimally conscious state, but the effect is the same, for our purposes.)

First published as a regular column called In Perpetuity in Cryonics Magazine, May 2013.

Cryonics and Natural Selection

“…it is not the strongest that survives; but the species that survives is the one that is able best to adapt and adjust to the changing environment in which it finds itself” so reads a quote that, in modified form, often has been mistakenly attributed to Charles Darwin but was in fact a description of Darwin’s views penned down by a Professor of Management and Marketing named Leon C. Megginson in 1963. But, surely, one reason for the popularity of this quote is that it captures the modern view of evolution quite well. In this column I would like to briefly reflect on what cryonics means in the context of evolution and natural selection.

Any cryonicist that has not kept his support of cryonics completely to himself must have found himself in a situation where even the most reasonable arguments seemed to leave someone else completely indifferent, or even hostile. Even in the case of family members or friends there comes a point where one cannot help thinking, “well, if you would rather die than think, fine, I am not going to stop you.” It appears, then, that people who make cryonics arrangements are part of an extremely small group of people that will escape the common fate of all humans (i.e. death), as a consequence of being extremely open-minded and adaptable.  But is this the “survival” that the theory of natural selection speaks of?

The modern theory of natural selection is essentially about reproduction. It is not necessarily the longest-lived species (the survivors) whose (genetic) traits will become more common in a population but the ones whose fitness leads to greater reproductive success. It can hardly be denied that cryonicists are extraordinarily capable of adapting to change (or ready to adapt to future change) but it has also been quite firmly observed that cryonicists (or life extentionists in general) are lagging the general population in terms of reproduction, either because of the higher number of single persons or because of the lower interest in having children. It is sometimes observed that whereas most people seek “immortality” by ensuring their genes will survive in future generations, cryonicists see immortality by seeking to survive themselves. In addition, even allowing for a growing interest in cryonics, the number of people making cryonics arrangements is simply too small to have a meaningful effect on the genetic and mental traits of future generations. At best, cryonicists may find themselves being perceived as independent, courageous, individuals that were simply more capable of anticipating the future of science and medicine.

It is tempting, indeed, to think of cryonicists as a homogeneous group of people who are extraordinarily analytic and adaptable but a closer inspection of the motives of people who make cryonics arrangements suggests something different. Indeed, if we look at the early days of cryonics, we see a disproportionate number of cryonicists who where extraordinary visionaries, sometimes independently arriving at the same conclusions (think of Robert Ettinger and Ev Cooper). As cryonics received more mainstream exposure, however, we see different reasons why people endorse cryonics. A partner has cryonics arrangements and the other person is persuaded to do so, too. Subcultures in which making cryonics arrangements is strongly endorsed (like transhumanism). A strong fear of death that prompts a person to do anything to not die, regardless of a dispassionate assessment of cryonics. In more recent times, even career considerations can be a factor as more “market-based” salaries are available in the field of cryonics. Still, despite the possibility that the personality type that chooses cryonics is increasingly getting more diverse, it still makes sense to talk about the demographics of cryonics for as long as the cryonics population is substantially different from the general population.

Where does all this leave us concerning cryonics and natural selection? Since natural selection is basically about reproductive success despite death it would not be correct to characterize the small group of cryonicists that will survive (where others do not) as an example of Darwinian evolution in action, I think. It may be tempting to use Darwinian terminology to characterize our situation but upon closer scrutiny there are problems with this. What might be said, though, is that (successful) cryonicists will be in the extraordinary situation to live for such a long time that they can see human evolution further unfold and even be in a position to consciously direct it through human enhancement.

This is a web-exclusive edition of the Quod incepimus conficiemus column that is published in Cryonics magazine but was omitted from the December 2014 issue.  

Ultrastructural Signatures of Information-Theoretic Death

On October 11, 2013, the Wall Street Journal featured a cover story about the unintended consequences of Norway’s long-time insistence on “plastic graves” (“Grave Problem: Nothing is Rotting in the State of Norway”). You see, after World War II the Norwegians wrapped the dead in plastic prior to burial and now they are faced with…corpses that are not decomposing. Since cemetery real estate is scarce in Norway this creates a rather complicated and sensitive problem. One of the solutions is to poke holes in the ground and plastic to inject a lime-based solution to accelerate decomposition.

Not many people would expect the brains of these plastic-preserved Norwegian corpses to be in pristine condition at the ultrastructural level but this strange story does illustrate that decomposition is a process that is highly sensitive to variables like the presence of oxygen, water, microorganisms, and temperature. Of course, some of these variables are related. When temperatures are lower there will be reduced microbial activity. As a consequence, at cold temperatures the rate of decomposition can be even slower than what one would predict based on the decrease of the brain’s metabolism alone. Cold ischemia is not just warm ischemia slowed down (and vice versa).

My company, Advanced Neural Biosciences, Inc., is currently collaborating with Alcor to produce a series of electron micrographs of brain tissue exposed to very long times of cold ischemia (0 degrees Celsius). One of the reasons we are doing this project is to bring actual data to the decision making process concerning the question when to accept and when no longer to accept a patient who has been stored at low temperatures prior to contacting Alcor for cryonics arrangements.

Ultimately, what we are looking for is an ultrastructural signature of “information-theoretic death.” This presents a formidable problem because information-theoretic death is not an unambiguous identifiable property of an image but concerns our best guestimate about how much structure a future technology might still be able to infer from a given state of damage. For existing patients and members who want to be preserved under any conditions this is not a directly relevant question (the future will tell). But when you have to make a decision whether to accept a third-party “post-mortem” patient, arbitrary decisions have to be made because Alcor simply cannot accept every case brought to its attention.

We have now produced electron micrographs of up to 1 month of cold ischemia. When we shared these 1 month images with the Alcor Research and Development committee one member remarked that he “would not have guessed that so much structure could remain after one month.” When we presented an image from this series at a recent conference, attendees were also surprised about this level of preservation.

Of course, this is not the end of the story because a patient with such a long period of cold ischemia will still need to be cooled to cryogenic temperatures for long-term care and a “straight freeze” on top of such extensive ischemic damage could tip the balance towards informationtheoretic death. These results raise one interesting possibility, however. If the damage of a straight freeze is a lot worse than the damage from moderate times of cold ischemia, cryoprotecting the brain (or both hemispheres separately) by soaking it in cryoprotectant could be a superior protocol for a select number of Alcor cases. There is still much to be learned.

Originally published as a column (Quod incepimus conficiemus) in Cryonics magazine, November, 2013

Chemopreservation in the real world

It is generally not the task of scientists to consider the legal, financial, and logistical limitations when searching for biomedical breakthroughs but there are good examples where considering the real-world applications of a technology can be instructive. Research aimed at preservation of brains (or the “connectome”) is such an example. Even if chemopreservation can be demonstrated to preserve the intricate wiring of the brain, it can be safely assumed that there will not be a massive change in demand for brain preservation technologies (especially if the technology is too strongly tied to mind uploading). As a consequence, providers of chemopreservation will most likely operate in the same environment as providers of cryonics. That means that, as a general rule, there will be a delay between pronouncement of legal death and the start of procedures.

There is now more than 40 years of mainstream biomedical research demonstrating that even short interruptions of circulation (under normothermic conditions) can produce perfusion impairment in the brain. As has been demonstrated by cryonics researcher Mike Darwin and my own lab, Advanced Neural Biosciences, this “no-reflow” can produce poor distribution of cryoprotectants (including vitrification agents) and associated freezing. One serious concern that cryonics researchers have about chemopreservation-in-the-real-world is that poorly chemically fixed brains will be prone to autolysis during long-term storage. This limitation of chemopreservation applies to both “conventional” biological resuscitation scenarios as to whole brain emulation. One can only recover (or “upload”) what is preserved – or can be inferred. And as far as we understand things today, the advantage of temperature as a long-term preservation method is that it does not depend on a healthy, non-ischemic circulatory system. Cryopreservation of an ischemic brain can produce ice formation, but as soon as it is placed in liquid nitrogen, cold will “fix” whatever there is without further degradation. The same thing cannot be said about chemopreservation under poor conditions.

There is an understandable tendency to compare brain preservation protocols under ideal conditions and favor the method that produces the best preservation. But support for either technology cannot be solely based on results produces under controlled lab conditions. Personal survival technologies should be evaluated under conditions that are most likely to be encountered by organizations that will offer them. Demonstrating that chemical fixation (and plastination) can preserve the connectome is a laudable goal but the case for chemopreservation as a clinical experimental preservation method requires a persuasive response to the objection that delays in fixation can frustrate the aims of chemopreservation in the most fundamental manner.

One interesting aspect of the cryonics vs chemopreservation debate, though, is that it appears that some people simply feel more comfortable with one of the approaches. People who have shown the slightest interest in human cryopreservation can get really excited about the idea of chemical brain preservation. This indicates that if both approaches would be pursued actively, the growth of chemopreservation would not necessarily be at the expense of cryonics but there would be a growth in the total number of people making bio-preservation arrangements aimed at personal survival. But as Mike Darwin has recently pointed out, chemopreservation is not at the stage where it can be responsibly offered. The growth of this field requires a committed group of individuals who will research, develop, and implement this program. Chemopreservation does not need to be perfected before being offered (neither was cryonics) but so far most advocacy has been mostly at the conceptual level.

Steve Jobs’ morbid glorification of death

According to Steve Jobs, death is such a great benefit to mankind that it would have to be invented if it did not exist:

No one wants to die. Even people who want to go to heaven don’t want to die to get there. And yet death is the destination we all share. No one has ever escaped it. And that is as it should be, because Death is very likely the single best invention of Life. It is Life’s change agent. It clears out the old to make way for the new. Right now the new is you, but someday not too long from now, you will gradually become the old and be cleared away. Sorry to be so dramatic, but it is quite true.

As the baby boomers age, we can be sure to hear a lot more of what the cryonicist Mark Plus has called, ‘Humanist Death Apologetics.’ Never mind the horror, the destruction, and the suffering that comes with death, because, “it clears out the old to make way for the new.” Fortunately, a more enlightening perspective on death has been offered by the philosopher Herbert Marcuse:

It is remarkable to what extent the notion of death as not only biological but ontological necessity has permeated Western philosophy–remarkable because the overcoming and mastery of mere natural necessity has otherwise been regarded as the distinction of human existence and endeavor…

A brute biological fact, permeated with pain, horror, and despair, is transformed into an existential privilege. From the beginning to the end, philosophy has exhibited this strange masochism–and sadism, for the exaltation of one’s own death involved the exaltation of the death of others…

Modern market economies demonstrate on a daily basis that death is not necessary for the old to make way for the new. Neither do people have to be faced with death to have a meaningful life. Steve Jobs invites us not to be “trapped by dogma” but, unfortunately, he embraced the biggest dogma of all; the idea that human mortality is a good thing and gives meaning to life.

The reader is encouraged to explore some alternative views about death and aging:

Robert Freitas Jr – Death is an Outrage

Ben Best – Why Life Extension?

Aubrey de Grey – Old People Are People Too: Why It Is Our Duty to Fight Aging to the Death

Medico-Legal Aspects of Human Cryopreservation Optimization

Introduction

Ongoing legal challenges and hostile interference of relatives have increased awareness among cryonicists that addressing the likelihood that one will be cryopreserved at all should take center stage among other strategies for survival. As a consequence, a number of individuals have recently taken on the task of working out the conceptual and legal challenges to minimize hostile interference (for a contribution on the ethical aspects of cryonics interference, look here).

One aspect of cryonics optimization planning that has received little attention to date is to develop legal strategies to deal with medical and legal issues surrounding one’s death, terminal illness, and the dying phase. In this memo I will outline some of the most important medical and medico-legal issues, how cryonicists could benefit from recognizing them, and suggest some legal and practical solutions. Before I get to the substance of these issues I would like to briefly identify all the stages in which proactive cryonics planning can improve our odds of personal survival.

Opportunities for cryonics optimization

The first and most obvious decision is to make cryonics arrangements. Alcor members face complicated decision making because the organization offers both whole body cryopreservation and neuro cryopreservation. From the perspective of cryonics optimization many members choose neuropreservation because it enables the organization to exclusively focus on what matters most; the brain. There is also a logistical advantage. In case transport of the whole body across state lines is delayed the isolated head can be released in advance as a tissue sample. Additionally, a number of Alcor members have recognized that it is possible to have the best of both worlds and combine neuro-vitrification and separate cryopreservation of the trunk. This allows the member to take advantage of the superior preservation of the brain that is available for neuro patients without having to forego whole body cryopreservation. This option is not widely advertised so one is encouraged to contact Alcor about revisions in funding and paperwork.

The other obvious decision is to have secure funding in place. Many members have given extensive thought about funding mechanism and wealth preservation so there is little need to discuss this here. From the perspective of cryonics optimization it is important to emphasize the importance of over-funding your cryopreservation. This not only protects you against future price increases, but also enables you to take advantage of technical upgrades that cannot be offered at the current preservation minimums. Another aspect to consider is leaving money to cryonics research. Although it is reasonable to expect that general progress in science will include general cell repair, there may be areas that will only be pursued by those who have a scientific or personal interest in resuscitation of cryonics patients. As in many areas in life, diversification is key. One should not solely depend upon Alcor or CI for successful resuscitation research or efforts.

Another important opportunity for cryonics optimization is to recognize the importance of proximity. From a technical point of view, there is simply no comparison to de-animating near the cryonics facility of your choice. This is not just a matter of reducing ischemic time. Remote standby and stabilization is a fertile ground for all kinds of logistical and legal complications. Most cryonics members do recognize the importance of reducing transport times but it is an established fact that as soon people become terminally ill they become more resistant to the idea of relocating and often prefer to die among friends at home. It is important to anticipate this scenario and to not delay relocation plans until the last minute. Another advantage of relocating at an earlier stage is that one is better protected in case of a terminal disease with rapid decline or sudden death.

As mentioned above, one issue that is getting increasing attention is how to protect oneself against hostile relatives and third parties. The take-home message is to alter cryopreservation contracts and your paperwork in such a matter that there is an incentive *not* to interfere.

Last but not least, something should be said about community building. Cryonicists can greatly benefit from becoming active in their local cryonics group. Often these meetings are open to members of all cryonics organizations. Most cryonics groups organize standby and stabilization trainings where members can familiarize themselves with the basics of the initial cryonics procedures. Such groups may not only play a part in your own future cryopreservation but are also useful to get a basic understanding about what you can do in the case a local member or a loved one needs to be cryopreserved. Another important aspect of participation in a local cryonics group is that one remains in contact with other cryonicists. When people get older their friends and family members die and the member has little communication with those who are aware of his desire to be cryopreserved. If you live in an area where there are no local cryonics groups contact your cryonics organization and/or start your own local group.

Physician-assisted dying

If there was more widespread acceptance of cryonics the harmful delay between pronouncement of legal death and the start of cryonics procedures would not exist. After a determination of terminal illness, preparations would be made to ensure a smooth transition between the terminal phase and long term care at cryogenic temperatures.

Some states have enacted legislation that allows a terminally ill patient to request the means to terminate their life.  Assisted suicide is currently legal in the following three states: Oregon, Washington, and Montana. Physician-assisted dying does not remove the current obstacle that cryonics procedures can only be started after legal pronouncement of death but it can bring the timing of death (and thus of standby) under the patient’s control. Utilizing such laws can also greatly reduce the agonal phase of dying and its associated risk of damage to the brain.

The legal requirements for utilizing physician-assisted suicide can vary among states but, as a general rule, require that a patient has been diagnosed with a terminal illness with no more than six months to live, that the patient is of sound mind, and that the request is made in written form and witnessed. The State of Oregon has a residency requirement to discourage physician-assisted dying tourism.

Since cryonics procedures are performed after legal death, there is no reason why cryonics patients are exempt from utilizing these laws. Despite rumors to the contrary, there is no evidence that utilization of these laws require mandatory autopsy. After all, the cause of death in physician-assisted dying is clear; self- administration of the lethal drug. To avoid any possible accusations that cryonics organizations encourage the use of such laws, it is recommended that no person associated with the cryonics organization should be a witness, let alone be the physician that prescribes the lethal drugs.

Sudden death and autopsy

One of the worst things that can happen to a cryonics member is sudden death. Especially when the patient is young with no prior heart conditions, an autopsy is almost guaranteed. There is little one can do to avoid sudden death aside from choosing a lifestyle that reduces cardiovascular pathologies. The only preparation for dealing with sudden death is to become a religious objector to autopsy. Some states (including California, Maryland, New Jersey, New York and Ohio) have executed laws to restrict the power of the state to demand an autopsy. Although exceptions can still be made in cases of homicide or public health there is little to lose in using such provisions. The websites of Alcor and CI have links to the relevant forms to execute. The Venturists are offering a card for their members stating that they object to autopsy. This card can be requested from Michael Perry (mike@alcor.org) at Alcor. An example of such a card is provided below.

Sudden cardiac death is not the only reason for ordering an autopsy. An autopsy is typically ordered if there are criminal suspicions (homicide) or suicide. There is also a greater risk of autopsy when a patient dies in absence of other people. Since many old cryonicists are single and spent a lot of time alone they are also at an increased risk for autopsy. This is another good argument to remain involved with local cryonics groups and in frequent contact with other cryonicists.

If autopsy cannot be avoided it is important that the cryonics organization is notified promptly. Cryonics organizations can make another attempt to persuade the authorities to abstain from an autopsy or to request a non-invasive autopsy that exempts and protects the brain. The cryonics organization can also issue instructions for how the patient should be maintained prior, during and after autopsy. It might be worthwhile to generate a template of general autopsy instructions for cryonics patients. Such a document may not be binding but it could be useful in limiting the amount of ischemia and injury.

The dying phase and Advance Directives

Most cryonics members have a basic understanding of the importance of time and temperature to protect a cryonics patient after legal pronouncement of death. Fewer people recognize the effect of the dying process itself on the outcome of a cryonics case. In best case scenarios (physician-assisted dying, withdrawal of ventilation) the dying phase is relatively rapid while in worst case scenarios extensive ischemic injury to the brain is possible. Little work has been done to outline recommendations for the terminally ill cryonics patient. One of the main objectives of this article is to recognize that cryonics members could benefit from a general template that can be used in their Advance Directives and to guide surrogate decision makers.

At this point it is useful to briefly describe how the dying phase itself can affect the outcome of cryonics procedures (for a more detailed treatment see the appendix at the end of this article). A useful distinction is that between terminal illness and the agonal period. A patient is classified as terminal when medical professionals establish that the patient cannot be treated with contemporary medical technologies. During this period the patient is usually still of sound mind and able to breathe and take fluids on his/her own. Unless the patient has suffered an insult to the brain or a brain tumor, there is no risk for ischemic injury to the brain yet. At some point, however, the body’s defense mechanisms will be overwhelmed by the patient’s disease and the patient enters the agonal phase. The agonal phase, or active dying phase, can be characterized as a form of general exhaustion. The body is still fighting but with decreasing success and efficiency. One of the biggest concerns for cryonics patients is the development of (focal) brain ischemia while the (core) body is still mounting its defense.

It would be impossible to design an Advance Directives template that is optimal for all cryonics patients, but there are a number of general guidelines that can inform such a document:

* All health care decisions should be guided by the objective of preserving the identity of the patient throughout the terminal and dying phase.

* Measures to prolong dying should only be initiated or accepted if they result in less ischemic injury to the brain.

* Life-sustaining measures should be withheld in case of traumatic or ischemic insults to the brain.

To ensure that sensible decisions are made in situations that are not covered by these Advance Directives, a Health Care Proxy can be executed that designates a person to make those decisions. It is understandable to give such power to the person closest to you but in the case of cryonics it is recommended that this responsibility should be given to a person with a strong commitment to your desires and a detailed understanding of the medical needs of cryonics patients.

Pre-medication of cryonics patients

If a critically ill cryonics member is at risk of ischemic brain injury during the dying phase it stands to reason that some palliative treatment options are better than others. One possibility for cryonics patients is to specify such options in one’s Advance Directives. Another scenario in which pre-medication is possible is where the medical surrogate is strongly supportive of such measures. It should be noted that such a decision rests solely with the member or his/her medical representative. Cryonics organizations should not be involved in the pre-mortem treatment of the patient.

There are two important questions about pre-medication of cryonics patients:

1. Is it safe?

2. Is it beneficial?

The answer to the first question has a lot to do with the status of the pharmaceutical agents in question. For example, a supplement like melatonin is less controversial than a prescription drug like heparin. The most important thing to keep in mind is that drugs that may be beneficial after legal pronouncement of death could have adverse effects in critically ill patients. Good examples are drugs that have effects on blood rheology and clotting. One would rather forego the hypothetical benefit of a drug if there is a non-trivial change of triggering major controversies about drugs taken during the dying phase. This leaves only certain supplements as relatively safe options for pre-medication of cryonics patients.

The answer to the second question is not clear. The rationale behind pre-medication is that it can protect the brain during agonal shock and its associated ischemic events. Evidence for this belief is usually found in the peer reviewed literature on neuroprotection in ischemia. However, there is a clear difference between the administration of neuroprotective agents during the dying phase and the administration of neuroprotective agents prior to artificially-induced acute ischemia. One perspective is that such agents are beneficial but only delay the ischemic phase of the dying period. In this case supplements have little neuroprotective effect. An alternative perspective is one where such supplements do not alter the agonal course as such but provide more robust protection after circulatory arrest. Obviously, this matter is not of concern to conventional medicine so there is little evidence to make rational decisions. In light of the previous discussion, the current (tentative) verdict should be that a case can be made for pre-administration of neuroprotective agents but that these agents should be confined to “safe” supplements like melatonin, Vitamin E and curcumin. Whether such a regime would be beneficial needs to be decided on a case by case basis and is, therefore, more in the domain of the Health Care Proxy than Advance Directives.

Do Not Resuscitate Orders

Do Not Resuscitate (DNR) orders present one of the most challenging issues for cryonics optimization. On the one hand, we would like to benefit from any attempt to resuscitate us in case of sudden cardiac arrest (or any other acute events that can lead to death). On the other hand, we would not like to be subject to endless rounds of futile resuscitation attempts that can damage the brain.

One would be inclined to think that resuscitation attempts should be made in case of sudden insults or during surgery but that no resuscitation attempts should be made during terminal illness. In reality things are not that simple. For example, resuscitation may be possible after 8 minutes of cardiac arrest but the patient can suffer severe brain damage as a consequence. Such a scenario can be minimized by executing a DNR at the cost of foregoing any resuscitation attempts at all. Would this outweigh the benefits of successful resuscitation attempts? It is hard to see how an objective answer to this question can be given without taking a specific person’s views on risk and treatment into account. One way to mitigate this dilemma is to make a distinction in your Advance Directives between pre-arrest emergencies (for example, resuscitation should be permitted in the case of labored breathing but presence of heart beat) and full arrest. An in-hospital situation where resuscitation of a critically ill patient would be helpful would be where it would allow a cryonics standby team to deploy at the bedside of the patient. As can be seen from these examples, good resuscitation instructions for cryonics patients require a lot of attention to context. Because confusion could arise whether Advance Directives would include pre-hospital emergency procedures it is recommended to execute an explicit document if you want these cases to be covered – such a document could be complemented by wearing a bracelet.

Creating a general template

This article has identified a number of important medico-legal issues that need to be addressed by cryonicists to optimize their cryopreservation. It has become clear that in the case of many topics we would all benefit from uniform and effective language. The next step is to translate the concerns discussed in this document in clear legal language so that templates can be offered to all members of cryonics organizations to draft their own Living Will and Advance Directives. One potential problem of such a general template is that it may not conform to state regulations and needs additional tweaking to make it valid in the state where the person lives.

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Appendix :  Neurological damage during the dying phase

Securing viability of the brain by contemporary criteria is the most important objective of cryonics standby and stabilization. Recognition of how pathological events in the central nervous system can defeat this objective is of great importance. As a general rule, the risk for increased brain damage is higher during slow dying. For example, when the ventilator is removed from the patient who is not able to breathe on his own the time between this action and circulatory arrest can be short. Conversely, when a patient is going through a prolonged terminal and agonal phase (regional) injury to the brain can occur while the body itself is still fighting for its survival.

The human brain has little storage of excess energy. As a result, hypoxia causes the brain to deplete its oxygen reserves within 30 seconds. The energy depletion that follows cerebral hypoxia during the dying phase has a number of distinct effects: 1) excitation or depression of certain processes in the brain, 2) alteration in the maintenance of structural integrity of tissues and cells, and 3) alteration of neuromediator synthesis and release. The depletion of oxygen leads to a switch from aerobic to anaerobic energy production. As a consequence, there is an increase in the metabolic end-products of glycolysis such as lactic acid which decreases pH in the brain. After 5 minutes no useful energy sources remain in the brain, which can explain why the limit for conventional resuscitation without neurological deficits is put at 5 minutes as well. Because the dying phase leads to progressively worse hypotension and hypoxia the metabolic state of the brain after the agonal phase is worse than if there would have been sudden cardiac arrest.

Light microscopic changes have been observed in brain cells after 5 minutes of ischemia. Prolonged hypotension, as can occur in the agonal patient, can lead to the appearance of “ghost cells” and disappearance of nerve cells. Such observations provide evidence that structural changes, including cell death, can occur prior to clinical death. Another manifestation of hypoxia (or hypotension) is the progressive development of cerebral edema. The resulting narrowing of vessels and decrease of intercellular space can, in turn, aggravate energy delivery to tissues. Of particular importance for cryonics stabilization procedures is the development of no-reflow which can prevent complete restoration of perfusion to parts of the brain during cardiopulmonary support. There is no consensus as to whether no-reflow can occur as a result of prolonged hypotension (as opposed to complete cessation of blood flow), but an extended dying phase can set the stage for cerebral perfusion impairment after circulatory arrest.

The central nervous system does not shut down at once. Throughout the terminal and agonal phase alternations in the brain progress from minor changes in awareness and perception to deep coma. As a general rule, more recent and complex functions of the brain disappear earlier than the most basic functions of the brain. The uneven brain response to hypoxia may reflect different energy requirements, biochemical and structural differences, and/or the activation of protective mechanisms to preserve the “core” functions of the brain. The CA1 region of the hippocampus has been demonstrated to be uniquely vulnerable to ischemia. This presents a problem for contemporary cryonics since the objective of human cryopreservation is to preserve identity-relevant information in the brain.

This article is a slightly revised version of a paper that was submitted for the 4th Asset Preservation Meeting near Gloucester, Massachusetts.