04. April 2017 · Comments Off on Changing the Subject on Cryonics · Categories: Cryonics, Society

Every Alcor member has experienced this. What appears to start as a discussion about the feasibility of cryonics quickly turns into a conversation about “overpopulation,” “selfishness,” “immortality,” “mind uploading,” “transhumanism,” etc. This predictable course of events is quite frustrating to the cryonics advocate but rather convenient for the critic because the actual technical and rational arguments in favor of cryonics no longer need to be scrutinized. I would be the first to admit, however, that this response often reflects a form of anxiety associated with cryonics that a critic does not want to deal with. But I think we should also recognize that often we have only ourselves to blame when someone tries to change the subject.

Since the beginning of cryonics the field has always been associated or even bundled with “something else.” Specifically, many public advocates of cryonics have also strongly advocated physical immortality, transhumanism, or the idea of substrate-independent minds (“mind uploading”). In particular, transhumanists are prone to present cryonics as just one component in a broader set of beliefs. While such an approach can be great for community building between like-minded people, it can present a serious obstacle to reaching out to the rest of the world. Not only does such rhetoric have limited appeal to the general public, it is not consistent with the idea of cryonics being an experimental critical care procedure.

I became painfully aware of this phenomenon when I read a “refutation” of cryonics by the economist Bryan Caplan that was essentially a critique of mind uploading. Now, some cryonics advocates do believe in substrate-independent minds, but mind uploading is not an essential part of cryonics and suggesting otherwise will just provide a convenient excuse to avoid discussing the merits of cryonics at all. I have seen many, many other such examples where a skeptical investigator simply confined himself to offering a critique of immortality or transhumanism and left it at that. Why does this happen?

I think we often do a lot ourselves to “prime” our presentation of cryonics to produce such a response. Could you imagine if someone introduces a new life-saving technology while also advocating socialism, atheism, or immortality? We would feel obliged to point out that medicine should have universal aspirations and not be tied to political or (anti-)religious notions. It should not be any different in the case of cryonics.

In fact, recognizing this neutral and universal aim of cryonics will also provide us with sensible responses to counter some of the arguments that are made against it by asking why cryonics is held to different standards than other experimental medical procedures. “Selfishness? Our desire is to make cryonics available to all and save lives.” “Immortality? All we are saying is that we should replace our existing, dated, definition of death with a more rigorous definition.” “Transhumanism? The belief systems of some cryonics advocates have little bearing on its feasibility.” There are many arguments against cryonics that make little sense, or would even be considered abhorrent, if used against more mainstream experimental treatments, and it is important to consistently reiterate this position. But it is going to be challenging if we keep presenting cryonics in a matter that induces the audience to change the subject.

One objection I have heard against this perspective is that it is rather fear-driven, if not cowardly. Instead, we should not be embarrassed about our beliefs and be honest about our ultimate objectives and convictions. I think this argument is mistaken because it assumes that cryonics advocates are a homogenous group with identical beliefs and values. As cryonics keeps growing, this will become more and more untenable. The real risk is to waste such membership growth opportunities by essentially encouraging an inward-looking outlook.

Looking at this issue from the perspective of individual survival, such public indulgence with other controversial ideas strikes me as counterproductive. If your survival depends on the exercise of some personal restraint, and resisting the desire to argue all kinds of other issues that you care about, can you not do this? Would you rather be “right” but dead?

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

03. April 2017 · Comments Off on How to Validate New Cryonics Technologies · Categories: Cryonics, Science

Evidence in cryonics is a complicated concept. For starters, it is not possible to “prove” cryonics will work, here and now, because the fundamental idea of cryonics is to stabilize critically ill patients (people considered “dead” by less rigorous criteria) in anticipation of more advanced future medical technologies. What we can do is validate cryonics technologies with reversible cryopreservation (“suspended animation”) as a benchmark. As a general rule, we can state that we make progress in cryonics when stabilization, cryopreservation, and maintenance (“storage”) technologies cause less damage than the technologies that preceded them. But how do we know if this is the case?

The most rigorous form of validation, human clinical trials, is usually not available in cryonics. There are often new (approved) emergency medical technologies, however, that can be modified to be used in cryonics procedures. A major advantage of adopting such technologies is that the validation has already been done by other organizations or companies. Examples of such technologies will often fall under the rubric of emergency medicine. For example, an FDA-approved technology that improves blood flow during cardiopulmonary resuscitation can be added to Alcor’s stabilization equipment to improve stabilization procedures.

One step down from rigorously designed human clinical trials are animal studies. In cryonics we often make a distinction between small animal studies (e.g., mice, rats) and large animal studies (e.g., pigs, dogs) etc. It seems common sense to think that large mammals provide stronger evidence for a technology than smaller animals but the real issue at stake here is not how large an animal is but how closely an animal model tracks what happens in humans. For example, if cat brains have an uncharacteristically high tolerance for cerebral ischemia, the (smaller) rat may actually be a more realistic model for validating neuroprotective strategies in humans.

One area where choosing the correct animal model has proven itself to be of crucial importance concerns the effect of cryoprotectants on the brain. Most mammalian species experience dehydration of the brain after equilibration with a vitrification agent. Because it is reasonable to assume that severe dehydration adversely affects brain viability it is tempting to select an animal model that experiences little cryoprotectant-induced dehydration. But one thing that we have learned from burhole measurements and CT scans in human cryonics patients is that under optimal conditions cryoprotective perfusion with both glycerol and the modern vitrification agents produces severe shrinkage of the brain. So if we want to validate strategies to eliminate this dehydration the most important consideration is not how “large” the animal is but how well the animal tracks the effects of cryoprotectants on the human brain.

Most technologies in cryonics need to be evaluated with ultrastructure and/or viability as an endpoint. But there are also new developments in cryonics where such a benchmark would not make a lot of sense. For example, if we build a new patient enclosure to keep the patient cold during cryoprotective perfusion we can just measure the core temperature of the patient to see if we have done a satisfactory engineering job. Another example is the design of new dewars where we can look at variables like the boiloff rate and long-term durability of the design.

In conclusion, there are a number of ways to validate new technologies in cryonics. If a new technology has undergone human clinical trials we often can just adapt that technology for cryonics without designing new experiments. In the case of more cryonics-specific technologies animal studies can be conducted and the choice of animal model will be dictated by how close a model tracks what we know to occur in humans (among other considerations like ethics and cost). Finally, when a new development in cryonics is mostly an engineering challenge, validating its efficacy is often just an issue of doing basic physiological measurements or practical tests.

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

01. April 2017 · Comments Off on I’m Not Dead Yet! · Categories: Cryonics, Death

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

31. March 2017 · Comments Off on Killing Yourself to Live · Categories: Cryonics, Death

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

30. March 2017 · Comments Off on Who’s Leaving Whom? · Categories: Cryonics, Health

It is well established that cryonics can be a formidable source of division within families. A classic example is the claim that a person who makes cryonics arrangements has reduced the amount of money available to spend on other goods and services—and will ultimately leave less money behind after passing away. We may think that such a perspective leaves little room for financial autonomy and tolerance in a family but experience confirms that many families operate exactly like that.

A related non-financial argument is that a person who makes cryonics arrangements is “selfish” by going it alone and leaving his family to die. Naturally, this argument can be turned on its head. A friend of mine once stated that, given the interest of her boyfriend in cryonics, the decision not to make cryonics arrangements herself would be akin to a decision to (eventually) abandon him. From the perspective of a cryonics advocate this argument can be further strengthened. If one believes that a cryonics patient is not dead, the decision not to make cryonics arrangements would be akin to walking away from someone who is critically ill (or in a coma).

In the examples so far we have faced a situation in which one person responds to the decision of another person. In many cases, however, the decision whether to make cryonics arrangements is the subject of joint deliberation. If we approach the subject from the perspective of not wanting to abandon a loved one there are a number of good reasons to decide in favor of a family making cryonics arrangements.

First of all, the decision not to make cryonics arrangements will lead to a predictable outcome: death (at least for the foreseeable future). And death is not a joint experience but the cessation of a family as a living entity. Why would a family voluntarily put a predictable expiration date on its existence?

Secondly, family members usually do not die at the same time. This not only applies to children but to couples as well. Couples think that the best they can do is to stick together “till death do us part.” In principle, cryonics can break with this tradition by placing one person in cryopreservation (and eventually both of them). While the relationship of the “survivor” to the cryonics patient is not identical to both being alive it is a whole lot better than throwing them in a hole or burning them because today’s medicine is not able to sustain them.

But what if we consider a whole family making cryonics arrangements and some will make it and others do not? This is indeed a heart wrenching scenario but these kinds of things happen in mainstream life, too. Survivors usually do not respond by taking out the whole family but mourn, remember, and pick up the pieces. A more dispassionate response is to say that some family members surviving is still preferable in that the surviving person’s situation is improved (compared to being clinically dead) without worsening the situation of the non-survivors (who are now non-existent). It is also important to emphasize here that survival is not an external event that “just happens.” We can do a lot to improve the probability that a whole family sticks together by executing the right paperwork and ensuring that younger family members will be able to take advantage of rejuvenation biotechnologies.

There are examples of individuals and families who made cryonics arrangements pretty much upon hearing about the idea. Most families take a little more time (or never get to it). One good piece of advice is to take out
life insurance for the whole family while rates are still affordable (especially for very young children). For most families there are very good general reasons to take out life insurance, such as providing financial stability for the surviving partners and children. So getting life insurance is a good idea while the conversation about the subject continues. It is not trivial to make last-minute cryonics arrangements, but it is impossible to get life insurance for a person who is dying or already dead and most people cannot pay for cryonics in cash.

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

29. March 2017 · Comments Off on Technological Advances in Cryonics: What’s Next? · Categories: Cryonics

In the history of cryonics we can identify a number of major technological developments: the introduction of cryoprotectants to reduce ice formation, the use of mechanical chest compression devices to restore brain perfusion and accelerate cooling, comprehensive multi-modal medications protocols to mitigate warm ischemia and favor good cryoprotective perfusion, remote blood washout with an organ preservation solution to protect against cold ischemia, closed-circuit cryoprotective perfusion to reduce osmotic damage, and, of course, the introduction of vitrification agents to eliminate ice formation altogether.

What are the kinds of major technological developments that we can expect in cryonics in the foreseeable future? When we talk about technological progress we should distinguish among advances in medical science that simply require implementation in cryonics, advances in medical science that require various degrees of modification to be used in cryonics, and technological developments that are conceived and developed within cryonics. These distinctions are important to recognize because they can tell us whether new advances “simply” require acquiring these technologies or whether an ambitious research and development program needs to be launched to validate, develop, and introduce these technologies.

The three most important future technological advances that I can foresee are:

1. Liquid ventilation (cyclic cold lung lavage). Currently there are two basic modes of cooling in cryonics: (a) external cooling in an ice bath and (b) internal cooling with an organ preservation solution. Considering the harmful effects of warm ischemia on the structure of the brain and distribution of the vitrification agent, it is very important to introduce a rapid method of initial cooling that does not require surgery and can approximate the rates of internal cooling. The most potent candidate here is liquid ventilation in which a cold perfluorocarbon is pumped in and out of the lungs to accelerate cooling of the patient.

2. Intermediate temperature storage (ITS). As vitrification eliminates ice formation, fracturing remains the only mechanical form of injury in contemporary cryonics. The most obvious solution is to store patients below the glass transition temperature ((‑123°C for the M22 vitrification solution) but not so low as to induce fracturing. Functional neuro ITS units have been built and detailed designs for whole body ITS units have been developed. Concerns that have not been fully addressed yet include optimal storage temperature and cost. The most pressing practical question at this point is whether fracture-free storage may be possible at liquid nitrogen temperatures if ischemia-induced ice formation is eliminated and a proper cooling protocol is used. Also, would it possible to eliminate the need for ITS altogether if a cold gas is circulated through the patient’s circulatory system instead?

3. Opening the blood-brain barrier. It has been well established that under good conditions loading of the vitrification agent produces severe dehydration of the brain. While dehydration may not substantially alter brain structure, it is a problem in terms of maintaining viability of the brain and producing good electron micrographs. We now know of a number of agents that can modify the blood-brain barrier to allow cryoprotective perfusion without severe dehydration. Current concerns include whether such agents produce edema in other parts of the body, what the optimum protocol and dosage should be for humans, and whether the use of such agents reduces or favors ice formation in ischemic brains.

Other conceivable advantages that can improve cryonics include lower toxicity vitrification agents, drugs that can substantially reduce metabolism in the brain, and integration of brain imaging and cryoprotectant perfusion.

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

28. March 2017 · Comments Off on Low Cost Cryonics · Categories: Cryonics

Over the years some cryonics proponents have expressed interest and support for offering an inexpensive form of cryonics. Before discussing what such a form of cryonics might entail I first would like to briefly address the question of whether the idea of low cost cryonics is a solution to a non-existent problem. After all, for low cost cryonics to make sense, there must be a substantial number of people being priced out of cryonics arrangements who would make arrangements if it were more affordable. For this to occur a person must not only not be able to afford Alcor’s services but also not be able to afford the Cryonics Institute’s either. As far as I am aware, this problem is mostly confined to people who are basically uninsurable due to a medical condition or advanced age, or who wish to cryopreserve someone else where funding is insufficient.

In some cases, however, people who have found themselves priced out of cryonics arrangements have been the beneficiary of fund raising campaigns within the cryonics community. While it may not be possible to provide funding for all such cases, this development does raise the question of how many people who had a strong public desire to be cryopreserved did not get their wishes honored. The major reason to advocate low cost cryonics is to bring the service within the reach of more people. Thus it is important to understand how many people are actually excluded from being cryopreserved due to financial challenges. If access to cryonics is mostly a non-issue one might argue that strategies to simply aim at more people making cryonics arrangements can be more effective than offering lower priced options.

There are roughly three areas where cost savings can be realized in cryonics: (a) long term care costs, (b) cryoprotection, and (c) standby and stabilization. It is not possible to do justice to all the potential cost savings in these areas so let me briefly discuss the major themes.

While it is reasonable to assume that some long term care costs can be reduced by reducing expenses associated with running a cryonics organization (staff, administrative costs, rent) the bulk of long-term care expenses arise from the need to keep patients in cryopreservation until resuscitation efforts will be possible. If there is one thing we have learned since the early days of cryonics it is that it is not wise to compromise on demanding pre-payment (life insurance or cash) or to use wildly optimistic growth assumptions for these funds. A pay-as-you-go system would not just subject many patients to premature thawing but also endanger the reputation of the cryonics field as a whole.

This mostly leaves cryoprotection and standby services as potential cost saving measures. Clearly, offering standby and stabilization without subsequent cryoprotection would be an incoherent approach because attempts to preserve the viability of the brain would be followed by straight freezing. Offering sophisticated cryoprotection procedures without standby is not particularly logical either because optimal cryopreservation requires rapid stabilization and cooling after clinical death. To really realize substantial cost savings a cryonics organization would need to exclude both standby and cryoprotection from its protocol and focus on the isolated brain. Is it responsible for a cryonics organization to offer such a form of low cost cryonics? It is hard to answer this question because it is difficult to predict how much damage is still compatible with inferring the original state of the brain. One research program, however, that could give us preliminary answers to such questions is reconstructive connectomics. We can model these low cost cryonics protocols and then see if we can recognize or reconstruct the original structure of the brain using either conventional electron microscopy or more recent 3D brain mapping technologies. If this project provides reasons for optimism there is a strong ethical argument for an organization to offer this service.

In short, the most credible realization of “low cost cryonics” would entail a financially conservative cryonics organization that offers secure, isolated-brain cryopreservation without standby and without the state-of-the-art
cryoprotection now done at Alcor with a trained team, though a less training-intensive, inexpensive, method of cryoprotection (immersion of the brain in cryoprotectant after chemical fixation) might still be possible.

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

28. March 2017 · Comments Off on Forever Lost? The First Cryonics Brain Repair Paper · Categories: Cryonics

For more than a year now I have been trying to locate Jerome B. White’s paper “Viral Induced Repair of Damaged Neurons with Preservation of Long Term Information Content.” This paper is referred to in a number of books and articles, including Robert Ettinger’s Man into Superman (1972), Eric Drexler’s Engines of Creation, and Mike Darwin’s biological repair proposal in his article The Anabolocyte (1977). Despite being recognized as the first presentation about repair of the brain of cryonics patients, I am not aware of any actual quotes or discussion of the paper, raising the question of how many authors who have referenced the paper have actually read it. The best I have been able to find is what amounts to the complete abstract of the paper in Robert Ettinger’s Man into Superman:

“An organic cell is a self repairing automaton, but if environmental interference exceeds a certain limit, damage will become total. Freezing can be used to halt progressive damage along with all metabolism, but means are required to restore or augment the cellular genetic control program, or enrich the environment to enhance repair ability. It has been proposed that appropriate genetic information be introduced by means of artificially constructed virus particles into a congenitally defective cell for remedy; similar means may be used for the more general case of repair. Progress has been made in many relevant areas. The repair program must use means such as protein synthesis and metabolic pathways to diagnose and repair any damage. Applied to brain neurons, this might destroy long term information content, which appears to be stored in molecular form, often suggested to be in a feedback cycle involving mRNA and protein. This information can be preserved by specifying that the repair program incorporate appropriate RNA tapes into itself upon entry and release them on termination of repair.”

Jerome B. White’s paper was presented at the Second National Cryonics Conference in Ann Arbor, Michigan, in 1969. Unfortunately, only the proceedings of the First Annual Cryonics Conference in 1968 have been made available as a book. We can state with reasonable certainty, though, that White spoke on this topic at the second conference because Saul Kent briefly mentions his presentation in a review of the conference for Cryonics Reports, April-May 1969. Even more intriguing, the reference for this paper in Man into Superman includes “reprints available [emphasis added] from the Cryonics Society of Michigan,” which provides evidence that this presentation was either transcribed or an actual paper was prepared prior to or after the conference. Notwithstanding this encouraging point, I have not been able to locate this paper so far, despite asking individuals such as Michael Darwin, Michael Perry, Stephen Bridge, and Catherine Donaldson. Could it be possible that a paper was produced and distributed on a small scale but no copies of the paper have survived? This would be a tragedy, especially in light of the fact that it was the first proposal for a cell repair machine to resuscitate cryonics patients.

One person we cannot consult is Jerome Butler White (b. 1938) himself. The “good” news is that Mr. White has not passed away but, after a struggle with AIDS, was cryopreserved in 1994 by the American Cryonics Society (ACS) in collaboration with BioPreservation. (He is now stored at the Cryonics Institute.) Some of his other presentations include “The Technology of Cryonic Suspension,” Cryonics Conference and Scientific Congress, San Francisco, 1971, and “Heat Flow in the Human Patient,” Lake Tahoe Life Extension Festival, 1985. In the internet age it is hard to imagine that any information can be lost forever but we cannot rule out here that only a few individuals who have heard this presentation in 1969 are still alive today (some who have made cryonics arrangements) and that all physical copies may have been (irretrievably) lost. If that is the case, the text of this first paper on viral cell repair of cryonics patients will never be known and we can only speculate on its contents based on the abstract and any recollections of people who were present. One cannot think about this scenario and fail to reflect on the fragile nature of the personal memories stored in our own brains….

Note added by Mike Perry: Someone I know who is a prominent cryonicist thinks he has notes or text for the speech that was given by Jerry White at the 1969 Cryonics Conference. I have been waiting for the scanned document and will report when something comes to light.

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

Postscript: Jerome White’s paper was (re)discovered by Art Quaife in September, 2014 and published in Cryonics Magazine, October, 2014. The paper is now available online here.

27. March 2017 · Comments Off on The Case for Brain Cryopreservation · Categories: Cryonics, Neuroscience

Cryopreservation of just the head is as old as Alcor itself. In fact, some people identify Alcor with its “neuro-preservation” option. It is important, however, to recognize that the objective of preserving the head is really to preserve what is inside the head, i.e. the brain. While I am aware of (contrived) technical arguments that prefer head preservation over brain preservation for information-theoretical reasons, I suspect that no advocate of neuro-preservation is anxious about the prospect of having only his/her brain preserved in a pristine state.

This raises an important question – one that is not immediately evident to the general public. Why not just preserve the naked brain instead? I am aware of at least three major arguments against it and I think that these arguments are based on incomplete information or a lack of imagination.

Myth 1: The isolated brain is not a stable organ and will collapse upon itself in a jellylike state if it is removed from the skull.

Answer: In human cryopreservation the brain would only be extracted at low temperatures which provide a lot more stability to the brain. In addition, in a good case the brain will also be loaded with a cryoprotectant and exist in a dehydrated state, which will provide even more stability.

Myth 2: Removing the brain from the skull will damage the brain and will erase identity-critical information.

Answer: It is correct that morticians typically remove the brain with little regard for its ultrastructural integrity but there is no reason why a cryonics organization should engage in such traumatic brain removal. Safe brain removal protocols are technically possible and cryonics organizations have a strong incentive to develop and refine such techniques.

Myth 3: The skull is necessary to provide protection to the brain.

Answer: It is undeniable that the skull provides robust protection to the brain but from that it does not follow that a cryonics organization cannot design a long-term enclosure and maintenance method that provides strong protection of the naked brain, too.

I do not claim that brain preservation is equal in all respects to neuro-preservation. For example, extraction of the brain from the skull requires additional time after completion of cryoprotectant perfusion and during this time the brain will be exposed to high levels of cryoprotectant (strictly speaking, isolated brain perfusion is possible but this requires a very advanced surgical procedure). Keeping the brain temperature low and uniform during brain removal is also a challenge.

On the other hand, there are potential advantages as well. An isolated brain can be placed in the cryoprotectant to allow diffusion of the vitrification agent prior to cryogenic cooldown to compensate for any ischemia-induced cortical perfusion impairment. In fact, if perfusion is no longer an option, immersion of the (fixed) brain in cryoprotectant is the only means to mitigate ice formation during cryostasis. Another advantage is a decrease in long-term care costs (at least 50%), which allows for lower cryopreservation minimums.

But the most important advantage of brain preservation is that public perception and negative PR would be substantially lower than that with neuro-preservation. Even if the procedure were a little riskier (technically speaking) one could still argue that it is safer in general because images of cryopreserved brains do not risk the kind of visceral response that neuro-preservation triggers.

I cannot do justice to all the technical, logistical, and financial issues associated with brain-only cryopreservation here but the topic requires more study for the reason alone that cryonics organizations occasionally receive fixed brains, or patients with long ischemic times, for whom immersion cryoprotection could be superior to straight freezing. Brain cryopreservation does not exist as an option yet, but it has been the reality for a number of patients.

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

27. March 2017 · Comments Off on Multiple Sclerosis and Human Enhancement · Categories: Health, Neuroscience

Multiple sclerosis is a disease that raises a lot of interesting questions for people interested in biogerontology, human enhancement, and even cryonics. It raises questions about immunosenescence and draws attention to possible immune improvements for biological human enhancement. Biotechnologies to induce myelin repair may even be useful for the repair of cryopreserved brains. Before I discuss multiple sclerosis from these perspectives, let us take a closer look at this medical condition.

Multiple sclerosis (MS) is an inflammatory autoimmune disorder of the central nervous system that results in axonal degeneration in the brain and spinal cord. In simple terms, multiple sclerosis is a disease wherein the body’s immune system attacks and damages the myelin sheath, the fatty tissue that surrounds axons in the central nervous system. The myelin sheath is important because it facilitates the conduction of electrical signals along neural pathways. Like electrical wires, neuronal axons require insulation to ensure that they are able to transmit a signal accurately and at high speeds. It is these millions of nerves that carry messages from the brain to other parts of the body and vice versa.

More specifically, MS involves the loss of oligodendrocytes, the cells responsible for creating and maintaining the myelin sheath. This results in a thinning or complete loss of myelin (i.e., demyelination) and, as the disease advances, the breakdown of the axons of neurons. A repair process, called remyelination, takes place in early phases of the disease, but the oligodendrocytes are unable to completely rebuild the cell’s myelin sheath. Repeated attacks lead to successively less effective remyelinations, until a scar-like plaque is built up around the damaged axons.

The name multiple sclerosis refers to the scars (sclerae—better known as plaques or lesions) that form in the nervous system. These scars most commonly affect the white matter in the optic nerve, brain stem, basal ganglia, and spinal cord or white matter tracts close to the lateral ventricles of the brain. The peripheral nervous system is rarely involved. These lesions are the origin of the symptoms during an MS “attack.”

In addition to immune-mediated loss of myelin, which is thought to be carried out by T lymphocytes, B lymphocytes, and macrophages, another characteristic feature of MS is inflammation caused by a class of white blood cells called T cells, a kind of lymphocyte that plays an important role in the body’s defenses. In MS, T cells enter the brain via disruptions in the blood-brain barrier. The T cells recognize myelin as foreign and attack it, which is why these cells are also called “autoreactive lymphocytes.”

The attack of myelin starts inflammatory processes which trigger other immune cells and the release of soluble factors like cytokines and antibodies. Further breakdown of the blood–brain barrier in turn causes a number of other damaging effects such as swelling, activation of macrophages, and more activation of cytokines and other destructive proteins. These inflammatory factors could lead to or enhance the loss of myelin, or they may cause the axon to break down completely.

Because multiple sclerosis is not selective for specific neurons, and can progress through the brain and spinal cord at random, each patient’s symptoms may vary considerably. When a patient experiences an “attack” of increased disease activity, the impairment of neuronal communication can manifest as a broad spectrum of symptoms affecting sensory processing, locomotion, and cognition.

Some of the most common symptoms include: numbness and/or tingling of the limbs, like pins and needles; extreme and constant fatigue; slurring or stuttering; dragging of feet; vision problems, especially blurred vision; loss of coordination; inability to walk without veering and bumping into things; weakness; tremors; pain, especially in the legs; dizziness; and insomnia. There are many other symptoms, as well, such as loss of bowel or bladder control, the inability to process thoughts (which leads to confusion), and passing out. Some MS patients lose their vision and many lose their ability to walk. The symptoms are not necessarily the same for all patients and, in fact, an individual MS patient does not always have the same symptoms from day to day or even from minute to minute.

One of the most prevalent symptoms of MS is extreme and chronic fatigue. Assessment of fatigue in MS is difficult because it may be multifactorial, caused by immunologic abnormalities as well as other conditions that contribute to fatigue such as depression and disordered sleep (Braley and Chervin, 2010). Pharmacologic treatments such as amantadine and modafinil have shown favorable results for subjective measures of fatigue. Both drugs are well tolerated and have a mild side-effect profile (Life Extension Foundation, 2013).

It is estimated that multiple sclerosis affects approximately 85 out of every 100,000 people (Apatoff, 2002). The number of known patients is about 400,000 in the United States and about 2.5 million worldwide (Braley & Chervin, 2010). In recent years, there has been an increase of identified multiple sclerosis patients with about 50 percent more women reporting the disease. Indeed, between two and three times as many women have MS than men. Most patients are diagnosed between the ages of 20 and 50 but MS can strike at any age (National Multiple Sclerosis Society, 2013).

Incidence of multiple sclerosis varies by geographic region and certain demographic groups (Apatoff, 2002; Midgard, 2001). There is evidence that worldwide distribution of MS may be linked to latitude (Midgard, 2001). In the U.S., for instance, there is a lower rate of MS in the South than in other regions (Apatoff, 2002). Data regarding race shows 54 percent of MS patients are white, 25 percent are black and 19 percent are classified as other (Apatoff, 2002).

There are four disease courses identified in MS:

Relapsing-Remitting: Patients have clearly defined acute attacks or flare-ups that are referred to as relapses. During the relapse, the patient experiences worsening of neurologic function—the body or mind will not function properly. The relapse is followed by either partial or total recovery, called remissions, when symptoms are alleviated. About 85 percent of MS patients fall into this category (National Multiple
Sclerosis Society, 2013).

Primary-Progressive: The disease slowly and consistently gets worse with no relapses or remissions. Progression of the disease occurs over time and the patient may experience temporary slight improvements of functioning. About 10 percent of MS patients fall into this category (National Multiple Sclerosis Society, 2013).

Secondary-Progressive: Patient appears to have relapsing-remitting MS, but after time the disease becomes steadily worse. There may or may not be plateaus, flareups, or remissions. About half the people originally diagnosed with relapsing remitting will move into this category within 10 years (National Multiple Sclerosis Society, 2013).

Progressive-Relapsing: Quick disease progression with few, if any, remissions. About 5 percent of MS patients fall into this category at diagnosis (National Multiple Sclerosis Society, 2003).

The cause(s) of multiple sclerosis remain unknown although research suggests that both genetic and environmental factors contribute to the development of the disease (National Multiple Sclerosis Society, 2013; Compston and Coles, 2002). The current prevailing theory is that MS is a complex multifactorial disease based on a genetic susceptibility but requiring an environmental trigger, and which causes tissue damage through inflammatory/ immune mechanisms. Widely varying environmental factors have been found to be associated with the disease, ranging from infectious agents to Vitamin D deficiency and smoking. The debate these days revolves primarily around whether immune pathogenesis is primary, or acts secondarily to some other trigger (Braley & Chervin, 2010).

Risk factors for multiple sclerosis include genetics and family history, though it is believed that up to 75% of MS must be attributable to non-genetic or environmental factors. Infection is one of the more widely suspected non-genetic risk factors. A commonly held theory is that viruses involved in the development of autoimmune diseases could mimic the proteins found on nerves, making those nerves a target for antibodies. The potential roles of several viruses have been investigated including herpes simplex virus (HSV), rubella, measles, mumps, and Epstein Barr virus (EBV). The strongest correlation between a virus and MS exists with EBV—virtually 100% of patients who have MS are seropositive for EBV (the rate in the general public is about 90%)— but potential causality remains strongly debated (Ludwin and Jacobson, 2011).

It is important to keep in mind that infectious agents such as viruses may, in fact, have nothing to do with causing MS. The association of a virus with MS is based on increased antibody response and may be epiphenomenal of a dysregulated global immune response. “Proving” causality will require consistent molecular findings as well as consistent results from well-controlled clinical trials of virus-specific antiviral therapies (as yet to be developed). In the end, any theory concerning causality in MS should also account for the strong association with other environmental factors such as Vitamin D deficiency and smoking. Indeed, a landmark study found that, compared to those with the highest levels of vitamin D, those with the lowest blood levels were 62% more likely to develop MS. Additionally, a literature review evaluating more than 3000 MS cases and 45,000 controls indicates that smoking increases the risk of developing MS by approximately 50% (Life Extension Foundation, 2013).

Recently, researchers have pinpointed a specific toxin they believe may be responsible for the onset of MS. Epsilon toxin—a byproduct of the bacterium Clostridium perfringens—is able to permeate the blood brain barrier and has been demonstrated to kill oligodendrocytes and meningeal cells. Loss of oligodendrocytes and meningeal inflammation are both part of the MS disease process, and may be triggered by exposure to epsilon toxin.

The fact that females are more susceptible to inflammatory autoimmune diseases, including multiple sclerosis, points to the potential role of hormones in the etiology of multiple sclerosis. Interestingly, the course of disease is affected by the fluctuation of steroid hormones during the female menstrual cycle and female MS patients generally experience clinical improvements during pregnancy (Life Extension Foundation, 2013). Additionally, pregnancy appears to be protective against the development of MS. A study in 2012 demonstrated that women who have been pregnant two or more times had a significantly reduced risk of developing MS, while women who have had five or more pregnancies had one-twentieth the risk of developing MS compared to women who were never pregnant. (The increase in MS prevalence over the last few decades could reflect the fact that women are having fewer children.) A growing body of evidence supports the therapeutic potential of hormones (both testosterone and estrogens) in animal models of multiple sclerosis, but more research is needed to understand the pathways and mechanisms underlying the beneficial effects of sex hormones on MS pathology (Gold and Voskuhl, 2009).

No single test gives a definitive diagnosis for MS, and variable symptoms and disease course make early diagnosis a challenge. Most diagnoses are presumptive and are based on the clinical symptoms seen in an acute attack. Supporting evidence of these presumptions is then sought, usually from a combination of magnetic resonance imaging (MRI) of the brain, testing the cerebrospinal fluid (CSF) for antibodies, measuring the
efficiency of nerve impulse conduction, and monitoring symptoms over time.

As there is still much work to be done in understanding the nature of multiple sclerosis, a cure has yet to be discovered. Conventional medical treatment typically focuses on strategies to treat acute attacks, to slow the progression of the disease, and to treat symptoms. Corticosteriods such as methylprednisolone are the first line of defense against acute MS attacks and are administered in high doses to suppress the immune system and decrease the production of proinflammatory factors. Plasma exchange is also used to physically remove antibodies and proinflammatory factors from the blood.

The use of beta interferons is a longstanding MS treatment strategy, originally envisioned as an antiviral compound. Beta interferons reduce inflammation and slow disease progression, but the mechanism of action is poorly understood. Other immunosuppressant drugs such as Mitoxantrone and Fingolimod also slow disease progression, but are not used as first-line treatments due to their severe side effects. More recently, researchers at Oregon Health & Science University have noted that an antioxidant called MitoQ has been shown to significantly reverse symptoms in a mouse model of MS (Mao, Manczak, Shirendeb, and Reddy (2013).

Besides pharmacological treatments, MS patients may benefit from therapies (such as physical and speech therapy) and from an optimized nutritional protocol. Supplementation with Vitamin D, Omega-3 and -6 fatty acids, Vitamin E, lipoic acid, Vitamin b12, and Coenzyme Q10 appear to be of particular potential benefit (Life Extension Foundation, 2013). Until a definitive cause for MS can be defined and a cure developed, such strategies, including hormone therapy, offer possible ways to improve quality of life over the course of disease progression.

Unlike Alzheimer’s disease, there does not appear to be a Mendelian variant of MS that will invariably produce the disease in people who have the gene. A somewhat puzzling variable is that MS predominantly tends to occur between the ages of 20 and 50. This appears to exclude approaching MS as a form of immunosenescence. After all, if MS would be a function of the aging immune system, we would see progressively more cases of MS as people get older (or in AIDS patients), ultimately involving many very old people. More likely, MS is a non age-related form of dysfunction of the immune system that is triggered by environmental factors (such as a viral infection). While many discussions about the role of viruses in debilitating diseases like Alzheimer’s and MS still suffer from an incomplete understanding of cause and effect, it seems reasonable to conclude that enhancement of the human immune system can greatly reduce disease and improve the quality of life, even in healthy humans.

One potential treatment for MS is to induce remyelination (or inhibit processes that interfere with efficient remyelination). Stem cells can be administered to produce oligodendrocyte precursor cells to produce the oligodendrocyte glial cells that are responsible for remyelination of axons. While the myelin sheaths of these remyelated axons are not as thick as the myelin sheaths that are formed during development, remyelination can improve conduction velocity and prevent the destruction of axons. While the dominant repair strategies envisioned for cryonics involve molecular nanotechnologies that can build any biochemical structures that physical law permits, it is encouraging to know that specific stem cell therapies will be available to repair and restore myelin function in cryonics patients as damage to myelin should be expected as a result of (prolonged) ischemia and cryoprotectant toxicity.

An interesting possibility is that remyelination therapies may also be used for human enhancement if these therapies can be tweaked to improve conduction velocity in humans or to induce certain desirable physiological responses by varying the composition and strength of the myelin sheath in various parts of the central nervous system.


Apatoff, Brian R. (2002). MS on the rise in the US. Neurology Alert 20(7), 55(2).

Braley, Tiffany J., Chervin, Ronald D. (2010). Fatigue in Multiple Sclerosis: Mechanisms, evaluation, and treatment. Sleep 33(8), 1061-1067.

Compston, Alastair, and Coles, Alasdair (2002). The Lancet 359(9313), 1221.

Gold, Stefan M., and Voskuhl, Rhonda R. (2009). Estrogen and testosterone therapies in multiple sclerosis. Progress in Brain Research 175: 239-251.

Life Extension Foundation (2013). Multiple Sclerosis, in: Disease Prevention and Treatment, 5th edition, 947-956.

Ludwin, SK, and Jacobson, S. (2011). Epstein- Barr Virus and MS: Causality or association? The International MS Journal 17.2: 39-43.

Mao, Peizhong, Manczak, Maria, Shirendeb, Ulziibat P., and Reddy, P. Hemachandra (2013). MitoQ, a mitochondira-targeted antioxidant, delays disease progression and alleviates pathogenesis in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. Biochimica et Biophysica Acta Molecular Basis of Disease 1832(12): 2322- 2331.

Midgard, R. (2001). Epidemiology of multiple sclerosis: an overview. Journal of Neurology, Neurosurgery and Psychiatry 71(3), 422.

Originally published as an article (in the Cooler Minds Prevail series) in Cryonics magazine, February, 2014