21. May 2017 · Comments Off on Cryofixation and Chemopreservation · Categories: Cryonics, Neuroscience

The most common modern protocol for imaging brain structure at high magnification is to chemically fix the brain with aldehydes (formaldehyde, glutaraldehyde) and heavy metals like osmium and then prepare it for electron microscopy imaging. Using this method, a tremendous amount of detailed anatomical information about the structure of the brain in its healthy and pathological state has been obtained, including the effects of (prolonged) ischemia.

Almost from its inception, however, the limitations of this method have been recognized. In particular, when fixatives are introduced to the brain through the process of perfusion a number of distinct artifacts are produced, notably shrinking of the brain and a reduction of the extracellular space. While different solutions and protocols have been developed to reduce these artifacts, the gold standard for ultrastructural analysis is a method that does not use aldehydes at all; cryofixation.

In cryofixation small tissue samples are rapidly cooled (without freezing) and then prepared for electron microscopy. This method produces the most realistic images of the ultrastructure of the brain, as evidenced by papers that compared this method with aldehyde fixation or used advanced tools to understand the properties of the brain without doing electron microscopy.

Although the word “vitrification” is rarely used in the context of cryofixation, the pristine images in this method can only be achieved when ice formation is avoided through ultra-rapid cooling. Vitrification without the use of high concentrations of (toxic) cryoprotectants would be quite attractive if it could be scaled to the size of organs (or even humans!) but unfortunately this method can only be used on very small tissue samples.

The pristine images obtained from cryofixation raise some important issues. Does conventional aldehyde fixation produce only predictable distortions or is identity-specific information irreversibly lost? What are the ultrstructural effects of the heavy metal exposure when cryofixed samples are prepared for electron microscopy? In a more general sense, to what degree can we be confident that a technology can produce a completely realistic image of the ultrastructure of the brain?

Will computer simulations of scanned fixed brains need extensive correction if they are to serve as a simulation of the brain? One clear advantage of using viability assays in addition to electron microscopy is that we can test brain slices or whole brains for resumption of function (or retention of memory) after subjecting them to experimental protocols. This is a clear advantage of the use of cryopreservation technologies over chemical fixation. In a cryonics case we can monitor the patient from the start of our procedures to the point of long term care and collect data and viability information. In the case of chemopreservation no such feedback is possible and taking brain biopsies for electron microscopy is all we can do to assess the effects of our cryopreservation procedures.

It is tempting for a cryonics organization to choose the method of preservation that produces the most crisp electron micrographs. In reality, however, there are challenges and unknown issues. Cryofixation cannot be scaled to work for cryonics. What is the effect of conventional aldehyde perfusion in ischemic brains? How do aldehyde fixed brains look on the molecular level compared to cryopreserved brains? How can we know that identity-critical information is not irreversibly altered? And, last but not least, any preservation technology that renders tissue dead by conventional criteria cannot be considered as a means for achieving true human suspended animation.

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

18. May 2017 · Comments Off on Charisma: The Missing Link in Cryonics? · Categories: Cryonics

In the June issue of Cryonics magazine, I published an article called “Concepts of Identity and the Growth of Cryonics.” With the exception of my co-authored article on hostile partners in cryonics this article garnered the most feedback that I have ever received on an opinion piece about cryonics. Many people seemed to be sympathetic to the point that the lack of popularity of cryonics cannot be simply attributed to its lack of technological feasibility but I am not sure how widely my suggestion for cryonics organizations to embrace a broader concept of identity is shared. In fact, one person wrote to tell me that my perspective still ignores a rather fundamental point about the successful adoption of ideas and beliefs; the importance of charisma. He writes:

“Your list of rational responses to alleged shortcomings in cryopreservation procedures was good, but I think it misses the point. We can be rational about this, day after day, and get nowhere—because you are omitting the key factor, which I think is the ability to *close a deal*…The ability to sell entails persistence, force of personality, confidence, charm, and a kind of charisma. Most of these attributes are rare among cryonics activists…Why should charisma be necessary? Because of the “disconnect,” which I have seen so often. I run through the rational reasons for cryonics, and I answer all the questions. The person I am speaking to becomes reflective. The person often says, something like, “I guess it does make sense.” Then I say, “How about for you?” The person blinks, looking surprised, and pulls back a little. “Oh no, not for ME!”… This is the disconnect, between abstract agreement and personal commitment. I don’t think the perception of identity has much to do with it. That’s just another in the long list of issues such as religious faith, fear of the future, and concern about depriving heirs of a life insurance payout.”

I am quite persuaded by this response because it can both explain why ideas with no scientific credibility whatsoever can persuade so many people and why ideas with solid reasoning and evidence behind them have remained in obscurity. But I do think this is still only part of the puzzle. Having a very charismatic proponent of cryonics may be be sufficient for rapid growth, but is it necessary? Let’s look at my favorite example, astrology, again. I think that the rather widespread belief in astrology cannot be attributed to one charismatic person, or a number of charismatic persons. Astrology seems to offer something so important that many people demand little in terms of scientific evidence. In this case if offers assurance about personal identity and the future. Interestingly enough, cryonics presents an interesting contrast because people believe that it raises even more uncertainty about personal identity and the future. An unorthodox way to put this would be to say that the idea of astrology itself has “charisma” because it appeals to the hopes and aspirations of many people.

An obvious rejoinder to this would be to point out that the idea of immortality or overcoming death should have the biggest draw of all. That idea of eternal life that is often associated with cryonics is such an appealing prospect that even people with “negative charisma” would not be able to prevent its widespread endorsement. Well, that is not quite the situation we have found ourselves in (to put it mildly). I actually think that for many people the idea of overcoming death or (true) immortality sounds great but as in most fiction and SF movies, the idea of indefinite life has often been associated with “bad” events. A prevalent one in popular fiction is to associate the desire for immortality with the selling of one’s “soul.” In the case of cryonics many people think that the price for indefinite life is alienation and loss of family and friends.

So I remain convinced that offering a vision of cryonics that does justice to those concerns has a much higher chance of gaining in popularity but we also still need a charismatic person to close that deal. Let’s go for both!

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

17. May 2017 · Comments Off on Cryonics for Families · Categories: Cryonics, Society

Alcor allows members to specify the conditions under which they do or do not want to be cryopreserved. One popular option reads as follows: “I wish Alcor to place into cryopreservation any biological remains that they may be able to recover, regardless of the severity of the damage from such causes as fire, decomposition, autopsy, embalming, etc.” Interestingly, the options available in the Alcor membership application all concern scenarios in which the circumstances of only the individual member determines whether to proceed with cryopreservation.

But what about scenarios in which, for example, a whole family makes cryonics arrangements and a catastrophic accident permits only one family member to be placed in cryopreservation? When most people consider cryonics, one of their most immediate concerns is that the procedure could be disruptive of their social and family life. Is making cryonics arrangements without considering the preferences of those around me considered to be going it alone? If we all make cryonics arrangements and one person is the victim of a terrorist attack or plane crash, would I still want to proceed? How can I be sure that my whole family will be cryopreserved under acceptable conditions?

Default cryonics wisdom has it that it is better for a person to live than to die but the outlook of someone who is anxious about the idea of cryonics seems to conform more to something like this:

I would like everyone I care about to be cryopreserved and revived but if I lose someone I care for, I’d rather not come back either.

Now this is a rather bold version of the position I am trying to characterize but it does raise an important point. Would cryonics perhaps appeal to more people if cryonics organizations offered a number of options that reflect concerns about joint cryopreservation and revival?

In this document I use conditions for cryopreservation and survival together but we are really talking about two distinct issues here. For example, it is possible that a whole family is cryopreserved but meaningful revival is only possible for one of them. Successful cryopreservation is not necessarily equivalent to successful revival. Would it be feasible and desirable to allow more flexibility regarding such scenarios? For example, should members be permitted to insist on joint revival even if a family member has been cryopreserved under conditions that permits faster resuscitation? Should a cryonics organization allow members to be thawed out and buried in case circumstances prevent their other family members to be cryopreserved?

These are difficult questions and need to be considered in more detail. We do know that most people who make cryonics arrangements care about these issues and that many people care about these issues to such an extent that they conclude that cryonics presents more of a risk than a potential benefit. In general, what would it mean for a cryonics organization to incorporate the joint preferences of families in the services it offers?

Comment by Mike Perry

About 25 years ago a case came up in which an Alcor member stated they didn’t want to be revived unless all of their children could be, and were, revived. Alcor in effect was being asked to kill this member if it was unable to save one or more others. Alcor could not agree to such an option. (This individual remained a member and is still a member today.) Short of that, however, it might be reasonable to time revivals so that all in a group are brought back together.

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

16. May 2017 · Comments Off on Moving The Goalposts · Categories: Cryonics

Being a cryonicist can sometimes be exasperating. We like to think that making (technological) progress in our field will persuade more people to make cryonics arrangements. Are you concerned about the long-term stability of cryonics organizations? We set up a patient care trust fund designed to maintain patients in perpetuity. Are you concerned about ice formation? We introduce a new technology that eliminates freezing and turns tissue into a “glass.” Are you concerned about fracturing? We can store a patient at intermediate temperatures. Are you concerned about the use of volunteers? We contract with a company that uses professional surgeons and perfusionists. Are you concerned about long transport times? We develop protocols that allow us to do cryoprotective perfusion in the field. Are you concerned about a cryonics organization’s operations being dependent on bequests and donations from wealthy donors? We insist that the operating expenses of the organization should be covered by membership dues.

One would think that each time Alcor introduces new technologies and policies skeptics will re-calibrate and a larger number of them start making cryonics arrangements. For example, ice formation is generally perceived to produce a lot of damage to tissues. As a consequence, the transition from conventional cryopreservation with glycerol to vitrification should have produced a sharp increase in membership. It did not. Strangely enough, the publication of Eric Drexler’s Engines of Creation produced a larger increase in membership than the introduction of ice free cryopreservation. How can this be reconciled with the emphasis many of our critics place on empirical evidence? After all, Drexler’s book was a popular but theoretical argument about the feasibility and desirability of molecular nanotechnology and the introduction of vitrification was an actual, real-world, upgrade of cryonics procedures.

This failure of technological progress to translate into an increased acceptance of cryonics is often observed within the same person. First it is ice formation that is posited to be the obstacle to making cryonics arrangements. Then, when vitrification is introduced, the objection changes from ice formation to fracturing. When it is shown that storing at intermediate temperatures can mitigate fracturing the person suddenly is concerned about cryoprotective toxicity. And the list goes on and on. A clearer example of someone moving the goalposts cannot be found. The question is “why.” I think a close examination of these scientific and technological issues will not answer the question.

If something has become increasingly clear in informal conversations about cryonics it is that these kinds of objections are often superficial and follow-up conversations usually reveal more personal, psychological reservations. If we look for the common denominator of these objections we find that to many people cryonics does not offer the prospect of the continuation of life but a disruption and threat to personal identity. Cryonics may present the prospect of survival but the fear is that outside of our brain and bodies not much else will survive (family members, friends, careers, assets, money etc.).

Is the weak correlation between technological progress and the growth of cryonics a reason for pessimism? Not necessarily. If we really want cryonics to take off and grow we should re-frame our presentation of cryonics and present it as an attractive means to continue one’s life, expand one’s social connections and relationships, grow one’s assets, and improve one’s body and well-being. If we succeed in delivering a friendlier presentation of cryonics, more people will make cryonics arrangements, which will lower the threshold for other people to make cryonics arrangements, which will further arouse interest in cryonics, et cetera. And then, ironically, more money and resources will be available for research to bring us closer to real human suspended animation.

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

 

 

15. May 2017 · Comments Off on Competition and Cooperation in Cryonics · Categories: Cryonics

When I told Jordan Sparks that his new cryonics organization, Oregon Cryonics, would be featured in Cryonics magazine he was quite surprised. To me it is obvious. I think that cryonics is still in such a fragile state that new organizations can have a positive effect on other existing organizations. I also believe that the existence of multiple cryonics organizations with different services and pricing will bring cryonics within the reach of more people and can create a safer environment for already existing organizations.

Of course, not every new cryonics organization should be enthusiastically welcomed by existing cryonics organizations. A cryonics organization which does not disclose any information about its protocols or cases should be treated with great caution. An organization that accepts patients on a “pay as you go” basis is at much greater risk of having to thaw their patients and cause a bad reputation to the field as a whole. A cryonics organization that seeks to gain members through the dissemination of unrealistic promises or denigrating statements about other organizations would not be helpful either.

One reason why I think existing cryonics organizations should not feel threatened by the existence of other organizations is because I do not think that a membership gain by one organization is necessarily at the expense of the other organizations. At this point the two major existing cryonics organizations (Alcor and the Cryonics Institute) approach cryonics from a different philosophy and have different price structures. It is also conceivable that in the future there will be a new cryonics organization that pursues an explicit for-profit model.

The existence of multiple cryonics organizations also spurs innovation and quicker adoption of new technologies. After all, most cryonics organizations would like to be perceived as “state of the art” and the introduction of a new technology at one organization often causes the other organization to adopt it (sooner) as well. The most prominent example of this is the transition from conventional cryoprotection to vitrification. No sane cryonics organization today would decide to offer freezing with a poor cryoprotectant as the preferred protocol. In the future we may see a wider embrace of brain-only cryopreservation, or even the addition of chemical preservation as a low-cost option. The existence of multiple cryonics organizations also leads to greater national and international press coverage.

In an ideal world, a cryonics organization should be close enough to do prompt stabilization and cryoprotection without the need for air transport or prolonged ground transport. If cooperation among organizations is excellent we may even see that organizations make available (for a fee) their space to stabilize and cryoprotect a patient of another organization to minimize long periods of cold ischemia. Such an arrangement could be advantageous for all organizations involved.

I admit being also rather relieved. Other than KrioRus, there has not been a new all-service cryonics provider since the mid-1990s, and none at all in the Western Hemisphere. Running a cryonics organization is not trivial so it is extremely encouraging to see there are still people who want to to do it. Let us wish Oregon Cryonics good luck and hope that cryonics in general grows faster as a result.

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

10. May 2017 · Comments Off on Medical Myopia and Brain Death · Categories: Cryonics, Death, Neuroscience

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

08. May 2017 · Comments Off on Deconstructing Future Shock · Categories: Cryonics, Society

There is a growing consensus in the cryonics community that for many people it is not technical feasibility but fear of an unknown future that makes them uncomfortable with the idea of cryonics. In fact, to some the future is not just “unknown” but they fear that by the time they will be resuscitated their skills and knowledge will have become obsolete, they will no longer own any assets, and worse, all their family and friends will be dead and gone.

If we want to effectively counter these fears, or at least provide some reasons for optimism, we need to dig a little deeper into this issue. First of all, we should not treat all (potential) cryonics patients as a homogenous group. Someone who was cryopreserved in the mid-20th century will face a much longer period of nonparticipation in society than a young person who has just made cryonics arrangements and who will be cryopreserved at a time which is closer to the first resuscitation attempts. It should also be mentioned that the ease of adapting to a new society is itself a function of age. If history is any indication, younger people usually adapt more easily to a changing society.

Which in turn draws attention to a much neglected point about cryonics. Cryonics patients will be resuscitated in a youthful state without the typical challenges and ailments that are associated with old age. We should expect a resuscitated patient to have at least the youthful vigor and brain plasticity of a young person, albeit with perhaps more “wisdom.”

A credible cryonics organization will not have as its only mandate just to keep the patient in cryostasis but also to successfully rejuvenate the person and re-integrate him/her into society. It is important in our communication to emphasize that reintegration does not start after the person has been resuscitated but should start as soon as the patient has been placed in long term care. The person’s assets can be managed in a trust and real estate can be maintained, or acquired, to ensure it will be up-to-date to the prevailing era’s preferences and standards. If proper thought is given to this issue, the person should at least have access to a modern home and money in the prevailing currency of the time (if “money” as we know it has something like the same significance then).

The biggest worry, however, concerns the prospect of being introduced to an era with radically different morals, conventions, and forms of human interaction. There is a good reason to believe, however, that such changes might actually be quite modest. Our morality has been shaped over millions of years of evolution and it is not realistic to assume fundamentally different forms of morality will dominate in the next century, even if humans increasingly merge with technology.

All this still assumes that the cryonics organization does not play a proactive role in the mental re-integration of cryonics patients. I think that the longer that cryonics organizations will be around, and the closer we get to a time where advanced molecular medicine is feasible, the more thought will be given to minimizing future shock for cryonics patients. The aim of cryonics organizations is not just the restoration of a patient’s physical health but also his/her mental health—and that implies minimization of stress and alienation.

And what about friends and family? Will they not be left behind? Well, I think the more assurance about the future a cryonics organization can provide for potential members, the lower the threshold for whole groups of people to make arrangements. It will be the person who does not make cryonics arrangements who makes the odd, solitary, decision. At that point, the human tendency to conform will start working in our favor.

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

04. May 2017 · Comments Off on Cryonics as an Employee Benefit · Categories: Cryonics

Since Alcor introduced Associate Membership in 2012 the results have been quite encouraging. There a lot of people who support our mission but are not able, or ready yet, to make cryonics arrangements themselves. For others, it is simply the first step towards making cryonics arrangements. Clearly, the threshold for becoming an Associate Member is substantially lower than the threshold for becoming a fully funded Alcor member. Is there anything we can do to further lower the threshold for making cryonics arrangements with Alcor?

Most people who have made cryonics arrangements did not come to this decision by reflecting on aging and death and then consulting the library or searching the internet for technological solutions. Most people were first introduced to cryonics when it was covered in the media (newspapers, radio, television, etc.) or through family, friends, or colleagues.

What has not happened to date is that cryonics arrangements are offered to (potential) employees as part of an employee benefit package.

Many employers continue to offer employees a basic or enhanced benefits package as part of compensation. In fact, as times change, the kinds of benefits that organizations offer have evolved as well. Currently we are seeing an increased emphasis on preventive care, more flexibility for parents, and self-directed retirement investments. To cater to the increasing number of women entering the labor market, and the increased preference to have children at a later age, some forward-looking companies are even offering to cryopreserve the eggs of their employees in order to facilitate this change.

Unfortunately, employee benefits are still largely driven by an attitude towards life that passively accepts aging and conforms to conventional, but outdated, notions of “death.” We are encouraged to save money for “retirement,” that point in life where our physiology starts to fall behind the needs of the labor market. We encourage people to provide for their families in case of “death.” It would be a major step forward if companies did not just offer the tools to remain healthy but also provided a choice to be cryopreserved in case a person is afflicted with a critical illness for which contemporary medicine does not have an answer.

It is well established that cryonics draws a lot of people of extraordinary intelligence and ability. Not surprisingly, many of these people run successful businesses and organizations. If the life extension community can come together and persuade these companies to offer cryonics as an electable employee benefit, the interest in cryonics will most likely increase, even among those who do not elect to benefit from these services. Not all companies may be in a position to offer such benefits for financial or public image reasons, but I suspect that a non-trivial number of Alcor members with companies should be able to do so. And as soon as some companies do, the threshold and administrative challenges for others will drop. We should at least expect this benefit to be offered at companies whose officials are public about their cryonics arrangements (like Alcor!)

Some companies already offer term or whole life insurance as a benefit and it should not be too hard to tweak this benefit to transform this into a funding mechanism for cryonics. Employers then will also pick up (or partially pay) the annual membership dues (and CMS payments) for all employees who choose cryonics as a company benefit. Transferability is an important consideration if cryonics is offered as an employee benefit so that departing employees can take their arrangements with them without having to start the life insurance or funding process all over again.

Offering cryonics arrangements as an employee benefit should be as common as offering health insurance. No matter how much emphasis a company puts on preventive care, protection against critical illness and catastrophic accidents needs to be a part of that package if the concept of a long and healthy life is to be embraced.

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

06. April 2017 · Comments Off on Alcor For The Living · Categories: Cryonics

At the recent annual Alcor Annual Strategic Meeting a number of rather encouraging motions were passed that will lower the cost of cryonics for many members. Membership dues are reduced by 10%, one uniform (lower) additional fee for overseas cases was established, and members now have the option of either paying annual CMS dues or paying higher cryopreservation minimums. The last decision in particular should have some positive effects for (potential) younger members who usually can take out substantial amounts of life insurance for only a modest monthly premium. It will also provide a strong incentive for members to remain funded well above the current cryopreservation minimums. Last, but not least, Alcor will also become somewhat more flexible in accepting different kinds of funding (for example, 50% cash and the rest in assets), which can make a big difference for older members who can no longer increase their insurance policies. These changes do not mean that Alcor has become inexpensive by any means; we still are losing too many members due to affordability issues. More progress will be needed.

Member retention, however, is not only about affordability and cost. Members should also feel involved and appreciated by the organization. On the financial front Alcor has made a step towards recognizing long-term members for their support in the form of membership discounts. But there are a lot of other ways to strengthen the bond between Alcor and its membership.

One of the unintended consequences of standby and stabilization services transitioning from a member / volunteer basis to a paid / professional basis is that one of the major reasons for Alcor members to get together (i.e. standby training) is no longer that important. While there is the occasional regional social gathering, there has not been a deliberate effort to stimulate and encourage local members to get together. For example, in regional areas that used to be hotbeds of cryonics activity and that still have a lot of members, like New York, there is little physical or social cryonics infrastructure left. For most members, I suspect that the occasional meeting in California, or a conference, is not going to cut it. If we want members to feel more involved with our organization we need to think of new ways of bringing them together, either through actual meetings or online. The popularity of the annual Teens and Twenties events indicate that many members thoroughly enjoy more interaction.

Also, recognition for long-time membership can have many forms. Membership discounts are a good start but what about invitation-only gatherings for long-time members at Alcor? Flying big donors in to observe the progress made at the facility and in introducing new technologies, and giving them more opportunity to provide feedback on important strategic decisions would be a great start. For too many older members, Alcor has simply become an organization that sends them invoices.

The most important recommendation that I would like to make is that Alcor should have something to offer to members before they are cryopreserved. Or to put it another way, people should feel that it also makes a lot of sense to join Alcor while “alive.” We can think of offering additional benefits that are exclusive to Alcor members; complimentary magazines and newsletters from like-minded organizations, discounts on conferences and events, affordable access to state-of-the-art physiological monitoring or alarm systems, a designated Alcor email address and secure data storage for each member etc. Alcor membership should not be perceived as a desperate attempt to escape the current limitations of medicine to get launched into an unknown, distant future, but more as becoming part of a smart and forward-looking community that is creating that very future.

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

05. April 2017 · Comments Off on Biological Repair Technologies · Categories: Cryonics

While I believe it is very hard to irreversibly destroy information, I had become quite concerned that the earliest presentation about future cell repair technologies for cryonics patients might have become lost forever. Jerome “Jerry” White’s paper, “Virus-Induced Repair of Damaged Neurons with Preservation of Long-Term Information Content,” was frequently referred to in papers on the topic of revival technologies, but I had never seen the actual paper and was curious and determined to find it. When I discovered that even the people in cryonics who usually own (or can access) a wealth of historical cryonics materials (Mike Perry, Mike Darwin, Steve Bridge, etc.) were not able to track down a copy I became progressively pessimistic and even started questioning whether the presentation was actually transcribed at all. I wrote a column about the missing paper in which I put forward the sad possibility that the paper was lost to us forever. I never gave up though. Then, in September 2014, Mike Perry wrote me to tell that Alcor member Art Quaife was in possession of the paper and would send a copy to him. After receiving the paper, a PDF copy was soon produced and Mike also spent considerable time creating an editable text version.

The premise of White’s paper is straightforward but ingenious (especially considering the fact that it was presented in 1969). We already know of biological “machines” that can enter the body of the patient and make modifications to cells and DNA. They are called viruses. When this is recognized it is not too far fetched to recognize the possibility of separating the virus as a biologically active delivery vehicle from its adverse health effects. The idea of using viruses to deliver genetic material has now become fully established in modern gene therapy. For example, the virus responsible for causing HIV and AIDS can be stripped of these properties but can still be used as a vehicle to modify genes within a cell. In his paper on biological cell repair, White proposed to modify viruses to engage in information gathering, gene modification, and cell repair.

Space does not permit me here to analyze the paper in detail but I would like to briefly discuss two issues concerning the feasibility of biological cell repair for the revival of cryonics patients, namely, capabilities and temperature.

Modifying a virus to change genes is one thing, but rebuilding damaged cell membranes and intracellular organelles is another and it is not fully clear how a virus can be modified to accomplish this. In addition, for non-neural cells a case could be made that it is often more time- and cost-effective to simply destroy and remove cells and cell structures with severe damage (after gathering sufficient information about the cells and their organization). For brain cells there is a special difficulty in that the ultrastructure appears to be identity-critical in a way not expected in non-neural tissue. So the conservative approach here would dictate repairing these cells instead of replacing them. The challenge is that although human physiology already has endogenous mechanisms to maintain DNA integrity and repair damaged DNA, the human genome does not encode for wholesale repair of cells (including their genomic content) that have sustained substantial damage. This, I should add, combined with only limited neurogenesis in the brain, may explain why aging and dementia are strongly correlated. One of the challenges of viral-induced repair of cells is that inserting new genetic information that allows for novel endogenous repair capabilities is itself dependent on the existence of viable cells in the body of the patient. This challenge is also identified in White’s paper when he proposes to create artificial viruses that “carry out degrees of repair greater than those the cell in its damaged condition would itself provide.”

An even bigger challenge for biological repair is temperature limitations. While it has been established that some enzymes still function (albeit at a slower pace) at low or even subzero temperatures, the temperatures that cryonics patients are stored at are substantially lower than that. This would seem to require that we first thaw the patient before conducting repairs. This course of action could create serious problems for the average cryonics patient. In the case of frozen patients, the ice will turn to water again and (damaged) biomolecules that were locked into place could dissolve into solution (which may constitute irreversible loss of identity-critical information). In the case of vitrified patients, ice nuclei that formed during the descent to cold temperatures (or continued forming during intermediate temperature storage) can organize themselves into ice during thawing. Another problem with conducting repairs after thawing is that ischemia will be permitted to continue, causing more damage. While White stipulates that “repair proceed faster than deterioration, whatever the temperature” it is not likely that credible future repair scenarios will permit substantial deterioration to occur during, or prior to, repair.

Does this close the door on biological cell repair? Not necessarily. We can imagine breakthroughs in cryoprotectant design that reconcile negligible toxicity with extreme resistance to ice formation. Patients cryopreserved with such agents could be thawed without risk of ice damage. When temperatures are raised to a point where meaningful enzymatic activity is possible, various biological strategies (metabolic inhibition, reversible fixation) could be used to allow time for repairs. Another idea is to pursue a hybrid strategy in which (crude) nano-size mechanical machines are used to access and open the circulatory system while disrupting nucleation and/ or delivering anti-nucleating molecules. After completing this task at cryogenic temperatures, the patient can be thawed and biological cell repair technologies introduced.

This discussion of the (potential) limitations of biological repair technologies draws attention to the relationship between cryopreservation technologies and repair technologies. We tend to think of preservation and repair technologies as independent endeavours but it has been shown here that the choice of cryoprotectant technology can influence the choice of the most effective repair technology. For example, if a cryoprotectant is just a moderately strong glass former, ice formation upon warming should be expected and mechanical repair technologies may be necessary for conducting the initial steps of repair (preventing ice formation). Or consider intermediate temperature storage. If we store patients just below the glass transition temperature of the vitrification solution, nucleation may still continue, which would favor ice formation upon warming, and thus, again, the need for initial mechanical cell repair technologies to stabilize the patient during the initial stages of repair. Some people think that biological cell repair is an inefficient and impractical (if not impossible) task and the resuscitation of cryonics patients will require mechanical nanoscale repair devices. This may very well turn out to be the case, but demonstrating the technical feasibility of biological cell repair would further strengthen the case for cryonics. Let us hope that Jerry White, who is currently cryopreserved, will be one of the beneficiaries of such powerful technologies.

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