Brain Preservation and Personal Survival: The Importance of Promoting Cryonics-Specific Research

The Brain Preservation Foundation’s mission to validate structural preservation of the brain has been very successful but the link with mind uploading as a means of personal survival raises some important questions. Alexandre Erler makes the case for a distinct cryonics research program based on biological survival.

INTRODUCTION: CRYONICS AND THE BRAIN PRESERVATION FOUNDATION

As someone who is fully supportive of the ultimate goals of the cryonics enterprise, but still views the current state of the practice with some degree of skepticism, I make a point of acquainting myself with the latest evidence regarding the quality of cryonics procedures and their ability to preserve the foundations of a person’s identity through time. Over the past two years or so, I have increasingly seen a recent achievement by 21st-Century Medicine (21CM) cited by some cryonics supporters as demonstrating the scientific validity of those procedures: namely 21CM’s research on aldehyde-stabilized cryopreservation (ASC). This new technique has allowed them to win, in 2016, the Small Mammal Prize, and just this year, the full Technology Prize awarded by the Brain Preservation Foundation (BPF), by demonstrating excellent preservation of the ultrastructure in, respectively, a whole rabbit brain (McIntyre and Fahy, 2015) and a whole pig brain (The Brain Preservation Foundation, 2018). Were I to follow this line of reasoning, I could happily set aside my concerns about the adequacy of today’s cryopreservation procedures, which had now been verified by scientific experts; the proper focus would now need to be on how to responsibly introduce those procedures into a clinical setting, for patients at the end of their lives who might request them.

It turns out, however, that things are not so simple. ASC is no doubt a step forward for the field of brain banking, and as its name indicates, it it is indeed a form of cryopreservation, since it involves vitrification of the brain at -135 °C. Nonetheless, ASC does not count as cryonics, insofar as it uses a fixative solution prior to vitrification and cooling, which could potentially preclude revival of the original biological brain (an essential part of cryonics as traditionally understood). And indeed, biological revival with the help of future technology is not a priority for the BPF’s president, Dr Kenneth Hayworth. Rather, he envisages brain preservation as conducive to life extension via mind uploading: a process that would involve cutting the preserved brain into thin slices, scanning each slice, and feeding the resulting data to an advanced computer that would thereby be able to map out the entire network of neural connections in the person’s original brain, and ultimately to emulate that person’s mind (Hayworth, 2010). This is quite different from cryonics.

Assuming that a technique like ASC is compatible with mind uploading, but not with the revival of the original brain, it should not be treated as a landmark in cryonics research. Admittedly, there is some uncertainty about the truth of that assumption. It seems at least conceivable that the chemical cross-links created by the fixation process could be reversed, and the original brain revived, using future technology. Nonetheless, ASC introduces empirical and philosophical uncertainties (e.g. could we really restore, as opposed to recreating, the original neural structure following the various molecular changes involved?) to a much greater degree than traditional cryonics does.

But why, it might be asked, should one remained fixated on pursuing biological revival via cryonics, if the evidence in favour of good ultrastructure preservation is better for ASC than it is for contemporary cryonics procedures? It is for instance known that, up to now, 21CM’s cryonics protocol involving the use of cryoprotectant M22 has been causing the brain to shrink to almost 50% of its natural size due to osmotic dehydration, hindering our ability to establish the quality of ultrastructure preservation using electron microscopy (The Brain Preservation Foundation, n.d.; De Wolf, 2017). If so, why not join the BPF in focusing simply on the type of brain preservation that seems to yield the best evidence of success, even if this means turning away from cryonics towards mind uploading?

In what follows, I will argue that, given the current state of our scientific and philosophical knowledge, doing so would be irresponsible. The BPF’s commitment to holding brain preservation research to the highest standards of scientific rigour is laudable, and worth emulating. Nonetheless, for those interested in brain preservation with a view to enabling life extension, supporting cryonics-specific research remains the safer bet. We should not simply rely on the BPF’s approach if our goal is to try and save those whom medicine in its current state cannot restore to life and health.

TWO DIFFERENT VIEWS ABOUT PERSONAL IDENTITY AND SURVIVAL

To see why this is so, let us begin by noting the two main philosophical theories of personal identity through time that are relevant when discussing the respective merits of cryonics and mind uploading in this context. The first one, which we can call the “Physical Continuity” (PhyCon) theory, asserts that a person is identical with the physical substratum from which her mind emerges: that is to say, her brain, with its intricate web of neurons and synaptic connections. (For a good exposition of the theory, see e.g. McMahan, 2002.) According to this theory, saving a person from destruction after she has been pronounced dead requires preserving enough of her brain, in a state in which that brain retains at least its potential for viability. What exactly counts as “enough” of the brain is of course a difficult question that would deserve much more discussion. While we can safely say that, all else being equal, it is always preferable to preserve as much of the original brain as we can, the survival of the person arguably does not require perfect preservation. Intuitively, people can survive limited forms of brain damage, such as those caused by strokes. What is more, as cryonicists have pointed out, brain damage that causes significant disability today might no longer be a serious problem (as long as it is limited enough not to undermine personal identity) in a future where cryonic revival has become possible, as the technological means will then likely exist to fully repair that damage, e.g. based on inferences from the state of the person’s brain prior to repair.

The second relevant theory can be referred to as the “Psychological Continuity” (PsyCon) theory. Roughly speaking, it says that you are to identical with the set of psychological features (memories, beliefs, desires, personality traits, etc.) that constitutes your mind. On this view, preserving you after you have been pronounced dead requires ensuring the persistence of enough of those psychological features, in an embodied mind of some sort (but one that need not be embodied in your current biological brain). One variant of PsyCon, endorsed by many supporters of mind uploading including Hayworth, states that preserving a person after legal death requires preserving her connectome, understood as the mapping of neural circuitry encoding one’s memories, skills, and other psychological features – that is to say, the connectome as an informational entity rather than a physical one (Hayworth, 2010), even though the information in question will by necessity be stored in some physical substratum, whether a brain or a computer.

Like virtually all philosophical theories, both the PhyCon and PsyCon theories have their partisans and detractors. PhyCon, for instance, has been said to imply that there is a fundamental difference between a scenario in which a person had her brain suddenly destroyed and replaced by an exact copy of it, perhaps produced via scanning and 3D printing using neurons as basic material; and a scenario in which the person’s brain cells were gradually replaced by new ones over an extended period of time, in the same way as the rest of the human body regularly regenerates itself. While most PhyCon theorists would agree that the second scenario is compatible with the preservation of the person’s identity through time, they will deny that the first is – if the original brain gets destroyed, they will say, so must the person as well, and the new replica brain must belong to a new person not numerically identical with the first one. Some find this difference of treatment between the two scenarios arbitrary (e.g. Parfit, 1984).

Some versions of PsyCon, on the other hand, imply that multiple copies of yourself could all be you. Indeed, suppose that after scanning your brain to obtain a map of your connectome, we then created two identical copies of your mind running on two different computers. Since both copies would demonstrate the same degree of psychological continuity with your previous self, we would have to conclude that both are you – something many find intuitively unacceptable. Other versions of PsyCon strive to avoid that implication by stipulating that you are only identical with an upload of your mind if no more than one copy of it has been created, yet this move leads to other philosophical problems. Hayworth, however, happily endorses the implication that multiple copies of a single individual can co-exist at the same time, and contends that those who object to that implication are simply confused (Hayworth, 2010).

HOW TO MAKE A PRUDENT CHOICE UNDER (PHILOSOPHICAL) UNCERTAINTY

For the record, I personally find PhyCon more plausible than PsyCon (although I also agree that the preservation of one’s psychological features after cryonic revival is highly desirable, regardless of its significance for sheer survival). On that basis, I do not support further animal research targeted exclusively at the development of mind uploading technology. However, my personal opinion on the matter can be set aside for the sake of the present discussion. The important fact is that there are reasonable, honest and intelligent people on both sides of that debate, and that neither side has so far managed to present arguments that would convince all reasonable people on the other side. In such a situation, the intellectually responsible path to take is surely to eschew certainty, and acknowledge that the other side could be right, even if one thinks that this is unlikely and that the arguments favoring one’s own position are very strong.

If that is the case, what is the prudent choice to make for those who wish to promote life extension through brain preservation? I submit that traditional cryonics is the more prudent option to pursue. (This remark could be extended to ASC if one could show that it is in principle compatible with the revival of the original brain, and provided that it is not combined with destructive mind uploading.) This can be demonstrated using a simple argument that considers what the implications are if we assume that PhyCon and, respectively, PsyCon are true.

Suppose first that PhyCon is true. If so, a cryonics procedure carried out properly will save a person’s life, whereas using a technique like ASC that compromises the brain’s potential for viability, followed by destructive scanning and uploading, will kill that person. If PsyCon is true, on the other hand, both methods can ensure survival. Indeed, adequate cryonic preservation of a person’s brain would also preserve the ultrastructure grounding the various psychological features that defined that person. Insofar as traditional cryonics (at least once sufficiently perfected) can secure survival whether PhyCon or PsyCon is true, whereas mind uploading of the kind envisaged by the BPF can only do so if PsyCon is correct, traditional cryonics is the safest bet.

This conclusion is reinforced by the fact that the success of mind uploading at securing personal survival might depend on an additional factor, namely the possibility of creating conscious or sentient machines. If, for whatever reason, computers – which, unlike biological brains, rely on hardware rather than “wetware” – happen to fundamentally lack the capacity for consciouness, regardless of how powerful and sophisticated they might be, then uploads turn out to be no more than computer “zombies” mimicking now deceased people. It’s unclear that someone could “survive” as such an entity. And even if we assume that they could, the value of such survival, devoid of the conscious experiences that make our lives worth living, would be dubious, somewhat like the value of surviving with only a brain stem. This point about machine consciousness equally applies to the idea of a “Moravec transfer”, i.e. a procedure involving gradually uploading a person’s mind to a computer (neuron by neuron if necessary), unlike the BPF’s proposed method (Moravec, 1988). Traditional cryonics, by contrast, can succeed at preserving a person regardless of whether or not computers can be conscious.

Hayworth would presumably deny that any such doubts about the possibility of machine consciousness are legitimate. Indeed, he seems to confidently embrace the so-called computational theory of consciousness, according to which consciousness is fundamentally the product of – highly complex – computation, which we know computers to be capable of at least in principle (e.g. Hayworth, 2015). However, there is currently no general agreement among philosophers of mind or neuroscientists that the computational theory of consciousness is correct, and Hayworth does not demonstrate that it is (although he dogmatically equates the idea that there might be physical properties required for the production of conscious experience which are found in wetware, but not computer hardware, with invoking “magic”).

Furthermore, even if taken for granted, the computational theory of consciousness cannot, absent additional philosophical arguments, show mind uploading to be consistent with personal survival. Assuming that R2-D2 from Star Wars is conscious does not commit us to accepting that a perfect replica of R2-D2 built from fresh parts, after – let us assume – it was destroyed by the Empire’s forces, is numerically identical with the original robot. In response, Hayworth could perhaps abandon PsyCon and instead invoke the claim, famously defended by philosopher Derek Parfit, that personal identity does not actually matter in the way many of us tend to think – rather, psychological continuity is what really matters (Parfit, 1984). (In his reply to an article by neuroscientist Michael Hendricks critical of cryonics, Hayworth actually appears to move in that direction: see Hayworth, 2015.) However, besides the fact that this is again a controversial philosophical view, it notably led Parfit to dissociate psychological continuity from personal survival, and to conclude that the latter was, in itself, also overrated. This position is very much at odds with the life extension project, which the BPF claims to be pursuing.

I cannot but see some irony in the fact that Hayworth, the author of an essay titled “Killed by Bad Philosophy”, should show a degree of overconfidence in his philosophical views that might potentially lead his followers to experience the very same outcome his essay is warning against.

The differences previously highlighted between traditional cryonics and the BPF’s approach are summarised in the table below:

If: Traditional cryonics* ASC + mind uploading*
Physical continuity theory is true Survival Death
Psychological continuity theory is true Survival Survival
Machines can’t be conscious Unaffected Compromised (creates computer “zombie”)

(*It is assumed that the relevant procedures are performed in accordance with the highest standards of quality)

WHAT THE CRYONICS MOVEMENT CAN LEARN FROM THE BPF

None of this is meant to imply that the work of the BPF is without merit. On the contrary, the Foundation’s approach demonstrates a number of virtues that can provide a model for the cryonics movement to follow. These include a commitment to rigorously and impartially evaluating the quality of brain preservation procedures, in accordance with the standards of scientific peer-review. Another example is the BPF’s successful effort at crowdfunding its incentive prizes for brain preservation research, such as the two prizes won by 21CM. For those seeking to promote life extension through brain preservation, who I have argued need to prioritize cryonics-specific research, this suggests two main paths worth pursuing in the future:

(a) Incentive prizes. Such prizes are a powerful tool for stimulating research, particularly in neglected areas of science. Unfortunately (and perhaps unsurprisingly, given Hayworth’s philosophical beliefs), the BPF does not at this point appear inclined to set up any new prize that would include a requirement to preserve the brain’s potential for viability. On the basis of the arguments I have provided so far, I submit that the institution of a prize (possibly crowdfunded) incorporating that requirement would be highly desirable.

How demanding such an incentive prize should be with regards to the winning entry is a matter for further debate. A relatively modest version would require demonstrating adequate ultrastructure preservation in a small mammalian brain, but using a procedure that could in principle be reversed by future technology, making it possible for the original brain to eventually be “re-started”. However, based on a recent talk by Dr Greg Fahy from 21CM, which I attended in May 2017 at the International Longevity and Cryopreservation Summit in Madrid, such a goal may soon be achieved. Indeed, Dr Fahy reported having found a way to largely overcome the abovementioned problem of dehydration and shrinking that has so far prevented a proper assessment of the quality of ultrastructure preservation offered by traditional cryonics protocols (e.g. using M22). Assuming Fahy has now reached that milestone (and I look forward to the publication of his paper on the topic), one could set up a prize with a more ambitious goal: for instance, one could add that besides showing good ultrastructure preservation and retaining the preserved brain’s potential for viability, one should also demonstrate actual viability, say via measurable electrical activity, either at the level of the whole brain or in slices obtained from that brain. Ultimately, the details of such a prize should be worked out by scientists with the relevant expertise (as long as the constraints I have outlined here are respected).

Those who believe that ASC holds greater promise could support a prize rewarding the first team who found a way to reverse the fixative process involved in that procedure, and restore the original neural structure.

(b) Research funds. Such a fund, which could also be crowdfunded, would be managed in a transparent manner by an organization committed to promoting cryonics-specific research. In accordance with standard practice when it comes to funding scientific research, project proposals would be solicited from active researchers in cryobiology (and other relevant fields), and a committee of experts would select the proposals that it deemed most worthy of funding. The organization would then help disseminate the results of the completed projects (e.g. as laid out in peer-reviewed publications).

The scientific experts tasked with evaluating the submissions for either an incentive prize or a research fund should ideally be publicly identified, and sufficiently independent of both the authors of the submissions and of cryonics companies (e.g. they should not be receiving research funding from those companies). Furthermore, while an organization that might implement solution a) or b) could be created de novo, existing institutions might already be able to fulfill that role. One example would be the UK Cryonics and Cryopreservation Research Network (http://cryonics-research.org.uk), led by Dr João Pedro de Magalhães, who has connections with other scientific experts, including Ken Hayworth. Despite the scientific rigour with which it approaches the issue of cryonics, the network is currently underfunded.

While most people may understandably not be able to commit substantial amounts of resources to supporting cryonics research, the success that the BPF has enjoyed so far with its incentive prizes demonstrates that large numbers of even small donations can foster impressive technical breakthroughs and help strengthen the credibility of research projects of the most audacious sort. I believe it is now time to apply a similar approach to the safer bet of cryonics-specific research. Further raising the public profile of such research, and improving its status in the eyes of the mainstream scientific community, can help promote a virtuous cycle leading in turn to more funding and greater professionalization. The sooner we can make this happen, the better.

An earlier version of this article appeared in Cryonics magazine, November-December, 2017.

REFERENCES:

DE WOLF, A. August 21 2017. Cryonics Without Cerebral Dehydration? Evidence-Based Cryonics [Online]. Available from: http://www.evidencebasedcryonics.org/2017/08/21/cryonics-without-cerebral-dehydration/.

HAYWORTH, K. 2010. Killed by Bad Philosophy: Why Brain Preservation Followed by Mind Uploading Is a Cure for Death. Available: http://www.brainpreservation.org/content-2/killed-bad-philosophy/.

HAYWORTH, K. September 16 2015. Ken Hayworth’s Personal Response to MIT Technology Review Article. Brain Preservation Foundation [Online]. Available from: http://www.brainpreservation.org/ken-hayworths-personal-response-to-mit-technology-review-article/.

MCINTYRE, R. L. & FAHY, G. M. 2015. Aldehyde-Stabilized Cryopreservation. Cryobiology, 71, 448-58.

MCMAHAN, J. 2002. The Ethics of Killing : Problems at the Margins of Life, Oxford, Oxford University Press.

MORAVEC, H. P. 1988. Mind Children : The Future of Robot and Human Intelligence, Cambridge, Mass., Harvard University Press.

PARFIT, D. 1984. Reasons and Persons, Oxford, Clarendon Press.

THE BRAIN PRESERVATION FOUNDATION. n.d. Overview of 21st Century Medicine’s Cryopreservation for Viability Research [Online]. Available: http://www.brainpreservation.org/21cm-cryopreservation-eval-page/.

THE BRAIN PRESERVATION FOUNDATION. 2018. Aldehyde-Stabilized Cryopreservation Wins Final Phase of Brain Preservation Prize [Online]. Available: http://www.prweb.com/releases/prweb15276833.htm.

Groundbreaking Scientific Results Support that the Proposition of Human Medical Biostasis has Potential and Needs to be Brought into Mainstream Scientific and Medical Focus

March 13, 2018: A team from 21st Century Medicine has developed a technology that has been published in peer-review and then independently verified to enable near-perfect, long-term structural preservation of a whole, intact, large mammalian brain. This is a truly groundbreaking result and puts the proposition of human medical biostasis as a way to save humans, who otherwise would die, squarely within the realm of what may be possible in the foreseeable future.

This follows recent scientific evidence that long-term memory is not modified by the process of whole organism cryopreservation and revival in simple animal models.

The new breakthrough comes eight years after the Brain Preservation Foundation (BPF) launched the Brain Preservation Prize and today won that very prize.

Left Picture:  Vitrified pig brain at -135° Celsius (-211° Fahrenheit) – a temperature at which chemical and biological actively virtually has stopped and storage without any change or degradation is possible for centuries if not millennia.

Right Picture: Previously vitrified brain after rewarming later subjected to extensive electron microscopic examination, showing that near perfect ultrastructure was preserved.  Source: 21st Century Medicine / can also be accesses at BPF here.

As the two leading think-tanks and scientific networks in cryonics we have put together this brief, with  more information and our perspectives on what this important breakthrough means and does not mean for cryonics. ​

The Case for Field Cryoprotection

The last major technological innovation at Alcor was vitrification (cryopreservation without ice formation). Viability assays of brain slices and electron micrographs of brains cryopreserved with vitrification solutions show substantial improvements over the older cryopreservation protocols. But this was almost 20 years ago and it is time for another technological innovation that will improve patient care. I want to suggest that the strongest candidate for such an innovation is to introduce field cryoprotection for all Alcor members.

Field cryoprotection aims to close the gap in outcome between patients that are pronounced legally dead in the Scottsdale area (where Alcor is located) and patients that are pronounced legally dead in other US states by conducting the cryoprotective portion of Alcor’s procedure prior to transport to Alcor.

Currently the procedure would be to deploy a standby team to the patient’s bedside, start rapid cooling and cardiopulmonary support, replace the blood with an organ preservation solution, and then ship the patient to Alcor for cryoprotection and long term care. Those organ preservation solutions have been designed to counter the adverse effects of cold ischemia but are from for perfect. After about 6 hours of cold ischemia, the brain is rendered non-viable (no EEG can be recovered). Electron micrographs of mammalian brains show that the fine ultrastructure of the brain degrades in a time-dependent manner and blood vessels start to leak. As a general rule, when a patient is shipped to Alcor by air transport the blood brain barrier of the patient has been compromised, which can lead to swelling of the brain during cryoprotection. In whole body patients, substantial abdominal swelling during cryoprotective perfusion occurs, despite remote blood washout.

The good news is that preventing these outcomes does not require novel scientific breakthroughs but a simple commitment to eliminate shipment of patients on water ice in favor of doing field cryoprotection and subzero cooling in the field instead. This procedure is named “field cryoprotection.”

The reason why we call it “field cryoprotection” instead of “field cryopreservation” (or “field vitrification”) is because the patient is not cooled all the way down to liquid nitrogen temperature. While this is theoretically possible (and desirable), the logistics of this procedure are too demanding at this point. So instead of cooling the patient to liquid nitrogen temperature (-196° Celsius) the patient is shipped to Alcor on dry ice (-78.5° Celsius) where further cooldown begins. Research supports this is a safe temperature for shipping patients, provided stabilization and cryoprotection procedures are done timely and competently. From the patient’s perspective the advantages include minimization of cold ischemia, preservation of integrity of the vessels and blood brain barrier, and, under good conditions, cryoprotection can start when the brain is still in a viable state.

One of the most remarkable aspects of making field cryoprotection the default option for all eligible patients is that it does not just improve patient care but reduces cost as well. Right now, for non-local cases Alcor needs to deploy a team consisting of surgeons and technicians twice. Once at the patient’s bebside and later again at Alcor for cryoprotective perfusion. Field cryoprotection would eliminate this double employment in favor of one single deployment at the patient’s location. As a consequence, remote stabilization costs will go up but Alcor HQ costs will be basically eliminated except for a small cooling expense. This should allow for a non-trivial
decrease in costs per case, which can be passed on to the member in the form of lower cryopreservation costs or can be used to eliminate or decrease future increases.

During the last couple of years Steve Graber and Hugh Hixon have collaborated to improve neuro field cryoprotection technologies and the gap between conducting cryoprotection in Scottsdale or “on the road” has increasingly been closed.

Field cryoprotection procedures are currently only available to neuro members (or for whole body members who agree to neuro-cryoprotection only) but various approaches are currently being discussed to extend this technology to whole body members, too.

Field cryoprotection constitutes the next big step in cryonics. Currently only overseas members can benefit from this procedure but the time has come to cautiously extend this procedure to more members.  Eliminating water ice shipment in favor of field cryoprotection will be need to be incremental and closely evaluated but the patient care and cost advantages are evident.

Originally published as a column in Cryonics magazine, November -December, 2017

Keeping Cryonics Affordable

What can be done to keep cryonics affordable? Or perhaps one should say; what can be done to maintain your cryonics arrangements until the time you will need them?

Let’s start by asking the question whether cryonics is an expensive procedure. One might argue that cryonics is comparable to other advanced medical procedures such as bypass surgery or brain tumor removal, and a lot less expensive than the (futile) end-of- life care costs that are incurred by many individuals late in life. The monthly costs of life insurance and membership dues are lower than the typical health insurance premium. Unfortunately, one thing that sets cryonics apart from many of these examples is that it requires an active, ongoing, effort to maintain this affordability and neglect (not paying one’s life insurance premiums) can render all of one’s efforts in vain. As affordable as the monthly costs of cryonics may be for many people, most of us do not have the resources to fork over the total cryopreservation minimums (either neuro or whole body) without utilizing insurance or a well-designed estate plan.

The first step is to take out life insurance that is at least appropriate for the cryopreservation arrangements of one’s choice. This has been emphasized before but cannot be reiterated enough. When you are young and healthy, life insurance premiums are much lower. Even if you are not sure whether to make cryonics arrangements yet, having a life insurance policy in place can give you that peace of mind and allow you to secure lower premiums. If income permits, you can take out more insurance than is needed to cover your cryopreservation minimums so that future cost increases can be accommodated. With “premium funding” of at least $20,000 above your minimum, Alcor waives the annual $180 Comprehensive Standby Fee (the “CMS Waiver”).

In my experience many cryonics members spent little time reviewing their existing life insurance policies after they put them in place. This is not a prudent approach, especially for members whose life insurance policies were just sufficient to cover their cryopreservation minimums at the time of joining. If your income increases and this looks like a relatively dependable feature of your future, it can make good sense to increase the coverage of your life insurance policy. This is especially a smart thing to do for members who are still relatively young but further along in their careers.

Another important step is to keep your cryonics arrangements in place throughout your life. Alcor is increasingly moving towards a loyalty-based dues system in which one’s dues diminish over time, for those whose membership in good standing is uninterrupted. One advantage of this decreasing dues system is that your dues will go down when you reach a point in your life when you may no longer work.

What can Alcor do to keep cryonics affordable for you? From the administrative side it can “nudge” you to ensure you do not fall behind on dues (automatic deductions) and remind you to upgrade insufficient or poorly-performing insurance policies. It should aim to take advantage of economies of scale by automating administrative and technical functions and use unexpected surplus income to reduce costs in the long run. Eventually there may come a point where the patient number is high enough to create storage solutions that substantially reduce liquid nitrogen boil-off.

The most important step that Alcor can take now to reduce costs and increase the quality of care is to merge the remote standby/stabilization phase of its procedures with its cryoprotection phase. This “field cryoprotection” is already our recommended protocol for overseas cases. If it can be implemented in many major areas in the US, significant cost reductions may be possible. It is not often that a cryonics organization can improve its procedures and save money at the same time.

Originally published as a column in Cryonics magazine, September -October, 2017

Premedication in Cryonics Revisited

Disclaimer: Alcor cannot provide medical care for living patients and must regard the care and medication of legally living members as the sole responsibility of members and their treating physicians. To avoid conflict of interest Alcor cannot advocate premedication protocols for cryonics patients.

If there are medications, nutrients, minerals, and/ or vitamins that can mitigate the adverse effects of ischemia after circulatory arrest, it stands to reason that some of these strategies may even confer greater benefits if they are already being pursued prior to pronouncement of legal death.

Two surveys of the topic of premedication, the only such writings that I know of, were penned by Michael Darwin many years ago. The first is “Reducing Ischemic Damage in Cryonic Suspension Patients by Premedication” (Cryonics, April 1991). The second, more extensive treatment is “Premedication of the Human Cryopreservation Patient,” Chapter 7 of the 1994 cryonics manual Standby: End-Stage Care of the Human Cryopreservation Patient. One case report showing use of premedication is that of James Gallagher, 1995 (Alcor Patient A-1871).

In his contributions, Darwin covers topics such as medico-legal issues, risks and benefits, patient evaluation, drug categories, specific medications, evidence, contraindications, etc. Here I briefly review some recent stabilization medications research for its relevance to premedication protocols.

Broadly speaking, there are two categories of premedication drugs: (1) Drugs aimed at preventing certain events following circulatory arrest and (2) drugs aimed at mitigating the damage that (inevitably) follows circulatory arrest. An example of the former is prevention of blood clots and an example of the latter is ischemia-induced free radical generation.

When our lab, Advanced Neural Biosciences, conducted stabilization medications research we administered medications prior to or concurrent with circulatory arrest. This model is effective in
looking at the efficacy of drugs but in real human cryopreservation administration of medications is often delayed. An interesting feature of this model, however, is that it may tell us something about the efficacy of these medications had they been part of a premedication regime.

As reported in our research summary in the January-February, 2017 issue of Cryonics magazine, we only found consistent and beneficial effects for two medications; heparin and sodium citrate. Both agents prevent the formation of blood clots, although sodium citrate may also exhibit general neuroprotective properties as a calcium chelator.

If we reflect on these results with the two categories of drugs discussed above in mind, it is tempting to conclude that only drugs that can prevent a specific ischemia-induced effect (like blood clotting) can improve the cryopreservation of the patient. This would be premature to conclude at this stage. Not just because of our choice of animal model and sample size, but because some of the medications in Alcor’s stabilization protocol may better help to sustain biological viability after the start of cryonics procedures and/or inhibit biochemical events that degrade brain ultrastructure.

Stabilization medications research can provide data to formulate an evidence-based premedication program, but there are issues that are unique to premedication. For example, a highly effective agent like sodium citrate cannot be administered prior pronouncement of legal death because it immediately stops the heart. There are also medications that may be effective for the critically ill patient (for example, drugs aimed at preventing arrhythmias and sudden death during decline) that have no meaningful role to play in cryonics stabilization procedures.

Originally published as a column in Cryonics magazine, May-June, 2017

The False Hope of Cryonics

One of the most common accusations leveled at cryonics organizations is that they offer “false hope.” For this accusation to make sense, critics would have to demonstrate it is impossible in principle, or at least highly unlikely, for cryonics to work.

What would it mean for cryonics organizations to offer a service which, at best, is “highly unlikely to work”? If the cryonics premise, that cryogenically preserved individuals could eventually be revived in a functioning, healthy state with memories reasonably intact, contradicted the known (or well-accepted) laws of physics, one could certainly justify the charge of “false hope.” But who has ever shown this? No one, of course. Nor have they approximated it by arguing that “well, it probably contradicts what is physically possible, including any technology likely to ever be developed in the future.” Has anyone shown this? (Have you seen any of their probability estimates and do you agree with them?) For cryonics to have the best chance of working, deterioration of the body needs to be halted as soon as possible and future medical technologies will need to cure the original disease of the patient – and any additional damage sustained during the cryopreservation process itself. It is commonly assumed that some kind of medical technology will be needed that can manipulate matter at the molecular level. Such developments are envisioned and being developed right now. Human biology itself demonstrates on a daily basis that it is possible to conduct biochemical actions with molecular precision.

A more empirical, biological, argument that could be made is that deterioration of the brain after pronouncement of legal death is so rapid that there is not enough left of the brain to repair or even infer its original state. It can be admitted that resuscitation without cognitive deficits is challenging or presently impossible after circulatory arrest of 10 minutes or more. But this does not mean that the ultrastructure of the brain itself has been wiped out. In fact, experimental studies that actually look at this ultrastructure do not show major changes to identity-critical structures for hours after cardiac arrest.

Critics also tend to conflate their criticism of cryonics done under good conditions with what is done under difficult, suboptimal circumstances, as if the obviously bad scenarios could not be improved upon even under the best of circumstances. Current cryonics protocol at Alcor is to start cryonics procedures (restoring circulation, cooling) immediately after pronouncement of legal death. (If cryonics were recognized as an elective medical procedure, there would be an even smoother transition, with less stress to the tissues, from terminal illness to cryopreservation.)

What about freezing damage? If a human brain is frozen without cryoprotection the freezing damage will be considerable. But does this damage preclude inferring the undamaged state of the brain from the damaged state? I am not aware of any serious arguments or empirical studies that show this. One important point that always needs to be kept in mind about cryonics is that damage occurs at the same time as molecular motion is arrested by cold, and cold is not a reliable means of erasing information. But more importantly, the freezing-damage argument is misplaced because in cryonics the brain is vitrified instead of frozen, which largely eliminates freezing damage. True, the high concentrations of cryoprotectants needed for vitrification still cause some degree of toxicity. But this kind of injury is not the mechanical damage seen in freezing, and may even be difficult to detect on an ultrastructural level at all.

As far as I can tell, the naïve and irresponsible accusation that cryonics offers a “false hope” rests on either a misunderstanding about what is involved in cryonics (or would be needed for success) or what cryonics organizations communicate to (prospective) members.  Considering the trends toward reversible cryopreservation and further miniaturization in engineering and medicine, it is reasonable to expect that the conditions for cryonics to work will be met in the future. Cryonics is not just an “act of faith” but an “act of reason.”

I would even go further and claim that those who uncritically throw around phrases like “false hope” are encouraging a form of “false despair.” For they categorically refuse to engage with the logical arguments and science that support cryonics. Their reckless talk instead is a further supporting buttress for  rationalizations of aging, disease, and death. All this we firmly reject, and instead are working toward further human enhancement.

Originally submitted as a column for Cryonics magazine, March-April, 2017. Readers may want to compare with the alternative exposition by Ralph Merkle that was published.

Alcor Associate Membership

As of writing, Alcor has more than 1100 members with cryonics arrangements. The Alcor Facebook page, however, has more than 14,000 likes. While it is easy to “like” something on social media, this number indicates that there are a lot of people who support our mission and research but are not quite ready to make cryonics arrangements for themselves. In 2012, I sent a proposal to the Alcor Advisors and Board of Directors to introduce a new kind of membership that allows people who support Alcor’s mission to join the organization as Associate Members. Associate Members pay a small annual fee ($60 or $5 a month) and get a paper copy of Alcor’s magazine, discounts on conferences and events, access to the Alcor forum, and the paid fees can be used to lower or eliminate the application fee for full membership. Alcor now has 317 Associate Members. This is not bad at all, but membership statistics at other cryonics organizations, such as the Cryonics Institute, indicate that it should be possible to have at least twice the amount of Associate Members as members with full cryonics arrangements.

One attractive feature of Associate Membership is that, unlike full membership, it can be easily gifted to friends and family, too. In fact, what I would like to achieve with this column is to encourage each and every reader (yes, you, too!) to think of someone who supports cryonics and life extension and encourage them to become an Associate Member, or even gift it to them.

You know this friend who is still figuring out her life insurance…Associate Membership!

What about that person who would like to join Alcor in the future but only when they introduce fracture free storage… Associate Membership!

That colleague who is fascinated with the idea of cryonics needs to think about it a little more…Associate Membership.

And there is this person who has been saying for 5 years now that they will sign up but never gets around to start the process…. Associate Membership.

Not sure about which cryonics organization to join? Join both major US cryonics organizations as a non-funded member and learn more.

What would it be like if Alcor had 5,000 Associate Members instead of 300? For starters, more resources would be available for publication of the magazine, social media presence, bigger conferences, and other outreach events. Local life extension and cryonics groups would see substantial growth in attendance, and new groups can be started to bring people with shared interests together. Support for cryonics research would grow. And when cryonics is under threat by hostile critics or legislators, we can draw from more people to mount an effective response. And perhaps, most importantly, a larger membership will allow Alcor to recruit more (young) talented writers, advocates, and researchers who can work together to bring human suspended animation closer to reality and strengthen the scientific and legal status of human cryopreservation.

So think hard about all these conversations you had over the last couple of years, or the people you’d really, really, like to see reading more about cryonics and Alcor and call Alcor (480) 905-1906 or head over here, and give the gift of life:

http://www.alcor.org/BecomeMember/ associate.html

Originally published as a column in Cryonics magazine, January-February, 2017

Advances in Cryoprotectant Toxicity Research

There is little disagreement among cryobiologists that the biggest limiting factor to reversible organ cryopreservation is cryoprotectant toxicity. It is actually not that hard to create vitrification solutions that completely inhibit ice formation at even the slowest cooling rates. The problem is that such highly concentrated vitrification solutions are too toxic to permit recovery of complex organs. The least toxic vitrification solution for complex mammalian organs as of writing is M22. M22 is the culmination of many years of experimental and theoretical work by cryobiologist Greg Fahy and colleagues.

Studying cryoprotectant mixtures on rabbit kidney slices, Fahy and colleagues came to the following conclusions:

1. High concentrations of a cryoprotective agent (or a mixture of different cryoprotective agents)
can prevent ice formation during cooldown and warming.

2. The toxicity of some cryoprotectants can be neutralized by combining them with other cryoprotectants.

3. The non-specific toxicity of a cryoprotectant solution can be predicted by calculating a quantity (“qv*”) which is intended to measure the average hydrogen-bonding strength of the cryoprotectant polar groups with the water molecules in the solution.

4. Within limits, non-penetrating agents can reduce the exposure of cells to toxic amounts of cryoprotectants without reducing vitrification ability.

5. Synthetic “ice blockers” can be included in a vitrification mixture to reduce the concentration of toxic cryoprotective agents necessary to achieve vitrification.

While M22 is a low toxicity solution, its toxicity profile still necessitates minimizing exposure time and introduction and removal at low (subzero) temperatures. If we had a better understanding of the mechanisms of cryoprotectant toxicity, vitrification solutions with no toxicity at all could be introduced at higher temperatures and exposure times could be increased to optimize complete equilibration of the tissue with the cryoprotectant.

Two major reviews of cryoprotectant toxicity were published in the last 5 years; Gregory Fahy’s“Cryoprotectant Toxicity Neutralization” (Cryobiology, 2010) and Benjamin Best’s “Cryoprotective Toxicity: Facts, Issues, and Questions” (Rejuvenation Research, 2015).

Greg Fahy’s paper is a rigorous exposition of experimental results concerning the phenomenon of cryoprotectant toxicity neutralization. The paper is mostly limited to the discovery that DMSO can block the toxic effects of amides such as formamide. The combination of DMSO and formamide (or other amides such as urea and acetamide) is indeed one of the building blocks of M22 but this combination cannot be used without limit and the paper includes data that indicate the maximum molar concentrations (and ratios) that still permit full viability. In theory, if two (or more) cryoprotectants would completely neutralize each other’s toxicity they could be the sole components of a vitrification solution. But as the formulation of M22 shows, it is still necessary to add weak glass formers such as ethylene glycol, extracellular CPA’s, and “ice blockers” to supplement the toxicity neutralization obtained with formamide and DMSO. An important finding in Fahy’s paper is that n-methylation abolishes toxicity neutralization for amides and combining methylated amides also does not lead to toxicity neutralization between
them. In fact, Fahy found that the presence of n-methylated compounds renders even small amounts of DMSO toxic. The remainder of the paper discusses the mechanisms of cryoprotectant toxicity and Fahy now favors protein denaturation as a plausible mechanism of (non-specific) toxicity. While other cases of toxicity neutralization have been reported in the literature, no rigorous studies have been done to produce a body of knowledge that is comparable to what we know about amide-DMSO interactions.

Benjamin Best’s paper is more general in scope but discusses a lot of experimental data from other papers and also critically discusses Fahy’s work on cryoprotectant toxicity. As Ben Best points out, different (and seemingly contradictory) results do not necessarily mean that cryoprotectant toxicity is a species or cell-type dependent phenomenon. One could imagine a meta-analysis of cryobiology data in which variables such as concentration, loading and unloading protocols, exposure temperature, exposure time, and the type of viability assay are matched to ensure methodological consistency. It is also important to compare cryoprotectants at their minimum concentration to vitrify to make meaningful toxicity comparisons.

If the work at 21st Century Medicine is an indication, universal low-toxicity cryoprotective solutions should be feasible. Perhaps the most interesting part of the paper is where Best offers a critique of Greg Fahy’s “qv* hypothesis of cryoprotectant toxicity,” which aims to show that non-specfic toxicity concerns the degree to which cryoprotectants leave water available to hydrate macromolecules. This discovery allowed for the substitution of ethylene glycol for propylene glycol in Fahy’s lower toxicity vitrification solutions, despite the resulting higher CPA concentrations. Best observes, “it seems contradictory that water remains available for hydration, but not available for ice formation.” A potential rejoinder to this observation is that so called “bound water” does not participate in ice formation but can be disturbed by strong glass formers. Best also suggests a potential refinement of qv* that allows for more precise calculation of the hydrogen bonding strength of the polar groups that are used to calculate qv*. It is conceivable that such a refinement would eliminate the few remaining outliers in the data that support the qv* hypothesis. The paper also draws attention to the possibility of kosmotropic co-solvents and changes of pH and microenvironment polarity to mitigate cryoprotectant toxicity.

Neither of the papers discusses cryopreservation of the mammalian brain, but there is good reason to believe that in the case of this organ, modification of low-toxicity vitrification solutions is required. Conventional cryoprotective agents such as PG, EG, and DMSO have poor blood brain barrier (BBB) penetration and the brain may not tolerate the CPA exposure times that other organs do. For example, while M22 can be used for cryopreservation of the brain, many of its component have poor BBB penetration and PVP and the ice blockers (X-1000 and Z-1000) are assumed not to cross the (non-ischemic) BBB at all. One potential solution is to (reversibly) open the BBB with so-called BBB modifying agents like detergents or perhaps to search for cryoprotective agents that can cross the BBB.

The most fundamental question in the design of vitrification solutions remains whether it is possible at all to introduce high concentrations of cryoprotectants without creating any kind of irreversible molecular and ultrastructural adverse effects. Understanding what specific and nonspecific cryoprotectant toxicity exactly is should enable us to answer this question.

Originally published as a column in Cryonics magazine, August-September, 2016

Scientific Proof for Cryonics?

A cryonics advocate makes an eloquent case for cryonics. Then a scientist is called upon to dismiss the idea of cryonics because there is “no proof” for it. Unfortunately, such a statement reveals that the “scientist” in question does not know the difference between empirical science and logic, and also does not understand the difference between cryonics and suspended animation.

As the evolutionary biologist Satoshi Kanazawa writes in a November 16, 2008 column for Psychology Today “The knowledge that there is no such thing as a scientific proof should give you a very easy way to tell real scientists from hacks and wannabes… Proofs exist only in mathematics and logic, not in science. Mathematics and logic are both closed, self-contained systems of propositions, whereas science is empirical and deals with nature as it exists. The primary criterion and standard of evaluation of scientific theory is evidence, not proof.” He goes on to write that “all scientific knowledge is tentative and provisional, and nothing is final. There is no such thing as final proven knowledge in science.”

What is the proper role of science in cryonics? Let’s say that a person proposes that if we freeze a person after clinical death there is a reasonable expectation that more advanced medical technologies can reverse the freezing damage, the medical condition that gave rise to this person’s critical condition, and also the aging process that caused this medical condition in the first place. We can respond to this proposal by asking a number of questions. What will freezing do to the fine structure of the brain? How will future medical technologies infer the original state of the brain from the frozen state? What kind of technologies are required to repair the brain and restore the person to a healthy and youthful state?

These are the kinds of questions where science (and reasonable extrapolations of where science will be heading) is important in evaluating the idea of cryonics. And we are not limited to just consulting existing science, we can also push science in the direction of minimizing the damage incurred during cryopreservation so the odds of revival for the typical cryonics patient will increase. For example, in 2000 Alcor changed its protocol from limiting freezing to eliminating it through a technology called vitrification. Advances in gene editing, virus modification, and nano-scale 3D printing can make the idea of cell repair more plausible. Advances in science and technology of this nature can make people update their prior (subjective) estimates about the probability of cryonics being successful.

What such advances in science cannot do is to provide “proof ” that cryonics will work. They cannot do this because all scientific knowledge is “tentative and provisional,” but it also cannot do this for a more fundamental reason. Cryonics is not suspended animation. Cryonics concerns
stabilizing people for whom no successful medical treatment is available to permit them to benefit from future advances in medicine. By definition, it is not possible to prove that these technologies will become available.

What people who insist on “proof ” for cryonics want to see is evidence of reversible cryopreservation. Human suspended animation is indeed a research- and clinical objective that a credible cryonics organization should aim for. But it cannot be emphasized enough that while “proof ” of suspended animation would provide strong support for the practice of cryonics is it is not necessary for the cryonics idea to be plausible. What is necessary for cryonics to work is that the brain (and rest of the body) of a person are preserved to a degree that the original, healthy, state of the brain can be inferred from the preserved state. Perhaps future “neurological archeology” technologies will reveal that even freezing of the brain without cryoprotectant allows for complete revival.

A proper understanding of cryonics requires that scientists recognize the difference between providing proof and updating expectations based on empirical evidence. But it also requires the scientist, as the great cryonics writer Thomas Donaldson once recognized, to make peace with the unknown because the capabilities of future science remain a matter of debate and we cannot say for certain when a person is dead by information-theoretic criteria.

Originally published as a column in Cryonics magazine, July-August, 2016

How “Repair Denialism” Prevents a Rational Discussion About Cryonics

Scientific critics of cryonics often do not seem to understand the basics of cryobiology (freezing does not “burst” cells), or remain ignorant that cryopreservation without freezing (“vitrification”) has been a routine procedure in cryonics since 2000. It is not surprising, then, that some advocates of cryonics question the integrity of such critics. Are they deliberately ignoring or distorting the evidence that supports the technical feasibility of cryonics?

One Alcor official has informally called such critics “cryonics deniers.” One might object to using such a strong characterization because the feasibility of cryonics is a conjecture, not a fact. I would like to suggest a more specific kind of denial. Many critics of cryonics seem unwilling to recognize the possibility of repair, or at least not factor it in when evaluating the coherence of arguments in favor of cryonics.

The ultimate goal of cryonics organizations is to offer reversible human cryopreservation (suspended animation) but is proof of suspended animation necessary for cryonics to be plausible?

The answer to this question is a resounding ‘NO.” To reiterate the premise of cryonics; long term care at cryogenic temperatures allows the person to take advantage of medical advances of the future, including cell repair. Cryonics permits the use of an imperfect preservation technique, provided that the damage produced by sub-optimal technologies does not exclude inferring the original state of the brain (or body) from the damaged state. This is a subtle, but important implication of the idea of medical time travel. Pointing out that existing cryopreservation techniques are imperfect does not refute the cryonics premise, unless it can be shown that such techniques produce information-theoretic death.

Not all injuries to the brain can be repaired. For example, when the period of cerebral ischemia is so extensive that bacteria-driven putrefaction has erased most of the brain structure, meaningful restoration is not likely to be possible. Do all sub-optimal cryopreservation technologies that fall short of true suspended animation produce this kind of damage? Not likely! For example, let’s assume that modern vitrification solutions produce some degree of protein denaturation and membrane damage that compromise viability. Is it plausible to argue that this completely renders the idea of repair impossible? Does ice formation produce alterations in the brain that do not allow future “reconstructive connectomics” techniques to infer the non-frozen state from the frozen state? Sweeping claims about “freezing damage” are not acceptable substitutes for detailed structural arguments, especially given the fact that damage incurred during the cryopreservation process is also locked into place by those same low temperatures.

One might object that the idea of cell repair is itself implausible, i.e. that the laws of physics do not permit the idea of healing at the molecular level. The problem with this argument is that human biology already features molecular assembly and DNA repair. Whether one subscribes to the idea of mechanical molecular nanotechnology, modification of viruses or white blood cells, or further miniaturization of 3D printing, it is reasonable to assume that some kind of nanomedicine will be developed in the future.

I once called the idea that human suspended animation is a necessary condition for cryonics to be taken seriously the “Prehoda fallacy.” (Robert Prehoda in the 1960s was an early champion of this position.) It does not serve advocates of cryonics well to discuss the feasibility of cryonics without discussing the plausibility of molecular medicine. If a critic of cryonics claims that cryonics is not technically feasible, insist upon a detailed exposition why the forms of damage associated with today’s technologies cannot be repaired by future medical technologies.

Originally published as a column in Cryonics magazine, May-June, 2016