January 2013 • Volume 34:1

Chemical Brain Preservation and Human Suspended Animation Page 17

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is on Become a fan and encourage interested friends, family members, and colleagues to support us too. lume 34:1 ary 2013 • Vo Janu on and vati CONTENTS rain Pre ser nded Chemical B pe man Susn 5 Quod incepimus Hu atio Anim conficiemus Page 17 In Praise of Cold COVER STORY: PAGE 17 Cryonics magazine editor Aschwin de Wolf’s column aims Chemical Brain Preservation and to further the cause of human Human Suspended Animation cryopreservation by debunking

The renewedISSN 1054-4305 interest in chemical brain misconceptions and offering preservation and the formation of the fresh perspectives. earch andnt Res pme vBrainelo Preservation$9.95 Foundation have De te r-40 pda Alco ence U 12 Research and nfer Pagetriggered 12 a debate about the advantages Co rt Repo Development Update Page 6 and disadvantages of chemical preservation and cryopreservation If you attended the recent as technologies to preserve personal Alcor-40 conference you cannot have missed the large identity for future resuscitation. In CT scans of brains on the this extensive review Aschwin de Wolf Cover Photo: screen. Steve Graber reports on CT scan of Alcor patient situates cryonics as an ongoing research the exciting possibilities of CT program towards reversible human scans in studying instrument suspended animation and distinguishes placement, ice formation, and it from technologies that merely seek to cryoprotectant distribution in preserve the ultrastructure of the brain. Alcor patients. Unlike chemical brain preservation, 26 In Perpetuity contemporary vitrification technologies Who Speaks for the Dead? can be scaled to humans and safely In this first installment Keegan practiced under non-optimal conditions. Macintosh provides a general framework for his new column about the legal issues 6 Alcor-40 Conference Report surrounding cryonics and life On October 19-12 the Alcor Life Extension Foundation extension. celebrated its 40th anniversary by organizing one of its best conferences to date. This report covers the event and breaks 28 Membership Statistics down the presentations, which included presentations on How many cryopreservation cryobiology research, cryonics technologies, and interventive members, associate members, and patients does Alcor have? biogerontology.

www.alcor.org Cryonics / January 2013 3 2013 Annual Giving Program lcor provides a wide array of services for you the member, and the general Editorial Board public. We inform and educate, we protect and preserve, and we strive to remain Saul Kent A at the forefront of cryonics technology. Ralph C. Merkle, Ph.D. Since its founding, Alcor has relied on member support to maintain its mission Brian Wowk, Ph.D. and attract new members. Your support, regardless of size, can provide a better future for all cryonicists. Please act now. Editor Aschwin de Wolf Suggested Giving Levels

Art Director $20 Friend Jill Grasse $60 Junior Supporter Contributing Writers Aschwin de Wolf $120 Sustaining Supporter Chana de Wolf $500 Advocate Supporter Steve Graber Keegan Macintosh $1,000 Leading Supporter ______Copyright 2013 $2,500 Visionary Supporter by Alcor Life Extension Foundation $5,000 Silver Supporter All rights reserved. Reproduction, in whole or part, $10,000 Gold Supporter without permission is prohibited. $25,000 Titanium Supporter Cryonics magazine is published monthly. $50,000 Vanguard Supporter

To subscribe to the printed edition: We encourage every member to donate. Even if you can only afford $5 right now, call 480.905.1906 x101or visit the you will make a significant contribution to Alcor’s future. magazine website: Donations may be made via the Donations button on the Alcor website or by http://www.alcor.org/magazine/ contacting Alcor’s Financial Director, Bonnie Magee, at [email protected]. Your  ______donation may be made as a lump sum or divided into easy monthly payments. Address correspondence to: Cryonics Magazine 7895 East Acoma Drive, Suite 110 Scottsdale, Arizona 85260 Phone: 480.905.1906 Toll free: 877.462.5267 The James Bedford Society Fax: 480.922.9027 ifts have played a fundamental role in the cryonics Letters to the Editor welcome: movement since its earliest days. Dr. James Bedford, a [email protected] Gman whose extraordinary vision led him to become the first person to be cryopreserved, and the first to make a bequest Advertising inquiries: to a cryonics organization, exemplified the determination of the 480.905.1906 x113 early pioneers of cryonics. We invite you to follow in his footsteps, [email protected] and join the James Bedford Society. ISSN: 1054-4305 The James Bedford Society recognizes those who make a bequest of any size to the Alcor Life Extension Visit us on the web at www.alcor.org Foundation. If you have already provided a gift for Alcor in your estate, please send a copy of your relevant documents to Alcor’s Member Alcor News Blog Communications Director, Lisa Shock. http://www.alcor.org/blog/ If you’d like to learn more about setting up a bequest, send an email to [email protected] or call 877-462-5267 x115 to discuss your gift. 

4 Cryonics / January 2013 www.alcor.org Quod incepimus conficiemus

Photo: Cryo-Care Equipment Corporation on Indian School Road in Phoenix, AZ. Dr. Bedford’s “home” from 1967 to 1969.

In Praise of Cold By Aschwin de Wolf

ome observers believe that cryonics preserve the brain. In my case, this concern inhibit residual biochemical activity? To my advocates are reluctant to subject was not just “theoretical.” In my lab I have knowledge, there is no known embedding Stheir theories to experimental scrutiny spent many years looking at the effects of protocol that is scalable to human brains due because this could damage their (uncritical) cerebral ischemia on cryopreservation and to the extreme viscosity of these plastics. belief in future resuscitation. Similarly, one chemical fixation. Last year we decided Recently these issues took a more personal might think that cryonicists would react to broaden our investigations to delayed nature for me when I had to think really with a mix of hostility and dismissal to chemical fixation and we have not been hard about a reasonable but affordable long- alternative strategies for personal survival. pleased at what we have observed so far. term preservation protocol for a companion Nothing could be further from the truth. After 1.5 years of room temperature storage animal. I spent many days reading the In fact, it is exactly because our personal the delayed aldehyde fixed brains are falling electron microscopy and fixation literature survival is at stake that forces us to be wary apart and continue to decompose. In to come up with a protocol that was better of dogmatism. small animals one might imagine that such than aldehyde fixation and low temperature For this reason, I have always been perfusion impairment could be overcome storage. Adding calcium to the fixative? interested in chemical fixation as a (low by immersing the brains in the fixative instead What about phenol? Post-fixation perfusion cost) alternative for cryonics. In fact, years but human brains are simply too large. By of a viscous cryoprotectant to allow storage before all the talk about the “connectome” the time that the fixative would have reached at subzero temperatures? That is when I and “plastination” I spent considerable time the core of the brain, extensive autolysis will really started appreciating the “magic” of exchanging messages with Michael Perry have occurred. cold temperatures. at Alcor about the technical and practical Another complex problem is to identify Absent a vitrification agent, cryogenic feasibility of chemical brain preservation. a fixation and polymerization protocol that temperatures can cause extensive damage But no matter how open minded I tried to fixes all identity-critical parts of the brain. to cells. But one thing we know: whatever be about this approach, I kept running into If aldehydes do not completely fix the lipids the nature of this damage, as soon the brain the same challenges over and over again. in the brain, should we add strong oxidizing is below the glass transition temperature of The challenge that has concerned me the heavy metals to stabilize lipids? This is -130°C, all water is either frozen or a vitrified most is whether a delayed start of chemical possible in theory but, as a general rule, rigid solid. We do not have to worry about brain fixation will produce incomplete these chemicals are either very expensive or any damage getting worse over time, or distribution of the chemical fixative in the dangerous to use (or both). Even if we are whether some biomolecules have not been brain because of ischemia-induced perfusion able to identify a chemical fixation protocol fixed. Cold may be “crude” in its effects impairment. Thinking about the technical for the brain that can do the job, how can but it is exactly because no biochemical problem of “no-reflow” is not the first thing we know that such brains are stable for very process can escape inhibition at very low on the mind of someone who first hears long periods of time? Should we follow temperatures that makes it such a powerful about the idea of using chemical fixatives to fixation by embedding with a polymer to personal survival technology. 

www.alcor.org Cryonics / January 2013 5 REVIEW

By Chana de Wolf

n honor of its 40th anniversary, Alcor results in electrophysiological studies held its first conference in 5 years on of cryopreserved brain slices, including IOctober 19-21, 2012, in Scottsdale, the persistence of LTP in adult rabbit Arizona. The program featured a wide hippocampal slices and recent forays variety of topics for presentation, with into electromagnetic warming as a way to themes regarding how to improve the ensure thermal uniformity across samples odds of a successful cryopreservation and during rewarming. Fahy also discussed theories of aging and their implications for improvements in cold storage solutions stopping or reversing aging (as argued by and the long-sought ability to reproduce their primary scientific proponents). earlier successful results with M22, Alcor’s Registration to the event opened on primary vitrification solution, in the rabbit Friday and a reception was held where many kidney after 5 long years of complications. attendees spent the evening networking and An interesting discussion about saying hello to old and new friends alike. shrinking of the brain as a side-effect But the real fun began Saturday morning of cryopreservation highlighted the role with the start of the conference. of the intact blood brain barrier (BBB) ------in perfusion of cryoprotectants through Greg Fahy, Ph.D. the circulatory system to reach the brain. The Chief Scientific Officer of 21st Fahy gave several examples of attempts Century Medicine, Inc. (21CM), Greg Fahy, to open the BBB in order to reduce or kicked off the event with an overview eliminate shrinking, including the use of of the work being carried out at 21CM high perfusion pressures, eliminating large in his talk “Progress Toward Reversible polymers such as polyvinylpropinol (PVP) Cryopreservation of Complex Systems.” from cryoprotectant solutions, “preloading” Because cryonics is reliant upon of cryoprotectants, and perfusing at technologies that do not yet exist, it is higher temperatures – all of which were sometimes likened to religion. “Unlike unsatisfactory. Ultimately, though, the religion, cryonics must be based on question is whether preventing brain evidence,” Fahy began, emphasizing that shrinkage improves neural ultrastructure. reversibility is the key component of Fahy rounded things out with an update successful suspended animation. on 21CM’s “20 year plan.” Begun in 2010, Incorporating elements of the ongoing their work in whole body vitrification “debate” concerning chemopreservation has marched forward with the ultimate as an alternative to cryopreservation, Fahy goal of reversibility by 2030. Precision questioned chemopreservation and its perfusion control systems have allowed for underlying dependence on mind uploading, unprecedented data collection during whole arguing that “a map of a city is not the city.” body vitrification experiments. Currently, A review of progress in the company is focusing on studies of cryopreservation included exciting cryoprotectant toxicity to make the next

6 Cryonics / January 2013 www.alcor.org advance toward reversible cryoprotection at least 48 hours of cold ischemia but the Then and Now.” Thomas Donaldson, of the most complex system of all, the advantage of a field vitrification protocol is Ph.D., was an Alcor member who, when whole organism. that it eliminates cold ischemic injury to the diagnosed with Grade II astrocytoma, ------brain and the severe (whole body) edema fought for a declaration that he had Chana de Wolf, M.S. that usually is seen during cryoprotective a constitutionally-protected right to a Following Greg Fahy was my own perfusion after long periods of cold “premortem cryopreservation.” Ultimately, presentation of the work being carried ischemia. his request was denied by California out by Advanced Neural Biosciences, In closing, I announced the funding Superior Court. Inc. (ANB). ANB is a neural cryobiology we received from the Life Extension In his talk, Macintosh critically analyzed research lab founded in 2008 by Chana Foundation to conduct whole brain how the case was argued and decided at and Aschwin de Wolf with an emphasis on electrophysiology (EEG) studies after the appeal level. Macintosh emphasized optimizing protocols for ischemic patients. cooling and vitrification. “meaningful access” to cryonics, explaining In particular, ANB has focused on research ------that Donaldson’s desire for euthanasia via involving perfusion and cryopreservation Kim Suozzi cryopreservation was in order to preserve of the ischemic brain. In order to do so, After a mid-morning break, Max More his brain and personality intact rather than a rat model is used to simulate cryonics explained that he was giving up one of his in the state he would be in after his “natural” procedures under realistic conditions. speaking slots to Kim Suozzi, whom he death. The presented issue was whether The main theme of the presentation was introduced as a young woman diagnosed Donaldson has a right to premortem that there is a distinct difference between with cancer who wished to be cryopreserved cryopreservation, but it was addressed by the ice free brain preservation that can be at Alcor. Max announced that Alcor would the courts in terms of assisted suicide. achieved in the lab and the conditions under provide services at reduced cost and Because of the very different intentions which a typical cryonics patient is being that staff would be volunteering time to of these two approaches, Macintosh feels cryopreserved. In particular, the variable cryopreserve Kim. that the issue was considerably confused. He periods of warm and cold ischemia which Kim Suozzi, who attended the argues that by approaching it as an assisted precede cryoprotective perfusion produce conference with her boyfriend, then suicide case, the Court could avoid having perfusion impairment (“no-reflow”) and spoke about her terminal diagnosis and to consider the possibility of cryonics ever ice formation in the brain after cryogenic efforts to raise money in support of her succeeding. Simply considering relevant cooling. In the case of cold ischemia we cryopreservation. Only 23 years old, Kim state interests, such as preventing suicide found that remote blood substitution with was a psychology student in her senior and preserving life, should have actually an organ preservation solution can prolong year at Truman University planning to do worked for Donaldson’s side rather than the the period of cold ischemia after which graduate work in neuroscience when she State’s. Other interests, such as protection ice free preservation is still possible. Some was diagnosed with Grade IV glioblastoma of innocent third parties and protection of organ preservations are better than others (i.e., brain tumor) after experiencing a vulnerable persons and preventing abuse, and we observed the best results with multiform seizure in March 2011. were not relevant at all. MHP-2 (Alcor’s current organ preservation Kim had already become interested Macintosh believes that we can learn solution). Even after a warm ischemic delay in transhumanism, the singularity, and important lessons from analyzing the blood substitution still produces better cryonics after reading The Age of Spiritual Donaldson case. In particular, not to results than not removing the blood prior Machines by Ray Kurzweil, but thought avoid the actual issue at hand. After to cold ischemia, but as the period of she still had enough time to consider the fast-forwarding to the present and warm ischemia increases, so does perfusion cryonics option. When diagnosed, she was discussing some important changes in impairment and ice formation. I stressed reticent to ask her parents for financial physician-assisted-suicide legislation in that warm ischemia is not just accelerated support, so she posted her request online the U.S., Macintosh argued that a case like cold ischemia, hard to mitigate, and a instead. After getting “unexpectedly good Donaldson’s may stand a better chance today serious obstacle to good cryopreservation. support,” her campaign was picked up if these lessons are observed. Interestingly, We also presented the results of our by the Society for Venturism, which is the successful argument of such a case may “field vitrification” research for Alcor. A currently accepting donations for the Kim be even more probable under the Canadian protocol in which cryoprotective perfusion Suozzi Charity through their website. constitution. In particular, novel arguments of the patient is conducted in the field using ------could be made under Canada’s Charter of a simplified protocol followed by shipping Keegan Macintosh, J.D. Rights and Freedoms that are not available on dry ice permits ice free preservation of Keegan Macintosh, a young Canadian under the U.S. Constitution. the brain up to at least 48 hours of dry ice lawyer and Alcor member since 2011, ------transport. Blood substitution with MHP- then presented an in-depth analysis of Panel: Long-Term Financial Planning 2 and shipping at water ice also permits the Thomas Donaldson legal case entitled Rounding out the morning was a useful ice free cryopreservation of the brain for “Access to Cryonics: Legal Strategies – panel on long-term financial planning

www.alcor.org Cryonics / January 2013 7 led by Rudi Hoffman, Michael Seidl, and revocable, meaning that one may take the able to notify Alcor. Because time is of the Ralph Merkle. money out of the trust at any time. Merkle essence in getting a patient from bedside pointed out that the trust also covers other to perfusion, Drake explained that Alcor Rudi Hoffman situations separate from financial decisions, keeps a cloud-based watch list to track Insurance agent and Alcor member Rudi such as whether one has been successfully potential cases (e.g., members with known Hoffman introduced the audience to the revived. These decisions are handled by health issues). By doing so, Alcor has basics of cryonics funding, including a Alcor and the trust advisors, not the trustee. increased bedside access to dying members discussion comparing term vs. permanent Ultimately, Merkle reminds us, there from 33% (in the 1990s) to 86%. life insurance funding options. He is no precedent for a trust intended to Improving upon 86%, Drake said, highlighted the role life insurance plays in maintain personal assets in perpetuity. “It will require more sophisticated medical allowing access to cryonics for all and how looks like it should work,” he said, “but monitoring. Lots of devices exist for important it is to emphasize the affordability we’ll find out.” measuring all sorts of physiological of cryonics to those considering signing up responses. They may be worn on the body or but who may think that it is available only Michael Seidl, J.D. in the fabric of the clothes. Such devices are to the wealthy. The last presenter in the financial planning not only good for Alcor response, but also That said, Hoffman acknowledged panel, Alcor board member Michael Seidl for getting to a hospital for immediate care. that technological advances and inflation spoke briefly but passionately about ways are inevitable and that cryopreservation to ensure that funding is available for your Ben Best costs will increase. He urged new and cryopreservation when needed. “Cryonicists Ben Best, former President of Cryonics existing members to take these issues are adventurers,” he said, “but we don’t Institute, followed Drake’s presentation into serious consideration when planning know how long the adventure will take, so with a discussion of current monitoring cryonics funding and to obtain inflation- we should plan and provision accordingly.” devices that might be useful to cryonics. robust coverage beyond today’s minimums Seidl parsed his recommendations into He began by pointing out that a chain is ($200,000 whole body and $80,000 neuro). three commandments: only as strong as its weakest link, and that 1. Protect your noggin. Think first “the time until pronouncement [of legal Ralph Merkle, Ph.D. about providing for your own death] needs more resources thrown at it.” Ralph Merkle then announced and cryopreservation. Secure funding He is particularly concerned about elderly discussed the Alcor Model Revocable Asset that will increase over time. cryonicists living alone. Preservation Trust, recently made available While panic-button systems like Life by Alcor to enable cryonics members to 2. Don’t give people incentive to Alert® could be useful, Best thinks it preserve their personal assets. In short, frustrate your cryopreservation. A might be better to monitor vital signs (e.g., Merkle explained, “Your Trust maintains large liquid estate can make people movement, respiration, heartbeat), which your assets so you ‘wake up’ with your crazy. Leaving everything to Alcor doesn’t require the patient to be alert. money as well as your life.” could incentivize interference. Desired features of a device would include Utilizing an attorney who had written Provide for these folks so that this rapid detection of loss of vital signs, a few wealth preservation trusts for incentive is removed. comfortable wear, ability to send messages, wealthy cryonicists, Alcor drafted a model 3. Give people incentive to support low power consumption, wireless, and trust that can be used by most members. your arrangements. For example, minimal false alarms. Merkle noted that the model trust is provide a financial incentive for Lastly, Best described several ongoing used as a starting point to be taken by a family member to ensure your commercial efforts such as Athena GTX, an individual to his or her attorney to cryopreservation. NUVANT Mobile, and MyPulse, as well modify to suit their particular situation ------as some cryonics-specific applications in and purposes. In general, one will need Panel: Medical Monitoring Devices development, but lamented the fact that to name a trustee organization (which can A post-lunch panel on the current state working, successful devices still have not be provided by a bank) and three trust of medical monitoring devices was hosted materialized. advisors (two appointed by the member by Aaron Drake, Ben Best, and Martine and one appointed by Alcor). The trust Rothblatt. As in the previous panel, each Martine Rothblatt, Ph.D. advisors look after the trustee to ensure person was allotted a few moments to Martine Rothblatt, Director of the they do a good job in making financial speak about the subject. Terasem Foundation, then spoke about decisions affecting the trust. Alcor detection of heartbeat cessation. First she provides continuity after the member’s Aaron Drake reviewed some statistics describing the way cryopreservation and appoints successor Alcor’s Readiness Coordinator, Aaron our time is spent and leading to the 2.9% trust advisors. Drake, emphasized that a cryonicist’s probability (1 in 34) that an Alcor member Importantly, the Alcor model trust is worst fear is dying alone without being may suffer delayed response (due to lack

8 Cryonics/November–December 2012 www.alcor.org of notification of death). The solution to Max More, Ph.D. current efforts include fluorescence this problem, she said, lies in wireless or In an effort to educate old and new imaging, neural reconstruction algorithms, Bluetooth external heartbeat detectors or members alike, Max More lectured the antibody staining, and embedding. The even less sophisticated, wrist-watch style audience on “How to Be an Exemplary impact of such technologies on cryonics, pulse detection devices. Cryonicist.” He provided a step-by step Huffman explained, would be in the form The sometimes low price of these outline of the myriad things an Alcor of an increase in conventional structural devices lends itself to various economic member can do to improve their prospects neuroscience data and the ability to models that Alcor could implement to for an optimal preservation, beginning reconstruct and evaluate procedures. generate additional revenue. Rothblatt with health maintenance including regular ------outlined various models such as: charging physical checkups and keeping Alcor Sebastian Seung, Ph.D. for an app and device; giving the app away informed of changes in medical condition. Day One of the conference ended with as a membership benefit; selling or giving He stressed the importance of keeping your Sebastian Seung’s “Connectomics and away the app and making it modifiable (i.e., Alcor paperwork updated, wearing your Cryonics,” followed by a discussion not just Alcor-related); and partnering the bracelet, and talking to your friends and of his talk. Seung began by explaining app and device with one or more PERS family about your cryonics arrangements to that connectomics is the application (Personal Emergency Response System) build understanding and support. He also of techniques such as 3D imaging to companies. PERS is a $125M annual advocated relocating to the Scottsdale area, build high-resolution maps of neural market now, and predicted to be $250M avoiding conflicts in financial arrangements, connections. The resulting map is known by 2020. If Alcor would take advantage and planning ahead to keep in pace with as the connectome. While working in the of the 15% annual growth rate of this inflation and maintain adequate funding. field at MIT, Seung met Alcor member market, it could generate an additional More discussed the things one can do to and Harvard neuroscientist Kenneth $1.7M – 27M annually. improve Alcor’s patient care such as giving Hayworth. When talking with Hayworth ------Alcor access to your medical records and one day, Seung realized the implications of Anders Sandberg, Ph.D. allowing them to perform a CT scan or a connectomics for cryonics and included In “Rational Decision Making About sample from the central nervous system to some of his thoughts on the subject in Future Technology,” philosopher Anders obtain objective feedback about the quality his book Connectome, which elicited varied Sandberg talked with us about “handling of cryopreservation. Lastly, contributing reactions. the unknowable and undecidable.” He one’s skills or resources to Alcor as a Starting with the hypothesis that “you pointed out that even really smart people volunteer and starting or attending a local are your connectome” (reminiscent of make really stupid decisions consistently. cryonics group meeting are other great “The Astonishing Hypothesis” of Francis As a general rule, humans are reasonably ways to stay involved and to improve your Crick), Seung presented evidence from good at handling “human” problems, but chances of an optimal preservation. neuroscience that chemopreservation as we get further out of our comfort zone, ------successfully preserves brain structure as we start getting bad at decision-making. Todd Huffman, M.S. evidenced by reconstructions using serial Sandberg described several approaches Following the late-afternoon break, electron micrographs (EM). He then asked to decision-making, such as rationality Todd Huffman presented “Advances in whether memories can be “read” from such [rational agents maximize their expected Neuroscience: Implications for Cryonics.” connectomes and discussed what kinds of utility; but humans don’t have a utility Huffman’s focus was on large-scale structural information might be important function], irrationality [acting under imaging technologies that can be used to to answering such questions. Ultimately, ignorance and uncertainty isn’t irrational – scan and model the brain at various levels he concluded that connectivity, including it’s how we live our lives], and uncertainty of encoding. Particularly interested in the shapes of neurons and locations of [there are some things we can’t or don’t neural structure and high throughput light synapses, is what must be preserved in order know; we can lack knowledge about microscopy, Huffman’s company 3Scan to construct the identity contained within. parameters or about the rules of a has developed the Knife-Edge Scanning But Seung wonders how well cryonics system, or even about what is good]. Microscope (KESM), capable of imaging preserves brain structure compared to Unprecedented events are important to tissue while slicing it with a diamond blade chemical preservation methods. consider in the light of uncertainty – “the to create a stack of images that can be put To that end, Seung and Hayworth absence of evidence is not evidence of together to create a 3D image. announced the Technology Prize to absence,” Sandberg said. “A true rational Huffman included several beautiful be awarded by the Brain Preservation person considers the probability of any photos of the 3D images captured by the Foundation to the first individual or team event as between 0 and 100%. Just because KESM, from an image of the vasculature of to demonstrate a technique capable of cryonic resuscitation has not occurred does a mouse brain to Nissl stains for cell bodies preserving a human brain for long-term not mean that it won’t.” such as the Purkinje cells of the cerebellum storage with high fidelity. The current ------and pyramidal cells of the cortex. 3Scan’s contenders for the first stage of the prize

www.alcor.org Cryonics / January 2013 9 have employed both chemo- and cryo- cooling using the lungs as a heat exchanger. Joshua Mitteldorf, Ph.D. preservation methods, but the required Gene expression profiling is being “In 1997, everyone thought that free imaging and analyses of these samples has explored to profile blood from patients radicals were the cause of aging and that not yet been completed. using PCR. And finally, Baldwin thinks that antioxidants were the cure. In 2012, we Seung’s presentation was followed by a by leveraging the network of professionals think it seems to be controlled by genes relatively long discussion with the audience, they’ve developed, SA will be able to build at a very high level and that signaling which quickly turned into a debate about a network of clinical facility partners that dysregulation is the problem.” Mitteldorf ’s the merits of chemopreservation and will allow SA to start or carry out cryonics hypothesis is that aging is not a result of cryopreservation. Topics discussed included procedures within their facilities. dysregulation of some earlier homeostatic the long-term stability of chemopreserved ------mechanism at all, but that it is programmed brains and whether the Technology Prize is Aubrey de Grey, Ph.D. into us, and that “we live and die according neutral between both approaches. The last segment of the conference to a schedule.” ------focused on alternative theories of aging He addressed four opportunities to Catherine Baldwin, M.S. as argued by their primary proponents. preventing aging: (1) Preserving telomeres; In her talk “From Bedside to Clinic: First at bat was Aubrey de Grey, founder (2) Damping inflammation; (3) Regulation The Evolving Care of Cryopreservation of Strategies for Engineered Negligible of apoptosis; and (4) Restoring youthful Patients,” General Manager of Suspended Senescence (SENS). De Grey believes that gene expression. Animation, Inc. (SA), Catherine Baldwin aging is the result of cumulative damage Regarding the first strategy, Mitteldorf provided an overview of SA’s stabilization caused by normal metabolism. Pointing out explained that telomeres are segments of capabilities, which she described as that the presenters will disagree on some “nonsense” at the ends of chromosomes “science, technology, and medicine in the topics, de Grey stated that he thinks that that can be lost without causing any service of cryonics.” Suspended Animation damage does continue to accumulate in all damage to the DNA. But DNA replication does patient recovery and stabilization for individuals no matter how old they get. results in the shortening of telomeres over cryonics organizations, including Alcor. In Traditional approaches to intervention in time, eventually resulting in cell death. An fact, SA is contracted to perform standby the aging process include gerontology (i.e., enzyme called telomerase, however, can add and stabilization for all Alcor patients intervene between metabolism and damage base pairs back to the chromosomes. The outside of the state of Arizona. to “slow it down”) and geriatrics (i.e., rationing of telomerase is a programmed Baldwin described the stabilization intervene between damage and pathology to death mechanism that evolution exploits and transport process, beginning with “patch it up”). Both have been ineffective, to force the sharing of genes. In terms rapid induction of hypothermia followed and so we must consider another option – of pushing for telomerase therapies, by cardiopulmonary support (CPS) the maintenance approach. Mitteldorf said he felt that “we’re ready and administration of medications in The maintenance approach advocates for this” and that he felt very safe doing preparation for the surgical procedure repairing damage directly. It does not require so. He discussed a number of (expensive) of cannulation to connect the circulatory understanding of complicated metabolic supplements that aim to activate telomerase. system to the perfusion circuit. She stressed pathways leading to damage, but only how Inflammation is an essential first-line that the skills required to carry out these to repair the damage itself. “Not necessarily defense against invading pathogens. In procedures are the same as you find in all of the damage,” de Grey says, “but youth it is wholly beneficial, but as we get emergency and medical personnel. enough of it to buy time so we can make it older our bodies begin to target healthy cells Baldwin started recruiting EMS and to the point that we can repair more of the rather than just outside pathogens. All of surgical personnel early in her employment damage.” His claim is that, unlike the others, the diseases of old age are associated with with SA. Because surgical and perfusion the maintenance approach may achieve a big higher levels of inflammation. Some drugs coverage is too expensive on a full-time extension of healthy human lifespan quite that combat inflammation are cheap and basis, SA has contracted with companies soon and that it could help people who have easy, such as aspirin, omega-3 fatty acids, that provide temporary coverage and now reached middle age or older already. curcumin, and ginger. Other approaches has four on-call cardiothoracic surgeons To that end, SENS Foundation does to damping inflammation carry substantial and eight cardiac perfusionists. Recently, research to implement SENS, including tradeoffs, however. SA has also contracted with a company cell therapies and strategies to clean up Apoptosis, or cell suicide, is an ancient that provides hospice and skilled nursing extracellular “junk” that are in human mode of programmed death found in even on-call. They also have 3 air transportable clinical trials. And though some of these the earliest eukaryotes. When the body perfusion (ATP) kits and several vehicles strategies alone have not achieved the needs to get rid of diseased cells it does supporting surgery (one on each coast). clinical endpoints, de Grey believes that so through apoptosis. But apoptosis is also In the future, Baldwin expects SA to roll what is probably needed are combination linked to diseases of old age, including out portable liquid ventilation, requiring therapies to address particular pathologies. Parkinson’s disease, sarcopenia, and glial only intubation to start efficient internal ------cell loss. Strategies to limit apoptosis have

10 Cryonics / January 2013 www.alcor.org very strong tradeoffs. We would need to Grey’s platform). “Biological immortality C. elegans can increase lifespan by 10 times. find a way to make apoptosis “smart” so evolves,” he said. “We’ve shown that aging How do you explain that?” that it kills the “bad” cells and keeps the stops at the level of the individual, we’ve Rose agreed that deleting even “one “good” ones. shown that we can explain it evolutionarily, particularly bad thing” can have significant Lastly, Mitteldorf discussed gene and we have experimental proof of such.” effects on longevity. “Evolution has already expression, which changes as we age. To control aging we must try to get immortal built life-history flexibility,” he said. “If He explained that we do not have the sooner – to cut off aging – and bring the you give up one of those major things, like same gene expression profile when we aging plateau down to a younger age. building sperm, you will see great increases get older as when we were younger and Rose is interested in using environmental in lifespan.” that this makes for a very fertile area of manipulation to effect this change. Aubrey de Grey clearly disagreed with research. There is a major effort underway Importantly, he asserted, the timing of Michael Rose and noted that the absence to understand enough to manipulate the cessation of aging depends on environment of natural selection does not mean the signals that determine gene expression, and lifestyle such as the food we eat. The absence of accumulation of damage. and if we are successful we may be able to key is to do what is natural for humans, Many more technical arguments like restore youthful gene expression. “It may or what we are adapted to. Rose argued this were exchanged, but at the end of the not be easy,’ Mitteldorf concluded, “but my that while young people of Eurasian panel it became clear that there is no real dream is to slow aging from the top down.” ancestry are well-adapted to evolutionarily consensus about what aging is and what ------recent agricultural lifestyles, at later ages would be the most efficient way to stop or Michael Rose, Ph.D. we progressively revert to physiology that reverse it. Rounding out the speakers on aging was is better adapted to the hunter-gatherer Michael Rose, an evolutionary biologist lifestyle. Conclusion who spoke on “How to Control Your To control your aging Rose suggests (a) In all, Alcor’s 40th anniversary conference Aging” (or “Looking Good in Liquid adopt the hunter-gatherer lifestyle after 30- was an enjoyable weekend for old and new Nitrogen”). 40 years of age if Eurasian and earlier (10- Alcor members alike. The agenda was Rose regards aging as “one of the 25 years) if ’your ancestry is less Eurasian, well-planned and the quality of speakers most completely solved problems in (b) use the best of modern medicine to and presentations was very high. From science today.” He discussed the theory lower your mortality level during the last the science of cryopreservation to the of the evolution of aging, explaining that decades of aging and during the plateau, implications of neural network research some organisms don’t age at all and that and (c) use autologous tissue repair when it on cryonics to strategies for preserving eukaryotic molecular and cell biology becomes available. your assets as well as yourself, no stone was allows for indefinite life without aging, ------left unturned and no question unasked. but that “the force of natural selection Panel with Mitteldorf, de Grey, and We may not always have the answers, but acting on survival falls with adult age in Rose with meetings like Alcor-40 stimulating animals like us.” The age of reproduction, Wrapping up the conference was an discussion and ideas we can better he stated, is the key to aging. Experiments interesting panel discussion with the determine where to look for them.  carried out in the 1970s delaying the first three aging researchers, Mitteldorf, de age of reproduction in fruit flies resulted in Grey, and Rose, mediated by Greg Fahy. substantially slowing the process of aging Each scientist had an opportunity to ask across subsequent generations. This has the others questions and to defend their allowed us to form a very powerful formal respective theories in light of data they may theory of aging. not have addressed in their talks. Looking at other laboratory data, Rose Mitteldorf wondered how Rose would indicated that experiments with medflies model real societal changes that have large in the 1990s suggest that aging is only a and lasting impacts on humans. Rose said transitory phase and that aging, in fact, that the Price equation attempts to take ceases at some point in late life. After the these changes into account, but that it cessation of aging there is a stabilization of is hard to model such things and that he some functional physiological characters “didn’t wish to underestimate the difficulty while others continue to decline. The of this.” resulting plateau in late-life mortality is Dr. Fahy then posed a challenge to caused by the decline of natural selection. de Grey and Rose: “Aubrey would say Rose then argued that aging is not a that metabolism is too complicated, and cumulative process of deterioration, Michael would say something similar. But contrary to cell dogmas (and Aubrey de we’ve seen that knocking out ONE gene in

www.alcor.org Cryonics / January 2013 11 Research and Development Update

By Steve Graber

ecent neuro patient imaging via neuro storage canister. Once we started with the ‘Dummy in a Can’ series. Within CT scan has shown that we can analyzing the data it became apparent that a short time I had successfully revealed Robtain a highly detailed view of we were seeing much more than we had the dummy head within the aluminum the outcome of cryoprotective perfusion. anticipated. canister (fig.1). Furthermore I was able From this information we believe it is to determine the inner workings of the possible to determine with a high level dummy head and, with some quick analysis of confidence the exact location and came to the conclusion that due to the proportion of cryoprotectant perfusion expanded foam and plastic insert detected throughout the brain. When we match within the structure, at least she is not a up the perfusion data against additional complete air-head. The aluminum can is case data, such as the time elapsed from almost impossible to completely eliminate pronouncement of death to perfusion, we from the viewer but with adequate can generate a deeper understanding of the cropping and slicing capabilities I was effects that time has on the quality of brain able to reveal the ‘patient’ inside the can, cryoprotection. This data has the potential including detailed variations in the foam to fundamentally change our approach to density, the air bubbles within the foam, pre-mortem and immediate post-mortem and the “patient’s” hair. patient care. During a subsequent trip to the medical During the first phase of our experiment imaging lab we were able to successfully our expectations for the CT scanning image specific components of our M22 project were much less lofty. We were Figure 1: Cross section of dummy head cryoprotectant. That event is what led to simply looking to determine the location showing expanding foam in blue and center our greatest progress, which I will address and placement of acoustic “crackphone” support in orange. CLUT manipulation later in this article. sensors within the skull. Crackphone data tool (inset) which allowed this image to Following the aluminum can analysis I appear from the data. Less dense materials collection and the subsequent analysis (foam and hair in blue) to the left side next converted and opened up the first of and reporting of fracturing events are an with more dense plastics to the right. the patient scan data series. At this point integral part of our cooldown process prior I was able to successfully determine the to long term care. We feel it is important to placement of the crackphone elements, determine the position of the crackphone The software I used was the open as well as location of the burhole and elements because these fracturing events source, freely available, 3D MRI and nasopharangeal thermocouples. are recorded and analyzed during patient CAT scan viewer ‘mricroGL’. In order to Below are a series of screen-captures cooldown. All reasonable attempts at view our DICOM images in mricroGL I which have been chosen to represent the 3D correct placement are taken by the surgeon first converted the DICOM data into the imaging process. These images were taken during the cryoprotection procedure native mricroGL NIfTI format, using the of two patients, A-1546 and A-1088. Due but knowing the exact placement is not dcm2nii.exe program. Once the conversion to the fact that A-1546 was pronounced possible during surgery. In addition, there is process was completed I was able to open on the east coast he/she experienced typically considerable shrinking of the brain and view the acquisition series images in approximately 18 hours of delay from during the procedure, which can affect the 3D format. pronouncement to cryopreservation. It location of the elements. A secondary goal One of my main software tasks was to should be noted that by all of our standard for us was to determine if a CAT scan can develop color lookup tables (CLUTs) for measures with the exception of travel be performed while the patient cephalon each of the materials I desired to view time, patient A-1546 was an almost ideal is secured within our standard aluminum within the images, and for that I started case who underwent a very successful

12 Cryonics / January 2013 www.alcor.org cryopreservation. Patient A-1088 unfortunately legally died of a sudden, massive hemorrhagic stroke on the east coast and did not undergo a cryoprotection. These flat images don’t fully express the actual 3D visualization (rotation in real-time) of our images at the native DICOM scanning resolution of ~0.3mm. This delivers an impressive level of detail which can only be fully appreciated using the mricroGL or some other data program. With a CLUT setting optimized to highlight dense objects in white and yellow, and less dense matter in red and blue I used the ‘Slice’ tool to remove a small section of the skull (fig.2.) We can easily make out the crackphone wires and the thermocouple wire traversing through the burholes into the brain cavity. The nasopharyngeal TC location is a complete surprise, having been pushed so far into the nasal cavity that the tip of the probe ends up all the way into the throat under the jaw. Variations in brain density Figure 2: Crackphone element and are starting to be visible in the red and blue range. NOTE: Color Thermocouple placement – A 1546. designations are entirely arbitrary.

As you read this, you might be asking yourself “Why weren’t we doing this a long time ago?” The answer is that we had to wait for large computers to shrink down to desktop machines, and for software to be written that we could afford.

A sagittal section of A-1546 (fig.3) directly through the mid-line highlights some very interesting density variations throughout the brain. I have inset the CLUT adjustment control window to help explain the density range, opacity and colorizing in this image. This particular cross-section also highlights the position of the mid-line crackphone as a white dot at the top center of the brain. White and Figure 3 yellow are once again the densest region while orange/red is mid- density and blue is least dense. My initial expectation was to see a fairly uniform density map throughout the brain but it appears not the case in this patient. I will draw more detailed conclusions further in my report after showing our non-perfused brain using the same CLUT settings. For reference, here is a sagittal section through the mid-line (fig. 4) this time of patient A-1088, who was a recent straight freeze. The placement of the nasophyrangeal probe is clear. X-ray scattering from metal denture fixtures shows up as white and orange/red noise horizontally across the bottom of the image. The terminal hematoma is visible in fig. 4 as a red shape spread throughout the brain cavity behind the nasal passages. Homogeneity of electron density is evident throughout the brain of A-1088. When compared to the identically composed, sectioned and CLUT displayed image of A-1546 (fig. 3) it is clear that there is great disparity in overall density between these two brains. A-1546 shows a significantly greater electron density than Figure 4 A-1088 throughout the majority of the brain, but there are areas www.alcor.org Cryonics / January 2013 13 Figure 6: In this image blue is most electron-dense, followed by yellow, to red, and white is least dense. I have selectively removed the majority of the skull’s electron density by taking its opacity to 0 and highlighted the metallic crackphone and thermocouple wires to determine their placement within the skull. Additional details appear at this specific density including staples, teeth, and two structures deep within the skull which appear to be sockets for the jawbone.

Figure 5: Another image showing a comparison of electron density using identical CLUT settings. In this image the hematoma in the frontal lobe of A-1088 appears in white. Bone opacity has been lowered to zero. White is still more dense than red. We can very clearly see a significant difference in relative density between our two subjects.

of lower density which refute this generalization. Overall the A-1546 brain is much more electron dense and we believe this to be evidence that perfusion did occur, at least in certain areas. It is important to note that we do not feel that homogeneous perfusion of cryoprotectant was achieved across the entire brain. This may be due to the fact that patient A-1546 was pronounced out of state and experienced a travel time of 18 hours from pronouncement to the beginning of the cryoprotective ramp in the Alcor O.R. Figure 7: A variation on the slice tool. This one was taken In September 2012 we CT scanned in high resolution a variety of in the transverse direction, and clearly shows the location specific chemical compounds which are common in the M22x1.25 of the brain hematoma of patient A-1088. Although it’s vitrification solution. We created a package of 5 cryogenic hard to believe, the CLUT parameters used to achieve this vials individually containing water, ethylene glycol, formamide, image are the same as used for a previous image of A-1546 M22x1.25 and a last one containing dimethyl sulfoxide. Once these (fig. 6). The structures highlighted by the software at these ‘marker’ scans were brought back to Alcor I was able to isolate and particular electron densities are completely different. enhance the absorbtion and scattering properties for the contents

14 Cryonics / January 2013 www.alcor.org Figure 8: CT visualization of specific chemical compounds and the corresponding color lookup table (CLUT) of the five individual nunc tubes in my CT Visualization software. Figure 9: From the video shown at the 2012 Alcor Conference: I then created a “CLUT Map” and saved it to disk. A brain CT Scan of an Alcor patient with an 18 hour travel The new CLUT map was applied to our earlier patient CT Scans time from pronouncement of death to perfusion. The CLUT and the initial results from this additional analysis effort have created for this image was based upon our CT Scan of specific proven quite extraordinary. These findings were significant enough chemicals found in M22 cryoprotectant. Dark Blue to Light that I created a short video which was displayed during breaks at Blue colors are most likely water ice and frost while White the Alcor 40th anniversary conference. Inside of each patient’s to Red are quite possibly blood and cerebrospinal fluid. scan file is revealed a great wealth of information which we believe Colors from Green to Light Yellow are Cryoprotectants. should be able to potentially determine success, failure, or some combination thereof of the Alcor perfusion procedure. We believe we have the ability to visualize perfusion. This is important because we can then compare it against a number of external variables including but not limited to: hours of warm or cold ischemia, travel time, effects of various post mortem medications, etc. The end result is that we may be able to definitively answer some important questions. Is perfusability adversely affected over long transport times? etc... We are in the very early stages of research with this technique but it holds a lot of promise. As you read this, you might be asking yourself, “Why weren’t we doing this a long time ago?” The answer is that we had to wait for large computers to shrink down to desktop machines, and for software to be written that we could afford. Also, we just didn’t know; there’s not a lot of brain cryoprotection being done, and we’re apparently the first people to ever look. 

Figure 10 - From the video shown at the 2012 Alcor Conference: Brain CT Scan of an Alcor patient with a straight freeze. This CLUT is basically identical to the one in Fig. 9 above.

www.alcor.org Cryonics / January 2013 15 Preserving Minds, Saving Lives: 35 Years of the Best Cryonics Writing of The Alcor Life Extension Foundation

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Why We are Cryonicists Notes on the First Human Freezing Dear Dr. Bedford How Cryoprotectants Work How Cold is Cold Enough? The Death of Death in Cryonics The Society for The Recovery of Persons Apparently Dead Frozen Souls: Can A Religious Person Choose Cryonics? But What Will the Neighbors Think?! Systems for Intermediate Temperature Storage for Fracture Reduction and Avoidance

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16 Cryonics / January 2013 www.alcor.org Chemical Brain Preservation and Human Suspended Animation

By Aschwin de Wolf

Executive Summary Scientific and practical considerations strongly support cryopreservation rather than chemopreservation for the stabilization of critically ill patients. Technology for achieving solid state chemopreservation of brains larger than a mouse brain does not yet exist. Chemical fixation is irreversible without very advanced technologies. Chemical fixation permits no functional feedback or development pathway toward reversible suspended animation. By contrast, cryopreservation seeks to maintain viability of the brain as far downstream as our capabilities and resources permit – an approach that reflects our view of cryonics as an extension of contemporary medicine. Cryopreservation preserves more options in that a cryopreserved brain could be scanned in future, or later chemically fixed, but the process of chemical fixation cannot be reversed and replaced by just low temperature storage. The cost benefits of chemopreservation over cryopreservation are exaggerated, largely because the standby and treatment procedures for effective chemopreservation would be just as extensive as for cryopreservation, if not more so, even assuming that highly toxic chemicals could be worked with safely in the field. Chemopreservation is being inherently tied to mind uploading, an association that is likely to limit its acceptance as a form of experimental critical care medicine by apparently requiring acceptance of the idea of substrate independent minds.

Introduction also respond to some of the recurrent crucial identity-encoding parts of the brain. The formation of the Brain Preservation arguments that have been made in favor of This is not just a theoretical concern. Recent Foundation and the recent publication of chemical brain preservation. discussions about chemical preservation of Sebastian Seung’s book Connectome1 have One seemingly paradoxical position that the “connectome” (pattern of connections given rise to a renewed interest in chemical will be clarified in this article is that Alcor between brain cells) have made it quite preservation as a means of personal survival. aims for better preservation technologies evident that absent functional recovery Alcor welcomes these developments and than can be offered through chemical of the brain, there is no shortage of has even attempted to donate to the Brain preservation but is also more optimistic arguments that seek to show that chemical Preservation Technology Prize to stimulate about the resuscitation of patients preservation will fail to produce the desired validation of both cryopreservation preserved under suboptimal conditions outcome. Some of these arguments invoke and chemopreservation as preservation with older cryopreservation technologies. rather unorthodox views about how technologies.2 In fact, in 2008 Alcor memory is encoded in the brain (such as received a grant to conduct a preliminary Suspended animation the necessity of locking neurotransmitters investigation into chemopreservation.3 In What distinguishes the long-term objective in place).7 However, absent a test showing addition, Alcor staff member Mike Perry of Alcor from chemopreservation that memory is preserved after reversal of published an extensive article about low- proposals is that we are not satisfied with the preservation procedure, we will not be cost alternatives for cryonics4 and Aschwin preservation of the ultrastructure of the able to progress beyond a debate in which de Wolf published the first technical review brain alone. The aim of Alcor is to keep different perspectives compete without of chemopreservation as an alternative the patient viable by contemporary medical empirical resolution. method of biostasis in Cryonics magazine.5 criteria as far into our procedures as Another important reason why Alcor A common denominator in our research possible.6 There are a number of reasons seeks to maintain viability of the brain and writings has been the recognition that for this choice. as far downstream as our capabilities and chemical preservation may constitute a The most important of these reasons is resources permit is that we view cryonics viable alternative to cryopreservation on that restoring function after reversal of our as an extension of contemporary medicine a theoretical level but that scientific and procedures is the most credible test of the and allowing unnecessary damage would practical considerations strongly support efficacy of our procedures. We are reluctant contradict this perspective. Contemporary cryopreservation for the stabilization to settle for preservation of ultrastructure chemopreservation methods depend on of critically ill patients. In this article alone because this goal can always trigger extensive cross-linking of proteins and we will further explore these issues and objections that we are failing to preserve this cannot be reversed by contemporary

www.alcor.org Cryonics / January 2013 17 “Obviously brain preservation technologies based on methods used to prepare tissue for electron microscopy (chemical fixation, staining and embedding) have a natural advantage when the evaluation method is electron microscopy.” medical technologies. In a sense, one could much damage in our procedures can be preserving the connectome is not enough. argue that chemopreservation has to “kill” effectively countered and the remaining One could argue that we also would need the brain to preserve it. Although even in debate will be about the technical feasibility to preserve detailed information about all “ideal” cryonics cases we are not yet able of rejuvenating the patient and restoring different kinds of neurons, the molecular to sustain viability throughout all parts our them to good health. As currently conceived state of synapses (“synaptome”), ion procedures, Alcor’s research efforts and chemopreservation is fundamentally channels, microtubules, neurotransmitters, resources are dedicated to attacking this incapable of securing viability of the brain extrasynaptic interactions and so forth. The limitation from all angles (rapid cooling and cannot be brought under the rubric of most extreme position would be to argue that during stabilization, development of low evidence-based medicine. for meaningful brain preservation complete toxicity vitrification agents, intermediate preservation of the brain (or a molecular temperature storage, etc.). Our friends in the future brain scan) would be required. Now some Yet another argument of seeking A common objection to cryonics has been of these objections can be countered by reversible preservation procedures is that that future generations may have little interest arguing that the biochemical basis for brain we want to minimize the time the patient in resuscitating cryopreserved patients. At functioning and short-term memory does has to be retained in low temperature care. Alcor we do not want to rely solely on the not need to be preserved to preserve the The shorter the period the patient has to goodwill of future generations and we have individual. But such arguments may not be maintained in biostasis the less risk there set a substantial amount of funding aside to completely satisfy critics who believe there is that social and financial challenges will deal with this issue ourselves. Still, the first is more to identity preservation than the force cryonics providers to discontinue thing we should recognize, as former Alcor connectome. Without functional tests, care of their patients. Another benefit of President Michael Darwin has pointed out,8 biostasis proposals will remain a source of minimizing injury prior to long term care that friendship should come from both criticism for people who want more robust is that earlier resuscitation may reduce the sides. Preservation technologies that transfer empirical corroboration for the efficacy of amount of alienation for the resuscitated many challenges and puzzles to people in the proposed procedures. patient. the future may not make us many friends. The prevailing proposal is to subject an Finally, a more general argument can If the term “friends in the future” has any experimental animal brain to a series of be offered in favor of this approach. The meaning at all it should require minimizing procedures and then re-construct the brain conventional case for cryonics rests on the the burden on future generations and even through 3D imaging technologies. And expectation that we (a) can cure the terminal provide them an incentive for wanting to here is where we think there is a formidable disease the patient suffered from prior to resuscitate us. This understanding informs challenge for chemical preservation. cryopreservation; (b) will have available Alcor’s decision to offer the best procedures Because functional tests are not possible credible rejuvenation technologies to possible and not to send off a compromised in cross-linked brains, the only available prevent the patient succumbing to another brain to an unknown future based on just a reference for looking at the efficacy of age-associated illness; and (c) will be able series of logical arguments. chemopreservation is to compare the to repair the damage associated with the results of this procedure against images cryopreservation process itself. Since most Limits of connectome preservation that have been obtained through chemical of the scientific skepticism concerns the How do we know if our procedures are preservation as well! Granted, electron damage being done by biostasis methods good enough? As discussed above, if we microscopy has taught us a lot about themselves, eliminating this form of can demonstrate that a person (or relevant brain anatomy but we cannot say for sure damage would further strengthen the case animal) can survive our procedures intact whether the procedures employed to for human cryopreservation. without loss of identity and memory, prepare specimens for electron microscopy Reversible cryopreservation would this will inspire confidence. But how can (irreversibly) damage specific areas of constitute true suspended animation for advocates of chemical preservation of the the brain that are crucial for memory and humans. At Alcor we believe that a credible connectome know that what they are doing identity. In neural cryobiology, on the cryonics organization should aim for is good enough? other hand, it is possible to subject the perfecting human suspended animation. If If one confines oneself to structural cryopreserved brain tissue to both a viability we can achieve reversible cryopreservation, preservation of the connectome, it is test and (subsequently) to ultrastructural the objection that our patients sustain too always possible to object that “just” examination.

18 Cryonics / January 2013 www.alcor.org The response of people advocating brains are currently very dehydrated. the idea of chemical brain preservation chemopreservation as a means of personal Due to this dehydration, which typically use the more narrow term ‘plastination.’ survival is to supplement their arguments persists even after cryoprotectant removal, Plastination is usually described as a with a substantial amount of philosophy it is not yet clear that cryopreserved technique first developed by Gunther von to make their point. But philosophical brains can be effectively evaluated by Hagens in 1977 to preserve body parts for arguments are no substitute for empirical the Prize organizers. To be specific, the anatomical or educational purposes. This is evidence and the only empirical evidence criterion for success is preservation of the a rather “harsh” technique, which requires that will be persuasive to critical observers connectome, which requires two things: dehydration by alcohol and replacement of is to seek functional recovery. Absent that, preservation of synapses and preservation the lipids by a polymer. To our knowledge, cynics will continue to invoke the existence of enough information to infer the there are no credible peer reviewed of some “platonic” fragile brain that no pattern of connections between them. ultrastructural studies of brains plastinated preservation technique can salvage. Neural cryobiology researchers believe in such a manner. that they can achieve good ultrastructural The Brain Preservation Technology preservation of the brain but dehydration Prize compactifies the neuropil, reduces space “At Alcor, we believe that a In 2010 the Brain Preservation Foundation between structures, and makes the tissue credible cryonics organization established the Brain Preservation so dark in the electron microscope that it Technology Prize. The Prize seeks to is hard to actually observe the synapses. should aim for perfecting human validate chemical preservation and/or So if a quick scanning method doesn’t suspended animation.” cryopreservation of the brain for personal discern all synapses that are actually identity preservation, and develop there, it will fail. There are techniques for protocols to apply these technologies doing electron microscopy at cryogenic What most writers have in mind when to large mammalian brains. Although temperatures in the vitrified state, but they use the word “plastination” as a means the Prize is open to both chemical and these depend on the tissue being sliced of biostasis is a procedure in which chemical cryobiological preservation methods, before vitrification. Making slices out of fixation with an aldehyde is followed by the endpoint for evaluating the quality a whole vitrified brain while vitrified is a treatment with osmium tetroxide and resin of preservation involves advanced 3D tough problem. It is easier to make thin embedding. While previous proposals for electron microscopic imaging techniques. slices out of a whole brain that’s been chemical brain preservation only discuss Obviously brain preservation technologies turned into solid plastic because the resin the use of fixatives such as formaldehyde based on methods used to prepare tissue for used is designed for being cut into thin to crosslink and immobilize proteins, the electron microscopy (chemical fixation, slices for microscopy. So plastination has addition of osmium tetroxide and resin staining and embedding) have a natural a natural advantage in this competition — (plastic) embedding provide greater long- advantage when the evaluation method in terms of processing for the tests rather term stability. Osmium tetroxide stabilizes is electron microscopy. Cryopreservation than in actual results. unsaturated lipids in the cell membrane, methods are at a comparative disadvantage We have no doubt that the designers of and replacement of cell water with a solid because they are designed to achieve the prize sought to design a neutral prize, polymer resin stops diffusion of molecules different preservation objectives than but it is challenging to develop a prize that in a manner similar to cryopreservation. preparation for electron microscopy. is truly neutral in term of evaluation. For While theoretically sufficient, the empirical To succeed, Prize competitors using example, if the prize used viability as a sufficiency of these measures for preserving cryopreservation must successfully load criterion, cryopreserved brains would be identity-critical information for centuries cryoprotectant chemicals into a whole at a great advantage. In fact, the effects is not currently known, and may require brain, cool to cryogenic temperatures, of using aldehydes and powerful oxidizers complex accelerated aging studies. Another unload cryoprotectant chemicals, and then would render the chemopreserved brains reason for including the two additional steps still perform the chemical preservation dead by even the most charitable functional of osmium tetroxide fixation and resin steps necessary to prepare tissue for criteria. It is our belief that a prize that embedding is to prepare the brain for slicing electron microscopy. An advantage aims to corroborate the case for personal and scanning for resuscitation in the future. cryopreservation has is that Prize survival technologies should embrace both Whatever “plastination” method is officials are permitting cryopreservation ultrastructure and viability. chosen, the consequence will be that competitors to perform the chemical the brain is rendered non-viable by preservation steps on small tissue pieces What is plastination? contemporary medical criteria. In fact, after whole brain cryopreservation. While the term chemopreservation chemical fixation and osmium tetroxide A specific concern for Brain Preservation has been used to describe the idea of are routinely used with the explicit aim Technology Prize competitors using chemical fixation as an alternative to of killing life and irreversibly stopping cryopreservation is that cryopreserved cryopreservation, many proponents of biochemical activity.

www.alcor.org Cryonics / January 2013 19 The cost of chemical brain medicine it will not be available as an elective need to deploy standbys and stabilize preservation hospital-based procedure. Like cryonics, patients in the field. However, it is doubtful One of the proposed advantages of chemopreservation should be practiced as that one form of preservation would be chemical preservation of the brain is to a form of emergency medicine. As such, accepted and the other would be rejected. be its comparatively low cost compared to it will require the same kinds of “standby” As a consequence, if acceptance would human cryopreservation. It can be admitted and “stabilization” procedures to prevent reduce costs, this would happen to both that an isolated chemically preserved brain post-arrest deterioration of the brain. In chemical preservation and low temperature reduces long term space requirements cryonics, professional teams capable of preservation of the brain. compared to a typical Alcor neuropatient. performing stabilization procedures rapidly The space saving, however, is modest since and effectively cost tens of thousands of The no-reflow phenomenon the annual storage cost for a neuropatient dollars to bring to the bedside. The cost One of our biggest concerns about offering is only a few hundred dollars per year. A to deploy teams to restore circulation and chemopreservation as a practical means chemically fixed brain can be removed from perfuse solutions after clinical death would of stabilizing critically ill patients is that the skull and may not require a dedicated be no different for chemical preservation, if the procedure is practiced in non-ideal (low temperature) storage environment. and they would be even more critical for circumstances, the effects could include In reality, however, we do not expect most preservation to be successful. progressive decomposition of brain tissue people to be comfortable with the idea of An additional complication for chemical despite chemical fixation. In terms of long-term brain preservation without any brain preservation is the toxicity of the tolerance of warm and cold ischemic delays, kind of institutional structure. (Would you necessary chemicals to the team and chemopreservation is a lot more demanding. want your chemopreserved brain to be surrounding personnel. In simple terms, Since the 1960s it has been recognized by sitting unsecured on the shelf of a person chemicals powerful enough to bind and many biomedical researchers that even who has no contractual obligation or inactivate biological molecules must by short periods of warm circulatory arrest can means to protect you and eventually revive their nature be very reactive and toxic to produce perfusion impairment in the brain.9 you?) So the real cost difference may more living people. (This is in contradistinction to Any credible chemopreservation proposal reflect reductions in storage space and chemicals used for cryopreservation, which requires access to the vessels of the patient. long-term maintenance than elimination of are practically innocuous by comparison.) This means that in the case of delays due organizations that protect these brains and The initial steps of chemical preservation to warm and cold ischemia, there will be initiate resuscitation. require perfusion with aldehyde fixative incomplete distribution of the fixatives. In Whether the cost of resuscitation of chemicals such as formaldehyde, fact, the recognition of this challenge is a chemically preserved brains will exceed glutaraldehyde, or acrolein. Even fumes of standard part of textbooks on preparing that of cryopreserved patients will depend these chemicals at low concentration are specimens for electron microscopy. on the method of resuscitation. If biological powerful irritants to eyes and lungs. They Ischemia-induced “no-reflow” is a or mechanical cell repair machines are could not be used in an ordinary hospital problem for both chemopreservation used to restore function, the costs of room or hospice setting. (Being similar to and cryopreservation, but even more so chemopreservation may actually be higher embalming fluid, aldehyde fixatives could for chemopreservation. In the case of because the informational and logistical possibly be used in a mortuary.) After cryopreservation, incomplete distribution requirements of restoring a brain to its initial stabilization with aldehyde fixatives, and equilibration of a cryoprotectant can pre-cross-linked state may be even more a chemopreservation patient would have produce ice formation, but long term care daunting than that of a “straight frozen” to be transported to a dedicated facility for at cryogenic temperatures will stabilize the brain. An alternative for brain repair is to treatment with even more toxic chemicals tissue with no further degradation. In the slice the brain, scan it, and upload it to a such as osmium tetroxide and plastic case of chemopreservation, the absence computer. Such a revival scenario may be resin monomers. Osmium tetroxide is a of low temperatures could permit ongoing substantially less expensive than repairing a volatile and extremely powerful oxidizer, degradation of poorly fixed and embedded cryopreserved brain but it cannot be taken and epoxy resin monomers are mutagenic tissue. for granted that such revival attempts will carcinogens. In addition to being very While it is possible that resin embedding constitute meaningful resuscitation of dangerous, these chemicals are also (solidification) would halt autolysis, the the individual. In addition, this method, expensive and would bring the costs of ischemia- induced perfusion impairment destructive mind uploading, is possible for chemical brain preservation closer to the that prevents complete distribution of cryopreserved brains as well. costs associated with vitrification solutions aldehydes would also prevent adequate The expected cost of preparing the brain in cryonics. perfusion of the organic solvents and for long term chemical preservation cannot If chemical brain preservation were to monomers for resin embedding. (Whether be separated from the issue of acceptance be accepted as a routine hospital-based resin embedding could be achieved by of the procedure. If chemical brain procedure, costs would be reduced because perfusion even under ideal conditions is preservation is not accepted by mainstream of economies of scale and the reduced still an open question.)

20 Cryonics / January 2013 www.alcor.org Chemopreservation as emergency whole human brains doesn’t exist yet. At was perfected. He reiterated this stance in medicine? the time of writing, the chemopreservation a 1969 interview in which he said: “I am Even if chemical brain preservation would technology competing for the Brain still opposed, as I was before Dr. Bedford’s be accepted as a routine hospital procedure Preservation Technology Prize uses death, to freezing people at the present time there will still be many cases in which this external diffusion to introduce osmium because this money should be spent on procedure will have to be applied on short tetroxide and resin into a mouse brain by research. Any human freezing is premature notice outside of the hospital or after long soaking it in various solutions for more and without scientific basis until a mammal delays. For example, people can experience than 250 hours. Since diffusion time varies can be revived from the frozen state.”11 sudden cardiac arrest in the street, die in as the square of distance, a similar soaking Prehoda’s objection to offering their sleep, or be involved in a traumatic protocol applied to a human brain would cryopreservation continues to be made accident in a remote area. In these require six years. As a practical matter, in either a strong or a weak version. In circumstances chemical preservation will such a protocol would almost certainly its strongest form it is argued that it is have to be conducted after a (prolonged) fail because of resin polymerization not “scientific” to offer cryonics services period of circulatory arrest. As discussed during the long soaking time. Rather as long as reversible cryopreservation of above, delayed chemical fixation will most than diffusion, perfusion protocols that a whole mammalian organism has not likely fail to completely fix all areas of circulate all chemicals through the vascular been demonstrated. Such claims are often the brain as a consequence of perfusion system appear essential for solid state presented in the form that there is no impairment. This major inadequacy of chemopreservation of large mammalian scientific “proof ” that cryonics will work. chemopreservation leaves cryopreservation brains. Such protocols have yet to be A weaker version of the argument also as an irreplaceable biostasis technology for developed, and face considerable obstacles exists in which it is claimed that without cases of unexpected cardiac arrest. Cold is of viscosity and blood-brain barrier evidence of reversible cryopreservation the only biostasis-inducing agent that penetration. the general public and scientists have good can rapidly penetrate tissue regardless reason to reject it. of its state of injury. The “Prehoda fallacy” These views rest on a fundamental Practicing chemical fixation as The impossibility of conducting functional misunderstanding of the rationale of emergency medicine raises another assays in chemically preserved brains is cryonics and do not recognize the distinction complex logistical issue. One part of the one of our concerns and reflects our aim between the objective of science and the procedures is to perfuse the brain with to develop technologies that are reversible objective of medicine. The objective of the dangerous chemical osmium tetroxide with contemporary technologies. On the science is to generate knowledge about (or any other oxidizing agent that can other hand, a dominant perspective in the the physical world by testing hypotheses. stabilize lipids). We wonder whether it is advocacy of chemical brain preservation The objective of medicine is to treat possible to establish a protocol that would is that perfect preservation is a necessary people (or non-human animals) by using permit a safe environment to conduct this condition for medical acceptance of the best knowledge from science and procedure in the field. While it is true that cryonics or chemopreservation. practical experience available. Medicine osmium tetroxide does not necessarily One of the most prevalent objections is inherently “messy” because it cannot need to be administered in the field, and to cryonics among the educated public and avoid acting on incomplete information in aldehyde fixation would buy enough scientists is that absent proof of reversible conjunction with a (subjective) assessment time to transport to dedicated facilities, cryopreservation cryonics should not be of risk. For example, if a person is in even the practice of emergency aldehyde offered to the public. One of the most overall good health most people would fixation would create much greater health outspoken representatives of this kind of not support subjecting this person to an hazards than the practice of remote blood reasoning was the author Robert Prehoda. experimental treatment with potential substitution in cryonics, or even field In 1969 Prehoda published the book severe adverse effects for a minor illness. cryopreservation. As far as we are aware, Suspended Animation: The Research Possibility On the other hand, if a person is born even the most “toxic” solution used in That May Allow Man to Conquer the Limiting with a highly lethal single gene mutation, cryonics (the vitrification agent) is less Chains of Time.10 In this visionary book, he more risky experimental treatments could dangerous than the least toxic solution covered a variety of means to extend the be justified. What distinguishes cryonics (formaldehyde and/or glutaraldehyde) maximum human life span including, but from conventional medicine is not decision envisioned for chemopreservation. not limited to, chemical anabiosis, human making under uncertainty but the temporal hibernation, suspended animation, and separation of stabilization and treatment. Solid state chemopreservation is not controlling the aging process. Despite his Evidence-based medicine is inherently applicable to human brains at present participation in the 1967 cryopreservation conservative and the idea of cryonics The clinical application of chemo- of James Bedford (who is still a patient extends this conservatism to end-of- preservation is still hypothetical because at Alcor) he was opposed to offering life decisions. The fact that society has technology for fixing and plastic embedding cryopreservation before the technology exhausted all means of curing critically ill

www.alcor.org Cryonics / January 2013 21 patients does not mean that future medicine that we have observed a milder form among the body) restoring the original healthy state will not be able to treat this patient. The advocates of chemical brain preservation. should be possible.12 This argument does objective of cryonics is to ensure that a Although lip service is being paid to not just apply to biostasis procedures that patient is stabilized to reach that future the rationale of cryonics, the argument introduce known and predictable forms of with as little additional damage as possible. seems to be that technical feasibility is an damage but also applies to any patient who The fact that current cryopreservation important reason for scientists to reject suffers some degree of ischemia prior to methods are not reversible and cause cryonics. Such a perspective seems quite preservation. In fact, a perfect preservation (additional) damage cannot be used as an reasonable but it fails a basic reality check. of an ischemic brain might be classified as argument against this reasoning because Most scientists who comment on cryonics not being successful if it does not conform the argument that treatments may be in public have made little effort to educate to the preservation of the connectome of a available for presently terminal illnesses themselves about the procedure and control brain. But whether this dooms such can also be extended to cover the damage often make uninformed statements about preservations to failure depends on whether associated with the cryopreservation cryobiology and the ultrastructural effects the original state can be inferred from what process. The “Prehoda fallacy” consists of of cerebral ischemia that even contradict was preserved, which itself is a function of not recognizing the point that a procedure the established knowledge in those the degree and duration of ischemia. that aims to take advantage of future fields of research. And when cryonics We believe that a research program aimed developments in science by definition organizations introduce new procedures at demonstrating under which conditions the cannot be experimentally demonstrated (such as vitrification) that aim to eliminate original structure can be inferred from the by contemporary science. Exercising our a scientific objection, the criticism simply injured brain could be at least as persuasive best judgment in this matter is neither moves to another part of the procedure. as a program to demonstrate successful “scientific” nor “unscientific” although The residual element of uncertainty that preservation of the connectome of non- one can question whether the reasoning characterizes cryonics can always be compromised brains. Demonstrating the involved is coherent or not. exploited to claim that the procedure lacks scope and limits of such reconstructions will This of course does not mean that scientific proof. Eliminating ice formation also corroborate the premise of cryonics science should not play a role in making or fracturing, or demonstrating preservation that using a preservation technique that such decisions. Certainly it should. The of the connectome will not satisfy critics itself adds damage is not necessarily a dead cryonics proposal can be submitted to the who use these kinds of arguments to end provided there is systematic knowledge test of whether it contradicts known laws of shield more subjective psychological and of how this preservation method alters the physics or exceeds realistic computational social objections to cryonics. Successful structural and functional properties of the abilities required for cell repair. More preservation of the connectome may win brain. specifically, reasonable expectations about over some doubters but it is not likely that future medicine can be strengthened by it will move chemopreservation and/or Neural archeology and suspended improvements in cryopreservation or cell cryonics into the mainstream until these animation repair technologies. And, of course, we can psychological and social objections can be There is a wide gap between the aim generate experimental evidence to choose effectively countered. of moving toward reversible human between alternative biostasis methods such cryopreservation and the state of the as the use of cold temperatures or chemical brain of many cryopreservation patients. fixation. But ultimately, cryonics cannot “Cold is the only biostasis- It might be tempting to conclude that be “proven” in the conventional sense a commitment to developing true of the word because if all components inducing agent that can rapidly human suspended animation implies a of the proposal (curing the terminal penetrate tissue regardless of its pessimistic outlook on the prospects of disease, reversing cryopreservation, and resuscitating patients that were preserved rejuvenation) could be demonstrated now, state of injury.” under suboptimal conditions with cryonics would be redundant. We can older technologies. In our view, such a make efforts to minimize this element of perspective ignores the important point uncertainty but eliminating it completely What constitutes preservation? that one can aim for the best preservation may never be possible as there may always Insistence on demonstrated preservation of technologies possible but at the same time be diseases and traumatic insults that the connectome as a condition for offering hold that advanced “neural archeology” contemporary technologies cannot treat. In a bio-preservation method to the terminally might be able to infer the original state this sense, the acceptance of uncertainty in ill could backfire. Actually, we don’t know from a brain with severe damage.13 What conjunction with reasonable expectations if the connectome is either necessary or makes Alcor’s perspective unique is that we about future technological development is sufficient. As long as it, and whatever else share both the belief that our procedures an intrinsic element of cryonics. that is essential, if anything, can be inferred should be subjected to the most rigorous The reason why we highlight this fallacy is from the preserved brain (and the rest of testing possible with the goal of perfecting

22 Cryonics / January 2013 www.alcor.org preservation technologies but that we also recognize that our understanding of the limits of “inferability” will remain Resin Embedding of Mouse Brains incomplete as long as our scanning, computational, and repair technologies In 2012 a group from the Max-Planck Institute for Medical Research in Germany evolve. There is no question that providing published a method for resin embedding an entire intact mouse brain suitable the best technologies that we can offers the for electron microscopy*. This group is also one of the announced competitors best prospects of resuscitating our patients for the Brain Preservation Technology Prize. Their recently-published method in the future but this argument cannot be may qualify for the Stage 1 (small brain) portion of the Prize. used to categorically claim which patients are beyond repair and which are not.14 In They achieved a technical tour-de-force because a mouse brain is much larger our opinion, the perspective that informs than the tiny milligram size previously required for tissue pieces to be prepared many advocates of chemopreservation sets for electron microscopy. However their basic approach is still the same as the bar too low and too high. traditional methods for preparing small tissue pieces. First, proteins are chemically fixed by perfusing an aldehyde solution through the whole animal. Are there advantages to chemical Second, the brain is removed and then soaked in solutions containing osmium brain preservation? tetroxide to fix and stain membranes. Third, the brain is soaked in organic One of the envisioned advantages of solvents to replace water. Finally the brain is soaked in solutions of resin chemopreservation over cryopreservation monomer molecules that eventually polymerize, turning the tissue completely is that plastinated brains do not solid. require continued maintenance or even organizational continuity. This may be true Except for the first protein fixation step, this approach relies completely on but there are a number of qualifications passive diffusion (soaking) rather than perfusion. According to the paper, to that need to be discussed. As discussed resin embed a mouse brain, the time required for the soaking steps is: above, this advantage only applies to brains that were preserved under ideal conditions. 5 x 8 hours (buffer rinses) In non-ideal conditions, the brain will most 3 x 48 hours (wbPATCO osmium stain) likely experience regional or global autolysis 4 x 12 hours (acetone dehydration) over time. Strictly speaking, we do not even 3 x 12 hours (resin monomer infiltration) know anything about the fate of well------preserved brains after very long periods of 268 hours total time and it might still be the case that even these brains benefit from storage at low Calculation of the time that theoretically would be required to perform these (non-freezing) temperatures. steps on a human brain is sobering. A human brain is 1500 grams / 0.5 grams While it is technically feasible that = 3000 times more massive than a mouse brain. Taking the cube root of such brains do not need a permanent 3000, that translates to 14 times greater diameter than a mouse brain. Using storage facility like cryonics patients, it the rule that diffusion time scales quadratically with distance, the extrapolated is hard to imagine chemopreservation preparation time for a human brain would be being offered without the existence of an organization that is committed to the fate 14 * 14 * 268 hours = 52,528 hours of such patients and maintains sufficient funding for future resuscitation attempts. which is six years. In practice, the process would likely stop early in the resin It cannot be denied that cryopreservation soaking phase as monomers polymerized in the outer layers of the brain, patients require ongoing replenishment increasing viscosity and preventing deeper infiltration. of liquid nitrogen to keep them at low temperatures but this does not mean Development of fundamentally new technology – technology using perfusion that cryonics patients would be adversely for all phases – is required before resin embedding can be seriously considered affected by short interruptions of liquid for biostasis of large mammalian brains. nitrogen deliveries. Calculations at Alcor predict that it will take at least three months *S. Mikula, J. Binding, W. Denk, Staining and embedding the whole mouse of non-delivery of liquid nitrogen before brain for electron microscopy, Nature Methods, published online 21 October the brains of patients would start dangerous 2012; doi:10.1038/nmeth.2213 warming. If such a scenario is due to supplier unavailability (such as a refusal to

www.alcor.org Cryonics / January 2013 23 deliver to Alcor) Alcor could purchase and preservation that identified mechanical than chemical brain preservation, we transport liquid nitrogen from elsewhere, or biological cell repair technologies strongly support any technologies that start producing liquid nitrogen itself, or as the means of resuscitation. What is draw attention to the inadequacies of (temporarily) switch to other means of unfortunate about the almost exclusive contemporary practices surrounding death. maintaining cryogenic temperatures. focus on mind uploading is that it not Throughout history the medical definition In case cryonics patients cannot be only requires potential supporters to take of death has been subject to continuous maintained in dewars at all, emergency seriously the idea of chemical preservation revision as medical and resuscitation chemopreservation will be an option. of the brain but also commit to the idea of technologies have advanced.16 There This can be achieved by either perfusing substrate independent minds. can be no doubt that many people who the formerly cryopreserved patients or It is no surprise that the defense of mind are written off by today’s medicine will by slicing the brains and using passive uploading depends on mainly philosophical simply be considered critically ill in the diffusion to chemically fix them. arguments because at this point these are the future.17 Both cryonics and chemical brain The most negative scenario would only possible arguments to defend it. While preservation constitute a means to stabilize be a prohibition of cryonics and forced the arguments in favor of mind uploading patients to reach that future. In the coming burial of patients. While not impossible, deserve critical scrutiny, we think that years we may see additional proposals to it is doubtful that in such an environment ultimately the feasibility of this approach is stabilize critically ill patients such as “room chemically fixed brains will be permitted an empirical matter and cannot be settled temperature vitrification” or biostasis to exist. Both cryopreservation and by thought experiments or analogies.15 For induced by advanced nanotechnology. chemopreservation would have to continue example, both proponents and skeptics of Clearly, the idea that death should be defined as underground operations. mind uploading accuse each other of not relative to today’s medical capabilities is no being consistent “materialists.” longer adequate and needs to be replaced “Even the most “toxic” solution used in cryonics (the vitrification agent) is less dangerous than the least toxic solution (formaldehyde and/or glutaraldehyde) envisioned for chemopreservation.”

Chemopreservation and mind In fact, by subjecting the preservation by a concept of death that recognizes uploading method to empirical scrutiny but using that clinical death can only be considered One of the lessons that we have learned philosophical arguments to corroborate irreversible if identity-critical information in cryonics is that it is not helpful to make the resuscitation method, we think that the has been erased beyond recognition.18  the idea more controversial than necessary. Brain Preservation Foundation conveys Cryonics (or chemical brain preservation) a mixed perspective about validation This article greatly benefited from is already controversial enough on its own of personal survival technologies. The the encouragement and contributions and we do not see the benefit of associating kinds of cell repair technologies that are of Max More and Brian Wowk. I it with ideas such as immortalism, envisioned for the resuscitation of cryonics also want to thank the Alcor R&D transhumanism, mind uploading, or any patients are highly advanced, but do not Committee for carefully reviewing political ideologies. This is not just a require a shift in thinking about human earlier versions of this article. strategic or public relations consideration biology and identity. Mind uploading, on 1. Sebastian Seung, Connectome: How but reflects our view of offering cryonics the other hand, is neither conceptually the Brain’s Wiring Makes Us Who We as a form of experimental critical care necessary for resuscitation of chemically Are, Houghton Mifflin Harcourt medicine. preserved brains nor does it constitute an Trade, 2012. See also Aschwin de In many ways the promotion of chemical appealing idea to gain more support for Wolf’s review in Cryonics magazine, brain preservation has been characterized by chemopreservation. September-October, 2012. many of the PR mistakes that characterized the beginning of cryonics. In particular, we Toward a new definition of death 2. “Alcor Donation to Brain are concerned that, instead of remaining In this article we have critically investigated Preservation Technology Prize agnostic about resuscitation methods the claims in favor of chemopreservation, Declined”: http://www.alcor.org/ including mind uploading, chemical brain and its (envisioned) advantages over blog/?p=2629 preservation is now closely associated with cryopreservation. While, everything this one method. carefully considered, we believe that 3. See “Alcor Administrative Report,” There is something decidedly ad hoc cryopreservation is more suitable for January 25, 2008: http://www. about this association. One could just as robust scientific validation and presents a alcor.org/blog/?p=163 well imagine a campaign for chemical brain more versatile, practical, and safe option

24 Cryonics / January 2013 www.alcor.org 4. Michael Perry, “The Road Less ischemia, II: the no-reflow 15. “Can You Build a Locomotive Out Traveled: Alternatives to Cryonics,” phenomenon,” Am J Pathol. 1968; of Helium? Robert Ettinger on Cryonics magazine, 3rd Quarter, 52: 437–447. Substrate-Independent Minds,” 2007, Volume 28:3 Cryonics magazine, 4th Quarter, 10. Robert W. Prehoda , Suspended 2011 and Patrick D. Hopkins, 5. Aschwin de Wolf, animation: the research possibility that “Why Uploading Will Not “Chemopreservation: The Good, may allow man to conquer the limiting Work, or, the Ghosts Haunting the Bad and the Ugly,” Cryonics chains of time, Chilton Book Co., Transhumanism,” International magazine, 4th Quarter, 2009. 1969. Journal of Machine Consciousness, Vol. 4, No. 1 (2012). 6. Aschwin de Wolf, “Securing 11. “Interview with Robert W. Viability of the Brain in Cryonics,” Prehoda,” first published in 16. Steven B. Harris, “The Society Cryonics magazine, 2nd Quarter, Cryonics Reports, Vol. 4, No. 1, for the Recovery of Persons 2007. January, 1969. Online: http:// Apparently Dead,” Cryonics www.evidencebasedcryonics. magazine, September, 1990. 7. Michael G. Darwin, “Ray Kurzweil org/interview-with-robert-w- on Memory and Cryonics,” Cryonics prehoda-1969/ 17. Max More, “The Terminus magazine, November-December, of the Self,” chapter 2 of The 2012. 12. Aschwin de Wolf, “Preserving Diachronic Self: Identity, Continuity, and Inferring,” Cryonics magazine, Transformation, doctoral dissertation 8. Michael G. Darwin, “Postmortem September-October, 2012. 1995, http://www.maxmore.com/ Results: Some Perspectives,” chapter2.htm. Cryonics magazine, September, 13. Thomas Donaldson, “Neural 1984. Archeology,” Cryonics magazine, 18. Ralph C. Merkle, “The Technical February, 1987. Feasibility of Cryonics,” Medical 9. See Majno G, Ames AIII, Chiang Hypotheses 39(1992):6-16. J, et al. “No reflow after cerebral 14. Brian Wowk, “Ethics of Non-Ideal ischaemia,” Lancet. 1967; 2: Cryopreservation Cases,” Cryonics 569–570 and Ames III A, Wright magazine, Fall, 2006. RL, Kowada M, et al. “Cerebral

Retraction

The original paper version of this article included the results of an experimental model to understand the effects of ischemia on perfusion fixation of the rat brain. Subsequent comments and questions prompted me to omit them from the current (online) version because these results raise complex methodological issues about modelling perfusion fixation of the ischemic human brain in a rat model and I believe that those cannot be done justice without changing the nature of the article. The author wishes to convey that these results are part of an ongoing research project and using them as an illustration of the potential consequences of conducting perfusion fixation in the ischemic human brain would be premature. Excluding these preliminary results does not affect the general arguments made in this article and restores its intended aim as an opinion piece. Omitting them should not be interpreted as an endorsement of the idea of perfusion fixation of ischemic human brains as a life extension strategy.

www.alcor.org Cryonics / January 2013 25 IN PERPETUITY

Who Speaks for the dead? By Keegan Macintosh

o the dead have rights, in the proper your estate as a medium. And, as such, it do (or rather, pay) if they do not perform sense of the word? That is to say, really isn’t about you anymore — it’s about their primary obligations. These secondary Dwhen someone is obligated to do your stuff, and who gets it. Yes, you can (and obligations are the damages, and they something with a dead person, like bury should, and hopefully do) have a will that are a part of the contract from the very them, for whose benefit are they doing it? references your cryonics arrangements, but beginning without anything being written For the dead? Or for the living? practically speaking, the interest that your about them. You might well ask, is this really estate has in that contract you made for So, the potential pecuniary ($) interest important? In short, yes. The person to things to be done for you after you died, is your estate has in the cryopreservation whom the obligation is owed is the person the fact that something about that contract agreement, since your estate is just a who may sue for enforcement of that could result in more stuff for the estate’s medium that can only really have an interest right, and their identity may also determine beneficiaries. That’s really all the estate can in things and stuff, is in the failure of your the remedies which are available to them (be care about, because the real, live person CSP to do what it promised to do for you. it money, compulsory performance of or who was capable of having immaterial (or And unfortunately for you, in cryonics abstinence from a particular act). So, the better still, “non-pecuniary”) interests in there are no do-overs. question of whose rights are engaged in the contract is now gone. Hence why it is important to know who dealing with the dead is fundamentally But wait? How can the cryopreservation speaks for you when you are dead. The important from the cryonics patient agreement (cat’s out of the bag — that beneficiaries of your will, however friendly advocate’s perspective. contract was about cryonics after all) result to your arrangements and well-intentioned An illustration: If you make a contract in more stuff for the estate? Your cryonics they are, have no vested, personal, legal with someone, both of you intending that service provider (CSP) didn’t promise to interest in the CSP’s performance of its a substantial portion of what you have give anything, or pay anything. You, the primary obligations to you under the promised to do will only be done after patient promised to give something, and cryopreservation agreement. The executor (and in fact as a result of) your legal death, in fact cleverly entered into other contracts of your will, on the other hand, has certain and vice versa that a substantial portion of with other people to automatically transfer obligations to carry out promises made by what they have promised to do will likewise money to your CSP upon your legal you when you were alive, and (sometimes) only be done after your legal death: who death. So how could the cryopreservation to ensure that your body is dealt with as you has promised what to whom? agreement possibly represent a source of directed by will or other instrument. The While you remain alive, the answer seems “stuff ” for the estate? Well, that’s because executor may even have an obligation to quite obvious. But once you are dead, you there were really two layers of promises — ensure that you remain interred as directed. are no longer a person. You, sadly, are not two sets of obligations in every contract. The But how long must they keep vigil? When an entity recognized by law. You are your top layer, or primary obligations, are what they, too, are dead, does their executor now estate. Your estate has legal personality of you actually bargained for. The secondary watch over the both of you? At a certain a kind, but it is probably better to think of obligations are what the other party must point (if not right away) this clearly becomes

26 Cryonics / January 2013 www.alcor.org impossibly impractical. Alternately, if your does not comply with the formalities of throughout the world. Cryonics has fairly CSP’s custody of your body was effected execution applying in California, is the will deep roots in America, but are we certain by a consent to body donation for research valid — and if so, is it valid for all purposes, there is no better soil on Earth in which it (which is the more robustly enforceable or only some? This is the domain of private might flourish? method, generally), even your executor international law, aka “conflict of laws,” All of the above areas of law overlap has essentially no standing with respect which refers to how one legal jurisdiction and interact, and there are other relevant to your body. And this is good, because deals with foreign legal elements: foreign ones that I have not mentioned (insurance above all else we trust that our CSPs want parties, parties asking for application of law, notably), and no doubt a few I am not the same thing we want — and I have foreign law, or foreign judgments. This is yet even aware of. I also plan to report on no reason to believe that is anything but a particularly complicated area, but one live cases of interest, as they arise. true. But what if, someday down the road which cannot be ignored, since so many One last, but significant point: due to when your executor and next-of-kin are cryonicists do not live in the same legal variations between the laws of different now in the dewar next to you, your CSP’s jurisdiction as their cryonics organization. jurisdictions (even within a single nation) performance dips demonstrably below the Another theme I will be exploring in you cannot simply assume that paperwork threshold of “good faith best efforts”? Is this column is access to cryonics and other designed to work in one jurisdiction will there anyone who can claim authority to forms of life extension. In the case of work as intended in yours. You need to move you or to enforce performance of cryonics, impediments to access can take find a cryonics-friendly advisor where you your CSP’s primary obligations under the the very blatant form of a law directly live and have them review your cryonics cryopreservation agreement? prohibiting it, or essential procedures arrangements, and revise them if necessary The above is not an exhaustive analysis thereof, or else operate indirectly, like to work in your home jurisdiction. You are by any measure. I write it hoping only that mandatory autopsy provisions. Access to fighting for your life — you cannot afford it will illustrate how peculiarly vulnerable cryonics is also context-specific — taking to wear ill-fitting armor.  cryonics patients are under the laws on a very different meaning for someone currently applying to them. What I plan to diagnosed with a brain-threatening disorder, do with this column is explore intersections for instance. As such, the availability of Keegan Macintosh is an articled of law and cryonics & life extension (and legal assistance in dying is a topic which student with David Borins Law there are many), and one theme I expect might be dealt with under this heading, and Corporation in Vancouver, British to visit frequently is cryonics patient whether the practical benefits accruing to Columbia, where he is working advocacy. This is the issue of “who speaks those patients outweighs the risks, both to address issues of access to life for the dead” adverted to above, though in individually and to cryonics generally. How extension technologies. truth it starts long before legal death, and is the law defines death, and public policy [email protected] more about how the dead or incapacitated debates over whether to move to new can speak for themselves through legally definitions for reasons quite separate from recognized documentary evidence of their cryonics, also fall neatly here. intentions: wills, trusts, powers of attorney Access to life extension, more generally, (financial and health care), advance is also interesting to examine from a legal directives, consents to body donation, perspective. Are the current models of etc. However, all of these need agents to regulation applying to drug development carry them out, and others still may seek sufficiently flexible to accommodate to tear them down, so the more complex the advent of SENS-type rejuvenation questions deal with how to build checks and therapies? One could say that cryonics balances into your supplementary cryonics aspires to being ordinary health care documents and otherwise incentivize someday, at which time we can expect compliance of possible threats. that it will be subject to some form of One specific topic I plan to look at regulation. What should it look like? And soon: Just how uniform is the Uniform how can cryonics organizations today best Anatomical Gift Act in its implementation self-monitor and self-regulate to ease that by the various States? Are body donation eventual transition? consent forms executed under the authority Finally, constitutional rights instruments of the UAGA enforceable outside America? have immense potential as tools for Another, somewhat related question: If securing meaningful access to cryonics and a cryonicist executes a valid will in Oregon, other forms of life extension. However, moves to California, and dies there without the content and implementation of these executing a new will, but the original will fundamental rights documents vary

www.alcor.org Cryonics / January 2013 27 Discuss Alcor and cryonics topics with other members and Alcor officials.

• The Alcor Foundation • Financial • Cell Repair Technologies • Rejuvenation • Cryobiology • Stabilization • Events and Meetings

Other features include pseudonyms (pending verification of membership status) and a private forum.

http://www.alcor.org/forums/

Membership Statistics

As of October 31, 2012, Alcor had 982 cryopreservation members, 24 associate members, and 112 patients.

28 Cryonics / January 2013 www.alcor.org

MEETINGS

About the Alcor Foundation For information about upcoming The Alcor Life Extension Foundation is a nonprofit tax-exempt scientific and meetings and events go to: http:// educational organization dedicated to advancing the science of cryopreservation www.cryonicsnw.org/ and http://www. and promoting cryonics as a rational option. Being an Alcor member means facebook.com/cryonics.northwest knowing that—should the worst happen—Alcor’s Emergency Response Team is A Yahoo mailing list is also maintained ready to respond for you, 24 hours a day, 365 days a year. for cryonicists in the Pacific Northwest at http://tech.groups.yahoo.com/group/ Alcor’s Emergency Response capability includes specially trained technicians and CryonicsNW/. customized equipment in Arizona, northern California, southern California, and south Florida, as well as many additional certified technicians on-call around the British Columbia (Canada): United States. Alcor’s Arizona facility includes a full-time staff, and the Patient The contact person for meetings in Care Bay is personally monitored 24 hours a day. the Vancouver area is Keegan Macintosh: [email protected] ARIZONA Although monthly meetings are not held Flagstaff: regularly, you can meet Los Angeles Alcor Oregon: Arizona without the inferno. Cryonics members by contacting Peter. The contact person for meetings in the group in beautiful, high-altitude Flagstaff. Portland area is Chana de Wolf: chana. Two-hour drive to Alcor. Contact eric@ San Francisco Bay: [email protected] flagstaffcryo.com for more information. Alcor Northern California Meetings are held quarterly in January, April, July, and ALCOR PORTUGAL Scottsdale: October. A CryoFeast is held once a year. Alcor Portugal is working to have good This group meets the third Friday of For information on Northern California stabilization and transport capabilities. The each month and gatherings are hosted at meetings,call Mark Galeck at (408) 245- group meets every Saturday for two hours. a home near Alcor. To RSVP, visit http:// 4928 or email [email protected]. For information about meetings, contact cryonics.meetup.com/45/. Nuno Martins at n-martins@n-martins. FLORIDA com. The Alcor Portugal website is: www. At Alcor: Central Florida Life Extension group alcorportugal.com. Alcor Board of Directors Meetings and meets once a month in the Tampa Bay Facility Tours – Alcor business meetings area (Tampa and St. Petersburg) for TEXAS are generally held on the first Saturday of discussion and socializing. The group Dallas: every month starting at 11:00 AM MST. has been active since 2007. Email North Texas Cryonauts, please sign up Guests are welcome. Facility tours are held [email protected] for more for our announcements list for meetings every Tuesday and Friday at 2:00 PM. For information. (http://groups.yahoo.com/group/ more information or to schedule a tour, call cryonauts-announce) or contact David D’Bora Tarrant at (877) 462-5267 x101 or NEW ENGLAND Wallace Croft at (214) 636-3790 for details email [email protected]. Cambridge: of upcoming meetings. The Alcor Volunteer Network, The New England regional group Scottsdale Chapter has a variety of strives to meet monthly in Cambridge, Austin/Central Texas: meetings on topics including: member MA – for information or to be added to We meet at least quarterly for training, education, training, community outreach, the Alcor NE mailing list,please contact transport kit updates,and discussion. For and fundraising. To RSVP, visit: http:// Bret Kulakovich at 617-824-8982, information: Steve Jackson, 512-447-7866, www.meetup.com/AVNScottsdale/ [email protected], or on [email protected]. members/ FACEBOOK via the Cryonics Special Interest Group. UNITED KINGDOM CALIFORNIA There is an Alcor chapter in England. Los Angeles: PACIFIC NORTHWEST For information about meetings, contact Alcor Southern California Meetings—For Cryonics Northwest holds regular Alan Sinclair at [email protected]. information,call Peter Voss at (310) 822- meetings for members of all cryonics See the web site at www.alcor-uk.org. 4533 or e-mail him at [email protected]. organizations living in the Pacific Northwest.

If you are interested in hosting regular meetings in your area, contact Alcor at 877-462-5267, ext. 113. Meetings are a great way to learn about cryonics, meet others with similar interests, and introduce your friends and family to Alcor members!

30 Cryonics / January 2013 www.alcor.org What is Cryonics?

ryonics is an attempt to preserve and protect human life, not reverse death. It is the practice of using extreme cold to attempt to preserve the life of a person who can no longer be Csupported by today’s medicine. Will future medicine, including mature nanotechnology, have the ability to heal at the cellular and molecular levels? Can cryonics successfully carry the cryopreserved person forward through time, for however many decades or centuries might be necessary, until the cryopreservation process can be reversed and the person restored to full health? While cryonics may sound like science fiction, there is a basis for it in real science. The complete scientific story of cryonics is seldom told in media reports, leaving cryonics widely misunderstood. We invite you to reach your own conclusions.

How do I find out more?

he Alcor Life Extension Foundation is the world leader in cryonics research and technology. Alcor is a non-profit organization located in Scottsdale, Arizona,founded in 1972. Our website Tis one of the best sources of detailed introductory information about Alcor and cryopreservation ( www.alcor.org). We also invite you to request our FREE information package on the “Free Information” section of our website. It includes:

A fully illustrated color brochure

• A sample of our magazine

• An application for membership and brochure explaining how to join

• And more!

Your free package should arrive in 1-2 weeks. (The complete package will be sent free in the U.S., Canada, and the United Kingdom.)

How do I enroll? Signing up for a cryopreservation is easy! Step 1: Fill out an application and submit it with your $150 application fee. Step 2: You will then be sent a set of contracts to review and sign. Step 3: Fund your cryopreservation. While most people use life insurance to fund their cryopreservation, other forms of prepayment are also accepted. Alcor’s Membership Coordinator can provide you with a list of insurance agents familiar with satisfying Alcor’s current funding requirements. Finally: After enrolling, you will wear emergency alert tags or carry a special card in your wallet. This is your confirmation that Alcor will respond immediately to an emergency call on your behalf.

Call toll-free today to start your application:

877-462-5267 ext. 132 [email protected] www.alcor.org Your best chance at achieving future immortality is to protect exceed your membership dues. You’ll receive a directory listing your precious health now so you can benefit from future medical the latest vitamins and supplements, backed by scientific breakthroughs. Staying informed about the latest health discoveries research and available through a unique buyers club. can mean the difference between life and premature death. FREE BONUS! And the Life Extension Foundation can be your passport to the future. As the largest anti-aging organization in the world, • Disease Prevention and Treatment book ($49.95 we are dedicated to finding scientific ways to prevent disease, cover price)...this hardbound fourth edition provides novel slow aging, and eventually stop death. information on complementary therapies for 133 diseases For more than three decades, Life Extension has been at the and illnesses—from Alzheimer’s disease to cancer, from forefront of the movement to support revolutionary anti-aging arthritis to heart disease—that is based on thousands of research that is taking us closer to our goal of extending the healthy scientific studies. human life span indefinitely. We inform our members about path- Life Extension Foundation funds advanced vitrification and breaking therapies to help keep them healthy and alive. gene-chip research. Your $75 membership fee helps support scientific projects that could literally save your life. Join today and you’ll receive these life-prolonging benefits:

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