3rd quarter 2011 • Volume 32:3

Systems for Intermediate Temperature Storage Page 7

Readiness Update Page 15

A New Choice for Immortalists Page 17

ISSN 1054-4305

$9.95 Improve Your Odds of a Good Cryopreservation

You have your cryonics funding and contracts in place but have you considered other steps you can take to prevent problems down the road?

__ Keep Alcor up-to-date about personal and medical changes. __ Update your Alcor paperwork to reflect your current wishes. __ Execute a cryonics-friendly Living Will and Durable Power of Attorney for Health Care. __ Wear your bracelet and talk to your friends and family about your desire to be cryopreserved. __ Ask your relatives to sign Affidavits stating that they will not interfere with your cryopreservation. __ Attend local cryonics meetings or start a local group yourself.

__ Contribute to Alcor’s operations and research.

Contact Alcor (1-877-462-5267) and let us know how we can assist you.

Take a look at the Your source for news about: ALCOR BLOG • Cryonics technology • Cryopreservation cases • Television programs about cryonics http://www.alcor.org/blog/ • Speaking events and meetings • Employment opportunities

Alcor Life Connect with Alcor members and supporters on our official Facebook page: Extension http://www.facebook.com/alcor.life.extension.foundation Foundation Become a fan and encourage interested is on friends, family members, and colleagues to support us too. 2nd quarter 2008 • Volume 29:2

2nd quarter 2008 • Volume 29:2

32:3 • Volume 2011 3rd quarter

32:3 CONTENTS • Volume 2011 3rd quarter

Systems for COVER STORY: PAGE 7 CONTENTS Intermediate 5 CEO Update Temperature StoragePage 7 Why does fracturing occur in Thanks to wearing his cryonicsCOVER patients? STORY: Which PAGE repair 7 seatbelt, Alcor CEO Page 15 technologies are envisioned? 5 Max CEO More Update is still with us Readiness Update WhyWhat does are the fracturing prospects occur for in and Thanks reports to onwearing the latest his A NewImmortalists Choice forPage 17 cryonicseliminating patients? fracturing? Which In repair developmentsseatbelt, Alcor atCEO Alcor. technologiesthis comprehensive are envisioned? review, Max More is still with us Whatcryobiologist are the Brianprospects Wowk for reviews 13 and Membership reports on the latest eliminatingthe topic and fracturing? provides Inan update developments at Alcor. thison Alcor’s comprehensive efforts to review,develop Statistics and validate Intermediate The latest statistics on cryobiologist Brian Wowk reviews 13 Membership theTemperature topic and Storageprovides (ITS). an update Alcor membership on Alcor’s efforts to develop growth.Statistics and validate Intermediate The latest statistics on Cover Photo: Intermediate Temperature StorageTemperature Storage (ITS). Alcor membership (ITS) Neurodewar for safe storage at temperatures 14 Chronology of warmer than liquid nitrogen to reduce fracturing. growth.Developments Cover Photo: Intermediate Temperature Storage Related to Fracturing 14 Chronology of (ITS) Neurodewar for safe storage at temperatures and Intermediate warmer than liquid nitrogen to reduce fracturing. Developments 17 A New Choice for Immortalists Temperature Storage Related to Fracturing Biogerontologist Michael Rose, Ph.D. contrasts his evolutionary and Intermediate perspective of the aging process with alternative approaches and 15 Readiness Update 17 introduces A New Choice the topic for of Immortalists his new co-authored book Does Aging Temperature Storage Aaron Drake reports Stop?Biogerontologist He also suggests Michael practical Rose, Ph.D.lifestyle contrasts guidelines his evolutionaryto remain on on Alcor’s new portable anperspective aging-arrested of the plateau aging process indefinitely with alternativebefore old approachesage sets in. and 15 Readiness Update introduces the topic of his new co-authored book Does Aging ice water recirculation Aaron Drake reports Stop? He also suggests practical lifestyle guidelines to remain on system to conduct rapid 19 on Alcor’s new portable an aging-arrested plateau indefinitely before old age sets in. hypothermia in the field Alcor member Cairn Idun contributes a member profile of Alcor andice water the recent recirculation Pacific advisor, Cryonics editor and researcher Aschwin de Wolf. From Northwestsystem to conduct training. rapid 19 his early youth to his current views on cryonics – Cairn covers it hypothermia in the field all. Alcor member Cairn Idun contributes a member profile of Alcor and the recent Pacific advisor, Cryonics editor and researcher Aschwin de Wolf. From Northwest training. his early youth to his current views on cryonics – Cairn covers it www.alcor.orgall. Cryonics/Third Quarter 2011 3

www.alcor.org Cryonics/Third Quarter 2011 3 FROM THE EDITOR

3rd quarter 2011 • Volume 32:3

Editorial Board dmittedly, there are times when it is a challenge to gather enough original and excit- Saul Kent ing materials for the next issue of Cryonics. When I considered devoting this issue Ralph Merkle, Ph.D. of the magazine to research and development in cryonics I was not sure whether Brian Wowk, Ph.D. A there was enough going on to fill the pages of the magazine. As it turned out, the materials that I received not only vastly exceeded the usual number of pages allotted to the magazine, Editor but I had to stop soliciting for this issue. It also became clear that if I reported on the neural Aschwin de Wolf cryobiology research that Chana de Wolf and I conduct at Advanced Neural Biosciences the situation would become really unmanageable! As a result, this report will be published in Art Director another issue of the magazine or as a web exclusive. Jill Grasse Despite limiting the number of articles, we are still forced to publish some other mate- rial—research updates—as a web exclusive rather than in the magazine. In 2008, Alcor Staff Contributing Writers member Michael Perry received a grant to research low cost alternatives to cryonics, then Aaron Drake solicited experiments to develop an algorithm to estimate the degree of ischemic damage in Michael Rose, Ph.D. electron micrographs of rodent brain samples. His first official report can be consulted here Aschwin de Wolf (www.alcor.org/Library/pdfs/Algorithmic_Estimation_of_Cortical_Autolysis.pdf). Mike Brian Wowk, Ph.D also collaborated on a series of experiments to study the effects of chemical fixation on the ______ischemic brain. A report of this work will be published in the future as a broader update about Copyright 2011 low cost alternatives to cryonics. by Alcor Life Extension Foundation I am thrilled that our cover article for this issue is an update on Intermediate Tem- All rights reserved. perature Storage (ITS). Since learning that most patients will experience fracturing during Reproduction, in whole or part, their descent to liquid nitrogen temperature, Alcor has made efforts to document, investigate without permission is prohibited. and resolve this issue to offer improved human cryopreservation technologies. Since Alcor published the last update on ITS there have been some new developments, including the Cryonics Magazine is published quarterly. acquisition of our first custom-designed ITS unit for neuro patients. As the article shows, our knowledge about ITS and fracturing events remains incomplete but we hope this article To subscribe to the paper edition: will spark interest to resume R&D in this area and trigger debate as to whether and how ITS call 480.905.1906 x101or visit the should be made available to Alcor members. magazine website: Stopping or reversing the aging process will be an intrinsic component of cryonics for http://www.alcor.org/magazine/ most members. This issue of Cryonics features an article by bio-gerontologist Michael Rose, ______Ph.D. in which he presents a novel theory about the aging process and why he believes it can Address correspondence to: be halted mid-age by adopting a lifestyle comparable to those of our hunter-gathering ances- Cryonics Magazine tors, a topic that is explored in more detail in his new co-authored book, Does Aging Stop? 7895 East Acoma Drive, Suite 110 Just before the first draft of this issue of the magazine was completed, the “father” of Scottsdale, Arizona 85260 cryonics, Robert Ettinger was cryopreserved at the Cryonics Institute. Look forward to a lot Phone: 480.905.1906 more about Robert Ettinger in the next issue of Cryonics. Toll free: 877.462.5267 Fax: 480.922.9027 Aschwin de Wolf

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4 Cryonics/Third Quarter 2011 www.alcor.org CEO Update

By Max More

Fasten your seatbelt; tighten up your cryonics arrangements

just survived my second car wreck. was in my pocket but I hadn’t been wearing If the person had signed a Declaration of Having returned from giving a cryonics it because the nickel in the chain makes my Intent, it might not have been sufficient to I talk in Southern California, I was driv- skin break out. The bracelet is too loose and enable us to proceed, but it would have made ing home from the Phoenix airport when I annoying. Some of you probably have the it more likely. got into a situation that caused me to swerve same problem. If so, get in touch with Diane Cryopreservations: In late June, it to avoid a collision. At freeway speed, that Cremeens. We’re ordering new bracelets that looked likely that Alcor would have to con- swerve was hard enough to send my car out use a snug and more stylish black band. duct three cryopreservations in one week. I of control. It spun around and ran head first In case you crash and don’t walk away, asked resident math genius Mike Perry to into the high concrete divider wall of the 51 also ensure that your paperwork is current. calculate the odds of this, given our current freeway. I remember thinking, “This is it.” Although Diane has been contacting mem- membership size. Based on numbers of cas- My car was totaled. To my astonish- bers with the oldest paperwork, plenty of es over the past few years, he estimated this ment, I stepped out of the car and found you still should update your forms, or com- should occur once every 27 years per thou- myself almost completely uninjured. plete a fresh set. sand members. (Alcor’s current membership Praise be to seat belts and airbags. My Are there more Relatives’ Affidavits you stands near a thousand.) Two patients sta- old car had no side air bag, so it was fortu- should get signed? Do you have a medical bilized, at least for a while, so we ended up nate that I slammed into the wall head on. power of attorney? Is your funding at the calling off a standby (supported by Sandra The first time I survived the thorough current minimum levels or, preferably, higher? Russell and Joan O’Farrell from Critical Care wrecking of a car was 600 miles south of If you can afford it, have you provided fund- Research) while conducting just one cryo- Tijuana in Baja California during a return trip ing for an air ambulance? preservation. from observing the total solar eclipse of July Updates: My updates appear in three The case that did go ahead in May was 1991. That time, I was asleep in the back of different forms: monthly in brief reports to Alcor member A-1408 (the patient’s wish is a truck when it rolled over and I was thrown the board, monthly in Alcor News, and quar- for anonymity). This was a classic example out, somehow landing almost unhurt. terly in Cryonics magazine. From now on, of how a patient can have unpredictable ups (Having survived twice practically unscathed Alcor News will come out right after a board and downs in condition. A few days earlier, tempts me to believe I’m like Bruce Willis in meeting. My Updates for Cryonics will include the patient was talking, smiling and shaving. Unbreakable. If only.) Mike Perry, who was in some information from those monthly up- On Tuesday May 24th everyone agreed that the passenger seat, was not so lucky. Among dates, but will always include new material. the “patient is doing much better.” Two days other damage, he suffered dangerous head Declaration of Intent: Do you know later, clinical death was declared. We are espe- injuries. Thanks to an air ambulance and someone who seems interested in and fa- cially grateful that Suspended Animation did a San Diego hospital, he made a full re- vorable to cryonics but who hasn’t made the standby, stabilization, and transport on covery. (For more details on this incident, any arrangements yet? If it’s something you this case. This was especially taxing for the SA see: http://www.depressedmetabolism. think they want to do, but they aren’t will- team since the standby began the day imme- com/2008/11/01/interview-with-alcor- ing to put everything in place, you might at diately following their conference in Florida. readiness-coordinator-regina-pancake/) least urge them to execute a Declaration of One of the other three cases, Arizona No doubt everyone reading this uses a Intent. (This is available on the Alcor website member A-2357, held on for a while, but was seat belt and drives in a car with at least a in the “Become a Member” section.) We re- finally cryopreserved on June 17. The heavy front air bag. But what if they aren’t enough? cently had a frustrating case where an Alcor case load in 2010 led to a backlog of case Are all your cryonics arrangements fully in member offered to pay for a friend’s cryo- reports. We’ve accelerated the preparation place and up to date? Do you wear your preservation but it never happened because of these reports, which you can find on the emergency neck tag or wristband? I con- the friend could no longer make decisions website. fess that I was not wearing my neck tag. It and her S.O. and family were not interested. Improvements: We’re making im-

www.alcor.org Cryonics/Third Quarter 2011 5 provements to the building, security, energy opportunity to report on new developments efficiency, and other areas. We’re exploring at Alcor. Other talks by Alcor-related speak- options for further improving patient protec- ers included Brian Wowk on “Reversible tion and overall security. In my last update I Solid State Suspended Animation,” Steve talked about the problems with perfectionist Harris on a “New Portable Liquid Ventilation thinking. It’s just not possible to achieve per- System,” and Ralph Merkle on “Developing fect security. Attempts to do so would drain Technology for the Revival of Cryopreserved all of Alcor’s resources. For obvious reasons, Humans,” as well as panel contributions by I’m not going to detail existing weaknesses, Saul Kent and Michael Korns. Following the and will only report on new security mea- conference, Suspended Animation conduct- sures once they are fully in place. ed tours of their facility. The event enabled Improvements will be made to the roof me to get better acquainted with the princi- insulation and sun shielding to reduce the air pals at SA. conditioning bill inevitable in Arizona’s heat. I also spoke to a receptive audience at Other continuing facility improvements in- the Atlas Society’s Free Minds conference clude the reception area and to the floors in in Anaheim in July. In pursuit of the goal the OR and other areas. There will be a full of presenting the idea of cryopreservation report on these upgrades in a month or two, to new (carefully selected) audiences, I’ll be once complete. speaking at least a couple more times this Infrastructure improvements include year on cryonics and related ideas. Among progress with redesigning and cleaning up these are Aubrey de Grey’s SENS conference the hardware and software of the database in Cambridge. We would be delighted to hear and server, and fixes to the website making it from you if you can help Alcor grow by sug- possible to apply for membership online and gesting companies, forums, conferences, and to directly print the info pack. other arenas where I or other Alcor repre- I’m making it a priority to study critical sentatives could give a presentation. evaluations of Alcor’s practices written over Besides talking at conferences, I aim to the last ten years, with an eye to prioritizing boost Alcor’s relatively slow recent growth the most high-payoff, practical, and affordable rate by other forms of communication. measures. You will find regular updates on im- Later this year, I’ll make use of Web video by provements at Alcor in my Cryonics columns. posting short (no more than 5-minute) vid- Other news: I’ve been giving talks in eos on YouTube and/or Vimeo, answering diverse venues to raise awareness and un- common questions, refuting common objec- derstanding of what we do at Alcor and to tions, and addressing misconceptions. We try to spur membership growth. Alcor was will also look into other forms of targeted represented at the Humanity+ @ Parsons social media. Conference in New York on the weekend I’d like to thank Cryonics Institute of May 14 and 15. More than one speaker President Ben Best for inviting me to attend was an Alcor member, as were several at- and participate in CI’s annual general meet- tendees. Around 200 people showed up. ing in September. Ben and I are on good The conference was co-organized by Alcor terms and agree that “co-opetition” rather member Natasha Vita-More together with than competition makes better sense for Ed Keller of the Parsons School of Design. both our organizations. The idea of cryonics seemed to receive a Finally, I have begun very early plan- mostly friendly reception. Whether or not ning of a proposed 2012 Alcor 40th Year Alcor gets some new members out of the Conference, and will be soliciting input over talk, awareness and appreciation of what we the next few months. n do and why we do it was definitely improved. In Florida the following weekend, Alcor participated in the Suspended Animation conference. This was the first cryonics con- ference in a few years, so I was glad of the

6 Cryonics/Third Quarter 2011 www.alcor.org Systems for Intermediate Temperature Storage for Fracture Reduction and Avoidance

By Brian Wowk, Ph.D.

Introduction liquid nitrogen and the glass transition tem- mal contraction of a cryoprotectant solution Cryopreservation by vitrification par- perature. ITS technologies are more com- cooled in a test tube. Warmer solution in the tially replaces water inside cells and tissue plex and expensive than simple immersion in center of the test tube continues cooling and with chemicals called cryoprotectants that liquid nitrogen. Although ITS technologies contracting after solution near the walls has prevent ice formation. At high enough for cooling and storing tissue in relative safe- solidified, creating a dimple. concentrations, cryoprotectants can prevent ty at adjustable temperatures now exist, the freezing. Instead of freezing, the mixture basic science knowledge of how to control of water and cryoprotectants becomes more temperature to avoid fracturing in tissues as and more viscous like syrup during cooling. large as a whole human body still does not At a temperature near 120°C the viscous exist. Only fracture reduction is presently solution solidifies, an event called the “glass possible. transition.” This solidification without freez- ing is the physical basis of cryopreservation Physical Causes of Fracturing by vitrification. The vibration of molecules gives rise Liquid nitrogen provides an inexpensive, to a characteristic volume, or density, of a stable, and highly reliable storage environ- liquid or solid material at a given tempera- ment for cryopreserved tissue at a tempera- ture. As temperature decreases, the volume ture of -196°C. Unfortunately the process of an object slightly decreases. This is called of cooling to this very cold temperature thermal contraction. Figure 1 shows ther- tends to cause cryopreserved tissues to fracture. Such fractures probably do not compromise the neuroanatomical informa- tion preservation goals of cryonics as long as tissue remains cold and solid. However fractures prevent future recovery of cryopre- served tissue by any simple means. They are also alarming by contemporary biomedical standards. Fig. 2. A two liter volume of solidified Fracturing can be reduced, and some- M22 vitrification solution shown (a) just times avoided, by cooling through the glass below the glass transition temperature and transition temperature slowly and stopping (b) after further cooling. The solidified cooling at temperatures warmer than liquid solution fractured during further cooling nitrogen. Much progress has been made below the glass transition temperature. ______within the past decade at developing systems Fig. 1. Differential thermal contraction of Thermal contraction can cause cryopro- able to safely store tissue at temperatures vitrification solution cooled in a test tube warmer than liquid nitrogen. Such systems causes a dimple to form. The warmer tectant glasses (solidified vitrification solu- have come to be called “intermediate tem- inside of the solution continues contracting tion) to fracture by several different mecha- perature storage” (ITS) systems because they after the colder outside has solidified nisms (1). Figure 2 shows a cryoprotectant store at temperatures intermediate between and begun cooling at a slower rate. solution in a borosilicate glass flask fractur- ______

www.alcor.org Cryonics/Third Quarter 2011 7 ing after vitrification and cooling. This frac- ery, causing mechanical stress, which causes turing occurred because the cryoprotectant fracturing if the mechanical strength of the solution adhered to the glass wall when it solid is exceeded. This phenomenon is illus- solidified. Cryoprotectant glasses have ther- trated schematically in Fig. 3. mal expansion coefficients ten times greater In practice, it’s difficult to cool volumes than the flask container walls. Therefore of more than a few milliliters of vitrification cryoprotectant glasses will shrink ten times solution to the temperature of liquid nitro- as much during cooling as glass containers gen without fracturing. This is because the that hold them. The cryoprotectant glass in thermomechanical properties of cryoprotec- Fig. 2 broke due to accumulated stress as it tant glasses (thermal expansion coefficient tried to retract away from the flask wall dur- 40 x 10-6 per °C, fracture strain 0.3%, frac- Fig. 4. Acoustic events believed to be ing cooling. Vitrified cryoprotectant solu- ture stress 3 MPa (5, 6)) make them much fractures detected in the brain of Alcor tions or tissues are less likely to fracture if weaker than other glasses we are accustomed patient A-2063 during cooling after perfusion held in containers made of hydrophobic ma- to. For example, window glass has a fracture with B2C vitrification solution. Such events terials that solutions don’t adhere to, such as stress of approximately 100 MPa due to its are detected in all patients during cooling between the glass transition temperature polyethylene plastic. strong covalent chemical bonds. (-123°C) and liquid nitrogen (-196°C). Cryoprotectant glasses or vitrified tissue Fibrous material present in a vitrifica- ______can also fracture due to internal stress during tion solution will increase the vitrified solu- temperature change regardless of container tion’s fracture strength, and reduce the likeli- In 1997 Alcor brought into regular use material. If different parts of tissue have dif- hood and extent of fracturing. Tissue itself an acoustic fracture detection system called ferent thermal expansion properties, the dif- is fibrous, so tissues and organs generally do the “crackphone.” The crackphone is a cus- ferent parts will seek to contract by different not fracture as easily or extensively as bare tom designed system that performs digital amounts during cooling, causing stress that cryoprotectant solutions like the solution in data processing of sound signals recorded can result in fractures. Fig. 2(b). However organs are still capable by microphones placed in contact with the Even completely homogeneous tissue of fracturing during cooling. brain during deep cooling of cryonics pa- or pure cryoprotectant solutions can frac- tients. It detects and records acoustic events ture during cooling. If different parts of a Prevelance of Fracturing in Cryonics believed to correlate with fracturing. material cool at different rates, the rates of In late 1983 Alcor performed post- Acoustic events consistent with fractur- thermal volume contraction will be differ- mortem examinations of three whole body ing were found to be universal during cool- ent. For example, near the end of cooling, cryonics patients who had been transferred ing through the cryogenic temperature range. the outside of an object may only contract from another cryonics facility for conversion They occurred whether patients were frozen at 0.1% per minute as its temperature nears to neuropreservation and continued storage or vitrified. If cryoprotection is good, they that of the surroundings. However the in- at Alcor. In every patient, several full thick- typically begin below the glass transition side of the object may be trying to contract ness fractures of the skin were observed as temperature (–123°C for M22 vitrification at 0.2% per minute because it is warmer and well as multiple fractures of most internal solution). If cryoprotective perfusion does still cooling faster. The core of the object organs. The spinal cord of one patient was not go well, then fracturing events begin therefore tends to pull away from the periph- cleanly fractured every 6 cm over a 20 cm at temperatures as warm as -90°C. Higher length examined. These patients were fro- fracturing temperatures are believed to occur zen with low concentrations of cryoprotec- when tissue freezes instead of vitrifies be- tant rather than vitrified, so fracturing is a cause freezing increases the glass transition phenomenon that can occur in either frozen temperature of solution between ice crystals. or vitrified tissue during cooling to liquid ni- The temperature at which fractures begin is trogen temperature. It is not unique to vit- therefore believed to be a surrogate measure rification. These findings were documented of goodness of cryoprotection, with lower in a report in the September 1984 issue of temperatures being better. Cryonics magazine (7). There was further dis- The crackphone is believed to be highly cussion of these findings on page 28 of the sensitive to fractures, but its specificity is not 1st Quarter 1995 issue of Cryonics (8). clear. Cracking sounds can often be heard In 1994 Alcor performed a postmortem during cooling of vitification solutions or examination of the brain of Alcor patient vitrified tissue with no fractures later being Fig. 3. As cooling slows at the cold exterior A-1242 who had been ordered removed found (unpublished observations of the au- of a vitrified object, the warmer interior from cryopreservation after a court over- thor). So it is not clear whether every acous- will cool faster until a uniform temperature turned the 1990 cryopreservation arrange- tic event detected during cooling is neces- is reached throughout the object. Faster ments made by her husband. It was discov- sarily a fracture. Studies correlating acoustic interior cooling causes faster thermal contraction of the interior, causing the ered that the brain had fractured into five events with physical fracturing have not been interior to pull away from the exterior major pieces. Details were reported on page done. Still, it is believed that the brain and along the dotted line. These forces can 29 of the 1st Quarter 1995 issue of Cryon- other major organs of every cryonics patient cause the vitrified object to fracture. ics (8). cooled to the temperature of liquid nitrogen ______

8 Cryonics/Third Quarter 2011 www.alcor.org to date have some fractures.

Significance of Fracturing Fracturing does not cause tissue to break into widely separated pieces at the time of fracture. As shown in Fig. 5, frac- tures are not macroscopically obvious at cryogenic temperature. The actual physical displacements associated with fracturing are small, and are believed to remain small as long as tissue remains solid. Future re- pair strategies for fracturing are therefore anticipated to begin at low temperature with the tissue still in the solid state (2, 3). Fig. 6. Slow cooling and warming protocol followed for a vitrified rabbit kidney that was successfully stored under liquid nitrogen for two weeks prior to Factures in bare cryoprotectant solu- transplantation without fractures. (Data courtesy 21st Century Medicine, Inc.) tions such as those in Fig. 2 are observed ______to be optically smooth. In other words, the fracture surfaces are smooth on a scale future means exists to match and restore Reduction and Elimination of Fracturing smaller than a wavelength of light, which structure across fracture faces. However To prevent fracturing, stresses such as is less than one millionth of a meter. Al- further study is needed. those shown in Fig. 3 need to be minimized. though the fracture faces of vitrified tissue Unfortunately fracturing excludes This can be achieved by slowing cooling have not been specifically studied, it is as- any future repair strategy that might begin as the glass transition is approached so sumed that they are also relatively smooth. by simple warming and reperfusion. It’s that the temperature is as uniform as pos- When frozen tissue is fractured for mi- therefore a barrier to the development of sible within tissue during descent through croscopy in a procedure called “freeze reversible suspended animation of large or- the glass transition. Holding for a period fracture,” the resulting faces are smooth gans or humans no matter how good cryo- of time near or just below the glass transi- enough for electron micrographic study of protectant technology becomes. Fracturing tion to allow stress relaxation before fur- cell membranes. From an information the- underscores that cryonics as currently prac- ther cooling is especially helpful. Figure oretic standpoint, it seems likely that frac- ticed is an information archiving technol- 6 shows a cooling protocol that permitted turing does not cause loss of neural con- ogy that will require very arcane technol- storage of a rabbit kidney under liquid ni- nectivity information provided that tissue ogy to reverse. It is not anything close to trogen with no evidence of fracturing dur- remains vitrified, and provided that some suspended animation. ing later transplantation (4). Faster cooling has been observed to result in fracturing. Another strategy has allowed even bare vitrification solutions, which are high- ly susceptible to fracturing, to reach liquid nitrogen temperature without fracturing. That strategy is to cool slightly below the glass transition temperature, then rewarm above it, and then finally resume cooling

Fig. 7. Warming above the glass transition temperature after descending slightly below it can reduce temperature gradients Fig. 5. Vitrified brain of Alcor patient A-2077 under liquid nitrogen. This brain is almost and associated stress, allowing 10 mL certainly fractured, yet it remains an integrated whole. Movements between fracture solution volumes to reach liquid nitrogen planes appear to remain microscopic provided that tissue stays cold and solid. temperature without fracturing. ______

www.alcor.org Cryonics/Third Quarter 2011 9 as shown schematically in Fig. 7. This allows interior temperatures to catch up to the cooler exterior temperature so that the whole object passes through the glass transition at a more uniform temperature and cooling rate. This avoids “locking in” stresses that would otherwise result from non-uniform passage through the glass transition. Molten silicate glass (window glass) that is cooled too quickly will also fracture for the same reasons that cryoprotectant glasses do. To prevent this, silicate glasses are held during manufacturing for a period of time near their glass transition tempera- ture to reduce stress. This process is called annealing. After annealing and slow cool- ing to a lower temperature, called the strain temperature, silicate glass can be quickly cooled to room temperature without frac- turing. A similar annealing process allow- ing cooling of large volumes of cryoprotec- tant glasses to liquid nitrogen temperature without fracturing is theoretically possible. Fig. 8. (a) The temperature in the vapor space above liquid nitrogen. (b) Unfortunately, due to the physical weak- More uniform temperature inside an insulated storage container with a ness of cryoprotectant glasses compared thermally-conductive inner liner. (c) Calculated heat flows inside container. (d) Adjustment of container temperature with electrical heat. to silicate glass, very long annealing times ______may be necessary. Whether for long periods of annealing “Vapor phase” storage systems that or permanent storage, systems for storing store at temperatures warmer than liquid cryopreserved tissue at temperatures be- nitrogen in the vapor space above liquid tween the glass transition temperature and nitrogen have long been available. How- liquid nitrogen temperature are necessary ever as shown in Fig. 8(a), they suffer from if fracturing is to be avoided. In cryon- large uncontrolled temperature differences ics, such systems have come to be called in the vapor space. They are used in cryo- Intermediate Temperature Storage (ITS) biology not because of their warmer tem- systems. perature, but because they prevent transfer of pathogens between samples stored under Progress in Development of Intermedi- a common pool of liquid nitrogen. ate Temperature Storage (ITS) Systems Figures 8(b) and 8(c) show that if an For decades mechanical laboratory insulated container with a conductive in- Fig. 9. Prototype neuropod suitable for freezers have been available that are ca- ner liner is placed above liquid nitrogen, maintaining single neuropatients at a pable of maintaining temperatures as the non-uniform temperature outside the stable and adjustable intermediate storage low as -140ºC. They’ve been sold under container becomes converted into a more temperature, (a) showing neurocan inside, (b) with top insulation in place, (c) and (d) inside names such as Queue and CryoStar. In uniform temperature inside the container. a small dewar with 8 liters of liquid nitrogen the year 2000 a 10 cubic foot CryoStar The addition of a small thermostat-con- at the bottom able to maintain -140°C inside freezer was acquired for testing by Alcor trolled electric heater inside the container the neuropod for 90 hours between refills. for possible use storing neuropatients. It as shown in Fig. 8(d) allows the uniform Longer times between refills are possible with included a liquid nitrogen backup system interior temperature to be adjustable. 21st larger dewars. The blue cable connects to able to maintain temperature in the event Century Medicine, Inc., obtained US Pat- a small temperature controller that supplies of a power failure, and was also filled with ent 7,278,278 for this and related types of electrical heat to the inside of the neuropod dry ice as thermal ballast. Alcor used it intermediate temperature storage systems to maintain the desired interior temperature. for two patients between 2002 and 2006 in 2007. The neuropod requires 0.15 watts heating for each °C temperature difference between before advancing to newer liquid nitrogen In 2003, Alcor acquired the prototype the interior and mean exterior temperature. ITS systems. The newer systems had much “neuropod” storage device shown in Fig. 9 ______lower power consumption, no temperature for testing. Using the principles explained cycling, and other advantages described in Fig. 8, the neuropod was designed to uniform, and stable intermediate tempera- below. hold a single neuropatient at an adjustable, ture. The neuropod itself could be placed

10 Cryonics/Third Quarter 2011 www.alcor.org temperature inside the neuropod. The heat automatically adjusts to maintain a stable internal temperature even when the outside temperature fluctuates, such as during dew- ar refilling (temperature drop) or transfer through ambient air between dewars (tem- perature rise). The power requirements of the controller are so low (<10 watts) that they can easily be met by small battery backup systems. The advantages of this type of ITS sys- tem are numerous. ♦♦ No moving parts ♦♦ Low power requirements ♦♦ Individual temperature control ♦♦ Power failure results in cooling rather than warming ♦♦ Temperature stability in presence of external instability or non- uniformity ♦♦ Storage flexibility (containers Fig. 10. Collections of neuropods could be stored in the vapor space of conventional will function in any cryogenic liquid nitrogen dewars. The temperature inside each one could be individually controlled environment that is on average to manage complex cooling plans for annealing protocols lasting years if necessary. ______colder than the target interior temperature) into any uncontrolled cryogenic environ- An electric heater supplied by a tempera- ment, such as the vapor space above liquid ture controller added small amounts of In 2004 Alcor acquired and began test- nitrogen in a conventional storage dewar. heat as necessary to maintain the desired ing another neuropod that was designed to be “patient rated.” It incorporated dual re- dundant temperature controllers and heat- ers, and other safety features. The advantage of individual storage pod temperature control is a disadvantage in terms of complexity and cost. An al- ternative approach is to construct an inter- mediate temperature storage system that maintains a large common volume at the same temperature. In 2003 21st Century Medicine, Inc., developed and constructed an ITS storage dewar for cryobiology ap- plications capable of maintaining adjust- able and uniform storage temperatures in the -120°C to -150°C range using liquid nitrogen. Since then, such dewars have been used at 21st Century Medicine instead of laboratory freezers. Unlike mechanical freezers, ITS dewars have very low power consumption, no heat output, no moving parts, no noise, and limited temperature ex- cursion if they fail. In 2005 Alcor placed an order with 21st Century Medicine for an ITS dewar large Fig. 11. Instead of containers with individual environment control, the ITS Neurodewar system enough to hold 14 neuropatients. After stores 14 smaller uninsulated neurocontainers in a common temperature environment inside tedious development efforts, the ITS Neu- a liquid nitrogen dewar. One large storage chamber with thermally-conductive walls ensures a uniform shared storage temperature. Like the neuropod system, small amounts of electrical heat rodewar shown schematically in Fig. 11 and under active control maintain the desired storage temperature in the shared environment. photographically in Figs. 12 and 13 was de- ______livered to Alcor in 2008. The unit has been

www.alcor.org Cryonics/Third Quarter 2011 11 in uneventful operation and evaluation at Al- cor since then. The specifications are: Storage Volume: 15.5 cubic feet

Temperature 3°C Uniformity (top- to-bottom): Temperature 2°C during 2” Stability (empty liquid nitrogen fill chamber): Fig. 12. (Left) ITS Neurodewar under construction, showing storage chamber Operating Tem- -159°C to -124°C with seven storage compartments. (Right) Neurodewar in operation perature Limits: with main lid open, showing closed storage compartment lids. ______

Lower Failsafe -159°C (0 watts Temperature: heater power)

Upper Failsafe -124°C (48 watts Temperature: heater power)

Maximum Liquid 6.0” or 118 liters Nitrogen Capacity: Liquid Nitrogen 0.6” or 12 liters Consumption at per day -159°C: Liquid Nitrogen 1.0” or 20 liters Consumption at per day Fig. 13. (Left) ITS Neurodewar with dual redundant temperature controllers -145°C: and displays on the right side of the unit. (Right) Neurodewar in operation Liquid Nitrogen 1.2” or 24 liters at Alcor, maintaining an internal temperature of -140°C. The unit Consumption at per day automatically refills itself from the connected liquid nitrogen tank. -140°C: ______Rate of Warming 1°C per hour automatically refill themselves from external applied to the design of whole body ITS liquid nitrogen tanks (or be manually refilled storage systems. Cryogenic engineer Mi- Following LN2 Depletion: if electric power is unavailable), but this is in- chael Iarocci and architect Stephen Valen- trinsically less reliable than having the liquid tine of the Timeship Project have designed nitrogen already in the dewar. several different whole body ITS systems. Comparision of ITS vs. Liquid Nitrogen The ITS Neurodewar of Fig. 13 costs Some systems even consume less liquid ni- Immersion Storage as much as a Bigfoot dewar, but has only trogen per patient than Bigfoot dewars, but The storage method traditionally used one third the neuropatient holding capac- at greater capital cost. in cryonics is immersion in liquid nitrogen ity. When operated at -140°C it consumes at a temperature of -196°C. Storage vessels liquid nitrogen at twice the rate of a Bigfoot Unresolved Issues that hold liquid nitrogen are kept almost full dewar. (Liquid nitrogen consumption can The most important unresolved issue to the top. ITS systems use dewars that are be reduced in future units if the operating of intermediate temperature storage is how only partially filled with liquid nitrogen. For temperature range is made smaller.) Trans- to use it to avoid fracturing. Despite some example, the ITS dewar of Fig. 13 contains fer losses are also expected to be larger due to attempts to avoid fracturing over the last only about 120 liters of liquid nitrogen in a more frequent filling. Therefore the cost of decade, some including months of anneal- pool at the bottom. This is sufficient to last ITS storage is at least three times that of con- ing, acoustic data indicated that fracturing only 5 days when operating at a temperature ventional liquid nitrogen immersion storage. was still occurring during descent to target of -140°C. In contrast, the tall “Bigfoot” intermediate storage temperatures. There- dewars used by Alcor for liquid nitrogen Whole Body ITS Systems fore ITS is presently a means to reduce frac- immersion storage contain more than 1000 The same concepts of individual tem- turing, not avoid fracturing. Perhaps ITS liters of liquid nitrogen that can last weeks perature-controlled storage pods, and com- is best characterized as a necessary tool to between refills without catastrophic warm- mon temperature storage dewars, can be develop future protocols to avoid fracturing. ing. As shown in Fig. 13, ITS dewars can

12 Cryonics/Third Quarter 2011 www.alcor.org However presently it is not even possible to highly concentrated cryoprotectant solutions 4. G. Fahy, “Vitrification as an approach say whether pod-type storage systems per- is still poorly understood (1). to cryopreservation: General mitting individual temperature control are More research is required on fracturing perspectives,” Cryobiology 51 (2005) cost-justified over common temperature en- avoidance for large cryopreserved organs and 348-414. vironments because it is not known how to tissues. Valuable research may continue to 5. J.L. Jimenez Rios, Y. Rabin, “Thermal use either system to avoid fracturing. There come from mainstream cryobiology, but some expansion of blood vessels in low is only a general presumption that a future research will need to be specific to cryonics. In cryogenic temperatures, part II: fracturing avoidance protocol may require the meantime, cryonics organizations face dif- Vitrification with VS55, DP6, and 7.05 lengthy individual temperature conditioning. ficult decisions in whether to make an expen- M DMSO”, Cryobiology 52 (2006) A related question is what storage tem- sive and complex technology that is still unsuc- 284–294. perature is appropriate for ITS. The lower cessful in its final objective clinically available. 6. Y. Rabin, P.S. Steif, K.C. Hess, J.L. the temperature the more stable the storage, ITS is not unlike cryonics itself. n Jimenez-Rios, M.C. Palastro, “Fracture but the more difficult it is to avoid fracturing. formation in vitrified thin films of cryoprotectants”, Cryobiology 53 Viscosity at and below the glass transition is References (2006) 75–95. so high that chemical reactions can probably 1. B. Wowk, “Thermodynamic aspects of 7. M. Federowicz, H. Hixon, J. Leaf, be neglected over less than geologic times- vitrification,” Cryobiology 60 (2010) “Postmortem Examination of Three cales. However a phenomenon called ice nu- 11-22. cleation happens at high a rate near the glass Cryonic Suspension Patients,” 2. R.C. Merkle, R.A. Freitas, “A Cryonics September (1984) 16-28. transition temperature, and in some studies Cryopreservation Revival Scenario 8. H. Hixon, “Exploring Cracking doesn’t become undetectable until 20 degrees Using Molecular Nanotechnology,” Phenomena,” Cryonics 1st Quarter below it. Ice nucleation-- the local reorienta- Cryonics 4th Quarter (2008) 6-8. (1995) 27-32. tion of water molecules into nanoscale ice 3. “Appendix B. A ‘Realistic’ Scenario crystals --doesn’t cause immediate structural for Nanotechnological Repair of the damage. However it can make avoiding ice Frozen Human Brain,” in Brian Wowk, growth and associated structural damage Michael Darwin, eds., Cryonics: during future rewarming more difficult. The Reaching for Tommorow, Alcor Life extent and significance of ice nucleation in Extension Foundation, 1991.

Membership Statistics

On June 30, 2011, Alcor had 948 members on its Emergency Responsibility List. Thirty-eight (38) memberships were approved during the first six months of 2011, five (5) memberships were reinstated, twenty-four (24) memberships were cancelled and four (4) members were cryopreserved. Overall, there was a net gain of eighteen (18) members this year to date.

www.alcor.org Cryonics/Third Quarter 2011 13 Chronology of Developments Related to Fracturing and Intermediate Temperature Storage

1966: Kroener and Luyet observed fracturing in vitrified glycerol 2003 June: In Ontario, California, presentations were made to solutions. (C. Kroener, B. Luyet, “Formation of cracks during the the Alcor board of directors by Brian Wowk, Mike Iarocci, and vitrification of glycerol solutions and disappearance of the cracks Stephen Valentine on new designs for intermediate temperature during rewarming,” Biodynamica 10, (1966) 47-52. storage systems. Alcor purchased and took delivery of an experimental single-patient “neuropod” intermediate temperature storage system developed by Brian Wowk at 21CM.(Alcor News 1984: Alcor noted fractures in human cryopreservation patients. #13, July 1st, 2003 and Alcor News #14, August 1st, 2003) (Federowicz, M., Hixon, H., and Leaf, J. Postmortem Examination of Three Cryonic Suspension Patients. Cryonics, September, 16-28 (1984) 2003 July: The first patient transferred to the CryoStar freezer was transitioned to liquid nitrogen storage because fracture avoidance 1990: Fahy published a detailed study of fracturing in large during slow cooling to -140°C was not successful. volumes of vitrification solution. (Fahy, G., Saur, J., and Williams, R. Physical Problems with the Vitrification of Large Biological Systems. 2003 August: Alcor Research Fellow Hugh Hixon began Cryobiology 27, 492-510 (1990) photoelasticity studies of fracturing using a polariscope and polarized light to image stress in cryoprotectant glasses. 1993 March: A detailed discussion and design exercise for a -130ºC “Cold Room” of 100-person capacity took place on the CryoNet Carnegie Mellon University received a $1.3 million grant from the email list. U.S. government to study fracturing during vitrification of tissue for medical applications, resulting in many new and valuable 1994: Alcor noted fractures in the brain of a patient following papers in the scientific literature about this subject. (Carnegie removal from cryopreservation. Various other aspects of the Mellon Researchers Developing New Ways to Store Tissue,Organs, fracturing problem were discussed in the same article, including Science Daily, August 13, 2003) possible intermediate temperature storage systems, and the development of a new acoustic fracturing monitoring device, 2003 October: 21st Century Medicine, Inc., constructed a the “crackphone.” (Hixon, H. Exploring Cracking Phenomena, prototype laboratory ITS dewar in which most of the volume of the Cryonics 1st Qtr. 1995 pags 27-32) dewar was converted into a uniform-temperature storage space kept cold by liquid nitrogen. Architect Stephen Valentine began studying Cold Room intermediate temperature storage design concepts as part of a large cryonics facility design that would eventually be called Timeship. 2004 March: Alcor purchased and took delivery of a “patient rated” neuropod intermediate temperature storage unit for individual neuropatients. 1997: The crackphone acoustic fracturing monitoring device was brought into clinical use by Alcor. 2005 November: Alcor placed an order with 21st Century Medicine, Inc., for a custom ITS dewar large enough to hold 2000: Alcor acquired a -130ºC Harris CryoStar laboratory freezer 14 neuropatients at a stable intermediate temperature (“ITS from GS Laboratory Equipment and began testing its utility for Neurodewar”). possible storage of neuropatients. (BioTransport Purchases CryoStar Freezer, Cryonics 3rd Qtr. 2000, page 11) 2006 January: US Patent 6,988,370, Cryogenic storage system with improved temperature control, was awarded to Mike Iarocci, 2002: Physicist Brian Wowk and Brookhaven National Laboratory Stephen Valentine, and Brian Wowk. cryogenic engineer Mike Iarocci began an intensive collaboration with architect Stephen Valentine to design intermediate temperature 2006 April: Alcor transferred patient A-1034 from the CryoStar storage systems suitable for cryonics in connection with the Timeship freezer to the validated neuropod purchased in 2004. Project.

In summer 2002 an Alcor neuropatient reached the lowest 2007 October: US Patent 7,278,278, Cryogenic storage system, temperature ever recorded without fracturing, –128°C. This was was awarded to Brian Wowk and Mike Iarocci. attributed to a uniformly low glass transition temperature resulting from excellent cryoprotective perfusion. Professional cryobiologist consultants expressed the opinion that the case may have been 2008 December: Alcor took delivery of the ITS neurodewar the best cryopreservation of any cryonics patient to date, and ordered in 2005. Patient A-1034 was transferred into the new recommended transfer to the CryoStar freezer for continued slow storage unit, and three cryopreserved brains that had been stored cooling and annealing for fracture avoidance. In December another by private individuals were accepted into ITS storage. patient, A-1034, was also placed into the CryoStar to accommodate wishes of the family for this type of storage.

14 Cryonics/Third Quarter 2011 www.alcor.org 2011 Q3 Readiness Update

By Aaron Drake, NREMT-P CCT

Alcor’s Recent Cryopreservations Aaron Drake and Steve Graber in adminis- 2. immersing the patient in a portable This past quarter, Alcor cryopreserved tering the medications, cooling and prepar- ice bath filled with a water/ice slur- two of its members. The first member lived ing the patient for transport. They both ry will increase that rate to about just north of the Tampa, FL area. Alcor followed the rescue vehicle back to Alcor so 10°C per hour; team members initiated a standby at the they could observe the procedure and see the 3. adding the Squid to circulate the hospital for three days during the time the facilities. Being impressed with the overall water/ice slurry increases the rate individual was listed as critical and medi- process, the physician expressed the desire to to about 15°C per hour. cal providers anticipated that he might stop provide services for future Alcor members. breathing. The member stabilized and Alcor This new relationship, along with the exist- Alcor’s Readiness Coordinator, Steve ended the standby while continuing to moni- ing hospice that we have used in the past, Graber, redesigned and built a compact, high tor the patient’s condition remotely. When will provide us with a stronger network of output portable ice water recirculation sys- his medical condition deteriorated again, Al- hospice options in the greater Phoenix area. tem, better known as a “SQUID.” This sys- cor was on the verge of initiating a standby A-2357 is now Alcor’s 106th patient. tem is designed for a small sump pump to sit for another member and therefore decided near the feet of the patient. Tubing from the to request Suspended Animation to provide Alcor’s Redesigned SQUID pump runs up the legs and across the torso, the standby this time. What’s a SQUID? This device, resem- and wraps over the neck and on the head. On the afternoon of the fourth day of bling the marine animal characterized by Chilled ice water then circulates around the the standby, the member was pronounced, multiple tentacles, is designed to accelerate patient to dramatically increase the cooling stabilized and cooled on-site, followed by a the speed at which a patient is cooled. rate. field washout. The transport commenced the next morning by commercial airlines and the patient was brought to Alcor with the surgical team at the ready. After the neuro cryopreservation ensued, member A-1408 became Alcor’s 105th patient. Alcor’s Arizona response team pro- vided standby services twice at the home of A-2357 on the west side of the Phoenix valley, approximately 50 miles from Alcor in Scottsdale. The first standby lasted six days before the member’s condition improved enough for the team to stand down. While continuing to monitor the individual’s health through a very supportive hospice organiza- tion, the attending physician determined that Immediate cooling is very important This new unit was tested in Alcor’s ice it was time to restart the standby just a mere as it reduces the metabolic demand of the bath to determine flow characteristics and two weeks later. On the second day of the body. The more rapidly this occurs, the less battery duration. Based on the battery and standby, despite relatively strong vital signs, ischemic damage is incurred. pump specifications we expected around 850 the member’s breathing became weaker until This graph shows that: gallons per hour flow with a power duration he finally just ceased to take a breath. of 2.5 hours. Not only did we achieve our 1. surrounding the patient with ice expected flow rate but were also surprised At the prior request of the hospice phy- bags will provide cooling at about sician, both she and a hospice nurse assisted when the pump was still flowing strong at 5°C per hour; 3.5 hours.

www.alcor.org Cryonics/Third Quarter 2011 15 the equipment, supplies and medications. On the second day, everyone reviewed the ob- jectives and then participated in a scenario- based exercise on a mannequin, in real-time, to test the newly acquired skills. Up until now, the team has only had a partial kit with zero training and would have been unable to provide much support if called upon. Now that a full response kit is in place and there are multiple people who have been through Alcor’s training, they feel comfortable and willing to assist in an emergency.

Dewars Alcor has acquired three new Big- 12v Battery Powered SQUID features: ◊ Compact design fitting into a small foot dewars from a new vendor. They were ◊ Small and highly portable ice water water resistant soft-sided carrying shipped in an enclosed 40’ semi-trailer, well recirculation system. Total system case with handle. wrapped and strapped to custom pallets. Al- weight: 11.5Lbs. ◊ Additional 115v power charger cor used two forklifts in tandem to unload ◊ Single 12v 7Ah Gel Cell Battery with intelligent charging/mainte- and upright the dewars. We were immediate- mated to a powerful micro-sized nance mode. ly pleased with the high quality of the welds pump with 1-1/4” outlet. and attention to detail throughout their con- Team Training struction. The dewars now await testing for ◊ Greater than 3.5hr run-time (tested). n The Pacific Northwest team, based in boiloff rates before being put in service. ◊ Hugh Hixon-designed water dis- Portland, OR, hosted a two day training ses- persal system with high volume sion at the home of former Alcor president About the flow and multiple flow branches Carlos Mondragon. Along with team leader Author using separate drain line. Aschwin de Wolf, Aaron Drake instructed ◊ Double tubing slit-cover design the twelve who attended. The first day con- Aaron Drake with negligible splash characteristic. sisted of classroom and practical training on NREMT-P, CCT, Medical Response Director

Aaron Drake is a Nationally Registered EMT-Paramedic (NREMT-P) and a Certified Cardiovascular Technologist (CCT) who serves as Alcor’s Medical Response Director. In this position he is responsible for the standby, stabilization and transport operations of the Alcor Foundation.

16 Cryonics/Third Quarter 2011 www.alcor.org A New Choice for Immortalists

By Michael R. Rose Department of Ecology and Evolutionary Biology, University of California

veryone whom I know to be registered radical, Aubrey is thoroughly conventional. My turning on the Road to Damascus for cryopreservation does so because In this respect, he more or less agrees with started one day in 1992 when my good col- Ethey don’t want to die, for good and the National Institute on Aging, of the NIH, league Larry Mueller showed me two articles forever. That is to say, they are some type of and innumerable other cell and molecular from the journal Science, articles from the immortalist. They may not be cyber-immor- biologists. While some of these cell-molec- laboratories of our colleagues Jim Curt- talists waiting to be uploaded to a successor ular aging researchers think that free-radical singer and Jim Carrey. The data in those to the present world-wide web. But basically damage is the central cause of cumulative articles were mind-blowing. They showed they want the prospect, at least the possibility, damage, others think that progressive dys- the complete cessation of the acceleration of living forever. Like an agnostic contem- regulation is more important. Classical-era in age-specific death-rates that evolutionary plating the possibility that God does in fact ex- biologists, from 2500 to 1600 years ago, biologists like Larry and myself regarded as ist, and a God in the business of providing ac- thought that aging was due to a progressively the hallmark of aging. It looked as if aging commodations comfortable or uncomfortable worsening balance between the earth, water, came to a stop. in the afterlife, immortalists are confronted fire, and air that were thought to make up the Both Larry Mueller and I were intensely with a menu of relatively stark, and often un- human body. In effect, classical thinking was skeptical about these results, and we voiced appealing, alternatives, given that no one has that these four elements were combined to some of our skepticism in print, in corre- yet brought a cryopreserved human, as body yield life in an unstable mixture, whereby ag- spondence that was published in Science to- or head, back from the freezer alive. ing involves the drying out and cooling of the gether with our colleagues Joe Graves and I am not going to argue against cyber- body’s physiology. Modern-day cell biolo- Ted Nusbaum, as well as in other articles that immortality or cryo-immortality here. After gists instead write about cumulative damage involved Larry and Joe Graves only. But I all, the value of back-up plans is self-evident. and/or dysregulation of pathways controlled was deeply troubled by these findings from Instead, what I am going to offer is an infor- by sirtuins, TOR, and the like. Regardless of the two Jim’s, and thought about them inter- mal introduction to a third possibility. This details, all of these people agree with Aristo- mittently throughout the next two years. possibility is one in which aging is stopped, tle’s original hypothesis that aging is a cumu- By 1994, I was thinking that perhaps and then repair and refurbishment are used lative physiological process of some type. evolutionary biologists had misconceived the to achieve immortality by the simple expedi- But I don’t. Not anymore. And this problem of the evolution of aging. Perhaps ent of not dying in the first place. break with the long Western academic tradi- it was NOT natural selection just letting go, Let me confess straightaway that if tion of aging theory is the key to the new but something that specifically tracked Ham- somebody had proposed this possibility to me choice I wish to offer here. ilton’s forces of natural selection. just three years ago, I would have laughed at I should be clear that my present view is This led me to convince Larry Mueller them outright. But I have spent the last two also not one generally held, at least not yet, to do some explicit simulations of evolution, years reinterpreting my life’s work, at least my even by most evolutionary biologists who simulations in which we looked at what hap- research since 1976, when Brian Charlesworth work on aging. Like them, I spent more than pened at very late ages, long after Hamilton’s first started working me over to get me to do thirty years thinking that William Hamilton’s forces of natural selection bottom out and my doctoral thesis on the evolution of aging. declining forces of natural selection, which stabilize. What the simulations generated Here is one of the key points, really the he published in 1966, showed that evolution were late-life plateaus in mortality, just as the central intuitive idea that the present article by natural selection would allow cumulative Curtsinger and Carrey labs had found. We hinges on. Since Aristotle, virtually everyone processes of physiological deterioration to published this result in PNAS in 1996. who has worked on the biology of aging has proceed unchecked, provided they killed off With this result in hand, we then checked conceived of it in terms of an underlying their victims at sufficiently late ages. And how changes in Hamilton’s forces would cumulative physiological process. The most thus my very definition of aging, which I change the age at which mortality plateaus famous, and indeed notorious, present-day published in my 1991 book Evolutionary Biol- occur, based on explicit simulations. These proponent of this view is the inimitable Au- ogy of Aging, assumed that endogenous pro- simulations showed that changing the last age brey de Grey. Aubrey characterizes aging as a cesses of physiological deterioration, wheth- of reproduction in a biological population, process of cumulative damage, chiefly at the er due to damage or dysregulation, would the parameter that Hugh Hefner is working cell and molecular levels. As such, notwith- proceed without remit until all members of on as I write, would tune the age at which standing his media reputation as a wild-eyed a sheltered cohort given good conditions die. mortality rates would plateau.

www.alcor.org Cryonics/Third Quarter 2011 17 So Larry Mueller, my then graduate So why is this physiological illusion so tion? How to find a third option for immor- student Casandra Rauser, and many under- convincing, and so reliable? It is convincing talists, a less drastic choice before cryonic or graduate students working in my laboratory and obvious because the falls in Hamilton’s cyber immortality? tested populations that had been evolving in forces of natural selection are so predictable As we explain in some detail in our book my laboratory for this predicted relationship and so intense, at least in most animal species. Does Aging Stop? (Mueller, Rauser, & Rose, between the last age of reproduction and the Hamilton’s evolutionary forces are as strongly 2011; Oxford University Press), shifting back start of the plateau in mortality rates. Quali- determinative of deterioration as any acute to lifestyles that are physiologically compa- tatively, it worked. Shifting the last age of re- disease process. Only the illusory ‘physiologi- rable to those of hunter-gatherers provides production, which is when Hamilton’s force cal aging processes’ that they produce is ex- a possibility of stopping aging at earlier ages, of natural selection acting on mortality itself tremely protracted in the human case. and in better shape. [For those who aren’t plateaus, produces the qualitatively predict- If this view is correct, then those spe- scientists, I have presented this possibility in able shift in observed mortality plateaus in cies in which Hamilton’s forces of natural some detail at the website Rob Patterson has our fruit fly experiments. Not immediately, selection do NOT fall should be free of ag- built for me: 55theses.org.] This possibility is as a physiological effect, but eventually, over ing. Even if they have the same basic cell particularly available for those whose ances- many generations, as a result of evolution biology as we do, and even if they are as tors have never adapted to agriculture, such as occurring in my laboratory under controlled subject to mechanical injury and oxidation the northern First Nations of Canada or the conditions. as we are. This alternative view thus makes non-agricultural tribes of tropical rainforests. Not only is the rate of aging, consid- some strong predictions, predictions which For them, Larry Mueller’s calculations suggest ered demographically, readily tuned by evo- are readily falsified by comparative data. IF, that they may be able to stop aging in middle- lution, so is the age at which aging stops a big if, this theory is wrong. age in particularly good shape. demographically readily tuned by evolution. And the comparative data show that such For the rest of us, the prospects are not And this is true not only of those aspects species DO indeed exist. For example, sea quite as good, if we switch to hunter-gather- of aging that affect survival. It is also true anemones that reproduce only by symmetri- er lifestyles. But the possibility does present of reproductive aging, the main theme of cal fission are animal species that are thought itself that we may be able to stop our aging the doctoral research of Cassie Rauser in my to be free of aging, from experiments cultur- phase, not our “aging process,” by an age like laboratory. Reproductive aging is tuned by ing them in aquaria. Similar results have been 70, and do so in much better condition than Hamilton’s other force of natural selection, found among other fissile coelenterates, par- present-day 70 year-olds can sustain. the one that tunes age-specific fecundity. ticularly in the work of Daniel Martinez. And Then, as medicine becomes still better at Still for more than a decade I thought Graham Bell has found results like these in rescuing us from the accidents of thromboses, of aging as a physiological process, just one flatworms that can also reproduce by splitting malignancies, and car collisions, we could re- that comes to an end when the late-life pla- in two. So, not only can aging stop, some- main on this aging-arrested plateau indefinitely. teaus in mortality and fecundity are reached. times it doesn’t even get started. Something for you all to think about. n But I now think that this was the wrong con- The problem for people is that when clusion to draw from our work. our aging normally stops, we are about a I am grateful to Max More for suggesting that Consider the following point. If aging hundred years old, very fragile, and often de- I write this article, and to Joseph L. Graves Jr. and is a physiological process, however multifari- mented. So who would want to sustain that Marta Santos for their comments on an earlier draft. ous, why should it come to a halt just when state indefinitely? the organism is most debilitated? In the hu- But I kept on thinking about the cessa- About the man case, demographic aging stops when tion of aging. In the last two years I started the death rate is between 30 and 50 % per thinking about some data that Cassie Rauser Author year, particularly among centenarians. These had collected on the cessation of reproduc- Michael R. Rose are very frail people, yet their aging abruptly tive aging in our fruit flies. She showed that stops. How is this supposed to make sense? the timing of this cessation, and the repro- Instead, imagine an entirely different ductive function of flies that have stopped view. Suppose instead that aging only seems reproductive aging, depended on their en- Michael Rose went to the University of like a physiological process, but actually is no vironment. These findings raised the pos- Sussex in 1976 for his doctoral studies such thing. Suppose instead that aging is the sibility, in my mind, that we might be able to on aging in Drosophila melanogaster. age-dependent tuning of Darwinian adapta- manipulate when mortality declines stop too, There he began his work on the tion, where the tuning is determined by the using environmental manipulation, in fruit evolution of aging and created patterns of Hamilton’s forces of natural se- flies or humans. Drosophila stocks with postponed lection. Not a physiological process at all. A few fruit fly experiments later, we are aging. In 1991, his Evolutionary On this view, what seems like a physi- already seeing signs of such an opportunity: Biology of Aging appeared, offering ological process is a scientific illusion, fully declining and stabilizing mortality too can be a view of aging that was a complete parallel to the illusion of the sun rising in the manipulated environmentally. This work is departure from the views that had morning, crossing the sky, and setting in the by Marta Santos and her team in my lab, and dominated the aging field since 1960. evening. Because, of course, the sun does no will be submitted for publication soon. Evolution described the field of such thing. Sunrise and sunset are optical illu- So, how to manipulate humans so as to gerontology as now “after Rose.” sions produced by the rotation of the Earth. stop our aging sooner, and in better condi-

18 Cryonics/Third Quarter 2011 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 supported by Ctoday’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.

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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 is one of Tthe 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:

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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.

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877-462-5267 ext. 132 [email protected] www.alcor.org 24 Cryonics/Third Quarter 2011 www.alcor.org