Annotated bibliography of cryoprotectant toxicity

Introduction

Cryoprotectant toxicity should be distinguished from other mechanisms of cryopreservation injury such as chilling injury (injury produced by too low temperatures as such) and cold shock  (injury produced by rapid cooling). Cryoprotectant toxicity itself can again be divided into general cryoprotectant toxicity and specific cryoprotectant toxicity. General cryoprotectant toxicity involves concentration (water substitution) effects of cryoprotectants and specific cryoprotectant toxicity involves the effects of individual compounds on cellular viability. General cryoprotectant toxicity presents a formidable obstacle for cryopreservation methods that require very high concentrations of cryoprotectant agents (such as vitrification).

Another mechanism of injury that is rarely discussed in the cryobiology literature but that can complicate cryopreservation of complex organs is “non-specific” dehydration injury. In light of the fact that the current generation of vitrification agents are delivered in hypertonic carrier solutions and contain non-penatrating cryoprotective agents which do not cross the blood brain barrier, this form of damage may be especially important in cryopreservation of the brain.

Systemic reviews of cryoprotectant toxicity are rare but some mechanisms for (specific) cryoprotectant toxicity have been proposed including, but not limited to, protein denaturation, modification of biomolecules, membrane injury, destabilization of the cytoskeleton, oxidative damage, and ATP depletion. It is important to stress that some of the mechanisms may be downstream effects of other mechanisms. For example, ATP depletion can cause oxidative damage. And as Gregory Fahy has pointed out, cryoprotectant toxicity should be distinguished from injury associated with the method of introduction and washout of the cryoprotectant. In 2004, Fahy, Wowk et al., proposed a compositional variable to predict general cryoprotectant toxicity.

Cryoprotectant toxicity can also vary by species and organ type. Cryoprotectants that are moderately toxic in one species can be highly toxic in others. Similarly, cryoprotectants that are moderately toxic in one organ can be highly toxic in others (or even between different types of cells within organs). This raises the question of whether universal non-toxic cryoprotective agents are attainable (a requirement for reversible vitrification in complex organisms).

Cryoprotectant toxicty can be investigated by cryopreserving an organ (or cell) and measuring its viability after rewarming and washout of the cryoprotective agent. To eliminate the influence of other mechanisms of injury associated with cryopreservation (such as ice formation), a cell can just be loaded and unloaded with the cryoprotectant without cryopreservation. The effects of hypothermia on viability can be eliminated altogether by normothermic perfusion of the organ. This, of course,  introduces a challenge for hypoxia sensitive organs such as the heart and the brain because cryoprotective agents may not be good oxygen carriers.

Papers

Baxter SJ, Lathe GH (1971). Biochemical effects of kidney of exposure to high concentrations of dimethyl sulphoxide.
Biochemical Pharmacology. Jun; 20(6): 1079-91.

Baxter and Lathe investigated the effect of high concentrations of DMSO on kidney preparations. In a series of illuminating experiments, the investigators established that anaerobic glycolysis was reduced in slices and homogenates as a result of increased activation of the gluconeogenesis enzyme Fructose 1,6-diphosphatase (FDPase). DMSO-induced activation of FDPase can be inhibited by adding an amide or lysine to DMSO. The finding that a combination of DMSO and an amide allows for less toxic cryoprotectants formed the basis of subsequent investigations of GM Fahy for potent vitrification solutions.

Fahy GM (1983). Cryoprotectant Toxicity Neutralizers Reduce Freezing Damage.
Cryo-Letters 4: 309-314.

In this paper GM Fahy reports the ability of toxicity neutralizers urea, formamide, and acetamide (all amides) to reduce injury of cryopreserved renal cortical slices with DMSO. In later research papers Fahy will establish that DMSO neutralizes the toxicity of formamide, and not the other way around.

Fahy GM (1984). Cryoprotectant toxicity: biochemical or osmotic?
Cryo-Letters 5: 79-90.

If osmotic stress is an important cause of injury during introduction and removal of cryoprotectant agents, improved viability can be obtained by reducing the rate of cryoprotective agent introduction and removal. Fahy reviews the literature and presents data obtained in renal cortical slices that indicate that substantial hypertonic osmotic stress does not produce major changes in viability. Conversely, reducing exposure time to higher concentrations of the cryoprotectant can contribute to improved viability. These results suggest that biochemical toxicity, not osmotic stress, is the major factor in cryoprotectant-induced injury.

Fahy GM (1984). Cryoprotectant toxicity: specific or non-specific?
Cryo-Letters 5: 287-294

Fahy reviews the argument (Morris, Cryoletters 4, 339-340, 1983) that the lower toxity of cryoprotectant solutions that contain DMSO and amides can be entirely explained by the lower absolute concentration of DMSO. Fahy points out that the original Bexter and Lathe experiments demonstrated that solutions with the same absolute amount of DMSO (4.6 M) but with or without amides had different effects on glucose utilization. The author also presents data showing that “simple substitution (“dilution”) of one agent for another strikingly fails to reduce overall toxicity over a very critical range of DMSO concentration.” Also briefly discussed is the possibility of mutual toxicity neutralization between DMSO and amides, a topic that would be further explored by Fahy in future research.

Fahy GM, MacFarlane DR, Angell CA, Meryman HT (1984). Vitrification as an approach to cryopreservation.
Cryobiology.  Aug ; 21(4): 407-26.

In this paper on vitrification as an alternative to conventional cryoprotection, Fahy et al., list a number of methods for reducing cryoprotectant toxicity:

Primary (direct) methods:

  1. Maintain temperature as low as possible;
  2. Select an appropriate carrier solution;
  3. Keep exposure time at higher concentrations to a minimum;
  4. When possible, employ specific cryoprotectant toxicity neutralizers.

Secondary (indirect) methods:

  1. Avoid osmotic injury;
  2. Mutual dilution of cryoprotectants may be helpful in some instances;
  3. Use extracellular cryoprotectant to reduce exposure to intracellular cryoprotectant when possible.

The most important insights, some of which are still maintained in the current generation of vitrification solutions, concern toxicity neutralization, the choice of an appropriate carrier solution, and the use of extracellular cryoprotectants.

Fahy GM (1986). The relevance of cryoprotectant “toxicity” to cryobiology.
Cryobiology. Feb; 23(1) :1-13.

Fahy presents evidence that cryoprotectants themselves can present a source of injury. As a consequence, the advantages of higher concentrations of the cryoprotective agents does not necessarily produce higher viability after freezing, even when this allows for greater ice inhibition. He reviews data on “cryoprotectant-associated freezing injury” for DMSO, ethylene glycol, methanol, ethanol, and glycerol.  Because vitrification requires very high concentrations of cryoprotective agents, toxicity is the key limiting factor in reversible vitrification of organs.

Fahy GM, Lilley TH, Linsdell H, Douglas MS, Meryman HT (1990). Cryoprotectant toxicity and cryoprotectant toxicity reduction: in search of molecular mechanisms.
Cryobiology. Jun; 27(3): 247-68.

Fah,y et al., delineate 6 criteria that must all be met simultaneously in order for a putative mechanism of cryoprotectant toxicity to be implicated:

  1. The relationship between observed biochemical alteration and cellular viability must be clear or easily plausible;
  2. The maginitude of the cryoprotectant effect must be large enough to be significant;
  3. The effect must be irreversible over a reasonable time span after removal of the cryoprotectant;
  4. The time course of the observed effect must be consistent with the time course of observed injury;
  5. The cryoprotectant effect must be possible under conditions that could reasonably be encountered inside a living cell being prepared for freezing or being subjected to freezing and thawing itself;
  6. The cryoprotectant effect must be due to the cryoprotectant itself and not due to the technique of introduction and washout.

The authors investigate the proposed mechanisms for the biochemical effects of DMSO toxicity in the 1971 Baxter study and find that a) the effect of DMSO on FDPase activation is too small to affect the normal respiration of the cell and therefore fails to meet criterion 2 to be a significant mechanism of cryoprotectant toxicity; b) the presence of formamide does not affect the interaction between DMSO and lysine; and c) toxicity is not consistently reduced by blocking alteration of FDPase rather than substituting those compounds for DMSO.

The authors further present results that do not support the theory that generalized  protein denaturation is related to cryoprotectant toxicity.  The article ends with a referenced list of phenomena possibly related to mechanisms of cryoprotectant toxicity.

Fahy GM, da Mouta C, Tsonev L, Khirabadi BS, Mehl P,  Meryman HT (1995). Cellular injury associated with organ cryopreservation: Chemical toxicity and cooling injury.
Editors: John J. Lemasters, Constance Oliver. Cell Biology of Trauma, CRC Press

Fahy, et al., review different mechanisms of cryoprotectant toxicity with a particular focus on DMSO-medicated chemical injury. Mechanisms discussed include fructose-1,6-bisphosphatase activation, sulfhydryl oxidation, activation of extracellular proteinases and endothelial cell detachment and death. The article lists a number of interventions that do not change CPA-medicated injury such as inhibition calcium mediated injury or protein denaturation. The authors also report how the toxicity of formamide can be completely reversed by addition of DMSO.

Bakaltcheva IB,  Odeyale CO, Spargo BJ (1996). Effects of alkanols, alkanediols and glycerol on red blood cell shape and hemolysis.
Biochimica et Biophysica Acta. 1280: 73-80

In this elegant and thoughtful paper, the authors use the human red blood cell to study cryoprotectant toxicity. Morphological observations, quantification of hemolysis, measurements of the dielectric constant of the incubation medium (Ds) and the dielectric constant of the erythrocyte membrane in the presence of organic solutes (Dm), are used to investigate cryoprotectant toxicity in a series of alkanols, alkanediols, and glycerol. The authors propose that toxicity of a cryoprotectant is related to its ability to change the ratio of Ds/Dm. Changes in this ratio reflect changes in the difference between hydrophobicity of the solution and the membrane, with decreases in this ratio leading to increased exposure of membrane surface area and vesiculation, and increases in this ratio leading to decreased exposure of membrane surface area and cell fusion. The authors suggest that the design of less toxic cryoprotective agents should involve the maintenance of dielectric homeostasis of the medium and the membrane. Their findings also throw light on the observation that combinations of various cryoprotectant agents (such as DMSO and formamide) can reduce the overall toxicity of a solution.

Fahy GM, Wowk B, Wu J, Paynter S (2004). Improved vitrification solutions based on the predictability of vitrification solution toxicity.
Cryobiology. Feb; 48(1): 22-35.

This seminal paper on non-specific cryoprotectant toxicity represents a major contribution to the cryobiology literature in general, and enabled the authors to formulate less toxic vitrification solutions for the cryopreservation of whole organs. In the paper the authors propose a new compositional variable that reflects the strength of water-cryoprotectant hydrogen bonding called qv*. Contrary to the cryobiology wisdom to date, the authors found that weaker glass formers favor higher viability. As a consequence, vitrification agents with higher concentrations of cryoprotective agents are not necessarily more toxic. Although qv* is not helpful in predicting specific cryoprotectant toxicity, this paper, and the research that is reflected in it, suggests that non-specific cryoprotectant toxicity is mediated through the effects of penetrating cryoprotectant agents on the hydration of biomolecules.

Posted in Cryonics, Science | Tagged , , , , , , , | Comments Off

The 2011 Calorie Restriction Society Conference

On October 27-29 I attended CR VII, the 2011 Calorie Restriction Society Conference held in Las Vegas, Nevada.

Members of the Calorie Restriction Society restrict their calories while maintaining adequate nutrition as a means of extending their lifespan (or improving their healthspan), as has been proven to work in lower animals.

Although I was still in a wheelchair as a result of falling from a ladder and hip surgery, I got my airline to give me handicapped-support (wheelchair assistance), and I rented a wheelchair in Las Vegas.

CR VII was the seventh CR Society conference held in the ten years since the first such conference was held in the same city, in the same hotel, and in the same meeting-room ten years earlier in 2001. Thursday, October 27 featured presentations by Calorie Restriction Society Members, whereas Friday and Saturday featured presentations by PhD scientific researchers. I am a CR Society Member, so I was invited to speak on cryonics on Thursday. It was a small conference, so there were not many more than forty people attending on any of the days.

My presentation was preceded by a presentation by Peter Voss, who is both a CR Society Member and a Member of Alcor. Peter and his companion Louise Gold were the only CR Society Members other than me attending  the conference who are cryonicists. Peter spoke of the ultimate goal of indefinite lifespan, sharing his wisdom based on his experience practicing calorie restriction, describing cryonics as a “safety net of unknown fabric”, and mostly speaking of his goal of developing Artificial General Intelligence to accelerate research in life extension technologies. Concerning his CR practice, he noted that CR is not binary, and that people receive the benefits to the degree that they restrict their calories. He said that he does not count calories, but simply weighs himself and adjusts his calories appropriately, which is the practice I have adopted. Peter is not worried about hostile AIs because he believes that rationality is positively associated with morality. (See http://www.adaptiveai.com/ for a sample of Peter’s work.)

Although it was not a large group, I expected that such a group of dedicated life extensionists willing to go to extremes in restricting their calories would be very receptive to the practice of cryonics. On the other hand, Shannon Vyff warned me that although CR Society Members can be enthusiastic to hear about cryonics, they don’t sign-up. I gave considerable thought to the marketing aspect of my presentation. I decided to be very up-front about being a salesman, while nonetheless attempting to side-step salesmanship (and sales resistance) by concentrating on the technical issues and encouraging a technical discussion (although I did mention prices and insurance funding).

Alcor Member (and long-time cryonics promoter) Brenda Peters lives in Las Vegas, so I invited her to be my guest at the CR Society Conference. My thought was simply that Brenda and I could renew our friendship while enjoying the conference together.

I began my presentation by describing my and experience and mistakes in practicing calorie restriction as well as my fall in September which resulted in hip surgery and no prospect of walking again for many weeks — and how this had interrupted by exercise/CRAN program. When I asked who felt familiar with their knowledge of technical issues of cryonics, I was surprised that none of the non-cryonicists raised their hands.

After giving my presentation of the technical issues in cryonics I asked the audience to pair-up to discuss both their understanding of my presentation, and reasons they may have for thinking that cryonics may not work. After the paired discussions I asked for questions and objections. Brenda was more enthusiastic than I expected about raising her hand to comment. I somewhat bluntly said that I would rather hear from anyone but her, which was apparently confusing to people who weren’t aware that we knew each other. I was wanting to hear the unvarnished objections to the idea of cryonics which CR Society Members might have. I did not mean to hurt Brenda’s feelings, and I blame myself for not discussing my expectations with her beforehand. I did, nonetheless, allow Brenda to speak a couple of times.

It proved to be hard work getting CR Society Members to explain whatever objections they might have to cryonics. One fellow expressed his belief that not enough is known about the mind to know that cryonics can preserve it. I replied that the mind is based on the synaptic “connectome” and that minds recover from low-temperature surgery in which there is no electrical activity in the brain. Another fellow wanted to hear the experimental evidence that cryonics patients have been revived, to which I could only reply that cryonics is dependent on technologies which do not yet exist, and that revival seems inevitable to me if technology continues to progress and the anatomical basis of mind is preserved. One man believed that dogs had already been cryopreserved and revived, but I corrected his misconception by stating that the dogs have only been revived from cooling down to just above the melting temperature of water. When someone said that most businesses don’t last long, I replied that it is a mistake to compare the durability of cryonics organizations to efforts to start a diner in a location where the success is uncertain. One woman raised the overpopulation issue, which I noted is no more a plausible threat than the danger that too many people will practice Calorie Restriction. I added that the same logic would ban all medical research, especially research into preventing infectious diseases.

Although there were not many objections, neither did I hear much enthusiasm for cryonics. Perhaps they were stunned by an unfamiliar idea, and it takes time for resistance to be overcome. I had been hoping for some sign-ups. I had placed Membership forms on the literature table. It was as if they had no objections to cryonics, but still weren’t interested. Which left me thinking that I shouldn’t have asked for reasons why they think cryonics won’t work, but instead asked for reasons why they won’t sign-up.

A number of people complimented me on the quality of my presentation. But during subsequent discussions with CR Society Members at the conference, I heard further objections to cryonics. One CR Society Member told me that he hoped my presentation would motivate him to sign-up for cryonics. He said that he had mentioned cryonics to his mother several years ago, but she was freaked-out by the thought of being reanimated in a strange and alien world. Since then she had become demented, and he thought it would be wrong to foist cryonics upon her while she is in that condition.

Another CR Society presenter spoke of his project to develop an eco-friendly farm with local barter and community-building that would be sustainable through the disastrous global warming and prolonged depression he was expecting. His bleak vision of the future of technology left no possibility for cryonics, but at least he corrected himself when he started to say “cryogenics”.

Another fellow I spoke with later was concerned that cryonics organizations could not survive in light of the acrimony he saw between Members. His biggest concern, however, was that people of the future would be vastly superior, and treat him with contempt or worse upon his revival. A female CR Society Member told me that she is restricting calories entirely to increase her health-span, not her lifespan. She does not think that life is very good, and she has the hope and belief that the afterlife will be better.

Over lunch, one fellow suggested promoting cryonics as a means of cutting the astronomical health-care costs that so many people incur in their last year of life. I replied that any association of euthanasia with cryonics or any hastening of death on the expectation that cryonics may work would be disastrous for cryonics — and all the moreso if done as a cost-cutting measure.

I had difficulty moving around in the conference room due to the tables and my wheelchair, which made it difficult to chat with people during breaks. I had a similar problem during meal breaks. Whether I would have gotten a better understanding of why no-one seemed eager to sign-up for cryonics if my mobility had been better remains to be seen. I would think that after years of giving presentations about cryonics I would become blunted to lack of interest, but each such experience remains uniquely poignant and disappointing.

I learned much from the scientific presentations, but I won’t attempt to summarize very much. I was, however, very impressed by the extent to which a linkage was made between the blockage of the insulin/IGF-1 pathways in lower organisms and the practice of calorie restriction by humans. There is evidence that protein restriction may be the essence of calorie restriction, and that low protein diets are associated with reduced levels of IGF-1, but only when protein is less than 12% of macronutrients. Increasing insulin sensitivity seems to be the key to extending lifespan, yet although exercise is the most powerful intervention increasing insulin sensitivity, exercise does not increase lifespan.

Stephen Spindler and Luigi Fontana are scientists who have a long and intimate relationship with the CR Society. Both were speakers at this conference. Luigi in particular has been conducting studies on the physiology of long-time calorie restriction practitioners, and the benefits that are seen in the risk factors for various aging-associated diseases. He has published many studies of this research:

http://www.ncbi.nlm.nih.gov/pubmed/21402069

http://www.ncbi.nlm.nih.gov/pubmed/21841020

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2724865/

http://ajpheart.physiology.org/content/294/3/H1174.long

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829867/

A DVD of the presentations is being made by the CR Society, and will be available for sale within a few weeks, I expect.

Posted in Cryonics, Health | Tagged , , , , , , , , , | Comments Off

Fifth SENS Conference

August 31 to September 4, 2011 I attended fifth biannual SENS Conference (SENS5, Strategies for Engineered Negligible Senescence) at Cambridge University in the United Kingdom.

People who attend SENS conferences are the demographic that is the most receptive to cryonics of any identifiable group I have yet found. They are mostly scientists interested in intervening in the aging process. Quite a number of attendees are already cryonicists, including Aubrey de Grey, the originator of SENS and the organizer of the conference. But cryonicists are nonetheless a distinct minority. In previous years I brought a few Cryonics Institute brochures, which were soon taken. This year I brought enough brochures for as many of the 240 attendees as might want one (there were many left over).  I also brought a few copies of my “Scientific Justification of Cryonics Practice” (the published write-up of my SENS3 cryonics presentation) which I gave to a few attendees who seemed most receptive.

In addition to my oral presentation on cryonics I also had a poster. Scientific conferences usually have poster sessions where scientists present research, reviews, or ideas in the form of a poster. Poster presenters stand by their posters at scheduled times to discuss their work on a one-to-one basis with individuals rather than to an audience. My poster dealt with challenging the concept of biological age and denying the possibility of a biomarker of aging that could determine biological age. I contended that biological age and biomarkers of aging assume a singular underlying aging process, which I denied on the grounds that aging is multiple forms of damage. I sought to make maximum use of the one-to-one interaction by preparing Socratic questions to stimulate thinking and discussion with the attendees. The process also gave me another means of meeting and speaking to those attending. One interesting person I met was a Torontonian who is currently studying for his PhD at University of Glasgow. His work involves developing gene vectors that can precisely target and modify genes on chromosomes. I consider gene therapy to be an essential tool for the ultimate implementation of SENS, and a deficiency of SENS that there is so little attention paid to this technology. I don’t see how SENS can be implemented by any means other than genetic re-programming. LysoSENS, for example, would require new genes to create new, more effective enzymes for the lysosomes. MitoSENS would require all mitochondrial proteins be made in the nucleus and imported into the mitochondria.

Partly in this connection, was my aggressive lobbying of Aubrey de Grey to have Argentinian biogerontologist and Cryonics Institute member Rodolfo Goya as an invited speaker at SENS5. I began lobbying in January when Dr. de Grey was at ConFusion 2011. Aubrey was initially reluctant based on the first batch of Dr. Goya’s papers that I sent, but a later batch in which Dr. Goya was principle investigator proved to be effective. In Dr. Goya’s presentation at SENS5 he described his use of viral vectors attached to magnetic nanoparticles to deliver IGF-1 genes to senescent female rats to rejuvenate dopamine-producing cells in the hypothalamus. He injects the particles into the venticles, so the technique is somewhat invasive. Another speaker, Matthew Wood, described exosome nanoparticles which can cross the blood-brain barrier so I am hopeful that Dr. Goya can adopt this technique. Dr. Goya ended his presentation with a short pitch for cryonics (showing CI’s cryostats), which even I found embarrassingly awkward. I introduced Dr. Goya to a number of other cryonicists attending SENS5, including Igor Artyuhov, who is the scientific advisor for KrioRus, and Alcor Member Maria Entraigues, who is the SENS volunteer co-ordinator, and a native of Argentina (now living in Los Angeles).

Russian biogerontologist Alexey Moskalev reported on decreasing the number of single-strand DNA breaks and increasing the maximum lifespan in fruit flies by overexpressing the stress response/DNA repair gene GADD45 in the nervous system. That such a presentation would be included in SENS5 was of special interest to me insofar as I have contended that (and debated with Aubrey de Grey concerning) nuclear DNA damage possibly being a significant cause of aging damage that is missing from SENS:

http://www.benbest.com/lifeext/Nuclear_DNA_in_Aging.pdf

http://www.alcor.org/magazine/2011/02/28/deficiencies-in-the-sens-approach-to-rejuvenation/

http://www.alcor.org/magazine/2011/06/07/sens-a-reply-to-ben-best/

Alexey later told me that he had read my paper in REJUVENATION RESEARCH, and I’d like to think that I helped inspire his work.

Alexey announced that there will be a genetics of aging conference in Moscow in April 2012. I entertained the thought of going, partly because of my desire to see KrioRus, but I would rather go later when KrioRus is established in its new building, and has a research program in full swing.

Alexey’s research was partly funded by the Science for Life Foundation (the organization of the wealthy life-extensionist Russian Mikhail Batin). Maria Konovalenko (who was featured in LONG LIFE magazine) reported on her work at the Science for Life Foundation to build an open web-based database of age-related changes (molecular and phenotypic). Maria has her own blog.

I am not going to attempt to describe the other very excellent SENS5 presentations other than to say that great progress has been made in starting research programs on each of the SENS strategies, and by 2012 research on all the strategies is expected to be in progress.

Alcor President Max More was an invited speaker, which means that he had a half-hour time-slot immediately preceding my 15-minute time-slot near the end of the program. Max gave an overview of cryonics, whereas I concentrated on technical and scientific issues associated with vascular and neuronal injury from ischemia and reperfusion. During the question period I was asked if we are interacting with hospital staff to limit pre-mortem ischemia in cryonics patients. I said that the current legal environment limits such interactions, but that pre-mortem anti-oxidant protocol has been recommended and used.

I arranged to send more information to a few people in the audience, including a man who was interested in hydrogen sulfide to limit ischemic injury in cryonics, and an Italian neuroscientist who is interested in neurophysiology studies of vitrified brain tissue as well as contact information for Italian cryonicists.

At the final banquet I sat with CI Member Dr. Gunther Kletetschka, who is now living in the Czech Republic and is pursuing a number of imaginative cryonics-related research projects. One of these involves carbon nanotubes to deliver non-toxic metals to cells to use magnetocaloric cooling. Such a technique could cool tissues uniformly rather than externally, thereby eliminate the thermal stress that causes cracking when vitrified cryonics patients are cooled at cryogenic temperatures.

The last day was spent punting on the Cam River, with dinner in the evening. This provided an opportunity for more networking and information exchange, although most of this was in connection with biogerontology.

There was much biogerontology to be learned at SENS5. What I learned at SENS5 can potentially extend my life and that of others. To postpone cryopreservation by life extension is to benefit from technical advances, to extend the time in which I can contribute to technical advancement, and to enjoy more present life. In the best case, rejuvenation will become a reality in my lifetime and I won’t need to be cryopreserved at all. I work for this possibility as well as for improved cryopreservation. Moreover, in doing research for my cryonics presentation at SENS5 — and in giving the presentation — I learned many things that can help me make more informed choices in directing the research that Aschwin and Chana de Wolf do for the Cryonics Institute.

A video of my presentation may eventually be placed on the SENS5 YouTube site.

Posted in Cryonics, Rejuvenation | Tagged , , , , , , , , , , , | Comments Off

What you don’t eat can’t hurt you

Many people in the life extension community follow some kind of diet. Historically, caloric restriction (CR) has been the most popular and most discussed option. Other popular diets include the Mediterranean diet and the Paleolithic diet.  In one sense, comparing these diets is like comparing apples and pears. The emphasis of caloric restriction is on how much we eat (given adequate nutrition) and the other diets are more concerned with what we eat. People who follow certain diets may also have different aims. In the case of CR, life extension. In the case of the Mediterranean diet, preventing and delaying cardiovascular and neurodegenerative diseases. And many who adopt a low-carb diet are (initially) motivated by securing sustainable weight loss.

Assuming that diet plays some role in longevity and disease, it is rather obvious that cryonicists should take a strong interest in choosing the right diet. As it looks to me, there are a number of important considerations.

1. The most important aim of a diet for cryonicists should be to avoid, or delay, neurodegenerative diseases. Extending your life and ending up with advanced Alzheimer’s Disease is worse than dying young and being cryopreserved under circumstances that optimize preservation of personal identity.

2. The choice to follow a particular diet should work for your genotype. Admittedly, nutrigenetics is a very young field but there is a growing recognition that human evolution has not stopped since the start of agriculture and that different populations respond differently to certain diets. And even within these populations we should expect individuals to respond differently to diet.

3. A decision to follow a certain diet should be based on empirical evidence, not on intuition, abstract theories, or thought experiments. In the case of choosing diets, this  means identifying a diet that has shown a favorable ratio of good outcomes in experimental studies, and humans in particular.

Putting this all together, it seems to me that a low calorie diet remains the most defensible choice for most cryonicists because it has been studied longer, studied more extensively, and has the most robust favorable outcomes. CR also seems to stand out favorably in that there are relatively few studies that find detrimental outcomes and its benefits seem to embrace many species and populations. Another advantage of CR is that it can capture all the important goals that life extentionists seeks from a diet: longevity, weight loss and prevention (or delay) of neurodegenerative diseases.

It may be the case that many of the benefits of CR actually come from a reduction of carbohydrates. But one of the problems with a paleolithic diet is that it may be more beneficial for certain populations than others. As Gregory Cochran and Henry Harpending demonstrate in their seminal book The 10,000 Year Explosion: How Civilization Accelerated Human Evolution, human evolution did not stop when hunter gatherers started agriculture, and some populations are more adapted to agricultural products (such as milk) than others. Another concern about the paleolithic diet is the controversy surrounding saturated fat. For life extentionists who carry one or two copies of the ApoE4 gene, a diet high in saturated fat may actually increase the probability of Alzheimer’s disease. Others dispute this and recommend a diet high in (saturated) fat to prevent dementia.  In light of this uncertainty, the most prudent course of action may be to incorporate the emerging evidence against carbohydrates into a CR diet without emphasizing saturated fat.

There is an ongoing debate whether the longevity benefits of CR will be as great in humans as in lower species but the evidence so far seems to be that there are at least benefits in terms of delaying the onset of age-associated diseases. Whether these benefits are conferred through a change in gene expression or because they reduce the amount of chemicals that can participate in pathological events is not clear, but our incomplete knowledge about the mechanisms involved should not deter anyone from following CR. As I currently see it, the role of ongoing research into nutrigenetics and other diets should be to further calibrate and refine a low calorie diet to optimize it for a specific individual and to further delay the onset of neurodegenerative diseases.

CR seems to come closer to being a universal diet than other diets but it may be contra-indicated for some people, such as certain athletes and extreme ectomorphs. There are also cases in the life extension community of people who pushed it too hard (or neglected good nutrition), offsetting all the gains from the diet, or even endangering their own health. A diet that does not make a person feel good, is generally not a diet that is good, let alone one that can be sustained over time.  The aim of a diet should not be to conform to an impersonal set of recommendations, but to monitor your own response and increase the chance for personal survival.

Posted in Cryonics, Health, Personal Genomics | Tagged , , , , , , , , , , , | Comments Off

Steve Jobs’ morbid glorification of death

According to Steve Jobs, death is such a great benefit to mankind that it would have to be invented if it did not exist:

No one wants to die. Even people who want to go to heaven don’t want to die to get there. And yet death is the destination we all share. No one has ever escaped it. And that is as it should be, because Death is very likely the single best invention of Life. It is Life’s change agent. It clears out the old to make way for the new. Right now the new is you, but someday not too long from now, you will gradually become the old and be cleared away. Sorry to be so dramatic, but it is quite true.

As the baby boomers age, we can be sure to hear a lot more of what the cryonicist Mark Plus has called, ‘Humanist Death Apologetics.’ Never mind the horror, the destruction, and the suffering that comes with death, because, “it clears out the old to make way for the new.” Fortunately, a more enlightening perspective on death has been offered by the philosopher Herbert Marcuse:

It is remarkable to what extent the notion of death as not only biological but ontological necessity has permeated Western philosophy–remarkable because the overcoming and mastery of mere natural necessity has otherwise been regarded as the distinction of human existence and endeavor…

A brute biological fact, permeated with pain, horror, and despair, is transformed into an existential privilege. From the beginning to the end, philosophy has exhibited this strange masochism–and sadism, for the exaltation of one’s own death involved the exaltation of the death of others…

Modern market economies demonstrate on a daily basis that death is not necessary for the old to make way for the new. Neither do people have to be faced with death to have a meaningful life. Steve Jobs invites us not to be “trapped by dogma” but, unfortunately, he embraced the biggest dogma of all; the idea that human mortality is a good thing and gives meaning to life.

The reader is encouraged to explore some alternative views about death and aging:

Robert Freitas Jr – Death is an Outrage

Ben Best – Why Life Extension?

Aubrey de Grey – Old People Are People Too: Why It Is Our Duty to Fight Aging to the Death

Posted in Arts & Living, Death | Tagged , , , , | Comments Off

Smartphone Apps for the Smart Cryonicist

As every modern consumer knows, smartphones are today’s go-to portable technology. Everything from GPS navigation to finding a good deal on your next meal or haircut right NOW to a wide variety of games and applications may be had at the touch of a button. But developers of smartphone applications (i.e, “apps”) are only just beginning to realize the true capabilities of having so much computing power in the palm of your hand. Indeed, the possibilities for health monitoring applications in combination with GPS location bodes well for cryonicists.

Until cryonics-specific apps become available, there are several existing applications useful to cryonics members and organizations. Here are some of the most interesting from the Android Market:

ICE (In Case of Emergency):   Emergency personnel look for ICE information in patient mobile phones. This ICE app has a couple of widget options and can be accessed even when the phone is locked. My favorite feature is the ability to put any special instructions (like the protocol from your Alcor bracelet) on the main screen. The app acts primarily as an emergency contact list. Your cryonics service provider should be #1, followed by family and friends who support your cryonics arrangements. Additionally, you may enter your vital stats, medical and dental insurance information, and any known allergies, conditions, and/or medications.

For those with “dumb phones,” just create a contact called “ICE” and enter your cryonics organization’s emergency number. Additional information about placing ICE  numbers in your cell phone may be found in this article by Fred and Linda Chamberlain.

Emergency Button: Emergency Button sends a distress signal with your coordinates to a defined recipient when pressed. This has obvious utility for all matters of personal safety, and can be used to alert your cryonics organization to emergency health situations as soon as they emerge.

Google Latitude: Latitude is a GPS location tracking app. It allows for various privacy settings and can be configured to share only with specific people. A cryonics organization could, with its members’ permission, use such an app for real-time location tracking.

These are just three basic apps that are commonly available and useful to cryonicists now. I hope to be updating this list as improvements in smartphone technology continue.

Posted in Cryonics, Health | Tagged , , , , | Comments Off

Personalized Cryonics

Personalized Cryonics is an approach to cryonics that emphasizes the use of individual (health) information to optimize a person’s cryopreservation circumstances and outcomes.

To exchange information and empower individuals, a moderated discussion list was created by the Institute for Evidence Based Cryonics. It is a discussion list for members of existing cryonics organizations who seek to understand and change their personal circumstances to optimize their own survival and (potential) cryopreservation.

Typical topics on this list include personal genomics, personalized medicine, diet options, fitness, nutrigenetics, cryonics first-aid, custom-built stabilization equipment, advance directives and living wills, third-party interference, brain threatening diseases, and local support groups.

Posted in Cryonics | Tagged , | Comments Off

Intermediate temperature storage in cryonics

The recent issue of Cryonics magazine features a comprehensive update on intermediate temperature storage (ITS). This article contains an important observation:

Acoustic events consistent with fracturing were found to be universal during cooling through the cryogenic temperature range.  They occurred whether patients were frozen or vitrified.  If cryoprotection is good, they typically begin below the glass transition temperature (‑123°C for M22 vitrification solution).  If cryoprotective perfusion does not go well, then fracturing events begin at temperatures as warm as -90°C.  Higher fracturing temperatures are believed to occur when tissue freezes instead of vitrifies because freezing increases the glass transition temperature of solution between ice crystals.  The temperature at which fractures begin is therefore believed to be a surrogate measure of goodness of cryoprotection, with lower temperatures being better.

This is an important observation because one of the arguments that has been made against intermediate temperature storage is that Alcor routinely records fracturing events above the nominal glass transition temperature (Tg) of the vitrification solution. But if we recognize that such events can be (partly) attributed to ice formation due to ischemia-induced perfusion impairment it should be obvious that the recording of fracturing events above Tg as such cannot be an argument against ITS. After all, we also do not argue against the use of vitrification solutions because ice formation will still occur in ischemic patients that are perfused with vitrification solutions. Because cryonics patients almost invariably suffer some degree of ischemia prior to cryoprotective perfusion and cryopreservation, our knowledge about fracturing events in “ideal” human cases remains incomplete.

But even if ITS would only be successful in reducing fracturing events, instead of completely eliminating them, this should not be an argument against ITS. To argue that a technology should not be used because it does not completely eliminate a problem would constitute a sharp departure from the philosophy that has informed Alcor since its formation. In many areas, the evolution of Alcor’s technologies has been one of incremental evidence-based progress towards better procedures and storage conditions, not one of radical change.

The worst argument against ITS is that mature repair technologies will be able to repair clean fractures. It is a poor argument because one could similarly argue that advanced cell repair technologies will also be able to reverse the biochemical effects of short periods of ischemia and moderate degrees of ice formation. What distinguishes Alcor from other cryonics organizations is that it aims to secure viability of the brain as far into its procedures as it practically can. In ideal cases, this currently means meeting the challenge of further reducing cryoprotectant toxicity during cryoprotectant perfusion and reducing/ eliminating fracturing.

Perhaps the biggest obstacle to offering ITS to the general Alcor membership is cost. An obvious solution would be to offer ITS in addition to conventional liquid nitrogen storage. An alternative would be to gradually phase out conventional liquid nitrogen storage by no longer offering it to new neuro members and to raise cryopreservation minimums accordingly. The (preliminary) cost estimates in the article indicate that this would bring the cost of ITS for neuros closer to that of conventional liquid nitrogen whole body cryopreservation. The article does not provide specific information on the “greater capital costs” of whole body ITS systems but the reported lower liquid nitrogen consumption per patient for whole body systems suggests that it might be possible to offer whole body ITS without putting it beyond the reach of most (new) members with adequate funding.

Posted in Cryonics | Tagged , , , , , , | Comments Off

Alcor member profile of Aschwin de Wolf

The latest issue of Cryonics magazine features my member profile. This profile was written by Cairn Idun, a long-time Alcor member and cryonics activist who is currently known for organizing the annual asset preservation and teens and twenties meetings.

To generate this member profile, I answered a list of questions and submitted a short autobiographical piece that I wrote a little while ago. Cairn decided that in the case of some topics it would be best to retain my own language. As far as my ideas on cryonics are concerned, long-time readers of Depressed Metabolism will recognize most of the themes. This profile also contains some information about the cerebral ischemia and neural cryobiology research Chana and I are conducting at Advanced Neural Biosciences, Inc.

Posted in Arts & Living, Cryonics | Tagged , , , , , , , , , | Comments Off

The 2011 Cryobiology Conference

July 24-27 I attended the 2011 annual Society for Cryobiology conference in Corvallis, Oregon.

A number of the first presentations were concerned with means to *avoid* cryopreservation. Room temperature storage is much less expensive and troublesome, and improves ease of transport, especially in remote areas. One such technology “shrink wrapped” DNA in a glass  and another used trehalose to protect lipid membranes in a similar manner. Applied to cells, such technologies are viewed as a form of room-temperature vitrification.

Another researcher had successfully freeze-dried hematopoietic stem cells using trehalose and other additives without losing the ability of the stem cells to differentiate. Stress proteins in combination with trehalose allowed for desiccation of mammalian embryonic kidney cells without loss of viability. Late Embryogenesis Abundant (LEA) proteins also assist trehalose in dehydration tolerance.

Christoph Stoll showed that depleting red blood cell membranes of cholesterol can increase
trehalose uptake, but when I asked him in person about it, he said that the uptake was not enough to make much difference. Depleting cell membranes of cholesterol makes them more vulnerable to chilling injury, so I don’t think cholesterol depletion is a very good idea.

Masakazu Matsumoto spoke about some of the interesting anomalous properties of water.

Andrew Brooks spoke about the largest University cell and DNA repository in the world at Rutgers University.  They store DNA by plunging in liquid nitrogen.  He told me that 10 freezings and thawings does not impair DNA quality. That is encouraging for CI’s tissue/DNA storage program, because we plunge our samples into liquid nitrogen. Brooks gave data  showing that RNA is much less hardy in liquid nitrogen than DNA.

David Denlinger noted that HSP70 RNAi can block cold tolerance in insects. He also mentioned a Czech study which found that insect larva fed proline could survive liquid nitrogen. Perhaps we should be feeding proline to terminal cryonics patients.

In preparation for this conference, I had done a lot of reading on the subject of chilling injury and was hoping to question researchers on the subject. Steve Mullen showed a video of meiotic spindles dissociating at low temperature.

Spindles are a form of microtubules. Microtubules are known to dissociate at low temperature, but can spontaneously re-associate upon rewarming. But that would not be so beneficial when the microtubules are functioning as centrosomes because the reassembly would not be a reconstruction of the original structure. This is probably why cell division often  stops at low temperature.

Tiantian Zhang is one of the two candidates to become the new Society for Cryobiology President. Her field of study is cryopreservation of fish embryos and oocytes, which are especially vulnerable to chilling injury.

Fish are useful scientific models because they have a much simpler genome than mammals. 50% of endangered species are fish, but fish don’t get anywhere near the concern that pandas do. In both her lecture, and when I spoke to her in person, Dr. Zhang had apparently not learned any more than what was in her 2009 paper.

Why does reducing yolk content reduce chilling injury? Why is methanol the most non-toxic cryoprotectant for fish embryos, and so protective? If microtubule dissociation were a mechanism of chilling injury, it is indeed ironic that a 2006 Society of Cryobiology meeting presentation found that methanol causes proteolysis.

Kevin Brockbank spoke on the oxygenated hypothermic machine perfusion that he used to preserve pig livers at 4-6deg C for 12 hours. As a somewhat off-the-wall question, I asked him if he had assayed for chilling injury. This was off-the-wall because I have never heard of anyone assaying chilling injury. He responded that he had not, but that there were plans to use gene arrays to assay for chilling injury. This is like gene arrays to assay for aging — it requires deeper analysis, especially if chilling injury — like aging — is due to multiple mechanisms, the mechanisms are controversial, and no one mechanism is dominant. Northern wood frogs, arctic insects, and polar fish don’t have problems with chilling injury, although their adaptations include heat shock proteins and highly unsaturated cell membranes.

Much to my frustration, I have not had a good conversation with Peter Mazur (the uncrowned guru of cryobiology) since he got me to tell him I am a cryonicist several years ago. I have repeatedly asked him questions, and he has repeatedly been rude and dismissive. This year was different, for some reason. When I asked him about frozen water expansion contributing to mechanical damage he noted that cells could tolerate a 9% expansion without lysis even if freezing was intracellular. When I asked him how much dehydration cells could tolerate without damage, he said cells could lose all of the osmotic water (90% of cell water), and could lose more in freeze-drying with proper protectants (like trehalose). I was somewhat stunned by this answer, which takes no account of intracellular electolyte concentration increasing on dehydration. Next year I will be more optimistic about the possibility of talking with him, and I will prepare questions more carefully.

I spoke to Society for Cryobiology President John Crowe about his negative remarks concerning trehalose, in light of the fact that he is very aware of many of its benefits. John told me that a new method of manufacturing trehalose from starch is making trehalose as inexpensive as sucrose. If trehalose is used on bakery sugar, the sugar will not melt and run after a couple of days, as happens with sucrose. I mentioned to John that Robert Ettinger had just died. I had imagined that he might ask me to say a few words about the matter to the cryobiologists at their business meeting, but John treated the matter as a non-event, and I got the distinct impression that he would have preferred that I had not mentioned it.

At the business meeting it was noted that membership has dropped from close to 300 in 2008 and 2009 to just above 200 in 2011. There is concern that web access to the journal
CRYOBIOLOGY is becoming so easy that the incentives for membership have dropped. Or the global financial crisis is taking its toll on Society for Cryobiology membership. CRYOBIOLOGY journal impact factor has fallen to 1.830 from a high of 2.044 in 2002.

I appreciate being able to attend the business meetings, but one of the vehemently anti-cryonics cryobiologists gives me dirty looks. I have not been kicked-out yet, though, and decreasingly worry that I will be. A similar thought goes through my head as when I attend an Alcor meeting: “Spy in the House of Love.” But I really want the Society to prosper and grow, not be harmed, because I appreciate their good work (as with Alcor), even if they view me as a threat.

I had a brief chat with the cryonics-friendly Treasurer, who asked me when I think a cryonics patient will be reanimated. When I told him not less than 50 years, he said that a lot of surprising things can happen in 20 years. He is a more optimistic cryonicist than I am! At least as remarkable is that he is currently working with biotechnologists who are engineering scaffolds that can be used for growing organs from stem cells. That is a very cryonics-relevant project!

Every year I exchange a few words with Arthur Rowe (the cryobiologist who repeatedly compares cryonics to restoring a cow from hamburger — as he did in “Death in the Deep Freeze” – a comparison which probably originated with Peter Mazur). This year Arthur spent a lot of time hanging out with John G. Baust (the man who compared publishing cryonics science research with publishing Nazi hypothermia experiments). At the end of the conference I lost patience trying to catch Arthur alone, so I approached Arthur to say “hi”. Arthur said that he had seen on TV that Robert Ettinger had just died. He asked me about Robert’s educational credentials, and about my taking Robert’s place as CI President. Then he introduced me to John Baust. John was politely quiet, and said very little.

As with the 2010 Cryobiology Conference, I felt decreasingly paranoid as the meeting proceeded, but my level of paranoia was nonetheless very high near the beginning of this meeting. Overall, the amount by which I “came out” as a cryonicist was modest this year, and my softening of the hostility of cryobiologists to cryonics was modest this year compared to the previous one. The 2012 Society for Cryobiology Conference is scheduled to be held in Argentina.

Posted in Cryonics, Science | Tagged , , , , , , | Comments Off

ApoE4 – The Ancestral Allele

Reportedly, when James Watson and Steven Pinker had their genome sequenced, they declined to know their risk for Alzheimer’s disease. Clearly this is not an option for life extensionists and cryonicists, who are better off knowing whether they have a copy or, worse, two copies of the ApoE4 gene.

Patri Friedman, son of the libertarian economist David Friedman (who in turn is the son of the Nobel laureate Milton Friedman), recently learned that he has two copies of the ApoE4 gene when 23andMe updated their reports. Caucasian and Japanese carriers of two E4 alleles have between 10 and 30 times the risk of developing Alzheimer’s by 75 years of age, as compared to those not carrying any E4 alleles. Patri is a life extensionist, practitioner of the paleo diet, and recently made cryonics arrangements with his whole family at Alcor – and is thus far more prone to a pro-active course of action.

When he realized that there was no good central resource for people with copies of the ApoE4 gene he started a new blog called ApoE4 – The Ancestral Allele, which aims to share practical information and research for health-conscious E4 carriers. The first posts discuss some of the benefits of having the E4 gene (better episodic memory) and what kind of diet is recommended for E4 carriers. He also encourages guest posts and other co-bloggers to help run the website.

Posted in Health, Neuroscience, Personal Genomics | Tagged , , , , , , , , | Comments Off

The double standard about cryonics

One of the most predictable features of public debates about cryonics is that those arguing in favor of cryonics are held to more rigorous standards than those seeking conventional medical treatment. Advocates of cryonics do not just have to prove that cryonics will work, they are also supposed to solve problems like overpopulation and the presumed boredom arising from expended lifespans. To some, people who make cryonics arrangements have an inflated perception of their own importance and should just forgo such selfish attempts to extend their lives. The default position seems to be that people should not exist and that life needs justification. Could you imagine such antinatalist rhetoric being employed when a person seeks conventional medical treatment to extend their life? We can’t, and such responses are quite indicative of the fact that people are not interested in serious evaluation of the cryonics argument.

The most striking case of cryonics being held to higher standards than conventional medicine concerns the requirement that “cryonics” needs to “work.” Even people who have made cryonics arrangements routinely say something like, “I estimate the probability of cryonics working as 5% but life insurance premiums are low and I have nothing to lose if it does not work.” To see how strange such a statement is, let’s look at these two terms, “cryonics” and “working.”

Cryonics is an experimental medical procedure to stabilize critically ill patients at low temperature to benefit from future advances in medicine. Such a definition can include a wide variety of cases, ranging from ice-free cryopreservation (vitrification) as an elective medical procedure in a hospital to the freezing of a person who is found days after circulatory arrest. Considering the enormous variability under which people can be cryopreserved, to claim that “cryonics” will not work without specifying under what conditions a cryopreservation is performed is akin to saying that “emergency medicine” or “chemotherapy” does not work — an absurd claim.

Usually when people argue that cryonics does not work they refer to the mistaken view that cryopreservation that is not initiated within hours, or even within minutes, after death does not make sense because the brain has “died” at that point. Such a view completely ignores the fundamental cryonics argument that lack of function of the brain does not imply that the neuroanatomical basis of identity is irreversibly destroyed.

But let us accept this position the sake of the argument. What such a critic is basically saying is that cryonics cannot work because cryonics patients are cryopreserved under conditions that do not allow it to work. To see how strange such a position is, imagine a country where law would prohibit CPR until 15 minutes of death. Would anyone be impressed if someone would argue that CPR does not work because patients suffer irreversible brain damage after 15 minutes of circulatory arrest? Of course not. We would instead insist that such obstacles should be removed so that these life-saving technologies can be employed as soon as needed. Clearly, whatever the merits of cryonics are, it is not reasonable to conflate the conditions under which cryonics is often conducted with the idea of cryonics as such.

Now let’s look at the second term. What does it mean for cryonics to “work?” Naturally, we would like a medical procedure to cure the disease and restore the patient to the condition than he was in prior to the disease. In real life this often happens, especially in the case of minor infections and minor insults. But there are also many cases where (heroic) medical interventions are aimed at keeping the patient alive without expecting a full recovery without side effects. This is often the case in acute cardio-respiratory arrest and stroke. Would we prefer a complete recovery for such patients? Of course. But would we say that interventions that aim to save a patient’s life did not work if we fail to meet such an ideal – say, a permanent loss of movement in one arm or reduced memory function? No, our first concern would be with the patient’s survival and his perception of the quality of his “new” life.

In the case of cryonics things are not much different. We hope that advanced cell repair technologies will be successful in completely restoring the patient to good health in a rejuvenated state. For some patients complete inference of the original structure of the brain might not be possible, but advanced neural archeology and neurogenomics may restore a significant degree of the original person. We do not heap scorn on such scenarios in today’s medicine and there is no reason to hold cryonics to higher standards, especially if one also advocates the very restrictions that are responsible for such less than perfect outcomes. In fact, there is no reason to be scathing about any credible attempts to save or prolong a life, even if the attempt will not necessarily succeed. Such a perspective is a given in conventional medicine or rescue operations.

One objection to this position is to argue that cryonics cannot work even under the most favorable conditions. Such an argument would basically entail that if a critically ill patient is stabilized without ischemic delays, without ice formation, and without fracturing, it should be categorically ruled out that technologies will ever be developed to repair the original disease of the patient and any form of injury that occurs during the cryopreservation process itself. I personally would consider such a position extremely dogmatic (would anyone argue such a position of long-term technological stasis if the cryonics context were dropped?) but it raises a fundamental question about the burden of proof. Should it rest with the person who aims to prolong life or should it rest with the person who aims to prohibit such attempts? Asking the question is answering it.

Posted in Cryonics | Tagged , , , , , | Comments Off

Teens & Twenties 2011 Gathering

On the evening of Thursday, May 19 and on Friday, May 20, I attended the 2011 (2nd annual) Teens & Twenties young cryonicists gathering which preceded the Suspended Animation, Inc. conference in Fort Lauderdale, Florida. The Teens & Twenties gathering (for young cryonicists having human cryopreservation contracts in place with some cryonics organization) is an offshoot of the cryonics Asset Preservation Group. Like the Asset Preservation Group, this event was created-by and is run-by Cairn Idun. Bill Faloon funds Teens & Twenties through a Life Extension Foundation education grant. Members of the Asset Preservation Group, such as myself, are permitted to attend despite being more than 30 years old. Of the 52 people who attended, ten were Asset Preservation Group members, and 42 were young cryonicists.

When asked who did not want to be photographed, only one person in the group raised his hand. I will refrain from mentioning any of the young cryonicists by name. Writing about this very people-oriented event without mentioning individual young cryonicists is like writing about lemonade without mentioning lemon. Some of the personalities were particularly colorful and memorable. But I know that many of the individuals do not want the publicity, and in my experience people get very emotional about what is said and not said about them. Even with explicit permission I am concerned that many of the young cryonicists might not fully appreciate the kinds of problems writing about them in connection with cryonics might cause for their future careers.

This year the demographics of the young cryonicists more closely matched what is typical of cryonicists. Last year about one third of those attending were female, and there was a high representation of people from the entertainment industry. This year, the attendees were overwhelmingly male, with most of the females being companions of males (which is not to say they were not cryonicists). Many members of this group were impressively highly educated, mostly in computer technologies, and secondarily in biotechnologies.

EXCELLENT MEALS WERE INCLUDED IN THE SCHOLARSHIPS

There were six Russians: five from KrioRus, and one from CryoFreedom. KrioRus is located near Moscow, whereas CryoFreedom is further south in Russia, closer to Ukraine. Dr. Yuri Pichugin (formerly the Cryonics Institute’s cryobiologist, is associated with CryoFreedom. CryoFreedom advertises neuropreservation for $7,500. Although it currently has no human patients, two pets are in liquid nitrogen. (I also learned that there is a man named Eugen Shumilov who is working to start a new cryonics company in St. Petersburg, Russia, but there was no representation of Shumilov’s organization at this event.

There are two overlapping goals of the Teens & Twenties event. One is the opportunity for members of the Asset Presevation Group to meet the young cryonicists. The other is the opportunity for the widely dispersed young cryonicists to become acquainted with each other, and to build lasting networks (community building). Cairn Idun has designed a number of “getting to Know You” exercises to facilitate the networking.

There are two self-introductions: the first lasting one minute, and the second lasting two minutes. I was the most anal-retentive of any of the participants in these exercises. I wrote-out my self-introductions, and practiced reading them to myself until I was sure I was within a few seconds of the one and two minute allocations. The one-minute self-introductions were on Thursday evening, and the two-minute self-introductions were Friday morning.

The Thursday evening self-introductions were followed by the exercise wherein participants classified themselves by “color”: (Green:Conceptual, Curious, Wise, Versatile), (Red:Adventuresome, Skillful, Competitive,Spontaneous), (Gold:Responsible, Dependable, Helpful, Sensible), and (Blue:Warm, Communicative, Compassionate, Feeling), as described in my write-up of last year’s Teens & Twenties event.

Once again, Greens were most numerous, followed by Reds. Cairn directed the participants to gather into groups by color. No directions were given for these meetings, so it was to foster socialization between “like-colored” individuals.

Last year a number of people had little to say in their second self-introductions, imagining that they had said all that could be said about themselves in their first self-introduction. I concerned myself quite a bit about how to prevent this from happening again. I made a number of suggestions in the Young Cryonicists Facebook Group, as did others. Cairn had participants list wants and “not-wants” of various kinds before the second self-introductions as a means of facilitating self-awareness. I tried to make my second self-introduction very personal in the hope that it would inspire others. There weren’t too many who were at a loss for words in the second self-introductions this year. Many of the participants passed-out business cards or other self-descriptive materials in conjunction with their second self-introduction.

There was a breakout session in which those with special interests had an opportunity to discuss their interests or how they might work together on those interests. The interest areas were entertainment, research, computer sciences, communication networking, and psychology/philosophy of self.

INTEREST GROUPS

Bill Faloon encouraged the participants to share thoughts about types of research that could lead to reanimation — with the thought that many of the young cryonicists would be in charge of large revival trust funds with income that can be used for research on reanimation technologies. I won’t attempt to summarize the thoughts of others, but I can say a few things about what I said.

Some people don’t want cryonics because they are afraid that they will not be restored in their original condition. The mother of one cryonicist is a stroke victim, and she has had a frightening first-hand experience of losing mental & movement capacity. Hollywood plays into this vision by depicting reanimated beings as zombies who are criminally insane.

Few people want to be the first of those reanimated — they would prefer that many others be reanimated first to ensure that the process works perfectly. I suggested that the first people reanimated might be brought back by next-of-kin who are overly eager to see their loved-ones as soon as possible. The idea of reviving pets first would not be popular with many pet owners. Reanimation technologies might be perfected on non-pet animals, although even today there is increasing sentiment against animal research. Animal rights activists seek legislation to protect animals from “unnecessary research”, which would likely include anything cryonics-related. Austria banned research on apes in 2006, and the number of countries with similar legislation continues to grow [SCIENCE; 332:28-31 (April 2011)]. Even if reanimation research was conducted on apes, the extrapolation of restoring ape consciousness/identity to restoring of human consciousness/identity is non-trivial.

I worry that as more wealthy cryonicists are cryopreserved, their only concern will be for reanimation research. Many of them will not appreciate that improved cryopreservation methods will advance cryonics and thereby enhance their chances of reanimation.

The next “getting to know you” exercise was what Cairn calls “speed dating”. Each participant is to spend two minutes with every other participant having a one-to-one conversation. For myself, it gave me an opportunity to talk to many people I would not have spoken with otherwise, and to have personal conversations with many individuals that I cannot imagine happening in any other way. Spontaneous socializing more often results in people talking only to those they already know. This exercise is a good ice-breaker, but it does involve some effort. It can be a strain to be starting conversations again-and-again, and again-and-again having to break them off once they become interesting — but the result was well worth the effort for me. Having a personal connection with individuals enables me to interact with them more productively, and this must also be true of the others. I rate speed-dating as the most valuable of all of the exercises, along with self-introductions.

Participants filled out a sheet indicating their interest level in cryonics — including such things as whether they planned to have a cryonics-related career, do volunteer work for a cryonics organization, or simply be a consumer.

GATHERING FOR THE GROUP PHOTO

he final event was the group photo, after which was a dinner and then reception for the Suspended Animation conference. The photographer who made the group photo was employed to make photographs only intended sor private use of Suspended Animation, Inc., but we did not learn this until later (even the photographer did not know).

All the young cryonicists had the fees, hotel expenses, and meals associated with the Suspended Animation conference paid-for. The opportunity for some of the young cryonicists who have an interest in science to directly interact with current cryonics researchers could eventually lead to large scientific dividends for cryonics research in the future.

There were reportedly many exaggerated rumors about what happened in the evening hot-tub sessions in the 2010 Teens & Twenties gathering. I brought my bathing suit this year, but did not spend a great deal of time in the hot tub. The conversation was a bit more playful than it was in other contexts, and there was more of a party-spirit in the hot tub — which some of the participants relished. I would guess that about half of the Teens & Twenties participants spent at least some time in the hot tub.

Despite all of the intensive social interaction and “getting to know you” exercises, I would have a hard time making a connection between names, faces, and biographies of at least a third of the young cryonicists. I don’t believe that I am unique in that regard. The “speed-dating” exercise was particularly helpful in strengthening and deepening the name/face/biography connections. Memories of the individuals and their personalities are likely to be more easily refreshed in the future thanks to the meetings and exercises of this gathering.

YOUNG CRYONICISTS VISIT WITH SAUL KENT
Posted in Cryonics | Tagged , , , , , , | Comments Off

Gerald Feinberg on physics and life extension

Gerald Feinberg, a Columbia university physicist who, among other things, hypothesized the existence of the muon neutrino, had a strong interest in the future of science and life extension. In 1966 he published the article “Physics and Life Prolongation” in Physics Today in which he reviews cryobiology research with the aim of realizing medical time travel. Unlike most of his scientific colleagues, Feinberg recognized that it might be possible for people dying today to benefit from future advances in science in the absence of perfected techniques:

For the living it is necessary to await successful completion of freezing research before attempting to freeze them. For the newly dead this consideration is irrelevant since the dead have nothing to lose by being frozen, even by imperfect methods…

He doubts, however, whether “the primitive freezing techniques now available” would be good enough to permit successful resuscitation in the future.  Although his article ends in endorsing cryonics as a procedure, Feinberg did not make cryopreservation arrangements himself, despite his familiarity with molecular nanotechnology and his association with the Foresight Institute.

In the June 1992 issue of Cryonics magazine, Mike Perry writes:

Only a few days ago, as I write this, Gerald Feinberg, aged 58, died of cancer.  He was not frozen.  It appears  that he didn’t lack the means to make the arrangements, nor the time. Somehow, he was just not interested enough.  Friends or acquaintances I’ve talked to could give little in the way of definite reasons for the lack of  interest, but I get the impression that, when all was said and done, the  interest he did show was mainly academic after all.  Another factor may  have been hostility from colleagues and family members.  Apparently he was well criticized for the Physics Today article on the prolongation of life, though not for something really scientifically daring, like the tachyon  theory.

Human cryopreservation procedures have changed considerably since 1992 and cryonics researcher Mike Darwin has composed an ambitious article to answer the question whether current cryopreservation techniques can preserve identity. One of the most important observations in this article is that we do not need to wait until the future to get a better understanding of how good our current procedures are in this regard.

As long as we keep in mind that the absence of ultrastructural evidence for the preservation of identity-critical information does not necessarily mean the absence of this information as such (after all, future imaging and data gathering technologies may be more powerful than today’s) it is very important for cryonics advocates to recognize that preliminary work to infer the original structure of the brain from (3D) images of ischemic and cryopreserved tissue can start right now. Even in the absence of physical technologies to restore those structures to their native state, demonstrating that we can infer the original state, and visually reconstruct it, can be another argument in favor of human cryopreservation.

Further reading: Gerald Feinberg – Physics and Life Prolongation

Posted in Cryonics | Tagged , , , , , | Comments Off

Medico-Legal Aspects of Human Cryopreservation Optimization

Introduction

Ongoing legal challenges and hostile interference of relatives have increased awareness among cryonicists that addressing the likelihood that one will be cryopreserved at all should take center stage among other strategies for survival. As a consequence, a number of individuals have recently taken on the task of working out the conceptual and legal challenges to minimize hostile interference (for a contribution on the ethical aspects of cryonics interference, look here).

One aspect of cryonics optimization planning that has received little attention to date is to develop legal strategies to deal with medical and legal issues surrounding one’s death, terminal illness, and the dying phase. In this memo I will outline some of the most important medical and medico-legal issues, how cryonicists could benefit from recognizing them, and suggest some legal and practical solutions. Before I get to the substance of these issues I would like to briefly identify all the stages in which proactive cryonics planning can improve our odds of personal survival.

Opportunities for cryonics optimization

The first and most obvious decision is to make cryonics arrangements. Alcor members face complicated decision making because the organization offers both whole body cryopreservation and neuro cryopreservation. From the perspective of cryonics optimization many members choose neuropreservation because it enables the organization to exclusively focus on what matters most; the brain. There is also a logistical advantage. In case transport of the whole body across state lines is delayed the isolated head can be released in advance as a tissue sample. Additionally, a number of Alcor members have recognized that it is possible to have the best of both worlds and combine neuro-vitrification and separate cryopreservation of the trunk. This allows the member to take advantage of the superior preservation of the brain that is available for neuro patients without having to forego whole body cryopreservation. This option is not widely advertised so one is encouraged to contact Alcor about revisions in funding and paperwork.

The other obvious decision is to have secure funding in place. Many members have given extensive thought about funding mechanism and wealth preservation so there is little need to discuss this here. From the perspective of cryonics optimization it is important to emphasize the importance of over-funding your cryopreservation. This not only protects you against future price increases, but also enables you to take advantage of technical upgrades that cannot be offered at the current preservation minimums. Another aspect to consider is leaving money to cryonics research. Although it is reasonable to expect that general progress in science will include general cell repair, there may be areas that will only be pursued by those who have a scientific or personal interest in resuscitation of cryonics patients. As in many areas in life, diversification is key. One should not solely depend upon Alcor or CI for successful resuscitation research or efforts.

Another important opportunity for cryonics optimization is to recognize the importance of proximity. From a technical point of view, there is simply no comparison to de-animating near the cryonics facility of your choice. This is not just a matter of reducing ischemic time. Remote standby and stabilization is a fertile ground for all kinds of logistical and legal complications. Most cryonics members do recognize the importance of reducing transport times but it is an established fact that as soon people become terminally ill they become more resistant to the idea of relocating and often prefer to die among friends at home. It is important to anticipate this scenario and to not delay relocation plans until the last minute. Another advantage of relocating at an earlier stage is that one is better protected in case of a terminal disease with rapid decline or sudden death.

As mentioned above, one issue that is getting increasing attention is how to protect oneself against hostile relatives and third parties. The take-home message is to alter cryopreservation contracts and your paperwork in such a matter that there is an incentive *not* to interfere.

Last but not least, something should be said about community building. Cryonicists can greatly benefit from becoming active in their local cryonics group. Often these meetings are open to members of all cryonics organizations. Most cryonics groups organize standby and stabilization trainings where members can familiarize themselves with the basics of the initial cryonics procedures. Such groups may not only play a part in your own future cryopreservation but are also useful to get a basic understanding about what you can do in the case a local member or a loved one needs to be cryopreserved. Another important aspect of participation in a local cryonics group is that one remains in contact with other cryonicists. When people get older their friends and family members die and the member has little communication with those who are aware of his desire to be cryopreserved. If you live in an area where there are no local cryonics groups contact your cryonics organization and/or start your own local group.

Physician-assisted dying

If there was more widespread acceptance of cryonics the harmful delay between pronouncement of legal death and the start of cryonics procedures would not exist. After a determination of terminal illness, preparations would be made to ensure a smooth transition between the terminal phase and long term care at cryogenic temperatures.

Some states have enacted legislation that allows a terminally ill patient to request the means to terminate their life.  Assisted suicide is currently legal in the following three states: Oregon, Washington, and Montana. Physician-assisted dying does not remove the current obstacle that cryonics procedures can only be started after legal pronouncement of death but it can bring the timing of death (and thus of standby) under the patient’s control. Utilizing such laws can also greatly reduce the agonal phase of dying and its associated risk of damage to the brain.

The legal requirements for utilizing physician-assisted suicide can vary among states but, as a general rule, require that a patient has been diagnosed with a terminal illness with no more than six months to live, that the patient is of sound mind, and that the request is made in written form and witnessed. The State of Oregon has a residency requirement to discourage physician-assisted dying tourism.

Since cryonics procedures are performed after legal death, there is no reason why cryonics patients are exempt from utilizing these laws. Despite rumors to the contrary, there is no evidence that utilization of these laws require mandatory autopsy. After all, the cause of death in physician-assisted dying is clear; self- administration of the lethal drug. To avoid any possible accusations that cryonics organizations encourage the use of such laws, it is recommended that no person associated with the cryonics organization should be a witness, let alone be the physician that prescribes the lethal drugs.

Sudden death and autopsy

One of the worst things that can happen to a cryonics member is sudden death. Especially when the patient is young with no prior heart conditions, an autopsy is almost guaranteed. There is little one can do to avoid sudden death aside from choosing a lifestyle that reduces cardiovascular pathologies. The only preparation for dealing with sudden death is to become a religious objector to autopsy. Some states (including California, Maryland, New Jersey, New York and Ohio) have executed laws to restrict the power of the state to demand an autopsy. Although exceptions can still be made in cases of homicide or public health there is little to lose in using such provisions. The websites of Alcor and CI have links to the relevant forms to execute. The Venturists are offering a card for their members stating that they object to autopsy. This card can be requested from Michael Perry (mike@alcor.org) at Alcor. An example of such a card is provided below.

Sudden cardiac death is not the only reason for ordering an autopsy. An autopsy is typically ordered if there are criminal suspicions (homicide) or suicide. There is also a greater risk of autopsy when a patient dies in absence of other people. Since many old cryonicists are single and spent a lot of time alone they are also at an increased risk for autopsy. This is another good argument to remain involved with local cryonics groups and in frequent contact with other cryonicists.

If autopsy cannot be avoided it is important that the cryonics organization is notified promptly. Cryonics organizations can make another attempt to persuade the authorities to abstain from an autopsy or to request a non-invasive autopsy that exempts and protects the brain. The cryonics organization can also issue instructions for how the patient should be maintained prior, during and after autopsy. It might be worthwhile to generate a template of general autopsy instructions for cryonics patients. Such a document may not be binding but it could be useful in limiting the amount of ischemia and injury.

The dying phase and Advance Directives

Most cryonics members have a basic understanding of the importance of time and temperature to protect a cryonics patient after legal pronouncement of death. Fewer people recognize the effect of the dying process itself on the outcome of a cryonics case. In best case scenarios (physician-assisted dying, withdrawal of ventilation) the dying phase is relatively rapid while in worst case scenarios extensive ischemic injury to the brain is possible. Little work has been done to outline recommendations for the terminally ill cryonics patient. One of the main objectives of this article is to recognize that cryonics members could benefit from a general template that can be used in their Advance Directives and to guide surrogate decision makers.

At this point it is useful to briefly describe how the dying phase itself can affect the outcome of cryonics procedures (for a more detailed treatment see the appendix at the end of this article). A useful distinction is that between terminal illness and the agonal period. A patient is classified as terminal when medical professionals establish that the patient cannot be treated with contemporary medical technologies. During this period the patient is usually still of sound mind and able to breathe and take fluids on his/her own. Unless the patient has suffered an insult to the brain or a brain tumor, there is no risk for ischemic injury to the brain yet. At some point, however, the body’s defense mechanisms will be overwhelmed by the patient’s disease and the patient enters the agonal phase. The agonal phase, or active dying phase, can be characterized as a form of general exhaustion. The body is still fighting but with decreasing success and efficiency. One of the biggest concerns for cryonics patients is the development of (focal) brain ischemia while the (core) body is still mounting its defense.

It would be impossible to design an Advance Directives template that is optimal for all cryonics patients, but there are a number of general guidelines that can inform such a document:

* All health care decisions should be guided by the objective of preserving the identity of the patient throughout the terminal and dying phase.

* Measures to prolong dying should only be initiated or accepted if they result in less ischemic injury to the brain.

* Life-sustaining measures should be withheld in case of traumatic or ischemic insults to the brain.

To ensure that sensible decisions are made in situations that are not covered by these Advance Directives, a Health Care Proxy can be executed that designates a person to make those decisions. It is understandable to give such power to the person closest to you but in the case of cryonics it is recommended that this responsibility should be given to a person with a strong commitment to your desires and a detailed understanding of the medical needs of cryonics patients.

Pre-medication of cryonics patients

If a critically ill cryonics member is at risk of ischemic brain injury during the dying phase it stands to reason that some palliative treatment options are better than others. One possibility for cryonics patients is to specify such options in one’s Advance Directives. Another scenario in which pre-medication is possible is where the medical surrogate is strongly supportive of such measures. It should be noted that such a decision rests solely with the member or his/her medical representative. Cryonics organizations should not be involved in the pre-mortem treatment of the patient.

There are two important questions about pre-medication of cryonics patients:

1. Is it safe?

2. Is it beneficial?

The answer to the first question has a lot to do with the status of the pharmaceutical agents in question. For example, a supplement like melatonin is less controversial than a prescription drug like heparin. The most important thing to keep in mind is that drugs that may be beneficial after legal pronouncement of death could have adverse effects in critically ill patients. Good examples are drugs that have effects on blood rheology and clotting. One would rather forego the hypothetical benefit of a drug if there is a non-trivial change of triggering major controversies about drugs taken during the dying phase. This leaves only certain supplements as relatively safe options for pre-medication of cryonics patients.

The answer to the second question is not clear. The rationale behind pre-medication is that it can protect the brain during agonal shock and its associated ischemic events. Evidence for this belief is usually found in the peer reviewed literature on neuroprotection in ischemia. However, there is a clear difference between the administration of neuroprotective agents during the dying phase and the administration of neuroprotective agents prior to artificially-induced acute ischemia. One perspective is that such agents are beneficial but only delay the ischemic phase of the dying period. In this case supplements have little neuroprotective effect. An alternative perspective is one where such supplements do not alter the agonal course as such but provide more robust protection after circulatory arrest. Obviously, this matter is not of concern to conventional medicine so there is little evidence to make rational decisions. In light of the previous discussion, the current (tentative) verdict should be that a case can be made for pre-administration of neuroprotective agents but that these agents should be confined to “safe” supplements like melatonin, Vitamin E and curcumin. Whether such a regime would be beneficial needs to be decided on a case by case basis and is, therefore, more in the domain of the Health Care Proxy than Advance Directives.

Do Not Resuscitate Orders

Do Not Resuscitate (DNR) orders present one of the most challenging issues for cryonics optimization. On the one hand, we would like to benefit from any attempt to resuscitate us in case of sudden cardiac arrest (or any other acute events that can lead to death). On the other hand, we would not like to be subject to endless rounds of futile resuscitation attempts that can damage the brain.

One would be inclined to think that resuscitation attempts should be made in case of sudden insults or during surgery but that no resuscitation attempts should be made during terminal illness. In reality things are not that simple. For example, resuscitation may be possible after 8 minutes of cardiac arrest but the patient can suffer severe brain damage as a consequence. Such a scenario can be minimized by executing a DNR at the cost of foregoing any resuscitation attempts at all. Would this outweigh the benefits of successful resuscitation attempts? It is hard to see how an objective answer to this question can be given without taking a specific person’s views on risk and treatment into account. One way to mitigate this dilemma is to make a distinction in your Advance Directives between pre-arrest emergencies (for example, resuscitation should be permitted in the case of labored breathing but presence of heart beat) and full arrest. An in-hospital situation where resuscitation of a critically ill patient would be helpful would be where it would allow a cryonics standby team to deploy at the bedside of the patient. As can be seen from these examples, good resuscitation instructions for cryonics patients require a lot of attention to context. Because confusion could arise whether Advance Directives would include pre-hospital emergency procedures it is recommended to execute an explicit document if you want these cases to be covered – such a document could be complemented by wearing a bracelet.

Creating a general template

This article has identified a number of important medico-legal issues that need to be addressed by cryonicists to optimize their cryopreservation. It has become clear that in the case of many topics we would all benefit from uniform and effective language. The next step is to translate the concerns discussed in this document in clear legal language so that templates can be offered to all members of cryonics organizations to draft their own Living Will and Advance Directives. One potential problem of such a general template is that it may not conform to state regulations and needs additional tweaking to make it valid in the state where the person lives.

——————————————————————————————–

Appendix :  Neurological damage during the dying phase

Securing viability of the brain by contemporary criteria is the most important objective of cryonics standby and stabilization. Recognition of how pathological events in the central nervous system can defeat this objective is of great importance. As a general rule, the risk for increased brain damage is higher during slow dying. For example, when the ventilator is removed from the patient who is not able to breathe on his own the time between this action and circulatory arrest can be short. Conversely, when a patient is going through a prolonged terminal and agonal phase (regional) injury to the brain can occur while the body itself is still fighting for its survival.

The human brain has little storage of excess energy. As a result, hypoxia causes the brain to deplete its oxygen reserves within 30 seconds. The energy depletion that follows cerebral hypoxia during the dying phase has a number of distinct effects: 1) excitation or depression of certain processes in the brain, 2) alteration in the maintenance of structural integrity of tissues and cells, and 3) alteration of neuromediator synthesis and release. The depletion of oxygen leads to a switch from aerobic to anaerobic energy production. As a consequence, there is an increase in the metabolic end-products of glycolysis such as lactic acid which decreases pH in the brain. After 5 minutes no useful energy sources remain in the brain, which can explain why the limit for conventional resuscitation without neurological deficits is put at 5 minutes as well. Because the dying phase leads to progressively worse hypotension and hypoxia the metabolic state of the brain after the agonal phase is worse than if there would have been sudden cardiac arrest.

Light microscopic changes have been observed in brain cells after 5 minutes of ischemia. Prolonged hypotension, as can occur in the agonal patient, can lead to the appearance of “ghost cells” and disappearance of nerve cells. Such observations provide evidence that structural changes, including cell death, can occur prior to clinical death. Another manifestation of hypoxia (or hypotension) is the progressive development of cerebral edema. The resulting narrowing of vessels and decrease of intercellular space can, in turn, aggravate energy delivery to tissues. Of particular importance for cryonics stabilization procedures is the development of no-reflow which can prevent complete restoration of perfusion to parts of the brain during cardiopulmonary support. There is no consensus as to whether no-reflow can occur as a result of prolonged hypotension (as opposed to complete cessation of blood flow), but an extended dying phase can set the stage for cerebral perfusion impairment after circulatory arrest.

The central nervous system does not shut down at once. Throughout the terminal and agonal phase alternations in the brain progress from minor changes in awareness and perception to deep coma. As a general rule, more recent and complex functions of the brain disappear earlier than the most basic functions of the brain. The uneven brain response to hypoxia may reflect different energy requirements, biochemical and structural differences, and/or the activation of protective mechanisms to preserve the “core” functions of the brain. The CA1 region of the hippocampus has been demonstrated to be uniquely vulnerable to ischemia. This presents a problem for contemporary cryonics since the objective of human cryopreservation is to preserve identity-relevant information in the brain.

This article is a slightly revised version of a paper that was submitted for the 4th Asset Preservation Meeting near Gloucester, Massachusetts.

Posted in Cryonics, Death, Health, Neuroscience | Tagged , , , , , , , , , , , , | Comments Off

Neural cryobiology and the legal recognition of cryonics

It has been said that if you want to persuade someone, you need to find common ground. But one of the defining characteristics of cryonics is that proponents and opponents cannot even seem to agree on the criteria that should be employed in discussing cryonics. The cryonics skeptic will argue that the idea of cryonics is dead on arrival because cryonics patients are dead. The response of the cryonics advocate is that death is not a state but a process and there is good reason to believe that a person who is considered dead today may not be considered dead by a future physician. In essence, the cryonics advocate is arguing that his skeptical opponent would agree with him if he would just embrace his conception of death….

Cryonicists have named their favorite conception of death “information-theoretic death.” In a nutshell, a person is said to be dead in the information-theoretic sense of the word if no future technologies are capable of inferring the original state of the brain that encodes the person’s memories and identity. There are a lot of good things to be said about substituting this more rigorous criterion of death for our current definitions of death. However, in this brief paper I will argue that our best response does not necessarily need to depend on skeptics embracing such alternative definitions of death and that we may be able to argue that opponents of cryonics should support legal protection for cryonics patients or risk contradicting conventional definitions of death.

In contemporary medicine, death can be pronounced using two distinct criteria; cardiorespiratory arrest or brain death. A lot of ink has been spilled over the co-existence of those criteria and its bioethical implications but I think that most people would agree that the practice of medicine requires this kind of flexibility. What is interesting for us is that clinical brain death (or brain stem death) is defined as “the stage at which all functions of the brain have permanently and irreversibly ceased.” There are a number of ways how such a diagnosis can be made, but in this context I want to focus on the absence of organized electrical activity in the brain.

We first should note the use of the word “irreversible.” After all, if a patient is cooled down to a low core temperature to permit complicated neurosurgical procedures most of us would not say that this person is “temporarily brain dead.” As a matter of fact, one could argue that cryonics is just an experimental extension of clinical hypothermic circulatory arrest in which there is a temporal separation of stabilization and treatment. Now, we could argue that what may be irreversible by today’s standards may not be irreversible by future standards but then, again, we are trying to persuade the other person to accept our view of future medicine. It would be much better, and I hope much easier, to argue that contemporary cryopreservation techniques can preserve organized electrical activity in the brain. The advantage of this approach is obvious. Instead of arguing in favor of our own criterion of death we can argue that, according to mainstream criteria for determination of death, cryonics patients are not dead. This is an interesting case in which a scientist (i.e., a cryobiologist) may be able to make a major contribution to the legal recognition and protection of cryonics patients.

So where are we standing right now? How good are our preservation techniques? If we aim for reversible whole brain cryopreservation a cryoprotective agent should have two properties: (1) elimination of ice formation, and (2) negligible toxicity. In the early days of cryonics, we were not able to satisfy both criteria at once. Using just a little bit of glycerol would not be toxic but it would still allow massive ice formation. Using a lot of a strong glass former such as DMSO would eliminate ice formation but at the price of severe toxicity. Mostly due to the groundbreaking work of cryobiologists Gregory Fahy and Brian Wowk, in the year 2000 the Alcor Life Extension Foundation introduced a vitrification agent called B2C that eliminated ice formation and had a more favorable toxicity profile. In the year 2005, the separation between the state of the art in experimental cryobiology and cryonics practice was further narrowed when Alcor introduced M22 as their new vitrification agent. M22 is the least toxic vitrification agent in the academic cryobiology literature that permits vitrification of complex mammalian organs at a realistic cooling rate.

M22 and other solutions derived from the same cryobiological principles have been validated in the brain as well. Former Cryonics Institute researcher Yuri Pichugin and collaborators used a related vitrification solution for the preservation of rat hippocampal brain slices without loss of viability after vitrification and rewarming. At a cryonics conference in 2007, 21st Century Medicine announced that the use of M22-based solutions permitted the maintenance of organized electrical activity in rabbit brain slices. So, at this stage we can argue that our existing vitrification solutions have a reasonable chance of maintaining organized electrical activity in brain slices. The next challenge is to demonstrate this property in whole brains.

Whole brain cryopreservation is not just the cryopreservation of a great number of individual brain slices. Brain slices can be cryopreserved by (step-wise) immersion in the vitrification solution. Vitrification of whole brains (even small brains such as rodent brains) requires the introduction of the vitrification solution through the circulatory system. This aspect of whole brain vitrification presents a number of technical challenges. Electron micrographs of vitrified tissue from whole brains, however, indicate that these challenges can be overcome. The current research objective is to perfect perfusion techniques and optimize vitrification solutions to maintain organized electrical activity in whole brains. We know that this objective is possible in principle because the famous surgeon Robert White demonstrated retention of electrical activity in whole isolated brains after cooling them to ~2-3°C. Isolated brain perfusion is a complicated surgical procedure, but the current writer and cryobiologist Brian Wowk have recognized that validation of whole brain activity is also feasible in situ.

Reversible cryopreservation of the whole brain without losing organized electrical activity is not a trivial research objective but it should be easier to achieve than reversible cryopreservation of the whole body and, perhaps, some other organs. If and when we accomplish this, we will no longer be dependent on “rationalist” arguments that appeal to logic and optimism about the future. We can argue that our patients should not be considered dead by the most rigorous criterion for determination of death in current medical practice. We can then even mount some smart legal challenges to seek better protection for cryonics patients. If we can make this step forward we should also aim at improved protection of existing cryonics patients, which will allow them, among other things, to own assets and bank accounts. This is how science can be employed in legal strategies for asset preservation.

This article is a slightly revised version of a paper that accompanied a recent presentation on neural cryobiology and the legal recognition of  cryonics at the 5th Asset Preservation Meeting in Benicia, California.

Posted in Cryonics, Death, Neuroscience | Tagged , , , , , , , , , , , , | Comments Off

Comments on the book YOUNIVERSE by Robert Ettinger

Robert Ettinger‘s book Youniverse: Toward a Self-Centered Philosophy of Immortalism and Cryonics is a book containing many insights and deep thoughts, yet has such an informal writing style that many readers might not take it seriously. I know of no other work of philosophy in which the author begins a sentence with “Anyway,”. Ettinger writes that the first cryonics-related organization was founded “in 1962 or 1963, I forget which”, then says “Why don’t I look it up?” and justifies himself by reference to a Woody Allen movie. This is not the kind of writing one expects from a philosophy treatise.

Ettinger may not take himself too seriously, but he is even more dismissive of most of the world’s foremost philosophers and religious figures. The writings of Aristotle are called “ramblings”. In describing William James’s statement that James was only able to understand Hegel while under the influence of nitrous oxide, Ettinger notes how appropriate it is that nitrous oxide is also called laughing gas. Ettinger wrote that “Rousseau has been extravagantly praised, and not only by himself”, but dismisses Rousseau as unoriginal, incoherent, not profound, and frequently wrong. Ettinger describes the philosopher G.E. Moore as being “definitely confused as well as confusing, abounding in contradictions and non-sequiturs, sometimes substituting assertions for arguments.” Ettinger often seems himself guilty of the last accusation. He faults Isaac Asimov for the “absurdity” that without the “saving grace of death” the rigid views of the old would prevent further progress — but leaves a critique of Asimov’s argument “as an exercise for the reader”. Ettinger writes that “Paeans of praise have poured from the pens of platoons of panting pundits” concerning Godel’s Incompleteness theorem, which he dismisses as a linguistic trick associated with the failure of physics to correspond identically with formal (mathematical) systems. By finding the quote from Wittgenstein “I don’t know why we are here, but I am pretty sure that it is not in order to enjoy ourselves”, Ettinger has massively deflated my respect for the philosopher Ludwig Wittgenstein. Ettinger describes the modern “self-styled bioethicist” as a “new type of vermin or parasite” whose major accomplishment has been to create “the illusion of looking down on people far above them.”

Ettinger wrote that “fear of God” is generally really fear of parents, neighbors, and a lifetime of conditioning. He says people too readily submit to tradition rather than use reason. To be “normal” is to have the same delusions as the neighbors. He says loyalty “is frequently a worthy habit”, but sometimes nothing more than an unjustified habit. Ettinger says faith is arrogant certainty in the absence of evidence, which ultimately “boils down to sacrificing your integrity for a bit of comfort”. To Ettinger it is obvious that non-human animals have consciousness and feelings, and that a God that disregarded the suffering of animals on the grounds that animals have no soul “would have less compassion than the average human”. Like many physicists, Ettinger seems accepting of the idea that time and the universe began with the Big Bang, but wonders where God would be before He created time and the universe. Ettinger can make no sense of an omniscient, omnipotent God creating people who need to live their lives to prove whether they deserve Heaven or Hell. Ettinger says that a benevolent God would forgive the skeptics, who should therefore have no reason to compromise their integrity and disbelief.

Ettinger’s irreverence extends to the legal system. Frequent use of appeals courts and split decisions in the Supreme Court are given as evidence that laws are unclear or that bias is pervasive. He describes juries as “ignorant, stupid and readily swayed by irrelevancies and by histrionics”. In connection with the adversarial system, Ettinger wrote “All lawyers are frightening, and specialty litigators are terrifying. Some firms are said to keep their lead litigators chained in a tower room and fed raw meat until needed.” I asked Mr. Ettinger what his beloved son (a lead litigator at a prestigious law firm) had to say about the law chapter, but I got no definitive response.

As the book title YOUNIVERSE implies, Ettinger believes that “me-first” and “feel-good” are the only possible basis for conscious motivation. He also states that a person ought to want whatever will maximize future “feel-good”, and that people do not always want what they ought to want. Ettinger believes that “figuring out what we ought to want is the primary problem of philosophy”. He says that a main aim of YOUNIVERSE is to debunk the views that values are arbitrary or externally given.

Ettinger challenges the claim of David Hume that “You can’t derive an ‘ought’ from an ‘is’”, and — like Ayn Rand with her Objectivist Ethics — he does so by reference to values being rooted in biology. Ettinger disparagingly dismisses Rand’s views as narcissism, “me generation”, and “looking out for number one” without explaining how this differs from “me-first”. Rooted in biology, Rand makes survival the basis of her ethics, rather than “feel-good”. Ironically, Ettinger writes more approvingly of Nietzsche’s self-centeredness, although Ettinger faults Nietzsche’s belief in the importance of power over other people as a core value. (Ettinger notes that Nietzsche believed Russians and Jews, rather than Germans, would be the “master races” of Europe.)

I disagree with the arguments of Rand and Ettinger for deriving “ought” from biology. Biology dictates that animals value food and water, but many humans have committed suicide by refusing food and water. To assert that such people are “wrong” and did not do what they ought to have done would be attempting to externally impose values upon them. Ettinger could argue that such people were acting in such a way as to maximize their satisfaction — “me-first” and “feel-good” (he gives the examples of a woman rushing into a burning building to save her baby, or “saints” who gain personal satisfaction from ascetic service to others). But by that argument they were wanting what they ought to want. The point Ettinger seems to be making is that people should not allow others to impose their values upon them — should not be driven by guilt, social pressure, the need to conform. But if people are driven by these motives, they are nonetheless still maximizing their satisfaction. Ettinger might say that such people are acting without integrity by not being true to themselves, but why should people be blamed for valuing the opinions of others and for this being important to them? If it is “impossible to be motivated by anything other than self interest, because motivation means what is important to the self”, then the word “ought” is inappropriate. If “me-first” and “feel-good” are the only possible bases for conscious motivation, then the word “ought” is inappropriate. The only reason that people fail to want what they ought to want is because of matters of fact, not matters of value — people failing to appreciate the consequences of their actions in the context of their values.

The issue of determinism and free will is a subject about which I have thought, read, and written about considerably (see A Case for Free Will AND Determinism ), yet I found Ettinger’s chapter on this subject impressively thoughtful and informative. I mostly agree with Ettinger’s views, about which we are both very much in the minority. I won’t say much about the issues or insights I gained in the determinism chapter, but I will comment on how he applies determinism to cryonics. Ettinger notes that “determinism is very nearly equivalent to” conservation of information, which implies that any human who ever lived could be reconstructed without having been cryonically preserved — except that there may never be adequate computing power.

Although I can conceive of retaining my personal identity in the total absence of any memories that I have, I nonetheless find the idea hard to relate-to. I am even less comfortable about the idea that the essence of my personal identity is feeling. Ettinger has firmer opinions on these subjects than I do, but I sense that his emphasis on feeling as the essence of personal identity contradicts his admonishments about the use of reason against intuition, tradition, and conditioning.

Ettinger skims over the subject of ischemic damage in cryonics, and I think he is wrong to say that “cryothermic damage will in most cases be the most difficult to reverse”. Freezing damage is like broken pieces that are nonetheless intact, whereas ischemic damage is like dissolution or decomposition of structure. Nonetheless, I cannot quantify my argument in terms of “most cases”. I think Ettinger is wrong to cling to the word “immortality” as meaning “indefinitely extended life” when its literal meaning is “eternal life”. His use of the word “immortality” presents cryonics as an alternative to religion rather than an extension of medicine.

Although Ettinger acknowledges that death will mean an end to suffering, he sees a number of disadvantages, including
“…it’s hard to enjoy life when you’re dead.
…daisies are prettier when viewed from above.
…you can only vote in Chicago.
…you need extra strength deodorant.”
But mainly, “Life is better than death because it is more interesting.” (For my own views on the subject, see: Why Life Extension?)

In his lifetime of reading Ettinger has collected numerous notable quotes, and these gems are liberally sprinkled throughout YOUNIVERSE. Some of my favorites include “‘Love thy neighbor as thyself’ presupposes that you love yourself” (Miguel de Unamuno), “The greatest part of our happiness depends on our disposition, not our circumstances” (Martha Washington), and Will Rogers’s WWII suggestion for getting rid of German U-boats: “Boil the Atlantic Ocean. How do we do that? Hey, I’m just an idea man, I leave the details to the engineers.”

Ettinger also has a chapter called “Misunderstandings” which deals with his insights into a wide variety of subjects. Indicative of my “anti-intellectual” bias, is the fact that my favorite is Ettinger’s observation that torque (force X lever arm length) has identical units to work (newton-meters), despite the fact that work and torque are completely different. He offers no solution or explanation, however.

A consequence of Ettinger’s informal writing style is that there is much autobiographical material throughout YOUNIVERSE. But the last formal chapter (I am not counting the Appendix) is explicitly autobiographical. He says “I have perhaps a few thousand admirers, hardly any of whom give me much thought or attention”. Ettinger speaks of his loneliness in having experienced the loss of all his friends and family of his generation, and that there is nobody left whom he wants to impress. Indicative of Ettinger’s world-weariness is his quote of a comment made by his brother that all of life is “killing time and amusing oneself while waiting to die”.

Ettinger’s final comments concern his plan to have a pre-mortem “jolly wake” with music, speakers, toasts, and other festivities prior to a suicide intended to improve the conditions of his cryonic preservation. Ettinger notes earlier in the book that “many people are more afraid of seeming cowardly than of facing danger”, which is why suicide with an audience of friends and family would boost his courage. The last line of the chapter reads “If I never wake up, my last experience will have been better than most — a very brief comfort, to be sure.”

Although there are some cryonicists who believe that Robert Ettinger would be the perfect cryonicist to win sympathy for voluntary self-euthanasia to improve cryopreservation, I am not one of them. How can you justify voluntary euthanasia in a non-terminal person when there is no way of knowing how many years of life that person could be expected to live? How can you justify voluntary euthanasia for ANYONE not suffering from a terminal disease, or expect the public to be sympathetic to voluntary self-euthanasia under these conditions? Even for terminal cryonics patients, I would not be to eager to see a public association of cryonics with self-euthanasia or physician-assisted suicide. Cryonicists would be accused of taking advantage of mentally-compliant sick and elderly people for monetary reasons, which would lead to even more cryonics-unfriendly legislation.

And there are practical problems, not the least of which is the danger of autopsy. Many cryonicists, myself included, cling to life tenaciously — much more tenaciously than the average person. I would find it very difficult to euthanize myself or have myself euthanized. The ideal situation is when death is nearly certain to occur within a week. But this is the condition in which standbys are typically initiated, not the condition in which standbys fail to occur. Heart attack is a common cause of death, and this is most often unexpected. Most cryonicists who receive standby are people dying of cancer, and whose slide toward death is along a more predictable path. The ability of cancer victims to euthanize themselves would make the standby process easier, but that would have no effect on reducing the number of cryonicists who deanimate without standby, despite having arranged for standby. There are no convincing arguments that simplifying self-euthanasia or physician-assisted suicide will lead to the majority of cryonics cases having greatly improved cryopreservation by significantly reducing the number of cryonicists deanimating under unfavorable conditions.

Posted in Cryonics | Tagged , , , , , , , , | Comments Off

The case against cryonics

What is striking about cryonics is that those who have taken serious efforts to understand the arguments in favor of its technical feasibility generally endorse the idea. Those who have not made cryonics arrangements usually give non-technical arguments (anxiety about the future, loss of family and friends, etc), lack funding or life insurance, or are (self-identified) procrastinators. In contrast, those who reject cryonics are almost invariably uninformed. They do not understand what happens to cells when they freeze, they are not aware of vitrification (solidification without ice formation), they think that brain cells “disappear” five minutes after cardiac arrest, they demand proof of suspended animation as a condition for endorsing cryonics, etc.

This does not mean that no serious arguments could be presented. I can see two major technical arguments that could be made against cryonics:

1. Memory and identity are encoded in such a fragile and delicate manner that cerebral ischemia, ice formation or cryoprotectant toxicity irreversibly destroy it. Considering our limited understanding of the nature of consciousness, and the biochemical and molecular basis of memory, this cannot be ruled out. Cryonics advocates can respond to such a challenge by producing an argument that pairs our current understanding of the neuroanatomical basis of identity and memory to a cryobiological argument in order to argue that existing cryonics procedures are expected to preserve it. An excellent, knowledgeable, response of this kind is offered in Mike Darwin’s Does Personal Identity Survive Cryopreservation? Cryonics skeptics in turn could produce evidence that existing cryonics procedures fall short of this goal.

2. The cell repair technologies that are required for cryonics are not technically feasible. This argument should be presented with care and rigor because the general argument that cell repair technologies as such are not possible contradicts existing biology. A distinct difference from the first argument is that it is harder, if not impossible, to use existing empirical evidence to settle this issue. After all, making cryonics arrangements is a form of decision making under uncertainty and such decisions are not straightforwardly “correct” or “incorrect,” “right” or “wrong.” What can be done is to provide a detailed scientific exposition of the nature and scope of the the kind of repairs that are necessary for meaningful resuscitation and to argue that both biological and mechanical cell repair technologies are not conceivable – or are conceivable.

One thing that becomes immediately clear from this exercise is that there is no single answer to the question of whether cryonics can work because the answer to this question depends on the conditions and technologies that prevail during the cryopreservation of a patient. This introduces a set of more subtle distinctions concerning the question of what kind of cryonics should be assessed. It also produces an argument in favor of continuous improvement of cryonics technologies, and standby and stabilization services.

This short examination of technical arguments that could be made against cryonics gives advocates of the practice two talking points in discussion with skeptics or hostile critics:

(a) If a critic flat-out denies that cryonics is technically feasible, it is not unreasonable to ask him/her to be specific about what (s)he means by cryonics. This simple question often will reveal a poor understanding of existing cryonics technologies and procedures.

(b) A decision made on the basis of incomplete knowledge cannot be “right” or “wrong” and should be respected as one’s best efforts to deal with uncertainty.

Posted in Cryonics, Neuroscience | Tagged , , , , , , , , , | Comments Off

The Future of Aging: Pathways to Human Life Extension

This book review was originally published in Cryonics magazine, 1st Quarter, 2011.

Editor-in-chief, cryobiologist, and aging researcher Gregory M. Fahy and his associate editors Michael D. West, L. Stephen Cole and Steven B. Harris have compiled what might be the most impressive collection of articles on interventive gerontology to date in their 866 page collection The Future of Aging: Pathways to Human Life Extension. The book is divided into 2 parts. The first part includes general, scientific, social and philosophical perspectives on life extension. The second part is a collection of proposed interventions, which are organized in chronological order, starting with the (projected) earliest interventions first. Of course, such an organization of the materials necessitates a subjective estimation of when such technologies will be available and is bound to be controversial. The collection closes with a number of appendices about contemporary anti-aging funding and projects (SENS, Manhattan Beach Project).

I have read the book with the following two questions in mind:

1.     Which approaches for increasing the maximum life span show clear near-term potential?

2.     Is meaningful rejuvenation possible without advanced cell repair technologies?

What follows are my comments on selected chapters of the book.

I cannot say that I am a big fan of Ray Kurzweil’s work. His general introduction to life extension, “Bridges to Life,” co-written with Terry Grossman, starts out on a restrained note, discussing the benefits of caloric restriction, exercise, basic supplementation, and predictive genomics. But it then ratchets up into bold claims about the future that rest on controversial premises: about biology and health following the same path as information technology; about the technical feasibility of molecular nanotechnology; and about the nature of mind. One thing that remains a mystery to me is how such an accelerating pace of anti-aging technologies could be validated considering the relatively long life expectancy of humans. Presumably we are expected to adopt a lot of these technologies based on their theoretical merits, success in animal studies, or short-term effects in humans.

Associate Editor Stephen Cole contributes a chapter on the ethical basis for using human embryonic stem cells. I suspect that his argument in favor of these therapies relies on adopting a definition of personhood that has more far-reaching, and more controversial, consequences than just permitting the use of human embryonic stem cells. One of the most disconcerting aspects of the bioethical debate on stem cell research is that many of its advocates seem to feel that if they do not see an ethical case against it, government funding for such research should be permitted.  In essence, this means that opponents of embryonic stem cell research are obliged to financially support it as well. This is a recipe for further aggravating what has already become a passionate political debate.

As someone with relatively limited exposure to the biogerontology literature I should be cautious in singling out one technical contribution for high praise, but Joshua Mitteldorf’s chapter on the evolutionary origins of aging is one of the best and most inspiring articles in the field of aging research I have read and worth the hefty price of the book alone. Mitteldorf outlines a case for the theory that evolution has selected aging for its own sake and presents experimental findings that falsify other explanations for aging such as wear-and-tear and metabolic trade-offs. That aging is firmly under genetic control may appear the most pessimistic finding in terms of the prospects of halting aging but in fact allows for the manipulation of a number of selected upstream interventions that can inhibit or mitigate these programs.

It is clear from this ambitious book that cryobiologist Greg Fahy also has a strong interest in biogerontology but nothing prepared me for the encyclopedic knowledge that he displays in his lengthy chapter on the precedents for the biological control of aging. Fahy’s chapter further corroborates the view that aging is under genetic control. He also reviews a great number of beneficial mutations and interventions in animals and humans that can extend lifespan. Reading all these inspiring examples, however, I found myself faced with the same kind of despair as when reading about all the neuroprotective interventions in stroke and cardiac arrest. There is great uncertainty how such interventions would fare in humans (or other animals) and, more specific to the objective of human life extension, how we ourselves can ascertain that there are no long-term adverse consequences. Fahy does not run away from the most formidable challenge of all, rejuvenation of the brain without losing identity-critical information, but points out that identity-critical information might be retained despite the turnover and replacement of components that a meaningful life extension program for the brain would most likely require. Fortunately, people who make cryonics arrangements can feel a little better about this issue because their survival is not dependent on safe technologies becoming available in their lifetime.

Zheng Sui’s report on using high potency granulocytes to cure cancer in mice is one of the more exciting chapters in the book and a fine example of the role of chance discoveries in biomedical research (Zheng by accident discovered a mouse innately resistant to cancer). With substantial support of the Life Extension Foundation and other private donors, Sui is aggressively pursuing Leukocyte Infusion Therapy (LIFT) human trials instead of pursuing the torturous path of trying to illuminate the biochemical and molecular mechanisms that drive the successful results in mice. I should mention that a unique concern for cryonicists is that eliminating cancer in the absence of other effective anti-aging technologies could increase the likelihood of dying as result of identity-threatening insults such as cardio-vascular complications, ischemic stroke, or Alzheimer’s disease.

I must admit being somewhat disappointed in the chapter about “evolutionary nutrigenomics” by Michael Rose and his collaborators. Michael Rose has always struck me as one of the more level-headed and empirical aging researchers, and his work with fruit flies is a resounding demonstration of using evolutionary tools to investigate and combat aging. His short contribution to this book reads more as a quickly thrown together status update of their company, Genescient, than a rigorous treatment of the issues. Dispersed throughout the text are a number of interesting perspectives on alternative approaches to aging research and the validation of anti-aging interventions, but these issues are not discussed in much detail. Michael Rose’s work is of great interest, but this chapter is neither a good introduction to his work nor an in-depth treatment of the practical applications of his research.

Anthony Atala’s chapter, “Life Extension by Tissue and Organ Replacement,” is a fascinating update on the current status and potential of regenerative medicine and tissue engineering. Unlike most of the chapters in this book, the author reports a number of examples of successful clinical applications. It is a good example of how working with nature (instead of trying to improve upon it) can have meaningful near-term benefits. Unfortunately, there is no discussion of the progress in regenerative medicine for the brain. Obviously, such strategies cannot involve a simple replacement of the brain with a newly grown brain but selected repair technologies can play an important role in brain-damaging diseases and insults. The inclusion of “life extension” in the chapter title seems somewhat artificial to me because there is no distinct treatment about how tissue and organ replacement will be expected to contribute to life extension. Additionally, there is little discussion of contemporary artificial and mechanical alternatives to organs (or biological structural components) in this chapter, or in any other chapters in the book, which I think is a minor oversight.

Robert J. Shmookler Reis and Joan E. McEwen contribute a chapter about identifying genes that can extend longevity. Their discussion of the prospects for mammals includes the sobering observation that “many of the gains we can attain by a single mutation in the simpler organism may already have been incorporated in the course of achieving our present longevities.” Then again, unless aging is firmly under genetic control in simple organisms but the result of wear and tear in humans there should be (unique) approaches in humans that should confer similar benefits as well.

The publication of this book came to my attention when I learned about Robert Freitas’s contribution, “Comprehensive Nanorobotic Control of Human Morbidity (PDF),” so I was quite interested in reading this final chapter of the book. I am not qualified to comment on the technical aspects of his vision of nanotechnology. I think it is fair to say, though, that if resuscitation of cryonics patients is possible they will most likely be resuscitated in a future that has nanomedical capabilities resembling those that are outlined in this chapter. For this reason alone, this chapter should be of great interest to readers of this magazine. Of particular interest is the discussion of cell repair technologies and brain rejuvenation, a topic of great interest to cryonics. Freitas devotes considerable space discussing how anti-aging strategies like SENS can be achieved with medical nanorobots but the chapter falls short of offering a distinct exposition of a nanomedical approach to aging and rejuvenation. With such profound molecular capabilities one would think that such an approach would not just consist of updating existing biotechnological approaches to eliminate aging related damage with more powerful tools. I think that the distinct capabilities that molecular technologies have to offer would have benefitted from a more extensive discussion of their transformative capabilities. In particular, the section on nanorobot-medicated rejuvenation could have benefitted from a more rigorous treatment of the question of how these interventions would produce actual rejuvenation. Rejuvenation will be a practical requirement for most cryonics patients and it would be interesting to see a more detailed technical discussion of this topic.

Robert Freitas introduces the phrase NENS (Nanomedically Engineered Negligible Senescence) for his vision of how the goals of SENS can be achieved through nanomedicine. This raises an important question: is there any reason to believe that the timeline for “conventional” SENS will be different from the timeline for mature molecular medicine? It is hard to tell, but one could argue that the development of mature nanotechnology is more comprehensive than any strategies designed to deal with the causes or effects of the aging process. So why not just fund the work of biological and mechanical molecular nanotechnologists to accelerate meaningful re-design of the human organism? I think that the best answer is that our current state of knowledge does not justify giving a privileged position to any particular approach and having these visions of the future compete may be the best hope that we have for seeing meaningful rejuvenation and the resuscitation of cryonics patients in the future.

If there is one serious omission in this impressive collection of articles it is a more comprehensive chapter on the topic of biomarkers of aging in humans. As reiterated throughout this review, the gold standard and most rigorous determination of the efficacy of anti-aging therapies and interventions is to empirically determine whether they increase maximum human lifespan. For obvious reasons, most medical professionals and healthcare consumers are pressed to make decisions based on less rigorous criteria and the development of a set of reliable biomarkers of aging is highly desirable. Of course, the most rigorous case for successful biomarkers would require the same kind of long-term studies, leading to an infinite regress problem. How to break out of this predicament while retaining a framework to make rational decisions about life extension technologies is not a trivial problem and can be the topic of a whole new volume of articles. Interestingly enough, one of the most insightful perspectives on this issue is given in Appendix A by SENS researcher Michael Rae when he points out that therapies aimed at rejuvenation can be tested at much more rapid timescales than therapies to retard the aging process or increase the maximum lifespan.

Michael Rae also notes that SENS’s “engineering heuristic” is well established in other fields of biomedicine. It is certainly the case that aging research could benefit from a stronger emphasis on solving problems and repairing damage instead of completely trying to understand the underlying pathologies but it also needs to be pointed out that the engineering approach has not fared much better in areas of research that are notoriously resistant to effective solutions such as neuroprotection in stroke. Ultimately, the SENS approach cannot completely escape studying the mechanisms and metabolic pathways involved when treatments are compared and side-effects are studied. In this sense, the difference between SENS and alternative approaches is a matter of degree, not principle.

I think that the editors are justified in claiming that the prospects for solving the aging challenge have never looked better. A close inspection of all the chapters, however, shows that no significant interventions in the aging process in humans are available now, and I doubt they will become available in the near future. And even if the aging process can be eliminated, there will still be medical conditions and accidents that require placing a person in cryostasis until effective treatment is available. For the foreseeable future there is good reason to agree with Thomas Donaldson’s advice* that making cryonics arrangements is the most fundamental and sensible decision one can make in order to reap the benefits of powerful future life extension therapies.

*Thomas Donaldson – Why Cryonics Will Probably Help You More Than Antiaging, Physical Immortality 2(4) 28-29 (4th Q 2004)


Posted in Rejuvenation, Science | Tagged , , , , , , , , , , , , , , | Comments Off

Case reports in cryonics

This article was originally published in Cryonics magazine, 4th Quarter, 2010.

Introduction

The most important reasons for writing case reports are:

1. To provide a transparent and detailed description of procedures and techniques for members of the cryonics organization and the general public. A cryonics organization that never writes anything about its cases and procedures should be treated with more caution than an organization that does.

2. To validate current protocol and procedures in general, and its actual implementation in particular. A case report should not only record what happened but should be used for guidance as to what should happen in the future. A detailed case report, especially when a variety of physiological data has been collected, contains a wealth of information that can be analyzed for the team members’ and patient’s benefit. Cryonics cases are relatively rare (compared with other medical procedures), so we should try to learn as much as we can from the cases we perform.

3. To serve as a medical record to assist with future attempts to revive the patient. Although advanced future medical technologies may make it possible to determine the physiological condition of the patient down to the molecular level, it is important to provide as much medical information as possible to help in efforts to revive patients. Having a detailed record of the patient’s condition prior to pronouncement, subsequent stabilization, and cryoprotection, may also help the organization in establishing the desired sequence of revival attempts.

4. To gain more scientific credibility. If we want scientists and physicians to take us seriously, we need to convince them that we attempting to cryopreserve our patients in a scientific manner.  Professional case reports can provide this kind of credibility.

This article will mainly concern itself with the general question of how a case report can help a cryonics organization in improving protocol, techniques and skills.

Protocol

To be able to assess the quality of patient care in a cryonics case, it is important to specify what the intended protocol was prior to writing about the case. Only if we know what the organization was supposed to do will we be able to assess how successful the care was. For example, if there is no mention of collecting (and analyzing) blood gases during a case this may have been because it is currently not a part of the organization’s protocol, but it may also be the result of a shortage of skilled personnel, defective equipment, or other problems or deficiencies. Unless the writer of the report specifies what should have happened, it is difficult to assess the quality of preparation and performance. If preparation for the case was poor and there was no (functional) extracorporeal perfusion equipment available, the case report should not simply state that the organization attempted to do a

case without substituting the blood with an organ preservation solution, but also why the blood washout was not attempted.

In reality there will be many deviations between the organization’s protocol and what actually happens. Human cryopreservation cases are not controlled laboratory experiments, and as many people who have extensive experience doing cases know, unique situations present themselves, including frustrating events that are beyond the control of even the most skilled medical professional. Nevertheless, the inherent unpredictability and uniqueness of cryonics cases is too often used as an excuse or justification for failing to follow established protocol, or for serious errors and omissions in the care of the patient. Documenting the prospective protocol will help us to gain a more systematic understanding of what is possible (or essential) and within our control, versus that which is not.

Detail

The importance of writing detailed descriptions of the procedures and techniques employed during a case cannot be overestimated. This not only enables the reader to gain a comprehensive understanding of the techniques used, it also allows detailed analysis of the difficulties that were encountered during a case that would not have been noticed if there is only a brief mention of it. For example, instead of simply noting that medications were administered, providing comprehensive details is essential. There are many reasons why this is the case.

Case reports should be prepared with the possibility in mind that what may seem mysterious, or inexplicable, to the writer may be crystal clear to an expert or perceptive reader when provided with sufficient detail.

Providing as much detail as possible also serves to allow for replication of the techniques used by others. This is a critical component of the scientific method. Other investigators or practitioners must be able to duplicate the procedures and obtain the same outcome. Yet another consideration is that factors not now perceived or considered to be important may become so in the future. There are many examples of this in the history of cryonics that have proved essential to improving patient care. For example (1), in the early days of cryonics bags of ice were used to facilitate external cooling. It was not until comprehensive and consistent core cooling data were collected that it became apparent that this technique required 6-8 hours to cool a patient to ~ +20°C (room temperature!) with the patient cooling at a rate of 0.064°C/min. Documentation of these appallingly slow cooling rates provided powerful incentive to develop stirred water ice baths which increased cooling rates to between 0.15°C/min  and 0.33°C /min, allowing cooling to ~15°C within 90 minutes to 2 hours after the start of cardiopulmonary support (CPS) (see graph below).

Comparison of Cooling Methods: Above are actual cooling curves for three adult human cryopreservation patients on Thumper support, using ice bags, the Portable Ice Bath (PIB), and the PIB augmented by SCCD (squid) cooling. Patient A-1133 weighed 56.8 kg, patient A-1169 weighed 57.3 kg, and patient A-1049 weighed 36.4 kg. As this data indicates PIB cooling is approximately twice as efficient as ice bag cooling. The SCCD appears to increase the rate of cooling by an additional 50% over that of the PIB (roughly adjusting for the difference in the patients’ body mass).

This example is even more instructive because continued diligent and comprehensive monitoring of cooling in multiple patients made clear other factors that were critically important to good outcome or, conversely, prohibited it. A large-framed obese male with heavy fat cover and a large amount of thermal inertia will not cool at anywhere near the rate that an emaciated, petite woman will. Evaluating the patient for fat cover and body mass index before deanimation allows reasonably accurate prediction of the cooling rate and may suggest the need for the addition of other cooling modalities such as peritoneal lavage with chilled fluid. Favorable results from application of peritoneal cooling in turn will suggest that even greater rates of cooling are possible for all patients and lead to the addition of the modality as a standard part of the protocol.

Failure to gather and promptly analyze data as basic as cooling rate precludes realization that problems exist as well as any possibility of solving them.

It is important to note that an incomplete case report doesn’t necessarily indicate failure on the part of a cryonics organization. In a case where the number of team members is limited, all resources may have to be devoted to doing the case, instead of collecting data, or assigning an essential person to the job of taking notes. In the case of limited personnel it is better to do a good case without documentation than to document a bad case. To some degree this conflict between tasks can be avoided by having some of the team members (the team leader, paramedic, etc.) use a voice recorder with a clip-on microphone. But if the number of team members is insufficient, and data collection is not possible, this should be reported in the case report and recommendations should be made and implemented to prevent this situation from occurring again in the future. Good data acquisition and scribe work are essential for a good case report and, if feasible, should be a full-time job during a case.

Analysis

Specifying the protocol and describing the case in great detail is necessary but is not sufficient. A critical review of the information and data culminating in a list of desired changes and specific plans to address them should complement this. Ideally every discrepancy between protocol and reality that has been observed during the case should be discussed. Even in a case where stabilization started promptly after pronouncement, and the protocol was followed to the letter, there is still a lot of (physiological) data that, once analyzed, may require a change in the protocol in future cases.

To assess skills, identify critical failures, formulate solutions, and compare cases in a meaningful and valid way, a consistent and systematic format of reporting cases is essential. A typical case report should be divided into sections describing protocol, patient assessment, preparation and deployment of standby assets, the details of the case (divided in sections such as  airway management, cardiopulmonary support, external and other cooling methods, blood washout, cryoprotective perfusion, and cooling to storage temperature), analysis, recommendations, and a variety of (public or non-public) appendices. Such appendices should include time-lines and graphic presentation of data, medications, cryoprotectants, and statistical analysis and comparisons to other cases.

Each case report should not only present solutions, or suggest tests and experiments to identify solutions, but provide a plan of action as to how these things can be accomplished. One approach to ensure that research and tests to validate solutions are implemented, and appropriate remedial action is taken, is to appoint an officer in the organization who is responsible for quality assurance and quality control. This individual’s job will be to ensure that case reports are written in a manner consistent with the guidelines as outlined by the organization, as well as to ensure implementation of required changes.

Another critical role of case reports is to educate the organization’s staff as well as consultants and, where appropriate, the patients’ physicians and other health care providers about protocol, procedures and techniques. Although case reports are not and should not be a substitute for comprehensive written protocols, standard operating procedures (SOPs), and thorough training of personnel, sometimes solutions to problems can only be found in case reports where a team member was presented with an unusual problem. Consistent and systematic organization of case reports will greatly enhance the utility of case reports for this purpose. For example, if a reader wants to know about surgical techniques, and problems encountered in gaining access to the circulatory system for blood washout, consulting a case report will be far easier if they’re organized in a consistent and predictable manner.

Answering Objections

One objection to writing up a case report is that it is not a controlled experiment and at best provides only anecdotal evidence. This is not the case for the following reasons.

Not all the mistakes and issues identified are of a hypothesis testing nature. For example, if a patient presents the human cryopreservation team members with a problem that could not be managed with the equipment at hand, the cryonics organization doesn’t necessarily need a larger number of cases to decide to make a change to their equipment, and to start teaching employees the necessary skills.

Similarly, what may be perceived as anecdotal evidence for the cryonics organization may be a consistent finding in nearly identical settings in mainstream medicine. For example, some issues during a human cryopreservation case may be well known in hemodynamic management of potential organ donors in hospitals, or, for example, a medication in the protocol that is undergoing trial as a stroke therapy may demonstrate the same adverse effects observed during transport of a cryonics patient.

Of course, such lessons are impossible to learn without both broad and deep knowledge of medicine and the relevant research literature. Considering the ever growing number of publications and hyper-specialization, case reports may increasingly become collaborations between numbers of people with expertise in diverse areas. The individuals with the most valuable input do not necessarily have to be the ones who did the case. A physician dealing with similar issues in a neuro-intensive care unit may identify problems and propose solutions not obvious to those delivering cryonics care to the patient.

Monitoring

We don’t know how our patient is going to fare in the future but we can know a lot about how our patient fared up to the point of long term low temperature care if we monitor his condition continuously. This starts from collecting detailed pre-mortem medical data to monitoring fracturing events during cooldown.

It is tempting to say that a case went very well if all the steps of the protocol were followed in a timely manner. This is not unreasonable because one would expect a strong correlation between an evidence based protocol and optimal care. But it is important to keep in mind that the goal of stabilization and cryopreservation is to treat the patient and not the book (as a saying in emergency medicine goes).

Without comprehensive monitoring of the patient through all parts of the procedures a case report will only document a predictable series of mechanical steps and some crude visual indicators of (relative) success at best. The things we are really interested in, like (quantitative) end-tidal CO2 measurements, cardiac output, pH, and cerebral oxygenation, cannot be observed without sophisticated equipment.

Not only do we want to know how the patient is doing after the fact, we would also like to be able to intervene during a case if we observe a trend that suggests (alternative) treatment. Only in-depth reporting and analysis combined with a sound understanding of the physiopathology and available treatments will enable us to do so.

Presentation

A comprehensive list of dos and don’ts in writing case reports is not something that can be explored in this article, but some things are worth mentioning. Stylistically, a human cryopreservation report should resemble a medical or research report rather than a sensationalized adventure for the patient or the standby team. This should apply to the organization of the material as well as the choosing of words. As a general rule mainstream medical terminology should be used instead of cryonics jargon. Editorializing should be limited, and if perceived necessary, be moved to the proper section of the report. For example, jumping from a technical description of procedures to quarrelling among relatives or complaining about government regulation doesn’t look very professional.

Protocol, procedures and techniques should be the subject of the report, not people. Cryonics preparation and procedures are very demanding and exhausting for all people involved and mistakes are made and will be made. Errors should be presented as dispassionately as possible to avoid a culture of blame and personal conflict. Experience also teaches that (potential) participants are more open to transparent reporting if a case report will not single out individuals in describing procedures.

No matter how competent the writer of the report is, each report should be proofread by most or all individuals who were involved in the case and, if possible, a variety of outsiders with appropriate technical and medical knowledge, before it is released to the general public.

Patient Care

Writing case reports as presented in this article may be more demanding and time-consuming than generally has been done in human cryopreservation, but the results may improve patient care to a degree not previously seen.  Ultimately, the most ambitious use of case reports will be one in which the case reports are analyzed as a series, measurements are compared, and patterns are established. Reading (and evaluating) a series of case reports in a systematic manner  will even enable us to answer some very fundamental questions as to whether, or the degree to which, protocol, procedures and techniques  have improved over the years.

Providing the best patient care possible for current and future patients is the reason why cryonics organizations exist, and considering how powerful a tool a good case report can be, a responsible cryonics organization should devote considerable resources and time to writing them.

As our members and resources increase, and human cryopreservation gradually becomes a part of mainstream medicine, the successful transition from basic algorithm, volunteer driven case to evidence-based cryonics will be an important mandate.

Case reports and increasing caseload

One of the biggest challenges facing a growing cryonics organization is that the organization will be faced with a growing number of cases per year. This challenge is further amplified if all these cases need to be documented. As a consequence, a cryonics organization will find itself allocating an increasing amount of time to writing case reports and falling behind publication schedule. One of the most unfortunate responses to such a development would be to make an attempt to keep writing case reports in the old style but to lower standards and take short cuts.

An alternative approach is to develop a new format for case reports that allows for a shorter report but still captures the essential objectives of case reporting. One approach is to eliminate all the narrative that is not essential for following the mechanics of the case and evaluating the quality of care. In the past there have been a number of case reports with excessive narrative but little technical reporting or analysis. For a cryonics organization with a growing caseload the opposite approach should be followed. Another approach is to eliminate detail about procedures that were performed without deviations from past protocol and expectations, provided that this is made explicit in the report. As a result, case reports will increasingly read as a description and commentary on events that diverged from protocol or new observations about existing procedures.

To establish a template for such case reports the following approach can be followed. First, it is established what kind of information is essential for doing a meta-analysis of all cryonics cases. Then these parameters are reverse-engineered to create a template for writing case reports that reconcile the need for economy of expression and documenting all the relevant aspects of a case.  One important advantage of producing such case reports is they permit easier consultation of the technical details of the case and still meet the fundamental objectives of writing case reports.

The history of case report writing in cryonics shows an erratic potpourri of approaches and styles. One of the most unfortunate victims has been the objective of using case reports to improve the practice of human cryopreservation and to formulate meaningful research questions for the sciences that inform cryonics. But if systematic thought is given to the objectives of case reporting outlined in this document, steps can be taken to leave this unsatisfactory situation behind while meeting the needs of a growing cryonics organization.

Notes

(1) I am grateful to Mike Darwin for this example and for reviewing earlier drafts of this article.

Posted in Cryonics | Tagged , , , , , , , , | Comments Off

Philosophy of science and life extension

Paul Edwards concludes his chapter ‘The Semantic Challenge’ in his book God and the Philosophers with the following observation about logical positivism:

It is not uncommon nowadays to hear logical positivism dismissed as a set of crude errors and confusions. This is done with an air condescension by philosophers whose writings are usually models of obscurity. To people of my generation who came to philosophy in the 1940s, when traditional metaphysicians  were a dominating force, logical positivism was a liberating movement. Occasionally the leading figures were guilty of dogmatism, and on some important issues, such as the mind body problem and the question of free will, the logical positivists made no significant contributions, but the main doctrines seem to me substantially sound. The verification principle in particular, when stated with suitable amendments, is a powerful weapon against pretentious humbug.

Do life extensionists need to take an interest in philosophy of science and metaphysics? In his review of James Ladyman and Don Ross’s Every Thing Must Go: Metaphysics Naturalized, Alcor staff member Mike Perry notes that “as immortalists we hope to be in the world for a good long while, thus we are interested in the nature of reality. Reality determines, among other things, what our prospects are for our own longterm survival.”

Alternatively, one could argue that metaphysics is not a theoretically legitimate discipline and that the verifiable claims of physics exhaust what we can say about “reality.” Perhaps the most useful benefit of familiarizing oneself with philosophy of science and analytic philosophy is that it enables one to get a better appreciation of the difference between meaningful experimental science and sweeping generalizations deduced from shaky metaphysics.

Further reading: Five important empiricist philosophy books

Posted in Science | Tagged , , , , | Comments Off

The RhinoChill: A New Way to Cool the Brain Quickly

We scientists are difficult, cranky, and above all, maddeningly frustrating people. Want to turn lead into gold? No problem, we can tell you how to do that, and in fact have even done it already: the only catch is that the cost of such ‘nuclear transmutation’ is many times that of even the most expensive mined gold. You say you want to travel to the moon? Done! That will be ~$80 billion (in 2005 US dollars). Want to increase average life expectancy from ~45 to ~80 years? Your wish is our command, but be mindful, you will, on average, spend the last few of those years as a fleshpot in the sunroom garden of an extended care facility.

And so it has been with an effective treatment for cerebral ischemia-reperfusion injury following cardiac arrest. Thirty years ago, laboratory scientists found a way to ameliorate most (and in many cases all) of the damage that would result from ~15 minutes of cardiac arrest, and what’s more, it was simple! All that is required is that the brain be cooled just 3oC within 15 minutes of the restoration of circulation. The catch? Well, this is surprisingly difficult thing to do because the brain is connected to the body and requires its support in order to survive. And the body, as it turns out, represents an enormous heat sink from which it is very difficult to remove the necessary amount of heat in such short time. Thus, the solution exists and has been proven in the laboratory, but it has been impossible to implement clinically.  This may be about to change as a variety of different cooling technologies, such as cold intravenous saline and external cooling of the head begin to be applied in concert with each other. Separately, they cannot achieve the required 3oC of cooling, but when added together they may allow for such cooling in a way that is both effective and practical to apply in the field.  A newly developed modality that cools the brain via the nasal cavity may provide the technological edge required to achieve the -3oC philosopher’s stone of cerebroprotection.

Read the complete article in PDF here.

Posted in Neuroscience, Science | Tagged , , , , , , | Comments Off

Imagine there’s no sleep

Imagine that human culture has never experienced sleep, but suddenly must experience it to survive. Would they be apprehensive about experiencing it for the first time?

Of course!

Just picture… this total suspension of consciousness, experienced for the very first time in human history. The notion would totally blow our minds. It would be completely shocking. We might even make up stories about dying and being replaced by an identical clone being, or trying to console ourselves that at least we will have a successor on the following day to carry out our desires.

Contrary to popular belief, there is no particular reason to assume that humans who “survive” events like freezing or vitrification would be any different from humans that “survive” sleep or anesthesia. The definition of consciousness we care about is the lifelong continuity of experiences created by memories. We might not like donating 8 hours out of every 24 to a form of comatose oblivion, but we are able to tolerate it. We would die without it — and who wants to die?

Suppose we were to meet an alien culture that undergoes 8 hour periods of liquid nitrogen immersion every night instead of sleeping. We wouldn’t find it a significant barrier to relating to them as fellow sentient beings. We wouldn’t find it socially necessary to mourn their deaths every night or become reacquainted with their newly generated “progeny” every morning. We would just think their suspension habits are an interesting facet of their biological existence, much like they might regard our sleeping habits.

Some people seem to have the idea that cryonics patients can only be “dead” by definition — that the cessation of metabolic activity somehow makes survival via cryonics an absurdity. It is true that current cryonics patients are legally and clinically dead, but that is a matter that will probably change as scientific and social progress is made. In the mean time, there needs to be a clear distinction between destruction and deanimation — which unlike “death” are not social, legal, or philosophical terms but empirical events, much like sleep.

Posted in Cryonics | Tagged , , | Comments Off

Paul Edwards on the fear of death

In his book God and the Philosophers, the Austrian American atheist philosopher Paul Edwards writes:

When we die we do not return to the “bosom of Nature” or the bosom of anything. After death we will have no experiences at all for ever and ever; and this is what is so terrible about death. The fear of death is no doubt instinctive, but it is also entirely rational. The usual consolation that we also did not exist for an infinite period before birth is not really to the point. The non-existence before birth was followed by life, but our present life will not be followed by another life after we die.

Whether the fear of death is rational or not, there is also a more common sense perspective available on this issue. Fear of death seems to be hardwired in human nature, only the intensity of  this fear differs among humans. Instead of trying to overcome this fear of death with logical arguments, it would be more productive to seek meaningful rejuvenation and human enhancement therapies that would substantially reduce the probability of death by tackling aging and the fragility of human life.

It is surprising that the work of Paul Edwards has not received more attention by life extension advocates. His book Heidegger and Death and his collection of articles about Immortality indicate a serious interest in the topic of personal survival.

Posted in Death | Tagged , , , , | Comments Off

Prospects for Mild Therapeutic Hypothermia and Improved CPR in Cardiopulmonary Cerebral Resuscitation

There are two kinds of hypothermia: protective or preservative hypothermia, and therapeutic hypothermia. The former is easy and straightforward to understand for most, clinicians and laymen, alike.  However, therapeutic hypothermia has proved to be a far more difficult idea to communicate, probably because it is so easy to conflate it with protective hypothermia.

Anyone who has had any contact with refrigeration will at once understand the concept of protective hypothermia. Foodstuffs, and other biological materials that are cooled, experience protection against spoilage and decay roughly in proportion to the degree to which they are cooled. A little cooling slows decomposition a bit, and enough cooling will stop it altogether. Again, the temperature-induced decrease in the rate of chemical reaction is a fundamental property of chemistry which is understood intuitively by anyone who lives where it gets cold, or where refrigeration is in use.

By contrast, therapeutic hypothermia does not rely primarily upon the slowing of metabolism or the rate of chemical reactions that occurs as a result of cooling, but rather upon the effects very modest degrees of cooling have on gene activation and signal transduction in mammals. Controlled, mild therapeutic hypothermia (MTH) is generally understood to constitute a reduction in body temperature from ‘normal’ for the species being treated, to 3oC below normal. In the case of humans, this would mean a reduction in body temperature from 37oC to 34oC. Such a modest reduction in temperature results in profound down-regulation of pro-inflammatory cell-signaling pathways and causes the inactivation of genes involved in a multiplicity of deleterious cellular and systemic processes. Similarly, MTH can inhibit apoptosis of brain cells, and slow or halt the downward spiral of excessive metabolic demand by injured cells, causing yet more non-productive hyper-metabolism, and consequently even more cell death. In this article, the biomechanics of MTH are briefly explored, as well as the prospects for improved outcomes in patients who suffer anoxic-ischemic brain injury as a result of cardiac arrest as a result of the rapid application of MTH following the insult.

Read the complete paper in PDF here.

Posted in Neuroscience, Science | Comments Off

Alcor update from CEO Max More

The Kurzweil Accelerating Intelligence blog features a short interview with new Alcor CEO Max More:

Q: Where do you see cryonics in the future?

We’ll look back on this 50 to 100 years from now — we’ll shake our heads and say, “What were people thinking? They took these people who were very nearly viable, just barely dysfunctional, and they put them in an oven or buried them under the ground, when there were people who could have put them into cryopreservation. I think we’ll look at this just as we look today at slavery, beating women, and human sacrifice, and we’ll say, “this was insane — a huge tragedy.”

More here.

Posted in Cryonics | Tagged , , , | Comments Off

Suspended Animation Conference 2011

The cryonics company Suspended Animation “will sponsor the conference, “Suspended Animation – The Company and The Goal,” which will be held in Fort Lauderdale in May, 2011. The conference will feature speakers on the latest strategies and advances toward perfecting reversible human suspended animation. During the conference, SA will also host tours and demonstrations at its facility in Boynton Beach.”

More information about the program, registration, and the free live webcast can be found on the Suspended Animation 2011 conference page.

From the conference brochure:

“The Whole-Body Vitrification Project – Greg Fahy, PhD — 21st Century Medicine, Inc. Major new findings from Phase I of a revolutionary longterm project to achieve reversible whole-body solid state suspended animation in humans. This project, conducted at 21st Century Medicine, is the only whole body vitrification research being conducted in mammals and was funded entirely by a $5.6 million dollar grant from the Life Extension Foundation. Cryobiologist Greg Fahy will discuss how well whole animals can be cryopreserved right now, the possibility of using a single advanced vitrification solution to cryopreserve entire animals and, eventually, humans, and a unique, newly-invented technology to produce large, cryopreserved tissue slices for scanning and transmission electron microscopy. A proposal and budget for Phase II of the Whole-Body Vitrification Project will also be presented.”

Posted in Cryonics, Science | Tagged , , , | Comments Off

Support real progress in life extension

As we start the new year, it is helpful to draw attention to the sobering fact that no credible human rejuvenation therapies are available today, and it is doubtful that such therapies will see the light of day in the short term. Greg Fahy’s recent monumental collection of  interventive gerontology articles, The Future of Aging: Pathways to Human Life Extension (review forthcoming in Cryonics magazine), leaves little doubt about this predicament. It should also be emphasized that, with the possible exception of Robert Freitas’s comprehensive nanomedical overhaul of human biology, none of the envisioned strategies for life extension and rejuvenation (including SENS) confer increased protection to the brain in the case of severe traumatic insults or accidents. This fact alone highlights the fundamental importance of cryonics as  the core element in life extension. The idea that rejuvenation will make cryonics redundant has been one of the main obstacles for young people to engage in cryonics activism.

There is a broad consensus in the life extension community that more resources need to be allocated to combating aging as such, as opposed to increasingly futile efforts to extend life by treating aging-associated diseases. Unfortunately, the objective to launch a serious rejuvenation research program has limited mass appeal so far. As a consequence, we will have to get involved ourselves. Hopefully we can shift the focus from extensive hypothetical discussion about the consequences of human enhancement technologies to supporting and engaging in real experimental research to make these technologies facts of life.

In line with the foregoing observations, we suggest to consider the following areas for your support.

1. Cryonics. The first sensible step is making cryonics arrangements. Without cryonics arrangements you may not be able reap the benefits of anti-aging and rejuvenation treatments. Without cryonics arrangements you will remain vulnerable to a large number of personality-destroying diseases and accidents. In addition to making cryonics arrangements, support the major cryonics organizations and their research efforts.

2. Chemical Brain Preservation. Chemical brain preservation is an envisioned alternative (or complement) for human cryopreservation. At this point, there are no organizations offering chemopreservation of the brain but there is a new organization that aims to research the technical feasibility of the procedure.

3. Rejuvenation Research. The emphasis of interventive gerontology should be on rejuvenation as opposed to extending the maximum human lifespan by halting or slowing aging. Interventions aimed at rejuvenation have the distinct advantage that short-term empirical validation of their efficacy is possible. Rejuvenation therapies may include genetic manipulation, regenerative medicine, organ replacement and reversal of accumulated damage. A this stage of our knowledge, no privileged position should be claimed for any approach absent hard empirical breakthroughs in rejuvenation.

4. Nanomedicine Research. The logical evolution of medicine is to intervene at a progressively smaller scales. From “crudely” cutting into tissue, to pharmacology, to manipulating bio-molecules at the molecular level, nanomedical control of morbidity and aging is a prerequisite for resuscitation of cryonics patients and comprehensive rejuvenation. Biological and mechanical pathways to nanomedicine have been outlined. Whatever your position is on the relative technical merits and projected timelines  of such alternative approaches, the evolution of medicine into nanomedicine should be supported and accelerated.

Posted in Cryonics, Rejuvenation | Tagged , , , , , | Comments Off

Is a life worth starting? Some personal views

For life—the life of any sentient creature—to be worth living, there must, as Robert Ettinger has often said, be a preponderance of satisfaction over dissatisfaction. If this overall slant toward good rather than bad is maintained, it seems reasonable that one stands to gain by continued existence. I am not sure what fraction of the human (or other sentient) population achieves this positive balance and will not speculate except to note that by appearances there are many humans who do achieve it, along with other creatures, pets in particular, so at least for them, life is worth continuing. To say that life once started is worth continuing does not, as David Benatar points out, imply that it was worth starting in the first place, or should have been started. But I think that, barring certain problematic cases,  it is fair to conclude that a human life at least is worth starting, if there are responsible prospective parents who would like to start it. Here I think it is reasonable to expect that the resulting person will feel that life is overall a benefit, and additionally, that others, the parents in particular, will stand to gain from the new life that has entered their lives. I don’t accept Benatar’s arguments that by and large life is pretty terrible and people delude themselves who think otherwise.

Also I reject his “asymmetry” argument, that it is “good” if a life that would be bad does not come into existence, but merely “not good” rather than “bad” if a life that would be good does not come into existence. (It is easy to see how this asymmetry supports the argument that life should not start in the first place and Benatar refers to it often.) Benatar’s main rationale for this argument seems to be that, while we would consider someone morally at fault for deliberately bringing into existence someone who would be miserable and just want to die, we would not similarly hold someone culpable who elected not to bring into existence someone who would be happy and want to remain alive. This I think should not be the only consideration, for it is based only on the idea of when we should regard an action as bad, and not at all on when we should regard it as good and commendable. (Why this particular asymmetry?) Instead, weighing both sides of the issue as I think is justified, I would opt for the fully symmetric position that it is “not bad” if a life that would be bad does not come into existence, and similarly, “not good” if a life that would be good does not come into existence. On the other hand, I question and doubt whether a life that comes into existence would be bad in the long run, given the prospect of immortality, which I think is a possibility through science (see below).

Life does, of course, have its problems, death in particular, that might call in question whether it is worthwhile after all and thus, whether the life of any sentient being is worth starting.  For this one problem there are a number of possible answers that will be satisfying to different people, and thus can serve as ground for a feeling that life is worthwhile and was worth starting despite one’s own mortality. There is the famous Epicurean argument that death is not really a problem because before it happens it causes no harm, and after it happens there is no victim. There is the Buddhist argument that, more fundamentally, the self is an illusion anyway, so that in fact no persons exist and death never really happens, though bliss can still occur through states of enlightenment which thus are worth seeking. There are various religious traditions that promise an afterlife and a happy immortality for those who prove worthy, or, in some versions, all who are born. Then there is scientific immortalism, which holds that at least substantial life extension through science and technology is possible, so that, irrespective of any supernatural or mystical process, persons of today have more to hope for as they get older than the usual biological ruin and oblivion.

The scientific possibilities for overcoming death come in different varieties that each have their own advocates. Some of these hopefuls, particularly younger ones, focus on the prospect that aging and now-terminal illnesses will be remedied in their natural lifetime, so that they will escape clinical death and need not specially prepare for it. Others who are not so confident have made arrangements for cryopreservation after clinical death, in hopes of resuscitation and cure of aging and diseases when the requisite technology becomes available. Still others hold out for advances on a more cosmic scale that will eventually make it possible to raise the dead comprehensively. (Some possible scenarios for this using multiple, parallel time streams rather than revisiting or recovering a hidden past are considered in my book, Forever for All, and the article at http://www.universalimmortalism.org/resurrection.htm.) The three possibilities are not mutually exclusive, so that, for example, persons who have chosen cryonics may also place varying hopes in the other two. In fact, my personal viewpoint as a scientific immortalist grants some validity to all three possibilities, but I think it is imperative now to be engaged in cryonics, which is almost unique and the clear favorite as a proactive, interventive strategy against death. Passive acceptance of the dying process simply does not feel right, whatever the prospects for near-term medical progress, or on the other hand, resurrections in a more distant, technologically superior future. It goes without saying that I also think future life will be worth living—it should be possible to make it so, if future developments can provide the opportunity.

Posted in Arts & Living, Cryonics, Death, Science | Tagged , , , , , , | Comments Off

Review of ‘Better Never to Have Been’

Review of  Better Never to Have Been: The Harm of Coming into Existence by David Benatar. New York: Oxford University Press, 2006

“Would that I had never been born” is a lament sometimes voiced in the depth of misfortune, a cry of despair we hope may be soon be stilled by something more positive, when the bad things, whatever they are, have run their course. Enter David Benatar, a respected professor of philosophy at the University of Cape Town, South Africa. In the volume here reviewed he offers the extreme view that in fact it would have been better, all things considered, if not one of us had ever existed, or even any sentient life whatever. Life is that bad, he says, and he bases this judgment on certain logical principles along with empirical evidence of the allegedly poor quality of life that most of us are forced to endure in this world. Among the consequences is that no more humans should be born, and the human race (and other sentient creatures) ought to become extinct.

Antinatalism—the viewpoint that birth of sentient life, human in particular, is bad and ought not to happen, is a recurring one theme history, a noted proponent being the philosopher Arthur Schopenhauer (1788-1860). It can also be founded, as Benatar proposes, on certain assumptions considered reasonable by many people today, particularly those of a scientific, materialist outlook who are not inclined to over-optimism. Among the assumptions are that anyone’s life, overall, is an exercise in futility. Death—eternal oblivion—is the eventual fate of each person, and will happen through the normal aging process if not sooner. (Thus there is no serious prospect of a religious afterlife. Though not stated in the book, it is clear also that radical life extension, whether by imminent medical breakthroughs or through an initial “holding action” such as cryonics, is discounted.) Moreover, the human species will eventually die out, as is the fate of all biological species, so the extinction advocated by Benatar must happen in the end regardless. Another important presumption, in this case justified at length, is that in most people’s lives sorrow and misery predominate heavily over joy and happiness, so that their lives are not worth living.

Benatar denies that any good is done in any act of procreation, even if the life of the offspring is predominantly happy and if that person expresses gratitude for having been given life. The very best that could happen, Benatar says, is that no harm would be done, but only if the offspring never experienced anything bad in his/her entire life, an unlikely prospect. Even then, no good would be done or moral credit accrue in bringing that person into existence—good is done only in not bringing into existence any person who, in the course of his/her life, would at least experience some amount of bad. Harm is done, and in any likely circumstance, unacceptably serious harm, in bringing anyone into the world.

Such arguments seem unpersuasive for any of a number of reasons, and many will also find them offensive. In the matter of family planning, the prospective parents will be motivated by thoughts such as a child would bring them joy even as they in turn strive to provide the child with a happy home life and a good upbringing. Overall the child can be expected to be grateful both during the period of childhood and later in life, something that seems borne out in practice, even if hardship also occurs. As tough as the going may be at times, most people do not feel their parents were morally at fault for having had them, and are not ready to end their lives over any perceived shortcomings in their present situation or future prospects.

Benatar devotes a chapter of his book to arguing, nonetheless, that actually life as most people live it is very bad, suggesting that those who disagree don’t realize just how bad it is and are suffering some kind of delusion. But this begs the question of who is to judge. Turning the argument around, is it not possible that Benatar himself is suffering from depression that clouds his judgment? Natural selection of course favors a brighter outlook: Benatar’s thinking is not conducive to reproductive fitness. Beyond that, it is hard to see that his point of view is more “logical” than a more life-affirming one, both being based, when the rhetoric has run its course, on basic gut feelings about what is pleasant or worthwhile or isn’t, in what relative amounts, and how the mix that occurs in life should be assessed.

Despite life’s alleged wretchedness, Benatar himself is not ready to commit suicide but insists that life once started, his in particular, may be worth continuing even if it should not have been started in the first place. (Sometimes this sort of argument is reasonable. A woman should not be raped, but a child born as a consequence should not be killed.) More generally Benatar’s stance is passive rather than proactive: having children should be legal, even though no one should have them, much as we might favor allowing smoking even though it is medically and socially inadvisable.

Benatar is aware that, despite these limited concessions, his stance will be unpopular and devotes much attention to defending it against various possible lines of attack. Still it is doubtful his arguments will persuade many who are not already strongly leaning his way. The rest of us, surely a robust majority of humanity, will find our varied reasons to demur. Religious people will argue that life is a gift of God, children are a blessing, hardships and sorrows happen but can and will be remedied, all will be well in the end. Secular humanists and others of scientific bent may believe with Benatar that their lives must permanently end, and even accept the eventual extinction of all earthly life, yet still remain optimistic, one of their arguments being that “since life is finite, even sometimes very short, each moment of life, handled rightly, is precious.” Scientific immortalists who are hoping for radical life extension will also discount Benatar’s pessimism, though possibly in an odd way supporting the end of the present human species—in this case, however, by replacing it with something better that includes themselves in an enhanced form.

Meanwhile, an antinatalist movement has grown up that has simple, passive annihilation of the human species as its goal, endeavoring as far as possible to discourage everyone from having more children. In addition to a claimed humanitarian purpose—eliminating suffering as Benatar proposes—there is an environmental motive some endorse, arguing that the earth’s biosphere would greatly benefit if there were no humans to befoul it, as they generally do. Potentially a conflict could erupt between antinatalists and immortalists, who hope to be in the world for a very long time. My feeling, though, is that the antinatalist movement is both unpopular and self-limiting—on both counts, natural selection so wills it. Immortalists in any case are not so much trying to populate the planet as trying to endure as individuals. So probably we should not worry too much. Instead let’s talk to these people. Some of them (Benatar included?) may be willing to rethink their position.

———————————————————————————————————————————————————————————————————————————————————————————————————

About the author: David Benatar is professor of philosophy and head of the Department of Philosophy at the University of Cape Town in Cape Town, South Africa. Though best known for his advocacy of antinatalism in his book Better Never to Have Been, he is also the author of a series of widely cited papers in medical ethics. His work has appeared in such journals as Ethics, Journal of Applied Philosophy, Social Theory and Practice, American Philosophical Quarterly, QJM: An International Journal of Medicine, Journal of Law and Religion and the British Medical Journal.

Posted in Arts & Living, Cryonics, Death | Tagged , , , , , , , | Comments Off

Non-existence is hard to do

A review of  contemporary antinatalist writings

Originally published in Cryonics, 2nd Quarter, 2010 (PDF)

“Coming into existence is bad in part because it invariably leads to the harm of ceasing to exist.” David Benatar

If they could get a corpse to sit up on an operating table, they would jubilantly exclaim, “It’s alive!” And so would we. Who cares that human beings evolved from slimy materials? We can live with that, or most of us can.” Thomas Ligotti

The persistence of pessimism

When I sent out an email message soliciting contributions on the topic of philosophical pessimism and antinatalism one person declined with the reasonable response that such positions are only taken seriously by a handful of far-out philosophers. Humans have evolved to procreate and seek happiness. What is the point?

The reason why I have not been inclined to so easily dismiss the recent renaissance of philosophical pessimism is because negative and tragic views about life are woven throughout human history and culture. Most dominant religions have little positive to say about the state of humanity (after the fall) and the prospects for a life devoid of suffering on earth. Despite its relative sophistication, even Buddhism presents a picture of the universe as a source of suffering. Much can be said about pessimism but not that its influence is outside the mainstream.

Even the antinatalist position that it is better never to have been and that we have a moral obligation not to procreate is not completely obscure. Who has not had the experience of talking to the grumpy old lady who wonders why anyone would want to bring children into this world? We routinely dismiss such positions as being out of touch with reality but modern culture persists in linking intellectualism to pessimism. This perhaps should not be surprising because, as a general rule, excessive thinking comes at the expense of sensual experience. One reason why many intellectuals are biased towards pessimism is because it provides them the opportunity to rescue us with their ideas. Antinatalism offers the triumph of Reason against existence itself; the ultimate triumph of the Intellectual.

Philosophical aversion to pessimism can be found among the finest thinkers in the history of philosophy. There is David Hume, the great empiricist thinker, and an amiable and optimistic person. Then there is Friedrich Nietzsche, who, despite a life of disease and isolation, recognized that pessimism is not an objective feature of the universe but the expression of a weak and oversensitive mind. The twentieth century witnessed a strong renaissance of the empiricism of David Hume in the form of logical positivism. These philosophers rightly abstained from putting forward a “philosophy of life,” but optimism about science and humanity’s potential is clear in their foundational writings. It is also interesting to note that the most recent forceful responses to pessimism have not come from professional philosophers but from libertarian economists who do not display the slightest intellectual embarrassment in claiming that life is getting better all the time.

In my opinion, the most obvious question that can be raised about philosophical pessimism is whether its supporting claims are factual descriptions of reality or just expressions of temperament. Another interesting question is whether philosophical pessimism necessarily obliges us to the antinatalist position. In seeking answers to these questions we turn to the literature of contemporary antinatalism.

Jim Crawford’s Confessions of an Antinatalist is a highly readable autobiographical exposition of antinatalism. Thomas Ligotti’s book The Conspiracy Against the Human Race is more ambitious in scope and contains a wealth of historical information on pessimism, discussions of modern science, and, not surprisingly, a review of the theme of pessimism in horror literature. David Benatar’s Better Never to Have Been: The Harm of Coming into Existence is the most rigorous exposition of antinatalism to date. This book covers a lot of ground and I will confine myself to some of its main topics only.

The harm of coming into existence

In its purest form antinatalism may not be attainable but the framework that informs this position rests on a couple of sound premises: (1) we do not impose a harm (or withhold a benefit) by not bringing someone into this world; (2) we do impose a harm by bringing someone into the world when this person’s life will be bad. Jim Crawford believes that these premises are evident and I see little reason to dispute him. The real debate about antinatalism is how to determine that a person’s life is (or will be) bad, and how much consideration the interests of parents should be given.

One of the most problematic aspects about the work of Crawford and other antinatalists is that they have little patience for the argument that life is better than they think it is. In some passages it is hard to distinguish the antinatalist from the Marxist. If people think that life is much better than Crawford makes it out to be, the standard rejoinder is that these people suffer from a form of false consciousness (pessimists frequently use words like “truly” and “really”). In some passages this attitude borders on intolerance. A prime example can be found in Crawford’s discussion of childhood. For many people growing up was a period of great happiness and discovery. Crawford’s agitated dismissal of such accounts introduces an element of illiberalism in what is otherwise a humanistic endeavor. It is in these passages that antinatalism turns into bitter ideology.

The way the term “bias” is employed is deeply problematic. It is used as if there is an objective perspective that can reached were it not for those pesky evolutionary biases coming between the person and the universe. At times the author appears to be saying that if evolution did not select in favor of those wanting to survive we would not want to survive. This is not particularly helpful. Some of these “biases” do not cover up anything but just make us happier.

Let us assume here the metaphysical premise that there is an objective, material reality that can be known through the use of reason and empirical observation. This does not mean that there is one “correct” fit between an organism and the world. A person who is manically depressed perceives the world in a different matter than a person who is not. How we are “wired” and respond to our environment is not a matter of “correct” or “incorrect.” Thinking otherwise would be hard to reconcile with an evolutionary outlook in which life is just the outcome of random interactions of organic molecules.

One argument that remains available to the pessimist would be that the probability of creating a miserable life is too high to warrant procreation. But it is at this point that the “transhumanist” can enter the debate and claim that our expected quality of life is no longer just the outcome of a “random” evolutionary process but can be brought under rational control. We should endeavor to make happy children.

In my opinion, the short response to empirical pessimism can take the following form. Pleasure and pain are both part of existence. For some sentient beings pleasure outweighs pain, for other sentient beings pain outweighs pleasure. A moral agent cannot add up, subtract, or divide these elements for life as a whole to produce an objective quality-of-existence function. The antinatalist runs into the same problems as all the utilitarians and welfare economists who have tried to define a social utility function as a guide for public policy. As Thomas Ligotti notes in his book, “…the reason for the eternal stalemate between optimists and pessimists, is that no possible formula can be established to measure proportions and types of hurt and happiness in the world. If such a formula could be established, then either pessimists or optimists would have to give in to their adversaries.” I think that the best response available to the antinatalist would be to follow David Benatar’s example and present a strictly formal argument, or simply argue that in case of doubt, we should abstain from procreation.

Escape strategies

After spending the bulk of his book persuading the reader that life is suffering, Crawford discusses what he calls “Escape Strategies.” In his treatment of Buddhism as an escape strategy he could simply have made the obvious internal critique that desire may be sufficient, but not necessary for suffering. Crawford’s treatment of Christianity is scathing, which may indicate regret because the author himself was a Christian for awhile. Why have children if there is the prospect of eternal damnation? Good question, but I think that a Christian can respond by saying that following Scripture is more important than applying human morality to God’s creation.

The last escape strategy that Crawford reviews is hope, which turns into a discussion of futurism and transhumanism. The argument that many of those pursuing life extension will not be around to benefit from it is too simplistic. Unless the brain is completely destroyed at death, the neuro-anatomical basis of identity can be preserved at cryogenic temperatures for a very long time. No delusional expectations about the future are required. People in cryostasis have time. But then the author delivers a critique that I think deserves serious treatment by transhumanists (discussions about “friendly AI” do not exhaust this topic by any means). In a nutshell, we should not expect that technological progress will necessarily produce moral progress. And even if it will, accidents happen. Technologies that can be designed to produce great joy can be used to create great suffering as well. If humanity can manufacture hell without God, the case for pessimism and antinatalism may be strengthened.

Interestingly enough, the anticipation of such dark future technologies may present a (subconscious) obstacle for many people considering cryonics. Hundreds of millions of people believe in the craziest things like astrology and psychoanalysis, but only a handful of people (around 1500) have made cryonics arrangements. This lack of interest can  hardly be attributed to ignorance, and perhaps the most persuasive answer may be hidden in Crawford’s book. Cryonics basically forces people to deal with the question whether they would like to be “born again” in a far and unknown future. As a general rule, the answer seems to be “no.” Antinatalists may find additional ammunition for their position in studying the reasons for the low sign-up rate for cryonics.

Mahayana antinatalism

Antinatalists should expect a lot of obvious questions such as “are most people not glad to be alive?” or “why not kill yourself?” I fear that Crawford’s answer to the question “why not kill yourself?” risks undermining the orthodox antinatalist project. If empathic sensibility can make an enlightened antinatalist who wants to stick around it is arguable  that antinatalists should make an effort to remain alive in an effort to reduce the amount of (future) suffering in the universe. Antinatalists then become life extensionists. To use conventional Buddhist terminology, perhaps at some point there will be a Theravada version of antinatalism (focused primarily on non-procreation) and a Mahayana version of antinatalism (concerned with the elimination of the suffering of all sentient beings).

David Benatar runs into a similar problem when he ponders the question whether bringing new people into the world could be justified to reduce the suffering of the last remaining people. It seems to me that how an antinatalist deals with such practical moral issues depends on how the ethics of antinatalism is conceived. Do we have a “right” not to come into existence or is the objective of antinatalism to juggle with small and great suffering towards the ultimate end of its complete abolition?

If antinatalism is conceived as a strictly individualistic endeavor, concerns about the suffering of all humans can be easily dismissed. But in that case antinatalism would just collapse into individualist pessimism. Who cares about suffering, as long as it is not me! This is not the kind of sentiment that is generally found in antinatalist writings. I do not think that the question whether there might be moral reasons to remain alive, and, yes, bring into being forms of life that are benevolent but ruthless towards suffering, can be easily dismissed.

At one point Crawford observes that secular and smart people are having fewer children. This does not look good for the inevitable triumph of antinatalism. Under such scenarios antinatalism produces dysgenics, and if one believes that stupidity and evil go hand in hand, increased suffering for more people.

To me it is not unlikely that, in practice, antinatalism leads to more suffering because it will only be adopted by sympathetic human beings such as Crawford. The antinatalist cannot argue that the amount of suffering in the universe cannot be increased nor decreased. The whole point of antinatalism after all is that suffering can and should be decreased. But how to go about this may be more complicated than it appears. A sober assessment of the practical implications of antinatalism may require revision of the antinatalist position itself.

Confessions of an Antinatalist is a fine and humane book, but in the end it is also a book of the converted written for the non-converted. Thomas Sowell has noted that in economics there are no solutions but only trade-offs. I would not be surprised if antinatalists will come to a similar conclusion at some point.

Suffering without meaning

Thomas Ligotti is a contemporary horror writer whose fiction work  is marked by cosmic nihilism, alienation and the fragile nature of reality. As a great admirer of the work of Ligotti I have been reluctant to comment on his non-fiction. Fortunately, unlike many other artists, Ligotti has little interest in “critical theory” or “progressive” politics. His book The Conspiracy Against the Human Race: A Contrivance of Horror is not concerned with such trivial topics but with the bleak fate of humanity in a deterministic and indifferent universe.

The book starts off with an introduction by obscurantist philosopher Ray Brassier, whose work would certainly qualify for the description that Ligotti gives to Schopenhauer’s oeuvre (“too overwrought in the proving to be anything more than another intellectual labyrinth for specialists in perplexity”).

Reading Ligotti’s account of why humans reject truly bleak views about life it would be interesting to see how antinatalists respond to the existence of orthodox Calvinism. Accepting a universe without free will that is ruled by an omnipotent God who has decreed that the majority of people will suffer in hell for His self-glorification seems a lot more terrifying to me. Nonetheless, millions of people have accepted this theological perspective. The existence of Reformed theology lays to rest the view that humans have an intrinsic desire to avoid doctrines that are too terrible too contemplate.

When Ligotti discusses the work of antinatalist Peter Wessel Zapfe once more we find the view that there is an objective predicament of mankind that is hidden by false consciousness. It is remarkable to see the similarities between those who argue that we do not want look our “oppression” straight in the face and those who argue that we avoid coming to terms with the horror of existence. What  is often lacking here is the recognition that there is also a wealth of literature about human suffering that supports the idea that we would be happier if we did look nature straight in the face. No nonsense about “moral responsibility,” “sin,” “duty,” “the greater good” etc. Marquis de Sade, Friedrich Nietzsche, and Max Stirner are representatives of this school of thought.

What is intriguing about Ligotti’s book is that it reads like a rather delicate balancing act. On one hand, we have the detached observer (my favorite) who is bemused at the show business of both the optimists and pessimists. On the other hand, it is unmistakable that Ligotti feels affinity with the philosophers of cosmic horror and pessimism. His fiction does not leave much room for any other conclusion. But The Conspiracy Against the Human Race contains more than a few (unintended) suggestions how someone who declines to take sides would present his argument.

Hard determinism and the illusion of the self

I have a hard time relating to the Ligotti’s discussion about determinism and pessimism. Hard determinism (or hard imcompatibilism) is just a part of the “scientific worldview” and it is not obvious to me why it should be a source of despair. Ligotti then discusses the existence of the “self.” I am inclined to think there is an important difference between free will and the self. Modern science can make sense of the world and human action without assuming free will. I am  not convinced that this is possible if the concept of the self is rejected. Unlike free will, the recognition of a “self” comes at a later stage in evolution. It has been argued that primitive people could not clearly distinguish the self from its surroundings and thus were not able to discover the laws of physics and manipulate it to their benefit. The philosopher Hans Reichenbach developed a pragmatic case for the existence of the external world and the self in his seminal work Experience And Prediction: An Analysis of the Foundations And the Structure of Knowledge. Ultimately, the Kantian question whether something “really” exists (or what something “really” looks like) does not seem particularly helpful in the study of reality, as the early logical positivists of Vienna understood well.

Why would anything that neuroscientists discover about the self and how it is constructed be a source of dread? If you believe that life is just the result of random meetings of organic molecules, it stands to reason that the physical basis of consciousness and the self reflects such a process. Why would accepting such ideas make one a “heroic pessimist?” Why the pessimism at all? Ligotti even agrees. “One would think that neuroscientists and geneticists would have as much reason to head for the cliffs because little by little they have been finding that much of our thought and behavior is attributable to neural wiring and heredity rather than to personal control over the individuals we are, or think we are. But they do not feel suicide to be mandatory just because their laboratory experiments are informing them that human nature may be nothing but puppet nature. Not the slightest tingle of uncanniness or horror runs up and down their spines, only the thrill of discovery. Most of them reproduce and do not believe there is anything questionable in doing so.”

Ligotti also discussed transhumanism, but not in much depth. As a transhumanism skeptic myself, I found little to object to but it seems that Ligotti’s real target is what is called Singularitarianism. This part in the book seems something of a missed opportunity because there is substantial overlap between Ligotti’s fiction and themes that are discussed by transhumanist writers: living in a computer simulation, parallel universes, alternate realities etc.

When Ligotti reviews near-death experiences and ego-death, the common-sense neurological explanations that were invoked in discussions of free will and the self are largely absent (a notable exception is his discussion of the possibility that a brain tumor can cause such an “enlightened” state). For critical-care physicians it is a given that many people suffer (regional) cerebral ischemia during the dying process. As such, it is surprising (but encouraging) that not more people claim enlightenment after they recover. These periods of  transient oxygen deprivation can produce long term damage and a “re-wiring” of the brain, which can explain the new perspectives these people adopt. From a physicalist perspective, death of the ego is (partial) death of the brain, something one may or may not want to celebrate.

In Ligotti’s book the reason for pessimism is multi-factorial. It includes the lack of meaning in an indifferent universe, the reality of hard determinism, and the illusion of the self. The works of Benatar and Crawford are more restricted in scope and mostly focus on more mundane suffering. Ligotti’s philosophical horror is much richer, but I wonder how much of it will resonate with people who embrace a scientific view of the universe. The Conspiracy against the Human Race may not have been designed as an argument against “unweaving the rainbow” (to use Richard Dawkin’s useful phrase) but it sometimes reads like one.

There is a lot in Ligotti’s fine book that I have not discussed such as the extensive treatment of pessimism in horror fiction, loads of interesting philosophical and scientific references, plus illuminating discussions of obscure authors such as Peter Wessel Zappfe and Philipp Mainlander. As such, it can also be considered as an indispensable reference for philosophical pessimism and cosmic horror.

Empiricism and non-existence

David Benatar is a rigorous philosopher. His work can be situated in the analytic tradition and he makes an honest attempt to anticipate objections to his own views. When he argues for positions using mainly logical arguments he is quite persuasive. A being that does not exist can neither be harmed nor benefited. I cannot see how this argument (or  tautology?) can be successfully refuted. But when Benatar attempts to argue that the quality of life of most people is much worse than they think it is, multiple challenges arise. I do not think this is the result of Benatar’s poor reasoning but because the fields that he relies on – evolution, social psychology, happiness research and the study of cognitive biases – are notorious for allowing competing views. It seems to me that ultimately Benatar cannot escape the charge that he pays excessive attention to theories that claim that we think we are happier than we really are. Perhaps I have spent too much time in the wrong subculture but it seems to me that the phenomenon of people claiming to be less happy than they really are should not be ignored either.

Like Crawford, Benatar cannot completely escape the charge of illiberalism. Classical liberalism takes very seriously the challenges in reaching satisfactory conclusions about the quality of other people’s lives. In practice this means that we exercise restraint in making strong cognitive and moral claims about the feelings and preferences of other people. This is a mindset that does not seem to come easily to antinatalists. Benatar is on more agreeable ground when he simply derives his antinatalism from uncertainty; “some know that their baby will be among the unfortunate. Nobody knows, however, that their baby will be one of the allegedly lucky few.”

Benatar believes that even if his empirical argument about the poor quality of our lives fails, his formal argument from asymmetry is still left standing. He thinks that even if there is one single painful pinprick in an otherwise good life, we still harm that person by bringing him into existence. I think that Benatar is “proving” too much here. We can agree that anyone who conceives a child cannot escape the prospect that this person will experience some harm. But from this it does not follow that the person is harmed in a meaningful moral sense without considering the expected overall quality of that life. Perhaps Benatar would respond that I have not understood his argument, and I will admit that I have a difficult time understanding why the possibility that a person’s pleasures are expected to outweigh the pains do not alter his argument. I think that both bringing into existence a life that is invariably good and a life that is generally good can be morally defended on the grounds that there will not be any post-natal moral objections from the person involved. Of course, we are not morally obliged to do so, because we will not deprive the unborn of such a good life if we don’t have children. But since most parents have a positive interest in having children, in practice this tips the scales in favor of some (but not all!) procreation. One problem I can see with my argument is that it might permit the creation of a life form that would experience great suffering but with an unalterable survival instinct and no cognitive possibility of moral blame or regret. Some antinatalists might even claim that this is a rather accurate description of the human race as it exists today.

As an empiricist, I generally give the benefit of doubt to empirical observations when they appear to conflict with logical reasoning. I think that this preference itself can be justified on historic and pragmatic grounds. The claim that coming into existence is always a harm is not consistent with the reports of all those who have come into existence. That seems to be a non-trivial epistemological roadblock for antinatalism.

When Benatar discusses the moral duty not to have children he runs into the obvious problem of how the interests of the parents should be weighed against the interests of the child. One does not need to be an ethical egoist to believe that the interests of the parents count for something. In this case the question returns to how bad the life of most people is and, as discussed, this is a rather vulnerable part of antinatalism. Benatar attempts to answer the obvious objection that most people who have been born do not regret this or blame their parents. But when I read his thoughts on “indoctrination” I only see further evidence of the anti-liberalism in his writings.

In fairness to Benatar (who seems to identify himself as a liberal of some sorts), he does defend the legal right to procreation because he admits that there can be reasonable disagreement about his views. I think this point is particularly important for antinatalism since reasonable objections often come from the very people whose lives Benatar characterizes as very bad. That is not to deny that society can choose to be less supportive of people who engage in reckless procreation. Such behavior can be substantially decreased by withholding benefits that encourage or reward such behavior. Benatar correctly argues that if one subscribes to a consistent interpretation of the Kantian argument that future people should not be treated as means, then all reproduction is morally dubious. But whether that highlights the virtues or defects of Kant’s ethics I leave to the reader to ponder.

Benatar highlights the importance of making a distinction between the decision to bring someone into existence and the decision to continue life. Even if we commit to the idea that it is better never to have been we can still have reasons for wanting to continue life. As a matter of fact, Benatar entertains the argument that the prospect of death itself is one of the reasons why existence is bad. Those who follow Epicurus believe that death cannot be experienced and thus cannot be a bad thing for the person. This is an extremely difficult argument to refute, but Benatar’s discussion of this topic is quite illuminating because he points out that those who hold this position may also have to commit to the view that death can never be good for a person. One only needs to imagine a person whose life is one of continuous suffering to see that this is not a plausible argument.

As an academic Benatar is less hostile to religion than Crawford and Ligotti but I do not think he can successfully escape the objection that antinatalism requires an atheist perspective. One does not have to be a scripturalist to note that Benatar is only concerned with the fate of humans and not with the interests of God. Perhaps Benatar cannot see any positive value in human suffering because his information about Creation is incomplete. Theodicies that reconcile the existence of God and the existence of Evil are not difficult to generate. As Plotinus has observed, “We are like people ignorant of painting who complain that the colours are not beautiful everywhere in the picture: but the Artist has laid on the appropriate tint to every spot.”

Antinatalists and life extensionists

One would think that cryonicists and life extensionists should be repulsed by antinatalism. I think such a view would be mistaken. All the antinatalist authors discussed here are motivated by empathy for the suffering of all sentient life. We should also welcome the analytical and physicalist perspectives that underpin their writings. Too much (Continental) philosophy is simply an insult to the intellect and a waste of time. If a case should be made for pessimism it needs be stated in a form that is amenable to reasoned debate and empirical investigation.

Of more specific interest to life extensionists is the plausible prospect that our abilities to decrease suffering will (necessarily?) be matched by our abilities to increase suffering too. This is a possibility that should be studied in great detail by advocates of molecular nanotechnology, strong AI, and Substrate Independent Minds.

It is no secret that cryonicists are underperforming in terms of reproduction. But as Howard V. Hendrix discusses in the article “Dual Immortality, No Kids: The Dink Link between Birthlessness and Deathlessness in Science Fiction,” this may not be a coincidence. If biological immortality becomes a credible option, having children as a substitute for personal survival will lose much of its appeal.

Most rewarding for cryonicists is the unique perspective that antinatalists can bring to the debate concerning why so few people have made cryonics arrangements. The hostility of many people towards cryonics cannot be explained if people categorically believe that  meaningful resuscitation (revival) is impossible. It is the prospect that cryonics may actually work that induces severe anxiety. If the antinatalists are correct in their assessment that coming into existence is always a harm, the unpopularity of cryonics might be indirect evidence for their position.

I want to close this review with one word of advice to those who engage in debates with antinatalists. Most antinatalists waste little time reminding their readers how controversial their ideas are. They think that they have uncovered the greatest taboo of all time. As an empirical matter, this is doubtful. Antinatalist ideas can be freely discussed in modern Western countries, something that cannot be said about a number of other controversial ideas. Antinatalists are also quick to point out that their pessimism should not be dismissed as an expression of weakness and depression. But then the antinatalists commit a similar error by too easily viewing optimism as a defense mechanism or a form of bias. But is it completely unreasonable to look for the neurophysiologic and genetic basis of pessimism and optimism? The uncompromising naturalism in the work of the antinatalists  supports such an inquiry.

Jim Crawford: Confessions of an Antinatalist (Nine Banded Books 2010)

Thomas Ligotti: The Conspiracy Against the Human Race: A Contrivance of Horror (Hippocampus Press 2010)

David Benatar: Better Never to Have Been: The Harm of Coming into Existence (Oxford University Press 2006)

Thanks to Dr. Michael Perry for discussing some of the topics in this review and proofreading an earlier version of this document.

Posted in Arts & Living, Cryonics, Death, Neuroscience, Science, Society | Tagged , , , , , , , , , , , , , | Comments Off

At last, a sure-cold way to sell cryonics with guaranteed success!

A humorous romp through a promising new technique in aesthetic medicine from one cryonicist’s (warped) point of view.

Figure 1: Before cryopreservation (L) and after cryopreservation (R).

As everyone involved in cryonics for more than a fortnight is sadly aware, cryonics doesn’t sell. Indeed, if we were pitching a poke in the eye with a sharp stick, we’d more than likely have more takers than we’ve had trying to ‘market’ cryonics to the public. To see evidence that this is so, you need only wander around a shopping mall on a weekend and observe all the (painfully) stainless steel lacerated and brightly colored needle-pierced flesh sported by the young and trendy and increasing by the old and worn, as well.

Yes, it’s clear; we misread the market, to our lasting detriment.

It’s true that we’ve tried the ‘you’ll be rich when you wake you up line,’ and heaven knows we’ve beaten the ‘you’ll be young and beautiful forever’ line, well, virtually beaten it to death. And while people are certainly interested in great fortune and youth, both of these things share the same unfortunate shortcoming, namely that they are things that people either don’t have but want, or do have and don’t want to lose. As anyone who is really savvy at marketing will tell you, the best way to sell something is to promise (and preferably be able to deliver) that you can get rid of something that people have and really don’t want – something that is ruining the quality of their life, destroying their health, draining their pocketbook and, worst of all, making them really, really ugly.

So, it turns out that for onto 50 years now, we’ve missed the real selling point of cryonics that’s been there all along: IT WILL MAKE YOU THIN! Guaranteed!

Can such a claim be true? Well, surprisingly, the answer would seem to be an almost unqualified, “Yes!”

Recently it’s been discovered that adipocytes, the cells responsible not only for making you fat, but for making you hungry, as well, are particularly susceptible to a phenomenon in cryobiology that has proved a nettlesome (and only recently (partially) overcome) barrier to solid organ cryopreservation: chilling injury. Quite apart from freezing damage due to ice crystals forming, adipocytes are selectively vulnerable to something called ‘chilling injury.’ 1-5 Chilling injury occurs when tissues are cooled to a temperature where the saturated fats that comprise their cell membranes (external and internal) freeze. You see, saturated fat, which is the predominant type of fat in us humans, freezes well above the temperature of water – in fact, it freezes at just below room temperature. That’s why that big gash of fat on the edge of your T-bone steak is stiff and waxy when it is simply refrigerated, and not frozen.

Figure 2: Chilling injury is thought to result from crystallization of cell membrane lipids.

Chilling injury isn’t really well understood. In the days before both cryobiology and indoor heating, humans used to experience a very painful manifestation of it in the form of chilblains – tender swelling and inflammation of the skin due to prolonged cold exposure (without freezing haven taken place). In the realm of organ preservation it is currently thought that chilling injury occurs when cell membranes are exposed to high subzero temperatures (-5oC to -20oC), again, in the absence of freezing.

There is evidence that the lipids (fats) that make up the smooth, lamellar cell membranes undergo crystallization when cells are cooled much below 0 deg C. Since the crystals are hexagonal in shape and have a hole in the middle, this has the effect of creating a pore or hole in the membrane. Cells don’t like that – those holes let all kinds of ions important to cells keeping their proper volume and carrying on their proper metabolic functions leak in and out, as the case may be. This isn’t merely an inconvenience for cells, it’s downright lethal. Without boring you with technical details, it is possible to partially address this state of affairs in organ preservation by adjusting the ‘tonicity’ of the solution bathing the cells: oversimplifying even more, this means by increasing  the concentration of salts to a concentration higher than would normally be present

Figure 3: Contouring of the skin in a pig subjected to brief, subzero cooling of subcutaneous fat.

But, to return to our chilled adipocytes and the promise not only of weight loss, but of a fat-free future; adipocytes are killed, en masse, when their temperature is dropped to between 0 and -7oC. Within a few days of exposure to such temperatures they undergo programmed cell death (apoptosis) and within a couple of months they are phagocytized by the body; and all that ugly and unwanted fat is carted off to be used as fuel by the liver. Now the rub would seem to be that this effect is most pronounced when the temperature of the tissue is cooled to below the freezing point of water and held there – preferably for a period of 10 minutes or longer.

That sounds dire, doesn’t it? What about the skin, the fascia, blood vessels, and the other subcutaneous tissues that will FREEZE (in the very conventional sense of having lots and lots of ice form in them)? Well, the answer, as any long-time experimental cryobiologist will know (even if he won’t tell you) is: pretty much nothing. Way back in the middle of the previous century, a scientist named Audrey Smith and her colleagues at Mill Hill, England found that you could freeze hamsters ‘solid’ – freeze 70+% of the water in their skin and 50% of the water in their bodies – and they would recover from this procedure none the worse for wear. Similarly, those of us who have carelessly handled dry ice for a good part of our lives will tell you that we see parts of our fingertips turn into stiff chalky islands of ice all the time, with the only side effect being a bit of temporary numbness that resolves in a few days to a week – certainly a side effect well worth it to avoid the considerable inconvenience of rummaging around to find a pair of protective gloves.

Figure 4: The Zeltiq Cool Sculpting Cryolipolysis device.

But alas, we scientists (most of us, anyway) are not a very entrepreneurial lot, and so we never thought either of inventing the ZeltiqTM cryolipolysis system, or using ‘the thin-new-you’ as a marketing tool for cryonics.

Yes, that’s right; some very clever folks have found a way to make a huge asset out of a colossal liability – to organ preservationists, anyway. Around 2004 a Minneapolis dermatologist named Brian Zellickson, MD, who specialized in laser and ultrasonic skin rejuvenating procedures, made a not so obvious connection. Both laser and skin ‘face-lifting’ and skin ‘rejuvenation’ procedures rely on the subcutaneous delivery of injuring thermal energy to the tissues of the face, or other treated parts of the body (cellulite of the buttocks and thighs are two other common areas for treatment). These energy sources actually inflict a second degree burn in a patchy and well defined way to the subdermal tissues.

Now this may seem a very counterintuitive thing to do if you are trying to induce ‘rejuvenation’ or ‘lift’ a sagging face. But if you think about it, it makes a great deal of sense. As any burn victim will tell you, one of the most difficult (and painful) parts of recovery is stretching the highly contracted scar tissue that has formed as a result of the burn injury. Indeed, for many patients with serious burns over much of their body, the waxy, rubbery and very constricting scar tissue prevents the return of normal movement, and can lock fingers and even limbs into a very limited range of motion. Many burn victims must do painful stretching exercises on a daily basis to avoid the return of this paralyzing skin (scar) contracture.

And it must be remembered that aged skin – even the skin of the very old – can still do one thing, despite the many abilities it has lost with age, and that thing is to form scar tissue in response to injury. Thus, laser and ultrasonic heating of normal (but aged) skin induces collagen proliferation and large-scale remodeling of the skin. For all the bad things said about scar tissue it is still a remarkable achievement in that it does constitute regenerated tissue. Regenerated tissue which does the minimum that normal skin must do to keep us alive: provide a durable covering that excludes microbial invasion, and prevents loss of body fluids. By injuring the tissue just below the complexly differentiated layer of the dermis (with its hair follicles, sweat glands and highly ordered pigmentation cells) much of the benefit of ‘scarring’ is obtained without the usual downsides.

The injured tissues respond by releasing collagen building cytokines as well as cytokines that result in angiogenesis (new blood vessel formation) and widespread tissue remodeling. And all that newly laid down collagen contracts over time, tightening and lifting the skin – and the face it is embedded in. These techniques may justly be considered much safer versions of the old fashioned chemical face peel, which could be quite effective at erasing wrinkles and achieving facial ‘rejuvenation,’ but was not titrateable and was occasionally highly unpredictable: every once in awhile the result was disastrous burning and accompanying long term scarring and disfiguration of the patient’s face.

St some point Dr. Zellickson seems to have realized that the selective vulnerability of adipocytes to chilling offered the perfect opportunity for a truly non-invasive approach to ‘liposuctioning’ by using the body’s own internal suctioning apparatuses, the phagocytes, to do the job with vastly greater elegance and panache than any surgeon with a trocar and a suction machine could ever hope to do. Thus was invented the Zeltiq Cool SculptTM cryolipolysis machine.6

Figure 5: The cooling head of the Zeltiq devive equipped with ultrasonic imaging equipment and a suction device to induce regional ischemia and hold the tissue against the cooling surface.

The beauty of cryolipolysis is that it is highly titrateable, seems never to result to in excessive injury to, or necrosis of the overlying skin, and yields a smooth and aesthetically pleasing result. Not unjustifiably for this reason it is marketed under the name Cool SculptingTM. The mechanics of the technique are the essence of simplicity. The desired area of superficial tissue to be remodeled is entrained by vacuum in a cooling head equipped with temperature sensors, an ultrasonic imaging device, and a mechanical vibrator. The tissue in the cooling head is sucked against a conductive surface (made evenly conductive by the application of a gel or gel-like dressing to the skin) where heat is extracted from it. The tissue is cooled to a temperature sufficient to induce apoptosis in the adipocytes, while at the same time leaving the overlying skin untouched. The depth of cooling/freezing is monitored by ultrasound imaging and controlled automatically by the Zeltiq device.  At the appropriate point in the cooling process the tissue is subjected to a 5 minute period of mechanical agitation (massage) which helps to exacerbate the chilling injury, perhaps by nucleating the unfrozen fat causing it to freeze.7 When the treatment is over, the device pages an attendant to return to the treatment room and remove it.

The tissue under vacuum is also made ischemic – blood ceases to flow, and this has the dual advantage of speeding the course of the treatment by preventing the blood borne delivery of unwanted heat – and more importantly, by making the cooling more uniform, predictable and reproducible. It also has the effect of superimposing ischemic injury on top of the chilling injury which is something that seems to enhance adipocyte apoptosis. The whole treatment, in terms of actual cooling time, takes about 60 minutes. In the pig work which served as the basis for the human clinical treatments, the duration of treatment was only 10 minutes: but the cooling temperature was also an ‘unnerving’ -7oC. The degree of temporary and fully reversible peripheral nerve damage (that temporary numbness us ‘dry ice handlers’ know so well) was more severe at this temperature, although it resolved in days to a week or two, without exception.

As previously noted, cryolipolysis causes apoptosis of adipocytes and this results in their subsequently being targeted by macrophages that engulf and digest them. This takes time, and immediately after treatment there are no visible changes in the subcutaneous fat. However, three days after treatment, there is microscopic evidence that an inflammatory process initiated by the apoptosis of the adipocytes is underway, as evidenced by an influx of inflammatory cells into the fat of the treated tissues. This inflammatory process matures between seven and fourteen days after treatment; and between fourteen and thirty days post-treatment, phagocytosis of lipids is well underway. Thirty days after treatment the inflammatory process has begun to decline, and by 60 days, the thickness of interlobular septa in the fat tissue has increased. This last effect is very important because it is weakness, or failure of the interlobular fat septae that is responsible for the ugly ‘cottage cheese’ bulging that is cellulite. Three months after the treatment you get the effect you see below on the ‘love handles’ of this fit, and otherwise trim fellow. Thus, it is fair to say that Cool SculptingTM is in no way a misnomer.

Figure 6: Art left is a healthy, fit young male who has persistent accumulation of fat in the form of ‘love handles’ that are resistant to diet and exercise and the same man 3 months after cryolipolysis.

Does cryolipolysis really work? The answer is that it works extremely well for regional remodeling or sculpting of adipose tissue – those pesky love handles, that belly bulge around the navel, that too plump bum, or those cellulite marred thighs. So far it has not been used to try and ablate large masses of fat – although there seems no reason, in principal, why this could not be done using invasive techniques such as pincushioning the fat pannus with chilling probes, as is done with cryoablation in prostate surgery. However, this would be invasive, vastly more expensive, and likely to result in serious side effects.

And that was one of the really interesting things about the research leading up to FDA approval of cryolipolysis: it seems to cause no perturbation in blood lipids, no disturbance of liver function (the organ that has to process all that suddenly available fat) and no global alterations in immune function. It seems to be safe and largely adverse effect free. There is some localized numbness (as is the case in freezing of skin resulting from handling dry ice) but it resolves without incident with a few weeks of the procedure.8

So, all of this makes me wonder, since human tissues tolerate ice formation and respond to it in much the same way as they do to laser or ultrasound ‘rejuvenation’ (depending upon the degree of damage) a logical question is, “would it be possible to use partial freezing of the skin – just enough to provoke the remodeling response – as a method of facial rejuvenation?” It should be safer than a chemical people and it is, like laser and ultrasound therapy, titrateable.

Figure 7: “Gad darn it, this shiny gold stuff keeps getting into the silt I’m tryin to git out of this here river!”

Which returns me to the whole subject of cryonics: fat is very poorly perfused and it seems unlikely that things done to moderate or abolish chilling injury will be nearly so effective for the adipocytes in fat (if it they are effective at all). That means that we might well all come back from our cryogenic naps not only young, via the magic of nanotechnology and stem cell medicine, and rich via the miracle of compound interest (which none other than Albert Einstein once remarked was “the most powerful force in the universe”), but also THIN! For all these years organ cryopreservationists, like Fahy and Wowk, have been panning for the mundane silt of a way around a chilling injury9 all the while discarding the gleaming nuggets of gold that were persistently clogging up their pans.

We cryonicists should not repeat their error and should realize a good thing when we see it. Now, for the first time, we can credibly claim that if you get cryopreserved you’ll come back not only young and rich, but young and rich and beautiful and thin!

Methinks there must be very few in the Western World today, man woman or child, who can resist a product that has all that to offer – and which, by the way, bestows practical immortality in the bargain.

Ok, Ok, maybe we shouldn’t mention that last part about immortality; it might scare the children.

REFERENCES:

1)     Wiandrowski TP, Marshman G. Subcutaneous fat necrosis of the newborn following hypothermia and complicated by pain and hypercalcaemia. Australas J Dermatol 2001;42:207–10.

2)     Diamantis S, Bastek T, Groben P, Morrell D. Subcutaneous fat necrosis in a newborn following icebag application for treatment of supraventricular tachycardia. J Perinatol 2006;26:518–

3)     Lidagoster MI, Cinelli PB, Levee´ EM, Sian CS. Comparison of autologous fat transfer in fresh, refrigerated, and frozen specimens: an animal model. Ann Plast Surg 2000;44:512–5.

4)      Wolter TP, von Heimburg D, Stoffels I, et al. Cryopreservation of mature human adipocytes: in vitro measurement of viability. Ann Plast Surg 2005;55:408–13.

5)      Manstein D, Laubach H, Watanabe K, Farinelli W, Zurakowski D, Anderson RR. Selective cryolysis: a nivel method of noninvasive fat removal. Lasers Surg Med 2008;40:595–604.

6)     Avram MM, Harry RS. Cryolipolysis for subcutaneous fat layer reduction. Lasers Surg Med. 2009 Dec;41(10):703-8. Review. PubMed PMID: 20014262.

7)     Zelickson B, Egbert BM, Preciado J, Allison J, Springer K, Rhoades RW, Manstein D. Cryolipolysis for noninvasive fat cell destruction: initial results from a pig model. Dermatol Surg. 2009 Oct;35(10):1462-70. Epub 2009 Jul 13. PubMed PMID: 19614940.

8)     Coleman SR, Sachdeva K, Egbert BM, Preciado J, Allison J. Clinical efficacy of noninvasive cryolipolysis and its effects on peripheral nerves. Aesthetic Plast Surg. 2009 ul;33(4):482-8. Epub 2009 Mar 19. PubMed PMID: 19296153.

9)     Fahy GM, Wowk B, Wu J, Phan J, Rasch C, Chang A, Zendejas E. Cryopreservation of organs by vitrification: perspectives and recent advances. Cryobiology. 2004 Apr;48(2):157-78.

Posted in Cryonics, Health, Science | Tagged , , , , , , , , , | Comments Off

Historical Death Meme

There’s a pretty simple explanation as to where motivated skepticism for cryonics originates. If you currently are skeptical of cryonics, you should carefully consider whether this applies.

Historically, there has been a powerfully optimized meme regarding the topic known as death. If you lost vital signs, you were irrevocably lost. There was nothing that could be done. The belief evolved that there is a mysterious point termed “death” which is in principle irreversible.

From this we developed a custom of honoring or dishonoring people who no longer exist by the mechanism of treating their corpse in certain ways. When criminals were were beheaded with their heads rolling around on the ground and subsequently being stuck on a pike, it was a highly visible sign of disrespect and disgust for the kind of life lived by the deceased. Similarly, steps taken to reduce grotesque appearance of the corpse by embalming or cremation have evolved as a token of respect.

This notion of “rewarding” or “punishing” people after their death serves purely as a signal to the living as to what kind of life should be considered worth living. Likewise, a person’s final moments take on a special significance, despite being just a tiny fraction of their total lifespan. What were they doing when they went? Were they anxious, or accepting? There is a certain poignancy of accepting death rather than fighting, which I imagine a hospice worker like Peggy Jackson would easily relate to. Collectively these special attitudes towards the experience in one’s final moments and state of one’s remains after death are the Historical Death Meme (HDM).

Now, bring cryonics into the picture. The cessation of vital signs is no longer a sign of irreversibility-in-principle. The best mechanism for survival at this point is stabilization followed by cryopreservation. Stabilization is not a cosmetically appealing procedure. If stabilization happens late, this causes disfiguring edema. The scientific fact that it is the best hope the patient has for preserving their brain structure is overshadowed by the cosmetic details — purely because of the HDM.

But this isn’t the only big issue. The bigger issue, which I think is where the bulk of the hostility originates, is that the HDM itself begins to look ethically questionable once you begin to consider that cryonics is admissible. In preparing someone’s corpse, in ignoring their ischemic state as soon as vital functions appear irrecoverable to today’s technology, you are doing the patient a disservice. It’s not just a disservice, but potentially fatal disservice. In fact, by denying them their one shot at life you are showing them a sort of disrespect.

In other words, the perfect conditions for cognitive dissonance have been established. The HDM is highly valued, and an integrated part of the identity of practically our whole society. Doctors must be comfortable giving up on patients, and morticians must be comfortable doing cosmetic rather than life-saving surgery. Heirs must be comfortable taking money that could have been used to cryopreserve their parents and grandparents. To admit that cryonics has a valid chance of working, is affordable, is ethically motivated, and is seriously scientifically motivated and well-researched, would be to strip them of that comfort.

The feelings of unease must be transferred to cryonics as a means of keeping the HDM from appearing unethical, silly, prescientific, and superstitious. Since cryonics is relatively unfamiliar (in terms of the supporting science and actual practice) and has a variety of associations with science-fiction’s hand-waving plot devices and religion’s resurrection fantasies, a motivated skeptic need not work very hard to make themselves feel this way.

Posted in Cryonics | Tagged , , , | Comments Off

The diminishing returns of reactive medicine

In an article for Slate, Jay Olshansky argues in favor of a position that one would expect to be common sense at this point:

While we can extend life in aging bodies through behavioral improvements and medical treatments, the time has arrived to acknowledge that our current model of reactive medicine, of trying to treat each separate disease of old age as it occurs, is reaching a point of diminishing returns.

So what is the reason why vast amounts of money are spent on research to treat age-associated diseases but so little on eliminating or mitigating aging as such? Why is this “one-disease-at-a-time model” so dominant? One reason might be that most people believe that overcoming one specific manifestation of aging is easier to do than overcoming aging itself. Not surprisingly, most academic and commercial research is shaped by short term ambitions or short-term financial interests.

Many people who deal with serious age-associated diseases hope that a cure can be found within their lifetime.  This is not so strange if you consider that many people who do advocate meaningful rejuvenation research are technological optimists who think the same thing about overcoming aging. In that sense, people show little interest in supporting research that has little personal benefit to them or close relatives. This is further evidenced by the fact that people are more inclined to contribute to anti-aging efforts that promise benefits in their lifetime. This in turn provokes criticism from mainstream scientists of not being realistic, which further discredits the field.

But as Olshansky indicates, the diminishing returns of the approach to just fight the symptoms of aging should force people to change perspective. Olshansky also observes  that “manufacturing survival time in the absence of decelerated aging” can produce a lot of hardship and suffering in old age:

It’s important to acknowledge the fundamental differences between disease and aging. Although age-associated changes in the body produce an increased risk of disease, the reverse is not true. That is, reducing the risk of disease has no influence on biological aging. Thus, if a population is preserved with increasing efficiency by advances in technology that reduce the risk of disease, those saved will live into increasingly later sections of the lifespan where aging takes a greater toll on body and mind. Life extension achieved in this way could extend old age by exposing survivors to the high-risk conditions of frailty that are common, and largely immutable, near the end of life—the very outcome that medicine and public health practitioners are trying to avoid.

For people who have made cryonics arrangements, there is another danger; the possibility of life extension at the price of increased vulnerability to identity-destroying diseases.  There is no shortage of cryonics patients with Alzheimer’s or impaired brain function. As much as we would like to deny it, there could be a disturbing trade-off between life extension and true personal survival as long as treatments for neurodegenerative diseases are not available.

Posted in Cryonics, Science | Tagged , , , , , , | Comments Off

Cryonics, trans-temporal communism and future squatters

Cryonics advocate Eugen Leitl puts forward some hard-hitting and thought-provoking observations about cryonics (reminiscent of Mike Darwin’s more recent thoughts on the subject):

Cryonics, like Natural Selection, or the theories of General and Special Relativity, is core-smashing in character, and in the case of cryonics, the idea is so antithetical to the existing order of civilization that it can it only be advanced by insurgent means. This is so because cryonics overturns the Vitalistic view of life, challenges the conventional definition of death, invalidates the core tenets of contemporary medicine, erodes the need for a mystical afterlife, radically redistributes capital (disrupts inheritance, bequests, and mortuary customs), mandates a complete change in reproductive behavior, perturbs generational succession, requires space colonization, requires (and supports) profoundly disruptive technologies such as cloning, regenerative medicine, nanotechnology, artificial intelligence, and finally, ends the species and enables, if not requires Transhumanism. As a consequence, cryonics creates adverse emotional and intellectual states within the existing culture such as survivorship guilt, indefinitely extended anxiety and uncertainty accompanying life-threatening illness (the cryonics patient remains ‘critically ill’ for decades or centuries), prevents the psychological closure that accompanies “true” death with disposition of remains, creates indefinite anxiety about the well being of cryopreserved loved ones, disrupts the intimacy of family interactions during the “dying” process, may bitterly divide family members who are opposed to cryonics versus those who are in favour, and blocks or disrupts deeply held mechanisms for coping with death and bereavement that are inculcated from childhood by eliminating the customary wake, funeral, and other comforting rituals.

In particular, he opines that “the idea that cryonics was just an extension of medicine and is compatible with religion and existing social and political institutions, while superficially satisfying, is both mistaken and bound to fail.” After this observation one would expect him to advocate some radical form of transhumanism as a vehicle to promote cryonics. But he further believes that:

Distinct from initialization failures, there are inherent in cryonics several corrosive and self destructive ideas that have grown over time until they have virtually overwhelmed cryonics today. The first of these is “temporal load shifting,” or more colloquially, the problem of ‘our friends in the future…his causes cryonicists to increasingly shift the burdens, technological and financial, present and future, onto the people (supermen) who we believe will revive us from cryopreservation, a concept that may fairly be called Trans-Temporal Communism: from cryonicists now according our ability (none); and from our ‘supermen friends in the future’ according to our needs (infinite). Trans-Temporal Communism leads to the creation of ‘Future Squatters; people who believe that technological advances will happen when conditions are right for them to occur. This is a brilliant position because it is never wrong; it is the perfect piece of circular reasoning that justifies doing nothing. This creates a perverse situation wherein intelligent and talented people who enter cryonics do not, as might at first be thought, find it impossible to believe that cryonics, vast extension of the human life span, or, for that matter, many of the transformational technologies of Transhumanism are impossible, but rather they that find it not only believable, but inevitable that these developments will occur within their lifetimes (i.e., Kurzweil and deGray)….The Future Squatters who have come to dominate contemporary cryonics are not merely parasites content to sit and wait until robots show up at their doors with immortality on a silver platter, all too often they are actively contemptuous and dismissive of the (fewer and fewer) people working hard to build a practical, sustainable and robust cryonics that withstand the tests of time and deliver its patients to a future they have created; a future not only technologically capable of restoring them to life; but morally and financially impelled to do so, as well.

If one rejects both cryonics-as-medicine and the futurist / transhumanist vehicle to communicate the idea of cryonics, one wonders what the correct approach should be. The observation that “the core problem in cryonics is the absence of a philosophical and moral basis for cryonics and the accompanying ethics and dogma required to enforce it” does not seem to follow from the preceding observations.  Most importantly, what is this “philosophical and moral basis for cryonics” that is required, and why is it separate and different from the general moral conduct that social interaction and reason generate?

It is becoming clearer and clearer that demonstrating the technological feasibility of cryonics is not sufficient for the acceptance of cryonics. There seems to be a growing consensus that “fear of the future” and lack of closure are among the biggest hurdles for giving the idea a charitable hearing.  But little thought is being given to this topic, and it is quite correct that this omission can be squarely attributed to a kind of simplistic futurism that is circulating in cryonics circles. If  even most self-identified transhumanists cannot bring themselves to make cryonics arrangements, why would one expect the rest of the population to embrace the idea?

Cryonics advocates often seem to believe that if they refute the common scientific and technical objections to cryonics (which is not that hard to do because the psychological resistance to the idea prevents critics of checking even the most basic facts about the rationale and practice of cryonics) the social and psychological reservations will take care of themselves. This is not just incorrect, such reservations are often the most fundamental.

One would be surprised if an invasive, experimental medical procedure would lack detailed information about post-procedure care, responsibilities of  the hospital and family members, and reintegration. Considering that for many people cryonics constitutes a solitary leap into an unknown and far-away future, is it reasonable that providers of such care, and advocates of cryonics, think about doing a better job of responding to these concerns. This is mostly unexplored territory because even the most alienating events in human life as we know it cannot capture this aspect of cryonics.  It is doubtful that such concerns can be removed by altering the philosophical and moral basis of cryonics.

 

Posted in Cryonics, Society | Tagged , , , , , | Comments Off