22. March 2013 · Comments Off · Categories: Cryonics, Health

Wikipedia tells us that iatrogenesis is “an inadvertent adverse effect or complication resulting from medical treatment or advice…” The key word in this definition is “inadvertent.” For example, a doctor who exposes a patient to a bacterial infection by accidentally donning non-surgical gloves is an example of iatrogenesis. A doctor who deliberately administers a lethal dose of an anesthetic is not. One source of iatrogenesis is adverse effects.

A defining characteristic of contemporary human cryopreservation is that it is not possible to stabilize patients at very low temperatures without producing additional damage. Forms of injury in cryonics include ice formation, cryoprotectant toxicity, and fracturing. The relevance of the concept of iatrogenic diseases to cryonics was first recognized by Thomas Donaldson in his article “Neural Archeology” (Cryonics, February 1987). What sets cryonics apart is that cost-benefit analysis favors cryopreservation in a sense not encountered in ordinary medicine. Cryonics is the last hope to save the life of the patient and the alternative course of action is irreversible death.

One could say that the adverse effects of cryonics are a form iatrogenic injury, but since the major adverse effects of cryonics are known and recognized, cryonics cannot be brought under the rubric of iatrogenesis. But just as medical researchers and pharmaceutical companies allocate resources to developing drugs with fewer or less serious adverse effects, Alcor aims to improve procedures to eliminate these forms of injury. Examples include vitrification agents to eliminate ice formation, intermediate temperature storage to eliminate (or reduce) fracturing, rapid cooling devices to decrease ischemic injury, etc. The ultimate goal is to create a low temperature stabilization procedure that does not induce any additional injury. Such an achievement would constitute true human suspended animation. We would not be able to treat the disease of the patient yet, but could induce biostasis and reverse it without any adverse effects.

There is narrower application of the idea of iatrogenic injury to specific elements of cryonics procedures. For example, if a multiperson team is present at the bedside with a portable ice bath, ice, and a functioning chest compression device, but later analysis of the temperature data reveals negligible cooling, negligence or error may be involved. This is a rather dramatic example and most examples of non-intrinsic iatrogenic injury in cryonics have a subtler character. Cryonics is particularly vulnerable to iatrogenic injury because of the lack of clear objectives for the individual procedures and the lack of
consistent and comprehensive monitoring.

A rather disappointing excuse for permitting additional injury is the view that since cryonics patients will require advanced repair technologies in the future anyway it is not of great importance to minimize adverse effects of the cryonics procedures themselves. Such an attitude encourages recklessness, makes a mockery of the idea of human cryopreservation as medicine, and is not the kind of cryonics that is going to win over scientists, medical professionals, and the educated public. We do not know at which point injury translates into irreversible identity destruction, but we do know that the closer our procedures conform to reversible human suspended animation the less likely it is that we are wandering into that territory.

Cryonics cannot be disqualified merely because it introduces adverse effects. We know it does and we have no choice but to accept this. But an aggressive pursuit of human suspended animation will eliminate these adverse effects step-by-step so a future doctor will no longer need to worry about the effects of the cryonics procedure itself.

Originally published as a column (Quod incepimus conficiemus) in Cryonics magazine 2013-2

14. December 2012 · Comments Off · Categories: Arts & Living, Health

In her book Reconstructing Illness: Studies in Pathography, Anne Hunsaker Hawkins proposes that the modern pathography is replacing the accounts of religious conversion that were popular in earlier eras. What is a pathography? One definition that I found is “the study of the life of an individual or the history of a community with regard to the influence of a particular disease or psychological disorder.” Reconstructing Illness is an extensive study of this genre, how individuals deal with a diagnosis of a serious illness, and its broader role for medical caregivers and society.

One thing that I was wondering about while reading this is whether there are any pathographies of aging. There is no shortage of pathographies about cancer, HIV/AIDS, dementia (etc.) but I was curious if anyone had ever considered writing about the individual experience of the aging process and its inevitable outcome, death. Hawkins’s book has a very useful list of pathographies organized by disease. Perusing this list provides one with a good understanding of which kind of pathographies are popular but I failed to find even one title that explicitly concerns aging. Similarly, a search on “pathography of aging” on the internet did not produce any results. Sure, there are many books about facing death (or dealing with the death of a loved one) or the challenges and opportunities associated with growing older. But I am not aware of any account that treats the aging process in a format that is remotely similar to the descriptions of disease we meet in the pathography, let alone one where the aging process is described as a battle to be undertaken.

This should not be surprising. For most of us, disease is an abnormal condition that is defined relative to the normal aging process. Although a lot of disease is closely associated with aging, most people hesitate to call the aging process itself a disease because it would render the conventional use of the word disease problematic. There are diseases that are characterized by rapid aging in children, such as progeria, but we do call such conditions a disease because the pace at which these children grow older is not normal. In fact, pathographies of accelerated aging diseases might be the closest thing that approaches a pathography of aging.

Regardless of one’s perspective on the causes or mechanisms of aging, if we look at aging at the molecular level we will find a progressive accumulation of damage as we grow older. Whatever we mean by “aging gracefully,” this accumulation of damage stops for no one and ultimately results in death. Because aging is normal, and no one is being diagnosed with aging, there is not a clear, identifiable, moment in life that triggers the experience and events that are documented in the typical pathography. In fact, the universal nature of human aging and our propensity to react more strongly to unexpected events strongly biases humans to respond to specific diseases and not the aging process itself. What we seem to care about is abnormal deterioration and death, not the deterioration and death that is universal and foreseeable.

Not all people react in such a passive manner to aging. Not anymore. To some of us the relatively slow pace of physiological deterioration is a source of anxiety and the fact that it is a universal phenomenon does not provide solace, especially when medical technologies to halt or reverse aging can be envisioned and pursued. What sets humans apart from other animals is that we can recognize a universal condition and not be satisfied with it. Aging is an undeniable source of suffering and loss of dignity, sets the stage for separation and death, and favors short-term thinking over long-term responsibilities. It will only be a matter of time before the first pathographies of those who succumbed to the process while consciously fighting it will reach us.

Originally published as a column (Quod incepimus conficiemus) in Cryonics magazine 2012-6

25. July 2012 · Comments Off · Categories: Health, Science

As we learn more about the human genome, there will be an increasing recognition that general diet recommendations are going to give way to diet recommendations that more closely track the genotype of individuals. For those interested in healthy life extension an important question concerns the relationship between ApoE status and diet. In Why We Age : What Science Is Discovering About the Body’s Journey Through Life (1997) Steven N. Austad writes:

.. piles of evidence suggest that certain genes have a major impact on the development of atherosclerosis, probably the major disease of aging in the Western world. One of those genes is the Apolipoprotein E, usually abbreviated ApoE, which is involved in processing dietary fat. People with one form of the gene, called e4, have higher blood cholesterol (as well as higher LDL, or ”bad” cholesterol) levels than people with other forms of the gene. Finns have the highest rate of atherosclerosis in the world and also have one of the world’s highest frequencies of e4. The Japanese have the world’s lowest national rate of atherosclerosis and also among the world’s lowest frequency of e4. So you could call e4 an atherosclerosis gene. But this would be misleading, because the world’s highest frequency of e4 is found in a country, Papua New Guinea, where until recently atherosclerosis was virtually unknown.

People living in the bush in Papua New Guinea eat a low-fat diet (less than 5 percent fat, compared with 30 to 40 percent fat in an American diet) from necessity rather than choice. Their daily life also involves exercise at levels that would cripple or kill most Americans, even the athletically inclined….So genes operate not in a vacuum but in a specific environment. This is something to bear in mind when reading of the discovery of new “longevity” genes. For instance, there is another form of the ApoE gene, e2, which appears to lower blood cholesterol and therefore probably protects against developing atherosclerosis. Is this a longevity gene? It depends on the environment. Where people eat a lot of fat and don’t exercise, it may well be a longevity gene. In fact, French centenarians are about twice as likely to have this gene as the French population as a whole. But in other environments, the gene may well have little or no effect.

What these examples suggest, besides the difficulty in defining genes with respect to longevity, is that unless we understand how a particular gene is influenced by a particular environment, it will be difficult to translate the effects of genes from animals to humans. This is why most gerontologists are hesitant to claim too much about the relevance to humans of genes now being found with increasing frequency in simple organisms such as fungi and worms that seem to slow aging dramatically. It is difficult to draw parallels between human and worm and fungal environments. (p-41-43)

It is important to keep this point in mind when one considers the pro- and cons of a popular diet. For example, the Paleo Diet has become increasingly popular in the life extension & transhumanist communities. But if the observations of Austad are correct, a diet high in (saturated) fat could have adverse consequences for carriers of one or two copies of the ApoE4 gene. In fact, in her book The Perfect Gene Diet Pamela McDonald steers ApoE4 carriers in the direction of a vegetarian / vegan diet. As we learn more about the ideal diet for carriers of the ApoE4 gene, further refinements may be expected.

Another interesting emerging finding about ApoE4 is that its effect on having a higher probability of developing late-onset Alzheimer’s disease may be dependent on gender. A number of preliminary studies have found that the risk for developing Alzheimer’s disease for males with just one copy of the ApoE4 gene may not be much different from that of individuals who carry the more common ApoE3 gene:

Together with the previous meta-analysis, the data support the idea that a man with one E4 allele may not have much more risk of AD than an E3 homozygote, Greicius said, but added, “If you have two copies of the E4 allele, whether you are a man or a woman, there is no question that your risk leaps tremendously.” He is analyzing older datasets to see if the interaction between gender and ApoE genotype holds, and is also looking for genes that act synergistically with ApoE in women but not men.

If there is anything that is becoming clear from such studies it is that it will be increasingly inadequate to make sweeping statements about lifestyle, diet, and longevity without taking into account ethnicity, gender, age, genotype, and environment of a person. This does not mean that all general recommendations should be discarded. For example, there could be good reasons to believe that a low calorie diet and (moderate) exercise benefit most people. But when it is comes to the nitty gritty of what to eat and how to exercise a more personalized approach is warranted.

25. July 2012 · Comments Off · Categories: Cryonics, Health, Neuroscience

The recent symposium on cryonics and brain-threatening disorders was a major success. On Saturday, July 7, 2012, around 30 people attended the first ever symposium on dementia and cryonics in Portland, Oregon. The symposium started with a brief introduction by Institute for Evidence Based Cryonics President Aschwin de Wolf, who emphasized why people with cryonics arrangements have a clear interest in understanding and avoiding dementia. The first speaker, Chana de Wolf, introduced the audience to the topic of adult neurogenesis, the two areas in the brain where it occurs, and how little we still understand about it. Aubrey de Grey then talked about the SENS approach to rejuvenation and how some emerging damage repair bio-technologies might be able to also reverse neurodegenerative diseases such as Alzheimer’s disease. Cryonics Institute President Ben Best followed Aubrey’s presentation with a technical introduction about the pathophysiology of Alzheimer’s disease and the treatments that are currently being investigated. Ben is maintaining a page about the molecular mechanisms of Alzheimer’s disease on his personal website.

After the break Alcor staff member Mike Perry presented a detailed analysis of a recent paper in which cerebrospinal fluid samples could predict the onset of Alzheimer’s diseases many years before the first signs of cognitive impairment, a finding that holds great promise for life-extensionists, and those with an increased risk for Alzheimer’s disease in particular. Institute for Evidence Based Cryonics Board member Keegan Macintosh then presented a rigorous legal analysis of the Thomas Donaldson case and indicated how the case could have been argued more persuasively then and now. The last speaker of the day was Alcor President Max More who introduced the concept of the extended mind and its relevance to cryonics and neurodegenerative diseases, which prompted a useful exchange about the desirability of cryonics organizations facilitating members to store identity-critical information. The official meeting ended with a panel discussion moderated by Aschwin de Wolf in which all the speakers took questions from the audience and other speakers.

The program and panel left ample time for interaction between speakers and the audience. The topic of avoiding dementia and what to do when a cryonicist is diagnosed with a brain threatening disorder received a lot of attention. Despite the rather disturbing subject of the symposium there seemed to be a general recognition that it was extremely valuable to explore this topic in the context of cryonics. Some suggestions of how to deal with dementia were made that had not been previously discussed in cryonics publications.

It is not likely that we will organize a symposium about this topic every year but there was a strong interest in organizing meetings about other topics on a regular basis in the Pacific Northwest.

The slides of all but one of the presenters are available on the symposium page and a video recording of Aubrey de Grey’s talk was made by one person in the audience. A more detailed report of the symposium will appear in an upcoming issue of Alcor’s Cryonics magazine.

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.

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.

26. September 2011 · Comments Off · Categories: Cryonics, Health · Tags: , , , ,

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.

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.

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.

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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.

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.