17. October 2012 · Comments Off · Categories: Cryonics, Science

A common complaint against cryonics is that existing cryopreservation technologies may not be good enough to preserve the ultrastructure of the human brain. Advocates of cryonics often object that such views do not reflect actual inspection of the evidence of cryopreserved brains but instead reflect misconceptions about “freezing” and ice formation rupturing cells. But the more fundamental misconception rests on the view that for cryonics to work flawless preservation of the brain is absolutely essential.

This view is not only mistaken but holds cryonics to higher standards than those applied in conventional medicine. In medicine it is routine for patients to present themselves with conditions in which an organ or tissue has been changed from its normal condition (or appearance) as a result of disease or trauma. Restoring normal structure or function is the essence of most medical treatments.

One might object that in the case of cryonics we are concerned with the brain, which distinguishes itself from other organs that encodes highly individual information. If a portion of the brain is erased we cannot consult another brain or medical textbook to infer its original state. We can admit that this is a valid observation but it is not necessarily a fatal argument against cryonics, provided the damage has not reached the point of complete destruction or indecipherability.

There is a difference between damage and obliteration. If we look at electron micrographs of brain tissue produced at various points in time after circulatory arrest (“death”) we will observe progressive alterations of synapses, cell membranes, organelles etc. We describe such changes with a mental (or actual) map of how they normally look like in mind. At this level the fact that the brain is a highly individual organ is no longer relevant because we know the universal biochemical language in which this identity is written. At this point the real question becomes at which point is it not even possible to infer the original condition of the brain. As far as we understand this today, this may be a question of many hours, if not days.

This robustness of identity-critical information in the brain may seem to contradict the routine observation in emergency medicine that there is a much narrower time limit for successful resuscitation from cardiac arrest. The crucial difference here is that we are no longer talking about the ability to infer identity-critical information but restore physiological function. But function is a lot more vulnerable to metabolic and biochemical changes than the wiring of the brain. In fact, if function were a necessary requirement to infer information a lot of existing forensic and archeological science would be impossible.

In approaching cryonics it is important to recognize the distinction between preserving and inferring. In this way we can better assess the prospects for resuscitating patients who were cryopreserved under nonideal conditions and/or with older technologies.

Originally published as a column (Quod incepimus conficiemus) in Cryonics magazine 2012-5.

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.

02. July 2012 · Comments Off · Categories: Cryonics

In a few days the Institute for Evidence Based Cryonics and Cryonics NW will host a symposium on Cryonics and Brain-Threatening Disorders. We care deeply about this issue and some of us have observed fellow cryonicists succumb to (advanced) dementia prior to their cryopreservation – or worse, the disease compromised their understanding of their cryonics arrangements and what it takes to keep them in place. Still, we have also observed that many cryonicists stick their head in the sand about this topic or are (excessively) optimistic that their diet or lifestyle will save them from such a fate. We would like to share this optimism but we think this line of thinking is neither realistic nor rational. In addition, dementia is not not necessarily an outcome of genes or age but can occur as a result of other diseases and accidents. We may feel comfortable about contemporary cryopreservation technologies but there is no clear answer to acute or progressive destruction of the brain. As Mike Darwin has pointed out, there is an urgent need for a “Brain Centered Approach to Geroprotection for Cryonicists.”

To facilitate more exchange between the presenters and the audience we have added a panel about cryonics and dementia at the end of the day. We have no illusions about being able to solve this problem soon but a better understanding of early diagnosis, available treatments, foreseeable interventions, and legal options for cryonicists is an important first step.

The expanded schedule is available here.

Registration and interaction with other attendees is available on the Facebook event page. You can also find more information there about pre-symposium socializing opportunities.

21. June 2012 · Comments Off · Categories: Cryonics, Science

From June 3 to 6, 2012 I attended the annual Society for Cryobiology meeting, which in 2012 was held in Rosario,Argentina.

Attending with Argentine biogerontologist and Cryonics Institute Member Rudy Goya may have reduced the interaction I had with the cryobiologists. There were fewer sessions than usual, and thus more free time. The welcome reception was not held until the evening of the first day of the sessions.

The first session dealt with an aspect of Argentine cultural heritage, the Llullaillaco children — three Inca children who had been mummified by dehydration high on a volcano and preserved for over 500 years. Two of children were selected by the Incas because they were “perfect” (beautiful and pure) at 6 or 7 years of age. It was believe to be an honor to go directly to heaven, not really death or sacrifice. The children were given an intoxicant and buried alive atop the Llullaillaco volcano. Much of the session focused on the conditions that caused the children to be so well-preserved, and the conditions the curators should use to preserve the children for the future — involving careful regulation of temperature, atmosphere, humidity, and an environment inhospitable to most microbes.

If reanimated cryonicists receive anything like the care these children are receiving, there should be no concerns about being welcome in the future. In a sense, the Incas had it right when thinking they were sending the children to heaven. Of course the Inca children were deprived of life and are unable to experience or enjoy their treatment by modern curators — and cryonicists should not encourage hastening death based on reliance on unproven future technologies.

At this conference there were special “How to do it?” sessions overlapping part of the lunch hour that focused on practical techniques unrelated to the experimental results and theoretical considerations covered in the regular sessions. Sunday’s topic was proteomic analysis, which covered removal, isolation, and identification of proteins from cells. The presenter (from the Institute of Molecular Cell Biology in Rosario) claimed that instrumentation allowing high throughput and resolution had given proteomics a maturity comparable to genomics.

The afternoon sessions were concerned with cell and tissue preservation. Elza Cabrita reported on improved cryopreservation of fish sperm through a combination of cryoprotectants and antioxidants. Locksley McGann reported on experiments sequentially exposing human articular cartilage to four CPAs (DMSO, glycerol, propylene glycol, and ethylene glycol) at lowering temperature (0ºC, −10ºC, −15ºC). Vitrified samples were cooled to liquid nitrogen temperature, and demonstrated 75% cell recovery when rewarmed.

Adam Higgins reported on an improved procedure for washing glycerol from red blood cells. Currently about 99% of banked blood is stored at refrigerator temperature (2-4ºC), with a shelf life of 42 days. Only 1% of blood (mostly rare blood types) is cryopreserved with glycerol and stored at −80ºC, with a shelf life of ten years. A major deterrent preventing more blood from being banked at −80ºC is the 30-60 minute glycerol washout procedure. Adam’s group developed a procedure that can wash the glycerol out in 30 seconds, but 5 seconds longer or shorter results in too much hemolysis. A three minute washout procedure is less time sensitive (one minute longer or shorter is tolerable), but the method needs to be scaled-up from the 0.5 milliliter test volumes being used.

On Monday, Peter Mazur reported that in vitrifying mouse oocytes, it is the warming rate and not the cooling rate that is most critical for success. He spoke of microwave warming and the problem of thermal runaway (uneven warming). Ice blockers would not cross cell membranes, and thus would not be of use against intracellular ice formation. Pier Morin reported on miRNA microarray assessment of miRNA expression of the freeze-tolerant insect goldenrod gall fly at control (+5ºC) and freezing (−15ºC) temperatures. mIR-210 was down-regulated and mIR-1 was up-regulated at freezing temperature (the latter is involved in cell cycle regulation).

Ali Eroglu reported on epigenetic perturbation resulting from human oocyte cryopreservation techniques. Both the slow freezing and vitrification methods he used resulted in down-regulated expression of H19 and Ube3a genes. Igf2r was down-regulated by vitrification, but not by slow freezing.

Monday’s “How to do it?” session described a combination of nanotechnology and stem cells for tissue engineering. Specifically, electrospinning can be used to create a nanometer scale web of biodegradable fibers that can be populated with mesenchymal stem cells by electrospraying. The main challenge is vascularization of the tissue. Vascular Endothelial Growth Factor (VEGF) increases cell adhesion, but not necessarily vascularization.

Barry Fuller reported on successful hypothermic perfusion of liver. A kidney hypothermic perfusion machine has been in operation for ten years, but liver has been more challenging, because of its large size and the fact that two vessels supply the organ (hepatic artery and portal vein). The liver hypothermia perfusion machine uses two pumps.

PhD student Na Guan described her study of gene expression changes associated with chilling injury of rat liver slices. Cryoprotectant solutions supplied by 21CM (Greg Fahy) were used to ensure no ice formation interfered with the process. ATP levels indicated that the cryoprotectant solutions used were causing no damage, although the composition of those solutions was not disclosed. 1108 genes were observed, of which 251 were up-regulated and 77 were down-regulated by chilling at −15ºC. Focusing on the top ten up- and down-regulated genes: inflammatory and DNA repair genes were considerably up-regulated, and genes associated with biosynthesis of cholesterol and polyunsaturated fatty acids were down-regulated. The latter seems paradoxical in light of the up-regulation of cell surface-linked signaling pathways, which indicate cell membrane injury.

During the question period, both Andreas Sputtek and Arthur Rowe were sharply critical of the undisclosed composition of the 21CM cryoprotectant solutions being used. Sputtek said that because science is about disclosure of methods and materials, Guan’s work was not science. Guan said she had begged 21CM for disclosure, but said she was told that anyone wanting to replicate the experiments could buy the solutions from 21CM. Tiantian Zhang said that gene analysis only done 30 minutes after chilling injury does not give the whole picture. She said that in her own work doing gene analysis of fish oocytes or embryoes after chilling injury, gene expression changes dramatically with time — that it is a mistake to only analyze the expression 30 minutes after exposure as Guan had done. After the presentation, Arthur Rowe spoke with Guan telling her how much trouble he has had over the years with her collaborator (Dr. Fahy) in connection with the non-disclosure issue. I spoke with Guan myself after her presentation. She told me that the greatest chilling injury occurs at −90ºC. She also said that she would be getting her PhD in July and did not know who would be continuing her work. When I spoke to Dr. Fahy about the presentation, he told me that the composition of the vitrification solution had been disclosed and that Guan was mistaken in believing that she could not disclose the composition.

Tuesday morning had been scheduled to begin with a lecture by Ken Storey. Storey typically has no interest in what other cryobiologists have to say, is fairly ignorant of areas of cryobiology outside of hibernation and effects of low temperature on animals in nature, and only comes for his own presentation before leaving. His ignorance is on display when journalists get him to do cryonics-bashing, which he does with relish, but the general public only sees the comments of a respected cryobiologist, not the ignorant misunderstandings of cryobiology. I would not have expected Storey to come all the way to Rosario, Argentina only for his own presentation, but this is what he attempted to do — and he missed one of his flight connections. Ironically, this year Storey was honored by being made a Fellow in the Society for Cryobiology. Storey does, admittedly, have a fabulous knowledge of molecular biology, and is an outstanding scientist in connection with his own work.

To compensate for Storey’s absence the conference organizers arranged a makeshift follow-up session on the Llullaillaco children. This wasn’t entirely a waste, because many issues had not been addressed in the first round. I was going to question using a 2% oxygen and 98% nitrogen atmosphere for the children rather than pure nitrogen, but Barry Fuller raised this objection before I was called upon. I did, nonetheless, suggest that the goal should be to perfect the preservation environment rather than try to recreate the conditions of the mountain. Even this had not been done because the relative humidity had been raised to 70% on the bad advice of an expert rather than held to the 40% present on the volcano. The children were reportedly gaining 300 grams per year, probably from the humidity. There is a lower humidity limit below which no microorganisms can grow, but 0% relative humidity in the −20ºC preservation chambers would run the risk of freeze-drying.

For the second session on Tuesday, John Crowe had been scheduled to lead a symposium composed of 3 other speakers besides himself, but all of the other 3 speakers cancelled-out. John, nonetheless, did an excellent job of speaking for the whole session on the basis of his own work. John is an expert in dehydration and freeze-drying of organisms as well as on tardigrades and trehalose. Drying DNA with trehalose prevents fragmentation, and drying proteins with trehalose prevents denaturation. John discovered that drying liposomes with trehalose prevents membrane fusion — although he lost most of the patent rights on commercially valuable processes by publishing too soon. Dehydration of samples containing sucrose drives the glass transition temperature (Tg) from 20ºC to 60ºC, but dehydration of samples containing trehalose raises the Tg from 20ºC to 120ºC. More recently, however, it has been found that LEA proteins can be as protective as trehalose, but in a way that is distinctive and complementary to trehalose — stopping liposome fusion, preventing protein aggregation, and changing sample Tg. Yeast cells are protected against dehydration damage not only by trehalose, but by the trehalose transporter protein which exports the trehalose to the exterior membrane surface and imports the trehalose to the internal membranes of organelles such as mitochondria. But although the genome of tardigrades has been sequenced, the tardigrade trehalose transporter has not yet been identified.

Barbara Reed is probably the world’s foremost expert on plant cryopreservation, and she has spoken a lot about the benefits of antioxidants for cryoprotection. But the presentation Barbara gave on Wednesday gave me the strongest indication that oxidative stress could be a significant mechanism of cryoprotectant toxicity. Not only because a variety of cryopreserved plants show improved viability with Vitamin E, Vitamin C (if iron is removed), lipoic acid, glutathione, and melatonin — but because oxidative damage was shown to increase significantly associated with cryoprotectant loading.

Roland Fleck works with the UK Stem Cell Bank. The Bank conducted studies indicating that a 2-step freezing protocol results in better viability than vitrification. But examining the results of 8 technicians showed that in the hands of the most experienced technician vitrification was as effective as the 2-step freezing protocol. Protocols should not be so highly dependent upon technician expertise. After his presentation, Roland told me he was concerned that he was only able to assay viability by the use of trypan blue, which only indicates membrane integrity and does not provide a very fine measure of cell function. He said that the requirement to use the trypan blue viability assay was imposed by bureaucrats or scientists who do not have much knowledge of cryobiology.

Igor Katkov said that he believes any sperm cell can be vitrified simply by choosing the right cooling and warming rate. He said he was advised by his patent attorney to drop seven slides from his PowerPoint presentation.

At the business meeting the Society membership was reported to be down to 186. The journal CRYOBIOLOGY continues to be profitable. CRYOBIOLOGY has a 33% rejection rate, a 1.83 impact factor, and 33 Members on the Editorial Board. The Society has $300,000, which the IRS thinks is too much for a charitable organization, but the IRS is allowing the society to retain tax-exempt status. Increasing travel awards is the preferred use of money, but there is a problem that on the one hand travel awards are a taxable benefit, and on the other hand it is illegal to pay the taxes on travel awards. The 2013 conference (the 50th annual conference) is to be held in Washington, DC, where the first conferences were held. The 2014 conference might be Istanbul, Turkey and the 2015 conference could be in Isreal, but definite decisions have not been made.

Last year’s new Society for Cryobiology Fellows Barbara Reed and John Crowe each gave presentations reviewing their careers. Barbara Reed began as a plant biologist in 1985, but was brought into the field of cryobiology by a need to preserve germ tissue. John Crowe said that after the Sputnik shock of 1957 the US government sought to encourage more young people to go into science, including him. As a teenager, John was sent to a number of different science laboratories on his summer vacations. John considers himself more of a “dryobiologist” than a cryobiologist. He entertained us with photos taken in the many exotic countries he and and his wife have visited since his retirement.

The two new Fellows for 2013 are Ken Storey and Mehmet Toner.

This conference was attended by not more than about 80 people, at least half of whom were South America. There were maybe 30 or so hard-core Society for Cryobiology Members. This was my 9th annual meeting in a row, but for the most part I made little effort to relate to the cryobiologists, although one of my intentions in attending these meetings has been to soften the hostility of cryobiologists to cryonicists. I sat near the front of the meetings with Rudy who told me that he learned a great deal about the cryobiology behind cryonics practices by attending this conference. Very many of the cryobiologists were reporting on using vitrification at this conference, and including articular cartilage and plant tissue as well as single cells. I was fairly active in my questioning and comments — about which a few of the cryobiologists complimented me.

I lost my sense of urgency about talking to Peter Mazur. Peter recently told a journalist that although it is not possible to prove that the chance of cryonics patients being reanimated are zero, “you can, I think demonstrated that the probability of its being done is so extremely low that effectively it is zero”  [CANADIAN MEDICAL ASSOCIATION JOURNAL; Monette, M; The Church of Cryopreservation; 184(7):749 (2012)] I am curious about the demonstration Peter has in mind, but I am also committed to learning from cryobiologists rather than arguing with them about cryonics. Peter walked away a few years ago when I asked him when solution effects rather than mechanical damage cause injury to cells due to slow cooling, so that may be a touchy subject with Peter as well.

I did, however, pepper John Crowe with questions — finding him to be friendly and informative. John confirmed what Peter Mazur had told me about cells being able to tolerate the loss of all osmotic water (freezable water, which constitutes at least 80% of cell water) without injury — a matter of great relevance in the vitrification of cryonics patients (assuming inter-cellular effects are not of great significance).

I sought-out Ali Eroglu, with whom I have had little interaction in the past, calling his attention to an article in the most recent issue of CRYOBIOLOGY about transfection of mammalian ovary cells with trehalose [CRYOBIOLOGY; Chakraborty,N; 64(2):91-96 (2012)]. Ali has microinjected oocytes with trehalose (along with low concentrations of DMSO to protect the mitochondria) [BIOLOGY OF REPRODUCTION; Eroglu,A; 80(1):70-78 (2009)]. Ali had not seen the CRYOBIOLOGY article, but he told me that ovarian tissue is easier to work with than oocytes.

At the final banquet I sat next to one of the conference organizers. He told me that John G Baust had been supposed to conduct a symposium, but had cancelled the whole thing a month before the conference without giving any explanation. He agreed with the comments I had made about the Llullaillaco children, and told me that a committee of cryobiologists was going to supplement the questionable advice that the Argentine government has been getting from a single advisor in New York. He told me that National Geographic had discovered the children and attempted to remove them from Argentina on a midnight flight, but the Argentine government got wind of the plan and intervened. Nonetheless, the children were simply kept in −20ºC freezers for several years while planning and building better preservation chambers.

The return bus trip to BA on Thursday took the entire afternoon — much longer than I would have expected. I sat next to Adam Higgins on the bus, and spoke with him much of the time, mostly about his life and work, as well as about our experiences in Argentina. Adam knew Spanish fairly well because he has spent four months of language immersion living in Equador (and visiting the Galapagos Islands). If he gets a patent for deglycerolizing blood, the University would get half the royalties and he would split his half with his collaborators. The advantages of his method would be the ten year rather than 42-day shelf life for banked blood, and the greatly reduced washout time. The latter is a significant savings in labor costs, but would have to be weighed against greater electrical costs for a −80ºC freezer as opposed to refrigeration. Even if he is successful in perfecting his methods, he thinks that the blood banking industry is too conservative to be captivated by superior storage methods. Adam has attended most of the annual conferences since I began attending in 2004, and told me that he would like to become a Governor of the Society. Not once did Adam ask me what work I do, and he evidently does not know because he was surprised when I told him I am not a Member of the Society for Cryobiology. Whether or not I am formally accepted as a Member, my attendance at these conferences is implanting me into the consciousness of the cryobiologists as being a member of their community.

20. June 2012 · Comments Off · Categories: Cryonics, Death, Neuroscience

It is generally not the task of scientists to consider the legal, financial, and logistical limitations when searching for biomedical breakthroughs but there are good examples where considering the real-world applications of a technology can be instructive. Research aimed at preservation of brains (or the “connectome”) is such an example. Even if chemopreservation can be demonstrated to preserve the intricate wiring of the brain, it can be safely assumed that there will not be a massive change in demand for brain preservation technologies (especially if the technology is too strongly tied to mind uploading). As a consequence, providers of chemopreservation will most likely operate in the same environment as providers of cryonics. That means that, as a general rule, there will be a delay between pronouncement of legal death and the start of procedures.

There is now more than 40 years of mainstream biomedical research demonstrating that even short interruptions of circulation (under normothermic conditions) can produce perfusion impairment in the brain. As has been demonstrated by cryonics researcher Mike Darwin and my own lab, Advanced Neural Biosciences, this “no-reflow” can produce poor distribution of cryoprotectants (including vitrification agents) and associated freezing. One serious concern that cryonics researchers have about chemopreservation-in-the-real-world is that poorly chemically fixed brains will be prone to autolysis during long-term storage. This limitation of chemopreservation applies to both “conventional” biological resuscitation scenarios as to whole brain emulation. One can only recover (or “upload”) what is preserved – or can be inferred. And as far as we understand things today, the advantage of temperature as a long-term preservation method is that it does not depend on a healthy, non-ischemic circulatory system. Cryopreservation of an ischemic brain can produce ice formation, but as soon as it is placed in liquid nitrogen, cold will “fix” whatever there is without further degradation. The same thing cannot be said about chemopreservation under poor conditions.

There is an understandable tendency to compare brain preservation protocols under ideal conditions and favor the method that produces the best preservation. But support for either technology cannot be solely based on results produces under controlled lab conditions. Personal survival technologies should be evaluated under conditions that are most likely to be encountered by organizations that will offer them. Demonstrating that chemical fixation (and plastination) can preserve the connectome is a laudable goal but the case for chemopreservation as a clinical experimental preservation method requires a persuasive response to the objection that delays in fixation can frustrate the aims of chemopreservation in the most fundamental manner.

One interesting aspect of the cryonics vs chemopreservation debate, though, is that it appears that some people simply feel more comfortable with one of the approaches. People who have shown the slightest interest in human cryopreservation can get really excited about the idea of chemical brain preservation. This indicates that if both approaches would be pursued actively, the growth of chemopreservation would not necessarily be at the expense of cryonics but there would be a growth in the total number of people making bio-preservation arrangements aimed at personal survival. But as Mike Darwin has recently pointed out, chemopreservation is not at the stage where it can be responsibly offered. The growth of this field requires a committed group of individuals who will research, develop, and implement this program. Chemopreservation does not need to be perfected before being offered (neither was cryonics) but so far most advocacy has been mostly at the conceptual level.

08. June 2012 · Comments Off · Categories: News

The schedule for the upcoming Portland Cryonics and Brain-Threatening Disorders Symposium has been published.

On July 7, 2012 a number of high-profile and upcoming speakers in the cryonics and life extension community will talk about identity-destroying brain disorders and how diseases like Alzheimer’s can frustrate the objectives of the most ambitious life extentionists. Topics that will be discussed include the pathophysiology of Alzheimer’s, emerging early-diagnosis technologies, neurogenesis in adults, repairing the aging brain, and legal options for people diagnosed with a brain-destroying disease.

Entrance to the symposium is free.

Other activities during this weekend will be announced soon.

The schedule is available here and you can register on our Facebook event page.

09. May 2012 · Comments Off · Categories: News

An additional speaker has been added to the Symposium on Cryonics and Brain-Threatening Disorders line-up.

Keegan Macintosh – Revisiting Donaldson v Van de Kamp: A Comparative Constitutional Analysis

Suffering from a malignant brain tumour, Thomas Donaldson petitioned the California Superior Court in 1990 for a declaration that he had a constitutionally-protected right to “premortem cryopreservation”.  His petition was denied, and his subsequent appeal dismissed.  In this talk, Keegan Macintosh will critically analyze how the case was argued and decided at the appeal level, discuss whether the same or similar arguments would be successful in the US or Canada today, and present novel arguments which would be available under Canada’s Charter of Rights and Freedoms that were and are not available under the US Constitution.
Keegan Macintosh will be receiving his J.D. in May, 2012, and sits on the board of directors of the Cryonics Society of Canada, as well as the Institute for Evidence Based Cryonics.  He is also President of a currently-incorporating life extension non-profit organization in British Columbia, and has been involved in educational outreach efforts in Vancouver on the topics of life extension and cryonics since 2010.

Please register for the event on our Facebook page so we know how many attendees to expect.

This article continues my survey of some of the various forms of legal protection for cryonics patients.  The previous article examined laws that directly affect what happens to a person’s body after legal death, both in the period immediately after declaration of legal death, and indefinitely thereafter.  We saw that the amount of prospective autonomy a person is permitted in this regard can vary significantly from jurisdiction to jurisdiction, with more or less consideration afforded to the wishes of the person’s next of kin, religious beliefs, societal norms and other public interests.  Two other legal structures which can and are used by cryonicists to promote the success and timeliness of cryopreservation, maintenance, and resuscitation are wills and trusts.

As before, this is a broad survey, with references to specific laws for explanatory purposes.  Given the context, it does not go too far to say that for your own safety, you must not rely on the following analysis as legal advice, and should instead consult an advisor licensed to practice in your jurisdiction.

Wills

While a person’s instructions regarding disposition of their human remains may not need to appear in their will in order to be enforceable (in those jurisdictions where such instructions are enforceable), the will’s primary function of distributing the deceased’s property can also be used to promote a cryonics patient’s interest in a timely cryopreservation and revival.

One option that should not be ignored on account of its simplicity, is that a cryonics patient can make gifts through their will to their long-term care provider, cryonics advocacy organizations, and/or relevant research organizations.  However, these gifts can only help the individual patient if they are successfully cryopreserved in the first place, and a cryonicist can use their will to promote that crucial objective as well.  In her article, “How to Protect Your Cryonics Arrangements from Interference by Third Parties”, Rebecca Lively discusses the use of “no contest” clauses in wills as financial dis-incentives to interference by next-of-kin.

“No contest” clauses are also known as in terrorem[1] clauses, or forfeiture clauses – but in terms of will construction, these clauses are actually conditional gifts, that is to say, gifts that are conditional on certain behaviour.  In the usual scenario, the trigger is contesting the will in some way: for example, applying to a court for a declaration that the will is invalid because the will-maker didn’t observe the proper formalities, or wasn’t competent to make a will at the time of its execution, etc.  A very simple forfeiture clause might read as follows: “I leave $50,000 to Mary unless she contests the validity of this Will or any part of it, in which case said $50,000 shall instead go to the Society for the Prevention of Cruelty to Animals.”  If that clause was in a cryonicist’s will, which also contained his/her consent to body donation and/or instructions regarding disposition of human remains[2] (or incorporated those directions by reference to documents outside the will[3]), then contesting the will or the validity of the consent or instruction would trigger the condition and the gift to Mary would lapse and go to the SPCA instead.  However, there are plenty of ways that next-of-kin can interfere with prompt stabilization and cryopreservation without making legal contest so, as Lively suggests, it may be wise to draft the triggering condition to include other forms of interference.  Of course, the difficulty with going beyond the categories courts are familiar with is the risk that, if challenged, a creative condition might be deemed void for uncertainty.  For instance, what quantum of delay in contacting a patient’s cryonics organization constitutes “interference”?  The answer to this question will vary by circumstance.  No doubt for this very reason, Lively suggests drafting such a clause to provide for “inheritance on a sliding scale based on the amount of time which passes between your legal death and your cryopreservation”[4], where, presumably, the entire estate goes to charity/cryonics organizations if the will-maker is not cryopreserved at all.  However, given the many factors that can contribute to delay or non-preservation over which the beneficiaries have little to no control, that kind of inflexible forfeiture clause might come across as unfair and have the undesirable effect of promoting legal interference with the patient’s will in circumstances that are already sub-optimal for other reasons.  A better alternative might be to draft a forfeiture clause that is triggered by intentional interference, the presence of which (whether by act or omission/delay) is to be decided by an expert delegate with no direct interest in the matter, with at least partial reference to specific criteria described in the will.[5]

The degree and requirements of enforceability of forfeiture clauses vary considerably from place to place.  One jurisdiction might require a “gift over” to a specific beneficiary (like the example above)[6], while another might hold valid a forfeiture clause where the gift simply lapses into the residue of the estate.[7]  As Rebecca Lively points out, forfeiture clauses are not allowed at all in Florida and Indiana[8], and in many jurisdictions where they are permitted, they will nevertheless not be enforced against beneficiaries who contest the will with “probable cause” (though this should exclude contests founded solely on hostility towards a deceased’s cryonics arrangements). Furthermore, if the will is contested successfully, and declared invalid, then the forfeiture clause goes along with the rest of it, and the next-of-kin will collect as per the jurisdiction’s intestate succession regime.  Finally, forfeiture clauses will be held void or unenforceable to the extent that they offend public policy.  For instance, some jurisdictions permit applications by a surviving spouse and/or children to “vary” a will that does not make adequate provision for them in the circumstances.[9] Strictly speaking, these support applications are not “contesting” the will, but in any case, a forfeiture clause that was drafted with the intent of foreclosing such applications may be held to be against public policy, and thus void.[10]

Support applications are not the only means whereby next-of-kin can avoid, or partly avoid the sting of a forfeiture clause.  Oregon (and thirty-nine other US states) allows a surviving spouse to opt for an “elective share” in lieu of what the deceased’s will gives them (or, presumably, doesn’t give them).[11]  The right to make this election can be waived by written agreement[12], so it stands to reason that a forfeiture clause written to exclude from the estate any person who interfered with the will-maker’s cryonics arrangements, would be declared void to the extent that it attempts to cut off an interfering spouse’s statutory elective share.  Thus, even if a spouse’s actions trigger a forfeiture provision pertaining to a specific gift to them in the will, they will still be able to elect to receive this mandated share in the deceased’s estate.

Ten of the other states operate instead on a “community property” system[13] which, generally described, means that any earnings of either spouse or partner after marriage or registration of domestic partnership becomes “community property”, as does any property acquired with such earnings or with other money expressly or impliedly designated as “community funds”.[14] In Washington, a surviving spouse automatically gets half of all community property[15]. This cannot be avoided by will[16], nor does the statute provide for waiving this right.

So what’s the moral here?  Well, depending on where a cryonicist lives, and whether he/she is married or partnered and/or has children, the use of forfeiture clauses in a will to disincentivize interference with cryonics arrangements requires not just that those special next-of-kin are given “something substantial” to ensure their abidance (as Lively suggests), but that they are given something substantial above and beyond what they are entitled to under any statutory claims they can make which either (a) avoid the effects of the forfeiture clause, or (b) don’t trigger it in the first place.  A further difficulty, for those cryonicists living in jurisdictions with support order provisions, is that the size of such an order is based on consideration of the circumstances of the surviving spouse and/or children, the size of the estate, and non-specific statutory language like “necessary and reasonable”[17], or “adequate, just, and equitable”[18], so it is impossible to know on the face of the statute just how much is enough.  In many cases, the utility of forfeiture clauses as legal protection from interference will be greater for cryonicists who do not have living spouses or children, which is unfortunate given that those particular family members often pose the biggest threat.[19]

As a final note, wills may be used to transfer assets into a patient care trust or personal revival trust, which will be examined in the next section.  However, such funds would be better insulated from the estate if they were transferred during the cryonicist’s (first) lifetime.

Trusts

The basic premise of trusts is that legal ownership of property and the right to “enjoy” (i.e. benefit from) property can be separated, the former belonging to one person or group of persons (trustees), and the latter belonging to another person or group of persons (beneficiaries).  The duties of a trustee towards the beneficiary’s interests are more onerous than the duties of contracting parties, so trusts are often used to protect and provide for vulnerable persons, like minor children and spendthrift relatives.  For this reason, one would expect trusts to play a role in the legal protection of cryonicists, and indeed they do.  The two most prominent examples are patient care trusts and personal revival trusts.

(i) Patient Care Trusts

Patient care trusts promote the maintenance and revival of cryonics patients in two important ways.  First, transferring legal ownership of the assets provided to fund those objectives to trustees protects the assets from third-party litigants.  Second, patient care trusts protect those same funds from misuse by the cryonics organization itself and misappropriation by its directors or employees, and even the organization’s dissolution.

The most intuitive way of accomplishing these objectives would be to execute a trust under which present and future patients were beneficiaries.  However, because cryonics patients are dead, legally speaking, they have no legal personality and cannot be the beneficiaries of a trust.  Hence, while the terms of the Alcor Patient Care Trust (“APCT”) do state that Alcor is “acting on behalf of the Patients in biostasis”, Alcor is designated the sole legal beneficiary.[20]  Protection against third-party litigants is effected through the magic words, “[t]he interests of the beneficiary in principal or income shall not be subject to the claims of any creditor or to legal process, and may not be voluntarily or involuntarily alienated or encumbered”[21], together with the sections of the Arizona Trust Code upholding the validity of such provisions.[22]

The APCT’s ability to protect patient care funds from misuse, misappropriation, or potential dissolution of the organization ultimately boils down to whether (or how easily) Alcor, as the sole legal beneficiary, can simply terminate the trust and reclaim legal ownership of the funds.  The only termination scenario contemplated by the APCT (wherein Alcor still exists[23]), is if all the patients are revived and reintroduced to society.  All of the Arizona Trust Code provisions addressing modification or termination of charitable purpose trusts (like the APCT[24]) require that the court hearing the application consider whether modification or termination is consistent with the purposes of the trust and, if the trust is terminated, that the trust property be distributed by the trustees in a manner consistent with the purposes of the trust.[25] Practically speaking, it would be very difficult for Alcor to appropriate the patient care trust funds for any purpose other than patient care.

The APCT was established in 1997 and became irrevocable in 1999. The Cryonics Institute (“CI”) established an Endowment Care Trust Fund in 2004, as part of its agreement with Michigan’s Department of Energy, Labour, and Economic Growth to become licensed and regulated as a cemetery.  According to the conditions of licensure, “[t]hese funds will be set aside for maintenance, which shall include liquid nitrogen storage of existing CI patients.”[26]  Obviously the scope of this trust is not as ambitious as the APCT (nor was it intended to be), but it does protect at least some of the assets earmarked for patient care from misuse or misappropriation.[27]

(ii) Personal Revival Trusts

In his article, “Personal Revival Trusts: If You Can’t Take It with You, Can You Come Back To Get It?”, Igor Levenberg points out that for all the benefits of patient care trusts, “those who are revived will eventually have to provide for their own care.”[28]  Patient care trusts provide legal protection for cryonics patients’ interests at an organizational level, but those who are interested in additional protection – during their time as cryonics patients as well as post-revival – can establish personal revival trusts for this purpose.

To some extent, personal revival trusts (aka reanimation trusts) suffer from the same legal hindrance as general patient care trusts, namely that the individual cryonics patient cannot simply name themselves beneficiary of the trust because upon cryopreservation they will lose their legal personality, and the trust would revert back to their estate.  However, Levenberg describes two ways a cryonicist can draft themselves into a trust that don’t require proof at the outset that human cryopreservation is reversible.  One option is that the revived patient is a contingent beneficiary of the trust[29]; the other is that the patient’s revival is a condition subsequent which terminates the trust, with disbursement of the trust property to the revived patient[30].  The distinction is subtle, but bears important implications.  If the revived patient is named as the contingent beneficiary, the trust must have another beneficiary in the interim, who could potentially call for modification or termination of the trust.[31]  However, on such an application, the court will have to consider the patient’s contingent future interest, and may appoint a guardian to represent that interest.[32]  On the other hand, if the revival of the patient is a condition subsequent terminating the trust, the cryonicist could choose between a trust with an interim beneficiary, or a purpose trust with no interim beneficiary (like a charitable purpose trust, or a trust for the maintenance of one’s “grave”).[33] Purpose trusts have the additional advantage of being available for this use in jurisdictions which do not otherwise allow perpetual trusts.[34]

Levenberg suggests that any concern over the possibility of the interim beneficiary hijacking the personal trust for their own benefit can be cured by designating one’s cryonics organization in that role.[35]  With the right drafting, in a jurisdiction that places emphasis on the original terms and purpose of the trust, this may well work (as with the APCT, discussed above).  An added level of assurance can be effected through the use of trust protectors, relatively recently emerged characters in trust law who can be empowered by the trust to, among other things, grant beneficial interests to new individuals – like newly revived cryonics patients… or newly legally recognized cryonics patients.[36]  Trust protectors feature in many of the personal revival trusts under development, including the Alcor Model Trust.[37]

Trusts clearly play an important role in the legal protection of cryonics patients.  However, on a critical note, it must be remembered that not all problems have financial solutions.  Cryonics patients benefit greatly from secure financial vehicles to support their continued maintenance, fund resuscitation research, and even revert to them if and when they are reanimated, but if the care of a particular patient or group of patients falls below reasonable standards due to negligent mismanagement, or is being threatened by hostile governmental policy, what can trustees really do?  Neither patient care trusts nor personal revival trusts have any means of exerting direct control over the patients themselves, regardless of circumstance.


Endnotes:

[1] Latin: “in fear”.

[2] Remember that these are actually separate legal mechanisms for transfer of custody of human remains. See Keegan Macintosh, “Legal Protection of Cryonics Patients, Part 1” Depressed Metabolism (23 February 2012), online: Institute for Evidence Based Cryonics <http://www.evidencebasedcryonics.org>.

[3] See e.g. Last Will and Testament for Human Remains and Authorization of Anatomical Donation, online: Alcor Life Extension Foundation <http://www.alcor.org/Library>.

[4] Rebecca Lively, “How to Protect Your Cryonics Arrangements from Interference by Third Parties”, online: Alcor Life Extension Foundation <http://www.alcor.org/Library>.

[5] This should be available in at least some jurisdictions.  See Re Tuck’s Settlement Trusts, [1977] EWCA Civ 11.

[6] Bellinger v Nuytten Estate, 2003 BCSC 563 [Bellinger].

[7] Peter G Lawson, “The rule against in terrorem conditions: What is it – Where did it come from – Do we really need it?” (2005) 25 ETPJ 71 at 80-81.

[8] Supra note 4.

[9] See Wills Variation Act, RSBC 1996 c 490, s 2; see also ORS § 114.015.

[10] See Kent v Mackay, [1982] 139 DLR (3d) 318 at para 20 (BC SC) (available on WL Can): “It is a matter of public policy that support and maintenance be provided for those defined individuals and it would be contrary to such policy to allow a testator to circumvent the provisions of the Wills Variation Act by the creation of such as [the no contest clause here].  It is important to the public as a whole that widows, widowers and children be at liberty to apply for adequate maintenance and support in the event that sufficient provision for them is not made in the will of their spouse or parent.”  This decision was followed by the court in Bellinger, supra note 6.

[11] ORS § 114.600.

[12] ORS 114.620.

[13] Leaving Georgia, which only provides a surviving spouse (along with any minor children) one year’s allowance from the deceased’s estate: OCGA § 53-3-1.

[14] See, for example RCW § 26.16.030.

[15] RCW § 11.02.070.

[16] RCW § 26.16.030(1).

[17] ORS § 114.015.

[18] Wills Variation Act, supra note 9.

[19] Mike Darwin, “Marcelon Johnson dies and is not cryopreserved” Depressed Metabolism (24 January 2009), online: Institute for Evidence Based Cryonics <http://www.evidencebasedcryonics.org>. See also supra note 4.

[20] Alcor Patient Care Trust, online: Alcor Life Extension Foundation <http://www.alcor.org/Library>.

[21] Ibid, art 3.

[22] ARS § 14-10502. These clauses are called “spendthrift provisions” due to their use in trusts drafted to support persons with bad borrowing habits.

[23] If Alcor ceases to exist, and the APCT cannot be converted into an independent legal entity, then the funds will be disbursed to another organization, or by some other means further the purposes of the Trust to support the care, revival, and rehabilitation of Alcor patients. See supra note 20, art 17.

[24] While Alcor drafted the APCT to be consistent with its 501(c)(3) status, whether the APCT is in fact a charitable purpose trust concerns the application of ARS § 14-10405(A). Framing the purpose of the trust in terms of scientific research and education is not necessarily conclusive of the matter.

[25] ARS § 14-10410, 14-10411, 14-10413, and 14-10414.  Not all jurisdictions mandate as strong deference to the original terms of the trust; see, for example, Trust and Settlement Variation Act, RSBC 1996 c 463.

[26] Ben Best, “Conditions to Licensure as a Cemetery” The Immortalist (March 2004), online: Cryonics Institute <http://www.cryonics.org/immortalist>.

[27] The assets designated for patient care on CI’s 2011 year-end financial report amount to more than double the contents of the Endowment Fund: Statement of Assets, Liabilities, and Fund Balance, online: Cryonics Institute <link:http://cryonics.org/financials.html>.

[28] Igor Levenberg, “Personal Revival Trusts: If You Can’t Take It with You, Can You Come Back To Get It?” (2009) 83:4 St John’s Law Review 1469 at 1494, n 129.

[29] Ibid at 1489.

[30] Ibid at 1495.

[31] Ibid.

[32] Ibid at 1489-90.

[33] Ibid at 1498.

[34] Ibid.

[35] Ibid 1495-96.

[36] See e.g. ARS § 14-10818(C)(1).

[37] Ben Best, “Asset Preservation Group Meeting” Long Life (July 2011) 23 at 24, online: Cryonics Institute <http://www.cryonics.org/immortalist>; see also Ben Best, “Fourth Asset Preservation Group Meeting” Depressed Metabolism (2 June 2010), online: Institute for Evidence Based Cryonics <http://www.evidencebasedcryonics.org>.

22. March 2012 · Comments Off · Categories: Cryonics

One of Alcor’s founders, Fred Chamberlain III, has been cryopreserved at Alcor. His wife, and co-founder of Alcor, Linda Chamberlain, has released a document to announce his cryopreservation and honor him:

“One of our great intellectual and emotional bonds was our interest in technological means of extending life. Fred and I incorporated the Alcor Life Extension Foundation in 1972; the minutes of those early Alcor meetings can be viewed by those who might be interested. Many details from those early years are available on Wikipedia.”

Fred and Linda were also supporters and occasional contributors to the Depressed Metabolism blog, and contributed one of the first articles about how modern cell phones can be used to communicate your cryonics arrangements in case of an emergency.

More accounts of Fred’s contributions to cryonics and Alcor should be forthcoming soon.