Cryonics Magazine, September-October 2012

On Saturday, July 7, 2012, I attended the Symposium on Cryonics and Brain-Threatening Disorders in Portland, Oregon. The symposium was the “brain child” of Aschwin de Wolf, who also kindly invited me to give a presentation on treatments to mitigate Alzheimer’s Disease (AD). The symposium was organized by the Institute for Evidence-Based Cryonics and Cryonics Northwest.

It has been said that cryonics arrangements are made by people who think about things other people would rather not think about – in this case, one’s personal mortality. Like the sun in the sky, we can be aware of its presence, but prefer not to look at it. Dementia is in the same category. Despite the fact that anyone who lives long enough (cryonicists are usually life-extensionists) is much more likely than not to get dementia, even cryonicists are often reluctant to plan for becoming demented. Aschwin deserves a lot of credit for not only being a cryonicist, but for organizing (with his wife Chana) the world’s first symposium/conference dealing with the subject of cryonics and dementia. It is all the more impressive because Aschwin is a man in his 30s.

The symposium required no registration, registration fee, or notification of attendance. One man attended because another attendee had informed his wife of the event while on an airplane to Portland. There were only about 30 people at the event, but the quality of the attendees and presenters was very high. The event was held at Kaos Softwear, a manufacturing company where Chana is a manager. All the talks were allotted one full hour.

Chana, who has a master’s degree in neuroscience, was the first presenter. Her topic was neurogenesis — the creation of new neurons. Although neurogenesis was discovered in 1965, because neurons are post-mitotic (are non-dividing cells), the discovery was viewed with skepticism until the discovery of neural stem cells in 1992. Neurogenesis only occurs in two discrete areas of the mammalian brain: in the olfactory system and in the hippocampus. The latter is more crucial, although the exclusion of the cerebral cortex is of great concern insofar as that is the probable location of memory, identity, and decision-making. The hippocampus prepares new memories for long-term storage in the cerebral cortex. Chana asked lots of questions for which there are yet no answers. Why does the hippocampus need to create new neurons in the creation of new memories? How is neurogenesis used? How is neurogenesis regulated? Neurogenesis declines with age, and is enhanced with exercise or ischemia. Ultimately, endogenous neurogenesis does not appear to hold much promise as a repair strategy for AD or other forms of dementia. However, it is a worthwhile endeavor to understand neurogenesis in order to guide our own attempts at neuronal repair and/or replacement.

Aubrey de Grey began his talk by acknowledging that none of the work being funded in the 2012 $4.5 million budget of his SENS (Strategies for Engineered Negligible Senescence) Foundation is focused on repairing the brain, although there is a project determining the rate of accumulation of epimutations, that is not focused on repair. He spent the first half-hour reviewing the SENS program, and the next 15 minutes explaining why 3 of the 7 SENS strategies are particularly applicable to dementia: (1) Neurofibrillary tangles and soluble amyloid in Alzheimer’s disease (AD), and their counterparts in other neurodegenerative diseases, are intracellular junk, (2) amyloid plaque in AD is extracellular junk, and (3) late-stage neurodegeneration involves cell loss. Dr. de Grey said that intracellular junk shows signs of failed autophagy. He said that most of the intracellular junk in dementia is protein. It should be easier to dispose of than the cholesterol degradation products which are the focus of SENS lysosome work on atherosclerosis, but which are not properly delivered to the lysosome. He outlined the circumstantial evidence that the main problem may be the same as in atherosclerosis, i.e. oxidized cholesterol poisoning the lysosome. He spoke of the current clinical trials for having microglia eliminate extracellular junk (amyloid plaques). The first human clinical trials had shown great promise, but were halted because 5% of the patients developed brain inflammations. The newer trials have apparently corrected that problem. Aubrey noted the widespread belief that the amyloid would be removed without being of much benefit – expressing his belief that this misses the point, because major postponement or reversal of AD will require fixing all three main problems, hence lack of benefit from fixing one is not evidence that that one need not be fixed. I am one of the skeptics because follow-up autopsies on the first trials showed that even when amyloid plaques had been completely removed, no reduction in degeneration had occurred [THE LANCET; Holmes,C; 372:216 (2008)]. By the time AD is diagnosed, neurodegeneration is too far along to be helped by removing amyloid (though there is rapid progress in improving very early diagnosis). Immunization to remove amyloid would be more effective if begun in the 20s or 30s, much like shots for measles or polio — as prevention rather than cure. Although amyloid may serve a positive function in repair or it would not have evolved. [Aubrey notes: who says it evolved? “Aging is a product of evolutionary neglect, not evolutionary intent” (Hayflick)]. Concerning cell loss, Aubrey was sanguine about Jean Hebert’s work exploiting the fact that certain neural progenitor cells are highly migratory, potentially facilitating widespread distribution of new neurons throughout the neocortex via stem cell therapies. Even if neurons can be replaced in the neocortex, I wonder how that would compensate for the loss of synaptic connections and strength of synaptic connections. Of the three approaches mentioned by Dr. de Grey, I would say that removal of intracellular junk has the best chance of being of benefit on its own, because it is the neurofibrillary tangles that tend to cause cell death rather than the amyloid plaques, which are an upstream event.

My talk was basically a summary of the “Alzheimer’s Disease: Molecular Mechanisms” page in the life extension section of my website BENBEST.COM. I wrote the page in 2003 between leaving my job as bond database support for Scotiabank in Toronto, Canada, and becoming president of the Cryonics Institute in Michigan. For the subsequent 9 years I have become increasingly displeased about how out-dated the webpage was becoming. So I was pleased at the opportunity to do the massive research required to update that webpage for this symposium. Unfortunately, it was all I could do to finish the updating before catching my flight to Portland. Aschwin and Chana allowed me to crash at their condominium. I missed the Friday evening social for those attending the symposium because I spent all evening and a couple of hours the next morning creating my PowerPoint. I was pleased with the result, however, and pleased with the presentation I was able to deliver.

I encourage anyone interested in the content of my talk to consult my Alzheimer’s webpage because that page has detailed linkable references which I could not include in my presentation. I believe that the most promising therapy is the targeting of copper with PBT2, which removes copper from amyloid without chelating essential element metals. Etanercept, which antagonizes the inflammatory cytokine TNF-alpha has also shown promising results. Possibly also, passive immunization with tau antibodies would be of greater benefit in stopping neurodegeneration than immunological approaches against amyloid. Concerning prevention, exercise, curcumin, pomegranate juice, and folic supplementation have shown good results. Seemingly conflicting results would indicate that ginko biloba can slow cognitive decline in Alzheimer’s patients, but is of no benefit in preventing the disease.

Mike Perry’s topic was Early Detection of Alzheimer’s Disease. On that subject he reported that the CerebroSpinal Fluid (CSF) is low in amyloid beta and high in phosphorylated tau protein. I had put much more detail on this subject into the biomarkers section of my webpage on Alzheimer’s Disease – which I showed to Mike later in the day. In his presentation Mike noted even for people who do not get AD, dementia of some kind is still very probable with aging. He commented that AD is not a terminal illness, which is defined as an illness in which two physicians have certified that the patient probably has no more than six months left to live. No AD patient dies of AD — the cause of death is usually infection (pneumonia, bedsores, urinary tract infection, etc.). I expressed concern that suicide by VSED (Voluntary Stopping of Eating and Drinking, as Mike calls it) by an AD victim could lead to autopsy. Mike denied that this was necessarily the case.  I was told that for anyone who had died by refusing food and water the cause of death would be obvious, and no autopsy would be required, though circumstances and policies will vary. Mike Darwin, however, noted that VSED could be harmful to the brain as cardiac arrest draws near, due to low respiration rates. Aschwin responded that this kind of brain damage is still relatively benign in comparison to the alternative (advanced dementia). James Swayze, who is a paraplegic with cryonics arrangements and was in attendance at this event, has expressed concerns that dehydration causes brain damage. Dehydration may reduce brain functionality, but brain dehydration is a key process in removing water from the brain in the vitrification point of view and is probably a benefit rather than a harm for cryonics purposes.  Alzeimer’s patients nearly always die of infection, and because infection may also occur early in the disease,  Mike Darwin recommended that anti-microbial treatment be refused by an Alzheimer’s victim as a way of hastening cryopreservation. If infection does not occur early in the disease, however, refusing antibiotics may not produce the desired result.

Keegan Macintosh, who recently graduated from a Canadian law school, presented on the subject of Thomas Donaldson’s 1988 lawsuit in California to be cryopreserved before his brain cancer destroyed too much of his brain to make cryonics a worthwhile effort. Keegan criticized the attorneys involved in the appeal for arguing that Donaldson’s right to “premortem cryopreservation” stemmed from a constitutionally-protected right to assisted suicide, rather than the right to pursue a risky, but potentially life-saving procedure. By framing the case this way, the Court was able to avoid having to consider Donaldson’s unique and crucially relevant motive, and thus the possibility of cryonics succeeding, for him or anyone else. Acknowledging, however, that options for assisted suicide could be of use to cryonicists with brain-threatening disorders, Keegan examined developments in American law on the issue, and then turned to Canadian jurisprudence. He pointed out a number of potentially significant differences between the U.S. Supreme Court’s substantive due process analysis in the more recent physician-assisted suicide cases, Washington v. Glucksberg and Vacco v. Quill, and Supreme Court of Canada’s approach to section 7 of Canada’s Charter Rights and Freedoms (right to life, liberty and security of the person) in Rodriguez v British Columbia, and cases since. The government’s position is presumably influenced by a desire to avoid a “slippery-slope” that disvalues human life. Keegan noted that although formerly other countries looked to the American Constitution for guidance, Canada’s constitution is now the world’s most popular role-model. Section 2 of Canada’s Charter of Rights and Freedoms emphasizes “freedom of conscience and religion.”

What would be the effect of someone acting on the belief that pre-mortem cremation is the road to salvation? “Freedom of conscience” implies that secular morality is as important as religious belief and there is some emerging jurisprudence to that effect. Would the belief that good-quality cryopreservation is necessary to live again at some future time not then receive equal protection to analogous beliefs and practices of religious origin? Keegan believes that an appeal such as Donaldson’s – and indeed any constitutional challenge against a law impeding access to cryonics – would have a better chance of success in Canada than in the United States.

Max More spoke without slides on the subject of “Survival, Identity, and Extended Mind.” The objective of Max’s talk was to consider how it could be possible to back-up personal identity-relevant information and then reintegrate that information to restore personality if cryopreservation has been imperfect. If cognitive processes and their inputs can be external to the brain, Max would like to take advantage of this to improve the chances of reviving people suffering from brain-threatening disorders. Andy Clark and David Chalmers wrote an authoritative paper entitled “The Extended Mind.” According to Max, for an outside object or process to be considered part of the mind, it has to produce results that are reasonably comparable to the components normally seen internally and biologically/neurologically. Clark and Chalmers propose three conditions for considering externally-located processes to be part of an individual’s cognitive processes: 1) constancy (the external component has to be there reliably); 2) accessibility (a natural ease of use of that component); and 3) automatic endorsement (the person must trust the component as they would trust any comparable part of their natural body). Max noted that a few years before the Clark/Chalmers paper he had considered the related issue of when an external technology could be considered part of the self (in chapter 4 of his dissertation: “Technological Transformation and Assimilation”). Although Max doubted Ray Kurzweil’s claim that an externally-convincing simulation of his father (made out of traces available) would actually have a self, Max did not argue that no well-simulated person could have a self. Max suggested that a notebook could be part of the thinking process, rather than just a tool. Nonetheless, he was dubious about the value of keeping lots of diaries, although it has been suggested that biographical information could assist in reconstruction of a cryonics patient and that cryonics organizations should take a more proactive role in fasciliting storage of identity- and memory relevant information. Max was also dubious that a computer that could convincingly simulate a person would have a self. He raised the question “What is self?” He referred to David Hume’s claim to introspectively only be able to discover thoughts and feelings, but no self. Dennett called self an illusion. This would lead me to believe that neither Hume nor Dennett should have much concern with their own survival (like most people?). Max said that he could lose a few memories without feeling his self was compromised — because he believes that personal identity is more than memory. It includes dispositions, values, and so on.

After the presentations there was a panel of all the presenters, plus Aschwin the host. I requested that each panelist explain what they would do if diagnosed with AD. Aschwin said he would immediately proceed to terminate his life under conditions favorable to cryopreservation provided that the diagnosis was credible and there are no short-term cures on the horizon. Keegan said that he would see first what, if any, time he had before symptoms such as apathy and denial would be expected to set in, and take some conservative portion of that time remaining to spend some quality time with family and friends. Keegan noted that, despite our best efforts, cryonics may not work, and thus it is rational to seek meaningful experiences in the moments one knows they have left, if such can be done without irreparably compromising one’s cryopreservation. I noted that Robert Ettinger also said he would terminate life by hypothermia in a cold bathtub at the end of a party with friends – but delayed such an action to the point where he lost consciousness and lost the ability to do any such thing at the age of 92 when he deanimated. I said that I would probably spend about a year attempting to confirm the diagnosis, and might delay further trying to determine if a cure was possible or forthcoming soon. Max said that he would want a second opinion, but like Keegan wanted to have some joyful time before self-termination. Chana said that she would be very concerned about how the decision to self-terminate would affect others, in particular how to explain to her family why she was ending her life while outwardly being in good health. Chana and Aschwin spoke of being sensitive to each other’s feelings about the matter. Aschwin noted that those who care for AD family members to a natural death often suffer from severe caregiver depression. Chana said that once she had decided to pull the plug that she would “find a way to take a bath in Agent Orange and take advantage of Oregon laws.” By this she meant she would find a way to give herself an aggressive form of cancer that would cause two Oregon physicians to declare that she is a terminal patient. Once this is done, an Oregon physician can write a prescription for phenobarbital which the patient can use for suicide by overdose at the time and place of their choosing. Aubrey said that he would delay the decision without worrying too much about loss of neurons. In addition to delaying because of diagnosis confirmation and evaluating hope for a cure within a short time period, Aubrey added evaluating the likelihood that cryopreservation procedures would be improved by waiting. Mike Perry said that he would try to confirm the diagnosis and if sure about it, “get it [deanimation] over with as soon as possible.”

I mentioned the case of a CI Member dying of cancer who, with her husband, called Suspended Animation, Inc., to be present at their suicide. Her 30-year-old husband was in good health, but did not want to live without his wife and planned to die along with her. CI terminated both their memberships and established a policy of reserving the right to cancel cryonics contracts in cases of suicide. Aschwin strongly disapproved of this CI policy. In his opinion, cryonics organizations should never encourage or condone suicide but should not refuse cryopreservation to those who have taken their own lives. I believe cryonics organizations cannot be seen as encouraging the hastening of death on the ground that cryonics may work, and must ensure that others do not get that impression. Not enough was said about what policies would be most appropriate for cryonics organizations.

I asked Aubrey if he thought that an AD patient would ever be so advanced that SENS could not save the self. Aubrey agreed that could happen, but it would be difficult to say when. The case is similar with straight frozen patients or patients with varying amounts of ischemic damage. The concept of “information theoretic death” is meaningful, but difficult to determine. Even if SENS methods could not recover enough memory and identity to save a person, some future molecular archeology might be able to do so.

There was some discussion about the most promising treatments for Alzheimer’s disease. Aschwin pointed out that both early-onset Alzheimer’s and late onset Alzheimer’s have a strong genetic component, which should favor the use of gene therapy.

Mike described the activities of the Venturists, which is offering to save Venturist Members who are being cryopreserved by a cryonics organization that fails. Another project of the Venturists is that they are seeking $50,000 for Mike Darwin, who lost his cryopreservation arrangements with Alcor due to financial difficulties.