Notes on the 1st Alcor New York Science Symposium

This past weekend, I was in New York City for a meeting organized by Alcor New York, a cryonics community group that is presently seeking to set up a more robust Biostasis Society of New York complete with well-organized standby capacity to help people achieve a successful cryopreservation at the end of life. Setting aside technical issues, the greatest challenge in cryopreservation is the fact the euthanasia, and thus the ability to arrange time of death, remains largely illegal. Hence there must be expensive standby operations, suboptimal deaths that cause significant damage to the brain, and a scramble to ensure rapid cooldown and preservation when death does occur. Since there are only two reputable cryonics providers in the US, local organizations capable of coordinating standby and transport are essential.

A number of folk in the cryonics community can be found in and around New York of late; Aschwin de Wolf and Chana Phaedra of Advanced Neural Biosciences, for example. In the introduction to the meeting, it was noted that early cryonics of the 60s and 70s started as much in New York as in California - there was a Cryonics Society of New York, and restoring that entity seems a worthy goal. There were a few noteworthy visitors from elsewhere, such as one of the Nectome folk, and a representative of the European Biostasis Foundation in Switzerland - this is not CryoSuisse, interestingly enough, but a distinct initiative with some overlapping members.

The talks at the meeting were divided between discussions of progress towards slowing aging or attaining rejuvenation, and discussions of cryonics itself. In general, cryonicists have a strong interest in not dying if all possible, and thus most are quite interested in what is going on in the newly formed longevity industry. The weight given to cryonics is tempered by expectations as to how soon rejuvenation therapies will arrive, and how effective they will be over time.

Joao de Magelhaes presented remotely from the UK, and gave his view on where things stand in working towards therapies to treat aging and thereby slow or reverse age-related degeneration and mortality. He is fairly conservative and pessimistic; he doesn't think that there will be enough progress in our lifetimes to achieve actuarial escape velocity, but he does think that we will see a slowing of aging in our later lives. Therefore cryonics is very important, and it is particularly important to achieve for cryonics the same that has already been achieved for work on the treatment of aging - to move it from a small, comparatively poorly regarded fringe concern to a field with notable technical successes and greater financial support. In this, there is little substitute for the hard work of bootstrapping, advocacy, research in resource constrained environment, and so forth. On the cryonics side of the house, de Magelhaes is involved in setting up the UK Cryonics and Cryopreservation Research Network to spur more academic research into relevant technologies.

Ben Best spoke about NAD+ upregulation and senolytics; he works at the Life Extension Foundation, and the principals there have recently started to heavily promote these approaches to treating aging. To the extent that they work, this is an example of what will happen to the "anti-aging" industry of fraud and hope and supplements that do little good: many of the people involved are motivated to do something about aging, and thus the good should chase out the bad, given time and therapies that actually work. Ben Best has experimented with these approaches to therapy, as one of the physicians connected with the LEF is willing to prescribe the senolytic dasatinib and NAD+ infusions, but committed the cardinal sin of not assessing metrics before and after. This is sadly prevalent in the self-experimentation community. If you don't measure, nothing happened. Still, there is evidence for both NAD+ upregulation and senolytics to be beneficial in older people, and sooner or later ever more physicians will become comfortable enough with the evidene to prescribe these therapies the many who might benefit.

Mike Perry gave a fascinating talk on the early history of cryonics, starting in the mid-1960s. It is eye-opening just how much information can be lost even at a distance of a mere fifty to sixty years. For example, James Bedford was the second preserved individual; the first may have been a woman called Sarah Gilbert, but this is uncertain. Of the fifteen people cryopreserved from 1966 to 1973, only Bedford remains. All of the others were lost to the haphazard, unprofessional nature of the early initiatives. Perry exhibited a short film made in 1968 by members of the New York Cryonics Society, showing the process of cryopreservation in one of the dewars of the time. It is quite the artifact of its era.

Chana Phaedra gave a presentation on paths towards optimization of cryopreservation. The success of cryopreservation depends upon delivery of cryoprotectant to the brain, efficiently and rapidly. At present, even in the best of circumstances the perfusion of cryoprotectant isn't optimal. This is challenging on a number of fronts: the skull is in the way; you can't just push fluid through tissue at high pressures; the blood-brain barrier blocks all cryoprotectants to some degree. The present conclusion based on work at Advanced Neural Biosciences is that the low-hanging fruit here is finding ways to bypass or open the blood-brain barrier. That may mean new cryoprotectants, or some chemical way of disrupting the blood-brain barrier rapidly and selectively. Other options to improve the situation: faster perfusion, less ischemia, and better assays that can be used in animal studies or on preserved human brains to reliably establish the quality of the preservation.

Aschwin de Wolf discussed the prospects for revival of patients who were frozen rather than vitrified, in part or in whole. The present wisdom is that straight freezing - which can and does occur in sections of the brain given a suboptimal perfusion of cryoprotectant - is highly destructive and causes large amounts of ice crystal formation. Can people with this sort of damage be repaired? De Wolf argued that the best approach, conceptually, is some form of low-temperature repair, via nanomachinery capable of operating in a preserved tissue at liquid nitrogen temperatures. The more interesting part of the discussion was a presentation of straight frozen and then thawed brain tissue that doesn't appear to have anywhere near as much damage as we might expect. The state of the tissue is worse than the same case for vitrification, but perhaps not as much worse as thought. More work is needed to assess this conjecture, however.

Since one of the presenters was ill, I filled in and gave an impromptu talk on self-experimentation: how to do it responsibly and effectively. We might consider four classes of self-experimentation at increasing levels of sophistication. Class 1: the sort of thing that everyone does with dieting for weight loss or eating foods and supplements for benefits. Class 2: compounds that are easy to obtain, easy to use, have great human safety data, and that may have effects on aging, such as metformin (a poor idea, I think) or senolytics (a better prospect). Class 3: treatments that are logistically challenging, and that may need a personal lab. Few people would be able to safety inject themselves with myostatin antibodies, for example. Get that wrong, and you die. But it is technically plausible, and helpful in terms of spurring muscle growth, given the evidence. Class 4: treatments that require a company or other significant effort to create. Liz Parrish's efforts with Bioviva , in order to self-experiment with telomerase gene therapy, for example. Or cryonics, for that matter. In near all cases, from dieting to quite sophisticated efforts, people tend self-experiment poorly. They do not do the one fundamental thing, which is to measure the effects.

Researchers in the fields of neurobiology and cryobiology gave a couple of technical presentations. One was an interesting outline of methods that could be used to evaluate the quality of brain preservation protocols, not limited to cryonics. It essentially boils down to examining labelled dendritic spines in neural tissue, which can be done before and after an experimental preservation to see how well the fine structures survived. It is even in principle possible to do this in a brain, rather than just in sections of brain tissue. The second presentation was on the use of computer modelling and machine learning to optimize cryopreservation procedures. There are many variables that can be tweaked, from cooldown trajectory to type and mix of cryoprotectants. Modelling could be used to find optimal parts of this large state space more effectively than other forms of experimentation.

The European Biostasis Foundation (EBF) representative outlined their efforts to build a professional cryonics provider in Switzerland, which would be the first in Europe if they are successful. I liked a lot of what he had to say, particularly that customer focus and scalability are the weak points of the present cryonics industry, given its non-profit roots. Thus one of the initial projects is to ramp up the professionalization of signup and standby. They are launching a brand called Tomorrow, which streamlines the process of signing up for cryopreservation, making it an entirely online process that runs more smoothly and requires less work on the part of the individual. They are also looking into how to make a for-profit cryonics organization viable through the path of long-term asset management, meaning partnership with life insurance companies. As you may know, most cryopreservations are funded by life insurance policies, making it quite cost-effective, particularly if started at a younger age. Middlemen in the the life insurance industry are a well established business model, and so this might be a path towards for-profit cryonics. Beyond these early stage efforts, EBF supports research efforts to improve the quality and reliability of cryopreservation, and is planning a storage facility, but this will be contingent on success in the initial for-profit path, opening the door to capital investment.

Unfortunately I had to leave before the final keynote by Robin Hanson, but it was an interesting event. The cryonics community needs to grow and find success: we live in a strange world, in which there is an alternative to oblivion and the grave, but it is poorly capitalized, poorly supported, and rarely used. Cryonics, as happened for the treatment of aging as a medical condition, must find its way to success and growth. I think that this will be achieved in part by the slow process of building technologies that work, such as reversible vitrification of donor organs, carried out in research communities that presently have little funding for rapid progress, and in part by efforts such as those of the EBF, the process of discovery in business models and persuasion.

Comments

What does de Magalhaes mean by "in our lifetime"? Most of those in the audience are between 30 and 70, and these extremes aren't the same - unless he thinks that not much will happen until the 22nd century.

Posted by: Barbara T. at November 25th, 2019 9:36 PM

Thanks, Reason. Did anyone at the event mention anything about recent progress regarding helium persufflation?

Barbara, I've noticed by watching Joao's presentations and reading his interviews that he seems conservative in general, so it wouldn't surprise me if he thought it would take that long (if not even longer), but I'm sure he'd be glad to be proven wrong by all of those rejuvenation therapies coming in 2036 like Aubrey thinks they might.

Posted by: Quinn at November 26th, 2019 5:31 AM

@Barbara T./Quinn: There are always gonna be pessimistic people and optimistic people regarding the future. Ray Kurzweil being the obvious counter view to opinions like the one quoted by Reason above.

Posted by: Steven B at November 26th, 2019 5:51 AM

Yep, Steven. What Kurzweil says about the future seems obvious to happen; the main parts where he and I differ are regarding supplements and timeframes (and even then, not by more than a few decades).

Biostasis makes sense according to the evidence (which is often ignored by journalists and even other experts) and the field deserves to become mainstream worldwide; while this statement is probably generally agreed upon on sites like this, it really needs to become a reality in order to help more people. As Reason often points out, many millions of people who are sadly suffering today could realistically benefit from future medicine by signing up for cryonics, yet there's only a few thousand people in total signed up at the moment.

Posted by: Quinn at November 26th, 2019 6:25 AM

"João de Magalhães"

Posted by: mcmp at November 26th, 2019 11:23 AM

Barbara: You can read his view on antiaging medicine here:

http://www.senescence.info/aging_cure.html

Basically, he thinks that a throrough knowledge of aging is required to intervene, so real antiaging is still far away and all we can have in our lifetimes is CR and the like.

Posted by: Antonio at November 26th, 2019 11:48 AM

@Antonio
In a way he is right. If you ignore senolytics we have incremental approaches tweaking the metabolism. It is plausible to increase the human lifespan to 150 with selective breeding, for example. However , that would take many generations and possibly thousands of years.

With small improvements here and there were can push the life expectancy and health span a few year higher. Probably even a couple of decades (put the whole population on CR, improved health care and such) with extremely public efforts.

And his pov makes sense sense. We, however, shoot for bigger gains that can make a real difference

Posted by: Cuberat at November 26th, 2019 12:42 PM

No, he is not.

If you "ignore senolytics", and mitoSENS, and amyloSENS and all the other SENS strategies, then yes, you only "have incremental approaches tweaking the metabolism". But there is absolutely no reason to ignore them.

Posted by: Antonio at November 26th, 2019 12:52 PM

Hi everyone,
Glad to see the enthusiasm about the 1st NYC Alcor Symposium here, and thanks to Reason for posting these excellent notes!

I'm the researcher who was ill, I'm also one of the co-organizers of the NYC Alcor group. I would like to add my thoughts to this discussion on the potential for progress of anti-aging in "our lifetimes" (I'll interpret that as "within the next 20 years" for clarity). My talk was to be on low-dose pharmaceuticals interventions for anti-aging -- I'll post the link to my rehersal talk and slides, if anyone is interested you can get a better descrioption of my below comments by listening to my talk.

No one can predict a future trajectory for what will happen, but I think the field of anti-aging interventions is moving fast in a positve direction. As for Class 2 interventions (as Reason listed, above), they already have the potential to reduce cancer risk substantially, as well as inflammation, both of which are huge contibutors to the process of aging. Discovery of such agents will only accelerate as researchers focus on understanding the biochemical pathways involved, many of which are already known (more detail in my talk).

DeMagalhaes makes a fabulous point in his talk that by extending life by only 7 years, you HALVE the incidence of disease in every age range. HALVE! For only a 7 year extension! That's positive.

Reason, I want to diagree on one small point - I think metformin used judiciously can be very beneficial. It binds and regulates the IGF-1 receptor, downregulating mTOR (among other factors) and modulating a cascade that results in cell damage. Turning down the gain on this receptor has been shown to be beneficial to throttling cellular aging processes. The use of low-dose metformin has been shown to reduce the overall incidence of cancer between 30-50%! I find that awesome.

I believe the potential to live to 90 if not 100 is here right now if you do just a few things that we already know about. These things are incredibly effective:
1) Practice some degree of caloric restriction
2) Exercise, with HIIT being the best but any exercise that gets your heart rate up will help extend life.
3) Eat healthily, not the "standard American diet".
4) Choose wisely among beneficial neutraceuticals and low-dose pharmaceuticals

IMHO, I think in the next 20 years we will see a number of pharmaceutiucal interventions that will extend life (delay aging) even more agressively. I think we will get to living to over 100 easily, if syuch research continues. The pharmaceuticals I discuss in my talk help to extend life merely as an off-label side effect! There is lots more to be done in this area.

Link to my rehersal talk for the 1st Alcor Symposium below. Nice to meet you all!
-Regina
My full talk is on YouTube,
Part 1:
https://youtu.be/ndSDeAlzoDk
Part 2:
https://youtu.be/2tqE-XCvLgA
Slides:
https://tinyurl.com/vxphs2f

Posted by: Re Rose at November 26th, 2019 1:53 PM

Thanks for your links, Re Rose! I'll take a look later.

As for this part: "I believe the potential to live to 90 if not 100 is here right now if you do just a few things", well, at least here in Western Europe, even if I do nothing, and simpy by extrapolating from past trends in life expectancy during the last 60 years or so (i.e., no antiaging) a middle-aged man like me can expect to live to 90 already. The target to aim for should be much higher.

Posted by: Antonio at November 26th, 2019 3:07 PM

Thanks for the information, Regina; I hope you're healthy and able to give a live presentation during the next event (which is hopefully next year and will hopefully include recorded talks given by Ralph Merkle and Robert Freitas).

I'm not sure if you can answer this question, but I'll give it a go - how close do you think persufflation is from being used instead of vitrification for cryonics patients?

I wouldn't be surprised if you're already familiar with it, but if you're not, the Life Extension Advocacy Foundation has a Rejuvenation Roadmap that keeps track of how close different rejuvenation therapies are from going into clinical trials, and I recommend following that site as well as Fight Aging.

That's all; thanks for reading. :)

Posted by: Quinn at November 26th, 2019 4:00 PM

Hi Antonio - Yes, certainly life expectancy is already ~90 in most of the western world, that was what I was trying to say - we're there now. Many people I speak with (admittedly not in this community) do not believe that. In any case, merely 90 is not my goal and I heartily agree that 90 is too low. I hope to see 140 in my lifetime, and I don't think that is particularly aggressive, but it does imply that I think new technologies (both pharma and medical) will be available within the next 20 years, indeed I actually expect some within the next 10.

On the technology side, I have been very excited to read about the latest findings at U of Maryland, where they are using extreme cooling "suspended animation" on victims of severe trauma: https://www.newscientist.com/article/2224004-exclusive-humans-placed-in-suspended-animation-for-the-first-time/. It's not freezing but it's certainly a step in the right direction, by mainstream medicine!

best
Regina

Posted by: Re Rose at November 26th, 2019 4:38 PM

Hi Quinn: Thanks for the good wishes! The last I heard about persufflation was a paper published by Dr. Klearchos Papppas in 2018. The findings are exciting, but I am not sure if it is good for long-term (over 25 years, for example) storage as superoxygenation carries its own risks long-term. I hope more work will be done using it as an adjunct method in cryopreservation - I guess we'll see!!
-Regina

Posted by: Re Rose at November 26th, 2019 4:48 PM

Many thanks for these great notes and also Re Rose materials.
@Re Rose. I was intrigued by the point made by on "extending life by only 7 years, you HALVE the incidence of disease in every age range". Any additional material on this I could check?

Posted by: albedo at December 3rd, 2019 6:33 AM

@albedo - sure - that is based on Roman Bauer's seminar, he made that observation which is based on the fact that aging damage accumulates exponentially over a lifetime. Several of his seminars are up on YouTube, you can check those out! The simplest explanation is that halving is a natural property of exponential functions.
Enjoy! Regina

Posted by: Re Rose at December 6th, 2019 7:46 AM

@De Rose
Thank you. I will check Roman Bauer's. From you post I was under the understanding the point was made by João Pedro de Magalhães.

Posted by: albedo at December 6th, 2019 11:02 AM

@albedo, thx and apologies - you are correct, the origin of that statement is from João Pedro de Magalhães. Sorry to misattribute and thanks for catching it! -Regina

Posted by: Re Rose at December 10th, 2019 12:58 PM

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