Summer 2021 Meta-Analysis Report

The second quarter 2021 issue of Cryonics includes a report on Alcor Case Metrics 2000-2020. This begins with a selection of case data for the years of 2019 and 2020 followed by a look at the 141 cases in the 21-year period from 2000 to 2020. (2000 was picked as the starting point because that year saw the introduction of vitrification technologies at Alcor.)

It’s not uncommon to find people on the internet making claims about the percentage of cases that are straight freezes, or that involve autopsies, and so on. Sometimes these lack any support and at other times the evidence is limited. The meta-analysis makes it possible to examine these numbers objectively and as accurately as possible.

For instance, in the 21 year period 2000 to 2020, 6% of cases involved an autopsy, 13 or 14% involved unattended deaths, and 23% were straight freeze. Cardiopulmonary support was provided in 66% of cases, cryoprotective perfusion was achieved in 77%, and (so far) 10% of cases have been “field cryopreservation”

See the accompanying article, “Alcor Case Metrics: Scope and Comments” by Aschwin de Wolf and Michael Benjamin for thoughts on the usefulness of the meta-analysis results. Although some factors influencing the quality of outcomes is very hard for a cryonics organization to control, none should be considered completely outside the realm of influence. This analysis helps to show where to focus our efforts. The next step in this project is to identify trends and correlation.

–Max More

Keep an eye on the Meta-Analysis Project

One Alcor-funded research project that I’m personally especially interested in is the Meta-Analysis Project. This project, led by Advanced Neural Biosciences’ Aschwin de Wolf and Michael Benjamin, gathers a vast amount of data on every one of Alcor’s cryopreservations and analyzes patterns. ANB began the Alcor Meta-Analysis Project in January 2019 with the goal of developing a quantitative method to evaluate the quality of each cryopreservation case based on a thorough review of all the available case data. The project has 3 phases.

In Phase 1, researchers review and collect relevant data points from all case reports, all raw data such as temperature data and any relevant scientific papers and, for the last decade of cases, CT scans of cryopreserved patients. In phase 2, new outcome metrics have been developed to look at variables such as cryoprotectant distribution and ice formation from the analysis of Phase 1 data. The goal of Phase 3 is to identify areas where protocol and procedure upgrades would likely have the maximum impact at improving patient preservation outcomes.

Alcor and cryonics as a whole can expect to benefit from the outcomes of this work, including:

  • a complete secure database of all the important case variables gleaned from case reports, raw data, and CT scans that can be updated with new cases.
  • important information about trends and outcomes of Alcor procedures.
  • a single or set of case metrics that provide a quantitative result that measures the quality of each patient preservation
  • information about the range of typical patient scenarios, including the modelling of unusual scenarios
  • Recommendations to improve procedures, case work, and case logistics
  • A paper to be published in a scientific journal including the exposition of the cryonics case outcome metric(s) and experimental validations

You can read the initial report in the third quarter 2020 issue of Cryonics. Next report will be published in the second quarter 2021 issue.

Support our new research initiative: RAPID! (Readiness And Procedure Innovation/Deployment)

In order to advance the science and reputation of cryonics, Alcor plans to conduct ongoing research to develop novel and near-future products related to cryopreservation procedures and protocols. The RAPID team is developing relationships and contracts to procure recently deceased human cadavers, which are not Alcor members or patients, but are already earmarked for medical research. The idea is to procure one to two cadavers per month to conduct research. We would go a “light standby” to enable fast access to cadavers.

The RAPID initiative will support cryonics research in multiple ways. Most immediately, it will help advance research into liquid ventilation – using a patient’s lungs as a heat exchanger to induce very rapid hypothermia. Animal studies along cannot take LV development to the next level due to different chest anatomy. LV research will include cooling rate control; chest compression studies; and timing and sensor feedback.

RAPID will also enable research comparing chemical fixation to perfusion and will support rewarming studies. Another benefit will be a great improvement in cryonics-specific surgical training. That includes raising and cannulating the carotids; cephalic isolation; raising and cannulating the femoral arteries; field neuro procedure training; median sternotomy training; and alternate surgical approaches.

Alcor is requesting donations through gofundme. All donors will receive quarterly reports from Alcor regarding the progress with fundraising and milestone achievements rising from the RAPID program! Please donate today to support Alcor’s RAPID initiative. Alcor is a non-profit, federally tax-exempt, 501(c)(3) corporation and your donation may be tax deductible. Donate here. For more information, see the presentation here.

Unprecedented $5 Million Contribution to Cryonics Research!

I am delighted to announce that Alcor has received a stunning $5,000,000 contribution to fund cryonics research. Alcor member Brad Armstrong (A-3000), came to visit Alcor in November 2016. After a tour and long and fascinating chat, before he left I suggested that he finally sit down and sign the membership paperwork. We would provide the witnesses and the Notary Public. 90 minutes later, Brad was done and handed us a check, making him a member. (See? It’s not as difficult as you think.)

Fast forward to April 2018. Brad’s assistant called to say that Brad wanted to make a major contribution to Alcor for the purposes of cryonics research. When I called Brad, I was immediately reminded that he is a down-to-earth, easygoing fellow who wants cryonics to work and is eager to fund what he knows matters.

Brad is an enthusiast of cryptocurrencies and an admirer of Hal Finney – the first recipient and early developer of Bitcoin – and an Alcor member cryopreserved in August 2014. The $5 million research contribution is being held in the name of the “Hal Finney Cryonics Research Fund”.

Brad’s cryptocurrency contribution was made by transferring it to an intermediary organization. Formally, we must therefore note that the funds were received from “Against Aging Fund at East Texas Communities Foundation”. But make no mistake. This funding came from Brad.

Brad has done well financially from his inventions and his cryptocurrency investments. Even so, we know that there are Alcor members of considerably greater means. Some of these are well into their later years. I imagine myself in the position of having a net worth of a billion dollars or more and being in my 60s, 70s, or 80s. Certainly, I would be funding life extension research. But I am certain that I would also be putting serious money into cryonics, not only for research to build up Alcor’s technical capabilities and strength.

On behalf of Alcor and the cryonics effort in general, I want to say thank you. But how can I possibly express those thanks adequately?

With a gift of this magnitude comes the responsibility of managing and spending it wisely for maximum impact. Until the Alcor board and Research Group determine how best to hold and use this funding, I have moved it from Alcor’s bank account into a money market fund earning 1.5%. As puny as that percentage sounds historically, it means a yield of $6,000 per month (after keeping $200,000 to shore up the Research Fund). Stay tuned as we determine how to use this remarkable influx of funding to boost Alcor’s cryonics research.

–Max More

Alcor Position Statement on Brain Preservation Foundation Prize

From Alcor President, Max More
March 13, 2018

In December 2015, 21st Century Medicine, Inc. published peer-reviewed results of a new cryobiological and neurobiological technique, aldehyde-stabilized cryopreservation (ASC) that provides strong proof that brains can be preserved well enough at cryogenic temperatures for neural connectivity (the connectome) to be completely visualized. This week the Brain Preservation Foundation (BPF), after independent evaluation by neuroscientists and Dr. Ken Hayworth, President of the BPF, awarded The Large Mammal Brain Preservation Prize to 21st Century Medicine based on these results. In 2016 the company had been previously awarded the Small Mammal Brain Preservation Prize for work using the same technology.

Many people are wondering whether Alcor plans to adopt the “Aldehyde-Stabilized Cryopreservation” (ASC) protocol used to win the prize and what the win means for cryonics in practice. Alcor’s position is as follows:

We are pleased that vitrification, the same basic approach that Alcor Life Extension Foundation has utilized since 2001, is finally being recognized by the scientific mainstream as able to eliminate ice damage in the brain during cryopreservation. Alcor first published results showing this in 2004. The technology and solutions that Alcor currently uses for vitrification (a technology from mainstream organ banking research) were actually developed by the same company that developed ASC and has now won both the Small Mammal and Large Mammal Brain Preservation Prize.

ASC under the name “fixation and vitrification” was first proposed for cryonics use in 1986. ASC enables excellent visualization of cellular structure – which was the objective that had to be met to win the prizes – and shows that brains can be preserved well enough at low temperature for neural connectivity to be shown to be preserved. Current brain vitrification methods without fixation lead to dehydration. Dehydration has effects on tissue contrast that make it difficult to see whether the connectome is preserved or not with electron microscopy. That does not mean that dehydration is especially damaging, nor that fixation with toxic aldehyde does less damage. In fact, the M22 vitrification solution used in current brain vitrification technology is believed to be relatively gentle to molecules because it preserves cell viability in other contexts, while still giving structural preservation that is impressive when it is possible to see it. For example, note the synapses visible in the images at the bottom of this page.

While ASC produces clearer images than current methods of vitrification without fixation, it does so at the expense of being toxic to the biological machinery of life by wreaking havoc on a molecular scale. Chemical fixation results in chemical changes (the same as embalming) that are extreme and difficult to evaluate in the absence of at least residual viability. Certainly, fixation is likely to be much harder to reverse so as to restore biological viability as compared to vitrification without fixation. Fixation is also known to increase freezing damage if cryoprotectant penetration is inadequate, further adding to the risk of using fixation under non-ideal conditions that are common in cryonics. Another reason for lack of interest in pursuing this approach is that it is a research dead end on the road to developing reversible tissue preservation in the nearer future.

Alcor looks forward to continued research in ASC and continued improvement in conventional vitrification technology to reduce cryoprotectant toxicity and tissue dehydration. We are especially interested in utilizing blood-brain barrier opening technology such as was used to win the prize.
It may remain unclear to some whether this research and associated prizes show whether ASC or current vitrification without pre-fixation is more likely to preserve cell structures and molecular structures necessary for memory and personal identity. What we can note is that Robert McIntyre, the lead researcher on ASC at 21st Century Medicine, made a point during his presentation at the Alcor 2015 Conference of recommending against adoption of ASC in cryonics at this time.

For cryonics under ideal conditions, the damage that still requires future repair is now more subtle than freezing damage. That damage is believed to be chiefly cryoprotectant toxicity and associated tissue dehydration. It’s time for cryonics debate to move past ill-informed beliefs of “cells bursting.”
This is a groundbreaking result that further strengthens the already strong case that medical biostasis now clearly warrants mainstream scientific discussion, evaluation, and focus.

For a more detailed statement, and one that Alcor endorses, see:
http://www.evidencebasedcryonics.org/2018/03/13/aldehyde-stabilized-large-brain-cryopreservation/
http://www.evidencebasedcryonics.org/media/LBASC.pdf

Alcor Position Statement on Brain Preservation Foundation Prize

From Alcor President, Max More
February 12, 2016

In December 2015, 21st Century Medicine, Inc. published peer-reviewed results of a new cryobiological and neurobiological technique, aldehyde-stabilized cryopreservation (ASC) that provides strong proof that brains can be preserved well enough at cryogenic temperatures for neural connectivity (the connectome) to be completely visualized. And this week the Brain Preservation Foundation (BPF), after independent evaluation by neuroscientists Dr. Sebastian Seung, Professor at Princeton, and Dr. Ken Hayworth, President of the BPF, awarded The Small Mammal Brain Preservation Prize to 21st Century Medicine based on these results.

The BPF press release says: “it is the first demonstration that near-perfect, long-term structural preservation of an intact mammalian brain is achievable, thus directly answering what has been a main scientific criticism against cryonics.”

Many people are wondering whether Alcor plans to adopt the “Aldehyde-Stabilized Cryopreservation” (ASC) protocol used to win the prize and what the win means for cryonics in practice. Alcor’s position is as follows:

We are pleased that vitrification, the same basic approach that Alcor Life Extension Foundation has utilized since 2001, is finally being recognized by the scientific mainstream as able to eliminate ice damage in the brain. Alcor first published results showing this in 2004. The technology and solutions that Alcor uses for vitrification (a technology from mainstream organ banking research) were actually developed by the same company that developed ASC and has now won the Brain Preservation Prize.

ASC under the name “fixation and vitrification” was first proposed for cryonics use in 1986. ASC enables excellent visualization of cellular structure – which was the objective that had to be met to win the prize – and shows that brains can be preserved well enough at low temperature for neural connectivity to be shown to be preserved. Current brain vitrification methods without fixation lead to dehydration. Dehydration has effects on tissue contrast that make it difficult to see whether the connectome is preserved or not with electron microscopy. That does not mean that dehydration is especially damaging, nor that fixation with toxic aldehyde does less damage. In fact, the M22 vitrification solution used in current brain vitrification technology is believed to be relatively gentle to molecules because it preserves cell viability in other contexts, while still giving structural preservation that is impressive when it is possible to see it. For example, note the synapses visible in the images at the bottom of this page.

While ASC produces clearer images than current methods of vitrification without fixation, it does so at the expense of being toxic to the biological machinery of life by wreaking havoc on a molecular scale. Chemical fixation results in chemical changes (the same as embalming) that are extreme and difficult to evaluate in the absence of at least residual viability. Certainly, fixation is likely to be much harder to reverse so as to restore biological viability as compared to vitrification without fixation. Fixation is also known to increase freezing damage if cryoprotectant penetration is inadequate, further adding to the risk of using fixation under non-ideal conditions that are common in cryonics. Another reason for lack of interest in pursuing this approach is that it is a research dead end on the road to developing reversible tissue preservation in the nearer future.

Alcor looks forward to continued research in ASC and continued improvement in conventional vitrification technology to reduce cryoprotectant toxicity and tissue dehydration. We are especially interested in utilizing blood-brain barrier opening technology such as was used to win the prize (but which pre-dated work on ASC).

It may remain unclear to many whether this research result shows whether ASC or current vitrification without pre-fixation is more likely to preserve cell structures and molecular structures necessary for memory and personal identity. What we can note is that Robert McIntyre, the lead researcher on ASC at 21st Century Medicine, made a point during his presentation at the Alcor 2015 Conference of recommending against adoption of ASC in cryonics at this time.

For cryonics under ideal conditions, the damage that still requires future repair is now more subtle than freezing damage. That damage is believed to be chiefly cryoprotectant toxicity and associated tissue dehydration. It’s time for cryonics debate to move past ill-informed beliefs of “cells bursting.”

This is a groundbreaking result that further strengthens the already strong case that medical biostasis now clearly warrants mainstream scientific discussion, evaluation, and focus.

For a more detailed statement, and one that Alcor endorses, see:
http://www.evidencebasedcryonics.org/media/MBPP.pdf

Research and Development

Emergency Response Vehicle
Regarding the planned renovations to Alcor’s emergency response vehicle, we have completed an intensive design and development phase. This consisted of several meetings between Steve Graber and the technical staff, with discussion of parts, vendors and viewing of product samples. Great care has been taken to select modular, off-the-shelf parts, although some custom-designed pieces will be required. Demolition began on the vehicle’s interior this past week and the approved design pieces are being acquired.

Remote Perfusion
Alcor is currently striving to further develop its remote perfusion capability. Before launching an initiative to train its emergency response staff, however, the appropriate equipment needs to be selected.

Read more

Research and Development

Semi-Annual IACUC Meeting
Our semi-annual IACUC meeting was held in December, with its regular review of the animal protocols and facility inspection. The committee requested a few modifications to safety protocols and the development of standardizing forms for some activities. Everything else was in order.

Whole-body Vitrification System
We have begun the large task of documenting the whole-body vitrification software, and work continues to refine the enclosure.

Research and Development

Whole-Body Vitrification System (Technical Version)
During the on-going development of the perfusion process control system, we found it necessary to remove one of the controllers from the system. We found the particular controller to be providing unreliable signals at low RPM speeds, in particular the signal we were using to determine main pump flow rates. The inconsistency was due to frictional effects as the pump rollers hit the pump shoe and the rotation rate slowed. Because we use a linear look-up table to estimate the flow rates, addressing this inconsistency would require a non- linear look-up table to fix.

Because non-linear look-up tables are hard to maintain and because we had another alternative available, we decided to remove that particular controller. This, in turn, necessitated modifying the code to accommodate this change and some re- wiring of the system. Fortunately, this means that we have a reduced amount of third-party hardware and wiring, and the control functions are actually easier.

The main issue with this removal is that we needed a new way to calculate flow rates, but a solution was readily at hand. We were able to take the main pump control module, which still had seven open channels for future scalability, and use its analog output signal to make the flow calculations (once again using a linear lookup table). Changes were tested with the perfusate process controller driving the main pump, using the controller to cause pressure changes following a sinusoidal curve.

Aschwin de Wolf becomes a Voting R&D Committee Member

Through unanimous vote of the Alcor board, Aschwin de Wolf was added as a voting member of the Research and Development Committee. Other voting members include Steve Harris, MD, Tanya Jones, Regina Pancake and Brian Wowk, PhD.