Alcor News

Alcor News

News Blog of the Alcor Life Extension Foundation

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.

Technical Updates

Research and Development
Refinements continue on the whole-body enclosure for the vitrification system. We have been working to adjust the liquid nitrogen flows and temperature distribution across both the cooling stage and the patient environment. The testing this month included:

1. Performing a trial run of the cDAQ – 9172 unit from National Instruments.
2. Performing an extreme cold test of the redesigned and prototyped enclosure lid.
3. Gaining and recording data on the cooling efficiency of the table for use in fine tuning of liquid nitrogen delivery.

Research and Development Committee
Through a unanimous vote from the Board, R. Pancake was added to the Research and Development Committee. Other voting members include Brian Wowk, PhD, Steve Harris, MD, and Tanya Jones. The Research and Development Committee determines uses for the Readiness Grant provided by the Life Extension Foundation, the Miller family, and Edward and Vivian Thorp.
Readiness Grant

LINK TO: READINESS GRANT

Alcor’s first use of the readiness grant was to help fund some much needed improvements to its stabilization and transport kits, which were featured in the August 2008 issue of AlcorNews. The funds were used to purchase the following:

9 new sets of medications, with assorted supplies for medication administration;
1 Michigan Instruments Thumper repair;
6 rescue baskets for the construction of new ice baths, with assorted materials;
1 box of arterial cannula for ATP;
Labor for construction of 6 new ice baths;
Labor for construction of 9 medication kits.

We thank the Life Extension Foundation, the Miller family and Edward and Vivian Thorp for their donation towards readiness improvements of $32,639.68.

Presently, all the below first response teams in the field have fresh medication kits with up-to-date medications:
Alcor Central
Massachusetts
Northern California
Southern California
Florida
Nevada
United Kingdom

Continued work is being done to improve the stabilization and transport kits.

Technical Updates

Cart Caddy
We have recently purchased a necessary piece of equipment called a Cart Caddy for our patient care bay. Whenever there is a need to fill new dewar(s) with liquid nitrogen or to transfer patients from a cool down unit into a permanent dewar, the dewar must be moved into position. This used to take a minimum of four strong people to manually push the dewar. With the Cart Caddy, it is now a two-person job (one to operate the machine, the other to supervise). It is also a much safer and easier approach to the moving a dewar that weighs 5500 lbs. We have adapted this unit so that the crescent shape hugs the dewar firmly and allows us to maneuver it with little effort.

As our patient population grows, this small piece of equipment will become an important asset to our patient care bay.

Research and Development
The development of the whole-body system progresses with some changes to the user interface which will make the system easier to use and yet also provide more clarity on the data being generated at any given moment. We have also expanded significantly the note-taking capability of the system. We are at the point of final engineering testing for the ramp generation portion of the system and have yet to verify our 3-point calibration.

ATP and Whole-Body Vitrification System — Alpha Tests

We held our alpha test of the new ATP and the whole-body vitrification system this month using a swine as test subject.

Given that this was our first large animal operation in many years, we had something of a learning curve with regard to animal handling and the specific surgical procedures necessary for performing bypass. We chose to cannulate the carotid artery and internal jugular vein for the procedure. I performed the cannulation and Regina Pancake assisted, and the surgery went quite smoothly. We had the animal on bypass in 45 minutes, which our observing veterinarian considered quite successful. We began our equipment testing with the new transport perfusion system.

We needed a mere five minutes to prepare and prime the system prior to cannulation, but this figure was artificially high because the two people preparing the system had to refresh their memories about how to hang the perfusate bag. A time of less than two minutes to prepare the system is the benchmark for our next test. All of the new elements worked well, and we had no problems at all with the new ATP. We did not test it fully on a closed circuit, only for open flush of the swine, in order to start testing the whole body system.

Our whole body system consists of two parts that we tested: the patient enclosure and the computer-controlled perfusion. The patient enclosure involves an operating stage that cools the patient using liquid nitrogen injected into a plenum underneath the patient, fans to circulate nitrogen around the patient, a transparent – but internally lighted – cover for the patient, and enough seals to keep the nitrogen – both vapor and liquid – precisely where they should be.

The cooling stage cooled quite rapidly to the set temperature. We added controllers for that only recently, because we were still modifying the enclosure based on previous test results. The temperature controllers need to be adjusted slightly by modifying how the cooling curve is handled, but it took less than ten minutes to cool the stage to three degrees C. We were quite pleased with the even nature of the temperature, and Randal Fry is to be commended for his efforts to adjust the nitrogen spray to accomplish this result. The table itself is also at a more comfortable height for performing surgeries.

The perfusion system itself was the biggest unknown. Of course, the programmer knew precisely how the system would respond to our tests; because it was doing everything he told it to do. The calibrations of the system went well, as did the system initialization. Our cryoprotectant ramp control handled itself very well. Pressure control did not go well, and this was because we had been using the pressure control in a way that worked with an unloaded system (there was no body in the loop). This made a big difference, and we will be adjusting that portion of the program accordingly.

Our alarm functionality worked quite well. A clamp on a line that causes the pressure to spike resulted in immediate shut off the main pump. Level indicators worked well, and all the pumps in the system responded appropriately. Both manual and automatic control of all parameters functioned as intended. We have some minor tweaks to make to the user interface, but those are primarily cosmetic.

Elements that were not quite ready for the test included the full reporting functionality, though the pure data collection elements are all working well; the bubble alarms are not installed; and neither is the emergency stop button we intend to place on the patient enclosure (in case the surgeon sees something requiring immediate cessation of perfusion). We will be performing additional tests on the system’s memory requirements, to ensure that we will not have any problems during a long case. Once we tested the perfusion system to that extent, we tested the final element of the patient enclosure: the ability of the system to perform first-stage cooling.

This is the step where we plunge the patient’s temperature to just above the glass transition point for M22, -110 degrees C. The table itself cooled to -110 in eleven minutes, though of course, it took longer for the swine to reach that stage. Using an animal that was not vitrified caused the temperature to be reduced more slowly because of the heat requirements for the ice formation, but the swine passed the freezing point in 3.5 hours. We considered this acceptable under the test conditions. The swine’s temperature continued to drop until it reached -95 degrees C, at which point we discontinued the test. That drop took approximately 18 hours. This time is good, given that not all elements of the system worked exactly as intended, and we expect faster times as adjustments are made. We did find it took a considerable amount of nitrogen to reach that stage, but part of this is because our environmental fans failed. We will be looking into different fans for the next test and other improvements to reduce nitrogen consumption.

Overall, everyone was quite pleased with the results, and we expect to make the necessary modifications quickly and are planning our second test for later this week.

This work was done under the supervision of the Alcor Institutional Animal Care and Use Committee under Alcor’s USDA registration as an animal research facility, and was fully compliant with the requirements and standards of the Animal Welfare Act. The animals used in these tests were procured from a USDA-registered laboratory animal breeder.

I would like to thank the team who participated in this equipment test, including: Dr. Craig Woods, Joel Anderson, Stephen Van Sickle, Hugh Hixon, Randal Fry and Regina Pancake. We would also like to thank all of the donors who made pursuing this project possible.