Large Mammal Brain Preservation Prize Won Using a Method of Vitrifixation

A few years ago, the Brain Preservation Foundation awarded the small mammal brain preservation prize to a team working with a vitrifixation method: chemical fixation combined with low temperature storage. It produces excellent preservation of the fine molecular structure of the brain, and of particular interest are those areas in which the data of the mind is thought to be encoded. It is not surprising to see the same approach working for a larger brain. While this isn't a completely straightforward step, as working with larger tissue sections is always harder in many ways than working with smaller tissue sections, it was expected.

The Brain Preservation Foundation is representative of a faction of our broader community who are (a) in favor of preserving brains, and thus individuals, from death and oblivion, (b) harshly critical of the technologies and methods of the present cryonics providers, and (c) inclusive of a fair number of pattern identity theorists. The latter viewpoint means that the self is identified with the pattern of information, not the location or matter used to store that pattern. So these are people comfortable with the idea of the data of the mind being read from a stored brain, used to run an emulation of consciousness in software, and the stored brain then discarded. In their view, the resulting artificial intelligence is still the self, rather than a copy. They are alive, not dead.

For those of us who adhere to the alternative viewpoint, the continuity theory of identity, the self is the combination of the pattern and its implementation in a specific set of matter: it is this mind as encoded in this brain. A copy is a copy, a new entity, not the self. Discarding the stored brain is death. The goal in the continuity theory view is to use some combination of future biotechnology and nanotechnology to reverse the storage methodology, repair any damage accumulated in the brain, and house it in a new body, restoring that individual to life.

I point this out because adoption of pattern versus continuity views of identity should determine an individual's view of the utility of vitrifixation for brain preservation. The primary point to consider here is that chemical fixation is a good deal less reversible than present day vitrification, low temperature storage with cryoprotectants. The reversible vitrification of organs is a near-future goal for a number of research groups. But reversing chemical fixation would require advanced molecular nanotechnology at the very least - it is in principle possible, but far, far distant in our science fiction future. The people advocating vitrifixation are generally of the pattern identity persuasion: they want, as soon as possible, a reliable, highest quality means of preserving the data of the mind. It doesn't matter to them that it is effectively irreversible, as they aren't hoping to use the brain again after the fact.

From a technical point of view, better high quality vitrifixation is an achievement. It will be of use in many areas of life science research, and is an important step forward. But in the matter of preservation of the self, for the countless people who will age to death prior to the advent of rejuvenation therapies, this is an excellent example of why philosophy matters. Wherever technological capacity catches up to desire, beliefs start to result in life or death choices. I think that pattern identity views of the world, just like much of religion, will lead to a great deal of unnecessary death and oblivion. This is one small sample of the development choices that lie ahead.

Before quoting some of the publicity materials, I'd like to revisit the point about the Brain Preservation Foundation folk being harshly critical of cryonics methodologies. It is one thing to say that there is considerable room for improvement. That is certainly true. Vitrification is currently irreversible in large tissues. It is challenging to correctly and sufficiently perfuse cryoprotectant into post-mortem brains; more and better automation would be very helpful. The cryopreservation services operate with too little funding for complete comfort, and would benefit from a greater connection to wealthier areas of biotech industry. This is something that will hopefully arise as reversible vitrification for organ storage becomes a reality. It is quite another thing, however, to claim that everyone stored is irreversibly dead, because the fine structure of the mind is no longer there. That is clearly not the case for a well conducted preservation, given the studies showing vitrification and and thaw of nematodes to preserve memory. The question is the degree of damage. Criticism is only useful when it is reasonable rather than a polemic.

Large Mammal BPF Prize Winning Announcement

Using a combination of ultrafast glutaraldehyde fixation and very low temperature storage, researchers have demonstrated for the first-time ever a way to preserve a brain's connectome (the 150 trillion synaptic connections presumed to encode all of a person's knowledge) for centuries-long storage in a large mammal. This laboratory demonstration clears the way to develop Aldehyde-Stabilized Cryopreservation into a 'last resort' medical option, one that would prevent the destruction of the patient's unique connectome, offering at least some hope for future revival via mind uploading. You can view images and videos demonstrating the quality of the preservation method for yourself at the evaluation page.

The Brain Preservation Foundation's (BPF) Large Mammal Brain Preservation Prize has been won by the cryobiology research company 21st Century Medicine (21CM) and lead researcher Robert McIntyre (an MIT-trained scientist who is now co-founder of the startup Nectome) and senior author Greg Fahy (Fellow of the Society for Cryobiology). The Prize required the successful preservation of synaptic connectivity across an entire pig brain in a manner compatible with centuries-long storage. To accomplish this, McIntyre's team scaled up the same procedure they used to previously preserve a rabbit brain, for which they won the BPF's Small Mammal Prize.

The first step in the ASC procedure is to perfuse the brain's vascular system with the toxic fixative glutaraldehyde, thereby instantly halting metabolic processes by covalently crosslinking the brain's proteins in place, and leading to death by contemporary standards (but not necessarily information-theoretic standards). Glutaraldehyde is sometimes used as an embalming fluid, but is more commonly used by neuroscientists to prepare brain tissue for the highest resolution electron microscopic and immunofluorescent examination. It should be obvious that such irreversible crosslinking results in a very, very dead brain making future revival of biological function impossible. So, it is reasonable to ask: "What is the point of a procedure that can preserve the nanoscale structure of a person's brain when biological revival is impossible?" The answer lies in the possibility of future non-biological revival.

A growing number of scientists and technologists believe that future technology may be capable of scanning a preserved brain's connectome and using it as the basis for constructing a whole brain emulation, thereby uploading that person's mind into a computer controlling a robotic, virtual, or synthetic body. The Brain Preservation Prize challenged the scientific community to develop a 'bridge' to that future mind uploading technology.

Implications of the BPF Large Mammal Brain Preservation Prize

Traditional cryogenic preservation faces two conflicting challenges: rapid decay and ice crystal formation. The brain begins decaying immediately upon death, and therefore must be chilled quickly to halt the decay. However, the water contained in the brain is at risk of freezing into ice crystals, which would slice through the organic matter. Consequently, a process known as vitrification is preferred, in which water descends below freezing without crystallizing, instead forming what is called an amorphous solid. Vitrification is achieved by perfusing the brain with cryoprotectants before lowering the temperature.

However, the perfusion and chilling process, better performed slowly and carefully, cannot be allowed an optimal timeframe in which to occur due to the rapid decay. The necessary frenzied approach can, therefore, still result in tissue damage. Another problem arises as well. To expedite the process, the method currently used by cryonics organizations forces the cryoprotectants into the brain so aggressively, and at such high concentrations, as to actually osmotically pull water out of the cells. The brain is literally dehydrated like a raisin, and with similar results: significant shrinkage and deformation. It is frankly difficult to imagine the large-scale, region-to-region connective relationships of the brain surviving such trauma.

This problem of getting to low temperatures quickly underlies the most serious challenge currently facing the cryonics industry, and gives many neuroscientists pause about the best interpretation of the standard practice, namely that it is quite likely destroying the patients' brains, rendering future revival impossible. As such, cryonics "patients" or "subjects" might be better called by a different word: cadavers. To their credit, advocates for traditional cryonics acknowledge this problem, expressing their hope that futuristic technologies will repair both the micro- and macroscale damage. However, if the damage is truly information-destroying in nature, then no future technology, regardless of advancement, can ever recover the information. That fact is a fundamental trait of information theory.

So we can summarize the problem with current cryonics in the following way: Since the brain decays rapidly upon death, it must be chilled quickly to initiate preservation, but this hasty approach prevents adequate cryoprotectant perfusion, thereby risking partial ice crystal damage, while furthermore, the aggressive perfusion process used to accelerate the timeline additionally causes shrinkage and deformation.

Alcor Position Statement on Brain Preservation Foundation Prize

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.

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.

Comments

@reason
hawking is dead now if people still do not understand the cost of lives they are completely dumb
Ps reason i know this is out of your concern but you should tribute a post on hawking and how can we save lives like hik

Posted by: salman at March 14th, 2018 1:33 PM

This aldahyde approach does demonstrate that brains can be preserved. Unfortunately, it does not allow for biological revival, thus requiring that either brain emulation is perfected (does anyone really believe that software can be developed to emulate the human brain?) or some kind of "Drexlerian" nanotechnology (which also strikes me as unlikely).

Posted by: Abelard Lindsey at March 14th, 2018 5:42 PM

Very interesting! This is an example of why Fightaging.org is part of my daily reading. This morning, I was just reading about John Locke at Wikipedia, and he would have been fascinated by the issues being brought up here (recommended and will only take you a few minutes). I've had debates with my son about copies of the physical brain, thinking how nice it would be to have several of me to get more things done (is that the ultimate narcissism?). How great it will be to live to see empirical data on these issues.

Posted by: Tom Schaefer at March 15th, 2018 9:22 AM

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