Implications of the BPF large mammal brain preservation prize

A follow-up to the similarly titled 2016 article concerning the BPF small mammal prize

Keith Wiley
Author of A Taxonomy and Metaphysics of Mind-Uploading
Brain Preservation Foundation fellow
Mar. 13, 2018

On March 13, 2018, the Brain Preservation Foundation (BPF, https://brainpreservation.org) announced the winner of its large mammal prize for the successful preservation of a pig brain. This is the second and more difficult of two BPF prizes awarded for such accomplishments, and indicates a significant step forward in validating brain preservation as a way to suspend life. The earlier small mammal prize, awarded in 2016, was won for the successful preservation of a rabbit brain. The pig brain presented a greater challenge and corresponding accomplishment due to the pig brain’s larger size and more complex structure. Put differently, the pig brain is more similar to a human brain and therefore its successful preservation further supports eventually developing a human brain preservation procedure. Both prizes were won by the same team, led by Rob McIntyre at 21st Century Medicine, and use the same technique, aldehyde-stabilized cryopreservation (ASC).

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 (similar to naturally occurring antifreeze chemicals exploited by some frogs and fish, which can go into a subfreezing stasis during winter). 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.

The awarding of the small and large mammal prizes is of tremendous significance because McIntyre’s team has demonstrably solved the serious problem of achieving proper cryogenic storage. The key feature of ASC is to precede the cryogenic stage with a room-temperature glutaraldehyde perfusion stage. Using glutaraldehyde to preserve tissues (including brains) for analysis has been an established practice for decades. Glutaraldehyde covalently crosslinks the brain’s proteins, immediately halting all metabolic processes. A glutaraldehyde perfused brain is extremely well preserved. However, while room temperature glutaraldehyde preservation is sufficient over a period of weeks, it is not up to the task of decadal or centurial preservation. For such spans of time, low temperatures are required. But since glutaraldehyde perfusion locks the brain into place for a timespan of weeks, it provides an intermediate window of time in which to lower the brain to cryogenic temperatures. Rather than trying desperately to complete the process in a matter of hours, technicians can instead perform the process hundreds of times slower. Furthermore, the steady temperature descent can be halted (and even reversed) along the way, for as long as a few days at a time, to perform verification and other analysis of the ongoing cryogenic process. In this way, not only may cryoprotectants be introduced more gently, thoroughly and effectively, but the technicians are further able to scrutinize the ongoing process, to catch any emerging problems early on, and to take necessary steps to insure that a high quality cryogenic storage is achieved. Brains preserved using ASC suffer no shrinkage or deformation at the macroscale, while microscale images clearly depict perfectly preserved synaptic features (see Figs. 1 & 2).

Figure 1: ASC preservation quality – This figure shows an electron microscopy imaged section of an ASC-preserved brain, taken from McIntyre’s 2015 paper. When professional neuroscientists are shown images of this sort, they see sufficient evidence of successful preservation of critical neural and synaptic features. See Fig. 2 for detail and further explanation.

Figure 2: ASC preservation quality detail – This figure shows a zoomed section of the same image shown in Fig. 1. This image shows a perfectly preserved synaptic bouton [1], by which a presynaptic neuron communicates with a postsynaptic neuron. The synaptic cleft or gap is clearly discernible by the thick shadow along the bouton’s lower edge [2]. This gap is where the synapse transmits signals from the bouton to the neighboring neuron’s dendrite [3]. Perhaps most impressive, we can easily make out the individual neurotransmitter vesicles contained inside the bouton [4], ready for traversal across the gap to receptors on the surface of the dendrite.

ASC comes with a catch however. Glutaraldehyde crosslinking is irreversible; a brain perfused with glutaraldehyde is irrevocably dead in the traditional sense. The whole point of the glutaraldehyde step is to absolutely cease all metabolic activity and it cannot be undone. Consequently, no person preserved in this fashion will ever be revived by traditional biological means. They will never “thaw out and wake up” as we see depicted in science fiction lore. Glutaraldehyde preservation has classically been used by laboratory scientists to study tissue samples, but never to preserve and then revive an animal subject, nor could there ever be any hope of doing so without relying on miraculous advances in nanotechnology (Drexler has speculated on this possibility, but it remains highly futuristic and hypothetical; we shouldn’t rely on it by design or intent at this early juncture). What then is the point of using ASC as a life-extension procedure?

The answer to this question ventures into the fairly abstruse metaphysical philosophy concerning the nature of the mind, consciousness, and personal identity, for there is another proposed method of revival aside from biological revival: pattern revival. Many pioneering cryonics patients, i.e., those people already in storage or currently signed up with cryonics companies to have their bodies (or just their heads in some cases) preserved upon their death, hold to a theory of personal identity known as body identity. They believe their brains, and in some cases their bodies, must be revived in order to consider the procedure a success. People of the body identity philosophical persuasion will not, at first glance, find ASC appealing since it offers no possibility for revival of their brain (or body).

But there are other philosophical positions on the relationship between the mind and the brain, on the underpinnings of consciousness, and on the nature of personal identity. One of the most common alternatives is psychological identity, in which the salient features of ourselves are not physical, but rather cognitive. Psychological identity claims that our memories indicate our identity. The prevailing theory within current neuroscience regarding memories is that they are encoded in the physical structure of the brain, with emphasis on its network layout and connection-point properties, known as the connectome comprising neurons and synapses. Coupling metaphysical psychological identity with this connectome basis for memory yields pattern identity, in which our identity is indicated by the pattern of information encoded in our brain’s neural structure. Under pattern identity, the atoms aren’t important; merely their arrangement with one another is important. There is a profound implication here: replicate the pattern and you have revived the identity.

The process of scanning a preserved brain to deduce its pattern, followed by instantiation of that pattern in a new system, is called whole brain emulation (WBE). WBE is generally expected to consist of a computer for the brain (of some reasonably advanced design, for example likely massively parallel on par with the brain’s own billion-factor neural and trillion-factor synaptic parallelism), and either an artificial or robotic body, or potentially a simulated body in a virtual world. Taking this line of reasoning to completion, philosophically interpreting WBE as the continuation of a person’s identity is called mind uploading.

The challenges to ASC revival by mind uploading can broadly be divided into two major categories: technical and philosophical. We currently don’t have the technological capability to scan the entire brain and capture its connectome pattern. However, we can already make partial progress on such a task, and furthermore, we have basic designs for tools that could accomplish this task. We also don’t yet have the technology to instantiate that pattern in a WBE or give the emulation a body to inhabit, be it physical or virtual. Substantial though these challenges are, there is good reason to expect them to fall to the ever-advancing vanguard of science and engineering. We know that ASC preserves the features that current neuroscience generally agrees to be the basis of our memories. Additionally, there is ongoing research into scanning a preserved brain, and into the development of computers powerful enough to run WBEs. In the coming decades, possibly centuries, but probably not longer than that, the technical challenges to achieving WBE of an ASC preserved brain will be solved.

One might ask why the BPF considers WBE a reasonable speculation on future technological capabilities, but not the necessary nanotechnology to reverse glutaraldehyde fixation for the purpose of biological revival. As profound as mind uploading can be for its philosophical implications (discussed below), the path to achieving the purely technical aspects of WBE is fairly straightforward, involving incremental improvements in already existing technologies. There is no major impediment here, just the steady march of engineering improvements, primarily in terms of scale. Alternatively, despite the fact that nanotechnology has enjoyed the limelight of public excitement, it is not a technology for which we have a merely incremental path forward. Rather, developing the advanced nanotechnology to repair dense brain tissue will involve whole new realms of chemistry and material science, requiring discrete, novel leaps in our ability to manipulate matter in confined spaces and under conditions of tremendous complexity. We honestly don’t know the limits of nanotechnology, and speculation on the topic frequently goes beyond our only existing proof of concept, biology. Those extended speculations may, in some cases, simply turn out to be impossible. It is preferable to not rely on such hope in our planning for the future.

Whether WBEs produced from scanned ASC brains will be deemed mind uploads hinges on the philosophical challenge to this approach of preservation and revival. As with most matters of philosophy, this challenge is less a matter of if or when it will be “solved” in the rigorous scientific sense, and more a matter of where any given person chooses to stand on the issue. For many people alive today, this challenge is already solved. They have chosen, in many cases for thoroughly considered reasons, to adopt a pattern identity position on the metaphysical question of personal identity. For these people, only the technical issues remain, and on the expectation that the technical challenges to WBE will inevitably be solved, the only remaining hurdle is the maturation of a standardized ASC medical practice and industry. A thorough presentation of the philosophical discussion, including popular challenges and counterarguments, will not fit here, but see Wiley 2014, Cerullo 2015, and Wiley & Koene 2016 for more information.

Brain preservation has been characterized as a bridge between the current time and some future time when scanning, emulation, and any required embodiment (be it physical or virtual) will be viable. It enables inhabitants of a very particular period of history, bounded by two momentous events, to participate in a future that they would otherwise precede and miss out on. That period of history is demarcated by the development of a viable brain preservation procedure at the early end and mind uploading at the later end. The awarding of the large mammal prize will, in historical retrospect, likely be appreciated in this epic manner: the moment when humanity entered a new period of history in which it is possible to survive into a future otherwise beyond conventional reach. This has never been possible before and indicates a very different sort of world to inhabit.

Some people will initially be against ASC and subsequent mind uploading on grounds of social, political, or religious beliefs. It is important to separate beliefs that dictate the rights and choices of action available to oneself and those offered to (or prevented from) others. The BPF’s position on this issue is that that unless a sufficient argument can be presented that ASC should be explicitly withheld from other people (not merely that people should choose to avoid it themselves), then the necessary next steps of further research, and the standardization of an associated medical practice, should be actively pursued. In the spirit of modern aesthetics of self-determination, any single person should have the option of making the ASC decision for themself regardless of the opinions of others on the matter.

The BPF intends that the awarding of large mammal prize will open a floodgate of research and discussion about these issues, and further hopes to inspire a vigorous debate in the public sphere. Energizing just such a debate is a crucial next goal of the BPF. Brain preservation should become a topic of growing consideration and discussion within our society as its practical viability approaches. In fact, that discussion should start in earnest right now, kick-started by this seminal announcement, the first successful preservation of a large mammalian brain with no crucial differences from our own. We are in a new era here. Let’s go build that bridge to the future.

About

Keith Wiley is a fellow with the Brain Preservation Foundation and a board member with Carboncopies, which promotes research and development into whole brain emulation. He has written several articles and papers on the philosophy of mind uploading. His book, A Taxonomy and Metaphysics of Mind-Uploading, is available on Amazon. Keith’s website is http://keithwiley.com.

References

Cerullo M. Uploading and branching identity. Minds and Machines, 25(1):17–36. 2015.

Costanzo J., Amaral M., Rosendale A., Lee Jr. R. Hibernation physiology, a freezing adaptation and extreme freeze tolerance in a northern population of the wood frog. Journal of Experimental Biology, 216:3461–3473. Aug 2013. doi: 10.1242/jeb.092007.

Drexler K. Engines of Creation: The Coming Era of Nanotechnology. Doubleday. 1986.

Hayat M. Glutaraldehyde: Role in electron microscopy. Micron and Microscopica Acta, 17(2):115–135. Feb 1986.

McIntyre R. and Faye G. Aldehyde-stabilized cryopreservation. Cryobiology, 71(3):448–58. Dec 2015.

Wiley K. A Taxonomy and Metaphysics of Mind-Uploading. Humanity+ Press and Alautun Press. 2014.

Wiley K. Implications of the BPF small mammal brain preservation prize, from the prosaic to the profound. Brain Preservation Foundation, online blog. Feb 2016. https://www.brainpreservation.org/implications-of-the-bpf-small-mammal-brain-preservation-prize-from-the-prosaic-to-the-profound/

Wiley K. and Koene R. The fallacy of favoring gradual replacement mind uploading over scan-and-copy. Journal of Consciousness Studies. 23(3–4):212–235. 2016.