The Brain Preservation Foundation’s Small Mammalian Brain Prize won
The Brain Preservation Foundation’s Small Mammalian Brain Prize has been won with fantastic preservation of a whole rabbit brain using a new fixative+slow-vitrification process.
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The process was published as “Aldehyde-stabilized cryopreservation”, McIntyre & Fahy 2015 (mirror)
(They had problems with 2 pigs and got 1 pig brain successfully cryopreserved but it wasn’t part of the entry. I’m not sure why: is that because the Large Mammalian Brain Prize is not yet set up?)We describe here a new cryobiological and neurobiological technique, aldehyde-stabilized cryopreservation (ASC), which demonstrates the relevance and utility of advanced cryopreservation science for the neurobiological research community. ASC is a new brain-banking technique designed to facilitate neuroanatomic research such as connectomics research, and has the unique ability to combine stable long term ice-free sample storage with excellent anatomical resolution. To demonstrate the feasibility of ASC, we perfuse-fixed rabbit and pig brains with a glutaraldehyde-based fixative, then slowly perfused increasing concentrations of ethylene glycol over several hours in a manner similar to techniques used for whole organ cryopreservation. Once 65% w/v ethylene glycol was reached, we vitrified brains at −135 °C for indefinite long-term storage. Vitrified brains were rewarmed and the cryoprotectant removed either by perfusion or gradual diffusion from brain slices. We evaluated ASC-processed brains by electron microscopy of multiple regions across the whole brain and by Focused Ion Beam Milling and Scanning Electron Microscopy (FIB-SEM) imaging of selected brain volumes. Preservation was uniformly excellent: processes were easily traceable and synapses were crisp in both species. Aldehyde-stabilized cryopreservation has many advantages over other brain-banking techniques: chemicals are delivered via perfusion, which enables easy scaling to brains of any size; vitrification ensures that the ultrastructure of the brain will not degrade even over very long storage times; and the cryoprotectant can be removed, yielding a perfusable aldehyde-preserved brain which is suitable for a wide variety of brain assays…We have shown that both rabbit brains (10 g) and pig brains (80 g) can be preserved equally well. We do not anticipate that there will be significant barriers to preserving even larger brains such as bovine, canine, or primate brains using ASC.
previous discussion: Mikula’s plastination came close but ultimately didn’t seem to preserve the whole brain when applied.
commentary: Alcor, Robin Hanson, John Smart, Evidence-Based Cryonics, Vice, Pop Sci
To summarize it, you might say that this is a hybrid of current plastination and vitrification methods, where instead of allowing slow plastination (with unknown decay & loss) or forcing fast cooling (with unknown damage and loss), a staged approach is taking: a fixative is injected into the brain first to immediately lock down all proteins and stop all decay/change, and then it is leisurely cooled down to be vitrified.
This is exciting progress because the new method may wind up preserving better than either of the parent methods, but also because it gives much greater visibility into the end-results: the aldehyde-vitrified brains can be easily scanned with electron microscopes and the results seen in high detail, showing fantastic preservation of structure, unlike regular vitrification where the scans leave opaque how good the preservation was. This opacity is one reason that as Mike Darwin has pointed out at length on his blog and jkaufman has also noted that we cannot be confident in how well ALCOR or CI’s vitrification works—because if it didn’t, we have little way of knowing.
EDIT: BPF’s founder Ken Hayworth (Reddit account) has posted a piece, arguing that ALCOR & CI cannot be trusted to do procedures well and that future work should be done via rigorous clinical trials and only then rolled out. “Opinion: The prize win is a vindication of the idea of cryonics, not of unaccountable cryonics service organizations”
…“Should cryonics service organizations immediately start offering this new ASC procedure to their ‘patients’?” My personal answer (speaking for myself, not on behalf of the BPF) has been a steadfast NO. It should be remembered that these same cryonics service organizations have been offering a different procedure for years. A procedure that was not able to demonstrate, to even my minimal expectations, preservation of the brain’s neural circuitry. This result, I must say, surprised and disappointed me personally, leading me to give up my membership in one such organization and to become extremely skeptical of all since. Again, I stress, current cryonics procedures were NOT able to meet our challenge EVEN UNDER IDEAL LABORATORY CONDITIONS despite being offered to paying customers for years[1]. Should we really expect that these same organizations can now be trusted to further develop and properly implement such a new, independently-invented technique for use under non-ideal conditions?
Let’s step back for a moment. A single, independently-researched, scientific publication has come out that demonstrates a method of structural brain preservation (ASC) compatible with long-term cryogenic storage in animal models (rabbit and pig) under ideal laboratory conditions (i.e. a healthy living animal immediately being perfused with fixative). Should this one paper instantly open the floodgates to human application? Under untested real-world conditions where the ‘patient’ is either terminally ill or already declared legally dead? Should it be performed by unlicensed persons, in unaccountable organizations, operating outside of the traditional medical establishment with its checks and balances designed to ensure high standards of quality and ethics? To me, the clear answer is NO. If this was a new drug for cancer therapy, or a new type of heart surgery, many additional steps would be expected before even clinical trials could start. Why should our expectations be any lower for this?
The fact that the ASC procedure has won the brain preservation prize should rightly be seen as a vindication of the central idea of cryonics –the brain’s delicate circuitry underlying memory and personality CAN in fact be preserved indefinitely, potentially serving as a lifesaving bridge to future revival technologies. But, this milestone should certainly not be interpreted as a vindication of the very different cryonics procedures that are practiced on human patients today. And it should not be seen as a mandate for more of the same but with an aldehyde stabilization step casually tacked on. …
Updated on the benefits of signing up for cryonics, thanks!
In what direction, given that the price didn’t use the standard cryonics tech?
More likely to do cryonics, since it’s been shown by this piece that successful cryonic preservation is more likely, even if not using standard cryonics tech.
I’m making the same update. If it’s not using standard cryonics tech, and it’s better than standard cryonics tech, presumably the usual suspects will adopt it in the not-too-distant future. As I understand it they’ve done that a couple of times already.
Yup, I was thinking along the same lines. In fact, I’ve taken action on my update, and called the Cryonics Institute to learn about getting the process started.
It is possible that it is better than standard cryonics for uploading, but worse for actual physical revival. So it may depend on how much people care about each of those possibilities.
At this point, I won’t be confident that i’ve been successfully preserved until ultra high resolution electron micrographs of my brain are in Amazon’s S3 storage, replicated across multiple regions. Any storage that doesn’t have redundancy doesn’t count as safe.
Would successfully preserving a human brain cause millions of people to sign up for cryonics?
Probably not. If you look at the comments on posts about the Prize, you can see how clearly people have already set up their fallback arguments once the soldier of ‘possible bad vitrification when scaled up to human brain size’ has been knocked down. For example, on HN: https://news.ycombinator.com/item?id=11070528
‘you may have preserved all the ultrastructure but despite the mechanism of crosslinking, I’m going to argue that all the real important information has been lost’
‘we already knew that glutaraldehyde does a good job of fixating, this isn’t news, it’s just a con job looking for some free money’
‘it irreversibly kills cells by fixing them in place so this is irrelevant’
‘regardless of how good the scans look, this is just a con job’
‘what’s the big deal, we already know frogs can do this, but what does it have to do with humans; anyway, it’s a quack science which we know will never work’
Even if a human brain is stored, successfully scanned, and emulated, the continued existence—nay, majority—of body-identity theorists ensures that there will always be many people who have a bulletproof argument against: ‘yeah, maybe there’s a perfect copy, but it’ll never really be you, it’s only a copy waking up’.
More broadly, we can see that there is probably never going to be any ‘Sputnik moment’ for cryonics, because the adoption curve of paid-up members or cryopreservations is almost eerily linear over the past 50 years and entirely independent of the evidence. Refutation of ‘exploding lysosomes’ didn’t produce any uptick. Long-term viability of ALCOR has not produced any uptick. Discoveries always pointing towards memory being a durable feature of neuronal connections rather than, as so often postulated, an evanescent dynamic property of electrical patterns, have never produced an uptick. Continued pushbacks of ‘death’ have not produced upticks. No improvement in scanning technology has produced an uptick. Moore’s law proceeding for decades has produced no uptick. Revival of rabbit kidney, demonstration of long-term memory continuity in revived C. elegans, improvements in plastination and vitrification—all have not or are not producing any uptick. Adoption is not about evidence.
Even more broadly, if you could convince anyone, how many do you expect to take action? To make such long-term plans on abstract bases for the sake of the future? We live in a world where most people cannot save for retirement and cannot stop becoming obese and diabetic despite knowing full well the highly negative consequences, and where people who have survived near-fatal heart attacks are generally unable to take their medicines and exercise consistently as their doctors keep begging them. And for what? Life sucks, but at least then you get to die. Even after a revival, I would predict that maybe 5% of the USA population (~16m people) would be meaningfully interested in cryonics, and of that only a fraction would go through with it, so ‘millions’ is an upper bound.
Is this really good phrasing or did you manage to naturally think that way? If you do it automatically: I would like to do it too.
It often takes me a long time to recognize an argument war. Until that moment, I’m confused as to how anyone could be unfazed by new information X w.r.t. some topic. How do you detect you’re not having a discussion but are walking on a battlefield?
Yes, I was referring to Eliezer’s essay there. I liked my little flourish there, so I’m glad someone noticed.
In this case it’s easy when you look over all the comments on HN and elsewhere. It’s like when Yvain is simultaneously accused of being racist Neo-reactionary scum and a Marxist SJW beta-cuckold Jew scum—it’s difficult to see how both sets of accusations could be right simultaneously, so clearly at least one set of accusers are unhinged.
Similarly, so the problem with this aldehyde-vitrification process is that it’s both too good at fixing everything in place and it’s not good enough at preserving information? It’s a con job despite offering far greater transparency into whether it’ll work? We know the process is quack science so it’s a con job and oh, we already know the process works so it’s a con job? It’ll never work and we know this a priori because a copy of you isn’t you? Each stroke against cryonics might seem reasonable or even probable on its own, but in total, like the 13th stroke of the clock which discredits all the previous ones’ accuracy, they show what’s really going on.
This is a choice?
The mind is what the brain does. Obesity can be a choice in the same way that going through with cryonics can be a choice. As a materialist, I see little difference; both are the outcome of many physical processes, some of which run through the brain, which typically can themselves can be traced causally further back. (For example, I have little doubt that were it possible to run such a study, we would find a high heritability to cryonics as well as the already-established obesity/BMI heritabilities, because cryonics seems to relate very heavily to various cognitive attitudes which are closely connected to other cognitive traits which are heritable, such as intuitive religious cognition which tends towards dualism or essentialism and against the reductionism & materialism which leads to patternism.)
For the purposes of this argument, it’s sufficient that merely some fraction of people can indeed choose to stop becoming obese, which does indeed appear to be the case.
The ‘Life sucks, but at least then you die’ post makes an excellent point. If LW wants to see more people sign up for cryonics, it needs to convincingly make the case that getting frozen and resurrected/uploaded/whatever is a good idea or at least better than the alternatives.
Does that mean a constant number of new sign ups per year, or an increasing number of new sign ups per year? Also, I’d love to see the data if you can link to it.
I recall looking at the historical data somewhere on the ALCOR site but not where specifically. IIRC, it’s a constant number of sign ups but due to age-skews, number of cryopreservations varies over time with an expected hump in coming years from older members dying.
Here’s an eerie line showing about 200 new Cryonics Institute members every 3 years.
I think it is safe to say that some process produces the kind of high-rationality person who makes the effort to sign up, and that process (genetics/culture/scifi etc) is relatively slowly changing over the timescale of ~ 1 decade.
In my opinion, there is almost certainly a much larger population of people who are one or two “steps” or “increments” away from signing up. For example, people who are pretty rich, philosophically materialistic, well educated and into the sci-fi scene, but they have only heard a passing mention of cryo, and it “sounds like a scam” to them, because they still think that cryo means literally freezing your head and thawing it out like a freezer bag of strawberries and expecting it to work again. Cryo needs three things to open the floodgates to this crowd in my opinion:
(1) an actual demonstration of extracting real memories and personality from a cryopreserved dog/monkey, so that we conclusively know that the full cryonics process preserves information.
(2) respectable scientific papers in high-status journals describing and analyzing said demonstration. These are the best weapon against naysayers, because if someone is saying that cryo is unscientific, or is a cult or a religion etc etc, they will look pretty silly when you start piling up papers from Nature in front of them that say it ain’t so.
(3) publicity in the right channels to get the message across. In a way, this is the easy bit once you have (1) and (2), because the kind of channels that you want to be in to reach your target demographic (e.g. Ars Technica, Scientific American, Slashdot, Reddit, etc etc) will eat this up like candy and report the shit out of it without you even asking.
Do you think those thinks are necessary or sufficient?
I think they’re sufficient, assuming there are no major scandals that happen at the same time.
And I think that the size of that demographic is 10,000 − 100,000 people, of which you should be able to get 30% to sign up, especially if the signup process is made smoother.
Basically reanimating a mammal is something that might take 100 years or more to be technically feasible given current cryonic tech and also alternatives such a plastification.
Having extremely advanced techology would change how the world treats cryonics that’s largely irrelevant for the fate of cryonics in the next decades.
I didn’t say reanimating, I said
for example, demonstrating neural correlates of specific memories or learned skills in sliced & scanned electron microscope images/connectomes. Given that MRI scans can already read people’s minds based on blood flow, (extremely crude), it doesn’t actually sound that difficult. I reckon we could already do this with enough investment in scaling the scanning and slicing technology using mice.
Not everyone buys into this philosophical point of view, and if continuity of identity were the only technical objection left, I think that hundreds of thousands of rich, well-educated people with a scientific mindset would sign up.
I think that lingering doubts about whether preservation actually works are still a significant barrier in the “filter funnel” of cryonics.
Right. But the point is, who is in the wrong between the adopters and the non-adopters?
It can be argued that there was never good evidence to sign up for cryonics, therefore the adopters did it for irrational reasons.
If the new evidence which is in favor of cryonics benefits causes no increase in adoption, then either there is also new countervailing evidence or changes in cost or non-adopters are the more irrational side. Since I can’t think of any body of new research or evidence which should neutralize the many pro-cryonics lines of research over the past several decades, and the costs have remained relatively constant in real terms, that tends to leave the third option.
(Alternatively, I could be wrong about whether non-adopters have updated towards cryonics; I wasn’t around for the ’60s or ’70s, so maybe all the neuroscience and cryopreservation work really has made a dent and people in general are much more favorable towards cryonics than they used to be.)
No. If evidence is against cryonics, and it has always been this way, then the number of rational adopters should be approximately zero, thus approximately all the adopters should be the irrational ones.
As you say, the historical adoption rate seems to be independent of cryonics-related evidence, which supports the hypothesis that the adopters don’t sign up because of an evidence-based rational decision process.
No. People have partial information and there are some who will have beliefs, experiences, or data which makes it rational for them to believe and also irrational reasons; additional rational reasons should push a few people over the edge of the decision if rational reasons play any meaningful role in non-adopters. (If you want to mathematicize it, imagine it as a liability-threshold model.)
Also no. I think you are not understanding my argument. Because all the new evidence is one-sided, we know the direction people should update in regardless of initial proportions of irrationality of either side. In the same way, we don’t know for sure how irrational it was to believe in mind-body dualism in 1500 but we do know that all the evidence that has come in since has been decisively in favor of materialism, and if we saw a group which had the same rate of mind-body dualism in 2016 as 1500, we could be certain that they were deeply irrational on that topic. The absence of any change in the large initial fraction of non-adopters in response to all the new evidence over a long time period implies their judgement is far more driven by irrational reasons than adopters. (By definition everyone is either a adopter or non-adopter, no change in non-adopters implies no change in adopters.)
I have the sense that there’s something wrong with this division into “adopters” and “non-adopters”. The lack of increase in cryonics-adopters while pro-cryonics evidence has been coming in does not mean that there is one group that updates their cryonics decisions rationally (the adopters) and one group that does not (the non-adopters). If that were the case then there would be an increase, as the rational ones gradually got on board as evidence came in. The stasis in the adoption curve wouldn’t just mean that the current non-adopters are irrational for not getting on board, it would also mean that the adopters were irrational for getting on board too soon, before the good evidence came in. Unless we want to say that from the get-go the pro-cryonics case was super strong.
I don’t think it has to be super-strong. It just has to be reasonable. It was reasonable at the time, and as excuses get knocked down without any decrease in fraction of non-adopters, it becomes increasingly clear that they were not the real reason for the non-adopters and that they are non-adopters for pre-determined reasons which have little to do with the science.
You can replace “excuses” with “justifications” and “non-adopters” with “adopters” and get a similar argument in the other direction.
This amounts to Bulverism: if you assume that your opponents are wrong (i.e. you assume that their excuses got successfully knocked down), then you can claim there must be some irrationality that explains why they remain your opponents. But you’re not supposed to assume that. It’s like saying “excuses for opposing homeopathy get knocked down, but the allopaths don’t become homeopaths. Obviously this shows they are alloapths for irrational reasons with nothing to do with the science”.
No, because you haven’t demonstrated that you successfully preserved it, where “successfully” means “able to revive in an intact and working shape”.
I’m not sure this distinction, while significant, would ensure “millions” of people wouldn’t sign up.
Presumably, preserving a human brain “successfully”, according to some reasonable definition of the term, would be a big deal and cause a lot of interest in cryonics. It would certainly seem like significant progress towards the sort of life-extension that LW’s been clambering about.
Exactly how many new contracts they would get seems hard to predict, but I don’t see a number larger than 1,000,000 to be unreasonable.
Millions of people do sign up for various expensive and invasive medical procedures that offer them a chance to extend their lives a few years or even a few months. If cryonics demonstrated a successful revival, then it would be considered a life-saving medical procedure and I’m pretty confident that millions of people would be willing to sign up for it.
People haven’t signed up for cryonics in droves because right now it looks less like a medical procedure and more like a weird burial ritual with a vague promise of future resurrection, a sort of reinterpretration of ancient Egyptian mummification with an added sci-fi vibe.
A major difference here is that if I sign up for those medical procedures, then I pretty much know what to expect: there is a slight chance that I get cured, and that’s it. This is not the case with cryonics. I find it quite likely that cryonics would work, but there’s hardly any certainty regarding happens then: I might wake up in just about any form (in a biological body, as an upload) in just about any kind of future society. I would have hardly any control over the outcome whatsoever.
Sure, maybe there would be many more who would sign up, but nevertheless I think it takes a very special kind of person to be ready to take such a leap into the unknown.
If revival had been already demonstrated then you would pretty much already know what form you will be going to wake up in
Well, yeah, but whatever society can demonstrate that doesn’t need to freeze people in the first place.
That’s not true. I can think of at least 3 ways in which a society which has demonstrated successful revival could also still need to freeze people:
You could die of something that will be curable in a few years and you know to high confidence what you will wake up as because society or revival methods won’t change much.
The emulation route could wind up being best long before magic nanobots cure all bodily ills, so you must die (so your brain is fixed well enough for slicing & scanning) but you know what you will wake up as almost immediately.
There could be treatments or cures but of poor enough efficacy that you rationally prefer the risks of immediate death-then-preservation than try them (you have a fatal disease which can be cured only by a prefrontal lobotomy; alternately, you can go into cryopreservation; which do you prefer?).
4.You have a neurodegenerative disease, you can survive for years but if you wait there will be little left to preserve by the time your heart stops.
I saw that as falling under #3. There are treatments for dementia and Alzheimer’s but they all suck and one can rationally prefer the risk of immediate death to losing it all. This comes up a lot linked with assisted-suicide, as does the attendant legal risks for oneself and the cryonics org (some of Mike Darwin’s blog touches on the effects of aging, and I think Ettinger himself took the dehydration route a few years ago).
Here’s hoping there’s increased conversation about both voluntary brain preservation, and voluntary brain death as both assisted suicide and an evidence-supported way to boost organ donation rates
Here’s hoping the Open Philanthropy Project and/or other EA organisations are willing to engage with negative utilitarian considerations and dare to fund humane deaths!. Many EA’s support the same for animals. Why not humans?
There are reliable avenues for people to do it anyway. May is well keep their dignity, keep their environment tidy, not scaring innocent witnesses.
While I’m a proponent of voluntary euthanasia under some conditions I think this post is overly dismissive of why people might shy away from it.
Also on the note of rhetoric:
If you want to promote the position it’s probably best to not jump straight into taboo tradeoffs.
Framing it as a way of boosting organ donation rates will cause people to have the same visceral reaction that they would to saying that baby-torture would boost company profits.
Terry Pratchett’s Richard Dimbleby lecture Shaking Hands With Death handles it pretty well as it frames it as not wanting to spend the end of your life with tubes trailing out of you which is more along the lines of trading sacred value for sacred value.
https://www.youtube.com/watch?v=90b1MBwnEHM