[LINK] blog on cryonics by someone who freezes things in a cell bio lab

post by mwengler · 2012-10-19T18:35:10.303Z · score: 5 (12 votes) · LW · GW · Legacy · 30 comments

http://www.strike-the-root.com/51/walker/walker12.html

Came across it pretty randomly, I found it quite intriguing.  Cryonics is "routine" for human embryos, not far-fetched for humans at all.  Makes the whole thing seem potentially very reasonable (and me someone who hasn't signed up and doesn't plan to).  

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comment by V_V · 2012-10-20T12:40:36.788Z · score: 17 (23 votes) · LW · GW

Don't confuse cryobiology with cryonics. Cryobiologists, the people who actually invent these tissue preservation techniques which are routinely used in hospitals and research labs all over the world, typically think that cryonics is a pseudoscience at best and a fraud at worst: http://en.wikipedia.org/wiki/Cryobiology#Scientific_societies

Reversible vitrification of individual cells or small samples of tissue is possible because they are small, thus they can be cooled quickly. Cryoprotectants are used to facilitate the process, but not in toxic concentrations.

Fast cooling of objects as large as a human body, or even a human head, is essentially impossible due to the square-cube law: the thermal capacity of an object is proportional to its mass, which, for a given density, is proportional to its volume, while its capacity to transfer heat is proportional to its surface area. As size increases, surface area grows quadratically while volume grows cubically, hence their ratio decreases.

If you attempt to cool a large object too fast, you will freeze or vitrify only a thin superficial layer, and probably even shatter it, since temperature gradients cause gradients of thermal contraction resulting in mechanical stress.

Cryonicists who attempt to preserve whole human cadavers or heads, perfuse them with large amounts of cryoprotectants in order to achieve vitrification. This has several problems:

  • In contrast with mainstream tissue preservation techniques, cryonicists use cryoprotectants in toxic concentrations. At these concentrations, unreversible damage occurs: proteins become denaturated and cell membranes become distorted.
  • Cryoprotectants are perfused post-mortem. It's unclear how deep they are actually able to diffuse. Any area where cryoprotectants don't reach the concentration required for vitrification will be destroyed by ice crystal formation. So far, no cryopreserved human brain has ever been examined to determine the extent of freezing damage.
  • The cryoprotectant perfusion process and the subsequent cooling are very slow. Typically, at least two days pass between the someone's terminal cardiac arrest and the time they reach glass transition temperature, during much of this time their brain has no significant oxygen and glucose supply (ischemia). Human nervous tissue is typically unrecoverably damaged after about one hour of ischemia.
  • For ease of storage, cryonicists cool cadavers past the glass transition temperature, down to liquid nitrogen temperature. Since different types of tissues in the human body thermally contract at different rates, mechanical stress causes multiple widespread macroscopic fractures in all organs including the brain. The extent of microscopic damage at the edges of these fractures is unknown.
comment by anon26 · 2012-10-22T08:41:34.150Z · score: 4 (6 votes) · LW · GW

Most cryobiologists don't know or care about cryonics, because it is the purview of a tiny (< 3000 peple) and eccentric minority.

However, there certainly are cryobiologists, even prominent ones, who have shown a great willingness to work with cryonics organizations and publicly associate with them.

Take Gregory Fahy as an example. He is an eminent cryobiologist who authored the seminal paper on vitrification of human embryos for reproductive medicine: http://www.biolreprod.org/content/67/6/1671.full

His company, 21st Century Medicine, created the M22 cryoprotectant compound used by Alcor, and he also led the team that successfully re-implanted a rabbit kidney that had been removed, vitrified, and thawed back into the rabbit from which it was removed, and then after removing the rabbit's other, unvitrified kidney, the rabbit survived (with slightly diminished renal function) on the formerly vitrified kidney. Fahy hopes that this technology will one day be used to greatly extend the "shelf life" of human organs for transplant.

Though Fahy is first and foremost a cryobiologist, he has spoken at life extension and cryonics conferences, and he is not at all opposed to seeing his technology used to improve cryonics: http://en.wikipedia.org/wiki/Gregory_Fahy

comment by V_V · 2012-10-22T16:10:40.538Z · score: -1 (5 votes) · LW · GW

Most cryobiologists don't know or care about cryonics, because it is the purview of a tiny (< 3000 peple) and eccentric minority.

The Society for Cryobiology doesn't allow cryonicists to become members and has issued statements that describe "cadaver freezing", as currently practiced by cryonicists, as an "act of faith, not science"

Though Fahy is first and foremost a cryobiologist, he has spoken at life extension and cryonics conferences, and he is not at all opposed to seeing his technology used to improve cryonics.

Does he endorse cryonics or is he signed up himself for cryopreservation?

comment by enoonsti · 2012-10-23T11:00:37.339Z · score: 3 (3 votes) · LW · GW

The Society for Cryobiology consists of only ~280 members (by contrast, the Society of Neuroscience has 40,000 members). Furthermore, those ~280 largely specialize in frogs, oocytes, etc.... but not in organ cryopreservation. For whatever it's worth, focus only on organ cryopreservationists and you'll find the percentage of cryonics supporters drastically increase.

I know you skimmed this article, but I encourage you to read it again. There you'll find your answer to Greg Fahy. Also, Brian Wowk is an organ cryopreservationist who supports cryonics. Peter Mazur, one of the most prominent cryobiologists discussed in the previous link, recently referenced Wowk's paper on the thermodynamic aspects of vitrification.

comment by V_V · 2012-10-23T14:17:26.273Z · score: 1 (1 votes) · LW · GW

Furthermore, those ~280 largely specialize in frogs, oocytes, etc.... but not in organ cryopreservation.

Reference? If I understand correctly, most of cryobiological research, including these rabbit kidney cryopreservation results, is published in the official journal of the Society for Cryobiology. Fahy used to be (still is?) a member of the Society and also the treasurer.

For whatever it's worth, focus only on organ cryopreservationists and you'll find the percentage of cryonics supporters drastically increase.

Reference?

I know you skimmed this article, but I encourage you to read it again. There you'll find your answer to Greg Fahy.

"Darwin" cites Fahy on an incident of a paper that was apparently rejected, according to Fahy because of prejudice, though others say it was rejected because it was bad science, he cites him again on uncontroversial arguments for vitrification.

I can't find anything implying that Fahy endorses cryonics as currently practiced. There is clearly a great difference between saying that cryopreservation of whole humans or human brains is an interesting area of research and suggesting people to make arrangments today to be cryopreserved with methods of unproven effectiveness.

Brian Wowk is an organ cryopreservationist who supports cryonics.

I've found this video of Wowk speaking at an Alcor conference. I find it quite balanced.

He mentions all the problematic issues with brain freezing and vitrification. He claims that the vitrification injury may be reversible in principle and in practice with future technology, but he admits that the argument is somewhat "hand-wavy" and won't convince critics.

I do disagree with the conclusion that, even if cryonics has a low probablity of success, we should do it. It is the sort of "Pascal's mugging" argument that is not instrumentally rational.

comment by enoonsti · 2012-10-24T06:21:46.313Z · score: 2 (2 votes) · LW · GW

I can't find anything implying that GF endorses cryonics as currently practiced.

ಠ_ಠ

Be honest. Did you simply ctrl-F and search for his name in that article? If yes, then here is a paragraph you missed: "In 1981, an internationally renowned organ cryopreservation researcher was called into his supervisor's office (the supervisor was also an Officer and Director of the Society) and threatened with dismissal if he continued not only his low profile association with cryonicists, but also his suspension membership. It was also pointed out to this researcher that if his association with or belief in cryonics in any way became public he would never again get grants from the NIH or other routine sources. This individual, who was already wearing his suspension bracelet on his ankle to avoid public comment, was thus faced with a terrible dilemma: a choice between his chance at continued life via cryonics, or his career."

Assuming you won't take the time to read that lengthy article, here is a shorter one. Look for the part about the prominent Southern California scientist recommending cryopreservation for someone severely afflicted with Alzheimer's. Like the Cold War piece above, the Marcelon Johnson article is also written by Mike "Darwin." If his nickname from his schoolmates irks you, then you'll love this piece: Dr. Dave Crippen, Professor of Critical Care Medicine and Neurological Surgery at the UPMC Medical Center in Pittsburgh, compares Mike to - drum roll please - Richard Feynman. For the record, I disagree with that comparison and I think Mike disagrees too (・。・;)

Both of your "Reference?" inquiries were historically answered in the Cold War article above. Assuming you haven't done this yet, google the words "organ cryopreservation" just for fun. Not only does Fahy's name dominate the results, but you should also see a 1988 book by David Pegg, who was mentioned in the Cold War article. Of course, as I made clear to this Reddit user, simple googling can be misleading (I apologize to Less Wrong users for my snark at that link... I tend to get irritated by stubborn individuals...)

Well anyways, it's impossible for me to know exactly how many organ cryopreservationists are currently in their labs - Elsevier searches do not inspire confidence - and their true views on cryonics. For example, here's a recent article on porcine uterus cryopreservation. Who are these authors? Did they show up at the annual meeting of the Society for Cryobiology in June? And even if they did, would they admit to Ben they support cryonics in light of the Society's strained history? Whatever the case, I always appreciated this article by Fahy, where he concludes: "Even after currently-possible manipulations of physics and biology have all been explored, nanotechnology will come into play, allowing someone to enter the field from a wholly new perspective and change the rules of the game in more radical ways than most cryobiologists living today can imagine."

XD

I do disagree with the conclusion that, even if cryonics has a low probablity of success, we should do it. It is the sort of "Pascal's mugging" argument that is not instrumentally rational.

I'm not going to argue the importance of cryonics in a comment section. I just want to focus on simpler corrections for now. Or in other words, please stop insinuating that no cryobiologists support cryonics.

comment by anon26 · 2012-10-23T04:10:48.238Z · score: 0 (0 votes) · LW · GW

I don't know, but he was/is involved with a stillborn cryoincs startup called Timeship. Also, he spoke at a cryonics and life extension conference recently with people like Ralph Merkle, and does seem to endorse present vitrification-based cryopreservation as "good enough." Search youtube for "fahy" and you should be able to find it.

comment by John_Maxwell (John_Maxwell_IV) · 2012-10-20T21:51:44.851Z · score: 3 (3 votes) · LW · GW

Fast cooling of objects as large as a human body, or even a human head, is essentially impossible due to the square-cube law: the thermal capacity of an object is proportional to its mass, which, for a given density, is proportional to its volume, while its capacity to transfer heat is proportional to its surface area. As size increases, surface area grows quadratically while volume grows cubically, hence their ratio decreases.

Has anyone thought about chopping brains in to slices and freezing the slices? I guess you'd have to match the slices up to each other extremely precisely to recover the brain though.

comment by David_Gerard · 2012-10-20T21:59:37.234Z · score: 9 (13 votes) · LW · GW

Per PZ Myers, the state of the art in neural preservation doesn't recoverably preserve usable amounts of state in zebrafish brains, which are a few hundred microns on a side. How thin slices were you thinking of? And how fast were you going to be slicing?

I’ve worked with tiny little zebrafish brains, things a few hundred microns long on one axis, and I’ve done lots of EM work on them. You can’t fix them into a state resembling life very accurately: even with chemical perfusion with strong aldehyedes of small tissue specimens that takes hundreds of milliseconds, you get degenerative changes. There’s a technique where you slam the specimen into a block cooled to liquid helium temperatures — even there you get variation in preservation, it still takes 0.1ms to cryofix the tissue, and what they’re interested in preserving is cell states in a single cell layer, not whole multi-layered tissues. With the most elaborate and careful procedures, they report excellent fixation within 5 microns of the surface, and disruption of the tissue by ice crystal formation within 20 microns. So even with the best techniques available now, we could possibly preserve the thinnest, outermost, single cell layer of your brain…but all the fine axons and dendrites that penetrate deeper? Forget those.

comment by John_Maxwell (John_Maxwell_IV) · 2012-10-21T03:17:17.371Z · score: 4 (4 votes) · LW · GW

I didn't have anything definite in mind; was just throwing the idea out there. Thanks for the info.

comment by 1986ED52 · 2012-10-21T13:41:04.191Z · score: 3 (7 votes) · LW · GW

Odd.

Human embryos are routinely cryogenically preserved, can be thawed and reimplanted to birth healthy human beings. Yet a blastocyst is roughly spherical, not homogenous, about 150-200 micrometers large, totals about 60 cells.

Also, even rabbit kidneys, which are a few centimeters large, can be preserved. Not very often, not very reliably so, but some could still function and sustain life for days after being thawed.

comment by David_Gerard · 2012-10-21T20:40:07.580Z · score: 6 (6 votes) · LW · GW

I believe such freezing is normally done at eight cells, no bigger. And you can in fact remove one of the eight cells and the child develops (apparently) normally - it's the one sure-fire way to sex-test an embryo (recalling from memory).

What we're talking about here is not making sure you can grow a brain at all (the embryo) nor making sure a filter can filter again (the kidney), but preserving the information that makes you you. It's a different kind of problem from getting a filter to work again. The people who actually work with this stuff day to day and would love to be able to recover state from preserved neurons, even in principle, say it's literally impossible with the present state of the art.

comment by JoshuaZ · 2012-10-21T18:39:21.409Z · score: 3 (3 votes) · LW · GW

Embryos in this context are a handful of cells and they end up reorganizing if they have a problem. And they don't have delicate connections.

Kidneys are an interesting example but they are one of the simplest organs in the body.

comment by Dolores1984 · 2012-10-22T22:42:14.144Z · score: 2 (6 votes) · LW · GW

Which is obvious nonsense. PZ Meyers thinks we need atom-scale accuracy in our preservation. Were that the case, a sharp blow to the head or a hot cup of coffee would render you information theoretically-dead. If you want to study living cell biology, frozen to nanosecond accuracy, then, no, we can't do that for large systems. If you want extremely accurate synaptic and glial structural preservation, with maintenance of gene expressions and approximate internal chemical state (minus some cryoprotectant-induced denaturing), then we absolutely can do that, and there's a very strong case to be made that that's adequate for a full functional reconstruction of a human mind.

comment by David_Gerard · 2012-10-22T23:45:26.171Z · score: 2 (2 votes) · LW · GW

As you'll see if you read his text, he's responding to proposals to emulate a brain without understanding how it all works, and is noting just how fine you'd need to actually go to do that.

If you want extremely accurate synaptic and glial structural preservation, with maintenance of gene expressions and approximate internal chemical state (minus some cryoprotectant-induced denaturing), then we absolutely can do that, and there's a very strong case to be made that that's adequate for a full functional reconstruction of a human mind.

I've heard the case made at length, but not of, e.g., a C. elegans that's learnt something, been frozen and shows it stil remembers it after it's unfrozen (to name one obvious experiment that, last time this precise Myers article was discussed, apparently no-one had ever done) or something of similar evidentiary value. Experiment beats arguing why you don't need an experiment. Edit: Not the last time this Myers article was discussed, but the discussion of kalla724's "what on earth" neuroscientist's opinion on cryonics practice.

comment by Dolores1984 · 2012-10-23T01:19:57.667Z · score: 0 (2 votes) · LW · GW

Right, but (virtually) nobody is actually proposing doing that. It's obviously stupid to try from chemical first principles. Cells might be another story. That's why we're studying neurons and glial cells to improve our computational models of them. We're pretty close to having adequate neuron models, though glia are probably still five to ten years off.

I believe there's at least one project working on exactly the experiment you describe. Unfortunately, C. elegans is a tough case study for a few reasons. If it turns out that they can't do it, I'll update then.

comment by jkaufman · 2012-10-24T10:44:25.827Z · score: 0 (0 votes) · LW · GW

You might find this earlier discussion useful on how far we've gotten with emulating C elegans: http://lesswrong.com/lw/88g/whole_brain_emulation_looking_at_progress_on_c/

comment by Maelin · 2012-10-23T05:11:01.145Z · score: 0 (2 votes) · LW · GW

Clarification: the current state of the art in neural preservation doesn't preserve amounts of state in zebrafish brains that are recoverable in usable form by the current state of the art.

If we had the ability to recover the information in usable form today, there would be no need for cryonics to exist.

comment by David_Gerard · 2012-10-23T07:12:32.870Z · score: 1 (1 votes) · LW · GW

You're assuming the information is even preserved. Neuroscientists look at what cryonics does and say "what on earth, the information is lost." (Again, that post wasn't that long ago.)

comment by mwengler · 2012-10-20T14:06:02.042Z · score: 3 (3 votes) · LW · GW

Cool info and summary, thanks.

You say no frozen human brain has been examined. Have any frozen brains been examined?

What about the claims in the original link that organ transplants could be greatly facilitated if organ freezing techniques were developed. Could you comment on that claim in the context of your knowledge?

comment by V_V · 2012-10-20T15:47:57.905Z · score: 6 (10 votes) · LW · GW

You say no frozen human brain has been examined. Have any frozen brains been examined?

I'm not an expert. To my knowledge mainstream cryobiological techniques allow the preservation of very thin slices of brain tissue maintaining structural and functional integrity, but larger samples don't seem to be preservable with current technology (read the opinion of PZ Myers, an evolutionary biologist who studies the vertebrate nervous system and applies these techniques in his research).

Alcor, a cryonics organization, appear to have performed cryopreservation experiments on a whole rabbit brain. Apparently, they found cell membrane distortions but no ice formation. I don't know whether these results were replicated by independent researchers or even whether they were published in peer-reviewed literature. In any case, a rabbit brain is less than 1/100th of a human brain by mass, hence it is obviously much easier both to perfuse with cryoprotectants and to cool quickly.

EDIT:

What about the claims in the original link that organ transplants could be greatly facilitated if organ freezing techniques were developed. Could you comment on that claim in the context of your knowledge?

I agree that if organ cryopreservation were available, it would facilitate organ transplants. In principle perhaps you could even clone your own organs and freeze them for future use instead of keeping them alive in an animal hosts. As far as I know, this is already possible in humans for samples of ovarian tissue large enough to restore reproductive function after chemotherapy and there is animal and human experimentation on whole ovary cryopreservation.

Preservation of larger organs is not possible with current technology, and we can't know whether it will be ever be possible, since the square-cube law appears to be an obstacle difficult to overcome. If I were to guess I'd say that it will require much better biocompatible cryoprotectants to be administered pre-ischemia (or maybe even genetic engineering to make the cells produce cryoprotectants themselves, like some species of animals do) and probably also some drug (or genetic agumentation) to significantly delay ischemic damage.

comment by RobinHanson · 2012-12-12T15:04:32.241Z · score: 2 (2 votes) · LW · GW

Um, the whole point of the blood system is to overcome the squared area vs cubed volume problem. So you can cool larger things fast if you use blood vessels to move fluid that carries out heat.

comment by V_V · 2012-12-27T14:42:50.922Z · score: 1 (3 votes) · LW · GW

Kinda.

If you circulate a coolant through the circulatory system, the cooling speed is limited by the coolant heat capacity and mass flow rate. For a given maximum pressure difference, the maximum flow that you can achieve depends on the fluid density, viscosity, and the structure of the circulatory system. In the simplified case of laminar flow through a stiff circular straight pipe Hagen–Poiseuille equation applies: mass flow rate is proportional to fluid density and the square of cross-sectional area, and inversely proportional to fluid viscosity and pipe length. The circulatory system is mostly made by long and thin capillaries, with curves and branching that add further resistence compared to a straight pipe.

Blood has approximately the same density of water and five times its viscosity, but it is a non-Newtonian fluid optimized for flowing through thin capillaries. With any water-based coolant, you wouldn't be able to achieve a much higher flow rate than normal circulatory flow rate, but you can use a water-based coolant since water would freeze. Anything more viscous, such as a cryoprotectant mixture, can be circulated at a much lower flow rate. That's why cryoprotectant perfusion as practiced by cryonicists takes many hours. Forcing an higher flow would not only risk rupturing the blood vessels, but also heat them instead of cooling. If you were to use cryoprotectant as a coolant (which, AFAIK, no cryo company does), viscosity would also increase as temperature decreases. And I presume that the maximum allowable pressure in blood vessels decreases with temperature: much like rubber hoses, I expect them to become brittle as they approach glass transition temperature.

Add the fact that a typical cryonics "patient" won't usually have an intact and highly functional circulatory system: hours of ischemia and pre-mortem conditions can usually result in stiff, obstructed, collapsed or outright ruptured blood vessels, making impossible to rely on circulatory function to perform cooling. In fact, it's even unclear whether proper cryoprotectant perfusion could be achieved in most cases.

comment by pengvado · 2012-10-22T20:45:31.483Z · score: 0 (0 votes) · LW · GW

Typically, at least two days pass between the someone's terminal cardiac arrest and the time they reach glass transition temperature, during much of this time their brain has no significant oxygen and glucose supply (ischemia). Human nervous tissue is typically unrecoverably damaged after about one hour of ischemia.

You say that as if those two durations are comparable. But what matters for the purpose of ischemia isn't the total duration of cooling, but rather the time-integral of the temperature-dependent rate of chemical reactions. And most of the contribution to that integral comes from the first ~10℃ of cooling, not the part anywhere near glass transition.

comment by fezziwig · 2012-10-19T20:56:11.223Z · score: 3 (3 votes) · LW · GW

Wasn't going to upvote until I got to this line:

...many are cold, but few are frozen.

comment by Viliam_Bur · 2012-10-21T19:21:04.138Z · score: 2 (4 votes) · LW · GW

I am suspicious about this argument:

Cryonics (and the rest of biotechnology) can be used to make individuals live longer than political parties, governments, and empires. People who have outlived three governments won't take the fourth so seriously.

I think that if people will live longer, then also the political parties will exist longer.

In extreme situations, sometimes a dictatorship falls only because the dictator died of old age. Now imagine a dictatorship where the dictator has the best technology for themselves, and a mediocre technology for their supporters; and of course their enemies get none. So they will have like thousand years old vampires ruling the country, opposed by some young folks who may try some cool tricks, but the vampires have already seen all those tricks dozen times.

Would it be interesting to have Thomas Jefferson alive and hear his opinions about the world today? Sure it would be. But remember that on the other side of the planet you would have Stalin alive. (At least Hitler would be dead.)

comment by [deleted] · 2012-10-21T22:46:08.049Z · score: 3 (3 votes) · LW · GW

My first thought was “Oh, crap!”. Then I told myself, “Apply a reversal test: if something happened that made it impossible for anyone to survive over 60, would you have thought ‘Well, at least this means dictators can't stay in charge too long’?”

comment by Viliam_Bur · 2012-10-22T08:10:47.351Z · score: 4 (4 votes) · LW · GW

It depends on how specifically it looks like in the alternative universe of the reversal test.

For example if it means "Stalin lives 6000 years, his henchmen live 600 years, other people live 60 years", then "everyone lives 60 years" could be an improvement.

comment by [deleted] · 2012-10-22T20:57:45.353Z · score: 1 (1 votes) · LW · GW

This is a bit of a side note, but apparently that link was from 2005, which was at the same time of the Alcor Rabbit Kidney Experiment. It looks like research into freezing may have advanced since then, because when I was looking into it, I heard about Norio Odawa and Vitrification Freezers, which came out after 2005 and don't appear to use chemicals at all:

http://en.wikipedia.org/wiki/Vitrification_freezer

http://www.forbes.com/global/2008/0602/053.html

http://singularityhub.com/2011/01/23/food-freezing-technology-preserves-human-teeth-organs-next/

I don't know if these are promising on brains or not, but if anyone has heard something, please let me know.

Edit: As a further note, he mentions using Fluctuating magnetic fields for reheating... Ironically, if I am reading this correctly, the fields are actually used during cooling itself instead.

comment by DaFranker · 2012-10-19T21:15:08.646Z · score: -2 (2 votes) · LW · GW

Also potentially relevant.

Basically, there already exist humans that are alive and living after a successful cryogenic trip. The thing is, they were both frozen and thawed before they were born and fertilized - only the eggs and sperm get frozen. We're not that good yet at freezing and particularly thawing them after they were born.