Luke Parrish points me to what is clearly by far the most serious critique of cryonics ever written: a 57-page treatment by Evelina Martinenaite and Juliette Tavenier, presented as a 3rd semester project at Roskilde University in Denmark supervised by Ole Andersen. I want to congratulate them both on raising the bar for cryonics criticism by a factor of about ten thousand. In 1994 Ralph Merkle wrote:

Interestingly (and somewhat to the author’s surprise) there are no published technical articles on cryonics that claim it won’t work.

After 44 years of cryonics, that has finally changed.

Cryonics

December 22nd, 2010

Evelina Martinenaite, Juliette Tavenier

Abstract: The preservation of cells, tissues and organs by cryopreservation is a promising technology nowadays. However, the primary purpose of this science has been diverted to a doubtful technology, cryonics. Cryopreservation techniques are now being adapted with the aim of preserving people’s bodies after death in hope that in the future, medicine will be able to revive them. In this report we analyze both scientific and social issues involved with this technology. We first studied the events taking place in the cells during regular freezing. Various research experiments show that freezing causes damage to the cells. Therefore, vitrification presented by cryonics companies as an alternative, seems to be reasonable. We also looked at all the difficulties of this procedure and at the injuries that such a treatment could cause to the human body. Studies show that the vitrification procedure suppresses the injuries related to freezing but the use of cryoprotectants, although necessary, is toxic to the cells. Organs, such as kidneys, are the largest entities ever vitrified and thawed with success. By analyzing all present scientific data, we conclude that there is a limit to the size of living matter that can be cryonised effectively; therefore we conclude that it is not possible to cryonize an entire human body with the current technology without causing severe damage to it.

Full paper

A brief response: Yes, cryonic preservation causes all sorts of severe damage far beyond our current ability to overcome; all the damage discussed in this paper is well understood and widely discussed by cryonics practitioners. This paper doesn’t seem to quite engage with the central contention of cryonics: that so long as the information that makes up memory and personality is preserved, future technology may find a way to repair the damage caused by cryopreservation. Two distinct paths to this end are widely talked about: molecular nanotechnology, and scanning/WBE. As far as I can tell, no argument is made in the paper that human cryopreservation causes information-theoretic death, and neither of these repair options are discussed at all. In fact it doesn’t seem to observe much more than the well-understood fact that reanimation is not feasible with current technology. As a result, this paper, while it is vastly vastly ahead of the arguments made by other critics of cryonics, is some way behind the arguments already considered and answered by cryonics advocates.

Radio 4’s weekly obituary program devoted five minutes to the death of cryonics founder Robert Ettinger, and spoke to longstanding cryonics foe Professor David Pegg of the University of York. Here’s a transcript of his broadcast remarks:

Pegg: There are three areas of damage (if you like) which have to be undone for this process to work: one is to bring the dead back to life, another is to cure the thing which caused them to be dead, and the third thing is that the process of preservation should not inflict any damage. It is possible to achieve effective cryopreservation of single-celled systems. What is not possible is to adapt that to multi-cellular systems. So although it might be advantageous to be able to cryopreserve kidneys for example, for transplantation, that is not possible. And the reason that it’s not possible is that the ice, which is innocuous to the cells in themselves, destroys the structure and the kidney will no longer function.

Interviewer: Well now, Robert Ettinger’s supporters would say you’re just being very very shortsighted, you’ve just got your head in the sand, because of course there are problems at the moment, but in the future, science will overcome all of these problems

Pegg: Yes, well that’s an item of faith. it’s not a question of — a scientific question. The fact is of course that we can’t predict the future, and we don’t pretend to do so. But nor can they.

Pegg (later in the programme): We are making progress, but we haven’t got the problem licked just yet. If that problem could be solved, then it would perhaps be reasonable to ask the question whether this should lead to the cryonics endeavour in practice. But at the moment, it’s frankly just premature.

Two technical points, both from Alcor’s cryonics myths page:

• Cryonics providers have used vitrification to eliminate ice crystal formation for a decade now, and even before that other cryoprotectant techniques greatly reduced freezing damage.
• While cryopreservation of kidneys is not yet advanced enough to be used for human transplants, it was demonstrated in rabbits in 2005. One of the rabbits tested survived for 48 days with the cryopreserved kidney as its sole kidney, before being euthanized for histological follow-up.

Perhaps Pegg was taking shortcuts because of the time pressure of radio; however sadly he has not taken the time to present a technically accurate argument in any forum. I once again urge him to do so.

BTW, sorry this blog has been neglected for so long. I’m now finally signed up for cryonics with the Cryonics Institute and Cryonics UK, but as you can see I’m still investigating the subject.

In further correspondence with Doug, he points out this rather odd sentence in Ben Best’s Molecular Mobility at Low Temperature:

Diffusion in a vitrified cryonics patient would presumably not be due to concentration gradients because there should be not concentration gradients.

Surely there can be no concentration gradients only if the whole sample is homogeneous? I’m pretty sure standard cryonics practice doesn’t involve putting the brain in a blender a la Britannia Hospital. I’ll email Best and ask for clarification.

[This is another guest post by Doug Clow — thanks Doug! I asked a question on LongeCity: is the 29 kJ/mol figure for the activation energy of the “catalase reaction” given in How Cold Is Cold Enough correct? Doug was kind enough to give a detailed answer, and permission to edit it a little and reproduce here.]

I did do a chemistry degree, with a lot of biochemistry in it. And even as a postgraduate student attended a research seminar by another postgrad who was investigating catalase analogues, which almost certainly touched directly on the question. But that was long ago and I haven’t done this stuff in anger for decades.

Alas, I don’t have good data books to hand and can’t answer the direct question (“What is the activation energy of the decomposition of hydrogen peroxide when catalysed by catalase”) authoritatively.

Partly, it’s because there isn’t a single answer, and anyone who tells you there is is fibbing. There are shedloads of different catalases (more if you include general peroxidases). They are indeed legendarily fast, and they are more or less ubiquitous in oxygen-metabolising species. The story goes that it’s as perfectly evolved an enzyme as you can hope for. It’s not a bad choice for the worst-case scenario for this context, although I wouldn’t go as far as to say it was the very worst without checking up for other very-fast enzymes in metabolic pathways and signal transduction (e.g. acetylcholinesterase is also legendarily fast). Which would be overkill.

I’d say using any value between 1 kJ/mol and 20 kJ/mol is not unreasonable, and if you pressed me for a value, I’d probably settle on 10 kJ/mol as a round value. (See e.g. http://www.ncbi.nlm.nih.gov/pubmed/8320233 which gave 10 kJ/mol for a catalase from a halophile bacterium — no reason for choice except I alighted on it quickly, or http://www.sciencedirect.com/… which found 11 kJ/mol but looks odd for several reasons.)

At the very top end, a value of 50 kJ/mol for a reaction that happens at a reasonable rate for practical experimental purposes at room temperature is fairly typical. There’s a (sorely abused) rule of thumb that says that reaction rate doubles with an increase of 10 C, which only applies under fairly restrictive conditions, one of which is that the Ea is 50 kJ/mol.

This does, of course, yield materially different results. I tried duplicating that big table in ‘How Cold is Cold Enough’ in a toy spreadsheet, and couldn’t quite reproduce his results, but did get within an order of magnitude which is close enough for these purposes. I played around looking at his ‘Rate relative to liquid N2’ column, for different values for the activation energy.

• 50 kJ/mol -> 2.2 x 10²⁵ times faster at 37C than at LN2
• 20 kJ/mol -> 1.4 x 10¹⁰ times faster
• 10 kJ/mol -> 1.2 x 10⁵ times faster
• 8 kJ/mol -> 1.1 x 10⁴
• 5 kJ/mol -> 340 times faster
• 2 kJ/mol -> 10 times faster
• 1 kJ/mol -> 3.2 times faster

For the question at hand, this makes a huge difference — to this analysis.

This analysis is likely to be wrong, anyway.

A quick look at the Arrhenius equation:

k = A e^-E_a/RT

Let’s take a very, very simplified reaction, where one molecule of reactant hits one catalyst to produce one product. The pre-exponential factor A represents the number of collisions that occur; the bit in the exponent tells you what proportion of those collisions have energy above the activation energy for the reaction.

Now, mathematical instinct might tell you that the bit in the exponent will give you all the action, but that’s not necessarily true. For practical purposes, the rate of catalase in vivo is limited by the rate at which molecules collide, not by the proportion of the molecules colliding which have greater than the activation energy needed for the reaction. Essentially, if a molecule of hydrogen peroxide bumps in to catalase, it’s breaking down. My biochemical intuition is likely to be sorely astray at LN2 temperatures, but I’d guess the same situation applied.

The pre-exponential factor A is probably more key: it’s the rate at which collisions occur between molecules that might react. If you have a perfectly efficient catalyst, this is the main factor affecting the rate of reaction — which makes sense, since they’d reduce the activation energy to a negligible value. Some enzymes — catalase is an excellent example — have been under geological periods of selection pressure in that direction. The Arrhenius equation is a simplification that works (better than it ought to) across a lot of practically-important situations. (One simplification is that the activation energy is not temperature-dependent. It sometimes is.)

If you get a phase change to solid — vitrification at very low temperatures — then you’ll get a staggering-number-of-orders-of-magnitude change in A. Those molecules are going nowhere fast, and so are flat out not going to bump in to each other. Never mind how much energy they’ve got when they do.

So I think that all is not lost for cryonics on this point.

[A guest post from Doug Clow. This was a comment in this article on Bostrom and Sandberg’s Whole Brain Emulation: a Roadmap, but given its length and substance I am with permission putting it here as a new blog post.]

I too am short of time, but have given this paper a quick run through. Here are some unstructured and unedited quick notes I made while I was at it. Apologies for brevity and errors — I almost certainly missed some of their points and have misrepresented parts of their case.

It does seem to be a serious and reasonably well-informed piece of work on speculative science and technology. Emphasis on the speculative, though — which they acknowledge.

The distinction between emulating a brain generically (which I reckon is probably feasible, eventually) and emulating a specific person’s brain (which I reckon is a lot harder), and emulating a specific dead person’s brain (which I reckon is probably not possible), is a crucial one. They do make this point and spell it out in Table 1 on p11, and rightly say it’s very hard.

p8 “An important hypothesis for WBE is that in order to emulate the brain we do not need to understand the whole system, but rather we just need a database containing all necessary low‐level information about the brain and knowledge of the local update rules that change brain states from moment to moment.”

I agree entirely. Without this the ambitious bit of the enterprise fails. (They make the case, correctly, that progress down these lines is useful even if it turns out the big project can’t be done.) I suspect that this hypothesis may be true, but we certainly need to know a lot more about how the whole system works in order to work out what the necessary low-level information and update rules are. And in fact we’ll make interesting scientific progress – as suggested here – by running emulations of bits of the brain we think we might understand and seeing if that produces emergent properties that look like what the brain does. Actually they say this on p15 “WBE appears to be a way of testing many of these assumptions experimentally” – I’d be a bit stronger than that.

Table 2 on levels of emulation makes sense. My gut instinct (note evidence base) is that we will need at least level 8 (states of protein complexes – i.e. what shape conformations the (important) proteins are in) to do WBE, and quite possibly higher ones (though I doubt the quantum level, 11, is needed but Roger Penrose would disagree). Proteins are the actually-existing nanobots that make our cells work. The 3D shape of proteins is critical to their role. Many proteins change shape – and hence what they do or don’t do – in to a smallish fixed number of conformations, and we already know that this can be hugely important to brain function at the gross level. (E.g. transmissible spongiform encaphalopathies – mad cow and all that – are essentially caused by prion proteins in the brain switching from the ordinary shape to the disease-causing one.)

The whole approach is based on scanning an existing brain, in sufficient detail that you can then implement an emulation. I think that’s possibly useful, but I think a more likely successful route to a simulated (!) intelligence will be to grow it, rather than to bring it in to existence fully-formed. By growing, I mean some process akin to the developmental process by which humans come to consciousness: an interaction between an environment and a substrate that can develop in the light of feedback from that environment. But based on their approach, their analysis of technological capabilities needed seems plausible.

The one that leaps out as really, really hard (to the point of impossibility in my mind) is the scanning component. There is the unknown of whether the thing is doable at all (what they call scale separation), which is a biggy, but falsifiable by trying out experiments in this direction.

 continue reading

For a change, here’s something that I hope those of you who disagree with me on cryonics can agree on — I think you would all agree that criticism of cryonics should be honest.

Stephen Barrett, M.D.’s QuackWatch (“Your Guide to Quackery, Health Fraud, and Intelligent Decisions”) has a page about cryonics, which places it firmly on the “quack” side. As evidence, they quote Michael Shermer’s Nano Nonsense and Cryonics:

Cryonicists believe that people can be frozen immediately after death and reanimated later when the cure for what ailed them is found. To see the flaw in this system, thaw out a can of frozen strawberries. During freezing, the water within each cell expands, crystallizes, and ruptures the cell membranes. When defrosted, all the intracellular goo oozes out, turning your strawberries into runny mush. This is your brain on cryonics.

But as regular readers know, this paragraph is entirely erroneous when it comes to cryonics practice. Shermer says as much himself.

I have sent six emails to Barrett and received two replies. The first was one of the many emails I sent to critics of cryonics asking for further reading; I accidentally lost track of who I had sent this to and so sent two such emails. Neither received a response. I later sent him a courtesy email advising him of my survey (since it mentions him), which garnered the response (in full) “Sorry, I am not interested in further involvement in your project”. I replied immediately to thank him for his time.

I then thought I should mention what Shermer had to say about the quote he uses on his website, and sent an email this morning linking to it. The response was (in full) “Kindly stop pestering me. ” I replied to that promising to “write up the outcome of this conversation” and send no further emails. (Of course, this means I now can’t alert him to this blog post — I should have thought of that before I sent it!)

Does anyone else think that using a quote to discredit cryonics which the author himself agrees is entirely misleading, and giving such short shrift to a brief polite email pointing this out, isn’t really in the spirit of scientific skepticism at its best?

OK, that’s enough on the technical side for now — here’s a space to talk about non-technical objections.

I think the strongest argument here is the relatively high danger of global catastrophe: that by some means or other, as a result of the very technological advancement that inspires cryonics, there will be some sort of global catastrophe that makes it impossible for cryonics firms to collect money from investments and/or buy liquid nitrogen with it. A climate change related catastrophe is one candidate, but there are all sorts of other existential risks to consider.

By far the best technical objection I’ve heard so far is David Matthewman’s comments here, discussing Bostrom and Sandberg’s Whole Brain Emulation: a Roadmap:

[…] I still wouldn’t get your hopes up. As far as I can see, it offers no way to discern the state of the neurons, and admits that while it might be possible to get the structure for a small slice of the brain, getting it in 5nm detail for the whole volume is currently impossible, with no known way to overcome the current technological limitations. Many of those limitations are imposed by the wavelength of the medium you’re scanning with, and there’s just no easy way round that. The speed of scanning (which is also currently a showstopper for the ~5nm technologies that might otherwise be attractive) might be able to be improved, but bear in mind that you’re working at levels where the energy of the electrons/photons that you’re using to scan risk damaging the sample, and using more of them in parallel may damage it more. The data transfer/storage problem probably is solvable, by contrast.

I find it a bit worrying that the most promising technologies in the table on page [53] — SOM and SEM, especially combined with array tomography — have relatively little discussion in the text that I can see. This makes me suspect that they’re only even superficially attractive because not enough is known about them to know they don’t work.

Also, given that the conclusion says ‘this sets a resolution requirement on the order of 5 nm at least in two directions,’ there’s far too much discussion of technologies that can only scan down to resolutions two orders of magnitude higher than this. So the text gives the optimistic prediction that ‘[KESM] enables the imaging of an entire macroscopic tissue volume such as a mouse brain in reasonable time’, but what good is that given that KSEM only scans down to 300nm x 500nm? It’s an obvious question, and I’d expect an honestly-written paper to answer it. Because this paper doesn’t, I smell a rat (or, more likely, someone clutching at straws).

The discussion starts ‘As this review shows, WBE on the neuronal/synaptic level requires relatively modest increases in microscopy resolution…’ which may be technically true but vastly understates the difficulty of increasing the resolution of the techniques discussed.

Again, though, I’ll defer to someone who’s done this stuff more recently than I have (and in a medical area — I was mostly looking at metal-matrix composites rather than anything organic).

This stands out from the field in that it is actually in reply to something that someone who believes in cryonics has actually said; it only doesn’t meet the criteria that I asked for in my open letter in that it is blog comment rather than an article, but knowing how busy David is it’s hard to imagine him finding the time to rewrite it in article form any time soon, so with his permission I’m posting it as is.

Updated 2010-02-20: Liam Proven steps up to the plate and meets three of my four criteria. Thanks Liam!

I’ve received lots of interesting comments on my recent posts about cryonics, for which many thanks. However, what I’m really hoping to provoke is something more: actual blog posts and other articles. In this regard, though I think it has many shortcomings, I’m grateful for the work that David Gerard has put into the RationalWiki article on cryonics.

This may seem like an arbitrary distinction; both are forms of writing that can help come to an informed decision, and ignoring someone’s writing on the sole grounds that it’s in the form of a blog comment could be a big mistake. However, for these purposes there are several advantages to articles/blog posts that make them much more useful for this project.

First, articles are meant to stand alone. A blog comment has an implicit context and assumes that the reader is familiar with it. Where an article needs context, it explains and links to the context as needed. This makes it easier to link to and more useful to the recipient.

Second, more work generally goes into articles. Every one of the posts to this blog, even the one that just lists statements from the Society for Cryobiology, has had more work put into it than all but a tiny fraction of my blog comments. That’s all work that’s meant to make the reading experience smoother and the argument clearer and easier.

Thirdly, more pride goes into articles. This is closely related and a little vaguer, but at least speaking for myself I’m often happy to dash off a blog post voicing my best guess at an opinion on something based on only the briefest understanding of the subject area. But an article in general will have a larger readership, and is I think more representative of what I think; much more care will go into trying to say only what I’m prepared to try and defend.

If all you’re trying to do is convince me, you probably don’t need to worry about any of that, and indeed I’m grateful for the work you’ve done so far. But I’m hoping to encourage more than this: I want to bring into being what I was looking for when I started this mission, not only so that I can read it but so that future others in the same position can do likewise. And if you think, as many seem to, that I’m already too hopelessly lost to motivated cognition to be turned around on this issue, then it is them rather than me you should really have in mind when you think about applying finger to keyboard to address this issue. Your comments on blog posts like these may help them a little, but if you’re able to find the time to write them, articles and blog posts of your own will help a lot more.

The focus of this article is the technical plausibility of cryonics; though there are many non-technical objections, I’d like to treat the technical issue in depth before moving on to the non-technical.

Though many experts in cryogenics and other relevant fields are quoted in the media as condemning cryonics practice, none have written at greater length to explain their reasons. The closest thing to such a reason I can find is Michael Shermer’s article “Nano Nonsense and Cryonics”, but the reason he gave was one that he knew at the time of writing was contrary to scientific reality, and in response to my email asking where I could learn more he recommended three authors all of whom consider cryonics technically plausible. The only other anti-cryonics expert to respond to my email asking for more detail was John Bischof, but his replies didn’t carry the detail I was hoping for. (See my earlier blog posts A survey of anti-cryonics writing and More on anti-cryonics writing for details). Strikingly, even when the Society for Cryobiology passed their 1982 by-law barring cryonicists from membership, they produced no detail to back up their claim that “it is the Board’s scientific judgement that the prospects for re-animation of a frozen human, particularly a legally dead human, are infinitesimally low.” (see Society for Cryobiology statements on cryonics).

If cryonics really is nonsense dressed as science, this lack of detail is surprising, and in sharp contrast to pseudosciences such as homeopathy, on which volumes have been written pointing out its dodgy provenance, scientific implausibility and evidential defeat. It’s also very frustrating: I’m left trying to make a judgement call on a debate that only one side is participating in.

So this is my plea to the scientific critics of cryonics:

Please criticise cryonics.

If you thought that someone else had done it, if you thought that the article you’d want a cryonics hopeful to read had already been written, I hope that the surveys above show you that it really hasn’t. If it has, and I either haven’t found it or haven’t treated it fairly, I welcome your comments.

I’ve been trying to think about the reasons why someone like David Pegg would feel strongly enough about cryonics to take part in drafting that 1982 by-law using such strong language in his draft statements and his statements to the media on the subject, yet have nothing to say in reply to an email asking what he would recommend I read to see the other side of the argument. The only hint I currently have from critics is this remark in personal email from John Bischof:

I think the distinction is between a tissue being dead vs. alive at the time of freezing. I don’t believe there is anything I can possibly write that would further clarify that distinction.

But thinking about that remark, and other suggestions that friends have made on why they don’t see the need for such an article, I’ve thought of ten reasons an expert might give for its absence, and tried to answer them.

 continue reading