Neil deGrasse Tyson on Cryonics

Question:

What are your thoughts on cryogenic preservation and the idea of medically treating aging?

His response:

A marvelous way to just convince people to give you money. Offer to freeze them for later. I'd have more confidence if we had previously managed to pull this off with other mammals. Until then I see it as a waste of money. I'd rather enjoy the money, and then be buried, offering my body back to the flora and fauna of which I have dined my whole life.

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The view of cryonics Tyson expresses here is, unfortunately, just the standard high-status-scientist conventional wisdom at the moment.

On the other hand, this is interesting:

What do you consider to be your greatest accomplishment scientifically? In life as a whole?

Made a prediction some years ago that there were 10x as many galaxies in the universe than had then been catalogued. based on a careful review of observation bias in how people obtained data on the universe. The actual number turned out to be about 5x as many galaxies. I got the wrong answer but for the right reasons, and it stimulated much further work on the subject.

In other words, he considers his greatest scientific achievement to be an improved estimate for a particular quantity, based on an analysis of biases in other people's data. That's rather...LWish.

It looks like he's just another smart guy who's no wiser outside the laboratory, which is very disappointing, as I greatly admire him as a scientist and advocate of science education. Bah. He's still on our side, or at least a fellow traveler.

(!) But look what he says here (emphasis added):

Do you think that Humans in our lifetime will achieve the technology to be able to live forever? [...]

Yes, I think it's inevitable. But that would eventually make for a very crowded Earth. So perhaps that's what we need to jumpstart the space program.

It seems this belief of his just hasn't yet propagated to the part of his mind that answers the cryonics question.

Yes, I think it's inevitable. But that would eventually make for a very crowded Earth. So perhaps that's what we need to jumpstart the space program.

Well.. It doesn't necessarily lead to that. You can just not have children.
And it doesn't have to be not to have children at all. Ie. 1 child for everyone happens to be 0.5 children per person.

Just saying that the "space program" probably isn't the best solution.. for now.

That's quite a leap to go from "he disagrees with me on one issue" to "[he's] no wiser outside the laboratory [than an average person]."

From his reply I suspect that cryonics is something he hasn't thought about very much, whereas he has thought quite a lot about other important (arguably more important) issues. For a celebrity scientist, I am actually quite surprised how insightful and independent his thinking is on a wide range of topics.

Cryonics is very expensive, and I would guess there's only about a 1% chance of it working as currently performed. Seeing it as a potentially rare and worthwhile opportunity, or as a waste of money both seem like reasonable positions depending on a persons values and finances to me...

What are the numbers that lead to your 1% estimate?

I will eventually sit down and make a back of the envelope calculation on this, but my current off-the-cuff estimate is about twenty (yes, twenty) orders of magnitude lower.

I see. So if you made a billion trillion independent statements of the form "cryonics won't work", on topics you were equally sure about, you'd be pretty confident you were right on all of them?

? No.

I fully admitted that I have only an off-the-cuff estimation (i.e. something I'm not very certain about).

Then I asked you if you have something better - some estimate based in reality?

OK, so you have some assumptions that you attach some high but not extreme amount of probability to, according to which the chances of cryonics working are on the rough order of 10^-22. Fair enough. But given that the relevant question is how certain you are about the assumptions, why even bring up the 20 orders of magnitude, if it doesn't matter whether it's 20 orders of magnitude or 1000 orders of magnitude? What role could the 20 orders of magnitude number play in anyone's decision making?

Note that I'm a different person than user:CasioTheSane.

Ok, now we are squeezing a comment way too far. Let me give you a fuller view: I am a neuroscientist, and I specialize in the biochemistry/biophysics of the synapse (and interactions with ER and mitochondria there). I also work on membranes and the effect on lipid composition in the opposing leaflets for all the organelles involved.

Looking at what happens during cryonics, I do not see any physically possible way this damage could ever be repaired. Reading the structure and "downloading it" is impossible, since many aspects of synaptic strength and connectivity are irretrievably lost as soon as the synaptic membrane gets distorted. You can't simply replace unfolded proteins, since their relative position and concentration (and modification, and current status in several different signalling pathways) determines what happens to the signals that go through that synapse; you would have to replace them manually, which is a) impossible to do without destroying surrounding membrane, and b) would take thousands of years at best, even if you assume maximally efficient robots doing it (during which period molecular drift would undo the previous work).

Etc, etc. I can't even begin to cover complications I see as soon as I look at what's happening here. I'm all for life extension, I just don't think cryonics is a viable way to accomplish it.

Instead of writing a series of posts in which I explain this in detail, I asked a quick side question, wondering whether there is some research into this I'm unaware of.

Does this clarify things a bit?

If you have a technical argument against cryonics, please write it up as an actual blog post, ideally under your real name so you can flash your credentials. It will be the most substantial essay arguing for such a point ever written: see my blog. I'm pretty convinced that if there was really a strong argument of the sort you're trying to make, someone would already have done this, so I take it as strong evidence that they haven't.

This was supposed to be a quick side-comment. I have now promised to eventually write a longer text on the subject, and I will do so - after the current "bundle" of texts I'm writing is finished. Be patient - it may be a year or so. I am not prepared to discuss it at the level approaching a scientific paper; not yet.

Keep in mind two things. I am in favor of life extension, and I do not want to discourage cryonic research (we never know what's possible, and research should go on).

Thanks. While a scientific paper would be wonderful, even a blog post would be a huge step forward. In so far as a technical case has been made against cryonics, it is either Martinenaite and Tavenier 2010, or it is technically erroneous, or it is in dashed-off blog comments that darkly hint and never get into the detail. The bar you have to clear to write the best ever technical criticism of cryonics is a touch higher than it was when I first blogged about it, but still pretty low.

I've signed up for cryonics (with Alcor) because I believe that if civilization doesn't collapse then within the next 100 years there will likely be an intelligence trillions upon trillions of times smarter than anyone alive today.

If such an intelligence did come into being do you think it would have the capacity to revive my frozen brain?

I don't think any intelligence can read information that is no longer there. So, no, I don't think it will help.

While I agree that this is a relevant consideration for the big picture, I just wanted to note in a non-confrontational way that it has the appearance of unfairly shifting cognitive workload to the skeptic -- which could perhaps result in the nasty side effect of preventing future skeptics from weighing in. Evaporative cooling and all that. A person specializing in synapse biochemistry probably shouldn't have to (at least at first) consider all the aspects of future superintelligence in quite the same way that an AI researcher would.

Just to unpack a little on James_Miller's idea: One example of how this could potentially come into play is that externally gathered data (for example -- chat logs, videos, even the recorded reactions of other humans) could be extrapolated to generate a personality sim, and connectome data could be used to verify it.

Mining data from a lot of different sources, the superintelligence could perhaps get much closer to the original than the mostly-blank, yet connectome matching and genetically identical clone we would otherwise have. Having that matching connectome as a starting point could conceivably be an important part of making sure that the personality matches for the right reasons, i.e. comes out with similar structural-functional mappings.

Again, I'm not sure how much of this maps to the domain specific knowledge that kalla724 has, but I'd be fascinated to hear more.

'Personality reconstruction' is both less satisfying and more difficult to automate. I think most people who buy into cryonics would prefer to wake up remembering the things they never said in public, rather than having a patched-together doppelganger wear their clothes in the 31st century equivalent of Colonial Williamsburg.

Well, if reliably remembering the things I never said in public were an option, I'd sort of like that ability now rather than waiting until I die for some entity who may or may not deserve the label "me" to have it. In the meantime, I'll go on reconstructing semifictional accounts of what might have happened based on the information I currently have handy, just like most people do.

Not weighing in either way on cryonics itself, but on the meta level: Why do you consider that strong evidence? It seems to me that most people who don't think cryonics will work simply aren't interested in it, and therefore haven't tried very hard to prove that they're right.

That's not my experience; a great deal of anti-cryonics stuff has been written, and it's my experience that a lot of people who think it won't work seem to have quite strong feelings about it, so if there is a strong argument that lots of people know then it is surprising that no-one has written it up properly.

kalia724's comment is an apparently-strong argument that I'd never heard, and you know I've actively looked for arguments for and against. I do think you're putting a bit much hope in absence of evidence of criticism as being non-negligible evidence of absence of possible criticism - the space of concepts working scientists don't bother thinking about is ridiculously huge, and cryonics hits quite a few green-ink heuristics (unfairly, IMO, but it does) which gets it filed with the mental spam in short order. edit: and see my Facebook post for a mutual friend of ours noting he has qualms about even writing something serious about cryonics as he risks a significant professional status hit by doing so - cryonics is that low-status.

kalia724 evidently doesn't have time to write this up properly in the foreseeable future, so I think we'd need to ask around to see if there is, at the least, a nameable neuroscientist who thinks kalia's assertions against cryonics have something to them. (I've just hit my socialmediasphere with the question. You, and everyone else interested, probably should too.)

cryonics hits quite a few green-ink heuristics (unfairly, IMO, but it does) which gets it filed with the mental spam in short order.

Even the stupidest pseudosciences or movements have received excellent debunking; for example, I would put the Urantia cult way down the list below cryonics, and yet, we still have Martin Gardner's 500 page examination/debunking, Urantia: The Great Cult Mystery.

(I would point out, incidentally, that 'nobody will criticize low-status things' is a fully comprehensive proof of the non-existence of the entire skeptics movement, which is pretty much all about criticizing low-status things, and you probably would prefer not to use such a claim as your explanation of the lack of good cryonics criticism...)

A quite obvious possibility is that would-be debunkers who want try to go deeper than Penn and Teller style mockery soon realize that they would have to engage much more seriously with cryonics than with Urantia to try to debunk it - sound like they were taking it seriously - implying a far greater loss of status than soaring casually above Urantia, effortlessly trashing it without a hint of sympathy.

"Everyone who's tried to 'debunk' this seems to have ended up writing casual mockery, and oddly enough no would-be skeptics ever seem to engage the arguments in technical detail, and the arguments are being made by people who sure look like they're trying to wear technical hats and include a number of otherwise highly technical figures" seems to me like a quite common position when both of these aspects are combined. There are arguments that skeptics don't bother engaging in detail, but they're not technical. There are physicists who believe crazy things because they're bad outside the laboratory, but then they are usually refuted by more than mockery. I may be prejudiced by being mostly interested only in things that are sensible to start with, but the overall state of affairs I have just described is pretty much what you'd expect a correct but weird-sounding idea to look like.

I have no status in science, so your last phrase is just silly. Scientists who are noted sceptics may want to criticise cryonics, and, of course, several have. But the effect I describe is something I saw someone who'd been specifically asked to comment as a scientist invoking, per the link which you should be able to read (rather than relying entirely on theoretical counterarguments, as you have); and I am, of course, noting it as one factor, not as the complete explanation you seem to have read it as.

I think you may be missing a silent majority of people who passively judge cryonics as unlikely to work, and do not develop strong feelings or opinions about it besides that, because they have no reason to. I think this category, together with "too expensive to think about right now", forms the bulk of intelligent friends with whom I've discussed cryonics.

I don't think you're addressing the subject of this thread, which is "does there exist a strong technical argument against cryonics that a lot of people already know".

Summary: Expanding on what maia wrote, I find it plausible that many people could produce good technical arguments against cryonics but don't simply because they're not writing about cryonics at all.

I was defending maia's point that there are many people who are uninterested in cryonics and don't think it will work. This class probably includes lots of people who have relevant expertise as well. So while there are a lot of people who develops strong anti-cryonics sentiments (and say so), I suspect they're only a minority of the people who don't think cryonics will work. So the fact that the bulk of anti-cryonics writings lack a tenable technical argument is only weak evidence that no one can produce one right now. It's just that the people who can produce them aren't interested enough to bother writing about cryonics at all.

I wholeheartedly agree that we should encourage people who may have them to write up strong technical arguments why cryonics won't work.

Fascinating. I've been waiting for a while for a well-educated neuroscientist to come here, as I think there are a lot of interesting questions that hinge on issues in neuroscience that are at least hard for me to answer (my only exposure to it is a semester-long class in undergrad). In particular, I'd be interested to know what level of resolution you think would be necessary to simulate a brain to actually get reasonable whole-brain emulations (for instance, is neuronal population level enough? Or do we need to look at individual neurons? Or even further, to look at local ion channel density on the membrane?)

Local ion channel density (i.e. active zones), plus the modification status of all those ion channels, plus the signalling status of all the presynaptic and postsynaptic modifiers (including NO and endocannabinoids).

You see, knowing the strength of all synapses for a particular neuron won't tell you how that neuron will react to inputs. You also need temporal resolution: when a signal hits the synapse #3489, what will be the exact state of that synapse? The state determines how and when the signal will be passed on. And when the potential from that input goes down the dendritic tree and passes by the synapse #9871, which is receiving an input at that precise moment - well, how is it going to affect synapse #9871, and what is the state of synaps #9871 at that precise moment?

Depending on the answer to this question, stimulation of #3498 followed very soon after with stimulation of #9871 might produce an action potential - or it might not. And this is still oversimplifying things, but I hope you get the general idea.

Thanks for the response. Do you think it is important to explicitly consider the tertiary structure of proteins along the membrane, or can we keep track of coarser things such as for instance whether or not a given NMDA channel is magnesium-blocked or not?

EDIT: Also, you mentioned optogenetics at some point. Do you work with Ed Boyden by any chance?

We are deep into guessing territory here, but I would think that coarser option (magnesium, phosphorylation states, other modifications, and presence and binding status of other cofactors, especially GTPases) would be sufficient. Certainly for a simulated upload.

No, I don't work with Ed. I don't use optogenetics in my work, although I plan to in not too distant future.

You also need temporal resolution: when a signal hits the synapse #3489, what will be the exact state of that synapse? The state determines how and when the signal will be passed on. And when the potential from that input goes down the dendritic tree and passes by the synapse #9871, which is receiving an input at that precise moment - well, how is it going to affect synapse #9871, and what is the state of synaps #9871 at that precise moment?

How much of this do we actually need in practice? Humans can be put in states where there's almost no brain activity, such as an induced coma, and brought out of it with no damage. That suggests that things like the precise state of #9871 at that moment shouldn't matter that much.

All of it! Coma is not a state where temporal resolution is lost!

You can silence or deactivate neurons in thousands of ways, by altering one or more signaling pathways within the cells, or by blocking a certain channel. The signaling slows down, but it doesn't stop. Stop it, and you kill the cell within a few minutes; and even if you restart things, signaling no longer works the way it did before.

So even in something like the Milwaukee protocol there's still ongoing activity in every neuron? So what is different between human neurons and say those of C. elegans? They can survive substantial reductions in temperature with neuronal activity intact. Even bringing them down to liquid nitrogen temperatures leaves a large fraction surviving and that's true if they are cooled slowly or quickly. What am I missing here?

In order, and briefly:

  • In Milwaukee protocol, you are giving people ketamine and some benzo to silence brain activity. Ketamine inhibits NMDA channels - which means that presynaptic neurons can still fire, but the signal won't be fully received. Benzos make GABA receptors more sensitive to GABA - so they don't do anything unless GABAergic neurons are still firing normally.

In essence, this tunes down excitatory signals, while tuning up the inhibitory signals. It doesn't actually stop either, and it certainly doesn't interfere with the signalling processes within the cell.

  • You are mixing three different processes here. First is cooling down. Cooling down is not the same as freezing. There are examples of people who went into deep hypothermia, and were revived even after not breathing for tens of minutes, with little to no brain damage. If the plan was to cool down human brains and then bring them back within a few hours (or maybe even days), I would put that into "possible" category.

Second is freezing. Some human neurons could survive freezing, if properly cultured. Many C. elegans neurons do not survive very deep freezing. It depends on the type of neuron and its processes. Many of your ganglionic neurons might survive freezing. Large spiny neurons, or spindle cells? Completely different story.

The third is freezing plus cryoprotectants. You need cryoprotectants, otherwise you destroy most cells, and especially most fine structures. But then you get membrane distortions and solvent replacement, and everything I've been talking about in other posts.

Thanks. This comment and your other comments have made me substantially reduce my confidence in some form of cryonics working.

No doubt you can identify particular local info that is causally effective in changing local states, and that is lost or destroyed in cryonics. The key question is the redundancy of this info with other info elsewhere. If there is lots of redundancy, then we only need one place where it is held to be preserved. Your comments here have not spoken to this key issue.

The brain has redundancy at the level of neurons: it is quite resilient against diffuse neuron loss, and in case of localized damage, unless the affected area is large or includes key regions such as the brainstem, impairment is often limited to one or a few functions, and in some cases it even reorganizes to transfer the lost functions to other areas, partially recovering them.

However, there is no expectation that the brain has redundancy against the loss of an information storage medium that is used in all neurons.

If you destroy half of your collection of DVDs, the information in the other half is still intact. If you destroy every odd-numbered track on all of your DVDs, instead, most of the remaining data will be too fragmentary to be of any use, even if the number of bits you destroyed is the same in both cases.

There can be a lot of redundancy within neurons as well. Just because you find causally relevant chemical densities that predict neuron states doesn't mean that there aren't other chemical densities that also predict those same states.

Is there any evidece of such large redundancy at the level of biochemical information storage? I'm not aware of it, and I can't see a good reason for such thing to have been evolved.

I'm not a neuroscientist, but AFAIK, I'm not sure that talking about chemical densities is the most appropriate way to frame the discourse here: synapses are small enough that the discrete nature of protein complexes and structures becomes relevant. While disrupting a single molecule wouldn't significantly affect the neuron state, a process that causes generalized misallignment between the active zones on one side and corresponding receptors on the other side, or between the two halves of electric gap junctions, or other widespread distortions, could easily do. Unless this process is reversible in the information-theoretic sense, these bits of information are lost forever.

IIUC, the type of distortions that occur during cryopreservation: membrane deformations due to changes of osmotic pressure and denaturation of cytoskeleton proteins, unfolding of information-bearing proteins, clumping and precipitation out of solution, tend to be irreversible, many-to-one, transitions.

The brain has redundancy at the level of neurons: it is quite resilient against diffuse neuron loss

Depends on what axis of resilience (as you alluded to).

For memory, confer grandmother cells.

A neuron for Halle Berry, for example, might respond "to the concept, the abstract entity, of Halle Berry", and would fire not only for images of Halle Berry, but also to the actual name "Halle Berry".[15] However, there is no suggestion in that study that only the cell being monitored responded to that concept, nor was it suggested that no other actress would cause that cell to respond (although several other presented images of actresses did not cause it to respond).

That wiki article looks dated. See these two, more recent abstracts: [1], [2].

Anyways, the point isn't whether there are actual grandmother cells, or "merely" a very small number of cells serving the same purpose. It is that there are crucial brain functions with little to no redundancy.

In general, uploading a C. elegans, i.e. creating an abstract artificial worm? Entirely doable. Will probably be done in not-too-distant future.

Uploading a particular C. elegans, so that the simulation reflects learning and experiences of that particular animal? Orders of magnitude more difficult. Might be possible, if we have really good technology and are looking at the living animal.

Uploading a frozen C. elegans, using current technology? Again, you might be able to create an abstract worm, with all the instinctive behaviors, and maybe a few particularly strong learned ones. But any fine detail is irretrievably lost. You lose the specific "personality" of the specific worm you are trying to upload.

I'm aware you wont reply to this - I'm writing for other archive-readers - but I think they meant "is it in-principle impossible to upload a particular frozen C. elegans?"

To which, I assume based on your other comments, you would answer "yes, the information simply isn't there anymore, IMO."

The point you're making seems to be that performing the repair is impossible in practice. Apart from that difficulty, do you think enough information is preserved in the location of all atoms in a cryopreserved brain, so that given detailed knowledge of how brains work in general this information would in theory be sufficient to reconstruct the initial person (even if this information is impractical to actually extract or process)? One possibility for avoiding the reconstruction of brains out of atoms is to instead reconstruct a Whole Brain Emulation of the original person. Do you think developing the technology of WBE is similarly impossible, or that there are analogous difficulties with use of WBE for this purpose?

I don't believe so. Distortion of the membranes and replacement of solvent irretrievably destroys information that I believe to be essential to the structure of the mind. I don't think that would ever be readable into anything but a pale copy of the original person, no matter what kind of technological advance occurs (information simply isn't there to be read, regardless of how advanced the reader may be).

Can you elaborate on the damage that is occurring, even with cryoprotectants?

Why/how would low temps in a cryoprotectant denature proteins?

If you have time I would really like to see the detailed posts, perhaps even in a new thread. I am also a bioengineer/biophysicist but I have little knowledge of neuroscience.

I'll eventually organize my thoughts in something worthy of a post. Until then, this has already gone into way more detail than I intended. Thus, briefly:

The damage that is occurring - distortion of membranes, denaturation of proteins (very likely), disruption of signalling pathways. Just changing the exact localization of Ca microdomains within a synapse can wreak havoc, replacing the liquid completely? Not going to work.

I don't necessarily think that low temps have anything to do with denaturation. Replacing the solvent, however, would do it almost unavoidably (adding the cryoprotectant might not, but removing it during rehydration will). With membrane-bound proteins you also have the issue of asymmetry. Proteins will seem fine in a symmetric membrane, but more and more data shows that many don't really work properly; there is a reason why cells keep phosphatydilserine and PIPs predominantly on the inner leaflet.

I don't necessarily think that low temps have anything to do with denaturation.

  1. Elsewhere you noted that the timing of signals within the synapses is important. Is the relative timing something that can be kept straight via careful induction of low temperatures?
  2. In your opinion, would less toxic cryoprotectants be sufficient and/or necessary for preserving the brain in a way that keeps a significant amount of the personality?
  3. What do you think of my notion that, for the sake of clarity, "cryonics" should be split into distinct categories; one for the research goal and one for the current ongoing practice?
  1. Yes, if you can avoid replacing the solvent. But how do you avoid that, and still avoid creation of ice crystals? Actually, now that I think of it, there is a possible solution: expressing icefish proteins within neuronal cells. Of course, who knows shat they would do to neuronal physiology, and you can't really express them after death...

  2. I'm not sure that less toxic cryoprotectants are really feasible. But yes, that would be a good step forward.

  3. I actually think it's better to keep them together. Trying theoretical approaches as quickly as possible and having an appliable goal ahead at all times are both good for the speed of progress. There is a reason science moves so much faster during times of conflict, for example.

As a layman I sort of lump icefish proteins under "cryoprotectants", though I am not sure this is accurate -- that might technically be reserved for penetrating antifreeze compounds.

The impression I have of the cryoprotectant toxicity problem is that we've already examined the small molecules that do the trick, and they are toxic in high (enough) concentrations over significant (enough) periods of time. Large molecules of a less toxic nature exist, but have a hard time passing through cell membranes, so they can't protect the interior of cells very well.

M22 uses large molecules (analogous to the ice-blocking proteins found in nature -- although these are actually polymers) to block ice formation on the outside of the cells (where there is a lower concentration of salts to start with), so a lower concentration of small-molecule CPAs are needed.

Another thing is that the different low-weight cryoprotective agents interact with each other somehow to block the toxicity effects -- thus certain mixtures get better results than pure solutions. This seemingly suggests that other ways to block their toxicity mechanisms could also be found.

My current favorite idea is reprogramming the cells to produce large molecules that block ice formation -- or which mitigate toxicity in cryoprotectants. We're talking basically about gene therapy here, and that's going to have complicated side effects, but not harder than some of the SENS proposals (e.g. WILT).

Another promising higher-tech idea is to use either bioengineered microbes or biomimetic nanotech (assuming that idea matures) to deliver large molecules to the insides of cells. Alternately, more rapid delivery and removal of small-molecule CPAs to reduce exposure time. In addition to this, reduced cooling times would be helpful, which makes me think of heat-conductive nanotech implants (CNTs maybe).

I will quickly remark that some aspects of this comment seem to betray a non-info-theoretic point of view. From the perspective of someone like me, the key question for cryonics are "Do two functionally different start states (two different people) map onto theoretically indistinguishable molecular end states?" You are not an expert on the future possibilities of molecular nanotechnology and will not be asked to testify as such, but of course we all accept that arbitrarily great physical power cannot reconstruct a canister of ash because the cremation process maps many different possible starting people to widely overlapping possible canisters of ash. It is this question of many-to-one mapping alone on which we are interested in your expertise, and I would ask you to please presume for the sake of discussion that the end states of interest will be distinguished to molecular granularity (albeit obviously not to a finer position than thermal noise, let alone quantum uncertainty).

That said, I think we will all be interested if you can expand on

many aspects of synaptic strength and connectivity are irretrievably lost as soon as the synaptic membrane gets distorted

and whether you mean this in the customary sense of "it won't boot back up when you switch it on" or in the info-theoretic sense of "this process will map functionally different synapses to exactly similar molecular states, or a spread of such states, up to thermal noise". You are not being asked to overcome a burden of infinite proof either - heuristic argument is fine, we're not asking for particular proofs you can't possibly provide - we just want to make sure that what is being argued is the precise question we are interested in, that of many-to-one mappings onto molecular end states up to thermal noise.

EDIT: Oops, didn't realize this was an old comment.

Shake your head. Vigorously. (Do it.)

There, I've just caused you to scramble a vast array of concentration gradients, proteins tumbling around in a merry free-for-all. I have thus killed the old king, vive le roi nouveau!

If that's not enough, consider the forces inertia exerts on all those precious gradients and precise molecule orientations when on a rollercoaster. Uh oh.

The molecular states may not have to be exactly similar after all to yield functional equivalency within an acceptable margin, a margin we deem acceptable throughout our lives. Let's not worry about a few non-injective transformations?

I was initially swayed by Kalla724's arguments (as well as a little molecular biology background), but it's missing the forest for the trees.

There, I've just caused you to scramble a vast array of concentration gradients, proteins tumbling around in a merry free-for-all.

You probably haven't actually, anymore then when you shake your hands vigorously back and forth the germs fly off. The force applied for so small a time is unlikely to have much of an effect on the cells which are dominated by chemical interactions,osmotic pressures,etc. Things don't scale the way you'd like them to. Your whole argument is just invalid.

Edit to incorporate a point made below: which is good as if you scrambled the proteins in your brain, you'd die.

False analogy; there is a change in medium going from the oiled up dermis to air.

Take a glass of water with a large number of tagged proteins. That is the model of e.g. presynaptic vesicles filled with neurotransmitters, swimming in the cytoplasmic matrix (which is mostly water). A significant amount of them is not attached to anything. I didn't say the folding structure would be scrambled, I said that the concentration gradients would be influenced, and that the orientation of non-attached proteins would change.

Shake the glass of water. What happens?

Shake the cytoplasmic matrix. What happens? What does such a rearrangement probably entail? That's right, some change in concentration gradients, and a host of non-attached proteins tumbling around in a merry free-for-all.

Your whole argument is just invalid.

We can arrange to bet on our beliefs about this, say a 4 figure sum going to a charity of the other's choice, with mutually agreed upon authorities in the field being the arbiters? If so send me a PM, and we can make the result public once we're done.

Postmortem for the bet:

EHeller was correct in so far as physical accelerations as occurring in every-day life do not have an effect on proteins and other small cell components which exceeds thermal noise.

I did win the bet since EHeller committed to a statement saying there would be no effect (on at least the order of magnitude of thermal noise) on any component of the cell, and as calculated by a referee, it turns out that larger cell organelles such as mitochondria are affected to such a degree (assuming 0.5g over 10s, 0.5g occurs e.g. when taking a car from 0 to 60mph in 6 seconds, so the 0.5g over 10s would occur for example when taking a car from 0 to 100mph over 10 seconds). Referee statement see here.

The wager goes to Miri, as chosen by Kawoomba, with thanks for all the fish.

I thank EHeller for his professional conduct and his charitable interpretations of my claims, resulting in the, well, result. Had he held me to my initial statements as made, he would have won.


I should have made my point in an entirely different way from the start: Namely, consider you took a psychoactive drug, such as an SSRI. Naturally, all sorts of channel configurations, concentration gradients and the such would be affected. But consider what happens after you stop taking it: you'd regress to some semblance (but not precisely the same state!) of the state you had before.

If someone paid you a large sum of money for taking SSRIs for 1 month, wouldn't you do so? I probably would. I wouldn't consider myself to be committing informational suicide, even though even post-SSRI-taking my state would still be different from my state now. That's my point; many-to-one transformations - variances between the original state and the reconstructed state - don't need to be functionally significant, and even when they are, it doesn't follow that we couldn't consider ourselves to be reconstituted, just as we don't consider ourselves to be committing identity-suicide when taking SSRIs for a month.

Just to verify- we made the bet and unfortunately I allowed the burden of proof to shift to myself, rather than to Kawoomba, and the statement we used for the bet was effectively "everyday scale accelerations will have an affect on proteins or other biologically important compounds at most an order of magnitude below thermal noise." This statement is technically not true, because fairly strong (~g), long-time-scale accelerations (10 s of seconds) will have an effect on the largest structures of just-about-thermal-noise (so basically if you get in one of those centrifuge-style-carnival-rides, you can affect your mitochrondia to order thermal noise).

A car doing 0-60 in 6 seconds won't quite do it, it needs to be 10s of seconds.

Also this should underscore that bets might not be the best way to go about truth seeking :)

Also, to respond to the SSRI point- I doubt Kawoomba would take a large sum of money to take ANY psychoactive drug for 1 month- rather he knows the specific affects of SSRIs. Some changes in brain chemistry can be more important than others.

Hmm, for sufficiently large values of 'large sum of money', as long as the drug was randomly (not maliciously) chosen from a pool of FDA-approved psychoactive drugs, I would. Wouldn't you, for one trillion dollars? If so, we're just haggling about price.

The original example used 0.5g, just to give an impression that would be on the scale of going 0-60 in 6 seconds, for 10 seconds just keep up the acceleration for 4 seconds longer.

Also, given "one magnitude less than thermal noise" (as in the statement), apparently normal rollercoasters are, after all, sufficient to affect even smaller structures such as lysosomes at >58 (fifty-eight) nm, see this amendment.

We can arrange to bet on our beliefs about this, say a 4 figure sum going to a charity of the other's choice, with mutually agreed upon authorities in the field being the arbiters? If so send me a PM, and we can make the result public once we're done.

To be clear, you want to bet that shaking your head side-to-side vigorously causes the same qualitative type of changes to protein concentrations along cell membranes as introducing a large concentration of toxic cryoprotectants?

I want to emphasize along cell membranes, as I believe those are the concentrations kalla was referring to, its where the information will be lost, and is why I referred to osmotic pressure and chemical interactions being very dominant, and such forces are not present in your glass of water analogy (other than shaking the glass will NOT cause the proteins to precipitate out), so I want to make sure we are talking about the same thing.

To be clear, you want to bet that shaking your head side-to-side vigorously causes the same qualitative type of changes to protein concentrations along cell membranes as introducing a large concentration of toxic cryoprotectants?

...

No, I am not saying that shaking your head will rupture many of your phospholipid bilayers and in effect kill you.

Glad we could clear that up.

(What I am saying is "after the damage (e.g. cell membranes) has been repaired, certain information was not recoverable" not being a death knell for cryonics, since we accept a considerable margin of error concerning e.g. specific neurotransmitter vesicle locations in daily life without considering ourselves a different person just because we've effected a host of changes in distributions and arrangements. An example other than shaking your head, which also strongly affects cross-membrane distributions: SSRIs)

I agree that bioactive drugs will have effects on distributions, as thats what they exist for, they also cause (sometimes mild, sometimes extreme) personality changes. What I'm interested in is how wrong can we get things and still have a "working" brain.

Things don't scale the way you'd like them to.

I'm not sure Kawoomba would really like brains to be scrambled by head shaking. I expect that all else being equal he would prefer as little disruption as possible.

Shake your head. Vigorously. (Do it.)

I tried that. Now I'm a whole different combination proteins and chemicals. And this new me doesn't understand how the point you are trying to illustrate relates to the grandparent any better than the old me.

Is it just tangential expression of your own position on broadly the same subject in loose agreement with Eliezer or is there an additional point you are trying to make?

I tried that. Now I'm a whole different combination proteins and chemicals. And this new me doesn't understand how the point you are trying to illustrate relates to the grandparent any better than the old me.

:-D

Take for example:

You can't simply replace unfolded proteins, since their relative position and concentration (and modification, and current status in several different signalling pathways) determines what happens to the signals that go through that synapse

I'm saying such a scrambling happens all the time anyways, and that preserving the exact relative position, concentration, folding status etcetera may not be all that important to the cognitive system at large, at least we don't fret about it when shaking our heads. Does that help?

Edit to respond to your edit:

Is it just tangential expression of your own position on broadly the same subject in loose agreement with Eliezer or is there an additional point you are trying to make?

I'd say it's an important point (naturally). If there were only one-to-one mappings, that would certainly be sufficient to establish that information-theoretically the original state information isn't lost. But that's a red herring, since we don't even need that strong a claim to argue for the theoretical viability of cryonics:

When voluntarily shaking your head (you madman!) you were content with a much, much more forgiving standard. That's the one that should be used for such discussions.

I'm saying such a scrambling happens all the time anyways, and that preserving the exact relative position, concentration, folding status etcetera may not be all that important to the cognitive system at large, at least we don't fret about it when shaking our heads.

That seems like a reasonable and important point.

When voluntarily shaking your head (you madman!) you were content with a much, much more forgiving standard.

I'd probably go as far as to use a standard that accepted even a severe concussion or three's worth of damage and information loss. Especially given that the ongoing functional impairment (albeit not the identity related loss) can presumably be trivially repaired.

Shaking your head applies relatively uniform forces, which elasticity and natural repair mechanisms can deal with. Even then it can be a close thing; people have been known to take permanent damage from trivial-seeming head injuries.

Freezing applies non-uniform forces. It's the difference between riding an elevator and hopping into a blender.

I'm not interested in damage so much as in changes in e.g. "the exact orientation of presynaptic vesicles" not being integral to our personal identity.

If e.g. someone said "we have no scanning techniques that can tell us how exactly each molecule was oriented, it could have been one of many ways (since you're e.g. trying to reverse a non-injective function", I'd say "well, we constantly change that orientation by random body movements, yet don't mind. So we can assume that change is not identity-constituting."

Edit: Even a uniform force will affect soluble elements differently from other elements. The stiffness is different for various body elements, which will lead to all sorts of tiny changes: Erythrocytes being pressed against the cell wall etcetera. That's not a significant change so that we'd say "we leave the elevator a different person", but that's precisely the point in the comparison with certain information that can't be read from a cell: It may not make all that much of a difference.

You'll need to read Molecular Repair of the Brain. Note that it discusses a variety of repair methods, including methods which carry out repairs at sufficiently low temperatures (between 4K and 77K) that there is no risk that "molecular drift" would undo previous work. By making incredibly conservative assumptions about the speed of operations, it is possible to stretch out the time required to repair a system the size of the human brain to three years, but really this time was chosen for psychological reasons. Repairing a person "too quickly" seems to annoy people.

You might also want to read Convergent Assembly. As this is a technical paper which makes no mention of controversial topics, it provides more realistic estimates of manufacturing times. Total manufacturing time for rigid objects such as a human brain at (say) 20K are likely to be 100 to 1000 seconds. This does not include the time required to analyze your cryopreserved brain and determine the healthy state, which is likely to be significantly longer. Note that some alterations to the healthy state (the blueprints) will be required prior to manufacture, including various modifications to facilitate manufacture, the inclusion of heating elements for rewarming, and various control systems to monitor and modulate the rewarming and metabolic start-up processes as well as the resumption of consciousness.

After you've had time to digest the paper, I'd be interested in your comments. As Ciphergoth has said, there are no (repeat no) credible arguments against the feasibility of cryonics in the extant literature. If you have any, it would be most interesting.

As a neuroscientist, you might also be amused by Large Scale Analysis of Neural Structures.

For recent work on vitrification, I refer you to Greg Fahy at 21st Century Medicine.

I'm reading your comment and am now thinking of this as startlingly optimistic, particularly this bit, which appears just wrong per your comment. Except I realise I don't understand the area enough to rewrite that bit. Gah. Are the Wikipedia articles on what you're talking about here any good for getting up to speed?

Mine was also just an off-the-cuff "guesstimate."

I am skeptical that it is possible to estimate the chances of cryonics working in a rigorous quantitative way. There's no way to know what technical hurdles are actually involved to make it work. How can you estimate your chances of success when you have no information about the difficulty of the problem?

Um...there is quite a bit of information. For instance, one major hurdle was ice crystal formation, which has been overcome - but at the price of toxicity (currently unspecified, but - in my moderately informed guesstimate - likely to be related to protein misfolding and membrane distortion).

We also have quite a bit of knowledge of synaptic structure and physiology. I can make a pretty good guess at some of the problems. There are likely many others (many more problems that I cannot predict), but the ones I can are pretty daunting.

I was unclear, I didn't mean that there's no information, just that there's potentially no information on specific areas that are critical for a meaningful prediction:

  • New technologies and ideas that bypass, rather than solve previously defined obstacles- thus making them far easier than anticipated
  • Newly discovered obstacles which are far more difficult to overcome than any of the previously defined obstacles, making the problem much more difficult than anticipated

Given that both of these types of events are common when developing new technology, attempting to predict how long it will take and how well it will work is basically a waste of time. Even if you synthesize all of the data you have in a rigorous way and come up with a number, I expect that the number would have error bars so large that it's merely a quantitative expression of the impossibility of accurately predicting such events with the data you have.

I am curious about what are the biggest obstacles you see that cause you to give 20 order of magnitude lower an estimate than I do. If that is accurate, thinking about and working on cryonics is a pointless waste of time.

I agree with you on both points. And also about the error bars - I don't think I can "prove" cryonics to be pointless.

But one has to make decisions based on something. I would rather build a school in Africa than have my body frozen (even though, to reiterate, I'm all for living longer, and I do not believe that death has inherent value).

Biggest obstacles are membrane distortions, solvent replacement and signalling event interruptions. Mind is not so much written into the structure of the brain as into the structure+dynamic activity. In a sense, in order to reconstruct the mind within a frozen brain, you would have to already know what that mind looks like when it's active. Then you need molecular tools which appear impossible from the fundamental principles of physics (uncertainty principle, molecular noise, molecular drift...).

My view of cryonics is that it is akin to mercuric antibiotics of the late 19th century. Didn't really work, but they were the only game in town. So perhaps with further research, new generation of mercuric substances will be developed which will solve all the problems, right? In reality, a much better solution was discovered. I believe this is also the case with life extension - cryonics will fade away, and we'll move in with a combination of stem cell treatments, technologies to eliminate certain accumulated toxins (primarily insoluble protein aggregates and lipid peroxidation byproducts), and methods to eliminate or constrain cellular senescence (I'm actually willing to bet ~$5 that these are going to be the first treatments to hit the market).

I agree with you that the enormous cost is probably not worth it, when you start thinking what else could be accomplished with the money in the context of it's low probability of success.

However, those technologies that increase human lifespan are really something entirely different than cryonics, not a replacement for it.

Even if we increase lifespan significantly, as long as we still have a lifespan cryonics would allow us to remain frozen until even more life extension technologies come about. It's also a potentially viable method for keeping people alive for long distance space travel at sub-relativistic speeds.

I'd look forward to seeing a more detailed post (or even a journal article) from you going into the biochemistry specifics of the problems with cryonics you mention in this post, and your other posts in this thread. I am particularly curious why rehydration would denature proteins which are naturally stable in water? And what sort of membrane distortions would occur that aren't reversible?

All good reason to keep working on it.

The questions you ask are very complex. The short answers (and then I'm really leaving the question at that point until a longer article is ready):

  • Rehydration involves pulling off the stabilizer molecules (glycerol, trehalose) and replacing them dynamically with water. This can induce folding changes, some of which are irreversible. This is not theoretical: many biochemists have to deal with this in their daily work.
  • Membrane distortions also distort relative position of proteins within that membrane (and the structure of synaptic scaffold, a complex protein structure that underlies the synaptic membrane). Regenerating the membrane and returning it to the original shape and position doesn't necessarily return membrane-bound molecules to their original position.

I said that because it seemed he was giving the pat, standard, "I haven't thought about this" answer. I don't know if Tyson is sloppy in all thinking outside the lab, but he seemed to be sloppy here. I wouldn't mind if he disagreed with cryonics after having examined the issue in detail, but he's giving an answer (seemingly) without having thought about it very much.

In short, I think I mostly agree with you.

That's quite a leap to go from "he disagrees with me on one issue" to "[he's] no wiser outside the laboratory [than an average person]."

Indeed. (As a non-cryonicist myself, I might well feel offended.)

A marvelous way to just convince people to give you money.

  1. The best way to convince people to give you money is to offer them something of exceptionally high value.

  2. It's perverse logic to imply that a service has lower value because people are willing to pay for the service.

  3. Tragically, the extremely small number of people who have signed up for cryonics proves it's not a "marvelous way" to "convince people to give you money."

I think the fixed version of the statement is that the persuasiveness-to-actual-value ratio is high, so even if persuasiveness is low, that just translates to the actual value being lower still.

I'd rather enjoy the money, and then be buried, offering my body back to the flora and fauna of which I have dined my whole life.

That's a lovely bit of rhetoric to appeal to the Greens. (I say rhetoric because if you are cremated, there's nothing to offer back, and if you are buried, you are usually embalmed and now 'the flora and fauna' will be poisoned if they try to take your offer anytime soon.) I wish I could manage that trick.

now 'the flora and fauna' will be poisoned if they try to take your offer anytime soon.

All the biological material will be cycled back into the ecosystem, most of it quite soon - even despite the presence of toxins (formaldehyde-eating bacteria, etc). His statement is correct in the sense that if you are cryopreserved, the net amount of carbon, nitrogen, phosphorus, etc in the biosphere will be slightly lower than it otherwise would have been.

Not attacking your position, just pointing that out.

(Nitpick: Cryogenics is the study of producing near absolute zero temperatures. You mean "cryonics".)

"I'd have more confidence if we had previously managed to pull this off with other mammals."

Some mammals are pretty good at doing it themselves... http://users.iab.uaf.edu/~brian_barnes/publications/1989barnes.pdf

You could say that billions of dollars spent on cancer research is a huge waste of money because curing cancer has not been proven to work in small mammals. There is no proof that cancer can be cured. I am not being entirely sarcastic about this, but I would give a higher probability for success to most of the Strategies for Engineered Negligible Senescence to achieve rejuvenation. Knowledge of the forms of damage that result in aging is the first step toward repairing that damage. With cryonics the problem is similar: there is damage to be repaired, and it is not unreasonable to believe that in 50 or 100 years the molecular repair technology will be available. It would be foolish to believe that humans will never be able to live on Mars until you see humans living on Mars. The ability to extrapolate from present technology to future technology requires more sophistication than simplistic empiricism.

If what you say were true - we "never cured cancer in small mammals" - then yes, the conclusion that cancer research is bullshit would have some merit.

But since we did cure a variety of cancers in small mammals, and since we are constantly (if slowly) improving both length of survival and cure rates in humans, the comparison does not stand.

(Also: the integration unit of human mind is not the synapse; it is an active zone, a molecular raft within a synapse. My personal view, as a molecular biophysicist turned neuroscientist, is that freezing damage is not fixable from basic principles (molecular drift over a few years is sufficient to prevent it completely). In my mind, the probability that some magical "damage repair" technique will be developed is within the same order of magnitude with probability that Rapture will occur. Cryonics is important primarily in the sense that it provides impetus for further research; but a radically different method of preservation is required before possibility of revivification reaches any reasonable level.)

I'm not quite sure what you mean by molecular raft, but do you think you need to record properties of molecular rafts or just properties of the population of molecular rafts in the neuron? (e.g. amount of each type)

Perhaps a better definition would help: I'm thinking about active zones within a synapse. You may have one "synapse" which has two or more active zones of differing sizes (the classic model, Drosophila NMJ, has many active zones within a synapse). The unit of integration (the unit you need to understand) is not always the synapse, but is often the active zone itself.

I might as well post this here because I don't think it's worth a new thread. Let's assume for the purposes of this argument that you have a suitably high confidence in cryonic revival at some future time. How much do you weigh the number of deaths as a direct consequence of electricity consumed keeping you frozen, against your irreplaceablity in the future society? I'm assuming that there is a non-trivial amount of electricity involved, and substituting the monetary costs of electricity per Folding@Home user per year, with the amount paid per person per year to purchase cryonics services.

Does this train of thought hold at all? If anyone has the time and knowledge to run some numbers, that would be great...

Cryonics storage doesn't consume even a visible fraction of industrially produced liquid nitrogen. And it won't for ten-thousands of patients to come.

Retracted after a bit of research; they just add more liquid nitrogen to counteract evaporation, and don't actually use any electricity. (I honestly didn't know this.)

Anyone who knows what these two picturse are and where they come from? Nemesis is doing some I think not very accurate critique of LessWrong on the Swedish Skeptics internet forum. It is in Swedish, and sorry, I have not time to translate into English. But though I do not know, I suspect that Nemesis have not produced them by himself but found them somewhere. If anyone knows I would be glad to know. (If someone should know already and recogises them, I do not ask anyone to spend significant time on it.)