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kalla724 comments on Neil deGrasse Tyson on Cryonics - Less Wrong Discussion

6 Post author: bekkerd 09 May 2012 03:17PM

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Comment author: kalla724 12 May 2012 09:58:56PM 54 points [-]

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?

Comment author: jsteinhardt 13 May 2012 02:55:21PM 13 points [-]

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?)

Comment author: kalla724 13 May 2012 09:55:50PM 24 points [-]

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.

Comment author: jsteinhardt 13 May 2012 10:06:50PM *  6 points [-]

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?

Comment author: kalla724 13 May 2012 10:15:39PM *  12 points [-]

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.

Comment author: JoshuaZ 13 May 2012 10:04:46PM 6 points [-]

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.

Comment author: kalla724 13 May 2012 10:14:09PM 13 points [-]

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.

Comment author: JoshuaZ 13 May 2012 10:29:20PM 7 points [-]

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?

Comment author: kalla724 14 May 2012 06:25:06PM 26 points [-]

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.

Comment author: JoshuaZ 14 May 2012 08:10:30PM 9 points [-]

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

Comment author: RobinHanson 12 December 2012 03:06:47PM 11 points [-]

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.

Comment author: V_V 18 December 2012 03:40:45PM 6 points [-]

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.

Comment author: RobinHanson 20 December 2012 04:34:57PM 2 points [-]

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.

Comment author: V_V 26 December 2012 02:16:00PM 3 points [-]

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.

Comment author: Kawoomba 18 December 2012 03:44:54PM 1 point [-]

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.

Comment author: V_V 18 December 2012 04:55:31PM 0 points [-]

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).

Comment author: Kawoomba 18 December 2012 05:29:48PM 1 point [-]

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.

Comment author: ciphergoth 13 May 2012 07:30:59PM 25 points [-]

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.

Comment author: kalla724 13 May 2012 10:08:30PM 28 points [-]

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).

Comment author: ciphergoth 14 May 2012 06:54:21AM 13 points [-]

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.

Comment author: James_Miller 14 May 2012 04:53:35AM *  0 points [-]

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?

Comment author: lsparrish 14 May 2012 05:00:09PM 20 points [-]

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.

Comment author: Strange7 21 March 2013 03:30:44PM 4 points [-]

'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.

Comment author: TheOtherDave 21 March 2013 04:02:37PM 5 points [-]

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.

Comment author: kalla724 14 May 2012 06:28:12PM 26 points [-]

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

Comment author: maia 06 June 2012 07:19:57PM 3 points [-]

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.

Comment author: ciphergoth 06 June 2012 07:44:06PM 3 points [-]

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.

Comment author: ScottMessick 17 June 2012 02:49:00AM 4 points [-]

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.

Comment author: ciphergoth 17 June 2012 06:54:19AM 2 points [-]

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".

Comment author: ScottMessick 19 June 2012 12:56:22AM *  5 points [-]

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.

Comment author: David_Gerard 10 June 2012 05:55:19PM *  10 points [-]

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.)

Comment author: gwern 10 June 2012 11:06:00PM *  18 points [-]

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...)

Comment author: Eliezer_Yudkowsky 21 March 2013 08:35:52AM 2 points [-]

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.

Comment author: David_Gerard 11 June 2012 07:01:02AM *  0 points [-]

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.

Comment author: Mitchell_Porter 13 May 2012 06:43:57PM 8 points [-]

Do you think uploading C. elegans is impossible?

Comment author: kalla724 13 May 2012 10:01:07PM 24 points [-]

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.

Comment author: MugaSofer 07 October 2013 06:39:11PM 1 point [-]

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."

Comment author: Vladimir_Nesov 13 May 2012 08:43:48PM *  7 points [-]

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?

Comment author: kalla724 13 May 2012 10:10:28PM 22 points [-]

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).

Comment author: CasioTheSane 13 May 2012 05:13:21PM 7 points [-]

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.

Comment author: kalla724 13 May 2012 09:37:06PM 12 points [-]

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.

Comment author: lsparrish 14 May 2012 04:08:55PM *  4 points [-]

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?
Comment author: kalla724 14 May 2012 06:38:46PM 11 points [-]
  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.

Comment author: lsparrish 14 May 2012 08:02:39PM 4 points [-]

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).

Comment author: Eliezer_Yudkowsky 21 March 2013 08:19:56AM 6 points [-]

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.

Comment author: Kawoomba 21 March 2013 08:37:13AM *  2 points [-]

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.

Comment author: wedrifid 21 March 2013 08:51:16AM *  10 points [-]

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?

Comment author: army1987 21 March 2013 05:52:25PM 3 points [-]

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

Comment author: Kawoomba 21 March 2013 08:55:38AM *  3 points [-]

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.

Comment author: wedrifid 21 March 2013 09:14:55AM 3 points [-]

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.

Comment author: EHeller 21 March 2013 02:21:54PM *  10 points [-]

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.

Comment author: Kawoomba 21 March 2013 06:37:48PM 2 points [-]

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.

Comment author: Kawoomba 28 March 2013 02:09:51PM *  8 points [-]

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.

Comment author: EHeller 28 March 2013 09:16:18PM 2 points [-]

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.

Comment author: Kawoomba 29 March 2013 06:23:34AM *  1 point [-]

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.

Comment author: EHeller 21 March 2013 11:56:15PM *  0 points [-]

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.

Comment author: Kawoomba 22 March 2013 06:45:25AM *  1 point [-]

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)

Comment author: EHeller 22 March 2013 07:05:02AM 0 points [-]

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.

Comment author: wedrifid 21 March 2013 02:59:36PM 0 points [-]

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.

Comment author: Strange7 21 March 2013 03:10:50PM 1 point [-]

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.

Comment author: Kawoomba 21 March 2013 06:42:37PM *  0 points [-]

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.

Comment author: Merkle 24 June 2012 03:43:33AM 5 points [-]

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.

Comment author: David_Gerard 02 June 2012 07:12:47AM 3 points [-]

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?