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Eliezer_Yudkowsky comments on Welcome to Less Wrong! (July 2012) - Less Wrong
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The cryoprotectants are toxic, they will damage proteins (misfolds, etc) and distort relative concentrations throughout the cell. This information is irretrievable once the damage is done. This is what I refereed to when I said obviously destroyed chemical information. It is our hope that such information is unimportant, but my (as I said above fairly uncertain) prior would be that the synaptic protein structures are probably important. My prior is so weak because I am not an expert on biochemistry or neuroscience.
As to the physical fracture, very detailed imaging would have to be done on either side of the fracture in order to match the sides back up, and this is related to a problem I do have some experience with. I'm familiar with attempts to use synchrotron radiation to image protein structures, which has a percolation problem- you are damaging what you are trying to image while you image it. If you have lots of copies of what you want to image, this is a solvable problem, but with only one original you are going to lose information.
Edit: in regards to the first point, kalla724 makes the same point with much more relevant expertise in this thread http://lesswrong.com/r/discussion/lw/8f4/neil_degrasse_tyson_on_cryogenics/ His experience working with synapses leads him to a much stronger estimate that cryoprotectants cause irreversible damage. I may strengthen my prior a bit.
How do you know? I'm not asking for some burden of infinite proof where you have to prove that the info can't be stored elsewhere. I am asking whether you know that widely functionally different start states are being mapped onto an overlapping spread of molecularly identical end states, and if so, how. E.g., "denaturing either conformation A or conformation B will both result in denatured conformation C and the A-vs.-B distinction is just a little twist of this spatially isolated thingy here so you wouldn't expect it to be echoed in any exact nearby positions of blah" or something.
So what I'm thinking about is something like this: imagine an enzyme,present at two sites on the membrane and regulated by an inhibitor. Now a toxin comes along and breaks the weak bonds to the inhibitor, stripping them off. Information about which site was inhibited is gone.
If the inhibitor has some further chemical involvement with the toxin, or if the toxin pops the enzymes off the membrane all together you have more problems. You might not know how many enzymes were inhibited, which sites were occupied, or which were inhibited.
I could also imagine more exotic cases where a toxin induces a folding change in one protein, which allows it to accept a regulator molecule meant for a different protein. Now to figure out our system we'd need to scan at significantly smaller scales to try to discern those regulator molecules. I don't have the expertise to estimate if this is likely.
To reiterate, I am not by any means a neuroscientist (my training is physics and my work is statistics), so its possible this sort of information just isn't that important, but my suspicion is that it is.
Edited to fix an embarrassing except/accept mistake.
(Scanning at significantly smaller scales should always be assumed to be fine as long as end states are distinguishable up to thermal noise!)
Okay, I agree that if this takes place at a temperature where molecules are still diffusing at a rapid pace and there's no molecular sign of the broken bond at the bonding site, then it sounds like info could be permanently destroyed in this way. Now why would you think this was likely with vitrification solutions currently used? Is there an intuition here about ranges of chemical interaction so wide that many interactions are likely to occur which break such bonds and at least one such interaction is likely to destroy functionally critical non-duplicated info? If so, should we toss out vitrification and go back to dropping the head in liquid nitrogen because shear damage from ice freezing will produce fewer many-to-one mappings than introducing a foreign chemical into the brain? I express some surprise because if destructive chemical interactions were that common with each new chemical introduced then the problem of having a whole cell not self-destruct should be computationally unsolvable for natural selection, unless the chemicals used in vitrification are unusually bad somehow.
This has some problems- fundamentally the length scale probed is inversely proportional to the energy required, which means increasing the resolution increases the damage done by scanning. You start getting into issues of 'how much of this can I scan before I've totally destroyed this?' which is a sort of percolation problem (how many amino acids can I randomly knock out of a protein before it collapses or rebonds into a different protein?), so scanning at resolutions with energy equivalent above peptide bonds is very problematic. Assuming peptide bond strength of a couple kj/mol, I get lower-limit length scales of a few microns (this is rough, and I'd appreciate if someone would double check).
The vitrification solutions currently used are know to be toxic, and are used at very high concentrations, so some of this sort of damage will occur. I don't know enough biochemistry to say anything else with any kind of definitety, but on the previous thread kalla724 seemed to have some domain specific knowledge and thought the problem would be severe.
No, not at all. The vitrification damage is orders of magnitude less. Destroying a few multi-unit proteins and removing some inhibitors seems much better than totally destroying the cell-membrane (which has many of the same "which sites were these guys attached to?" problems).
Its my (limited) understanding that the cell membrane exist to largely solve this problem. Also, introducing tiny bits of toxins here and there causes small amounts of damage but the cell could probably survive. Putting the cell in a toxic environment will inevitably kill it. The concentration matters. But here I'm stepping way outside anything I know about.
We seem to have very different assumptions here. I am assuming you can get up to the molecule and gently wave a tiny molecular probe in its direction, if required. I am not assuming that you are trying to use high-energy photons to photograph it.
You also still seem to be use a lot of functional-damage words like "destroying" which is why I don't trust your or kalla724's intuitions relative to the intuitions of other scientists with domain knowledge of neuroscience who use the language of information theory when assessing cryonic feasibility. If somebody is thinking in terms of functional damage (it doesn't restart when you reboot it, oh my gosh we changed the conformation look at that damage it can't play its functional role in the cell anymore!) then their intuitions don't bear very well on the real question of many-to-one mapping.
What does the vitrification solution actually do that's supposed to irreversibly map things, does anyone actually know? The fact that a cell can survive with a membrane, at all, considering the many different molecules inside it, imply that most molecules don't functionally damage most other molecules most of the time, never mind performing irreversible mappings on them. But then this is reasoning over molecules that may be of a different type then vitrificants. At the opposite extreme, I'd expect introducing hydrochloric acid into the brain to be quite destructive.
How are you imaging this works? I'm aware of chemistry that would allow you to say there are X whatever proteins, and Y such-and-such enzymes,etc, but such chemical processes I don't think are good enough for the sort of geometric reconstruction needed. Its not obvious to me that a molecular probe of the type you imagine can exist. What exactly is it measuring and how is it sensitive to it? Is it some sort of enzyme? Do we thaw the brain and then introduce these probes in solution? Do we somehow pulp the cell and run the constituents through a nanopore type thing and try to measure charge?
I would love to be convinced I am overly pessimistic, and pointing me in the direction of biochemists/neuroscientists/biophysicists who disagree with me would be welcome. I only know a few biophysicists and they are generally more pessimistic than I am.
I know ethylene glycol is cytotoxic, and so interacts with membrane proteins, but I don't know the mechanism.
I'll quickly point you at Drexler's Nanosystems and Freitas's Nanomedicine though they're rather long and technical reads. But we are visualizing molecularly specified machines, and 'hell no' to thawing first or pulping the cell. Seriously, this kind of background assumption is why I have to ask a lot of questions instead of just taking this sort of skeptical intuition at face value.
But rather than having to read through either of those sources, I would ask you to just take on assumption that two molecularly distinct (up to thermal noise) configurations will somehow be distinguishable by sufficiently advanced technology, and describe what your intuitions (and reasons) would be taking that premise at face value. It's not your job to be a physicist or to try to describe the theoretical limits of future technology, except of course that two systems physically identical up to thermal noise can be assumed to be technologically indistinguishable, and since thermal noise is much larger than exact quark positions it will not be possible to read off any subtle neural info by looking at exact quark positions (now that might be permanently impossible), etc. Aside from that I would encourage you to think in terms of doing cryptography to a vitrified brain rather than medicine. Don't ask whether ethylene glycol is toxic, ask whether it is a secure hard drive erasure mechanism that can obscure the contents of the brain from a powerful and intelligent adversary reading off the exact molecular positions in order to obtain tiny hints.
Checking over the open letter from scientists in support of cryonics to remember who has an explicitly neuroscience background, I am reminded that good old Anders Sandberg is wearing a doctorate in computational neuroscience from Stockholm, so I'll go ahead and name him.
Do you have a page number in Nanosystems for a references to a sensing probe? Also, this is tangential to the main discussion, so I'll take pointers to any reference you have and let this drop.
I was using cytotoxic in the very specific sense of "interacts and destabilizes the cell membrane," which is doing the sort of operations we agreed in principle can be irreversible. Estimates as to how important this sort of information actually is are impossible for me to make, as I lack the background. What I would love to see is someone with some domain specific knowledge explaining why this isn't an issue.
Sorry, but can you again expand on this? What happens?
Nanotechnology, not chemical analysis. Drexler's Engines of Creation contains a section on the feasibility of repairing molecular damage in this way. Since (if our current understanding holds) nanobots can be functional on a smaller scale than proteins (which are massive chunks held together Lego-style by van der Walls forces), they can be introduced within a cell membrane to probe, report on, and repair damaged proteins.
I have not read Engine's of Creation, but I have read his thesis and I was under the impression most of the proposed systems would only work in vacuum chambers as the would oxidize extremely rapidly in an environment like the body. Has someone worked around this problem, even in theory?
Also, I've seen molecular assembler designs of various types in various speculative papers, but I've never seen a sensing apparatus. Any references?
Later in the thread, Eliezer recommended Drexler's followup Nanosystems and Freitas' Nanomedicine, neither of which I've read, but I'd be surprised if the latter didn't address this issue. Sorry that I in particular don't think this is a worrisome objection, but it's on the same level as saying that electronics could never be helpful in the real world because water makes them malfunction. You start by showing that something works under ideal conditions, and then you find a way to waterproof it.
For the convenience of later readers: someone elsewhere in the thread linked an actual physical experimental example.
The end states don't need to be identical, just indistinguishable.
To presume that states non-identical up to thermal noise are indistinguishable seems to presume either lower technology than the sort of thing I have in mind, or that you know something I don't about how two physical states can be non-identical up to thermal noise and yet indistinguishable.