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CasioTheSane 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: 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).

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