What would be the hardest aspect of repair for potential biological revival?

[AndyMcKenzie]

I have been having a lot of discussions with people about the potential for biological revival via molecular nanotechnology in recent weeks.

One topic that has come up over and over again is that some people expect that specimens preserved with fixatives will be much more difficult to "repair" than those preserved without.

I wanted to make my position very clear as to why I disagree with this. To me, it depends on what aspect of "repair" you think would be the hardest aspect of a potential revival procedure:

#1: If you think it is the fact that information might be lost during the preservation process, requiring much more inference, and it might not even be possible at all to infer the original state to perform the necessary repairs, then it's best to choose the method that will better preserve the most molecular architecture information today. And the evidence clearly shows that fixation is the best validated method.

#2: If you think that the molecular manipulation itself will be the hardest part -- i.e. that reversing crosslinks or reconstructing from a fixed state would require significantly more advanced nanotechnology than repairing damage from pure cryopreservation alone -- then you might prefer to avoid fixation.

I personally think that #1 is by far the more concerning problem, because I expect that if revival ever becomes possible, our technology will be substantially advanced regardless.

I also think that the difference between adding fixation or not doesn't really affect the need for repair much anyways. In a pure cryopreservation case without fixatives, there would most likely be areas with ice damage, and there would certainly be other forms of molecular damage, such as molecular aggregation due to cryoprotectants or molecular alterations due to ischemia. I just don't see how those could be fixed without full strength molecular nanotechnology -- i.e., nanotechnology capable of arbitrary molecular rearrangements. So full strength molecular nanotechnology would be required in either case.

My belief is that the information loss from ice damage and osmotic dehydration in protocols that do not use fixatives is likely to be far greater, and therefore more difficult to repair, than the crosslinks, which have a well understood, local mechanism that locks molecules in place instead of causing large, stochastic disruptions of morphomolecular structure. Future repair systems would have detailed models of crosslinking mechanisms to work backward from.

I wanted to document this argument so that I can reference it in future discussions. And also so that others could have a place to disagree with me in case they do.