Some things I have in mind if it gets big include: subsidizing cryonics dues for low-income people, covering funding shortfalls for those unable to obtain life insurance, cryonics scholarships to support the development of expertise in neural cryobiology and other areas, and hiring a public relations team to fix the image of cryonics.
My own preference would be to donate to the Brain Preservation prize. Apparently no one has ever actually looked at imaging of how well cryonics procedures preserve brain cells, and the prize is a step towards really evidence-based cryonics. (If Bitcoin gains another order of magnitude or two, it would be even more valuable to see if you could fund a simple experiment like vitrifying & reviving some C. elegans or something to see if they retain learned memories like maze-running.)
Agreed, emphatically, that we need more funding to go for empirical validation of cryonics premises and procedures. However, Aschwin de Wolf has pointed out one reason it is difficult to compare vitrified brains to fixed-embedded, namely dehydration. So I’m somewhat suspicious of the usefulness of the prize at this point in time.
A specific concern for Brain Preservation Technology Prize competitors using cryopreservation is that cryopreserved brains are currently very dehydrated. Due to this dehydration, which typically persists even after cryoprotectant removal, it is not yet clear that cryopreserved brains can be effectively evaluated by the Prize organizers. To be specific, the criterion for success is preservation of the connectome, which requires two things: preservation of synapses and preservation of enough information to infer the pattern of connections between them. Neural cryobiology researchers believe that they can achieve good ultrastructural preservation of the brain but dehydration compactifies the neuropil, reduces space between structures, and makes the tissue so dark in the electron microscope that it is hard to actually observe the synapses. So if a quick scanning method doesn’t discern all synapses that are actually there, it will fail. There are techniques for doing electron microscopy at cryogenic temperatures in the vitrified state, but these depend on the tissue being sliced before vitrification. Making slices out of a whole vitrified brain while vitrified is a tough problem. It is easier to make thin slices out of a whole brain that’s been turned into solid plastic because the resin used is designed for being cut into thin slices for microscopy. So plastination has a natural advantage in this competition — in terms of processing for the tests rather than in actual results.
A non-dehydrated brain is not only more likely to survive by information-theoretic criteria, and to e.g. benefit from ice-blockers, it is easier to scan for evidence of survival. So a high priority should be to achieve reduction in dehydration. An earlier discussion with Mike Darwin had me thinking it was a problem with myelination, but currently I am given to understand (per Aschwin de Wolf and Greg Fahy) that it is primarily a matter of the blood-brain barrier. Aschwin also mentioned that there should be evidence in the literature of what ideas to try next, since this is a problem in conventional drug delivery. Yuri Pichigu has developed an approach to opening the BBB, however 21CM found that it did not increase viability in rabbit brain slices. I’m not sure whether that failure is limited to viability or also extends to the morphological characteristics we are interested in here.
Anyway, dehydration and the blood-brain barrier is high in the search order for the next thing to solve. Without it, vitrification is a bit of a shot in the dark. We can speculate that dehydration is okay as long as it is relatively uniform, but it may not be (and of course isn’t, in more poorly perfused patients).
That’s good too, but I think directly measuring the quality of cryonics as it is currently being practiced and people are being cryopreserved right now is more important than speeding up some work that will get done sooner or later.
That’s interesting, but what is their model of a cell like? I assume it’s not simulating protein synthesis, for example. There’s an awful lot of complexity in even a single-celled organism such as an amoeba that’s probably getting swept under the rug here...
Can memory be retained after cryopreservation? Our research has attempted to answer this long-standing question by using the nematode worm Caenorhabditis elegans (C. elegans), a well-known model organism for biological research that has generated revolutionary findings but has not been tested for memory retention after cryopreservation. Our study’s goal was to test C. elegans’ memory recall after vitrification and reviving. Using a method of sensory imprinting in the young C. elegans we established that learning acquired through olfactory cues shapes the animal’s behavior and the learning is retained at the adult stage after vitrification. Our research method included olfactory imprinting with the chemical benzaldehyde (C6H5CHO) for phase-sense olfactory imprinting at the L1 stage, the fast cooling SafeSpeed method for vitrification at the L2 stage, reviving, and a chemotaxis assay for testing memory retention of learning at the adult stage. Our results in testing memory retention after cryopreservation show that the mechanisms that regulate the odorant imprinting (a form of long-term memory) in C. elegans have not been modified by the process of vitrification or by slow freezing.
My own preference would be to donate to the Brain Preservation prize. Apparently no one has ever actually looked at imaging of how well cryonics procedures preserve brain cells, and the prize is a step towards really evidence-based cryonics. (If Bitcoin gains another order of magnitude or two, it would be even more valuable to see if you could fund a simple experiment like vitrifying & reviving some C. elegans or something to see if they retain learned memories like maze-running.)
Agreed, emphatically, that we need more funding to go for empirical validation of cryonics premises and procedures. However, Aschwin de Wolf has pointed out one reason it is difficult to compare vitrified brains to fixed-embedded, namely dehydration. So I’m somewhat suspicious of the usefulness of the prize at this point in time.
A non-dehydrated brain is not only more likely to survive by information-theoretic criteria, and to e.g. benefit from ice-blockers, it is easier to scan for evidence of survival. So a high priority should be to achieve reduction in dehydration. An earlier discussion with Mike Darwin had me thinking it was a problem with myelination, but currently I am given to understand (per Aschwin de Wolf and Greg Fahy) that it is primarily a matter of the blood-brain barrier. Aschwin also mentioned that there should be evidence in the literature of what ideas to try next, since this is a problem in conventional drug delivery. Yuri Pichigu has developed an approach to opening the BBB, however 21CM found that it did not increase viability in rabbit brain slices. I’m not sure whether that failure is limited to viability or also extends to the morphological characteristics we are interested in here.
Anyway, dehydration and the blood-brain barrier is high in the search order for the next thing to solve. Without it, vitrification is a bit of a shot in the dark. We can speculate that dehydration is okay as long as it is relatively uniform, but it may not be (and of course isn’t, in more poorly perfused patients).
OpenWorm could use some money too: http://www.openworm.org/donate.html
That’s good too, but I think directly measuring the quality of cryonics as it is currently being practiced and people are being cryopreserved right now is more important than speeding up some work that will get done sooner or later.
Agreed. Although BPF has been really quiet for months now, and I’d recommend them more strongly if they posted about their current status.
That’s interesting, but what is their model of a cell like? I assume it’s not simulating protein synthesis, for example. There’s an awful lot of complexity in even a single-celled organism such as an amoeba that’s probably getting swept under the rug here...
And it’s done! “Persistence of Long-Term Memory in Vitrified and Revived C. elegans”, Vita-More & Barranco 2015:
Following up on this: I contacted someone at BPF, and they say they have some initial images they will be posting soon.
Great. Some actual funded work will, even if useless, help BPF’s credibility.