Thank you so much for explaining where you think we agree and disagree. I totally agree that finding disagreements is more interesting, even though we overall seem to agree on this topic more than the vast majority of people in the world.
I agree with all of your bullet points with the partial except of the 7-15 minute perfusion one. I don’t think there’s necessarily a physical change that occurs in the vasculature within that time window that absolutely prevents subsequent perfusion. To me it seems more complicated on both the higher and lower ends of the range. For example, my understanding is that animals have been revived after global cerebral ischemia for up to 30 minutes. I think it depends on the perfusion system used and there also seems to be a significant amount of currently unexplained biological variability. But this is a topic I’d like to learn more about and I don’t pretend to totally understand it, so I’m curious to hear more of your reasoning.
Regarding standards for brain preservation, I find the discussion very important but not yet settled. To use an analogy from clinical medicine, we are discussing the use of surrogate endpoints to predict whether or not someone can be revived in the future when technology has improved. Unfortunately, we don’t have any well validated endpoints for this outcome. Ken has proposed the criteria of connectome tracing by contemporary volume EM. However, this completely ignores the possibility of future molecular mapping to infer the original states in the case of morphological alterations. If this is possible, which I think it is, it changes everything. So I think we first have to determine more rigorously what the surrogate endpoints are that indicate information theoretic death. Basically, while I agree with you that one or multiple surrogate endpoints are urgently needed in the field, I just don’t agree with the current ones that have been proposed so far. So I think there is more basic science research needed to determine that, specifically regarding (a) how different types of structural information such as molecules and morphology correlate with one another in the preserved brain and (b) what types of structural information can be used to infer cognitive information (such as research related to the Aspirational Neuroscience Prize). More on this here: https://brainpreservation.github.io/Assessment#volume-electron-microscopy
Thank you so much for explaining where you think we agree and disagree. I totally agree that finding disagreements is more interesting, even though we overall seem to agree on this topic more than the vast majority of people in the world.
I agree with all of your bullet points with the partial except of the 7-15 minute perfusion one. I don’t think there’s necessarily a physical change that occurs in the vasculature within that time window that absolutely prevents subsequent perfusion. To me it seems more complicated on both the higher and lower ends of the range. For example, my understanding is that animals have been revived after global cerebral ischemia for up to 30 minutes. I think it depends on the perfusion system used and there also seems to be a significant amount of currently unexplained biological variability. But this is a topic I’d like to learn more about and I don’t pretend to totally understand it, so I’m curious to hear more of your reasoning.
Regarding standards for brain preservation, I find the discussion very important but not yet settled. To use an analogy from clinical medicine, we are discussing the use of surrogate endpoints to predict whether or not someone can be revived in the future when technology has improved. Unfortunately, we don’t have any well validated endpoints for this outcome. Ken has proposed the criteria of connectome tracing by contemporary volume EM. However, this completely ignores the possibility of future molecular mapping to infer the original states in the case of morphological alterations. If this is possible, which I think it is, it changes everything. So I think we first have to determine more rigorously what the surrogate endpoints are that indicate information theoretic death. Basically, while I agree with you that one or multiple surrogate endpoints are urgently needed in the field, I just don’t agree with the current ones that have been proposed so far. So I think there is more basic science research needed to determine that, specifically regarding (a) how different types of structural information such as molecules and morphology correlate with one another in the preserved brain and (b) what types of structural information can be used to infer cognitive information (such as research related to the Aspirational Neuroscience Prize). More on this here: https://brainpreservation.github.io/Assessment#volume-electron-microscopy