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ciphergothI'm considering signing up with the Cryonics Institute. Are you signed up? I'd be interested to hear your reasons why or why not. It does of course sound crazy, but when you press past that initial reaction to find out why it's crazy, I haven't heard a really satisfactory argument yet, and I'm interested to hear what people think. There are many reasons it might not work, but are there reasons to think it's really unlikely to work? How likely does recovery need to be for it to be worth it?
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Date: 2010-01-21 01:58 pm (UTC)On Electron Microscopy, for example:
"How much of the functionally relevant information can be deduced from scanning in a particular modality (e.g. electron microscopy)? At present, electron microscopy appears to be the only scanning method that has the right resolution to reach synaptic connectivity, but it is limited in what chemical state information it can reveal. If it is possible to deduce the function of a neuron, synapse or other structure through image interpretation methods, then scanning would be far simpler than if this is not (in which case some form of hybrid method or entirely new scanning modality would have to be developed). This issue appears to form a potentially well‐defined research question that could be pursued. Answering it would require finding a suitable model system for which ground truth (the computational functionality of target system) was known, using the scanning modality to produce imagery and then testing out various forms of interpretation on the data."
You may translate that as 'it's plausible to imagine that EM can do this simply'. I would translate it as: 'EM's the only technology that could give us the resolution, and there is absolutely no way it can reveal the chemical state, nor is there any way of preparing a sample of organic tissue for EM that won't damage the very state you're trying to record. Charge build-up will be a real issue on a sample you don't make conductive (even with TEM), and making it conductive without masking the underlying detail you're searching for is probably impossible. It might be possible to overcome one of these limitations in the future, but nobody has a clue how to.'
Also, they're asking whether it's possible to deduce the 'function' of a neuron - even if that were possible, it's an altogether harder prospect to deduce the state of the neuron at the time of death, even if you know the function.
I find it difficult to imagine that that passage was written by anyone at all familiar with how EM works - it smacks of someone who thinks it's basically like optical microscopy with a bigger lens - and furthermore, in the twenty years since I first did any hands-on SEM and TEM, we've moved no closer to making brain scans with it a practical proposition (as far as I can tell from reading around Wikipedia).
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Date: 2010-01-21 02:03 pm (UTC)no subject
Date: 2010-01-21 02:06 pm (UTC)I'll probably make a series of posts about this each trying to get to the bottom of one the most common objections. I really hope they can attract more comments like that!
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Date: 2010-01-21 02:12 pm (UTC)You might want to find someone who's done actual Electron Microscopy since 1994, to check that my understanding is correct. ;-)
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Date: 2010-01-21 02:39 pm (UTC)no subject
Date: 2010-01-21 03:33 pm (UTC)I find it a bit worrying that the most promising technologies in the table on page 43 - SOM and SEM, especially combined with array tomography - have relatively little discussion in the text that I can see. This makes me suspect that they're only even superficially attractive because not enough is known about them to know they don't work.
Also, given that the conclusion says 'this sets a resolution requirement on the order of 5 nm at least in two directions,' there's far too much discussion of technologies that can only scan down to resolutions two orders of magnitude higher than this. So the text gives the optimistic prediction that '[KESM] enables the imaging of an entire macroscopic tissue volume such as a mouse brain in reasonable time', but what good is that given that KSEM only scans down to 300nm x 500nm? It's an obvious question, and I'd expect an honestly-written paper to answer it. Because this paper doesn't, I smell a rat (or, more likely, someone clutching at straws).
The discussion starts 'As this review shows, WBE on the neuronal/synaptic level requires relatively modest increases in microscopy resolution...' which may be technically true but vastly understates the difficulty of increasing the resolution of the techniques discussed.
Again, though, I'll defer to someone who's done this stuff more recently than I have (and in a medical area - I was mostly looking at metal-matrix composites rather than anything organic).
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Date: 2010-01-23 07:43 am (UTC)no subject
Date: 2010-01-23 08:36 am (UTC)no subject
Date: 2010-02-11 08:00 pm (UTC)You seem to be still treating the PDF as a serious roadmap. I'd characterise it as a 'map of the swamp, with several of the circling alligators marked with an "X"', which I suppose is a roadmap of sorts, but not one that's going to show you the way home.
I'm not sure if you simply don't find my objections credible (fair enough, given the source; my blog reply is hardly a peer-reviewed paper) or whether you have a rebuttal of them.
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Date: 2010-02-12 09:23 am (UTC)no subject
Date: 2010-02-13 08:20 am (UTC)no subject
Date: 2010-02-20 02:42 pm (UTC)though I haven't pointed Sandberg to it yet.
Thanks again!