I don’t think any intelligence can read information that is no longer there. So, no, I don’t think it will help.
kalla724
Karma: 1,257
In order, and briefly:
In Milwaukee protocol, you are giving people ketamine and some benzo to silence brain activity. Ketamine inhibits NMDA channels—which means that presynaptic neurons can still fire, but the signal won’t be fully received. Benzos make GABA receptors more sensitive to GABA—so they don’t do anything unless GABAergic neurons are still firing normally.
In essence, this tunes down excitatory signals, while tuning up the inhibitory signals. It doesn’t actually stop either, and it certainly doesn’t interfere with the signalling processes within the cell.
You are mixing three different processes here. First is cooling down. Cooling down is not the same as freezing. There are examples of people who went into deep hypothermia, and were revived even after not breathing for tens of minutes, with little to no brain damage. If the plan was to cool down human brains and then bring them back within a few hours (or maybe even days), I would put that into “possible” category.
Second is freezing. Some human neurons could survive freezing, if properly cultured. Many C. elegans neurons do not survive very deep freezing. It depends on the type of neuron and its processes. Many of your ganglionic neurons might survive freezing. Large spiny neurons, or spindle cells? Completely different story.
The third is freezing plus cryoprotectants. You need cryoprotectants, otherwise you destroy most cells, and especially most fine structures. But then you get membrane distortions and solvent replacement, and everything I’ve been talking about in other posts.
We are deep into guessing territory here, but I would think that coarser option (magnesium, phosphorylation states, other modifications, and presence and binding status of other cofactors, especially GTPases) would be sufficient. Certainly for a simulated upload.
No, I don’t work with Ed. I don’t use optogenetics in my work, although I plan to in not too distant future.
All of it! Coma is not a state where temporal resolution is lost!
You can silence or deactivate neurons in thousands of ways, by altering one or more signaling pathways within the cells, or by blocking a certain channel. The signaling slows down, but it doesn’t stop. Stop it, and you kill the cell within a few minutes; and even if you restart things, signaling no longer works the way it did before.
I don’t believe so. Distortion of the membranes and replacement of solvent irretrievably destroys information that I believe to be essential to the structure of the mind. I don’t think that would ever be readable into anything but a pale copy of the original person, no matter what kind of technological advance occurs (information simply isn’t there to be read, regardless of how advanced the reader may be).
This was supposed to be a quick side-comment. I have now promised to eventually write a longer text on the subject, and I will do so—after the current “bundle” of texts I’m writing is finished. Be patient—it may be a year or so. I am not prepared to discuss it at the level approaching a scientific paper; not yet.
Keep in mind two things. I am in favor of life extension, and I do not want to discourage cryonic research (we never know what’s possible, and research should go on).
Perhaps a better definition would help: I’m thinking about active zones within a synapse. You may have one “synapse” which has two or more active zones of differing sizes (the classic model, Drosophila NMJ, has many active zones within a synapse). The unit of integration (the unit you need to understand) is not always the synapse, but is often the active zone itself.
In general, uploading a C. elegans, i.e. creating an abstract artificial worm? Entirely doable. Will probably be done in not-too-distant future.
Uploading a particular C. elegans, so that the simulation reflects learning and experiences of that particular animal? Orders of magnitude more difficult. Might be possible, if we have really good technology and are looking at the living animal.
Uploading a frozen C. elegans, using current technology? Again, you might be able to create an abstract worm, with all the instinctive behaviors, and maybe a few particularly strong learned ones. But any fine detail is irretrievably lost. You lose the specific “personality” of the specific worm you are trying to upload.
Local ion channel density (i.e. active zones), plus the modification status of all those ion channels, plus the signalling status of all the presynaptic and postsynaptic modifiers (including NO and endocannabinoids).
You see, knowing the strength of all synapses for a particular neuron won’t tell you how that neuron will react to inputs. You also need temporal resolution: when a signal hits the synapse #3489, what will be the exact state of that synapse? The state determines how and when the signal will be passed on. And when the potential from that input goes down the dendritic tree and passes by the synapse #9871, which is receiving an input at that precise moment—well, how is it going to affect synapse #9871, and what is the state of synaps #9871 at that precise moment?
Depending on the answer to this question, stimulation of #3498 followed very soon after with stimulation of #9871 might produce an action potential—or it might not. And this is still oversimplifying things, but I hope you get the general idea.
I agree with you on both points. And also about the error bars—I don’t think I can “prove” cryonics to be pointless.
But one has to make decisions based on something. I would rather build a school in Africa than have my body frozen (even though, to reiterate, I’m all for living longer, and I do not believe that death has inherent value).
Biggest obstacles are membrane distortions, solvent replacement and signalling event interruptions. Mind is not so much written into the structure of the brain as into the structure+dynamic activity. In a sense, in order to reconstruct the mind within a frozen brain, you would have to already know what that mind looks like when it’s active. Then you need molecular tools which appear impossible from the fundamental principles of physics (uncertainty principle, molecular noise, molecular drift...).
My view of cryonics is that it is akin to mercuric antibiotics of the late 19th century. Didn’t really work, but they were the only game in town. So perhaps with further research, new generation of mercuric substances will be developed which will solve all the problems, right? In reality, a much better solution was discovered. I believe this is also the case with life extension—cryonics will fade away, and we’ll move in with a combination of stem cell treatments, technologies to eliminate certain accumulated toxins (primarily insoluble protein aggregates and lipid peroxidation byproducts), and methods to eliminate or constrain cellular senescence (I’m actually willing to bet ~$5 that these are going to be the first treatments to hit the market).
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.
Whether “working memory” is memory at all, or whether it is a process of attentional control as applied to normal long-term memory… we don’t know for sure. So in that sense, you are totally right.
But what is the exact nature of the process is, perhaps strangely, unimportant. The question is whether the process can be enhanced, and I would say that the answer is very likely to be yes.
Also, keep in mind that working memory enhancement scenario is just one I pulled from thin air as an example. The larger point is that we are rapidly gaining the ability to non-invasively monitor activities of single neuronal cells (with fluorescent markers, for instance), and we are, more importantly, gaining the ability to control them (with finely tuned and targeted optogenetics). Thus, reading and writing into the brain is no longer an impossible hurdle, requiring nanoimplants or teeny-tiny electrodes (with requisite wiring). All you need are optical fibers and existing optogenetic tools (in theory, at least).
To generalize the point even further: we have the tools and the know-how with which we could start manipulating and enhancing existing neural networks (including those in human brains). It would be bad, inefficient and with a great deal of side-effects, we don’t really understand the underlying architecture enough to really know what we are doing—but could still theoretically begin today, if for some reason we decided to (and lost our ethics along the way). On the other hand, we don’t have a clue how to build an AGI. Regardless of any ethical or eschatonic concerns, we simply couldn’t do it even if we wanted to. My personal estimate is, therefore, that we will make it to the first goal far sooner than we make it to the second one.
It would appear that all of us have very similar amounts of working memory space. It gets very complicated very fast, and there are some aspects that vary a lot. But in general, its capacity appears to be the bottleneck of fluid intelligence (and a lot of crystallized intelligence might be, in fact, learned adaptations for getting around this bottleneck).
How superior would it be? There are some strong indication that adding more “chunks” to the working space would be somewhat akin to adding more qubits to a quantum computer: if having four “chunks” (one of the most popular estimates for an average young adult) gives you 2^4 units of fluid intelligence, adding one more would increase your intelligence to 2^5 units. The implications seem clear.
Um...there is quite a bit of information. For instance, one major hurdle was ice crystal formation, which has been overcome—but at the price of toxicity (currently unspecified, but—in my moderately informed guesstimate—likely to be related to protein misfolding and membrane distortion).
We also have quite a bit of knowledge of synaptic structure and physiology. I can make a pretty good guess at some of the problems. There are likely many others (many more problems that I cannot predict), but the ones I can are pretty daunting.
Ok, now we are squeezing a comment way too far. Let me give you a fuller view: I am a neuroscientist, and I specialize in the biochemistry/biophysics of the synapse (and interactions with ER and mitochondria there). I also work on membranes and the effect on lipid composition in the opposing leaflets for all the organelles involved.
Looking at what happens during cryonics, I do not see any physically possible way this damage could ever be repaired. Reading the structure and “downloading it” is impossible, since many aspects of synaptic strength and connectivity are irretrievably lost as soon as the synaptic membrane gets distorted. You can’t simply replace unfolded proteins, since their relative position and concentration (and modification, and current status in several different signalling pathways) determines what happens to the signals that go through that synapse; you would have to replace them manually, which is a) impossible to do without destroying surrounding membrane, and b) would take thousands of years at best, even if you assume maximally efficient robots doing it (during which period molecular drift would undo the previous work).
Etc, etc. I can’t even begin to cover complications I see as soon as I look at what’s happening here. I’m all for life extension, I just don’t think cryonics is a viable way to accomplish it.
Instead of writing a series of posts in which I explain this in detail, I asked a quick side question, wondering whether there is some research into this I’m unaware of.
Does this clarify things a bit?
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Let me add to your description of the “Loci method” (also the basis of ancient Ars Memoria). You are using spatial memory (which is probably the evolutionarily oldest/most optimized) to piggyback the data you want to memorize.
There is an easier way for people who don’t do that well in visualization. Divide a sheet of paper into areas, then write down notes on what you are trying to remember. Make areas somewhat irregular, and connect them with lines, squiggles, or other unique markers. When you write them, and when you look them over, make note of their relative position—formula A is in the left top corner, while formula Z is down and to the right of it, just beyond the spiral squiggle.
For a lot of people, this works just as well as Ars Memoria, and is a lot easier to learn and execute on the fly.
I can try, but the issue is too complex for comments. A series of posts would be required to do it justice, so mind the relative shallowness of what follows.
I’ll focus on one thing. An artificial intelligence enhancement which adds more “spaces” to the working memory would create a human being capable of thinking far beyond any unenhanced human. This is not just a quantitative jump: we aren’t talking someone who thinks along the same lines, just faster. We are talking about a qualitative change, making connections that are literally impossible to make for anyone else.
(This is even more unclear than I thought it would be. So a tangent to, hopefully, clarify. You can hold, say, seven items in your mind while considering any subject. This vastly limits your ability to consider any complex system. In order to do so at all, you have to construct “composite items” out of many smaller items. For instance, you can think of a mathematical formula, matrix, or an operation as one “item,” which takes one space, and therefore allows you to cram “more math” into a thought than you would be able to otherwise. Alternate example: a novice chess player has to look at every piece, think about likely moves of every one, likely responses, etc. She becomes overwhelmed very quickly. An expert chess player quickly focuses on learned series of moves, known gambits and visible openings, which allows her to see several steps ahead.
One of the major failures in modern society is the illusion of understanding in complex systems. Any analysis picks out a small number of items we can keep in mind at one time, and then bases the “solutions” on them (Watts’s “Everything is Obvious” book has a great overview of this). Add more places to the working memory, and you suddenly have humans who have a qualitatively improved ability to understand complex systems. Maybe still not fully, but far better than anyone else. Sociology, psychology, neuroscience, economics… A human being with a few dozen working memory spaces would be for economy the same thing a quantum computer with eight qubits would be for cryptography—whoever develops one first, can take wreak havoc as they like.)
When this work starts in earnest (ten to twelve years from now would be my estimate), how do we control the outcomes? Will we have tightly controlled superhumans, surrounded and limited by safety mechanisms? Or will we try to find “humans we trust” to become first enhanced humans? Will we have a panic against such developments (which would then force further work to be done in secret, probably associated with military uses)?
Negative scenarios are manifold (lunatic superhumans destroying the world, or establishing tyranny; lobotomized/drugged superhumans used as weapons of war or for crowd manipulation; completely sane superhumans destroying civilization due to their still present and unmodified irrational biases; etc.). Positive scenarios are comparable to Friendly AI (unlimited scientific development, cooperation on a completely new scale, reorganization of human life and society...).
How do we avoid the negative scenarios, and increase the probability of the positive ones? Very few people seem to be talking about this (some because it still seems crazy to the average person, some explicitly because they worry about the panic/push into secrecy response).
? No.
I fully admitted that I have only an off-the-cuff estimation (i.e. something I’m not very certain about).
Then I asked you if you have something better—some estimate based in reality?
Good point. I’m trying to cast a wide net, to see whether there are highly transferable skills that I haven’t considered before. There are no plans (yet), this is simply a kind of musing that may (or may not) become a basis for thinking about plans later on.
All good reason to keep working on it.
The questions you ask are very complex. The short answers (and then I’m really leaving the question at that point until a longer article is ready):
Rehydration involves pulling off the stabilizer molecules (glycerol, trehalose) and replacing them dynamically with water. This can induce folding changes, some of which are irreversible. This is not theoretical: many biochemists have to deal with this in their daily work.
Membrane distortions also distort relative position of proteins within that membrane (and the structure of synaptic scaffold, a complex protein structure that underlies the synaptic membrane). Regenerating the membrane and returning it to the original shape and position doesn’t necessarily return membrane-bound molecules to their original position.