Comment author: Romashka 08 April 2015 09:37:01AM 3 points [-]

Which is why, I think, it's better to start from sea mammals and not shrimp; imagine if, for some reason, tiny ice crystals damage blood vessels - not even due to bloodflow - and upon thawing all those clotting factors are immediately, chaotically released. It can even happen in the brain.

Comment author: maxikov 08 April 2015 08:14:38PM 2 points [-]

I'm sure I'm following why mammals should be less susceptible to this problem, can you elaborate?

Doing this with mammals has a lot of challenges though, which it'd make sense to bypass in initial experiments. The deepest dive (aside from humans in DSVs) is only 3km, which accounts for 30 MPa. I guess it's safe to say that no mammal can withstand 350 MPa with air or any gas in its lungs, so total liquid ventilation is required, which is just as challenging to do with sea mammals as with land mammals. Also, mammals are warm-blooded, and usually experience asystole at abnormally low body temperatures, which are nonetheless far above freezing. So there's the issue of making it survive the time it takes to go form cardiac arrest to freezing, which is also probably just as hard to do with sea mammals as with land mammals. So although the ultimate goal is to develop a protocol for humans, it'd the much easier to start with an animal that's already capable of surviving 100 MPa of ambient pressure and +4C of its own body temperature.

Comment author: passive_fist 08 April 2015 03:15:54AM 11 points [-]

This is definitely an interesting idea but there may be a lot of unforeseen problems. At pressures as high as 350 MPa, chemical reactions that are energetically unfavorable under normal pressure suddenly become favorable (this is why, among other things, air becomes toxic). I have no idea how this would mess with the various chemical processes that go on in the body, but my guess is that unwanted reactions could lead to development of fatal toxins. Also, just as such high pressures cause phase changes in ice, they could cause phase changes in plenty of other molecules.

I'm sure someone who is more knowledgeable on this could weigh in, but googling around a bit revealed some studies on subjecting human cells to high pressure. This study subjected human amnion cells to 70 MPa and found significant changes in cell activity involving blebbing (this is when the cell membrane disassociates from the cytoskeleton), although they did point out that the effects of pressure were reversible, which is promising.

Comment author: maxikov 08 April 2015 07:58:54PM 7 points [-]

Hmm, I wonder what the exact biochemistry that prevents life forms (including, apparently, vertebrate fish) in Challenger Deep at 111 MPa from experiencing these problems is, and whether it can be replicated in mammals.

They also mentioned that blebbing first appears at 90-120 seconds, but that's way too short even for the fastest protocols possible. Theoretically, it's not unthinkable to cool the body to just above 0C, and then go straight to 632 MPa and above, to make it instantly freeze, before blebbing occurs. And then, if total liquid ventilation allows one to drop the pressure that quickly as well, just go from solid directly to a non-dangerous pressure range. But for any protocol that involves temperature changes under pressure, tens of seconds is positively too short to allow the temperature to stabilize.

As for toxicity though, I though it was entirely due to the increased partial pressure of oxygen (which thus creates too strong of an oxidizing environment) and having too many nitrogen atoms dissolved in tissues, physically messing with fine-grain biochemistry like ion channels. Is there another chemical component of toxicity beyond that?

Comment author: TrE 08 April 2015 08:35:52AM *  8 points [-]

Materials science undergraduate student here (not a mechanical engineer, my knowledge is limited in the area, I did not go to great lengths to ensure I'm right here, etc.).

A typical method to generate high pressures in research are diamond anvils. This is suitable for exploring the behavior of cells and microorganisms under high pressure.

For human preservation, however, you'd need a pressure vessel. As the yield strength of your typical steel is on the order of 100, maybe 300 MPa, you're really up against a wall here, materials-wise. I don't doubt that suitable alloys for human-sized pressure vessels at 350 MPa exist, however, such vessels will be expensive, and controlling processes within will be difficult. In any case, generating such pressures will probably not involve a moving piston.

I can't really tell whether or not the procedure you've outlined is viable, but I'm quite sure it's far from trivial, just from an engineering point of view.

The concerns of user passive_fist are also valid.

Comment author: maxikov 08 April 2015 06:47:39PM *  3 points [-]

That's an interesting observation! When I was looking into this, I found several suppliers[1][2][3][4] that claim to produce pressure vessels, tubing, and pumps all the way up to 150'000 psi (1GPa). If 300MPa are already pushing the boundaries of steel, do you know what they could use to achieve such pressures?

Comment author: gjm 07 April 2015 11:41:12PM 3 points [-]

Is "natines" in the title meant to be "nanites"?

Comment author: maxikov 08 April 2015 12:14:50AM 2 points [-]

Yep, fixed that, thanks.

Comment author: Joshua_Blaine 07 April 2015 10:08:00PM *  18 points [-]

First off, I love that you're actively pursuing alternative methods of human preservation. That's awesome, and I hope you manage to find some useful ideas in your search. However, I fear that this approach in particular doesn't really solve the problem that cryoprotectants successfully do (toxicity briefly aside).

without cryoprotectants the water will expand upon freezing, and break the cells.

This line in particular is my biggest point of contention. I am by no means an expert in this field, and my understanding may be moot in this context, but the expansion of water-ice crystals isn't the central concern for frozen biological cells. A quickly found source claims that:

Since ice is essentially pure H2O, ice formation can increase the concentration of minerals in the remaining cytosol to a toxic level. The increased mineral concentration in the cytosol will cause water to be drawn in from the surrounding cells by osmosis, which can cause the cell to swell and burst.

Alcor's official FAQ also says that:

When tissue is slowly cooled, ice first forms between cells. The growing ice crystals increase the concentration of solutes in the remaining liquid around them, causing osmotic dehydration of cells.

Your method doesn't prevent the formation of ice crystals, it merely changes the structure of the crystals, and at what temperature they form, so I suspect harmful cell osmosis can still occur. Of course, I could be insufficiently understanding why ice crystals effect the mineral concentration of cytosol, or the order in which certain biological areas freeze under variable conditions, and your smaller ice/lower freezing temperature would successfully prevent this issue. I don't believe this is necessarily the case, given your explanation, but if anyone who's more studied in these fields could speak up, I'd be happy to defer to their expertise.

Comment author: maxikov 07 April 2015 10:59:03PM *  10 points [-]

It seems like the approach of cooling the organism to -30C at 350MPa, and then raising pressure further to ~600Mps to freeze it could actually solve that. As far as I understand, the speed of diffusion in water it far slower that the speed of sound (speed of sound at 25C is 1497 m/s, while diffusion coefficient for protons at 25C is 9.31e-5 cm^2/s, which corresponds to 1.4e-4 m/s - 8 orders of magnitude less), which is the speed of pressure gradient propagation. So if we use raising pressure as a way to initiate phase transition, it will occur nearly simultaneously everywhere, and the solutes won't have time to diffuse anywhere.

ETA: I just realized that since diffusion propagates according to inverse square law, while sound is linear, they should be compared to each other at the shortest distance possible. So I checked the time it takes for a proton to cover 0.1nm (hydrogen atom diameter) in water - 5.37e-13s, which gives us 186 m/s. It's far greater than the original number, but still an order of magnitude smaller than the speed of sound. And if we take 4nm (the thickness of a cell membrane) we have 8.59e-10s - only 4 m/s, so it decreases very quickly, and we're pretty much safe.

Even better cryonics – because who needs nanites anyway?

49 maxikov 07 April 2015 08:10PM

Abstract: in this post I propose a protocol for cryonic preservation (with the central idea of using high pressure to prevent water from expanding rather than highly toxic cryoprotectants), which I think has a chance of being non-destructive enough for us to be able to preserve and then resuscitate an organism with modern technologies. In addition, I propose a simplified experimental protocol for a shrimp (or other small model organism (building a large pressure chamber is hard) capable of surviving in very deep and cold waters; shrimp is a nice trade-off between the depth of habitat and the ease of obtaining them on market), which is simple enough to be doable in a small lab or well-equipped garage setting.

Are there obvious problems with this, and how can they be addressed?

Is there a chance to pitch this experiment to a proper academic institution, or garage it is?

Originally posted here.


I do think that the odds of ever developing advanced nanomachines and/or brain scanning on molecular level plus algorithms for reversing information distortion - everything you need to undo the damage from conventional cryonic preservation and even to some extent that of brain death, according to its modern definition, if wasn't too late when the brain was preserved - for currently existing cryonics to be a bet worth taking. This is dead serious, and it's an actionable item.

Less of an action item: what if the future generations actually build quantum Bayesian superintelligence, close enough in its capabilities to Solomonoff induction, at which point even a mummified brain or the one preserved in formalin would be enough evidence to restore its original state? Or what if they invent read-only time travel, and make backups of everyone's mind right before they died (at which point it becomes indistinguishable from the belief in afterlife existing right now)? Even without time travel, they can just use a Universe-sized supercomputer to simulate every singe human physically possible, and naturally of of them is gonna be you. But aside from the obvious identity issues (and screw the timeless identity), that relies on unknown unknowns with uncomputable probabilities, and I'd like to have as few leaps of faith and quantum suicides in my life as possible.

So although vitrification right after diagnosed brain death relies on far smaller assumptions, and if totally worth doing - let me reiterate that: go sign up for cryonics - it'd be much better if we had preservation protocols so non-destructive that we could actually freeze a living human, and then bring them back alive. If nothing else, that would hugely increase the public outreach, grant the patient (rather than cadaver) status to the preserved, along with the human rights, get it recognized as a medical procedure covered by insurance or single payer, allow doctors to initiate the preservation of a dying patient before the brain death (again: I think everything short of information-theoretic death should potentially be reversible, but why take chances?), allow suffering patient opt for preservation rather than euthanasia (actually, I think it should be done right now: why on earth would anyone allow a person to do something that's guaranteed to kill them, but not allowed to do something that maybe will kill, or maybe will give the cure?), or even allow patients suffering from degrading brain conditions (e.g. Alzheimer's) to opt for preservation before their memory and personality are permanently destroyed.

Let's fix cryonics! First of all, why can't we do it on living organisms? Because of heparin poisoning - every cryoprotectant efficient enough to prevent the formation of ice crystals is a strong enough poison to kill the organism (leave alone that we can't even saturate the whole body with it - current technologies only allow to do it for the brain alone). But without cryoprotectants the water will expand upon freezing, and break the cells. But there's another way to prevent this. Under pressure above 350 MPa water slightly shrinks upon freezing rather than expanding:

Phase_diagram_of_water.svg

So that's basically that: the key idea is to freeze (and keep) everything under pressure. Now, there are some tricks to that too.

It's not easy to put basically any animal, especially a mammal, under 350 MPa (which is 3.5x higher than in Mariana Trench). At this point even Trimix becomes toxic. Basically the only remaining solution is total liquid ventilation, which has one problem: it has never been applied successfully to a human. There's one fix to that I see: as far as I can tell, no one has ever attempted to do perform it under high pressure, and the attempts were basically failing because of the insufficient solubility of oxygen and carbon dioxide in perfluorocarbons. Well then, let's increase the pressure! Namely, go to 3 MPa on Trimix, which is doable, and only then switch to TLV, whose efficiency is improved by the higher gas solubility under high pressure. But there's another solution too. If you just connect a cardiopulmonary bypass (10 hours should be enough for the whole procedure), you don't need the surrounding liquid to even be breathable - it can just be saline. CPB also solves the problem of surviving the period after the cardiac arrest (which will occur at around 30 centigrade) but before the freezing happens - you can just keep the blood circulating and delivering oxygen.

Speaking of hypoxia, even with the CPB it's still a problem. You positively don't want the blood to circulate when freezing starts, lest it act like an abrasive water cutter. It's not that much of a problem under near-freezing temperatures, but still. Fortunately, this effect can be mitigated by administering insulin first (yay, it's the first proper academic citation in this post! Also yay, I thought about this before I even discovered that it's actually true). This makes sense: if oxygen is primarily used to metabolize glucose, less glucose means less oxygen consumed, and less damage done by hypoxia. Then there's another thing: on the phase diagram you can see that before going into the area of high temperature ice at 632 MPa, freezing temperature actually dips down to roughly -30 centigrade at 209~350 MPa. That would allow to really shut down metabolism for good when water is still liquid, and blood can be pumped by the CPB. From this point we have two ways. First, we can do the normal thing, and start freezing very slowly, so minimize the formation of ice crystals (even though they're smaller than the original water volume, they may still be sharp). Second, we can increase the pressure. That would lead to near-instantaneous freezing everywhere, thus completely eliminating the problem of hypoxia - before the freezing, blood still circulated, and freezing is very quick - way faster than can ever be achieved even by throwing a body into liquid helium under normal pressure. Video evidence suggests that quick freezing of water leads to the formation of a huge number of crystals, which is bad, but I don't know near-instantaneous freezing from supercooled state and near-instantaneous freezing upon raising the pressure will lead to the same effect. More experiments are needed, preferably not on humans.

So here is my preservation protocol:

  1. Anesthetize a probably terminally ill, but still conscious person.
  2. Connect them to a cardiopulmonary bypass.
  3. Replacing their blood with perfluorohexane is not necessary, since we seem to be already doing a decent job at having medium-term (several days) cardiopulmonary bypasses, but that could still help.
  4. Submerge them in perfluorohexane, making sure that no air bubbles are left.
  5. Slowly raise the ambient pressure to 350 MPa (~3.5kBar) without stopping the bypass.
  6. Apply a huge dose of insulin to reduce all their metabolic processes.
  7. Slowly cool them to -30 centigrade (at which point, given such pressure, water is still liquid), while increasing the dose of insulin, and raising the oxygen supply to the barely subtoxic level.
  8. Slowly raise the pressure to 1 GPa (~10kBar), at which point the water solidifies, but does so with shrinking rather than expanding. Don't cutoff the blood circulation until the moment when ice crystals starts forming in the blood/perfluorohexane flow.
  9. Slowly lower the temperature to -173 centigrade or lower, as you wish.

 

And then back:

  1. Raise the temperature to -20 centigrade.
  2. Slowly lower the pressure to 350 MPa, at which point ice melts.
  3. Start artificial blood circulation with a barely subtoxic oxygen level.
  4. Slowly raise the temperature to +4 centigrade.
  5. Slowly lower the pressure to 1 Bar.
  6. Drain the ambient perfluorohexane and replace it with pure oxygen. Attach and start a medical ventilator.
  7. Slowly raise the temperature to +32 centigrade.
  8. Apply a huge dose of epinephrine and sugar, while transfusing the actual blood (preferably autotransfusion), to restart the heart.
  9. Rejoice.

 

I claim that this protocol allows you freeze a living human to an arbitrarily low temperature, and then bring them back alive without brain damage, thus being the first true victory over death.

But let's start with something easy and small, like a shrimp. They already live in water, so there's no need to figure out the protocol for putting them into liquid. And they're already adapted to live under high pressure (no swim bladders or other cavities). And they're already adapted to live in cold water, so they should be expected to survive further cooling.

Small ones can be about 1 inch big, so let's be safe and use a 5cm-wide cylinder. To form ice III we need about 350MPa, which gives us 350e6 * 3.14 * 0.025^2 / 9.8 = 70 tons or roughly 690kN of force. Applying it directly or with a lever is unreasonable, since 70 tons of bending force is a lot even for steel, given the 5cm target. Block and tackle system is probably a good solution - actually, two of them, on each side of a beam used for compression, so we have 345 kN per system. And it looks like you can buy 40~50 ton manual hoists from alibaba, though I have no idea about their quality.

cryoshrimp

I'm not sure to which extent Pascal's law applies to solids, but if it does, the whole setup can be vastly optimized by creating a bottle neck for the pistol. One problem is that we can no longer assume that water in completely incompressible - it had to be compressed to about 87% its original volume - but aside from that, 350MPa per a millimeter thick rod is just 28kg. To compress a 0.05m by 0.1m cylinder to 87% its original volume we need to pump extra 1e-4 m^3 of water there, which amounts to 148 meters of movement, which isn't terribly good. 1cm thick rod, on the other hand, would require almost 3 tons of force, but will move only 1.5 meters. Or the problem of applying the constant pressure can be solved by enclosing the water in a plastic bag, and filling the rest of chamber with a liquid with a lower freezing point, but the same density. Thus, it is guaranteed that all the time it takes the water to freeze, it is under uniform external pressure, and then it just had nowhere to go.

Alternatively, one can just buy a 90'000 psi pump and 100'000 psi tubes and vessels, but let's face it: it they don't even list the price on their website, you probably don't even wanna know it. And since no institutions that can afford this thing seem to be interested in cryonics research, we'll have to stick to makeshift solutions (until at least the shrimp thing works, which would probably give in a publication in Nature, and enough academic recognition for proper research to start).

Comment author: ChristianKl 18 February 2015 01:35:41PM *  3 points [-]

Giving our physical laws I don't see how "observing without interfering" is non-magical. There seems to be a lot of assumption you make about the term non-magical that aren't well founded.

Comment author: maxikov 18 February 2015 11:53:18PM 0 points [-]

If you only observe by absorbing particles, but not emitting them, you can be far enough away so that the light cone of your observation only intersects with the Earth later than the original departure point. That would only change the past of presumably uninhabited areas of space-time.

Comment author: maxikov 18 February 2015 07:55:56AM 2 points [-]

So where exactly do I go for that? Googling "freeze your cells" gives me the information about technical details of that, rather than a company that provides such service, or completely irrelevant weight loss surgery information.

Comment author: maxikov 18 February 2015 07:20:39AM 0 points [-]

What is the probability of having afterlife in a non-magical universe?

Aside from the simulation hypothesis (which is essentially another form of a magical universe), there is at leas one possibility for afterlife to exist: human ancestors travel back in time (or discover a way to get information from the past without passing anything back) to mind-upload everyone right before they die. There would be astrong incentive for them to not manifest themselves, as well as tolerate all the preventable suffering around the world: if changing the past leads to killing everyone in the original timeline, the price for altering the past is astronomical. Thus, they would have to only observe (with the reading of brain states as a form of observation) the past, but not change it, which is consistent with the observation of no signs of either time travelers or afterlife. But if will happen in future, it means it's already happening right now. How do you even approach estimating the probability of that?

Comment author: Lumifer 05 February 2015 04:42:24PM 1 point [-]

The question is too general. If you find yourself in front of a microwave antenna dish, yes, you should be very much concerned about RF radiation X-D and there's not much doubt about that.

The cell-phones-cause-brain-cancer scare was successfully debunked, wasn't it?

Comment author: maxikov 05 February 2015 07:12:15PM 2 points [-]

If the effect of RF doesn't go beyond thermal, then you probably shouldn't be concerned about sitting next to an antenna dish any more than about sitting next to light bulb of the equal power. At the same time, even if the effect is purely thermal, it may be different from the light bulb since RF penetrates deeper in tissues, and the organism may or may not react differently to the heat that comes from inside rather than from outside. Or it may not matter - I don't know.

And apparently, there is a noticeable body of research, in which I can poke some holes, but which at least adheres to basic standards of peer-reviewed journals, that suggests the existence of non-thermal effects, and links to various medical conditions. However, my background in medicine and biology is not enough to thoroughly evaluate this research, beyond noticing that there are some apparent problems with that, but it doesn't appear to be obviously false either.

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