Even better cryonics – because who needs nanites anyway?

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).