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CanaryActive5296 t1_is16gfz wrote

Hello! Not an expert in freezing and thawing live specimen but well practiced in freezing and thawing dead specimen while keeping organs and microstructures intact. The major concern with freezing biological matter is the formation of ice crystals. Water forms crystals and expands when frozen and can result in burst cells and organelles. To avoid this, we introduce cryoprotectants. These are basically antifreeze that diffuse into the cells and around it to avoid formation of crystals. It's very easy to diffuse these new compounds into microscopic specimen because the surface area to volume ratio is very high compared to humans. Very rapid freezing with liquid nitrogen, also known as flash freezing, also helps in avoiding formation of large crystals (slow freezing means more time for the molecules to align). So the simple answer is size. We can't introduce cryoprotectants into every part of a human being fast enough nor can we flash freeze a human body fast enough.

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Fogl3 t1_is181bj wrote

Are these cryoprotectants dangerous? Like if we found a way to put them all inside us could we freeze ourselves? Do we just need like a wolverine needle bath?

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CanaryActive5296 t1_is1amk1 wrote

There are multiple types cryoprotectants and while they are generally supposed to be non-toxic it is only to a certain extent of concentration and exposure time. Extended exposure will interfere with daily bodily functions and metabolism. So unfortunately impossible to walk around with it indefinitely. The wolverine question is interesting because some animals have evolved to have cryoprotectants for living in the arctic or surviving winters! I don't know of any mammal that can do it but I know of at least 1 frog and 1 fish species. Info may not be updated but last I checked both are being studied to study how to preserve human organs!

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regular_modern_girl t1_is2rpvn wrote

The only vertebrates I know of that can survive freezing completely solid are ectotherms, and I’ve also never heard of any bird or mammal species being able to withstand it, so it might just be that organisms that have evolved to operate with a constant core temperature aren’t able to survive the extreme cold leading up to freezing, even besides the problem of ice crystals damaging cells? But I don’t know, that’s mostly just a guess and it may just be coincidental that no endotherms have evolved this ability.

Interestingly, there has been some evidence to suggest that critically-injured trauma patients can sometimes be kept just barely alive long enough to be saved by being cooled down to very low temperatures in a controlled setting, as I guess this basically slows down a lot of physiological processes in such a way that essentially buys doctors time to do what they need to. The procedure is called EPR, or Emergency Preservation and Resuscitation, and is still experimental, and it’s obviously still a far cry from complete freezing, but it is something.

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sbeezee t1_is6fyaw wrote

There is some evidence that spruce at Arctic treeline increase simple sugars in needle tissue in late fall as a cryoprotectant. Do you know of any other species that use simple sugars (glucose, fructose, sucrose) as cryoprotectant?

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austinmiles t1_is1ble2 wrote

At some point we could use some sort of gene therapy to introduce cryoprotectants from some single cell organisms which would be awesome

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UrbanCoyotee t1_is1mtvl wrote

I just watched a Tom Scott YT video about how microwaves were used in the 50s to reanimate frozen rats. Long story short, they were successful in reanimated fully frozen rats using microwaves...in the 1950s.

To somewhat answer your question though, it had to do with scale. They scientists who reanimated the rats found that it did not work on scale simply in laymans due to size.

He promised it was an interesting video and he delivered...

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chitzk0i t1_is2qk1w wrote

I read an article about this research. They tried to move up to slightly larger animals like rabbits, but their results because inconsistent. Small critters like mice and hamsters worked fine, though.

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regular_modern_girl t1_is2q7ew wrote

This is mostly the same thing with other cryptobiotic states as well, like in organisms that can survive complete desiccation. Often the key chemical preservative there is actually a sugar called trehalose iirc, which at sufficiently high concentrations helps to keep cellular structures intact even in the near-complete absence of moisture, such that the inner processes of the cells are basically “frozen in time” when they dry out, and therefore able to spring back to life once they’re rehydrated.

Again, this only really works with small organisms below a certain level of anatomical complexity, and I’m sure there are certain cell or tissue types that just don’t respond well to this kind of preservation, but apparently it’s part of what allows tardigrades to enter their famously nigh-indestructible “tun” state, and is also found as an adaptation in some desert-dwelling insects, and the eggs of a number of aquatic creatures that have evolved to weather extended periods of desiccation (sometimes very extended; brine shrimp eggs from literally thousands of years ago dug up in the Bonneville Salt Flats of Utah have been found to still be viable).

Even though there are several reasons it probably would never be suitable for allowing an entire human to be basically mummified and then brought back to life, trehalose has seen a lot of use as a preservative for blood or tissue samples, making it so they can be completely dried out and then reconstituted as needed (like apparently dried blood samples preserved with trehalose will even retain the distinctive vivid red of fresh oxygenated blood, rather than the dull rusty brown we usually associate with old, heavily-oxidized, dried blood).

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Nyrin t1_is1jnee wrote

Speed and perfusion. Big problems both during freezing and thawing:

For freezing, water is the enemy. It expands and forms crystals as it freezes, which together rupture cell membranes and effectively ravage tissues. If you just drop someone into a cryonic vat as-is, the brick of icy cellular mush you get will be far too damaged to ever be viable again. If you're familiar with freezer-burned meat, imagine that happening to everything in your body, including your heart and brain. Not pretty.

The workaround for that is antifreeze. Yes, seriously. Get all the water out of a person that you can and replace it with something that won't crystallize and thaws early enough to allow replacement during resuscitation. But that's where speed and perfusion are nightmares: every minute you're waiting to freeze someone while you replace water is a minute that tissues are dying from anoxia. This is the worst with the brain: it dies really, really fast without oxygen and yet the blood-brain barrier makes it one of the hardest places to achieve non-water perfusion with.

That said, there have been advancements with this where cooling the body to just about freezing to slow neuronal cellular death combined with better antifreezes and techniques might get us close to reaching "frozen" with something that's still viable. A rabbit brain was successfully frozen and thawed using some of these -- though, notably, not yet in a rabbit: https://www.newscientist.com/article/2077140-mammal-brain-frozen-and-thawed-out-perfectly-for-first-time/

So we might be kinda-sorta close to getting cryonically frozen humans that are damaged lightly enough bring back. Very doubtful anyone frozen today is, but we might be there within a few decades.

Thawing is even harder, though. Even in the best-case scenario, you have a bunch of critically oxygen-starved tissue frozen; every second of anoxia counts once things unfreeze, and the brain in particular really needs to go from frozen to "warm and oxygen-perfused" very, very quickly. Human brains are really dense and, as mentioned, really hard to permeate -- we don't currently have much of any clue about how we'd warm a brain out of cryonic suspension enough to restore blood and oxygen without having orders of magnitude more anoxic duration than those brains can take. Exotic ideas abound about blood replacements that can achieve oxygen transport while still perfusing a very cold brain, but it's all total conjecture at this point.

And that aside, the dance when you restart everything else in the body is hard, too. You need to swap all of the liquid in the entirety of very complex human vasculature -- including at least most of what exists intercellular media and the like -- and restore circulation with oxygen very, very quickly and very, very consistently. Simplifying a bit, but if you hand reaches 1C while your arm is still -2C, you're going to have a bunch of things in your hand die while your arm is waiting.

We don't have any real line of sight on how to achieve this super-fast, super-consistent, super-precise reoxygenation of a big, complex organism with all of the systemic coordination that's necessary. There's nothing to say it shouldn't be achievable someday, but let's just say we have no reason to believe it'll come sooner than commercial fusion.

But why are embryos OK? Because they're small and easy to perfuse! You can get all of the damaging water out of embryonic structures and flash freeze it way before the lighter anoxic time constraints kick in, and it's not (comparatively) hard to warm and reoxygenate them quickly and consistently enough to have them in a good, healthy state years and years later. Smaller organisms -- especially ones that evolved resilient structures -- can already be revived that way, too: tardigrades and other similar animals have been thawed after tens of thousands of years: https://www.smithsonianmag.com/smart-news/scientists-revive-tiny-animals-spent-24000-years-ice-180977928/

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Nimynn OP t1_is1qc81 wrote

Thank you! Very thorough explanation.

I knew about the ice crystals but didn't know why that wouldn't apply to embryos. The antifreeze solution and related issues are exactly the answer I was looking for.

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EvoStarSC t1_is26bir wrote

The way you explained this is incredibly terrifying and fascinating at the same time.

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cruuzie t1_is27h2q wrote

So how small is small enough to reliably survive freezing with our current methods? Are we talking a few lumped together cells, ant-sized, mouse-sized?

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Nyrin t1_is2a3qt wrote

It's a continuum with bigger, denser, and otherwise harder to consistently rewarm and perfuse ramping the difficulty up, likely on a non-linear scale.

We may well see cryonically frozen lab rats fully resuscitated in the coming years (likely still with lots of complications at first), but we should contain our optimism given there's probably at least at much of a gap between cycling an embryo or tardigrade and cycling a rat as there will be between cycling a rat and cycling a human. We have notoriously hungry brains!

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Pastywhitebitch t1_is7athe wrote

This was magnificent! What is your background that this is just pocket information? Any opinions on the ethics of humans being frozen?

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ThyOtherMe t1_is176m9 wrote

Size. Mostly.

One of the problems of freezing and adult is that you can not "flash freeze/unfreeze" it. The speed of the process (and medium used) matters because the cells are suffering from lack of oxygen. The slower And the water content inside the process, the bigger the damage. And there is also the water crystals that form during freezing. Thet damage the cells too (by rupturing structures) and one of the ways to prevent it is to freeze the cells super fast, forming less/smaller crystals. Unfreezing may be a problem too, since the temperature needed to heat your core organs fast enough would burn out your skin, muscles and outer layers.

An embryo is a really smal cluster of cells. You can diffuse heat a lot faster since there are less to freeze An adult is a really big cluster of cells.

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facetious_guardian t1_is1dtuj wrote

Also on the size topic: I don’t think an adult human is small enough to be used for IVF.

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[deleted] t1_is1n3yr wrote

[deleted]

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urzu_seven t1_is31oi2 wrote

Wait there is fiction where an adult human is used for IVF? What weird fiction is that?!?

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Altyrmadiken t1_isv6ox3 wrote

What would that even look like? The other persons post is missing.

Like… an adult injected into a body to… grow? Be born (again)?

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oyvinol t1_is2dhv1 wrote

Can you recommend any reading on this subject? I find it a bit interesting. Something introductory or a pop sci book maybe?

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ThyOtherMe t1_is2ppwt wrote

Tom Scott has a video about it (kinda of ) and has some links in it. Ask a mortician has videos on cryonics here and was also interesting.

I'm one of those "got a life gathering facts and topics at random and connecting dots on the fly" and not someone that does science for a living. I know you asked for books, but I can't remember (or link) anything right now.

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SwordTaster t1_is2vdt9 wrote

Put simply, because an embryo is very very small so it's easy to freeze it quickly. Freezing quickly is vital in living things we wish to keep living because ice that forms slowly creates big crystals that tear apart cells. Defrosting cells that have been torn apart by ice gets you something very dead. Try it with a cucumber in the freezer, you'll get a very floppy cucumber. Small enough things can be flash frozen and be fine because small things can have every part frozen quickly enough that no cells get damaged in the process. Adult humans though are very big, flash freezing a person would at best get you a pretty decent skin suit but all the internal organs would be mushy like the frozen cucumber.

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seanbrockest t1_is1mna5 wrote

There's some interesting history about freezing and thawing live animals, and some of it is detailed in this video. They specifically describe why the same technique would never work in something as large as a human

https://youtu.be/2tdiKTSdE9Y

Yes, that's the right video. It involves microwaving animals who have been frozen.

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PerpetuallyLurking t1_is3pjsk wrote

Simplicity. An embryo is more simple-celled than the whole baby. It’s much, much easier to successfully freeze a zygote that’s only split into a couple pairs of cells (an embryo) than the millions of cells that a baby consists of (never mind the millions more a grown adult has compared to a baby).

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marouane53 t1_is3u6mm wrote

Embryos can be frozen because they are in a state of arrested development. This means that they are not actively growing or developing, so their metabolism is very low. This makes it possible to put them into a state of suspended animation, where they can be stored for long periods of time without damage.

Adult humans cannot be frozen because they are constantly growing and developing. This means that their metabolism is very high, and they would not be able to survive the process of being frozen.

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Larry_Phischman t1_isaucaw wrote

Embryos are more durable and do not have differentiated tissues. They’re just clumps of stem cells. Adult humans have differentiated body tissues.

Another reason is that embryos are very small and will freeze so fast that the water in their undifferentiated cells does not have time to crystallize.

Adult humans have too much thermal mass, and will have ice crystals form everywhere. That destroys the cells and tissues.

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