# How do you circulate cryoprotectants through the human body?

Context if you're interested

In the very near future, a planet teeming with alien life is discovered several light years away from our Solar System - and with a few precautions, it may be habitable to human life. Individual species have not been identified, but there are clear signs of biochemical reactions in the atmosphere, water is abundant, and the planet's vibrant colors are best explained by metabolism - rather than natural chemical occurrances. Additionally, this planet is old - complex life is likely, although no signs of intelligent life have been identified. The scientific community, knowing it will take decades if not centuries to send a mission, decides to skip the preemptive unmanned missions. Scientists collect all the information they needs to establish a colony, and plan to send a cryogenically frozen crew A S A P.

The main problem with freezing living things is that the cold tends to damage tissue. Ice crystals form between cells, dehydrating and shrinking them, and preventing intercellular connections; if you just froze these astronauts, you'd be left with a metal can of dead bodies.

Luckily, we know of cryoprotectants - substances developed by some living things that allow the cooling of tissue while stopping ice from forming. Many of these substances may even allow a human to survive frozen for hundreds of years - glucose, glycerol, sucrose, sodium phosphates, or polyols, for instance, would not kill a human being, and could theoretically keep them frozen for extended periods of time.

In nature, creatures that use these substances either have high contents in and around their cells, or they have systems in place to circulate the substances if it gets cold.

Humans don't have specialized transport systems in place - so how would you circulate an unspecified cryoprotectant through a human body to preserve its tissue for an extended period of time? And how would you address fluid-filled organs that your system does not address?

Note: There is no time limit. Fast would be appreciated, but if diet over time, for instance, is required to up cryoprotectant contents, then it will be accepted
Note II: The substance, as long as it is non-toxic, does not need to be removable

• There are 4 steps: (1) have subject or the legal guardian sign the agreement letter (2) ice bath + antibloodclog drug + oxygen tank (3) replace blood with antifreeze (4) pump liquid nitrogen into ice bath and seal it. – user6760 Nov 23 '16 at 8:33

Current methods

There is currently a method to preserve people who suffer cardiac arrest, called EPR-CAT, where one rapidly cools down the body to give the doctors more time to work before the patients suffer incurable damage due to lack of oxygen. While EPR-CAT currently does not freeze the patients, they are only cooled down to 10°C (50°F), they have shown that the lower the temperature is, the higher chance of survival the patient has.

Experiments on dogs have shown that it is possible to replace the blood with ice cold saline solution as the body does seems to allow for complete lack of oxygen in the blood stream as long as it gets cooled down. The problem, however, is how to rapidly replace the blood with saline solution.

The EPR-CAT technique is currently highly experimental, but show very high promise to increase survival and might, therefore, be the start for proper cryogenics, especially if freeze protection agents are used in the saline solution.

One concern raised in the question is how to deal with organs where the blood does not fully penetrate, such as eyes, and the answer would be plunge freezing. Extremely rapid cooling prevents crystal formation and forces the water to form amorphous ice, which will not damage delicate structures. The alternative, if plunge freezing is deemed to not work well on humans, would be to have very slow freezing with seeded ice formation to allow for more control of which ice structures that forms. Which method that is best will depend on which has the highest chance of success, although plunge freezing would be beneficial as it would allow for a rapid process.

So the way to cryogenically preserve a person would thus be:
1. Fully sedate the person (you will not want to be conscious when you get frozen).
2. Replace the blood with a cold saline solution with some cryoprotectant agents. This step needs to be quite rapid, so one would probably have to punch holes in either the femorial artery and vein, or the vertebral ones. The solution should be as cold as possible to help cool the body.
3. Plunge the patient into a vat of liquid ethane, propane or some science fiction-y solution with very cold properties. Liquid nitrogen does not work due to the Leidenfrost effect, the body would not freeze fast enough and ice crystals would form.
4. Figure out a way how to unfreeze the patients safely.
5. Realize that step 4. probably should have been considered before step 1.
Thawing

This is a bit of a tricky issue. As Faulkner pointed out in their answer, we have not yet revived a preserved person. So the short answer is "we have no clue how to safely thaw someone". However, we might learn something from nature seeing that there are ample of animals which gets frozen each ear and then safely thaws. I found a decent overview text written by a researcher on animal adaption for cold environments and will use that as a reference in this bit.

While the preferred method to freeze would be as fast as possible, an animal frozen as means to survive winter will thaw quite slowly as spring arrives. The key issue for those animals is that the freezing process will suck out a lot of the water from vital organs so that the ice formation is around them rather than in them; this requires slow freezing and also slow thawing to allow the water to migrate through membranes. The liquids left inside the vital organs will be a highly concentrated slurry of anti-freeze agents which prevents the organs from freezing entirely. Plunge freezing would go the other way around and cause amorphous ice to form throughout the body and might, therefore, allow for a more rapid thawing as no water need to migrate.

Body functions of someone frozen will be shut down; a frozen person will be technically dead while frozen since the heart will be stopped and no brain activity will take place. We currently do not know exactly how this function in frozen animals, but the signal to stop the organs is probably linked to the temperature of the body or ice formation in some vital region or similarly. This also means that we have no clue what it is that restarts the organs once the animal is thawed. However, for space traveling humans, this should not be an issue. As long as we can thaw the person without causing (too much) damage to the cells, then we can always use heart starters and modern technology to ensure that the body functions awakens properly.

The text I use as reference for this bit also states that animals which survive winter by getting frozen also have enhanced cell repair activated when they are thawed. If we manage to enhance our knowledge in stem-cell technology or just find other ways of how to stimulate and regulate how our bodies self-heal, then we should be able to make something akin to stim-pack drugs which would repair any damage induced by the freezing and thawing.

Soooo.... how to safely do the thawing?
1. Slowly increase the temperature in the cryo-pod.
2. Once the body is warm enough to allow the solution with anti-freeze in the circulatory system to move easily, then start replacing it with oxygenated (synthetic) blood.
3. Continue to slowly increase temperature and time the restart of organs to when the body reaches suitable temperatures. The restart will probably be aided with heart starter and similar medical devices.
4. If available, inject stimulants to improve cell repair
5. The eyes will likely hurt if they have not been exposed to light for a long time. Administration of sunglasses or keeping the light dimmed for a while in the ship is advised.
6. Administer either two Diazepam or a generous glass of whisky to the recently thawed person to help them cope with any mental and physical pain that the process likely causes.
Movie visuals

For a cryo-pod in a movie, I guess that the people would walk (Not naked! Thin clothes ought to be best*) in to a cocoon-like chamber and a device would close around their necks. This device would then first sedate them, then replace their blood with the anti-freeze and then the chamber would be showing gas streaming in as it would be tricky to fill the chamber fast enough with a liquid. However, the gas would have lower heat conductivity than a liquid and would not work properly for real freezing. If you're writing a book (or want to make a bit more shocking scene in the movie), the floor would rapidly be pulled down into a vat underneath the chamber and the chamber would be cooled down while the person freezes in the liquid. After a certain set-time, the floor would rise again with the person and s/he would be kept in the pod for the travel. Unfreezing would then simply be to slowly increase the temperature in the pod while the neck device pumps back the (probably synthetic) blood into the person. The final touch would be a heart starter that would extend and kick start the heart before the pod opens.

Final remark

I would never, ever volunteer as the first person to try the method. Especially not after having practical experience of cryo-microscopy and knowing how often the sample preparation fails due to improper freezing. But, with some time and trials, this would probably be close to how it'll be done.

Edit

*I originally stated that one ought to be naked in the cryopod as I thought that the clothes would help vapor film formation and prevent rapid freezing. However, once I actually thought it through, I realized I was wrong and that a thin cloth layer might actually help the freezing.

By adding a layer of thin cloth, the film formation from the Leidenfrost effect is actually prevented as the cloth retains the liquid better than naked skin. The cloth should be very tight fitting to prevent a vapor film from forming under the clothes (if it does form, then naked is better) and should have good thermal conductive properties. That is, tight, thin spandex (preferably with some science fiction-y materials incorporated) would work best.

I do not have any links for this claim, it's taken from the basic safety course I've had when working with liquid nitrogen. Most safety courses only states that "you have to wear a lot of clothes", although those with experience have taught me that "if the clothes are not thick and/or loose, then no clothes is safer".

• Why does methane etc. not have the same effect as nitrogen when touching a hot surface? – JDługosz Dec 14 '16 at 8:09
• The last link duplicates the destination of the previous; I think you meant something else. – JDługosz Dec 14 '16 at 8:11
• @JDługosz It has to do with the difference in boiling point, the higher Tboil for the hydrocarbons prevents the film boiling around the object from occurring and keeps the process at normal boiling. A lack of film around the object means that there will be better heat transfer as liquids transfer heat better than gasses. The last link was intentional as I thought clothes would help film formation, but I changed my mind once I had my morning coffee and realized that I was wrong; thanks for pointing it out. – Mrkvička Dec 14 '16 at 10:08
• They might wear a cloth that absorbs the liquid and thus keeps it close to the skin, instead. – JDługosz Dec 14 '16 at 11:23
• @JDługosz Yes, that is correct and I added that info to the edit I made. Essentially any cloth works as long as it's kept close and thin enough to not provide insulation, but skin tight spandex works better from a movie perspective. – Mrkvička Dec 14 '16 at 13:25

CRYOGENICS AND CRYONICS ARE DIFFERENT

This is something that I learned very recently. Cryogenics is a branch of physics that studies the production and effects of very low temperatures, while cryonics is the practice of using very low temperatures to try to preserve a human being. Not the same thing

Currently cryonics is a method that many people use in order to try to preserve their body after they're pronounced legally dead, in hopes that there will be some sort of future technology that can resuscitate and/or rejuvenate them. It does not involve freezing.

In cryonics, first the body is cooled slowly in order to slow the metabolism, and prevent further tissue damage. (During this time CPS or cardiopulmonary support is used to keep the blood flowing through the patient. This may not be necessary for your travelers since they are not legally dead and their blood can pump itself).

Next the patient is vitrified. This is where an amorphous solid called a cryoprotectant solution (which does not crystallize) is pumped through the entire body and replaces all of the patient's blood. The current method is to perform surgery through the chest and connect the major arteries to tubes that pump the solution through the body. Then the temperature is slowly decreased to -124ºC or the glass-transition temperature. "This is when the body’s liquid stays amorphous but rises so high in viscosity that no molecule can budge." Now the body has been vitrified and no decay or cellular activity can happen.

Open chest surgery may not be a reasonably option for your travelers, but maybe instead of opening them up, you could inject long needles through their chest and inject the serum and remove the blood simultaneously that way.

Vitrification has never been reversed on a human, because the only people who have ever been successfully vitrified are legally dead. However, scientists have successfully vitrified organs (like a rabbit kidney and brain), and rewarmed them to find that they still work. It is possible that your travelers could be slowly rewarmed and refilled with blood, and be brought back safely. I don't imagine that it would be very comfortable and you would probably want some sort of sedative or anesthesia involved but it is plausible.

• To the extent of my knowledge cooling to -126 C involves freezing. Still helpful, +1 – Zxyrra Dec 14 '16 at 20:29
• You say pumped through the entire body but the question specifically asks how to do the pumping; I already have most of the information you provide but I need a mechanism. – Zxyrra Dec 14 '16 at 20:30
• @Zxyrra -124 C would involve freezing if the fluid was water. The cryoprotectant has a lower freezing point. – Faulkner Dec 14 '16 at 20:40
• The way they do it now is by cutting a big hole in the patient's chest and pumping the fluid through an artery. I'm not sure if any of your travelers would be willing to undergo this sort of invasive procedure though. Maybe if there was a way to just stick a long needle into an artery by the heart? – Faulkner Dec 14 '16 at 20:42
• That information ^ seems more relevant to the question than a comment; perhaps it should be edited in and expanded upon. – Zxyrra Dec 14 '16 at 21:29

Circulating in the blood is easy: just inject it. Delivering stuff to all the cells is what blood is for.

The hard part is getting it taken up inside the cells.

The protectant can be disguised, in a molecular way, as a substance that all cells normally take into themselves. Once inside the cell, the molecule unwraps and leaves the target molecule inside the cell.

Note that the blood-brain barrier is particularly critical. Large molecules don’t get across without being specifically escorted, so unknown material won’t just diffuse into cells in the brain by simply being there. Using the disguise (or other way to trick the body into letting it cross) is essential or you’ll end up not protecting the organ you need the most!

So, exploiting natural trqnsport channels is essential.

For all the efforts of “team freezerburn”, the post-humans travelling as software in solid-state devices will get there first. Even if that technology develops slower, their ship will be tiny and thus faster.

• The bottom paragraph is actually one of my plot points - new colonists will not necessarily arrive as software but they will discover this ship after FTL travel is invented – Zxyrra Dec 11 '16 at 15:04
• Could you address how this substance will reach eyes, water-filled organs, etc - parts that either aren't completely full of cells or parts that don't have blood access, but that will still expand? – Zxyrra Dec 11 '16 at 15:07
• I think any fluid-filled part of the body has some mechanism regulating what exactly gets put in that fluid, so it’s not just the same as blood. – JDługosz Dec 11 '16 at 15:13
• I would love specifics as to where these substances should be put. Blood is easy but the where for those some mechanisms is part of the question too. – Zxyrra Dec 11 '16 at 15:15
• You ought to update the question to make that clear. Right now it reads «in and around cells». So why wouldn’t a large chamber be just fine, simply by reducing the volume first, since it won’t burst or cut up cells when freezing? – JDługosz Dec 11 '16 at 15:22

Injecting into the bloodstream might be a valid option. Something along the lines of an insulin pump could even automatically maintain a given concentration.

• My concern with this is that the eyes would still freeze. – Zxyrra Nov 23 '16 at 4:51
• Ooops, forgot about that. Eye-drops or wait until the stuff diffuses from blood in the retina to the liquid inside the eye and then to the cells? Pumping the stuff into the eye directly sounds... disturbing. – Matej Lieskovsky Nov 23 '16 at 5:02
• Given that people are given intraocular injections all the time, it doesn't seem so far fetched to have fluid syringed in and out to do this. Doesn't mean it couldn't be biocompatible with eye function if it was at the correct density/refractive index. – DrDanielSwan Nov 23 '16 at 12:39
• Just adding it to the blood wouldn’t get it inside all the cells. – JDługosz Dec 12 '16 at 3:01

i think it could be injected directly into the veins, or it could be dispensed as an aerosol: the cryoprotectants (treated in some way) would attach to the blood cells like oxygen does.

• Look up how red blood cells carry oxygen. O₂ is a small molecule and you really couldn’t attach a large complex molecule in the same place. – JDługosz Dec 12 '16 at 3:00

If you can get past the protesters genetic alteration shouldn't be too far a stretch. Either altering the human cells to mimic creatures that naturally produce cryoprotectants, or a harmless viral/bacterial transport system that attaches them to a cell.

Expanding on @Faulkner's wonderful answer: You send a ship that is half generational ship and half cold storage.

You freeze your new colonists, with all the training and skills they need to do their work, but you have a support crew of medical professionals, mechanics, and everything else you need to keep them alive and the ship heading to its destination. This crew will be generational, and will likely never leave the ship again (extended zero-G is a bitch). This gives your mission some robustness, as failures of a ship system doesn't mean death for everyone, it means Billie in maintenance gets to do some real work.

It also means you have a vessel ready to support the colony (since it will have to have good medical facilities and means of growing food) and it can even transport specimens back to earth much quicker than the new colony could build a return vessel. It could even be your first merchant vessel between the planets, and could continuously ferry goods and people between them.

Heck, you could even set up a slingshot maneuver and just have it constantly orbit the new system's star and Sol, and never have to actually slow down. Mount a few ion engines on that sucker and eventually it'll get up to a pretty good clip.

• This is interesting but it does not address the problem posed by the question of how to cycle cryoprotectants; consider a unique approach to that problem in addition to this information. – Zxyrra Dec 14 '16 at 22:07
• @Faulkner's answer is good in that regard, but it becomes far easier to implement if you don't have to automate the reanimation process and can, for example, reanimate a couple months away from the planet to give people time to heal from open chest surgery. – Marshall Tigerus Dec 15 '16 at 14:33