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Cryopreservation procedure (ASC)

Posted: Wed Apr 28, 2021 4:26 am
by Cool_Kiwi
What is the cryopreservation process like nowadays? I've read Robert Mcintyre's paper "Aldehyde-stabilized cryopreservation" and Ken Hayworth's articles on the Brain Preservation Foundation and found it very interesting. Is the procedure at Oregon Cryonics similar to the one in the research paper? I.e. washing out blood, perfusing fixative, and then cryoprotectant.

From the paper it says that fixation needs to be done quickly after death otherwise the perfusion doesn't work as well
"banks normally receive donated brains many hours after death, which we assume will make them difficult to adequately perfuse"
I guess the reason why Ken Hayworth wants euthanasia to be built in, but is probably way too controversial to be accepted.

Also from the it paper it says that "sodium dodecyl sulfate" prevents osmotic shrinkage from occurring, which is apparently quite important and why the 'cryoprotectant only procedure' from 21CM didn't win the brain prize? Is this chemical also used in Oregon Cryonics's fixation procedure?

It seems like Alcor and CI are pretty hesitant on adopting ASC which is a damn shame. They seem pretty stuck on the idea of "biological reversibility" instead of actually preserving the connectome. I think Oregon Cryonics really is the only hope for cryonics unless Robert's Nectome company works out.

Re: Cryopreservation procedure (ASC)

Posted: Thu Apr 29, 2021 4:30 pm
by jordansparks
First of all, just so we're clear, Oregon Cryonics doesn't have an actual process. We instead have a planned process. One scientific paper does not define exactly what our process might look like, but it does point us in the right direction. Once the building is done, we will begin the hard work of developing a reliable and effective protocol. I already did all the hard work to develop the surgical access protocol. The second and final stage is to determine exactly what chemicals will be used and how they will be reliably pumped.
The ASC paper used ethylene glycol as a monoagent. It's pretty obvious that we can do better. We've done all our preliminary work with a 50/50 mix of EG and DMSO, very similar to the cryoprotectant used at CI. The DMSO is needed in order to show contrast on the CT scan. I'm not sure whether SDS will be part of our protocol. We need lots and lots of real world experience to answer that. I can think of pros and cons. Edema is a real problem and I wouldn't want to encourage it. I suspect it will depend on our estimates of how long each brain has been hypoxic and anoxic. All of the human brains will have experienced some of both, unlike an experimental brain.
I guess what I'm getting at is that Alcor and CI are right to be hesitant. It would be negligent to use a new protocol without doing any testing first, and they don't really seem to have anyone driven or interested enough to do the testing. So, they are using the protocol that was most recently validated. I do remember various examples where people got eager and started using a new protocol without proper vetting. It was a disaster every time. So thank goodness there's still a little bit of institutional memory floating around to remind us of that history.

Re: Cryopreservation procedure (ASC)

Posted: Fri Apr 30, 2021 2:37 am
by Cool_Kiwi
Thanks Jordan for the reply! I can see now there needs to be a lot of testing and details need ironing out before it can be put into practice. I'm only in my 20s so I believe I will have a fair amount of time for cryonics to get better.

It's interesting to see the different cryoprotectants used by the different companies/studies. From the ASC paper it seemed like 65% ethylene glycol prevented all ice crystallization. But I just read your study on cryoprotectant concentrations which seems to point to a different conclusion. Alcor says their formula (M22) is better at preventing ice crystals/is less toxic (though toxicity is irrelevant in this context). Though tbh I'm no expert in any of this.

The issue I have with Alcor and CI is that the current procedure doesn't preserve the connectome that well. Robert stated that it only has a 0.1% chance of working because the damage to synapses would likely be far too great, irreversibly destroying information. Though granted, it's just his opinion which may be biased. To me, it feels like the current procedure at Alcor/CI is a dead end and there's no point sinking more into it. Though if they were to switch, it might be a tacit admission that previous cryopreservations were failures.

But Ken on the other hand wants it to accepted by the medical community and implemented in regular hospitals like heart surgery is now, which is an impossibly unrealistic standard. He is against any cryonics company adopting ASC until it's fully accepted by the mainstream, a hill he is literally willing to die on.

Re: Cryopreservation procedure (ASC)

Posted: Fri Apr 30, 2021 3:07 am
by Cool_Kiwi
Another question if I may, if you were to develop your procedure, in theory what would be the shortest possible time between death and cryopreservation?
Say you got prescribed lethal medication under the death with dignity act. You take the drugs near the cryonics facility, or even better, at the facility. Your heart stops beating and a doctor pronounces you legally dead. Then finally the operation begins. Could you do all that in a very short time say like half an hour? Or would it inevitably take a few hours at the very least?

Re: Cryopreservation procedure (ASC)

Posted: Tue May 11, 2021 6:51 pm
by jordansparks
There are so many tradeoffs between different protocols that you really need someone with a lot of expertise to make judgements. For example, I've been pushing for the very fast carotid approach. But the tradeoff is that the occipital area of the brain will likely be poorly perfused in a small subset of people because we're not including the vertebral arteries (unless we can figure out how to cannulate them after the carotids). With the carotid approach, in a controlled setting, I estimate we could have moderate molecular stabilization within about 5 minutes and complete cryopreservation within about 3 hours. If we decide that it's more important to ensure perfusion of the occipital region, then we might instead choose surgical access through the heart. We might have moderate molecular stabilization within about 10 minutes and cryopreservation within about 3 hours.
We don't have deep expertise with the DWDA. This expertise can only be developed with lots of experience. I would love to see the scenario you describe. I don't really think it would shorten the time. But there are other huge advantages:
1. You can plan for a convenient time when everyone is there and the equipment is ready. Lack of staff and equipment would definitely slow things down. Poor timing results in many poor cryonics cases.
2. Less agonal hypoxia. In other words, dying quickly is a lot better for the brain than a protracted dying process where areas of the brain are deprived of oxygen.

Re: Cryopreservation procedure (ASC)

Posted: Sun May 16, 2021 5:06 am
by Cool_Kiwi
Thanks again for the reply and clarification. I'm hopeful that Oregon Cryonics will succeed especially since you seem to be much more experienced in the medical and procedural side than what I've seen from the other organizations.

I'm a little worried though about a schism occurring in cryonics between those who believe in fixation and mind uploading and those that are intent on biological revival, ironically resulting in no revival at all. Cryonics is already a small community and I'd hate to see it split over philosophical, almost theological differences. I imagine cryonics could be developed far better if it had economies of scale, and more minds working on developing a good and sound procedure. But that becomes hard when you can't agree on what the procedure should be.

Case in point, this most recent post on "Evidence Based Cryonics"
http://www.evidencebasedcryonics.org/

Re: Cryopreservation procedure (ASC)

Posted: Mon May 17, 2021 2:49 pm
by jordansparks
Science is full of people who disagree with each other. It's no big deal. It's healthy.