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Syd Lonreiro's avatar

The obsession of Good Manufacturing Practice (BPF) with the “perfect” microscopic preservation of the connectome reflects a deep misunderstanding of what cryonics really is. We don’t practice cryonics because we can prove it works — we practice it because it is the only option available for terminal patients. Cryonics is fundamentally an emergency medical procedure performed on dying patients. In this context, imposing idealized laboratory standards is not only unrealistic but potentially dangerous, as it could discourage patients from accessing the only option they have left. Unlike chemical fixation, cryopreservation maintains the theoretical possibility of reversibility. A cryopreserved brain can still be examined, scanned, or even chemically fixed later on, but the reverse is not true. Chemical fixation with aldehydes and osmium tetroxide “kills” the brain definitively by all contemporary medical criteria. This fundamental difference makes cryopreservation a true extension of medicine, whereas chemopreservation is more akin to a sophisticated form of embalming. Our goal should be to maintain viability as long as possible, not to create perfect specimens for microscopy. The accreditation procedures described in the article are bureaucratically daunting. They would require expensive imaging equipment, minimally invasive biopsies, and constant monitoring that would multiply costs enormously. This approach would turn cryonics into a procedure accessible only to the wealthiest, which goes against the democratic goal of the movement. Moreover, these standards ignore the practical realities of emergency cryonics. When a patient suffers an unexpected cardiac arrest, we must act quickly with the means available. We cannot wait to have access to a CT scanner or perform biopsies under perfect conditions.

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Doug S.'s avatar

You don't have to be able to get the perfect preservation all the time because in the real world shit does happen, but not being able to get perfect preservation even under ideal circumstances would definitely be a problem.

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David's avatar

I think such an accreditation process would be quite valuable for those of us who accept the information theoretic view of death and care mostly about the preservation quality of the connectome. "eh, I bet it's fine" is not very reassuring to me. We should definitely think about the cost: a biopsy or scan run on every preservation *might* be expensive, but I don't think we need to assume it's going to be. If it is, I would be OK with proving the initial cases, then doing some sampling after the procedure has been locked down.

I don't have a lot of hope for the ability to completely reverse all aspects of aging, given the billions poured into osteoporosis research, only to find that taking vitamin D might slow down bone density loss by a little bit.

Even if you want biological viability, it would be good to be sure that the brain structure is preserved. If it isn't, you'll be waking up with severe brain damage.

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Syd Lonreiro's avatar

It is absurd to think that patients will wake up in a completely disabled state with a poor quality of life. Some people refuse to be cryopreserved as a last resort or after several days of ischemia because they fear waking up as vegetables. But this makes no sense. You might wake up with severe amnesia, but a post-human civilization capable of reviving you will have abolished all forms of disability. Damaged parts of your brain will be reconstructed using algorithmic models, allowing you to regain a comfortable and healthy life and mental functioning. Brian Wowk has already explained this. For these reasons, I want to be preserved—even under the worst imaginable conditions.

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David's avatar

If the information about brain connections is lost due to damage during the preservation process, there is nothing that can bring it back, no matter how advanced the civilization is, or how sophisticated the algorithm. Anything that reconstructs you (assuming it is possible) would need to make guesses on how to fill in the lost information.

We should strive to keep as much as possible: to be ourselves when we wake up and to make future revival easier.

An easier revival with less dependence on omnipotent future technology means less time spent waiting, exposed to cataclysmic events that loom large on long time horizons.

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Syd Lonreiro's avatar

I find you far too pessimistic about preservation methods,

but even patients who were frozen directly are in very good condition — contrary to what Jordan Spark claims (who is currently attacking us on his website; it's a one-sided rivalry against our community).

Here is what is written in Cryostasis Revival:

"Advanced Neural Biosciences (ANB) has been carefully comparing control (i.e., undamaged) neural tissue with straight-frozen tissue to assess the degree and type of damage in a straight freeze scenario. At a 2019 cryonics symposium, ANB CEO Aschwin de Wolf presented micrographs of brain tissue that had been straight frozen and then thawed, noting that "it doesn't appear to show nearly as much damage as we might expect. The tissue is in worse condition than in vitrified cases, but perhaps not as much worse as previously believed — and this might point to a lower-cost form of acceptable cryopreservation." He emphasized that freezing does cause damage, but by lowering the temperature sufficiently, identity-critical information might be preserved by inhibiting diffusion-based chemical processes.

De Wolf also introduced a deep learning algorithm capable of distinguishing between early and late stages of permanent cerebral ischemia, trained on electron micrographs of both damage states. Future versions of this algorithm — called "reconstructive connectomics" — might be able to computationally reconstruct the brain's pre-ischemic state from the ischemic one, or infer the non-frozen state from the frozen state (if there is freezing damage), offering a powerful tool for enabling nanorobotic repair and revival of poorly-perfused cryopreservation patients."

You see, the Brain Preservation Foundation (BPF) is worrying unnecessarily.

Of course, your concerns are completely legitimate, and we all want to improve preservation methods as much as possible.

But in reality, all patients — even those who are poorly preserved — should have a chance.

Therefore, introducing overly strict requirements at this stage becomes dangerous, as it could lead to an inhumane selection process among patients.

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David's avatar

If the information is there, even if it requires some reconstruction, then that's fine. That's preservation and I would accept that. But there are some kinds of destruction where you *cannot* reverse it. Where the information is lost. Until you have an algorithm that can actually reconstruct the connectome, it's just speculation that the preservation method works.

"Future versions might be able to" is not sufficient for me. Because it's entirely plausible that the information is just gone.

I would focus on making sure the preservation standards are fair and accurate, rather than arguing against any standards whatsoever.

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Syd Lonreiro's avatar

The safest methods are those used by Alcor. Oregon Brain Preservation is not safe enough for patients at the present time.

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Syd Lonreiro's avatar

Current methods work — we know that. There are a few articles you should read to understand this. And fixation is not a good approach. You've turned toward ASC because you're only focused on preserving the connectome, but we want patients, not frozen fossils. Chemical fixation—comparable to embalming or mummification—is a modern adaptation of a natural preservation process. It relies on large molecular fixatives that must diffuse into the tissue to take effect. However, this diffusion can be too slow to prevent autolysis in brains that have undergone even brief ischemia. Researchers have raised concerns about the loss of small molecules such as neurotransmitters, the denaturation of proteins, and damage to myelin sheaths. Nevertheless, fixed brains remain chemically active at room temperature and may degrade over time. For this reason, they must then be vitrified using highly concentrated cryoprotectants and cooled to cryogenic temperatures. If cryoprotectant penetration is insufficient, fixation can exacerbate freezing-related damage. Consequently, the molecular reconstruction of chemically fixed brains may require significantly more data processing than conventional cryopreservation: all crosslinks created by the fixatives must be identified, their influence on scanned data corrected, and the spatial distortions they cause reversed. The exact computational load remains unknown but could be two to ten times greater than that required for non-fixed cryopreserved brains, depending on the complexity and density of crosslinking. Once these corrections are made, molecular reconstruction of the patient could proceed using modern techniques in biological assembly or digital simulation.

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Syd Lonreiro's avatar

Thomas K. Donaldson introduced the concept of neuronal archaeology.

It seems evident that even patients who were frozen without any protection and those who experienced hours or even days of warm ischemia without assistance will be revived.

We have every reason to believe that molecular nanotechnology can repair all of this damage.

We are all aware of the damage caused by the methods used by Alcor and Tomorrow Biostasis, and none of it is irreversible.

Here is the list of damages to be repaired:

- Pre-Mortem Somatic Damage

- Energy Failure, Ionic Imbalance, and Excitotoxicity

- Nitrosative Stress

- Inflammation

- Protein, RNA, and DNA Stability

- Apoptosis, Necrosis, and Structural Degradation

- White Matter Damage

- Histological Ultrastructural Change

- Perfusion Damage

- Endogenous Perfusion Damage

- Iatrogenic Perfusion Damage

- Biochemical and Biophysical Cold Injury

- Non-Fracture-Related Mechanical Injury

- Fracture-Related Mechanical Injury

- Cryogenic Storage Damage

- Rewarming Damage

Nanorobots will be able to analyze all of this and repair the damage — we know this.

K. Eric Drexler presented all the arguments supporting this idea, and Ralph C. Merkle went even further by imagining that we could repair things at the level of individual atoms and molecules by completely disassembling the brain in an “off-board” scenario.

Even if much information is lost and structures are destroyed (which is indeed the case), there is still enough information left to conduct neuronal archaeology, using techniques akin to cryptanalysis, as explained by Ralph C. Merkle.

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David's avatar

I don't think you actually know that nanorobots would be able to repair all of it. Things work differently at small scales: machines you see at macro scale stop working when scaled down too far. Whether or not it's plausible depends on what engineering challenges pop up from trying to scale down. We don't even know what all the challenges are yet, much less if they'll be solvable. Can you make a robot with a sensor, motor, energy storage and manipulation that fits through a cell wall? We don't know. Even molecular based treatments like CAS9 have difficulties with delivery vehicles that are too large.

It could be that proteins and other "organic molecular machines" are the only things small enough to get around the body and do useful work, and that there may be limitations on what we are able to do with them.

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Syd Lonreiro's avatar

This has already been discussed in detail, and Robert A. Freitas Jr. has published the first complete revival protocol in two parts. The book is called Cryostasis Revival and spans 707 pages.

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Syd Lonreiro's avatar

Aldehyde preservation might be a good idea, but discrediting the cryonics community to promote what you consider a superior method is not helpful. Several articles (unfortunately all written for Alcor — I know this is not necessarily balanced or neutral) provide reasons to favor traditional cryopreservation for patients at the present time.

https://www.cryonicsarchive.org/library/chemopreservation/

https://www.cryonicsarchive.org/library/chemical-brain-preservation/

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David's avatar

There is nothing in these standards that would disqualify traditional cryopreservation if it sufficiently preserves brain structure.

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Syd Lonreiro's avatar

Ah, well, I won’t be liking this article. It’s full of additional evidence to prove that many supporters of ASC, like—and it’s no coincidence (Ariel)—have no respect for our community and do everything to quietly undermine us. Jordan Sparks recently wrote that cryonics is charlatanism, and now Ariel is making big demands that should never be enforced.

If we start having very strict requirements, many patients who deserve a chance will simply be rejected because the optimal standards cannot be applied in their cases. The ever-increasing demands will lead us to sorting out and abandoning patients, and gradually we will stop using the term “patients” and instead say “informational samples.” And we will forget why all this began in the 1960s, which is honestly sad.

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SF's avatar

Saying Ariel has no respect for cryonics is a bit too far, in my opinion. I view this article not as an attack on the cryopreservation procedure but rather an earnest push for higher standards of preservation. Indeed, while I favor regular cryopreservation over ASC, there are still many ways that the procedure can and should be optimized to result in the best outcomes. Further, I don't think that a push for stricter standards would necessarily lead to the abandonment of patients; if anything, I would imagine that these standards would actually be a draw.

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Syd Lonreiro's avatar

I don't include Ariel and Andy among the people I call the "ASC crazies," because they are serious and genuinely respectful. On the other hand, Jordan Spark hates cryonics and never misses an opportunity to call us charlatans doing pseudoscience...

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Syd Lonreiro's avatar

I don't include Ariel and Andy among the people I call the "ASC crazies," because they are serious and genuinely respectful. On the other hand, Jordan Spark hates cryonics and never misses an opportunity to call us charlatans doing pseudoscience...

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SF's avatar

I agree that Andy and Ariel are both respectful and serious, though I would take it a step further and say that--while they both seem to favor ASC--their viewpoints are not at all incompatible with those favoring more "commonplace" cryopreservation. Both have consistently pushed for greater access to brain preservation and neither has written cryopreservation off at all, to my knowledge. That being said, I can't say I'm all too familiar with Jordan Sparks' disparagement of cryonics. I do recall him making snide comments about a new cryonics effort some time ago which I felt were too dismissive, and if he has continued to cast aside cryonics that would be unfortunate. Even then, he is a (co?)-founder of OBP, which supposedly does offer cryopreservation in some instances and also does valuable research nonetheless, so even if he is an opponent of cryonics, I still think there are some contributions from him. However, I do think that disparagement of cryonics by people in tangential fields is unhelpful and serves to hold everyone back, especially if words like "charlatan" and "pseudoscience" are being levied towards us cryonicists. Whereas constructive comments like those Ariel made in this post absolutely have a place in the cryonics community, accusations of charlatanism are unfair criticisms.

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Albionic American's avatar

Cryonics is losing its traditional orientation anyway because of the RAPID generational turnover in the cryonicists who were running cryonics orgs or who at least had a say in what cryonics meant in the last couple decades of the 20th Century and the first couple decades in this century. Into this void we're seeing an influx of Millennials and Zoomers who are presenting themselves as cryonics authority figures - but based on what, exactly? Who are these people, and why should we trust them with positions of responsibility in the cryonics movement without getting a few years' acquaintance and experience with them so that we can evaluate their competency and character?

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SF's avatar

While the titans of the field remain some of the older cryonicists, I think that many of the new faces in the field are bringing needed funding and ideas. For instance, the group at CryoDAO has earmarked several million to enhance cryopreservation, Emil Kendziorra of Tomorrow Bio is pioneering cryonics in Europe, and Ariel--albeit while more in favor of ASC--has been a vociferous advocate for brain preservation optimization. Certainly much respect is owed to the Brian Wowks and Robert Ettingers of the field, but the new generation is bringing some great additions to the field.

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Valeriya's avatar

Dear Ariel, we will hold a meeting among our employees and the community. However, for me personally, setting such standards seems unethical, even cannibalistic. After all, if we adhere to this, we will deprive people in more complex cases, for example, after an autopsy, of the hope of revival in the future.

In addition, the authors of this idea subconsciously put a limit on progress, which is also wrong.

But let's see what our experts say.

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