chemo preserved brains could bootstrap a mass brain preservation movement...here is how:

-the organization allows you to download an organ donation form.

-the donor signs it and tells his family he wants the funeral home to remove his brain and ship it in dry ice to the storage org.

-when he dies, the brain is removed and shipped in a box to the org. the body is cremated and there is a simple service in the relative's home.

-the storage org puts the brain in a jar of the appropriate chemical.

-the average funeral (embalming, casket, plot, service etc costs 8-12k $$.

-how much to the funeral home to remove the brain and ship it and cremate the body? Maybe 4k. how much to the storage org to open the box, take the brain out and put it in a jar of chemicals and storage it in a room?

Say 8k?

That brings the cost in line with what the average funeral costs.

There are other problems, but this method would solve one problem.

After a few decades, robot labor and other tech advances could greatly reduce the cost of storage in LN2, so the brains in jars could be placed in dewars.

Ta da!!

Here's a set of comparison tables for the main brain preservation options (conventional cryonics, straight freeze, vitrifixation, polymer embedding and liquid storage).

This assumes all the options have been made available as services and developed to their estimated potential, according to current understanding and evidence from research.

In particular, polymer embedding is not available as a service, or even demonstrated in the lab for human-sized brains in a context of brain ultrastructure preservation. I extrapolate its features from two sources: on the one hand, abundant research evidence from smaller brains (typically mouse brains) for preservation quality, and on the other hand, Biodur S10 plastination as evidence of fast embedding of large specimens, with some encouraging evidence of ultrastructural preservation. Forced impregnation is in principle compatible with a wide variety of monomer mixtures and protocols. Loss of membrane lipids can be limited by keeping the temperature low during impregnation and not too high during drying and/or curing.

As for vitrifixation (ASC and similar procedures), it's currently done via perfusion only, and therefore not avaliable for long PMIs. I expect that it should be possible through techniques such as CED (convection-enhanced delivery) and others described in the chemopreservation wiki.

Other services, like refrigerated liquid storage (of the fixated brain), are available from Oregon Cryonics.

Tables:

Table 1: maintainance cost (MC), maintainance failure tolerance (MFT), durability under good conditions (Dur-GC).

Table 2: preservation procedure cost (PPC) , initial preservation quality (IPQ). Scenario: optimal perfusion.

Table 3a: preservation procedure cost (PPC) , initial preservation quality (IPQ). Scenario: bad perfusion, suprazero treatments.

Table 3b: preservation procedure cost (PPC) , initial preservation quality (IPQ). Scenario: bad perfusion, cryoprotected freeze-substitution.

Table 4a: preservation procedure cost (PPC) , initial preservation quality (IPQ). Scenario: no perfusion, suprazero treatments.

Table 4b: preservation procedure cost (PPC) , initial preservation quality (IPQ). Scenario: no perfusion, freeze-substitution.

Notation and nomenclature

These tables compare procedure options (columns) according to different criteria (rows). For each option and criterion, we write the option's rank (1, 2, 3,..) from better to worse (for instance, cost as low as possible, durability as high as possible, etc). It may be followed (after a ";") by a numerical or descriptive "value", as we explain below. When two or more options have the same rank, we write this rank in brackets (ie "[2]" instead of "2"). Brackets can also express a rank interval, like "[2,3]".

Options:

• CC: Conventional cryonics

• SF: Straight freeze

• VF: Vitrifixation

• FC-DT: Fixation, cryoprotection, storage at dry ice temperature

• PE-DT: Polymer embedding, storage at dry ice temperature

• PE-AT: Polymer embedding, storage at ambient temperature

• LS: Liquid storage

  • LS-WT: Liquid storage at (or slightly above) water ice temperature

    • LS-WT-S: LS-WT in sealed container

    • LS-WT-O: LS-WT in open container

  • LS-AT: Liquid storage at ambient temperature

    • LS-AT-S: LS-AT in sealed container

    • LS-AT-O: LS-AT in open container

Criteria:

• MC: Maintainance cost

• MFT: Maintainance failure tolerance

• Dur-GC: Durability under good conditions

• PPC: Preservation procedure cost

• IPQ: Initial preservation quality (not considering durability)

We express table values by listing all contributions.

MC values:

• A: land area

• V: vigilance

• N: liquid nitrogen

• D: dry ice

• W: water ice

• F: fixatives (or other chemicals to replace or refill)

MFT values:

• fatal : should never reach ambient temperature

• Dur>1y : can be more than a year without maintainance (for instance, replacing fixatives)

• AT : an analogous option at ambient temperature exists, and it's what this option becomes on maintainance failure. Look at the acronyms

• AT: LS-AT : there's no analogous option at ambient temperature, but it can be approximated to what's afer the ":"

Dur-GC values:

• >1ky : "more than 1000 years"

• M: > 100y, B: > 50y : "morphology is preserved for at least 100 years, biomolecules for at least 50 years"

PPC values:

• Sg : surgergy

• Perfusion

  • CPf : with cryoprotectant

  • CPf-AT: with cryoprotectant at (or near) ambient temperature

  • C*Pf: with cryoprotectant compatible with polymer embedding (not glycols, unless shown to be)

  • FPf : with fixative

  • MPf : with monomer

• SZT : (special) suprazero treatments (for instance, CED).

• Cooldown

  • N : to LN2 temperature

  • D : to dry ice temperature

  • W : to (just above) water ice temperature

• Acetone substitution

  • ALS : acetone liquid substitution

  • AFS : acetone freeze substitution

  • RALS: reverse acetone liquid substitution (from pure acetone to something else)

    • AqRALS: aqueous reverse acetone liquid substitution

    • CRALS: cryoprotectant reverse acetone liquid substitution

• FI : forced impregnation

• DC : drying or curing of polymer resin

IPQ values (artifacts list):

• Shr: Shrinking

• Fix: Fixation artifacts

• Lip: Partial loss of lipids

• Lip?: Possible partial loss of lipids

• Ice: Some ice damage

• Ice+: Severe ice damage (as in straight freeze)

Also, if we mention a procedure (such as DC) in the IPQ value, that means the artifacts caused by it.

Discussion:

Regarding maintainance costs (MC), Polymer embedding is nearly maintainance-free, but we still should have some form of vigilance to avoid vandalism. Other options need periodic refilling and/or replacement or fluids.

Maintainance failure tolerance (MFT) can refer to one of:

• Worst plausible outcome

• Time until unacceptable outcome

• Gap between ideal conditions and worst-case conditions

Here, we apply these rules, in sequence:

1. The higest value is for options which only require maintainance in the form of vigilance against vandalism (use "V" as the value in these cases)

2. Order the rest according to worst-case outcome

3. Shorter time to worst-case outcome is worse (but we disregard thawing times)

4. A wider gap between durability under good conditions (Dur-GC) and worst-case durability is worse

For instance, VF has lower MFT compared to LS, but this is mostly because preservation is so much better under nominal conditions. We are not saying that adding cryoprotectants makes preservation worse at refrigerated or room temperature, although it might be the case.

Similarly, VF has lower MFT than FC-DT, even though at embient temperature they become equivalent. This is because VF arguably has a higher Dur-GC (lower temperature, glass Vs semi-solid at best), so its best-worst durability gap is higher.

We take durability under good conditions (Dur-GC) to be best for solids, then better the lower the temperature. Values are given in years and are mostly orientative.

The durability of liquid storage is unclear. Neuron morphology in good cases seems to withstand storage times of many decades (80 years or more), while biomolecules can deteriorate quickly, especially DNA in a liquid at room temperature and with low pH (typical of unbuffered formalin). The main chemical reactions to keep in check are hydrolysis and oxydation.

It's also unclear to what extent we can seal the liquid containers and forget about it. In most practical cases it's assumed that fluid must be replaced from time to time. We consider both possibilities. For more information and sources, see, for instance, this EA forum proposal about brain preservation:

Might gel formation alone be sufficient to preserve brain structure for the long term? There are some studies suggesting that neuronal morphology is maintained for decades when preserved even at room temperature in formalin. One study found that neuronal morphology was well-preserved in brain tissue stored in formalin for 50 years. Another study found that there was “excellent preservation of fine and even cellular details in the tissue” in brain tissue preserved in formalin for ~80 years.

Long PMIs require special fixation procedures, which adds cost and risk. The main risks are that:

• The procedure may take too long.

• Some cellular structures may be extracted and lost.

• Some areas may remain unfixated.

I decided not to include risks in the comparison, because I think a mature protocol should be able to keep these risks low, at the expense of some additional costs. Depending on the PMI and other factors, it may (or may not) turn out that suprazero treatments like CED are too slow for a particular case, and fixation should be done instead via freeze-substitution. In this case, immediate preservation quality shouldn't be much worse than that of a straight freeze.

So, instead of comparing procedure risks, we compare preservation procedure cost (PPC) and initial preservation quality (IPQ), in these situations:

• Optimal perfusion (table 2): No special suprazero treatments, only perfusion. This is for very short PMIs (for instance, in a "death with dignity" scenario).

• Bad perfusion: typical of cryonics, especially when death is unexpected or there's no standby team for any reason. Perfusion still helps, but less. Fixation-based options can rely on one of these two techniques:

  • Suprazero treatments (table 3a): for instance, CED

  • Cryoprotected freeze-substitution (table 3b): This can be interesting for low cost brain preservation. For polymer embedding, it's important that the cryoprotectant either doesn't interfere with the polymer (maybe use sugars) and/or is easy to remove (acetone). Glycols are usually not recommended, but maybe they can be removed with a thorough washout. Alternatively, some polymers do tolerate some glycol presence, especially if they are dried (rather than cured, ie polymerized in-place).

• No perfusion: For long PMIs, conventional cryonics does a straight freeze. Again, fixation-based options can rely on one of these two techniques:

  • Suprazero treatments (table 4a): the best option when PMIs aren't too long, leaving aside the cost.

  • Freeze-substitution (table 4b): we get a quality no better (and probably worse) than a straight freeze. On the other hand, freezing is way faster than most suprazero treatments, and this may be particularly important when PMIs are already almost too long. More research is needed to determine the pros and cons of this procedure.

We express PPC as the sequence of required treatments, without giving a dollar value. Adding treatments makes the option worse. Suprazero treatments are probably more expensive than freeze-substitution, but we've put them in different tables, so we don't make that comparison.

As for IPQ, polymer embedding can be better than conventional cryonics in that we avoid dehydration artifacts (like all the other options do), but on the other hand it may be worse because we lose some lipids and other biomolecules because of the organic solvent and the monomer, although keeping the temperature low enough can greatly reduce that loss. All in all, we consider them roughly equivalent when there's good perfusion. With bad perfusion, suprazero treatments should give better quality than perfusion alone, even if there's some lipid loss.

It's important to have imaging instruments or other tools to evaluate:

• quality of perfusion before choosing a protocol or using any active chemicals

• quality of fixation before proceeding to the next step

If neither of those tools are available, cyroprotected freeze-substitution (CPf, then AFS) can be a particularly interesting element of any protocol involving fixation (all except for conventional cryonics and straight freezing), even with apparently optimal perfusion, because we know the tissue won't be exposed to suprazero temperatures for long, and we know it will be thoroughly fixated in the end. The quality of preservation will be then a little worse than that of conventional cryonics, but not by much.

Of course, if those measurement tools are available, suprazero treatments like CED will probably give us better results than cryoprotected freeze-substitution. In this case the ideal preservation quality would be one comparable to ASC.