Cryonics is the cryopreservation of a brain in liquid nitrogen. It is used by companies like Alcor and the Cryonics Institute.
Aldehyde preservation, also known as chemical preservation or chemical fixation, is the technique used here at Oregon Brain Preservation. The brain is stored in a liquid chemical at refrigerator or freezer temperature. While we do use liquid nitrogen sometimes, it's not our primary or preferred preservation technique.
Here is some information about the two different techniques:
Aldehyde is heavily used by scientists and is considered to be the gold standard in mainstream science for brain preservation. Nearly all microscopic images of brain tissue ever taken have used aldehyde. Cryopreservation is also used by scientists, but the quality is known to be inferior when the goal is to retain the structural connectome, so it's simply not used by anyone for that purpose.
Some scientists who are involved in cryonics defend its use because they see it as a path to Suspended Animation. They envision being able to cryopreserve organs and then revive them, and then eventually move to full suspended animation. Unfortunately, there is broad consensus among mainstream scientists that we are at least 100 years away from such technology.
Evidence-based medicine (EBM) means making clinical decisions based on the best current evidence and clinical expertise. The evidence must support currently available outcomes. At OBP, our desired outcome is structural brain preservation, so all evidence must support that outcome. Revival cannot be considered because it's not a currently available outcome. Evidence that might support the outcome of revival is completely ignored.
In cryonics, the desired outcome seems to instead be revival, even though that's not a currently available outcome. This makes it experimental rather than evidence-based. Experimental research should only be provided in a research setting and should never be applied to patients when evidence-based care is instead available. It's unethical to do so.
To qualify as legitimate research involving human subjects, there must be certain scientific elements present. These generally include things like feedback, iterative learning, knowledge gain, peer review publication, randomization, a control group, ethical oversight, falsifiability, and reproducibility. While these elements may be present in varioius side projects, they are not present in the patient care activities. There is no currently available outcome which is being measured. Cryopreservation of humans is not research in any meaningful sense, and it's unethical to claim that it is research.
Aldehyde works by creating covalent cross-links between proteins. This deliberate arrest of metabolism and molecular diffusion is exactly what makes aldehyde fixation so valuable for preserving brain structure. Cryonics advocates claim that this cross-linking is a form of damage that is incompatible with biological revival. But the technology for biological revival is at least 100 years in the future. Damage in current ideal cryonics cases is extensive, including at the molecular level. Technology that is capable of altering covalent bonds is already clearly going to be a requirement. It's inconsistent to reject aldehyde fixation for introducing covalent bonds when molecular damage of an equivalent nature is already present in all existing cryonics cases.
Most or possibly all cryonics patients suffer some ice crystal damage. This causes brain damage. Because it's not evidence-based and because the wrong outcome is being pursued, this damage is accepted as unavoidable. A fairly large percentage of cryonics patients are actually straight frozen because of logistical issues. A Straight Freeze may very well cause complete information-theoretic death. The damage is truly catastrophic. It's also entirely avoidable in all cases by using aldehyde prior to introduction of cryoprotective agent (CPA) over a longer timespan.
Cryonics companies promote revival as the goal rather than structural preservation. This sounds more exciting and more desireable than our goal of structural preservation. That marketing choice is causing patients to choose the wrong technology for their brain preservation. It's directly harming patients.
Aldehyde preservation cost can approach zero in many cases. This allows us to save many more lives and it also reduces the risk and complexity. When large amounts of money are not involved, everyone is safer. It means much lower overall risk of organizational failure. There is no need for a patient care trust because no money is involved.
Alcor has posted electron micrographs of brain tissue that has been preserved with their protocol in an ideal situation:
https://www.cryonicsarchive.org/library/alcor-new-york-academy-of-sciences-paper/
https://www.cryonicsarchive.org/library/new-cryopreservation-technology/
The images demonstrate significant dehydration and they don't even look like normal brain tissue. They claim that this mechanical damage is reversible, but this is debatable and lacks evidence. By using aldehyde instead of cryopreservation, this damage is avoided.
In 2016, Robert McIntyre and Greg Fahy published a paper describing Aldehyde Stabilized Cryopreservation, which combined both techniques into a single protocol and demonstrated excellent quality of preservation of brain tissue. But while they can be used together, there's simply no advantage over just using aldehyde alone. Also, perfusion of cryoprotectants in this manner depends on high-quality perfusion, which has not been shown to be reliably achievable for patients across the entire brain. Therefore, if storage below 0 C is desired, we believe that initial perfusion fixation followed by immersion of cryoprotective agents is the safer option because it reliably prevents ice damage.
This can be helpful to some people who struggle to choose between the two. Using aldehyde leaves the door open for subsequent cryopreservation. In this case, the quality is maintained during the subsequent cryopreservation step because of the aldehyde. Even though it's possible, we don't recommend it.
The Q10 rule of thumb applies between 0 C and 40 C. The rule states that biochemical reaction rates are cut in half for every reduction of 10 degrees. For this reason, ice baths are frequently used in cryonics to slow reaction rates to buy more time to perform the perfusion. In constrast, if aldehyde can be quickly introduced, then most reactions stop and the Q10 rule no longer applies. Aldehyde is an alternative to cooling in this temperature range.
When cryopreservation is used alone, it takes hours to perfuse the cryoprotectant chemicals through the circulatory system. During that entire time, there's nothing locking the molecules in place, which results in significant damage. Locking the molecules in place many hours earlier with aldehyde preserves more information.
Conversion from liquid to solid happens at -123 C in cryopreservation. After many hours, this phase change is what finally locks the molecules in place. When aldehyde is used, the molecules are locked in place much sooner and the temperature doesn't matter.
The reason we refrigerate (or even cool to -20 C) after using aldehyde is to keep the lipids solid. Aldehyde does a great job of quickly locking the proteins in place, but the lipids are only immobilized because they are trapped in a web of proteins. If we allow the lipids to remain liquid at room temperature, it's somewhat plausible that a small portion of the lipids might shift position. Cooling after aldehyde preservation is recognized in mainstream science to probably result in better long-term quality.
Pascal's Wager is an argument that has been adapted to cryonics. The argument is that if there’s even a small chance that cryonics could work, then choosing it would offer extraordinary benefit. If it fails, you would lose little because you'd be dead anyway. Therefore, the rational choice would to sign up for cryonics. With the original Pascal's Wager, the obvious fallacy is that you might choose the wrong god. The cryonics adaptation suffers from the same fallacy. You might choose cryonics, but aldehyde fixative might turn out to be the only way to get a good preservation.
Nobody has ever been able to provide an example of any clear benefit of cryopreservation compared to aldehyde fixation. Without any clear benefit, and with known lower quality, we cannot provide cryopreservation. Using cryopreservation after aldhyde would be technically harmless, so we might allow it. But we will make sure that you understand that we consider the additional expense to be a waste of money.
This is an argument for why cryonics might be better than aldehyde. But the argument quickly falls apart. Whether you use chemical fixative or cryoprotectant, you must get the chemicals to a given area of the brain or there will be poor preservation. In the case of cryopreservation, the poorly perfused areas would be subjected to a straight freeze. That’s probably not compatible with preservation of memories as explained here: Straight Freeze
One explanation for why Alcor and CI continue to only pursue cryonics is that it might just be social inertia. If everyone around you is telling you that cryonics is better than aldehyde, maybe you just believe it without questioning it too much. There are so few people involved in these fields that the debate can sometimes lack the necessary complexity and depth. But regardless of why they do it, our only option is to move forward with what we know to be the more rational approach and to work toward a future in which aldehyde preservation fully supplants cryonics, preventing further harm to vulnerable patients.