Cryonics Without Damage

Eliminating Damage Wherever We Can

It is currently not possible to practice cryonics without producing some degree of damage. I do not mean the damage caused by clinical errors and negligence (see my article “Cryonics and Iatrogensis”). We are talking about damage that currently is unavoidable.

To my knowledge, the most fundamental form of damage that is currently unavoidable is cryoprotectant toxicity. Cryoprotectant toxicity is a type of damage caused by the use of high concentrations of cryoprotectants. Several mechanisms have been proposed for the mechanisms of cryoprotectant toxicity (protein denaturation, perturbation of protein hydration shells) but for the purpose of this article it is sufficient to recognize that when we replace all of the liquid parts of the human body with a concentration of cryoprotectants necessary to inhibit ice formation, the exposure time to these solutions will compromise cellular viability. While this type of damage is not likely to alter identity-critical components of the patient, reversing the procedure by temporary medical technologies is not possible. Cryonics is not suspended animation.

Between damage caused by errors and negligence and damage that is currently inevitable, there is a category of damage that cryonics organization permit to happen as part of organizational practices or protocols. Dr. Emil Kendziorra of Tomorrow Biostasis raised this conceptual issue in his podcast with Max More when asked about offering fracture-free storage. Kendziorra’s observation made me think of types of damage that some providers often allow to occur, although we have the technical or clinical solutions to resolve it.

Standby, Stabilization, and Transport (SST)

At some cryonics organizations SST is “optional.” Given that the objective of SST is to stabilize the patient and keep the brain viable by contemporary biological criteria, omitting SST basically means that a form of cryonics is offered that permits damage to occur. While funeral directors can sometimes be relied upon to pick up the patient from a hospital, they do not have the sense of urgency or medical skills to really stabilize a patient well. Optional standby is really “optional damage.”

Metabolic Support

In principle, cryonics protocols mandate ventilation during cardiopulmonary support (CPS) and oxygenation during blood washout. In practice, this objective is often compromised during CPS. Given that external cooling alone is not fast enough to prevent cerebral ischemia, some degree of neural damage will occur if metabolic support is omitted. During washout, oxygenation is often omitted altogether. While brain metabolism is reduced at deep hypothermic temperatures, it is not non-existent. In fact, a case can be made to even continue to oxygenate during the early stages of cryoprotection.

Blood Substitution

Remote blood washout as a core stabilization procedure in cryonics has been a staple of Alcor since the early 1980s. Pioneering in-house research at Alcor showed that an “intracellular” whole-body organ preservation solution (MHP-2) permitted full recovery of dogs up to 5 hours after cooling to ultraprofound hypothermic temperatures. In addition, research at Advanced Neural Biosciences has yielded evidence that remote blood substitution favors better cryoprotection up to 48 hours of cold ischemia compared to leaving the blood in the patient prior to transport.

However, there is a better alternative in the form of field cryoprotection (FCP). If blood washout is immediately followed by on-site cryoprotection, transport to the cryonics facility on water ice, and the edema and compromised brain viability this entails, will be eliminated. Whole-body FCP is now standard procedure at Tomorrow Bio and soon will be offered to Cryonics Institute members through SST provider Suspended Animation.

Cryoprotection

There are at least three opportunities for cryonics organizations to further limit damage during cryoprotection.

(a) Provide metabolic support during the initial stages of cryoprotection.

(b) Provide improved temperature control to ensure that cryoprotectants are introduced at optimal temperatures to reduce toxicity (no hanging bags with cryoprotectant in the air, better chilling of solutions, and good tubing insulation etc.)

(c) Implement existing technologies to modify the blood-brain barrier to prevent cryoprotectant-induced shrinking of the brain.

Transport

FCP eliminates cold ischemia during transport but triggers a new concern about ice formation during transport. Vitrification solutions have a so-called “critical cooling rate” that needs to be adhered to to prevent ice formation. Dry ice cooling and transport favors ice formation because it entails slower deep cooling and holds a patient at dry ice temperature where ice formation is more likely. There is also evidence that prolonged storage of cryoprotected neural tissue at dry ice temperature causes biological viability to decline.

There are two solutions to this problem. To prevent increased risk of ice formation, so-called “equilibrium vitrification solutions” that cannot freeze regardless of cooling rate (including holding a patient at dry ice temperatures) can be used. These vitrification solutions may be slightly more toxic, though.

From a technological perspective, there is better solution. If patients would not only be cryoprotected on location but cooled to cryogenic temperatures as well, this problem would be solved altogether. Ultimately this is a logistical problem that concerns transport of patients at cryogenic (or at least intermediate) temperatures. For brain-only patients this can be more easily resolved through the use of a “dry shipper.” Within a continent, whole-body ground transport in a specifically designed cooling box is possible. Cryogenic transport between continents is more challenging.

Storage

When an organ (or whole-body) is cooled below the glass transition temperature (Tg) of the vitrification solution, thermal stress can cause fracturing. One practical solution is to store the patient slightly below the glass transition temperature to mitigate this phenomenon. Intermediate temperature storage solutions have been available to cryonics organizations for many years but uptake has been non-existent. Tomorrow Bio has completed a prototype for whole-body ITS storage, and aims to offer the service to its members sometime next year.

Trade-Offs (An Example)

A more difficult challenge is when a cryonics organizations needs to be decide between different types of damage. A recent example concerns aldehyde-stabilized cryoprotection by immersion of the brain (or iVitrifixation). Some patients suffer such long periods of ischemic delay that it is no longer possible to cryoprotect the brain by perfusion without compromising delivery of the cryoprotectant and causing swelling. Current practice is to do a so-called straight freeze (cryopreservation without cryoprotection).

iVitrifixation entails a different approach. Instead of freezing, the brain is removed and immersed in a chemical fixative. Upon completion of this procedure, the brain is placed in different concentrations of the vitrification agent until it can be cooled to cryogenic temperatures without freezing. The trade-off of this procedure is that it can take many days for the chemical fixative to completely penetrate the brain. In essence, some (cold) ischemia is allowed so as to enable ice-free cryopreservation. It is currently not clear which procedure should be favored. Research to model these two approaches to understand which one yields the best ultrastructure is currently underway.