In many presentations and interviews, I’ve argued that one should consider cryopreservation for as long as necessary to be absolutely sure this is what you want. And once that decision is made, sign up without delay.
Assuming that call is made, how do you select the best organization? Most of the points made also apply to every other type of preservation.
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Of course, I’m biased. After all, I’m running Tomorrow Bio. But apart from that, there is a list of questions everyone should get answers to before signing up.
Here’s that list and what you should expect as answers. If you think an important question is missing (bias and all), just post it in the comments, and I might, in fact, add it to the main text.
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1. Where can I find the most recent case reports? If not released yet, when will they be released?
Care reports should be published for every case in a timely manner (less than 1 year after the case) and include sufficient data to evaluate how well everything went. Furthermore, and most importantly, case reports should include comprehensive quality data. In addition, they should include all procedural data such as temperature, pressure, refractive index, etc. Last but not least, they should include a critical evaluation of what went wrong and how problems will be addressed.
Additional information is nice but less important.
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2. What is the main quality metric they use to evaluate preservation quality?
I would argue that preservation quality under real-world conditions is the most important metric of any organization and should be your primary decision factor.
The two main ways to evaluate preservation quality are:
- CT Scanning: CT scans should show uniform perfusion with cryoprotective agent, high enough in concentration to suppress ice crystal formation. This is the minimal requirement. If the CT scan does not look good, every other quality metric is not very relevant.
- Electron microscopy: To evaluate the fine structure of the brain (i.e., the ultrastructure), EM micrographs are needed. As far as we understand, the ultrastructure is the part that makes up memory, identity, and personality. All the things we care about. EM micrographs should show the least possible damage to the ultrastructure.
CT scans and ideally EM micrographs should be available for each case to comprehensively evaluate quality.
Other metrics (gross anatomy, cooling rate, speed of procedures, flow rate of perfusion, refractive index at the end of perfusion, etc) are helpful as additional data points, but are mostly indirect measures and not sufficient for decision making. Quality data collected under lab conditions is also not relevant, as they are not even close to the conditions under which cryopreservation cases are performed. Note: quality data collected under lab conditions is helpful to make informed decisions about how preservation procedures should be performed, but the quality needs to be evaluated directly from real-world cases and not inferred from what works under lab conditions.
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3. Is the organization getting better at what they do? Is preservation quality getting better?
As of today, it is not exactly clear how well we need to preserve to ensure that memory, identity, personality, etc., are recoverable in the future. (See our paper here for some insight: “What are memories made of? A survey of neuroscientists on the structural basis of long-term memory”, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0326920)
It is therefore prudent to operate under a thesis of “We always want to get better”. Therefore, all organizations should be getting better consistently. Compare case reports over the last years and check if preservation quality has improved. At the same time, problems should be solved as time goes by and not repeated.
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4. How exactly are patient funds managed? Are patient funds separated from operational accounts? How much funding is put aside for maintenance and revival?
All funds earmarked to ensure long-term maintenance of preservation should be kept separately from the other accounts and managed by a separate organization; they should not be touched, except for covering the direct cost of storage and to ensure the survival of the organization in emergency situations. They should be invested optimized for a long investment horizon while maintaining a low risk profile.
The highest possible amount of funds should be set aside to increase the probability of being able to weather adverse situations and pay for revival in the future.
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5. From a financial standpoint, how is the long-term financial stability of the organization ensured? How long has the organization been around?
There should be a financial model to keep all involved organizations stable while not relying on external donations, drawing from patient funds (apart from covering direct storage costs), or sign-ups increasing in a unrealistic fashion. Organizations involved in maintaining cryopreserved people should be significantly more stable than organizations involved in research or procedures.
While an in-depth analysis gives more information, organizations that have been around for longer should generally be considered safer.
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6. Who makes decisions for people in preservation? How is the leadership selected?
The organization tasked with ensuring the maintenance of people in cryostasis should be separated from all other functions. It should exclusively be the guardian for the people in cryostasis and manage the funds required for maintenance and revival. The leadership should be made up of people who have a deep understanding of the procedures, research, and long-term safety. To ensure full alignment with the mission, there should be an extensive list of additional rules and requirements for those who want to join leadership in the future. Furthermore, the organization should be protected from changing its purpose.
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‍7. Estimate the degree of innovation.
Without innovation, the field of preservation will not work in the long term. Not only research, but procedures, logistical capabilities, communication, etc, need to be improved significantly. There is just so much to do to bring cryopreservation into the mainstream. Last but not least, growth should be considered, as it helps with stability, being able to deploy more SST teams, having more funding for R&D, etc.
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8. Do they do research? What’s the focus of research?
Organizations should try to improve procedures and conduct/fund research to push the field forward. Due to the limited funding available, the focus should be on structural preservation (before viability) and on brain/neural tissue. Not because other research endeavors aren’t interesting or important, but because the very limited funding situation forces the field to laser-focus on what is most important.
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9. How exactly would a cryopreservation case be handled at the location where I live?
Logistics and procedural decisions are still the most impactful in ensuring good preservation. But with few SST teams around the world, the average case might not be indicative of your exact situation. Inquire how exactly everything would work if you are in need of cryopreservation. Example questions are: What exact procedure would be used (field washout, whole-body field cryoprotection, limited perfusion of just the brain, immersion vitrifixation, straight freeze)? Who exactly would deploy to my location? From where? How early? How long can they stay? How many people would come? How is the team trained? etc.
If I’m missing an important factor, let me know and I’ll consider adding it. Will also update this list once in a while.
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