Human Biostasis (e.g. via cryopreservation, usually called cryonics) was first performed in 1967 on Dr. James Bedford following his death from kidney cancer. Since then, 559 people have been cryopreserved after their (legal) death and over 4000 people have signed up to be cryopreserved when they die in the future. Practically everybody signing up does so with the assumption that if their brain is well preserved, they themselves are “preserved” including their memories, their personality, their identity, and their consciousness. And that they, potentially, can be resuscitated once medical technology has advanced enough. While it is possible today to choose cryopreservation, usually via a body donation agreement to science as an end of life choice, it is not yet possible to reverse the process and reanimate someone from cryostasis. In fact, the predictions on whether and when this will be possible, range from likely to impossible, and from decades to thousands of years, with neither prediction being based on partially reliable bottom-up argumentations. Nevertheless, a slowly growing group of people chooses this option with the argument that other end of life choices (most prominently cremation and burial) do not provide any chance whatsoever of living on or again. 

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Much has been written about the topic with ethical and moral considerations garnering only limited attention apart from some very high level discussions. Here we focus on the morality of offering human cryopreservation (or other types of biostasis), i.e. should human cryopreservation be offered at all considering the current limitation and if so, what responsibilities and guiding principles should a provider have. To start, we will briefly recap how cryopreservation works, where the science stands, and why revival from cryopreservation is not currently possible.

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Human Cryopreservation

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Human cryopreservation is an advanced research/medical procedure that involves cryoprotective agents and extremely low temperatures to preserve a body with as little damage as possible. Theoretically, a body could remain in this state indefinitely without any meaningful degradation. The exact procedures used to cryopreserve a patient can vary depending on individual circumstances (i.e. patient condition before pronouncement or amount of time between pronouncement and the start of the procedure). The fundamental logic is as follows: When a person’s heart stops beating, their cells stop receiving oxygen. In most conditions, the body can withstand only about 4 minutes without oxygen before (currently) irreparable brain damage occurs. However, lowering the body’s temperature decreases the metabolic rate and thereby decreases the amount of oxygen that a cell needs. This is demonstrated in cases like that of Anna Bågenholm, who survived 40 minutes of circulatory arrest in a frozen lake with no major repercussions. As a person’s temperature drops, their metabolism first slows, and once low enough, virtually comes to a complete halt. Once the temperature drops below the so-called glass-transition temperature (and if a cryoprotective agent was used), a patient can remain preserved without any (additional) damage for extremely long time frames. Achieving and maintaining this state with as little damage as possible is the primary goal of the first step of cryopreservation. The second step being revival, if and when possible.

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The Current State of Cryopreservation Science

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By current standards, the first cryopreservations were quite crude. These first cases were all ‘straight freezes’ meaning the patients were cooled to liquid nitrogen temperatures without the use of any cryoprotective agents (medical grade anti-freeze) leading to significant ice formation throughout the body. 

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Since these first cases, human cryopreservation procedures have improved significantly. Today, a patient’s blood is removed and replaced with specialized cryoprotective agents (CPAs) which lower the critical cooling rate (the required rate of cooling to avoid ice crystal formation) of a patient’s body. These CPAs are hyperosmolar which means they pull water out of the surrounding tissue. Under ideal conditions, this allows for patients to be cryopreserved with very little and even potentially negligible ice formation. CPAs are toxic, so patients are initially perfused with a very low concentrations. As the patient’s temperature is lowered (and thereby also their metabolism), the concentration of CPAs is gradually increased, avoiding toxicity as much as possible. 

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After perfusion the temperature is lowered further. At around -130°C the so-called glass transition temperature is crossed and the tissue becomes vitrified (which is a glass-like amorphous state). The temperature is then lowered to -196°C (or -140°C in case of Intermediate Temperature Storage) over the course of days to weeks to minimize thermal stress. Finally, the body is placed in a cryogenic dewar for long-term storage. 

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While it’s currently impossible to reanimate a cryopreserved patient, there is some research that indicates the potential for cryonics to be successful. Researchers were able to cryopreserve and then revive C. elegans with clear memory retention. Researchers have also been able to cryopreserve and rewarm a rabbit’s kidney, which was recently replicated in a rat. After the rewarming procedure, the organ was transplanted and demonstrated full functionality. Despite this, it must clearly be acknowledged that it remains speculative if, when, and in what state cryopreserved patients could be reanimated in the future.

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For revival to be possible there are multiple fundamental and detailed issues to be solved, such as ice formation, toxicity, rewarming technology, and cellular and molecular repair. Of course, there might also be unknown-unknowns, i.e. some features that are not preserved and would need to be preserved (or preserved differently) to make revival possible in principle. The book Cryostasis Revival: The Recovery of Cryonics Patients through Nanomedicine written by Robert A. Freitas Jr. is recommended to gain a deeper understanding of what would be required for revival and how it might potentially be achieved (see https://www.alcor.org/cryostasis-revival/). 

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Given that it’s uncertain if cryopreserved patients can ever be reanimated, the question arises whether it’s ethical to offer the option to be cryopreserved and if yes, how. 

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Cryonics is a “Last Ditch Effort”

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irst of all, it’s important to note that cryopreservation is only offered as a last resort. Cryopreservation is exclusively performed after legal pronouncement of death, when all other medical interventions have failed to keep the patient alive.

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There are a few established medical and legal precedents that deal with making choices in similar situations. While not directly comparable, they give an indication on how to act in these situations. Compassionate Use (sometimes called expanded access, early access, etc.) is a medical principle whereby people that have serious or life-threatening conditions can get access to unapproved medical treatments. In some European countries (Germany, UK, Austria, Spain, etc.) the government is even required to cover the costs of the experimental treatment for people who meet certain criteria. The Right to Try Act in the United States sets a similar precedent, giving terminally ill patients the right to access many treatments that have not completed the FDA approval process yet.

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While these examples include some degree of regulation and approval processes, it could be argued that human cryopreservation falls under a similar core argumentation. It should be, at least in principle, up to the individual to decide which potentially life-extending option they would like to try when all other options fail. Furthermore, in the case of cryopreservation, no public funds (in any country) are used to pay for a person’s preservation. The cost of the procedure falls solely on the individual wishing to have it performed.

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This right has been confirmed by court decisions in some countries, such as the decision by a UK High Court to grant a dying 14 year old girl the right to be cryopreserved, contributing to a precedent for cryopreservation to be a valid end of life option from a legal perspective. 

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Last but not least, especially in western countries, society is based on the fundamental concept that individuals can make a wide range of choices as long as they don’t negatively impact others.  Since human cryopreservation only impacts the finances and body of the individual choosing to be cryopreserved, it has only a miniscule capacity to cause harm to other individuals or society as a whole.

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Factors to Consider

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Informed consent

A core principle in medical ethics and medical law is informed consent, stating that a patient must have sufficient information and understanding before making decisions about their medical care. It includes ensuring understanding and consent to a) the nature of the procedure, b) the risks and benefits of the procedure, c) reasonable alternatives, and d) risks and benefits of alternatives.

For non-standard experimental procedures, ensuring informed consent is particularly important. Cryopreservation clearly falls into that category. 

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For informed consent to be met for cryopreservation, the member/patient should understand the following:

• No one can say when revival from cryopreservation may be possible or if it is possible in principle. 
• Even if revival is possible in principle, the individual preservation quality might be low, the organization might go out of business, there might be external risk, etc. that prevent the patient from being revived. 
• Even if revival is possible, there might be physical or mental limitations caused by the cryopreservation or revival procedures. 
• Cryopreservation is expensive and must be paid out of pocket.
• How the procedure works including long-term storage and potential revival.
• People signing up for cryopreservation have a relevant amount of responsibility to ensure that their cryopreservation can be carried out and done with high quality. 

Ensuring informed consent is not the responsibility of the people signing up but of the organization providing the service. Just like a doctor must ensure informed consent for medical procedures. 

In the case of cryopreservation informed consent is complicated as risks and benefits can only be estimated. It will not be possible to provide comprehensive descriptions of risks and benefits for decades, it might in fact only be possible after revival has been done at least a few times. While this makes ensuring informed consent more difficult, it is not fundamentally different from informed consent in Compassionate Use or Right To Try Act cases, where exact information about outcomes is not available either.

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From a practical standpoint, ensuring informed consent for cryopreservation is a multi-step process that does not have generally accepted best practices as they exist in medicine (and are, in fact, legally required).

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We propose to combine the following methods:

1. Provide comprehensive, but easy to understand information describing the process, internal risks, external risks, benefits and potential failure modes. (Example: https://www.tomorrow.bio/informed-consent)
2. Provide the option to go into more depth if questions remain. 
3. Try to have personal one on one conversations with people interested in signing up to gain insight into their state of mind and understanding of the topic.
4. Include relevant information in or with the cryopreservation agreement.
5. Do not explicitly or implicitly state that cryopreservation is anything other than a chance for future revival (do not even imply that success is likely/certain/guaranteed/…).
6. Ensure that it is understood that probabilities and timelines are unknown.

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The key is the combination. One or two of them should not be considered sufficient. All options should be offered and, apart from personal conversations which are difficult to make mandatory, should be required. 

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Cost

In the past, present, and unfortunately probably in the future, cryopreservation is prohibitively expensive for a large portion of the population. The cost of whole-body preservation is in the range of EUR 200,000 EUR/USD depending on the provider. There are more affordable options but they, at least on average, compromise on quality which should not be the solution to the issue of high cost. Other options which preserve only the brain or head cost around 60.000 to 90.000 EUR/USD.  

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Two questions regarding cost come up: a) Is it permissible for someone to spend large amounts of money on their own cryopreservation while other causes might lead to more quality-adjusted life years (QALYs)? and b) What responsibility does a cryopreservation provider have regarding cost?

(Note: arguments have been made that cryopreservation may lead to large QALYs increases as well)

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In medicine there has been an ongoing discussion on how much society can and should pay to extend life in case of terminal diseases. Currently, general practice in most western societies is to spend significant amounts with a tremendous percentage of medical expenses concentrated on the last years of life. 

Apart from these expenses covered by society directly (e.g. via the statutory healthcare system), society considers it as acceptable to spend, for argument's sake, all of someone’s own money on trying to extend their life with experimental treatments in case of terminal diseases. As a more general point, we usually consider it the prerogative of the individual to decide how they spend their money. 

As long as we consider it permissible to use someone’s own money to fund their experimental cancer treatments or, as a more “extreme” example, buy their second luxury car, cryopreservation would clearly be permissible as well. Not everybody might consider it “necessary”, just like they might not for a second luxury car, but it is considered acceptable by most. On the other hand, we would argue that cryopreservation should not be covered by statutory healthcare systems or similar until efficacy can be proven. Statutory systems should try to optimize average outcomes (e.g. measured by QALYs) and do so with a high burden of required proof.  

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Regardless of the above points, it’s imperative to bring the cost of cryopreservation down. Just as it is unacceptable (but also almost unavoidable for the time being) that some medical treatment might only be accessible to wealthy people, it is unacceptable that cryopreservation requires a comparatively large personal wealth. Ideally, choosing cryopreservation  should exclusively be a choice that someone makes after having weighed the pros and cons within their personal value system. 

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Unfortunately, it is likely not possible to fully achieve this ideal for many years if not many decades. While in principle, cryopreservations can be performed at very low costs if done at scale, this scale is the core problem. Currently, less that 50 cryopreservations are performed annually across all cryonics providers. Far below what would be required to reduce cost in a meaningful way.

As a short excurse: the four main costs of cryopreservation are medical/SST, liquid nitrogen, personnel to maintain long-term storage, and pro rata costs of the storage facility/infrastructure. In the long-term with 100s to 1000s of preservation performed in one region (e.g. Europe), all these costs can go down by an order of magnitude. Pro rata liquid nitrogen cost reduces once larger storage dewars (or room-sized setups) are used, medical/SST team and personnel for the facility would be covered by many more people and facility/infrastructure is almost a one-time cost with only very little marginal costs for each additional cryopreserved patient. 

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For all intents and purposes we need to assume that scale will not bring relevant cost reduction any time soon. It should nevertheless be the responsibility of a cryopreservation provider to try to enable cryopreservation independent of wealth. 

There are three fundamental paths to bring cost down:

1. Grow as fast as possible to achieve the described scale.
2.  Adapt procedures/model without a, based on best estimates, relevant reduction in preservation quality. Some approaches exist that most likely would fall into this category, which in some way should be implemented by cryopreservation providers. 

1. Offering lower cost options such as brain-only or neuro preservation.
2. Employing a means-tested model where cryopreservation can be subsidized by charging very wealthy members more.
3. Potentially, accept and/or support cryopreservation cases pro bono (means-tested) given that there is no impact on the long-term stability of the organization (e.g. with storage at donation-funded 3rd party storage locations).

1.  Adapt procedures with potential reduction in preservation quality. Some types of preservation can be done at costs from 10.000 EUR upward, but only with a (on average) significant reduction in preservation quality and funds for long-term maintenance. With more funding, quality can be increased in a stepwise function, with the most relevant step around 30.000 - 50.000 EUR depending on distance to a cryopreservation facility. As it is not known what degree of damage will be repairable in the (far) future, and how potential revival scenarios will look in detail (Cryostasis Revival by Robert Freitas gives some positive indications), there is an argument to be made that preservations should be performed even at lower than ideal quality levels if there is no other realistic option. The complex question here is how informed consent can be ensured. It should be made clear that a quality decrease might be absolutely detrimental, and that some researchers would consider these quality decreases large enough to make revival impossible. The option should probably not be offered if it is made to “save some money”, but only if otherwise preservation would not be possible at all.

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Public Communication / “Marketing” Activities

If morality is considered, offering cryopreservation services differs from marketing cryopreservation services. In fact, marketing, in the traditional sense of “getting someone to do something” should not be done at all, as it would be against the requirement of informed consent. “Marketing” should be focused on informing about the topic in general, about the availability of the service, and being available for discussions and questions.

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As a high level rule, activities should be more restrictive the larger the audience is and based on which channels are used. For example, on performance channels (e.g. Google Ads) and based on keyword selection and targeting it can be assumed that people who search for the topic have some amount of prior knowledge helping them to make an informed decision. While on mass-reach channels such as TV or PR it must be assumed that a relevant amount of people might hear about the topic for the first time (at least in a tangible way) requiring an even more neutral communication approach.

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The question remains if complete informed consent information should be included in the public communication / marketing message? Or does it suffice if informed consent is ensured at the time of formalizing an agreement?

Any type of public communication should probably not be completely devoid of informed consent-type of information.This again is more important if mass-reach channels are concerned. There is some precedent in medicine with a wide range of approaches across different countries. In some countries marketing for medical treatments or medication is highly restricted and the decision to recommend a certain course of action is left almost exclusively to the attending doctor. While in other countries marketing is quite common if not aggressive (e.g. medical/medication marketing in the USA). While some disclaimers need to be included here as well they would not rise to the requirement of real informed consent. Here, informed consent needs to be ensured before implementation of the treatment by the executing doctor.

With an established “path to access” (e.g. via doctors), it is possible to be very restrictive with what is allowed in public communication. But in the case of cryopreservation this established path to access does not exist. Opting for no public communication / marketing would lead to people who would have given full informed consent never hearing about the topic, which can be morally problematic as well. Public communication / marketing leads to more people being exposed to the topic in the first place, which obviously is required to then be able to weigh the pros and cons and to make an informed decision. In the end, organizations need to find a balance between too much or too little public communication.

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While public communication/marketing is likely required/permissible/good to some degree, biostasis providers should communicate the topic with caution. Providers should be particularly careful to avoid language or messaging that might instill a false sense of certainty about the chances of success of cryopreservation and subsequent revival. 

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Organizational Setup

After someone has signed up to be cryopreserved after their (legal) death, it is the organization's task to ensure that the patient stays in cryostasis for an indefinite amount of time, until (and if) it will be possible in the future to reverse the process and restore their life. While the patient needs to help to ensure this stability and security, by for example making sure that all documents are in order (cryopreservation contract, etc.), just like ensuring informed consent, it’s ultimately the organization’s responsibility. Four factors are key for a responsible organizational setup:

1. Storage should exclusively be with non-profit organizations. For profit organizations are not designed to be around for, potentially, hundreds of years, and can only to much lesser degree ensure continuous mission alignment. 
2. There should be a well thought out governance structure to ensure that the interests of preserved patients are represented equally. This alignment and the purpose of the organization should be set in stone e.g. in virtually unchangeable statues. There should be an extensive list of requirements for anybody interested in being involved in running the organizations. Primarily,  everybody should have been involved in the field of biostasis for many years, not have any financial interest, and most importantly be signed up to be cryopreserved themselves.
3. There should be a stable and sound financial plan to ensure the organization can maintain operations for decades, centuries, or beyond. E.g. The funds to maintain cryopreservation (mainly liquid nitrogen cost, personnel, fractions infrastructure) should be covered from interest / ROI from a patient care trust amount being invested into low risk assets. This is necessary as it is not known when revival might be possible, so funding needs to be available for an indefinite time frame.
4. There should be a clear separation between day to day operations and long-term storage. Legal guardianship and management of patient funds for long-term storage should be done by a purpose built organization that is not doing anything else. In most cases a trust or foundation are best suited for this activity. 

R&D

Any organization offering human cryopreservation (or, in fact, being involved in the space in any capacity), should allocate resources to R&D. This includes conducting, funding and advocating for R&D. Without tremendous research effort, revival from human cryopreservation will not become possible or it will only be possible if research findings that are not directly related to cryopreservation revival can be employed for cryostasis revival as well.

Research (and informed consent) may be the deciding factor between human cryopreservation being morally very problematic if not wrong and morally neutral or even good. 

Depending on available funding, R&D activities should include some or all of the following areas/types (some topics are not clearly demarcated) :

• Implementation type (e.g. implementation of existing medical or cryobiological knowledge into cryopreservation procedures)
• Development / Engineering type (e.g. improved perfusion techniques and new methods of cooling for stabilization)
• Applied / Translational research (e.g. improving CPA with blood brain barrier openers and optimization to reduce toxicity)
• Basic research (e.g. novel consistent and uniform rewarming technology and new approaches to CPA design) 

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Summary

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Offering services related to medicine always comes with a wide range of complex ethical and moral considerations. Human cryopreservation clearly falls in this category. Organizations offering human cryopreservation need to conscientiously stay within relatively narrow guide rails to do so ethically.

Among those guide rails, ensuring informed consent is by far the most important one. Anybody signing up for cryopreservation needs to clearly understand that cryopreservation is currently not reversible, it is not clear if damage can be repaired in the future, and it is not clear when and if it will ever work to revive anybody from cryostasis.
There are several other requirements, but if followed attentively and rigorously the authors would argue that offering human cryopreservation right now is morally permissible, if not warranted.

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Last but not least, this is a highly complex topic that we would like to discuss with the broader community. There are likely (substantially) different opinions and we expect changes over the next years and decades. Please reach out if you are interested in providing your insight, regardless of whether it agrees or disagrees with the points we have made.

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Conflict of Interest

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The authors declare the following conflicts of interest: EFK founded a non-profit cryopreservation research foundation (European Biostasis Foundation) as well as a cryopreservation provider (Tomorrow Bio) where he also is the chief executive. RZ previously worked at a cryopreservation provider (Tomorrow Bio) and co-runs a community server. Both also have cryopreservation contracts.

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