By Aschwin de Wolf

Advanced Neural Biosciences, Inc.

Adapted from a presentation in Dresden, Germany, October 5, 2014

Abstract

In an ideal world, promising cryonics technologies would be identified, followed by prompt validation and implementation. In the real world, however, there are multiple reasons why potential improvements in cryonics are not being recognized or endorsed. Even when the benefits of such technologies appear evident, institutional and financial obstacles can prevent timely experimental validation and introduction. This article briefly reviews the history of technological progress in cryonics, discusses the reasons that delayed or postponed the introduction of superior technologies, and offers solutions that may enable faster adoption of new advances.

Introduction

The practical production of liquid nitrogen from liquefied air was first achieved by Carl von Linde in 1905, although liquid nitrogen only became widely available commercially after World War II. The idea of cryonics was introduced to the general public in the mid-1960s. Since liquid nitrogen (or liquid helium) is an essential requirement for human cryopreservation it is interesting to recognize that there was only a difference of roughly 20 years between cryonics being technically possible and the first efforts to practice cryonics. Robert Ettinger published The Prospect of Immortality in 1964. In 1967 James Bedford was cryopreserved.

Similarly, the idea of vitrification by rapid cooling as a means of cryopreservation was first proposed by Basil L. Luyet in the 1930s, followed by Pierre Boutron’s screening of cryoprotectants for their glass forming abilities in the 1970s, and Gregory Fahy’s pioneering work in the 1980s and beyond to achieve vitrification by high concentrations of cryoprotectants. No more than 20 years after these investigations, vitrification solutions with high concentrations of cryoprotectants were introduced in cryonics. This appears to be a reasonably rapid translation of scientific breakthroughs into cryonics technologies.

In the case of combinational pharmacotherapy to mitigate cerebral ischemia, research and cryonics implementation often went hand-in-hand and observations in cryonics cases were used to refine experimental designs.

Despite all this, there is the public perception that cryonics suffers from a lack of research and sees little technological progress. Compared to fields such as biogerontology and the developments discussed above, I think this is a misunderstanding. A major reason for it is that the general public and most scientists do not recognize that technological progress is possible in cryonics without creating full fledged human suspended animation. For example, safe and cost-effective cryogenic storage, inhibition of ice formation, elimination of (cerebral) ischemia, et cetera, are possible without having fully reversible cryopreservation.

I do think, however, that there is a lot that can be done to further narrow the time between identification, validation, and implementation of cryonics technologies by obtaining a greater understanding of what fosters and limits the identification of technological improvements in cryonics.

Identification of new technologies

Identification of new cryonics technologies is a topic that is rarely discussed within cryonics.  Upon closer scrutiny, this is a rather complex topic. First of all, for the idea of identification of new technologies to make sense one has to subscribe to the idea that cryonics technologies can and must be improved. Closely related to this is the belief that the concept of “patient care” is meaningful in cryonics and can be empirically defined. This outlook on cryonics has not been universal and from its inception proponents of perfecting cryonics technologies often had to compete with a movement in cryonics that showed little interest in delivering cryonics services that aimed for more than placing the patient in liquid nitrogen after pronouncement of legal death.

The history of the Alcor Life Extension Foundation shows a different perspective. Since its inception, the organization has been shaped by individuals who aimed to close the gap between crude freezing and reversible human cryopreservation. One claim that I will be making in this article is that formal commitment to develop human suspended animation provides a framework to identify desirable research and development goals. When suspended animation is used as a benchmark to evaluate the state of cryonics technologies, it is possible to identify the gap between contemporary technologies and desired technologies. This, in turn, can direct the search for new developments in science and technology to replace existing technologies. For example, ice formation is clearly not compatible with human suspended animation and replacing freezing protocols with protocols that eliminate ice formation is a logical consequence of this mandate. Another example is fracturing. Long-term care protocols that induce too much thermal stress in the patient do not allow for reversible cryopreservation and need to be replaced with long term cryostasis protocols that avoid the formation of fractures, such as annealing or intermediate temperature storage (ITS).

It is important to stress here that a universal consensus to use human suspended animation as the ideal to strive for does not exclude debate over which new developments should be pursued and prioritized. I think there is a rather widespread consensus that the replacement of conventional cryopreservation with vitrification is highly desirable. But there can be a difference of opinion about how much effort to expend in developing completely non-toxic vitrification agents instead of accepting a small amount of toxicity and moving on to eliminating fracturing or cerebral dehydration first. Sometimes such differences in perspective reflect incomplete knowledge. For example, do we need to induce hypothermia faster during stabilization procedures, or are our existing technologies sufficient to keep the brain viable by contemporary medical criteria?

To my knowledge, no one in cryonics has ever attempted to offer a framework to make such decisions. In principle, such a framework should be possible. One could argue that the first mandate of a cryonics organization is to pursue technologies that preserve ultrastructure in such a state that no differences between controls and experimental brains can be observed. When this goal has been achieved, the next mandate is to eliminate gross mechanical damage, that is to say, prevent fracturing. The next step would be to prevent nano-scale modifications in proteins that compromise viability, that is, to develop non-toxic cryoprotectants. Such a ranking can also assist in cost-benefit analysis of proposed technologies.

Validation of new technologies

When we think of validation of new technologies we tend to exclusively think in terms of development and experimental validation within cryonics. A closer look at how new technologies are introduced in cryonics should lead to a more nuanced perspective. First of all, in some cases the scientific validation has already been done in mainstream science and clinical practice. In emergency medicine a routine procedure is to stabilize the patient for subsequent hospital admission and treatment. In cryonics we would like to stabilize the patient for long term care at low temperatures. In both cases, however, the aim is to prevent any further deterioration from the condition we find the patient in. If a new mechanical device can deliver more effective external chest compressions (and improve cerebral blood flow), then, everything else the same, this should translate into improved patient care in cryonics, too. The crucial part here is “everything else the same.” One subtle problem that is often underestimated by medical professionals who are new to cryonics is that the conditions in which cryonics patients present themselves can be so distinctly different that a departure from standard emergency medical protocol is necessary. Thus, often mainstream technologies need to be translated into cryonics technologies and sometimes this even requires additional experimental research. In general, though, adaptation of new mainstream technologies can accelerate the progress in cryonics technologies.

Another area in which the need for conducting experimental research is often minimal is when the technological changes in question are primarily engineering challenges. A good example concerns efforts to increase the cooling rate during initial stabilization. It is well recognized that faster cooling rates during this phase confer a substantial benefit and are instrumental to keep the patient’s brain viable. Any technology of internal or external cooling that can achieve this objective constitutes measurable progress. Or consider the development of computer-controlled perfusion that can optimize a perfusion protocol based on a number of chosen variables (pressure, cryoprotectant concentration, et cetera.)

When it comes to the core technologies in cryonics such as cryopreservation of the brain, however, there is no credible alternative to conducting experimental research in-house or contracting with other research labs. In an ideal world, prior to adaptation, new cryopreservation technologies would be independently verified  in a number of labs using different animal models and the new technology would then be progressively implemented in cryonics with extensive data collection and analysis. It is indisputable that this is the gold standard in cryonics but at this point it cannot be claimed that all cryonics technologies have been validated with such rigor. The rationale for using technologies in cryonics has ranged from theoretical extrapolations from the scientific literature to the use of technologies that have been validated in peer reviewed publications.

Conducting experimental research to validate new technologies is a non-trivial affair for the typical cryonics organization. Funding that can be allocated to research often needs to compete with other priorities such as maintaining qualified staff and promotion. There is also the increased recognition that combining patient care and experimental research is not prudent, which necessitates either outsourcing research or establishing separate research facilities. New technologies often produce new research questions. For example, the adoption of vitrification solutions has greatly increased interest in investigating low toxicity cryoprotectants.

Implementation of new technologies

After identification and validation, the final step is implementation of a new technology. As discussed above, in cases where the technology is already in use in mainstream medicine, implementation often requires some kind of adaptation for use in cryonics. Another important element of implementation is creating documentation and the training of staff and contractors to use the new technologies. In some cases, the lack of required skills can complicate or delay implementation.

Validation and implementation are not always distinct phases. Often, the only way experimental evidence can be obtained about a new technology is to carefully introduce it in human cases, collect data, and revise the technology if necessary. The introduction of new technologies should always be followed by focused and repeated data collection to evaluate its efficacy and to determine whether the addition of this technology brings the cryonics organization closer to its ultimate goal of reversible cryopreservation.

The technological progress that has been made in cryonics is impressive, especially considering its science and limited scientific support. Unlike a field such as biogerontology, cryonics protocols can usually be tested in a relatively short time span and there is little dispute over what kind of problems need to be solved to achieve reversible cryopreservation. In the remainder of this article I will give a number of reasons (some of them intrinsic to cryonics) that have prevented more rapid technological progress in cryonics.

Obstacles to rapid technological progress in cryonics

Before I start with reviewing a number of causes it will be helpful to reiterate an earlier observation; the idea of technological progress in cryonics follows the recognition that reversible cryopreservation (or human suspended animation) is the ultimate goal of cryonics procedures and that we can evaluate cryonics cases with this framework in mind. This leads us to the first reason that can explain a slower pace of technological development.

No formal commitment to human suspended animation

Without a strong commitment to human suspended animation as a goal, a cryonics organization is at risk of becoming a freeze-and-repair operation that just goes through the routines without a framework to identify a route forward. While it can be argued that repair of the frozen brain is technically feasible and plausible, placing a critically ill patient in suspended animation leaves no doubt that the medico-legal status of a cryonics patient should be considered “alive.” When human suspended animation is recognized as a formal goal, a cryonics organization can be judged by its efforts to close the gap between its current technologies and this goal.

No recognition of the concept of patient care

Closely related to establishing a formal commitment to human suspended animation is the recognition that the concept of patient care in cryonics is meaningful and allows for setting standards of care. For example, a cryonics organization can aim for keeping the brain viable by contemporary medical criteria during stabilization, prevent dehydration and freezing of the brain following cryoprotection and cooling, and eliminate fracturing during long term care by storing closer to the glass transition temperature. In each case, data need to be collected to determine to what degree these goals were achieved. Careful scrutiny of case data can lead to designing new research questions or pushing standards to an even more ambitious goal.

One of the most formidable challenges in the field of cryonics is that there is no direct feedback in a way that is obvious and recognizable for most people. There are no patients returning home after the procedure and the only way to determine whether a cryonics organization delivers care to the standards it is technically capable of is to collect data on cooling rates, take blood samples, perform viability assays on microliter brain tissue samples, inspect the brain for ice formation, and analyze CT scans after cooldown.

When a cryonics organization is deemed capable of producing reproducible outcomes in a typical cryonics case, the framework of suspended animation can then be used to identify new technological innovations that will further improve the level of patient care.

Competing priorities and financial constraints

Naturally, when there is no money available for research, or to fabricate or purchase the new technologies, a cryonics organization can remain in technological stasis. Technological innovation is important but can’t be the only goal for a cryonics organization. A credible cryonics organization has the secure care of its existing patients as its most import goal. Even more time-consuming can be a high caseload, which can consume most of the time of technical and medical staff at the expense of technological innovation. As a general rule, most cryonics organizations also devote some resources to outreach and growth.

While it is correct that technological advances are usually passed on to members in the form of higher cryopreservation minimums, the fear of making cryonics too expensive for the average member has often delayed introducing new technologies. A good example is intermediate temperature storage. Replacing care at liquid nitrogen temperature for ITS systems will increase the cost of long term care (at least in its current incarnation). One way for a cryonics organization to ensure that research and technological development is not pushed below other priorities is to create a separate research fund and solicit targeted contributions. Cryonics organizations that enjoy generous financial support can also consider spinning off a separate research organization.

Lack of competent technical and scientific staff

For a cryonics organization it is important to recruit staff members who are scientifically literate and committed to technological innovation. This is not only important for staff members with technical responsibilities. When the whole staff of an organization shows strong support for technological progress it is possible to create a culture of scientific excellence. In contrast, if a cryonics organization lacks staff with solid scientific or clinical credentials, technological progress and good patient care will be compromised. This is also the case when staff members have formal scientific or medical credentials but show little initiative or are incompetent. Cryonics organizations are small and poor hiring decisions can have profound effects on the nature of the organization. Since it is usually easier to hire than to fire, such problems can be persistent and hard to reverse.

One risk in cryonics is that staff members who have excellent scientific credentials are recruited to work in other organizations and companies. As a consequence, the most technically savvy cryonicists are not employed in cryonics organizations. This potential development is another reason for a cryonics organization to spin off a separate research organization. In such a structure the finest minds in cryonics can devote their time to scientific and technological issues relevant to cryonics without being slowed down by other aspects of a cryonics organization.

A good example of a technology that is held back by the lack of enough medically qualified staff is field cryoprotection. In a sense, the idea of conducting cryoprotection on-site prior to shipping the patient to a facility first is as old as the idea of cryonics itself. Eliminating the prolonged ischemic times times associated with remote blood washout and patient shipment in favor of doing field cryoprotection near the location where the patient is pronounced legally dead would constitute a major improvement in patient care. Prolonged transport times on water ice are fundamentally incompatible with the aim of reversible cryopreservation. Unfortunately, only a handful of remote cryonics cases have been conducted as field cryoprotection cases. If field cryoprotection is done for all cases where this is technically preferable, substantial cost savings could be reaped as well. Making such a transition, however, would require that a cryonics organization always have access to case personnel or contractors who are competent at surgery and perfusion, and have good cryobiological knowledge.

High turnover of staff and leadership

When there is a high turnover of management and/or staff within a cryonics organization it is hard to make technological progress or conduct long-term research projects. New management and staff members may also have different perspectives about which technological developments to pursue and, as a consequence, R&D in progress is discarded or put on hold.

Closely associated with this is the loss of institutional knowledge. Having a broad and deep understanding of cryonics is important to identify and pursue new technological directions and evaluate the quality of care at an organization. Absent such (distributed) knowledge, a cryonics organization can remain in stasis or move in reverse. At the Alcor Life Extension Foundation there have been multiple cases in which the quality of care worsened relative to prior administrations or where routine technological procedures were (unconsciously) abandoned because of poor intuitional knowledge transfer. In a worst case scenario the cryonics organization does not know that it does not know and promotes itself as delivering excellent care and committed to technological innovation while mistakes and poor R&D are rampant.

Faulty commitment to cryonics

Faulty commitment may seem a strange problem for a cryonics organization to have. But it certainly was a problem in the early days, when some naïve businessmen perceived cryonics to be a get-rich-quick scheme, or otherwise had unrealistic expectations. The popularity of cryonics turned out to be not as high as projected, and funding to undertake and continue operations, including long term care, proved very limited. Baffled by the problems, most of these people left the field, sometimes being forced to abandon patients.

In more recent years cryonics organizations have faced a different kind of problem. Organizations such as Alcor and Suspended Animation can afford to pay market wages for most of their positions and wages above prevailing market values are not unheard of. As a consequence, seeking employment at a cryonics organization can be a rational course of action, regardless of any personal or professional interest in cryonics. In such a situation, a strong commitment to patient care and research is often lacking. Requiring staff to have cryonics arrangements in place is no longer a sufficient guarantee of dedication in these circumstances because obtaining cryonics arrangements can be considered just a small inconvenience for a well-paid job that lacks the usual professional scrutiny.

“The perfect is the enemy of the good”

One cause for a substantial delay between validation and implementation is to aim for a perfect technological solution before authorizing a technology to be used in cryonics. In reality this can mean that a technology that can already make a substantial contribution to patient care is withheld from the field. A prime example of such a technology, in my opinion, is liquid ventilation (or cyclic lung lavage). The feasibility and desirability of such a technology was established in the mid 1990s but at least 20 years has passed without formal deployment of this technology in cryonics despite various organizations having pursued its development. In fact, in this case a lot of the reasons for technological stasis in cryonics (such as high turnover of management and staff) seem to have colluded.

Another example may be intermediate temperature storage (ITS). If the recommended ITS temperature substantially reduces the amount of cracking but does not always eliminate it, a case can still be made for implementation this technology. This is particularly true if the brain is saved from fracturing events and the only remaining fractures can be healed through conventional surgery or organ replacement.

A related, but more subtle problem is not recognizing that a technology can be considered mature enough to make a contribution to cryonics but cannot be considered sufficiently developed for clinical use. A good example is organ vitrification. One might argue that the knowledge that sufficiently high concentrations of cryoprotectant can prevent ice formation existed for a long time in cryonics before it was introduced in the field. Since neither conventional cryopreservation nor vitrification could produce high viability readings, the only useful indicators for cryonics could have been inhibition of ice formation and histology. By these criteria even the vitrification solutions that did not produce good viability in slice work would have been a sensible replacement for the prevailing glycerol protocols.

Conclusion

Without formalizing reversible cryopreservation as a research and clinical goal, a cryonics organization is at risk of technological stasis and poorly positioned to identify, validate, and implement superior technologies that aim to close the gap between prevailing procedures and human suspended animation. Rapid technological progress in cryonics requires prudent hiring, a tech-savvy and scientifically literate staff, a stable culture committed to cryonics, a distinct R&D program, generous financial support, and the ability to prioritize technological needs based on research and observations made in casework.

Perhaps the most formidable obstacle to creating and sustaining such an infrastructure is the lack of obvious feedback in cryonics procedures. There is no revival or healing that can easily be understood by members and the general public. Thus there is only limited validation of, or motivation to insist on, good patient care and ongoing technological innovation. The vision that cryonics organizations should offer something better than store-and-repair has always had its advocates but its influence has remained limited and fragile.

If cryonics organizations would introduce liquid ventilation, field cryoprotection, and fracture free storage, there are three remaining technological challenges to achieving human suspended animation. These are (1) the design of a vitrification agent with no or negligible toxicity, (2) eliminating severe cryoprotectant-induced dehydration of the brain, and (3) optimum distribution of the cryoprotectant in whole body cases.