A Suspended Animation Research Hierarchy

By Brian Wowk, Ph.D.

Reversible long-term suspended animation of humans or other mammals is a vastly complicated problem, the difficulty of which is often underappreciated.

This has implications for research.

The term “suspended animation” has been used to describe diverse procedures. They range from deep hypothermic circulatory arrest (DHCA) and emergency preservation and resuscitation (EPR) for minutes, to hypothetical slowing of metabolism (torpor) for weeks or months similar to hibernating animals, to solid state cryopreservation (biostasis) for indefinite periods of time.

Solid state cryopreservation below -120°C is essential to achieve a state that’s stable for long time periods (decades or centuries). With rare exceptions, freezing to any temperature naturally found on Earth isn’t cold enough for long-term stability. Even though frozen tissue may feel solid at -20°C, cell contents are still liquid between ice crystals.

True long-term stability is only achieved by cooling to a temperature below the glass transition temperature of unfrozen liquid (between -90°C and -130°C, depending on technical factors). Below the glass transition temperature, all unfrozen liquid becomes solid. However, returning an adult human to a healthy state after cooling to such cold temperatures is still hypothetical and highly theoretical because of extensive damage from ice crystals or cryoprotectant chemicals added to prevent ice crystals from forming.

Progress has been made on reversibly cryopreserving individual vital organs. However cryopreserving and recovering in parallel all vital organs and other body parts necessary for healthy life is a daunting problem for many reasons. They include differences in absorption of cryoprotectant chemicals, different response to toxicity of cryoprotectant chemicals, and different sensitivities to ice formation across tissue types.

Since the problem of demonstrably reversible solid state suspended animation of humans will not be solved anytime soon, it might be asked what can best be done to work toward that goal. Trying to revive whole animals from progressively lower such-zero temperatures is not the type of research needed now. (Nor would such research be ethical, in my opinion, precisely because it’s not very useful right now.) Instead, a hierarchical approach is needed, one that leverages existing technology and cryobiology knowledge to most rapidly achieve the objectives for which suspended animation is desired.

The Purpose of Suspended Animation

One of the most sought-after applications of suspended animation is medical time travel: travel to future treatments for diseases and injuries that aren’t presently treatable. Robert Ettinger was among the first to realize that cryopreservation itself was such an injury. This led to the practice of cryopreserving humans without demonstrable reversibility (cryonics) based on the premise of future treatment of cryopreservation injury. For cases in which such treatment proves to be possible, cryonics would be suspended animation, at least retrospectively.

The practice of cryonics compels questions about what are the most advanced medical technologies that could exist. These questions can be alternatively formulated as the question: What is the minimum requirement for human survival? The prospect of arbitrarily sophisticated analysis and repair on a molecular level led cryptography expert, Ralph Merkle, to articulate the concept of “information theoretic death.” Information theoretic death is the loss of brain structures encoding memory and personal identity to such an extent that the original person could not be uniquely recovered by any computational inference. Conversely, the minimum requirement for human survival is the persistence of sufficient brain information to permit inference and restoration of the brain and mind of the original person.

The recognition that preservation of brain structures encoding personal identity is the minimum necessary attribute of a suspended animation technology leads to the following research priorities for development of suspended animation for medical time travel:

1) Develop and validate preservation methods that preserve brain structures believed to encode memory.

2) Develop demonstrably reversible brain cryopreservation as direct evidence of life preservation and to reduce burden on future brain repair technology.

3) Progressively develop demonstrably reversible cryopreservation of all vital organs, other organs, tissues, and eventually the whole body in parallel.

Suspended animation research can thus be viewed as a hierarchy of three levels of importance: Human Life Preservation, Demonstrably Reversible Brain Preservation, and Demonstrably Reversible Suspended Animation, with each level including the ones above it.

Human Life Preservation

Definition:

The preservation of sufficient brain information to permit functional restoration of the preserved person, even if such restoration isn’t yet demonstrable. An equivalent definition is preservation that prevents information theoretic death.

Potential Contemporary Examples:

* Brain vitrification using state-of-the-art cryoprotectant solutions

* Aldehyde Stabilized Cryopreservation (ASC) of the brain

Commentary

If a preservation process isn’t demonstrably reversible, then assessing whether the process is life-preserving in any individual case or in general depends on theoretical neuroscience analysis. Hence there are debates about brain vitrification, ASC, chemical fixation, “straight freezing,” and whether or not they preserve the connectome and/or other essential neuroanatomical/chemical aspects of memory and personal identity.

While it’s been argued that destructive scanning and/or computer emulation of some preserved brains might permit “restoration” of a person sooner than in-situ repair and biological resuscitation, I’m not aware of any brain preservation method that commits to such exotica to the exclusion of biological revival. For example, aldehyde-stabilized cryopreservation (“fixation and vitrification”) was first proposed by Eric Drexler in conjunction with reversal by in-situ repair and biological restoration. For further reference, the book by Robert Freitas, Cryostasis Revival reviews practically every repair scenario ever proposed for preserved brains.

Relevance for Contemporary Suspended Animation Research

From the standpoint of personal survival of people living today, there is immediate utility in validating and improving the brain preservation quality of contemporary preservation methods. Medical repair technologies won’t stop advancing after demonstrably reversible suspended animation is achieved. Someday it will become apparent in hindsight that there were prior preservation methods that were “good enough” to carry people to technology sufficient for restoration from that preservation. Whether such methods exist today is still debated. Refinement and improvement to remove doubt is the most leveraged medical time travel research possible today.

It’s necessary to acknowledge adverse aspects of deploying life-preserving technologies that aren’t demonstrably reversible. Those effects include the slippery ethical slope of offering hope with minimal feedback loops, and the negative societal perception of that. Yet, without early use of preservation technologies that might be sufficient to save life from a long-term perspective, few people living today would see demonstrably reversible suspended animation.

Demonstrably Reversible Brain Preservation

Definition:

Brain cryopreservation with demonstrable return of normal brain function after cryopreservation.

Commentary

If brains restored after cryopreservation could be demonstrated to retain original memories and personality, this would be an empirically validated Human Life Preservation technology. The need to regenerate and properly reintegrate all the other tissue and organs, including nervous system, of a healthy person would still be an enormous challenge that might require the medical technology of a different century. But that a preserved person was still “there” could be known with certainty.

Proper anesthesia or sedation when reperfusing a living brain with warm oxygenated blood is of paramount ethical concern. Research assessments of functional integrity and memory preservation must be reconciled with this need.

Relevance for Contemporary Suspended Animation Research

Demonstrably Reversible Brain Preservation is a technological Holy Grail, of sorts, for suspended animation. It’s a major concern because the brain is the one and only organ that must be successfully preserved for suspended animation to be successful. The ability to reversibly cryopreserve other vital organs would be a of great medical value, but the importance of the brain for suspended animation is unique.

Demonstrably Reversible Suspended Animation

Definition:

Human cryopreservation with demonstrable long-term recovery of the whole intact person

Commentary

The first cryoprotectants were discovered almost 80 years ago. Yet cryopreserving whole large animals is still an extremely difficult problem. It’s difficult because career experts in cryobiology, with all their postdocs, graduate students, technologists, and infrastructure of large academic institutions still labor mightily to develop demonstrably reversible preservation methods for small organs and tissue pieces. Although there are reasons for optimism this century, not a single vital human organ has yet been reversibly cryopreserved. Cryopreservation methods for different cells and tissues are often distinct and optimized for the particular material of interest. There are thousands of different papers on sperm preservation alone. Of course sperm present at the time of cryopreservation need not necessarily survive for a suspended animation method to be consisted successful. But that so much effort can be expended on optimizing cryopreservation of one particular cell type is indicative of how challenging the problem of cryopreserving all cell types in parallel is.

Some tissues and organs could be acutely sacrificed and replaced for a suspended animation process to still be considered useful for medical time travel or space travel. Although cryobiology can almost certainly do better, in the worst case, the brain is the only organ for which repair and restoration is absolutely necessary for a suspended animation process; everything else can theoretically (albeit tediously and inconveniently) be regenerated.

The freedom to use tissue and organ regeneration as part of a suspended animation process is a good and necessary argument for the intrinsic feasibility of developing solid state suspended animation. Given the heterogeneity and vastly different perfusion properties of tissues and organs throughout the body, I personally believe it’s unlikely that there will ever be a way for a whole human to enter and then leave a solid state without sophisticated repairs to restore health. A cryopreserved person is likely to be a very sick person without a very sophisticated restoration process.

There’s even an argument to be made that practical reversible whole human suspended animation might intrinsically require molecular nanotechnology. This shouldn’t dissuade vigorous study of all aspects of cryobiology, including cryoprotectant toxicity, improved cryoprotectants, improved perfusion methods, improved cooling methods, improved cold tolerance, improved warming methods, improved recovery interventions, all leading to successful cryopreservation of an ever-increasing complexity and diversity of living things. But even all that might not be enough for solid state whole human suspended animation without medicine that diagnoses and treats on a molecular level.

Relevance for Contemporary Suspended Animation Research

Cryobiology has finally reached a stage where reversible cryopreservation of individual vital organs is within reach. It’s already being achieved for some small animal organs. It’s conceivable that in the not-to-distant future, some lab might cryopreserve a whole rat, reperfuse it with warm oxygenated blood, and then briefly recover some type of cardiac activity. Sensational headlines would result. However it would be a mistake to consider it a successful suspended animation experiment. As exciting as successful individual organ cryopreservation is, recovery of whole adult mammals from cryopreservation below -100°C without lethal injuries is realistically many decades away. While that work is done, the most important organ to master cryopreservation of for medical time travel purposes is the brain.