An Interview with Aschwin de Wolf on Cryonics at LongeCity
Aschwin de Wolf of Advanced Neural Biosciences and the Institute for Evidence-Based Cryonics (IEBC) is a noted advocate for cryonics as an industry and area of research. He was recently interviewed by the folk over at LongeCity, and as usual it makes for interesting reading. You might also look at a 2013 interview for more of the same, and in addition you'll find many articles at the IEBC site covering a mix of technical and non-technical topics in the the cryonics field. This is one slice of a great deal of technical writing and advocacy for cryonics published over the course of the past few decades, a fair portion of it by people who are now themselves cryopreserved at Alcor or the Cryonics Institute.
The term cryonics covers the technology, community, and practice of placing people into a vitrified state as soon as possible following clinical death. Tissues are perfused with cryoprotectant and cooled to liquid nitrogen temperatures in stages, leading to a glass-like state of minimal ice-crystal formation. Under good conditions, this preserves the fine structures of neural tissue, the synapses, dendrites, and dendritic spines within which the data of the mind is thought to be stored. For so long as that data remains intact, and the vitrified individual in low-temperature storage, there is the possibility of future restoration in an era with more proficient technology than our own. In this age of progress, cryonics is a necessary backup plan for those of who may not live long enough to benefit from the near future of rejuvenation therapies after the SENS model. It is a great pity that it remains a small and marginal undertaking, largely non-profit, and unknown to many who would benefit, even as tens of millions march towards their own personal oblivion each and every year.
While higher animals cannot yet be thawed, cleared of cryoprotectant, and brought back to life, that outcome can be achieved with lower animals such as nematode worms. Thawing and transplantation has also been demonstrated in prototype for mammalian organs in recent years. At present there is the makings of a small industry working on reversible cryopreservation for tissue engineering and organ transplantation, where such a technology would greatly reduce costs and simplify logistics. So when we talk about preserving people for the chance at a future restoration, this isn't done in a vacuum, and isn't a flight of fancy; there is good reason to think that there is a chance of success in this endeavor. It certainly beats the odds of revival from the grave, which is to say zero.
Interview with Aschwin de Wolf (February, 2017)
How has the cryopreservation procedure evolved since the first human was placed in cryostasis?
The most important element in the progress of cryopreservation procedures in cryonics is the progressive elimination of ice formation. When cryonics started, patients were often cryopreserved without any cryoprotection or very low concentrations of cryoprotectant. In the 1980's and 1990's organizations such as Alcor started adapting mainstream perfusion technologies to introduce high concentrations of cryoprotectants (such as glycerol) to mitigate ice formation. In 2000 Alcor formally introduced vitrification with the aim of eliminating freezing altogether.
The elimination of ice formation, which can be achieved in good cases, removes one major form of mechanical damage in the cryopreserved brain. One very attractive feature of a low-toxicity vitrification agent like M22 is that it does not require rapid cooling to prevent ice formation. Under good circumstances (no prior ischemia) it can also be used in whole-body patients without edema - a problem that seemed to plague prior DMSO-based cryoprotectants in cryonics. Elimination of ice formation and reduced toxicity has substantially reduced the degree of damage associated with cryopreservation.
Which foreseeable advances in the field of cryobiology do you believe will lead to improvements in cryonics?
I foresee further advances in two areas; a more detailed understanding of the nature of cryoprotectant toxicity and the design of brain-optimized cryoprotectants. Cryoprotectant toxicity is currently the most formidable obstacle preventing reversible cryopreservation of complex mammalian organs. With the exception of the work of Dr. Greg Fahy and his colleagues at 21st Century Medicine, it is rather surprising how little theoretical and experimental research has been done to illuminate the mechanisms of cryoprotectant toxicity. It is also increasingly recognized that the poor penetration of cryoprotectants across the blood-brain barrier causes dehydration of the brain. We need to develop brain-optimized vitrification solutions and/or identify better methods to deliver cryoprotectants to the brain without such significant changes in brain volume. Resolving these two issues will bring us much closer to reversible brain cryopreservation.
What evidence is there that the brain is not damaged by the cryopreservation process to such an extent that the information in it may be lost forever?
To start with, if we can eliminate ice formation in the brain, the damage associated with cryoprotectant toxicity is assumed to be mostly of a biochemical nature (i.e. denatured proteins) and does not alter the ultrastructure of the brain in a way that precludes inferring the original state. Cryoprotectant-induced dehydration of the brain is a little more of a wild card because we do not have much detailed information about the kind of ultrastructural changes associated with it. Hence, the priority to avoid the brain shrinking that is routinely observed in "good" cases. Ultimately, our incomplete knowledge of the neuroanatomical basis of identity, and about the exact capabilities and limits of future medicine, prompt us to be agnostic about the degree of damage that is still compatible with meaningful revival. Advocates of cryonics are sometimes accused of being too optimistic about future science, but perhaps skeptics are too pessimistic.
To our knowledge (which is based on cryobiological studies and theoretical calculations), deterioration of patients stored at cryogenic temperatures should be non-existent or negligible. Things get a little bit more complicated when we store patients at intermediate temperatures instead of liquid nitrogen temperatures. It has been suggested that nucleation may still occur slightly below the temperature where the vitrification solution turns into a glass (-123 degrees Celsius). At that temperature, however, nucleation does not translate into ice formation but it might create more challenging repair and revival scenarios.
Do you have any hypotheses on how the cryoprotectant could be removed from the body during the reanimation procedure and how hypoxic injury during this removal procedure could be prevented?
In the vision of researchers such as Robert Freitas and Ralph Merkle, a mature form of mechanical nanotechnology will be used to conduct the initial stages of repair and cryoprotectant removal at cryogenic temperatures. If this vision of nanotechnology is plausible, cryoprotectant can be removed while providing (local) metabolic and structural support to prevent damage or freezing. An alternative vision of nanomedicine will involve the use of biological repair machines such as modified viruses or modified white blood cells that operate using conventional diffusion-driven chemistry rather than molecular mechanical nanotechnology. Repair is more challenging in this biological scenario because tissue first needs to be warmed to temperatures at which the cryoprotectant solution inside cells and tissue becomes liquid. This risks movement of damaged structures, possible growth of ice, and cryoprotectant toxicity accumulation occurring at the same time as repairs are being made.
Cryogenic storage of genetic mutants is already a common procedure in the roundworm C. elegans. Are you aware of any research taking place that tries to expand cryogenic storage to other model organisms?
Natasha Vita-Moore, who conducted recent studies on the effects of vitrification on memory in C. elegans, has suggested that the next step would be a slightly more complex organism such as the Greenland Woolly Bear Caterpillar or the ozobranchid leech. One of the most common suggestions I get is to attempt suspended animation on a mouse or rat. This would definitely provide powerful proof of principle for the feasibility of human suspended animation, but I do not think that the challenges in achieving reversible biostasis in a small mammal are that much smaller than in humans. We would need to overcome the same obstacles: minimizing cryoprotectant toxicity, chilling injury, dehydration of the brain, ischemia during cooling, and cryoprotective perfusion, etc. The majority opinion in cryonics is to solve these individual problems more thoroughly before attempting reversible cryopreservation of a complete animal.
"the poor penetration of cryoprotectants across the blood-brain barrier causes dehydration of the brain" This reminded me of an article about research on using focal ultrasound to treat Alzheimers. It claimed that the ultrasound could temporarily open the blood-brain barrier and allow metabolic garbage to flow out. (This correlated with an association of insomnia with higher risk of Alzheimers, because recent research shows that during sleep the lymphatic vessels in the brain dilate and allow metabolic garbage to traverse the blood-brain barrier.) My question is whether this focal ultrasound process would still work on those who have suffered very recent clinical death. If it did, could this facilitate getting cryoprotectants more effectively across the blood-brain barrier?