Neural cryobiology and the legal recognition of cryonics

It has been said that if you want to persuade someone, you need to find common ground. But one of the defining characteristics of cryonics is that proponents and opponents cannot even seem to agree on the criteria that should be employed in discussing cryonics. The cryonics skeptic will argue that the idea of cryonics is dead on arrival because cryonics patients are dead. The response of the cryonics advocate is that death is not a state but a process and there is good reason to believe that a person who is considered dead today may not be considered dead by a future physician. In essence, the cryonics advocate is arguing that his skeptical opponent would agree with him if he would just embrace his conception of death….

Cryonicists have named their favorite conception of death “information-theoretic death.” In a nutshell, a person is said to be dead in the information-theoretic sense of the word if no future technologies are capable of inferring the original state of the brain that encodes the person’s memories and identity. There are a lot of good things to be said about substituting this more rigorous criterion of death for our current definitions of death. However, in this brief paper I will argue that our best response does not necessarily need to depend on skeptics embracing such alternative definitions of death and that we may be able to argue that opponents of cryonics should support legal protection for cryonics patients or risk contradicting conventional definitions of death.

In contemporary medicine, death can be pronounced using two distinct criteria; cardiorespiratory arrest or brain death. A lot of ink has been spilled over the co-existence of those criteria and its bioethical implications but I think that most people would agree that the practice of medicine requires this kind of flexibility. What is interesting for us is that clinical brain death (or brain stem death) is defined as “the stage at which all functions of the brain have permanently and irreversibly ceased.” There are a number of ways how such a diagnosis can be made, but in this context I want to focus on the absence of organized electrical activity in the brain.

We first should note the use of the word “irreversible.” After all, if a patient is cooled down to a low core temperature to permit complicated neurosurgical procedures most of us would not say that this person is “temporarily brain dead.” As a matter of fact, one could argue that cryonics is just an experimental extension of clinical hypothermic circulatory arrest in which there is a temporal separation of stabilization and treatment. Now, we could argue that what may be irreversible by today’s standards may not be irreversible by future standards but then, again, we are trying to persuade the other person to accept our view of future medicine. It would be much better, and I hope much easier, to argue that contemporary cryopreservation techniques can preserve organized electrical activity in the brain. The advantage of this approach is obvious. Instead of arguing in favor of our own criterion of death we can argue that, according to mainstream criteria for determination of death, cryonics patients are not dead. This is an interesting case in which a scientist (i.e., a cryobiologist) may be able to make a major contribution to the legal recognition and protection of cryonics patients.

So where are we standing right now? How good are our preservation techniques? If we aim for reversible whole brain cryopreservation a cryoprotective agent should have two properties: (1) elimination of ice formation, and (2) negligible toxicity. In the early days of cryonics, we were not able to satisfy both criteria at once. Using just a little bit of glycerol would not be toxic but it would still allow massive ice formation. Using a lot of a strong glass former such as DMSO would eliminate ice formation but at the price of severe toxicity. Mostly due to the groundbreaking work of cryobiologists Gregory Fahy and Brian Wowk, in the year 2000 the Alcor Life Extension Foundation introduced a vitrification agent called B2C that eliminated ice formation and had a more favorable toxicity profile. In the year 2005, the separation between the state of the art in experimental cryobiology and cryonics practice was further narrowed when Alcor introduced M22 as their new vitrification agent. M22 is the least toxic vitrification agent in the academic cryobiology literature that permits vitrification of complex mammalian organs at a realistic cooling rate.

M22 and other solutions derived from the same cryobiological principles have been validated in the brain as well. Former Cryonics Institute researcher Yuri Pichugin and collaborators used a related vitrification solution for the preservation of rat hippocampal brain slices without loss of viability after vitrification and rewarming. At a cryonics conference in 2007, 21st Century Medicine announced that the use of M22-based solutions permitted the maintenance of organized electrical activity in rabbit brain slices. So, at this stage we can argue that our existing vitrification solutions have a reasonable chance of maintaining organized electrical activity in brain slices. The next challenge is to demonstrate this property in whole brains.

Whole brain cryopreservation is not just the cryopreservation of a great number of individual brain slices. Brain slices can be cryopreserved by (step-wise) immersion in the vitrification solution. Vitrification of whole brains (even small brains such as rodent brains) requires the introduction of the vitrification solution through the circulatory system. This aspect of whole brain vitrification presents a number of technical challenges. Electron micrographs of vitrified tissue from whole brains, however, indicate that these challenges can be overcome. The current research objective is to perfect perfusion techniques and optimize vitrification solutions to maintain organized electrical activity in whole brains. We know that this objective is possible in principle because the famous surgeon Robert White demonstrated retention of electrical activity in whole isolated brains after cooling them to ~2-3°C. Isolated brain perfusion is a complicated surgical procedure, but the current writer and cryobiologist Brian Wowk have recognized that validation of whole brain activity is also feasible in situ.

Reversible cryopreservation of the whole brain without losing organized electrical activity is not a trivial research objective but it should be easier to achieve than reversible cryopreservation of the whole body and, perhaps, some other organs. If and when we accomplish this, we will no longer be dependent on “rationalist” arguments that appeal to logic and optimism about the future. We can argue that our patients should not be considered dead by the most rigorous criterion for determination of death in current medical practice. We can then even mount some smart legal challenges to seek better protection for cryonics patients. If we can make this step forward we should also aim at improved protection of existing cryonics patients, which will allow them, among other things, to own assets and bank accounts. This is how science can be employed in legal strategies for asset preservation.

This article is a slightly revised version of a paper that accompanied a recent presentation on neural cryobiology and the legal recognition of  cryonics at the 5th Asset Preservation Meeting in Benicia, California.

Cryonics and philosophy of science

The 2008-3 issue of Alcor’s Cryonics Magazine contains a number of articles about the pitfalls of (excessive) scientific optimism and its potential adverse effects on the organizational and practical aspects of cryonics. My own contribution contrasts cryonics as medical conservatism with the kind of scientific meliorism that is often associated with movements such as transhumanism and singularitarianism. In particular, I express reservations about the arguments that intend to show that reversible cryopreservation and resuscitation of cryonics patients is inevitable because the required technological advances do not contradict our current understanding of the laws of physics. Instead of relying on abstract “rationalist” arguments I propose to focus more strongly on generating and disseminating empirical evidence that people who are engaged in science and medicine today will find persuasive, especially as it pertains to revising our contemporary definitions of death.

The same issue also contains an important contribution by Glen Donovan about the relationship between science and cryonics. Is cryonics a science? If it is not a science, what is it? This piece discusses cryonics from the perspective of the philosophy of science. This is an approach that has received little attention to date but it seems to me that the status of cryonics and its associated research programs can benefit from  discussing cryonics utilizing the tools and concepts of analytic philosophy. In particular, one project that could constitute an  important contribution would be to give specific empirical meaning to a concept like information-theoretic death.

Aschwin de Wolf – Scientific Optimism and Progress in Cryonics (2009)

The purple prose of suspended animation

Esquire magazine features an article on scientist Mark Roth and his research into “suspended animation.” As the website title “The Mad Scientist Bringing Back the Dead…. Really” indicates, this is not supposed to be a detailed account of Ikaria’s recent advances in induction of depressed metabolism but a sensationalist piece on mad scientists. Although the piece states that “Ikaria’s first suspended-animation product” has “completed Phase 1 trials in Australia and Canada” and is “being tested on humans, to make sure it’s safe” it remains to be seen if this technology involves major advances in rapid induction of depressed metabolism in humans or offers just another treatment option for various hypoxic-ischemic conditions as the press release (pdf) seems to indicate.

The article misses a number of opportunities to set the record straight on the proper use of terminology and prevailing definitions of death. The ability to resuscitate an organism from circulatory arrest, depressed metabolism, or suspended animation implicates that the organism was not dead to start with. This is not just a matter of semantics. The phenomenon of death is surrounded by many cultural and religious taboos and the difference between saying that we can  bring back the dead instead of  observing that recent advances in science and medicine requires us to redefine our definition of death  is not a trivial matter. Most religious people do not object to cardiopulmonary resuscitation or hypothermic circulatory arrest because they do not believe that a patient who is resuscitated in such medical procedures was (temporarily) dead. The word death should be reserved for a condition in which integrated biological function cannot be restored by either contemporary or future technological means.

Increasingly, the phrase “suspended animation” is thrown around to describe a number of distinct phenomena ranging from modest drops in metabolism to complete metabolic arrest. If the word  is taken literally, however, only complete metabolic arrest constitutes real suspended animation. Such a state cannot be achieved in humans by the use of hydrogen sulfide (or its injectable derivatives) and requires either the use of extreme cold such as practiced through vitrification in cryonics or the use of advanced nanotechnology in warm biostasis.

Popular reports on recent developments in “suspended animation” do not carefully distinguish between the results obtained with hydrogen sulfide and carbon monoxide in C. elegans and mice and its applications in humans. Until more detailed information is available on the use of these substances in large animals or humans it should not be assumed  that rapid pharmacological induction of depressed metabolism in humans is a clinical possibility.