16. May 2011 · Comments Off on Neural cryobiology and the legal recognition of cryonics · Categories: Cryonics, Death, Neuroscience · Tags: , , , , , , , , , , , ,

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.

24. December 2008 · Comments Off on Robert White on brain death · Categories: Cryonics, Death, Neuroscience · Tags: , , ,

Robert J. White is most known, or perhaps most notorious, for his work on primate head transplants. Less known, but more relevant to the practice of human cryopreservation, is his work in cerebral ischemia, hypothermia, and brain preservation. Most of White’s innovative work was published in the 1960s and 1970s. White also published a substantial number of opinion pieces on a variety of topics. One of these topics is brain death.

In an 1972 editorial for the publication Hospital Progress, “The Scientific Limitation of Brain Death,” White notes that:

…we have to acknowledge the probability that eventually all of the major cellular complexes of the human body will be replaceable either by transplanted organs (man or animal) or by sophisticated engineering modules.

As a consequence, the clinical definition of death is shifting from cardiopulmonary criteria to the central nervous system. But unlike other organs,

…this system is not replicatable, representing as it does the repository of the highest functions of man…when this elite cellular system fails it would seem reasonable to assume that what is characteristically ‘human’ is also being lost from the body.

But just as the cardio-respiratory definition of death has evolved and changed with the clinical practice of cardiopulmonary resuscitation,  a similar fate may be in store for the definition of brain death. The clinical use of general anesthesia and hypothermic circulatory arrest, in which the brain can be put “on pause,” emphasize how important the aspect of “irreversibility” is.

As presently defined, the definition of brain death puts much emphasis on brain function upon physical examination. A major limitation of this definition is that it categorically ignores the prospect that brain function could be restored in the future by technologies more advanced than practiced today, provided the material basis of brain function is preserved.

Another challenge is that the science of cryobiology has advanced to such a state where brain slices can be preserved at subzero temperatures and recovered without loss of viability through vitrification. When recovery of organized electrical activity can be demonstrated in vitrified mammalian whole brains, the prevailing definition of brain death will need to be challenged again because it will open the practical possibility to maintain critically ill people in a state of low temperature circulatory arrest without producing one of the indicators of irreversible brain death. Such advances would be an extension of the  experiments Robert White did on isolated hypothermic brains.

As White stresses in the final paragraph of his paper:

…like all biological activity, life and death merge into one another representing a continuum and the neuro-scientist can only in the final analysis determine the point of irreversibility of this highly complex system at which the possibility of organized activity that characterizes human behaviour  has been exceeded.