The case against cryonics

11. March 2011 · Comments Off · Categories: Cryonics, Neuroscience · Tags: , , , , , , , , ,

What is striking about cryonics is that those who have taken serious efforts to understand the arguments in favor of its technical feasibility generally endorse the idea. Those who have not made cryonics arrangements usually give non-technical arguments (anxiety about the future, loss of family and friends, etc), lack funding or life insurance, or are (self-identified) procrastinators. In contrast, those who reject cryonics are almost invariably uninformed. They do not understand what happens to cells when they freeze, they are not aware of vitrification (solidification without ice formation), they think that brain cells “disappear” five minutes after cardiac arrest, they demand proof of suspended animation as a condition for endorsing cryonics, etc.

This does not mean that no serious arguments could be presented. I can see two major technical arguments that could be made against cryonics:

1. Memory and identity are encoded in such a fragile and delicate manner that cerebral ischemia, ice formation or cryoprotectant toxicity irreversibly destroy it. Considering our limited understanding of the nature of consciousness, and the biochemical and molecular basis of memory, this cannot be ruled out. Cryonics advocates can respond to such a challenge by producing an argument that pairs our current understanding of the neuroanatomical basis of identity and memory to a cryobiological argument in order to argue that existing cryonics procedures are expected to preserve it. An excellent, knowledgeable, response of this kind is offered in Mike Darwin’s Does Personal Identity Survive Cryopreservation? Cryonics skeptics in turn could produce evidence that existing cryonics procedures fall short of this goal.

2. The cell repair technologies that are required for cryonics are not technically feasible. This argument should be presented with care and rigor because the general argument that cell repair technologies as such are not possible contradicts existing biology. A distinct difference from the first argument is that it is harder, if not impossible, to use existing empirical evidence to settle this issue. After all, making cryonics arrangements is a form of decision making under uncertainty and such decisions are not straightforwardly “correct” or “incorrect,” “right” or “wrong.” What can be done is to provide a detailed scientific exposition of the nature and scope of the the kind of repairs that are necessary for meaningful resuscitation and to argue that both biological and mechanical cell repair technologies are not conceivable – or are conceivable.

One thing that becomes immediately clear from this exercise is that there is no single answer to the question of whether cryonics can work because the answer to this question depends on the conditions and technologies that prevail during the cryopreservation of a patient. This introduces a set of more subtle distinctions concerning the question of what kind of cryonics should be assessed. It also produces an argument in favor of continuous improvement of cryonics technologies, and standby and stabilization services.

This short examination of technical arguments that could be made against cryonics gives advocates of the practice two talking points in discussion with skeptics or hostile critics:

(a) If a critic flat-out denies that cryonics is technically feasible, it is not unreasonable to ask him/her to be specific about what (s)he means by cryonics. This simple question often will reveal a poor understanding of existing cryonics technologies and procedures.

(b) A decision made on the basis of incomplete knowledge cannot be “right” or “wrong” and should be respected as one’s best efforts to deal with uncertainty.

Behavioral effects of ultraprofound hypothermia in rats

04. January 2009 · Comments Off · Categories: Death, Science · Tags: , , , , ,

This is the sixth entry in a series about resuscitation of non-hibernating rodents from circulatory arrest at ultraprofound hypothermic and high subzero temperatures. After successfully reanimating rats from deep body temperatures of 0 – 2 degrees C and subsequent respiratory and cardiac arrest, Andjus allowed the survivors to live for many months afterward in order to observe any long-term effects of hypothermia. What he noticed, beyond temporary weight loss and a couple of rats with impaired temperature regulation, was that animals that had been cooled did not appear to suffer any gross or debilitating effects. Although food intake and sexual behavior were initially diminished, the rats regained healthy appetites within a few days and went on to produce normal offspring within 3 months of cooling.

Andjus, having pioneered a method of resuscitation of rats from ultraprofound hypothermia, also had occasion to take the first look at the effects of hypothermia on learning and memory. In his brief 1955 Nature publication, “Effects of Hypothermia on Behaviour,” Andjus first compared the ability of cooled (0-1 degrees C) vs. untreated (control) rats to learn a serial problem-solving task. Next, he compared two groups of rats cooled to different temperature ranges (0-1 degrees C and 13.4 – 18.5 degrees C) to controls in a classical maze-learning paradigm. Rats were trained on the maze, cooled, tested for retention, and finally trained on a serial problem-solving task.

The results showed a significant impairment in problem-solving ability in rats cooled to 0-1 degrees C compared to controls, but not in rats cooled to 13.4 – 18.5 degrees C. However, the effect was only temporary, as demonstrated by the fact that impairment decreased as the interval between cooling and testing increased. And though memory retention was also affected by hypothermia, Andjus stated that “the differences among experimental and control groups were very small, and in no instance were they statistically significant,” indicating that even severe hypothermia does not produce permanent long-term physical or behavioral changes.

These initial results were supported in another experiment by N. Mrosovsky in 1963, who reported that severe hypothermia did not affect the response of rats to a conditioned avoidance task when cooling was begun only 15 minutes after animals were trained to criterion. In this task, rats were placed in an apparatus with electrified wire flooring such that either side of the cage floor was capable of shocking the animal. To facilitate one-session avoidance learning, the rats were first taught that they could escape from shock by undergoing 20 shock trials at varied time intervals (30, 60, 90, and 120 seconds) in random order. Then they were conditioned to avoid the shock (conditioned response) by responding immediately to a light (conditioned stimulus) that came on inside the dark experimental room 8 seconds before the shock. The light stayed on until the rat crossed the dividing line between the two sides of the apparatus. When they reached the criterion of six successive avoidance responses, experimental animals were returned to their home cages for 15 minutes before cooling was initiated and rewarming was carried out under a bench lamp. Control animals remained in their home cages until retesting.

Both experimental (cooled) and control (untreated) groups were retrained in the avoidance task 13 days after hypothermia. On Day 14, after three successive avoidance responses, training was continued, but the shock came on in the opposite side of the box at the same time as the light (both were on for 8 seconds). The rat was successful in this “reversal procedure” if it stayed on its side of the apparatus while the light was on six consecutive times.

He reported no significant differences in initial learning, citing a median number of trials to criterion of 9.5 for cooled animals and 11.0 for controls on Day 13 retesting. The median number of shocks received was also similar (3 vs. 2) in both groups. There were also no significant differences in reaching criterion on Day 14 re-testing, nor in the reversal procedure.

Mrosovsky wisely points out in his interpretation of these results that

It must not however be assumed from the lack of evidence that hypothermia readily disrupts retention that behavior is unaltered. In the work of Andjus et al. (1956) and that of Sudak and Essman (1961), while retention was not changed, the ability on problem solving and habit reversal were decreased, even several weeks after the cooling.

He goes on to mention that the “motivating conditions” of those experiments are different from his own, which may explain differences in results, but also says that it may be possible that initial learning is more likely to be altered than retention after hypothermia. According to this hypothesis, he classes hypothermia along with anesthetics in  the category of agents having mild retroactive effects on learning and memory (i.e., those affecting memories consolidated immediately before the interfering event).

Viability in brain cryopreservation

12. May 2008 · Comments Off · Categories: Cryonics, Neuroscience · Tags: , , , , , ,

Because the current generation of vitrification agents permit cryopreservation of the brain without ice formation, the current objective of cryonics research is maintenance of viability of the brain during cryopreservation. The most popular viability assay that has been used in cryonics and cryonics-associated cryobiology research is the potassium/sodium ratio (K+/Na+ ratio). Because the ability of a cell to regulate its ionic composition reflects and affects many other biochemical processes, the K+/Na+ ratio is a good measurement of viability in general. For example, all the brain slice experiments to validate the Cryonics Institute’s vitrification agent VM-1, were assessed using the K+/Na+ ratio as a measure of viability.

In the case of the brain, demonstrating such “basic” viability after vitrification is a necessary, but perhaps not sufficient, condition for reversible vitrification of the brain without adverse (long term) effects. Recovery of function in the brain is a more subtle concept than in other organs. In 2007, 21st Century Medicine reported maintenance of long-term potentiation (LTP) in vitrified brain slices. Chana de Wolf proposed more specific experiments to demonstrate maintenance of memory after cryopreservation. And more specific molecular assays could assist in illuminating the effects of cryoprotective perfusion, cryoprotectant toxicity, and cryogenic cooling on the brain. Such viability and functional assays can be correlated and combined with structural assays to assist in developing cryoprotective solutions, and perfusion and cooling protocols that will permit successful resuscitation of whole brains after vitrification.

Further reading: Securing Viability of the Brain in Cryonics

Characterization of afterhyperpolarization (AHP) in cryopreserved brain slices

13. September 2007 · Comments Off · Categories: Cryonics, Neuroscience · Tags: , , , , ,

An ongoing quest in cryonics is the successful demonstration of memory sustainment after cryopreservation of the brain and rewarming from cryogenic temperatures. To that end, landmark experiments were performed by Pichugin, et al. (2006) on rat hippocampal brain slices which indicate that the hippocampus retains excellent structural integrity and viability (as measured by Na+/K+ ion pump recovery) after vitrification, rewarming, cryoprotectant removal, and exposure to 35°C for over an hour. To address the question of memory itself, investigations into the maintenance of long-term potentiation (LTP) after vitrification of the brain are currently in progress. But even successful observation of LTP after cryopreservation provides only indirect evidence for memory maintenance.

Alternatively, post-burst afterhyperpolarization (AHP) of hippocampal CA1 neurons may be characterized after cryopreservation of animals that have successfully acquired a hippocampus-dependent task. CA1 pyramidal neurons show decreased post-burst AHPs and less accommodation (i.e., increased firing frequency) following learning of such hippocampus-dependent tasks as trace eyeblink conditioning (Moyer et al., 1996, 2000; Thompson et al., 1996) and spatial watermaze training (Oh et al., 2003) with a time course appropriate to support memory consolidation. Furthermore, CA1 neurons of aging animals (i.e., animals at ages that exhibit learning deficits) show greater AHPs and more accommodation than those of young animals (Landfield & Pitler, 1984; Moyer et al., 1992, 2000), indicating an age-related decrease in neuronal excitability in the hippocampus that may underlie learning deficits related to aging.

A carefully designed experiment demonstrating reduced afterhyperpolarization and accommodation in hippocampal CA1 neurons after acquisition of a hippocampus-dependent task and subsequent cryopreservation of the brain would be a huge step in the direction of proving that memories can be cryopreserved.