Tag: Suspended Animation

Life in non-aqueous solutions

Can life exist without water? This is one of the questions that fascinates astrobiologists. The behavior of biomolecules in non-aqueous solutions is also of interest to cryobiologists and cryoenzymologists. Ice formation below zero degrees Celsius can be prevented by high concentrations of cryoprotective agents. But what are the effects of such vitrification agents on proteins?

In 1989 Alexander M. Klibanov published a paper called “Enzymatic Catalysis in Anhydrous Organic Solvents” that reports that enzymes are not only able to function in anhydrous organic solvents, but that some display remarkable properties in such environments like enhanced storage stability, solvent-induced changes of enzyme stereoselectivity, molecular memory, and reactions that are normally inhibited in aqueous solutions.

Upon reading the paper it is clear that when the author speaks of anhydrous solvents it is not implied that enzymes do not require water at all:

“…the key question should be not whether, but how much, water is required for enzymatic activity. Clearly, the enzyme molecule cannot ‘see’ more than a monolayer or so of water around it. Therefore, if this layer of ‘essential’ water is  somehow localized and kept on the surface of the enzyme, then all the bulk water should be replaceable with organic solvents with no adverse effects on the enzyme.”

To assure enzymatic activity in organic solvents two rules must be followed. First, hydrophobic solvents are preferred.  The authors propose that hydrophilic solvents ‘strip’ the essential water from the enzymes, and thereby reduce or eliminate the activity of enzymes. Second, the enzymes to be used in organic solvents need to be lyophilized (freeze dried) from aqueous solutions  with the pH optimal for their activity. This last requirement reflects the phenomenon of “pH memory” in which the enzymes retain the ionization state they had at that pH in the aqueous solution during freeze-drying and in organic solvents.

As surprising as some of these findings may be, the requirement of bound water for enzymes to  function is still consistent with the orthodox view that life requires water. At best, such findings can explain the existence or preservation of life in low water environments.

For cryobiologists, such findings raise interesting questions. In 2004, Fahy, Wowk et al. speculate that one of the mechanisms of cryoprotectant toxicity may involve “reduced hydration of biomolecules.” Understanding how solvents, and the combination of solvents, affect the intracellular milieu and the hydration and stability of biomolecules, should contribute to the design of less toxic vitrification solutions. Such vitrification solutions can be optimized for the human brain to allow for real suspended animation and improved prospects of resuscitation of cryonics patients.

Robert Prehoda in Cryonics Reports

Now online is an old interview with Robert W. Prehoda. Prehoda was a prolific science writer who published on topics such as aging, life extension, and technological forecasting. In 1969 Prehoda published the book “Suspended Animation: The Research Possibility That May Allow Man to Conquer the Limiting Chains of Time.” In this visionary book, Prehoda covered a variety of means to extend the maximum human life span including, but not limited to, chemical  anabiosis, human hibernation, suspended animation, and controlling the aging process.

Although Prehoda was involved in the James Bedford cryopreservation, he did  not advocate offering cryonics services before reversible cryopreservation could be demonstrated in a mammal. In this he does not differ from many other (cryobiological) researchers. A major problem with this perspective is that future technologies may be able to reverse the damage caused by today’s preservation methods. It offers no hope for people who are terminally ill today. And as recent history has demonstrated, engaging in cryonics now can also create a stronger infrastructure to support legitimate cryobiology research. The least toxic vitrification agent to date, M22, would not have existed today without an existing cryonics infrastructure.

Despite attempts from Mike Perry and Mike Darwin to locate Robert Prehoda, it is not known if he is still alive.

Interview with Robert W. Prehoda (1969)

Suspended animation is not cryonics

On the Immortality Institute cryonics forum, Alcor Board member and researcher Brian Wowk has posted some insightful comments on the difference between suspended animation and cryonics. Although  impressive technical advances in cryonics to date, such as vitrification, have failed to translate into increased membership growth for cryonics organizations, many cryonics observers believe that demonstration of reversible vitrification of a small mammal will be a turning point in cryonics.

But as Brian points out, the key idea of cryonics is that patients should continue to be cared for, even if contemporary technologies cannot reverse cryopreservation. As has been reiterated on this blog before, even when suspended animation is perfected, there still will be a need for cryonics to care for patients that cannot be treated by contemporary medical technologies. Dismissing cryonics until there is proof of successful suspended animation ignores the fundamental, and humane, premise of cryonics to use  low temperature  biostasis  so that critically ill people may benefit from medical technologies that have not yet arrived.

Suspended animation is not cryonics. The paradigm shift of cryonics is something different. It is a paradigm shift that could happen before suspended animation is perfected, or perhaps not even after suspended animation is perfected. The key idea of cryonics– the paradigm shift of cryonics –is the idea that patients should continue to be cared for even if they are beyond recovery by contemporary means. It’s the idea that almost everything that medicine calls “death” in a particular era is destined to become a treatable pathology in a later era. That is an idea that transcends suspended animation, and that is so far from normal social mores that it may never be accepted by the mainstream whether there is suspended animation or not. It is a paradigm shift that requires overturning the idea of closure, which is a deeply uncomfortable proposition for most people regardless of demonstrated technology.

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When people say that they hope they never need cryonics, I’m not sure in what sense they mean this. Do they mean that in the same sense that we all hope we never have to go to a hospital, even though the probability of eventually being hospitalized for some reason converges to near certainty? Or do they actually believe that they may never need cryonics? Such a belief is equivalent to the belief that one will never suffer a medical crisis that is untreatable by available medicine. I suppose an alternative possibility is the belief that one’s first and last major medical crisis will be vaporization. That doesn’t seem very likely. We live in a time when for the foreseeable future, Singularity or not, virtually everybody is going to need some form of cryonics at some time.

Brian Wowk quotes cryonics advocate Thomas Donaldson:

If you’re involved in cryonics, you’ve got to make your peace with the unknown, because it will always be there. You’ve simply got to make your peace with it.

Hydrogen sulfide does not induce hypometabolism in sheep

In a widely publicized series of experiments by Blackstone et al., hydrogen sulfide (H2S) was found to induce hypometabolism in mice. These experiments raised interest in whether such “suspended animation” could be achieved in humans. If administration of H2S would be able to reduce metabolic rate in humans to the same extent as observed in mice, the practical applications could range from management of trauma victims to space travel.

Recent work by Haouzi et al. is not encouraging. The researchers were able to induce hypometabolism in mice but did not find any change in metabolic rate in sedated sheep after exposing them to 60 ppm H2S. What the investigators did report, and which was left implicit in previous experiments with mice, is that H2S-induced hypometabolism preceded hypothermia. H2S-induced hypometabolism in mice is not just the result of hypothermia, so the inability of H2S to produce hypometabolism in sheep cannot be attributed to thermal inertia of large animals.

How can H2S induce hypometabolism in mice? The authors state that “the present results have little to offer on the pathways that are responsible for H2S-induced decrease of metabolism.” They raise the point that in small animals such as mice a large portion of metabolism is devoted to heat production instead of ATP production. In contrast, small reductions in oxygen utilization in humans, as produced by H2S exposure, will affect ATP generation. Or as Ikaria‘s Csaba Szabo speculates in “Hydrogen sulphide and its therapeutic potential”, “the window of opportunity to compromise oxidative phosphorylation in a human, therefore, must be smaller than in the mouse.“

The authors do not expect that higher dosages of H2S will produce hypometabolism in large mammals because the 60 ppm that was administered to sheep already exceeds what is known to be toxic in humans.

The search for molecules that induce hypometabolism, let alone hibernation-on-demand, in humans remains elusive. So far most research in this area involves attempts to activate conserved metabolic pathways of hibernating animals in non-hibernating animals instead of direct pharmacological inhibition of high energy consuming physiological activities.