Category Archives: Cryonics

Humans have been ingesting mindand mood-altering substances for millennia, but it has only rather recently become possible to begin to elucidate drug mechanisms of action and to use this information, along with our burgeoning knowledge of neuroscience, to design drugs intended to have a specific effect. And though most people think of pharmaceuticals as medicine, it has become increasingly popular to discuss the possibilities for the use of drugs in enhancement, or improvement of human form or functioning beyond what is necessary to sustain or restore good health (E.T. Juengst; in Parens, 1998, p 29).

Some (transhumansits) believe that enhancement may not only be possible, but that it may even be a moral duty. Others (bioconservatives) fear that enhancement may cause us to lose sight of what it means to be human altogether. It is not the intention of this article to advocate enhancement or to denounce it. Instead, lets review some of the drugs (and/or classes of drugs) that have been identified as the most promisingly cognitive- or mood-enhancing. Many of the drugs we will cover can be read about in further depth in Botox for the brain: enhancement of cognition, mood and pro-social behavior and blunting of unwanted memories (Jongh, R., et al., Neuroscience and Biobehavioral Reviews 32 (2008): 760-776).

Of most importance in considering potentially cognitive enhancer drugs is to keep in mind that, to date, no magic bullets appear to exist. That is, there are no drugs exhibiting such specificity as to have only the primary, desired effect. Indeed, a general principle of trade-offs (particularly in the form of side effects) appears to exist when it comes to drug administration for any purpose, whether treatment or enhancement. Such facts may constitute barriers to the practical use of pharmacological enhancers and should be taken into consideration when discussing the ethics of enhancement.

Some currently available cognitive enhancers include donepezil, modafinil, dopamine agonists, guanfacine, and methylphenidate. There are also efforts underway to develop memory-enhancing drugs, and we will discuss a few of the mechanisms by which they are proposed to act. Besides cognitive enhancement, the enhancement of mood and prosocial behavior in normal individuals are other types of enhancement that may be affected pharmacologically, most usually by antidepressants or oxytocin. Lets briefly cover the evidence for the efficacy of each of these in enhancing cognition and/or mood before embarking on a more general discussion of the general principles of enhancement and ethical concerns.

One of the most widely cited cognitive enhancement drugs is donepezil (Aricept), an acetylcholinesterase inhibitor. In 2002, Yesavage et al. reported the improved retention of training in healthy pilots tested in a flight simulator. In this study, after training in a flight simulator, half of the 18 subjects took 5 mg of donepezil for 30 days and the other half were given a placebo. The subjects returned to the lab to perform two test flights on day 30. The donepezil group was found to perform similarly to the initial test flight, while placebo group performance declined. These results were interpreted as an improvement in the ability to retain a practiced skill. Instead it seems possible that the better performance of the donepezil group could have been due to improved attention or working memory during the test flights on day 30.

Another experiment by Gron et al. (2005) looked at the effects of donepezil (5 mg/day for 30 days) on performance of healthy male subjects on a variety of neuropsychological tests probing attention, executive function, visual and verbal short-term and working memory, semantic memory, and verbal and visual episodic memory. They reported a selective enhancement of episodic memory performance, and suggested that the improved performance in Yesavage et al.s study is not due to enhanced visual attention, but to increased episodic memory performance.

Ultimately, there is scarce evidence that donepezil improves retention of training. Better designed experiments need to be conducted before we can come to any firm conclusions regarding its efficacy as a cognitive-enhancing.

The wake-promoting agent modafinil (Provigil) is another currently availabledrug that is purported to have cognitive enhancing effects. Provigil is indicated for the treatment of excessive daytime sleepiness and is often prescribed to those with narcolepsy, obstructive sleep apnea, and shift work sleep disorder. Its mechanisms of action are unclear, but it is supposed that modafinil increases hypothalamic histamine release, thereby promoting wakefulness by indirect activation of the histaminergic system. However, some suggest that modafinil works by inhibiting GABA release in the cerebral cortex.

In normal, healthy subjects, modafinil (100-200 mg) appears to be an effective countermeasure for sleep loss. In several studies, it sustained alertness and performance of sleep-deprived subjects(up to 54.5 hours) and has also been found to improve subjective attention and alertness, spatial planning, stop signal reaction time, digit-span and visual pattern recognition memory. However, at least one study (Randall et al., 2003) reported increased psychological anxiety and aggressive mood and failed to find an effect on more complex forms of memory, suggesting that modafinil enhances performance only in very specific, simple tasks.

The dopamine agonists d-amphetamine, bromocriptine, and pergolide have all been shown to improve cognition in healthy volunteers, specifically working memory and executive function. Historically, amphetamines have been used by the military during World War II and the Korean War, and more recently as a treatment for ADHD (Adderall). But usage statistics suggest that it is commonly used for enhancement by normal, healthy peopleparticularly college students.

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Institute for Evidence-Based Cryonics

by Ben Best CONTENTS: LINKS TO SECTIONS VITRIFICATION IN NATURE THE PHYSICAL CHEMISTRY OF VITRIFICATION ICE BLOCKERS (INCLUDING ANTI-FREEZE PROTEINS) CRYOPRESERVATION OF CELLS, TISSUES & ORGANS CRYOPRESERVATION OF ORGANS & CRYONICS PATIENTS USING GLYCEROL CRYOPRESERVATION WITH SUGARS VITRIFICATION WITH NON-GLYCEROL CRYOPROTECTANTS THE DEVITRIFICATION PROBLEM FRACTURING OF VITRIFIED SUBSTANCES I. VITRIFICATION IN NATURE

Although most living organisms are composed of large amounts of water, it is not inevitable that freezing these organisms results in ice-formation. Among amphibians and insects that can tolerate freezing, there is wide variation in the amount of freezing they can tolerate.

Species of frogs can spend days or weeks "with as much as 65 percent of their total body water as ice". Some amphibians achieve their protection due to the glycerol manufactured by their livers. Glycerol is "antifreeze", it reduces ice formation and lowers freezing point. Glycerol (glycerin), like ethylene glycol (automobile anti-freeze) is a cryoprotectant. The sugar glucose is also a cryoprotectant and arctic frogs have a special form of insulin that accelerates glucose release and absorption into cells as temperatures approach freezing. A cryoprotectant can make water harden like glass with no crystal formation a process called vitrification. Freezing-damage to cells is due to the formation of ice-crystals.

Insects most often used sugars for cryoprotectant. They may also refrain from eating (not such a hardship because their metabolism slows at low temperature) and utilize tough waxy coverings to keep nucleating substances out of their body when temperature drops. Adult arctic beetles (Pterostichus brevicornis) normally endure temperatures below 35C. These beetles have been frozen in the laboratory to 87C for 5 hours without apparent injury, ie, they demonstrated "directed, coordinated activity such as walking, feeding, and avoidance response, and no paralysis or erratic behavior..." [SCIENCE166:106-7 (1-OCT-69)]. (A replication of this experiment would be of value to confirm or challenge the results.) This would seem to indicate that neurological tissue can, in principle, recover in a functional way from vitrification. The glycerol, sugars, and other cryoprotectants which are produced naturally in these organisms, are not found in levels that adequately explain (with current knowledge of cryobiology) the remarkable freezing-tolerance.

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Water is not very viscous, therefore it can be vitrified only by an extremely rapid "flash-freezing" of a small sample about 3millionC per second to 135C. Under such rapid cooling, water molecules don't have time to arrange themselves into a crystalline lattice structure. Viscosity increases very little when water is cooled, but at freezing temperature a sudden phase transition occurs to an ice crystal. Molten silica (silicon dioxide, SiO2, liquid glass), by contrast, is very viscous. This viscosity is the result of the tendency of silica to form amorphous networks of polymers rather than to arrange in an orderly crystal lattice.

Quartz (rock-crystal) & sand are examples of SiO2 as pure crystal. SiO2 which has been made to exist in noncrystalline form is called vitreous silica (fused silica). Oxides can be added to prevent crystallization and promote vitrification. About 90% of all manufactured glass (called soda-lime glass) contains about 12% each of soda (Na2O or Na2CO3) and lime (CaO) added to the SiO2. The soda is analogous to cryoprotectants in preventing crystallization (the lime is added to prevent the glass from dissolving in water).

By cooling silica very slowly it is possible to form rock crystal, having very high density and low volume. By cooling faster, resistance to crystallization due to viscosity & the absence of nucleators causes silica to pass below its freezing temperature (supercool) and vitrify at some glass transition temperature (Tg). Viscosity increases rapidly to solidification near Tg, but over a small temperature range rather than at a precise temperature (in contrast to crystallization or fusion, which occurs at a precise temperature). The change that happens at Tg is simply a rapid increase in viscosity, not a change of state. Viscosity becomes very high near Tg when cooling from above, which means that Tg is better characterized as a "rubber/glass transition" than a "liquid/glass transition". Moreover, Tg is a function of cooling-rate. A faster cooling-rate results in Tg at a higher temperature leading to a solid that has a high volume (lower density), is more amorphous and less viscous. A slower cooling-rate results in Tg at a lower temperature leading to a solid that has a low volume (higher density), is less amorphous and is more viscous. In practice, Tg occurs within a narrow temperature range because changing cooling rate an order of magnitude (ie, by a factor of ten) only changes Tg by 35C.

But volume continues to decrease and viscosity continues to increase below Tg. The change at Tg is quantitative, not qualitative (in contrast to crystallization). Because cooling occurs from outside to inside, overly rapid cooling creates stress when the warmer core needs to contract more than the cooler surface. This is the reason why slow cooling reduces cracking. At Tg there is a sudden increase in viscosity and heat capacity (usually many orders of magnitude), but there is no comparable sudden decrease in volume. In fact, Tg is characterized as a temperature-range where the rate of decrease of volume decreases, although volume does continue to decrease (and viscosity continues to increase) linearly below Tg. Tg could be a temperature critical to cracking because the sudden increase in viscosity would be likely to affect heat conduction as well as stress. [For further discussion of Tg, stress and cooling rates, see my essays Physical Parameters of Cooling in Cryonics and Lessons for Cryonics from Metallurgy and Ceramics.]

Sugar, like silica, can form a crystal (rock candy) or a glass (cotton candy) depending on the rate of cooling. Like molten glass, liquid sugar is very viscous and prone to formation of amorphous polymers. In silica the polymerization bonds tend to be of a "mixed" covalent-ionic type, whereas for sugar the polymerization is assisted by weaker forces (van der Waals or hydrogen bonding). In neither case do these bonds have the defined bond-lengths and bond-angles of covalent bonds. Glycerol/water in the human body is more like sugar than like silica. But the situation is complicated by the presence of many salts, proteins, fats, etc.

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Vitrification in Cryonics - Ben Best

Top 5 Facts About Cryonics
James Whale goes through the Top 5 facts about Cryonics. Cryonics is no longer the stuff of science fiction it is already being put into action. Video in the Endcard: http://www.youtube.com/watch?v=_s2K7...

By: Top 5 at 5

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Top 5 Facts About Cryonics - Video

Cryonics Funding Inflationary Universe
Flexible funding options using Index Universal Life Insurance for funding cryonics in an inflationary universe.

By: MrRudiHoffman

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Cryonics Funding Inflationary Universe - Video

Cryonics Sign Up Process
How to sign up for Cryonics.

By: MrRudiHoffman

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Cryonics Sign Up Process - Video

Science Scene: Cryonics
The Daily Texan investigates cryonics: the preservation of humans or animals through freezing their bodies in hopes to promote healing.

By: The Daily Texan

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Science Scene: Cryonics - Video