CryoNet #32611 - #32612

CryoNet - Sat 12 Jun 2010

    #32611: Silver Platters Ignored, in Cryonics [Melody Maxim]
    #32612: Freezing 'to Death' and Living to Tell About It [oberon]

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Message #32611
Date: Fri, 11 Jun 2010 13:27:01 +0000 (UTC)
From: Melody Maxim <[email protected]>
Subject: Silver Platters Ignored, in Cryonics

The television show, (recently mentioned on Cryonet), regarding a toddler who was revived after wandering off into the snow, doesn't reflect any great new knowledge. The little girl was clinically dead, with a core temperature of 16 degrees Celsius, when she arrived at the hospital, where she was successfully rewarmed and resuscitated. Cardiovascular surgeons and neurosurgeons have been successfully using deep hypothermia (18-degrees Celsius, and below) combined with circulatory arrest (DHCA), for more than half a century. This technology was based on cases similar to the little girl's, and is the medical science on which cryonics should be based. 

The medical procedures and equipment needed, for delivering cryonics solutions to patients, (basically, the same equipment and techniques used to perform DHCA), were handed to cryonics organizations on a silver platter, decades ago, courtesy of conventional medicine. Why the organizations have wasted somewhere in the neighborhood of four decades, and many, many millions of dollars, building their own equipment, is truly perplexing. For example, a heart-lung machine will maintain given parameters (flows, pressures, etc.), for a number of pumps; react to air by clamping lines and shutting off pumps; monitor in-line labs (such as blood gases); and automatically produce a detailed record (chart). Other than minor variations, I believe the only truly unique additional feature needed for a vitri
 fication circuit would be something to accommodate the ramping of the vitrification solution. Even this has a basis in existing technology, as many heart-lung machines already allow for varying concentrations of cardioplegia to be delivered, using the same bag of solution. This relies on someone determining the concentration to be delivered, but it should be possible to develop a system, which would operate on concentration feedback and pre-determined parameters/delivery protocols. (IMPORTANT: When I suggest something should be "developed," I mean by companies, which specialize in developing this type of equipment, not by an amateur who just happens to be working in cryonics, or a friend of someone who is working in cryonics, who will sit around writing programs on their laptop, for year
 s, all the while charging excessive "consulting" fees. It is that type of foolishness, which has kept cryonics in the dark ages of hypothermic medicine.) 

Not long after I started working in cryonics, in 2006, I took a tour of the Alcor facility, during their conference. At the time, (not being familiar with the amount of time and money, which had already been invested), I thought I was witnessing a case of people not being aware of existing equipment, or not having enough money to purchase existing "state of the art" perfusion equipment. The vitrification circuit didn't even begin to compare to perfusion circuits I had been using, more than a decade prior to that time. The field perfusion circuit had the oxygenator placed higher than the reservoir, (something almost guaranteed to introduce air to patients, a problem I've heard Alcor has been plagued with, over the years). The perfusion equipment is of paramount importance, to cryonics proce
 dures. So, why did the perfusion equipment, at both Alcor and Suspended Animation, mostly resemble amateur DIY projects, less than four years ago? My guess is, for the money they have spent on salaries and consulting fees related to their perfusion equipment, over the years, those two companies could have purchased quite a few top-of-the-line heart-lung machines, and outsourced the development of the vitrification solution ramping system to a company capable of completing the project, at a reasonable cost and within a reasonable amount of time. I'm guessing little has changed, at Alcor, and I believe the only reason the field equipment changed at SA, was in response to my public criticisms

I believe my criticisms are accurate, when applied to a lot of cryonics equipment. There are reputable companies, which specialize in building cryogenic cooldown boxes and shipping containers, and others that develop and produce automatic chest compression devices. Suspended Animation should have called those manufacturers, regarding the projects they were doing four years ago, (as was suggested to them, at the time). Instead, they invested well into six figures, (with the lion's share being man-hours paid to two people), and at least three years, on their Autopulse modification project, only to have a division of Medtronic announce their affordable battery-powered "Lucas 2" device. When I resigned from SA, people were running out to Home Depot, to purchase materials for the cooldown box p
 roject, when the cost of a professionally-built, custom-made cryogenic container wouldn't have been much more than one week of man-hours, for the two people working on SA's project. Then, there's the liquid ventilation project, which according to LEF's magazine, was complete except for portability, back in February 2000. A big deal was made of this project, more than seven years later, at the 2007 Alcor conference, where it was announced the device was more efficient, but still not portable. How many man-hours have been paid to a handful of people for these seemingly-endless, mostly-fruitless cryonics projects, over the years? How many dogs has CCR subjected to experimentation, for such projects? Might the projects have been finished, years ago, if they had been outsourced to reputable m
 anufacturers of similar devices? In recent years, many respectable research institutions have been investigating methods of inducing hypothermia in a field setting, (and some of those investigations have included lung lavage with perfluorocarbons).

For a very long time, I have been convinced there's a handful of people, with a lot of influence in cryonics, who have limited skills and talent, when it comes to building medical equipment and/or performing medical procedures, and I think they do whatever is necessary, to protect their own incomes, and those of their "loyal" friends, (sort of a nerdy version of "good ol' boy politics"). Witness what happened, after I went public with my criticisms of Suspended Animation's activities. A physician who has ties to Alcor, Critical Care Research, 21CM, Suspended Animation, and even Cryonics Institute, posted a number of blatant lies about me, on the Internet. This person didn't know me. He worked in California and, by his own admission, had no firsthand knowledge of my daily activities at SA, 
 in Florida, but that didn't stop him from making false accusations, in response to criticisms of an organization funded by his benefactors. I think the level of corruption, in cryonics, is truly astounding, and I fail to understand why people who have, repeatedly, engaged in questionable behaviors continue to be revered, in cryonics. I think it should be obvious people like these, not only hold cryonics back, but drag it down. Think of some of the most well-known names in cryonics, and ask how many of them would be considered credible witnesses, in a court of law. If Alcor doesn't settle the Johnson case, or win it based on his alleged obligations to not disclose information about their activities, who is going to testify on Alcor's behalf, if Johnson's audiotapes are played in court?

In response to my repeated criticisms, some people have asked me to quit criticizing and make constructive suggestions. It's unreasonable to expect anyone to instruct a pool of mostly-unqualified people on how to perform the well-established tasks of paramedics, vascular surgeons and perfusionists, (especially when the previous response to polite suggestions has been a series of attempts to undermine such suggestions in favor of keeping things the same, followed by lies and personal attacks). Cryonics organizations need strong leaders, who will build on existing "state of the art," equipment, related to conventional hypothermic medicine, not highly-paid, underqualified people who will keep trying to "reinvent the wheel," with the apparent goal of maintaining the status quo. Again, the equi
 pment needed to perform chest compressions, ventilate patients, administer IV meds, perform vascular cannulations and perfusion was, basically, perfected decades ago. If the people funding cryonics activities aren't aware of this, I can't help but believe it's because a handful of people have a strong financial interest in making cryonics mostly a never-ending DIY amateur equipment engineering project. It would be much more productive, and a lot less costly, to purchase existing equipment and outsource any needed modifications, to reputable manufacturers of such equipment. Then, all the millions, which are being spent on these projects could be spent on hiring competent care providers; developing better washout and vitrification solutions; perfecting cooling and storage parameters; and t
 hinking about future reanimation efforts, (none of these "DIY" projects, to be assigned to amateurs). Here are some suggestions, for changing the image, and technological status, of cryonics organizations, (not necessarily in order of importance):

1. Enlist leaders who are familiar with protocols, techniques and equipment, currently being used in conventional hypothermic medical procedures, and build on what already exists.
2. Outsource engineering projects to companies, which manufacture similar medical equipment, and quit wasting time and money on DIY garage projects.
3. Invest in ensuring activities, (including those of field teams), will not be in violation of state and/or federal law.
4. Cut all ties with people who have repeatedly engaged in questionable activities, related to their work in cryonics.
5. Don't mistake a willingness to engage in questionable behaviors, which bring negative attention to cryonics, as "loyalty."
6. Establish a policy of holding members accountable for ensuring their wishes for cryopreservation will be carried out. Things like fighting for someone who has been buried (decaying) for more than a year, comes at the cost of public ridicule and a huge financial drain. (Think "Tragedy of the Commons.")
7. Invest in reputable organizations performing research, related to hypothermia. There are plenty of respectable research organizations and scientists currently investigating hypothermic technologies, which may be of benefit to cryonics.
8. Hire professionals to perform medical procedures, and quit allowing unqualified persons to perform vascular cannulations and other medical procedures. Competency in performing these procedures requires a significant amount of properly supervised instruction and experience. Attempting to train unqualified persons, by allowing them to "play doctor" with dead pigs, a few times a year, is only going to result in more (well-deserved) ridicule.

The bottom line: Unless cryonicists want another 40 years of little progress, and lots of scandal, some of the faces need to change, starting at the top. It doesn't matter how much money any given benefactor pours in. Unless it is funding progress, that money is of no benefit to anyone, other than those on the payroll.

Melody Maxim

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Message #32612
Date: Fri, 11 Jun 2010 19:09:45 -0700 (PDT)
From: [email protected]
Subject: Freezing 'to Death' and Living to Tell About It

[I'd prefer to see some work done with human cells first, before putting too much faith in this. Is there a nitric oxide connection here?]

Freezing 'to Death' and Living to Tell About It: Study Reveals How Suspended Animation Protects Against Lethal Hypothermia
ScienceDaily (June 10, 2010) - How is it that some people who apparently freeze to death, with no heart rate or respiration for extended periods, can be brought back to life with no long-term negative health consequences? New findings from the laboratory of cell biologist Mark B. Roth, Ph.D., of Fred Hutchinson Cancer Research Center, may help explain the mechanics behind this widely documented phenomenon.

Reporting online ahead of the July 1 print issue of Molecular Biology of the Cell, Roth, a member of the Hutchinson Center's Basic Sciences Division, and colleagues show that two widely divergent model organisms -- yeast and nematodes, or garden worms -- can survive hypothermia, or potentially lethal cold, if they are first put into a state of suspended animation by means of anoxia, or extreme oxygen deprivation.
Roth and colleagues found that under normal conditions, yeast and nematode embryos cannot survive extreme cold. After 24 hours of exposure to temperatures just above freezing, 99 percent of the creatures expire. In contrast, if the organisms are first deprived of oxygen and thus enter a state of anoxia-induced suspended animation, 66 percent of the yeast and 97 percent of the nematode embryos will survive the cold. Once normal growth conditions are resumed -- upon rewarming and reintroduction of oxygen -- the organisms will reanimate and go on to live a normal lifespan.
A better understanding of the potentially beneficial, symbiotic relationship between low oxygen and low temperatures may one day lead to the development of improved techniques for extending the shelf life of human organs for transplantation, Roth said.
"We have found that extension of survival limits in the cold is possible if oxygen consumption is first diminished," he said. "Our experiments in yeast and nematodes suggest that organs may last longer outside the body if their oxygen consumption is first reduced before they are made cold."
Roth's laboratory studies the potential clinical benefits of metabolic flexibility -- from anoxia-induced reversible suspended animation to metabolic hibernation brought on by exposure to agents such as hydrogen sulfide. The ultimate goal of this work is to find ways to temporarily lower metabolism -- like dialing down a dimmer switch on a lamp -- as a means to "buy time" for patients in trauma situations, such as victims of heart attack or blood-loss injury, by reducing their need for oxygen until definitive medical care can be given.
Roth first got the idea to study the link between anoxia-induced suspended animation and hypothermia from documented cases in which humans have managed to make complete recoveries after apparently freezing to death. Widely publicized cases include Canadian toddler Erica Nordby, who in the winter of 2001 wandered outside clad only in a diaper. Her heart had stopped beating for two hours and her body temperature had plummeted to 61 degrees Fahreneit before she was discovered, rewarmed and resuscitated. Another incident that made headlines was that of a Japanese man, Mitsutaka Uchikoshi, who in 2006 fell asleep on a snowy mountain and was found by rescuers 23 days later with a core body temperature of 71 degrees Fahrenheit. He, too, was resuscitated and made a full recovery.
"There are many examples in the scientific literature of humans who appear frozen to death. They have no heartbeat and are clinically dead. But they can be reanimated. Similarly, the organisms in my lab can be put into a state of reversible suspended animation through oxygen deprivation and other means. They appear dead but are not. We wondered if what was happening with the organisms in my laboratory was also happening in people like the toddler and the Japanese mountain climber. Before they got cold did they somehow manage to decrease their oxygen consumption? Is that what protected them? Our work in nematodes and yeast suggests that this may be the case, and it may bring us a step closer to understanding what happens to people who appear to freeze to death but can be reanimated," Roth s
 aid.
The mechanism by which anoxia-induced suspended animation protects against extreme cold has to do with preventing the cascade of events that lead to biological instability and, ultimately, death. For example, suspended animation preserves the integrity of cell-cycle control by preventing an organism's cells from dividing in an error-prone fashion. During suspended animation, the cell cycle is reversibly halted. Upon reanimation, the cycle resumes as normal.
"When an organism is suspended its biological processes cannot do anything wrong," Roth said. "Under conditions of extreme cold, sometimes that is the correct thing to be doing; when you can't do it right, don't do it at all."
The first author of the paper, Kin Chan, Ph.D., formerly a postdoctoral research associate in the Roth lab, is now with the Laboratory of Molecular Genetics in the National Institute of Environmental Health Sciences at the National Institutes of Health. The NIH and the National Science Foundation funded this research.
Note: a video showing anoxia-induced suspended animation in a nematode embryo can be found on YouTube at: http://www.youtube.com/watch?v=6okurk9O1ow

Story Source:
The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Fred Hutchinson Cancer Research Center.

Journal Reference:

Mol Biol Cell. 2010 May 12. [Epub ahead of print]
Suspended Animation Extends Survival Limits of Caenorhabditis elegans and Saccharomyces cerevisiae at Low Temperature.
Chan K, Goldmark JP, Roth MB. Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109.
Abstract
    Monitoring Editor: David G. Drubin The orderly progression through the cell division cycle is of paramount importance to all organisms, as improper progression through the cycle could result in defects with grave consequences. Previously, our lab has shown that model eukaryotes such as Saccharomyces cerevisiae, Caenorhabditis elegans, and Danio rerio all retain high viability after prolonged arrest in a state of anoxia-induced suspended animation, implying that in such a state, progression through the cell division cycle is reversibly arrested in an orderly manner. Here, we show that S. cerevisiae (both wild-type and several cold-sensitive strains) and C. elegans embryos exhibit a dramatic decrease in viability that is associated with dysregulation of the cell cycle when exposed to low
  temperatures. Further, we find that when the yeast or worms are first transitioned into a state of anoxia-induced suspended animation before cold exposure, the associated cold-induced viability defects are largely abrogated. We present evidence that by imposing an anoxia-induced reversible arrest of the cell cycle, the cells are prevented from engaging in aberrant cell cycle events in the cold, thus allowing the organisms to avoid the lethality that would have occurred in a cold, oxygenated environment.
PMID: 20462960
Free text>
http://www.molbiolcell.org/cgi/reprint/E09-07-0614v1

EMBO J. 2003 Feb 3;22(3):580-7.
Nitric oxide-induced suspended animation promotes survival during hypoxia.
Teodoro RO, O'Farrell PH. Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143-0448, USA.
Abstract
    Oxygen plays a key role in energy metabolism. However, there are organisms that survive severe shortfalls in oxygen. Drosophila embryos rapidly arrest development upon severe hypoxia and recover upon restoration of oxygen, even days later. Stabilization of the normally unstable engrailed RNA and protein preserved the localized striped pattern of this embryonic patterning gene during 3 days in hypoxia. Severe hypoxia blocked expression of a heat-shock-inducible lacZ transgene. Cyanide, a metabolic poison, did not immediately block gene expression or turnover, arguing against a passive response to energy limitation. In contrast, nitric oxide, a putative hypoxia signal, induced a reversible arrest of development, gene expression and turnover. Reciprocally, a nitric oxide scavenger allowed
  continued gene expression and turnover during hypoxia, but it reduced hypoxia tolerance. We suggest that hypoxia-induced stasis preserves the status quo of embryonic processes and promotes survival. Our data implicate nitric oxide as a mediator of this response and provide a system in which to investigate its action.
PMID: 12554658
Free text>
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC140754/pdf/cdg070.pdf

[Interesting.]

J Neurochem. 2007 Jan;100(2):382-94. Epub 2006 Nov 20.
Nitric oxide regulates cell survival in purified cultures of avian retinal neurons: involvement of multiple transduction pathways.
Mejia-Garcia TA, Paes-de-Carvalho R. Department of Neurobiology and Program of Neuroimmunology, Institute of Biology, Federal Fluminense University, Niteroi, Brazil.
Abstract
    Nitric oxide (NO) is an important signaling molecule in the CNS, regulating neuronal survival, proliferation and differentiation. Here, we explored the mechanism by which NO, produced from the NO donor S-nitroso-acetyl-d-l-penicillamine (SNAP), exerts its neuroprotective effect in purified cultures of chick retinal neurons. Cultures prepared from 8-day-old chick embryo retinas and incubated for 24 h (1 day in culture, C1) were treated or not with SNAP, incubated for a further 72 h (up to 4 days in culture, C4), fixed, and the number of cells estimated, or processed for cell death estimation, by measuring the reduction of the metabolic dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Experimental cultures were run in parallel but were re-fed with fresh medium in t
 he absence or presence of SNAP at culture day 3 (C3), incubated for a further 24 h up to C4, then fixed or processed for the MTT assay. Previous studies showed that the re-feeding procedure promotes extensive cell death. SNAP prevented this death in a concentration- and time-dependent manner through the activation of soluble guanylate cyclase; this protection was significantly reversed by the enzyme inhibitors 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) or LY83583, and mimicked by 8-bromo cyclic guanosine 5'-phosphate (8Br-cGMP) (GMP) or 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1), guanylate cyclase activators. The effect was blocked by the NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO). The effect of NO was also suppressed by LY294002, Wortm
 annin, PD98059, KN93 or H89, indicating the involvement, respectively, of phosphatidylinositol-3 kinase, extracellular-regulated kinases, calmodulin-dependent kinases and protein kinase A signaling pathways. NO also induced a significant increase of neurite outgrowth, indicative of neuronal differentiation, and blocked cell death induced by hydrogen peroxide. Cyclosporin A, an inhibitor of the mitochondrial permeability transition pore considered an important mediator of apoptosis and necrosis, as well as boc-aspartyl (OMe) fluoromethylketone (BAF), a caspase inhibitor, also blocked cell death induced by re-feeding the cultures. These findings demonstrate that NO inhibits apoptosis of retinal neurons in a cGMP/protein kinase G (PKG)-dependent way, and strengthens the notion that NO plays
  an important role during CNS development.
PMID: 17116229

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