X-Message-Number: 32812 Date: Wed, 01 Sep 2010 07:34:49 -0400 From: Subject: Re: a proposal to stimulate cryonics research Nearly three weeks ago Douglas Skrecky posted his message "a proposal to stimulate cryonics research": http://www.cryonet.org/cgi-bin/dsp.cgi?msg=32767 to which this is my belated reply. The focus of Doug's message on cryoprotectant toxicity shows that his heart and mind are in the right place, so I hope that my acknowledgment of this fact is not lost because I have some criticisms of the details of his message. In particular, I disagree with his claim that: "By pulling out all the stops, expense be damned, and actually using these less toxic but pricey cryoprotective agents such as ectoin, DESO, and KF7G; fully reversible liquid nitrogen cryopreservation of entire animals is IMHO quite possible right now." KF7G is an anti-freeze flavonol glycoside, comparable to anti-freeze proteins and ice blockers in its mechanism of action. Although the 9oC freezing-point depression of KF7G is more impressive than that of any other ice-blocker, KF7G is not a cryoprotectant and can do no more than assist cryoprotectants a bit in achieving and maintaining vitrification. Doug cites a single paper showing the effectiveness of DESO as a cryoprotectant on a single organism, the bacterium Escherichia coli. Although 85% viability for 45% DESO concentration is impressive, it is not the same as 100% viability and E. coli is not a mammalian cell. The relative toxicities of the various cryoprotectants varies remarkably with cell type: http://www.benbest.com/cryonics/viable.html#toxicity The University of Michigan does not have or have access to the paper you cited for ectoin, although I similarly note that 72% survival of a single cell type is not the same as 100% viability for all cell types. As I have been saying for years, the greatest breakthrough for cryonics would be the elimination of cryoprotectant toxicity, and the focus on research should be on understanding what cryoprotectant toxicity is. If we do not understand the mechanisms of cryoprotectant toxicity, we are poorly equipped to eliminate it. Current understanding of the mechanisms of cryoprotectant toxicity is sketchy, in my opinion: http://www.benbest.com/cryonics/viable.html#mechanisms If we could have a Manhatten project for studying cryoprotectant toxicity we could have a significant chance of dramatically advancing cryonics. But this requires lots of money and lots of recognition of the importance of this problem. Many cryobiologists have been aware for many years that cryoprotectant toxicity is "the central problem blocking successful cryopreservation by vitification": http://www.ncbi.nlm.nih.gov/pubmed/3595164 but in cryobiology, as in cryonics, the money and commitment have not been in place to solve what is the most important problem. Nor has there been sufficient understanding that it is the most important problem. I appreciate, Doug, that you have this recognition. -- Ben Best Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=32812