X-Message-Number: 7575 From: Brian Wowk <> Date: Mon, 27 Jan 1997 16:37:58 -0600 Subject: DMF toxicity clarification Thomas Donaldson writes on CryoNet: >The recent postings about its toxicity make me very interested in what I >will see at the Alcor Science Festival a week from now. And I shall try >to watch Visser's experiment VERY closely. I am not a magician, and do not >know any magic tricks, but now that I know more about the cryoprotectant >a lot looks WRONG WRONG WRONG... Not necessarily. With the number of people who've now seen it, I'd be very surprised if the Visser experiment didn't work (sometimes). It's also hard to imagine what would motivate deception in something like this. Any benefit from transient attention would be undone by the ensuing fallout once the truth became known. It's important to realize that systemic toxicity and cryobiological toxicity are two entirely different things. DMF is a potent systemic toxin when administered to normothermic living people (as are many of the "second generation" cryoprotectants now being investigated by 21CM). This issue has only been brought up because of Visser's use of the agent on living people. The real issue for cryonics is cryobiological toxicity-- the toxicity to specific tissues at temperatures near or below freezing. Visser's 25% DMF solution is in fact almost completely non-toxic cryobiologically. Even red blood cell membranes will withstand exposure to this concentration for hours near 0'C. The toxicity only really kicks at concentrations above about 30%. The problem is this: 25% DMF doesn't vitrify (we'd be immortal if it did!), it freezes. Because freezing forms crystals of pure water ice, the DMF concentration rises in residual unfrozen solution as cooling progresses. Tissues are therefore exposed to very high concentrations of DMF during freezing, with the exposure time depending on how fast you freeze. Thus if you freeze fast enough, and if your tissue can tolerate up to 60% ice formation, then 25% DMF is an effective cryoprotectant. In fact, according to the Medline literature, DMF excels as a cryoprotectant for FAST FREEZING. And so do other erstwhile toxic agents such as methanol, which beats out many "conventional" cryoprotectants when the freezing rate passes a certain threshold. So given that hearts are known to retain residual function with up to 60% ice formation, and that the toxicity of high DMF concentrations can be minimized by cooling quickly, the Visser result is plausible. It may even be repeatable with methanol instead of DMF. That doesn't mean methanol has any potential to replace glycerol in cryonics. Thus the question is not whether the Visser experiment works, but rather the more complicated question of what the success of this experiment means for the vastly different cryobiological regime of cryonics. This question is not addressed by yet more fast-freezing demonstrations. *************************************************************************** Brian Wowk CryoCare Foundation 1-800-TOP-CARE President Human Cryopreservation Services http://www.cryocare.org/cryocare/ Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=7575