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/

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