X-Message-Number: 14879
Date: Wed, 08 Nov 2000 13:43:22 -0800
From: Jeff Davis <>
Subject: Re: Frogs and fish

Marta Sandberg wrote, referring to natural, antarctic-fish cryoprotectant:

>The last point is moot. The molecules are too large to be absorbed into 
>cells. Unless they can be slimmed down they can't be used as a perfusate 

"Can't be used.." is pretty strong language.

Always be aware--or try to occasionally remind yourself--of the natural
human tendency to think 'habitually': to mistake the way things are with
the way things will always be, mistake the way things are done now, with
the way they will always be done.  

Compared to the seeming 'magicalness' of future technologies, the current
suspension techniques will shortly be sources of derision and
embarrassment.  Laughable in their first generation crudeness.

Consider.  As mentioned above, cellular penetration of a given
cryoprotectent candidate, is consider AT PRESENT an absolutely crucial
consideration.  The large molecules mentioned in the above quote, and
trehelose, and a long list of other and otherwise-promising cryoprotectant
candidates don't penetrate the cell membrane worth a hoot.  So they're of
no use, right?  Not at all.  We're simply in need of a method of efficient
transmembrane transport.  

Now this could be something as yet undreamed of, or it could be dreamed of
but not perfected--like a buckyball nanobot transport vesicle such as can
be found in Frietas's Nanomedicine (available full text on the web--sorry,
I don't have a link), or it could be something already in early use, a
hijacked viral-shell vector or a customized liposome. (Check the web to see
the extent to which liposome technology is already developed, and how
strikingly cheap it is.  The liposome 'bubbles' are created by blowing
phospholipid 'soap' through a perforated plastic sieve.)  

Consider this last item. (Vesicles=liposomes)  A cryoprotectant
phospholipid vesicle iv solution would contain a mix of vesicles
appropriate for the full range cell types.  Each individual vesicle type
would contain the cryoprotectant (or cryoprotectant mix) of choice FOR ONE
SPECIFIC CELL TYPE, and would have have the complementary transmembrane
docking protein/cellular identifier for THAT SPECIFIC CELL TYPE.  It would
dock to that cell, and that cell only, the phospholipid membrane of the
vesicle would fuse with that of the cell, and the contents of the vesicle
would then 'be inside' the cell.  Job done.  Next problem.

Specific cellular targeting is here today or just around the corner,
because it is one of the several state-of-the-art approaches to cancer and
other therapies.

The only 'real' question is "How long?"  I'll be fifty-two in December.  If
I can hold out for another twenty years--my health is good but my family
has a history of cancer--I expect to have available to me a vastly improved
suspension capability.  Perhaps even 'routine' reversible suspension.
Perhaps even socially-mandated, universal, legally-guaranteed access to
suspension as medical entitlement.  It is, after all, a life-saving procedure.

Like my boy, Ray, says.

			Best, Jeff Davis

	   "Everything's hard till you know how to do it."
					Ray Charles				

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