X-Message-Number: 3353
From: Ralph Merkle <>
Subject: CRYONICS Chemical fixation
Date: 	Tue, 25 Oct 1994 18:28:11 PDT

>From "Molecular Repair of the Brain"
(URL ftp://parcftp.xerox.com/pub/merkle/techFeas.html):

   As an aside, the vascular perfusion of chemical fixatives to
   improve stability of tissue structures prior to perfusion
   with cryoprotectants and subsequent storage in liquid
   nitrogen would seem to offer significant advantages.  The
   main issue that would require resolution prior to such use is
   the risk that fixation might obstruct circulation, thus
   impeding subsequent perfusion with cryoprotectants.  Other
   than this risk, the use of chemical fixatives (such as
   aldehydes and in particular glutaraldehyde) should reliably
   improve structural preservation and would be effective at
   halting almost all further deterioration within minutes of
   perfusion[67].  The utility of chemical preservation has been
   discussed by Drexler[1] and by Olson[90], among others.

1.  "Engines of Creation" by K. Eric Drexler, Anchor Press, 1986.
67. "Fixation for Electron Microscopy" by M. A. Hayat, Academic
       Press, 1981.
90. "A Possible Cure for Death" by Charles B. Olson, Medical
       Hypotheses 1988 Vol 26, pages 77-84.

The use of chemical fixation is debated from time to time and would
seem to offer definite advantages.  Current suspension methods do
not preserve function, and the evidence that they preserve structure
is at present based largely on light and electron microscopic images.
If we wish to produce the best possible light and electron microscopic
images (and hence provide the best currently obtainable evidence of structural
preservation), it would seem natural to adopt the methods developed over
many years by microscopists interested in high quality images.

The reluctance to adopt chemical fixation appears to stem from 4 sources:

1)  We have less experience with chemical fixation followed by perfusion
    of cryoprotectants followed by freezing, and in particular we need
    evidence that chemical fixation can be done in a manner that leaves
    the circulatory system available for the subsequent introduction of
    cryoprotectants.  Futher, chemical fixatives are not always benign.
    Spilling glycerol is unlikely to harm the suspension team, while
    exposure to glutaraldehyde or osmium tetroxide would be significantly
    more damaging.  Thus, procedures for the safe handling of the
    chemical fixatives would have to be adopted and followed.  

2)  The use of chemical fixatives would appear to require an explicit
    up-front decision to depend on the future development of nanotechnology,
    completely abandoning the (in my opinion rather remote) hope that someone
    suspended with current technology might be revived in the future by a
    technology that was simpler and more easily developed than full blown

3)  The use of chemical fixation by itself (without subsequent freezing)
    appears less attractive because of the uncertainty surrounding the
    long term effectiveness of chemical fixatives in blocking further
    deterioration.  Freezing to the temperature of liquid nitrogen offers
    a virtual guarantee that subsequent deterioration will be insignificant.

4)  Inability to perfuse all regions of the brain (which might occur if clots
    or other blockages are present in the circulatory system) can prevent
    chemical fixation of some regions, thus resulting (in the absence of
    freezing) in complete deterioration of those regions.  Cold, on the
    other hand, is guaranteed to penetrate to all regions of the brain (even
    though blockage of the circulatory system might result in a "straight
    freeze" of those regions).

Objections (3) and (4) can be avoided by freezing the tissue after fixation and
perfusion with cryoprotectants.  Objection (2) is (in my opinion) rather weak.
I think current suspension damage is sufficient to insure that technologies
significantly simpler or less powerful than full blown nanotechnology are

unlikely to produce satisfactory results.  Effectively, we are already dependent
on the future development of nanotechnology.  It is possible that advances in
suspension technology might change these conclusions in the future -- at which
point a re-evaluation of the available alternatives might be appropriate.

Objection (1) thus remains as the major impediment to adoption of chemical
fixation as an adjunct to freezing.  This objection, however, is primarily
based on the relative absence of experience in the use of this approach.
This could be changed, given a sufficiently motivated effort.  To date,
there have not been enough people who felt that chemical fixation offered
sufficient advantages over the present methods to fund and staff the
needed effort.  It looks like a lot of work.  I would expect, as cryonics
grows, that at some point this approach will be investigated more seriously.

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