X-Message-Number: 4983
Date: 13 Oct 95 18:38:53 EDT
From: Mike Darwin <>
Subject: CRYONICS:what goes there?

Joe Strout writes:

>>>We are witnessing the gestation of a myth here on Cryonet, probably 
fathered by Mike Darwin but carried by most of the list, which I will 
attempt to abort before it gets too big.

Straight freeze, despite appearances, is NOT the same thing as a tissue 
homogenate.  A homogenate is made by placing tissue in a blender, which 
has two effects:

	1. parts are physically disconnected from their neighbors
	2. the relative location of each part is essentially randomized

(Note on #2: not really randomized, of course, but each part takes a 
chaotic path -- see physics of mixing.)  It is especially this second 
effect which makes reconstruction nearly impossible, even in principle.

A straight freeze, on the other hand, causes only effect #1, but not 
effect #2 since each "part" (disconnected bit of tissue) is locked firmly 
in place by the ice around it.  Position is preserved, and probably 
orientation as well.

A simple analogy should serve to illustrate the difference.  Imagine a
large, completed jigsaw puzzle.  For a homogenate, take the puzzle apart,
put the pieces back in the box, shake well, and then lay the pieces out
again (in random order) flat on the table.  For a straight freeze, take
the puzzle apart carefully, and put each piece back right where you found
it (spreading them out or overlapping a bit). 

If you stand back a bit and squint -- or turn the pieces over so you 
can't see the big picture -- then these two cases look very similar.  
This is, in fact, how it appears to the electron microscopist.  But when 
you actually sit down and start putting the puzzle back together, it is 
obvious that the first case is difficult, while the second is trivial.

Now.  I'm not actually suggesting that straight freeze be offered as 
anything but an emergency option -- a last-resort variation on what's 
already a last-resort procedure.  But it's not useless either, as the 
"hamburger" camp would have you believe.>>

I was quite careful to point out in my "blender=homogenate" remarks exactly 
the points Joe makes.  The critical question is WHAT IS LEFT IN THE FROZEN 
STATE???!!  Here, I pointed out that it is hard to know, because when we 
look for structure with freeze substitution we see everything is squashed 
down or dehydrated into dense, narrow channels.  If Joe will recall, I 
asked him about freeze fracture capabilities sometime ago, but not much 
came from the help he (Joe) tried to supply (BTW thanks for the refferrals, 
Joe!).  Lots of freeze fracture on straight frozen tissue would help to 
answer this question.  My using the blender experiment was to point up 
(somewhat whimsically) that AFTER THAWING the results LOOK the same at the 
SAME level of examination.  This point may well be lost on people not 
conversant with the science involved here, as both Joe and I are, and I am 
grateful to Joe for pointing out the differences and clarifying points.

Now, having said all this I must take issue with Joe's remarks about what 
goes on during freezing (particularly straight freezing).  Joe says:

>A simple analogy should serve to illustrate the difference.  Imagine a
>large, completed jigsaw puzzle.  For a homogenate, take the puzzle apart,
>put the pieces back in the box, shake well, and then lay the pieces out
>again (in random order) flat on the table.  For a straight freeze, take
>the puzzle apart carefully, and put each piece back right where you found
>it (spreading them out or overlapping a bit). 

>If you stand back a bit and squint -- or turn the pieces over so you 
>can't see the big picture -- then these two cases look very similar.  
>This is, in fact, how it appears to the electron microscopist.  But when 
>you actually sit down and start putting the puzzle back together, it is 
>obvious that the first case is difficult, while the second is trivial.

This is only partly true.  This is also the same kind of argument (and I 
believe mistake) that nonbiologists like Merkle, Drexler and others make.  
Here I specfically exclude Donaldson who understands what I am about to say 
quite well.  Here too I will have recourse to an analogy.

Since the time of Leonardo through Harvey, John Hunter and to almost 
present times biology has been increasingly viewed and modeled from the 
perspective of "engineering", of looking at living systems as machines.  
This is fine and has done much good, in part by banishing vitalism and 
opening up investigation of living systems to investigation using the the 
same scientific approach that is used in all other areas of science and 
technology.

I call  this phase in biology (and medicine to a lesser extent) the 
"Newtonian Phase."  The Newtonian guys view of living systems is like 
bridges, automobiles, newsprint, clocks, integrated circuits, etc.  This is 
not a useless way to view these things; it is very useful and has resulted 
in great advances in understing.  However, it is, in short, a necessary but 
NOT sufficient model of living systems.

It is not sufficient because it breaks down, much like Newtonian mechanics 
does as you drop down in scale.  If you put a wrist-watch in a vice and 
squeeze it tight, or you have a bridge fall down in an earthquake you get 
the kind of situation Joe describes and that Merkle preaches.  But cells 
and tissues are NOT made of up of those kind of of parts.  If you stress a 
bridge to the point that it falls apart, the pieces don't fall into the 
canyon or river, reassemmble themselves in "amorphous" bubbles and float 
away.  Indeed, no pieces undergo reorginzation such that an I-beam turns 
into a steel tube with rivets from a neaby or distant joint now studded  
into its walls.  Similarly, cables snapped from stress don't attach 
themselves to other cables, or change shape into sheets. When we watch 
cells being frozen under a cryomicroscope we see incredible things.  We see 
blebs of membrane material being budded off under osmotic stress, we see 
great turbulence as ice grows and vast (on a nanometer scale) flow of water 
out of cells as ice fronts move forward.  

A good analogy here would be glaciation where we see things like mineral 
markers for the presence of diamonds moved hundred or thousands of miles 
from the volcanic tubes (where the diamonds really are) by ice. We know 
when we freeze cells, even with cryoprotectant, that surface antigens and 
bits of membrane material are exuded or "extruded (?)". In fact, even the 
high glyc (6M glycerol) freezing technique for red cells yeilds cells that 
have fewer surface antigens than cells that are comparably loaded with CPA 
and washed clean of it.  (Just glycing and deglycing DOES cause some 
antigen loss).

When you freeze living systems you do not JUST get a collapsed bridge or a 
distorted puzzle.  You get mechanisms coming into play which are very 
different.  You get BIOCHEMISTRY and self assembly, and all sorts of 
phenomenon that are NOT like the molecular bearing designs in NANOSYSTEMS.  
What you get is biology.  What you get is the physics equivalent of the 
transition from Newtonian to Quantum Mechanical environments.

It is no accident that this has been lost on most cryonicists because most 
of them (no accident here!) are computer people or engineers, very few 
biologists, fewer still biologists who have an intimate understanding of 
how cells do the magic they do.  And we know its magic not in the DNA.  I 
doubt whether you could fit the volume of DNA required to specify the 
PRECISE position of every atom in the human body into the volume of that 
human body.  I rest assured here that Merkle or someone else will soon have 
an exact volme, bit number, and estimate of input/readout equipment volme, 
calculated in no time at all :).  This example is relevant because it 
points out that living systems operate like capitalist economies; using 
self order, chaos, and a host of other poorly understood but LOCAL 
processes to carry on their fabrication and repair.

Donalson, Fahy, and I (I think I speak broadly for these others, and they 
can correct me if I'm wrong) do not look at molecular and cell-level 
biology from the top down, engineering specified, planned economy 
perspective of the big N nanotechnologists.  A corollary of this world-view 
is that when you view systems from our perspective, you find yourself in a 
land with contours and possibilities as removed from each other as West 
Berlin was from East, or Newton from Plank, Einstein and Heisenberg.

Joe and others should give some thought to this.


Mike Darwin


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