X-Message-Number: 9638
Date:  Wed, 06 May 98 09:36:28 
From: Mike Perry <>
Subject: Re: Unasked Questions

Saul Kent, #9620, wrote:
>
>        One thing that's been totally missing from 
> the discussion to date, however, is questions about 
> *why* we've changed our minds about promoting
> cryonics, and why we're now so negative about 
> today's product.  We've pointed out that we want
> to make the product better, but why do we think
> it's so bad *now*?
>
>        Isn't anyone interested in seeing the 
> evidence that's caused us to change our minds 
> about today's cryonics methods?  Isn't anyone 
> curious about *how* severely today's methods 
> damage the brain?  Or what type of damage 
> we should concern ourselves with most?
>
I for one am very interested in these things. Some years ago I wrote 
an article for *Cryonics* with the subtitle "Why Cryonics Probably 
Will Work" ("For the Record," *Cryonics* Apr. '92). It was based 
largely on the Suda experiments, in which, among other things, a cat 
brain cooled to -20C and rewarmed after 5 days showed a brainwave 
autocorrelogram very similar to a live control. (Brain waves were 
detected after up to 7.25 years storage though differing 
more, as might be expected, from live controls the longer the brains 
stayed in storage.) The brains in all 
cases were anesthetized and unconscious. But quite a lot of brain 
activity is going on in a live unconscious brain, so I took the 5-day 
result as evidence that the Suda protocol probably left the brain 
fairly intact. It was a good bet, I thought, that memories, etc. 
would survive the perfusion (a rather crude one that did not get as 
much cryoprotectant in as is usually done with cryonic suspension 
today) and cooldown to -20. Put another way, it seemed unlikely that 
whatever damage there was would selectively and massively destroy
memories but leave other functions as intact as they seemed to be.

I consulted with a well-known cryobiologist, who is still 
active today and interested in this subject, and in fact it was he 
who suggested focusing specifically on the 5-day results, since they 
made the best case for what I was trying to argue. To complete the 
argument, I reasoned that, while cooling to well below -20 is needed 
for longterm stabilization of the tissues, this cooling on the face 
of it did not seem likely to induce the kind of damage that would 
massively obliterate information, based on what I knew. On the other
hand, cryonics patients, using protocols with which I am familiar,
are certainly not kept in the vicinity of -20 or warmer for anything
like 5 days, but are fairly quickly cooled to around dry ice 
temperature (-78) or below.

About this time I first learned of EM studies using 
freeze-substitution, in which the water content can be removed from
tissue frozen to around dry ice temperature, without warming the 
tissue. When this is done, *a remarkable pattern of extensive damage 
is shown to occur*--mainly, the tissue is riddled with voids 
presumably occupied by ice crystals, and the cells are shrunken into 
small dark lumps much tinier than they appear at higher temperatures. 
The numerous breaks between cells, however, are very clean with 
little sign of debris, suggesting (though not proving) 
that the sort of damage that occurs 
is not of the "dissolving" or "molecular stirring" variety that would 
especially signify massive obliteration of information. (And clearly 
the cells are not simply dissolved into a uniform soup that could 
leave clean breaks on freeze-fracturing.) As it turns out,
Suda was unable 
to obtain good brainwave results from tissue cooled to much lower
than -20; I think he got nothing from -90, and this would seem to be 
explained by the formation of the myriad small ice crystals.

The formation of ice too is not the only damage that goes on if we 
cool below -20. Roughly speaking, pure water is expressed from cells 
and freezes outside them, which concentrates various chemical species 
within the cells. This concentrated chemical mix itself could be a 
worse source of damage than the ice. Chemical attack is to be feared 
much more than mechanical damage as a cause of information loss. 
Again though, the clean breaks are some cause for optimism and speak 
against *some* types of massive cellular damage occurring. There 
could still be significant damage though, and, as I understand it, 
there is damage such as protein denaturation and trashing of cell 
organelles. More or less, the damage seems to affect non-covalent 
bonds that occur between and within proteins, while the stronger 
covalent bonds are more resistant and relatively little affected. 
Longterm memory, on the other hand, which endures for decades and in 
other ways seems quite durable, seems to involve covalent bonding 
(e.g. protein phosphorylation) and/or larger-scale structures such as 
synapse configurations, which ought to be reconstructible even after 
considerable damage. Unfortunately we still don't 
understand the physical basis of memory in the brain well enough
to know how durable we can expect our memories to be.

At the recent Alcor conference I heard some well-presented talks by 
Mike Darwin and Brian Wowk. Mike addressed the problems of warm 
ischemia which might be expected to occur early in a cryonic 
suspension or even before, and Brian the problems of freezing 
damage as we go down from 0C to -100 and below. There are good 
reasons to be worried on both counts. Certainly we need more 
research, and better suspension protocols. I am happy 21st Century 
Medicine is undertaking and working toward these things, wish them 
every success, and hope I can support the effort in some significant 
ways.

On the other hand there are certain reasons for cautious optimism.
There are the Suda results--unfortunately they haven't been
repeated or extended (unless you count some recent work with rabbit 
brains by Pichugin et al) but still seem valid. This suggests that 
the ischemia problem may not be unmanageable, especially if we take 
into account the repair capabilities future technology should offer. 
(Some other evidence that is positive toward the ischemia problem, 
though as usual within limits,
comes from the work with dogs in the '80s at Alcor 
and elsewhere, in which the animals survived total body
washout and cooling to near the ice point without apparent
deficits.) Similarly, when it comes to the freezing damage problem,
there is evidence that memories will survive the sort of insults that 
seem likely, plus other positive evidence (some brain cells do 
survive freezing to liquid nitrogen temperature, for instance).

Overall, I remain cautiously optimistic about the prospects of people 
frozen under good conditions today being reanimated. Additional 
factors are the likely redundancy of brain memory information, and 
the likely capabilities, as I see it, of future repair technology 
including nanotechnology. But I would like to hear more
of "why we think it's so bad *now*" and correct any
misunderstandings I may have.

I thank Hugh Hixon for consultation in this writing.

Mike Perry

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