X-Message-Number: 2892
Date: 15 Jul 94 19:04:42 EDT
From: Mike Darwin <>
Subject: SCI.CRYONICS Cracking
Bob Ettinger writes:
<<Dr. Yuri Pichugin and Dr. Gennadi Zhegunov have completed the microscopic
examination of the sheep head frozen to liquid nitrogen temperature according
to the Cryonics Institute protocol, but without perfusion. Results show
expected freezing damage, but only micro-cracks, not the larger scale
cracking reported with other procedures. Detailed report with photos will be
forthcoming; the report and some of the photos will be published in THE
IMMORTALIST in due course, and the full set will be made available to
interested parties.
The Ukrainian scientists are encouraged by this result to think that, with
glycerine perfusion as we do it, cracking may be avoided altogether, although
this remains to be seen. The next phase will be the full procedure, including
perfusion.>>
Perhaps my previous posts have been unclear on this, but these are *exactly* the
results that "everyone" else has encountered -- with unglycerolized brains. In
fact, as I know I pointed out previously, Jerry Leaf and I did a series of
experiments in the early '80's with neonatal lambs frozen to liquid nitrogen
temperature without cryoprotective perfusion. We used a variety of techniques
to saw off the heads of these animals and then examined the body and head/brain
for cracks. We saw no gross macroscopic fractures, only small ones (.5 mm) and
very few of those. Similarly, rabbits and cats cooled to -196*C without
cryoprotective perfusion showed only microscopoic fractures on histological
examination.
By contrast, glycerolization before cooling to -196C was associated with
macroscopic fracturing, as was perfusion with Me2SO (DMSO). Once again, I
would point out that this property of glass forming agents is well understood
and I have previously cited work in my posts by Luyet, Fahy, and Rapatz which
document this effect in solutions *and in organs* loaded with cryoprotectant.
Bob has also repeatedly stated or implied in the past that only CI uses very
slow cooling rates to dry ice or liquid nitrogen temperature. This is not so.
To the best of my knowledge most if not all Alcor patients since Terri Cannon
was cryopreserved in February of *1985* have been very slowly cooled to liquid
nitrogen temperature. In fact, the rate at which Terri was cooled makes CI's
one week protocol (to -196C) look fast. It took us roughly 300 hours (or 12
days) to get Terri from -79C to -196C. Similarly, Terri was cooled at a
controlled rate to -79C and this took about 25 hours -- and I might add that
there was a period of annealing allowed at around -110C to -120C, to further
minimize the chances of cracking.
More to the point, the complete protocol used to treat Terri has been published
and this data has been public record for nearl;y a decade. Copies of reprints
of this article are available from Alcor (800)367-2228 and the text first
appears in CRYONICS magazine in 1986 (Darwin, MG, Leaf, JD, Hixon, HL. Case
Report, neuropreservation of Alcor patient A-1068. Cryonics 1986;7:17-32.
While I do not have access to much of the Alcor data, those case histories which
I had completed (and thus have copies of) and those patients whom I have raw
data on, bear out my assertion. For instance, Patient A-1049 was cooled to LN2
temperature over about a 150 hour interval! I believe that while whole body
patients were cooled a little faster (about 1 week) they were still cooled very
slowly with one or two possible exceptions where there were technical
diffculties. In fact, one patient was cooled over a period of 450 hours! These
numbers are, as far as I can tell, as slow as Bob's or slower. Furthermore, all
Alcor patients were instrumented with multiple surface and core thermocouple
probes which detailed not only the rate of temperature descent, but also the
differential between body surface and brain surface, and the differential
between body surface and core (such as rectal or esophageal) temperatures.
Acquiring and maintaining such data is critical for many reasons (liability
protection, discipline and feedback for those administering the treatment...)
but also because it is critically important to help us understand what is going
on and what has gone on. In the past, at least three partients have been
converted from whole body to neuro and the opportunity presented by this
unfortunate even used to get feedback about the effects of cryopreservation
techniques (indeed it was these autopsies which first alerted us to the cracking
problem). Over the same period of time at least two and possibly three
patients' cryopreservations have been terminated. Most recently an Alcor
patient was removed from suspension. As much as a tragedy as these situations
are, we need to be realistic and realize that they will continue to happen from
time to time *and* we need to profit from them.
Certainly to a man and woman all of the patients who I have know (before cardiac
arrest) who underwent cryopreservation were adamant that, if nothing else,
*something be learned from what was done to them so that someone else could
benefit, even if they themselves did not benefit by revival.* Several patients
have even prompted us to do experiments on the noncryopreserved portion of their
bodies to advance the state of the art -- here I am thinking of Arlene Fried who
had her kidneys sent off for evaluation of viability after transport (and yes,
they were still viable enough to have been considered for transplantation).
However, without good data one what was done to patients to prepare them for
cryopreservation, we can't make any sense out of either invasive or noninvasive
tests subsequent to their cryopreservation. (keep in mind that it may be
possible to safely noninvasible examine patients in the coming years for cracks
or other things of interest).
The points I am trying to make here are simple, straightforward, and have been
learned long ago in many other areas of science.
1) None of us is done any service by "media releases" of results. The first
results should be carefully documented as to material and methods and should be
presented in a detailed and orderly way. To go around saying or implying that
"we think our technique may stop this serious problem from occuring" without
carefully defining *what exactly is being done* is counterproductive and gives
people no real basis on which to make decisions. (Here I plead guilty to having
engaged in similar behavior from time to time).
2) An integral part of the science is writing up the materials and methods and
your results. I would go so far as to say that you cannot really learn properly
unless you order your data and write it up. You are kidding yourself and
everyone else if you think otherwise. Often, seemingly inconsequential things
become very important. I am reminded of the entomologist who discovered "paper
towel factor" by failing to mention that he wiped his glassware off with paper
towels instead of allowing it air dry. As it turned out there was a wood pulp
factor which acts as a signaling hormore for a certain specices of insect to
undergo metamorphosis! No one could reproduce his results until they started
wiping down their glassware with Zellerbach paper towels.
3) A detailed description of materials and methods is critical to allowing other
investigators to reproduce the work and/or to interpret it. Several individuals
in the cryonics community have made remarkable claims for reducing injury
without any subsequent disclosure of *how* this was done. Indeed, they have
even gone so far as to indicate that they have no intention of (for the
forseeable future) even writing it up. It is thus impossible for anyone to
realistically evaluate these claims or seek to reproduce them, which is an
absolutely critical part of science.
Years ago, an investigator named Guttman claimed that he was able to freeze and
thaw kidneys successfully after DMSO and helium gas perfusion. This work caused
a great deal of excitement. Subsequently David Pegg and others tried to
reduplicate the work and could not. The probable reason was that Guttman was
using faulty temperature measuring techniques which did not give the true core
temperature of the organs (and they were thus not really being frozen).
The whole polywater debacle is another example. Good science requires good
documentation. Period.
I have no idea what Bob really did to his sheep heads. I certainly have no idea
what is really being done for his patients in terms of perfusion. The devil is
in the detail.
Until we get a disciplined and full disclosure about what is going on we cannot
make informed choices about what we want done to us, and just as much to the
point, we can't learn how to improve what we are doing to ourselves.
Finally, this not about politics or interorganizational rivalries. It is about
*science*. Yes, I know that sometimes there will have to be delays about
disclosures for patent reasons and for legal reasons. We must do the best we
can to minimize these and work around them. But there is no excuse for not
making disclosures, the vast majority of which are not constrained by such
problems.
I for one am very tired of people making claims about what others do or don't do
(either directly or by implication) without first disclosing what *they are
doing* in sufficient detail to allow for a meaningful evaluation -- and without
taking the time to responsibly examine the literature. This is why BPI has
posted its patient case histories, has posted reasonably detailed summaries of
research work, and why we will continue to do so.
Anything else isn't just bad science -- its suicide.
Mike Darwstrained by suchEnd of 2892
echo 2893 1>&2
cat >2893 <<'End of 2893'
Date: Fri, 15 Jul 94 18:13:03 PDT
From: (Ted Skrecky)
Subject: CRYONICS
NOTE: Douglas Skrecky currently doesn't have access to the Internet.
However, his brother (that's me) does. I have collected the last few
weeks of messages posted on the Cryonet and have mailed them on a disk
to him. In return, he sent me this message which he would like posted
on the Cryonet:
Message-Subject: CRYONICS SUSPENSION TERMINATION
A FEW THOUGHTS ABOUT THE SYLVIA GRAHAM CASE
By Douglas Skrecky
What appears to be lacking in cases like the suspension termination
of Sylvia Graham is a credible backup plan so that if the primary mode
of preservation fails not all is lost. The competing demands for the
preservation of Sylvia's corpse (by her husband) and for a Christian
burial (by her sister) are not entirely mutually exclusive. Although
permafrost burial or desiccation would appear to be unacceptible to one
party there is yet still another alternative. The demands of both
parties might have been satisfied by chemical preservation with an
alcohol based fixative such as Omnifix and subsequent storage in a
corrosion resistent casket, which was then encased in concrete treated
with calcium nitrate corrosion inhibitor.
Sylvia Graham's hopes for physical resurrection are now lost. She
is the first lost by Alcor. There will be others.
End of 2893
echo 2894 1>&2
cat >2894 <<'End of 2894'
From:
Date: Fri, 15 Jul 94 22:52:21 EDT
Subject: CRYONICS cracking/Darwin
Mike Darwin says the Cryonics Institute cooling procedure is not slower than
some others had used, and others also had similar results when there was no
perfusion--i.e., only micro-cracks. He also complains that our published
procedures were not sufficiently detailed, and that we shouldn't make
premature claims.
First, we haven't made any premature claims, or any claims at all about our
own work that have not been factual. If I had wrong or incomplete information
about previous work of others, then I made a mistake.
As to reporting ongoing Ulkrainian work, and possible conjectures based
thereon, I don't see anything inappropriate in that. Almost everybody likes
to be kept up to date on intreresting work, even when it isn't completed or
definitive. Scientists exchange such messages all the time.The completed
reports will be available in full when they are ready.
MIke says Terri Cannon was cooled from dry ice to liquid nitrogen temperature
in about 12 days, whereas we usually take only 7 days. However, he also says
she was cooled to dry ice temperature in only two days, whereas we take 7
days for this phase also.
That cracking occurs more readily in the presence of concentrated glycerol
seems to imply--other things equal--that high concentrations are undesirable.
The push by Mike (and Alcor when Mike was there) toward very high
concentrations seems to be related (my impression) to the push toward
vitrification rather than freezing. But since vitrification is still
unperfected, it may be that imperfect freezing is better than imperfect
vitrification. We'll see.
I give Mike and Alcor high marks for documentation. We will make equal
efforts for full detail when it seems relevant and useful. In fact, this was
one of the reasons for asking the Ukrainians (and Russians and Alcor) to
duplicate and extend our work. We never try to hide anything--but neither do
we go to great lengths to provide details or documents of doubtful or
marginal value when we have many other demands on our time.
If work of Dr. Pichugin and Dr. Zhegunov shows that the CI protocol has some
advantages, of course we will be gratified. In any case, we will learn
something. The Cryonics Institute will always work toward utilizing the most
effective procedures known, subject to restrictions of law and cost. And if
the only obstacle is cost, we will probably offer it as an option. (In fact,
we already offer our members the option of perfusion by other organizations,
at higher cost, if they wish; if we are ever convinced this really
significantly improves the patient's overall chances, we will recommend it.)
Robert Ettinger
End of 2894
echo 2895 1>&2
cat >2895 <<'End of 2895'
From:
Date: Fri, 15 Jul 94 22:55:53 EDT
Subject: SCI.CRYONICS Dolinoff/Merkle
Subj: Dolinoff & Merkle
Date: 94-07-15 22:17:59 EDT
From: Ettinger
To:
Anatole Dolinoff (President of the Cryonics
Society of France), although for many years a champion of cryonics in the
French media, had for years been increasingly pessimistic about the chances
of reviving patients frozen by present methods--mostly because he just felt
the job was too formidable, too many atoms and molecules to move around.
Generalized arguments didn't move him, nor did the nanotech concept (to the
degree that he was acquainted with it).
Now, however, he is studying, and at the same time translating into French,
Ralph Merkle's two-part article from CRYONICS on molecular repair of the
brain. He seems much impressed with this--although he estimates it may take
months to finish the job. So apparently Dr. Merkle's arguments and
calculations have made an impression where nothing else had. We can probably
expect that at least some others will have a similar reaction.
Robert Ettinger
End of 2895
echo 2896 1>&2
cat >2896 <<'End of 2896'
From: Ralph Merkle <>
Subject: CRYONICS neuroscience on the web
Date: Fri, 15 Jul 1994 20:46:47 PDT
I noticed an interesting WWW page on the neurosciences which
provides "... a guide to selected Neuroscience resources available
via the Internet."
It has links to a number of brain atlases (including a sheep's brain).
The URL is: http://http2.sils.umich.edu/Public/nirg/nirg1.html
There is another page on 3D reconstruction of tissue,
the URL is: http://neuron.arc.nasa.gov:80/3dreconstruction/
Cheers!
Ralph
End of 2896
echo 2897 1>&2
cat >2897 <<'End of 2897'
From:
Date: Fri, 15 Jul 94 23:53:37 EDT
Subject: CRYONICS crack p.s.
In my earlier reply to Mike Darwin's criticism I neglected to return the
focus to the main issue--the fact that, in the Cryonics Institute sheep head
experiments, we observed no visible cracks, and no leaks in the vasculature,
WITH glycerol perfusion, after rewarming from liquid nitrogen temperature,
whereas others had reported cracks at all levels with their procedures. This
is what was new (as far as we know) and potentially important.
If the result of our combination of procedures (not just cooling/warming
rates) is confirmed by the Ukrainian work, this will be gratifying and
useful--if the microscopic results are also good. If our results are not
confirmed, we will have to try to find out the reason. If our results are
confirmed but the microscopic results show offsetting disadvantages, at least
we will have learned something.
Robert Ettinger
End of 2897
echo 2898 1>&2
cat >2898 <<'End of 2898'
Date: Fri, 15 Jul 1994 19:06:41 -0700
From: "Leonard N. Zubkoff" <>
Subject: CRYONICS Storing PostScript
Regarding:
[ Brian, now I'm a little confused. Aren't postscript files always
ASCII files? If so, then uuencode will not be needed for them. - KQB ]
I agree with Brian on this. PostScript files are indeed ASCII and often even
huma--readable, but mail transfer systems have (unfortunately) been known to
modify ASCII files, so it would be safest to uuencode them as well.
Leonard
End of 2898
echo 2899 1>&2
cat >2899 <<'End of 2899'
Date: Sat, 16 Jul 94 01:23:48 CDT
From:
Subject: CRYONICS Postscript
Kevin:
> Brian, now I'm a little confused. Aren't postscript files always
> ASCII files? If so, then uuencode will not be needed for them. - KQB
The nice thing about a good uudecode utility is that it
automatically strips off email headers leaving you with the final
postscript file after issuing only one command. Otherwise you would
have to go in with a text editor and manually remove the headers
before the file is useable. Also, I'm not sure whether raw postscript
files are email-able. In particular, do carriage returns occur
regularly enough so that line length limits on mailers and editors
will not be exceeded? Never tried it.
--- Brian Wowk
End of 2899
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