X-Message-Number: 15528
Date: Fri, 02 Feb 2001 04:48:52 -0500
From: Paul Antonik Wakfer <>
Subject: Comments Re: CryoNet #15499, #15500, #15502, #15507
References: <>

> Message #15499
> Date: Wed, 31 Jan 2001 07:10:58 -0800
> From: Kennita Watson <>
> Subject: To the disputants...
> 
> To all those involved in the recent disputes on Cryonet:
> Despite any vituperations or accusations, I *will* believe
> that everyone involved is honest and hardworking, and that
> disagreements are due to misunderstandings, incomplete
> knowledge, and/or human psychology.

I am not quite sure of the purpose or intent of Kennita's message here.
However, I want to assure her that from my pov there is no "dispute".
I am merely correctly errors, misconceptions and misunderstandings about
science, cryobiology, and logic.
Jeff Grimes appears to be merely asking questions in a sincere effort to
acquire clear information.
About the others, I wouldn't know.

> So please don't feel
> compelled to defend your honor or impugn anyone else's on
> my account.

My "honor" (read rationality) is automatically supported by almost every
word that I write, so you can be quite assured on my part.

> Message #15500
> From: 
> Date: Wed, 31 Jan 2001 11:03:51 EST
> Subject: Wakfer & bias
> 
> Just one extract from Wakfer's #15497:
> 
> I had written:
> 
> >>But as for guessing which approach is best, based on general background
> >>information, that is a potential snare. What counts, in the end, is the
> testing and >>the evaluation of the tests by independent professionals.
> 
> And Wakfer replies:
> 
> >If the "independent professionals" are not professionals within the field of
> science >which they are being asked to evaluate, and do not know the purpose
> and source of >what they are evaluating then their evaluations are of little
> worth. In addition, it is not >unheard of for an independent professional to
> happily take your money, wink to his
> >associates about your purposes, and then proceed to make an analysis and to
> give >you a report biased toward what you want to hear.
> 
> The first sentence is nonsense. A microscopist/pathologist looks for
> deviations from the normal, which is what we are interested in.

Mr Ettinger's black and white simplistic view of a highly complex area
once again shows his lack of experience in the experimental biological
sciences. During my several years of association first with Mike Darwin
and then with a current 21CM scientist, the problems with EM use were
discussed many times. While I am no expert in the details, I clearly
remember that there were different preparation methods, and which were
best to use and the details of their use depended on many factors
related to the experimental subjects and purpose. This was in fact so
important that different preparations could often show major differences
in the same uniform tissue. OTOH, some preparations would also show that
all tissue looked great even though others would show a mess. 

> As to bias or dishonest evaluations:
> 
> Our first evaluator was Dr. Pichugin et al, when he was in the Ukraine. If
> Wakfer suspects him of being untrustworthy, it seems odd that INC hired him
> to work in California.

Yuri Pichugin was hired to be INC's experimentalist first, because we
could not find anyone else in the short time-frame that we had, and
secondly because he had shown himself to be a dedicated, and
hard-working cryonicist who had some biology lab experience and
qualifications. Very frankly, the HSCP management team was quite
concerned about his suitability both in terms of rigorous understanding
of proper scientific procedures, and his basic objectivity in his
reporting to those for whom he worked, but we had very little choice if
the HSCP was to get started when it needed to and so we took a chance.
As I have reported before, after the first 6-9 months that chance looked
like it had been a mistake (to me at least) but at the end of 1999 Yuri
made a dramatic turn around, much to his credit, and he has become a
first rate experimenter under the direction of the HSCP's principal
investigator, turning out highly valuable work about which we (HSCP
management team) are delighted.

> Our current evaluation lab is headed by someone on the faculty of a major
> Canadian university. They are perfectly willing to be identified, and have
> said so in response to my direct question, but I am not willing to subject
> them to the possibility of harassment by people like Platt or Wakfer or

> Grimes. That wasn't in their contract; they aren't being paid enough for that.

Since when is the asking of questions considered "harassment"?

> And there is no possibility that they told us what they thought we wanted to
> hear, because the work was blind. They compared specimens, not knowing how
> they had been prepared.

As I explained above, this is not a sufficient safeguard since the wrong
method of preparation can sometimes make everything look equally good
(or bad). Frankly, since Mr Ettinger has already stated that no
differences were *seen* in specimens from areas which would be almost
certainly different diffusion distances for the glycerol (which
certainly must actually have *been* different), I suspect that the
preparation made everything, control or experimental from different
places, all look about the same.  

> (Yes, we are perfectly aware that not knowing the
> method of preparation of the specimen can have drawbacks in terms of
> preparing it for examination, but that is secondary. Washout before
> microscopy would also introduce new variables.)

All such processing introduces changes, but preparation is not at all
secondary as I have tried to describe above in my inexpert fashion from
old memories. I only wish that we had more knowledgeable people here to
give us the full story of EM work. Where is Mike Darwin when we need
him? :-)

> Message #15502
> From: 
> Date: Wed, 31 Jan 2001 11:49:35 EST
> Subject: Grimes notes

[snip]

> The first independent professionals were Dr. Yuri Pichugin and associates in
> the Ukraine, beginning around 1994. They did not do the original sheep head
> work-we did. But they repeated and then evaluated it.

In what peer-reviewed publication is this to be found so that we can
read of the detailed precision of the processing and the exact methods
of evaluation? Once again, the standard in current experimental science
is that the experiment is not complete and no results exist until it is
published in a peer-reviewed journal.
 
> As I remarked in my
> comment on one of Wakfer's posts, Wakfer's own INC and associates later hired
> Dr. Pichugin to work in California on their most advanced project, so
> presumably they had confidence in him, and still do.

Mr Ettinger's presumption is quite misleadingly stated as I have
explained before and again above.

> As for our current evaluators in Canada, I repeat, they are willing to be
> identified, but I am not willing to expose them to the possibility of
> harassment. They don't need or deserve that.

Again, since when are questions equivalent to harassment?

> About cooling rates: After perfusion, CI cools slowly, using first dry ice
> and then liquid nitrogen, because we have found that avoids cracking (which I
> believe no one else has avoided). As to whether that is the best possible
> trade-off, we can't be certain, but so far that has been our decision.

For those who might be concerning about the importance of large
macroscopic cracks in patients, think of cracking as what happens to
100s of thousands of persons everyday worldwide on whom surgeons are
operating. They suffer large macroscopic "splitting" of their flesh
during the operation. However, this is a relatively minor trauma to the
body when treated properly and sutured closed and, within a timeframe of
weeks to months, completely self-repairs.
While this is certainly added damage which it would be nice to prevent,
it pales in comparison to the damage of toxicity or ice crystals which
can affect the patient at the cellular level in every part of his
cryopreserved tissue, destroying trillions of minute important
structures either chemically or physically.
Again, I recall in many discussion with Darwin and currently involved
scientists, that it was made very clear that the importance of cracking
damage was far less than the others. Certainly, any decision to allow
toxicity and ice crystallization damage in order to prevent macroscopic
cracking would make no sense at all.

> Newcomers and watchers have several choices. One is to pick an organization
> and join and make your arrangements, and then, if you have the time and
> inclination, become active in the improvement of the organization. Another is
> to emulate Platt and Wakfer and perhaps Grimes and some others and say a pox
> on all your houses, you aren't good enough and I won't deal with any of you,
> so there.

For myself, I have repeatedly stated that if and when I need to be
cryopreserved, I will go money in hand to the organization which at that
time I believe to be the best, because then I will have no other choice
but clear death. Living in Canada, I have little hope of emergency
service anyway. In the meantime, I will not associate myself with
organizations with which I have no confidence in their procedures or
their management. This is not saying "a pox on all your houses". Instead
it is saying "clean up your act and you will have me with you!"

>Message #15507
>From: 
>Date: Wed, 31 Jan 2001 16:03:14 EST
>Subject: Pharmacology

[snip]

>Now, "pharmacology" essentially refers to administration of drugs or 
>chemicals, or possibly also biological agents, through a variety of 
>avenues--ingestion by mouth, inhalation, topical application to skin or 
>mucosa, injection into the vasculature, injection into specific organs or 
>tissues, intestinal lavage, perhaps a few others. But in order for a thawed 
>patient to benefit from pharmacology, he must first be "alive"-functioning 
>sufficiently to allow utilization of the pharmacologicals. 

Actually, Mr Ettinger has omitted the most important aspect of
pharmacology. The administered chemicals must be administered in
"pharmacological" doses as opposed to physiological doses, ie doses
which the body does not get or produce from a standard or even a strange
diet. For xenobiotics this means any dosage at all, but for chemicals
found in food or produced by the body, this means in higher dosages than
might be reasonably obtained from food or is ever produced by the body.

>As I recall, published reports tell us that, with the rat brain slices, 
>specimens that showed 53% function by the K/Na criterion did not recover 
>further after hours of culturing or incubation. In other words, today's 
>pharmacology could not restore them to normal function.

This is not correct at all. The culture and incubation was most
certainly not the limit of today's technology!
For example if the tissue was grafted it might all recover. We have
tried that because there is no need to do so at this stage. There are
more important things to do first, such as continuing to devise less
damaging cryoprotectant mixtures and methods.

>Maybe tomorrow's 
>pharmacology will do better, but we don't know. After all, in the absence of 
>actual repair of the machinery, all pharmacology can do is offer nutrition or 
>medicine, so to speak; if the tissues are not sufficiently functional to 
>utilize this nutrition or medication, then it won't help.

Currently, we can't possibly generate any external environment for
tissue which compares to the ability of the "crucible" of the body to
nurture tissue. However, if all the tissue is in poor enough health then
it will not likely be able to nurture itself back to better health. So
while his explanation is inadequate, I agree with Mr Ettinger's main
thesis here. A whole brain with tissue at only 55% viability would not
likely be able to self repair (although it might if transplanted to a
completely healthy body). 

>With advanced nanotech, on the other hand, the degree of damage just doesn't 
>matter (except possibly from a cost or time perspective), so long as the 
>original structure is present or inferable.

Two things here.
1. Please define "advance nanotech" and specify how and when we will
attain it. If you cannot, then it is a pipe-dream no more certain than
perfected suspended animation.
2. Please provide detailed proof that "the original structure in present
or inferable" for any patient in storage today or to be preserved with
the best of any current procedures.

> And housekeeping structures 
>(mitochondria, glial cells?) can "simply" be replaced if necessary, since 
>they are generic and probably not related to the individuality of the patient.

Actually, the mitochondria are. One person's mitochondria are not the
same as anothers, but I grant the difference is relatively minor
(although it could well affect individual lifespan).
In any case, once more please specify how all the mitochondria and glial
cells will be replaced in situ without affecting the structures which
relate to memory and personality (which, of course, we do not even know,
BTW).

>Again, today's "life support" systems obviously will not suffice to restore 
>and maintain enough function in thawed cryo patients to allow uptake and 
>utilization of chemical or biological medications, even if those medications 
>by themselves could permit self-repair of the tissues.

Again, this is incorrect because it is unknown. Not all methods have
been tried since it is premature to attempt this.

> Tomorrow's might--but 
>the reports to date on the rat brain slices do not seem encouraging.

This is Mr Ettinger's distorted view. Many others are very encouraged.

> After 
>all, those slices--as far as I know--were already getting the best available 
>environment, the right nutrients and oxygen etc.

This shows how little Mr Ettinger understands biology.

>It isn't easy to see how any 
>further additions to the nutrient bath could improve matters.

Nutrient baths are not equivalent to within-body environments.

>How much post mortem delay is allowable before viability by the K/Na 
>criterion becomes very low? I have tried to find out, and seen estimates from 
>a few minutes to about an hour--and that is with originally young and healthy 
>specimens, under ideal laboratory conditions. Since cryonics patients are 
>almost never young and healthy and cryopreserved under ideal laboratory 
>conditions, we can probably estimate that patients will have much less K/Na 
>viability than reported with the rat brain slices.
>
>That suggests that it is unlikely that pharmacology alone will suffice, even 
>with actual full vitrification. 

I have addressed the warped logic of this before and it can all be
avoided if the cryonics organization uses the right procedures (at least
in those patients who deanimate in a controlled manner). Besides, if we
continue to get close enough to viability after cryopreservation, then
hospitals may take over the preparation job (extra income is always an
inducement) and minimize the ischemia time before a washout preservative
and transport solution is placed in the patient.


-- Paul --

The Institute for Neural Cryobiology - http://neurocryo.org
A California charitable corporation funding research to
perfect cryopreservation of central nervous system tissue
for neuroscience research & medical repair of the brain.
Voice-mail: 416-968-6291  Fax: 559-663-5511

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