X-Message-Number: 12472
Date: Wed, 29 Sep 1999 01:32:00 -0400
From: Mike Darwin <>
Subject: Further Comments on Patent

As expected, I left out several things in my narrative yesterday. I also
apologize for the roughness of the text, but  my time constraints are such
that I neither spell-check nor proof-read any communications of a
non-critical (i.e., core business) nature.

First, I Ieft out a *key* credit in my narrative when I stated:

" I also want to make very clear that the intellecual property in this
patent was the work of three people: Wowk, Darwin and Russell. Each made
pivotal contributions and spent countless back-breaking hours in the
laboratory."

Added to this should have been Steve Harris, M.D. (who *is* credited
elsewhere). Further, I wanted to mention that Steve's abilities as a
synthetic organic chemist are nothing short of incredible. One of the
molecules not claimed in the posted patent and which has, in my opinion,
shown incredible *specific* promise for improved brain cryopreservation
(and was used in the two brain vitrification studies presented at  the 21CM
Seminar, and to achieve the high quality post-thaw brain EMs posted on the
ACS website) was extremely costly, and in very short supply. In fact, to my
kowledge, at one point in time the entire world's supply of this molecule
resided in our hands. Very experienced synthetic chemists and custom
synthesis chemical companies around the world were quoting outrageous
figures for manufacturing this molecule, even in large quantities. Steve
applied himself to the problem, discovered a de novo, very simple and very
elegant synthetic pathway. He then found a graduate student in an
appropriate laboratory to produce the compound in quantities sufficient to
allow for toxicological and ultrastrucural evaluation in the standard
kidney slice model, and for post cryopreservation ultrastructural
evaluation in the intact mammalian brain.

I also want to mention the enormous number of hours Chris Rasch has spent
doing many hundreds, and perhaps now, *thousands* of grueling, repetetive
and boring toxicological evaluations of these cryoprotective agents (CPAs)
using the kidney slice model developed by Greg Fahy at the Red Cross many
years ago. (FYI: the toxicological response of  kidney parenchyma,
particularly the tubule cells, appears to closely approximate that of brain
neurons and gials cells.) I would conservatively estimate that Chris has
single-handledly put in over 10,000 hours each year, for the past 2 years
to evaluate these agents *and* the use of drugs to mitigate toxicity and
enhance recovery/viability following loading and unloading with novel and
conventional CPAs. What was not adequately communicated in my narrative is
that in 21CM we have a "science factory" in operation in Rancho Cucamonga a
la Edison with the considerable "plus" of a fair amount of the theoretical
genius of Nikola Tesla thrown in as well.

A point I left out regarding comments made on Cryonet was a response to the
following remarks from Thomas Donaldson:

>As for congratulations, it seems to me that the most congratulations are
>due to Saul Kent and Bill Faloon, who funded 21st Century Medicine in the
>first place. Yes, such advances do require redoubtable technical and
>scientific knowledge, too, but they could not have occurred without 
>funding ... and in my own personal estimation, they might have occurred
>as long as 10 years ago, if only the funding had then existed.

No one owes a deeper debt of gratitude to Bill and Saul than I, for they
have supported my efforts unstintingly,  first with Alcor and later with
other endeavors over the past 15 years. However, I do not agree that "the
*most* congratulations are due to Saul Kent and Bill Faloon" (emphasis
mine). In fact, I believe this attitude is pernicious, corrosive, demeaning
and most importantly *inaccurate.* Yes, Saul and Bill have provided
enormous sums of money which have taken good chunks of their time (and thus
their lives) to produce. But the kind of work required for the advances
being made at Critical Care Research and 21st Century Medicine are not
confined to  "redoubtable technical and scientific knowledge." Rather, they
extend deeply into the most personal aspects of the lives of the principals
involved in the day-to-day research and business operation of these
companies. As examples: giving up virtually all spare time, and most "home
life," including major compromises in virtually every aspect of their
non-working life: including but not limited to serious disruption of
"normal" social activity and even serious sleep deprivation.  I cannot
count the days I've seen Joan O'Farrell our COO here at CCRI till 0400
after starting her day at 0900 the day before, only to be here at 0900 the
following day and so on, day after day... Eugne Leitl is often ashen and
severely sleep-deprived running on coffee and "Jolt" cola in order to put
in inhumanly long days. My own personal and social life have all but
vanished, and that is true for many others here at CCRI and, I believe, at
21CM as well.

Money is all well and good. It is precious, damn hard to come by, and
absolutely essential. But it CANNOT, IT ABSOLUTELY CANNOT buy the kind of
effort that has been going on here for the past few years. That cost *is* a
large part of  the very lives of the people who give it, and it is
unarguably as valuable, if not more so, than hard cash. It is time quite
possibly forever lost, which for many of us, will likely not be regained.
Speaking for myself, I am 45 years old now, and at the very end of a period
in my life that I could spend in pursuits which require stamina and
physical capabilities which will not be there even 5 years from now. I am
also ever mindful of men like Jerry Leaf, who most people on this list
probably have not even heard of (!) who's lives ended well before they
expected in no small measure as a result of their efforts to advance this
field of endeavor, and whose *indefinitely*  "postponed gratification"
rests with them in liquid nitrogen in Phoenix, Arizona. The men and women
involved in this endeavor are paying with capital as dear as any gold or
dollars ever  minted or earned. And many are paying for it *without being
compensated in money now* and at considerable risk of NEVER being
compensated.  (Such compensation *may* come later, but it may well not, and
it is a gamble damn few are willing to make in life, and a gamble which,
with few exceptions, *none* of the people on this list have made or been
willing to make, Thomas Donaldson included.)

This not to denigrate the fine efforts put forth by many on this list who
have worked hard and long for advancing cryobiology or cryonics now, or in
the past. However, speaking from my unique perspective (having been around
for so long (since 1968) and involved with so many cryonics operations), I
have never seen anything even remotely approaching the sustained,
*cooperative and productive effort of this magnitiude in the entire history
of this idea.* In fact, I have rarely personally witnessed it any sector of
 life: business, social, charitable, or religious, although I am acutely
aware of many contemporary and historical examples.

As thanks for these efforts they have mostly been ignored and have often
been denigrated or made to seem superfluous by the most outspoken on this
list. Robert Ettinger's response to expose Olga and Ziggy Visser as the
frauds they were was to ban any cryopatient treated by me (BioPreservation
(BPI)) from being stored in CI's facilites thus ending contracts between
ACS members desiring both services and ending the contract between CI and
CryoCare for storage, which, BTW, probably cost CI arrangements with Bill
Faloon and several other CryoCare members who did not wish to be stored
with CryoSpan. His reason: "my unethical disclosure of the active
ingredient in Visser's Virodene and cryoprotectant frauds."

And this does not include the Nanoluddite postings of George Smith.

Finally, one individual from CryoNet wrote to me asking the following
questions which deserve at least cursory answers:

Regarding my comments on the Visser affair:

>I don't understand this yet.  You might be saying:

>1. The Visser affair depleted a resevoir of money that would otherwise
>have been spent on doing the clinical trials.  (But why are they part
>of the same pool of money?)

>2. The Visser affair caused the regulatory authorities to be
>predjudiced against 21CM.  (In this case have you considered licensing
>the technology to someone else who might want to bring it forward?)

>3. The Visser affair caused the regulatory authorities to be
>predjudiced against certain technologies, including the drugs that
>were going to go through the trials.  (But what is the resemblance
>between DMF and the drug that were going to go through clinical
>trials?)

>4. The Visser affair screwed up the regulatory structure of South
>Africa enough that attempting clinical trials in South Africa in
>general is pointless.  (But why is South Africa the only option?)

>5. Something else?

The answer is #4 above. It is simply impossible to realize the impact the
Virodene fiasco had on clinical trials and experimental medicine in SA. And
no, SA is not the only option but it was, until recently, a particularly
attractive one for the following reasons:

1) Acute resuscitation research in the U.S. has been brought to a virtual
halt due to the FDA's and other regulatory agencies' stance on the need for
*informed consent.*  Obviously, it is"difficult" (read: impossible) to get
informed consent from someone in cardiac arrest, or their next of kin, in a
timely fashion. Proposals that ads be placed in on public access TV and
newspapers in communities where trials are to be conducted allowing people
to "opt out" have been rejected. 

This kind of "public notice" for important, life impacting projects
(government and private) are done all the time in your local newspaper.
When the government wants to build a highway through where your home is
located, or a corporation wants to put a 24-hour petrol station next door
to your home it is handled in precisely this way. While it also true that
most people rarely read these endless pages of small type in their local
newspaper, nevertheless this fine print public notice sometimes ends up
determining where and/or how they will be living a year or two later.
Sometimes it determines whether they will be alive at all: dams, waste
disposal sites, military testing of nuclear or biological weapons were and
are often vetted through these channels in far finer print and far more
obtuse language that we've proposed be used.

2) It is our position that current methods of CPR are grossly clinically
inadequate (survival to discharge is 1% in New York City (one of the worst)
and 12% in Seattale (one of the best) and the incidence of post
resuscitation neurological deficit overall in survivors is ~80%). Further,
closed chest CPR was never properly clinically validated (no Randomized
Clinical Trials against the previously used, and in our opinion, (and
supported in the literature) superior open chest cardiac massage: overall
survival rate ~30% with <15% neurological deficit). Perhaps most
importantly, INFORMED CONSENT is NOT obtained before closed chest CPR is
applied today! BTW, closed chest CPR was never subjected to FDA review and
was put into universal practice on the basis of limited, often clinically
irrelevant, and frequently scientifically invalid, animal and small-scale
human research studies conducted in the early 1960s. 

3) Most Western countries tow the FDA line, and most countries that do not,
lack the high quality infrastructure and medical care available in places
like South Africa which, despite being a Third World country, has excellent
tertiary care facilities with superbly trained physicians, nursing staff,
and support infrastructure: autoclaves, clean linens, modern analytical
equipment, staff who understand the scientific method, and so on). We could
certainly "do" a study in Mexico or China, but we would be faced with
rampant corruption ("mordita" or the "the bite" as they call it in Mexico
and Latin America) and tertiary medical facilities out of the 16th Century
where even soap and water, let alone sterile technique are practiced on a
casual basis, if at all.  That infrastructure is absolutely critical to the
success of sophisticated technological and pharmacological intervention
which is integral to CCRI's protocols.

Perhaps most importantly, many Third World countries such as China boast
seemingly "well educated and credentialed" medical personnel who in reality
operate as "robots" and are, apparently for cultural reasons, incapable of
understanding the real mechanics of science: statistical design, the
concept of statistical "power" in terms of the number of *appropriate*
patients required to have confidence in a given % improvement in outcome,
the absolute necessity for sophisticated qualitative and quantitative data
collection, and above all, the theoretical basis for the work being done.
This last point determines *practical* (real world) study exclusion and
inclusion criteria, as well as possible conofunding and invalidatig factors
(prior medical history, off protocol drug treatment, and so on).    

There are other countries where this work is possible. But language
barriers, cultural differences, and many other factors add tremendous
complications and costs. Speaking as someone who has worked "out of
country" in clinical research settings I can attest to the magnitude of the
difficulties. South Africa, until recently, has had a good tertiary medical
infrastructure which is utilized homogenously by both whites and blacks of
all classes (a very important consideration when an "American" company is
doing drug tests: read experimenting on uneducated blacks). SA has had a
history of extremely high quality, aggressive, and scientifically
sophisticated research and tertiary medical care (remember that the first
heart transplant was done in Capetown). And, very importantly, it is
academically and medically an english speaking country with a fundamental
culture reasonably close to that of the United States': Far closer than
that, say, of China, or even Japan. 

>>And the ultimate irony is, the storage costs will probably be lower and
the
>>up-front technology not more than 20% to 30% more costly than that
employed
>>by Alcor  now (the only high technology player left in the human
>>cryopreservation field).

>I, for one, would be interested in a description of what would be
>required to do this, and some numbers supporting the cost estimates.
>I am not at all clear on the difference between what you're proposing
>and what BioTransport is trying to do.

This is beyond the scope of the time I have here. The numbers for storage,
including detailed technological and design considerations, were worked out
largely by Brian Wowk (with some minimal input from me) about 6 months ago
and seemed persuasive to others with the requisite technical backgrounds
and critical minds suitable to evaluate these scenarios.

Regarding BioTransport: as I understand it, BioTransport plans to license
some of the innovations in cryopreservation technology made by 21CM, but
has an "incremental approach" (my words) and is not inclined to pursue a
full-thrust program of vitrification for the forseeable future (my
impression). They also appear deeply committed to a "motor home" rescue to
dry-ice approach which I believe will be severely technically limiting.
However, Michael Riskin, CEO of BioTransport , and Saul Kent, CEO of 21CM
would be FAR better qualified by far to answer this last question, as I am
now very far removed from the mechanics of cryonics activity.

Mike Darwin, Director of Research
Critical Care Reserch, Inc.
10743 Civic Center Drive
Rancho Cucamonga, CA 91730
Phone: (909) 987-3883
FAX: (909) 987-7253

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