X-Message-Number: 6777
Date: Mon, 19 Aug 96 00:34:38 UT
From: "Robert Ettinger" <>
Subject: SCI. CRYONICS re-posts
[These are reposted, since they apparently didn't get through. Possibly they
were rejected by Dr. Brown's new filter, because CryoNet sends mail to me at
<> but I usually send mail from <>.]
1. I want to extend public thanks to Bill Faloon for his help in connection
with Cryonics Institute's latest patient. Bill gave the patient's family the
names and contacts of several cryonics organizations, and spoke well of us.
2. Regarding Mr. Platt's recent remarks about some comments of mine on
possible uses of funds alternative to Prometheus:
First, Mr. Platt puts his own spin on my statement that uses of funds
alternative to Prometheus (including other research) might be worth
considering. He even concludes that I am complacent about present suspension
methods and not interested in research. That just isn't true. When I say
"worth considering" (or the equivalent) that is what I mean--it is not a code
phrase for "the devil with research," or even "the devil with Prometheus."
As for his conclusion that large sums spent for public relations would
necessarily have little effect on cryonics recruitment, based on history, I
think his reasoning is far from tight, for reasons too numerous to spell out
today. Primarily, though, one cannot equate the large amounts of free
"publicity" cryonics has received with the kind of marketing we could buy with
equivalent dollars--marketing WE would control, as opposed to the scattered,
diffuse, sporadic, and lukewarm (at best) coverage we have received for free.
Neither can one equate previous conditions with those of today.
As for the causes of the recent improvement in the (still very small)
acceptance of cryonics, and the probable effect of "proven" brain
cryopreservation, again his argument is questionable for many reasons. My own
impression is that perhaps the largest single influence on improved growth (in
addition to Alcor's David-vs.-Goliath act in the Dora Kent case) has been the
growth in computer-related industries. Computer people are better than average
(although still poor) prospects because: (a) they often think of the brain as
a computer, and in general tend to be mechanists; if you want something you
build it, and if it isn't good enough you improve it, and if something goes
wrong you fix it; (b) they are accustomed to rapid and radical progress,
"revolutions" in the ordinary course of business, quick changes and quick
fixes; (c) they are accustomed to seeing logic prove itself, over and over
again, in the course of the day's work--if a logic string leads to a
conclusion, no matter how startling, then you had better believe it (or else
question your premises).
Charles Platt and Paul Wakfer have done very well in many respects; they would
do even better if they would resist the temptation to ascribe bad motives or
incompetence to those who don't entirely agree with their ideas.
3. Olga Visser's post #6722 is extremely encouraging. Her suggestions about
organization of research should also be given the most serious attention.
Robert Ettinger
Cryonics Institute
Immortalist Society
Subj: SCI. CRYONICS fungibility, due diligence
Date: 96-08-16 11:59:04 EDT
From: Ettinger
To:
1. The major merit of the Prometheus Project is that--for the first time--it
has elicited promises of serious money for cryonics research. The goal is $10
million over ten years, and over 30% of that has now been pledged (subject to
approval by the pledgers of the research plan and business plan before actual
signing of contracts in 1998). Promoters of PP probably feel that such
potential money is not fungible--that it is not realistic to talk about other
possible applications of such money, or part of it, or of alternative research
projects--because the enthusiasm generated is specfiic to PP and cannot be
diverted. On another tack, PP promoters say (or seem to suggest) that research
avenues other than their flagship vitrification approach could be INCORPORATED
into PP.
I don't think these questions have clear answers yet. Paul Wakfer, Brian Wowk,
Saul Kent and others have certainly done a splendid job of consciousness
raising--possibly so good that the pledges, and other pledges under
consideration, might indeed be fungible to some extent, in the right
environment. As for PP incorporating other projects than vitrification, or
otherwise changing its focus, it remains to be seen whether that can or will
be done, or whether such moves would tend to weaken the pull of PP by making
it seem less definite and confident.
2. How solid is the PP hope of proven reversible brain cryopreservation in 10
years for $10 million? Wakfer, Wowk, and others seem to be saying that one or
more qualified cryobiologists believe the prospect is solid; and Thomas
Donaldson has suggested that we read the article on vitrification by Dr. G.M.
Fahy in the 1996 book ADVANCES IN ANTI-AGING MEDICINE, ed. R.M. Klatz, pub.
Mary Ann Liebert Inc., Larchmont NY 10538.
No responsible scientist or business man willingly takes anyone's word for
anything. If possible, you verify; and if you can't verify, you become
exceedingly cautious. In business, this is called "due diligence." Now what
can we say about the assurances given on the question of the realism of the
goal of PP?
Vague (or overly broad), second-hand statements are hardly satisfying. Mr.
Wowk has said that we should regard the goal as realistic because the
scientist(s) that will be involved have prior records of submitting research
plans, obtaining funding, and then delivering on objectives. Can we accept his
evaluation of a record unknown to us? We would like verified details. Indeed,
it is scarcely credible that any scientist has a record of delivering on a
COMPARABLE project even once in the past, let alone consistently.
It may seem unfair to demand verified details, since we know PP is not yet
ready to name the proposed principal investigator(s). I recognize the problem,
but it is still a problem. If the scientist(s) cannot be named, and if their
records cannot be examined in detail to determine the degree to which they
support the claims of realism, then how do we achieve due diligence?
Is it enough to study the literature on vitrification? Hardly. There is a
theoretical potential, but the experimental successes have been limited and
very slow in coming. We are all too well aware of the disappointments, from
time to time, in all fields of experimental science--e.g. controlled fusion,
where "another ten years" has been the watchword for several decades now.
Further, the scope of PP is very large--PROOF of reversible cryopreservation
of human brains. For example, how do we prove that memories have been
preserved, when we don't yet even know how to characterize memories in the
anatomy/physiology of the brain? I doubt that any thawee is going to sit up
and talk to us within ten years.
Of course, one can say that ANY advance will be valuable, and this large an
effort is bound to produce something. I certainly agree. But if PP promoters
back off their large goal, and perhaps their focus on vitrification, and just
say let's throw unprecedented money at cryonics research, adjusting as we go
along--there's nothing wrong with that, but it deletes the unique character of
PP and makes it just another research program, in competition with others. And
that is probably the way it should be.
Robert Ettinger
Cryonics Institute
Immortalist Society
FAHY ARTICLE
In connection with the Prometheus Project, Dr. Thomas Donaldson has suggested
that everyone
interested, if not already acquainted with the rationale behind the
vitrification approach to
cryopreservation, should read the article by Dr. G.M. Fahy, "Organ
Preservation," in Advances
in Anti-Aging Medicine, ed. R.M. Klatz, published by Mary Ann Liebert Inc.,
Larchmont NY
10538.
Following is my own attempt to summarize the article (or that part of it that
relates most directly to the rationale for vitrification):
Very low temperatures ordinarily cause ice formation in biological specimens,
which generally causes some damage at least in relatively large organs of
adult mammals. [I omit discussion of mechanisms of damage.] However, some
solutions do not freeze (form noticeable ice crystals) at any temperature;
instead, they just get stiffer, like glass or tar. This process is called
"vitrification" or "glassification" (from the Latin word for "glass").
Vitrification potentially has much the same long-term storage advantages as
freezing, but without the mechanical and chemical changes caused by formation
of ice crystals.
Problems with vitrification:
(1) The necessary high concentrations of vitrification-inducing cryoprotective
agents (CPAs) can be toxic, either generally or in process of introduction or
removal.
(2) When a specimen is cooled without freezing, damage may occur which is not
well understood, although it may be partly a result of additional time of
exposure to the CPA.
(3) When a vitrified specimen is warmed, crystallization ("devitrification")
tends to occur. To minimize this kind of damage, warming must be uniform and
rapid--on the order of 300 deg C per minute; total rewarming time (to 0 C)
must not be more than about 20 seconds. (This seems to imply a banking
temperature of about - 100 C.)
Dealing with the problems:
TOXICITY: To minimize toxicity, Dr. Fahy's group have used a computer-operated
organ perfus-
ion machine to coordinate rate of cooling with rate of perfusion, using mostly
rabbit kidneys but also rat livers.
Around 1989 they obtained 100% survival of transplanted kidneys, using a low
concentration of CPA that would only permit vitrification when used with high
pressures, 500 to 1,000
atmospheres. (I believe this means they obtained the survival in the absence
of pressure or cool-
ing, testing only for toxicity of CPA.) Vitrification using the combination of
high pressure and CPA perfusate allowed no survival.
COOLING INJURY
Cooling injury was found to be more severe with higher concentrations of CPA.
Therefore a
relatively low concentration of CPA was used initially, and the rest needed to
vitrify added when the temperature was near - 30 C.
"At the lowest concentrations needed for vitrification, 100% survival
resulted, and at the next higher concentration, 100% survival was attained
after cooling to - 32 C. These results
emboldened us enough to try concentrations that will vitrify with no applied
pressure."
As at other points in the article, there seems to be a certain lack of clarity
here. We are not given any clearly stated data on vitrification temperatures
(or glass transition temperatures) as related to CPA concentrations and to
pressure, or explicitly and in full what was done when. (Of course, space was
a consideration, and possibly proprietary information.) I think the quotation
above means using CPA and cooling without pressure.
Next, apparently they used a similar approach with higher concentrations,
enough to vitrify
without pressure. In their [then] most recent series, both of two kidneys
survived, with good life support function after transplantation. Another of
them also survived after further cooling to - 46 C.
Tissue slice experiments suggest that further cooling (beyond - 46 C) will
induce little or no
further injury.
DEVITRIFICATION:
Ruggera and Fahy have had "success" in rewarming test CPA solutions at rates
of over 400
C/min. Plans were under way to finish perfecting the heating technique.
QUESTIONS:
The following quotation is somewhat puzzling to me:
"Vitrification has been successfully applied to human islets of Langerhans,
human monocytes,
human red blood cells, human liver cells in culture, certain kinds of plants
and plant tissues, and to animal embryos and egg cells. It has been applied
with partial success to human corneas. It is also clear that, if earlier
researchers had understood the scientific issues as well as we do today, they
could have successfully vitrified whole organs (particularly guinea pig uteri
and adult frog hearts) in 1965. Our laboratory has obtained encouragement that
it may be possible to vitrify both rabbit kidneys and rat livers. These
observations illustrate the universal nature of cryopreservation by
vitrification and imply that success with one type of major organ can be
followed by success
with virtually any other type of organ or human tissue desired for banking."
The above quotation has several strange features. He says that it "may" be
possible to vitrify
rabbit kidneys and rat livers, but it is "clear" that researchers in 1965
"could have successfully
vitrified whole organs."
Nor do I see why the named successes imply further successes with "virtually
any other type..." WHY do the named successes show the "universal" nature of
crypreservation by vitrification? It seems to me one would have been just as
much justified, in 1948, when Rostand cryopreserved frog sperm with
glycerol--or at most a few years later, when many cell and tissue types had
been cryo-preserved with glycerol--to say that the way was now clear to
cryopreserve anything by similar methods. In fact, the researchers of that
time knew and stated clearly that methods required for other types of
specimen, and especially for whole adult mammalian organs, might not be simple
extensions of previous ones. As far as I can see, that is still true.
FOR ALL WE KNOW, THERE MAY BE MORE DIFFERENCES IN CRYOPRESERVATION
REQUIREMENTS BETWEEN DIFFERENT REGIONS OF THE BRAIN THAN BETWEEN (SAY) HEARTS
AND LIVERS.
Olga Visser has also said that her novel CPA, which has had apparently
complete success with
rat hearts (THE BIGGEST BREAK-THROUGH SINCE 1948) and at least partial success
with pig hearts and other organs, has in her opinion the potential to work
with all organs--although with many individual modifications required. With
all due respect--and I am extremely hopeful about her technology, and full of
admiration for her achievements against odds, as well as for Dr.
Fahy's achievements--I am uneasy with short term optimism about all these
things, even though
I yield to no one on long term optimism (well, no one except maybe Tipler).
Thomas Donaldson seemed to feel that Fahy's article would do much to convince
readers of the
high probability of success of the Prometheus Project as currently outlined.
It doesn't seem
terribly persuasive to me in that context.
In short, once more, we should indeed multiply our research efforts--but I
don't think PP deserves anything like a monopoly on new money.
Robert Ettinger
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