X-Message-Number: 9403
Date: Fri, 3 Apr 1998 14:45:58 -0500 (EST)
From: Charles Platt <>
Subject: Damage to CI Patients?
At the upcoming Alcor conference, we will hear about progress
that is being made toward zero-damage human cryopreservation
by scientists who provide detailed substantiation of their
work. These reports create a puzzling contrast with Bob
Ettinger's claims that vastly simpler protocol still produces
acceptable results at The Cryonics Institute (CI), the
organization that Bob founded and ran for many years.
Since Bob has never substantiated his claims with data from
human cases, and since the claims are contradicted by recent
research, I feel it is time to ask some questions about CI's
procedures and their probable effects. So far as I can tell,
based on elementary knowledge of cryobiology, the procedures
at CI do not produce acceptable results; on the contrary, I
believe they inflict substantial damage that could be avoided
with simple modifications.
To those who dislike squabbling in cryonics I suggest that
public disagreement is a normal, integral part of science.
Indeed, it's a prerequisite for progress. I do not question
Bob's sincerity, or CI's management; and clearly, CI is the
most financially secure of all cryonics organizations. I
simply question the scientific validity of its procedures.
1. Damage Caused by Slow Freezing.
Broadly speaking, the freezing process causes two kinds of
cell damage: chemical and mechanical. As the temperature
falls, water is drawn out of cells via osmosis, leaving
behind increasingly toxic concentrations of salts. A red
blood cell (one of the more robust types of human cell) can
only withstand 3 or 4 times the normal concentration of these
salts.
Meanwhile, ice crystals form in the water that gathers
between the cells, and if these crystals are allowed to grow
excessively large, they sever long cell processes (such as
connections between neurons) and literally scramble brain
structure to the point where reconstruction will be
problematic. In fact, based on pictures that I've seen, I
feel that reconstruction of severely scrambled tissue is
implausible.
The longer a cell takes to freeze, the more time there is for
chemical and mechanical damage to occur. (This is why
vegetables are "flash frozen," minimizing structural damage
that would make the food "mushy" otherwise.) Also, autolysis
and decomposition may continue until the temperature drops
well below zero Celsius; this is another reason why freezing
should not occur too slowly.
I would like to ask Bob Ettinger if he is aware of these
basic facts; and if so, what steps CI takes to freeze
patients reasonably quickly.
I have been told that a typical patient at CI is cooled
merely via air convection, beneath blocks of dry ice. Is this
true? If so, why doesn't CI use liquid immersion as a simple
means to achieve much faster cooling?
Before cooling begins, I understand that CI wraps the patient
in a sleeping bag. Since the sleeping bag is an insulator, it
will retard the freezing rate still further. Consequently, I
believe CI's patients take _one week_ to reach dry-ice
temperature. This is seven times slower than the rate
achieved in cases at other cryonics organizations, where
immersion cooling is used.
Can Bob confirm that my description of CI procedures is
correct? if it is, can he explain why CI continues to freeze
its patients slowly, even though this is known to allow more
cellular damage to occur?
2. Damage Caused by Improper Cryoprotection
If glycerol is used as a cryoprotectant, its concentration
should be low initially. A high initial concentration will
force rapid extraction of water from cells without allowing
time for the glycerol to replace the water, and the results
can be devastating. In the words of one cryobiologist, if
cells are perfused with an initial concentration of 70
percent glycerol (by volume), "you will kill almost every
cell on contact because of the rate of fluid extraction."
Is it true, Bob, that CI uses a concentration even higher
than this--typically 75 percent glycerol by volume--with no
attempt to begin at a lower value, regardless of the
potentially devastating effects?
The need to increase concentration gradually has been known
in the cryonics community for many years. For instance, in
the October, 1988 issue of Cryonics magazine Mike Perry
wrote: "The considerable osmotic activity of CPAs
[cryoprotective agents] ... dictates that introduction be
gradual. This allows time for the agent to diffuse across
capillary and cell membranes and slowly exchange with
water.... Too rapid a rate of introduction of CPA will result
in dehydration (shrinkage) of the cells and injury due to
osmotic stress."
Alcor and BioPreservation use a properly instrumented system
to increase glycerol concentration over a period lasting as
long as four hours. Also they recirculate the cryoprotectant
via a closed circuit, to maximize penetration, which will be
insufficient otherwise. Mike Perry's study, mentioned above,
concluded that three hours of closed-circuit perfusion
typically may be required to replace 30 percent of the water
in human tissues (the approximate minimum established by
Audrey Smith back in the 1950s).
As I understand it, CI does not use a closed circuit. A
mortician performs blood washout with 15 liters of Ringer's
solution, then passes approximately 15 liters of 75 percent
(v/v) glycerol through the patient in a simple one-shot
procedure. The venous effluent is not recirculated.
Let us assume that this open-circuit perfusion lasts no more
than 1 hour (probably less). I believe that CI does not
measure the venous concentration of perfusate as it flows out
of the patient; therefore, no one knows what is happening in
the body. But bearing in mind Mike Perry's calculations cited
above, personally I would guess that the open-circuit system
is sufficient to replace no more than 10 percent of water in
the tissues overall. By comparison, in recent cases processed
by BioPreservation, about 50 percent of water in the tissues,
by volume, was replaced.
As a result, while cells near capillaries in CI patients may
be destroyed by high concentrations of glycerol, cells beyond
this zone should still contain ample water to form large,
destructive ice crystals during slow freezing. Therefore, the
CI protocol appears to give us the worst of both worlds: high
cryoprotectant toxicity in some cells, and major ice damage
in others.
3. Damage Permitted by Inadequate Equipment.
I believe that CI's mortician typically uses an embalming
pump or a simple roller pump. In the case of an embalming
pump, I believe it can create pressure spikes that rupture
capillaries. Also, excessive pressure may contribute to
edema. I believe, however, that CI never attempts to measure
mean arterial pressure, and does not take the basic
precaution of drilling a burr hole in the cranium, allowing
noninvasive observation of the surface of the brain. A burr
hole would also provide visual confirmation of blood washout,
especially if inexpensive, non-toxic dyes are added to the
perfusate. A set of bits to drill a burr hole would cost less
than $200 and could be used with a simple hand-brace,
available in hardware stores.
If CI were willing to spend just a little more money (and
with more than $1 million in the bank, surely it could afford
to do so), a fiber optic probe could be used for realtime
observation of brain capillaries during perfusion, enabling
better verification of blood washout. If CI has made a policy
decision not to bother with these monitoring procedures,
which are cheap and easily implemented, I'd like to know why.
4. Claims of Independent Verification.
For several years now, Bob, I think you have been claiming
that the Russian cryobiologist Yuri Pichugin has verified
your procedures. But in Pichugin's report, he describes using
a series of stepped concentrations of glycerol, presumably
because his training taught him that this was essential in
order to avoid massive cell damage.
As I understand it, CI does _not_ use this same procedure.
Therefore, how can you claim that Pichugin verified your
protocol, if his was completely different?
Even using stepped increases in concentration, the electron
micrographs that Pichugin produced showed severe injury, in
the opinion of one of the world's leading cryobiologists who
inspected the pictures. The micrographs also were evaluated
by neurologists who found that the damage was so severe, they
couldn't tell what kind of neurological tissue they were
looking at. In view of this, how can you claim that CI's
even _harsher_ treatment produces acceptable results?
5. Conclusions.
My comments should not be interpreted as criticism of
morticians who conduct CI's procedures. If a mortician is
properly instructed, s/he may be able to do a competent job
of blood washout and cryoprotective perfusion. However, so
far as we can determine, CI does not give elaborate
instructions to its morticians.
I suspect that CI's members are unworried by deficiencies in
its cryoprotective protocol because they share Bob's faith
that scientists in the future will fix everything for us, no
matter how bad the damage is. But since we have no guarantee
that major damage will be reversible, and since we can reduce
it by applying well-known principles of cryobiology at a very
moderate cost, I cannot understand why CI doesn't take steps
in this direction.
Finally I find it impossible to understand Bob's suggestion
that CI's protocol can produce results as good as those
attained elsewhere using more elaborate procedures. This is
very hard to believe, if the information that I have
presented here is correct.
Charles Platt
President, CryoCare Foundation
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