X-Message-Number: 17803
Date: Mon, 22 Oct 2001 01:19:44 EDT
Subject: Quality Control and Cryonics

Charles Platt and others have commented about quality control in cryonics and 
have referenced my earlier proposals for patient sampling, in particular 
brain biopsies of cryopatients. No one has got it quite right (at least from 
my point of view) but then it was a long time ago, and, as Charles has noted 
a simple matter became contentious. I'll number my points for clarity.

1) Animal research can be remarkably predictive of outcomes in humans if you 
are clever, wise, and lucky. Most cancer research has been historically done 
with rodents and particularly mice. Countless billions of dollars have been 
spent on various models of human cancers in murine (mouse) models. It is now 
possible to cure a large number of cancers in mice. However, this did not 
proved to be true for humans. Almost all of the money spent since President 
Nixon's declaration of a war on cancer in the 1970s was misspent. Animal 
rights activists may now take a bow: this stupidity gave you vast and 
accurate ammunition against the animal research community.

Monkeys would seem better models to evaluate treatments for head injury and 
prolonged cardiac arrest in humans since they are phylogenetically closer to 
us than, say, dogs. But the fact is that monkeys are much more resistant to 
ischemia than humans. Dogs map humans in terms of timeline, degree and 
distribution of neuronal injury more closely than any other animal I have 
researched (and I am not alone in this conclusion). They also demonstrate 
truly awful behavioral deficits with increasing ischemic times which are 
comparable to those observed in humans similarly injured. Sheep and other 
grazing animals can suffer devastating neuronal losses with none or very 
little change in behavior.

Choosing and validating the right animal model is critical. Even in the 
veterinary world there is enormous interspecies difference. The drug you see 
advertised on TV for arthritic and elderly dogs (Rimadyl made by Pfizer) does 
not work on cats. Similarly, 4-methylpyrazole, a drug which can rescue dogs 
from ethylene glycol toxicity is useless in cats.

Closer to the home front, glycerol does not penetrate bovine erythrocytes 
significantly below 10 C and several cryoprotectants are impermeant to the 
intact rat brain. Rat brains have historically been avoided as models in 
cryobiology (perhaps not with justice) because of the extremely dense 
neuronal architecture and the idiosyncratic response to cryoprotectants 
observed by some scientists in the little work that has been published in 
this area.

Scientists engaged in animal research now call this work comparative medicine 
and there are staggeringly knowledgeable and prolific Internet lists which 
provide both ongoing discourse and a vast reservoir of knowledge to draw upon.

The take home message is that you pick your model and then validate it as 
many ways as you can in other relevant systems. This not a criticism of CI or 
anyone else. The plans laid out by David Pascal that Yuri Pichugin plans to 
follow seem reasonable. Similarly, Charles' concerns about applying research 
insights to humans have some merit. You don't really know till you try it, 
which brings me to point 2) below:

2) Human cadavers obtained with reasonably short postmortem intervals are 
obtainable for about $2,000 each in the greater Los Angeles area. Timing is 
the hard part, but if you are a cryonics organization and plan this kind of 
work in advance that issue should not be onerous since you should be prepared 
for it anyway. 

The ethical issues do not trouble me, nor do I think they trouble other 
researchers in cryonics. Several of us have already had access to human 
brains post mortem which were cryopreserved and subsequently dissected and 
examined in some cases. The results were presented at meetings of cryonicists 
without objection (i.e., the Lake Tahoe Cryonics meeting in the 1980s and 
1990s). If people don't want cryonics but do want to make a contribution by 
donating their bodies and brains for irreversible destructive research this 
is morally and ethically acceptable. Indeed, acting contrary to this wish 
would constitute the assault on the person and the ethically unacceptable 

To do this kind of work is no different from to work in hospital (as I have) 
and to follow a patient's instructions to discontinue dialysis or other life 
sustaining treatment even though the quality of life is still high (by my own 
standards and those of most of the rest of society). This is done all the 
time. To do otherwise constitutes false imprisonment and battery. It also 
bespeaks a deep disrespect for the right of the individual to make an 
informed choice. Yes, people make bad decisions in this regard. And yes, they 
are irreversible. But it is their right to make them and this has been 
acknowledged by both social norms and the legal system. Greater evil has 
historically come from _imposed_ decisions by governments or individuals who 
are not party to all the information or who are driven by ideological or 
political agendas.

3) The spinal cord is a good surrogate for the brain, especially as applied 
to cryopreservation. Spinal cord samples can be removed from neuropatients 
for a variety of evaluations. In the cryopreservation of James Gallagher (a 
CryoCare patient) BioPreservation removed a large section of spinal cord and 
lumbar nerves. We also removed cryoprotected samples of kidney, liver and 
heart. These fairly substantial samples were cooled with the patient at the 
same rate and under the same conditions. These samples (which are 
CryoCare/BPI property) are, as far as I know, still in the neurocan with the 
patient. The purpose of this kind of sample taking was to evaluate by both 
freeze substitution electron microscopy and post-thaw electron microscopy how 
effective (or damaging) the cryopreservation technique had been.

Unfortunately, my research objectives changed and BPI did not have the money 
to pursue this investigation. However, the opportunity still exists and 
should be exploited. Had we been better prepared we could have taken a second 
set of samples and fixed them immediately following glycerol perfusion and 
then examined them under light and electron microscopy. These would have 
served as pre-freeze controls for the frozen samples. We were not prepared 
for this maneuver (which requires that terminal CPA concentration solution be 
made up containing fixative for immediate immersion of the samples after 

4) As to brain biopsies via the burr hole: this was one of the most ludicrous 
episodes in the history of cryonics which has had many a ludicrous episode. 
The proposal was to take two needle biopsies of non-critical areas of the 
cerebral cortex via the burr holes. The amount of biopsied material would 
have been equal to about the same volume of tissue contained in a 16 g blood 
collection needle (for those of you who have donated blood). A superficial 
cortical sample such as this has never caused anyone any detectable 
neurological deficit. If you've had as much experience as I have (and other 
medically knowledgeable people in cryonics) you would realize that a) this 
kind of thing is done every day without problems and b) most patients with 
brain tumors (and those around them) do not notice any change in mentation 
until the mass is at least the size of a walnut and usually the size of a 
golf ball; if not larger. We are not talking about the midbrain here, or the 
hippocampus. This procedure was simple, safe and a "no-brainer" as the slang 
of the time went.

The tissue would be handled in two ways: One sample would be cooled with the 
patient at the same rate and under the same conditions. (Today, if one were 
vitrifying the patient the sample could be inserted in a removable capsule in 
the esophagus or terminal pharynx to give a worse case cooling rate and then 
be removed following cooling.) The other sample would be processed by 
immediate post-removal fixation so that the effect of cryoprotective 
perfusion could be separated from that of subsequent cryopreservation. While 
not perfect, this kind of sampling would return an incredible wealth of 
general information and a similar bonanza of information about the quality of 
how that particular patient was treated. It is also possible to collect a 
sample prior to the start of cryoprotective perfusion to see what condition 
the brain is in following legal death and initial cooling and stabilization.

This language is, I believe, already standard in the CI contract. 

The issue could have easily been resolved by simply having the client say 
"no" if they did not want this procedure done. And, of course, the procedure 
would have to be explained in the client's agreement with the cryonics 
organization. This did not seem a major obstacle.

Because this practice has not become routine or even occasional, there is 
virtually no objectifiable feedback from _any_ cryonics society about what 
condition their patients are in. Thus, there is endless and unnecessary 
argument that testing could resolve. I did remove cord biopsy samples from 
patients frozen by Trans Time in the 1970s and these samples were incredibly 
valuable and led to major alterations in practice.

Mike Darwin

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