X-Message-Number: 1926 Date: 09 Mar 93 23:34:17 EST From: Mike Darwin <> Subject: CRYONICS Letter to Ettinger Michael Darwin Cryovita Laboratories 1220 E. Washington St. #24 Colton, CA 92324 9 March, 1993 Robert Ettinger Cryonics Institute 2443 Roanoke Oak Park, Michigan 48237 Dear Bob, I have spoken with Greg and he will hopefully respond to you directly. He informs me that he has been able to cool 500 cc quantities of material to about 25 degrees below TG if he cools VERY slowly and if he allows annealing time at or near TG. He said he has been able to cool smaller samples (i.e., 100 cc) to as low as - 160*C. He feels that very slow cooling to within 20 degrees below TG ought to work. However, he has done only one experiment and clearly more are needed. This is an area where CI might be able to make great progress for all involved: would you be willing to carry out carefully designed experiments cooling bulk solutions to below TG and determine their fracture points, stability, etc. I am sure Greg could design some experiments that would help to clarify matters considerably, and perhaps help to advance his own organ preservation work as well (since it also relies on fracture-free storage of vitreous materials). Further, I should be able to provide you with uniformly glycerolized animals (dogs or pigs) which could be shipped to you at dry ice temperature and subjected to further slow, controlled cooling to a temperature deemed safe. It is possible that tissue will behave either better or worse than bulk solutions. I say this because I observed far less fracturing in the fiber reinforced tissue areas of glycerolized animals which fractured on cooling. By contrast the lungs, brain, and spinal cord were very hard hit. Structures like the spinal cord and nerves which extend through small openings and snake over long distances may be far more vulnerable to fracturing than a relatively homogenous mass of solution. Yes, you are quite right about the variation in concentration from area to area of the body. As no doubt you yourself have observed, perfusion is often very poor in the lower extremities in ischemic patients. What we will probably have to content ourselves with here is protecting the brain. You raise the larger issue of the importance of eliminating the fracturing from an ultimate benefit standpoint. This is a much tougher question and one for which I have no hard and fast answers. If fracturing can be eliminated with a modest exertion of effort and a modest (or no) increase in cost then I think we are all agreed it should be eliminated. How important this will be to the typical patient today I can't say. However, if the cost is likely to be very high, then it probably should not be an immediate issue for concern. In any event, if it is do-able and people can make an informed choice, I think that the option should be available. I would not propose that cheaper, fracture-free LN2 storage be eliminated if it will exclude patients -- not unless it can be demonstrated with a reasonable degree of confidence that fracturing is causing serious information loss. What are your concerns about ethyl chloride? It would be containerized and not in direct contact with the patient. Regarding your comments with respect to the hypothermic phase of the procedure I wish I could be more sanguine. Unfortunately, cold water drowning is not really comparable to what happens to the typical cryonics patient. I believe that very serious injury is occurring during ischemia and reperfusion. I believe that some of this injury results in immediate and serious destruction of ultrastructure. Other injury is secondary to loss of capillary integrity, leukocyte plugging of capillaries, and other problems which compromise subsequent cryoprotective perfusion. This has been borne out by both ultrastructural and histological studies conducted in-house -- as well as by the response of human patients to various transport scenarios. How significant this injury is to the ultimate recovery of the patient remains an unknown since we do not know the full extent of the damage, the structures which encode memory and personality, and so on. Indeed, as the pages of THE IMMORTALIST attest, there is even now wide debate and little consensus about the very nature of what we seek to preserve (human identity). I have great respect for cerebral ischemia as I have tried several times to reverse it (11 minutes) using every pharmacologic and other tool at my disposal (including external cooling of the dog's head). In this I have failed dismally each and every time but the last time. Every organ system would recover fine but one: the brain. What I do know is that there truly is no comparison between patients who have long ischemic episodes and those who are transported under good conditions. And this bears directly on how well or poorly the patient equlibrates with cryoprotectant. However, as you point out, in the final analysis the decision belongs with the member. It is his or her pocketbook and his or her chances. Ultimately, it should be his or her decision. Sincerely, Mike Darwin Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=1926