X-Message-Number: 4656 Date: 21 Jul 95 01:10:15 EDT From: Mike Darwin <> Subject: CryoNet #4642 - #4645 This is response to Bob's posting: Message #4642 From: Date: Tue, 18 Jul 1995 12:20:51 -0400 >1. (a) First, a slight correction to Mike Darwin's thoughtful posting #4634. >We did not estimate 25% glycerine in the sheep brains by measuring it at that >amount in venous effluent, but by noting the loss of glycerine in the >effluent. Whatever didn't come out must have stayed in. This is a reasonable assumption and what I actually assumed you did: look at the vernous effluent concentration. We have found a reasonably good correlation between effluent and tissue concentration in our hands. > I think it is fairly widely known--that BioTime has >recently pushed the envelope appreciably.) Not known by me? And by what criteria have they pushed the envelope? Where are the micrographs, functional studies, and/or other hard data to support this? In fact, until this remark from Bob I had heard nothing of the sort: only that they were having good luck with an oxygen-carrying blood substitute of potential utility in trauma, hypothermic medicine, and surgery. I'm sure we'd all be interested to hear of progress beraring on the problem of cryopreserving brains made by BioTime or anyone else. >(c) Mike and Alcor used to use the term "state of the art" in describing >their procedures. This really meant just their current capabilities, no more >and no less, on the assumption (or on the evidence) that no other >organization offered better. I always pointed out that a genuine "state of >the art" suspension would demand using those procedures reported in the >literature yielding the best results FOR EVERY KIND OF TISSUE, including >every kind of brain tissue. >This in turn would demand many teams of surgeons working together to dissect >the patient and perfuse each tissue separately--an impossible goal. Here we have Bob trotting out ther old state-of-the-art debate again. I've already stated and restated my position on this matter in this forum several times. And no, neither in my definition nor, more to the point, Webster's is anything even remotely like the one which Bob gives. Bob's definition springs from his own prejudices and/or idiosyncratic beliefs about its meaning. Here, I will have recourse to Webster: "state of the art: the current level of sophistication of a debveloping technology, as of computer science." This by no means implies perfection or utilizatuion of every modality to preserve structure (or carry out computing!) in the best possible way allowed for by current knowledge or physical law. The average person knows what state of the art means quite well: it means the difference between walking into living room with a 1955 black and white TV to watch a program or and an old 78 rpm record player to listen to music, and walking into a living room with high quality contemporary audio and video technology (either analog, which I prefer, or digital). Bob goes on to hammer away at this position of the "theoretically optimum" as a plausible definition of state of the art: >Over thirty years ago I suggested that, if necessary, the brain might be >teased apart to allow easier access to different parts and tissues, if this >would be necessary for optimum access and treatment. I hope it won't come to >that. This would hardly be the state of the art unless you had some pretty damn good way of putting the patient's brain together after such a trick. One of the ways I illustrate cryoinjury and the importance of gross and histology-level structure when I speak to lay audiences (which I no longer do) is to ask the following questions: "Here's a puzzle: how could every cell in your body be alive and well, and you be dead? Does anyone know the answer?" The answer: tease all your cells apart and put them in little flasks that nourish them individually. All your cells may be there, but you ARE NOT. In fact, it can be argued that, if we knew enough about the culture needs of each cell that we could do a better job keeping them alive in such flasks than the body does. But to what end? >(d) The CI approach to perfusion has always been conservative in the sense >that dependability of storage comes first. If we can't keep a patient stored, >then how he was perfused won't matter at all. One could turn this around and >say that, if he isn't perfused in a potentially reversible way, then whether >he is stored won't matter. But there is no symmetry in the clarity or >predictability; if a particular method of perfusion is too expensive for most >people, then that ends it (for those people). Sadly, I must disagree with Bob here. It is not conservative to let patients experience wide scale ultrastructural disruption from ischemia, cryoinjury and other causes if you can avoid them. Nor is it financially prudent to freeze people with little or no financial safety margins and to rely on (by sweep of historuy criteria) unrealistic rates of financial return to sustain those patients. In CI's case so far they havesurvived from overfunding and/or volunteer by some to the benefit of others. I have no problem with this as long as everybody knows what the rules of the game are. >Thus we regard cost as crucial, in the absence of demonstrated reversible >suspended animation. For some it would be crucial even then. Furthermore, if >part of the cost of "state of the art" perfusion stems from unnecessary or >immaterial aspects, then that money being diverted from other uses--perhaps >including further research!--increases the overall long term risk. Some >aspects of Alcor/BPI procedures have always seemed to us to be very >questionable on a cost/benefit basis. Hopefully, such questions will >gradually find consensus answers, as our cooperation has improved and our >research increased. Aye! Here's the rub: >Thus we regard cost as crucial, in the absence of demonstrated reversible >suspended animation. For some it would be crucial even then. Furthermore, if >part of the cost of "state of the art" perfusion stems from unnecessary or >immaterial aspects, then that money being diverted from other uses--perhaps >including further research!--increases the overall long term risk. Well Bob, you're not alone. Maybe BPI and Alcor are using "unnecesaary or immaterial" procedures which add cost. What might be equally the case is that CI is failing to use adequate procedures to preserve their patients well enough to allow recovery. Now, if that is all we had: charge and counter charge without evidence, we could sit here at our keyboards till hell freezes over and get about as far Medieval theologians did begging the question of how many angels can dance on the head of a pin. That, happily, is NOT the case anymore. BPI has EM's of frozen thawed brain tissue and freeze-substituted brain tissue that are, in my prejudiced, but alsop informed opinion the best currently achieved by the technology. THAT is state of the art. THAT is what I mean by state of the art. And it has not been easy or cost free to reach. Now, the customer can judge which approach he wants. Rest assured, that we will trim unnessary things as we find them. And we already do (on a case by case basis) trim monitoring and lab evaluations in cases where money is tight. And we will be making changes to our protocol to offer less costly options as we identify what we can safely trim. True, we started out on the "high side" being careful to use approaches which have been shown in contemporary clinical settings to radically affect outcome in a positive way (such as ameliorating ischemic injury or preventing it by the use of costly standbys). That too is conservative in that no matter how long you keep a pile of ashes of frozen (to use an extreme example), you aren't going to get a person back out of it given our current domain of understanding of physical law and information theory. Doing good standby/transport/perfusion can be viewed as conservative too! Equally true, it will not do the patient any good to get the best preservation if s/he doesn't stay frozen long enough. Clearly there is a TENSION here between two desirable things. Men of good intentions and fine intellect may differ on where that tension should be. Such is life, and such choices are made every day in investing, in career moves, and so on. >(2) I think Ralph Merkle has the better of the debate with Thomas Donaldson. I couldn't disagree more, but Thomas defends himself better than I. >(a) The sweep of history tells us that cryptanalysis can do amazing things, >and that persistent and subtle detectives of all kinds can accomplish feats >of inference that might have seemed impossible--and that future feats will >almost certainly eclipse those of the past. Any evidence of improved >cryptanalytic capability IS INDEED relevant to our concerns. >(b) Despite chaos phenomena and despite the assumptions of interpretation of >quantum theory, effectively unlimited inference of history is not yet ruled >out. >(c) To the degree that the present and past may indeed turn out to be >fundamentally and irrevocably blurred, IT DOESN'T MATTER. A difference that >makes no difference is no difference. If there is no way whatsoever, in >principle, to determine what you were or are, then all conditions inside the >dark zone are shoulder-shrugs. This is bizzare. And further, as a man who spends a disciplined amount of time each day reading history, I can say that sweep history has been more often into the garbage. In fact., the sweep of history tells us NOTHING about what whether what we want personally is achieveable. Much depends on where you are and who you are. Most on this net live in the bosom of a very benign time. History tells us, if it tells us nothing else, that such benighted ages are few and brief. The fact that this one has reached higher and farther than any in the past may mean little (although I personally disagree). Is this an argument for despair? NO! But neither is Bob's assessment a guarantee of success. I can feel the broom straws of history tickling my ass towards the dust bin as I write this. The story is far from over. The outcome is far from certain. If you need to believe otherwise to get up in the morining the wold is full of organizations, cryonics and otherwise, who will help you down that happy path. It is not, however, my approach, nor within my range of skills or desires to spend time blowing sunshine up people's asses. Let's get objective criteria in place based, hopefully, on reversible brain cryopreservation. Otherwise we may spend another 25 years, as we've spent the past 25: in numbing uncertainty. Mike Darwin Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=4656