X-Message-Number: 4503 Date: 13 Jun 95 03:43:39 EDT From: Mike Darwin <> Subject: BPI Research A couple of comments about Charles Platt's messages and Bob Ettinger's: 1) Charles makes the point that nobody got very excited about the BPI results. This is understandable because most people have no basis of comparison. One of the still great weaknesses of communicating through this medium is the relative difficulty of making visual information available. Charles is in a much better position to appreciate the work because the pictures he is preparing for publication are not only of our current good results, but also of past (horrible) results as directly contrasted with current good ones. Even he can SEE the difference. And here I mean no insult, reading EMs is a skilled art that takes much time and experience to develop: I rank myself only as a gifted amateur. In science we must all *to some extent or another)be Doubting Thomas' (for non-Christians: Thomas was the disciplie who said "Resurrected from the dead? Suuuuure, I'll believe it when I see it!). We must be able to PUT our fingers (or our eyes)in the wounds. And it is most certainly not the case( in this discipline in particular) that those who believe WITHOUT HAVING SEEN are more blessed than those who believe only after seeing the hard proof. However, having sad the above, I note that only two requests have come in for the pictures: one from Bob (who would have received them anyway) and one from Thomas (who would also have received them anyway). 2) Bob's comments about the difference between LN2 and -90xC are a bit of a red herring. We HAVE cooled tissue blkocks further to -196xC and, ultrastructurally, it doesn't make a whit of difference. Almost all the injury goes on between the start of the procedure (in humans this includes antemortem insults as well) and cooling to below the freezing point of the cryoprotectant/water mixture: i.e., for systems now in use by all cryonicsd groups I know that equals -80xC). 3) Bob's comments do have some bearing in relation to *cracking*. But that was NOT a major objective of this study, other than to demonstrate that it did NOT occur at -90xC, even with mechanical loading (dry ice on top of the unsupported dog). That is good news, but not terribly surprising. 4) I actually HATE the idea of doing cracking studies. In fact, it is STUPID for me to go to all the trouble to do these studies when Alcor is reportedly doing them. So inconvient and out of the way is this kind of work for me that I will happily (and at my own expense) ship a dog to Bob prepared by our techniques and cooled to -79xC and let him cool down-rewarm. I'll even fly in for the autopsy and reperfusion at CI's facilities. I made a similar offer to Alcor. This would be easier on me than tooling to do this work when my focus is completely elsewhere at this point. Why re-invent the wheel? I don't want to spend time developing crack-phones, and doing this kind of work. That's crazy! Yes, of course I can do it, but why? 5) Alcor has published lovely sonograms of apparent cracks, but given no data on whether the heads/brain were really cracked. Guys, this would save us all a lot of time and money. ( And, nobody can or at least should) accuse BPI of not being forthcoming with our results. Pictures (EMs) will appear in the next issue of CryoCare Report and a full paper is being preapred for TKDs NEUROCRYOBIOLOGY. Furthermore, as soon as Charles Platt get's more of the pictures scanned in so they can be easily and cost-effectively duplicated with HIGH quality, the pictures will be distributed to those who have cooperated with us in the past, and to selected other who want them. 6) Thomas' remarks about ischemic injury are well taken. What has surprised the hell out of me is that we have a dog walking around after a 20 minute insult (10 minutes of global ischemia and 10 of trickle flow) and everybody just yawns. Every dog we've given 10 minutes of global ischemia to using cardiac arrest in the past has ended up FRIED and dead. Thomas' assertions about people recovering longer than 10 minutes (i.e., 15) of ischemia are anecdotal. Believe me, I've looked and looked and I've never seen even a marginally believeable retro- or prospective study that even comes close to showing anything else. His comments about cats and monkeys are well taken, but, as I have grown in my understanding of cerebral resuscitation I've come to understand that cats and, in particular macaques (monkeys) are NOT representative models of human cerebral ischemia. In study after study you will see the occassional cat (or more likely) monkey recovering after 15, 17 minutes or sometimes even an hour (although in the case of the hour only minimally: it was a single cat in one of Hossman's studies). Not so dogs and most certainly not so people. Dogs seem not only to tolerate ischemia as poorly as people do, but they seem to respond much morepredictively to therauputic interventions that people do, who suffer this kind of insult. For instance, clinical trials of most calcium channel blockers and a lot of other drugs like NMDA receptor inhibitors have been not only unsuccessful in humans, but have in some cases increased mortality! I've seen some popular press accounts (mostly in the financial pages :)) that indicate that Upjohn is shitting a brick over their human Lazardoid trial results. Reportedlythey (21-aminosteroids) are making injury worse in humans treated with them! This stuff is nothing short of miraculous in cats, rabbits, mice and primates in inhibiting cord and peripheral nerve injury due to trauma and ischemia (including stroke). In fact, if Christopher Reeve were a rat and been given lazardoids he'd probably be walking by now instead of facing a near certain future as a ventilator dependent quad. But there were few if any published studies in dogs: in fact only two I've been able to come up with, neither very exciting, both involving blood loss induced shock/ischemia. We think we've picked the right model for looking at ischemic injury. And we note that pretty sharp guys including Peter Safar, the grand old man of clinical cerebral resuscitation research has used dogs for over 20 years, is using dogs, and continues to use dogs. One thing I note that dogs and people have in common: both have remarkably well protected heads, albeit from very different approaches. Every dog in the world has the best motorcycle helmet on imagineable. Their brains are covered with a heavy layer of muscle with enormous shock absorbing capacity. When you look at a dog you are misled: the big head is mostly bone and muscle and the brain is small and deeply buried/protected. When humans stopped swinging from branches and walked upright they took their heads out of the line of fire. Head injuries are NOT a singificant source of death or morbidity for aboriginal peoples. They become significant for humans only when they get on hrses, into automobiles (or (better yet) motorcycles), or climb up on ladders (which incidentally, humans are singularly unsuited for doing and falls from ladders are not only frequent, but account for most of the worst nonvehicular sources of accidental head trauma (the person's foot hooks in the ladder ands/he lands on the concrete on the crown of their head). Monkeys still swing from trees and still fall a lot. Cats a real climbers too, and both cats and monkeys have poorly armored brains (in the case of both of them it makes them delightful to use for EEG and neuro studies compared to dogs, which are very difficult to use!). I think cats and monkeys went the evolutionary route of beefing up tolerance to inujury and repair of it rather than trying to armor (and thus increase weight/decrease flexibility) their heads/sense organs which are critical to their survival behavior that puts them at risk. Dogs by contrast are heavily armoroed and have massive muscle groups protecting both cervical spine and brain. Not very practical for quick pouncers or lithe little things that move from branch to branch solving spartial problems of enormous complexity based on a dazzling input of sensory information. But, enough of this. Mike Darwin Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=4503