X-Message-Number: 15653 Date: Thu, 15 Feb 2001 22:55:06 -0500 Subject: A Formal Apology And Some Informal Remarks From: I would like to thank Mr. Jeff Grimes for bringing something to my attention, and I would also like to apologize to Alcor. No, Reader, you are not hallucinating; I'm quite sincere. You see, what happened was, a while ago I wrote a post in response to Mr. Charles Platt about summarized extracts from a report (apparently unpublished) purporting to examine the effects of a 'simplified protocol'. CI was not mentioned in the report, but privately I was told that the protocol was intended to simulate CI's protocols, and was dreadful. However, the only thing -- I mean, quite literally, the *only* thing in the article describing the 'simplified protocol', was one single sentence, quote: "The brain was glycerolized to a lower level (4M) at a faster rate (700 mM/minute) before being frozen to - 77 C for one week, thawed, and reperfused with fixative." On the basis of this single line, I had been told (privately) that CI methods were, quote, worthless, and that all CI patients were irrecoverably dead. Charles Platt -- noble soul! -- was good enough to come out of the closet and share this opinon with us all publicly, however, at which point I pointed out to Charles that the above not only did not describe CI's protocol, but that it wasn't even substantive enough to describe *any* protocol, much less CI's. Charles conceded that the researchers in question -- members of a competing organization, some of whom had criticized CI and Robert Ettinger in rather personal terms -- were making a guess at what they thought CI protocols were. Given that there was therefore therefore perhaps a possibility of error, nay, bias in all this, I asked for a detailed account of what the 'simplified protocol' really was. Charles responded that the researcher could not be easily contacted by him and was in any event propably too busy to look it up. Now John de Rivaz read my post and asked if he could take a chunk out of it and put it in Longevity Report, which he publishes. I said OK. He did so. I assumed it would run under the title that I had posted it under, however, apparently whoever put it up gave it a new title -- 'Analysis of the Differences of Procedure Used by Alcor and the Cryonics Institute'. It is no such thing. The text refers to BPI twice, 21CM once, and to Alcor only in that it says that Alcor performs (or did perform) tests on dog brains rather than sheep brains. That is the only point on which Alcor is mentioned. Mr. Grimes, locating the article upon publication for a good thrashing, produced several criticisms which are, needless to say, a trifle askew since no Alcor procedures at all are discussed there. It seems to me that anyone reading it would have figured that out; particularly Mr. Grimes, since he went so far as to get a copy of the CryoCare Report issue itself, and could hardly have missed the fact that the extracts explicitly refer to BioPreservation protocols rather than Alcor ones. Nonetheless, if one person could miss it, others could. And while I have some disagreements with Alcor's policies, I certainly do not want to criticize Alcor inaccurately or unfairly. Therefore I thank Mr. Grimes for bringing it to my attention, and I wish to apologize -- sincerely -- to Alcor, for I bear a little bit of the responsibility. When a writer lets something out under his byline, he ought to at least check the title. I didn't, and that was sloppy of me. On learning of the mistake, I contacted John de Rivaz at once, of course, and asked him to re-title it. He has. Mea maxima culpa, Fred: I will be more careful in the future. As for Mr. Grimes -- well, his post contained some things... that bear commenting on, I guess. Grimes: >> Blood doesn't cause damage. Water inside cells causes damage. If you flow a protective solution through the blood vessels, it can penetrate and replace the water in cells. This may seem a minor point but really it is very basic, and if David Pascal cannot even get the most basic things right, this makes me doubt his competence in more complicated areas. << Technically, it is not the water inside cells, but the water outside and between cells that causes the most damage in freezing. I confess I do not quite understand the remainder of Mr. Grimes' point. My extensive studies in the fields of cryobiology, biophysics, and neurobiology have led me to the conclusion that blood is wet. I believe I also saw an article once in the Journal of Cryobiology which tentatively suggested that wet stuff freezes. I therefore conclude that if you freeze someone with all the blood inside, the result is -- to use the technical term -- a mess. Now it is true that there is water in and between cells that is not blood, but there really is no practical way to get to it apart from circulating cryoprotectant in the vascular system, and the only way to do this in to replace blood with cryoprotectant solution. Does Mr. Grimes perhaps think that I believe that there is no other sort of fluid in the body except blood? Having peed once early in the 1960's, I believe I am aware of the existence of other fluids. >> As for one-pass vs. recirculation in increasing concentrations, if David does not define the other variables, this is a meaningless statement. Like, what percentages? For how long? At what temperature? If the two procedures take an equal amount of time, using the same concentration at the same temperature, why should there be any difference at all?<< A very good point, which was why I made it myself in reference to the CryoCare Report article. 7M at 700mM/minute does not cover any of the above questions, nor indeed several dozen others (nor even makes a lot of sense just on its own). Lacking this, comparisons are impossible. That nonetheless did not stop at least one person and I don't know how many others from passing off the 'simplified protocol' as a -- fatal! -- CI protocol for perhaps years. >> the "charge" is that HIGHLY CONCENTRATED glycerol causes the damage. The idea of increasing the concentration gradually is to reduce this problem. Obviously you can do this in one pass, or by altering the concentration as the solution recirculates. One-pass itself has nothing to do with causing osmotic shock.<< I realize this is kind of a silly question, but -- er -- is Mr. Grimes aware that that article is more in the realm of historical interest rather than current procedure? I mean, CI is not doing one-pass anymore -- it's doing stepped. If he wishes to regale Cryonet with his views on the glories and/or miseries of one-pass -- I'm not really sure if he's pro or anti from his remarks -- well, OK. That's fine. But it's not what CI does. Sorry. >> Again this is meaningless if you don't define your terms. What concentration? How long? What temperature? Some of this is on the CI web site << Another good point by Mr. Grimes. Yes, so it is, describing the CI protocol. But none of it is in the article purporting to describe the 'simplified protocol'. >> I would prefer to know what people actually said. Why is David not willing to tell me? << (a) Because Mr. Grimes never asked me before, (b) because the post was originally intended to Charles Platt, who knows the folks involved, not Mr. Grimes, (c) because the post was written before I ever heard of Mr. Grimes, (d) because what people have to say is already available out on the web -- why ask me to look it up when you can do it yourself?, and most importantly, (e) because as a CI supporter I am a registered Servant Of Evil despatched by Satan to torment humble peasants on Cryonet by summarizing multiple statements rather than listing the lot in toto. >> In fact I think people must have been surprised by the CI results simply because experienced researchers have never matched these findings. When only one organization makes a claim that contradicts all of the other work in a scientific field, and when the organization doesn't provide a proper report showing exactly what it did, of course people will be dubious.<< Justly so. I myself was dubious when I read the CryoCare Report extracts. (Well, to be honest, I was quite disheartened. I looked at a page of technical terms and thought -- 'Gosh -- big words -- they must know what they're talking about!' It was not till I actually sat down and took a close look at the article, medical dictionary in hand, that I discovered that the entire article was in fact about a competing BioPreservation protocol that was lauded to the skies. The only actual description of the pseudo-CI protocol was just that one sentence. Then I was angry at myself for being scared off by the technical terms at first and not reading closely from the very beginning. One lives and learns.) The assumptions in the rest of Mr. Grimes' statement bear comment, however. He writes, "When only one organization makes a claim that contradicts all of the other work in a scientific field..." I am of course very impressed that, after reading my article the day before yesterday, Mr. Grimes found the time to not merely locate but review all the other work in an entire scientific field. Um -- would he be so good as to name a couple of the papers he personally reviewed? "...and when the organization doesn't provide a proper report showing exactly what it did." Yes, BPI's failure to show a proper report was a great sadness to my heart too; it wasn't at all like the CI reports provided on our web site Research page. >> David continues to quote his version of what other people said, without actually including any verbatim quotes. This is a poor debating tactic, especially since he does not even NAME the people he is referring to. No one can reach any conclusion from this except that David Pascal is not debating the issue fairly. He is doing PR, much like a politician.<< No, I simply don't wish to be bring up unfortunate episodes, and to repeat foul words that have come out of people's mouths in, perhaps, a moment of carelessness. If you really must know, the person who referred to CI's protocols as 'B.S.' -- or rather 'canned B.S.', to be precise, in response to Mr. Ettinger's statement of them -- was the first researcher named in the CryoCare Report article, which you have. He has had his ups and downs, as have we all, and I didn't and don't want to drag him into these terrible Cryonet brawls. It really is awful to have to run around all day thinking of responses to the cruel and incoherent things said on this very rude and witless list; one has to be a child not to find more constructive pastimes; and it is twice awful to have your old words thrown back at you years after the fact. We grow older and wiser and shouldn't be hobbled with old snap remarks forever. I don't want to saddle this person with that, and I wish you would extend him the same courtesy. >> Ramping can be done fast or slow. One-pass can be done fast or slow. Recirculation can be done for a long time or a short time. What he really seems to be saying is that the CI one-pass system takes less time than the Alcor recirculating system. Maybe this is so. << I was going to write a lengthy paragraph proving it to be definitely so, but of course, CI isn't doing one-pass anymore, so what's the point? I do feel I should say, however, that while you can in fact ramp very slowly, it is surely obvious that you can't ramp as quickly as you would like. Perfusate is generally pretty viscous -- thick -- and you simply can't pump fifteen or twenty liters into a person in three seconds, three minutes, or often even three hours. There are pressure constraints. Obviously. >> CI takes LONGER than any other organization to cool a person after the perfusion has been done. If David is concerned about speed, why does CI allow so long for deterioration to occur? Wouldn't it make sense to do faster cooling (I believe Alcor's method is ten times as fast), and allow more time during perfusion, for the glycerol to penetrate? << A good point. Perhaps it would. CI does not take that longer time with the goal of producing deterioration (obviously), but because doing so has produced fewer negative effects, such as fracturing. Alcor's faster rates are accompanied by fracturing -- ie the patient's brain splits into separate chunks. CI feels that splitting patients' brains into chunks might possibly result in unacceptable expenditures on aspirin at some point in the future. Consequently we try to avoid it. CI procedure here, as everywhere, is based on test results. They froze quick, they froze slow. Slow got better results. I have to confess that I would like to see CI do further studies to see if it could freeze somewhat more quickly in the initial stages, and in fact such studies are upcoming. But we can't run a hundred tests all at once, and we can't just chuck our present procedures and test results without hard evidence that another method is better. I mean, OK -- Alcor cools ten times faster. Suppose ACS started cooling twenty times faster. Are patients *automatically* better for it? Suppose TransTime started cooling *fifty* times faster. Heck, throwing people directly into vats of liquid nitrogen would probably cool fastest of all! Do you adopt a procedure on the basis of one criteria, or what the other guy is doing, or because you 'think' its better and it 'ought' to work, or do you run *tests*? CI runs tests. >> Elsewhere in CryoNet posts Robert Ettinger has said that the CI system of perfusion does not take long enough to allow glycerol to penetrate completely. This means some parts of the brain are well protected, some may be damaged by the excessive concentration, and some may be left unprotected. This seems to be the result of fast perfusion with a highly concentrated solution. I have asked repeatedly on CryoNet, why CI does this. Ettinger has not answered, perhaps because he regrets that he ever revealed that the solution doesn't penetrate fully, and he is afraid of making any more statements that will cause embarrassment later.<< Intuitive speculation into the dark abysm that is the soul of Robert Ettinger is, of course, one of the great mystic Ouiji Board pastimes on Cryonet, but I am afraid it does not contribute much in the way of hard data. The answer to the above is very simple and has been stated before -- even by Mr. Grimes himself, though he apparently has not added two and two. If you send in highly concentrated glycerol to the point of equilibration you get more concentrate in, and so more toxicity. You also have to keep the patient at higher temperatures longer while the stuff recirculates, and the longer the patient is at higher temperatures (and I do not mean on-the-way-to-dry-ice temp but warm enough to promote rapid viscous fluid circulation through the vasculature), you get more deterioration. Conversely, if you skip equilibration, you get less toxicity, and less higher-temperature deterioration -- but you also get less cryoprotectant in there, which is not great either. In other words, it's a trade-off. Which is best? The answer to the question, as to most cryonics questions, lies in practice rather than theory. You run tests and go for the best results. The very latest results CI has says that stepped on an open circuit gets the best result. Does that mean the book is closed? No. It'll keep trying other variations too. There's just no other way to improve. >> When I contacted Alcor, they told me they have not done any experiments using perfusates on dogs for many years. << Really? Did they mean that they had not done any tests at all for many years, or that they had just not done any on dogs for -- er, how many exactly years? Or did you not bother to ask? >> When I ordered a back issue of CryoCare Report containing a comparison of procedures used by the company named BioPreservation, and the procedures believed to be used at CI, the article said quite clearly that the procedure was NOT started immediately, because the researchers wanted to simulate the delay that a typical cryonics case might experience.<< You don't say? Well, I've read that article several times -- the July 1995 issue -- several times. In fact I have it before me right now. And I cannot find a single passage stating that the procedure was 'NOT started immediately'. Would you be so good as to share it with us in an exact quote? (By the way. The only person I know that's out there peddling back issues of that issue of CryoCare Report is Charles Platt. Would that be the fellow you talked to while placing an order? What a pleasant and completely unexpected surprise! Why, you couldn't find a fairer and more unbiased soul in all cryonics. How I miss his jolly upbeat chat. Do give Charlie my best when next you talk, eh? A note of warning, though. He's always using capital letters when he posts -- rather like yourself, strangely enough. Do be careful. Poor style is infectious.) >> CI is making a virtue out of using heads from a slaughterhouse, but there is no virtue in this at all, since it means the specimen is not properly controlled. Given that numerous such heads are selected at random, and that the heads are roughly similiar in age, free from disease and abnormality, etc., it seems to me that a control situation does exist. But more important, it seems to me obvious that if you want to find out what happens to brains under real-life conditions, you try to simulate those conditions as much as possible. The fact is, no human being is anesthetized in good health and then perfused, which is how virtually every non-CI study has been run. It just doesn't approximate what really happens. Human beings die in bad shape. That's why they die. To try to approximate what you are actually dealing with seems to me to be to be a sensible thing to do. I do not say that other sorts of research are pointless or uniformative. In fact I try to keep up with them. But it seems to me that real-life applications are the main business of cryonics providers. The simple fact is, we're not multi-million dollar research labs. We're people who have to deal in crisis situations with dead and dying and often deeply injured people surrounded by grief-stricken relatives; we work like hell to provide the best care possible in the teeth of laws and prejudices and obstacles that make providing good care nightmarish. We don't lose people in labs -- we lose them on autopsy tables and in five-car pile-ups. All that we can offer is the best we can; but that much we *can* offer, provided we have something that is deliverable in concrete terms. Hyper-expensive, hyper-complex, 'laboratory' cryonics generally is not. >> The style of this para is so different from everything else David wrote, I can't help wondering if he actually wrote it himself.... I don't think he knows what "granulocyte" means, and I certainly don't.<< Humble words from a man who claims to have not only paramedic but EMT training. A granulocyte's a white blood cell with cytoplasm that's got a granule -- a small particle -- in it. >> CI uses a higher concentration of glycerol than anyone else << Good grief, how long have we all had to put up with that one? Mr. Grimes, instead of posting the same lame charge ten times in a row, go read Alcor's web page. Its web site site states and I quote: "After the surgical access is completed, a cold (about 5oC, just above freezing) perfusate is recirculated through the patient while the cryoprotective agent (glycerol) is gradually increased from a 4% glycerol solution to 75%..." This was the concentration it claimed to use on all patients, although now I presume it is restricted only to whole body patients; although I have also been told, unauthoritatively, that despite their web page, they in fact have a new secret whole-body CPA (as distinct from the super-secret neurovitro CPA). Is the new one 75%? More than 75%? Less than 75%? Beats me. Is it published? No. Is anyone talking? No. Will Jeff Grimes post Notices and Warnings and other juvenile scare tactics every day till he finds out? Of course not. These are *real* secrets. >> Also it does not take into account the ramping-up of concentration, used by other organizations. << Since CI *does* ramp up concentration, in applying it in a stepped manner, how can it not take it into account? >> He has compared CI to other, unnamed organizations, has not supplied any references, and has not defined how the procedures are actually done, either at CI or elsewhere. Therefore the comparison is meaningless.<< That article did not compare CI to any other organizations, but merely pointed out that researchers in a named organization, BioPreservation, reported in a named publication, CryoCare Report, tested a protocol that was five years later publicly said to simulate CI's. The people making the simulation did not know what CI's procedures was, they did not ask CI what it was, and they gave no description whatever as to the protocol or procedures they were implementing, beyond the one bare sentence I have quoted. Therefore the comparison is indeed meaningless -- which did not stop it from being aired, negatively and in private and at last publicly, to God knows how many people. >> No, it does not lean toward gradual ramping, because you would have to do multiple experiments, changing one variable each time, to make such a sweeping statement. First you vary the concentration slowly, then faster; then you try a lower starting concentration, a higher terminal concentration, a higher starting concentration, a lower terminal concentration, a different temperature, and on and on. Then you make comparisons with single-pass procedures that are comparable, and finally you find which way works best.<< Which is what we did, starting ten years ago in labs at Kharkov, and are continuing to do at present at Canadian labs. >> The really irritating thing about this is that I believe this kind of experiment has already been done, in properly run laboratories, by real scientists, who have published their results.<< If you are referring to Dr. Yuri Pichugin of the Institute of Cryobiology at Kharhov, the largest such institute in the world, and the results published on our web site, or the other reports by done by university faculty PhD researchers at independent labs, you are once again correct. (He's really doing good this time, isn't he, gang?) >> But apparently CI refuses to use anyone else's results. It would rather do an amateur job, and then brag about it, while making sly sneering references to its competitors. << BioPreservation and CryoCare are not our competitors. They went out of business. In our sly sneering way, CI's amateurs then rewrote the company rules to take in CryoCare's patients, as well as new rules to cover any CryoCare members who still wanted to maintain a dual membership in both organizations. >> Maybe this impresses some people (David himself seems impressed). But it does not impress me very much. << Yes: I am very impressed -- with CI. When I started looking around to get signed up, I did quite a lot of reading and quite a lot of thinking. I could afford to join any organization, but I wanted to join the best one -- not just the best one for me, but the one I thought was most likely to give other people a chance as well, that could give cryonics itself a good name. And two years later I find myself sitting at home watching ABC TV World News sending out a message to 100 million people about CI's latest patient: "like so much else in medicine, cryonics, once considered on the outer edge, is moving rapidly closer to reality - which means the woman who died and was frozen last week may have a future after all." When professional journalists and investigators say things like that, when independent scientists and labs say this procedure proved better than that one, when memberships in one organization breaks records while others stagnate -- yes, it impresses me. I think that CI is arguably the best and most significant cryonics organization in existence. And the day is coming when that will be unarguable. David Pascal Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=15653