X-Message-Number: 3062 Date: 05 Sep 94 03:19:09 EDT From: Mike Darwin <> Subject: SCI.CRYONICS research This posting is in response to remarks by Donaldson, Kunan, and Ettinger. It will be briefier than I would like because I am extremely rushed at the moment. Please forgive me if I am disorganized. 1) Mr. Kunan speculates at some lenngths about the use of hyperbaric chambers, perfusion with cryoprotectants used by overwintering vertebrates, etc. He is apparently unaware of the kind of procedures used by those cryonics groups which have historically had a great deal of concern about "up front preparation" of the patient. I would make the following points: 1) BPI, ACS, Alcor and I believe some other groups use technques which initially oxygenate and support circulation using cardiopulmonary bypass. There is no need for hyperbaria during early phases of cooling because the patient's blood is both present and sufficient to carry both oxygen and other needed substrate. 2) Surface and extracorporeal cooling can be used to quite rapidly lower a patient's temperature to 15xC; at which time blood washout can be safely carried out and the blood replaced with a suitable asanguineous solution (most groups are currently using DuPont Pharmaceutical's Viaspan organ preservation solution). At 15xC and below the increased solubility of oxygen and the decreased metabolic rate of the patient allow for safe asanguineous perfusion. Indeed, here at 21st Century Medicine and Biopreservation we routinely recover dogs from 5-6 hours of bloodless perfusion with no neurological or other deficits. In fact, one of the reasons I'm rushed is that I have to take the staples out of last 5-hour survivor and get ready to do another animal this coming week. This part of the technique is well worked out, safe and fully reversible. It does not require hyperbaric chambers which are costly, cannot be brought into the patient's home, hospice, hospital or nursing home and which further severely limit access to the patient during their application. 2) Detailed case histories of how human cryopreservation patients are prepared can be had by contacting me at the above e-mail adress or contacting Kevin Brown, the Sysop for Cryonet. We routinely introduce multimolar concentrations of cryoprotective agent (glycerol) via perfusion and employ controlled and monitored cooling to -196xC. Further, we are painfully aware of and involved in solving the injury which results from the application of our current methods. Again, a bibliography is beyond me here, but papers documenting the gross, histological and ultrastructural condition of patients cryopreserved using varying approaches are available. Please contact me if you have interest. I found Bob Ettinger's posting very sad. Yes, it may well be that the universe is completely deterministic. But there is no yet, as far as I am aware, compelling proof of that. Bob's inability or lack of desire to imagine that the universe is any other than the way he imagines it to be probably has little to do with the reality. Nor, for that matter, do my feelings or thoughts on the way the universe works. Bob's posting is of use in that it shows quite nicely that there are two distinctly different classes of cryonicist. Bob is in one class. I am in another. I do not mean to make judgments here in some perjorative way. Everyone is entitled to believe what they want. I would point out however that my criteria for cryonics working are far more restrictive than Bob's. To me and to those working with me, we must stay within the envelope of known physical law. When I see autolytic changes associated with long postmortem delay and/or the ravages that occur with cryoinjury it is by no means clear to me (based on what I understand of physical law) that such damage will be reversible. To some extent we could take this debate out indefinitely far to the point where we begin to discuss how many angels can dance on the head of a pin. I am *not* interested in such debates. Nor are most terminally ill people who reach out to cryonics as method of saving their lives in something approaching real time. I am especially not interested in such sterile debates when I see before me the prospects of dramatic improvements in cryopreservation techniques possibly resulting in reversible brain cryopreservation. The ugly fact is that we have painfully little idea of exactly what kind of damage we are doing to human patients on the ultrastructural level after freezing them with existing techniques. Yes, we do have some information, but it is far from adequate and far from encouraging. A major focus of our efforts here at BPI is to both document how well or poorly we are doing and to extend the technology to the point of achieving reversible brain cryopreservation. We currently have our first pictures back from 6M glycerol frozen-thawed dogs and from a variety of control animals and more animals are scheduled for preparation this coming week. Additionally, Greg Fahy has been quietly and diligently working to evaluate both different cryoprotectahts singly and in combination and to evaluate vitrification on rabbit brain slices. This large and growing database will be used by an MD (neurologist), myself and others starting this Spring here at BPI to begin trying to achieve REVERSIBLE brain cryopreservation. 4) While Bob is entitled to his opinion, I would point out that it is my opinion that his post did nothing to enhance the scientific credibility of his position or of cryonics in general, and I wish to both point out personally, and urge others who think as I do to do the same, that Bob's position regarding the recovery of patients *does not represent my position, BPI's position, or that of most of us working here to improve human cryopreservation techniques.* 5) As to Thomas Donaldson's remarks. All well and good. No one says you should contribute to or invest in anything you don't believe will work. There are, however, a family of research options out there now. Bob Ettinger's CI is supporting work in Ukraine, Alcor is preparing to undertake research to begin in the Fall, and we have had an aggressive program of work underway here for several years with cryoprotective perfusion, freezing and evaluation both by freeze-substitution and after rewarming in dogs and rabbits for at least 8-months. In the Spring that work will be extended to electrophysiological evaluations and the first thing on our plate is to repeat Suda's work in addition to begining to map out the application of vitrification technology (with Greg's help) to brains. 6) While work can be done cheaply in Ukraine, I would note that there are also very serious limits on that work. We are doing work quite cheaply here too: for example I just had over 400 EM's and 200 light micrographs done from the RAS, CA1 area of the hippocampus, molecular layer of the gray matter, white matter, corpus collosum, thalamus and cerebellum from several animals for $1,200. And these animals were prepared using cardiopulmonary bypass and state-of-the-art procedures for perfusion exactly as we would use on humans. And the personnel preparing them include a physician (Steve Harris), a Board certified perfusionist, a respiratory therapist, me and others. The point being that these animals are being prepared in exactly the way we prepare cryopreservation patients. Further, we are able to immediately get feedback from the system and make changes. We also have high tech analtical equipment available to evaluate viability and markers for injury in real-time which are not available in Ukraine. While I would in no way discourage the Ukraine work, I would point out that we get a hell of a lot bang for our buck here too. The take home message here is simple really, regardless of *who* he supports, Donaldson should consider supporting someone. Finally, finally, in order to apply the techniques Greg has developed to brains we will need computer controlled perfusion and cooling equipment. With every kind of cost containment imagineable we still estimate that will take at least 30-40K for the hardware. Most of that is in the cost of the refractometers and process control equipment. And that, ladies and gentlemen, is not available in Ukraine. It's barely available here. Our interest in brain cryopreservation is not purely to save our own lives (although that is clearly the biggest interest). Rather we not only suspect, but we *know* that there will have to be significant additional work done to develop this technology for use on brains. Such work will be patentable and proprietary. We have reason to believe that this technology will be quite commercially valuable. And I am not at all ashamed to say that making it so is a high priority for BPI. As to his remarks about the Mormons. I do not agree. One of the really striking things about the Mormons to me was the degree to which they have remained iconoclasts and the unique way in which they have accomodated on key points of doctrine. These things were why I marked them out for study. Thomas would do well to order one of their videos and be visted by two of their young missonaries. (Keep in mind that as the Momorm point out, most of the conversions to Mormonism occur not by the missionaries converting others, but by the missionaries converting themselves during the course of their mission). I use the Mormons, even today, as examples of what a determined people can achieve in every sphere of their lives (commercial, social, political, etc.) in the face of intense hostility and handicapped by beliefs which are, to say the least, bizzare. Handicapped most of all by a book (The Book of Mormon) which Mark Twain quite rightly described as "chloroform in print. I stand by those remarks as being both carefully considered and accurate. And I repeat my advice to cryonicists to do a little digging into their history. I would also point out that if cryonicists remote from major centers of cryonics apploied themselves with 1% of the diligence of the typical Mormon family to studying transport techniques, building up their local capabilities, and contributing 10% of their income to THEIR local set-up, research, etc., there would be no stopping them and there would be a lot fewer autolytically/cryobiologically chewed up patients in bargain. Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=3062