X-Message-Number: 11238 Date: Mon, 8 Feb 1999 12:46:12 -0500 (EST) From: Charles Platt <> Subject: 21st Century Medicine Seminar Summary: Part 3 The following text is the third of three parts of a summary of the seminar sponsored by 21st Century Medicine in Ontario, California, on November 8th last year. This seminar presented preliminary results of research that promises to eliminate damage in cryopreserved organs caused by ice, toxicity, and rewarming. Originally I had hoped to circulate my summary of this exciting research last December. I was delayed by problems transcribing the tape, and by conflicting obligations. I regret the delay but am now able to offer my summary, accompanied by excellent reproductions of brain electron micrographs, in a 16-page leaflet. Members of CryoCare Foundation will receive this publication automatically; anyone else can receive a copy free by sending a self- addressed 9" x 12" envelope to Charles Platt, P.O.Box M, Jerome, AZ 86331. Alcor members will find a version of this text, with lower-resolution photos, in the current issue of Cryonics magazine. An abridged version, with fewer photographs, is scheduled to appear in The Immortalist. The complete seminar is available on a set of five video tapes for $50. Individual tapes are also available for $15 each. Call toll-free 877-277-0322 or send a check or money order payable to Life Extension Foundation, Box 229120 Dept. 21MED, Hollywood, FL 33022. -------------------------------------------------------- Part Three Questions and Answers After the formal presentations, Mike Darwin, Steve Harris, MD, Gregory Fahy, and Brian Wowk received questions from the audience. Linda Chamberlain of Alcor Foundation asked about the price and availability of perfluorocarbon compounds. Mike Darwin replied that it had been difficult to obtain them, but recently he located a new supplier with a large stock. The compounds may cost between $20 and $35 per pound, but in a perfluorocarbon perfusion circuit most of the chemicals can be retained and reused. Another questioner asked exactly how antifreeze proteins prevent ice from forming. Brian Wowk explained that they "form a kind of antibody-antigen match onto the a-axis face of ice. They coat it and prevent growth in that direction." Fred Chamberlain of Alcor wondered what happens if you increase the concentration of ice blockers or methoxylated compounds, and whether they will be prohibitively expensive. Brian Wowk answered that a higher concentration of methoxylated compounds will tend to dissolve cell membranes. "We're cruising on the edge of that," he said. A problem with X1 is that it tends to increase viscosity of cryoprotectants. Overall, Wowk said he expects that the optimum concentration of X1 will be "a few percent." Saul Kent said it was premature to talk about pricing, but Brian Wowk pointed out that anyone with a chemical catalogue could find methoxylated compounds available off- the-shelf. "Technically the only thing to stop you from using them is infringement on our pending patent," he said. As for ice blockers, "We could probably supply as much as you want at a reasonable price. . . . Chemical synthesis houses making this compound for us are not giving us anywhere near the kind of sticker shock that antifreeze protein synthesis gives us." Another questioner asked how long we have to wait for viable suspended animation. Brian Wowk said it should be possible within ten years for the brain, but much sooner for kidneys, because this is the major focus of research. "If sufficient funds become available from people who are interested in the [brain] problem," he went on, "we could tackle the brain just like any other organ. Mike Darwin agreed that "somebody has to fund the work on brains, and it isn't going to be the people funding the work on hearts or kidneys or livers," because that research has an obvious financial payoff, while brain preservation interests only cryonicists. Consequently, according to Darwin, "this audience and the people they represent are going to be the ones who pay for it, else it just isn't going to get done." "To get to the point where a brain is successfully cryopreserved in every sense of the word is an enormously complicated and resource intensive process," Gregory Fahy commented. "We don't have the manpower to divert a lot of extra attention into those areas unless they are funded." He said he expects to discover "all kinds of adverse things that we have no clue exist right now, all kinds of things we haven't thought of, and we'll have to solve those problems. This will take a dedicated team working week in, week out, year in year out, relentlessly, until the problem is solved. We just don't have the assets for that now." Another questioner asked how much it might cost. "$10 million has been speculated," Brian Wowk answered, adding that this is a reasonable guess. He didn't think it would cost as much as $100 million, but he was sure it would cost more than $5 million. The panel discussion broke up shortly after this, and many of the attendees visited the two laboratories where the research has been done. Some people complained that the presentations had been overly technical, while others wondered whether the owners of the new technology will make it available on an affordable basis. Saul Kent said subsequently that he intends to offer results of the research at a reasonable price to all cryonics organizations. Obviously 21st Century Medicine hopes to reap profits from applications outside cryonics, which is a minuscule market by comparison. Conclusion The prospects for human cryopreservation have never looked better. Prospects, however, don't turn into realities without an infusion of money and labor. The new brain studies at 21st Century Medicine are immensely promising, but in the immediate future the company must pursue research that will generate revenue, and brain research is unlikely to fulfill this need. Therefore, if we want zero-damage, reversible brain cryopreservation, we can't count on outside investors to pay for it. We, as cryonicists, probably will have to pay for it ourselves. Six years ago, I bought $10,000 of stock in 21st Century Medicine. This represented about one-quarter of my savings at that time. Some others also purchased stock, but the wealthiest people in cryonics showed only a token interest-- or no interest at all. Consequently, Bill Faloon and Saul Kent shouldered the primary burden. By my estimate, they have spent about $10 million so far. I am constantly amazed by the reluctance of wealthy cryonicists to put money into research that could increase their own chances of survival. It seems grossly irresponsible to assume that others in the future will fix freezing damage for us, when there is no absolute guarantee it will be reparable, and we could be addressing the problem ourselves. In the past, there was some doubt that investment in research would pay off. This doubt should be dispelled, now, by the evidence presented at the 21st Century Medicine seminar. Kent and Faloon have demonstrated that money really can buy remarkable progress within a short space of time, and almost certainly reversible cryopreservation can be ours if we really want it. Within the next year we will see whether cryonicists are willing to acknowledge this fact--or whether "Let someone else deal with the problem" will continue as the dominant motto in cryonics, as it has for the past thirty years. -------------------------------------------------------- 21st Century Medicine Team Led by Mike Darwin Now Holds World Record for Survival of Ischemia at Normal Body Temperature For several years, Mike Darwin has been looking for new techniques to inhibit or treat brain damage that occurs after blood circulation stops suddenly, as in a heart attack. In his presentation at the 21st Century Medicine seminar, Darwin noted that sudden cardiac arrest is the leading cause of death in the United States, afflicting 540,000 people annually. He said that despite the advent of CPR and widespread deployment of paramedic teams, fewer than 1 percent of cardiac patients survive without any brain damage if they suffer four to six minutes of cardiac arrest. Any treatment that can improve these dismal statistics obviously would be extremely valuable in emergency medicine, and Darwin told his audience that the methods he has developed with his primary team, Steven B. Harris, MD, Sandra Russell, Joan O'Farrell, and Carlotta Pengelley, could save 300,000 lives each year. The research is important also to cryonicists, since we are concerned with preserving the brain with minimal damage in all phases of our procedures, including the first crucial minutes after legal death is pronounced. Darwin and his team have been remarkably successful, routinely reviving dogs after 15 to 17 minutes of cardiac arrest at normal canine body temperature, under anesthesia. (These results should not be confused with those of previous dog experiments where much longer survival times were achieved with deep hypothermia.) A major factor in the success of recent resuscitation research was Steve Harris's suggestion that ischemic injury can be viewed and treated as an inflammatory response, similar in some ways to the swelling and inflammation that occur after any localized injury. Darwin reported that in eight separate experiments with dogs, three achieved excellent recovery after six weeks (showing no neurological deficit at all), three showed good results, and two did not survive. He claimed that these results have not been matched by any other laboratory. Unfortunately the protocol is complicated. After blood flow is restored, multiple drugs must be delivered within 5 to 15 seconds, while body temperature must be lowered by about 4 degrees Celsius within 3 to 5 minutes. How can this be achieved by paramedics working on human patients out in the field? Darwin said that a computer-controlled system will be needed to deliver the drugs. The FDA has been reluctant to approve biomedical software, and also is generally opposed to multidrug cocktails. Consequently, the approach developed by Darwin and his team may be applied only outside of the United States, initially at least. The challenge of rapid cooling seems severe. Darwin told the audience at the seminar that external cooling via a stirred ice-water bath typically requires about 80 minutes to lower body temperature by 5 degrees Celsius. This is far too slow, and requires about 300 pounds of ice and 200 pounds of water, making it impractical for use in the field. However, Darwin said that the lungs can be used as a heat exchanger. Since all cardiac output flows through the lungs, which have a huge surface area of 70 square meters, they provide an excellent opportunity to draw heat out of the blood, which then cools the brain. Cold air cannot remove heat rapidly enough, but a breathable liquid is effective and can be applied by intubating the patient, which is a standard emergency procedure. According to Darwin, experiments with dogs have proved that mixed-mode liquid ventilation using a perfluorocarbon at about 2 degrees Celsius can provide more than enough breathable oxygen while lowering body temperature by about four degrees in the first five minutes. An average cooling rate of 0.36 degrees Celsius per minute has been achieved, and dogs have recovered fully after their temperature has been reduced by as much as 10 degrees. Since liquid ventilation is not only effective but could be deployed relatively easily in the field, it has a clear advantage over any other method of reducing temperature. It could be used to treat head injuries as well as ischemic injury caused by cardiac arrest, according to Darwin. He said that inspection of lungs after liquid ventilation showed "some isolated areas of injury," particularly at the bottom part of the lungs, probably from contact with the very cold perfluorocarbon liquid. Still, the animals showed no sign of distress, and light and electron microscopy revealed no sign of structural damage in other areas of the lungs. "If you can automate this process, any paramedic can do it," Darwin told his audience. He predicted that it could be "a potential profit center" that could save a lot of lives, and said he hopes to see clinical trials 2 to 3 years from now. Although Darwin didn't mention the use of liquid ventilation in cryonics cases, obviously it would be extremely valuable and could be applied in the very near future. ------------------------------------------------------------- Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=11238