Life Extension Society 990 N. Powhatan St. Arlington VA 22205 703-534-7277 1996 No. 4 LIFE EXTENSION SOCIETY NEWS Oct. 1996 Reversible Cryogenic Preservation Demonstrated The team of Michelle Olga Visser and Siegfried Visser, a cryobiologist and consulting engineer, respectively, demonstrated the apparently reversible cryopreservation of rat hearts at the CryoSearch research facility in Scottsdale, Arizona in August, 1996. In experiments over a span of several days, the Vissers perfused a number of rat hearts with a new cryoprotective agent (CPA), froze the hearts to within a few degrees of liquid nitrogen temperature (minus 320 degrees Fahrenheit), and then rewarmed the hearts. Behold, three of the hearts began to beat again, one strongly. A mammalian organ had survived an incredible journey. Mrs. Visser is the Head of Research at the Department of Thoracic Surgery, Faculty of Medicine, University of Pretoria, South Africa. She is an experienced perfusionist and a Ph.D. candidate in cryobiology. She started the first homograft bank in Pretoria eight years ago and has been doing research in organ cryopreservation for the last three years. The Vissers say that they also have frozen and revived rat livers and a pig's heart at their lab in Pretoria. The technique has been patented or has patents pending in South Africa, the United States, Russia, Australia, New Zealand and the European Union nations. With three co-authors, Mrs. Visser submitted a paper on her experiments to Cryobiology in December, 1995 and is revising it for publication. Her recent experiments at CryoSearch demonstrated the techniques and CPA used in the soon-to-be-published research. Visser's result is of immediate importance to cryobiology and transplantation research. Cryobiologists study the effects of low temperatures on organisms, from hibernating frogs and salamanders to organs cold-stored for transplantation. Preserving whole organs for transplantation has been a goal of cryobiologists for decades. Thus far, only certain types of cells and tissues, such as sperm, embryos and small blood vessels, have been frozen and re-warmed for use. The problem is freezing itself. Ice formation is virtually unstoppable. An ice crystal pierces all cell structures in its path, causing great destruction. CPA's are chemical concoctions, usually involving sugar-based molecules, that mimic chemicals produced in the bodies of hibernating amphibians. These amphibians' bodies actually fall below freezing temperatures, but the sugars in their blood cause the cells to shrink so that ice forms between the cells rather than forming within the cells and destroying them. If a CPA can be perfected that permits the deep-freezing of an organ, the organ can be stored indefinitely, giving doctors time to test the organ for disease or find an optimum match with a recipient. Animal models are used to perfect each CPA before being used on human organs. Hence, Visser's research could be the first step in perfecting a CPA for human hearts or other organs. Some cryobiologists are skeptical, waiting to see the published results or claiming that funds would be better spent on finding ways to reduce organ rejection by recipients. The CryoSearch facility is associated with the Alcor Life Extension Foundation, a cryonics organization also located in Scottsdale. Alcor and the Cryonics Institute (CI), of Clinton Township, Michigan, teamed up to fly the South African researchers to Scottsdale. Cryonicists believe that this type of cryobiological research eventually will result in a way to reversibly cryopreserve human brains and bodies. The Vissers are raising money for the next research step, transplantation of a revived organ into a lab animal. They hope that their transplantation experiments will lead to human cryogenic organ banking. Alcor and CI have agreed to help the Vissers obtain financing for further research. (Alcor Director Dave Pizer is heading up Alcor's part of the fund raising drive.) In return, the Vissers have given Alcor and CI exclusive license to use their current and future technology for cryonics purposes. This includes the right to sub-license. After Alcor and CI announced the results of the Visser's visit, lively discussions ensued among cryonicists. One topic of discussion was the relationship of the Vissers' work to the Prometheus Project, a multi-million dollar research project into the cryopreservation of mammalian brains that is being spearheaded by Paul Wakfer (See LES News, 1996 no. 3, July 1996). Wakfer states that the Prometheus Project will investigate the most promising technologies, no matter what they may be. In addition to the Vissers' techniques, a second cryopreservation method to be considered for the Prometheus research is called vitrification. With vitrification, a CPA is used and temperature and pressure are controlled so that the fluids in the organ under study solidify without crystallization, that is, they behave as a glass. The differences between Wakfer's project and the Alcor/CI initiative are twofold: 1) Wakfer is collecting pledges ($3 million plus so far) for a future effort, while Alcor/CI are applying their funds to current research; and 2) Wakfer's effort is focused on cryonics (the market for transplantable brains being limited), while the Visser's efforts have more immediate application to organ and tissue banking. Rather than being in competition with the Prometheus Project, the Vissers' research, if successful, could lend credibility to Wakfer's longer-term effort. If the Visser techniques do not prove out, the Prometheus Project simply would focus on other techniques. This article was adapted from a World Wide Web posting of September 22, 1996 by Samuel Blackman and from an article in the September, 1996 Alcor Phoenix. LES Member Completes Training in Cryogenic Preservation LES member Keith Lynch participated in the BioPreservation, Inc. training course in human cryopreservation, which was held from September 3 to September 10, 1996 at the BioPreservation laboratory in Rancho Cucamonga, California. The course covered the first phases of human cryopreservation: standby and transport, also collectively known as "cryonic stabilization." The primary instructors for the course were Mike Darwin, Steven B. Harris, M.D., and Carlotta Pengelley, L.V.N. BioPreservation is the cryopreservation contractor for the CryoCare Foundation and also has performed cryopreservations for the American Cryonics Society. [Author's note: The Alcor Foundation periodically offers a similar course in standby and transport, which is taught by Tanya Jones and Hugh Hixon, among others. The course curriculum is very similar, although the materials and techniques used differ in many particulars.] The objective of the course was to familiarize the graduate with the principles and techniques to give ethical and quality care to the terminally ill cryopreservation patient. Specific areas covered were: * Psychology of death, dying and bereavement relating to cryonics. * Psychosocial support and intervention during standby and transport for the cryo-patient and his/her family. * Interface with primary care personnel to insure optimum cryopreservation. * Interface with hospice programs for cryonics compatible terminal care. * Premedication of the cryopreservation patient for prophylaxis of ischemic injury before legal death: pharmacologic, logistic and legal considerations. * Site assessment and logistic considerations in deploying for a local or remote Standby. * Pathophysiology of cerebral ischemic injury. * Administrative procedures: record keeping, data acquisition, quality control. * Cardiopulmonary support: options, evaluation and intervention. * External and internal (non-extracorporeal) cooling. * Establishing IV access. * Preparation and administration of medications to inhibit ischemia-reperfusion injury. * Physical transportation of the patient to the cryoprotective perfusion facility. * Infection control in the standby and transport setting. Included in the above was training in using the newly developed, pneumatically driven, high impulse, active compression - decompression CPR units and the newly developed technique of liquid ventilation. Technical training was hands-on using animal models. Keith has prepared an extensive trip report, which is available from LES. In addition, each trainee received a course manual, portions of which are proprietary. Material in this article is from the BioPreservation course announcement. Dr. Michael Fossel Discusses "Reversing Human Aging" Dr. Michael Fossel, M.D., Ph.D., gave a presentation on "Reversing Human Aging" at the National Institutes of Health's Natcher Center on April 16, 1996. The presentation was sponsored by the Smithsonian Institution's Smithsonian Associates. LES members and subscribers were notified of the talk, and a number of LES members attended. For years, Dr. Fossel has studied progeria and related accelerated aging syndromes. He is convinced that the evidence from these diseases, together with the fact that germ cells and cancer cells do not age, indicates that aging is a regulated process, that is, a function of gene expression, and not a function of "wear and tear." His recent book, "Reversing Human Aging," reviews recent research into "telomere" that identifies a mechanism for the regulation of aging. This research shows that telomere, or "nonsense" DNA at the end of each chromosome, is shortened with each cell division in dividing cells. Telomere functions like the tip of a shoelace. Snip off the tip bit by bit, and eventually the shoelace will unravel. Once telomere in a dividing cell becomes too short, the cell unravels, that is, it ceases to divide, senesces, and dies. This explains why we have limited life spans, why calorie restriction and other methods that slow down metabolism and cell division may extend life, and why progeria victims have short lives (they are born with already-shortened telomere). Why, then, don't we just stay young and healthy, then drop like rocks at our appointed time? The answer is that on each chromosome the regulatory genes are located near the tips, that is, near the telomere, and the expression of these regulatory genes is influenced by telomere length. With each division beyond a certain point, the regulatory genes in dividing cells get a little more out of whack. Germ cells and cancer cells are the exception. They are immortal because they produce an enzyme, telomerase, that replaces the telomere that otherwise would be lost in each division. It doesn't restore already lost telomere, but it prevents further losses. Organisms with telomere-limited cells have a survival advantage because damaged or mutated telomere-limited cells die off before they can kill the organism. Cancer, in which telomerase production is turned on, is the exception. Although gene expression leads to cell disfunction after numerous divisions, changes in gene expression early in life are important to individual development, maturation, and reproduction. Telomere may be involved in the master "clock" that regulates both maturational and senescent changes in gene expression. (Death, then, would be the inadvertent byproduct of the continued ticking of the "clock" after maturation and reproduction had been taken care of.) Unfortunately, achieving immortality is not simply a matter of introducing telomerase into normal cells. First, some types of cells do not divide (heart muscle or brain cells, for instance). Second, many potentially cancerous cells fail to become immortal and die off because they do not also become telomerase-producing. Introducing telomerase wholesale would enable runaway mutant cells to divide indefinitely. Perhaps some day we will be able to enable normal cells to produce telomerase and to limit telomerase production in abnormal cells. Right now, research into telomerase inhibition (cancer control) is ahead of research into telomerase induction. Dr. Fossel cautions that advances in telomerase induction may not significantly extend lives right away. There are still too many other things -- viruses, bacteria, trauma, poison, genetic errors -- that can happen to bodies. LES Members Host "Life Extension and Nanotechnology" Party LES members Greg F*hy and Nooshin Mesbah-Karimi hosted the LES fall bash on November 10, 1996. The party, which had the theme of "Life Extension and Nanotechnology," offered party-goers the opportunity to share their interests and learn from each other about life extension, nutrition, anti-aging medicine and biology, nanotechnology, and cryonics. In addition to some LES regulars, a number of new faces in the sciences and medicine chose to come. Nearly thirty people came in all. Many thanks to Greg and Nooshin! LES Meeting To Lay Plans for 1997 The next LES meeting will take place on December 8, 1996 at President Mark Mugler's house, 990 N. Powhatan St., Arlington. The meeting will focus on 1997 and beyond: priorities for outreach, public information, and equipment acquisition and training; funding needs; dues; the slate of candidates for 1997 offices; and similar matters. LES members are welcome. From Route 66 westbound, take Sycamore Street exit, turn left under the overpass. From Route 66 eastbound, exit for Washington Blvd., turn right at 2nd light (Sycamore) under the overpass. Follow Sycamore about 1/3 mile. Take last left before light (11th Road). Turn right at T and take immediate left (still on 11th road). Three short blocks. Right on Powhatan. House is near end of block on right. Upcoming Events The Fourth Annual Anti-Aging Medicine Conference will be held December 14-16, 1996 in Las Vegas at the Alexis Park Hotel. Contact the American Academy of Anti-Aging Medicine at 401 N. Michigan Avenue, Suite 2400, Chicago IL 60611-4267. Phone 312-622-7401; Fax 312-622-1071. The Alcor Foundation's ACT (Advancing Cryonics Technology) Festival will be held January 31-February 2, 1997 at Alcor in Scottsdale, Arizona.