BPI TECH BRIEFS (January 11, 1994) Biopreservation, Inc. is a human cryopreservation services provider and brain cryopreservation research and development company. While BPI's structure is a for-profit one, it is our intention to foster the growth of knowledge and scientific advancement as rapidly as possible. In order to facilitate these objectives we have decided to begin publishing technical and nontechnical material of relevance to the field of human cryopreservation in a rapid fashion. While some of our research will remain proprietary or will be undisclosed until patenting, much of what we do and learn will be appropriate for immediate dissemination. Aside from the previously stated objectives of advancing the state-of-the-art we strongly believe that such disclosures will enhance our position and profitability a goal which we also believe is a worthy one. Below is an introduction to BPI, its facilities and its staff. Future BPI TECH BRIEFS (BPITB) will concentrate on specific technical problems in the field of human cryopreservation and related disciplines. Individuals wishing to submit material to BPI for inclusion in BPITB should fell free to do so. Anyone wishing more information about the company should contact Michael Darwin with *specific* questions. Since BPI does not provide services directly to the public we do not have promotional literature. Introducing BioPreservation ------------------------------------------------------------- The best equipment The most highly qualified personnel A serious commitment to suspended animation research ------------------------------------------------------------- Introduction BioPreservation, Inc. (BPI) is a for-profit company which specializes in medicating, perfusing, and cooling people who are under the legal control of cryonics organizations such as CryoCare Foundation and The American Cryonics Society. We offer unmatched experience and expertise in the clinical procedures that are essential for optimum, controlled cryopreservation. Preliminary Steps Working closely with the patient's cryonics organization, we take an active role to insure that long before cryopreservation procedures actually begin, the elements which are critical to a high-quality outcome are firmly in-place. Ideally, the first step is to insure that the patient has exhausted all medical options to remain alive with an acceptable quality of life at the present time. Our medical staff reviews the patient's medical records, consults with other experts, and reviews appropriate medical databases in an attempt to determine the patient's likely prognosis and current therapeutic options. The patient is informed of the results of this search and therapeutic options, if any are available, are discussed. Since cryopreservation of humans is not yet a recognized medical procedure, we cannot begin cryopreservation while the patient is still alive. However, there is much that we can and will do to insure that when legal death is pronounced, within the limits of current techniques, the patient will receive the best possible care and minimal injury. If the patient has in fact exhausted the resources of contemporary medicine and is terminally ill, we begin working with the patient's cryonics organization, family, and medical personnel, to achieve the following objectives: * We establish a rapport with the treating medical staff and secure their informed cooperation, as much as possible, to facilitate the patient's cryopreservation under optimum conditions. * In conjunction with the patient's treating physician, the patient, and (where appropriate) the patient's family, we begin a program of pre-cryopreservation medication to minimize the effect of the ischemic interval (i.e. the period where the person experiences deep shock/no blood flow) which inevitably occurs between the time legal death is pronounced and cryopreservation procedures begin. * Working closely with the patient's cryonics organization, we evaluate the patient's home, hospital, hospice, or nursing home to insure that facilities are adequate to begin the initial phases of cryopreservation. For instance, we will try to insure that the patient is physically accessible, in a room that is big enough, with no obstacles such staircases or impossibly narrow hallways. Again, in conjunction with the patient's cryonics organization, we also work to establish a liason with a local mortuary so that the patient can be moved promptly and legally to our facilities in Southern California for cryoprotective treatment and cooling to -79 degrees Centigrade. * If the patient wishes to remain at home for pre- suspension (i.e., terminal) care, we work with the patient and the patient's family and cryonics organization to insure that the patient is enrolled in a home-hospice program in which the hospice personnel and local authorities (where appropriate) are adequatedly informed regarding special needs such as prompt pronouncement of legal death and avoidance of medico-legal autopsy (postmortem dissection). * When the patient's condition reaches the point where the need for cryopreservation is imminent, we move our equipment, medications, and personnel as near to the patient as possible and stand by on a twenty-four hour basis, ready to perform cardiopulmonary support after legal death is pronounced. Mechanically augmented CPR is used initially. Subsequently, a heart-lung machine supports circulation, oxygenation, and cooling of the patient's blood. The blood is then replaced with Viaspan R(1) organ preservation solution. The patient is cooled to a degree or two above freezing and is then moved via air or surface transporation (depending upon distance and logistics) to our facility in Southern California for the next phase of the treatment. Our standby team includes a perfusionist, emergency medical technicians, and other certified cryopreservation transport technicians. Our Medical Director (a licensed physician) is also available for standbys and has considerable experience dealing with attending physicians, hospital/hospice/nursing home administration, and other medical staff. Perfusion In a spacious operating room at our facility, the patient is perfused with a cryoprotective solution that will minimize tissue damage when the temperature is subsequently lowered and deep cooling to -79 degrees Centigrade is begun. We are better equipped than any comparable organization to control and monitor the lengthy, complex procedure of cryoprotective perfusion. Our duties end when the patient's temperature dips to -79 degrees Centigrade (the temperature of solid carbon dioxide, or "dry ice"). At this point, the patient's cryonics organization supervises transfer of the patient to the service provider responsible for long-term care at -196 degrees Centigrade (the temperature of boiling liquid nitrogen). Research At BioPreservation, we recognize that the techniques of cryoprotective perfusion are imperfect at present and must be actively refined and improved as rapidly as possible. In pursuit of this goal, we are conducting privately funded research in conjunction with several other companies aimed at perfecting a reversible method of cryopreservation for the brain (suspened animation). In canine Total Body Washouts (TBW), we have revived dogs successfully after they have been perfused with a preservative solution (perfusate) and held without vital signs for up to 5 hours at 3 degrees Centigrade. This research is unmatched by any other laboratory in the world, and it has already yielded important results leading to significant improvements in the techniques of cryoprotective perfusion. Perhaps most importantly, we have made a major commitment to understanding and defining the limitis of current human cryopreservation techniques, and we are working to improve them further. Currently, we are undertaking an aggressive research program with both dogs and rabbits, hoping to improve the degree of fine structural preservation of the brain and eliminate the gross mechanical injury from cracks or fractures which develop in tissues that are cooled to liquid nitrogen temperature. The first phases of this work have already resulted in significant improvements in our human cryopreservation protocol. The complete results of these studies (including a variety of evaluations of brain structure at the organ, tissue, and molecular level) should be available by mid-1995. Our Facility BioPreservation is located in Southern California, forty-five minutes from downtown Los Angeles and five minutes from the international airport at Ontario, California. The modern, 7200 square foot building is larger and better equipped than any comparable facility specializing in human cryopreservation. It is divided as follows: Function Square Feet Operating room 1400 Laboratory 1000 Materials prep/Sterile processing 300 Rest area for staff 200 Operating room staging area 450 Ambulance bay, workshop, storage 3000 Library/Conference room 200 Operating Room Details The 1,400 square foot operating room is equipped with cardiovascular perfusion and monitoring equipment of the same type found in state-of-the-art medical centers. Blood gases and electrolytes (including glucose, sodium, potassium, calcium, chloride, pH, pO2, pCO2 and hematocrit) can be monitored continuously while the patient is perfused with cryoprotectants. Precise knowledge of these parameters provides important information for the long-term benefit of the patient and short-term benefit of others who may follow. Such feedback is critical to improving the quality of the cryopreservation treatment. Monitoring is carried out with an in-line CDI 300 extracorporeal monitor and a Nova Stat 5 blood gas/electrolyte analyzer. The CDI 300 provides continuous feedback, enabling minute-by-minute adjustment of critical blood gas parameters without the usual lag time which occurs with off-line blood gas equipment. The Nova Stat 5 provides a double-check of blood gases and allows for electrolyte measurements during perfusion. Additional back-up capability is provided by an IL1302 blood gas system, an IL282 co- oximeter, and a Nova 1 electrolyte system. The composition of sweep gas being delivered to the oxygenator during bypass is precisely controlled with the use of a Cobe Laboratories air, oxygen, CO2 blender which is monitored by a Critikon Oxycheck oxygen concentration monitor. The operating room is equipped with three compete sets of cardiothoracic surgical instruments, numerous non- cardiovascular procedure instruments sets, and linens, drapes, and sterile disposable supplies to allow for the conduct of TBW cerebral resuscitation research and human cryopreservation at or beyond the level of any major university. Laboratory Equipment A Kodak Ektachem DT system measures clinical blood chemistry factors such as albumin, ALKP, AST, ALT, CK, CKMB, Creatinine, GGT, LDH, lipase, ammonia, amylase, total bilirubin, BUN/urea, lactate, magnesium, phosphorus, and total protein. Using the Ektachem system, a researcher has most of the analytical capabilities of a commercial clinical laboratory, in-house, twenty-four hours a day. Our facility is also equipped with a wide range of supportive equipment including osmometers, oncometers, refractometers, centrifuges, pH meters, microscopes, balances, autoclaves, shaker baths, controlled temperature baths, and so on, to facilitate biomedical research. Ambulances/Mobile Advanced Life Support System Two ambulances are available at all times. (No other cryopreservation organization has a backup ambulance.) One is a late-model vehicle manufactured by Leader Industries, extensively modified to accomodate a custom-fabricated Mobile Advanced Life Support System (MALSS). This unit provides rapid, controlled cooldown externally and internally (by perfusion). It also monitors blood gases and pH and contains its own independent power supply. The MALSS is equipped with a Michigan Instruments Thumper closed-chest heart-lung resuscitator so that CPR can be reliably delivered as a bridge to the initiation of extracorporeal support. The MALSS is currently configured to run the Sarns hollow-fiber membrane oxygenator/heat exchanger for extracorporeal oxygenation and cooling. The second ambulance, a van-type unit, serves as back- up for the first and is equipped to respond to a local emergency if the primary vehicle is out in the field on a standby. Staff Quarters To enable true twenty-four-hour capabilities, our facility includes comfortable sleeping quarters for up to six support staff. Cryopreservation To facilitate cryopreservation studies, excellent equipment and consumables are available for isolated cryoprotective perfusion of brains, kidneys, and whole animals. A range of cryogenic refrigerators and temperature monitoring and control equipment is available, including a wide array of large- and narrow-mouth cryogenic dewars for liquid-nitrogen storage of specimens as well as a Revco Ultra Low -115C freezer which allows for fracture-free storage of organs and small animals. Work in progress We are currently constructing automated systems that will give us precise control of the introduction and removal of cryoprotective drugs and the cooling of humans to -79 degrees Celsius. Personnel Our personnel have extensive experience in either deep hypothermic canine perfusion, cerebral resuscitation research, or both. Medical Director: Steven B. Harris, MD. Dr. Harris is board certified internist and gerontologist with extensive ICU and Emergency Room experience. In addition to being a professional gerontological researcher, Dr. Harris has also served as physician and participated extensively in canine deep hypothermia experiments sponsored by 21st Century Medicine, using various bloodless perfusion protocols. Team Leader: Michael Darwin, CRT. Mr. Darwin is a certified hemodialysis technician with over 20 years experience in deep hypothermia research. Mr. Darwin served as President of the Alcor Life Extension Foundation from July of 1982 to February of 1988. He was Alcor's director of Research from 1988 to 1991, and is responsible for the development of many of the transport and perfusion techniques currently used in human cryopreservation today. Additionally, Mr. Darwin has authored numerous technical papers and two textbook/procedure manuals on human cryopreservation and asanguineous perfusion procedures. Mr. Darwin is also director of research for 21st Century Medicine's canine TBW and cerebral resuscitation research projects. Scribe: Sandra Russell, BS (Biochemistry/Cell Biology). Ms. Russell is a professional educator and businesswoman who serves as scribe/perfusion monitor and blood gas technician. She has extensive experience performing data acquisition and ICU care in 21st Century Medicine's canine TBW and cerebral resuscitation programs. Ms. Russell has also had extensive clinical experience as a cardiac technician in a large hospital where her duties included ECG testing/analysis, treadmill monitoring, and Holter monitor analysis. Facilities Manager: Paul Wakfer, BASc (Engineering Physics), MA (Applied Mathematics). Mr. Wakfer's duties are logistical support for research personnel, in-house equipment technician, and business manager. He has participated also in 21st Century Medicine's canine TBW and cerebral resuscitation experiments. Respiratory Therapist, Equipment Technician: Michael Fletcher, RT. Mr. Fletcher is a respiratory therapist, respiratory equipment technician, and an EEG technician. Mr. Fletcher's duties are equipment maintenance during research (he has worked as a mechanic and sheet metal worker and has extensive shop/fabrication/mechanical skills), and respiratory therapist during in 21st Century Medicine's canine research programs. Engineering Support: Mark Connaughton, MS (Professional Engineer). Mr. Connaughton has participated in canine TBW research performing blood/perfusate analyses, and is currently involved in the design of computer controlled perfusion software and hardware for BioPreservation. Primary Perfusionist: Paiboon Plookvongpanit, CCP. Mr. Plookvongpanit is a certified clinical perfusionist with experience in canine TBW research and canine cerebral resuscitation experiments. Mr. Plookvongpanit is director of clinical perfusion at Riverside Community Hospital and has extensive experience in both research and clinical perfusion. Perfusionist: Shawn Shermer, BS. (Physiology). Ms. Shermer has 6 years' experience as operations manager in the largest contract biomedical research facility in the Western United States. In this capacity, she functioned as perfusionist, surgical assistant, animal care technician, recovery room nurse, and ICU nurse. She has also participated in deep hypothermia/TBW experiments employing dogs, primates, and sheep. Ms. Shermer participated in (and was laboratory manager for the facility during) the testing and development of the Johnson and Johnson hemopump intra-aortic turbine pump. Perfusate Preparation: Larry Wood, BS (Biochemistry). Mr. Wood's duties are perfusate preparation and surgical assistant. Mr. Wood has long experience in drug and parenteral preparation and has participated in most of 21st Century Medicine's canine TBW and Cerebral Resuscitation experiments. Scrub Nurse: Faye Smith, RN. F.S. is a surgical scrub nurse at a large community hospital. She has over 10 years' experience and has served as a consultant in sterile processing and sterile technique. Mrs. Smith has also served as scrub nurse during most of 21st Century Medicine's canine research operations. Circulator: Candy Wood. Candy Wood has been trained as circulator in-house during 21st Century Medicine canine experiments.