RESEARCH AND DEVELOPMENT
Within the Army Medical Service, research and development activities are currently organized into an integrated program under direction of the U.S. Army Medical Research and Development Command. This has resulted in increased efficiency in the management of personnel, funds, and facilities, and has provided research personnel with a sense of cooperative family efforts. The program is conducted almost equally between an ?in-house? and an extramural contract and grant program, with the idea of maintaining an effective professional and scientific capability within the Army Medical Service and, at the same time, taking maximum advantage of available civilian scientific resources.
?The AMEDS Research and Development Program, FY 1962-1966? was published in April 1961. This program is drawn as a concerted effort to provide integrated research, over an extended period, to meet military requirements. The program encompasses the anticipated activities to be conducted in 16 budget line items, and estimates the personnel, funds, and facilities required over the next 5 years to attain the desired objectives. The program was coordinated with the chiefs of other Army technical services as well as with other Federal agencies supporting medical research.
The previously requested research and development budget for fiscal year 1962, of $16,384,000, was augmented by $7 million late in fiscal year 1961, in an effort to concentrate attention upon those research and development items which would best serve the interests of increasing the Army?s capabilities in limited and special warfare operations. The planning for the use of these added moneys necessitated considerable activity on the part of the command and inservice laboratory personnel, in order to insure the most effective utilization of this budgetary increase.
Commensurate with the announced policy of improving the Army?s capabilities for limited-warfare situations, the attention of all investigative agencies has been directed particularly to problems concerned with operations in remote or underdeveloped areas throughout the world. Medical problems associated with geography, new environments, extremes of climate, and new or heretofore unknown diseases received maximum attention. At widely scattered points throughout the world, diseases of military importance are being sought, their causes studied and determined, preventive measures developed, and insofar as possible, effective therapeutic methods accomplished.
To implement these increased activities, a new U.S. Army Medical Research Unit has been established as a U.S. component of the SEATO (Southeast Asia Treaty Organization) Medical Research Laboratory in Bangkok, Thailand. This unit receives technical supervision from WRAIR and has been the recipient of a modest buildup of professional personnel. A continuous research program will be conducted on infectious diseases in that area of the world, including enteric diseases. Investigators from WRAIR have already made several field trips to various countries in Southeast Asia, to Pakistan, and to some of the African nations to study infectious diseases of military importance.
By agreement between The Quartermaster General and The Surgeon General, those aspects of the research program of each technical service dealing with climatic influences will be conducted at the U.S. Army Research Institute of Environmental Medicine. This is a new class II activity, under the jurisdiction of The Surgeon General, and is based at the Quartermaster Research and Engineering Center, in Massachusetts. This arrangement should result in a well-balanced and better coordinated effort.
A discussion of the progress made during the fiscal year within the various applicable areas of medical research and development follows.
Experimental studies have shown there is actually an increased food requirement for men living in extreme heat. Accumulated data indicate that a moderately active soldier, adequately clothed, requires the same number of calories in temperate environments as in arctic environments. In hot climates, the requirement, in contrast to previous concepts, is actually greater than in cold environments. Results of these studies imply a direct contradiction to the long accepted and established standards of the past.
The U.S. Army Medical Research and Development Command, participating with the Southern Regional Laboratories, New Orleans, La., has further purified one of the emulsifiers (TEM (triethylene melamine)) used in the studies on fat emulsions for intravenous use. Results on animals have shown promise, and next year, further studies may be possible with human beings.
A new device called the volumeter, which measures the human body volume, composition, and lung capacity, has been designed and constructed by personnel of the U.S. Army Medical Research and Nutrition Laboratory. Measurements, based on the displacement of water when a man is lowered into a calibrated tank, require less than 5 minutes. The amount of body fat can be assessed with an accuracy
within 1 kilogram. This device was used by an assessment team in a testing program among native military and civilian personnel in Bangkok.
At the U.S. Army Medical Research and Nutrition Laboratory, green algae have been studied as a possible food supplement for human consumption. It is highly nutritive but has a repulsive taste which present efforts aim to correct. Bleaching of the algae under fluorescent light during the latter stages of growth has made some improvement in the direction of achieving a more palatable substance. Other studies have indicated the algae are reasonably palatable when small amounts are mixed with foods. The various studies and tests are being continued, since it is believed that algae may provide an important well-balanced food supplement in concentrated form.
Studies have shown folic acid in tablet form to be much more potent than the folic acid consumed in daily diets. This has been a major factor for consideration by the Food and Drug Administration in curtailing the inclusion of folic acid in multivitamin preparations.
Development of a highly sensitive and accurate chemical method for determination of isoniazid in blood has raised the question of the relationship between results obtained by this procedure and the results obtained by the microbiological procedures usually employed for this determination. Studies have revealed an excellent correlation between the two assay procedures. Findings suggest that the two procedures are measuring the same entities. Consequently, results which formerly required 12 days are now obtainable in 5 days.
Studies of the effects of wind in cold climates indicated that available data must be further developed to show how cold a man will actually get at a given temperature and wind velocity. Investigations to obtain more precise data will be conducted at the U.S. Army Research Institute of Environmental Medicine. The acclimatization of soldiers to extremes of heat and cold is a subject of study currently being conducted in inservice and contractual laboratories. Exposure of subjects in a chamber at 12? C., for 8 hours daily, for 30 days, produced a degree of acclimatization which persisted for at least 11 months.
Penicillinase, the ?enzyme? which destroys penicillin and is produced by staphylococcus, has been isolated in its natural form. The antigenicity of this substance will be studied in an attempt to improve the
treatment of resistant staphylococcal infections. Studies on a new antibiotic material have indicated that a new penicillin compound (staphcillin) has the capability of remaining effective in the presence of organisms resistant to other types of penicillin. To date, no organisms resistant to the new antibiotic have developed.
Recent studies in the healing of tendons suggest that healing does not take place by the growth of the tendon tissue from the severed ends. Rather, the observations suggest that healing results from adhesions which connect the gaps between the severed ends.
Extramural studies demonstrated conclusively that proliferation of spinal cord fibers across a defect can occur, but these fibers have not yet been demonstrated to extend beyond the defect. Successful regeneration of peripheral nerves, to bridge defects measuring as much as 9.0 cm., has been accomplished by using long cable grafts of homologous nerves covered with millepore material.
Contract support has provided for studies on the survival of renal homotransplants. By the use of an initial dose of total body radiation, supplemented intermittently throughout the early postoperative course by the administration of cortisone and smaller doses of radiation, investigators have succeeded in obtaining at least 18 months? survival of a homotransplanted kidney in a nonidentical human twin. This remarkable achievement represents major progress in this important field.
Focused ultrasound waves have been found highly effective in the treatment of painful and recurring neuromas which occur rather frequently in amputation stumps or as the result of other trauma. The nerve fibers responsible for the sensation of pain are destroyed without significant impairment of sensory perception. The use of focused ultrasound in the treatment of experimental traumatic epilepsy has also been highly successful, and studies of this method of treatment of lesions of the brain in human beings are being initiated.
A method for using electricity to produce anesthesia has been developed and has proved to be well tolerated in animals over prolonged periods. This technique has also been used successfully with a few selected patients. The carefully controlled electrical current is applied through electrodes placed on the patient?s temples. Surgery can be initiated a few seconds after the current is turned on, and recovery of consciousness also takes place in a remarkably short period. It has also been found that the undesirable effects of conventional anesthesia are generally avoided. Further studies will be conducted to determine the full range of usefulness of this technique.
Studies have demonstrated that substances closely related to the metabolism of protein and carbohydrates?thiamine, riboflavin, niacin,
and ascorbic acid?are utilized at greatly increased rates in the presence of trauma, including surgical procedures. In the presence of injuries as encountered among battle casualties, the requirements for these substances might well have a high priority, and investigations in this field may lead to substantial advances in the management of the severely injured soldier.
An artificial heart pump, an adaptation of the Davol Pump, to relieve the workload of the heart has been developed. This electronically controlled device allows heart action to return to normal much more rapidly, and the blood supply to the heart itself, as well as to other organs, is greatly improved. The pump has been successfully utilized, and it may prove to be an important aid in the treatment of hemorrhagic shock.
Research studies have been conducted on the use of epsilon aminocaproic acid to treat the hemorrhagic diathesis of shock. This substance competes with other amino substrates for incorporation into the fibrinolysin molecule to form a nonlytic substance. Clinical trials are being conducted to evaluate further the success of this method of treatment.
A dextran with an average molecular weight of 42,000 has been developed in cooperation with the U.S. Department of Agriculture. This molecular weight is about one-half that of the ordinary dextran. If the previous dextrans are associated with impairment of the coagulation mechanism as a result of the larger molecular compound, then it may be that the newer dextran will be effective in overcoming this defect. Other synthetic expanders are being studied.
Studies in the physiologic alterations following thermal burns have demonstrated a tremendous water and caloric loss accompanying the convalescent period in an extensive third-degree burn. This prohibitive caloric loss undoubtedly is the cause of death in many instances. Also, studies have demonstrated that positive nitrogen balance in extensive burns cannot be supported even though as much as 7,000 calories per day are given to the patient. The negativity of the nitrogen balance can be minimized, but not until about the 14th postburn day can the balance be changed to a positive one. Since patients obviously survive in spite of this extensive and prolonged negative nitrogen balance, the question of whether a positive nitrogen balance is necessary must be answered.
The development of a porous plastic laminate for the use in sockets of artificial limb prostheses has resulted in a great improvement in these devices. This laminate allows evaporation of perspiration from the
socket and eliminates infection and maceration which previously resulted from accumulation of perspiration.
A new synthetic artificial vascular prosthesis has been developed. Preliminary results from laboratory and clinical studies indicate that the technique will allow successful replacement of small arterial defects. In the past, injury to arterial vessels has been a major problem resulting in a 25-percent amputation rate.
Studies have been completed on the behavior of wax patterns used in the indirect inlay casting procedure. Results have shown that a more accurate casting can be produced by using a soft wax and small increments of wax additions rather than the present practice of using hard wax and large additions. These results provide a direct and immediate application to the practice of clinical dentistry.
Experiments have been conducted on animals in the field of fluoride metabolism to demonstrate the effect of various concentrations of sodium fluoride on the development of teeth. Three separate groups of animals have been used in this study. Marked changes were noted in the ameloblastic layer, the enamel matrix, the odontoblastic layer, and the dentin matrix of animals maintained on the varied diets used and receiving normal-to-challenge doses of sodium fluoride.
A study of the microbial flora of deep dentinal caries has resulted in the isolation of a new species of micro-organism. Seven additional strains of lactobacilli isolated from deep dentinal caries were classified biochemically according to their carbohydrate fermentations. Six strains were nontrehalose fermenters, anaerobic, and fastidious in their growth requirements, and produced no growth on Rogosa?s medium and fermented relatively few carbohydrates. Several of the strains were identical biochemically to those previously isolated.
The oral mycotic biota has been investigated in an attempt to define the fungal content of the oral cavity and to correlate such data with susceptibility to dental caries, but more particularly with the periodontal disease index.
Studies to determine the factors affecting the setting expansion of dental casting investments have revealed that thick mixes and over?spatulation of gypsum materials, which normally tend to increase expansion, actually cause a reduction in effective lateral expansion. This project will allow good reproducibility of precision dental castings. This, in turn, will result in better military dentistry, in terms of a saving of time, and money, and in reducing the man-hours lost by having to recast improper castings.
Preventive Medicine Research
A new and superior method of prophylaxis against malaria has been developed. This consists of a single pill, combining chloroquine and primaquine, administered orally on a weekly basis. This preparation is much more effective against drug-resistant strains of malaria than that used formerly, and is much simpler to administer, especially when dealing with large numbers of troops flying home from a endemic area. Field tests have demonstrated that this antimalarial regimen is safe, effective, and feasible.
Extensive tests are underway on a vaccine against measles, a disease which has been a military problem in basic training camps and upon mobilization This new vaccine is of the type containing living but attenuated virus, and preliminary tests have shown that it confers an adequate level of immunity and lacks the undesirable side effects of earlier vaccines. A large-scale trial of this vaccine is underway in Africa.
A method has been developed which may enable more rapid production of influenza vaccine. It has been shown that by recombining an inactive, adapted influenza virus (PR8) with an infective, recently isolated Asian influenza virus (A2), a virus is obtained with characteristics that result in increased yields when grown in eggs to produce influenza vaccine. By combining these two types of viruses, genetic reactions result which produce an Asian virus with the growth characteristics of the PR8 virus, while at the same time retaining the capability of immunizing against influenza.
Supportive research studies disclose that at least five or six different viruses are in the dengue complex, and not merely two as was believed a few years ago. Each of these viruses may produce a disease that may vary in its clinical manifestations and hence be difficult to diagnose at times.
Rapid progress continues to be made in the identification and characterization of about 125 different agents believed to belong to the arthropodborne virus group discovered in the past few years. These isolates have been obtained from almost every temperate and tropical area of the world. Many are recognized as causes of explosive epidemics with extremely high morbidity or high case fatality.
A hemorrhagic disease has been experimentally produced in laboratory animals inoculated with virus recovered from a patient with Thai hemorrhagic fever. This was apparently the first such hemorrhagic disease found to be experimentally reproducible in the lower animals. Thai hemorrhagic fever is a syndrome that may be caused by several etiological agents, and it is closely related to the Chikunzunya
virus of Africa, which belongs in Casal?s ?Group A? section of arthropodborne viruses.
Strains of sandfly fever virus have been recovered from both sandflies and patients in Pakistan and Iran. A second team operating in Pakistan succeeded in recovering additional strains of virus and in transporting to the United States sufficient live sandflies to establish colonies of two species, thereby making it possible to undertake sorely needed laboratory studies on the epidemiology and control of this disease.
The germ-free animal technique has proved to be of prime importance in medical research. Special funds were made available during the year for expansion of this program. Using the germ-free animal (one born, raised, and bred under sterile or germ-free conditions) as a laboratory tool, studies will be continued on the pathogenesis of infection, treatment, shock, and immunization. It is planned to extend research on the etiology, epidemiology, and control of epidemic and enzootic infections of laboratory animals.
Ionizing Radiation Research
The Nuclear Energy Division of the U.S. Army Medical Research and Development Command was organized in August 1960 for the purpose of providing guidance and assistance in Army medical research matters pertaining to ionizing radiation, except the preservation of food by irradiation.
Ionizing radiation injury prevention and treatment.?During the past fiscal year, work has continued toward the development of a chemical agent which will be effective in minimizing the undesirable effects of ionizing radiation. The mass effort has been toward the testing of related compounds. Many chemicals have been tested by various chemical and biological systems, such as disulfide exchange, to determine concomitantly their protection and toxic characteristics. Some have merited more sophisticated biological testing. The mercaptomines still appear to be the most promising agents; however, the Bunte analogs also appear to be effective.
The major effort in the area of management of radiation to injury by using biological agents has been directed toward postexposure treatment with certain substances including endotoxins, metabolic precursors, endocrine secretions, tissue extracts, homogenates, blood elements, and transplants, with recent emphasis being toward bone marrow transfusions. One great difficulty encountered so far is species specificity. Investigation will continue in this area of biological counter-measures in consonance with the emergence of new ideas. The use of biological agents such as antibiotics, metabolic precursors, and tissue
extracts used in the treatment of mechanical or thermal trauma combined with ionizing radiation injury is another area of interest and obvious importance.
Experimental work by many investigators has revealed apparent benefits by shielding various portions of the body. Effects observed are those expected with much lower doses. Research is continuing to find that portion of the marrow-producing bone that can be shielded from X-ray and gamma radiation and best serve as a source of bone marrow regeneration or for autologous marrow transplants.
Tissue dosimetry.?Studies are underway to develop a biological determinant which will confidently reflect the total biological injury from ionizing radiation at any given time. The dynamic and complex processes occurring in the biological economy as a result of injury cannot be measured by the physical dosimetry that is available today. Current work with acute exposure to large amounts of gamma irradiation gives some indication that perhaps a biological dosimeter may be found in certain enzyme systems, endocrine systems, formed blood elements, serum proteins, and specific immunochemical responses, separately or in combination.
Total and partial body irradiation.?Studies are being made with total body X-ray or gamma radiation alone or in combination with other stresses, such as mechanical injury, trauma, fractures, burns, and bacterial contamination, at the organ and total organism levels. The relationship of this radiation to the healing of wounds, to anesthesia, and to other therapeutic measures is receiving attention. Studies also indicate that germ-free animals appear more resistant to irradiation than those ?contaminated? or kept under normal laboratory conditions. Limited studies to date show that some effect on the performance capability of certain primates during and after large single doses of radiation is manifested by inability to perform certain tasks for which they have been previously conditioned. When compared to total body irradiations, partial body irradiation, based on limited data to date in animals and in man, either therapeutically or accidentally exposed, shows that the effects are commensurate with those of much lower total body dose levels.
Biological hazards of fallout.?At the present time, there are several whole body counters that are engaged in this particular phase of research, one located at WRAIR and another at the Landstuhl Army
Medical Center in Germany. They have been measuring the levels of radioactivity in man, particularly for strontium 90, cesium 137, and other fission products which have been identified and measured. The
blood of animals exposed to weapon tests has also been studied for
neutron-induced radioactivity (sodium 22). By use of these facilities, one is also able to study the retention of various forms of treatment to relieve the body of its unwanted burdens.
The use of radioisotopes in clinical medicine is being evaluated at WRAIR. These isotopes include the use of radioactive iodine, in the diagnosis of liver disease; cobalt 57 and 58 in the diagnosis of megaloblastic anemias; chromium 51 in blood volume studies; and gold 198 for estimation of liver blood flow.
An analytical system for estimating, with respect to time, the numbers and types of casualties resulting from nuclear explosions has been developed, and this system is being continued with field trials and evaluations.
Neuropsychiatry and Psychophysiology
Measurements have been made of impulse-type noise characteristics, and the sounds produced by a variety of Army weapons have been recorded and analyzed. Tentative guidelines and protective measures against high intensity gunfire noise are being studied. Factual data are being accumulated about sound pressure levels accompanying the firing of new weapon systems, and these data will be related to hearing loss data in the interests of developing damage risk criteria. Studies on the use of the acoustic reflex as a ?built-in? physiological protective device have continued to show promise.
Studies have shown that the pattern of drop in intellectual ability of schizophrenic patients is similar to that of patients with brain injury, but the total amount of deficit is less in the former than in the latter.
Current research studies are confirming the hypothesis that many of the endocrine glands are involved in the overall response of the body to stress. It has been indicated that the basic pattern of endocrine responses to stress might be modified by learning or by repeated experience with stress.
Electrical responses in the brain evoked by auditory and visual stimuli have been found in brain areas far removed from classical afferent pathways. Severing the auditory pathway did not prevent electrical responses from appearing in the auditory cortical area. In some locations, brain activity elicited by light was indistinguishable from that evoked by sound.
Studies on the use of electrical stimulation of the skin as a possible additional mode of communication have continued to show promise.
Increased emphasis has been focused on operations research studies in evaluating the capability of the Army Medical Service to accomplish its mission. The initial study, specifically undertaken for this purpose, was an evaluation of the medical support provided to the field army up to combat command level. A test model was developed, suitable for computer programming, into which can be introduced the factors affecting medical support; that is, the combat situation, weather and terrain, logistic implications, and unit staffing. The result is the status of medical support provided, and by varying one or more of the factors, numerous situations may be evaluated with great rapidity. Such evaluations may be of unlimited value in designing medical units of the future and in assisting commanders to arrive at decisions regarding their operations.
Studies are continuing to extend this capability throughout the field army medical support and will, in the near future, be expanded to consider other problems affecting the mission of the Army Medical Service.
Development of Material
Several prototypes of items developed during this fiscal year are being considered for service test. One is a mechanical resuscitator which operates by a simple on-off switch and is powered by gas from a standard oxygen cylinder or suction and pressure apparatus. Automatic controls adjust to meet the impedance created by the condition of the victim regardless of age, size, or amount of fluid in the lungs. Another item under consideration is a folding bed litter which has a very practical application. Developed to reduce the amount of handling required in the care of sick and wounded, this litter is designed to be compatible with all modes of military transportation, such as motor vehicles, helicopters, and trains. When used as a bed, accessories, such as a tray holder, cup holder, and intravenous support, materially assist the ward personnel in simplifying and reducing their workload.
Continued efforts are being made to develop medical equipment which will be compatible with the concepts of future transportation. The results of initial feasibility studies for air transportable medical treatment and medical support facilities are very promising. Work on the conversion of armored personnel carriers to ambulances is progressing, and an expansible-type command post vehicle will soon be made available to the Army Medical Service to develop a conversion unit which will enable the vehicle to be used as a mobile aid station.
Long-range development plans in effect are complementary to the newly established requirements, created by unconventional warfare. By endeavoring to reduce weight and cubature, a portable autoclave, one light enough to be hand carried, is considered feasible and soon will be developed for service testing by Special Forces units. Efforts are also directed to packaging intravenous solutions in a dry state in suitable plastic containers so that water prepared at the site can be used when the occasion arises. Plans are in effect to test prototypes of plastic bags containing dextran which appear to prevent loss of vapor and which will not be damaged by exposure to extreme temperatures while in storage or in use. These plans also include prototypes of water purification units which presumably will provide intravenous pure water after two processings. The current model is 4 cubic feet.
The continued effort to screen the development program by means of inprocess review by the Army Medical Service Technical Committee has proved to be the best method to direct an effective program. Material requirements and development tasks are carefully evaluated from all aspects by the Office of The Surgeon General. Changes or modifications necessary to meet new concepts of warfare are efficiently integrated into the program.