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Chapter 8

A Decade of Progress - Contents

Army Medical Research and Development

Nothing has such power to broaden the mind as the ability to investigate systematically and truly all that comes under thy observation in life.-MARCUS AURELIUS.

OBJECTIVES

The broad-range research and development program of the Army Medical Department covered the spectrum of medical scientific experimentation. The goal was to develop the best means to protect the health of Army troops, from the swamps and jungles of Southeast Asia to the muskeg and tundra of the North.

The primary objectives of the program remained constant throughout the 1960's. One was to provide improved solutions for longstanding medical problems. Infectious diseases remained the scourge of armies, both in garrison and in the field. Trauma and shock continued to take their toll in the operating room and on the battlefield. Environmental stress reduced the fighting effectiveness of the combat soldier as it had in the past. The reason for men's actions and the means to influence their behavior under the stress of military operations were still little understood. A second was to find answers to urgent new needs caused by the rapid change in weapons, equipment, and tactics. Advocating a bold approach to military medical research, General Heaton urged the Army Medical Department as early as 1959 to undertake "active research aimed at


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discovering measures which will increase man's resistance to radiation and protect him against the incapacitating and lethal effects of toxic chemicals." Since that date, projects for medical defense against biological and chemical agents, the biological effects of lasers, and others to provide prophylaxis and treatment of ionizing radiation injury have been included in the Army medical research and development program. A third was to study the etiology of little known and poorly understood diseases in remote areas to support the Army's global mission and to promote higher levels of medical care in the underdeveloped nations of the world. Another was to develop more effective, lightweight, and transportable field medical equipment.

The main thrust of military medical research was toward the resolution of problems that will improve the performance of the soldier in the field by reducing losses from wounds, infectious diseases, and environmental stress. But certain basic research to contribute new knowledge and advancement in the field of medical science was also included in the program. Representative studies included metabolic patterns of pathogenic bacteria, pathophysiologic activities of microbial agents, role of endotoxins in shock, genetic mechanisms of enteric bacteria, etiology of viral hepatitis, biochemistry of wound healing, organic repair and replacement, immunohematology, and anaphylaxis and purification of antigens and antibodies.

Management of the Program

Within the Army Medical Department, research in progress was under the direction of the U.S. Army Medical Research and Development Command, which was established in 1958. Stimulated by the demands of the time, the budget for military medical research grew more than fivefold, from the sum of $12 million in 1958 to more than $53 million in 1968. As the volume and scope of medical research activities increased,


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the size and responsibilities of the U.S. Army Medical Research and Development Command grew correspondingly in the decade since it was activated.

During 1968, the U.S. Army Medical Research and Development Command provided management, personnel, and research facilities for 31 multiarea projects at a cost of $53 million. These efforts were about equally divided between intramural and extramural programs.

Intramural research was conducted in 14 research institutes, 15 military hospitals, and the Armed Forces Institute of Pathology. The largest of the research institutes under the U.S. Army Medical Research and Development Command was the Walter Reed Army Institute of Research, where nearly half of the Command's intramural research effort was conducted. The professional staff at the Walter Reed Army Institute of Research, composed of more than 300 doctoral-level scientists, was engaged in a wide range of activities, embracing basic and applied research in all aspects of military medicine, especially infectious diseases. The Walter Reed Army Institute of Research also served as an educational and advisory center. Additionally, the Walter Reed Army Institute of Research supported large field teams at the SEATO Medical Research Laboratory, Bangkok, Thailand, and in Saigon, South Vietnam, these teams conducted extensive research in tropical medicine.

Specialized research programs were also conducted at the following institutes and laboratories of the U.S. Army Medical Research and Development Command:

Institute or laboratory

Program

U.S. Army Medical Research Institute of Infectious Diseases, Frederick, Md.

Exotic infectious diseases.

U.S. Army Medical Research Laboratory, Fort Knox, Ky.

Blood transfusion, biophysics, psychophysiology.

U.S. Army Medical Research and Nutrition Laboratory, Denver, Colo.

Metabolism and nutrition.

 


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U.S. Army Research Institute of Environmental Medicine, Natick, Mass.

Physiology of heat, cold, and high elevation.

U. S. Army Institute of Surgical Research, Fort Sam Houston, Tex.

Burns, trauma.

Letterman Army Institute of Research, San Francisco, Calif.

Skin disease, general medicine.

U.S. Army Institute of Dental Research, Washington, DC.

Oral diseases.

U.S. Army Medical Equipment Research and Development Laboratory, Fort Totten, N.Y.

Field medical equipment.

U.S. Army Aeromedical Research Laboratory, Fort Rucker, Ala.

Helicopter medicine.

U.S. Army Medical Biomechanical Research Laboratory, Washington, D.C.

Prosthetics.

U.S. Army Medical Research Unit, Panama

Tropical medicine.

U.S. Army Medical Research Unit, Malaysia

Tropical medicine.

 

The extramural program of the U.S. Army Medical Research and Development Command consisted of contracts and grants with universities and other research institutions, as well as fund transfers to other Government research institutes. More than 1,000 contracts, grants, and fund transfers were awarded during 1968.

Highlights of Progress

Malaria program.-A major focus of Army medical research and the largest single program of medical research in the history of the Army has been in malaria. Malaria research efforts for fiscal year 1968 alone included more than 200 contracts and grants with universities, research institutes, and private concerns, as well as studies at Army installations, and totaled more than $10 million.

Most of this effort was directed toward developing new chemoprophylactic drugs for the control of chloro-


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quine resistant falciparum malaria. More than 130,000 chemicals were screened in a 4-year period. Additional aspects of the program focused on the more basic problems of biological and immunological characteristics of the parasite, host-parasite relationships, and vector control.

The use of prophylactic diaminodiphenylsulfone in South Vietnam was a result of this program. This interim solution of the problem, however, required daily administration of the drug. A new diformyl preparation of diaminodiphenylsulfone, which required administration only once a week, was sent to South Vietnam for field trials in late 1968.

New advances in malaria chemotherapy came from studies conducted at the Walter Reed Army Institute of Research and in South Vietnam which showed that single doses of a combination of the long-acting sulfonamides, sulphormethoxine and pyrimethamine, were successful in the treatment of falciparum malaria when given alone or with quinine.

Another study showed that these drugs when used with quinine reduced relapse rates to 2 percent, whereas it had been as high as 41 percent on chloroquine therapy alone. Other investigators, working under contract with the U.S. Army Medical Research and Development Command, have shown that a single dose of a new drug combination, trimethoprim and Kelfizina, rapidly eradicated both chloroquine sensitive and resistant falciparum malaria strains obtained from Africa and Southeast Asia.

Scientists at the Walter Reed Army Institute of Research also developed a battery of in vitro techniques for screening antimalarial drug activity. A most promising version was based upon inhibition of C14-methionine uptake by parasitized red blood cells; other automated in vitro tests were also under investigation. These should provide rapid and effective screening methods for new antimalarial compounds, allowing investigators to bypass present costly in vivo screening tests.


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Further developments in malaria research involved immunofluorescent assays for serological detection of malarial antibodies, utilizing a soluble antigen obtained from Plasmodium falciparum grown in chimpanzees. The successful transmission of human malaria to monkeys gave promise of large volume effectiveness testing of drugs before the necessary final tests in man.

Other infectious diseases.-The program of research in military medical problems in South Vietnam included, in addition to malaria, studies of the prevention and treatment of many infectious diseases; for example, plague, dengue, cholera, hepatitis, melioidosis, scrub typhus, leptospirosis, and the diarrheas.

Marking the culmination of sustained research efforts, other notable accomplishments were made in 1968 in this area of military medicine. The Walter Reed Army Institute of Research developed a meningococcal vaccine, consisting of purified polysaccharides of Neisseria meningitidis. This substance has been prepared from both types A and C.

Studies at Fort Dix, N.J., with type C polysaccharide showed that vaccinated groups had a markedly lower meningococcus carrier rate when compared with controls. Also studied was coagulation defects in meningococcal septicemia. The therapeutic efficacy of heparin and clotting factor replacements was under investigation.

Hepatitis researchers have developed the first satisfactory animal model to study this disease. Recent studies have shown that the marmoset develops typical histological and biochemical evidence of hepatitis when given infected human serum.

Another landmark was the first fully documented study in which infected pooled plasma was orally administered to 10 volunteers, three of whom developed clinical infectious hepatitis 28 to 30 days later. Diagnostic confirmation was by biopsy and serial enzyme studies. These plasma pools were distributed to other


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investigators who will attempt to isolate the etiological agent.

It was anticipated that long-term hepatitis studies will be significantly aided by collaboration between the Walter Reed Army Institute of Research and the Armed Forces Institute of Pathology in the establishment of a central laboratory where reference sera, candidate viruses, and tissue culture stocks will be maintained and distributed.

Large-scale field trials of orally administered vaccine of adenovirus type 4 demonstrated its ability to terminate, abruptly, an epidemic of type 4 acute respiratory disease. Cross-immunity against other types was under study, as well as the use of vaccines of other adenovirus types.

Parasitic infections.-The U.S. Army Medical Research and Development Command unit in Panama devised more accurate laboratory methods for the serological identification and tissue culture of Leishmania organisms. Additionally, this laboratory proved Camolar, originally an antimalarial, to be effective against cutaneous and mucocutaneous leishmaniasis, a significant therapeutic advance over the previously available toxic pentavalent antimony compounds.

Burn research.-The U.S. Army Institute of Surgical Research, Brooke Army Medical Center, Fort Sam Houston, Tex., developed a new topical antibacterial preparation, Sulfamylon, which resulted in a 50-percent reduction of burn mortalities due to infection.

Combat surgery.-The U.S. Army Medical Research Team, South Vietnam, included a surgical team which developed improved techniques for the treatment of trauma and shock. The management of shock was also assisted by the introduction of cardiodensitometers, blood gas analyzers, and flame photometers into field hospitals. The pulmonary effects of nonthoracic trauma were highlighted by the work of this team, and new studies were in progress at the Walter Reed Army Institute of Research and by university contractors.


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The control of hemorrhage with new chemical polymers-a butyl cyanoacrylate spray-was found to be remarkably successful. Tissue adhesives and new techniques of repairing internal organs without sutures were other promising developments.

Blood preservation.-The logistics of furnishing fresh whole blood to combat medical facilities is limited by its 21-day shelf life. Studies at the U.S. Army Medical Research Laboratory, Fort Knox, Ky., demonstrated a twofold prolongation of shelf life by the addition of adenine to the preservative.

Dental research.-Stimulated by the need to reduce time-consuming dental emergencies occurring in troops in South Vietnam, clinical testing of a new dental restorative material that could be inserted quickly in individual teeth, was easily manipulated, and set in 2 minutes was initiated in 1968.

New methods for the fixation of mandibular fractures were placed under study. Furthermore, the investigation of a new technique for managing avulsive wounds of the oral region which utilized a silicone plastic that cures at room temperature was started. After debridement, this material was placed directly into the defect to restore oral integrity until the time of reconstructive surgery.

Medical material.-The Army Medical Department took great pride in its development of a totally new concept in combat hospital design-the MUST (Medical Unit, Self-contained, Transportable) hospital (fig. 11). This concept combined quick assembly and easy transport capability with self-contained power, utility, and air conditioning features in a new shelter design.

The first MUST hospital was deployed to South Vietnam in 1966 with the 45th Surgical Hospital for testing in a combat situation. Its first commanding officer, Major Gary P. Wratten, MC, was killed in action when the hospital was attacked. Six other MUST hospitals were later deployed to South Vietnam, four supporting the Army and two supporting the Marines. The MUST


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FIGURE 11.-A 60-bed surgical hospital displayed the use of MUST (Medical Unit, Self-contained, Transportable) equipment in a demonstration at Camp Bullis, Tex., in September 1968. (Army Medical Pictorial Service photograph by William W. Warrell.)

hospital has come under mortar and small arms attack and has withstood both extremely well.

Although the basic elements of the MUST hospital were in use in South Vietnam, ancillary parts, chiefly the food service, were still under test in the United States. In addition, a completely new water and waste management system was under development, with prototypes due for delivery in early 1969. This system included toilets, showers and lavatories, water treatment and purification units, and a large incinerator.

In addition to the MUST hospital, the U.S. Army Medical Research and Development Command was actively engaged in the development of new medical materiel for use in the field. Development has been completed on a new lightweight field hospital bed offering more stability and flexibility, a lightweight and portable X-ray apparatus with an accompanying film processing


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unit, a field resuscitator, a surgical operating light, a scrub sink, a hypodermic jet injection gun (fig. 12), and a helicopter-mounted insecticide sprayer.

FIGURE 12.-Hypodermic jet injection gun, developed by the U.S. Army Medical Research and Development Command, being used to administer an inoculation. This device provides a fast, safe method for giving mass inoculations to troops.

A new field medical laboratory system was developed which was fully mobile and built on a modular concept. It was capable of providing up-to-date and sophisticated laboratory support on an area basis for a large field army located anywhere in the world. Individual items of equipment for the laboratory were tested and modularized.

Other equipment development soon to be completed for use in the field included an improved surgical operating table and a lightweight distiller to produce sterile water in conjunction with prepackaged bags of electrolytes.


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Environmental medicine.-Commensurate with the policy of improving the Army's capabilities for limited-warfare situations, the attention of all investigative agencies was directed particularly to problems concerned with operations in remote or underdeveloped areas throughout the world. Medical problems associated with geography, new environments, and extremes of climate received particular attention. The effects of hot and cold climates and high terrestrial altitude on the soldier's performance, for example, had been under investigation by scientists of the U.S. Army Medical Research and Development Command for several years.

Spearheading the U.S. Army Medical Research and Development Command effort in this area was the U.S. Army Research Institute of Environmental Medicine, located at Natick, Mass. A new laboratory for the U.S. Army Research Institute of Environmental Medicine was dedicated in October 1968. This modern building, with its research facilities in environmental and altitude chambers, provided the finest single laboratory in the country for the study of environmental medicine. A subordinate unit of the U.S. Army Research Institute of Environmental Medicine was stationed at Fort Wainwright, Alaska, to perform clinical research on cold injury.

Pikes Peak was the site of studies of the performance of infantrymen at high altitude-14,000 feet. These studies showed a significant decrement in gross motor performance during the first 5 days, but revealed that fine motor performance and some aspects of cognitive behavior were relatively unaffected at that altitude.

The question of the influence of heat rash on heat exhaustion was investigated in a collaborative study between the U.S. Army Research Institute of Environmental Medicine and the Letterman Army Institute of Research, Presidio of San Francisco. These studies demonstrated that heat rash can predispose to heat exhaustion and that this predisposition can persist for as long as 3 weeks after the skin appears to be clinically


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healed. The effect has been shown to be due to the slower recovery of sweat glands following heat rash, with a subsequent decrease in sweat production and evaporative cooling.

Skin diseases.-Skin diseases constitute a leading cause of morbidity in any tropical military campaign. Unfortunately, this fact is as true today in South Vietnam as it was during the North African and South Pacific campaigns of World War II.

The tactical situation, particularly in the Mekong Delta region, may require continuous and prolonged exposure to a wet environment, predisposing the infantryman to bacterial and fungal invasions of the skin.

A field team from the U.S. Army Medical Research and Development Command research unit located at the Presidio of San Francisco has been working in the delta region of South Vietnam. Its research seeks to identify the causative agents of skin disease there and to evaluate therapeutic and prophylactic measures. Preliminary studies have shown that daily administration of griseofulvin is an effective prophylactic against fungus diseases of the skin, and that its use has reduced incapacitating dermatophytosis in certain special military units from 36 percent to 6 percent.

GOALS IN SIGHT

As a result of the broad-based military medical program conducted under the aegis of the U.S. Army Medical Research and Development Command in the decade from 1959 to 1969, the solution of several major military medical problems was in sight. Progress in the malaria program was outstanding, and it was anticipated that much more effective control should be achieved within the next few years. Needed was a family of agents effective against all forms and stages of this parasite and better methods of vector control. It must be anticipated that new drug-resistant forms of this and other infectious diseases will continue to emerge. Thus, a pro-


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gram of research will always be needed despite the considerable progress to date.

Enteric diseases, especially diarrhea, required continual study. Major needs were agent identification, development of suitable prophylactic drugs, and immunization programs.

Although great strides were made in the control of epidemic respiratory diseases, the eradication of one agent, type 4 adenovirus, did not solve the problem, as it permitted another agent, type 7 adenovirus, to appear in epidemic proportions. This emphasized the continuing need for studies in the epidemiology of this group of diseases. The influence of newer respiratory disease agents such as mycoplasmas, rhinoviruses, and ECHO viruses required further study as did the possibility of chemoprophylaxis and treatment.

The resolution of medical problems resulting from new or heretofore unknown diseases at widely scattered points throughout the world demanded maximum attention. Such diseases as schistosomiasis, African sleeping disease, and viral encephalitis constituted a few of the major risks American troops might contract should they be deployed to parts of the earth where these diseases occur.

Widespread antibiotic usage had created new problems in military medicine. The availability of antibiotics for the treatment of plague in South Vietnam, for example, had resulted in resistant organisms and had complicated the epidemiological picture. This pattern could be expected in other areas of the world, adding another dimension to the problem of disease prevention and treatment.

Great strides were made in combat surgery, but the Army surgical research effort must continue to be directed toward enhancing the survival of the severely wounded. Helicopter evacuation from the battlefield to the hospital had resulted in the arrival of patients in profound shock who would not have survived the slower chain of evacuation in the days before helicopter


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ambulances. Shock, now better understood as a disorder of microcirculation, must be investigated by methods directed toward the solution of facets of the larger problem.

It is a corollary of science that the solution of a problem brings forth several more that beg for study. This is nowhere more evident than in the research program of the U.S. Army Medical Research and Development Command. Future efforts in the program of the Command will continue to emphasize the prevention of manpower losses due to infectious diseases, extremes of climate, and the more effective treatment of wounds.