A Decade of Progress - Contents
Army Medical Research and Development
Nothing has such power to broaden the mind asthe ability to investigate systematically and truly all that comes under thyobservation in life.-MARCUS AURELIUS.
OBJECTIVES
The broad-range research and development programof the Army Medical Department covered the spectrum of medical scientificexperimentation. The goal was to develop the best means to protect the health ofArmy troops, from the swamps and jungles of Southeast Asia to the muskeg andtundra of the North.
The primary objectives of the program remained constantthroughout the 1960's. One was to provide improved solutions for longstandingmedical problems. Infectious diseases remained the scourge of armies, both ingarrison and in the field. Trauma and shock continued to take their toll in theoperating room and on the battlefield. Environmental stress reduced the fightingeffectiveness of the combat soldier as it had in the past. The reason for men'sactions and the means to influence their behavior under the stress of militaryoperations were still little understood. A second was to find answers to urgentnew needs caused by the rapid change in weapons, equipment, and tactics.Advocating a bold approach to military medical research, General Heaton urgedthe Army Medical Department as early as 1959 to undertake "active researchaimed at
172
discovering measures which willincrease man's resistance to radiation and protect him against theincapacitating and lethal effects of toxic chemicals." Since that date,projects for medical defense against biological and chemical agents, thebiological effects of lasers, and others to provide prophylaxis and treatment ofionizing radiation injury have been included in the Army medical research anddevelopment program. A third was to study the etiology of little known andpoorly understood diseases in remote areas to support the Army's globalmission and to promote higher levels of medical care in the underdevelopednations of the world. Another was to develop more effective, lightweight, andtransportable field medical equipment.
The main thrust of military medical research was toward theresolution of problems that will improve the performance of the soldier in thefield by reducing losses from wounds, infectious diseases, and environmentalstress. But certain basic research to contribute new knowledge and advancementin the field of medical science was also included in the program. Representativestudies included metabolic patterns of pathogenic bacteria, pathophysiologicactivities of microbial agents, role of endotoxins in shock, genetic mechanismsof enteric bacteria, etiology of viral hepatitis, biochemistry of wound healing,organic repair and replacement, immunohematology, and anaphylaxis andpurification of antigens and antibodies.
Management of the Program
Within the Army Medical Department, research inprogress was under the direction of the U.S. Army Medical Research andDevelopment Command, which was established in 1958. Stimulated by the demands ofthe time, the budget for military medical research grew more than fivefold, fromthe sum of $12 million in 1958 to more than $53 million in 1968. As the volumeand scope of medical research activities increased,
173
the size and responsibilities of the U.S. Army MedicalResearch and Development Command grew correspondingly in the decade since it wasactivated.
During 1968, the U.S. Army Medical Research and DevelopmentCommand provided management, personnel, and research facilities for 31 multiareaprojects at a cost of $53 million. These efforts were about equally dividedbetween intramural and extramural programs.
Intramural research was conducted in 14 research institutes,15 military hospitals, and the Armed Forces Institute of Pathology. The largestof the research institutes under the U.S. Army Medical Research and DevelopmentCommand was the Walter Reed Army Institute of Research, where nearly half of theCommand's intramural research effort was conducted. The professional staff atthe Walter Reed Army Institute of Research, composed of more than 300doctoral-level scientists, was engaged in a wide range of activities, embracingbasic and applied research in all aspects of military medicine, especiallyinfectious diseases. The Walter Reed Army Institute of Research also served asan educational and advisory center. Additionally, the Walter Reed Army Instituteof Research supported large field teams at the SEATO Medical ResearchLaboratory, Bangkok, Thailand, and in Saigon, South Vietnam, these teamsconducted extensive research in tropical medicine.
Specialized research programs were also conducted at thefollowing institutes and laboratories of the U.S. Army Medical Research andDevelopment 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. |
174
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 medicalresearch and the largest single program of medical research in the history ofthe Army has been in malaria. Malaria research efforts for fiscal year 1968alone included more than 200 contracts and grants with universities, researchinstitutes, and private concerns, as well as studies at Army installations, andtotaled more than $10 million.
Most of this effort was directed toward developing new chemoprophylacticdrugs for the control of chloro-
175
quine resistant falciparum malaria. More than 130,000chemicals were screened in a 4-year period. Additional aspects of the programfocused on the more basic problems of biological and immunologicalcharacteristics of the parasite, host-parasite relationships, and vectorcontrol.
The use of prophylactic diaminodiphenylsulfone in SouthVietnam was a result of this program. This interim solution of the problem,however, required daily administration of the drug. A new diformyl preparationof diaminodiphenylsulfone, which required administration only once a week, wassent to South Vietnam for field trials in late 1968.
New advances in malaria chemotherapy came from studiesconducted at the Walter Reed Army Institute of Research and in South Vietnamwhich showed that single doses of a combination of the long-acting sulfonamides,sulphormethoxine and pyrimethamine, were successful in the treatment offalciparum malaria when given alone or with quinine.
Another study showed that these drugs when used with quininereduced relapse rates to 2 percent, whereas it had been as high as 41 percent onchloroquine therapy alone. Other investigators, working under contract with theU.S. Army Medical Research and Development Command, have shown that a singledose of a new drug combination, trimethoprim and Kelfizina, rapidly eradicatedboth chloroquine sensitive and resistant falciparum malaria strains obtainedfrom Africa and Southeast Asia.
Scientists at the Walter Reed Army Institute of Research alsodeveloped a battery of in vitro techniques for screening antimalarial drugactivity. A most promising version was based upon inhibition of C14-methionineuptake by parasitized red blood cells; other automated in vitro tests were alsounder investigation. These should provide rapid and effective screening methodsfor new antimalarial compounds, allowing investigators to bypass present costlyin vivo screening tests.
176
Further developments in malaria researchinvolved immunofluorescent assays for serological detection of malarialantibodies, utilizing a soluble antigen obtained from Plasmodiumfalciparum grown in chimpanzees. The successfultransmission of human malaria to monkeys gave promise of large volumeeffectiveness testing of drugs before the necessary final tests in man.
Other infectious diseases.-The program of researchin military medical problems in South Vietnam included, in addition to malaria,studies of the prevention and treatment of many infectious diseases; forexample, plague, dengue, cholera, hepatitis, melioidosis, scrub typhus,leptospirosis, and the diarrheas.
Marking the culmination of sustained research efforts, othernotable accomplishments were made in 1968 in this area of military medicine. TheWalter Reed Army Institute of Research developed a meningococcal vaccine,consisting of purified polysaccharides of Neisseriameningitidis. This substance hasbeen prepared from both types A and C.
Studies at Fort Dix, N.J., with type C polysaccharide showedthat vaccinated groups had a markedly lower meningococcus carrier rate whencompared with controls. Also studied was coagulation defects in meningococcalsepticemia. The therapeutic efficacy of heparin and clotting factor replacementswas under investigation.
Hepatitis researchers have developed the first satisfactoryanimal model to study this disease. Recent studies have shown that the marmosetdevelops typical histological and biochemical evidence of hepatitis when giveninfected human serum.
Another landmark was the first fully documented study inwhich infected pooled plasma was orally administered to 10 volunteers, three ofwhom developed clinical infectious hepatitis 28 to 30 days later. Diagnosticconfirmation was by biopsy and serial enzyme studies. These plasma pools weredistributed to other
177
investigators who will attempt to isolate the etiologicalagent.
It was anticipated that long-term hepatitisstudies will be significantly aided by collaboration between the Walter ReedArmy Institute of Research and the Armed Forces Institute of Pathology in theestablishment of a central laboratory where reference sera, candidate viruses,and tissue culture stocks will be maintained and distributed.
Large-scale field trials of orallyadministered vaccine of adenovirus type 4 demonstrated its ability to terminate,abruptly, an epidemic of type 4 acute respiratory disease. Cross-immunityagainst other types was under study, as well as the use of vaccines of otheradenovirus types.
Parasitic infections.-The U.S. ArmyMedical Research and Development Command unit in Panama devised more accuratelaboratory methods for the serological identification and tissue culture of Leishmaniaorganisms. Additionally, this laboratory proved Camolar, originally anantimalarial, to be effective against cutaneous and mucocutaneous leishmaniasis,a significant therapeutic advance over the previously available toxicpentavalent antimony compounds.
Burn research.-The U.S. ArmyInstitute of Surgical Research, Brooke Army Medical Center, Fort Sam Houston,Tex., developed a new topical antibacterial preparation, Sulfamylon, whichresulted in a 50-percent reduction of burn mortalities due to infection.
Combat surgery.-The U.S. Army MedicalResearch Team, South Vietnam, included a surgical team which developed improvedtechniques for the treatment of trauma and shock. The management of shock wasalso assisted by the introduction of cardiodensitometers, blood gas analyzers,and flame photometers into field hospitals. The pulmonary effects of nonthoracictrauma were highlighted by the work of this team, and new studies were inprogress at the Walter Reed Army Institute of Research and by universitycontractors.
178
The control of hemorrhage with new chemicalpolymers-a butyl cyanoacrylate spray-was found to be remarkably successful.Tissue adhesives and new techniques of repairing internal organs without sutureswere other promising developments.
Blood preservation.-The logistics of furnishingfresh whole blood to combat medical facilities is limited by its 21-day shelflife. Studies at the U.S. Army Medical Research Laboratory, Fort Knox, Ky.,demonstrated a twofold prolongation of shelf life by the addition of adenine tothe preservative.
Dental research.-Stimulated by the need to reducetime-consuming dental emergencies occurring in troops in South Vietnam, clinicaltesting of a new dental restorative material that could be inserted quickly inindividual teeth, was easily manipulated, and set in 2 minutes was initiated in1968.
New methods for the fixation of mandibular fractures wereplaced under study. Furthermore, the investigation of a new technique formanaging avulsive wounds of the oral region which utilized a silicone plasticthat cures at room temperature was started. After debridement, this material wasplaced directly into the defect to restore oral integrity until the time ofreconstructive surgery.
Medical material.-The Army Medical Department tookgreat pride in its development of a totally new concept in combat hospitaldesign-the MUST (Medical Unit, Self-contained, Transportable) hospital (fig.11). This concept combined quick assembly and easy transport capability withself-contained power, utility, and air conditioning features in a new shelterdesign.
The first MUST hospital was deployed to South Vietnam in 1966with the 45th Surgical Hospital for testing in a combat situation. Its firstcommanding officer, Major Gary P. Wratten, MC, was killed in action when thehospital was attacked. Six other MUST hospitals were later deployed to SouthVietnam, four supporting the Army and two supporting the Marines. The MUST
179
FIGURE11.-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 WilliamW. Warrell.)
hospital has come under mortar and small armsattack and has withstood both extremely well.
Although the basic elements of the MUST hospital were in usein South Vietnam, ancillary parts, chiefly the food service, were still undertest in the United States. In addition, a completely new water and wastemanagement system was under development, with prototypes due for delivery inearly 1969. This system included toilets, showers and lavatories, watertreatment and purification units, and a large incinerator.
In addition to the MUST hospital, the U.S. Army MedicalResearch and Development Command was actively engaged in the development of newmedical materiel for use in the field. Development has been completed on a newlightweight field hospital bed offering more stability and flexibility, alightweight and portable X-ray apparatus with an accompanying film processing
180
unit, a field resuscitator, a surgical operating light, a scrub sink, ahypodermic jet injection gun (fig. 12), and a helicopter-mounted insecticidesprayer.
FIGURE12.-Hypodermic jet injection gun, developed by the U.S. Army Medical Researchand Development Command, being used to administer an inoculation. This deviceprovides a fast, safe method for giving mass inoculations to troops.
A new field medical laboratory system was developed which wasfully mobile and built on a modular concept. It was capable of providingup-to-date and sophisticated laboratory support on an area basis for a largefield army located anywhere in the world. Individual items of equipment for thelaboratory were tested and modularized.
Other equipment development soon to be completed for use inthe field included an improved surgical operating table and a lightweightdistiller to produce sterile water in conjunction with prepackaged bags ofelectrolytes.
181
Environmental medicine.-Commensurate with thepolicy of improving the Army's capabilities for limited-warfaresituations, the attention of all investigative agencies was directedparticularly to problems concerned with operations in remote or underdevelopedareas throughout the world. Medical problems associated with geography, newenvironments, and extremes of climate received particular attention. The effectsof hot and cold climates and high terrestrial altitude on the soldier'sperformance, 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 Researchand Development Command effort in this area was the U.S. Army Research Instituteof Environmental Medicine, located at Natick, Mass. A new laboratory for theU.S. Army Research Institute of Environmental Medicine was dedicated in October1968. This modern building, with its research facilities in environmental andaltitude chambers, provided the finest single laboratory in the country for thestudy of environmental medicine. A subordinate unit of the U.S. Army ResearchInstitute of Environmental Medicine was stationed at Fort Wainwright, Alaska, toperform clinical research on cold injury.
Pikes Peak was the site of studies of theperformance of infantrymen at high altitude-14,000 feet. These studies showeda significant decrement in gross motor performance during the first 5 days, butrevealed that fine motor performance and some aspects of cognitive behavior wererelatively unaffected at that altitude.
The question of the influence of heat rash onheat exhaustion was investigated in a collaborative study between the U.S. ArmyResearch Institute of Environmental Medicine and the Letterman Army Institute ofResearch, Presidio of San Francisco. These studies demonstrated that heat rashcan predispose to heat exhaustion and that this predisposition can persist foras long as 3 weeks after the skin appears to be clinically
182
healed. The effect has been shown to be due tothe slower recovery of sweat glands following heat rash, with a subsequentdecrease in sweat production and evaporative cooling.
Skin diseases.-Skin diseases constitute a leadingcause of morbidity in any tropical military campaign. Unfortunately, this factis as true today in South Vietnam as it was during the North African and SouthPacific campaigns of World War II.
The tactical situation, particularly in the Mekong Deltaregion, 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 andDevelopment Command research unit located at the Presidio of San Francisco hasbeen working in the delta region of South Vietnam. Its research seeks toidentify the causative agents of skin disease there and to evaluate therapeuticand prophylactic measures. Preliminary studies have shown that dailyadministration of griseofulvin is an effective prophylactic against fungusdiseases of the skin, and that its use has reduced incapacitatingdermatophytosis in certain special military units from 36 percent to 6 percent.
GOALS IN SIGHT
As a result of the broad-based military medical programconducted under the aegis of the U.S. Army Medical Research and DevelopmentCommand in the decade from 1959 to 1969, the solution of several major militarymedical problems was in sight. Progress in the malaria program was outstanding,and it was anticipated that much more effective control should be achievedwithin the next few years. Needed was a family of agents effective against allforms and stages of this parasite and better methods of vector control. It mustbe anticipated that new drug-resistant forms of this and other infectiousdiseases will continue to emerge. Thus, a pro-
183
gram of research will always be needed despite theconsiderable progress to date.
Enteric diseases, especially diarrhea, required continualstudy. Major needs were agent identification, development of suitableprophylactic drugs, and immunization programs.
Although great strides were made in the control of epidemicrespiratory diseases, the eradication of one agent, type 4 adenovirus, did notsolve the problem, as it permitted another agent, type 7 adenovirus, to appearin epidemic proportions. This emphasized the continuing need for studies in theepidemiology of this group of diseases. The influence of newer respiratorydisease agents such as mycoplasmas, rhinoviruses, and ECHO viruses requiredfurther study as did the possibility of chemoprophylaxis and treatment.
The resolution of medical problems resulting from new orheretofore unknown diseases at widely scattered points throughout the worlddemanded maximum attention. Such diseases as schistosomiasis, African sleepingdisease, and viral encephalitis constituted a few of the major risks Americantroops might contract should they be deployed to parts of the earth where thesediseases occur.
Widespread antibiotic usage had created new problems inmilitary medicine. The availability of antibiotics for the treatment of plaguein South Vietnam, for example, had resulted in resistant organisms and hadcomplicated the epidemiological picture. This pattern could be expected in otherareas of the world, adding another dimension to the problem of diseaseprevention and treatment.
Great strides were made in combat surgery, but the Armysurgical research effort must continue to be directed toward enhancing thesurvival of the severely wounded. Helicopter evacuation from the battlefield tothe hospital had resulted in the arrival of patients in profound shock who wouldnot have survived the slower chain of evacuation in the days before helicopter
184
ambulances. Shock, now better understood as a disorder ofmicrocirculation, must be investigated by methods directed toward the solutionof facets of the larger problem.
It is a corollary of science that the solution of a problembrings forth several more that beg for study. This is nowhere more evident thanin the research program of the U.S. Army Medical Research and DevelopmentCommand. Future efforts in the program of the Command will continue to emphasizethe prevention of manpower losses due to infectious diseases, extremes ofclimate, and the more effective treatment of wounds.
