In the courtyard of the Taipei headquarters of a U.S. Navy organization, medical workers bow their heads in silent prayer once a year while Buddhist monks chant the Sutra. The commander, a uniformed Navy Captain, presents offerings of fruit and flowers.
This strange service is held at the U.S. Naval Medical Research Unit No. 2 in Taipei in deference to Buddhist canons that forbid the taking of any life, even the most insignificant. Doctors and research technicians of NAMRU-2 make use of thousands of animals and insects in their attack on the diseases of man. The ceremony comforts the 'souls of the sacrificed and assures them that they gave their lives in a worthy cause.
The worthiness is not exaggerated. As of 1966, cholera was still the most dreaded killer in the East. An epidemic in Pakistan claimed 2,000 lives that year. More than 76,000 people in 23 countries around the world died of this killer disease in a five-year period ending in 1966. India formerly had 200,000 cholera deaths a year. The Russian composer Tchaikovsky was a cholera victim in 1891.
NAMRU-2 has stemmed the tide of this historic scourge with a simple yet effective treatment that costs little, requires only simple equipment and is well adapted to field use. Cholera used to kill 40 per cent of its victims. NAMRU-2 has reduced this to less than 2 per cent. In a 1964 Saigon outbreak, NAMRU-2 personnel treated 2,000 of the stricken with only three deaths. The method has been used to combat cholera epidemics in Dacca, East Pakistan, in 1958; Bangkok in 1958-60; the Philippines in 1961-67; and Korea in 1963.
Cholera is only one of many diseases challenged by the NAMRU-2 men against death. For the more than a decade since "establishment in Taipei, the Unit has warred against an assortment of exotic ills that might frustrate Drs. Kildare and Casey.
U.S. Navy doctors are perfecting a vaccine against trachoma, an eye infection that threatens the sight of at least 400 million people in Asia, Africa, Central and South America and the Caribbean. They are isolating the mosquitoes that transmit Japanese encephalitis, which inflames the brain, and they hope to wipe out schistosomiasis, which is caused by a parasitic worm that penetrates the skin and damages the intestines. Among their other out-of-the-ordinary enemies is paragonimiasis, a debilitating lung ailment carried by parasites lodged in fresh-water crabs, a delicacy of Chinese cuisine.
The primary interest of NAMRU-2 has centered on the more infectious and lethal diseases of the East. Cholera, Japanese encephalitis, small pox and other epidemic diseases with sizable reservoirs of infection are on the list. However, the largest single assault has been against the elusive and destructive virus that causes trachoma. Except for the common cold, trachoma is the most common disease of humanity. It is the principal cause of blindness and has taken the sight or impaired the vision of more than 250 million people.
The virus that causes trachoma is unusually complex. It is one of the few viruses large enough to be seen through a powerful microscope, yet too small and elusive to have been isolated prior to 1957. Credit for the isolation goes to a Chinese scientist, Dr. F.P. Tang, who was trained at Peking Union Medical College. In 1957, Dr. Tang found that by exposing infected cultures to a streptomycin solution strong enough to kill contaminating bacteria, the trachoma virus, which is almost unaffected by streptomycin, could be isolated and concentrated for the growth of pure cultures. Dr. Tang disappeared in the Communist purges which followed the "Hundred Flowers" period on the mainland.
NAMRU-2 was among the first laboratories to work on trachoma vaccines. In 1958, NAMRU-2 microbiologists isolated a particularly virulent strain of the trachoma virus, one potent enough to produce a vaccine. This was done by the Department of Virology in 1959. After preliminary potency and safety testing, a large-scale field evaluation was made in central Taiwan. Eyes of several thousand school children were examined periodically over a period of six years. The vaccine has prevented the frequent recurrences of infection that ultimately lead to blindness and is superior to field-type antibiotic treatments that must be repeated at frequent intervals. More potent vaccines have been developed and are being evaluated. It is certain that vaccines can give protection in endemic areas. The trachoma studies have also contributed to increased understanding of the pathology and epidemiology of the disease and in time should lead to effective control.
NAMRU-2's efforts have helped the free Chinese authorities reduce the Taiwan infection rate from 50 to 5 per cent. Six years ago, sampling conducted by the World Health Organization and the United Nations Children's Fund showed that one of every two persons had trachoma. The Taiwan Provincial Health Department announced on December 30, 1968, that new samples of the two U.N. organizations showed a drop to 5 per cent. Both WHO and UNICEF have contributed material and technical support to the Chinese trachoma prevention program initiated six years ago with NAMRU-2 assistance:
Japanese encephalitis is common to almost every part of the Far East. In infected zones virtually every adult has had the disease, usually in mild form, and has acquired immunity. Consequently, seriously affected victims are almost always children or unexposed adults from other areas who have no immunity. This latter factor makes Japanese encephalitis of special interest to NAMRU-2. Each year a nearly predictable number of American visitors to the Far East fall victim to the disease. About half of such cases either do not recover or are left with some degree of brain damage. No effective therapy is known.
Since Japanese encephalitis is carried by a mosquito, a promising approach should be to break the cycle of transmission by eliminating the carrier. "NAMRU-2 'has an Entomology Department established primarily to find a solution to this problem. The mosquito involved has the formidable name of Culex tritaeniorhyncus and is an abundant species of a numerous family. It is not, unfortunately, susceptible to many of the control techniques that have proved effective in the case of Anopheles minimus, the intermediate host for malaria: chiefly because it does not normally enter houses or come in contact with DDT-treated surfaces. It prefers the open, favoring rural areas where paddy fields and sluggish drainage ditches give it ample' breeding space. NAMRU-2 collections in the Taipei area indicate that it is the most common single species during the summer months when Japanese encephalitis flourishes.
The search for a vaccine continues as it has for than 30 years. None of those developed has been really successful. There is, however, good reason for optimism. The mere fact that a majority of Asians probably have acquired immunity after exposure is a clear indication that antibodies develop readily and promptly. They also retain their effectiveness through out the lifetime of the average individual.
One phase of the NAMRU-2 research has been the day-in-day-out checking of encephalitis viruses re covered from thousands of mosquitoes, most of them from Taiwan and Okinawa. Aside from the scientific study of the mosquito and the virus, NAMRU-2's ultimate aim is to discover an aberrant viral strain which will induce the development of antibodies without causing symptoms of the disease.
NAMRU-2 is also interested in other disorders that are of less consequence statistically but constitute unsolved medical mysteries. Blackfoot disease, or spontaneous gangrene, which apparently occurs only in Taiwan, is in this group.
Statistically, blackfoot disease is a minor matter. No more than 400 sufferers can be found at any given time. Blackfoot is rarely, if ever, the direct cause of death. All the victims are found in an area of a few hundred square miles extending inland for some 20 miles from the west central coast of Taiwan. In this zone, a sprinkling of men, women and children are afflicted with gangrenous infections in toes or fingers that turn black and literally rot off. The gangrene may spread and cause the loss of hands or feet or both.
The NAMRU-2 research is largely aimed at finding the cause of the disease. One conclusion is that no single, uncomplicated cause is likely to be found. The population of the "blackfoot area" is roughly 200,000. Most of the people have approximately the same standard of living. Rarely do two blackfoot viotims appear in the same family. A higher than usual rate of infection sometimes occurs in two or three villages but the incidence is erratic and hard to pin down. Adult males are most commonly affected but not significantly so. Age and sex appear to have little relevance.
Capt. Robert Phillips (wearing glasses) presents offerings in a Buddhist ceremony dedicated to the souls of animals and insects that die to save the lives of men. (File photo)
NAMRU-2 researchers have established that in many villages of the area, drinking water from deep wells has a high content of arsenic. Blackfoot victims and their neighbors show elevated body concentrations of arsenic but not of a level to cause alarm under ordinary conditions. Another factor with possible meaning is the heavy reliance on dried sweet potato chips as a basic food. A number of fungi have been found growing on the dried chips. However, no specific fungus seems to have any immediate bearing on the blackfoot condition. The number of Taiwan residents subsisting in part on similar fare would run into the millions.
Although blackfoot disease is apparently linked to the environment, no single environmental factor has been isolated. The conclusion is that blackfoot is caused by a multiplication of factors that triggers gangrene in a toe or finger. Once started, the process is difficult to arrest. Specialists at NAMRU-2 can only assume that the victim might protect himself by moving to another area, but even this is not an assured method of treatment. In NAMRU-2's hospital ward of 22 beds, some 100 blackfoot victims have shown a satisfactory response to better food and various techniques of improving peripheral circulation.
The parasitic ailments of Asia make up a major research area of NAMRU-2. Because of poor sanitation and the wide use of human excrement as fertilizer, the Far East abounds in a variety of trouble some and often dangerous parasitic organisms. Some, like the amoebas found in at least 20 per cent of Asian intestinal tracts, may remain there for years without causing any symptoms of illness. Others invariably cripple or kill. Even the amoeba on occasion becomes a killer, especially if his host has not developed a tolerance for his presence and some ability to resist.
The work of NAMRU-2 has been centered on three relatively common parasitic ailments that share a common characteristic: the organisms responsible pass through a cycle in the body of a fresh-water snail. One of these, paragonimiasis has a relatively low incidence of human infection and is easily avoided. NAMRU-2 is seeking a method for making quick and inexpensive diagnosis in the field.
Schistosomiasis is a more serious affliction and has at least 50 million victims in the Orient. The cause is a tiny flatworm or fluke which enters through the skin while still in a larval stage and grows to adulthood in the blood vessels and organs of the abdomen. The life cycle is not as complex as with Paragonimus, which needs both a snail and a crab as immediate hosts. Schistosomiasis needs only one variety of snail. As with paragonimiasis, the disease which results is not normally a direct cause of death but frequently causes a gradual deterioration that reduces the victim's ability to work.
A third disease, which also goes through a stage in a fresh-water snail, is fasciolopsiasis. This is a common and less serious ailment than paragonimiasis or schistosomiasis and can be cleared up with relative ease. No really effective treatment has yet been found for the other two. All three can infect mammals other than man. Part of NAMRU-2's research involves study of the course of the disease in animals so as to deter mine which ones will be most useful in the laboratory.
Possibly the most deadly known parasitic disease is Capillaria phillipina, discovered fairly recently in the Philippines. A nematode that infects man, Capillaria (species unknown) has a high mortality rate. NAMRU-2 has two field teams helping the Philippine Health Department study this disease. One group of physicians and technicians is collaborating with Philippine health authorities in Tagudin, Ilocos Sur. The other is studying the clinical aspects of the disease at San Lazaro Hospital in Manila.
Detection of this new parasitic ailment took place about three years ago when a fatal case was autopsied in Ilocos Sur province of west central Luzon. A previously undescribed nematode was found in the intestinal tract. In February 1967, a Jesuit missionary working in Tagudin, Luzon, reported the occurrence of an unusual number of deaths following a wasting illness lasting several months. The disease was characterized by mild chronic abdominal distress and diarrhea and severe loss of weight. The first victims were from the small village of Pudoc in Ilocos Sur. The local press carried reports of a mysterious disease that killed 20 people. An investigation by the Philippine health authorities initially revealed approximately 200 infections due to an unidentified species of Capillaria. Since then approximately 1,000 cases have been reported with over 100 deaths, a 10 per cent mortality rate. Similar infections have been found in several villages within 10 kilometers of Pudoc. Preliminary reports of the joint investigation in the Tagudin area have not revealed any information on the mode of transmission, vectors or other hosts. Clinical studies of patients in Manila have indicated a massive infection of the upper gastrointestinal tract with the 1-mm parasite causing a severe malabsorption syndrome. Marked disturbances of nutrition, metabolism, electrolytes and vitamin storage occur and the patient literally wastes away.
Villagers first tried to combat the disease by bringing in witch doctors; they believed the sickness was caused by a curse. When one of the witch doctors contracted the disease, they began to change their minds about a cure.
The overall problem of parasitic infestation is immense. Conservatively speaking, the health of at least half the population of Asia-well over 500,000,000 people-is affected by parasites of one kind or another. Even the work of finding and classifying parasites is far from complete. Only the major species are known.
Every aspect of disease in Asia is included in NAMRU-2's area of interest. Both staff members and research fellows are selected with a view to having as wide a range of talents and experience as possible. As a consequence and on what might be termed the more purely medical side, a substantial portion of the Unit's attention has been given to targets of opportunity unusual clinical materials which happen to turn up in the Asian area.
An example is Wilson's disease, a rare affliction and one seldom reported in the Orient. In this condition, there is a gradual accumulation of copper salt deposits in the brain, liver and other organs. This is caused by a metabolic deficiency which appears to be of genetic origin. Loss of mental acuity is an early symptom and death is virtually inevitable.
NAMRU-2's study of Wilson cases has resulted in much useful data. The disease is believed to result from a combination of recessive characteristics which might arise, for example, from too much inbreeding. The general Chinese objection to consanguinous marriage provides an opportunity to study the condition in an area where its occurrence should be minimal.
Another of NAMRU-2's "targets of opportunity" is rubella, commonly known as German measles. The Unit became aware of its opportunity 11 years ago when an epidemic of rubella occurred in Taipei. Doctors followed the disease as it progressed throughout Taiwan, collecting valuable information on its epidemiology, the use of gamma globulin prophylaxis and the occurrence of congenital malformations in the offspring of women who had had the disease.
Two years later a vaccine was developed by Dr. Raymond Watten, now commanding officer of the Unit, and an associate. In February of 1968, rubella appeared in Taipei once more and NAMRU-2 was ready to meet the challenge of an epidemic. In cooperation with Chinese health authorities, the Navy doctors formulated a research plan. Within three weeks, 6,000 schoolboys in Taipei and Taichung in central Taiwan had been vaccinated with the newly developed vaccine. Simultaneously, immunization of married women school teachers and young mothers, two groups expected to have the greatest exposure to rubella and the most likely to become pregnant during the epidemic, was carried out.
Two rubella experts from the University of Washington joined in the research. With their help, surveillance of rubella was begun in the rest of Taiwan. Tests were designed to measure the efficacy of the vaccine when given with other vaccines' or gamma globulin alone to prevent infection in school boy's. Information gained from the' studies will contribute greatly to the ultimate, goal of preventing congenital defects due to rubella.
A recent addition to NAMRU-2's source material is bubonic plague - the dreaded "black death" of the Middle Ages. 'The disease struck the Indonesian island of Java in early 1968. A total of 102 persons contracted the disease and 49 died. Focal point of the outbreak was high on the slopes of Java's Mt. Merapi, a 10,000-foot active volcano. The plague has long been endemic in Java, which has 75 million of Indonesia's 115 million people and a population density of 1,500 persons to the square mile. For uncertain reasons, the Mt. Merapi area has been subject to plague outbreaks every 6 to 10 years since the turn of the century. Thousands died in the epidemic between 1957 and 1959.
NAMRU-2 and the U.S. Public Health Service were asked· to help in 1968. A team from NAMRU-2 and the U.S. National Communicable Disease Center started working with Indonesian health officials on control measures in January. By March the disease was under control. From then until September 15, three NAMRU-2 teams were stationed in Bojolali, central Java, conducting research to determine what factors cause plague to spill over from the rodent population and infect humans. The NAMRU-2 specialists spent four and a half months trapping more than 2,400 rats and other rodents at 3,000 to 5,000-foot elevations on Mt. Merapi.
Indonesian authorities say fatalities in the 1968 outbreak might have been much higher had it not been for the quick response of the American agencies. The importance of the NAMRU-2 research is indicated by the history of plague in Indonesia.
The disease is believed to have reached the islands from India, where 12 million persons died of the pestilence between 1896 and 1933. The disease was recorded at Surabaja, Java's second largest city, in 1910. In 1919 another severe outbreak occurred at Semarang. Three years later Tegal in central Java was hit. In 1924 the disease affected western Java's coastal areas. Nearly 17,000 persons died of plague on Java in 1933.
Another NAMRU-2 project is research on Vietnam FUO (fever of unknown origin). This involves the diagnosis of acute febrile illnesses which have been a major headache for military physicians in Vietnam. Through its DaNang Detachment, the Unit initiated a~ infectious disease study designed to define the etiologies and clinical spectrum of diseases infecting American personnel of the I Corps.
But NAMRU-2's greatest success has been against cholera. The simplified method for treatment of the disease has won worldwide acclaim for the Unit and Captain Robert A. Phillips, its commanding officer for 10 years until 1965.
The NAMRU-2 method has advanced to a point where cholera deaths are common only in untreated cases. Unless the patient is already in a state of irreversible shock or is suffering from a complicating heart or kidney ailment, recovery is virtually assured.
Cholera victims die because of massive losses of sodium, potassium and water through intestinal secretion during the course of the disease. If the proper amounts of these essential elements are added intravenously until the body can muster its defenses and drive out the invading bacteria, the patient lives. If this cannot be done and the body defenses are insufficient, he dies. Death can come quickly as the vital materials disappear and body fluids thicken.
NAMRU-2 researchers take blood samples from aborigines of Orchid island off the coast of Taiwan. The U.S. navy disease fighters combat tropical illnesses in out-of-the-way places that tourists never see. Their most dramatic success is against cholera. (File photo)
Also known as the U.S. Navy method, the treatment developed by Captain Phillips takes the form of a salt-base solution that is easily injected. The fluid can be stored in all kinds of weather without special equipment. The essential problem is to determine the dosages of sodium or potassium salts and water needed to restore the proper electrolyte balance. This can be done 'with a small battery of ordinary glass bottles filled with inexpensive solutions of copper sulfate in differing concentrations. Such a testing device is an example of the ideal type of laboratory equipment for use in Asia. All necessary steps can be conducted by a relatively untrained technician under field conditions. As Captain Phillips put it, "we can even use it during storm at sea; the rolling of ships makes no difference as long as the bottles are secured."
The final merit of this method of cholera treatment is that it costs practically nothing. Any kind of clear glass bottles can be used; copper sulfate of adequate purity is obtainable almost anywhere at negligible cost. Other requirements are ordinary water to make the solution, a scale to weigh dry copper sulfate and the graduated flasks to determine solution concentrations. These are standard equipment in any medical laboratory.
In a limited sense, cholera has been defeated. The patient can be nursed to recovery provided he gets care which can be given almost anywhere. But from the viewpoint of a research scientist, this is not enough. NAMRU-2 toxicologists are continuing their work against this disease. They want to know what happens when a human being gets cholera, how the microorganisms work, and most important of all, what can be done to see that they don't get started on their work at all. Doctors and technicians of NAMRU-2 are still deployed in Manila, Saigon and other places where cholera has struck.
Most of the credit for the partial conquest of cholera goes to Captain Phillips, the hard-fighting doctor who set up NAMRU-2 in 1955 and who guided the research and perfected the lifesaving treatment. For this work, he was made a member of the Order of the British Empire and recently was awarded the highest U.S. medical citation, the Lasker Award. The $10,000 Lasker prize carries international as well as national prestige. No fewer than 17 of the past recipients have subsequently received Nobel Awards.
Since retirement from the U.S. Navy and relinquishment of the NAMRU-2 command to Captain Watten in November, 1967, the 61-year-old Iowa-born Dr. Phillips has continued his life-long fight against disease as director of the Pakistan-SEATO Cholera Research Laboratory at Dacca.
NAMRU-2's host country, the Republic of China; recognized the great 'importance of the Unit's service to Asian peoples with a grant of US$175,000 to help in a five-year maternal nutrition 'study that began January 1, 1967.
Research is being conducted at Suilin township near the city of Chiayi in west central Taiwan. Women of 14 villages are receiving daily food supplements during an entire period of pregnancy and lactation. Infants born during the supplementation period will be compared in growth and metabolic studies with siblings born previously. Approximately 100 babies from diet supplemented mothers are expected to be available for growth and metabolism observation.
The program is an outgrowth of experimental work carried out with rats by Professor Bacon F. Chou at Johns Hopkins University School of Hygiene and Public Health, Baltimore. Dr. Chow is serving as chief investigator and 25 Chinese technicians and nurses are working fulltime in addition to two co-investigators of NAMRU-2. Providing technical assistance and professional advice are Dr. S.C. Hsu of the Sino-American Joint Commission on Rural Reconstruction and several other Chinese physicians and scientists.
In its war against disease, NAMRU-2 is engaged in a continuous pursuit of microbes. Members of the Unit travel widely from the outer edge of India to the northern tip of Japan, usually in spots well off beat en tourist trails. They wade into flooded rice paddies to collect water samples, climb hillsides to pluck ticks off a bullock and even forage in dung heaps for interesting bacterial inhabitants. One field trip took a biological and geomedical team to British North Borneo. There the fauna collected for study ranged from fleas to pythons. Other countries visited by the NAMRU-2 investigators are Japan, Korea, the Philippines, Indonesia, Thailand, India and Pakistan.
NAMRU-2's Parasitology Department has emerged as a major supplier of specimens to scientific research institutes in almost every corner of the world. Bird lice are sent to the British Museum in London. Round worms go to McGill University in Tornoto. Mites are in demand in Panama, where the U.S. Public Health Service laboratory specializes in their study. Ticks go to NAMRU-3, the NAMRU-2 sister organization and counterpart in Cairo. Lung mites from snakes are supplied to research institutes in Kuala Lumpur, Malaysia.
Most of the birds, mammals and fish collected are deposited in the Smithsonian Institution in Washington, D.C. Other specimens are sent to U.S. universities engaged in specialized research programs. The University of Nebraska receives a steady supply of tape worms; Howard University gets acanthocephalans (spiny headed intestinal parasites); and the University of Oklahoma is supplied with pentastomids, degenerate anthropodes which usually live in lung tissues. Most of the snails collected are sent to a U.S. Army research center in Japan and another in the U.S. Some reptiles go to research workers at the National Defense Medical Center in Taipei.
From the start, NAMRU-2 has relied on Chinese technicians in all phases of research. Chinese scientists are invited to use equipment and laboratory facilities for their own projects or the treatment of patients. Not long after the Unit was established, this policy was formalized with the inauguration of a visiting fellow program. Chinese doctors on university faculties and graduate students in scientific fields related to medicine who accepted appointment as fellows are given modest allowances to meet living costs while conducting their researches.
In 1959, the scope of the fellowship program was expanded to include similarly qualified scientists from other Asian countries and the United States. The normal term of appointment was set at one year, although the time may be extended or shortened in individual cases.
A related activity which also began in 1959 is the invitation extended each summer to a dozen senior medical students at the National Taiwan University Medical School and the National Defense Medical Center at Taipei to spend their vacation period working in NAMRU-2 laboratories. These student fellows are given a small allowance to cover their expenses and one meal daily while on duty. This was originally intended as a purely local project. In the summer of 1960 an American medical student traveled to Taiwan during his summer vacation and claimed the same modest privileges. Subsequently, a German and two other American medical students asked to take part.
Some 110 medical research fellows from several Asian countries have received training. No hard and fast rules have set to establish eligibility for participation. The most important consideration in selecting candidates is the extent to which they seem likely to benefit in their personal study programs and their probable opportunity to pass on findings to other scientists. The tendency has been to favor applicants who already have teaching assignments to which they will return after their work with NAMRU-2. However, the first of the foreign visiting fellows not only failed to return to her home country, Thailand, but seems unlikely to do so. She was the charming Dr. Boo-nam Sarojaman from Bangkok's Chulalongkorn Hospital Medical School. She is now Mrs. R. Quentin Blackwell, wife of the head of NAMRU-2's Biochemistry Department.
Despite the range of its services, NAMRU-2 is a small organization operated at low cost. Personnel of the 10 departments at home base in Taipei plus the DaNang detachment and special field teams totals only 410 Chinese and Americans. Of these, 35 are U.S. military officers and 14 are enlisted men, 8 are American civil service officers, and 25 are Chinese doctors and technicians. The Unit has a panel of consultants -10 Chinese and 6 Americans. The budget is about US$1 million annually.
Theoretically, NAMRU-2 is a practical, workaday organization. Its principal purpose is to obtain information about tropical and subtropical diseases and thereby keep U.S. Navy personnel healthy when in Asian climes. But this is an oversimplification. The only practical way to accomplish the NAMRU-2 mission is to eliminate the diseases or find ways to treat them. In either case, the benefits to the health of Asians who suffer from the same diseases are incalculable.