San-pin Wang, M.D., M.P.H., Dr. Med. Sci.
1920 - 2001
San-pin Wang's name is synonymous with the micro-immunofluorescence (micro-IF) test, which was developed by him in 1970 (Am J Ophthalmol 1970;70:367-374). Until today the micro-IF test remains the only type specific serological test for laboratory diagnosis of chlamydial infection and serotyping of chlamydial isolates. This is the test that led us to discover new disease syndromes and to understand the epidemiology and immunopathology of chlamydial infection.
San-pin Wang was born on November 7, 1920 in the small town of Changhwa in the central part of Taiwan, while Taiwan was under Japanese rule. He studied medicine at the Keio University School of Medicine in Tokyo, Japan. He graduated from the medical school in 1944 in the thick of World War II. He intended to become a surgeon. However, his father who was a physician advised him to pursue an academic career in basic medical science so his education and training would not be disrupted by military service. San-pin took his father's advice and entered the Department of Bacteriology at the Keio University. This was the first turning point in his life which led him to become one of the great microbiologists of his time. After the war ended, he returned to Taiwan in 1946 and worked for the Taiwan Provincial Health Laboratory in Taipei. He came to the United States in 1951 to study virology at the University of Michigan School of Public Health under the famous virologist, Thomas Francis, and obtained an MPH degree in 1952. He went back to Taiwan and worked for the Taiwan Serum & Vaccine Laboratory in Taipei, first as the division head of the Viral Vaccine Division in 1952, and then as the Vice Director in 1956. During this time, he also taught microbiology at the National Taiwan University College of Medicine and the National Defense Medical School in Taipei.
The second turning point in his career occurred in 1958 when he met J. Thomas Grayston who was serving as a civilian consultant and Head of the Department of Microbiology at the U.S. Naval Medical Research Unit-2 (NAMRU-2) in Taipei, Taiwan. Tom invited Dr. Wang to join him to work on viral diseases at NAMRU-2 on influenza, Japanese encephalitis, and trachoma (at that time trachoma was thought to be a viral agent). Both Japanese encephalitis and trachoma were endemic in Taiwan during this period. In 1957 the first isolates of trachoma were obtained by F.F. T'ang in Peking, China (Chin Med J 1957;75:429-47) in chick embryo. When this report reached the hands of Grayston and Wang, the isolation of the trachoma virus was attempted at NAMRU-2, and in 1958 T'ang's finding was confirmed. The encounter with Tom and the successful trachoma research sealed the life long association between the two and devotion of their remaining productive research career to chlamydia until San-pin's death.
Soon numerous trachoma isolates were obtained in Taiwan. As any bacteriologist would do, a typing method was developed to categorize isolates. This method was a cumbersome mouse toxicity prevention test. In this test, mice are immunized with isolates to prevent death from intravenous challenge with live trachoma organisms of the same but not different serotypes. The homologous protection observed in the mouse challenge experiment produced an idea that trachoma might be prevented by vaccination. This idea led Wang and Grayston to develop a monkey model of trachoma to study the immunopathology of blinding trachoma and to develop a vaccine for prevention of trachoma. The Taiwan monkey turned out to be the only species in which the typical trachoma syndrome of conjunctival scarring, pannus formation and corneal opacity identical to human disease, can be produced. A trachoma vaccine using formalin killed trachoma organisms grown in the chick embryo yolk sac was tried in monkeys and human volunteers in Taiwan and India. Two important concepts on chalmydial infection were developed from these studies. The first concept is that trachoma (blindness) is a disease of immunopathology resulting from repeated infections (Grayston JT et al. Rev Infect Dis 1985;7:717-25). This trachoma pathology was later reproduced in a monkey model of fallopian tube obstruction (infertility) from chronic Chlamydia trachomatis salpingitis by his student (Patton DL et al. J Infect Dis 1987;155:1292-9). The second concept was that it is possible to prevent chlamydial infection by immunization. The latter concept is a rationale for the development of vaccine for prevention of C. trachomatis STD and Chlamydia pneumoniae respiratory and coronary heart diseases.
San-pin emigrated to the U.S. in 1964 to join Tom at the University of Washington in Seattle, Washington to continue their productive chlamydial research until San-pin's death in 2001. San-pin developed the micro-IF test in 1970 for classification of isolates and serological diagnosis of C. trachomatis (Wang & Grayston, Am J Ophthalmol 1970;63:267-374). Using the micro-IF test, a series of important discoveries on human chlamydial infection were made by San-pin and his colleagues and students. First, C. trachomatis as an important pathogen of sexually transmitted disease was defined in 1975 (Holmes KK et al. N Eng J Med 1975;292:1199-1205). Second, the new chlamydia agent which causes respiratory disease was discovered in 1986 (Grayston JT et al. N Engl J Med 1986;315:161-8) and later speciated as Chlamydia pneumoniae in 1989 (Grayston JT et al. Int J Syst Bacteriol 1989;38:265-268). Finally, the association of C. pneumoniae and coronary heart disease was established in 1988 (Saikku et al. Lancet 2:983-986). For these contributions, San-pin received the Kimble Award from the American Public Health Association in 1991 for a person who developed a laboratory test of significant impact on public health. He also received a special recognition of his research contribution to chlamydia by the International Chlamydia Society at the Seventh International Symposium on Human Chlamydial Infections in 1990.
San-pin's research career had been influenced greatly by the philosophy of his bacteriology professor Roku-zo Kobayashi at the Keio University. It's the philosophy San-pin also tried to imprint in me when I came to the University of Washington to join Grayston and Wang in 1967. Professor Kobayashi's philosophy is that to be a successful scientist you have to have three N's [un, don-(sai), kon-(ki)] in Japanese. Translated it means: fate (or luck), perception, and patience. This motto truly painted San-pin's scientific career since his student year until his death. First, chlamydia research would not have San-pin if he did not take his father's advice not to become a surgeon. Because if he had chosen the surgical residency training on his graduation from medical school, he would have been drafted into the Japanese army and most likely died in mainland China or South East Asia as many of his fellow medical school graduates did. The chance encounter with Tom Grayston and the report on the first isolates of trachoma agents soon after he moved to the NAMRU-2 subsequently destined him to devote his research career entirely to trachoma (chlamydia) field. Finally, his move to the University of Washington to continue his research in chlamydia. All these events were fate and luck as his professor had predicted.
After he developed the micro-IF technique, he soon realized the potential of applying this technique in his research. The micro-IF test has been criticized as subjective, not specific and difficult to perform and it is not a challenging science. However, his perception told him the other way. These critiques are silenced by the fact that the typing scheme of C. trachomatis based on the micro-IF was proven so precise by the monoclonal antibody technique and DNA sequencing.
Finally, his patience dictated to him to continue using the micro-IF as a tool in the epidemiological studies. His perseverance to stick to the micro-IF and not to chase fashionable research enabled him to define the role of C. trachomatis in STD, discover C. pneumoniae as an important respiratory pathogen, and finally associate C. pneumoniae with coronary heart disease and atherosclerosis.
San-pin had other virtues which made him successful. He often told me that a research finding no matter how great it is it will not be accepted unless it can be repeated. Because of this belief, he was very open on his research work. I remember clearly the visit of Barry Jones from the Institute of Ophthalmology in London to Seattle in 1969. San-pin taught him the detail of the micro-IF technique when this technique was still in the developmental stage because he wanted somebody else to be able to repeat his findings. Barry went back to London, taught the technique to John Treharne, and was able to repeat and confirm the typing scheme developed by San-pin. The serotypes of C. trachomatis isolates based on the micro-IF test was subsequently reported simultaneously in separate papers by Wang and Treharne at the Third International Chlamydial Meeting held in Boston in 1970 (Trachoma and related disorders caused by chlamydial agents: Proceedings of a Symposium held in Boston, Massachusetts 17-20 August 1970). It typifies San-pin's unselfishness and devotion to science throughout his research career. Chlamydia research is fortunate to have had such a great person like San-pin.
San-pin was a humble person. He would never claim his achievement while he was alive because he believed that a judgment on a person's achievement should be left to historians to make. I was privileged to have had a mentor like San-pin and to have worked with him. He was truly a great person.
Cho-chou Kuo, M.D., Ph.D.