Te-Wen Chang

Te-Wen Chang: Virologist, Herpes Specialist and Discoverer of Clostridium Difficile Toxin

Dr. Te-Wen Chang of Brookline, MA, died peacefully in Brookline on January 12, 2025, at the age of 104. The patriarch of the Chang family, Dr. Chang will be remembered for his generosity, commitment to his family, and groundbreaking research in infectious diseases. An emeritus professor at Tufts Medical School and physician at Tufts-New England Medical Center, Dr. Chang made contributions to medical science and public health that have improved the lives of millions.

He was born on Oct. 12, 1920 in the town of Sanjiangkou near Nanchang, China  江西南昌三江口, the fifth of six children born to Kung-chiu 張功久 and Wan Chang 張萬氏. He earned his B.S. degree in 1940 from National Central University and his medical degree in 1945 from the National Central University College of Medicine 國立中央大學醫學院  in Nanjing. In the early 1940s during the Second Sino-Japanese War (WWII), the Japanese army had occupied many of China’s major cities where they destroyed factories and paralyzed the economy, ultimately impoverishing the country.  The Chinese government subsequently subsidized all public college tuition, room and board. As the war ravaged eastern and southern China, universities moved their operations to the southwest, and National Central University moved to Chongqing and Chengdu in Sichuan province to flee Japanese military advances. Toward the end of the war in 1945, Chang and his fellow students were recruited by the government for medical service in a new division of the Chinese army called the Youth Expeditionary Force 青年遠征軍, in which Chang served in Sichuan with the rank of captain. Comprised entirely of high school graduates and young college students, this army was intended to become a main force to drive out the Japanese military. Fortunately, the Japanese surrendered in September 1945, allowing Chang to return to Nanjing to take residency training at the Central University Hospital there.

In February 1950, he emigrated to the United States and completed his residency and fellowship at the University of Kansas Medical Center. He became a Research Associate at the University of Kansas School of Medicine where he helped to categorize polio virus in monkeys.

 In 1952, he married Dr. Diana Yueh-ming Tan, a radiologist and former schoolmate from National Central University Medical College, and moved to Boston, working at Boston University Haynes Memorial Hospital as a fellow in infectious disease under Louis Weinstein, MD. In 1957, he joined Dr. Weinstein at Tufts-New England Medical Center, initially as an Assistant Professor working in four departments (microbiology, medicine, community health and public health). Chang served on the faculty of Tufts Medical School until his retirement in 1992.

Dr. Chang spent most of his time in research, having published over 200 papers, edited two books and contributed a dozen book chapters. Among his publications were articles and editorials in the New England Journal of Medicine, Annals of Internal Medicine, and the Journal of Infectious Diseases. 

Chang, with his colleagues Dr. Frederick P. Li and Dr. John Morrison, saw the need for cultural understanding and bilingual services when delivering primary health care to the adjacent Boston Chinatown community. They established a walk-in evening clinic for local Chinese residents, taking in patients once a week without charge. The word-of-mouth growth of this “Chinese Clinic” reflected the strong need for community health care in Chinatown. In the late 1960s, residents organized the Chinese Community Health Projects Task Force, continuing the effort to deliver quality primary care to Boston’s Asian community.

During the 1950s and 1960s, Dr. Chang worked on various aspects of viral infections, including vaccines against polio and rubella. During the 1970s, Dr. Chang reported a rising incidence of genital herpes from oro-genital transmission and found that indomethacin provided pain relief to women with primary genital herpes. The knowledge he gained on the transmission and inactivation of the herpes simplex virus from caring for these patients led to the publication of two dozen articles in the Journal of the American Medical Association and other leading journals on the transmission and inactivation of the herpes simplex virus, and he edited a book in the Clinics in Dermatology series entitled "Herpes Simplex Virus."

In June 1985, Dr. Chang was invited by the US Army Medical Research Institute of Infectious Diseases (USAMRIID) to serve as an advisor at Hubei Medical College in Wuchang, China to help develop an experimental treatment against epidemic hemorrhagic fever. This fever had spread to China during the Korean War and still affected American servicemen based in Korea.

Dr. Chang’s most consequential work involved research on the bacterium Clostridium difficile, the most frequently identified enteric pathogen in patients with antibiotic-associated diarrhea and colitis and a significant international public health problem. According to the Centers for Disease Control, the disease had a worldwide distribution, and in the US alone there were half a million cases reported, with tens of thousands of deaths per year. In May 1977, Dr. Chang obtained a few drops of guinea pig diarrhea from Dr. John Bartlett of the Boston VA Hospital, who studied clindamycin colitis in guinea pigs as a model of antibiotic-associated diarrhea in humans. To his great surprise, Dr. Chang discovered that the stool was so toxic to the cultured human cells that the toxicity was still evident at a dilution of 1:100,000.  The unexpected discovery drew excitement and his complete attention. He began to work virtually day and night trying to identify the mysterious agent.  Within one month Dr. Chang had made a series of new discoveries in quick succession and confirmed that a toxin produced by Clostridium difficile was the cause of antibiotic associated diarrhea.

The identification of the toxin was not met with enthusiastic recognition until an article appeared in The British Medical Journal, describing the presence of an unknown toxin in stools from patients with antibiotic-associated diarrhea. Dr. Chang sent a piece of filter paper impregnated with antitoxin to the author in London. Within one week, the author successfully neutralized all toxic stools tested. With this, a sense of urgency for publication became obvious. The first paper was published in the New England Journal of Medicine. Subsequently, more than 50 articles, book chapters, or abstracts were published, describing the toxin, unusual clinical features, diagnosis, and treatment of Clostridium difficile colitis. 

This research attracted widespread attention. Every month, hundreds of requests for diagnosis arrived at Dr. Chang’s laboratory from all over the country, and it became difficult to process so many samples. Dr. Chang’s lab was visited by Dr. Jerome Grossman, President of the Tufts-New England Medical Center Hospitals, accompanied by Dr. Sheldon Wolf, Chief of Medicine, and Dr. Sherwood Gorbach, Chief of Infectious Diseases, all of whom were deeply impressed by the scope and scale of research. 

Given the volume and enormity of the work, new lab space was needed. Dr. Morton Madoff, Dean of the Tufts Medical School, allocated $100,000 for the purpose and in 1986 the new “Tufts Medical Laboratory” was established in the Department of Community Health. Dr. Chang continued to run that lab until his retirement in 1992. 

In 1987, the Chinese American Medical Society presented Chang their Scientific Award at Columbia University, after which he spoke on “Clostridium Difficile Disease: A Decade of Reminiscence.” In recognition of his pioneering work in infectious diseases, the Tufts Medical School awarded Chang the Dean’s Medal in 2015. Dr. Harris Berman, dean of the medical school, noted that Chang brought much more than scientific acumen to his work. Quoting a research partner of Dr. Chang’s, he said: “He was a brilliant scientist, but quiet about it. He was also lots of fun to have in the lab.”   

In 2022, Dr. Chang received a Certificate of Recognition from the City of Boston from Mayor Michelle Wu for his “contributions to the medical field and as a trailblazer for Boston’s Asian American community.”

In his personal life, Te-Wen was a devoted husband, father, grandfather and great-grandfather who loved his family dearly, offering support and wise advice when needed. Even with his busy medical career, Te-Wen found time to share with Diana the active raising of their five children. He joyously celebrated the accomplishments of all of his children and was fully engaged in their activities. For many years he also stayed in touch with family members back in China. Earlier in his life, he enjoyed saving memories of family events and world travel through photography. After he retired, he enthusiastically pursued gardening as a hobby with an enviable green thumb, and his plants and flowers always flourished. He enjoyed listening to classical music and was also an ardent fan of the Boston Red Sox and Celtics, enjoying the latter even up to his final days this month.

Dr. Chang is survived by his beloved wife, Dr. Diana (Tan) Chang, his children Lynn (Lisa Wong), Frank, Joe (Sylvia Ong), Janet (Robert Murowchick), and Cathy (Frank Lee), eight grandchildren (Jennifer, Christopher, Michael, Andrew, Kevin, Nikki, Melissa, Jonathan), and two great-grandchildren (Casey, Annalise).

The funeral and Celebration of Life will be held on Saturday, February 1 at 11:30 a.m. at Grace Episcopal Church, 76 Eldredge St, Newton, MA 02458.  

In lieu of flowers, donations may be made online to the “Dr. Te-Wen Chang Difficile Scholarship for Travel” at Tufts University School of Medicine at go.tufts.edu/changtravel or by check made payable to Trustees of Tufts College. In the memo field indicate the donation is for the Dr. Te-Wen Chang Difficile Travel Award in memory of Dr. Chang. Mail to Tufts University School of Medicine, PO Box 3306, Boston, MA 02241-3306.

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