Research Yields Advances in Eradication of HBV

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Research Yields Major Advances in Eradication of HBV — R. Palmer Beasley, M.D.: Researcher and Humanitarian



BY Michael A. Snyder



When R. Palmer Beasley, M.D., lived in Taiwan in the mid-1970s, his daily workplace was a U.S. Naval research installation in Taipei. But outside the laboratory, in the communities around him, Dr. Beasley was intrigued by the high rates of two serious liver diseases: hepatitis B (HBV) and liver cancer. Dr. Beasley, then a member of the University of Washington Medical School faculty, began to suspect a correlation between the two, and he set about testing this hypothesis with the same scientific rigor he brought to all of his work.



Virus-Cancer Link



From the outset, many in the scientific community were skeptical. In the United States, President Richard M. Nixon’s "War on Cancer" reflected a strong focus on environmental causes of cancer; the idea of a link between viruses and cancer had fallen out of favor. In part, this was because previous efforts to establish such a connection had failed.



"When people had thought which cancers might have a viral cause, it was thought that leukemia was a good candidate and a variety of others, but solid tumors of the GI tract were not on anybody’s horizon," Dr. Beasley says. "When I came along and said viruses again, it was like the door had been shut on that notion."



Persistance Pays Off



But Dr. Beasley persisted. Ultimately he and his colleagues proved that hepatitis B causes the most common form of liver cancer, known as hepatocellular carcinoma. His 30 years of research also have demonstrated that transmission from mother to infant during childbirth is the principal factor sustaining hepatitis B worldwide, causing 40 percent of cases; that immunizing at-risk newborns within hours of birth prevents 95 percent of these infections; that a test for a small protein near the core of the virus accurately predicts which mothers will infect their infants; and that children, once infected, are more likely than adults to remain chronic carriers of the virus. These findings have been central to international efforts to curb the spread of hepatitis B, which infects an estimated 2 billion people around the world.



Vaccine Prevents Cancer



Today, as dean of the University of Texas-Houston Health Science Center School of Public Health, Dr. Beasley continues to conduct hepatitis B research and to campaign tirelessly for universal immunization. In 1992, he persuaded the World Health Assembly to make the hepatitis B vaccine its seventh global vaccine. It is now in use in about 100 countries and is the only vaccine that prevents a major human cancer.



Building on these achievements, Dr. Beasley has set his sights on elimination of the hepatitis B virus.



"I’m now arguing that eradication should be the goal, not just control," Dr. Beasley says. "This is an eradicable disease. It could occur more rapidly than anyone dares dream."



Dr. Beasley’s achievements have brought him widespread acclaim. Last January, Queen Sirikit of Thailand presented him with the 1999 Prince Mahidol Award for Medicine for his work on the hepatitis B virus. The annual award, named in honor of a Thai prince who worked to improve public health in his native country, is bestowed annually based on the recommendation of an international panel of experts.



"Few, if any, medical professionals in the world have done more to prevent cancer than Palmer Beasley," said M. David Low, M.D., Ph.D., president of the UT-Houston Health Science Center.



Stanley M. Lemon, M.D., a hepatitis C researcher at the University of Texas Medical Branch in Galveston (UTMB), said Dr. Beasley’s work on hepatitis B has been a model for other scientists.



Dr. Beasley’s research "demonstrated clearly the link between hepatitis B and liver cancer in a region where both were very prevalent," said Dr. Lemon, who is dean pro tem of the School of Medicine at UTMB. "It stands as a lesson to all concerning the power of epidemiology as an investigative approach in this area of research." Epidemiology is the study of how infectious diseases move through populations.



Human Side of Research



Indeed, for Dr. Beasley, the human side of research has always been at least as interesting and challenging as the work he and his colleagues do in the laboratory. When he first went to Taiwan in 1972, he says, he wondered about the reasons for the high prevalence of hepatitis B in the local population. Since it appeared to be a relatively old disease, he considered how this blood-borne virus might have been transmitted in nature prior to the advent of blood transfusions, a recent procedure.



"What is the most common way human blood is exchanged?" Dr. Beasley asked rhetorically. "From mothers to babies." His research eventually demonstrated that this was in fact the most common mode of transmission.



"This was the first time any chronic infection that was silent (asymptomatic) in the mother was identified as being transmissible to the baby and establishing a chronic and silent infection in the baby," he says. "These perfectly health-appearing carrier mothers — on their way, however, to chronic liver disease — infected the babies, and the babies almost always became carriers if they were infected by their mothers."



This discovery led to another important finding: the likelihood that a person infected with hepatitis B will become a chronic carrier is age-related. Infected children almost always become chronic carriers, while adults seldom do. This meant that immunizing children as early as possible would be the most effective way to slow the spread of hepatitis B.



Resistance Hostile Toward Infant Immunization in Taiwan



Initially, Dr. Beasley’s efforts to promote immunization of newborn babies met with resistance from world health officials. Conventional wisdom held that immunizations should not begin until children were two years old. Another obstacle emerged when Taiwanese newspapers published front-page articles suggesting that the immunization campaign amounted to experimentation on Taiwanese children. Some of the coverage was so hostile that Dr. Beasley’s wife, hepatitis researcher Lu-Hu Hwang, refused to translate the articles for her husband. To counter perceptions that the immunizations were dangerous, Dr. Beasley had himself photographed receiving the first inoculation.



The hostile publicity led the pharmaceutical company funding the vaccine trials to withdraw its support. Dr. Beasley persisted, however, and eventually completed the field trials and won the full support of the Taiwanese government.



The findings of Dr. Beasley’s research team in Taiwan have prevented countless infections. "Taiwan was the very first place to get a nationwide immunization program going, and they’ve had absolutely incredible results," Dr. Beasley says. The virus carrier rate among Taiwanese children has declined from about 12 percent to 1 percent. Liver cancer rates also are dropping.



Unanswered Questions



One question that neither Dr. Beasley nor other researchers have answered conclusively is why hepatitis B prevalence rates historically have been so much higher in Asia than in the West. "Many people thought the Chinese were genetically different," he says, "but we now know it has nothing to do with race." Hepatitis B can be spread through saliva, and Dr. Beasley suspects that the common Chinese practice of mothers pre-chewing food for their babies may have contributed to the high prevalence of the disease.



Today, Dr. Beasley says, Asia and Africa continue to have the highest prevalence rates for hepatitis B, and the success of immunization programs has been mixed. Poverty and political instability in Africa have made it difficult to introduce programs there, he says. China now reports about a 60 percent coverage rate nationwide, "which is pretty good considering t