Photo: Courtesy of Murdoch Childrens Research Institute
If fate had been kinder to Ruth Bishop, she might have enjoyed the rare satisfaction of discovering what causes one of the world's deadliest infectious diseases, and the means to prevent it. She helped accomplish the first feat with remarkable ease almost 30 years ago, but as she nears the end of a distinguished medical research career, its sequel remains maddeningly elusive.
Now 69, Bishop is self-effacing about the headway she and her small research team at the Royal Children's Hospital in Melbourne, Australia, have made into understanding the role that rotaviruses play in severe gastroenteritis. Rotaviral gastroenteritis kills as many as 2,000 children daily.
Her modesty and aversion to publicity have left Bishop little known outside her field. But Sir Gustav Nossal, president of the Australian Academy of Science, regards her as one of his nation's most esteemed researchers. As director of the World Health Organization's (WHO) Collaborating Laboratory for Research on Human Rotaviruses, Bishop has had a major influence in the battle against rotaviral diseases since their discovery in 1973.
"Ruth really has made an important contribution, both with her initial discovery and her continuing efforts to demonstrate that immunity developed after neonatal infection protects kids from serious disease," says Roger I. Glass, director of the Viral Gastroenteritis Section at the Centers for Disease Control and Prevention. "She's had a constant involvement through her connections with the WHO and has trained many outstanding rotavirologists in Australia over the years. She has been gracious and kind in her support of this field as well, which is a wonderful attribute for a scientist." Her curriculum vitae lists more than 120 published scientific papers and a string of honors--notably 1998 recipient of the WHO Children's Vaccine Initiatives' Pasteur Award, along with Glass and Albert Z. Kapikian, of the National Institute of Allergy and Infectious Diseases.
Bishop says that working in Melbourne and staying in close contact with clinicians has kept her content, although at times she experienced limited resources and uncertain funding for basic research. "It's probably because I've been happy to remain working with a small group in a children's hospital rather than join a large research team," she says. "I think to some extent my reluctance to step into the limelight has hampered our prospects somewhat."
Those prospects began in the early 1970s when Bishop, a bacteriologist, was researching the causes of childhood diarrhea and concluded that a nonbacterial infectious agent was probably to blame. To broaden her search she teamed up with clinical research fellow Geoff Davidson at the Royal Children's Hospital, and virologist Ian Holmes and electron microscopist Brian Ruck, both of Melbourne University. Serendipity and calculated investigation paid instant dividends.
In 1973, electron microscopy revealed a previously unknown virus in the first bowel biopsy sample the team studied.1 The researchers subsequently found the virus in other patients' specimens. Bishop concedes that she did not appreciate the discovery's real significance until its publication provoked a global response. "It was like pressing a whole lot of light bulbs on a world map," she later recalled. "Everyone was saying 'we have found the virus too.' It was turning up everywhere."2 Later named for its wheel-like appearance in electron micrographs, rotavirus was soon recognized as the most common cause of severe diarrhea in infants and young children worldwide.3-5
Her team went on to develop a clinical diagnostic test and is credited with helping to pave the way for development of a live oral vaccine. But numerous problems have kept a viable vaccine from reaching the market. (See "Rotavirus Vaccines, Take Two" on Page 34.) Bishop says that she is frustrated and saddened that the struggle to prevent the disease has become protracted, complex, and political.
Appearing recently at the 10th International Conference on Infectious Diseases in Singapore, Bishop observed: "I'm on record in 1974, in response to a journalist's question, 'How long will it take to get a vaccine?' for saying 'five years.' And here we are, nearly 30 years later, trying to get a vaccine that is safe and effective."
A nonvirulent human strain of rotavirus that her team initially discovered in the late 1970s has been tested successfully in Phase I and II trials, where it remains sidelined through lack of commercial support. No Australian manufacturer with sufficient resources is available, and international interest is focused on two other vaccine trials, Bishop says.
Her main hopes, she says, are pinned on the Indonesian Government, which has expressed interest in her candidate vaccine and has its own facility through its large vaccine manufacturer, Biofarma; and on the Bill and Melinda Gates Children's Vaccine Program. Another candidate vaccine designed for use in India is being developed jointly with US and Indian partners, and is expected on the market by 2006, the program announced recently.6
Vaccine research is a process that has become increasingly difficult to negotiate as standards have risen higher and higher, especially in the United States. Says Bishop, "Once upon a time, the benefits of vaccines were accepted as far outweighing the side effects. I doubt whether the vaccines for smallpox, pertussis, and even polio would win such easy approval if they were introduced today."
Bob Beale (www.bob.beale.org) is a freelance writer in Australia.
1. R.F. Bishop et al., "Virus particles in epithelial cells of duodenal mucosa from children with acute non-bacterial gastroenteritis," Lancet, 1:1281-3, 1973.
2. A. Tattam, "Ruth Bishop: Rotaviruses and vaccines," Lancet, 353:1860, 1999.
3. I. de Zoysa, R.V. Feachem, "Interventions for the control of diarrhoeal diseases among young children: rotavirus and cholera immunisation," Bulletin of the World Health Organization, 63:569-83, 1985.
4. A.Z. Kapikian, R.M. Chanock, "Rotaviruses," In: Fields Virology, Vol. 2, 3rd ed., B.N. Fields et al., eds., Philadelphia: Lippincott-Raven Publishers, 1996, pp. 1657-708.
5. M.K. Estes, "Rotaviruses and their replication," In: Fields Virology, Vol. 2, 3rd ed., B.N. Fields et al., eds., Philadelphia: Lippincott-Raven Publishers, 1996, pp.1625-55.