Australasian Science: Australia's authority on science since 1938

Saving young lives by the million

Professor Ruth Bishop has been named the 2013 CSL Florey Medallist for her discovery of the rotavirus responsible for the deaths of half a million children each year.

By their third birthday, just about every child in the world has had a rotavirus infection. Every day about 1200 children die from it; half a million children every year. That’s changing. We’re fighting back thanks to a discovery made in 1973 by a quiet Melbourne researcher—this year’s winner of the 2013 CSL Florey Medal.

That was when Ruth Bishop, Brian Ruck, Geoffrey Davidson and Ian Holmes at the Royal Children’s Hospital and the University of Melbourne’s microbiology department found a virus, now known as rotavirus. Until the middle of the last decade, it put about 10,000 Australian children in hospital each year with acute gastroenteritis. In the next decade, as a direct result of their research, millions of young lives will be saved.

The discovery initiated a life’s work for Ruth—understanding the virus, working out how it spreads and fighting back with treatments and vaccines. As a result, vaccination against “gastro” has been part of the National Immunisation Program for all Australian infants since July 2007. And the number of hospital admissions has dropped by more than 70 per cent.

Globally, rotavirus infection still leads to more than 450,000 child deaths each year. But that’s changing too. Fifty million children in the poorest countries will be vaccinated by 2015 by GAVI, the Global Alliance for Vaccines and Immunisation, and their partners, supported by the Bill and Melinda Gates Foundation. Figures available from Bolivia, the first low-income country to take part in the program, show a drop of about three-quarters of all hospitalisations.

Yet Ruth Bishop, a quietly-spoken Australian microbiologist now in her eighties, won’t be fully satisfied until a new vaccine she helped develop becomes available. It’s intended for newborns, “the only time children in many developing countries are likely to be near a hospital,” she says. The vaccine is currently being trialled in Indonesia and New Zealand.

For her work in saving the lives of young children worldwide and inspiring a revolution in public health, Professor Ruth Bishop has won the 2013 CSL Florey Medal, a $50,000 biennial award made by the Australian Institute of Policy and Science. The medal honours Australian researchers who have made significant achievements in biomedical science and/or in advancing human health.

The main problem with gastroenteritis is dehydration. The infection destroys mature cells lining the small intestine that absorb nutrients, fluids and electrolytes. “If they can’t do their job,” Ruth says, “you get watery diarrhoea. Children can lose up to 10 per cent of their bodyweight in fluid, and then they are in real strife.”

Ruth started on the hunt for the cause of gastro when she returned to work at Melbourne’s Royal Children’s Hospital (RCH) in 1965 after a post-doctoral fellowship in the UK. She looked initially for a bacterium, but couldn’t find any candidate that could be linked to gastroenteritis. Then, in the early 70s, she got another chance. By this stage there were hints emerging in the scientific journals that a virus may be involved.

Researchers from the RCH Department of Gastroenterology had started to study another nasty aspect of gastroenteritis—long-term malnourishment and sugar intolerance. They had developed a biopsy technique for the small intestine, and were using it to examine whether it was possible to predict sugar intolerance and thus move early to treat it. Ruth realised she could put the samples they took to further use by examining them under an electron microscope.

She was assisted by two colleagues at the University of Melbourne—electron microscopist Mr Brian Ruck and virologist Dr Ian Holmes. When Ruck first put the thin slices of intestinal lining under his microscope, he became entranced by the cell structures—so entranced he said that he overlooked hundreds of distinctive little shapes. It was only when a colleague walked in and said, “Looks like you’ve got a new virus there”, that he realised what he had found. It was called Rotavirus for its distinctive wheel-like shape.

When Ruck phoned to tell Ruth what he had seen, it completely changed her life. “I was a bacteriologist, and I now had to learn a lot about virology very quickly.” But that was only the beginning.

Having found a possible viral cause, the researchers still had to be absolutely sure—they had to forge the link between what they had seen under microscope and the illness in children. The group worked on calves, where a similar virus that caused gastro had been discovered. With the help of veterinary colleagues a technique was developed to identify rotavirus in faeces. Diarrhoeal faeces from children with acute gastroenteritis showed rotavirus particles that were absent from faeces of children after recovery.

A viral cause of gastro presented something of a problem, however. While you could now diagnose the condition and treat symptoms such as dehydration, you could not simply prescribe an antibiotic to rid the body of the virus. In fact, Ruth and her colleagues came to the conclusion that only effective treatment would be to develop a vaccine. “But that takes a long time. You have to know quite a lot about the natural history of a virus to develop a vaccine successfully.”

The first step was to establish that children could develop antibodies to protect them from re-infection with the virus. In proving that to be so, they also found out some other surprising facts. Almost every child encounters rotavirus in the first 2-3 years of their life. Most show symptoms of diarrhoea, but breast-fed babies are typically protected by antibodies in their mother’s milk.

Development of a successful vaccine was to take a long time but by 2005 two vaccines were available from GlaxoSmithKline (GSK) and Merck. In 2007 both were added to Australia’s National Immunisation Program. Then in June 2009, the World Health Organization (WHO) recommended that rotavirus vaccine be included in all national immunisation programs.

More than 2.4 million child deaths can be prevented by 2030 by accelerating access to rotavirus vaccines in the world’s poorest countries according to GAVI, the Global Alliance for Vaccines and Immunisation.

Countries that have introduced rotavirus vaccines have seen a dramatic improvement in child health. Recent studies show the swift and significant impact of rotavirus vaccines in the two to three years following their introduction in national immunisation programmes.

In Mexico, diarrhoeal deaths in children five years of age and younger plummeted by 46% during 2007-2009, in the three years following vaccine introduction. In the United States, El Salvador, Belgium, and Australia, between 2007 and 2010, hospitalisations and clinic visits for rotavirus-related diarrhoea in children five years of age and younger have declined by a striking 60% to 94%.

GAVI is currently working with its partners to reach the world’s poorest 30 nations by 2015.

Meanwhile Ruth and her colleagues have been developing a vaccine that could be given to newborns. The current vaccines are given from six weeks. “As a result of studies at RCH, we found a natural strain of Rotavirus that infects newborns and stimulates the development of antibodies, but doesn’t cause diarrhoea,” she says. The project almost foundered due to funding problems and in 2004 they were down to their last box of vaccine sitting in a fridge. But, finally, a candidate vaccine is undergoing Phase 2 trials in Indonesia and New Zealand. And the Bill and Melinda Gates Foundation has contributed a one million dollar grant to support the vaccine’s development.

Meanwhile, furthering her knowledge of rotavirus led to a huge diversification of Ruth’s expertise. She went from being a microbiologist to becoming skilled in immunology, histology, tissue culture and many other fields. She developed new assays for rotavirus, and her work had spin-offs for other conditions of the gut—coeliac disease, Crohn’s disease and even cystic fibrosis.

Rotavirus made waves in other ways too. “The World Health Organisation (WHO) became much more aware of the impact of intestinal infection in children in developing countries,” Ruth says. So she was invited to chair a committee to allocate money and supervise research in the area, a job at which she worked for many years.

Given the enormous impact she has had on children’s health worldwide, there’s a certain irony in the fact that she chose her field of research almost by chance. “My life was not planned,” she says.

She initially decided to do a science degree at Melbourne University. Then she developed an interest in the biomedical sciences. “So I skipped classes and went to the library to learn about physiology. It really got a grip on me. I found I like learning about the human body and its processes.”

Finally, after majoring in microbiology and graduating first in her class, she was not awarded a research scholarship. Happily she ended up working at the Royal Children’s Hospital in Melbourne as an assistant to Professor Charlotte Anderson, a world-class researcher and pioneer of the field of paediatric gastroenterology.

At 80, Ruth Bishop is officially retired, but is still often seen around the brand new premises of the Murdoch Childrens Research Institute at the RCH, where she worked for so many years.

There, a team of researchers is following in her footsteps, working on the improved rotavirus vaccine and also tracking the evolution of the virus around the world and how it changes in response to vaccine programs.

“Rotavirus will always be around,” says Ruth, “but we can stop it from being a killer.”

Written by Tim Thwaites and Niall Byrne, Science in Public.