Written for Skoda's "The Mind Behind" series for BBC Culture
How did Professor Ian Frazer’s diligent dedication to scientific research lead to the chance discovery of a revolutionary vaccine for cervical cancer?
How would you describe a discovery that could potentially save 250,000 people each year from death and painful medical procedures? Ground-breaking? A miracle perhaps?
Professor Ian Frazer prefers not to dabble in superlatives when describing his life’s work and is more likely to use the term “useful”. It’s clear when speaking to the acclaimed immunologist and former Australian of the Year that his intention has always been to simply do good work rather than chase plaudits.
“I never really thought my science career was going to end up producing a useful product. I was very much interested in how the immune system works, an intellectual interest if you like, but being trained as a doctor you always think about the practical aspect of things.”
It’s this intellectual interest in the immune system and a desire to develop something “practical” that drove Professor Frazer and his colleague Dr Jian Zhou to a revolutionary discovery in a laboratory at the University of Queensland that promises to save tens of millions of lives over the coming decades.
“I’ve always felt a sense of responsibility as I was given an education in medicine and chose to use it to enable research rather than clinical service. On top of that, I was given public money to pursue research and an opportunity to work with really clever and dedicated scientists.”
Young women around the world now have protection against the second biggest cause of female death, cervical cancer, thanks to Gardasil, a vaccination against the human papilloma virus (HPV) that causes 90% of these cancers. Professor Frazer’s vaccine has now been administered 200 million times globally, since he personally administered the first dose of Gardasil to a young woman in 2006.
“It was exciting knowing the world was watching and almost unbelievable as I was thinking, ‘This can’t really be happening’. It was incredibly satisfying to see that research effort does produce tangible outcomes.”
From his early years studying pathology and medicine in Scotland to the chance encounters that led to his research into HPV, the road to the creation of Gardasil was not always clear but Professor Frazer has diligently followed it every step of the way.
Cause and effect
The link between sexually transmitted infections and cervical cancer had been postulated for about 150 years before Professor Frazer began his own research. An Italian epidemiologist, Domenico Rigoni-Stern, made a very simple observation in 1841: that nuns never got cervical cancer while prostitutes very frequently did, and correctly assumed there was something transmitted sexually that caused the disease.
After moving to Australia in 1981, Professor Frazer had begun his research career working on hepatitis B and the causes of liver diseases. It was during this period that he had two serendipitous meetings that convinced him to change direction towards what would become his life’s work in HPV research.
“I had the good fortune to visit an expert in liver disease in Germany who introduced me to his boss, who turned out to be Harald zur Hausen, the professor who first discovered that HPV was involved in certain cancers. He said, ‘Don't worry about working on liver disease, why not work on a virus which is causing cancer?’.”
Back in Melbourne, Professor Frazer had also been looking at patients with HIV infections in the very early days of the AIDS epidemic. Realising the problems these men were having with genital warts caused by HPV, Frazer worked with Dr Gabrielle Medley, a gynaecological pathologist who encouraged him to further explore the links between HPV and cancer.
“We found out HPV was actually causing cancers, not only in the cervix in women but also in the anal passage in men. That brought me a little bit of international attention because we wrote a paper which got into a big international journal as we’d found another cancer apparently caused by HPV.”
Building blocks
Professor Frazer’s original approach to HPV was trying to determine if a treatment could be developed for people who already had the HPV infection. To do so, he had to actually grow HPV in a lab, a feat that nobody had achieved at that time.
Beginning his partnership with the talented virologist Dr Jian Zhou, the pair began their work in earnest on what they initially hoped could become a treatment for HPV. Using the new discipline of recombinant DNA, they set out to build the virus in a very sophisticated environment, and after viewing the results through an electron microscope they made an astounding discovery.
“When we were building the virus, we realised we could assemble the shell of the virus without having to do anything other than just build one of the building blocks and they would all self-assemble. That was a surprise to us and something that we didn’t expect.”
This was the eureka moment in 1991 that would begin a 15-year process to creating the world’s first cancer vaccine. At the time, however, Professor Frazer was typically pragmatic in his outlook.
“We were beginning to realise that all cervical cancers were caused by this virus and therefore a vaccine became a really useful proposition. While we could see there was a prospect for a vaccine to prevent a cancer and that was exciting, we also realised that an awful lot of things you do in research never actually turn out to work.”
Undeterred, Professor Frazer and Dr Zhou set about the task of taking their technology from the lab and testing the waters with companies which would be able to provide the commercial scale and investment to actually develop the vaccine. Even after the process had begun, Professor Frazer says there were never any certainties they would ever achieve their goal.
“We sat in the back row watching and we didn't really get excited until about 10 years after we came up with the technology. It wasn’t until the first clinical trial results were looking very positive when we felt, ‘Yes, OK, now we're going to do something that might be useful’.”
That “useful” technology has been hailed as one of the greatest medical discoveries in recent history and a landmark piece of research in the battle against cancer. Dr Zhou sadly passed away in 1999 and wasn’t able to see his discovery reach fruition, but Professor Frazer continues to pay tribute to his colleague and has overseen posthumous honours including a commemorative ceremony for Dr Zhou at Parliament House in Brisbane in 2008.
Professor Frazer was the proud recipient of the Australian of the Year in 2006 and has since gone on to collect dozens of honours, including becoming a Companion of the Order of Australia (AC) in 2012 for his “eminent service to medical research, particularly through leadership roles in the discovery of the Human Papilloma Virus vaccine and its role in preventing cervical cancer, to higher education and as a supporter of charitable organisations”.
His work has continued on multiple fronts as a former adviser to the World Health Organisation and the Bill and Melinda Gates Foundation on papillomavirus vaccines, as well as being a member of the Commonwealth Science Council and president of the Australian Academy of Health and Medical Science. Reflecting on whether he’d ever imagined his work would have achieved such remarkable results, his response is delivered with typical humility.
“The idea of a vaccine drove me in the right direction but I never really thought I would get there. It started off almost as an imaginary concept – could we actually do something useful with the technology we have? The most important message that I tell the next generation of researchers – you, too, can get there and do something really useful if you think it's worthwhile.”