Profiles: Professor Ian Frazer

By Louise Williams

A vaccine for cervical cancer? It took this man to make it happen

Flying back into Australia recently, it suddenly hit Professor Ian Frazer that his life really had changed. Here, perhaps, was a chance to bask in a moment of hard-earned glory after decades of solid backroom work. So he put his characteristic humility to one side. And instead of filling in “medical researcher” under profession on his landing card, he carefully wrote out “Australian of the Year”. “No-one even noticed,” he laughs, recalling how an immigration clerk processed his documents and nodded him through without a second glance.

Such is the modest public profile of a man now standing on the brink of medical history. Frazer’s cervical cancer vaccine was approved in June for use in Australia and the US. Other countries are expected to follow suit and, as a result, the next generation of women around the world may well dismiss the human papillomavirus (HPV) as a scourge from a bygone age, just as we take for granted the end of polio.

 Until now, this common sexually transmitted virus – which can go on to cause cervical cancer – has killed some 250,000 women a year. Cervical cancer is the only human cancer yet proven to be caused entirely by a virus. And Frazer’s vaccine, developed with his late research partner, Dr Jian Zhou, makes it possible for us to wipe it out.

Professor Peter Doherty, an Australian Nobel laureate who made one of last century’s most significant medical discoveries in physiology and immunology, says that in a world of daily headline claims and hype, Frazer’s work truly can be called a breakthrough – one that surprised even the scientific community, because it works so well. “Ian has made an incredible contribution to human wellbeing,” he says.

Growing up in the cold, smoggy cities of Edinburgh and Aberdeen, Scotland, in the late 1950s, Ian Frazer plus a chemistry set equalled an explosive combination. His father was a professor of medicine; his mother had a PhD in science. Little wonder that by early primary school, Frazer had decided he wanted to be a physicist.

Then, when he was about nine, he remembers lining up with schoolmates for their polio vaccinations. “The needle got my attention,” he says – which is where most kids are happy to leave it. “Then, I realised there were [crippled] kids around who had had polio. That got me interested in how the body fights infection … how the body repairs itself.”

Frazer studied medicine at university, graduating in 1977. From there, the young Scot with a brilliant eye for detail could have walked into a research job at Cambridge University. Instead, he had figured that much of the best work in immunology was coming out of the Walter and Eliza Hall Institute of Medical Research in Melbourne. He’d spent several months as an intern there in 1974 and liked the laid-back Aussie lifestyle, so he emigrated. “In retrospect, it was a risky strategy,” says the immunologist, now 53. But he also had a deliberate plan.

A strange new illness was brewing. Frazer began working on liver diseases linked to hepatitis B in gay men. And when an US researcher dropped by the institute and mentioned a mysterious immunity problem among gay men in the US, Frazer realised his patients had a similar problem, later recognised as HIV-AIDS.

Frazer also noticed his patients were commonly afflicted with genital warts caused by the human papillomavirus. HPV wasn’t just a nuisance; the warts seemed to be associated with abnormal cells that were on their way to becoming cancer.

To link a virus to cancer was contentious. At that time, only one other scientist, German virologist Harald zur Hausen, had linked HPV in women to cervical cancer. But Frazer was convinced this needed further investigation. 

Research grants were easier to find in Queensland, and with his wife Caroline, whom he had met while at university in Scotland, and their two children (with a third on the way), he moved to Brisbane and was soon running his own lab at the Princess Alexandra Hospital, the University of Queensland’s teaching hospital. The relaxed, friendly environment was some compensation for the long hours Frazer spent on his medical research. Then, in 1989, he was offered the chance to go and spend some time in Cambridge on a sabbatical.

It was an academic’s dream, and once more Frazer and his family were unpacking suitcases in a new location. It wasn’t long, however, before the Frazers realised their Australian dollar savings converted to too few British pounds. In just such a precarious financial situation were a Chinese couple, Dr Jian Zhou and his wife and assistant Dr Xiao-Yi Sun, toiling long hours in the lab next door. “Jian’s English was limited and his wife’s was nonexistent, but somehow we managed to talk,” Frazer says. And as they talked, they connected – a Scottish immigrant and a young Chinese molecular biologist who’d survived the proletariat farm and factory labour of the Cultural Revolution.

“We just traded off each other. I could see what he was trying to do, and what I was trying to do was very similar,” says Frazer of their common interest in the papillomavirus. But for Zhou, a talented virologist, the interest was in the behaviour and characteristics of the virus itself. As an immunologist, Frazer was working on how the human body responded to it. It was a perfect scientific match.

Zhou and Sun explained to Frazer how they weren’t keen to go back to China. “We wanted the opportunity to advance our careers and work with leading international scientists, whether that be in the UK, US, Germany or Australia,” says Sun.

“I encouraged Jian to think about Australia. And everyone else at Cambridge egged him on,” Frazer says.

In the end, it took nine months for Frazer to get the papers necessary to get the two researchers to Brisbane and to clear some space in Frazer’s lab. It would be many more long months before the couple’s son, Andreas, was finally able to get permission from the Chinese authorities to fly to Australia to join his parents.

The lab partnership, meanwhile, thrived. In March 1991, six months after they began working together in Brisbane, the team was stunned by the results of an experiment.

 Unlike most other viruses, the papillomavirus cannot be grown in a test tube; it grows only on intact, living skin. But to create a vaccine, they needed something that so closely resembled the real virus that the body would be tricked into recognising it and – as with all vaccines – trigger a mild immune response that it could quickly draw on if it ever had to deal with a serious attack. When the group examined the electron microscope photographs of their tests to combine two proteins, they spotted virus-like particles and they realised they’d managed to mimic the “coat” of the real virus; it was the building block they needed to create their revolutionary vaccine.

“We’d cracked it. I don’t think any of us doubted for a moment that we had done it. We got very excited, but then we weren’t sure we should tell other people,” says Frazer. It wasn’t, he explains, “exactly a champagne moment”. They realised there was so much work still to be done.

As it turned out, it was two more years before the vaccine was turned over to the Melbourne-based biopharmaceutical company CSL Limited, and another 13 years before the general public would see the benefit of the team’s work.

The biggest regret Frazer has now is that Zhou’s sudden death in 1999, from a complication to a routine medical problem during a trip to China, means he can’t share the success with his partner of so many years.

But the work is continuing. With a carbon copy of the papillomavirus in a test tube, Frazer has been able to conduct previously impossible tests on how it works. And now his lab is chasing down the next vaccine: one that can be used to treat someone who already has the virus in her system.

What advice does Frazer have to other medical researchers to keep believing in what they’re doing? “The art in science is to make sure you are trying to answer answerable questions,” he says. “I tell my students, don’t go into science if you want to be famous.”

And indeed it’s been a very long, uncertain road, 20 years at least since the first germ of an idea to a vaccine. But now Frazer’s discovery is the stuff of history, not mere celebrity.

And that’s far more durable than a brief glance of recognition at the immigration counter.�