Ian H. Frazer
Balzan Prize 2008 for Preventive Medicine, Including Vaccination
Ian Frazer (1953), a Scottish-born Australian physician, is Head of the University of Queensland Diamantina Institute at the Princess Alexandra Hospital in Brisbane. In 1981 – at the very beginning of the AIDS epidemic, but before AIDS was known – he was working on the origin of chronic liver disease in homosexual men and was intrigued by their apparent inability to get rid of the papillomavirus that caused their genital warts. A colleague, aware of Professor Harald zur Hausen’s group’s discovery of the association of cervical cancer with the papillomavirus (HPV), suggested that he should look for malignancies that might be associated with the papillomavirus, and indeed, in 1984, he found evidence for the existence of yet another HPV-associated malignancy, anal cancer. He was intrigued by the fact that his immune-deficient patients (by that time AIDS had been recognized) seemed to lack protection against this virus-induced cancer and suspected that immune-deficiency was indeed the key to the infection by the virus with subsequent malignant transformation of epithelial cells.
The logical consequence of this line of thought was the idea of immunisation. Ian Frazer decided to focus his interest on HPV and cervical cancer – much more prevalent and devastating than anal cancer in immune-deficient men – and on the possibility of devising an effective vaccine against it.
Initially, Ian Frazer thought of a therapeutic vaccine which, in infected cells, would interfere with the action of key viral proteins involved in malignant transformation (E6 and E7). Since HPV cannot be grown in vitro, this meant that a synthetic infectious virus had to be produced. In this, he succeeded thanks to his partner, the late Jian Zhou, a Chinese molecular virologist whom he met while on sabbatical in Cambridge and who returned to Australia with him. Initially they built the outer coat of the virus by cloning the genes of the virus’s major capsid proteins (L1 and L2) from clinical material and expressing them in epithelial cells using vaccinia virus. With the help of early comparative genomics, they managed to identify the correct initiation code with which to start expression. In the end, they succeeded, and were surprised to find that the proteins of the synthetic virus coat spontaneously assembled into virus-like particles – immunologically identical to the virus, but without its noxious genetic material. These particles proved to be ideally immunogenic. They form the basis of the vaccines which, after successful field-testing, are now in use in large parts of the world and are hoped to ultimately save as many as 250,000 lives per year.
Thus Ian Frazer has laid the basis for a very important step in the fight against cancer and made a large and lasting contribution to preventive medicine. He is committed to making these and future therapeutic HPV-vaccines affordable for all inhabitants of the world.