Ian Hector Frazer | |
---|---|
Born | Glasgow, Scotland | 6 January 1953
Nationality | Australian, British |
Alma mater | University of Edinburgh (BSc), (M.B.B.S.); Walter and Eliza Hall Institute of Medical Research; University of Melbourne (M.D.) |
Known for | HPV vaccine creation |
Awards | Australian of the Year (2006), Prime Minister's Prize for Science (2008), Australian Living Treasure (2012), Companion of the Order of Australia (2012) |
Scientific career | |
Fields | Immunology |
Institutions | Translational Research Institute, University of Queensland |
Ian Hector Frazer AC (born 6 January 1953) is a Scottish-born Australian immunologist, the founding CEO and Director of Research of the Translational Research Institute (Australia). [1] Frazer and Jian Zhou developed and patented the basic technology behind the HPV vaccine against cervical cancer at the University of Queensland. Researchers at the National Cancer Institute, Georgetown University, and University of Rochester also contributed to the further development of the cervical cancer vaccine in parallel. [2] [3]
Frazer was born in Glasgow, Scotland. His parents were medical scientists, [4] and he was drawn to science from a young age. [5]
Frazer attended Aberdeen private school Robert Gordon's College. [4] He chose to pursue medicine over an earlier interest in physics due to physics having fewer research opportunities, [6] and he received his Bachelor of Science and Bachelor of Medicine and Bachelor of Surgery, at the University of Edinburgh in 1974 and 1977 respectively. It was during this time that he met his wife Caroline, whom he married in 1976. His 1978–79 residency was in the Edinburgh Eastern General Hospital, the Edinburgh Royal Infirmary and the Roodlands General Hospital in Haddington.
In 1980/81 Frazer immigrated to Melbourne after he was headhunted by Dr. Ian Mackay at the Walter and Eliza Hall Institute of Medical Research [7] to research viral immunology. In 1981 he discovered that the immunodeficiency afflicting homosexuals in San Francisco was also found in the gay men in his hepatitis B study, and in 1984 helped to confirm that HIV was a cause. [8] It was also found that another sexually transmitted virus was having a surprising effect: the human papilloma virus (HPV) infection seemed to be inducing precancerous cells. [9]
In 1985 he moved to the University of Queensland as a Senior Lecturer, with the opportunity to establish his own research laboratory. It was here in the Lions Human Immunology Laboratories he continued to research HPV in men, and contributed to HIV research. [10] During this time Frazer also taught at the university and ran diagnostic tests for the Princess Alexandra Hospital and [4] received his Doctor of Medicine qualification in 1988. [11]
On a 1989 sabbatical he met virologist Jian Zhou, and the two considered the problem of developing a vaccine for HPV – a virus that cannot be cultured without living tissue. [12] Frazer convinced Zhou to join him, and in 1990 they began to use molecular biology to synthesize particles in vitro that could mimic the virus. In March 1991 Zhou's wife and fellow researcher, Xiao-Yi Sun, [8] assembled by Zhou's instructions [13] two proteins into a virus-like particle (VLP), [14] resembling the HPV shell, from which HPV vaccine would ultimately be made. [5] The vaccine completely protects unexposed women against four HPV strains responsible for 70% of cervical cancers, [15] [16] which kill about 250,000 women annually. [17] [18] Frazer and Zhou filed a provisional patent in June 1991 and began work on developing the vaccine within UQ. To finance clinical trials, Australian medical company CSL, and later Merck, were sold partial patents. [19] (CSL has the exclusive license to sell Gardasil in New Zealand and Australia, Merck the license elsewhere.) [20] GlaxoSmithKline independently used the same VLP-approach to develop Cervarix, under a later US patent, licensing Frazer's intellectual property in 2005. [21]
Later in 1991 the research was presented at a US scientific meeting, and Frazer became Director of the Centre for Immunology and Cancer Research at the University of Queensland (later renamed The Diamantina Institute for Cancer, Immunology and Metabolic Medicine, where he held a personal chair as director). After three years in design, Gardasil went into testing, and Frazer became a professor in the university's Department of Medicine. In 1998 Frazer completed the first human trials for Gardasil, and became an Australian citizen. [4] [14]
US. 7,476,389, titled "Papilloma Virus Vaccines", was granted to co-inventors Ian Frazer and Jian Zhou (posthumously) on 13 January 2009. Its U.S. application was filed on 19 January 1994, but claimed priority under a 20 July 1992 PCT filing to the date of an initial [AU] Australian patent application filed on 19 July 1991.
In 2006 results from the four-year Phase III trials led to Australian and US regulatory approval. [14] Frazer's studies showed 100% efficacious protective immunity in HPV naïve women, but could not directly test protective immunity (against HPV exposure) in adolescent girls. As a surrogate test, antibody titer levels in vaccinated 9 to 15-year-old girls was shown high enough to give them the same level of immunity as vaccinated women. [22] It has been suggested that one way to bring cheaper equivalent vaccines to market is to mandate a similar induced immune response. [23]
Frazer administered the first official HPV-vaccination, [24] and was made 2006 Queenslander of the Year and Australian of the Year. [25] [26]
In the 2007 resolution of their US patent lawsuit, Frazer's and Jian Zhou's heirs (Zhou, who died in 1999, was survived by his widow Xiao-Yi Sun and a son Andreas) world-wide rights to the fundamental VLP science, and Frazer's and Zhou's priority to invention of that fundamental VLP science, were both established. [6] [21]
After 2009 reports of adverse Gardasil reactions, Frazer said "Apart from a very, very rare instance where you get an allergic reaction from the vaccine, which is about one in a million, there is nothing else that can be directly attributable to the vaccine." [27] Ian Frazer is one of the "most trusted" Australians, and some critics have accused Gardasil's advocates of exploiting patriotism [28] to promote its rapid Australian release. [29] (Australia's government had the world's most generous coverage for the drug, though it is the nation with the lowest cervical cancer mortality.) [20]
Ian Frazer lives in Brisbane, Australia with his wife Caroline. As of 2010, two of his sons are medical students and the third is a veterinary scientist. [30]
In 1999 Frazer received the Australian Biotechnology Award, and has since received more than twenty awards for science: [30]
In 2012 Frazer was named as a National Living Treasure by the National Trust of Australia (NSW). [39]
On 11 June 2012, Frazer was named a Companion of the Order of Australia (AC) for "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." [40]
In February 2014, it was announced that Frazer's new vaccine against genital herpes has passed human safety trials in a trial of 20 Australians. The vaccine is designed to prevent new infections. [41]
From February 2011 to February 2015, Frazer was the CEO and Director of Research at the Translational Research Institute, a joint initiative of The University of Queensland, Queensland University of Technology, the Mater Medical Research Institute and the Princess Alexandra Hospital. [42] He is researching immunoregulation and immunotherapeutic vaccines, supported by several US and Australian research funding bodies. [43] He is working on a VLP-based vaccine against hepatitis C, and is researching extensions to the VLP production technology for dengue fever and Japanese encephalitis vaccines. Frazer expects (50% effective) HIV vaccines to be available by 2028. [44] He is already overseeing trials of the first vaccine for skin cancer (the Squamous cancer, [45] caused by HPV) which might be ready before 2020. [46]
Frazer is the inaugural holder of the Queensland Government Smart State premier's fellowship, worth $2.5 million over 5 years. He has held continuous research funding from the National Health and Medical Research Council (NHMRC) since 1985, mostly relating to papilloma viruses or tumor immunology. He is currently a joint Chief Investigator on an NHMRC program grant and a NHMRC/Wellcome program grant, together worth more than $2 million a year.
He teaches immunology to undergraduates and graduate students at the University of Queensland, is Cancer Council Australia president, [47] Chairman of the ACRF's Medical Research Advisory Committee, and advises the WHO and the Gates Foundation on papillomavirus vaccines.
Frazer consults for many pharmaceutical companies on Immunomodulatory drugs, prophylactic and therapeutic vaccines. He sits on the board of three for-profit small biotech companies and a number of not for profit organisations.
Warts are non-cancerous viral growths usually occurring on the hands and feet but which can also affect other locations, such as the genitals or face. One or many warts may appear. They are distinguished from cancerous tumors as they are caused by a viral infection, such as a human papillomavirus, rather than a cancer growth.
Cervical cancer is a cancer arising from the cervix or in any layer of the wall of the cervix. It is due to the abnormal growth of cells that have the ability to invade or spread to other parts of the body. Early on, typically no symptoms are seen. Later symptoms may include abnormal vaginal bleeding, pelvic pain or pain during sexual intercourse. While bleeding after sex may not be serious, it may also indicate the presence of cervical cancer.
Human papillomavirus infection is caused by a DNA virus from the Papillomaviridae family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and results in either warts or precancerous lesions. These lesions, depending on the site affected, increase the risk of cancer of the cervix, vulva, vagina, penis, anus, mouth, tonsils, or throat. Nearly all cervical cancer is due to HPV, and two strains – HPV16 and HPV18 – account for 70% of all cases. HPV16 is responsible for almost 90% of HPV-positive oropharyngeal cancers. Between 60% and 90% of the other cancers listed above are also linked to HPV. HPV6 and HPV11 are common causes of genital warts and laryngeal papillomatosis.
The University of Queensland is a public research university located primarily in Brisbane, the capital city of the Australian state of Queensland. Founded in 1909 by the Queensland parliament, UQ is one of the six sandstone universities, an informal designation of the oldest university in each state. UQ is also a founding member of edX, Australia's leading Group of Eight and the international research-intensive Association of Pacific Rim Universities.
Anal cancer is a cancer which arises from the anus, the distal opening of the gastrointestinal tract. Symptoms may include bleeding from the anus or a lump near the anus. Other symptoms may include pain, itchiness, or discharge from the anus. A change in bowel movements may also occur.
Virus-like particles (VLPs) are molecules that closely resemble viruses, but are non-infectious because they contain no viral genetic material. They can be naturally occurring or synthesized through the individual expression of viral structural proteins, which can then self assemble into the virus-like structure. Combinations of structural capsid proteins from different viruses can be used to create recombinant VLPs. Both in-vivo assembly and in-vitro assembly have been successfully shown to form virus-like particles. VLPs derived from the Hepatitis B virus (HBV) and composed of the small HBV derived surface antigen (HBsAg) were described in 1968 from patient sera. VLPs have been produced from components of a wide variety of virus families including Parvoviridae, Retroviridae, Flaviviridae, Paramyxoviridae and bacteriophages. VLPs can be produced in multiple cell culture systems including bacteria, mammalian cell lines, insect cell lines, yeast and plant cells.
Human papillomavirus (HPV) vaccines are vaccines intended to provide acquired immunity against infection by certain types of human papillomavirus (HPV). The first HPV vaccine became available in 2006. Currently there are six licensed HPV vaccines: three bivalent, two quadrivalent, and one nonavalent vaccine All have excellent safety profiles and are highly efficacious, or have met immunobridging standards. All of them protect against HPV types 16 and 18, which are together responsible for approximately 70% of cervical cancer cases globally. The quadrivalent vaccines provide additional protection against HPV types 6 and 11. The nonavalent provides additional protection against HPV types 31, 33, 45, 52 and 58. It is estimated that HPV vaccines may prevent 70% of cervical cancer, 80% of anal cancer, 60% of vaginal cancer, 40% of vulvar cancer, and show more than 90% effectiveness in preventing HPV-positive oropharyngeal cancers. They also protect against penile cancer. They additionally prevent genital warts, with the quadrivalent and nonavalent vaccines providing virtually complete protection. The WHO recommends a one or two-dose schedule for girls aged 9-14 years, the same for girls and women aged 15-20 years, and two doses with a 6-month interval for women older than 21 years. The vaccines provide protection for at least five to ten years.
Ruth Arnon is an Israeli biochemist and codeveloper of the multiple sclerosis drug Copaxone. She is currently the Paul Ehrlich Professor of Immunology at the Weizmann Institute of Science, where she is researching anti-cancer and influenza vaccinations.
Gardasil is an HPV vaccine for use in the prevention of certain strains of human papillomavirus (HPV). It was developed by Merck & Co. High-risk human papilloma virus (hr-HPV) genital infection is the most common sexually transmitted infection among women. The HPV strains that Gardasil protects against are sexually transmitted, specifically HPV types 6, 11, 16 and 18. HPV types 16 and 18 cause an estimated 70% of cervical cancers, and are responsible for most HPV-induced anal, vulvar, vaginal, and penile cancer cases. HPV types 6 and 11 cause an estimated 90% of genital warts cases. HPV type 16 is responsible for almost 90% of HPV-positive oropharyngeal cancers, and the prevalence is higher in males than females. Though Gardasil does not treat existing infection, vaccination is still recommended for HPV-positive individuals, as it may protect against one or more different strains of the disease.
Cervarix is a vaccine against certain types of cancer-causing human papillomavirus (HPV).
Margaret Anne Stanley, OBE FMedSc, is a British virologist and epithelial biologist. She attended the Universities of London, Bristol, and Adelaide. As of 2018, she is an Emeritus Professor of Epithelial Biology in the Department of Pathology at the University of Cambridge and a Fellow of the Academy of Medical Sciences. She is also an Honorary Fellow of the UK Royal College of Obstetricians and Gynaecologists and an honorary fellow of Christ's College, Cambridge. Stanley is a research scientist in virology focusing on the human papillomavirus (HPV). Her research work has led to new scientific findings on HPV. Additionally, she uses her expertise on HPV to serve on multiple advisory committees and journal editorial boards.
Established in 1993 by Ludwig Cancer Research and McGill University, the Ludwig / McGill Cohort is one of the world's largest longitudinal studies of the natural history of human papillomavirus (HPV) infection and cervical cancer risk.
Harald zur Hausen NAS EASA APS was a German virologist. He carried out research on cervical cancer and discovered the role of papilloma viruses in cervical cancer, for which he received the Nobel Prize in Physiology or Medicine in 2008. He was chairman of the German Cancer Research Center in Heidelberg.
HspE7 is an investigational therapeutic vaccine candidate being developed by Nventa Biopharmaceuticals for the treatment of precancerous and cancerous lesions caused by the human papillomavirus (HPV). HspE7 uses recombinant DNA technology to covalently fuse a heat shock protein (Hsp) to a target antigen, thereby stimulating cellular immune system responses to specific diseases. HspE7 is a patented construct consisting of the HPV Type 16 E7 protein and heat shock protein 65 (Hsp65) and is currently the only candidate using Hsp technology to target the over 20 million Americans already infected with HPV.
A subunit vaccine is a vaccine that contains purified parts of the pathogen that are antigenic, or necessary to elicit a protective immune response. Subunit vaccine can be made from dissembled viral particles in cell culture or recombinant DNA expression, in which case it is a recombinant subunit vaccine.
The Australian Cancer Research Foundation (ACRF) is an Australian not-for-profit organisation which funds research into the prevention, diagnosis and treatment of all types of cancer. It provides multimillion-dollar grants for high-end research equipment, technologies, and infrastructure development to support the work of Australian cancer scientists.
Jian Zhou was a Chinese virologist and cancer researcher, who with fellow researcher Ian Frazer, invented Gardasil and Cervarix, the vaccines for stimulating human immunological resistance to the cervical cancer-inducing human papilloma virus.
Diane Medved Harper is a United States professor in the Department of Family Medicine at the University of Michigan. Her area of expertise is human papillomavirus (HPV) and the diseases associated with it, as well as colposcopy, and she was one of the investigators in the clinical trials of Gardasil and Cervarix, vaccines against HPV.
The Translational Research Institute (TRI) is Australia's first translational medical research institute dedicated to translating scientific discoveries into applications for medical practice.
Eighty per cent of Australian secondary schoolgirls have been vaccinated with Gardasil
'Ian went to huge efforts and he got them visas to Australia,' recalls Margaret Stanley. 'It says a lot about Ian. If anything should come over in your article, it's that Ian is an extremely kind man.'
Ian Frazer was set for a career in physics when a chance encounter with an immunologist, the father of his pen-friends girlfriend, changed his course.
Previous reports showed a remarkable 100% efficacy of a quadrivalent vaccine targeting HPV types 6, 11, 16, and 18 on outcomes related to vaccine HPV types in women with no evidence of previous exposure to those types [...] subgroups of subjects with no evidence of previous exposure to relevant vaccine HPV types were evaluated separately for vaccine efficacy. In these subgroups, efficacy of nearly 100% against all grades of cervical intraepithelial neoplasia and adenocarcinoma in situ related to vaccine HPV types was reported [...] Why is vaccine efficacy modest in the entire cohort? One factor is the apparent lack of efficacy among subjects with evidence of previous exposure to HPV types included in the vaccine. The FUTURE II trial showed no effect of vaccination
Ian Frazer's break-through vaccine is 100 per cent effective against the most common form of the virus that causes cervical cancer, according to final-stage trial results [...] a delighted Professor Frazer, 52, said last night: 'It is very rare, almost unheard of, to achieve a 100 per cent efficacy rate in any treatment, so these results are truly wonderful.'
Professor Frazer said Australia and other developed nations had effective Pap smear programs to reduce the incidence of cervical cancer. 'Despite this, cervical cancer continues to be a shocking disease for women in the developed world. Women living in poverty in the developing world, where Pap smears are not widely available, account for most of the 250,000 deaths from cervical cancer each year. So this vaccine has the potential to do most good in the developing world, where it could help lift women out of poverty by relieving the burden of disease
Ian Frazer was made Australian of the Year in 2006. He and his team at Princess Alexandra Hospital in Brisbane have developed a vaccine to beat cervical cancers that kill 250,000 women a year worldwide.
A woman dies of cervical cancer approximately every 2 minutes. In less developed countries, this type of cancer is the second most common in women and accounts for up to 300,000 annual deaths.
Cervarix may also protect against other types that cause cervical cancer, but more research is needed to confirm this. ... GlaxoSmithKline's] estimate of the prevalence of cervical cancer in United States roughly matches the National Cancer Institute's statistics. But according to the World Health Organization, the disease is far more common in developing countries, which account for 80 percent of the annual cases worldwide and about 190,000 deaths a year (compared to about 4,000 deaths in United States).
The federal government will also cover young women who are not in school and are still under 27 years through their general practitioners and community immunization clinics. This age group will receive the vaccine free from July 2007, until the end of June 2009.
Jian Zhou died in 1999, but he was an equal partner
with no breakthrough HPV infections due to waning immunity, the minimum protective anti-HPV antibody level could not be ascertained. Nevertheless, antibody titer has been used as a surrogate marker of protection in clinical trials, particularly in adolescent populations in whom efficacy studies are not feasible.(The 100% efficacious immunity is against HPV 16 and 18-related cervical cancer indicators.)
Evaluating the ability of a vaccine to induce a specific immune response is far less complex, less costly, and less time-consuming, than performing clinical trials to assess the ability of the vaccine to confer protective immunity.
It will mean a 70 per cent reduction in abnormal pap smears, and in parts of the world where there are no pap smears, a 70 per cent reduction in cervical cancer."
Ian embodies Australian know-how, determination and innovation
"For 23 million doses that have been given out, we received 12,424 reports of adverse events", Centers for Disease Control and Prevention study author Barbara Slade said. [...] Of the adverse reports in the US, 772 cases were considered serious
Frazer: "God's Gift to Women" proclaimed the cover of The Weekend Australian's magazine [...] In Australia, critics are almost perceived as national traitors
It was only on 23–24 February 2008 that the Victorian Cytology Service ran a job advertisement for a 'newly created position' to 'help establish and operate the new National HPV Vaccination Program' ( The Australian , 23–24 February 2008). That's 11 months after thousands of school girls had already received the jab.
'What is the most unusual or fun thing you've done in your job?' Being Australian of the Year and carrying the Commonwealth Games torch around Darling Harbour on a boat on Australia Day
For his creation of the first vaccine designed to protect against a cancer, Ian Frazer receives the Prime Ministers Prize for Science.
Through the development of vaccines, Ian has helped protect the lives of countless women
According to Frazer, the opportunity for vaccine improvement comes from novel adjuvants [...] and recombinant DNA
It's not exactly the same virus and therefore the vaccine we already have will not protect against that particular cancer. But the technology that we've used to develop a vaccine for cervical cancer should in principle be possible to use for prevention of some skin cancers.
If we can get encouraging results we will try and push it on as fast as we can. It's really a given that we try to focus on health problems that are significant ones.
Sometimes it seems almost impossible to believe that something we did all those years ago could have such a dramatic impact on so many people[ permanent dead link ]
I saw becoming a fellow of the AAS as recognition received towards the end of a career, whereas I see myself working in research for a lot longer yet