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Professor Judith A. Whitworth Director of the John Curtin School of Medical Research and Howard Florey Professor of Medical Research at the Australian National University

udith Whitworth is the Director of the John Curtin School of Medical Research (JCSMR)and Howard Florey Professor of Medical Research Jat the Australian National University in Canberra, and heads the High Blood Pressure Research Unit at JCSMR. She is an Ambassador for Canberra and an Ambassador for Women, and was the Telstra ACT Business Woman of the Year in 2002 and ACT Australian of the Year in 2004.

Professor Whitmore graduated with an MBBS from the University of Melbourne in 1967, an MD in 1974, a PhD in 1978 and a DSc in 1992; and has honorary degrees from the University of Sydney and the University of New South Wales. She has practiced medicine and conducted extivesive researched both in Australia and overseas. She chaired the Medical Research Committee of the National Health and Medical Research Council of Australia, and is a Past-President of the Australian Society for Medical Research and the High Blood Pressure Research Council of Australia. She also has been Australia’s Commonwealth Chief Medical Officer. She is currently chair of the WHO Global Advisory Committee on Health Research (2004–2007) and a member of the Board of the Global Forum forfo Health Research.

Pro Professorfessor Whitworth was made a ComCompanionpanion of the Order of Australiaalia in 2001 for her service to the advancementadvanceadvanc m of academic medicine,dicine, and as a major contribcontributor to research ppolicyo and medical rresearchesearch aadministrationdministration in AustraAustraliAustralialia anandd internationinternationally.a

Professor Whitworth’s research has focused on clinical and experimental studies in hypertension, ranging from studies of the mechanisms of glucocorticoid-induced hypertension to guideline Judithdevelopment and research for health policy.

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Studies on High Blood Pressure— Unravelling the Mysteries of Glucocorticoid Hypertension

My major research interest is in how adrenal glucocorticoids (GCs) raise blood pressure.

Glucocorticoid hypertension occurs naturally (e.g. Cushing’s syndrome, apparent mineralocorticoid excess, liquorice abuse) and is a common iatrogenic problem, given the extensive use of anti- inflammatory GC in clinical medicine.

My studies have shown that the major naturally occurring glucocorticoid, cortisol, contributes to the hypertension of chronic kidney disease and to essential hypertension.

It had been widely assumed that the hypertension produced by GCs was a consequence of salt and water retention, a mineralocorticoid (MC)-type action of GCs at high dose. Accordingly, synthetic GC for clinical use were designed to have minimal MC activity. I showed that, although this salt and water retention may occur, it is not the cause of GC hypertension. Blood pressure rises are seen with extremely low sodium intake, around 10% of normal intake; the hypertension produced by synthetic steroids is not associated with salt and water retention; and MC receptor antagonism does not modify GC hypertension.

Thus, other mechanisms must be involved. My work has excluded a major role for a range of vasoactive hormones and for the sympathetic nervous system, and has delineated the key hemodynamic changes. The clue to the etiology came from our observation in rats that the amino acid L-arginine—the substrate for vasodilator nitric oxide, prevented adrenocorticoid hornone hypertension, implicating abnormalities in the nitric oxide (NO) system. My group went on to show that reactive nitrogen intermediates (a marker of NO production) were reduced by GC treatment in both humans and rats, that forearm pressor responsiveness to acetylcholine (which stimulates NO) was decreased by GCs, and that both ACTH and the major rat GCS corticosterone suppressed expression of NO synthase (NOS 2 and 3) in the kidney. The superoxide scavenger tempol, which increases NO bioavailability, also prevents GC hypertension. Increase in reactive oxygen species is prominent in GC hypertension and lis ikely due to increased activity of the enzyme NADPH oxidase, at least in the rat. Antioxidants are being tested in human studies.

In summary, my work has overturned conventional dogma on the causation of GC hypertension and has identified a causal mechanism, that is amenable to therapy. This is particularly important, as my work and that of others suggest that cortisol may be involved in as much as 30% of all human hypertension.

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Improving the Management of People with Hypertension

Over 600 million people worldwide have high blood pressure, and may suffer the consequences of stroke, heart attack, and kidney disease. I was a member of the writing group for the World Health Organization/ International Society of Hypertension (WHO/ISH) Guidelines on Management of Hypertension, published in 1999 and now cited over 2000 times. I also contributed to WHO/ISH statements on global prevention of hypertension and the safety of calcium channel blockers as well as on hypertension and stroke, and was a corresponding author for the 2003 WHO/ISH Statement on Hypertension Management.

Why did you choose science as a career? I had polio as a child and spent many years in and out of hospitals. Not long after, effective polio vaccines were developed. Thus, from an early age I was interested in medicine and well aware of the great power of medical research. After graduating from university, I spent a term in the clinical research unit at the Royal Melbourne Hospital. Research at that time was a lot of fun, and it has continued to be so.

How have you helped to improve or shape the advancement of science in your country? I became interested in research policy through my membership to the Australian Society for Medical Research. I served on the Board of Directors and as the President, and became active in promoting medical research to the community and in lobbying for increased investment in medical research in Australia.

Chairmanship of Australia’s Medical Research Committee, and then a period as Commonwealth Chief Medical Officer, allowed me to help shape national medical research policy; and my current position as Chair of the WHO’s Global Advisory Committee on Health Research provides an avenue for shaping research policy and policy for health research at an international level.

My own institution, the John Curtin School of Medical Research, is very active in promoting science and research to the public, particularly to young people. We are developing a display of our research achievements (including our Nobel Prize medals) as part of the new Jackie Chan Science Center at JCSMR, made possible by a generous donation from Asia’s biggest movie star.

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Why is science so important in our current day and age? A role I particularly enjoy is membership of the Editorial Board of Cosmos (http://www.comsosmagazine.com), an award-winning Australian science magazine. Cosmos covers the science of everything, because so much of everything we take for granted in daily life is based on science. Our homes, our transport, our communications, our health, our defense, our environment— they are all in large part products of science, research, and innovation.

Discuss the development and current status of science in your country.

Australia became a nation following federation in 1901. Medical research was relatively underdeveloped in the first half of the 20th century, but there were some outstanding individual contributions. For example, Norman Gregg identified the causal relationship between rubella in early pregnancy and subsequent congenital defects, Macfarlane Burnet made fundamental contributions to the knowledge of infectious disease and John Cade discovered the value of lithium for the control of manic- depressive disease.

Since then, Australians have produced a raft of pivotal clinical and fundamental studies. Working in Australia, Burnet won the Nobel Prize in 1960 for the discovery of acquired immunologic tolerance, Eccles in 1963 for studies on neurotransmission, Doherty and Zinkernagel in 1996 for understanding how the immune system recognizes virus-infected cells, and Warren and Marshall in 2005 for the discovery of H. pylori and its role in peptic ulcer disease. Other examples include the global eradication of small pox (Fenner), the identification of the function of the thymus (Miller), the identification of colony-stimulating factors (Metcalf), and the discovery of apoptosis (Kerr).

Medical research in Australia enjoys strong public support, and this has been reflected by increased government investment. A recent study by Access Economics (2003) found that, on average, every dollar invested in Australian health and medical research gave a fivefold return. Australians value medical research and recognize the important role it has played in helping them live longer and healthier lives.

Contact Details: Professor Judith Whitworth The John Curtin School of Medical Research Building 54 The Australian National University Canberra ACT 0200 Australia Tel: +61 2 6125 2589 Fax: +61 2 6125 2337 URL: http://jcsmr.anu.edu.au

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