Pathologist

Born: 11 June 1937, Adelaide

Dr J Robin Warren was born in 1937 in Adelaide, South Australia. He graduated MB BS from the University of Adelaide in 1961. After training at the Royal Melbourne Hospital, he was admitted to the Royal College of Pathologists of Australasia in 1967. Since then, he has been a senior pathologist at the Royal Perth Hospital in Western Australia.

In 1979, Dr Warren first observed the presence of small curved bacteria on a biopsy of the gastric mucosa. Follow-up during the next two years showed that the bacteria were frequently present only on gastric-type epithelium, and were closely linked to a specific variety of gastritis. In 1981, Dr Warren met Barry Marshall, registrar in the gastroenterology department, and a fruitful partnership followed which demonstrated the clinical significance of the bacteria. They cultured the bacteria, identified as a new species and now called Helicobacter pylori. They demonstrated the association of H. pylori and peptic ulcers, particularly duodenal ulcers. Eradication of the bacteria resulted in healing of the gastritis and the ulcers rarely recurred.

Dr Warren was the guest of honour at the Sixth International Workshop on Campylobacter, Helicobacter and Related Organisms in 1991. He received the Distinguished Fellows Award of the College of Pathologists in 1995; the Inaugural Award of the First Western Pacific Helicobacter Congress in 1996; and the Medal of the University of Hiroshima in 1996. He received, jointly with Professor Marshall, the Warren Alpert Foundation Prize at Harvard University in 1994; the Australian Medical Association (WA) Award in 1995; the Paul Ehrlich and Ludwig Darmstaedter Award, Goethe-Universitat, Frankfurt, Germany in 1997; and the honorary degree of Doctor of Medicine from the University of Western Australia in 1997.

His work with Marshall

Peptic ulcer disease has been a major medical problem in most countries of the developed world: in Australia alone, one in ten people might expect to suffer from ulcer disease over their lifetime. Ulcer medications could provide temporary healing, but 80% of patients would suffer a relapse within a year of stopping treatment. It seemed that ulcer sufferers were destined to hear the familiar phrase, "You'll just have to learn to live with it" for a long while yet. Thanks to the persistence of two Australian researchers, this is no longer the case.

In 1979, Dr Robin Warren, a pathologist at the Royal Perth Hospital, reported the presence of an unusual bacterium in biopsies from patients suffering gastritis (stomach inflammation). The report was greeted with scepticism: no bacteria could survive in the acidic environment of the stomach, or so everyone thought. Nevertheless, Warren continued his studies of this bacterium over the next two years, confirming that the infection was common and closely linked to a specific type of gastritis. Warren could not proceed further without active clinical assistance, to provide better biopsies and demonstrate any clinico-pathological correlation. Then in 1981, Dr Barry Marshall, a gastroenterology registrar at the hospital, approached Warren looking for a research project. The ensuing collaboration was to result in what has been described as possibly the most significant event in medicine in Australia in the last 20 to 30 years.

Warren and Marshall commenced their research by studying a large group of patients who had undergone endoscopy for gastric conditions. They reconfirmed the link between gastritis and the presence of the bacterium that Warren had first noticed two years earlier, and also noted that the bacterium was present in all the patients with duodenal ulcer, most patients with gastric ulcer, and about half the patients with gastric cancer. It seemed that it was rare to have the specific gastritis or to develop an ulcer without also being infected with this new bacterium.

In 1982, Warren and Marshall succeeded in culturing the bacterium, and discovered that it was similar to campylobacter, which can cause enteritis. Eventually, the newly discovered bacterium was to be declared part of a new genus, Helicobacter, and given the name Helicobacter pylori. The proposed hypothesis was that infection with H. pylori would cause gastritis, which could in turn lead to ulceration.

The peer response showed the same scepticism that greeted Warren's initial observations, and for a number of years the majority of the medical profession dismissed the hypothesis. Despite this, the Perth team continued to gather evidence of their theory, dramatically in one case. Deciding that the best way to prove the findings was to show exactly what happened when infected with H. pylori, Marshall swallowed a culture of the bacterium. A week later, he began suffering acute symptoms of gastritis, and biopsies revealed that he had developed both infection with H. pylori and severe acute gastritis. Fortunately, the sequel was a successful case of "Physician, heal thyself"!

At this stage, bismuth subcitrate was commonly used to treat ulcers, although it was uncertain how the drug worked. Marshall surmised that it might kill the H. pylori bacteria, and he subsequently discovered that a combination of bismuth with antibiotics completely eradicated the bacteria. He then set out to test the hypothesis that elimination of H. pylori could result in a permanent cure of gastric ulcer.

From 1985 to 1987, Warren and Marshall studied the use of antibiotics as treatment for ulcer. Their finding that 80% of patients were permanently cured of their ulcer if H. pylori were eradicated, proved a landmark in clinical gastroenterology practice. It resulted in a complete reassessment of ulcer treatment, and this therapy is now accepted as an essential part of the management of ulcer disease.

The question remained as to how H. pylori could survive in the acidic environment of the stomach. Warren showed that the bacteria grow on the surface epithelium, covered with a thick layer of normal mucus. They need only withstand the same conditions as the surface cells. In addition, Marshall found that the bacteria produce a large amount of urease, an enzyme that breaks down urea into ammonia and carbon dioxide to form a protective alkaline layer around them. This discovery enabled Marshall to devise the rapid urease test, which allowed patients to have a diagnosis within 20 minutes of having a biopsy, and so start curative therapy immediately. Going a step further, Marshall later developed a non-invasive breath test: patients could swallow a small amount of urea labelled with a carbon isotope, and if H. pylori were present, the urea would break down to release carbon dioxide in the breath. Following clinical trials of this test between 1993 and 1997, it has become a very popular and accurate means of diagnosing H. pylori in patients.

Since Warren and Marshall's first articles on Helicobacter pylori appeared in the prestigious medical journal The Lancet in 1983, interest in, and articles about, H. pylori have proliferated, and the study of this bacterium has become a research industry in itself. This fact alone demonstrates the importance of Warren and Marshall's discovery in the clinical field of gastroenterology.

The significance of Warren and Marshall's discovery has also been reflected in the awards they have won for their work in uncovering H. pylori, including: the Warren Alpert Prize, Harvard Medical School (1995), the Paul Ehrlich and Ludwig Darmstaedter German medical research prize (1997), and the inaugural Florey Medal Award (1998) for a major Australian discovery in the biomedical sciences of benefit to human health. Both researchers have also been honoured individually. Among other awards, Robin Warren has received the Distinguished Fellows Award of the College of Pathologists (1995), the Medal of the University of Hiroshima (1996), and the honorary degree of Doctor of Medicine from the University of Western Australia (1997). Barry Marshall's awards include the Albert Lasker Award (1995), the Australian Achiever Award (1998), the Burnet Fellowship of the National Health & Medical Research Council (1998), and the Benjamin Franklin Award for Life Sciences (1999).