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).
The discovery of H. pylori as the cause of gastritis and gastric
ulcer has had profound implications: finally, it was possible to cure
a disease previously considered intractable, and thus spare countless
people a lifetime of pain, distress and inconvenience. It is indeed
fortunate for ulcer sufferers worldwide that Robin Warren and Barry
Marshall possessed all the traits of outstanding scientific researchers:
ability, persistence in the face of scepticism and setbacks, salesmanship
and, not least, team spirit.
References: Faulding Florey Medal nomination (Prof. A Lee);
NHMRC 1998 Annual Report, pp20-22
