The Nobel Prize in

Medicine or
Physiology 2005
Barry James Marshall (Australian
Gastroenterologist)
John Robin Warren (Australian Pathologist)

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Barry James Marshall

Born in 30 September 1951 in
Kalgoorlie
Attended high school in Newman
College
Graduate from University of
Western Australia MBBS program
in 1975
Married with Adrienne in 1972
when he was in Year 5
Began training as a specialised
physician in 1978
Moved to Royal Perth Hospital in
1979.
Meet J. Robin Warren in 1981
and started on gastroenterology
project with him.
http://blogs.bmj.com/fg/files/2014/12/Prof-Barry-Marshall-acknowledge-Adrienne-Marshall-

John Robin Warren AC

Born on the 11th of June 1937 in North
Adelaide, SA.
Attended Westbourne Park School and
St. Peters College before receiving his
M.B.B.S. degree from the University of
Adelaide in 1961.
Married Winifred Theresa Warren in
the early 1960s and had five children.
Elected to the Royal College
Pathologists of Australasia in 1967

of

Met with Dr. Barry Marshall in 1981

and undertook research into H. pylori.
After receiving the Nobel Prize, he was
elected a Fellow of the Australian
Academy of Science in 2006.
Made a Companion of the Order of
Australia in 2007.
http://www.chinadaily.com.cn/english/doc/200510/03/xin_5010020321057042064430.jpg

Helicobacter pylori
Its Role in Gastritis and Peptic Ulcer Disease

What is Helicobacter
pylori?
Spiral-shaped, gram-negative,
microaerophilic (need low level
of O2) bacterium
Class 1
cancer)

carcinogen

(induce

Invades the mucosal lining and

cause 95% DU and 75% GU
Associated with gastric cancer
and lymphoma
Patients infected with H.pylori
has been found to have higher
levels of gastrin and pepsinogen
and reduced level of
somatostatin and impaired
duodenal bicarbonate secretion
Increase pH in stomach,
promote colonization, promoting
https://wellnessbysilvia.files.wordpress.com/
development of gastric
2014/09/helicobacter.jpg

Timeline of H. pylori Discovery

16th century BC first description of
gastric symptoms, and relation of
gastric symptoms and meal times
16th century findings and description
of gastric and duodenal ulcers on
autopsies
1893 first well-known of gastric
helicobacters; description of
spirochetes inhabiting gastric gland
and canaliculi of parietal cells

H pylori in 20 century
th

1924 discover urease in stomach, thought that is

naturally occurring
1940 Freedburg observes spiral-like bacteria in 40%
of specimens
1950s 1960s Ito observed spirilli in gastric mucosa
appearance under electron microscope
1954 There is no bacteria in human stomach
presence of bacteria is contamination
1964 First treatment of PUD using anti-bacterial
agent; rejected due to lack of clinical trials
1970s study presence of bacteria and inflammation
during gastric ulcer. Found that carbonexolone treated
gastric ulcers

Discovery of H. pylori by
Marshall and Warren
1979, Warren discovered the bacteria on a chronic gastritis biopsy
using Warthin-Starry silver stainsmall curved, spiral bacteria were
observed!
1982, Marshall and Warren studied to determine the relationship
between H. pylori and PUD and a new genus of helicobacter was
successfully cultured.
1984, Marshall intentionally consumed H. pylori after failing to infect
pigs. Then he used antibiotics to relieve his symptoms.
1985, Marshall published the results of self-induced infection in MJA.
1987, NEJM published a study on H. pylori which agrees on their
discovery
1989, Warren developed the 14C-urea breath test for the detection of
gastric Campylobacter pylori infection, and was published in MJA.
1994, WHO accepted that H. pylori as a causative factor in stomach
cancer.

Problems with
researching H. pylori
Skepticism
Lack of good quality biopsies
Use of surgical or post mortem
specimens
Inadequate clinical specimens and
technology to culture bacteria

Why Worth a Nobel Prize

Award?
Before the discovery
in era of 1980s
the cause of peptic ulcer was assumed to be due to
excess gastric acid secretion from:
lifestyle, diet, alcohol and drugs, or is genetically determined

accepted that bacteria could not survive in acidic

environment of normal human stomach stomach is
sterile!!!
H2 receptor antagonist drugs to lower stomach acid
secretion were found effective to treat peptic ulcer
ranitidine (Zantac)
cimetidine (Tagamet)

helicobacter in gastric lining was never linked to

be the causative
was seen as a non-pathogenic commensal flora

Why Worth a Nobel Prize

Award?

Treatments before Discovery

lifelong treatment of acid-blocking drugs

Only ease symptoms not treat underlying
disease
almost always recurring as soon as the drug
stopped

removal surgery of the lower third of the

stomach
Cause difficulty in maintaining weight reduce
ghrelin secreting cell
Sometimes cause gastric cripple

Took long time treatment

Why Worth a Nobel Prize

Award?
After Discovery
The first to prove the association of H. pylori as pathogen for
peptic ulcer disease
Dramatic change over the medical perspective and
understanding
Prove some bacteria can survive stomach acid
Urease in H. pylori produces ammonia to neutralise stomach
acid
NH2CONH2 + H+ + 2H2O 2NH4+ + HCO3-

Flagella which allows motility in viscous mucus

Adhesins which facilitate adherence to stomach wall
Provides a suitable environment for survival and colonisation

Prove H. pylori is not a commensal but a cause of PUD and

stomach cancer
H. pylori attack stomach lining, causes acid to get through the lining
Enhanced production of free radicals and causes increased rate of host cell
mutation

Impact of discovery
towards current medical
practice

Treatment and management of peptic ulcers

decline in PUD and gastric cancer in late 20th
century
Provide simple, much cheaper antibiotic cure for
PUD

Reduce usage of stomach surgery

Reduce medical cost burden
Faster treatment
Effective recovery
Reduces ulcer relapse

http://www.faseb.org/portals/2/pdfs/opa/pylori.pdf

Impact of discovery
towards current research
Made H. pylori infection one of the most
studied paradigms of pathogen biology
1. Listed as carcinogen associated with
gastric carcinoma and MALT lymphoma
2. Association with other conditions
3. Further research; genomic diversity,
pathogenicity, mechanism, development of
urea breath test

Whats next?
Antibiotic resistance
Metronidazole
In U.S., Clarithromycin resistance is found in
20% of H. pylori positive patients

Association of lifestyle, H. pylori, and

development of gastric cancer
Why does certain population have higher risk
of developing gastric cancer than others
despite similar infection rates?

Possible Future
Development
Changing epidemiology of upper gastrointestinal
diseases (peptic ulceration, oesophageal and gastric
adenocarcinoma, gastro-oesophageal reflux disease
and sequelae) with changing prevalence of colonisation
with Helicobacter pylori
Recognition of host factors that predispose to diseases
induced by H pylori
Definition of genetic characteristics of H pylori that are
associated with significant variance in risk of disease
Vaccinations against certain diseases based on specific
interactions between H pylori and host
Colonisation of some hosts with strains of H pylori with
low virulence to reduce risk of particular diseases

Possible Future
Development
In 1989, Strachan proposed the hygiene
hypothesis, stating that the exposure to infectious
agents and living in an unhygienic environment
might educate the immune system and thus
protect against the development of allergic diseases.
Ondek has created and patented a derivative of H.
pylori that has retained its immune regulatory
properties to combat the escalating problem of
allergy.
Current targets are eczema, food allergies and
allergic asthma.
Further research to target more allergic reactions.

References:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3047919/
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1113159/
http://ondek.com/our-approach/
http://www.nobelprize.org/nobel_prizes/medicine/laurea
tes/2005
/
http://www.ncbi.nlm.nih.gov/books/NBK2432/.
http://
www.nobelprize.org/nobel_prizes/medicine/laureates/200
5/marshall-lecture.pdf
http://www.ncbi.nlm.nih.gov/pubmed/2593958
http://www.ncbi.nlm.nih.gov/pubmed/3335917
https://
www.science.org.au/teacher-notes-dr-robin-warren
http://www.faseb.org/portals/2/pdfs/opa/pylori.pdf