Timeline of peptic ulcer disease and Helicobacter pylori
This is a timeline of the events relating to the discovery that peptic ulcer disease is caused by "H. pylori".In 2005, Barry Marshalland Robin Warrenwere awarded the Nobel Prize in Physiology or Medicinefor their discovery that peptic ulcer disease(PUD) was primarily caused by " Helicobacter pylori", a bacteriumwith affinity for acidic enivironments, such as the stomach. As a result, PUD that is associated with "H. pylori" is currently treated with antibiotics used to eradicate the infection. For 30 years prior to their discovery it was widely believed that PUD was caused by excess acidin the stomach. During this time, acid control was the primary method of treatment for PUD, to only partial success; among other effects, we now know that acid suppression alters the stomach milieu to make it less amenable to "H. pylori" infection.
Before the 1950s, there were many microbiological descriptions of bacteria in the stomach and in gastric acid secretions, lending credence to both the infective theory and the hyperacidity theory as being causes of peptic ulcer disease. A single study, conducted in 1954, did not find evidence of bacteria on biopsies of the stomach stained traditionally; this effectively established the acid theory as
dogma. This paradigm was altered when Warren and Marshall effectively proved Koch's postulatesfor causation of PUD by "H. pylori" through a series of experiments in the 1980s; however, an extensive effort was required to convince the medical community of the relevance of their work. Now, all major gastrointestinal societies agree that "H. pylori" is the primary non-drug cause of PUD worldwide, and advocate its eradication as essential to treatment of gastric and duodenal ulcers. Additionally, "H. pylori" has been associated with lymphomas and adenocarcinomasof the stomach, and has been classified by the World Health Organizationas a carcinogen. Advances in molecular biologyin the late twentieth century led to the sequencing of the "H. pylori" genome, resulting in a better understanding of virulence factors responsible for its colonization and infection, on the DNA level. ;1761:Pain is associated with stomach ulcers.cite journal |last=Buckley | first=Martin J.M |coauthors=Colm A. O'Morain |year=1998 |title="Helicobacter" biology - discovery|journal=British Medical Bulletin |volume=54|issue=1|pages=7–16 | pmid = 9604426 ]
;Pre 16th century:
Hippocratesfirst describes gastricsymptoms.cite journal |last=Kidd | first=Mark |coauthors=Irvin M. Modlin |year=1998 |title=A century of "Helicobacter pylori" |journal=Digestion |volume=59 |pages=1–15 |pmid = 9468093 |url=http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=dig59001 |doi=10.1159/000007461] : Avicennanotes the relationship between gastric pain and mealtimes.
;1586:Marcellus Donatus of Mantua performs autopsies and describes
gastric ulcers.cite book |last=Unge |first=Peter |editor=Barry Marshall |title=Helicobacter Pioneers: Firsthand Accounts from the Scientists Who Discovered Helicobacters |year=2002 |publisher=Blackwell Science Asia |location=Victoria, Australia |pages=203-213 |chapter="Helicobacter pylori" treatment in the past and in the 21st century |id = ISBN 0-86793-035-7]
;1812:Broussais discovers that if acute
gastritisin untreated, it can become chronic.
;1868:Kussmaul suggests using
bismuthcompounds, an anti-bacterial agent, in order to treat peptic ulcers ( bismuth subsalicylatehas since been used in many commercial drugs, including Pepto Bismolas part of antibacterial "H. pylori" treatment). The antibacterial properties of bismuth were not known until much later.
;1880:J. Cohnheim suggests that ulcers may be caused by chemical factors.
;1881:Klebs notes the presence of bacteria-like organisms in the lumen of the
gastric glands. Fukuda, Yoshihiro "et al.", "Kasai, Kobayashi and Koch's postulates in the history of "Helicobacter pylori", in "Helicobacter Pioneers", pp. 15-24.]
Giulio Bizzozeroobserves spiral organisms in the stomach of dogs. [cite journal |last=Bizzozero |first=Giulio |authorlink=Giulio Bizzozero |year=1893 |title=Ueber die schlauchförmigen Drüsen des Magendarmkanals und die Beziehungen ihres Epitheles zu dem Oberflächenepithel der Schleimhaut |journal=Archiv für mikroskopische Anatomie |volume=42 |pages=82–152] Figura, Natale & Laura Bianciardi, "Helicobacters were discovered in Italy in 1892: An episode in the scientific life of an eclectic pathologist, Giulio Bizzozero", in "Helicobacter Pioneers", pp. 1-13.]
;1906:Krienitz finds bacteria in the stomach of people with gastric cancer.:Turck feeds dogs "Bacillus coli" and produces ulcers. [cite journal |last=Turck | first=F.B. J.M |year=1906 |title=Ulcer of the stomach: Pathogenesis and pathology: Experiments in producing artificial gastric ulcer and genuine induced peptic ulcer|journal=Journal of the American Medical Association|volume=46|pages=872 ]
;1910:Schwartz publishes the excess acid theory of the ulcer, coining the famous phrase "no acid, no ulcer.":Gibelli claims to be unable to reproduce Turck's study where he artificially created ulcers by feeding dogs bacteria.
;1913:Rosenow suggests that
Streptococciproduce ulcers. [cite journal |last=Rosenow | first=E.C. J.M |year=1913 |title=The production of ulcer of the stomach by injection of streptococci|journal=Journal of the American Medical Association |volume=61|pages=1947 ]
Antacids are first recommended for the treatment of PUD.:Bacteria are associated with PUD, but it is assumed that the bacteria reside in the mouth. [cite journal |last=Rosenow |first=E.C. |coauthors=A.H. Sanford |year=1915 |title=The Bacteriology of Ulcer of the Stomach and Duodenum in Man|journal=Journal of Infectious Diseases |volume=15|pages=219–226 ]
;1919:Kasai and Kobayashi isolate
spirochetes in cats and transmit them to rabbits, producing ulcers. [cite journal |last=Kasai |first=K. |coauthors=R. Kobayashi |year=1919 |title=The stomach Spirochete Occurring in Mammals |journal=Journal of Parasitology |issue=6|pages=1–11 ]
;1924:Luck and Seth discover
ureasein the human stomach, which they believe is naturally occurring. [cite journal |last=Luck |first= |coauthors=Seth|year=1924 |title=Gastric Urease |journal=Biochemical Journal |volume=37 |pages=1227–1231] It is now known that one of the virulence factors of "H. pylori" is the urease enzyme, which splits ureainto ammonia
;1925:Hoffman injects a small sample from a human with PUD into a guinea pig, producing ulcers, and isolates a bacterium which he believes caused the ulcers. [cite journal |last=Hoffman | first=A |year=1925 |title=Experimental gastric duodenal inflammation and ulcer, produced with a specific organism fulfilling Koch's postulates|journal=American Journal of Medical Science |volume=170|pages=212 ]
;1936:First edition of the Russian "Large Medical Encyclopedia" suggests infection is one of the causes of PUD.Mozorov, Igor A., "Helicobacter pylori" was discovered in Russia in 1974", in "Helicobacter Pioneers", pp. 105-118.]
;1939:A. Stone Freedberg begins a study to look for bacteria in the human stomach at
Beth Israel Hospital. He finds "H. pylori". It is rumored that others cannot reproduce the results, although no negative results are published.Freedberg, A. Stone, "An Early Study of Human Stomach Bacteria", in "Helicobacter Pioneers", pp. 25-28.] :James Doenges describes spirochetes in autopsies. [cite journal |last=Doenges |first=James |year=1939 |title=Spirochaetes in the gastric glands of the Macaus Rhesus and Human without definite history of related disease |journal=Archives of Pathology |volume=27 |pages=469–477]
;1940:Freedberg and Baron observe spirochetes in autopsies. [cite journal |last=Freedberg |first=A.S. |coauthors=L.E. Baron |year=1940 |title=The presence of spirochaetes in human gastric mucosa |journal=American Journal of Digestive Diseases |volume=7 |pages=443–445]
;1948:Fitzgerald and Murphy hypothesize that PUD is caused by acid eating away mucosa, and demonstrate the effectiveness of
ureaas a treatment for PUD.O'Connor, Humphrey J. and Colm A. O'Morain, "Gastric urease in ulcer patients in the 1940s: The Irish connection", in "Helicobacter Pioneers", pp. 29-38.]
;1953:Dintzis and Hastings are able to stop
ureaseproduction in mice with antibiotics, suggesting a relationship between urease and a bacterial infection. [cite journal |last=Dintzis |first=R.Z. |coauthors=A.B. Hastings |year=1953 |title=The effect of Antibiotics on Urea Breakdown in Mice. |journal=Proceedings of the National Academy of Sciences of the USA |volume=39 |pages=571–8 |pmid = 16589306 |url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=16589306 |doi=10.1073/pnas.39.7.571]
;1954:Palmer publishes a study which finds no bacteria in the human stomach. He concludes earlier discoveries were a result of contamination. Unfortunately, he chooses not to use a silver
staining method, which will be later used to reveal "H. pylori" by Warren and Marshall. [cite journal |last=Palmer |first=E.D. |year=1954 |title=Investigation of the gastric mucosa spirochetes of the human |journal=Gastroenterology |volume=27 |issue=2 |pages=218–220 | pmid = 13183283]
;1955:Tarnopolskaya observes that penicillin cures some peptic ulcers.:Moutier and Cornet suggest treating gastritis with antibiotics.:Kornberg and Davies observe that antibiotics reduce urease in cats. [cite journal |last=Kornberg |first=H.L. |coauthors=R.E. Davies |year=1955 |title=Gastric Urease |journal=Physiology Review|volume=35 |issue=1|pages=169–177|pmid = 14356931]
;1957:Charles Lieber and Andre Lefèvre discover that antibiotics reduce gastric urea to
ammoniaconversion. [cite journal |last=Lieber |first=C.S. |coauthors=A. Lefèvre |year=1957 |title=Effect of oxytetracycline on acidity, ammonia, and urea in gastric juice in normal and uremic subjects |journal=Comptes Rendus des Séances et Mémoires de la Société de Biologie |volume=151|issue=5|pages=1038–1042|pmid = 13500735]
;1958:Gordon observes that penicillin cures some peptic ulcers.:
John Lykoudissuccessfully treats his own gastroenteritiswith antibiotics.Rigas, Basil and Efstathios D. Papavassiliou, "John Lykoudis: The general practitioner in Greece who in 1958 discovered etiology of, and a treatment for, peptic ulcer disease", in "Helicobacter Pioneers", pp. 75-84.] :Lieber and Lefèvre present their results at the World Congress of Gastroenterology in Washington. It is not well received because of the widespread belief that bacteria cannot survive in the human stomach, due to Palmer.Lieber, Charles S. J., "How it was discovered in Belgium and the USA (1955-1976) that Gastric Urease was Caused by a Bacterial Infectio", in "Helicobacter Pioneers", pp. 39-52.]
;1959:Lieber and Lefèvre publish a follow-up study demonstrating that antibiotics prevent the conversion of urea to ammonia in the human stomach. [cite journal |last=Lieber |first=C.S. |coauthors=A. Lefèvre |year=1959 |title=Ammonia as a source of gastric hypoacidity in patients with uremia|journal=Journal of Clinical Investigation |volume=38|pages=1271–7|pmid = 13673083|url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=13673083 |unused_data=|issue8 |doi=10.1172/JCI103902] :Conway "et al." call into question the extent of urease produced by bacteria in mice, as an argument against the bacterial theory of PUD. [cite journal |last=Conway |first=E.J. |coauthors=O. Fitzgerald, K. McGeeney, and F. Geoghegan |year=1959 |title=The location and origin of gastric urease |journal=Gastroenterology |volume=37 |pages=449–56|pmid = 13811656]
;1960:Vital and Orrego observe
campylobacter-like organisms in the stomachs of cats and dogs. [cite journal |last=Vital |first=J.D. |coauthors= H. Orrego |year=1960 |title=Electron microscope observations on the fine structure of parietal cells |journal=Journal of Biophysical and Biochemical Cytology |volume= 7|pages=367–72|pmid = 13842039|url=http://www.jcb.org/cgi/reprint/7/2/367 |doi=10.1083/jcb.7.2.367 ] :Lykoudis is awarded a Greek patent (#22,453) for his antibiotic treatment of PUD.
;1962:Susser and Stein publish a paper identifying a cohort phenomenon of PUD in England. This is taken as evidence for stress causing PUD. [cite journal |last=Susser |first=M. |coauthors=Z. Stein|year=1962 |title=Civilization and peptic ulcer|journal=Lancet|volume=1 |pages=115–9|pmid = 13918500. Reprinted as cite journal | author = Susser M, Stein Z | title = Civilization and peptic ulcer. 1962. | journal = International Journal of Epidemiology | volume = 31 | issue = 1 | pages = 13–7 | year = 2002 | pmid = 11914283|url=http://ije.oxfordjournals.org/cgi/content/full/31/1/13 | doi = 10.1093/ije/31.1.13]
;1967:Susumu Ito describes campylobacter-like organisms attached to a gastric
epithelial cell. [cite book |last=Ito |first=Susumu | editor=Heidel, US and Code, CF | title=Handbook of Physiology Section 6 Volume 2 | year= 1967 |publisher= American Physiological Society| pages= 705-741 | chapter= Anatomic structure of the gastric mucosa]
;1971:Howard Steer observes "H. pylori" from biopsies of a patient with ulcers.Steer, Howard W., "The discovery of "Helicobacter pylori" in England in the 1970s", in "Helicobacter Pioneers", pp. 119-129.]
;1972:The first report of successfully using
furazolidone(an anti-bacterial agent) to treat PUD in China.Xiao, Shu Dong "et al.", "How we discovered in China in 1972 that antibiotics cure peptic ulcer", in "Helicobacter Pioneers", pp. 165-202.]
;1974:Morozov observes "H. pylori"; he does not connect this discovery to PUD.:A well regarded study of PUD is published which does not mention bacteria. [cite journal |last=Patrick |first=W.J.A. |coauthors=D. Denham, and A.P.M. Forrest|year=1974 |title=Mucous change in the human duodenum: a light and electron microscopic study and correlation with disease and gastric acid secretion |journal=Gut |volume=15 |issue=10|pages=767–76| pmid = 4434919 |doi=10.1136/gut.15.10.767 ]
;1975 :Steer and Colin-Jones publish their results regarding "H. pylori" and its relation to PUD. They decide that it was "
Pseudomonas", a contaminant, and not related to PUD. [cite journal |last=Steer |first=H.W. |coauthors=D.G. Colin-Jones |year=1975 |title=Mucosal changes in gastric ulceration and their response to carbenoxolone sodium |journal=Gut |volume=16 |issue=8|pages=590–7| pmid = 810394 |doi=10.1136/gut.16.8.590]
;1978:At a meeting of the American Gastroenterology Association in Las Vegas, several papers are presented which suggest that acid control via H2 blockers is ineffective at curing PUD.Peterson, Walter L., "The Dallas experience with acute "Helicobacter pylori" infection", in "Helicobacter Pioneers", pp. 143-150.]
;1979:Ramsey publishes a study demonstrating that bismuth can help eradicate PUD. Bismuth is an antibacterial agent, although this is not recognized by Ramsey. [cite journal |last=Ramsey |first=E.J. |coauthors=K.V. Carey, W.L. Peterson, "et al". |year=1979 |title=Epidemic gastritis with hypochlorhydria |journal=Gastroenterology |volume=76|issue=6 |pages=1449–57 | pmid = 437444] :J. Robin Warren first observes "H. pylori" in a gastric biopsy.Warren, J. Robin, "The discovery of "Helicobacter pylori" in Perth, Western Australia", in "Helicobacter Pioneers", pp. 151-164] :Fung, Papadimitriou, and Matz observe "H. pylori". [cite journal |last=Fung |first=W.P. |coauthors=J.M Papadimitriou and L.R. Matz |year=1979 |title=Endoscopic, histological and ultrastructural correlations in chronic gastritis |journal=American Journal of Gastroenterology |volume=71|issue = 3 |pages=269–79| pmid = 443229 ]
;1981:Yao Shi observes bacteria in the stomach, but he believes they are bacteria that are passing through the stomach and not colonizing it.:"July" - Barry Marshall joins gastroenterology division of
Royal Perth Hospitaland meets Robin WarrenMarshall, Barry, "The discovery that "Helicobacter pylori", a spiral bacterium, caused peptic ulcer disease", in "Helicobacter Pioneers", pp. 165-202.] :"October" - Marshall and Warren successfully treat their first PUD patient with antibiotics.
;1982:Satoha "et al." find evidence for an infectious cause of ulcers in rats. [cite journal |last=Satoh |first=H. |coauthors=P.H. Guth, and M.I. Grossman |year=1983 |title=Role of bacteria in gastric ulceration produced by indomethacin in the rat: cytoprotective action of antibiotics |journal=Gastroenterology |volume=84 |issue=3|pages=483–9| pmid = 6822322] :Marshall and Warren begin their first study to determine the relationship between "H. pylori" and PUD.:First successful culturing of "H. pylori" performed; it occurs almost by accident.:"October" - Marshall discovers the bacteria he is investigating are not campylobacters, by looking at
electron micrographs.:"October 2" - Marshall presents his and Warren's results at a local College of Physicians meeting. He meets with criticism, which Marshall later admits was well-founded (at least in part).
;1983:"January" - Two letters authored by Warren and Marshall respectively are sent to "The Lancet" describing their results.:"February" - Gastroenterological Society of Australia rejects Marshall's abstract to present his research at their yearly conference. They deem it in the bottom 10% of papers submitted. The same abstract is accepted for presentation at a Campylobacter workshop in Brussels.:"April" - Marshall and Ian Hislop begin a study to compare bismuth treatment with
cimetidine. The study is abandoned because it is inconclusive.:"June" - Warren and Marshall's letter appears in "The Lancet".cite journal |last=Warren |first=J.R. |coauthors=Barry Marshall |year=1983 |title=Unidentified curved bacilli on gastric epithelium in active chronic gastritis |journal=Lancet |volume= 1| issue = 8336 |pages=1273–5| pmid = 6134060] :"September" - "H. pylori" is observed in patients outside of Australia.:After the appearance of the letters in "The Lancet", groups around the world begin isolating "H. pylori".
;1984:A paper describing Marshall and Warren's results is accepted by the Gastroenterological Society of Australia for presentation.:Marshall and Goodwin attempt to infect pigs with "H. pylori" in an attempt to demonstrate that it causes PUD. The experiment fails.:Marshall and Warren's paper is accepted by "The Lancet" in May and published in June. Many reviewers dislike the paper.:McNulty and Watson are able to reproduce Marshall and Warren's results. [cite journal |last=McNulty |first=C.A. |coauthors=D.M. Watson |year=1984 |title=Spiral bacteria of the gastric antrum |journal=The Lancet |volume = 1 | issue = 8385|pages=1068–9 | pmid = 6143990 |doi=10.1016/S0140-6736(84)91469-7] :"June 12" - Marshall intentionally consumes "H. pylori" and becomes ill. He takes antibiotics and is relieved of his symptoms.:The
National Health and Medical Research Councilof Australia fully funds Marshall's research into "H. pylori".:A study is published in China about the effectiveness of treating PUD with an antibacterial agent.
;1987:Morris intentionally consumes "H. pylori". Like Marshall, he become ill, but unlike Marshall, he is not completely cured by antibiotics. The infection will remain with him for three years. [cite journal |last=Morris |first=A. |coauthors=G. Nicholson |year=1987 |title=Ingestion of Campylobacter pyloridis causes gastritis and raised fasting gastric pH |journal=American Journal of Gastroenterology | volume = 82 | issue = 3|pages=192–9| pmid = 3826027 ] :An extensive study in Dublin demonstrates that eradicating "H. pylori" substantially reduces recurrence of ulcers. [cite journal |last=Coghlan |first=J.G. |coauthors=H. Humphrise, C. Dooley, "et al". |year=1987 |title=Campylobacter pylori and recurrence of duodenal ulcers—a 12-month follow-up study |journal=The Lancet |volume = 2 | issue = 8568|pages=109–11| pmid = 2890019 ]
;1990:Rauws and Tytgat describe cure of duodenal ulcer by eradication of "H. pylori" using a triple-therapy regimen, consisting of bismuth and two antibiotics. [cite journal | author = Rauws E, Tytgat G | title = Cure of duodenal ulcer associated with eradication of Helicobacter pylori | journal = Lancet | volume = 335 | issue = 8700 | pages = 1233–5 | year = 1990 | pmid = 1971318 | doi = 10.1016/0140-6736(90)91301-P] Triple-therapy, modernized to a
proton pump inhibitorand two antibiotics soon becomes first line therapy for eradication.:World Congress of Gastroenterology recommends eradicating "H. pylori" in order to cure duodenal ulcers. [ cite journal |last=Rauws |first=E.A.J. |coauthors=G.N.J. Tytgat |year=1990 |title=Cure of duodenal ulcer associated with eradication of Helicobacter pylori |journal=The Lancet |volume = 335 | issue = 8700|pages=1233–5| pmid = 1971318 |doi=10.1016/0140-6736(90)91301-P ] :First report of resistance of "H. pylori" to the antibiotic metronidazole. [cite journal | author = Becx M, Janssen A, "et al."| title = Metronidazole-resistant Helicobacter pylori | journal = Lancet | volume = 335 | issue = 8688 | pages = 539–40 | year = 1990 | pmid = 1968548| doi = 10.1016/0140-6736(90)90772-W] Resistance of "H. pylori" to treatment will lead to the development of many different antibiotic and proton pump inhibitorregimens for eradication.cite journal | author = Malfertheiner P, Mégraud F, O'Morain C, "et al."| title = Current concepts in the management of Helicobacter pylori infection--the Maastricht 2-2000 Consensus Report | journal = Aliment Pharmacol Ther | volume = 16 | issue = 2 | pages = 167–80 | year = 2002 | pmid = 11860399| doi = 10.1046/j.1365-2036.2002.01169.x]
;1992:Fukuda "et al." prove ingestion of "H. pylori" causes gastritis in
rhesus monkeys.:Covacci "et al." sequence the "CagA" gene, which encodes for a cytotoxin-associated surface protein, which correlated strongly with strains of "H. pylori" that caused duodenal ulcers. This was the first description of a virulence factorfor "H. pylori" infection determined by molecular techniques. [cite journal | author = Covacci A, Censini S, Bugnoli M, "et al."| title = Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer | journal = Proc Natl Acad Sci U S A | volume = 90 | issue = 12 | pages = 5791–5 | year = 1993 | pmid = 8516329| doi = 10.1073/pnas.90.12.5791]
;1994:Fujioka "et al." prove similar results as those from Fukuda "et al.":
Patents for acid reducing drugs expire, removing financial incentive to resist antibiotics as treatment of PUD.:Conference held by National Institute of Health (USA) demonstrating the general acceptance of "H. pylori" as cause of PUD in the US.:The World Health Organization's International Agency for Research on Cancer declares "H. pylori" a Group 1 carcinogen. [cite journal|year=1994 |title=IARC Monograph on the Evaluation of Carcinogenic Risks to Humans |journal=Lyon: World Health Organization |pages=177–240 ] :Parsonnet "et al." describe an association between "H. pylori" and lymphomas of the gastrointestinal tract. These malignant ulcers can also be treated by eradicating "Helicobacter". [cite journal | author = Parsonnet J, Hansen S, Rodriguez L, "et al" | title = Helicobacter pylori infection and gastric lymphoma | journal = New England Journal of Medicine | volume = 330 | issue = 18 | pages = 1267–71 | year = 1994 | pmid = 8145781 | doi = 10.1056/NEJM199405053301803]
;1997:Tomb "et al." complete sequencing of the entire 1,667,867
base pair"H. pylori" genome. This assists in identifying new virulence factors for the infectivity of "H. pylori" on the molecular level. [cite journal | author = Tomb J, White O, Kerlavage A, "et al."| title = The complete genome sequence of the gastric pathogen Helicobacter pylori | journal = Nature | volume = 388 | issue = 6642 | pages = 539–47 | year = 1997 | pmid = 9252185| doi = 10.1038/41483] [cite journal | author = Aspholm-Hurtig M, Dailide G, Lahmann M, "et al."| title = Functional adaptation of BabA, the H. pylori ABO blood group antigen binding adhesin | journal = Science | volume = 305 | issue = 5683 | pages = 519–22 | year = 2004 | pmid = 15273394| doi = 10.1126/science.1098801]
;2001:Chan "et al." show in a randomized control trial that eradication of "H. pylori" even prevents bleeding from ulcers that are caused by
aspirinand non-steroidal antiinflammatory drugs. [cite journal | author = Chan F, Chung S, Suen B, "et al." | title = Preventing recurrent upper gastrointestinal bleeding in patients with Helicobacter pylori infection who are taking low-dose aspirin or naproxen | journal = N Engl J Med | volume = 344 | issue = 13 | pages = 967–73 | year = 2001 | pmid = 11274623 | doi = 10.1056/NEJM200103293441304]
;2002:The European Helicobacter Pylori Study Group published the Maastricht 2-2000 Consensus Report, suggesting a "test-and-treat" strategy for "H. pylori" in young patients without atypical symptoms. This strategy advocates the use of non-invasive testing to evaluate for "H. pylori" and simply treating if found, even in the absence of ulcer disease documented on
;2005:Warren and Marshall are awarded the
Nobel Prize in Physiology or Medicinefor their work on "H. pylori" and PUD. [cite web | url=http://nobelprize.org/nobel_prizes/medicine/laureates/2005/index.html | title=Nobel Prize in Medicine 2005 | publisher= Nobel Foundation | accessmonthday= October 3| accessyear= 2006]
* Barry J. Marshall (2001). [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hp.chapter.178 "One hundred years of discovery and rediscovery of "Helicobacter pylori" and its association with peptic ulcer disease"] . Chapter 3 of [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=hp.TOC&depth=2 Helicobacter pylori:" Physiology and Genetics"] ed. by Harry L. T. Mobley, George L. Mendz, and Stuart L. Hazell. ASM Press. ISBN 1-55581-213-9.
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