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The History of H. pylori-Induced Peptic Ulcers and Gastritis, and the Man Who Infected Himself to Prove It 

Writer: FibonacciMD
FibonacciMD
Oct 9
6 min read
Helicobacter pylori seen in stomach biopsy from a gastritis patient
Helicobacter pylori  seen in stomach biopsy from a gastritis patient

Throughout most of the 20th century, gastritis and peptic ulcers (both gastric and duodenal) were commonly attributed to stress, lifestyle factors, and excessive gastric acid.  It wasn’t until the early 1980s, after some luck and potentially hazardous self-experimentation, that scientists recognized that the bacterium Helicobacter pylori  (H. pylori) played a major role in these diseases. 


One of the earliest well-known reports of finding spiral bacteria in gastric samples was published in 1893 by Italian anatomist Giulio Bizzozero.  He documented finding "spirochetes," or corkscrew-shaped bacteria, in the gastric mucosa of dogs.  (Note: Early investigators described the spiral organisms they observed as “spirochetes,” but H. pylori is now classified as a curved or spiral rod-shaped bacterium with multiple flagella that allow it to move through the gastric mucus layer.)  


In 1940, A. Stone Freedberg and Louis Barron reported finding spirochetes in 40% of human gastrectomy specimens.  However, their findings were largely dismissed after a 1954 study by E. D. Palmer failed to find spirochetes in more than 1,000 gastric biopsies. 


Electron micrograph of H. pylori with multiple flagella
Electron micrograph of H. pylori with multiple flagella

In 1975, researchers H. W. Steer and D. G. Colin-Jones identified spiral bacteria in 80% of gastric ulcer specimens.  However, they were unable to culture the spiral organism and instead cultured Pseudomonas aeruginosa.


In the early 1980s, Australian physicians and researchers Robin Warren and Barry Marshall successfully solved the puzzle.  Warren had observed spiral bacteria in gastric biopsies and recognized that they were consistently associated with gastric inflammation, but repeated attempts to culture the organism failed.  

In 1982, during a prospective study of patients with gastritis or peptic ulcer disease, they unexpectedly succeeded in culturing the organism from a patient’s biopsy specimens.  Standard laboratory protocol called for inspecting and then discarding culture plates after 48 hours if no bacterial growth occurred, to prevent overgrowth by normal flora that might lead to erroneous results.  Due to an extended Easter holiday weekend in 1982, the culture plates were left in the incubator for five days, revealing colonies of the previously unidentified organism.  H. pylori had previously eluded investigators partly because of its slow growth, which required prolonged incubation.  In their study of more than 100 patients, most of whom had gastritis, Marshall and Warren found that about two-thirds were infected with H. pylori.  Every patient with a duodenal ulcer in their series was infected, as was the majority of patients with gastric ulcers.  They concluded that infection played an important role in these disorders, challenging the prevailing view that they were primarily psychosomatic in origin.


Drs. Barry Marshall (left) and Robin Warren (right)
Drs. Barry Marshall (left) and Robin Warren (right)

However, the medical establishment greeted their reports with skepticism and was reluctant to accept that ulcers and gastritis could be caused by infection.  Critics pointed to several factors to support their doubts.  At the time, ulcers were widely believed to be caused by stress and lifestyle.  There was also the long-held belief that the stomach’s highly acidic environment could not support bacterial colonization, and any bacteria found were merely secondary invaders colonizing inflamed or damaged tissue.  Furthermore, early attempts to reproduce H. pylori infection in animal models did not provide the experimental evidence traditionally expected to establish an infectious cause.


That is when Marshall did something remarkable.  In 1984, he first underwent gastroscopy that confirmed he was free from H. pylori infection.  Marshall then deliberately infected himself by drinking a “cocktail” containing Campylobacter pyloridis (as H. pylori was called at the time) isolated from a patient with gastritis.  Within days, he developed symptoms of acute gastritis, and repeat endoscopy and biopsy confirmed inflammation and H. pylori colonization.  Marshall’s self-experiment provided compelling evidence that the bacterium could cause acute gastritis.  He later treated himself with antibiotics and bismuth, after which his symptoms improved rapidly.  His subsequent publication of the experiment, continued research, and later corroborating evidence from other investigators helped change the course of medical history by providing powerful evidence that many cases of gastritis and peptic ulcer disease were caused by a treatable infectious disease rather than chronic stress.  Marshall and Warren received the Nobel Prize in Physiology or Medicine in 2005, “for their discovery of the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease.”


Summary

For much of the 20th century, peptic ulcer disease and gastritis were thought to be lifestyle or psychosomatic conditions, managed primarily with acid-suppressing medications and, in severe or complicated cases, surgery.  Marshall and Warren’s willingness to pursue an unpopular theory, along with Marshall’s audacious decision to infect himself, helped convince the medical establishment that H. pylori  was an important cause of peptic ulcers and gastritis.  Beyond treating peptic ulcer disease, eradicating H. pylori infection is also an important strategy for reducing gastric cancer risk and treating gastric MALT (mucosa-associated lymphoid tissue) lymphoma. 


Today, it is difficult to imagine that this concept was once considered so radical.  However, as this story so clearly illustrates, established but incorrect medical beliefs are sometimes discarded only after scientific heretics, such as Marshall and Warren, produce compelling evidence that challenges conventional wisdom. 


References


If you liked this article, here are more fascinating topics in the FibonacciMedicine history of medicine series:


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