The Prize:
The 2005 Nobel Prize in Physiology or Medicine went to Barry J. Marshall and J. Robin Warren “for the discovery of the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease.”
The Science:
Not many scientists are willing to take the leap of faith that Barry Marshall took to prove the hypothesis that he and J. Robin Warren shared about the origins of stomach ulcers and cancers: he drank a flask of the bacteria Helicobacter pylori. His subsequent illness unequivocally proved that H. pylori, and not stress and lifestyle, cause the painful stomach diseases that affect a large portion of the population.
Until the 1980s, doctors believed that ulcers and stomach inflammation were caused by stress, spicy food, and poor eating habits. So when Warren (a pathologist) found that half of all biopsies taken from patients with stomach ulcers or painful stomach inflammation were colonized with a bacterium now known as H. pylori, he was intrigued.
At the time, the stomach was thought to be sterile as scientists believed that no bacterium could withstand the acidity of stomach fluids. Warren’s discovery of H. pylori interested Marshall (then a clinical fellow) who began working with Warren on a more thorough study of patient biopsies.
They found that the bacterium Warren discovered was present in almost all of the stomach inflammation and ulcer biopsies they looked at. Irrefutable causal proof came after Warren’s self-inoculation with H. pylori and his development of stomach inflammation. Their clinical studies showed that patients, including Warren, could be cured by antibiotics and prescription antacids.
When Warren and Marshall’s hypothesis was initially published, many doctors and scientists were skeptical of the conclusions, but within a few years it became firmly established and garnered Warner and Marshall numerous awards, including the 2005 Nobel Prize.
We now know that over half of the world’s population has a chronic, lifetime infection of H. pylori, making it the most common infection affecting humans. It is thought to be acquired in early childhood, possibly passed down from mother to child.
Infection manifests in the helical-shaped bacterium burying itself in the mucosal lining of the stomach, where it colonizes the stomach cellular lining. To withstand the extreme conditions of the stomach, H. pylori secretes an enzyme to neutralize the acid. At the stomach lining, it adheres to stomach cells and injects proteins into those cells to induce inflammation. This sets up a chain of events resulting in the activation and recruitment of immune cells to the stomach lining, yet these cells do not attack the H. pylori colonies. Instead, H. pylori secrete a toxin that kills the killer T-cells that normally recognize and attack invaders—one of the reasons it can remain in the stomach for a lifetime. If inflammation continues unabated, the stomach acid and enzymes can actually damage the stomach lining, causing an ulcer. This is thought to happen in 10 to 15 per cent of the H. pylori infected population.
In a small percentage of the population, stomach inflammation and H. pylori toxin production can progress into stomach and upper digestive tract cancers which kill about 800,000 people a year worldwide. The exact mechanism of this transformation and why only some infections proceed to cancer is unknown. It is thought to be a result of the genetic predisposition of the patient and genetic variability within the H. pylori population. There also appears to be a link between the amount of acid the stomach secretes, which can be a genetic or lifestyle effect, and the progression towards cancer. Increased stomach acid production seems to have a protective effect against the progression from inflammation or ulcers to cancer.
For now, only those patients that have ulcers and test positive for a simple and non-invasive breath test for H. pylori receive antibiotic treatment. This public health stance was adopted to ensure that H. pylori does not evolve resistance to antibiotics that may arise if used to clear infections in all people.
Today, research aims at understanding not only the pathogenesis of H. pylori, but also how we can use it against disease. H. pylori’s known immune-generating effects have made it an ideal candidate as a “vehicle” for vaccination. By molecularly “tying” pieces of HIV, tuberculosis, or malaria onto the surface of an H. pylori bacterium (that has been made non-pathogenic) scientists may be able to harmlessly deliver “ID tags” of these viruses and bacteria to the body’s immune system, thus making it easier for the body to recognize a real infection and to prevent the progression to disease.
What you may not know:
Interestingly, where you live in the world may affect whether or not an H. pylori infection can proceed to cancer. Genetic variability of the bacterium is highest in East Africa, and decreases with distance from there. This indicates that H. pylori evolved as a human pathogen before humans left Africa. The Asian strains of H. pylori are known to be more toxic than strains in the Western world. This correlates well with stomach cancer rates, too. In Asia, where 95 per cent of H. pylori infections are of a toxic strain, there is a higher rate of stomach cancer than in the U.S., where the toxic strain only makes up 60 per cent of stomach infections.
