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October 03, 2011 | By:  Nature Education
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Peptic Ulcers and a Nobel Prize

A guest post by Eric Sawyer. Also check out Eric's own Scitable blog, Bio 2.0. 'Dissecting the next revolution in biology'

Today the Nobel Prize in physiology or medicine for 2011 was awarded to three immunologists, whose pioneering work paved the way for greater understanding of human disease and treatment approaches. What better way to celebrate Nobel Prize week 2011 than to reminisce about Nobel Prizes past? As a biologist in training, I find the 2005 prize in physiology or medicine particularly striking. It was awarded to two Australians, Barry Marshall (see image) and Robin Warren, "for their discovery of the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease," in the words of the Nobel committee.

Peptic ulcers are, as the name suggests, ulcerations of the stomach or the early stretches of the small bowel. Historically they were believed to be caused by environmental stressors: spicy food, an acidic stomach, and even stress. Marshall and Warren overturned this assumption by showing that, surprisingly, the bacterium Helicobacter pylori plays a significant role in most peptic ulcer cases.

In his Nobel autobiography, Marshall says that he went through a period of difficulty in publishing his results and obtaining support from the scientific community. Add to that the fact that he was having trouble infecting his animals with the H. pylori. As a result he made the highly unusual decision to instead experiment on himself by downing a culture of the bacteria. The result was, as he described, an infection more severe than he would have expected. That changed people's minds pretty quickly.

Now, we all learn that the stomach is acidic for a reason: acid helps break down the complex, life sustaining molecules in our food and kills any microbes along for the ride. The pH of the stomach varies, but 2 is a rough average. Because the pH scale is logarithmic, H. pylori is up against 100,000 times the number of hydrogen ions as it would be in ordinary water of pH 7. So how do the bacteria make a living in our stomach? It turns out that, among other things, they produce the enzyme urease (see image; cross your eyes to see the protein model in 3D!), which converts our body's own urea to ammonia and CO2. Ammonia is a base, so it acts to neutralize stomach acid in its immediate vicinity. The bacterium also burrows into the mucous and epithelial layer that lines the stomach by beating its flagella and producing surface proteins that help it to adhere. It is this behavior that enables H. pylori to play a role in stomach ulcers.

Since H. pylori causes illness in some of its hosts, clinicians obviously need ways to eradicate it from their patients. While there's no vaccine against the bacteria on the market, a course of antibiotics can cure the infection. Prior to this Nobel winning discovery, the only treatment was to alleviate the symptoms by reducing the acid in the stomach with simple antacids or proton pump inhibitors (which prevent acid from being produced in the first place). However, as with most modern bacterial diseases, antibiotic resistant strains of H. pylori have emerged that resist treatment. Even though we have fingered the culprit, a cure for stomach ulcers is still to come. Perhaps we will soon have a H. pylori vaccine in circulation.

The great thing about Nobel Prizes is that, rather than marking the end of a line of experiments and thinking, they are often pivotal advances that lead to further study in the respective field. In the case of H. pylori, we still have a lot to learn about how the bacterium works and how to treat it. More generally, we also have a lot to learn about the interactions between the human body and the microbes that live within it, and outnumber it.

Image Credits: H. pylori image by CDC (via Wikimedia Commons); Barry Marshall image by Barjammar (via Wikimedia Commons); Urease model adapted from PDB file 1E9Z


Helicobacter pylori. Wikipedia.

The Nobel Prize in Physiology or Medicine 2005.

Peptic Ulcer. PubMed Health.

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