Over the last 20 years, research on a tiny, S-shaped stomach bacterium has overturned doctors' notions about the origins and history of diseases from ulcers to cancer of the stomach.
Now, some scientists who study the bacterium, Helicobacter pylori, say the tiny bug may help trace the migration of human populations across the globe.
Next week, enthusiasts from around the globe will gather in Australia to celebrate the discovery of H. pylori. While the discovery of a stomach bacterium may seem an odd thing to celebrate, this one did something big.
Two Australian scientists discovered H. pylori. Pathologist Robin Warren had noticed tiny bacteria in stomach ulcer specimens and his group managed to grow them where others had failed, in part because the members left the cultures incubating for an extra long time during their Easter vacation.
When it later proved impossible to infect animals with the microbes, colleague Barry Marshall swallowed some of the bacteria to find out if they really induced stomach inflammation.
A biopsy from his stomach showed they did.
"In retrospect, it was a little bit risky," recalls Marshall, now a scientist at the University of Western Australia's department of microbiology. "But at the time it was the only way I could see to advance knowledge of the new bug."
In the years that followed, doctors tossed out theories about stress and salty food as the primary causes of ulcers. (At one time, even "obsessional and dominant" mothers were blamed for the ulcers of their children.)
In came a new model of infectious disease--and new therapeutic approaches with antibiotics to treat ulcers and prevent stomach cancer, the world's second-leading cancer killer.
Researchers now know far more about the bacterium. They know that once inside the stomach, the bacterium uses a set of whip-like tails--called flagella--to swim briskly toward the layer of mucus that protects the lining of the stomach.
Inside the mucus, H. pylori sticks to the cells lining the stomach and uses an enzyme to neutralize the stomach's fierce acidity. While there, the microbe produces proteins that cause changes in stomach cells. Those changes, in turn, lead to inflammations that over time can produce ulcers or cancer.
Researchers also have determined the precise structure of the microbe's genome several times over. They're beginning to understand how its genes function to help it survive in the stomach and trigger disease.
They've discovered that roughly half of all human beings are infected with H. pylori--but that rates of infection vary enormously from place to place. In countries and communities with impure water, poor sanitation and crowding, infection rates are high--and higher, too, are incidences of stomach cancer and ulcers.
Microbe's DNA Varies Greatly
Scientists also have snaked tubes into stomachs all over the world to study H. pylori more closely--and, by doing so, have found great genetic variability in the microbe's DNA. Even individual stomachs can contain dozens of genetically distinct bacteria, as if H. pylori is constantly reshaping its genome.
But there are clear, more global patterns also. Strains sampled from Asian stomachs, European stomachs and African stomachs differ distinctly--and the differences persist in the stomachs of offspring, even when they're now living in other parts of the world.
"Give me a bacterium and I can tell you generally where a person's ancestors came from," says Dr. David Graham, chief of gastroenterology at the Veterans Affairs Medical Center in Houston, one of the scientists who has made a study of this florid variability.
These global genetic signatures offer much more than the chance to perform a neat party trick: by comparing strains, scientists hope to track where and when H. pylori first took up residence in humans, and how it traveled to stomachs across the globe.
Though the details of H. pylori infection are unclear, it is believed to occur via the mouth, possibly via water, during the early years of life. And it clearly involves close community contact: in a study recently reported at a conference at UCLA, Himalayan Buddhists and Muslims who have lived in the same area for several hundred years retained genetically distinguishable populations of the microbe. But where did H. pylori come from? Is it a new or ancient resident in the human body?
Some researchers argue that H. pylori got into human stomachs hundreds of thousands, even millions of years ago. Others believe that the bug took up residence far more recently--perhaps caught from close contact with animals after the advent of agriculture, says Douglas Berg, professor of microbiology and genetics at Washington University School of Medicine in St. Louis.