Read Online Happy Accidents: Serendipity in Major Medical Breakthroughs in the Twentieth Century by Morton A. Meyers - Free Book Online Page B
Authors: Morton A. Meyers
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associated with gastritis and were present in 80 percent of patients with gastric (stomach) ulcers and in 100 percent of patients with duodenal (intestinal) ulcers, in contrast to 50 percent of patients with a normal stomach. 6 The literature strongly indicated not only that chronic gastritis was associated with peptic ulcers but also that acid-reducing drugs, such as cimetidine, merely healed rather than cured duodenal ulcers. Clearly, stomach acid was not the sole cause.
Then Marshall had an idea. Early in the century, Paul Ehrlich had used arsenical compounds against the spirochete of syphilis. Bismuth, an element in the same chemical group, had long been used as a remedy for abdominal discomfort and peptic ulceration. As recently as 1980 it had been reported that duodenal ulcers treated with a bismuth compound—marketed over the counter as Pepto-Bismol—had a diminished relapse rate. “This suggested to me,” reasoned Marshall, “that bismuth compounds might inhibit the spiral bacteria” and thereby heal ulcers and gastritis.
The proper treatment regimen revealed itself in an unexpected circumstantial way. Marshall had earlier determined that, within a day of applying bismuth to a colony growing on an agar plate, all the bacteria died. In clinical trials, chewable bismuth tablets eradicated all signs of ulcers or gastritis, but to Marshall's disappointment, after discontinuing the treatment, nearly every patient suffered a relapse. Why, he wondered, would bismuth kill bacteria in a Petri dish but not in a patient's stomach? Then he noticed something strange. One patient, months after treatment with chewable bismuth tablets, continued to show no signs of recurrence. Reviewing the patient's record, Marshall saw that the man had suffered from a gum infection and, to treat it, had been given an antibiotic. Marshall hypothesized that bismuth alone did not reach all of the bacteria enshrouded in the stomach's thick mucus layer and had to be used in combination with an antibiotic.
The next development in the saga occurred due to another technological advance—the development of electron microscopy. A detailed morphology using the new equipment revealed that the stomach bacterium was not campylobacter. Clearly, this misidentification had been the cause of Marshall and Warren's earlier failures in growing the organism, as campylobacter required only a couple of days to get established. It would take another seven years, after RNA analysis and other studies, for these bacteria to be assigned to a new genus, Helicobacter, and receive a proper name, H. pylori. Helicobacter refers to its helical shape and pylori refers to the pylorus (“gateway”), the exit from the stomach to the duodenum.
The H. pylori Lifestyle
That Helicobacter flourishes in the human stomach is a testament to evolutionary ingenuity. Both its shape and its biochemistry favor the adaptation of the bacterium to its harsh acidic environment. The lining of the stomach is protected from the acid by a thick viscous layer of mucus, in which H. pylori can take refuge. Four whiplike flagella at one pole of each bacterium provide rapid motility through the gastric juice, and the helical structure of the bacteria facilitates a burrowing corkscrew path from the stomach cavity through the thick mucus to establish colonies next to the lining cells.
Once H. pylori is safely sheltered in the mucus, it is able to fight the stomach acid that does reach it with an enzyme it possesses called urease. Urease converts urea, which is abundantly present in the gastric juices, into bicarbonate (a natural Alka-Seltzer) and ammonia. These are both strong alkalis. In this fashion, the Helicobacter cocoons itself in a protective acid-neutralizing mist. Furthermore, the bacteria thrive best in 5 percent oxygen—exactly the level found in the stomach's mucus layer.
Helicobacter colonies may thrive for a long time before symptoms appear—indeed, for decades, as recent studies have
Then Marshall had an idea. Early in the century, Paul Ehrlich had used arsenical compounds against the spirochete of syphilis. Bismuth, an element in the same chemical group, had long been used as a remedy for abdominal discomfort and peptic ulceration. As recently as 1980 it had been reported that duodenal ulcers treated with a bismuth compound—marketed over the counter as Pepto-Bismol—had a diminished relapse rate. “This suggested to me,” reasoned Marshall, “that bismuth compounds might inhibit the spiral bacteria” and thereby heal ulcers and gastritis.
The proper treatment regimen revealed itself in an unexpected circumstantial way. Marshall had earlier determined that, within a day of applying bismuth to a colony growing on an agar plate, all the bacteria died. In clinical trials, chewable bismuth tablets eradicated all signs of ulcers or gastritis, but to Marshall's disappointment, after discontinuing the treatment, nearly every patient suffered a relapse. Why, he wondered, would bismuth kill bacteria in a Petri dish but not in a patient's stomach? Then he noticed something strange. One patient, months after treatment with chewable bismuth tablets, continued to show no signs of recurrence. Reviewing the patient's record, Marshall saw that the man had suffered from a gum infection and, to treat it, had been given an antibiotic. Marshall hypothesized that bismuth alone did not reach all of the bacteria enshrouded in the stomach's thick mucus layer and had to be used in combination with an antibiotic.
The next development in the saga occurred due to another technological advance—the development of electron microscopy. A detailed morphology using the new equipment revealed that the stomach bacterium was not campylobacter. Clearly, this misidentification had been the cause of Marshall and Warren's earlier failures in growing the organism, as campylobacter required only a couple of days to get established. It would take another seven years, after RNA analysis and other studies, for these bacteria to be assigned to a new genus, Helicobacter, and receive a proper name, H. pylori. Helicobacter refers to its helical shape and pylori refers to the pylorus (“gateway”), the exit from the stomach to the duodenum.
The H. pylori Lifestyle
That Helicobacter flourishes in the human stomach is a testament to evolutionary ingenuity. Both its shape and its biochemistry favor the adaptation of the bacterium to its harsh acidic environment. The lining of the stomach is protected from the acid by a thick viscous layer of mucus, in which H. pylori can take refuge. Four whiplike flagella at one pole of each bacterium provide rapid motility through the gastric juice, and the helical structure of the bacteria facilitates a burrowing corkscrew path from the stomach cavity through the thick mucus to establish colonies next to the lining cells.
Once H. pylori is safely sheltered in the mucus, it is able to fight the stomach acid that does reach it with an enzyme it possesses called urease. Urease converts urea, which is abundantly present in the gastric juices, into bicarbonate (a natural Alka-Seltzer) and ammonia. These are both strong alkalis. In this fashion, the Helicobacter cocoons itself in a protective acid-neutralizing mist. Furthermore, the bacteria thrive best in 5 percent oxygen—exactly the level found in the stomach's mucus layer.
Helicobacter colonies may thrive for a long time before symptoms appear—indeed, for decades, as recent studies have
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