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Doubts Raised About Appetite-Reducing Peptide

7 July 2004 (All day)
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Food fight. Matthias Tschöp (right) reports that 12 labs can't confirm that PYY3-36 suppresses appetite in mice. Stephen Bloom (left) says they are doing the experiments badly.

Two years ago, Stephen Bloom and his group at Imperial College London touched off a scramble in labs around the world with the latest discovery of how the body regulates appetite. The investigators reported in Nature that a molecule called peptide YY3-36 (PYY3-36), when injected into rodents, dampens appetite for 12 hours or more. But in an unusual joint letter published online today by Nature, more than 40 scientists announced that they cannot reproduce Bloom's central findings.

Endocrinologist Bloom and his colleagues reported that PYY3-36 is formed in the digestive tract after eating and travels to the brain, where the peptide controls short-term appetite. Subsequently, other teams tried to reproduce the findings--without success. As word spread that several labs were experiencing similar troubles, the investigators decided to collaborate. They bought rodents from the same vendor as Bloom, purchased food from the same supplier, and injected animals at exactly the same time of day with the same kind of syringes filled with PYY3-36 manufactured by the same chemical supply house. "And still we weren't able to reproduce the results," says Mattias Tschöp of the University of Cincinnati in Ohio.

Bloom remains steadfast. Other labs "are doing the experiments badly," he suggests. He thinks the problem is stress. If an animal is handled roughly and jabbed with a needle, Bloom says, it reacts to danger by not eating. The appetite loss can negate PYY3-36's appetite-suppressing effects. (Tschöp counters that in his lab animals injected with saline did not eat any less than uninjected animals.) Bloom also points out that in two earlier cases when his initial data were challenged, he turned out to be correct after years of extra work. "It kind of gets wearing," he says.

At least one scientist has corroborated Bloom's results in rodents: Andrew Young, vice president and senior research fellow at Amylin Pharmaceuticals, headquartered in San Diego, California. His firm has a financial stake; it intends to market a drug based on PYY3-36. Asked if he knows the reason for the discrepancy, Young says, "I can't explain it. Maybe it's [a difference in] the peptide." Despite the controversy, Amylin intends to test the drug in human trials.

Tschöp admits it's possible that PYY3-36 could emerge as a powerful antiobesity drug. (His group has done no studies in people.) And one pioneer in the field, Bruce Schneider, associate vice president for clinical research at the Association of American Medical Colleges in Washington, D.C., says that conflicting data should not present a regulatory problem. The main concern is that a new drug be "reasonably" safe before entering clinical trials, says Schneider, a former medical officer at the U.S. Food and Drug Administration.

Related sites
Tschöp and colleagues' letter
Response to the letter by Bloom and colleagues

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