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Bulletin, Institute

Stomach Stapling Paves a Pathway

Original Article Featured on Biotech Primer Weekly

Identifying Gut Proteins to Tackle Metabolic Disorders

Historians of science love to tell about “eureka moments”—simple observations leading to major insight. Greek mathematician Archimedes allegedly exclaimed the original “Eureka!”—meaning “I have found it!”—upon witnessing the volume of water displaced by his body in the bathtub equaled the volume of the body part he had submerged. Medicine’s most famous eureka moment is probably the discovery of penicillin in 1928 when microbiologist Alexander Fleming observed the absence of bacteria developing on his growth plates in areas where the mold Penicillium rubens happened to be sprouting.

The roots of NGM Biopharmaceuticals (South San Francisco, CA) are based on a eureka moment as well—the simple observation that many recipients of gastric bypass surgery begin to see almost immediate improvement in blood glucose levels before the occurrence of weight loss, and in some cases even without significant dietary changes. In this issue, we’ll find out how the science of gastric bypass surgery is being used to discover new drugs in the metabolic space.

Bypassing Normal Digestive Routes

Gastric bypass surgery is pretty much “stomach stapling” and then a change-up in the route of digestion. A portion of an obese patient’s stomach is made physically smaller, and therefore only capable of holding about a cup or so of food at a time. Then the new, smaller stomach is disconnected from the upper part of the small intestine and reconnected lower down, thereby reducing absorption of food through the small intestine. Less food and less absorption of food lead to weight loss.

The initial understanding of surgery results implied positive outcomes came from weight loss (averaging 60% of excess weight). However, the significant improvement in blood glucose levels seen in many patients immediately following the surgery—before weight loss occurs—remained unexplained.

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