March 06, 2006

Hormones

William Bayliss and Ernest Starling, The Mechanism of Pancreatic Secretion, 1902

Nerves were discovered by the ancient Greeks, and until Bayliss and Starling discovered the first hormone, nerves were considered to be the only method used by the body to communicate with and regulate itself. To modern biochemists, used to thinking of the body primarily as a chemical machine, this can be somewhat surprising, but it really makes perfect sense. Nerves are large enough to be discovered during a disection, as indeed they were, while chemical messengers are impossible to detect directly with the unaided senses.

How, then, did Bayliss and Starling figure out that a chemical messenger was being created by the intestine to signal the pancreas that it should produce digestive juices? This is the point at which we leave the abstract and enter the gory. Those easily upset by vivisection should skip the next paragraph.

Bayliss and Starling took an anesthetized dog, immersed it in saline solution, and pumped its lungs with oxygen to keep it alive. Then they cut open the dog's abdomen, attached a device to measure the amount of fluid being produced by the pancreas, isolated a loop of the small intestine, and severed all the nerves attaching it to the rest of the body while leaving the blood vessels intact. Then they poured dilute hydrochloric acid (about what you would expect to enter the intestine from the stomach) into one end of the isolated segment of intestine. Much to their surprise, the pancreas started producing digestive juices.

Up until this point, Bayliss and Starling had been performing a control experiment. That is, they thought that the secretion of the pancreas was triggered by a nerve, and they were doing a sanity check. When they severed all the nerves, they expected the pancreas to stop reacting to hydrochloric acid in the small intestine. Instead, they discovered a new communication system in the body, one unrelated to nerves.

Since there were no theories to support them, Bayliss and Starling relied on experiment... lots and lots of experiments. In the most important one, they ground up some of the mucous membrand of a small intestine with sand and hydrochloric acid, filtered it, and injected the remaining fluid into a vein. The result: the pancreas secreted its juices. In further experiments, they showed: secretin (their name for the substance causing the effect) is unaffected by boiling; it is not produced by the lower end of the intestine; it has no effect on any other glands in the body; the same effect cannot be reproduced by extracts from any other part of the body; the effect cannot be reproduced with the ash of the extract, proving that the inorganic constituents are not responsible; secretin does not evaporate or diffuse easily; secretin is destroyed by tryptic solutions (digestive juices that work on proteins); secretin made from the intestines of cats, rabbits, oxen, monkeys, men, and frogs are all active on the pancreases of dogs; secretin from dogs, rabbits, monkeys, and men are all active on rabbits and monkeys.

I have to admit that although I took a lot of biology courses, it never occurred to me to ask "Just how did anyone figure out that secretin exists?" or similar questions. The dissections and experiments on living animals I did for classes, although interesting and informative, seemed like a needlessly wasteful way to teach students biology. Why not teach them with pictures, theory, and simulation?

I see now that lab dissections are not just teaching known information, but teaching the next generation of experimentalists the tools of their trade. Without the training, many future researchers would be uncomfortable, and worse, unskilled at their work, and much knowledge would remain undiscovered. And there is definitely a lot left to discover in biology: I know of at least a dozen things that have been learned through experiment in the last 5 years, and that's just the stuff interesting enough to make it to the mainstream press.

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