Enzymes at the Frontier (1822-1833) Alan Mellors University of Guelph, Guelph. ON. Canada N1G 2W1 Enzymology has its origins in curiosity about the workings of the human hodv and in s~eculationabout the common biotransformations of everyday life, especially fermentation and food chemistrv. One hundred sixty years ago, a series of pioneer experiments was carried out in an unlikely location, on the western frontier of the infant Republic of the United States of America. The investigator was a U.S. army surgeon, William Beaumont, whose army service gave him a remarkable opportunity to ohserve the human digestive process. William Beaumont was born in Connecticut in 1785, the son of a farmer. He was a village schoolmaster, and then a self-taught physician's aide, before securing an army post as an assistant surgeon. In 1812, war broke out between the British in Canada, and the United States. Beaumont did not have to wait long to practice his surgery. He was part of a U.S. force that crossed Lake Ontario to attack the British a t Fort York, now the site of the city of Toronto, Ontario. The U.S. troops quickly drove out the defenders but not before the British had boohy-trapped the Fort. When the Americans entered, the powder magazine exploded, killing 60 and wounding 300 U.S. troops. The surgeons were kept busy for days; in Beaumont's words, "I cut and I slashed for 36 hours without food or sleep." After the war, Beaumont practiced medicine as a civilian in New York State, hut in 1820 he re-enlisted as an Army sureeon and was nosted to Fort Mackinac, in Michigan Territ&, close to the Canadian border. Fort ~ a c k i n a c & o d on Markinar Island and was an important strategic fort guarding the entrance to Lake Michigan and the American Midwest. The fort had been established by the French to protect their fur trade, had been captured by the British, and was ceded to the United States after the War of Independence. In 1820 the fort was the scene of active fur-trade traffic, with many Canadian and American voyageurs travelling to and from the West in their lake canoes. In June 1822, an 18-yearold fur-trapper from Montreal, named Alexis St. Martin, was visiting the company store a t Mackinac Island when he was accidentally shot in the abdomen with a shotgun a t a range of 1m. Beaumont saw him 30 min later and declared that the patient would be dead in 36 h. In fact, St. Martin recovered and lived to the age of 83 years, but for theremainder of his life he possessed a gastric fistula, that is, an opening between the lumen of the stomach and the external abdominal surface, through which the process of gastric digestion could he observed (see figure). Beaumont nursed the ~ a t i e nback t to health and over the next 11 years undertook a series of experiments to observe eastricdieestion and the secretion of castric iuire. St. Martin was not tbe ideal guinea pig; he resented the attentions of the surgeon and naturally wanted an independent life for himself. For a 4-year period he went back to his old life as a fur-trader; he married and had two children. Beaumont persuaded St. Martin to join him a t his new posting on the upper Mississippi. The stamina of the patient can be judged by a journey that he undertook with his wife and his children in an open canoe, from the upper Mississippi down to St. Louis, then u p the Ohio River to Lake Erie, by the Niagara River to Lake Ontario, and finally down the St. Lawrence to Montreal, a journey of over 1,600 miles. 194
Journal of Chemical Education
In 1833 Beaumont published his research in a monograph entitled "Experiments and Observations on the Gastric Juice and the Physiology of Digestion". He gave much credit to the previous European studies on the topic, notably by Spallanzani. Beaumont's observations firmly established the ability of the gastric juice to dissolve food material. He showed that the gastric juice was a clear acidic secretion, which contained considerable HC1, potassium, sodium, magnesium and calcium salts, phosphates and chloride. In addition, the gastric secretion contained organic matter that was soluble in the cold but precipitated by heating. Mild heat was necessary, he discovered, for the in vitro digestion of foodstuffs by the gastric juice. He confirmed that i t was the gastric juice, and not mucus or mechanical action, that was responsible for digestion in the stomach. Beaumont noticed that the gastric juice would coagulate and then dissolve egg albumen and fish gelatin. He reported
This engraving represents the ordinary appearance of the left breast and side, the aperture filled with the valve; the subject in an erect position. A A A T h e circumference and edge of the aperture, within which is seen the valve. B The attachment of the valvular portion of the stomach to the superior part of the aperture. C T h e nipple. D The anterior portion of the breast. E The scar where the opening was made with the scalpel, and the cartilages taken out. F F F F Cicatrice of the original wound, around the aperture. An engraving showing the left side of Alexis St. Martin and the gastric fistula.
the ability of the gastric secretions to stop the putrefaction of tainted meat and showed that the juice would help the healine of infected skin lesions. The latter e x ~ e r i m e n tis probacly the first reported use of a proteolyticenzyme for the debridine of wound tissue. He observed the digestion of many different foods within the stomach of St. arti in and saw that raw veeetahle and raw meat were slowly digested, whereas cooked.food was quickly liquefied. Man; years before Pavlov, Beaumont observed that the secretion of gastric juice was induced by the psychological anticipation of a meal. From his measurements of gastric processes, h e concluded that alcohol, tea, and coffee interfered with rapid digestion. I t is not known what happened to the samples of
gastric juice that Beaumont sent to Sweden for analysis by the chemist, Berzelius. The gastric fistula experiments of Beaumont were contemporary with the study of Theodor Schwann of the digestive principle from the gastric juice, which Schwann named pepsin and which we consider to be the first named enzyme. William Beaumont and Alexis St. Martin deserve an honourable mention in the early history of enzymology. References Beaumont, W. Experiments and Obseruorionaon the Gastric Juiceand the Physiolomol Digestion: Dover: New York,1833 (reprinted 19591. Havighurat. W. Three F I ~ E atsthe Sfmits: The Forts d Mockinoc: PrentiaHall: Englewood Cliffs, NJ, 1966.
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Volume 67
Number 3 March 1990
195
