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Diabetes Detectives

The other scientific finding Goss mentioned was the identification of diastase—the first enzyme ever recognized and isolated (from a malt solution, by the French chemist Anselme Payen in 1833). Goss suggested that perhaps abnormal diastase action on starch in the stomach contributed to hyperglycemia. This was another prescient supposition, for themodern antidiabetic drug acarbose (which goes by the brand name Precose) acts by inhibiting polysaccharidemetabolism in the intestine.

But despite Goss's insightful leaps, and his comprehensive review of all the then-current therapies, he listed none beyond those posited by Rollo 60 years earlier.

The final two student theses on diabetes date from 1880—Fred Spafford's "History, Pathology and Treatment of Diabetes Mellitus" and Hoell Tyler's "Pathology of Diabetes Mellitus." Their papers present most of the then-known thoughts about diabetes and glucose metabolism.

Spafford leaned heavily on the French physiologist Bernard, citing his important observation that diabetes could be induced by making lesions in the floor of the brain's fourth ventricle, indicating a neural contribution. This understanding presaged observations by Dr. Bernardo Houssay about the role of pituitary hormones in the onset of diabetes—work that won him the 1947 Nobel Prize. Spafford even suggested a genetic role in the disease—despite the fact that human genetics did not yet exist as a discipline—in his mention of twin boys with diabetes mellitus and of a mother and her two children who died of the disease. This, too, presaged later knowledge: the modern recognition of an inherited form of the disease.

Tyler's 1880 thesis contained references to both the past and the future. He reached back to the first century in citing descriptions of diabetes by the Roman encyclopedist Celsus. But he also correctly theorized that a contributing factor in the development of hyperglycemia was "increased introduction [of glucose], decreased destruction, or both." This is consistent with modern understanding of the mechanisms involved in the elevation of blood glucose.

William Pratt's 1825 thesis was the first of five dissertations on diabetes written during the 19th century by Dartmouth medical students. On this page, he predicts that "future experiments" will eventually reveal the cause of the then-fatal disease.

The "cure" for diabetes, wrote a student in his 1828 thesis, lay in perfecting a regimen of "strict diet control"—an idea in line with modern thinking. He appears to be the only one of the six thesis-writers who had ever seen a case of diabetes.

From William Ellsworth's 1806 notes to these two 1880 theses, the documents in Dartmouth's archives show an evolving comprehension about the nature of diabetes. Interestingly, however, the conceptual leaps that occurred during this period did not lead to a parallel evolution in treatments. As late as 1880, Spafford and Tyler still listed nearly the same remedies that Nathan Smith, borrowing from John Rollo, had taught in the first decade of the century. Furthermore, all these remedies were entirely empirical reflecting the ignorance that then prevailed regarding the genesis of diabetes mellitus.

But less than a decade after Spafford and

Tyler penned their theses, Minkowski and von Mering's 1889 observation regarding the role of the pancreas finally pierced the cloud of ignorance around the disease's metabolic derangements. And that led to the discovery of insulin just three decades later. Yet, as is the case with all advancements in medical science, the discovery of insulin was hardly due to the work and imagination of just a few investigators. Louis Pasteur once said, "If the fruit has appeared, there must have been some cultivation of the tree." This cultivation, in the case of diabetes mellitus, occurred over the course of many centuries—but especially during the period encompassed by the Dartmouth documents. These medical students of the 19th century bore witness to a dramatic unraveling of the mysteries of "dropsy of the chamber pot."

Jonathan Brown concluded his 1828 thesis with this qualification: "These desultory remarks, which be . . . called 'observations vented in mangled form,' possess perhaps more imperfections than would be ponderable even in a juvenile debut. . . . With truth I assert that nothing short of a law of this institution induced me to attempt the discussion of this medical subject which would come to the inspection of my elders in the sciences." (Let it be noted that though Brown deemed his thesis a "mangled" effort, he went on to a career of some distinction. He later studied with Dr. Walter Channing—Boston's leading obstetrician, the dean from 1826 to 1847 of Harvard Medical School, and a founding editor of the New England Journal of Medicine. Brown also—after living in Santo Domingo, now Haiti, in 1833-34—wrote one of the important early histories of that nation, from its French colonization to its independence.)

Brown went on to end with these words: "With a lively sense of gratitude, I express my acknowledgements to the learned professors of this school and wish them and the institution that prosperity and eminence which learning joined to virtue so much deserves."

Similarly, it is "with a lively sense of gratitude" that today's medical detectives acknowledge the clues left behind by Brown and others regarding that era's growing understanding of diabetes mellitus.

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Witters is the Eugene W. Leonard Professor of Medicine and Biochemistry at Dartmouth Medical School and also holds an appointment as a professor of biological sciences at Dartmouth College. Luciano and Williams, both '09s, and Yang, a '10, are Dartmouth undergraduates; all have an interest in both medicine and history. All the images illustrating the article are courtesy of the Dartmouth Libraries. The authors are indebted for assistance in researching this article to the archivists in Dartmouth's Rauner Special Collections Library—especially Barbara Krieger and Jay Satterfield—as well as to the staff of Dartmouth's Dana Biomedical Library. Some of the punctuation in the historical quotations has been standardized for ease of comprehension, but the words are rendered exactly as they appear in the source documents.

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