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Diabetes Detectives

Sometimes illumination comes from looking to the future—teasing out new knowledge at the lab bench or in a clinical trial. But sometimes it comes from delving into the past. A professor of endocrinology and three undergraduates perused 19th-century documents for clues to the changing understanding about one of today's most common chronic conditions.

By Lee A. Witters, M.D., Marcus Luciano, Carla Williams, and Jessica Yang

In handwriting embellished with the curlicues of a bygone era, James Goodwin recorded his professor's remarks about diabetes in the fall of 1813. Goodwin had entered Dartmouth College from South Berwick, Maine, in 1807; earned his undergraduate degree in 1811; and by the fall of 1813 was less than a year away from earning his M.D. He and his classmates were learning about diabetes from no less a luminary than Dartmouth Medical School's founder, Dr. Nathan Smith.

"Diabetes," Smith told the students—according to Goodwin's notebook, which today resides in the Dartmouth College archives—is a condition "in which the urine is discharged in great quantities and of a peculiar quality. The quantity depends upon the circumstances of the system. The quality depends upon hysteria."

This disease—now referred to by physicians as diabetes mellitus, to distinguish it from diabetes insipidus, which has similar symptoms but a different origin—was well represented inm edical teaching as far back as the early 19th century. But it was as poorly understood then as it had been over the prior two millennia.

Hippocrates, in 400 B.C., recognized diabetes but termed it very rare. Six hundred years later, another famous Greek physician, Galen, admitted to seeing two cases during his lifetime.

Today, however, over 240 million individuals worldwide—more people than live in the United Kingdom and France combined—have diabetes mellitus. In the United States, nearly 25 million individuals—8% of the population—suffer from the disease, and almost 25%of those over the age of 60 have been diagnosed with it. Its incidence is disproportionately high among Native Americans, Hispanics, and African-Americans. It is the nation's seventh-leading cause of death; it rose to that rank over the course of the 20th century, in good measure due to the concurrent rise in the prevalence of obesity.

The disease's effects are serious. It is a major contributor to atherosclerosis, known popularly as "hardening of the arteries," which is the leading cause of death in the U.S. It is also the leading

Dartmouth medical students of the era represented here—except for the skinny guy holding the sign—were required to write a thesis before graduating. Students wrote on many subjects, from variola (smallpox) to diphtheria and fracture repair to diabetes mellitus. The latter was very uncommon then but is today a leading cause of death.

cause of blindness in individuals aged 20 to 74, of renal failure, and of nontraumatic lower-limb amputations. And it is a major risk factor among pregnant women for fetal death and for birth defects.

The earliest medical texts, and Smith's lectures, contained descriptions of the disease's symptoms. But the understanding of its pathology and pathophysiology required the emergence of the disciplines of chemistry, histology, and cellular pathology and physiology later in the 19th century. These spawned, in turn, the birth of endocrinology—the branch of medicine dealing with glands such as the thyroid and pituitary. This journey of understanding can be revealed by looking into the notebooks and theses of Dartmouth medical students through the course of the 19th century—the period during which the study of the disease became a fixture in medical school curriculums.

Another Dartmouth medical student, William Pratt, wrote in his 1825 thesis: "Perhaps future experiments may discover the real nature of the proximate cause of diabetes and establish a different mode of treatment from what has hitherto been tried. But until such a discovery is made, the physician must be

guided by the symptoms that appear in the disease in the treatment of it."

Indeed, it was the symptoms and signs of diabetes that dominated its story from ancient times until the late 19th century. The Ebers Papyrus, a document that dates from 1500 B.C., tells of a disease in Egypt characterized by the "passing of too much urine" and even suggests a remedy: "Mix cakes, wheat grains, fresh grits, green lead, earth, and water. Let stand moist, then strain, then take for four days."

Sushruta—in 500 B.C. India, an early exponent of Ayurvedic medicine—observed that the urine of such patients tasted like honey, was sticky to the touch, and attracted ants. He even described two forms of the disease—one occurring in older, obese individuals and the other in young individuals who did not live long after the diagnosis. This exactly parallels the modern conception of, respectively, type 2 and type 1 diabetes mellitus. Ancient Arabic texts—such as those of the great Islamic physician Avicenna, who practiced and wrote about medicine 1,000 years ago—also referred to a disease characterized by excessive urination (known as "polyuria") and sweet-tasting urine.

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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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