November 2018 Issue [Investigation]

Discovery, Interrupted

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How World War I delayed a treatment for diabetes and derailed one man’s chance at immortality

Imagine what it must have felt like to be the parent of a child who contracted diabetes before the discovery of insulin. Children with the disease would typically start feeling tired and would then find themselves unable to focus at school, before moving on to stranger symptoms, like frequent urination paired with constant thirst, and drastic weight loss despite ravenous eating. If you took a child with these symptoms to the doctor in, say, 1920, a urine test would be administered, and if glucose levels were found to be elevated, you would be told that your child had diabetes,…

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Jeffrey Friedmanis a professor of molecular genetics at the Howard Hughes Medical Institute at Rockefeller University.

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My research began as a browsing of letters and laboratory notes in the Rockefeller University archives, and later expanded to include study of the materials housed at Yale, Johns Hopkins, and the American Philosophical Society in Philadelphia, as well as conversations with members of Kleiner’s family. I published an earlier consideration of the scientific aspects of Kleiner’s story in Nature Medicine, a medical journal, in 2010.

In 1913, Frederick Madison Allen, a leading authority on the disease who was also at the institute, developed a treatment for childhood diabetes that was little better than the illness: a starvation diet. Allen showed that death could be forestalled if caloric intake was restricted, and some patients were sustained just long enough to receive insulin when it became available

Minkowski, who was trying to evaluate the role of the pancreas in digestion, observed that the previously housebroken dog urinated constantly after the surgery, and he surmised that it had developed diabetes.

“Gorgas’s nightmare was of an epidemic sweeping through those camps,” John M. Barry writes in The Great Influenza, his definitive history of the Spanish flu. The book also chronicles the role the Rockerfeller Institute played in helping Gorgas establish modern approaches to managing infectious disease among the troops.

Animals were the source of insulin until the 1980s, when recombinant-DNA technology enabled scientists to synthesize human insulin in the laboratory.

The epidemic had exploded around the globe in precisely the manner that Gorgas had feared, with soldiers disseminating the disease as they returned home. At least 50 million people would die before it was over, in 1920.

Flexner may also have been concerned about a wave of anti-immigrant and anti-Semitic sentiment that had begun to build in the United States during the war and was still growing. Meltzer, a Jewish immigrant who had worked in Germany, had been accused of pro-German sympathies because of the Brotherhood, as reported in a 1916 New York Times article. Flexner was himself Jewish, and had been a target of anti-Semitism while at the University of Pennsylvania. He must have been aware that the institute—whose faculty included many immigrants and Jews, and whose funding was entirely dependent on one donor—could suffer if it were viewed as “too foreign” or “too Jewish.”

It’s interesting to note that the two men’s backgrounds were not dissimilar. Like Kleiner, Flexner came from modest beginnings and Jewish-immigrant roots: he’d grown up the elder son of Bohemian Jewish immigrants in Louisville, Kentucky, where his father, a former teacher, had peddled wares for a time from a mule-drawn cart. But unlike the diligent young Kleiner, Flexner was a difficult, rebellious youth. His younger brother, Abraham, would later say that despite his outward confidence, Simon had “never lost his insecurities.”

Kleiner’s concern that the patent would deprive indigent patients of the new treatment was allayed a few months later, when John D. Rockefeller Jr. distributed $150,000, an enormous sum at the time, to buy insulin for all patients in the United States who couldn’t afford it. Rockefeller was responding to a handwritten letter from W. J. Kerns, a postman living in Brooklyn whose daughter’s life had been saved by the new miracle drug. Kerns wrote to suggest that Rockefeller ensure that other less affluent parents could benefit from the lifesaving treatment. (In a strange twist, Rockefeller chose Flexner to oversee the distribution of the “insulin fund.”) Nearly a century later, however, Eli Lilly and the two other major manufacturers of insulin, Novo Nordisk and Sanofi, are being widely criticized for extreme price hikes in recent years that are leaving many patients unable to afford the drug.

These included, among many others, physicians in India and Egypt thousands of years ago, who identified signs of diabetes including the sweetness of urine; the experimental physiologist Matthew Dobson, who in 1772 concluded that the sweetness was caused by sugar; Paul Langerhans, a pathologist who in 1869 identified small islands of cells in the pancreas, later called islets of Langerhans, that would eventually be recognized as the source of insulin; and the physician Eugene Opie, who showed, in 1901, that there were pathological changes in these structures in diabetic patients.

This view of progress helps explain why nearly all the greatest discoveries have been made (or would have been made) by more than one group simultaneously. In 1922 William Ogburn and Dorothy Thomas listed the greatest discoveries to that point, noting that all had been made by more than one person at around the same time. Robert Merton, perhaps the leading sociologist of science, went further, arguing that all “scientific discoveries are in principle multiples,” because accumulated knowledge sets the stage for pivotal advances. Thus, even though Kleiner did not have the opportunity to discover insulin, only a few years elapsed before the Toronto group did. And in 1921 a Romanian, Nicolae Paulescu, was endeavoring to purify insulin at precisely the same time as the Toronto group. If it had not been the Canadians, it almost certainly would have been Paulescu, or someone else.

In a 1939 article for Harper’s Magazine, Abraham Flexner made the same point by noting that “most of the really great discoveries” had been made by “men and women who were driven not by the desire to be useful but merely the desire to satisfy their curiosity.”

Discovery, Interrupted

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