NINETEEN

The Crossroads of America, Indianapolis, Indiana, 1919—1921

ALEC CLOWES WAS A DAZZLING TORNADO OF A MAN. WHETHER careening around Indianapolis in his luxurious Duesenberg automobile or pelting a fellow scientist with questions, he was constantly in motion, late for every meeting, often beginning conversations midsen- tence. He was impatient with details but did not like to delegate them. He wrote so rapidly that he had trouble deciphering his own handwriting. He ignored organizational hierarchy and abhorred committees. He was equally prone to outbursts of frustration and gestures of generosity. His handsome face was dominated by beetle brows under which his intense blue eyes often twinkled with ideas or mischief or both. Although he was not a medical doctor, those who knew him well called him “Doc.” He parked wherever he liked and played golf holes in the order that appealed to him, often beginning with the hole nearest to where he parked. Eli Lilly said of him, “He lived more hours in a day than any man I knew.”

Clowes (pronounced “Clues”) joined Eli Lilly and Company in 1919, charged with identifying medical research projects having commercial potential for Lilly. In this unusual capacity Clowes was at liberty, and had the professional obligation, to explore the rarefied world of medical research as his interest drew him. At that time, it was widely accepted that the interests of medical research and the pharmaceutical business were utterly and irreconcilably incompatible. Researchers were primarily concerned with contributing to a body of research by writing, presenting, and publishing scientific papers. Pharmaceutical firms were primarily concerned with making money by means of manufacturing and selling products. Any research effort conducted by a pharmaceutical manufacturer was viewed with contempt by physicians and university scientists. In 1915 the Council on Pharmacy of the American Medical Association opined “it is only from laboratories free from any relation with manufacturers that real pharmaceutical advances can be expected.” Certainly Banting and Macleod subscribed to the belief that a profit motive could only impair research. Furthermore, many biochemical research scientists, including Banting and Macleod, were also medical doctors who had taken the Hippocratic oath and were therefore proscribed from using their knowledge for purposes, such as profit, which might interfere with the physical benefit of humankind.

In the early twentieth century, pharmaceutical companies were much like the apothecaries and patent medicine makers of the nineteenth century. They generally sought to secure proprietary claims by improving products already on the market, rather than inventing new medicines. Around 1920, Eli Lilly and Company’s popular products included: Charcoal Lozenges for indigestion, Cape Aloes for constipation, Passola- ria for insomnia and anxiety, Liquid Blaud for anemia, and Elixir #63, containing catnip and fennel, for colds, headaches, colic and fever.

Eli Lilly, grandson of the company’s founder, thought that the future hinged on patenting fundamentally new ideas, not improvements of old ideas. Had not George Westinghouse and Thomas Edison proved that cooperation between inventors and industry could catalyze the development process and improve the product? An internal research and development division, Eli posited, would enable the company to develop and patent entirely new proprietary drugs. He held that the future of pharmaceutical manufacturing was in fundamental biological research. It was a radical idea. In essence he envisioned the model that would become the industry standard among Big Pharma companies for decades to come, even to the present day.

As Eli Lilly saw it, he faced two hurdles in creating a creditable new internal research group, and they were two sides of the same coin. The first hurdle was to persuade the company’s board of directors to invest in a fundamental research department. The second hurdle was to persuade a research scientist to climb down from the ivory tower to work in the world of commercial enterprise. In the first challenge Eli had a powerful ally—his father, J. K. Lilly Sr., president of the company.

J. K. Lilly Sr. was a man of uncommon judgment and beneficence who inspired respect and affection in almost everyone he encountered. He had been only fourteen years old when his father, Colonel Eli Lilly, founded Eli Lilly and Company in 1876. J.K. Sr. joined the company after graduating cum laude in 1882 from the first pharmacy school in North America, the Philadelphia College of Pharmacy. After the Colonel died, J. K. Lilly Sr. became president of the company in 1898. The development and introduction of North America’s first lifesaving drug could hardly have been entrusted to a better man.

Eli had been promoting novel ideas ever since his introduction into the family business in 1907 as a one-man finance department. Eli’s careful analysis of the Fluid Extract Department had resulted in the company saving fifteen thousand dollars annually by replacing wooden barrels with copper-lined barrels, eliminating loss through absorption of the product. He designed a slope-shouldered bottle for powdered extracts that helped pharmacists avoid wasted product trapped in the bottle’s interior. And taking a cue from Henry Ford, Eli introduced straight- line mass production to the pharmaceutical business with the help of a specially designed building and a complex system of conveyor belts, chutes, pulleys, and pipes.

There were many long discussions in the boardroom. Leading the charge for innovation was Eli. The conservative argument was often led by Charles Lynn, general manager and trusted right-hand man of Lilly Sr. Lynn held the distinction of being the first nonfamily member to direct the company. He was a ham-fisted, cigar-smoking pragmatist who was innately skeptical of innovative ideas, often with sound reasoning. In the end, Eli won the debate to establish a research department to seek out new products and begin the search for its director. Lynn bit down on his cigar with a savage intensity but he could say nothing. J. K. Lilly Sr. was gradually turning the business over to his eldest son, Eli.

Eli set out to find an experienced, well-respected medical researcher who would be willing to cross over to commercial industry. But who? Clearly it would be a man of such intellectual confidence, ambition, and curiosity as to be unintimidated by the potential disapproval of his peers in research, someone whose accomplishments were impressive enough to prevent those disapproving peers from dismissing him, someone able to bridge two very different cultures and see through those differences to practicable solutions. To accomplish all that, this someone would have to possess inexhaustible energy. Above all, this someone would have to be not just knowledgeable but imaginative. Lilly thought Clowes might be that man.

Clowes completed his medical studies in chemistry at the Royal College of Science in London, and went on to pursue his doctoral degree at the University of Gottingen. (In the late nineteenth and early twentieth century, England and Germany were considered the scientific leaders of the world.) In 1901 Clowes had fled the hidebound academic and professional hierarchies of Europe for America, where his intellectual ingenuity might find more opportunity for expression. For eighteen years he worked at Roswell Park Memorial Institute, a cancer laboratory in Buffalo, New York. In Buffalo he married Edith Whitehill Hinkel and started a family. During the war he joined the Chemical Warfare Service in Washington, D.C. When the war ended in 1918, Clowes was living at the Cosmos Club in Washington, D.C., casting about for a new direction. He was forty-one years old, not an age when the average man would consider making a risky career change, but Clowes was not an average man. Would he return to Buffalo or look for something new? Just then the Lillys invited him to Indianapolis for lunch and an interview. The timing could not have been better.

From the moment that he stepped off the train in December 1918 into the glorious Romanesque style Union Station, Clowes was favorably impressed with Indianapolis. The barrel-vaulted ceilings soared above him, and beams of sunlight streamed through skylights down onto the marble-inlaid floors. It reminded him of the great train stations of London. Built in 1852—53, Indianapolis’s Union Station held the distinction of being the nation’s first centralized train station. The growth of railroads led to building an even larger version in 1888.

Indianapolis then was home to several major industries, including automobile manufacturing and auto parts, railroad cars, and meat packing. The huge number of workers who kept these industries functioning relied on the world’s largest intercity electric railway system, the Inter- urban. In the year 1918 more than 7.5 million passengers were carried in 128,145 of these clean, convenient, and inexpensive trains. Interurbans traveled hundreds of miles in nearly all directions, from six o’clock in the morning to midnight, express and local, parlor and sleeper, all across the state’s twenty-three million acres and beyond.

The city’s architecturally appealing downtown area bustled with energy. There was the elegant Opera House, the striking State House and the solemnly beautiful 248-foot-tall Soldiers and Sailors Monument, anchoring the Circle at the center. In 1920 the state’s employment growth numbers would show that manufacturing and industry had surpassed agriculture for the first time. By 1925 Indianapolis would be dubbed “the Crossroads of America” by the National Geographic Society. Clowes could see that the city had much to recommend it, which would be important when he had to make a case to Edith Clowes that the family should relocate from her hometown of Buffalo, New York.

J. K. Lilly Sr., then fifty-seven years old and his son Eli, then thirty- three met Clowes at Union Station. They took him by chauffeured car on a forty-five-minute tour of Indianapolis, narrated in large part by an enthusiastic Eli Lilly, except when the elder Lilly could get a word in. Clowes loved cars and Indianapolis was steeped in American car culture. Eli informed his recruit that sixty or so different automobile makes were manufactured in Indianapolis, including Overland, Cole, Marmon, Stutz, Duesenberg, Atlas-Knight, Economycar, Hoosier Scout, and Pathfinder. The city competed with Detroit and Cleveland in automobile manufacturing. But only Indianapolis could claim the Indianapolis Raceway and the Stutz Bearcat, world champion of America and Europe in speedway, road race, and long distance competitions. Cannonball Baker had driven a Bearcat from San Diego to New York in eleven days, seven hours, and fifteen minutes. Ford’s large plant in Indianapolis manufactured twenty- five thousand Model Ts annually. Theodore Dreiser penned A Hoosier Holiday (1916), in which he described a car trip from New York to Indiana, and thus helped to spread the religion of the automobile to Americans everywhere.

Indianapolis also happened to be the home of Charles W. Fairbanks, who had served as a U.S. senator for eight years before becoming vice president under Theodore Roo sevelt and later the running mate of Charles Evans Hughes in the 1916 presidential election.

The three men dined at the Indianapolis Athletic Club, where the menu had been arranged in advance by the Lillys, specifically to indoctrinate their visitor’s palate to Hoosier cuisine. Over lunch the three men discussed the development of drugs, using aspirin as a case study. All three were familiar with the basic facts of the story; Clowes would have studied it thoroughly at Gottingen. In 400 B.C., Hippocrates used the powdered bark and leaves of the willow tree to help relieve pain and fever. By 1829, scientists had identified willow’s beneficial compound as salicin. Then French chemist Henri Leroux improved the extraction process and Italian chemist Raffaele Piria refined salicin, isolating salicylic acid. Salicylic acid is highly effective but it irritates the stomach. In 1853 another French chemist, Charles Gerhardt, succeeded in buffering salicylic acid without diminishing its efficacy. Like a true academic, Gerhardt published a paper to document his results and thought no more about it. It wasn’t until 1897—forty-four years after Gerhardt’s discovery—that a chemist named Felix Hoffman at Germany’s Friedrich Bayer & Co. began working with the compound in order to alleviate his father’s arthritis pain. By 1899 Bayer aspirin was selling around the world.

The younger Lilly practically crowed. “How many thousands of people suffered needlessly during the forty-six years between Gerhardt’s discovery and Bayer’s distribution of aspirin?”

Clowes nodded. The younger man’s enthusiasm appealed to him. It was true that if Bayer had been involved in the process in 1853, a clinical application would almost certainly have been available to patients sooner. “Ideas don’t cure people. Drugs cure people.” Lilly continued, “That’s why we must bring the research scientists and the drug manufacturers together.”

To do so would require considerable risk for both parties. As Clowes’s longtime secretary once put it, at that time a man dedicated to theoretical research who shifted to commercial objectives was somewhat in the position among his fellow scientists of having sold his birthright for a mess of porridge. For the Lillys it would require an enormous financial investment with no guaranteed return. Such entrepreneurial ventures were not entirely new to the Lillys. When Colonel Lilly saw that what deterred the ailing individual from taking medicine was that most of it was so unpalatable, he sought a new delivery mechanism that would solve the problem. While his peers were sweetening and flavoring their medicines, Colonel Lilly built its first gelatin capsule plant in 1895. In 1898 empty, easy-to-swallow gelatin capsules, in seven sizes, appeared on the Lilly price list. They were hugely successful. In 1905, company sales passed the $1 million mark.

And so the three men reached an agreement and the gamble that Clowes began in 1901 with his immigration to America would continue with his leaving the familiar world of research to join a commercial pharmaceutical company in 1919. Alec and Edith Clowes and their two sons moved from Buffalo to Indianapolis in the spring of 1919. At Clowes’s behest, the Lillys funded a research facility in Woods Hole, Massachusetts, so that Clowes could continue to pursue his interest in marine biology. Every summer he invited guest scientists to join him there and so facilitated partnerships between Lilly and the research world. He enjoyed sailing, and the sea breezes relieved his hayfever. He often lingered at Woods Hole until early October. For two and a half years the Lillys had treated Clowes with the greatest generosity, creating a pure research position and allowing him full freedom to work wherever and whenever he pleased. All this openhanded munificence only drove Clowes harder toward the objective of finding a golden opportunity. And yet, there had been no dramatic discoveries or developments in his two years in Indianapolis. The stakes were no longer his alone. The Lillys had taken the leap of faith, and, of course, Edith had also, having moved across the country. Now it all came down to Christmas day, 1921.

Admittedly his decision to attend the American Physiological Society meeting was based on a hunch, but it was a hunch with J. J. R. Macleod’s name attached to it. The history of diabetes research had been particularly riddled with false claims and near misses and Clowes felt sure that J. J. R. Macleod was both too proud and too savvy to attach his name to an idea he wasn’t completely sure of. Still, Canada did seem an unlikely location for a medical breakthrough of such sweeping importance. What had driven a man of Macleod’s standing to move to Toronto was certainly a mystery to Clowes, but he supposed Macleod would say the same about Clowes’s choice to defect to the even more exotic territory of commercial industry.

Nearly everything about Clowes’s attendance at the meeting in New Haven, Connecticut, in December 1921 was unlikely. He was an Englishman working in America. He was a researcher working in industry. His focus was cancer, not diabetes. Charles Hughes and Alec Clowes did not know each other, but they would soon have a powerful impact on each other’s lives. They had one thing in common—they each had lost a child to disease. Hughes had lost Helen and Clowes had lost a three- year-old son to leukemia in Buffalo. So it was no small sacrifice that attendance at the meeting meant that he could not spend Christmas Day with his family. But if the rumors from Toronto were true then millions of mothers and fathers would be spared the suffering of losing a child.

While Banting and Macleod prepared to make their announcement in New Haven, the world’s diplomatic powers continued to negotiate disarmament in Washington. In December 1921 the front page of The Indianapolis Newsregularly featured articles on the progress of the Washington Conference. One headline read “Conference Takes A Day Off At Last: Insatiable Mr. Hughes Permits a Lapse for Christmas but All Would Work Monday.” The inner pages were crammed with advertisements. The Circle Talking Machine Shop offered “Victrolas for everybody. $25 to $1,500.” Children both naughty and nice would be delighted with sleds from one dollar to five dollars fifty cents. The “Photoplay Attractions” for the week listed the movies featuring Mary Pickford, Norma Talmadge, Jackie Coogan, and Buster Keaton. The Spinks-Arms Hotel was celebrating its first anniversary with an old-fashioned, mid-day Christmas dinner for one dollar and fifty cents per plate. No fewer than fifty-seven churches announced the times of their Christmas Day services and the topics of their sermons. Alec and Edith rarely missed a Sunday at the Christ Episcopal Church on The Circle, where they usually saw fellow parishioners Eli Lilly with his wife Evelyn and daughter Evie.

Every December Edith Clowes took her sons, George Jr. and Allen, to see the Christmas displays in downtown Indianapolis. With a child in each graceful, gloved hand, the threesome strolled along the Italianate storefronts on Meridian Street to the southwest corner of Meridian and Washington streets. There stood L. S. Ayres, the finest of the Indianapolis department stores, which rose eight stories high with six elevators and two hundred and fifty feet of windows. At Christmastime, each window was transformed with an elaborate diorama. Inside, on a balcony above the main floor, a white-robed chorus serenaded the shoppers with cheery carols and the entire sixth floor was transformed into “Toyland,” where towering displays of toys fitting every description waited to dazzle small, wide-eyed visitors. For the Clowes family, Christmas of 1921 would be different from all the rest. Before the sun rose on December 25th, Alec Clowes would leave the Duchess—his fond nickname for his clever and refined wife—and their two boys to board a train bound for Pennsylvania Station in New York City, where he would walk across town to Grand Central Terminal to board another train to New Haven.

Clowes was not a particularly good sleeper anyway. Sometimes he went out walking before the sun was up, accompanied by his walking stick and the family dog, a collie named Roddy. These last few months he had seemed particularly restless, often rising at four o’clock in the morning to read and to think. But on Christmas morning, attired in his habitual un-pressed British tweed, Alec Clowes would find himself at Indianapolis’s Union train station, where his adventure with Eli Lilly had begun two years before. He could not possibly imagine how frequently he would walk across that marble floor over the following eighteen months. During that time Clowes would travel so often that it would not be uncommon for him to arrive at a station, step dazedly onto the platform, go to a telephone, and place a call to Frances to ask her where exactly he was going.

On Christmas Eve the temperature in Indianapolis dropped thirty degrees. The following morning Union Station was so empty that Clowes could hear his footsteps echoing as he strode to his train. Settling into his seat in a first class train compartment, he put his briefcase on the empty seat across from him and closed his eyes. His mind wandered to the brick Tudor house he’d just left. He imagined the first sun glittering in the icy branches of the poplar trees in the front yard. He imagined his sons racing each other down the front stairs to the Christmas tree.

The train lumbered through the city and picked up speed across the great white plains, deep with snowdrifts. Clowes thought of the upcoming conference and the odds that the news from Toronto was true. Just because no one had been able to isolate the pancreatic extract yet didn’t mean that they couldn’t do it now. Was it so unreasonable to imagine that on Christmas 1922, one year hence, J. K. Lilly Sr. would receive dozens of cards and letters from strong, active diabetic children thanking him for their very lives and describing in delirious detail the foods that they could now consume? Was it absurd to dream that within twenty years, the life expectancy of a ten-year-old diabetic child would be more than twenty-five times greater than it was on that lonely Christmas Day 1921?

Perhaps, but that is exactly what happened.