The Great Influenza

by John M. Barry

  Nonetheless, despite this lack of scientific achievement, Welch did not live one of those lives that began with great promise and ended in bitterness and disappointment. Despite his minimal production in the laboratory, people like Mall were drawn to him. As a prominent scientist said, 'Everyone agrees that Welch himself was the great attraction at the Pathological' . [H]is example, his intelligence, and his comprehensive knowledge formed the keystone of the arch of scientific medicine in America.'

  For William Welch's real genius lay in two areas.

  *

  First, he had not only knowledge but judgment. He had an extraordinary ability to hear someone describe his or her experiments, or read a paper, and immediately define the crucial points still obscure, the crucial series of experiments needed to clarify them. It was as if, although he could not himself conjure, he knew the techniques of conjuring and could teach others conjury.

  He had an equally extraordinary ability to judge people, to identify those with the promise to do what he had not done. He largely chose the medical school faculty, and he chose brilliantly. All were young when appointed. Welch was thirty-four; William Osler, a Canadian and arguably the most famous clinical physician of the modern era, forty; William Halsted, a surgeon who changed the way surgeons thought, thirty-seven; Howard Kelly, a gynecologist and pioneer in radiation therapy, thirty-one; J. J. Abel, a chemist and pharmacologist who would discover adrenaline and help revolutionize pharmacopoeia, thirty-six; W. H. Howell, a physiologist, thirty-three; and Mall, thirty-one. (Howell, Abel, and Mall had been graduate students at the Hopkins.)

  Second, Welch inspired. He inspired unconsciously, simply by being himself. In the early days of the school, Welch was heavy but not yet fat, short, with bright blue eyes that flashed above a dark beard called an 'imperial' - a mustache and pointed goatee. He dressed conservatively but well in dark clothes and often carried a derby hat in his hand. Despite his bulk, his hands and feet were conspicuously small and made him appear almost delicate. But his most singular quality was not physical. He seemed so centered and comfortable with himself that he gave comfort to those around him. He exuded confidence without arrogance, smugness, or pomposity. In his disputes (and he had many with those outsiders who resisted changes) he never raised his voice, never seemed to feel, according to a man who watched him for decades, 'the exuberant joy of putting an opponent down.'

  Everything about him was positive. His intelligence and the depth and breadth of his knowledge stimulated his teaching as well. He walked into the classroom without notes or preparation, often not knowing what subject he was to lecture on, and in an instant began discoursing lucidly and logically in ways that provoked thought and excitement. He was paternal without being paternalistic. Physicians sent him pathology samples for analysis and paid a hefty fee. His assistants did the work; he wrote up the results and gave them the money. He loved to eat and hosted lavish dinners at his club, the Maryland Club, often inviting junior colleagues or graduate students; one of them called these dinners among his 'rosiest memories' because of Welch's conversation, his ability to make students feel 'the richness of the world' - the world of art and literature as well as science.

  The total effect, said Simon Flexner, 'made for an atmosphere of achievement' The desire to be like Welch, the desire to win his approval, these were the principal incentives of the eager young men who crowded his lab.'

  Finally, a certain mystery clung to Welch. Although this was not part of his genius it explained part of his impact. For all his cordiality he remained distant. The cordiality itself was a barrier others could not penetrate. He paid little, and decreasing, attention to students until they did something significant enough to get his attention. He seemed casual, even sloppy. He would get so animated in conversation that his cigar ash would routinely drop onto his coat, where it would lie unnoticed. He was never on time. His desk would be piled with months of unanswered correspondence. Younger colleagues gave him a nickname, a nickname that spread from the Hopkins to younger scientists everywhere. They called him, never to his face, 'Popsy.'

  It was a comfortable, paternal, and warm nickname. But if he gave comfort, he took comfort from no one. Although he helped all whom he deemed worthy, although he surrounded himself with people, he neither encouraged nor allowed anyone to confide personal troubles to him. And he confided in no one. Mall once wrote his sister that he longed for a real friendship with Welch, not just an acquaintanceship. Even Mall would not get it. Welch took vacations alone in Atlantic City, where he enjoyed its tackiness.

  The students had a chant: 'Nobody knows where Popsy eats / Nobody knows where Popsy sleeps / Nobody knows whom Popsy keeps / But Popsy.'

  *

  The Hopkins medical school sat on the city's outskirts atop a hill, miles from the main campus of the university and downtown. The main building, the Pathological Laboratory, was ugly and squat, two stories of stone, with six tall windows on each floor, and square chimneys towering above the building itself. Inside, an amphitheater for autopsies hollowed out the building, and students on the top floor could peer down over railings; a long narrow room lined each floor, a pathology laboratory on the first floor, a bacteriology laboratory on the second.

  Even without the school, once the hospital opened in 1889, with sixteen buildings on fourteen acres, a small community began to develop. People breakfasted together and lunched together every day, and often met in the evening. Every Monday night a slightly more formal group of thirty to forty people gathered, including faculty, students who already had an M.D. or Ph.D., and clinicians. They would discuss current research or cases, and comments routinely generated new questions. Senior faculty sometimes dined in evening clothes at the 'high table' in a bay window overlooking the grounds. The younger men played poker together, entertained each other, and went to the 'Church' together - Hanselmann's restaurant and bar, at Wolfe and Monument, where they drank beer. A Harvard professor compared the Hopkins to a monastery. Harvey Cushing said, 'In the history of medicine there was never anything quite like it.' And they did have a mission.

  Elias Canetti, a Nobel laureate in literature, observed in his book Crowds and Power that large movements were often generated by what he called 'crowd crystals,' the small, rigid groups of men, strictly delimited and of great constancy, which serve to precipitate crowds. Their structure is such that they can be comprehended and taken in at a glance. Their unity is more important than their size. Their role must be familiar; people must know what they are there for'. The crowd crystal is constant'. Its members are trained in both action and faith'. The clarity, isolation, and constancy of the crystal form an uncanny contrast with the excited flux of the surrounding crowd.'

  In the same way that precipitates fall out of solution and coalesce around a crystal, individuals with extraordinary abilities and a shared vision had now coalesced about Welch at the Hopkins. Together, with a handful of others around the country, they intended to precipitate a revolution.

  CHAPTER FOUR

  AMERICAN MEDICAL EDUCATION needed a revolution. When the Hopkins medical school did at last open in 1893, most American medical schools had still not established any affiliation with either a teaching hospital or a university, most faculty salaries were still paid by student fees, and students still often graduated without ever touching a patient. Nor did Welch exaggerate when he said that, other than the Hopkins, no American 'medical school requires for admission knowledge approaching that necessary for entrance into the freshman class of a respectable college' . [S]ome require no evidence of preliminary education whatever.'

  By contrast, the Hopkins itself, not student fees, paid faculty salaries, and it required medical students to have not only a college degree but fluency in French and German and a background of science courses. Indeed, these requirements were so rigorous that Welch and Osler worried that the Hopkins would attract no students.

  But students did come. They came flocking. Motivated and self-selected, they flocked to a school whe
re students did not simply listen to lectures and take notes. They trooped through hospital rooms and examined patients, made diagnoses, heard the crepitant rales of a diseased lung, felt the alien and inhuman marble texture of a tumor. They performed autopsies, conducted laboratory experiments, and they explored: they explored organs with scalpels, nerves and muscles with electric currents, the invisible with microscopes.

  Those at the Hopkins were hardly alone in seeking reform. The need had been recognized for decades. Leaders at a few other medical schools - especially Vaughan at Michigan, William Pepper Jr. at the University of Pennsylvania, William Councilman (Welch's assistant until 1892) at Harvard, others at Northwestern, at New York's College of Physicians and Surgeons, at Tulane) were advancing the same values that Welch and the Hopkins were, and they were doing so with equal urgency. The American Medical Association had pushed reform since its inception, and individual physicians sought better training as well; the thousands who studied in Europe proved that.

  But relatively little change had occurred in the bulk of medical schools, and even at Harvard, Penn, and elsewhere, change had often come only after violent infighting, with continual rear-guard actions fought by reluctant faculty. William Pepper had made Penn good enough that the Hopkins raided its faculty, yet after sixteen years of fighting he spoke not of achievement but of 'long and painful controversy.'

  Even where change had occurred, a gap between the Hopkins and elsewhere still remained. Harvey Cushing trained at Harvard and came to Baltimore as Halsted's assistant. Nothing in Boston had prepared him for the difference. He found the Hopkins 'strange' . The talk was of pathology and bacteriology of which I knew so little that much of my time the first few months was passed alone at night in the room devoted to surgical pathology looking at specimens with a German textbook at hand.'

  The Hopkins did not limit its influence to medicine. Half a century after it opened, of 1,000 men starred in the 1926 edition of American Men of Science, 243 had Hopkins degrees; second was Harvard with 190. Even Harvard's Charles Eliot conceded that the Harvard Graduate School 'started feebly' and 'did not thrive, until the example of Johns Hopkins'. And what was true of Harvard was true of every other university in the land.'

  But in medicine the Hopkins made its chief mark. As early as 1900 Welch noted that at the Harvard-run Boston City Hospital 'they have only Hopkins men there, and want no others.' By 1913 a European acknowledged that research in the United States in his field rivaled that done in any European country and gave credit 'to one man - Franklin P. Mall at the Johns Hopkins University.' Of the first four American Nobel laureates in physiology or medicine, the Hopkins had trained three, while the fourth had received his highest degree in Europe.

  In patient care its impact was similar. As with all medical schools, most of its graduates became practicing physicians. And within thirty-five years after opening, more than 10 percent of all Hopkins graduates had become full professors, with many younger graduates on track to do so. Many of these men transformed entire medical schools at other universities - people like Councilman and Cushing at Harvard, William MacCallum at Columbia, Eugene Opie at Washington University, Milton Winternitz at Yale, George Whipple (a Nobel laureate) at Rochester.

  Howard Kelly, for all his strangeness (a fundamentalist who preached to prostitutes on street corners of whom one student said, 'The only interest he manifested in my classmates was whether they were saved') revolutionized gynecology and pioneered radiation therapy. And no individual had more impact on patient care than William Halsted, who introduced rubber gloves into surgery, who insisted upon preparation and thought prior to every step. He took such care that William Mayo once joked that his patients were healed by the time he finished, but the Mayo brothers also stated that they owed him a tremendous debt. So did all of American surgery: of seventy-two surgeons who served as residents or assistant residents under him, fifty-three became professors.

  In the meantime, Henry James described the Hopkins as a place where, despite 'the immensities of pain' one thought of 'fine poetry' and the high beauty of applied science' . Grim human alignments became, in their cool vistas, delicate symphonies in white' . Doctors ruled, for me, so gently, the whole still concert.'

  *

  Behind this still concert lay Welch, the impresario. By the first decade of the twentieth century, Welch had become the glue that cemented together the entire American medical establishment. His own person became a central clearinghouse of scientific medicine. Indeed, he became the central clearinghouse. As founding editor of the Journal of Experimental Medicine, the first and most important American research journal, he read submissions that made him familiar with every promising new idea and young investigator in the country.

  He became a national figure, first within the profession, then within science, then in the larger world, serving as president or chairman of nineteen different major scientific organizations, including the American Medical Association, the American Association for the Advancement of Science, and the National Academy of Sciences. Stanford president Ray Wilbur neither flattered nor overstated when in 1911 he wrote him, 'Not to turn to you for information in regard to the best men to fill vacancies in our medical school would be to violate all the best precedents of American medical education.' Welch had, said one colleague, 'the power to transform men's lives almost by the flick of a wrist.'

  But his use of power in placing people in positions (or for that matter using it for such things as defeating antivivisection legislation, which would have prevented using animals as experimental models and thus crippled medical research) was trivial in its impact compared to his application of power to two other areas.

  One area involved completing the reform of all medical education. The example of the Hopkins had forced more and faster reforms at the best schools. But too many medical schools remained almost entirely unaffected by the Hopkins example. Those schools would learn a harsh lesson, and soon.

  Welch's second interest involved starting and directing the flow of tens of millions of dollars into laboratory research.

  *

  In Europe governments, universities, and wealthy donors helped support medical research. In the United States, no government, institution, or philanthropist even began to approach a similar level of support. As the Hopkins medical school was opening, American theological schools enjoyed endowments of $18 million, while medical school endowments totaled $500,000. The difference in financial support as well as educational systems largely explained why Europeans had achieved the bulk of medical advances.

  Those advances had been extraordinary, for medicine in the late nineteenth and early twentieth centuries was experiencing arguably its most golden age - including anytime since. The germ theory had opened the door to that progress. Finally investigators began using that door.

  In 1880 Pasteur (who observed, 'Chance favors the prepared mind') was trying to prove he had isolated the cause of chicken cholera. He inoculated healthy chickens with the bacteria. They died. Then chance intervened. He had put aside a virulent culture for several days, then used it to inoculate more chickens. They lived. More significantly, those same chickens survived when exposed to other virulent cultures. Crediting Jenner for the idea, he tried to weaken, or 'attenuate,' his word, cultures and use them to immunize birds against lethal bacteria. He succeeded.

  He began applying these techniques to other infections. With anthrax he was not the first to experiment with weakened cultures, but his work was both definitive and very public. While a gallery of newspapermen and officials watched, he inoculated cattle, then exposed them to anthrax; the inoculuated ones lived, while the controls died. Three years later 3.3 million sheep and 438,000 cattle were vaccinated against anthrax in France. He also saved the life of a boy bitten by a rabid dog by giving him gradually stronger injections of fluid containing the pathogen. The next year, 1886, an international fund-raising drive created the Pasteur Institute. Almost immediately the German goverment funded research in
stitutes for Koch and a few other outstanding investigators, and research institutes were founded in Russia, Japan, and Britain.

  Meanwhile, public health measures were containing cholera and typhoid, and in Germany, Richard Pfeiffer, Koch's greatest disciple, and Wilhelm Kolle immunized two human volunteers with heat-killed typhoid bacilli. In Britain Sir Almroth Wright advanced upon this work and developed a vaccine against typhoid.

  All these advances prevented infectious disease. But no physician could yet cure a patient who was dying of one. That was about to change.

  One of the deadliest of childhood diseases was diphtheria. Usually it killed by choking its victims to death - by generating a membrane that closed the breathing passages. In Spain the disease was called el garrotillo, 'the strangler.'

  In 1884, German scientist Friedrich Loeffler isolated the diphtheria bacillus from throats of patients, grew it on a special medium (laboratories today still use 'Loeffler's serum slope' to grow the bacteria from suspected cases), and began careful experiments in animals that took several years. His work suggested that the bacteria themselves did not kill; the danger came from a toxin, a poison, that the bacteria excreted.

  In 1889 Pasteur's protegés Emile Roux and Alexandre Yersin grew broth thick with diphtheria bacteria and used compressed air to force the broth through a filter of unglazed porcelain. (The filter was designed by Charles Chamberland, a physicist working with Pasteur; though only a tool, the filter itself would prove to be immensely important.) No bacteria or solids could pass through the porcelain. Only liquid could. They then sterilized this liquid. It still killed. That proved that a soluble toxin did the killing.

  Meanwhile, an American physiologist named Henry Sewall at the University of Michigan was studying snake venom, which chemically resembles many bacterial toxins. In 1887 he immunized pigeons against rattlesnake poison.