The Great Influenza: The Epic Story of the Deadliest Plague in History - John M. Barry (2004)


Chapter 3

WELCH’S COURSE quickly became extraordinarily popular. Soon students from all three of New York City’s medical schools were lining up for it, attracted as Welch had been to this new science, to the microscope, to experimentation. And Welch did not simply teach; he inspired. His comments always seemed so solid, well grounded, well reasoned. A colleague observed, “He would leak knowledge.” And the excitement! Each time a student fixed a specimen on a slide and looked through a microscope, an entire universe opened to him! To some, discovering that universe, entering into it, beginning to manipulate it, was akin to creating it; they must have felt almost godlike.

The College of Physicians and Surgeons had to offer a laboratory course to compete. It beseeched Welch to teach it. He declined out of loyalty to Bellevue but recommended the hiring of T. Mitchell Prudden, an American he had known—and considered a rival for the Hopkins job—in Europe. It was the first of what would be uncounted job offers that he engineered. Meanwhile one of his students recalled “his serious, eager look, his smiling face, his interest in young men which bound them to him. He was always ready to drop any work in which he was engaged and answer even trivial questions on any subject—in fact he was never without an answer for his knowledge was encyclopedic. I felt instinctively that he was wasted at Bellevue, and was destined to have a larger circle of hearers.”

But despite the throngs of motivated students taking the two courses, neither Prudden nor Welch prospered. Two years went by, then three, then four. To cobble together a living, Welch did autopsies at a state hospital, served as an assistant to a prominent physician, and tutored medical students before their final exams. As he passed his thirtieth birthday he was doing no real science. He was making a reputation and it was clear if he chose to concentrate on practice he could become wealthy. Little medical research was being done in America—although the little that was done was significant—but even that little he had no part of. In Europe science was marching from advance to advance, breakthrough to breakthrough. The most important of these was the germ theory of disease.

Proving and elaborating upon the germ theory would ultimately open the way to confronting all infectious disease. It would also create the conceptual framework and technical tools that Welch and others later used to fight influenza.

Simply put, the germ theory said that minute living organisms invaded the body, multiplied, and caused disease, and that a specific germ caused a specific disease.

There was need for a new theory of disease. As the nineteenth century progressed, as autopsy findings were correlated with symptoms reported during life, as organs from animals and cadavers were put under a microscope, as normal organs were compared to diseased ones, as diseases became more defined, localized, and specific, scientists finally discarded the ideas of systemic illness and the humours of Hippocrates and Galen and began looking for better explanations.

Three theories stood as rivals to the germ theory.

The first involved “miasma.” Several variations of this concept existed, but they basically argued that many diseases were caused by some kind of putrefaction in the atmosphere, or by some climactic influence, or by noxious fumes from decaying organic materials. (In China the wind was originally regarded as a demon that caused illness.) Miasmas seemed a particularly good explanation of epidemics, and the unhealthiness of swamp regions seemed to support the theory. In 1885, when Welch considered the germ theory as proven, the New York City Board of Health warned that “laying of all telegraph wires under ground in one season…would prove highly detrimental to the health of the city…through the exposure to the atmosphere of so much subsoil, saturated, as most of it is, with noxious gases…. Harlem Flats [had] a sufficient supply of rotting filth to generate fetid gases adequate to the poisoning of half the population.” As late as the 1930s one prominent and highly regarded British epidemiologist continued to advocate the miasma theory, and after the 1918 influenza pandemic, climatic conditions were scrutinized in a search for correlations.

The “filth” theory of disease was almost a corollary of the miasma theory. It also suited Victorian mores perfectly. Fear of “swamp gas”—often a euphemism for the smells of fecal matter—and installation of indoor toilets were all part of the Victorian drive to improve sanitation and simultaneously to separate the human body from anything Victorians found distasteful. And filth often is associated with disease: lice carry typhus; contaminated water spreads typhoid and cholera; rats through their fleas spread plague.

Both the miasma and filth theories had sophisticated adherents, including public health officials and some extremely gifted scientists, but the most scientific rival of the germ theory explained disease in terms purely of chemistry. It saw disease as a chemical process. This theory had much to recommend it.

Not only had scientists used chemistry as a lens that brought much of biology into focus, but some chemical reactions seemed to mimic the actions of disease. For example, advocates of the chemical theory of disease argued that fire was a chemical process and a single match could set off a chain reaction that ignited an entire forest or city. They hypothesized that chemicals they called “zymes” acted like a match. A zyme started a series of chemical reactions in the body that could launch the equivalent of fermentation—infection. (The chemical theory of disease, without the name, has in fact largely been validated. Scientists have clearly demonstrated that chemicals, radiation, and environmental factors can cause disease, although usually only through long-term or massive exposure and not, as the zymote theory hypothesized, by suddenly igniting a cascade of reactions.)

Ultimately this theory evolved to suggest that zymes could reproduce in the body; thus they acted as both catalysts and living organisms. In fact, this more sophisticated version of the zymote theory essentially describes what is today called a virus.

Yet these theories left many scientists unsatisfied. Disease often seemed to germinate, grow, and spread. Did there not then have to be a point of origin, a seed? Jacob Henle in his 1840 essay “On Miasmata and Contagia” first formulated the modern germ theory; he also offered evidence for the theory and laid out criteria that, if met, would prove it.

Then, in 1860, Pasteur proved that living organisms, not a chemical chain reaction, caused fermentation, winning converts to the germ theory. The most important early convert was Joseph Lister, who immediately applied these findings to surgery, instituting antiseptic conditions in the operating room and slashing the percentage of patients who died from infections after surgery.

But the work of Robert Koch was most compelling. Koch himself was compelling. The son of an engineer, brilliant enough to teach himself to read at age five, he studied under Henle, was offered research posts, but became a clinician to support his family. He did not, however, stop investigating nature. Working alone, he conducted a series of experiments that met the most rigid tests and discovered the complete life cycle of the anthrax bacillus, showing that it formed spores that could lie dormant in the soil for years. In 1876 he walked into the laboratory of Ferdinand Cohn, one of Welch’s mentors, and presented his findings. They brought him instant fame.

He subsequently laid down what came to be known as “Koch’s postulates,” although Henle had earlier proposed much the same thing. The postulates state that before a microorganism can be said to cause a given disease, first, investigators had to find the germ in every case of the disease; second, they had to isolate the germ in pure culture; third, they had to inoculate a susceptible animal with the germ and the animal then had to get the disease; and, fourth, the germ had to be isolated from the test animal. Koch’s postulates became a standard almost immediately. (Meeting the standard is not simple; finding a test animal that suffered the same symptoms as humans when infected with a human pathogen, for example, is not always possible.)

In 1882 Koch’s discovery of the tubercle bacillus, the cause of tuberculosis, shook the scientific world and further confirmed the germ theory. Tuberculosis was a killer. Laymen called it “consumption,” and that name spoke to the awfulness of the disease. It consumed people. Like cancer, it attacked the young as well as the old, sucked the life out of them, turned them into cachectic shells, and then killed them.

It would be difficult to overstate the importance of Koch’s discovery to the believers in bacteriology. In New York, one of Welch’s friends came running into his bedroom with a newspaper account of the discovery. Welch jumped out of bed and together they rushed to tell another friend. Almost immediately afterward, Welch felt the excitement directly. He demonstrated Koch’s discovery to his class, copying Koch’s method, his class watching steam rise from the plate while he stained sputum from a consumption patient with carbol-fuchsin, the stain binding to the bacillus so that it became visible on a slide. Here was the newest and greatest of discoveries! Students looked at the slide through the microscope, saw what Koch had seen, and were electrified, many recalling the moment vividly years later. One of those students was Hermann Biggs, who became a giant in his own right; at that moment he decided to spend his life in bacteriology.

But for Welch, reproducing Koch’s finding must have been bittersweet. He knew the Germans, knew nearly all of these men adventuring into the unknowns of science. Yet here he was only keeping track of their work, doing none himself.

Then, in 1883, Koch achieved the first great triumph of science over disease. Earlier in the nineteenth century, two cholera epidemics had devastated Europe and the United States. As a new epidemic in Egypt threatened the borders of Europe, France dispatched investigators in this new field of bacteriology to track down the cause of the disease. Germany dispatched Koch.

Before this, medicine’s great successes had come about almost serendipitously, beginning with an observation. With smallpox Jenner started out by taking seriously the experiences of country folk inoculating themselves. But not here. In this case the target had been fixed in advance. Both the French and Koch rationally designed an approach, then turned the general tools of the laboratory and bacteriology to a particular target.

The French failed. Louis Thuillier, the youngest member of the expedition, died of cholera. Despite the bitter and nationalistic rivalry between Pasteur and Koch, Koch returned with the body to France and served as pallbearer at Thuillier’s funeral, dropping into the grave a laurel wreath “such as are given to the brave.”

Koch then returned to Egypt, isolated the cholera bacillus, and followed it to India to explore his findings in greater depth. John Snow’s earlier epidemiological study in London had proved only to some that contaminated water caused the disease. Now, in conjunction with Koch’s evidence, the germ theory seemed proven in cholera—and by implication the germ theory itself seemed proven.

Most leading physicians around the world, including in the United States, agreed with a prominent American public health expert who declared in 1885: “What was theory has become fact.”

But a minority, both in the United States and Europe, still resisted the germ theory, believing that Pasteur, Koch, and others had proven that germs existed but not that germs caused disease—or at least that they were the sole cause of disease.*

The most notable critic was Max von Pettenkofer, who had made real and major scientific contributions. He insisted that Koch’s bacteria were only one of many factors in the causation of cholera. His dispute with Koch became increasingly bitter and passionate. With a touch of both Barnum and a tightrope walker about him, Pettenkofer, determined to prove himself right, prepared test tubes thick with lethal cholera bacteria. Then he and several of his students drank them down. Amazingly, although two students developed minor cases of cholera, all survived. Pettenkofer claimed victory, and vindication.

It was a costly claim. In 1892 cholera contaminated the water supply of Hamburg and Altona, a smaller adjacent city. Altona filtered the water, and its citizens escaped the disease; Hamburg did not filter the water, and there 8,606 people died of cholera. Pettenkofer became not only a mocked but a reviled figure. He later committed suicide.

There was still no cure for cholera, but now science had demonstrated—the dead in Hamburg were the final evidence—that protecting the water supply and testing for the bacteria would prevent the disease. After that only an isolated and discredited group of recalcitrants continued to reject the germ theory.

By then Welch had arrived at the Hopkins. It had not been an easy journey to Baltimore.

When the offer finally came in 1884, Welch had become comfortable in New York, and wealth was his for the asking. Virtually every student who had ever passed through his course had the utmost respect for him, and by now many were physicians. He had already made a reputation; that and his charm entered him into society as much as he desired.

His closest friend was his preparatory school roommate Frederick Dennis, wealthy son of a railroad magnate and also a physician who had studied in Germany. At every opportunity Dennis had advanced Welch’s career, extolling his talents to editors of scientific journals, using his society connections to help him in New York, occasionally even subsidizing him indirectly. Indeed, Dennis behaved more like a lover trying to win affection than a friend, even a close friend.

But Dennis had always demanded a kind of fealty. Welch had heretofore been willing to give it. Now Dennis demanded that Welch stay in New York. When Welch did not immediately agree, Dennis orchestrated an elaborate campaign to keep him there. He convinced Welch’s father to advise him to stay, he convinced Andrew Carnegie to donate $50,000 for a laboratory at Bellevue, and he convinced Bellevue itself to pledge another $45,000; that would match any laboratory in Baltimore. And not only Dennis urged Welch to stay. A prominent attorney whose son had studied under Welch warned him that going to Baltimore would be “the mistake of your life. It is not in a century that a man of your age has acquired the reputation which you have gained.” Even the president of the United States Trust Company sent a message that “however bright the prospect is in Baltimore it is darkness compared with the career” before him in New York.

The pressure was not without effect. Dennis did get Welch to set conditions that, if met, would cause him to stay. For Welch had his own doubts. Some related to his own fitness. He had done almost no real science in the years since returning from Germany. He had only talked for years about how his need to make a living prevented him from conducting original research.

The Hopkins expected more than talk. It had been open for eight years and, tiny as it was, had earned an international reputation. Welch confessed to his stepmother, “Such great things are expected of the faculty at the Johns Hopkins in the way of achievement and of reform of medical education in this country that I feel oppressed by the weight of responsibility. A reputation there will not be so cheaply earned as at Bellevue.”

Yet precisely for that reason the Hopkins offered, he wrote, “undoubtedly the best opportunity in this country.” Declining would reveal him as a hypocrite and a coward. Meanwhile in New York, the conditions he had set were not met, although Dennis considered them to have been.

Welch accepted the Hopkins offer.

Dennis was furious. His friendship with Welch had been, at least on Dennis’s side, of great emotional depth and intensity. Now Dennis felt betrayed.

Welch confided to his stepmother, “I grieve that a life-long friendship should thus come to an end, but…[i]t looks almost as if Dr. Dennis thought he had a lien upon my whole future life. When he appealed to what he had done for me I told him that was a subject which I would in no way discuss with him.”

Later Dennis sent Welch a letter formally breaking off their friendship, a letter written with enough intensity that in the letter itself he asked Welch to burn it after reading.

For Welch too the breaking off of the friendship was intense. He would not have another. Over much of the next half century, Welch’s closest collaborator would be his protégé Simon Flexner. Together they would achieve enormous things. And yet Flexner too was kept distant. Flexner himself wrote that after Welch’s estrangement from Dennis, “Never again would he allow any person, woman or colleague, close…. The bachelor scientist moved on a high plane of loneliness that may have held the secret of some of his power.”

For the rest of his life Welch would remain alone. More than just alone, he would never dig in, never entrench himself, never root.

He never married. Despite working with others in ways that so often bind people together as comrades, with the single possible exception of the great and strange surgeon William Halsted—and that exception only a rumored possibility*—he had no known intimate relationship, sexual or otherwise, with either man or woman. Although he would live in Baltimore for half a century, he would never own a home there nor even have his own apartment; despite accumulating considerable wealth, he would live as a boarder, taking two rooms in the home of the same landlady, then moving with his landlady when she moved, and allowing his landlady’s daughter to inherit him as a boarder. He would take nearly every dinner in one of his gentlemen’s clubs, retreating to a world of men, cigars, and the conversations of an evening for the rest of his life. And he would, observed a young colleague, “deliberately break off relationships which seemed to threaten too strong an attachment.”

But if he lived on the surface of ordinary life, his life was not ordinary. He was free, not just alone but free, free of entanglements of people, free of encumbrances of property, utterly free.

He was free to do extraordinary things.

At the Hopkins—it became simply “Hopkins” gradually, over several decades—Welch was expected to create an institution that would alter American medicine forever. When he accepted this charge in 1884, he was thirty-four years old.

The Hopkins went about achieving its goal both directly and indirectly. It served as home, however temporary, to much of the first generation of men and women who were beginning the transformation of American medical science. And its example forced other institutions to follow its path—or disappear.

In the process Welch gradually accumulated enormous personal power, a power built slowly, as a collector builds a collection. His first step was to return to Germany. Already he had worked under Cohn, to whom Koch had brought his anthrax studies, Carl Ludwig, and Cohnheim, three of the leading scientists in the world, and had met the young Paul Ehrlich, his hands multicolored and dripping with dyes, whose insights combined with his knowledge of chemistry would allow him to make some of the greatest theoretical contributions to medicine of all.

Now Welch visited nearly every prominent investigator in Germany. He had rank now, for he happily reported that the Hopkins “already has a German reputation while our New York medical schools are not even known by name.” He could entertain with stories, recite a Shakespeare sonnet, or bring to bear an enormous and growing breadth of scientific knowledge. Even those scientists so competitive as to be nearly paranoid opened their laboratories and their private speculations to him. His combination of breadth and intelligence allowed him to see into the depths of their work as well as its broadest implications.

He also learned bacteriology from two Koch protégés. One gave a “class” whose students were scientists from around the world, many of whom had already made names for themselves. In this group too he shined; his colleagues gave him the honor of offering the first toast of appreciation to their teacher at a farewell banquet. And Welch learned the most from Koch himself, the greatest name in science, who accepted him into his famous course—given only once—for scientists who would teach others bacteriology.

Then, back in Baltimore, years before its hospital or medical school actually opened, even without patients and without students, the Hopkins began to precipitate change. For although the Hopkins medical hospital did not open until 1889, and the medical school until 1893, its laboratory opened almost immediately. That alone was enough.

In just its first year, twenty-six investigators not on the Hopkins faculty used the laboratories. Welch’s young assistant William Councilman—who later remade Harvard’s medical school in the Hopkins’s image—kept them supplied with organs by riding his tricycle to other hospitals, retrieving the organs, and carrying them back in buckets suspended from the handlebars. Many of these guests or graduate students were or became world-class investigators, including Walter Reed, James Carroll, and Jesse Lazear, three of the four doctors who defeated yellow fever. Within a few more years, fifty physicians would be doing graduate work at the same time.

And the Hopkins began assembling a faculty. Its institutional vision combined with Welch himself allowed it to recruit an extraordinary one. Typical was Franklin Mall.

Mall had gotten his medical degree from the University of Michigan in 1883 at age twenty-one, gone to Germany and worked with Carl Ludwig, done some graduate work at the Hopkins, and had already made a mark. He expected—required—the highest conceivable standards, and not just from his students. Victor Vaughan, dean of the Michigan medical school and second only to Welch in his influence on American medical education, considered the school’s chemistry lab the best in America and comparable to the best in the world. Mall dismissed it as “a small chemical lab” and called his Michigan education equal to that of a good high school.

When Welch offered Mall a job, Mall was at the University of Chicago where he was planning the expenditure of $4 million, an enormous sum—John D. Rockefeller was the major donor to Chicago—to do what Welch was attempting, to build a great institution. Mall responded to Welch’s offer by proposing instead that Welch leave the Hopkins for Chicago at a significant increase in salary.

By contrast, the Hopkins was desperate for resources but Welch rejected Mall’s proposal and replied, “I can think of but one motive which might influence you to come here with us and that is the desire to live here and a belief in our ideals and our future…. They will not appeal to the great mass of the public, not even to the medical public, for a considerable time. What we shall consider success, the mass of doctors will not consider a success.”

Mall considered the alternatives. At Chicago he had already, as he told Welch, “formulated the biological dept, got its outfit for $25,000 and have practically planned its building which will cost $200,000,” all of it funded, with more to come from Rockefeller. At the Hopkins there was a medical school faculty and, by now, a hospital, but no money yet with which to even open the school. (Its medical school finally opened only when a group of women, many of whom had also recently founded Bryn Mawr College, offered a $500,000 endowment provided that the medical school would accept women. The faculty and trustees reluctantly agreed.) But there was Welch.

Mall wired him, “Shall cast my lot with Hopkins…. I consider you the greatest attraction. You make the opportunities.”

Yet it was not Welch’s laboratory investigations that attracted, that made opportunities. For, unknown to Gilman and Billings, who hired him, and even to Welch himself, he had a failing.

Welch knew the methods of science, all right, could grasp immediately the significance of an experimental result, could see and execute the design of further experiments to confirm a finding or probe more deeply. But he had had those abilities during his six years in New York, when he did no science. He had told himself and others that the demands of making a living had precluded research.

Yet he had no family to support and others did magnificent science under far greater burdens. No scientist had faced more adverse conditions than George Sternberg, an autodidact whom Welch called “the real pioneer of modern bacteriologic work in this country…[who] mastered the technique and literature by sheer persistence and native ability.”

In 1878, as Welch met Billings in the same beer hall where legend had Faust meeting the Devil, Sternberg was an army medical officer in combat with the Nez Perce Indians. From there he traveled by stagecoach for four hundred and fifty miles—enduring day after day after day of the stink of sweat, of bone-shattering bumps that shot up the spine, of choking on the dust—only to reach a train, then by train for another twenty-five hundred miles of steaming discomfort, jostling elbows, and inedible food. He endured all this to attend a meeting of the American Public Health Association. While Welch was bemoaning his lack of facilities in New York, Sternberg was building a laboratory largely at his own expense at a frontier army post. In 1881 he became the first to isolate the pneumococcus, a few weeks before Pasteur and Koch. (None of the three recognized the bacteria’s full importance.) Sternberg also first observed that white blood cells engulfed bacteria, a key to understanding the immune system. He failed to follow up on these observations, but many of his other achievements were remarkable, especially his pioneering work taking photographs through microscopes and his careful experiments that determined both the temperature at which various kinds of bacteria died and the power of different disinfectants to kill them. That information allowed the creation of antiseptic conditions in both laboratory and public health work. Sternberg began that work too in a frontier post.

Meanwhile, in New York City Welch was swearing that if only he were free of economic worries his own research would flower.

In Baltimore his work did not flower. For there, even with talented young investigators helping him, his failing began to demonstrate itself.

His failing was this: in science as in the rest of his life, he lived upon the surface and did not root. His attention never settled upon one important or profound question.

The research he did was first-rate. But it was only first-rate—thorough, rounded, and even irrefutable, but not deep enough or provocative enough or profound enough to set himself or others down new paths, to show the world in a new way, to make sense out of great mysteries. His most important discoveries would be the bacteria now called Bacillus welchii, the cause of gas gangrene, and the finding that staphylococci live in layers of the skin, which meant that a surgeon had to disinfect not only the skin surface during an operation but layers beneath it. These were not unimportant findings, and, even in the absence of any single more brilliant success, if they had represented a tiny piece of a large body of comparable work, they might have added up to enough to rank Welch as a giant.

Instead they would be the only truly significant results of his research. In the context of an entire lifetime, especially at a time when an entire universe lay naked to exploration, this work did not amount to much.

The greatest challenge of science, its art, lies in asking an important question and framing it in a way that allows it to be broken into manageable pieces, into experiments that can be conducted that ultimately lead to answers. To do this requires a certain kind of genius, one that probes vertically and sees horizontally.

Horizontal vision allows someone to assimilate and weave together seemingly unconnected bits of information. It allows an investigator to see what others do not see, and to make leaps of connectivity and creativity. Probing vertically, going deeper and deeper into something, creates new information. Sometimes what one finds will shine brilliantly enough to illuminate the whole world.

At least one question connects the vertical and the horizontal. That question is “So what?” Like a word on a Scrabble board, this question can connect with and prompt movement in many directions. It can eliminate a piece of information as unimportant or, at least to the investigator asking the question, irrelevant. It can push an investigator to probe more deeply to understand a piece of information. It can also force an investigator to step back and see how to fit a finding into a broader context. To see questions in these ways requires a wonder, a deep wonder focused by discipline, like a lens focusing the sun’s rays on a spot of paper until it bursts into flame. It requires a kind of conjury.

Einstein reportedly once said that his own major scientific talent was his ability to look at an enormous number of experiments and journal articles, select the very few that were both correct and important, ignore the rest, and build a theory on the right ones. In that assessment of his own abilities, Einstein was very likely overly modest. But part of his genius was an instinct for what mattered and the ability to pursue it vertically and connect it horizontally.

Welch had a vital and wide curiosity, but he did not have this deeper wonder. The large aroused him. But he could not see the large in the small. No question ever aroused a great passion in him, no question ever became a compulsion, no question ever forced him to pursue it until it was either exhausted or led him to new questions. Instead he examined a problem, then moved on.

In his first years at the Hopkins he would constantly refer to his work, refer to his need to return to the laboratory. Later he abandoned the pretense and ceased even attempting to do research. Yet he never fully accepted his choice; to the end of his life he would sometimes express the wish that he had devoted himself to the laboratory.

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.