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Authors: John M Barry

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And no one else in the world had a better sense of what was going on in all the world's laboratories than Billings.

He traveled to Europe to meet possible candidates for the Hopkins faculty, including established scientists of international renown. But he also sought out young men, the next generation of leaders. He had heard of Welch, heard of his potential, heard that he had exposed himself not to one or two of the great scientists but to many, heard that he seemed to know everyone in Germany, including (even before they emerged as arguably the two greatest medical scientists of the nineteenth or early twentieth century) Robert Koch and Paul Ehrlich. (In fact, when Koch, then unknown, first made his dramatic demonstration of the life cycle of anthrax, Welch was in the same laboratory.)

Billings met with Welch in an ancient Leipzig beer hall, a hall that itself belonged to myth. On the wall were murals depicting the sixteenth-century meeting of Faust and the Devil, for the meeting had supposedly occurred in that very room. Billings and Welch talked passionately of science deep into the night, while the murals endowed their words with conspiratorial irony. Billings spoke of the plans for the Hopkins: unheard-of admission standards for students, labs that filled great buildings, the most modern hospital in the world, and of course a brilliant faculty. They talked also about life, about each other's goals. Welch knew perfectly well he was being interviewed. In response, he opened his soul.

After the dinner Billings told Francis King, president of the yet-to-be-built Johns Hopkins Hospital, that Welch 'should be one of the first men to be secured, when the time came.'


That time would not come for a while. The Hopkins had begun as a graduate school only, without even any undergraduate students, although it quickly expanded to include a college. Further expansion abruptly became problematic since its endowment was chiefly in Baltimore & Ohio Railroad stock. The country had been wallowing in depression for four years when the B&O and the Pennsylvania Railroad cut wages 10 percent, sparking violent strikes by railroad workers in Maryland that soon spread to Pittsburgh, Chicago, St. Louis, and farther west. B&O stock collapsed, and the plans to open the medical school had to be put off. There were no new faculty posts at the Hopkins to fill.

So in 1877 Welch returned to New York desperate for 'some opportunity' in science 'and at the same time making a modest livelihood.' Failing to find one, he returned to Europe. In 1878 he was back in New York.

At no time in history had medicine been advancing so rapidly. The thousands who flocked to Europe were proof of American physicians' intense interest in those advances. Yet in the United States neither Welch nor anyone else could support himself by either joining in that great march or teaching what had been learned.

Welch proposed to a former mentor at the College of Physicians and Surgeons that he teach a laboratory course. The school had no laboratory and wanted none. No medical school in the United States used a laboratory for instruction. The school rejected his suggestion but did offer to let Welch lecture (without salary) in pathology.

Welch turned to Bellevue, a medical school with a lesser reputation. It let him offer his course and provided three rooms for it, equipped only with empty kitchen tables. There were no microscopes, no glassware, no incubators, no instruments. Facing the empty rooms, discouraged, he wrote, 'I cannot make much of a success out of the affair at present. I seem to be thrown entirely upon my own resources for equipping the laboratory and do not think that I can accomplish much.'

He was also worried. His entire compensation would come from student fees, and the three-month course was not required. He confided to his sister, 'I sometimes feel rather blue when I look ahead and see that I am not going to be able to realize my aspirations in life' . There is no opportunity in this country, and it seems unlikely there ever will be' . I can teach microscopy and pathology, perhaps get some practice and make a living after a while, but that is all patchwork and the drudgery of life and what hundreds do.'

He was wrong.

In fact he would catalyze the creation of an entire generation of scientists who would transform American medicine, scientists who would confront influenza in 1918, scientists whose findings from that epidemic still echo today.

CHAPTER THREE

W
ELCH'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.

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