The Great Influenza (11 page)

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 institutes 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.

If pigeons could be immunized, humans likely could be too. As they had with cholera, French and German scientists raced each other, building upon Sewall's and each other's advances, studying both diphtheria and tetanus. In December 1890, Koch protegés Emil Behring, who would later win the Nobel Prize, and Shibasaburo Kitasato showed that serum (the fluid left after all solids are removed from blood (drawn from one animal made immune to tetanus could be injected into a different animal and protect it from disease.

The paper shook the scientific world. Work on diphtheria at a level of intensity heretofore unknown proceeded in laboratories. Over the Christmas holiday in 1891 in Berlin, the first attempt to cure a person of diphtheria was made. It succeeded.

Scientists had discovered a way not simply to prevent a disease. They had found a way to cure disease.
It was the first cure.

Over the next few years work continued. In 1894, Emile Roux of the Pasteur Institute read his paper summarizing experiments with diphtheria antitoxin before the International Congress on Hygiene in Budapest.

Many of the greatest scientists in the world sat in the audience. As Roux finished, these men, each renowned in his own right, began to clap, then stood on their seats, their hands making thunderous sounds, their voices shouting applause in half a dozen languages, their hats thrown to the ceiling. Welch then reported American experiences confirming the work of both the French and Germans. And each delegate returned to his home with a bottle of this marvelous curative agent in his possession.

* 

In the keynote speech at the next meeting of the Association of American Physicians, an association created to foster scientific medicine, Welch said, 'The discovery of the healing serum is entirely the result of laboratory work. In no sense was the discovery an accidental one. Every step leading to it can be traced, and every step was taken with a definite purpose and to solve a definite problem. These studies and resulting discoveries mark an epoch in the history of medicine.'

His comment was a declaration not of war but of victory. Scientific medicine had developed technologies that could both prevent and cure diseases that had previously killed in huge numbers, and killed gruesomely.

And if French and German scientists had found the antitoxin, Americans William Park, chief of the laboratory division of the New York City Health Department, and Anna Williams, his deputy and perhaps the leading female bacteriologist in this country (possibly anywhere (transformed it into something that every doctor in the developed world had easy access to. They were an odd couple: he with an original and creative mind but staid, even stolid, extremely precise and well organized; she, wild, risk taking, intensely curious, a woman who took new inventions apart to see how they worked. They complemented each other perfectly.

In 1894 they discovered a way to make a toxin five hundred times as potent as that used by Europeans. This lethality made a far more efficient stimulator of antitoxin and slashed the cost to one-tenth what it had been. Park then broke the production process into tasks that ordinary workers, not scientists, could perform and turned part of the laboratory into a virtual factory. It soon became by far the cheapest, most efficient, and reliable producer of the antitoxin in the world. Diphtheria-antitoxin production today is still based on their methods.

The lab distributed it free in New York and sold it elsewhere. Park used the money to subsidize basic research and make the city laboratories into arguably the best medical research institution in the country at the time. Its annual reports soon contained, according to one historian of medicine, 'a body of research of which any Institute in the world would be proud.'

And the antitoxin suddenly became available around the world. Diphtheria fatality rates quickly fell by almost two-thirds, and country doctors began to perform miracles. It was only the first miracle of what promised to be many.

* 

As the use of this antitoxin was becoming widespread, Frederick Gates, an intellectually curious Baptist minister who had a gift for seeing opportunities to exploit and was an assistant to John D. Rockefeller, picked up a medical textbook written by William Osler called
The Principles and Practice of Medicine,
a textbook that would go through many editions and find a readership among both physicians and informed laymen. In it Osler traced the evolution of medical ideas, explored controversies, and, most significantly, admitted uncertainty and ignorance.