The Remedy

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by Thomas Goetz


  In the end, Koch looked not back to Göttingen, but east to Breslau—known today as Wrocław, the second-largest city in Poland. Breslau was an established center of science, and one that was philosophically aligned with Koch’s work. The University of Breslau was home of the Institute of Plant Physiology, run by Ferdinand Cohn, an esteemed botanist who had spent the previous decade studying bacteria. (To justify the research at his institute, he first had to establish that bacteria were plants, not animals; they are now recognized as neither.) Koch had been closely reading Cohn’s journal, Beiträge zur Biologie der Pflanzen (“Contributions to the Biology of Plants”), where he had been publishing a series of papers under the heading “Studies of Bacteria.” In 1872, Cohn published a monograph titled “Bacteria: The Smallest Living Organisms,” in which he made an audacious declaration:

  In recent times, our knowledge of the effects which bacteria can have over the life and death of humans has been revealed. . . . All epidemics, cholera, pestilence, typhus, diphtheria, variola, scarlet fever, hospital gangrene, epizootic, and the like, have certain features in common. These diseases do not arise de novo, but are introduced from another place where they have been prevalent, by means of a diseased person or through material which has been in contact with such: they spread only through contagion.

  Koch read Cohn’s words and clearly thought he had found a comrade in arms. On April 22, 1876, he wrote to Cohn:

  Honored Professor!

  I have found your work on bacteria, published in the Beiträge zur Biologie der Pflanzen, very exciting. I have been working for some time on the contagion of anthrax. After many futile attempts I have finally succeeded in discovering the complete life cycle of Bacillus anthracis. I am certain, now, as a result of a large number of experiments, that my conclusions are correct. However, before I publish my work, I would like to request, honored professor, that you, as the best expert on bacteria, examine my results and give me your judgment on their validity.

  Koch asked if he might visit Cohn to demonstrate his experiments. Cohn was dubious that some random country doctor might have done anything worthwhile. But he was grateful that Koch knew of his journal and invited him to Breslau the next Sunday.

  Days later, Koch headed to the train station carrying microscopes, slides, cows’ eyes, mouse spleens, and boxes of rabbits, frogs, and mice—many, many mice, both living and dead. Some were flush with anthrax. Rushing through the Wöllstein station to make his train, laden with his boxes and trunks, he must have been quite a sight.

  At noon the next day, a Sunday, Koch knocked on the door of Cohn’s home. Cohn greeted him and sent him over to the institute, where Koch began arranging his materials for the next day’s demonstration. He must have been nervous. Not only would this be the first time he’d demonstrated his research, but it was surely the first time he’d worked in a professional lab since Göttingen. And now he was on the verge of revealing his kitchen-sink efforts to experts in the field.

  The next morning, Koch returned to the institute and began preparing the day’s experiments. He took blood from the spleen of a recently dead mouse and set up a culture in the cow’s-eye humor for Bacillus anthracis. He also injected some precultured bacteria just under the skin of a living frog. From time to time, a few of Cohn’s colleagues would stop by to check in on this unusual visitor, asking him a question or two about his work. Finally, the preparations were complete. Now he just had to wait for the bacteria to do its work. Koch met up with a friend and went to a local beer garden.

  On the second day, with Cohn and several assistants watching, Koch began to go through his samples and reveal the progress. The cultured bacteria had, as he had promised, grown into a chain of rods and filaments, along with some spores as well. Cohn was particularly entranced by the appearance of spores, which he himself had recently identified in another bacteria. Fascinated, Cohn took out a notebook and sketched what he saw under the microscope. Koch did the same in his own notebook; then they compared the drawings, looking for confirmation of what their own eyes had told them. The two sets of sketches were so similar they could barely be told apart.

  In what would become his trademark style, Koch was meticulous and thorough. The cultures were clean and well prepared, the observations under the microscope carefully conducted, with many redundant results. Koch’s confidence grew. “My experiments were well received,” he wrote in his diary that evening.

  By the third day, word of Koch’s experiments had spread throughout the university. Julius Cohnheim, the director of the Institute of Pathology, walked across the university grounds to visit Cohn’s laboratory. A former assistant of Virchow’s in Berlin and a national leader in medical science, Cohnheim was intrigued by the germ theory but not yet convinced—as such, he was a more impartial observer than Cohn. Koch showed Cohnheim his cultures and techniques, walking him through his checks and double-checks. Cohnheim followed along closely, fascinated by the work but also altogether astonished at the young man himself. He couldn’t get over how methodical and thorough this Koch was; he had apparently emerged from nowhere but was calmly demonstrating the most deliberate and decisive laboratory techniques Cohnheim had ever seen.

  Cohnheim complimented Koch on his scrupulous work and then left, rushing back across the campus to his pathology institute. Drop everything, he said to his assistants, and get over to Cohn’s lab. You must meet Koch. “This man has made a magnificent discovery,” he told them, explaining the precision with which Koch had conducted his experiments, despite the fact that he’d done it all in relative isolation. “I regard this as the greatest discovery in the field of pathology,” Cohnheim said, chasing his students out the door, “and believe that Koch will again surprise us and put us all to shame by further discoveries!”

  That evening, to celebrate Koch’s discovery—and to celebrate his discovery of Koch—Cohn invited Koch to join him at his house for dinner. Cohn’s home was warm and elegant, with an ornate study decorated with Persian rugs and all the accoutrements of a respected nineteenth-century scientist: busts, globes, and walls of books. The place, and the man, made a deep impression on Koch. He realized that he had far to go, but he now had a model, and perhaps a mentor, to guide him. Over dinner, Cohn was encouraging. Your work, he told Koch, is tremendously promising. It must be known throughout Europe. It might be a discovery for the ages.

  Koch returned to his room that night filled with satisfaction. It had been just a few days, barely more than a week, since he’d impetuously written to Cohn. Yet now he had shown his work and announced himself—and not only was his work considered valid, but he was himself being taken seriously. He had been scrutinized, his work examined, and he’d been deemed worthy. He filled his journal with a list of people he had met: the generous Cohn; the eminent Cohnheim; Eduard Eidam and Carl Weigert, Cohnheim’s two assistants, both of whom would turn out to be lifelong friends and allies. These were men of science, men of stature—and now they were his fellows.

  On Wednesday, Koch went back to Cohn’s lab for one last day, to finish his demonstrations for more visitors. By now Cohn was utterly convinced. He took Koch aside and offered to publish the work in his journal. Koch gladly accepted and returned to Wöllstein elated.

  The paper, which appeared in October 1876 in Cohn’s “Studies of Bacteria” series, marked Koch’s arrival from obscurity, his transition from a country doctor dabbling with farm animals in his kitchen to a full-fledged scientist. He quickly sent off copies to von Pettenkofer in Munich, to Virchow in Berlin, and to the editors of the German Medical Journal and the German Quarterly for Public Hygiene. Doing so was telling. Though the paper had appeared in Cohn’s journal, a respected publication, that journal’s subject was biological, not medical. It wasn’t enough to have the work simply published; Koch wanted to be sure it found its intended audience: medical researchers as well as biologists.

  The study was well received; a report in Virchow’s journal, Jahr
esbericht, wrote that Koch’s was “by far the most important study on the etiology of anthrax to appear in the year.” In retrospect, this is a historic understatement. In fact, Koch’s paper was not merely important for one disease for one year; it was a turning point for the whole conception of disease and, even more broadly, for the natural world. Naturalists such as Darwin had brought a new understanding to the world of the connections among animals, placing every creature within the arc of creation. Now, on a microscopic scale, bacteriology was doing the same: bringing clarity of perspective and consequence to the invisible world. Koch’s discovery constituted a new role for science, one that would soon go beyond the merely biological and into the new discipline of true medical science.

  Koch’s anthrax paper wasn’t, in itself, enough to make the germ theory triumph all at once. Virchow, in particular, was unconvinced, curtly dismissing Koch’s work as irrelevant to the understanding of disease. As he told Koch soon after when the latter visited Berlin, he had read the paper and still thought the “whole business seemed quite improbable.” But such doubts revealed more about Virchow’s recalcitrance than about Koch’s work. Taken on its merits, the research was unassailable, definitive, and like nothing to have appeared before. Koch’s paper was a seismic shift, an introduction of new information of such persuasiveness that it couldn’t be ignored.

  • • •

  ALAS, IF KOCH EXPECTED THE PUBLICATION OF HIS ANTHRAX PAPER to vault him to Europe’s greatest stage, he was soon enlightened. The world took notice of his work, to be sure, but the gatekeepers of science didn’t swing open the gates just because he had drawn nice pictures of things he’d seen under his microscope. Back in Wöllstein, as before, Koch had patients to attend to, and they didn’t care a bit about bacteriology. He had a wife and daughter to provide for, and he had a hodgepodge of a laboratory, filled with second-rate equipment, do-it-yourself contraptions, and barn-bred mice.

  As the months went by, and other papers followed his paper, he could see his work eclipsed. Feeling a bit sorry for himself, he wrote to Cohn: “I see from your letter that recently many new things have been reported which I, in my isolated corner of Germany, know nothing about. Well, there is nothing for it but I must come to Breslau on a visit and learn at first hand of all these exciting things.”

  Koch did visit Cohn in Breslau again, several times, and he’d soon publish other research in Cohn’s journal. But the connection was peripheral rather than official, and Koch’s visits were at Cohn’s convenience; after all, Cohn and his assistants had official duties and their own research to attend to. Koch remained, he realized, fairly on his own in Wöllstein. He had connections now, but he still had to make his own way.

  His next area for research, then, was especially significant. Rather than continue to study anthrax or move to another infectious disease, he instead pursued technological innovations rather than scientific discovery. In particular, he wanted to make it easier to prove the existence of bacteria by making it easier to document their existence—and he wanted to do it with photography.

  Like other scientists of the time, Koch had to sketch his observations. He was a perfectionist, and although a reasonably good draftsman himself, he realized that the use of drawings allowed skeptics to quibble about whether a scientist’s representation was real or accurate. The scientist was forced to be more than a witness to nature; he became nature’s representative. So, to make the case, to really prove the point that germs exist as causal agents, Koch knew that hand drawings must be replaced by photographs. The only trouble was that the technology didn’t yet exist that would capture images at that tiny scale.

  After the invention of photography in the early 1800s, scientists were among the first to adopt it for their own purposes. In 1840 the French physician Alfred Donné photographed sections of bone and teeth, and red blood cells. (He called his instrument the microscope-daguerreotype.) This resolution, on the level of cells and tissue, suited pathologists, who needed to show tumor or organ cells. But the cameras didn’t yet have a resolution capable of capturing the filaments and flagellations of bacteria.

  With characteristic initiative, Koch decided to invent a tool for his own purposes. With photomicrographs, he explained to Cohn in 1876, he could reveal the bacteria “true to nature and free of subjective misinterpretation.”

  Koch had his work cut out for him. Photography at the time was still relatively primitive, involving glass plates, bulky wooden cassettes, and silver-iodine emulsion baths. Adapting this apparatus to a microscope was a significant undertaking. Without electric lights, Koch was dependent on sunlight for exposure, and he had to jury-rig a series of mirrors to concentrate the sun’s rays toward the microscope. He began to correspond with other German scientists working on photomicroscopy, including Gustav Fritsch, a professor of physiology at the University of Berlin. (Fritsch had gained renown a few years earlier for identifying the motor areas of the brain.) Comparing techniques and workarounds, Fritsch and Koch both made the breakthrough to turn their setups horizontally, rather than stacking them vertically. This allowed for a much more stable apparatus, one capable of both better resolution and better magnification.

  Soon Koch was visiting the Carl Zeiss company headquarters in Jena, Germany, to consult with its chief engineer, Ernst Abbe, on his new invention for concentrating light more effectively. Called the Abbe condenser, it would significantly improve the ability of scientists to illuminate their plates, and Koch was among the first to test the technology.

  By November 1877, Koch had successfully developed a technique that would allow any scientist to record his or her work with photographs. In the paper that followed (published in Cohn’s journal), Koch explained his procedures—preparing and staining the bacteria, arranging the camera with the microscope—so that others could adopt his technique. His resulting images of Bacillus anthracis were the first-ever published microphotographs of bacteria. Writing to Fritsch, Koch tried to put the achievement in perspective: “I am well aware of how imperfect my photographic efforts have been, but I am absolutely certain that a bad photograph of a living organism is a hundred times better than a misleading or possibly inaccurate drawing.”

  Microphotography wasn’t Koch’s only innovation. Other improvements in laboratory tools were soon to follow, from new slide stains to culture media to plating techniques, many of which endure in basic lab protocols today. He wasn’t waiting for science to reach him. He saw, like few other researchers at the time, where science needed to go.

  With his new tools in hand, Koch was ready to return to his bacteriological experiments. For his next target, he chose a problem he had seen firsthand on the battlefields of France: wound infections. It had been six years since his return from the war, but the experience of seeing so many soldiers die, apparently from relatively minor wounds, had affected him deeply. Lister had provided measures that could mitigate these infections, but there was little experimental evidence demonstrating what, precisely, was happening in infected wounds, let alone which microbes were involved.

  Koch’s choice to study wound infections was telling, for several reasons. First and foremost, infection was a significant medical problem in his day, extracting a massive social cost in lives and resources. As Koch saw time and again in the war, a surgery might go perfectly well, with the patient apparently on the road to recovery, only to be followed by infection and the patient’s death days later. The same thing happened in civilian hospitals all too regularly. In Parisian hospitals in 1870, the death rate after surgery was a staggering 60 percent; in London it was scarcely better at 40 percent. And despite Lister’s efforts, conventional medicine was still a long way from reckoning with the issue. Surgery manuals of the 1870s and ’80s still welcomed “laudable pus”—which refers to the notion, dating back to the fourteenth century, that pus was a welcome healing agent. (In fact, it’s a worrisome buildup of white blood cells, agents of the body’s losing fight against infection.) />
  Part of the challenge here was that, so far, bacteriology had only confused the issue. Though Klebs had clearly associated microorganisms with war wounds in 1872, he had regrettably accepted the prevailing theory that all bacteria were the same, part of a universal organism he called Microsporum septicum—a concept so all-encompassing as to be useless. Moreover, Klebs’s organism could be found in and on perfectly healthy animals, including humans, inviting the same doubts that had dogged bacteriology and the germ theory prior to Koch’s anthrax work: Was bacteria the cause of inflammation and disease or was it simply a coincidence of inflammation, with the disease caused by some other means?

  Koch’s task was not only to establish causation, but also to associate specific microbes with specific diseases. If he could answer the deeper questions of causation and provide a scientific basis for the rigorous application of hygienic procedures, then he would be serving not just his profession, but also society at large. It didn’t hurt that the question of wounds and treatments had already gotten a great deal of attention from some of the most famous researchers in Europe: Lister, Davaine, and Klebs. There was scientific glory to be had here, and Koch knew it.

  It’s worth asking why science had yet failed to provide a satisfactory answer to such a profoundly important question. For decades, Semmelweis, Henle, Klebs, and scores of others had pointed their microscopes at the problem and had tried valiantly to prove that bacteria caused disease. The result was a bounty of suggestive research but nothing definitive, nothing that ultimately constituted proof, especially when measured by significant changes in hospital practices or a drop in death rates. There remained a chasm between what bacteriologists believed to be the case and what society could be convinced of.

 

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