The Remedy

by Thomas Goetz

  Koch’s research began suggesting a larger discovery than just causality between a microbe and a disease. He was, in fact, composing a portrait of the entire life cycle of the organism, a chronicle of its various stages, and the deadliness of the bacteria at each stage—because the bacteria, he had observed, weren’t just static long rods. They would swell and grow, forming long filaments. Those filaments shot off round spores that had materially different qualities from the rods. For instance, when a sample of rods was dried under heat, they would be rendered inert; injected into an animal, they would not produce disease. But the spores were hardier structures. Even after being heated and dried out, when introduced into the aqueous humor, they would awaken and generate new rods and new spheres.

  This, Koch began to realize, was the true secret of the bacteria’s deadly power. In spore form, anthrax can remain dormant for years, waiting for a suitable host—a grazing sheep, say—to come along. This was how anthrax could emerge, as if from the sky—because it had simply stayed well hidden in the ground.

  By April he was convinced that he had sufficient evidence. He had isolated the bacteria—which he would call Bacillus anthracis—in a dead animal, reproduced it in a culture, inoculated it into a healthy animal, and then, after that animal quickly died, found the bacteria in the blood, in plentitude. He had isolated the dormant spores and shown how they could be revived in culture. It was a clear demonstration of causation, one that pinpointed the very mechanism of the disease, and one that had never been demonstrated so thoroughly, exhaustively, or repeatedly. As he summarized in his notes, “In view of this fact, all doubts as to whether the Bacillus anthracis is really the cause and contagium of anthrax just fall silent.” He had succeeded, he said, “for the first time to shed light on the etiology of one of these strange diseases.”

  But if Koch had proven this to himself, he now faced an even more daunting task: How could he, a thirty-two-year-old country doctor, possibly convince the world? How could he even begin to communicate what he had discovered?

  • • •

  KOCH’S RESOURCES MIGHT HAVE BEEN MEAGER, HIS TECHNIQUE IMPROVISATIONAL, BUT THE QUESTION HE’D ANSWERED STOOD AS ONE of humanity’s most enduring mysteries: What causes disease? What are the mechanisms behind the ills that afflict us?

  For centuries the question had a straightforward, if increasingly unsatisfying answer. The ancient Greek physician Hippocrates proposed that the four humors (phlegm, black bile, yellow bile, and blood) governed all human health; disease was caused by an imbalance among these humors. In AD 150 the theory was endorsed and elaborated upon by Galen, and well into the nineteenth century, humoral medicine remained the status quo. It wasn’t until Virchow, with his revolutionary theory of cellular pathology, that humors would be pushed aside. But even he couldn’t fathom such a thing as germs.

  Here and there, though, an outspoken contrarian had peered through his microscope and seen a new way to explain disease. In the 1840s the Hungarian physician Ignaz Semmelweis was practicing in the General Hospital in Vienna. At the time, death in childbirth was a real worry, with about 5 percent of expectant mothers dying while giving birth, many from puerperal fever, known as “childbirth fever,” following delivery. The General Hospital had two maternity wards, divided by class: in the first, elite patients received care from physicians and medical students; in the second ward, lower classes were attended to by midwives. Semmelweis monitored the two clinics and found that, to his surprise, the death rate was far higher in the first ward than in the second. Fully 13 percent of women attended to by medical staff died, while just 2 percent of women with midwives did.

  Faced with these numbers, Semmelweis came to a horrific realization: The medical students were working on cadavers in the hospital morgue barehanded and then attending to the expectant mothers directly afterward, without washing their hands between. As they moved from corpse to mother, they carried the germs (which would later be identified as Staphylococcus and Streptococcus) with them.

  Semmelweis soon demonstrated a solution: He required that medical students wash their hands in a lime-chlorine solution after their autopsies. The process dramatically reduced fatalities in the first ward, putting them on par with those in the midwife ward. But that was as far as Semmelweis’s discovery went. In 1849 he was deemed too controversial and refused a reappointment at the hospital. He would spend the next years railing against medical standards and evangelizing against germs, but the medical establishment was unconvinced. Semmelweis would die in an insane asylum in 1865, tormented by the agony of having his work thrown on the rubbish heap. His tragedy, as the writer Céline would later write, was that “his discovery was too great for the strength of his genius.”

  But germs kept revealing themselves and kept tempting others to join the argument for the contagiousness of disease. In 1850 the Englishman John Grove published a treatise whose very title made his argument: Epidemics Examined and Explained: Or, Living Germs Proved by Analogy to Be a Source of Disease—the “by Analogy” being Grove’s admission that, though he had the argument, he lacked the evidence. A few years later, an outbreak of cholera in London drew John Snow to investigate; he famously demonstrated that contaminated drinking water, rather than miasma, was the conduit for the disease. Today, Snow is celebrated for his symbolic victory in having the handle removed from the culprit pump, and as the father of epidemiology. But in fact, his larger efforts to improve sanitation in London were thwarted.

  Most prominently of all, there was Louis Pasteur, who in the 1850s and ’60s offered remarkable evidence that microbes caused fermentation and spoilage. The work launched Pasteur on a crusade against spontaneous generation and led him to claim boldly in 1864 that “life is a germ, and a germ is life.” The germ theory finally had its great champion. But Pasteur’s evidence, alas, stemmed almost entirely from food and industry, not human disease. The connection between the two was neither explicit nor obvious, which made Pasteur’s claims, once again, conjecture. It wasn’t until Joseph Lister built on Pasteur’s work with his techniques for antiseptic surgery in the 1860s that the worlds began to align. Lister’s work convinced some surgeons to adopt sterilization methods, though theirs was largely a practical capitulation, not a philosophical one. Others remained recalcitrant. “Where are these little beasts?” scoffed John Hughes Bennett, a medical professor at Edinburgh. “Show them to us, and we shall believe in them. Has anyone seen them yet?”

  By the 1870s, many scientists, including Klebs and Henle, were hard at work conducting research that might prove the germ theory and preaching the new gospel at every opportunity. In 1877, Klebs was confident enough to maintain, in a talk entitled “On the Revolution in Medical Opinions in the Last Three Decades,” that most diseases considered routine were likely to be contagious—that is, caused by germs. If the germs “are found exclusively in the given disease process,” he explained, then “it can be decisive to convey the disease by means of organisms that have been isolated and cultivated outside the body.” Even tuberculosis, he maintained, was likely caused by germs.

  But Klebs’s laboratory efforts, time and again, fell short of a more thorough proof, leaving his exhortations thrilling but unconvincing rhetoric. Lacking certain evidence, the germ theory would remain a radical idea, outside the mainstream of medicine. Then as now, the principle of Occam’s razor prevailed: The simplest explanation wins out, and the notion of germs causing disease was too fantastic, too contrary to everything otherwise understood, to displace the prevailing understanding of disease.

  From today’s vantage point, it’s possible to see why the first wave of germ theorists failed to convince their peers of the certainty of their ideas. In each of these cases, the argument for germs was based on association and proximity. Each proposed a theory, offered some evidence, and made his argument. But there were too many holes and gaps, too much rhetorical hand waving. They were snagged on the shoals of the hypothetical, the if-it-were-possibl
es that had stymied Henle. Even Pasteur, who had worked for years to debunk the theory of spontaneous generation, seemed unable to marshal the chain of evidence that would uproot orthodoxy and convince the establishment that germs offered a simpler, more likely explanation.

  Lacking that clear chain toward causation, rather than mere association, it was too easy for the scientific status quo, not to mention the public at large, to reject the germ theory outright. Surely the idea of some secret world of tiny creatures, bent on killing us, was more outlandish than the evidence that lay before us: that the air itself was bad, and that as vapors spread, so did disease. That idea, known as miasma, sounded like common sense. As the scientific journal La Presse editorialized to Pasteur in 1860, “I am afraid that the experiments you quote, M. Pasteur, will turn against you. The world into which you wish to take us is really too fantastic.”

  In his book The Structure of Scientific Revolutions, written in 1962, Thomas Kuhn proposed a new way to look at science: not as the inevitable, persistent discovery of truth, but rather as “the piecemeal process by which . . . items are added, singly and in combination, to the ever growing stockpile that constitutes scientific technique and knowledge.” That piecemeal process typically happens slowly, in what Kuhn calls “normal science.” But it can also happen with a start, in an explosion of new research and new knowledge that upsets the stockpile (the status quo) with a new paradigm for understanding the world. New science, Kuhn argued, needs to be powerful enough not just to prove its point, but also to overwhelm the traditions that already explain the world.

  Kuhn’s essay was revolutionary in its own right for reframing the perception of how science happens. He suggested that this was not a smooth, regular process toward progress; it was traumatic and destructive and could be downright threatening. Though Kuhn, a physicist by training, was concerned mostly about revolutions in astronomy and physics—Newton’s discoveries, Einstein’s theory of relativity, and such—his framework applies very well to the germ theory and to Koch’s and Pasteur’s efforts to prove a valid, if revolutionary, framework for understanding disease.

  Kuhn’s point was that any revolution inevitably comes down to an overthrow, and that can be an especially difficult task when the opposition is other scientists. As Bernard Barber put it just a year before Kuhn, in a 1961 Science essay entitled “Resistance by Scientists to Scientific Discovery,” “as men in society, scientists are sometimes the agents, sometimes the objects, of resistance to their own discoveries.” For the would-be revolutionary, this obstinacy can be infuriating, and even, as Semmelweis showed, maddening.

  As one of those early germ theory revolutionaries, Lister bore the scars from his fights with the conventional wisdom. In an address to graduating medical students in 1877, he urged them to beware the easy temptation to reject an unfamiliar idea.

  In investigating nature you will do well to bear ever in mind that in every question there is the truth, whatever our notions may be. This seems perhaps a very simple consideration, yet it is strange how often it seems to be disregarded. I remember at an early period of my own life showing to a man of high reputation as a teacher some matters which I happened to have observed. And I was very much struck, and grieved, to find that while all the facts lay equally clear before him, those only which squared with his previous theories seemed to affect his organs of vision. Now this, Gentlemen, is a most pernicious though too prevalent frame of mind. When I was a little boy, I used to imagine that prejudice was a thing peculiar to some individuals. But, alas, I have since learned that we are all under its influence, and that it is only a question of degree. But let us ever contend against it, and remembering that the glorious truth is always present, let us strive patiently and humbly to discover it.

  This was the fray that Koch now entered into. This was the challenge he faced: not just to prove the existence of one disease, but to change the conception of all disease.

  • • •

  TODAY, OF COURSE, KOCH’S WORK IS SELF-EVIDENT. WE ALL KNOW about germs. We avoid them, and we fear them. Indeed, we have so internalized the idea of germs, we so take their existence for granted, that we respond to them viscerally, with disgust. When food falls on the floor, when somebody coughs in our face or sneezes on our necks, it’s revolting enough to cause some people to wretch. If anything feels like common sense to us, it is the existence of germs.

  But this is entirely learned behavior. We stand today on the far end of a process that began in makeshift laboratories such as Koch’s and that took decades of evidence and persuasion. Only after that process could there be a later, cultural shift—the revolution—where the existence of germs was accepted, not argued. To understand the scale of that shift is to fathom how radical an idea the germ theory was when Koch conducted his first experiments in Wöllstein.

  In fact, our world today is one that has been designed meticulously around the germ theory. We live in an antiseptic culture, with Purell dispensers and masked airplane passengers and Listerine (named, of course, after the surgeon), with its promise to kill germs. These are so much part of life that we can’t imagine tolerating otherwise. Even Lister might be shocked at how far our suspicion of germs has taken us.

  Indeed, the pervasiveness of germophobia has given rise to mysophobia, the pathological fear of germs. This has dramatic shades of Lady Macbeth, but it also has potential scientific consequences. Our culture of mysophobes has created what is called the hygiene hypothesis, the theory among some microbiologists that we have so thoroughly rid our environment of germs that we have left ourselves too clean. In our antiseptic homes and communities, the hypothesis goes, we are no longer exposed to necessary and helpful bacteria, and our immune systems have grown weak and flabby. The result, some scientists believe, is an increase in allergies, autoimmune deficiencies, and conditions such as Crohn’s disease, diabetes, and asthma.

  Though the hygiene hypothesis has been around since the late 1980s, a 2012 study published in the journal Science offered significant support. Researchers raised mice in a sterile environment, purged of bacteria and other germs. These mice had increased allergies and intestinal colitis. But when the researchers took other, germ-free mice and exposed them to microbes during their first weeks of life, these animals developed normal immune systems.

  The study was promising but, like the early work on the germ theory, mostly suggestive. The hygiene hypothesis remains just that, a hypothesis, and an especially difficult one to prove definitively at that, considering it would require humans to live in isolated environments over the span of many years. Nonetheless, the very existence of the hygiene hypothesis demonstrates how far our relationship with germs has evolved in just 130 years and how profound was the revolution that Koch and Pasteur and the rest incited.

  But in April 1876, science was still on the other side of history, still wandering in a pre-germ present. Unlike everything that had come before, Koch’s work on anthrax had the potential to constitute a new revolution, to compel a new conception of reality. He offered, to use Kuhn’s terminology, the paradigm shift that would push normal science to a crisis.

  From today’s vantage point, what was happening in 1876 looks like the inexorable march of progress. Koch, sitting alone at night, hunched over his field mice and microscopes, resembles a character in the first act of a movie: the not-yet-discovered hero who, though he might be ignorant of what’s in store for him, is plainly destined for greatness and glory. Moreover, lined up alongside Pasteur and Henle and the rest, Koch stands among the vanguard in a bold march toward a new, inevitable truth.

  But it’s important that we try, as much as we can, amid our antibacterial soaps and antiviral Kleenex, to recognize that these early champions of the germ theory did their work in isolation, and they faced routine resistance and outright rejection. History is inevitable, but progress is not. As Darwin’s work demonstrated, nature has many dead ends, and not all development is improvement. The evolutionary bi
ologist and scientific historian Stephen Jay Gould made this point elegantly, arguing that “great ideas, like species, do not have ‘eureka’ moments of sudden formulation in all their subtle complexity; rather, they ooze into existence along tortuous paths lined with blind alleys.” Today’s realities, in other words, were not foreordained by yesterday; they were the result of small changes and shifts that happened to lead this way.

  • • •

  IN APRIL 1876, KOCH TOOK OUT HIS NOTEBOOKS ONCE MORE AND checked his work. He had scoured the data dozens of times, double-checking his figures, testing his conclusions, probing for a mistake somewhere along the way. He needed to be certain, absolutely certain. At last he closed the notebooks. He knew this was real; he was sure of it. Though his tools were rudimentary, almost primitive, his methods were sound, his evidence thorough, and his conclusions reasonable. He had discovered something true, something that, as far as he could tell, nobody had ever discovered before. Now he just needed to tell someone.

  Over the next few days, Koch dutifully treated his patients for their sprained ankles and headaches, but inside, he had drifted far away from Wöllstein. He needed to bring his conclusions . . . somewhere. But where? How?

  In Wöllstein, he was far removed from any scientists or even other physicians; his closest friend may have been the Baron von Unruhe-Bomst. There were, of course, his teachers at Göttingen, including Henle. He had also studied with Hermann Lotze, a logician who pioneered the field of scientific philosophy; Lotze would certainly appreciate the rigor of Koch’s work. There were other acquaintances. There was Virchow in Berlin, though he was surely too busy. In the fall of 1875, just prior to his breakthrough work on anthrax, Koch had visited the laboratory of the famous hygienist Max von Pettenkofer in Munich. But von Pettenkofer was a germ theory skeptic and represented the authority and the argument that Koch was up against in making his claim.