The Remedy

by Thomas Goetz

  But for the unlucky 10 percent, the bacterium breaks down the granuloma, outstripping the body’s defenses, and begins to reproduce and spread. In classic consumption, the bacteria fester slowly, consuming the thin, soft tissue of the air sacs in the lungs. If the germs migrate and attack a blood vessel, this creates the “damned spot” John Keats saw one day on his handkerchief. (“It is arterial blood,” he wrote a friend a year before his death from consumption. “That drop of blood is my death warrant. I must die.”) But if the rot stays in the tissue, the bacteria continue their march through the body, month after month, year after year. Besides the telltale cough, sometimes the bacteria spread to the surface of the body, creating sores and abscesses on the skin; sometimes they moved to other internal organs, causing inflammation and threatening organ function. In some nineteenth-century victims, the bacteria ate away at bone, a particularly painful development. (A dreadful, and typical, treatment in the nineteenth century was to open the bone to the air, with the hope that the pus would drain and, somehow, the patient would heal. It didn’t work.) And all along, one patient would spread it to another, and to another, keeping the disease alive even as the victims died.

  Today’s epidemiologists have a metric for quantifying the contagiousness of a disease, known as the basic reproduction number. Denoted as R0, it designates how many people one contagious individual is likely to transmit disease to during the course of his illness. If the R0 falls below 1, then the disease will die out on its own; if the R0 is above 1, it will continue to spread through a population. The higher the R0, the faster a disease spreads and the harder it is to control. A disease such as influenza actually has a fairly low R0, around 2, while the R0 of HIV is between 2 and 5. Measles and pertussis, meanwhile, can be extremely contagious, each with an R0 over 15 commonly. (This is one reason public health officials are so adamant about vaccinating against these diseases: They must be kept out of a population altogether, since once they take hold, they’re extremely difficult to extinguish.) In the late nineteenth century, tuberculosis had an R0 of somewhere around 3, making it a tenacious if not explosive disease. That is comparable with viruses such as smallpox and polio, tuberculosis’s most common cousins, historically speaking. But the R0 is calculated over the lifetime of the illness for the diseased individual. Since smallpox and polio make quick work of their victims, these ancillary infections happen in a relatively brief time span. Tuberculosis, though, is a long-festering disease, twice over: People can live their whole lives with it in a latent, or dormant, state, and they can live with the disease in an active state for many years, if not decades. The R0 value for tuberculosis, then, reflects the disease’s constancy and tenacity.

  In the nineteenth century, in typical urban conditions, tuberculosis bacteria would be just about everywhere. They would be on food, on walls, on forks and plates and spoons. They would be on the communal drinking cups fastened on public water pumps. They would be, practically speaking, unavoidable. Given the high mortality rate for TB—66 percent of active cases would end in death—the math says that practically everyone in the nineteenth century carried the bacteria in his or her body. Who might go on to develop the disease—well, that was a trickier matter.

  This was the error of Dr. Williams and so many others who argued against the contagiousness of tuberculosis. Williams thought he had evidence on his side: His Brompton Hospital for Consumption, in London, had specialized in the care and treatment of consumptives since the 1840s, and the hospital had closely tracked its cases, from symptoms to outcomes. According to these data, there seemed to be little signs of contagion in TB cases, in the sense of being able to track the disease from one individual to another. Indeed, the hospital staff themselves were in generally good health and had relatively fewer cases of TB than the public, Williams estimated. If the disease were contagious, surely that wouldn’t be the case.

  But what Williams and his Brompton colleagues couldn’t see—what they didn’t know they could look for (the microbe)—was still there, quietly doing its work. Dr. Williams assumed that infections happened quickly, as in a measles outbreak. But tuberculosis works more slowly and stealthily. Indeed, it was the casualness of consumption—the fact that husbands could have it when their wives seemingly did not, for instance—that baffled those considering the matter.

  This almost aloof pace of consumption made it exceedingly difficult for medical men to perceive it as a contagion akin to diseases such as smallpox and whooping cough. In an 1864 paper entitled “Is Consumption Ever Contagious?” Dr. Henry Bowditch, a Boston physician, noted the slow development of cases he had treated. “If contagion had anything really to do with it,” he observed, “why did it prove so long in showing itself? Usually contagion shows itself soon. This was months in developing itself.” Bowditch’s conclusion adroitly skirts the question he posed; he decided that “consumption is not contagious in the usual acceptation of that word,” but, he added, “it might be infectious.” Using the alternate term phthisis, he concluded his paper with a description of the disease that could pass, today, as a fair expression of the basic reproductive number for tuberculosis. “By long attendance of the closest kind, by inhaling the breath of the phthisical patient, by living in the phthisical atmosphere, so to speak, and in general by a neglect of hygienic laws during such attendance, the health may be undermined and phthisis set in.” But whether this was the work of a germ—well, that was too speculative even to consider.

  • • •

  KOCH’S DISCOVERY WAS THE DEFINITIVE ANSWER TO BOWDITCH’S question, the solution to a mystery that had long dogged science. But it was a mystery that many would have denied even existed; after all, medicine already had perfectly reasonable explanations for consumption. Koch’s explanation was, for skeptics, just one more thrown onto the pile. “There is hardly any pathological question that has been so swayed by every wind of doctrine as this of tubercle,” lamented Dr. Sidney Coupland in an address to the Middlesex Hospital two months before Koch announced his discovery. “Not even the subject of inflammation has been viewed from so many standpoints, and received so many and varied explanations.”

  This disease, which the seventeenth-century writer John Bunyan called “the captain of all the men of death,” was thought, at various times, to stem from bad climate and from sloth. Most of all, it was considered hereditary, brought on by one’s family background. The hereditary theory for TB dated back to Hippocrates, who noted that “consumptives beget consumptives.” It would prove an exceptionally hard notion to shake, insofar as the disease did spread through families, with the onset between family members often occurring generationally, delayed by years or decades. What’s more, the symptoms of consumption (lassitude, lack of appetite, emaciation) seemed to endorse the notion that a consumptive had inherited an overall physical weakness that culminated in the disease, rather than the other way around.

  There was something to this notion. Recall that everyone in major cities was surely exposed to the bacterium, but only a fraction of those would develop the disease. Those who did were the weaker and more vulnerable, their immune systems less able to fight off the contagion. In that way, one’s inherited traits were an obvious factor in the disease. When the next generation started to show similar signs of weakness, it seemed obvious that the parents’ tendency toward poor health had simply been passed on to their spawn.

  The hereditary theory found an inadvertent ally in Charles Darwin, who began publishing his notions of inheritance in the 1830s. Darwin’s ideas about natural selection and the survival of the fittest appeared to neatly explain why consumption might run in some families and not others. An 1872 essay by Dr. James Ross of Manchester, elaborately titled The Graft Theory of Disease, Being an Application of Mr. Darwin’s Hypothesis of Pangenesis to the Explanation of the Phenomena of the Zymotic Diseases (“zymotic” referred to acute diseases, such as TB, that seemed to spread), overtly rejected speculation that some contagion caused tuberculosis. Dr.
Ross, a prolific author of wrongheaded medical treatises, found in Darwin’s theories a much more satisfying explanation:

  In developing certain qualities by sexual selection, man has also produced a tendency to disease and more especially to tubercular disease. . . . In the prosecution of this design, Mr. Darwin’s hypothesis of Pangenesis, by means of which he explains the various forms of genesis, inheritance reversion, and the phenomena of budding and grafting, was adopted because an hypothesis by which these great operations carried out through the whole biological series can be explained is much more deserving of credit than one specially constructed for the explanation of a more limited set of phenomena.

  The fact that Darwin’s work—just a few decades previous considered a heresy not just to science, but also to religion and all things sacred—was now being deployed as an argument against the emerging heresy of microbes was, to say the least, ironic. (Darwin himself died just three weeks after Koch’s discovery of the tuberculosis bacterium and therefore never addressed the debate.)

  As was the case with Darwin’s work when it was misapplied, the hereditary explanation for tuberculosis compounded the stigma of the disease. If tuberculosis was a manifestation of weakness, of poor stock, then consumptives were clearly genetically inferior creatures. In regard to patients with scrofula, the manifestation of tuberculosis on the skin, Dr. Ross put the argument plainly: “On an average, those who have the scrofulous diathesis are deficient in the intellectual and active mental characteristics, which give to their possessor a calm judgment, indomitable courage, and perseverance—the qualities which will ensure success in an open struggle for existence against all competitors.” The fact that cases of tuberculosis had been increasing during his century (that pesky R0 again), rather than being selected against and thus decreasing, didn’t seem to register with Dr. Ross. It seemed that he and others somehow hoped that consumptives might just go away on their own. It was a heavy burden to place on fully one-quarter of the population.

  Among those who believed in the hereditary origins of tuberculosis was Rudolf Virchow, who considered the disease to be a form of cancer, the tubercles in the lungs appearing to him as a sort of tumor. All disease from cells, Virchow believed, a mantra that consumption seemed to obey, given the tendency of the disease to migrate throughout the body—it seemed analogous to how cancer malignancies spread from organ to organ. Virchow’s argument packed considerable weight in medicine, and his explanation was routinely cited as definitive.

  The similarity with cancer made sense, in part, because tuberculosis had radically different manifestations in different regions of the body. Just as the taxonomy of cancer is still today governed by its area of affliction (colon cancer, pancreatic cancer, breast cancer, and so on), so TB then had been carved into several different diseases, depending on where it occured. The most common form was pulmonary tuberculosis, where it was known as consumption, or phthisis. When it turned up in the lymph system, revealing itself through swollen glands in the neck and eventually forming ulcers on the skin, it was called scrofula. This form of TB most commonly developed from drinking raw milk, which, in the days before pasteurization, could contain bovine tuberculosis, a closely related form of the disease in cattle. In the abdomen, it was known as lupus (or, more formally, Lupus vulgaris, in contrast to the autoimmune condition known today as Lupus erythematosus). In each incarnation of TB, it was possible to locate tubercles (waxy sacs of bacteria and pus that resembled a particularly odious cheese), but there was great debate whether these diseases were related or distinct phenomena. Add up the victims of all of them, though, and tuberculosis is believed to be the most lethal disease in history, having claimed more than a billion lives since it was first identified in ancient Greece.

  Virchow, the greatest pathologist and surgeon of his day—he was also a pioneering hygienist, having led the charge to clean up the water supply in Berlin and other German cities—was acting according to the best principles of pathology. His understanding of disease was rooted in direct empirical observation: He looked under his microscope and saw distinct growths. And when he looked at these signs and symptoms, he saw clear distinctions and differences among the various conditions. All this was similar to how cancer worked in the body, and since cancer was a known disease, surely it made more sense to attribute the growths to a known disease than to make up some other mechanism.

  Koch’s discovery, though, proved that despite outward resemblances between cancer and tuberculosis, the internal mechanisms were entirely different. What’s more, all tubercles, whether in consumption or scrofula or lupus, contained Mycobacterium tuberculosis—one disease caused by one pathogen. In a single presentation, built on just a few months of lab work, Koch had rendered obsolete libraries of medical textbooks representing decades of work by thousands of men. It was the first time that a pathological understanding of disease—the one that Virchow had spent his career establishing—was surpassed by a biological one.

  Koch’s Mycobacterium tuberculosis didn’t solve just one mystery—what causes tuberculosis?—but many mysteries at once. He had found a tiny, elusive microbe just two or three microns long (the period at the end of this sentence is about six hundred microns long). Yet the size of the microbe was in inverse proportion to the magnitude of his discovery. The latter was so big, so transcendentally significant, that hereafter it couldn’t be avoided in medicine.

  But it must be acknowledged: Koch wasn’t, in fact, the first. More than 150 years before, the English physician Benjamin Marten had suggested that some sort of minuscule animal might be the cause of the disease. Marten had observed too many coincidences, where one consumptive’s passing acquaintance with others had left them with the affliction. That relationship couldn’t be explained, he felt, except by something exchanged between the people involved—and this, he surmised, might certainly be a creature: “If the Blood and Juices of such distemper’d People, be charg’d with vast quantities of Animalcula, as I have conjectur’d, then their profuse sweats, and their Breath also, may be likewise charg’d with them, or their Ova or Eggs, which by that means may possibly be covey’d into the Bodies of those who lie, or are most conversant with them.” Though Marten had committed his proposal to print, his argument held no sway with his contemporaries.

  Nor did the enterprising epidemiology of William Budd carry much weight when he made a keen analysis of tuberculosis cases in Africa in 1867. Budd, who practiced medicine in the shipping port of Bristol, England, had noticed that a steady stream of African patients developed tuberculosis while working on British ships. After a series of investigations, he realized that this was widespread. “Everywhere along the African sea-board, where the blacks have come into contact and intimate relations with the whites, phthisis causes a large mortality among them.” But he had learned from none other than Dr. Livingstone (of “Stanley and Livingstone” fame) that in the interior of the continent, “where intercourse with Europeans has been limited to casual contact . . . there is reason to believe that phthisis does not exist.” Budd surmised that Europeans must be the vector for the disease, an astute act of epidemiology, if not politics. The disease, he argued in The Lancet, “is disseminated through specific germs contained in the tuberculous matter cast off by persons already suffering from the disease.” Budd’s observations, though well-founded, were apparently too divorced from the experience of most doctors to yield any practical result.

  The most substantial predecessor had been Jean-Antoine Ville-min, a French army surgeon who, in the 1860s, conducted a series of experiments testing whether tuberculosis could be transmitted from one animal to another. Villemin’s interest began when he observed how tuberculosis seemed to affect young men who moved to the city, even though they were previously healthy in their rural homes. He compared the effect to how glanders, a horse disease, seemed to spread when a team was yoked together. “The phthisical soldier is to his messmates what the glandered horse is to its yoke fellow,” Vill
e-min conjectured.

  He soon went beyond conjecture. In an experiment, he injected healthy rabbits with fluid from the lungs of a man who had died of TB. After three months, he killed the rabbits and examined their lungs. They were filled with tubercles. He conducted another experiment, this time taking tissue from a diseased cow and injecting it into rabbits. They got sick even faster. (This was the first experiment, as it happens, to explore the difference between the human and bovine forms of TB.) Villemin continued to run experiments, and in 1868 he published Studies on Tuberculosis, where he laid out evidence for his theory that tuberculosis could be spread from one animal to another.

  He was exuberant about the implications of his research and began lobbying for a number of social reforms, including improved living and working conditions and thorough disinfection measures. “These are the ideas which should direct us in the research for curative and prophylactic measures in turberculosis,” he wrote. “These are the hopes which our discovery luringly had held out for us.”

  But Villemin would be greatly disappointed. His work, while it did prompt some discussion, did not generate any fundamental changes. As later experiments by others failed to reproduce his results (almost certainly a result of their methods, not Villemin’s), his work was increasingly considered dubious. In 1881, on the eve of Koch’s presentation, Austin Flint issued the fifth edition of his textbook The Principles and Practice of Medicine. In its discussion of tuberculosis, the book dismissed any theories of contagion. “The doctrine of the contagiousness of the disease has . . . its advocates, but general belief is in its non-communicability.” And then came Koch, whose evidence, assembled over many months in the laboratory in Berlin, was enough to shift the burden of proof the other way.