The Blue Death Page 12

  He began those ten years bouncing from one small town to the next with his wife, Emmy, and their young daughter, Trudy, determined to support them on his income as a general practitioner. He finally found some stability as the district medical officer in Wollstein, a city in the Polish-speaking region of eastern Germany. He and his family moved into a solid two-story home with a horse barn and a large garden in the back.

  True to his motto, Koch was indeed never idle. He played the zither, bowled, socialized, and climbed the local mountains. He even established himself as a skilled amateur archaeologist. He accumulated a veritable zoo of pets and livestock ranging from pigeons and chickens to bees, rabbits, and even a pair of monkeys. Above all he was a superb physician. His patients loved the hardworking young doctor and flocked to the clinic he established in one half of a large, well-lit room that stretched across the south side of the house. In the other half of the room, hidden by a curtain, his future began to take shape.

  The life of a country doctor could not hold the ferocious intellect of Dr. Koch. As his financial situation improved and he was able to save money, his first purchase was not the carriage that he sorely needed for house calls in rural Germany, but a fine microscope. He placed it in the room behind the curtain, which was coming to look more and more like a laboratory.

  Far from the intellectual ferment of the late nineteenth century, Koch embarked on a solitary quest for understanding that began with the revolutionary ideas of Pasteur and led to a rigorous framework for identifying the cause of specific diseases. Koch took the world around him and placed it under his microscope. Every free moment found him peering into the microcosm that lay hidden in everything from pond water to drops of his patients’ blood to the organs of sick sheep. Through painstaking trial and error, Koch learned which dyes to add to his slides to create stark outlines around transparent microbes. The barn behind the house provided a steady supply of wild mice as he began to experiment with the transmission of infections. He had already developed a variety of methods for growing bacteria when late in 1875 a message arrived at his door. He was wanted at the police station.

  When he arrived the anxious officer escorted him to the object of his concern, the bloody hide of a sheep. A local farmer had tried to salvage the hide from an animal that had collapsed in a field with blood pouring from its mouth and nostrils. The farmer, the policemen, and Koch knew all too well what had happened. The animal had died of anthrax.

  The three years Koch had spent building his laboratory in Wollstein and developing methods for studying bacteria were preparation for this moment. Throughout the nineteenth century, anthrax infections routinely struck at the farms of Europe with devastating consequences. Other scientists had seen the bacteria responsible, but no one understood how the disease could strike suddenly at animals that had had no contact with victims of the disease.

  To study anthrax Koch would first need to transmit the disease to a new animal. This would assure him a supply of viable bacteria while he tried to culture them in the laboratory. On December 23 he selected a rabbit from among the animals that his wife, Emmy, maintained for him in the cages that filled their garden and horse barn. He drew a bit of the blood from the hide into a glass syringe, held the squirming rabbit with one hand, and injected a large vein in its left ear. By Christmas Eve the rabbit was dead.

  One month later Koch pulled back the curtain and entered his lab carrying a large jar of eyeballs. He set to work draining the fluid from each one and transferring it into glass culture tubes. He had discovered that the fluid provided a perfect culture medium for growing anthrax and had just returned from one of his routine trips to the local slaughterhouse to collect the eyes from cows, pigs, and sheep. He had even designed and constructed culture tubes for the specific purpose of growing the deadly bacteria. In one corner of his laboratory, a kerosene lamp warmed a bed of sand. Koch had built it after realizing the bacteria grew best at temperatures close to ninety degrees. All day long he monitored his cultures and adjusted the lamp.

  Within a month in his makeshift laboratory in a world without electricity he had worked out the life cycle of the bacteria including the crucial observation that anthrax could form spores. The spores proved to be both highly infectious and durable enough to remain viable for years in a harsh environment. This explained why simple exposure to soil long after an area was free from anthrax could cause disease. When he brought this landmark work to the world’s attention, the rigor of the methods and the level of innovation coming from a man working in almost complete isolation stunned the scientific establishment and launched Koch’s career.

  Five years later Koch joined a select group of the most prominent medical researchers in the world as they crowded into a laboratory at King’s College in London. The laboratory belonged to Joseph Lister. Lister had introduced sterile techniques to surgery, an innovation that, together with anesthesia, marked the beginning of modern surgery. A tall man with a handsome face framed by great bushy muttonchop sideburns, Lister commanded the attention of the eminent scientists he had invited to his laboratory, but he was not the man they had come to see. They had come to see Robert Koch.

  Before the attentive crowd, Koch demonstrated a technique he had developed for growing colonies of bacteria on plates of solid agar. A London physician stood to one side, translating Koch’s German into English. Koch selected individual colonies and demonstrated how one could obtain pure cultures of a specific bacterium with relative ease. Pure cultures were essential to meaningful research. The audience, all of whom had struggled with complex and often unsuccessful methods for selecting a single bacterium from a liquid broth, watched intently. In liquid broth the mixture of bacteria formed an almost inseparable soup. On Koch’s agar individual bacteria grew into homogeneous, well-defined colonies.

  The audience of the world’s finest microbiologists immediately grasped the value of Koch’s work. When he finished a man with a marked limp made his way forward to shake his hand. “C’est un grand progrès, monsieur!” he said, and extended his hand. Koch shook it and for the first time in his life looked into the eyes of Louis Pasteur.

  Both men were in London to attend the International Medical Congress. The universe of medicine was in the midst of an explosion of new ideas and techniques and all its luminaries were there. At age fifty-nine Pasteur was among the brightest stars in that universe. Koch at thirty-eight was ascendant. Just one year earlier, he had joined the Imperial Health Office in Berlin as the director of a group of microbiologists. He and Pasteur, however, were cut from different cloth. Koch had founded his accomplishments on relentless precision, a technique so imbued with care that it had allowed him to work safely with an agent as deadly as anthrax in a makeshift nineteenth-century laboratory. He brought to microbiology a rigor never before seen and reinvented the tools and techniques essential for the science. Pasteur was a careful scientist, but his brilliance derived from a series of bold cognitive leaps. In many ways the two men personified their countries and, in the months that followed the London meeting, they would reenact the war that had engulfed those countries ten years earlier.

  On the second to last day of the congress, Koch walked into St. James Hall in the heart of London to hear the words of Pasteur as he described, for the first time, the development of a technique to generate vaccines, one of the most important innovations in medical history. Koch struggled to hear Pasteur’s unamplified words as they rose up toward the sixty-foot-high ceilings of the hall. As Koch listened Pasteur also described his first successful application of the new method. Pasteur, he discovered, had developed and tested a vaccine for anthrax.

  Koch was stunned, but he could not listen to Pasteur with unbiased ears. He and both of his closest colleagues at the Imperial Health Office in Berlin had fought in the Franco-Prussian War. Although ten years had passed since the war, its wounds still festered. The antipathy between the countries remained so intense that when Lister arranged for a banquet for delegates to the congress, he
had to hold two, one for the French and one for the Germans.

  Nonetheless, it is hard to find anything in Pasteur’s speech that Koch could take as an insult. Undeterred, Koch took offense. Perhaps he expected greater recognition from Pasteur for his accomplishments. Perhaps he saw anthrax as somehow his disease. Whatever the reason, the battle was joined.

  Just two months after his return to Berlin, Koch published a blistering nine-page attack ridiculing Pasteur’s work on anthrax. It focused on what he saw as the lack of precision in Pasteur’s methods. A single, one-sentence paragraph from that paper sums up Koch’s position best. “Only a few of Pasteur’s beliefs about anthrax are new,” he wrote, “and they are false.”

  If Koch’s intention had been to get the attention of Pasteur, he succeeded. Pasteur, the son of a soldier in Napoleon Bonaparte’s army, had not fought in the war, but could never forgive the Germans for invading France and precipitating the fall of Napoleon III. He had not started the battle with Koch, but he did not shy away from it either. A bitter bilingual debate ensued as the two men took turns firing salvos at each other in the French and German medical literature. Koch’s critique of Pasteur focused on weaknesses in his methods and was well founded except for one thing. The vaccine worked.

  In the spring of 1882, a young French physicist by the name of Louis Thuillier drove the needle of his syringe through the hide of a sheep in the Prussian village of Packish and injected one sixth of its contents into the animal. Fifty sheep and a dozen cows bleated, mooed, and clattered across the floor as Thuillier moved from animal to animal.

  Thuillier had joined Pasteur’s lab just two years earlier and at twenty-six he was still its youngest scientist. His careful, precise manner in the lab had quickly made him a favorite of Pasteur who enlisted him to work on his most important projects. Pasteur had already sent his bright young star to Budapest to demonstrate the vaccine when he received a request from the Prussian government for a similar trial. Given his conflict with Koch, this was a delicate assignment. It would be conducted under a microscope of scrutiny with every detail of the experiment specified, right down to the concrete floor, an almost unheard-of feature, which would ensure that anthrax in contaminated soil could not disrupt the experiment. Pasteur had not hesitated to send Thuillier again.

  As the small man with meticulously cropped hair and an explosive beard refilled his syringe with a sample of Pasteur’s precious vaccine, a cluster of eminent Prussian scientists watched intently. The observers followed Thuillier from animal to animal, noting his every move.

  The trial would ultimately prove the value of Pasteur’s vaccine. Thuillier would so impress his handlers that he would receive the Cross of Knight of the Crown of Prussia for his work, but in the barn in Packish he worked under a cloud of uncertainty. The demonstration in Budapest had not gone smoothly, and success in Germany was far from assured as he rode back to Berlin, three hours by train and carriage, with his satchel of used syringes and empty vials of vaccine.

  After arriving in Berlin, Thuillier could only wait for the vaccine to generate immunity. Thuillier, like his mentor, was not one for idle moments. Determined to make use of his time and driven by his intense curiosity, he made the trip across the city to an unremarkable brick building just across from the Charité, Berlin’s largest and most famous hospital. There on the third floor, in a small, crowded laboratory, he found Robert Koch.

  In the same room, in a small dish, Thuillier found Koch’s newest and most famous conquest, the bacterium responsible for tuberculosis, a discovery that would eventually earn Koch the Nobel Prize. Thullier had received a prepublication copy of Koch’s paper on tuberculosis and could not resist a visit. This journey into the enemy camp must have been awkward at best. In writing about it, Thuillier seems to have been torn between his prejudices as a member of Pasteur’s camp and his natural predisposition to objectivity as a physicist. Despite a devotion to his mentor, an adulation he expressed in every letter he sent to France, Thuillier came away from Koch’s laboratory duly impressed. The most biting critique he could offer was a note to Pasteur describing Koch as “a bit of a rustic.” Koch kept no record of the meeting, but future events would suggest that he had been impressed by the serious young scientist as well. That future would involve a meeting of the two men in a place far from Berlin under far different circumstances.

  On August 16, 1883, Robert Koch climbed onto a train bound for Italy as porters loaded it with nine large wooden crates. Koch and his colleagues at the Imperial Health Office had spent the past week filling the crates with everything from microscopes and cover glass to sheep’s blood for culturing bacteria and wire mesh for covering mouse jars. They had packed everything they imagined they would need to track down a pathogen that none of them had ever studied in a land none of them had ever seen. Koch and his team would accompany the crates to Egypt, where they would begin the hunt for cholera.

  Cholera had slithered out of its nest in India once again and, with the opening of the Suez Canal in 1869, Europe no longer had the mountains of Asia and the long sailing trip around the horn of Africa to protect her. The French, upon learning that cholera had erupted in Egypt, had rushed to send a team to investigate. French ports were threatened. France had colonial roots in Egypt including their leadership role in construction of the canal, and in the wake of their humiliating defeat by Germany in the Franco-Prussian War, they wanted to find cholera before the Germans. Not to be outdone, the German government quickly assembled its own team, with Koch as its leader.

  Koch now had an opportunity to move beyond his war of words with Pasteur and prove, once and for all, his superiority in the laboratory. Like two seasoned gunfighters, they would meet in the streets of Alexandria with test tubes blazing until only one man was standing. Koch and his team rushed to assemble and pack the components of a state-of-the-art microbiological laboratory and, just a week after learning about the French expedition, he was on his way to Alexandria with three of the most skilled members of his research team. No amount of preparation could erase the fact that they had already given the French team a two-week head start.

  The train wound through the Alps, down to Verona, and on to the port of Brindisi where they boarded the steamer Mongolia. The heat grew with each day as Koch’s team sailed south to Port Said at the mouth of the Suez Canal. The Mediterranean was calm, but Koch spent much of the journey doubled over with seasickness. For this man who was thirty-six before he even saw the sea, the solid ground of Egypt was a welcome sight.

  After a day of quarantine in Port Said, the team boarded an Egyptian steamer for the trip to Alexandria. On August 24, eight days after they left Berlin, carts laden with wooden boxes and luggage rumbled through the busy streets of Alexandria from the Great Harbor to the Greek Hospital. With the completion of the canal, the city’s population had quintupled in just forty years and its narrow streets teemed with people and animals. As soon as the crates arrived in the sunlit room that would serve as their laboratory, they set to work unpacking their precious equipment and supplies. As the lab took shape, the room buzzed with the anticipation of the hunt.

  That evening, as Koch’s team pried open the wooden crates, a thirty-two-year-old Sudanese man arrived at the hospital, anxious, weak, and unable to speak. He had been vomiting and his stools were loose and bloody. His skin was cold and his pulse faint. He was sent to the cholera ward, but the care he received there did nothing to improve his condition and, at eleven o’clock the next morning, he died the graceless blue death. Chance had just made him the subject of Koch’s first study.

  Just after four o’clock on his second day in Alexandria, Robert Koch sliced open the unfortunate man’s abdomen. He carefully lifted the colon from the edge of the abdominal cavity and ran a scalpel across the thin bands of muscle that surrounded it. As the contents spilled out, Koch expected to find the gut filled with the so-called rice water that typified cholera. He had planned to culture this liquid and isolate the bacteria responsible. So stro
ng was his expectation that he had convinced himself he had seen this as a young doctor fresh from medical school during autopsies of cholera victims in the Hamburg hospital. He was mistaken.

  The gut was filled with all manner of bacteria and they seemed to be in the process of devouring its lining. Koch saw little hope of isolating anything from the purulent fluid. He then noticed that the intact portions of that lining were covered with angry red patches.

  He rushed back to the lab so that he could examine the red patches before the sun, the only source of light adequate for microscopy, dropped below the western desert. He placed the sample in a microtome, cut a razor-thin slice, and put it on a slide. At his microscope Koch adjusted the mirror, carefully bending the fading rays of sun until they flooded the slide with light. As he squinted into the lens, he saw hundreds of rodlike bacteria burrowing into the gut. When he switched to a higher magnification, he noticed that the rod was bent just slightly, like a comma.

  For Koch seeing the bacteria was far from conclusive. By his own rigorous standards, standards that would become a central tenet of microbiology known as Koch’s postulates, he would need to find the bacteria in every case of cholera, isolate it in culture, and produce cholera in another animal with the isolated organism if he wanted to demonstrate that it was the cause of cholera. The German team had a long way to go, but in their first day in Alexandria they had already made an important start.

  The German team, however, was not alone. The following morning, just after eight o’clock, a team of French scientists at the European Hospital sawed through the ribcage of Luisa Bigatti. The thirty-nine-year-old Italian woman had died of cholera the night before. They pulled back her ribs and began to examine her heart and lungs. They had already probed the length of her digestive tract, stopping as they went to take samples for later examination under the microscope. The process had become routine. After ten days in Alexandria, Luisa Bigatti was their thirteenth cadaver.