Sixty years old and debilitated by a stroke that had left him partially paralyzed fifteen years earlier, Pasteur had chosen to forgo the arduous trip to Egypt. Instead he had sent two of his most trusted assistants, Emile Roux and Louis Thuillier. A tall, thoughtful physician with a sparkle in his eye and a passion for research, Roux had played a key role in Pasteur’s work developing vaccines for anthrax and rabies.
Thuillier, the youngest member of the team, had been reluctant to go to Egypt. A growing romantic relationship had made him suddenly reluctant to travel so far from France. Pasteur saw the quiet, young physicist as a key member of the team and encouraged Thuillier to go. In the end, out of loyalty to his mentor, he relented.
In addition to Roux and Thuillier, Pasteur had sent a senior physician to lead the team and a skilled veterinary surgeon to manage their animal studies. His battle with Koch would be carried out by proxies, but Pasteur had given them a detailed plan of attack.
Like the Germans the French team carried out an exhaustive research program that began, but did not end, with the examination of cholera victims. They collected and examined vomit and stool samples. They placed hundreds of tissue samples under their microscopes. They scoured the bustling markets of Alexandria for test animals. They tried to induce cholera in everything from chickens, quail, and turkeys to pigs, dogs, and monkeys by injecting intestinal contents, blood, stool and even bits of the intestines themselves under the skin, into the blood, and into the gut of the hapless animals. They fed the assembled menagerie bits of the nerves, livers, spleens, kidneys, and lungs of cholera victims. Nothing seemed to work. On one occasion they suspected they had induced cholera in a chicken, but it is more likely they managed to induce some other sort of infection.
The French team had noticed the same bacteria that had caught the eye of Koch, but were more intrigued by the “small bodies” they found in the blood of cholera victims. They studied these small bodies in great detail and attempted to transmit the disease by isolating them. They even believed at one point they had cultured them. It now seems likely they were looking at nothing more remarkable than tiny, floating blood clots.
One early September evening, as the moon rose over the Nile delta, four bearded men on donkeys raced across the desert toward the sea. After a day spent in stiff European clothes that suited their status, but not the climate, the rush of cool air offered intoxicating relief from the relentless heat of the day. Robert Koch, the smallest of the four men, leaned forward, scanning the horizon as bits of sand and dust bounced off his thick glasses. Several Arab guides in flowing robes trailed behind. They galloped on into the fading light until they reached the end of the desert. There the strange caravan pulled to a halt on jagged cliffs that dropped to the waves below.
As the sky grew dark and exploded with stars, the German team sat on the cliffs above the Mediterranean around a fire prepared by their guides, eating supper and reflecting on their progress. Like the French team, they had been unable to reproduce cholera in laboratory animals, but they were far better equipped than the French to culture bacteria. They also had more experience than anyone in the world with the techniques Koch had pioneered using solid agar and the unique culture dish developed by a man named Petri who worked in his lab. They had even come prepared for the relentless desert sun. In Europe their labs had required heated incubators to grow bacteria but under the blistering Egyptian sun, the problem changed. The Germans found a supply of ice and placed it in a small ice box they had built especially for the trip in order to keep the agar in their culture media from melting.
The four Germans talked beneath the desert moon as the firelight played across their faces. Their words swung between the ripening promise of success and the looming possibility of failure. On one hand, they sensed they had found the cause of cholera. The small, comma-shaped bacteria inhabited the gut of each of the nine cholera victims they had dissected, but none of the cadavers who had died from other causes. Even more enticing, they seemed close to growing it in culture, a step that would free them from their grisly dependence on corpses. On the other hand, their research faced an almost insurmountable problem. That night, as their fire burned down, cholera was disappearing from Alexandria.
The outbreak had peaked just two days after the French team arrived, when fifty people died. On August 24, the day the Germans arrived, cholera killed twenty-two people. By September 3, they had conducted nine autopsies, but they did not get another until September 29, and that would be their last. With no material left to study, the frustrated scientists busied themselves investigating cholera in other cities. In Alexandria they could only turn their attention to other diseases.
Despite the fact that the French and German teams were working just a few blocks from each other, they had had no interaction. Even without the bitter antipathy between Koch and Pasteur that permeated the two groups, the teams might have found reasons to dislike each other. Edmond Nocard, the French veterinarian, had fought in the Franco-Prussian War, and Roux had lost two brothers in the conflict. Koch and Georg Gaffky had both served as physicians in Bismarck’s army, as had Friedrich Loeffler, their colleague in Berlin. In every sense, these two groups were quietly at war. Then tragedy struck.
In the weeks without cholera, Thuillier had chosen to study rinderpest, a disease that devastated cattle herds in Europe as well as Egypt. He and a colleague spent much of the third weekend of September at a slaughter yard, examining animals that had recently died. That Monday evening Thuillier tried to escape the heat by going for a swim in the sea. After an evening carriage ride and a late dinner with Roux, he went to bed for the last time in his life.
At three that morning, Roux woke to find Thuillier standing in his room. Thuillier managed to utter the words, “I feel very ill,” before collapsing face-first on the floor. Roux, together with Straus, the other doctor on the team, carried Thuillier back to his bed. He recovered his senses and they offered him opium. He drifted to sleep, but by eight o’clock that morning, he was suffering from profuse diarrhea as violent cramps tore through his body. Roux and Straus looked on in horror as their young colleague developed the obvious symptoms of cholera. The hunter had become the prey.
A group of Italian physicians came to assist and the assembled doctors agreed on a treatment regimen of “strong frictions,” ether injected under the skin and a drink of iced champagne. Despite their efforts (or perhaps hastened by their efforts), the twenty-seven-year-old scientist died that evening.
The source of Thuillier’s cholera is a mystery. He had had no contact with a cholera victim during the two weeks before his death, a period far longer than the incubation period for the disease. Neither could the slaughter yards have been a source for his infection as cholera does not affect livestock. Perhaps the answer lies in the safety precautions issued by Pasteur. He had wisely insisted that the team drink nothing but boiled water. He had also urged that they use boiled water to wash any fruits and vegetables. That washing would have been insufficient if Thuillier had chosen to eat unpeeled produce from a region in which the disease was active. Whatever the source of his cholera, the death of Thuillier melted the ice that had existed between the two teams.
Despite the acrimonious debate between Pasteur and Koch, the two men held a begrudging admiration for each other. The death served as a poignant reminder that their ultimate enemy was not each other, but the blind, heartless pathogen they both sought to defeat. When word of the disaster reached them at the Greek Hospital, Koch and his team rushed to offer their support to the devastated French team. In halting French Koch recalled Thuillier with admiration and kindness that moved even Roux. When they returned for the funeral, they brought two laurel wreaths, which they fastened to the coffin, a token that Koch described as “just suitable for one who deserves such glory.” Then Koch himself helped carry Thuillier’s casket.
The death took the heart out of the French expedition. News of it devastated Pasteur who had taken the promising young scientist under hi
s wing and convinced the reluctant Thuillier to go on the trip. “I felt such esteem and affection for him!” he wrote. “I would have gladly asked for him the Legion of Honor! His death was glorious, heroic. Let this be our consolation.” Soon after the tragedy, the team returned to France with little to show for their efforts.
Koch’s team had no intention of heading home empty-handed. If the beast had fled, Koch would follow it back to its lair. He sent a request to the German government asking for support for a trip to a place where the cholera epidemic never ended. By November he was steaming across the Indian Ocean, bound for Calcutta.
Until he could culture the pathogen, Koch existed in the ethical netherworld that required a steady supply of victims to continue his research. From the moment of his arrival at the Medical College of Calcutta, a grand colonial structure in the heart of the city, it was clear that cholera would provide. He and his two colleagues had had just one day to set up their equipment when the first cholera victim arrived, an anonymous crewman from one of the many ships that plied the busy harbor, identified only as a European sailor.
During his time in Alexandria, Koch had noticed that the shorter the time between death and autopsy, the more the comma bacillus dominated the contents of the gut. If he waited too long, the gut was overrun with every manner of bacteria, and culture was not possible. When he opened the abdomen of the unfortunate sailor, he realized the autopsy had not come soon enough.
The next day another victim arrived in his autopsy room. Again it was too late. Then on the afternoon of their fourth day in Calcutta, a hearse arrived outside the laboratory building with a young Indian man who had died just two hours earlier at a nearby hospital. Koch and his team rushed to the autopsy room and moments later he found what he had been looking for. As quickly as possible, they brought the sample down the hall to the lab where brilliant afternoon sun beamed through three large windows. When he aimed the sunlight through the microscope, the comma-shaped bacteria he had seen in Alexandria filled the slide.
Between cholera’s disappearance from Alexandria and Koch’s arrival in Calcutta, almost three months had passed, three months in which Koch could plan for this moment when he saw cholera again. He spread some of the specimen on agar that he had enriched with beef broth. The next morning the culture plate was covered with bacteria. When he looked at them in his microscope, he found that the comma-shaped bacteria had not only grown on culture, they had replicated into spirals, curlicues, and circles that squirmed wildly on his slide. He had his pathogen.
Koch was exuberant over his finding, but over the weeks that followed, that excitement would fade as he struggled to prove that the comma-shaped bacteria not only were present in cholera’s victims but also could transmit the disease. He followed the methods that had served him so well. He collected every type of animal he could find and injected one after another with massive doses of the bacteria. Each time he waited. Each time nothing happened. Cholera, as it turns out, has a unique capacity to infect humans, the one laboratory animal unavailable to him. Researchers would ultimately find a way to infect guinea pigs by surgically altering their intestines, but Koch never imagined that such extreme measures would be required.
Eight weeks later a frustrated Robert Koch closed the door of the animal room in the basement of the Medical College and walked upstairs to his laboratory on the second floor. He and his colleagues had tried in every way they could imagine to infect everything from mice to monkeys with the comma bacillus, but to no avail. As he sat down in his office to assess the situation, the punkah above his head flapped slowly back and forth. The primitive fan, driven by an impoverished Indian who pulled a rope in another room, discreetly out of sight, produced a feeble current of air that did little to break the heat. With daily high temperatures rising above 100 degrees, even their culture media were starting to melt. It would soon be impossible to maintain pure cultures. Koch was certain he had found the cause of cholera, but the time he needed to generate irrefutable proof was running out. Then he received a message from the sanitary commissioner for the British Government of India.
The water tanks (more accurately imagined as small man-made ponds) of Calcutta were, in the words of a British health officer, nothing less than a “means of committing sanitary suicide.” In the dry climate, these small reservoirs served as the sole repository of water for every purpose from bathing and washing clothes to drinking and cooking. The sanitary commissioner informed Koch that a cholera outbreak had killed seventeen people around one of these tanks. When Koch visited the tank, he could see how wastewater drained from the crude privies outside the walls of the surrounding houses toward the tank. He learned how the soiled clothes of a cholera victim had been washed in the tank and he took a sample of the water. Back in his office, Koch drew a map of the neighborhood. When he marked those homes where someone had died of cholera, it looked remarkably like Snow’s map of the area around the Broad Street pump. A circle of death surrounded the suspect tank.
Koch, however, with the tools of microbiology, could take this one step further than Snow. When he applied those tools to examine the water from the tank, he found it swarming with the bacteria he had seen so many times before. Nonetheless, in a twist of irony, the great bacteriologist still needed epidemiology to prove his point. Koch could not fulfill his postulates in the laboratory, but the water tank provided a natural experiment. His epidemiological study of that experiment, together with his other findings, convinced enough scientists that he could claim to have identified the agent responsible for cholera.
Koch embarked on the long trip back to Germany as a conquering hero. Kaiser Wilhelm received him upon his arrival and awarded him a medal created for the occasion. He was given an audience with Bismarck, a grand banquet, and a grant of 100,000 marks in gold for his research. But despite all of the adulation and awards, Koch’s discovery did not tell the world how to stop the waves of cholera epidemics. That answer would not arrive for eight years.
On August 22, 1892, a man walked into the triangular building that housed the newly constructed Institute for Infectious Disease in Berlin under the shadow of the Charité Hospital. He anxiously clutched a leather satchel, taking special care to protect it as he climbed to the second floor. In a well-lit office on the point of the triangle, he was greeted by a balding man with a trim gray beard, the founding director of the institute, Robert Koch.
The visitor opened the satchel and with exquisite care removed a culture tube and handed it to Koch. The man, a physician, had arrived on the train that morning from the city of Altona, just downstream from Hamburg. When Koch examined the contents of the culture tube, he saw, for the first time in years, the deadly crescent of cholera.
On that same day, the director of Hamburg General Hospital rushed to the office of Theodor Kraus, the chief medical officer for the city of Hamburg, to inform him that cholera had reached that city as well. In fact the epidemic had arrived almost a week before, but a stubborn partnership of denial and incompetence had kept the physicians from culturing and recognizing the organism. The hospital director expected that Kraus would immediately alert the city. To his horror Kraus dismissed the finding and would go on to use every power at his disposal to staunch the flow of information critical to the public health. Kraus belonged to a large group of physicians and public health officials who were unconvinced that Koch’s bacteria could cause cholera. This point of view sat well with the economic elite of this port city who had little stomach for quarantine.
Undaunted, the hospital director took matters into his own hands. He sent Kraus an official state telegram announcing the arrival of cholera in Hamburg. This meant that a copy would go to the central government in Berlin. Federal health officials responded by putting Dr. Koch on a train to Hamburg.
For Koch, a call about cholera must have come as a relief. As he rode through the early morning, he could, for a moment, leave the turmoil of his life in Berlin behind. Two years had passed since he had announced to great inte
rnational fanfare that he had found a cure for tuberculosis. In the intervening years, the man who prided himself on thoroughness and precision had been proven rash and wrong. His earlier success had bred jealous enemies and they seized on his moment of failure. His personal life had fared no better. His marriage to Emmy was falling apart, and at fifty-five he had launched an impassioned affair with an eighteen-year-old art student.
When Koch arrived in Hamburg, Kraus refused to meet him at the train station. When he went to Kraus’s office, the eminent scientist sat waiting for half an hour until Kraus arrived. In Kraus’s mind, there was no epidemic and no need for Koch. His denial did not stop the death toll from reaching 320 that day.
Unwavering and a bit indignant, Koch went on to tour Hamburg with members of the city’s government and medical community. What he saw left him shocked. He would later write to his young mistress that as he visited Hamburg’s hospitals and saw the condition of the ships and emigrants in its harbor, he felt as if he were “walking across a battlefield.” In the midst of the squalor of the city’s slums, Koch could not help but recall his time in Alexandria and Calcutta. “Gentlemen,” he said, turning to the other members of the entourage, “I forget I am in Europe.”
Indeed the outbreak would prove far worse than the one that had struck Alexandria. Over the next week almost 3,000 people would die. Before it was done, the epidemic would claim over 8,600 lives, most of them in just three weeks. Just downstream from Hamburg, in the city of Altona, the outbreak took a very different course.
The Blue Death Page 13
