The Blue Death Page 21

  Under Davis’s guidance, the team quickly assembled a series of questionnaires and in short order began to make phone calls. They would call hospitals, emergency rooms, businesses, schools, and nursing homes. They would even call the hockey teams that had played in the NCAA tournament. Above all they would call people in Milwaukee. They would talk to those who had been ill, but also to those who had remained healthy. At the core of epidemiology is the search for differences between those who contract a disease and those who do not. One of those differences is the cause.

  Gathering all this information was a tremendous undertaking. Liz Zelazek and her staff of public health nurses were brought in to begin making the hundreds of phone calls needed to conduct these studies and to respond to the growing flood of calls coming into the department from an increasingly confused and concerned public. The next three weeks would exhaust every resource and every person the health department could muster.

  As Wednesday marched by, the war room buzzed with activity related to the epidemiological studies. Samples continued to pour into the health department lab from around the city. The Internet was a rudimentary shadow of its current self, so reports of illness relied on faxes and even the fax machines were slow and unreliable. The flood of material and information left the health department staff reeling.

  For three weeks no one ate a meal on time. Even when they did find time to eat, they were usually interrupted. On that Wednesday afternoon, three days into the investigation, lunchtime had long since come and gone when Steve Gradus finally sat down to eat. Just as he did so, his phone rang.

  When he picked it up, Tom Taft was on the line from West Allis Hospital. “Hey, Steve,” he said, “I think I might have something here.”

  If the battle against this outbreak had become a war, Dr. Taft had become one of the commanders in the ground campaign. He had been called to see more and more patients who were suffering from the mysterious infection. Taft had enough experience that he could often identify an organism just by the pattern of signs and symptoms in his patients. How severe was the diarrhea? How intense were the cramps? How long did they last? Even the appearance of the stools could reveal the culprit. But so far the pathogen had not shown its hand. Then as he stood waiting for an elevator, another physician pulled him aside.

  Taft’s colleague was caring for a woman with severe diarrhea in the hospital’s intensive care unit. A gastroenterologist had already examined her. Using a flexible fiber-optic cable known as an endoscope, he had examined her esophagus, stomach, and small intestine. He saw no obvious explanation for her condition, so he had used a special attachment on the endoscope to clip a few small samples of tissue and had sent them to the pathology laboratory. When the pathologist had examined the samples, he had been surprised. In the lining of her small intestine, he had found what looked like cryptosporidium.

  A finding of cryptosporidium by itself would not have been unusual. It often appeared as a cause of severe diarrhea in people with AIDS. Even the fact that it had put this woman in the ICU was not extraordinary except for one thing. She did not have AIDS.

  As soon as he could, Taft made his way to the ICU to see the woman himself. In any hospital the intensive care unit defines a special territory where death holds watch as modern medicine wields all of its technical muscle in defiance. Like all physicians, he had learned to approach the ICU with a calm remove that allowed him to focus on the intellectual challenge of saving lives.

  As he entered the woman’s room, a pale yellow line traced the echo of her rapid heartbeat on a monitor above her bed. He gazed down at her frail body and examined her sunken features. A pump droned in the background as it steadily pushed saline through a catheter and into the veins of her withered arm. That pump was keeping her alive. He lifted her hand and took her twisted fingers in his own. Years of the slow and ultimately losing struggle against rheumatoid arthritis had contorted them at a tortured angle. Her skin had turned thin and paperlike from the side effects of the drugs used to treat her arthritis, drugs that also suppressed her immune system.

  The fact that this woman was overrun with cryptosporidium seemed unusual. The drugs she was taking for arthritis had weakened her immune system, but not to the extent that AIDS would. Nonetheless, Taft knew that strange things happen in medicine. He was considering the possibility that this was nothing more than an interesting case when his pager went off. He recognized the number as the microbiology laboratory.

  In twenty years as a laboratory technician at West Allis Hospital, Sandy Schroederus had seen nothing that compared to the first week in April 1993. Never had she seen the volume of samples received by the lab outstrip not only their stock of culture media, but the reserves of the surrounding hospitals from which they could have otherwise borrowed supplies. For almost a week, she and her colleagues in the lab had carefully spread tiny bits of stool samples across whatever culture media they could muster and placed it in the lab’s incubator, where the climate controls were tuned to match the moist, junglelike interior of the human body. Again and again the microbiologists at West Allis returned to the incubator, looking for bacteria that could explain what was happening to their town. Each time they opened the door, the warm air hit them in a rush filled with a fertile, musty smell as billions of bacteria divided over and over. Each time they had closed it without an answer.

  When Schroederus arrived for work on Wednesday, April 6, she had been hunting for the cause of the outbreak for almost a week. On that day she was due for a break from running stool cultures. It was her day to examine specimens for ova and parasites. Perhaps this was the day she would find something.

  Success and survival in a microbiology laboratory rely on a meticulous sense of organization that borders on the compulsive. A momentary lapse can cause a lab worker to misidentify an organism. A mistake in handling a sample from a seriously ill patient can even kill. When a disease has defied efforts to identify its cause, any sample must be handled with extra caution. In the laboratory at West Allis Hospital, the possibility that this was something new and possibly extremely dangerous hung in the air.

  Schroederus took several new samples and placed them under the hood, a laboratory bench surrounded by a vented enclosure to help prevent the exposure of the laboratory staff to pathogens. She carefully prepared the slides, placing a drop of iodine on each one. Then, one by one, she scanned the slides under a powerful microscope.

  The iodine would stain the parasites and their ova a dark purple. As she went through one slide and then another, nothing jumped out at her. Then one slide struck her as strange. As she scanned through the nondescript jumble of organisms and iodine, she saw nothing that looked like a pathogen, but she had the sense that there was something else there. Something she couldn’t see.

  The particles and organisms she could see seemed too spread out, as if something were pushing them apart. As she stared into the microscope, the visible defined the shape of the invisible. It appeared to her that the area of the slide that seemed empty at first glance was in fact filled with tiny spheres. She wasn’t sure what she had, but the stakes were high. She couldn’t afford to miss anything.

  So she went on a hunch. She carefully prepared a slide from the sample and added a preparation of fluorescent antibodies. When she looked at the sample, she was stunned. Hundreds of brilliant spheres jammed the field.

  She refused to believe her own eyes. She had to be sure there was no mistake. She made a new slide, double-checking every step. When she looked again, any doubt disappeared. The sample was filled with the egglike oocysts of cryptosporidium.

  When she spoke to her supervisor, he recalled the biopsy sample from the woman with diarrhea. That had looked like the active form of cryptosporidium but there are no antibodies to the organism, only to the oocysts, so they had no definitive proof. Now they had a confirmed case.

  Could this be the organism they had been scrambling to find? To get the input of a physician, they paged Tom Taft.

  Taft ans
wered the page and, as he learned what they had found, the pieces of a huge puzzle began to tumble into place. The finding from the woman in the ICU raised his suspicions, but here was an immunocompetent patient with severe cryptosporidiosis. The implications were staggering.

  Taft believed he might have the missing piece for which the health department had been searching. He immediately called Steve Gradus to tell him what he had found. Although it would take many more tests to be sure, these two cases raised the possibility that Milwaukee was experiencing an outbreak of cryptosporidiosis among people with normal immune systems. If so, how had so many people become so sick so fast? The answer began years earlier with a meeting between two scientists in the Arizona desert.

  The career of a successful scientist may be, as Edison suggests, 99 percent perspiration, but without those rare moments of inspiration, all that sweat is for naught. Seven years before the outbreak in Milwaukee, Joan Rose, a young postdoctoral fellow at the University of Arizona, had such a moment as she sat in the office of Chuck Sterling, a new faculty member in the Department of Microbiology.

  Tall and blond, with a blazing smile and boundless energy, Rose shatters any stereotypes of a cloistered laboratory scientist. Raised in the blast furnace of California’s Mojave Desert, she had been set on the path of science at a young age. An interest that began with ant farms and chemistry sets gave way to thoughts of medical school and volunteer work as a candy striper at the local hospital. Nothing in the hospital captured her imagination as much as the dazzling array of equipment she saw in its microbiology lab.

  By 1980 she had completed bachelor’s and master’s degrees in microbiology and was starting work on her PhD at the University of Arizona under the tutelage of Chuck Gerba, an iconoclastic environmental microbiologist with a particular interest in waterborne pathogens.

  At first glance the deserts of the Southwest might seem like an odd place to go to study water, but no area of the United States cares about it more. In the early 1980s, Arizona’s exploding sunbelt population was sucking water from the state’s aquifers so fast that they were losing 810 billion gallons of water each year. Today the desperate response to this unsustainable water consumption is a 336-mile canal that cuts across the entire state of Arizona. With a dozen tunnels and siphons and sixteen pumping stations, which along the way lift more than 300 billion gallons of water more than half a mile in the air every year, the aqueduct carries water from the Colorado River to the desert cities of Arizona ending in Tucson at the far corner of the state.

  Even with the canal, the state continues to deplete its precious groundwater. A plan is already in place for Tucson to treat and then drink its own sewage sometime in the next ten years. The state’s ever-expanding thirst created a critical job for Gerba and his doctoral student. The wastewater the people of Tucson were preparing to drink was loaded with viruses far smaller than the bacteria that had challenged Robert Koch and Louis Pasteur. Rose began working with Gerba to study the occurrence of viruses in treated sewage.

  In 1985 Rose found herself with a newly minted PhD in environmental microbiology, two young children to feed, and an uncertain future. She decided to stay on at the University of Arizona for a postdoctoral fellowship. Postdocs are academic purgatory. In a vicious job market, they buy the budding scientist some time to prove that she can get the grants and produce the papers essential to survival in academia.

  Her research moved from viruses to a protozoan by the name of giardia. Protozoa fall somewhere between bacteria and animals on the evolutionary scale. Like bacteria they are composed of a single cell, but a closer look shows that these cells include many of the key advances in cellular organization exhibited by animal cells and necessary to form higher organisms. More important for Rose and Gerba, protozoa cause some of the most serious human diseases, including malaria and amebic dysentery. Giardia had been recently recognized as a cause of severe, prolonged diarrhea and had been associated with outbreaks of waterborne disease.

  Rose had already begun her research on giardia when she met Chuck Sterling. Sterling had started out studying malaria, but he had moved on to look at a closely related protozoan called cryptosporidium. First identified in 1907, cryptosporidium commanded little interest until the 1960s, when veterinarians discovered that it was a major pathogen in livestock, particularly calves. The medical community took notice in 1981, when it began to show up in AIDS patients as a cause of severe, debilitating, often fatal diarrhea.

  Rose had never heard of cryptosporidium, but as Sterling laid out the life cycle of the parasite, she was struck by his description of its oocyst, a hard egglike structure that contains the organism in the dormant phase of its life cycle. Chitin, the protein that forms the oocyst, is the same compound that forms the outer shell of ants and other insects. Once in the environment the toughness of the chitin shell allows cryptosporidium to remain viable for months.

  As she listened, Rose had a moment inspiration that would change her career and with it the world of drinking water. This new bug sounded to her like an armor-plated version of giardia. Cryptosporidium, she realized, walked, swam, and quacked like a waterborne pathogen. What’s more, Sterling had just developed a tool that would be essential to any further research.

  If Rose wanted to study cryptosporidium, she had to be able to find it. Even under a microscope, oocysts are, for all practical purposes, invisible. Not only are they minute, they are also transparent. Its discoverer immortalized this elusiveness with a name that translates as “hidden seed.” Before Sterling introduced his improved methods, most oocysts escaped detection. He had shifted the balance in this war of concealment by using a recently developed microbiological tool known as an ELISA (enzyme linked immunosorbent assay). The use of an ELISA required a supply of antibodies to cryptosporidium oocysts and Sterling had just developed the capacity to produce those oocysts in his laboratory.

  Sterling’s antibodies, like most antibodies, had a shape similar to a pair of pliers. The jaws of those pliers have a unique contour that matches molecular projections that occur only on the surface of their target, in this case cryptosporidium oocysts. An oocyst, when combined with these molecular pliers, would emerge bristling with antibodies.

  Sterling’s antibodies were not just any antibodies. When exposed to ultraviolet light, the back end of the handles of the molecular pliers glowed like stars. These were the same antibodies that Sandy Schroederus would later use to find cryptosporidium oocysts in stool specimens in Milwaukee. This type of antibody is known as an immunofluorescent antibody and armed with it Rose could test a slide on which she had collected what might be oocysts. If Rose wanted to use Sterling’s technique to look for oocysts in water, she had only one problem: getting cryptosporidium onto a slide.

  Stool specimens, such as those tested by Schroederus, could contain billions of oocysts, so getting enough oocysts to ensure the test would work was not a concern. But in drinking water, Rose would usually be looking for fewer than one hundred oocysts in an entire liter. Perhaps fewer than ten oocysts. Drinking water containing just a few oocysts in a liter could trigger a massive outbreak of disease. Finding an oocyst in a child’s glass of water is comparable to finding a single pea in a glass more than a mile high and half a mile across. Rose’s experience with giardia told her that she would need to filter hundreds of gallons of water if she wanted to capture enough oocysts to make the antibodies useful.

  Rose set to work in the lab, and by 1986 had a test that, although it could not find every oocyst, could find enough for her to begin looking. She immediately set to work using it to test for cryptosporidium in water supplies. As she collected samples from different locations in the Southwest, she began to find cryptosporidium. Everywhere.

  Rose’s hunch had proven correct. Cryptosporidium could be found in water, but no one was sure what it meant. She was about to find out. In January 1987 Rose was in the midst of her hunt for oocysts in water supplies when she got a phone call from the EPA.

  Earl
ier that month a physician at the clinic for West Georgia College in Carrollton had been inundated with students complaining of diarrhea. When state and federal epidemiologists came to investigate, they discovered that the outbreak had hit not just the college, but the entire city as well. The outbreak was so widespread that the epidemiologists who came to investigate soon began to suspect the water supply.

  The majority of Carrollton’s homes still relied on wells rather than the public water supply. As they tried to follow the outbreak back to its source, epidemiologists found that people who had fallen ill were far more likely to have used the public water supply, either at home or at work. They also found that the outbreak had hit nursing homes using the public water supply far harder than those that relied on wells. Using techniques almost unchanged since John Snow first applied them in London, they pointed to the water supply as the source of the outbreak.

  Then investigators discovered cryptosporidium in samples from several hospital patients. A massive outbreak of cryptosporidiosis among people with normal immune systems was unprecedented. Since Rose’s work with Gerba and Sterling demonstrating the ubiquity of the organism in surface water was still unpublished, the possibility that it was waterborne came as a shock to public health workers. At this point the EPA became involved, including a scientist by the name of Walt Jakubowski, the man who had given Joan Rose her first grant for the study of cryptosporidium. When Jakubowski learned about the outbreak, she immediately came to mind.