1 COLD WAR, HOT PATHOGENS IN FEBRUARY 1951 Alexander Langmuir, the epidemiologist for the Communicable Disease Center (CDC) in Atlanta, Georgia, delivered a lecture at the Kansas City Medical Center. "Many pathogenic agents may be grown in almost limitless quantities and may be dispersed into the air as single cells," he said. Langmuir bent his six-foot-two-inch frame over the lectern, his booming baritone filling the hall. "The purposeful creation of such clouds is biological warfare." He described how atomizers could spray dangerous microbes in crowded enclosed spaces and how bombs could create smoglike pathogens that would hang over a city for hours. He spoke of contaminated water systems and of food infected at a banquet. "The planning of appropriate defensive measures must not be delayed," Langmuir advised. The press had warned of biological warfare since 1946.

But with the start of the Korean War in June 1950, fear and rhetoric escalated. By early 1951 Langmuir had convinced the federal government to support a ready-response team at the CDC. In June 1951 American soldiers in Korea began dying of a mysterious infection that started with high fever, aches, nausea, and vomiting. Then victims'' blood vessels burst, causing internal and often external bleeding. The infection, dubbed Korean hemorrhagic fever, affected twenty-five thousand United Nations (mostly American) troops, killing nearly three thousand of them during the course of the conflict. Fear of this new epidemic disease solidified funding for Langmuir''s trainees. The program was named the Epidemic Intelligence Service (EIS), deliberately employing a military term and implying a comparison with the recently created Central Intelligence Agency. The two-year EIS experience in the U.

S. Public Health Service Commissioned Corps would satisfy the new obligation for doctors to perform military service. Langmuir suddenly had bright young physicians who did not want to go to war begging to join the CDC. A Shoe-Leather Epidemiologist Born in 1910 in Santa Monica, California, and raised in Englewood, New Jersey, Alexander Langmuir graduated from Harvard and went to Cornell University Medical College. After finishing his internship, he began a career in public health. Before the war, he practiced what he called "shoe-leather epidemiology" in New York State, going into the field to investigate epidemics of polio, tuberculosis, pneumonia, and other diseases. During World War II he was tapped by the army to serve on the Commission on Acute Respiratory Diseases based at Fort Bragg, North Carolina. The commission feared another massive influenza epidemic such as the one that had killed so many in 1918.

No such pandemic materialized, but the soldiers, packed in crowded barracks, provided ideal subjects for Langmuir''s studies of acute respiratory disease epidemics. Armed with a high-security clearance, Langmuir was also admitted into the top-secret confines of Camp Detrick (renamed Fort ¬Detrick in 1956), in Frederick, Maryland, where military scientists experimented with infectious agents, trying to develop strategies to combat biological warfare if the enemy unleashed it, as well as preparing to inflict retaliatory epidemics. A Happy Hunting Ground The CDC was three years old when Langmuir arrived there in 1949, lured from an associate professorship in epidemiology at Johns Hopkins. His friends lamented his commitment to this "dying field," since antibiotics and vaccines presumably would solve everything. Langmuir countered, "I firmly believe that in the field of infectious diseases there is a happy hunting ground for major discoveries and contributions," and the CDC''s broad mandate impressed him. "The range of opportunity, the potential was obvious," he said later, "and with my considerable self-confidence, I had no trouble going." "Considerable self-confidence" was an understatement. "People knew when he entered a room," Langmuir''s daughter Lynn recalled.

"He tipped the boat. You had to scramble to keep your equilibrium." An EIS alum spoke of others quailing before "the peals of Langmuirian thunder." His successor as the head of the program described Langmuir after his death as "visionary, clairvoyant, tenacious, well-prepared, scientifically honest, and optimistic." Others used adjectives such as "loud, intimidating, pompous, bombastic, aggressive, and domineering." Yet most agree that without Alexander Langmuir''s strong leadership and vision, the EIS program would never have ¬endured. Epidemic Twists and Curves In tracing epidemics, Langmuir espoused what came to be called a cohort study of a carefully defined group of people (Who attended the church supper?), comparing their behavior (What did they eat? Where did they go? Who did they associate with?) and looking for key differences between those who had become ill and those who had not. Sometimes through such comparisons, the cause of an epidemic became obvious.

It was the potato salad! Langmuir stressed the importance of long division to find the rate of a given disease in a particular population--the number of ill over a defined period of time as a numerator and the population at risk as a denominator. "Stripped to its basics," he said, "epidemiology is simply a process of obtaining the appropriate numerator and denominator, determining a rate, and interpreting that rate." Thus, the three essential elements were time (when were people exposed and when did they become ill?), person (who was affected in what defined population?), and place (where did the epidemic take place?). But how do you know that an epidemic is occurring? First, you establish the "normal" rate of disease for that area. Langmuir talked about the importance of routine disease surveillance to establish baseline data and to look for anomalous blips. Traced on a time line that tracks the number of accumulating daily cases, most epidemics form a classic bell-shaped epidemic curve. In the simplest version, an outbreak begins in a particular community with an index case, spreads to others, reaches a peak, and then gradually burns itself out, as susceptibles either survive and become immune or die. Looking at this epi-curve, the disease detective could deduce a fair amount.

A common source epidemic, such as bad potato salad at a picnic, would have a sudden onset, sharp peak, and rapid resolution among a limited population, whereas an ongoing problem such as a contaminated water supply might affect an entire community for a longer time. Once a likely moment of exposure was determined, i.e., the time of the picnic, the epi-curve also revealed the average incubation period, the time between infection and disease onset. Tiny Parasites, Unwilling Hosts Fossilized bacteria have been found in rocks over 3 billion years old. These single-cell organisms reproduce by dividing by fission--often in less than twenty minutes. Some bacteria are helpful, such as those that help us digest food, while others release chemicals that poison our tissues. To fight off infections, our bodies developed an elaborate immune system that creates specific antibodies for specific microbes.

There are about two thousand known species of bacteria. Also ancient, a virus is a protein shell surrounding a strand of nucleic acid, either DNA or RNA. It cannot reproduce on its own but must invade a living cell, which it takes over, commanding the cell to reproduce the virus at an incredible rate. There are about fifteen hundred known viruses. Then there are the one-celled parasites, such as those that cause malaria, whose vector (delivery system) is the mosquito; larger bacteria called Rickettsia, usually inserted into humans by ticks or fleas; and fungi whose spores float from the air into the lungs or onto preexisting skin lesions. There are also chemical toxins produced by bacteria and other quick-acting poisons that, while not infectious, can kill people. Microbes have evolved mechanisms to proliferate--for example, measles and influenza victims cough, spraying virus into the air; Shigella causes diarrhea in order to spread bacteria. Man against microbes is a fight for survival.

The Hazards of Improved Sanitation Langmuir''s epidemiological techniques led to two important discoveries even before the creation of the EIS. When he arrived at the CDC, a $7 million budget was still devoted to fighting malaria because Southern doctors continued to report thousands of malaria cases when there was no other obvious cause of the fever. Langmuir''s first surveillance effort sent out teams to conduct surveys about the frequency of attacks, symptoms, treatment, and patient travels, and to collect blood samples. Investigations unearthed only nineteen positive cases of indigenous malaria and these were not in the significant clusters that would indicate a potential epidemic. Malaria had been virtually eliminated from the United States, but no one in the medical field had realized it. In 1950 Langmuir sent twenty-six-year-old Ira Myers, one of the few doctors he was able to recruit before the "doctor draft" of 1951, to Charleston, West Virginia, to determine if flies transmitted polio¬myelitis, the viral crippler that terrified postwar America. Myers discovered that there was a much higher rate of paralytic polio in upscale ¬Kanawha City, a suburb of Charleston, West Virginia, than in ¬Chandler Branch, a poor area where cesspools dumped into the drinking water supply. By the time they were six months old, most babies in Chandler Branch had developed mild infections and were immune to polio.

Poor sanitation had provided the Chandler Branch children with a surprising advantage over the kids in the more sanitary Kanawha City.