Epidemiology is a branch of medicine that is concerned with the incidence, spread, and control of disease. It depends in a critical way on the use of statistics to give insight into how disease is trans- mitted from individual to individual and place to place. Epidemiology is a fairly new branch of medicine. Its first great breakthrough was in the fight against the disease cholera. This famous application of statistics offers insight into the strengths and weaknesses of statistical methods.
Cholera is an ancient disease. It is caused by a bacterium, called
Vibrio cholerae, that for most of the history of humankind remained
within the borders of the Indian subcontinent. Cholera is a dra- matic disease. Its onset is sudden and violent, and the disease is sometimes fatal. The death rate of cholera varies widely from area
to area and outbreak to outbreak. It can be much higher or much lower than 50 percent.
Cholera is a disease of dehydration, and its progression has often been described as occurring in three stages. The onset of the disease is marked by violent vomiting and severe diarrhea. In a brief period the infected person can lose as much as 10 percent of his or her body weight. The first stage concludes with what early-19th-century physicians called “rice water diarrhea,” which consists of a clear liquid containing what we now know are frag- ments of the lining of the patient’s damaged intestine. During the second stage, which these physicians called the “collapse stage,” vomiting and diarrhea cease, the body temperature drops, the pulse becomes very weak, lips and fingernails turn blue, and the blood is very thick and dark—almost black. It is during the second stage that the majority of deaths occur. The third or “recovery stage” is marked by fever.
Outbreaks can be devastating. In 1781 in the Indian city of Haridwar, which is located on the banks of the Ganges River, there was an outbreak of cholera in which 20,000 individuals died in eight days. Although this was a particularly severe outbreak, it was typical in the sense that it was confined to the Indian subcon- tinent. In the year 1817 the situation changed.
The more recent history of cholera is described in terms of pan- demics, outbreaks of the disease that occur over very large geo- graphical areas. The first pandemic began in 1817. In that year cholera spread across the Indian subcontinent. By 1819 cholera could be found in what is now Sri Lanka. By 1820 East Africans were dying of cholera for the first time. By 1821 cholera was pres- ent on the Arabian Peninsula, and by 1822 Japan and China were suffering from cholera. In 1823 cholera began to make its way into Russia, with an outbreak in the city of Astrakhan in which there was a total of 392 reported cases and 205 fatalities. The disease then disappeared everywhere except the Indian subcontinent, where it is endemic. During this time not a single effective strate- gy for combating cholera was developed.
The second pandemic lasted from 1826 until 1837. Many histo- rians believe that the second pandemic began at Haridwar at one
of the great religious festivals that occur there. It is thought that religious pilgrims from Bengal introduced the disease to the festi- val at Haridwar, and from Haridwar it was dispersed throughout India. The disease followed rivers and trade routes. Again it appeared in the Russian city of Astrakhan. Within 24 hours of the
Nineteenth-century cartoon satirizing the sometimes-ridiculous measures taken by people to protect themselves from cholera. Before Snow’s work, however, no one understood how cholera was transmitted. The efforts of many physicians of the time were, in retrospect, no more effective than the efforts of this figure. (Library of Congress, Prints and Photographs Division)
first reported cases there were 200 deaths. Among the first to die were the civil governor and the chief of police. Panic ensued. The social order collapsed as much of the population fled into the sur- rounding countryside, taking the disease with them. Between July 4 and August 27, 1830, there were 3,633 cases of cholera record- ed at Astrakhan. About 90 percent of those who became ill at Astrakhan died.
Cholera made its way northward along the Volga River and then spread out. As it did so it became less deadly. By the time it reached Moscow the death rate was 50 percent of those who became infected. The Moscow outbreak attracted a great deal of attention throughout Europe, which had never had a cholera outbreak before. From Russia, cholera moved for the first time into the Baltic states and Poland. From Poland it moved from country to country as far west as France and Great Britain. It crossed the Atlantic Ocean, and for the first time cholera appeared in Canada and New York and then moved south and west. By the time the outbreak was over in 1837, cholera had become a worldwide epidemic.
Cholera inspired a great deal of fear, but statistical techniques were not applied to the study of cholera until the third pandemic (1846–63). Medically speaking, the second pandemic was note- worthy because a successful treatment for cholera was first devel- oped at this time. Unfortunately, physicians were not conducting carefully designed statistical experiments to compare various methods of treatment. Some applied leeches for the treatment of cholera, some administered laxatives, and one British physician, Thomas Latta, used a saline fluid injection to rehydrate patients who were on the verge of death. Since some people always get bet- ter, even with leeches, and since there were no objective statistical criteria to compare the different approaches, Latta’s innovation was ignored by the medical establishment of his time.
Although a treatment of cholera is important, it turns out that the prevention of cholera is an easier, more economical way of protecting the public health. This was discovered during the third pandemic well before the germ theory of disease was discovered, and it shows in a very dramatic way both the power and the weak-
ness of statistical methods. The scientist who made this discovery was the British physician John Snow (1813–58).
John Snow was the son of a farmer. He attended school until he was 14 and then was apprenticed to a surgeon. During the second pandemic he served as an assistant. He was ambitious, and over the course of many years he worked his way up into the medical estab- lishment. He graduated from the University of London in 1844, and in 1850 he was admitted to the Royal College of Physicians. Snow thought long and hard about the problem of cholera. He was especially interested in the process through which cholera is transmitted. He learned as much as he could about outbreaks that occurred during the second pandemic, and he studied previous patterns of transmission. He was as thorough as one man working alone could be.
The geographic patterns of transmission of cholera were quite complicated. Sometimes it struck one area and entirely missed neighboring population centers. Its transmission as a function of time was also very complicated. For example, in 1848, during the third pandemic, cholera caused 1,908 deaths in England and Wales. In 1849 there were 53,293 deaths due to cholera, but dur- ing the next two years no deaths in either England or Wales were attributed to cholera. Cholera returned in 1853 and 1854, when there were, respectively, 4,419 and 20,097 deaths attributed to the disease. Although the third pandemic continued until 1863 there were no further deaths in England or Wales during the pandemic. John Snow began his studies of the mechanism of cholera trans- mission under a serious handicap: Although no one understood how cholera was transmitted, a number of prominent individuals championed incorrect ideas. When Snow proposed his idea that cholera is transmitted through drinking water, there was no short- age of individuals to tell him that he was wrong. To be sure, Snow had collected and analyzed as much information on past outbreaks as he could. In 1849 he even published “a slender pamphlet” that described his theory, but it did not sway many minds. Instead, his idea that cholera, or at least the cause of cholera, was in the water was greeted with a great deal of skepticism. He did not become discouraged, but he realized that to convince others, and to save
lives, he would need to acquire better data. Snow’s big break- through occurred during a cholera outbreak in the Broadstreet area of London, beginning on August 31, 1853.
It was an especially virulent outbreak. During the first three days 127 people living in this compact neighborhood died. Within a week of the outbreak of the disease the majority of the survivors had locked their homes and businesses and fled. By September 10 there were 500 fatalities.
Meanwhile, Snow had already begun his investigation. The compactness of the outbreak gave Snow some hope that he could link the fatalities to a single polluted water source. He diligently began to interview families of victims on the first day of the epi- demic. He discovered that most of the families of the deceased got their water from the pump on Broadstreet, but several deaths were more difficult to explain. An elderly woman living some distance from Broadstreet also died of cholera. She was an isolated case in her neighborhood with no apparent connection to the outbreak on Broadstreet. Snow discovered, however, that she had once lived in the Broadstreet area and liked the taste of the water enough to have a bottle of it taken to her daily. All of his detective work, his statistical correlations, and his theories failed to convince the authorities, however. By the time they reluctantly agreed to remove the handle from the Broadstreet pump, the epidemic was already substantially over.
Snow received additional help when a minister in the area, the Reverend Henry Whitehead (1825–96), decided to investigate the outbreak himself. Initially, Whitehead did not accept Snow’s the- ory. Determined to prove him wrong Whitehead interviewed as many people as he could—occasionally he visited them several times—until he had found each victim’s name and age and had determined whether the individual drank water from the Broadstreet well, the hour the illness began, and what the sanitary conditions were. It was an enormous amount of information. More than 600 people had died over the course of the outbreak. The results of Snow’s and Whitehead’s efforts were a collection of tables, a complete analysis by Snow, and a map relating the loca- tions of the cases to the position of the well. They even discovered
the initial case: A five-month-old girl had contracted cholera shortly before the onset of the outbreak. Her family’s cesspool was located three feet from the pump.
Snow died before the germ theory of disease was accepted. He died, in fact, before his theory that cholera is transmitted through drinking water was widely accepted. The statistics did not identi- fy what cholera was. Snow’s theory was not an explanation in a sci- entific sense. It was a correlation between water and disease. Correlations, not explanations, however, are what statistical research excels at revealing.
In 1866, during the fourth pandemic there was a cholera outbreak in London. A government official and statistician named William Farr, who was familiar with Snow’s theory on the mechanism of transmission of cholera, examined the water supply to the area. He traced the water consumed by those individuals infected with cholera to some ponds used by a local water supply company. Farr found these ponds polluted with sewage. He used his influence within the government to prevent the company from distributing water from the pond. The epidemic quickly died out. This was the first time that statistics enabled a govern- ment to halt an epidemic.