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Vaccines for the 21st Century: A Tool for Decisionmaking
1910 to 1914 was about 6 cases per 100,000 population. The frequency of paralytic polio continued to increase during the subsequent decades, and the rate for 1952 was approximately 37 cases per 100,000 population.
In the early 1900s most deaths due to poliomyelitis were observed in infants under 1 year of age and in children 1 to 4 years of age. The death rate declined sharply in cases occurring at older ages (Health Information Foundation, 1959). However, by the early 1950s, poliomyelitis was observed with increasing frequency in school-age children and young adults. Around this period, sanitation and community conditions of hygiene began to improve significantly largely due to the efforts begun in the 1930s and 1940s. As living conditions improved, a good proportion of the population probably was not exposed to the virus until an older age. These observations may explain the apparent shift in the age of susceptibility to the development of paralytic disease between the 1900s and the 1950s (Health Information Foundation, 1959).
Polio Vaccine Development
Efforts to develop immunoprophylaxis against polioviruses began immediately after the isolation of the virus. Both killed and live virus candidate vaccines were developed as early as 1910, although at that time knowledge of the existence of three distinct poliovirus types was not available, and the fact that paralytic cases of polio represented only a tiny fraction of the total number of infections was not appreciated (Harrington, 1932; The National Foundation, 1961, 1962). For every known patient with paralysis, there may be as many as 100 to 1,000 patients who have subclinical infections (Harrington, 1932). During the early 1930s, studies were undertaken to vaccinate humans with infected monkey spinal cord suspensions inactivated with formalin or sodium ricinoleate (Brodie and Park, 1936; Kolmer et al., 1935). However, those trials failed because of a lack of adequate controls, the failure or inability to standardize vaccine preparations, and a lack of reproducible quantitative methods for virus titration.
The battle against polio began seriously at the national level with the establishment of the National Foundation for Infantile Paralysis-March of Dimes organization in 1938. During World War II, information became available regarding the distinct antigenic types of the virus, their ability to induce specific antibody responses after inactivation, the ability of inactivated virus to induce protection against intracerebral challenge (Bodian, 1949; Morgan, 1948), and the capacity of polioviruses to replicate in vitro in human and primate tissue culture cells (Enders, 1952; Enders et al., 1949). Other wartime efforts directed toward the control of epidemics of influenza with an inactivated vaccine resulted by 1953 in a renewed interest in the development of formalin-inactivated poliovirus vaccines (Salk, 1953). The introduction of tissue culture techniques and the characterization of poliovirus passage in tissue culture were breakthroughs, and represent the cornerstone of current knowledge of cell-virus interaction. These observations significantly facili-