In 1793, just before the introduction of vaccination but at a time when variolation was widely practised in Britain, John Haygarth published a remarkable pamphlet in which he proposed to 'exterminate' smallpox from that country by a scheme that included systematic variolation throughout the country, isolation of patients, decontamination of potentially contaminated objects, supervised inspectors responsible for specific duties, rewards for the observance by poor persons of rules for isolation, fines for transgression of those rules, inspection of vessels at ports and prayers every Sunday. A few years later, shortly after publication of his Inquiry, Jenner had a similar vision: 'it now becomes too manifest to admit of controversy, that the annihilation of the Small Pox, the most dreadful scourge of the human species, must be the final result of this practice.'

However, in spite of the practice of vaccination in many countries for almost a century, in 1900 smallpox was endemic in almost every country in the world. Australia, New Zealand and small islands of the Pacific Ocean and elsewhere were kept free of the disease because of their isolation and efficient quarantine services. So were the Scandinavian countries, thanks to well-conducted vaccination campaigns and containment of outbreaks.

The prevalence of the disease was greatly reduced in Europe until the disruption and mass movements of people associated with World War I exacerbated the disease in Russia, from whence it spread to Germany, Austria and Sweden—in 1919, there were some 300,000 cases in Europe. After 1923, statistics on whether smallpox was endemic in various countries was collected by the Health Commission of the League of Nations and from 1948 by the World Health Organization (WHO).

After World War II, there was a rapid fall in the numbers of endemic countries in Europe and North America, from which continents the disease was eliminated by 1953. A few of the smaller countries in Asia were also freed of smallpox, but it remained a common disease in most countries of Africa and Asia. Heartened by these results, in 1950, Fred Soper, a great enthusiast for the eradication of vector insects (A. gambiae and Ae. aegypti) and infectious diseases, persuaded the Pan American Sanitary Organization to undertake the eradication of smallpox from the Americas. Then, in 1953, the first Director-General of the WHO, Canadian Brock Chisholm, tried unsuccessfully to persuade the World Health Assembly to agree to a program for the global eradication of smallpox. The Assembly dismissed his proposal as unrealistic. Yet two years later, the same body, mesmerized by the new approach of using DDT for the control of Anopheles mosquitoes, agreed to a vastly more difficult program which called for the global eradication of malaria.

It was not until 1958 that global eradication of smallpox was again considered by the World Health Assembly. By that time, the malaria program, which had been strongly supported by the United States, had run into serious difficulties. The Soviet Union, which had been excluded from the Assembly for several years, returned in 1958 and, wishing to make its presence felt, put forward a carefully planned proposal for the global eradication of smallpox, which on this occasion was endorsed by the Assembly. The suggestion was that this could be achieved in 4-5 years, essentially by vaccinating and re-vaccinating up to 80 per cent of the population of each endemic country and thus producing a level of herd immunity sufficient to break the chains of transmission. The World Health Assembly resolution was accompanied by arrangements for the provision of freeze-dried vaccine to endemic countries, many of which were encouraged to set up national smallpox eradication programs. However, no WHO funds were set aside to provide for coordination of the program.

During the next few years country-wide elimination was achieved in several more countries in Asia, Africa and the Americas, but by 1966 it was clear that progress along these lines would never achieve global eradication. The countries in which smallpox remained endemic were the hard core of the problem; the Indian subcontinent, Ethiopia, sub-Saharan Africa, Indonesia and Brazil.