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The only other disease to have been banished from the earth is rinderpest, a little-known relative of measles that kills hoofed animals and once caused widespread starvation in Africa; it was eradicated in 2011.

Smallpox, caused by the variola virus, was long one of mankind’s most terrifying scourges.

it killed almost a third of its victims, often through pneumonia or brain inflammation.

Many others were left blind from corneal ulcerations or severely disfigured by pockmarks.

Because it killed 80 percent of the American Indians who caught it, it was a major factor in the European conquest of the New World.

In 1796, Dr. Edward Jenner, an English physician, infected a young boy with cowpox taken from a blister on a milkmaid’s hand. Cowpox, a mild disease, protected those who had it from smallpox, and the modern vaccine era began.

Dr. Henderson quickly realized that trying to vaccinate vast populations was futile and switched to “ring vaccination.”

Dr. Foege, who is considered the father of this tactic, said it was “invented by accident” during a 1967 Nigerian outbreak when he had very little vaccine on hand.

“The first night, we asked ourselves what we would do if we were a virus bent on immortality,”

In 1977, success in hand, Dr. Henderson became dean of the Johns Hopkins University School of Hygiene and Public Health.“He was an imposing guy — physically big and very confident,” said Dr. Michael J. Klag, the school’s current dean, who was a student in that era. “He did not suffer fools gladly, and you were never sure if you were a fool or not.”

He gloomily foresaw failure for most other disease-elimination campaigns. The “siren song of eradication,” he once wrote, had led to goals that were more “evangelical” than attainable.

The problem, he would explain, was that each viral foe was so different. Smallpox had many weaknesses to exploit; it had no animal host. Every case can be found because victims have pox on their faces, and one vaccination provides lifetime immunity.

In 2011, when Bill Gates threw the full weight of his foundation into fighting polio, he struggled to explain how he would overcome such obstacles and, at the end of an interview, turned to an aide and said aloud, “I’ve got to get my D. A. Henderson response down better.”

The campaign, many experts have noted, succeeded just in time. A few years later, the virus that causes AIDS spread across Africa. Because the live smallpox vaccine can grow in an immune-compromised person into a huge, rotting, ultimately fatal lesion, it would have been impossible to deploy it.