When a smallpox epidemic struck Boston in 1721, officials attempted to control it by isolating those afflicted with the disease in a “pesthouse” and quarantining ships and their crews in Boston Harbor. Cotton Mather, one of the city’s leading citizens and the foremost Puritan intellectual in New England, urged a different course. He pressed Boston’s doctors to embark on a program of inoculation. For centuries, a form of inoculation called variolation had been practiced in India to ward off smallpox. It involved making a cut in the skin, then rubbing it with a drop or two of fluid squeezed from the pustules of someone with a mild case of smallpox. Mather had read a Greek physician’s description of employing the procedure was employed in the Ottoman Empire. He also had a first-hand account from Onesimus, an African-born slave who had been inoculated against smallpox in his native country and never came down with the disease.

Convinced by what he had learned, Mather “strongly advocated inoculation,” writes John Froude in a new book, Plagued: Pandemics from the Black Death to COVID-19 and Beyond. His advice was fervently resisted. Mather’s efforts galvanized opposition so intense that “someone threw a bomb filled with gunpowder and turpentine through his window with a note: ‘Cotton Mather you dog, damn you, I’ll inoculate you with this.’” Mather was accused of offenses ranging from flouting God’s will (since inoculation isn’t mentioned in the Bible) to proposing something that would make the epidemic worse.

Ultimately, only one doctor followed Mather’s advice. Zabdiel Boylston inoculated 287 people, of whom all but six survived. Of the 5,889 un-inoculated Bostonians who caught the disease, 844 died, a mortality rate of nearly 15 percent.

Plagued was written during one of the worst global disease outbreaks in recent decades by a physician who specializes in infectious diseases. Combining scientific explanation with social history, Froude surveys the history of pestilence — one of the Four Horsemen of the Apocalypse — in a dozen of its most harrowing manifestations: bubonic plague, cholera, typhus, tuberculosis, syphilis, malaria, smallpox, yellow fever, Spanish flu, AIDS, the “rain forest viruses” (West Nile/Zika/Ebola), and COVID-19.

Froude doesn’t stint on the biology, devoting a chapter apiece to bacteria, viruses, and the ever-evolving human immune system. He documents the particular devastation wrought by pathogens on populations encountering them for the first time. The indigenous Taino people of Hispaniola, for example, were annihilated by the influenza unwittingly unleashed on their island by Christopher Columbus and his men, while the syphilis that the Spaniards first contracted in the Caribbean tore through Europe and then Asia when it accompanied them back across the ocean.

But the book’s most powerful theme is the one encapsulated in the story of Mather and Boston’s smallpox epidemic: denialism.

Again and again, Froude shows that when societies are struck by a plague, the urge to reject reality quickly follows.

Sometimes the deniers refuse to accept evidence of how the disease is caused. During a ghastly cholera outbreak in Britain in 1848, surgeon’s assistant John Snow meticulously investigated every case he learned of, noting not only the condition of the patients, but also the circumstances of their home life. He published a paper arguing (correctly) that cholera is transmitted by drinking water contaminated by feces. But the medical establishment dismissed Snow as a fanatical “contagionist” and insisting that the true cause of the disease was bad odors and poisonous vapors in the air. During a subsequent outbreak in London, Snow brilliantly tracked its source to a well on Broad Street from which virtually everyone infected had drunk. (The well had been dug just feet away from a cesspit that had started leaking.) When the pump handle was removed, the infections stopped.

But all Snow got for this tour de force of medical legwork and deduction was the experts’ scorn. The president of the General Board of Health derided his conclusion, and The Lancet, Britain’s leading medical journal, mocked him: “In riding his hobby very hard, he has fallen down theough a gully-hole… . Has he any facts to show in proof? No!” (In 2013, 155 years after Snow’s death, the Lancet published an apology for its egregious attack on a scientist now regarded as one of the founders of the field of epidemiology.)

Another form of denial is to minimize the severity of pandemics even as the bodies are piling up. Former president Donald Trump repeatedly insisted last year that COVID would soon “go away.” Other leaders have done the same. In 1900, bubonic plague erupted in San Francisco, but California’s governor vehemently contended that there was no plague “in the great and healthful city of San Francisco.” The San Francisco Examiner ran a magazine article explaining “Why San Francisco Is Plague-Proof,” while another paper proclaimed in March 1900 that the “Plague Farce Is Over.” In fact, it would persist until 1904.

As a sizable minority of Americans refuses to get the COVID vaccine, Froude supplies some historical perspective. “Despite the success of vaccines,” he writes, “there has always been an international minority opposition to their use.” The reasons for that opposition vary. Some objectors consider vaccines an infringement on their liberty. Others see vaccines as dangerous or contrary to nature’s plan. Still others convince themselves that vaccines are part of a nefarious plot.

At its most bizarre, denial actually celebrates sickness as a form of toughness or beauty.

When the Nigerian novelist Wole Soyinka, a Nobel laureate, was diagnosed with malaria during a visit to Switzerland, he discharged himself from the hospital. If he submitted to medical care, Froude quotes him as saying, he would be a laughingstock in his country. “And you know why? Because we in Nigeria have malaria for breakfast, lunch, and dinner.” Guy de Maupassant, the 19th-century French author, was elated to learn that he had contracted syphilis. “I’ve got the pox!” he rejoiced. “The real thing! … The majestic pox, pure and simple; the elegant syphilis.”

In the 18th and 19th centuries, tuberculosis (also called consumption) was praised as a sign of culture and refinement. Charlotte Bronte called the sickness, which would end up killing her and all her siblings, “a flattering malady.” Lord Byron said he hoped to die of consumption so that women would say, “See that poor Byron — how interesting he looks in dying!”

Science has made extraordinary advances against plagues, but human nature is unchanging. “Literate educated societies behave in the 21st century as illiterate uneducated societies did in the 17th,” concludes Froude. Pandemics are still with us. So is the compulsion to deny their reality. For as long as our species has existed, it has been ravaged not just by plagues but by the inability of so many of us to see them as they really are.

No pill or vaccine will cure denialism, conspiracy thinking, scapegoating, and polarized politics. The remedies for those habits of mind — harmful at any time, but especially in times of plague — remain what they have always been: education, goodwill, and patience.

(Jeff Jacoby is a columnist for The Boston Globe).