The stars are a few powerful individuals—presidents, monarchs, dictators—whose actions can shift a society's development one way or another.
But some influential actors are nasty and ruthless—and microscopic.
In his book Twelve Diseases That Changed Our World, Irwin Sherman, a professor emeritus of biology at the University of California Riverside, describes how bacteria, parasites, and viruses have swept through cities and devastated populations, felled great leaders and thinkers, and in their wake transformed politics, public health, and economies.
U.S.News & World Report spoke with Sherman about how 12 key diseases—smallpox, tuberculosis, syphilis, AIDS, influenza,bubonic plague, cholera, malaria, yellow fever, two noninfectious diseases (hemophilia and porphyria), and the plant disease behind the Irish Potato Famine—have altered history.
Sherman also answered our questions about how the threat of disease outbreaks is affecting our world today.
It's the only infectious disease that has been eradicated through vaccination.
The medical science of vaccination was a direct result of the devastating effects of smallpox.
Essentially, studies of immunity and vaccines emerged from studies of smallpox. That gives hope that other diseases, too, will be eradicated by similar means.
The struggle against TB stimulated some of the first quests for antibiotics.
The disease most likely promoted pasteurization, which heats and kills TB and other pathogens that can contaminate milk.
The infectious nature of tuberculosis also prompted the building of sanitariums, where people could be isolated and treated.
Once treated with heavy metals like mercury, which had devastating effects on patients, syphilis inspired the discovery of chemotherapeutic agents.
The sexually transmitted disease prompted chemotherapy pioneer Paul Ehrlich to look for what he called a magic bullet, which turned out to be the drug salvorsan.
The history of many drugs can be traced to Ehrlich's work with dye materials that stained not only fabrics but organisms as well, spurring him to look for drugs that could bind to and kill parasites.
"You can't talk about infectious diseases without discussing AIDS," Sherman declares.
While today's chemotherapy cocktails—when available—are effective at reducing the number of AIDS-related deaths, it's a disease that also can be controlled by what he calls the most difficult intervention: behavioral control. "It's also a disease that is modern and yet has its parallels with the past in the kind of reactions that populations have when there's an unforeseen epidemic," he says.
Few diseases have had such widespread effects on the number of deaths in the modern world as the flu, which remains a major threat worldwide despite the existence of vaccines against it.
The disease very likely influenced the course of World War I by sickening and killing soldiers and straining military healthcare systems.
Some have suggested that President Wilson's negotiations during the Treaty of Versailles were affected by the influenza infection he had at the time.
6. Bubonic plague.
Quarantine—the isolation of infected or potentially infected people as a way to stem the spread of disease—developed from Europeans' long and storied history with bubonic plague.
Sherman notes parallels between popular reactions to the plague in medieval times and reactions to HIV/AIDS in the modern era. Fear and ignorance, anxiety, prejudice, isolation, and panic can all result from not understanding the nature of a disease, he says.
Spread via paltry or nonexistent sewage systems and lack of clean water, cholera was—and still is—rampant in many parts of the world.
But improvements in sanitation have reduced cholera's impact in a number of regions.
The power of epidemiology allowed 19th-century English physician John Snow to deduce that the disease was present in the water, even though the bacterium wasn't identified until many years later.
One of the most lethal infectious diseases in history, malaria causes over 300 million cases worldwide and up to 3 million deaths a year.
It's one of the earliest examples of the importance of controlling vectors—animal or insect carriers (in this case, mosquitoes)—in preventing the transmission of disease.
One of the reasons Europeans managed to colonize Africa, according to Sherman, was that they utilized quinine, an antimalarial drug derived from the bark of the cinchona tree.
9. Yellow fever.
Although vanquished in some countries, this mosquito-borne disease hasn't been eradicated and probably never will be, says Sherman.
The disease influenced the building of the Panama Canal, the Louisiana Purchase, and, in fact, the pre-World War II development of the southern United States. "The stereotypes of the lazy, drawling southerner and the energetic, bright northerner were typical characterizations due to disease or the absence of disease," Sherman says. "In the North, mosquitoes couldn't survive overwintering, so there wasn't yellow fever. In the South, on the other hand, you had a population that was either decimated or debilitated by the disease."
10. Hemophilia and 11. Porphyria.
As genetic blood disorders, hemophilia and porphyria had serious effects on the crowned heads of Europe.
According to Sherman, the rise of Spanish dictator Francisco Franco can be traced to the lack of an heir to the throne because of hemophilia.
Another example is the collapse of the Romanov dynasty in Russia, which was due to hemophilia in the family.
The czar was debilitated and couldn't take over, setting the stage for the rise of the Bolsheviks.
Many of the British monarchs were unable to manage their kingdoms because of porphyria, which can cause a variety of mental problems, like hallucination, paranoia, and anxiety.
Some describe George III's treatment of his American subjects, which helped to trigger the American Revolution, as being in part affected by his porphyric attacks.
12. Potato blight (cause of the Irish Potato Famine).
Sherman expanded the range of maladies to indicate to readers that diseases affect not only humans but also sometimes what we eat.
Potato blight had a profound impact because it devastated a staple food that fed much of Ireland in the mid-1800s.
Other plant diseases could have similarly far-reaching consequences today, says Sherman.
Many agricultural economies focus on a particular crop, so a single disease could be a big threat—and a major historic force.
The Irish famine influenced America by generating an influx of Irish immigrants to U.S. cities; those newcomers expanded the Democratic Party, participated in the development of labor unions, and molded the nation's character in numerous other ways.