In 1793, the Aedes aegypti mosquito carried yellow fever from the tropics to Philadelphia, killing 10 percent of the population and forcing much of the rest - including President George Washington and his entire government - to flee.
That same mosquito is now spreading the Zika virus through Latin and South America. But the insect species no longer thrives anywhere near Philadelphia.
What has changed?
Modern living. Screens, air-conditioning, sewers, insecticide, and better health care combined to deprive this particular mosquito of its favored meal, human blood. Late-18th-century Philadelphia in some ways (but not climate) resembled today's favelas of Rio de Janeiro, where mosquito-borne illness is rampant.
"In 1793, the place was just filled with potential breeding grounds," said Randall M. Packard, history of medicine chair at Johns Hopkins Medicine, who is writing a book about the history of dengue fever.
Rainwater collected in barrels and pooled on rutted streets. Horse troughs were ubiquitous. Human waste piled up.
Evidence for the germ theory of disease - not to mention mosquitoes as key "vectors" for delivery of the virus - was still a century away when a frightening condition advanced rapidly from the Delaware River port through the young nation's largest city and most important commercial center.
"Those who were in health one day were buried the next," observed Samuel Breck, a newly arrived merchant. "The burning fever occasioned paroxysms of rage which drove the patient naked from his bed to the street, and in some instances to the river, where he was drowned. Insanity was often the last stage of its horrors."
Yellow fever had broken out here before, notably in 1699, 1741, and 1762. William Penn's "greene Country Towne" had been laid out next to a mosquito-filled marsh.
The summer of 1793 was unusually hot - hospitable weather for Aedes aegypti, a species that was native to Africa and had sailed to the American tropics with the first European traders. That same summer saw an explosion in refugees escaping violence as the French Revolution enveloped the colony of Saint-Domingue (now Haiti).
Some had yellow fever, named for the tint of skin and eyes that liver damage causes in some patients. Hitchhiking mosquitoes bit them and also transmitted the virus to other passengers during the two- to three-week voyage to Philadelphia. Mosquitoes and people then mixed with residents, and the cycle escalated.
The Aedes aegypti female loves city dwellers, and even evolved a preference for laying eggs in the containers that people leave lying around.
"It has adapted to humans, just like the rats and cockroaches," said Randy Gaugler, a professor and director of Rutgers University's Center for Vector Biology.
Neither the mosquito nor its eggs have adapted enough, however, to survive winters in temperate regions, although there may be occasional exceptions. Scientists recently published genetic evidence of a small subterranean colony in Washington's Capitol Hill neighborhood; they have yet to locate the actual hideout.
During colonial times, new mosquito populations mostly would have shipped in - usually without yellow fever - to Philadelphia every summer. With a life span of two to four weeks, they might have extended their stay for 10 generations before perishing with the first frost.
Aedes travels no more than a quarter-mile. Indeed, a modern-day map by Montana State University researchers relying on 1793 data shows the highest death rates - up to 67 percent - on streets within a quarter-mile of the port.
There were plenty of places to lay eggs: uneven footpaths, cisterns, privies - basically any place that eventually gets soaked, allowing the larva to emerge.
"The epidemic is dependent not only on the mosquito but also the quality of the housing, the health system," said George Dimopoulos, a microbiologist at Hopkins' Bloomberg School of Public Health who studies control of mosquito-borne pathogens.
Without window screens, A. aegypti will menace humans all day long. In the absence of quality medical care, people remain infected far longer for mosquitoes to bite and spread viruses to others. (A vaccine now protects against yellow fever, although it still kills an estimated 30,000 people a year, mainly in Africa.)
In the United States, a lack of people to feed on, combined with measures like swamp draining, conspired to gradually push aegypti out of areas where climate had always prevented a year-round presence.
"Humans in modern-day Pennsylvania live a different lifestyle. We don't open ourselves to that level of biting. We go inside," said Mike Hutchinson, an entomologist who directs the Department of Envirnonmental Protection laboratory that identifies and tests disease-carrying insects.
Aegypti still shows up on occasion. In 2002, Hutchinson found it in a sample collected in Bucks County. He suspects that the eggs arrived in tires - a favorite habitat in the tropics. New Jersey's last confirmed sample was up north in 1991, adjacent to a construction site that had used equipment from Alabama.
It would take "a miracle," Hutchinson said, for small colonies like these to serve as vectors for Zika because a mosquito would have to pick it up from an infected human and then the virus would need time to replicate in the insect's gut to reach numbers sufficient for transmission.
In 1793 Philadelphia, there were plenty of opportunities to pass virus along. The first yellow fever death was recorded in early August. By Sept. 9, according to one account, deaths were up to 45 a day; by Oct. 11, 100.
The numbers appear in church burial records and other sources. Benjamin Rush, the nation's leading physician, kept detailed journals of the epidemic that discussed what he suspected was the cause (rotting coffee left on the dock) and the best treatment (bloodletting), although many less prominent doctors strenuously disagreed.
The epidemic was a watershed event for the city's free blacks, many of whom - believing, incorrectly, that they were generally immune - stayed behind to care for the ill and bury the dead. Still, their sacrifice did not gain them the respect that community leaders had hoped for.
Perhaps 20,000 wealthier residents fled to nearby settlements like Germantown. Thomas Jefferson had rented a mansion on the east banks of the Schuylkill in Grays Ferry. Cities in surrounding states erected roadblocks and quarantine houses; a recovering Alexander Hamilton was held in New Jersey. The federal government, housed in Philadelphia until Washington was built, shut down.
By late October, after temperatures plunged below freezing and the death trend abruptly reversed, an estimated 5,000 of the city's 50,000 residents had perished.
In the years after the disaster, Philadelphia led the nation to take public health more seriously, starting with a general cleanup of city filth and the 1795 establishment of the Board of Health. A steam-powered waterworks that pumped drinking water from the Schuylkill later morphed into a hydraulic system that drew visitors from around the world.
"What was most striking about that epidemic was its scale," said P.J. Brennan, an infectious-diseases physician and amateur historian.
"I found it really fascinating, the impact that an infectious disease could have on an economy, a city, a government," said Brennan, chief medical officer of the University of Pennsylvania Health System. "Citizens really had to band together because government had broken down."