Rat urine. As we feast on succulent turkey, moist stuffing, and glistening cranberry sauce this Thanksgiving, the furthest thing from our minds is probably rat urine.

Yet it’s quite possible that America as we know it would not exist without rat urine and leptospirosis, the disease it spreads. The disease conveniently cleared coastal New England of Native Americans just prior to the Pilgrims’ arrival and later killed the helpful Squanto. It still lurks among us, underdiagnosed, an emerging menace.

In the winter of 1620, the Mayflower happened to dock at an abandoned village. It had been known in the local Wampanoag language as Patuxet. Pilgrims rejoiced; the land “hath been planted with corn three or four years ago, and there is a very sweet brook runs under the hillside.” In fact, the French explorer Samuel de Champlain had observed what would become Plymouth harbor 15 years earlier and drew a map of native homes surrounded by fields of corn.

Where had all the people gone? As the Pilgrims thanked God for their luck, they were unaware that the previous tenants had died of a gruesome infectious disease.

In the spring of 1621, the Pilgrims finally met their surviving neighbors. If the colonists thought God was good for guiding them to pretilled land and a sweet brook, they were even more thankful when the first Native American strolled into their midst, smiling and saying in English, “Welcome!” According to Pilgrim-era writings, he told them straight away that the previous villagers “died of an extraordinary plague.” A few days later, Tisquantum arrived. Called Squanto by Pilgrims, he was born in Patuxet, abducted by Englishman Thomas Hunt in 1614, and missed out on the epidemic that killed his entire village. During his years in captivity, he’d learned English, and he was now attached to a nearby branch of the Wampanoag.

The Pilgrim leader William Bradford was already aware of the death toll from “Indean fever.” His scouts had ventured inland and noted “sculs and bones were found in many places lying still above ground, where their houses and dwellings had been; a very sad spectackle to behould.” It’s estimated as many as nine out of 10 coastal Indians were killed in the epidemic between 1616 and 1619.

What killed so many people so quickly? The symptoms were a yellowing of the skin, pain and cramping, and profuse bleeding, especially from the nose. A recent analysis concludes the culprit was a disease called leptospirosis, caused by leptospira bacteria. Spread by rat urine.

Leptospirosis is what’s known as a zoonotic disease. The bacterium lives in animal hosts and is transmitted between animals and to people via urine in fresh water. Its favorite host is the black rat, Rattus rattus (the rat so nice they named it twice), a nonnative species that was inadvertently transported to North America on explorers’ ships. For unknown reasons, it’s the only animal whose kidney can sustain continuous leptospira infections. The tubules of an infected rat’s kidney are lousy with bacteria and excrete hundreds of thousands in every drop of urine (10 million leptospira per milliliter, according to one study). Meanwhile, just 10 bacteria, injected into the abdomen, will send a laboratory hamster to violently hemorrhagic death within days. Leptospira is in a family of spiral-shaped bacteria called spirochetes, along with the bugs that cause syphilis and Lyme disease.

Leptospira is shaped like a thin corkscrew, but at corkscrew width it’d be more than 4 feet long. Under the microscope, the bacteria look like delicate ramen or living handlebar mustaches. Holding one end rigid like a rudder, they spin the other like a motor to move. They are single cells with no brain, per se, but they quest about sniffing out food, such as blood. The more virulent the strain, the more the bacteria are drawn to blood cells. They metabolize iron to survive and secrete an enzyme enabling them to smash open a red blood cell and slurp up the sweet, sweet iron within.

Leptospira swim faster in higher viscosity; they are built to tunnel through organs and cell membranes in order to evade the immune system. With their unique shape and motility, they can pass straight through a cell, like a corkscrew through a candied sweet potato. If immune cells are able to catch and smash one, that is when the trouble starts. A robust immune response can actually be detrimental because the more leptospira get blown to smithereens, the more bacteria bits are floating about to activate the immune system. This may be one reason why leptospirosis is most fatal to otherwise healthy men.

Like Pilgrims in the New World, leptospira must first penetrate the host. Invisible in water, the bacterium enters the eyes, the nose, or scrapes in the skin. Then it disseminates, looking to colonize the kidney. Humans are a dead end; our kidneys aren’t the right environment for them to set up and multiply. Like colonies at Jamestown, Roanoke, and Popham, the bacteria get ambushed or die of starvation, and the infection is usually cleared within a month if it isn’t fatal.

According to the hypothesis, infected ship rats landed in the New World and excreted leptospira, infecting raccoons, mink, and muskrats whose urine further contaminated any standing fresh water. It is unclear why this particular infectious disease should afflict Native Americans and not subsequent European colonists. Prior exposure does not necessarily result in immunity because there are a number of different infectious strains.

A clue might lie in the way these different cultures interacted with natural environments. The Wampanoag gathered sharp-edged clams, skinned pelts from beaver and deer, canoed through streams, and were much fonder of bathing than were Europeans of that era. And they likely spent time hand-picking wild cranberries from bogs on Cape Cod. Wampanoag have long had seasonal feasts of thanksgiving, one of which celebrates the cranberry harvest. There is some evidence that cranberries were also used medicinally—raw, ground into a poultice, and applied to open wounds. Although modern research suggests that cranberries can be a potent antimicrobial, that might not have been enough to slay the spirochete. The more leptospira that initially invade the bloodstream (possibly via direct contact with berries), the more likely the disease is to be fatal.

Leptospirosis’ nonspecific presentation (fever, aches, “flu-like symptoms”) makes it challenging to diagnose. Outbreaks are possible any time water treatment is compromised or there is increased exposure to rat urine—such as during flooding. It made the short list of diseases we might expect if subway rats surfaced post-Sandy. Thankfully, they did not. Although there are fewer than five reported cases of leptospirosis annually in New York City, last year a 49-year-old construction worker came into Staten Island University Hospital with full-blown leptospirosis. His doctor recalls the man was in very bad shape: his calves cramping, his fever soaring, his eyes red with blood, and his organs rapidly failing. The patient survived and later recollected that he had come in contact with rat urine on a job site.

Travelers can bring leptospirosis home from tropical countries, and it may become more common as climate change brings warmer weather and more dramatic flooding. Leptospirosis cuts down healthy men in urban slums of Brazil and Thailand, where open sewers attract rats and flooding brings contaminated water up to people’s doorsteps. It affects affluent nature-lovers as well. In September, a group of Belgian boy scouts came down with it after messing with a muskrat on the banks of the Semois River. When not infecting rats or humans, the disease cycles through wild and domestic animals, causing spontaneous abortion in pigs and horses and recently killing off sea lions in Oregon.

While leptospirosis is referred to as a “neglected tropical disease,” Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine, says it is really a disease of poverty. It is neglected because the people who catch it are marginalized and ignored. In the United States, notable cases have occurred in the inner city in Detroit and Baltimore. Tokyo researchers recently captured rats and compared the leptospira strains they carried to those infecting 16 city residents over five years. Seventeen percent of the rats had lepto, and the people who had lepto worked or lived in conditions that exposed them to rat urine.

Symptoms of leptospirosis have changed over time. While nosebleed was originally a hallmark, extremely bloodshot eyes is now considered the disease’s signature. Severe hemorrhaging in the lungs is also seen more frequently, such as in a 1995 outbreak in Nicaragua in which 15 patients died after coughing up copious amounts of blood. In rare cases, leptospira can enter the brain and cause aseptic meningitis. The bacteria are too busy burrowing into tissue to be present in cerebrospinal fluid.

Squanto learned English in London in the early 1600s yet, remarkably, did not contract any deadly disease there. He didn’t become ill until a few years after he returned to his devastated, Pilgrim-occupied homeland on a Pilgrim-led trip to trade with a tribe on Cape Cod. He died “bleeding much at the nose,” according to Bradford.

So, did lepto kill Squanto? Did he wade through the wrong slimy puddle on Cape Cod and die as his village had a few years before?

There are other theories about this epidemic, and experts in modern leptospirosis think the death rate at Patuxet is a tad too high to jibe with the disease they see. It would have to have been an extremely virulent strain, or an extremely high exposure rate, to add up to 90 percent fatality. Although free-living, nonpathogenic bacteria from the same family as leptospira survive in Cape Cod and likely can outlast a New England winter, it’s not the ideal condition for the deadly forms of lepto. And while there were certainly black rats at Jamestown and other pre-Colonial sites, it is unknown if there were any in Patuxet.

Native Americans told the Pilgrims there was an epidemic, but some prominent archaeologists and historians aren’t sure such a mass death occurred. With the soil acidity of the Cape Cod region, skeletal remains dissolve quickly, so finding the truth may be impossible. Lepto leaves no marks on bone. Dental pulp would be needed to get lepto DNA, requiring breaking open teeth from ancestral remains. Paleomicrobiologists are at the ready, but there are no samples.

While experts have an academic discussion, many modern Wampanoag have no doubt that the 1616-1619 epidemic was real. Robert Charlebois, a Canadian Abenaki Indian who works at Plimoth Plantation 2 miles down the road from Plymouth Rock, is well aware of the leptospirosis hypothesis. He is certain it is true. Moccasins are water permeable, he says, and being in touch with the land and nature exposed the Wampanoag in ways that Pilgrims, with their thick-soled boots, would not have encountered.

There are 5.1 million American Indians today, according to the U.S. Census Bureau. They have almost double the poverty rate of the rest of the nation; sewers and solid waste removal are still lacking on some American Indian reservations, and thousands of families do not have safe drinking water. Nobody knows the rate of leptospirosis on reservations today.

Or the rate in the United States overall, for that matter. The illness has not been “reportable” since 1994, meaning doctors aren’t required to notify the Centers for Disease Control and Prevention when they have a lepto-positive patient. In 1994, there were 38 confirmed cases nationwide, and in the preceding years it afflicted only 0.02 percent of the population, so it was deleted from the list of notifiable diseases. Some states continue to require reporting to their health departments; there were 74 cases in Michigan in 2011, for example.

However, experts believe low rates are due to underdiagnosis. With a mild case, a patient might not go to the doctor. Scientists are developing better tests, but those currently available are clunky and take weeks. Unless patients are very sick and have the telltale sign of bloodshot eyes, they might not be tested or get lifesaving treatment in time. The CDC is one of many public health agencies that suspect lepto rates will be going up in the future. At the request of the Council of State and Territorial Epidemiologists (PDF), in 2013 the CDC will again require doctors to report every case they see.

Last Saturday, in the Wampanoag tent at the Plymouth Thanksgiving festivities, some tribe members were dressed in historically accurate clothing. They weren’t “in costume” in the same way as the Pilgrim recreationists who were playing at their roles. The sweet brook still flowed nearby; the smell of wood fire and sound of muskets filled the air.

Outside the tent, Darius Coombs, in traditional dress, greeted festivalgoers. With a smile, a man asked him, “So what are you supposed to be?” In some ways the Wampanoag are recreating themselves from records (including reclaiming their language) and struggling to preserve and maintain their culture, but they’re also growing, changing, and ready to share. “I am Wampanoag,” Darius asserted. Awareness of the epidemic that killed his ancestors is important to him.