Florida has spent years trying to address its Burmese python problem, and the results have been limited. Since 2017, state agencies, contractors, and licensed hunters have removed more than 10,000 pythons from the wild. The state’s annual Python Challenge sends hundreds of people into the marshes, though each event typically yields between one and 200 snakes. Professional trappers work along levees year-round, and volunteer hunters patrol canal banks at night with headlamps, catching snakes by hand.

The effort requires roughly 12 hours of combined work per snake captured. No one knows exactly how many pythons remain in the Everglades. Estimates range from tens of thousands to figures that wildlife officials avoid stating publicly. All population models agree on one point: the snakes reproduce faster than removal programs can keep up with them.

A single female python can lay dozens of eggs, sometimes up to a hundred. Adult pythons are difficult to spot in the sawgrass. They remain motionless for days while digesting meals and can disappear into the water completely. Researchers have found adult pythons that consumed full-sized deer, including hooves and antlers. In parts of the Everglades, raccoon and opossum populations have dropped by about 90 percent. Rabbits and marsh birds have declined under similar pressure.

A study using radio-tracked marsh rabbits confirmed that pythons were responsible for most of the deaths in the study area. The snakes were not merely present while small mammals disappeared; they were the cause.

Before the current situation in Florida, wildlife managers dealt with a similar invasion on the island of Guam. A brown tree snake arrived there in military cargo after World War II. The snake is about a meter long, mildly venomous, and harmless to humans. In its native range, it attracts little attention. On Guam, however, the local bird species had evolved for thousands of years without ground predators. They nested in low places and laid eggs in open grass. They had no instinct to flee from snakes.

Biologist Julie Savidge arrived on Guam to investigate why the birds were vanishing. She ruled out other explanations one by one. Her findings, published in the late 1980s, confirmed that the brown tree snake was responsible. By then, the snake population had grown dense in the island’s forests. Dozens of native bird species had stopped breeding, and most had declined by more than 90 percent. The loss of birds affected the island beyond the birds themselves. Spider populations increased without the birds that fed on them. Trees that depended on birds for seed dispersal stopped regenerating. The snakes also climbed utility poles and caused frequent power outages, disrupting the island’s infrastructure.

Savidge’s work prompted a search for a way to control the snakes before they spread to other Pacific islands. The solution that emerged was acetaminophen, the active ingredient in Tylenol. The drug is highly toxic to brown tree snakes. A dose of about 80 milligrams, roughly a quarter of a children’s dose, kills an adult snake. The snake’s liver cannot process the compound.

Wildlife researchers with the U.S. Department of Agriculture developed a delivery method. They placed the acetaminophen inside dead mice, attached the mice to small cardboard fins with paper tape designed to catch on branches, and dropped them from helicopters flying at low altitude. The mice hung in the upper canopy where tree snakes hunt, rather than falling to the ground. Federal regulators approved acetaminophen for use against brown tree snakes on Guam in 2003. Teams conducted multiple aerial drops, and treated areas showed reduced snake numbers.

The method worked partly because brown tree snakes will eat carrion, and the small dose posed little risk to larger animals that might consume the bait. In the rugged, mountainous terrain where ground traps were impractical, the aerial drops solved a distribution problem.

Research later suggested that Burmese pythons share the same metabolic vulnerability to acetaminophen. That raised an obvious question: could the same approach work in the Florida Everglades?

The answer is complicated by several factors. The first is size. Adult Burmese pythons, which can reach 16 feet and weigh over 160 pounds, do not hunt mice. The bait was designed for juvenile pythons, which are closer in size to adult brown tree snakes and do climb and hunt small rodents. Researchers who tracked juvenile pythons with radio transmitters found that they move upward into the branches, which is where the baited mice end up.

The strategy would not need to kill adult females directly. It would aim to prevent juveniles from reaching reproductive age. Each adult python that survives and reproduces continues the cycle, but removing juveniles before they mature would reduce future generations. The scale required, however, would be enormous. Millions of baits, deployed several times per year, for years.

That scale is where the plan encounters serious problems.

The Everglades is not Guam. By the time aerial drops began in Guam, the island had already lost most of its native birds. The ecosystem was severely degraded, and little remained to be accidentally harmed. The Everglades supports hundreds of species of birds, dozens of reptiles and mammals, and a large fish population. It is one of the most complex wetland ecosystems in North America.

Acetaminophen does not distinguish between target and non-target animals. Raccoons and opossums, whose populations have already dropped sharply due to python predation, eat carrion and would readily consume a dead mouse. The bait could deliver a second blow to species already under pressure.

Secondary poisoning is another concern. A small mammal that survives eating a poisoned mouse may retain the compound in its body. A predator that eats that mammal, such as an owl or hawk, could then be affected. Owl chicks are especially vulnerable. Vultures, hawks, and eagles might also take dead mice from low brush, especially during food shortages.

The Florida panther presents the most significant obstacle. Around 120 to 200 adult panthers remain in the wild, confined to the southwestern corner of Florida. Acetaminophen is highly toxic to cats. Their livers lack the enzyme needed to break it down safely. Even small doses can damage red blood cells and liver function. Panthers are apex predators that primarily hunt deer and wild hogs, but they are opportunistic and will scavenge. A dead mouse caught in low brush is the kind of easy meal an apex predator will take.

The current panther population is the result of decades of recovery work. By the mid-1990s, the population had fallen to a few dozen animals, with serious genetic problems caused by inbreeding, including heart defects and reproductive failure. The recovery program that followed brought the population back from the edge of extinction. Losing even two or three panthers to a baiting campaign would pose a serious risk to that recovery. Panther and python ranges overlap across most of South Florida.

Another native animal caught in the middle is the eastern indigo snake, the longest native snake in North America. It is one of the few animals in the region that actively hunts and eats juvenile Burmese pythons. Its population has declined for decades due to habitat loss, and state and federal programs are currently trying to breed and release it back into the wild. The eastern indigo snake also eats mice, and its sensitivity to acetaminophen has not been tested. A baiting program could inadvertently harm the one native predator that is already working against the pythons.

Aerial distribution is imprecise. Even under the best conditions, some baits land in water. Burmese pythons are semi-aquatic, so baits must be concentrated near water in the first place. Mice that land in water can be eaten by fish, and the compound can enter aquatic food chains in ways that are difficult to track. Rattlesnakes, cottonmouths, and native water snakes would also encounter the bait.

Public reaction is another factor. In the early 2020s, a biotechnology company received approval to release genetically modified mosquitoes in the Florida Keys. The science was sound: the modified males carried a gene that suppressed mosquito populations without chemical spraying, and similar approaches had worked elsewhere. Public opposition was immediate. Residents attended meetings with signs calling the mosquitoes “Frankenstein bugs,” and lawsuits followed. That was for mosquitoes, an insect few people defend. The reaction to dropping millions of dead, acetaminophen-laced mice into the Everglades, where they could be eaten by raccoons, panthers, eagles, indigo snakes, and family pets, would likely be far more intense.

In the meantime, Florida continues to rely on hunting and trapping. Trained dogs can detect pythons by scent. Another method uses captured female pythons fitted with radio transmitters. During mating season, males approach the female, and the transmitter leads hunters to clusters of snakes they would not have otherwise found.

None of these tools are ready to be deployed at the scale the crisis requires. None are as simple as dropping millions of mice and watching the population collapse. That simplicity is why the idea remains attractive, even with the known risks.

The Everglades, by its very nature, is the wrong place for such a weapon. The complexity of the food web, the number of species that would be exposed, and the presence of animals already at the edge of survival make broad chemical deployment impractical. The traits that make the Everglades one of the most biologically rich wetlands in North America are the same traits that make a wide-scale poison bait campaign too dangerous.

A female python can still be found somewhere in the sawgrass, coiled around a clutch of eggs, waiting. She is not aware of the decades of effort and hundreds of millions of dollars spent trying to find a way to reach her. So far, none of it has succeeded in changing the overall trajectory. The bold experiment that seemed promising on paper has become the one tool Florida appears unable to use.