The headline seemed too strange to be true, the animal equivalent of the 82nd Airborne parachuting behind enemy lines in Normandy:

"Two thousand mice dropped on Guam by parachute — to kill snakes."

Back in 2013, in an attempt to quell the out-of-control population of invasive brown tree snakes which was devastating Guam's local birds and mucking with electrical infrastructure, the United States Department of Agriculture's (USDA) Wildlife Service bombarded targeted areas owned by the U.S. Government with dead mice, each armed with 80 milligrams of acetaminophen, the active ingredient in Tylenol. The idea was that the snakes would eat the mice and die.

Photograph of a brown tree snake on Guam.

Unlike other attempts to combat invasive species, which regularly backfire, this one seemed to work pretty well. The acetaminophen"mice bombs" didn't harm other animals and killed the invasive snakes within 24 hours of consumption. More air drops are planned.

So why does 80 milligrams of acetaminophen – just a quarter of the amount in a regular Tylenol pill – kill a snake while it would take 500 times more to kill a similarly-sized mammal? That question was the subject of a recent study published to the journal Scientific Reports.

As evidenced in prior research, as little as 40 milligrams of acetaminophen can be acutely toxic to any reptile, not just snakes. USDA wildlife scientists Tom Mathies and Richard E. Mauldin were curious why. A previous study hypothesized that reptiles lack the enzymes needed to metabolize acetaminophen. Over just a few days, elevated levels of acetaminophen can kill liver cells. However, in only a matter of hours, they can convert an organism's oxygen-carrying hemoglobin molecules to methemoglobin, which cannot transport oxygen. The body's cells are thus starved of oxygen, resulting in death.

To test to see if this is indeed what occurs in snakes, Mathies and Mauldin gave a lethal dose of acetaminophen to 71 wild-caught brown tree snakes on Guam and compared their methemoglobin levels over time to 68 control snakes given a placebo.

Indeed, in just a few hours, the snakes given acetaminophen had methemoglobin levels that were drastically higher than those in control snakes, resulting in far lower levels of blood oxygen. These numerical changes were outwardly visible: control snakes' blood remained bright red, while blood from snakes given acetaminophen "ranged from dark red near the beginning of the test period to reddish brown near the end of the test period."

Hemoglobin levels of (A) oxyhemoglobin (O2Hb), (B) deoxyhemoglobin (RHb), (C) carboxyhemoglobin (COHb), and (D) methemoglobin(MetHb) in blood of brown trees nakes gavaged with an 80 mg tablet of acetaminophen (Treated group) or an 80 mg tablet of inert matrix (Control group) terminally sampled at 2.4 h intervals over a previously determined median time to death of 14.2 h.

These findings were in line with the researchers' hypothesis.

"The proximate cause of death in brown tree snakes that ingested the standard 80 mg dose of acetaminophen used operationally in the field for lethal control was acute methemoglobinemia and probable respiratory failure due to severe hypoxia," the authors concluded.

This death appears to be relatively humane. Most of the snakes drifted into unconsciousness and did not show signs of distress, pain, or discomfort besides lethargy and open-mouthed gaping or yawning.

"All snakes in this study assumed a typical coiled resting position following dosing and most remained immobile until sampled. The few snakes that began moving about their cages did so late in the test period, were lethargic, and made no more than two circuits of their cage before expiring," the researchers reported.

Armed with these findings, it's likely that the USDA's use of acetaminophen against invasive brown tree snakes in Guam will continue unabated.

Source: Mathies, T., Mauldin, R.E. "Lethal methemoglobinemia in the invasive brown treesnake after acetaminophen ingestion." Sci Rep 10, 845 (2020). https://doi.org/10.1038/s41598-019-56216-1