Sea lamprey reached the upper Great Lakes in the twentieth century and contributed heavily to the collapse of lake trout and other fisheries, since a single adult can kill a substantial mass of fish during its parasitic phase. Adults could not be practically targeted, but the larvae could: ammocoetes spend several years buried in the fine sediment of specific tributaries, a fixed, findable address.
A large screening programme through the 1950s tested thousands of compounds for something that would kill larval lamprey in those streams without wiping out everything else. The result was TFM, 3-trifluoromethyl-4-nitrophenol. Its selectivity turns on metabolism: most fish detoxify it faster than lamprey do, so a dose lethal to larvae is survivable for many co-occurring species.
The programme has held Great Lakes lamprey abundance far below its peak for decades, but it is a permanent treadmill rather than a cure, requiring repeated stream treatments in perpetuity, supported by barriers and trapping. Its margin of safety varies with water chemistry and with the non-target species present, and effects on some sensitive native fish and amphibians remain a live concern.