1970

Glyphosate

John E. Franz (b. 1921)

Glyphosate (known to many under its original trade name, Roundup) is surely the most widely used weed killer in the world. First synthesized in the 1950s but rediscovered as an herbicide by organic chemist John E. Franz in 1970, it’s an excellent example of the specialty that chemists know as “ag-chem.” Glyphosate is a small molecule and a powerful inhibitor of an enzyme with a name that only a chemist could love: 5-enolpyruvylshikimate-3-phosphate synthase. In living cells, this enzyme catalyzes a key step in the synthesis of three amino acids, so shutting it down is a tough obstacle for cells to overcome. The effect is strongest in growing plants, and because weeds are vigorous and spreading by definition, they are ideal targets. In recent years, some crops have been genetically modified to tolerate glyphosate, allowing farmers to use the chemical to kill other plants that show up in the fields without damaging them.

So why isn’t glyphosate poisonous to everything it touches? The amino acids whose production it shuts down are synthesized only in microorganisms and plants—not in animals, including humans (we have to get them from our diet). Since we and all other animals lack this enzyme completely, targeting it should, in theory, provide a plant-specific poison. There are other things to consider, though. First is selectivity: an inhibitor that works well against its target may hit other closely related enzymes at the same time. Fortunately, glyphosate’s target has no close relatives in higher organisms, but it still can hit related enzymes in bacteria, and considerable work has gone into finding out what that might lead to. As far as humans are concerned, some studies indicate that the surfactants and detergents in the commercial product might be more troublesome than the active ingredient itself.

But as with every other enzyme inhibitor, there’s always the chance of a mutated form of its target enzyme showing up—one that’s resistant to the poison. This happens again and again—viruses, bacteria, insects, plants, and cancer cells alike keep finding ways around our attempts to kill them off.

Spraying a weed with glyphosate. The chemical doesn’t kill just weeds; it will damage almost any plant that comes into contact with it, since weeds and plants all tend to use the same biochemical pathway for amino acid synthesis.