It could be on the casual trip to the local pharmacy superstore for some discounted items, or during a visit of a more serious nature while you wait in line for your prescription, when you spy the “herbal medicine” rack. While many of the items have a place in folklore—and much less than a scientific basis for their promotion—one item has gained some real traction for its medicinal qualities as an antibiotic, antiviral, antidepressant, and even recently as an anti-cancer agent: St. John’s wort. What is unique about this plant is that it is known to produce a specific molecule—hypericin, along with a partner molecule, hyperforin (and many others)—that is one of the principle active secondary metabolites of this plant, otherwise known as Hypericum perforatum. Hypericin is a naphthodianthrone that contains many ringed structures at its core, and this conglomeration of chromophores is what causes an increased sensitivity to light in animals that graze on a significant amount of St. John’s wort, since the molecule targets eye/ocular tissues preferentially. What is intriguing about hypericin production in St. John’s wort is that it accumulates only in focused dark spots called “dark glands” on leaves and other tissues, and to this point it had been a mystery about the genetic mechanisms that underlie the focused production of these ultrastructures. But as featured in a nicely written overview, some fundamental plant genetics recently paved the way to identify differences between tissues that do or do not produce hypericin. Researchers discovered a polymorphism—variations in hypericin production—that is specific to the placental tissue in the St. John’s Wort flower (the pistil, specifically). They identified some plants that had dark glands in their pistils (called the “G++ PT” phenotype; see the left photo above) and some that did not (called the “G- PT” phenotype; see the right photo above). This variation observed between different St. John’s Wort plants provided a molecular foothold for scientists to compare the mRNAs (transcriptome) and metabolites (metabolome) between the placental tissues with and without dark glands, and ultimately revealed that two transcription factors—Agamous-like 6 (AGL6) and MYB38—are strongly implicated in dark gland production. While this concept might seem as esoteric as the complexity of the herbal medicine aisle itself, uncovering the molecular developmental basis of dark gland generation in St. John’s wort is a major step towards unraveling the underlying biochemistry that occurs in these tiny hypericin factories. And once achieved, it will be this humble little weed that we will have to thank for providing a basis of what could be entire suites of targeted human therapeutics.