The Least of Us: True Tales of America and Hope in the Time of Fentanyl and Meth

by Sam Quinones

Studying the molecular structure of morphine and other opiates, Janssen learned that they had in common a six-sided section of their molecules known as the piperidine ring. This hexagon had a nitrogen atom attached. The combination, he surmised, must be essential to the molecule’s ability to attach to the receptor. So he did what medicinal chemists do: he manipulated the structure over and over, adding atoms to it, deleting portions, in an arduous trial and error. Finally, in 1959, he came up with a molecule that, tests showed, made its way through the brain’s protective barrier. His invention also fit on the receptor far more snugly and efficiently than did the morphine molecule. “A substantial portion of morphine doesn’t make it past that barrier in the brain,” said Carlos Valdez, a chemist at Lawrence Livermore National Laboratory in California, with whom I spoke as I tried to understand what Janssen had invented. “Heroin crosses the barrier much more easily, but then it partially converts into morphine once inside the brain tissue, slowing its absorption. The new molecule that Janssen invented crossed the blood-brain barrier very effectively, and most importantly, it wasn’t converted into anything else.” In other words, the new molecule did the same job as morphine, only quicker and more efficiently. Or, put another way, Janssen’s lab found that fifty to a hundred times less of this new drug was required to achieve the same pain relief as morphine. All this made the dr...