By Carolyn Johnson
Here’s how we think we discover powerful new medicines: Scientists dig deep into biology and zero in on a molecular Achilles’ heel that could disable a devastating disease, be it cancer or an infection. They concoct experimental drugs that hit the target. Then they conduct trials to find one that is safe and effective in people.
Here’s how we actually develop a surprising number of treatments: good old-fashioned observation, trial and error, and luck. Detailed scientific understanding of how a drug works often comes, ironically enough, near the end of the process.
“It’s sort of a fairy tale,” said Jon Clardy, a professor of biological chemistry and molecular pharmacology at Harvard Medical School, of the idea that drugs are born mostly from reason and not serendipity. “If you think of it as an aspirational goal, it’s fine.”
Understanding how drugs are developed matters crucially because the government and companies pour billions of dollars into the endeavor. But the dirty secret of modern medicine may be that the most logically alluring method for solving diseases – steadily accruing knowledge about human biology that we can act on – hasn’t always been the best way to hit home runs. An older method of just slinging possible drugs at cells, animals — or in some cases, people — and watching what works has often been the more productive starting point, with understanding to come later.
“We’re not as smart as we look,” said Michael Jordan, a physician in the immunobiology division at Cincinnati Children’s Hospital Medical Center.
Knowing why a drug works has historically trailed the treatment, sometimes by decades. Some of the most recognizable drugs — acetaminophen for pain relief, penicillin for infections, and lithium for bipolar disorder, continue to be scientific mysteries today.
