“The more we learn, the less we understand”

“The more we learn, the less we understand,” says geneticist Steve Jones about genes and genetics, in this Lost Lecture:

David Dobbs pursues this theme in the essay “Weighing The Promises Of Big Genomics“, in Buzzfeed:

…“Many genes of small effect” became a sort of tepid curse. I myself prefer the stronger, more memorable phrase “Many Assorted Genes of Tiny Significance,” or MAGOTS — a mass of barely significant genes explaining little.

MAGOTS infest most GWA studies for a simple, brutal reason: If a gene variant reliably plays a large role in causing disease, both the variant and the disease it causes tend to be rare, because its carriers tend to die without leaving offspring. This is why the genetic contributions for common diseases and conditions usually come from MAGOTS — the effects of which, it bears repeating, are usually maddeningly obscure and unpredictable. This applies even to diseases and traits that run in families. Take height: Hundreds of genes of small effect, few clues to how they contribute, and no real target to tweak if, say, you want to make someone tall. The best way to engineer a tall person? Tell two tall people to tango.

Similarly, deep digs at cancer, schizophrenia, heart disease, hypertension, diabetes, intelligence, bipolar disorder, and height have found mostly MAGOTS….

So let me offer a hype filter. This one comes courtesy of the oceanographer Henry Bryant Bigelow, who helped found Woods Hole Oceanographic Institute. A century ago, Bigelow opened a letter his brother had written him from Cuba. His brother reported that while weathering a hurricane there, he had seen, flying by, what he was almost sure was a donkey.

With three words, Bigelow gently told his brother he didn’t quite believe him — and stated a maxim for maintaining the ever-curious but ever-skeptical stance that marks the good scientist.

“Interesting if true,” he wrote.