The Cancer Chronicles

In chapter 9 of The Cancer Chronicles (or whatever it is called when it appears next spring), I write about how very complex cell biology has become since the revelations of Watson and Crick. I first touched on this (and how it affects our understanding of cancer) in a long piece last year for the Times, which was tied to the annual meeting of the American Association for Cancer Research. “Most DNA,” I wrote, “was long considered junk — a netherworld of detritus that had no important role in cancer or anything else. . . . These days ‘junk’ DNA is referred to more respectfully as ‘noncoding’ DNA, and researchers are finding clues that ‘pseudogenes’ lurking within this dark region may play a role in cancer.” Over the years, while I was attending to other things, Francis Crick’s “standard dogma” (DNA –> RNA –> protein) was becoming laden with complications. Now there were not just messenger RNAs and transfer RNAs — the stuff we learned about in basic biology — but also micro RNAs. And that was just the beginning:

Fueled by the free espresso offered by pharmaceutical companies hawking their wares, scientists at the Orlando meeting moved from session to session and browsed corridors of posters, looking for what might have recently been discovered about other exotic players: lincRNA (for large intervening noncoding), siRNA (small interfering), snoRNA (small nucleolar) and piRNA (Piwi-interacting (short for “P-element induced wimpy testis” (a peculiar term that threatens to pull this sentence into a regress of nested parenthetical explanations))).

The instructions for producing these newly recognized agents are coded in what was once regarded as junk DNA. Some of them appear to be important cogs in the cellular machinery, others may just be flotsam and jetsam — molecular noise.

Long before these discoveries it was recognized that other regions of DNA that don’t directly code for proteins serve important functions — switching genes on and off, providing the layers of complexity through which the genetic program gives rise to life. The importance of these molecular switches began to emerge in the early 1960s with the celebrated work of Monod and Jacob on the lac operon. But for all of that, most of the genome is still considered to be a molecular appendix — damaged genes that no longer serve a purpose or snippets of code smuggled in by retroviruses. Most of the junk really is junk. If every bit of an organisms’s DNA served an important use then why would the genome of an onion be five times bigger than that of a person?

I was taken aback last week when the big news broke about the ENCODE project (“Encyclopedia of DNA Elements”). At least 80 percent of the genome, it was reported, was performing an important function — and the figure might soon approach 100 percent. Junk DNA was a myth. Here is a typical passage from a mainstream news report (there are dozens to choose from):

What has been called junk DNA is actually teeming with an intricate web of molecular switches that play crucial roles in regulating genes. . . . These switches rev genes up. Calm them down. They orchestrate how the whole complex system works. Scientists have already started to figure out which switches control which genes. And that’s uncovered even more surprises. Genes can get instructions from up to dozens of switches. And some of the switches are nowhere near the genes they control.

But none of that was new. What was I missing? As I prepared to embark on serious revisions to my manuscript, I began searching the web, quickly encountering the backlash from scientists who considered the claims to be hype. It wasn’t so much the journalists who were to blame (though they should have been more skeptical) but the ENCODE scientists. John Horgan and I discussed this a few days ago on Science Saturday. But the best explanation of the controversy comes from Jon Timmer, the science editor at arstechnica. In presenting what was otherwise some very impressive research, the scientists chose to loosen the definition of “functional” almost to the point of being meaningless.

In the aftermath of the Jonah Lehrer scandal, there have been calls for science stories to be vetted in advance by scientists. The revelations about ENCODE suggest that this would make as much sense as having politicians review political coverage before publication.