June 18, 2007

On Human Genomes and “Rewriting the Textbooks”

I hate when the media proclaims, “They’ll have to rewrite the textbooks.” It’s easy for them to say. They don’t do it.

I do.

That phrase will likely be bandied about this week with the multiple publications from the ENCODE project. That stands for the Encyclopedia of DNA Elements Project, a mega-effort from 35 research groups around the globe to dissect a representative 1 percent of the human genome (The ENCODE Project Consortium, Genome Research).

True, the media/public may have gotten their fill of geno-news of late, what with the grandstanding PR event of James Watson having his 3 billion DNA bases exposed, so to speak, and the turning on of stemness genes in mice, apparently circumventing the embryonic route. And if Paris Hilton tries a jailbreak, all news of import will vanish.

I’m the author of a college-level human genetics textbook, currently working on the 8th edition – I now measure my lifespan in editions (Lewis, forever). It’s not written by a nameless committee with a lone EdD slapped on the cover, nor a computer, nor am I just an assistant to a “real” scientist. Forgive the defensiveness, but I get these comments often. People write textbooks, and people who write science textbooks are generally scientists.

Whether or not to make a radical change in a textbook is a judgment call based on knowledge of the field, and of science in general. Basically, a finding has to be repeated sufficiently to stand the test of time. It doesn’t necessarily have to make sense or go with the prevailing wisdom. This is the case with the ENCODE findings. Among a deluge of data, what has emerged is that much of the DNA sequence that evolution has apparently conserved in diverse genomes (I’m not talking an Italian compared to Nigerian, but, say, a wombat to an ape) needn’t have the same or even any apparent function. Yet disturbingly many DNA sequences that are diverse and unique and therefore not thought to be constrained by evolution can nonetheless have important functions. This will turn the idea that “if it’s important, evolution would have kept it much the same across species” on its head.

An equally important finding makes me want to get up and cheer. “Junk” DNA isn’t junk after all. I can hear a collective “duh” from the genetics community. The unfortunate term “junk DNA”, while possibly first uttered by geneticists back in the 1970s in the wake of the discovery of introns (Gilbert, 1977), quickly became a media term that has gained momentum, even as geneticists have indeed discovered what much of the DNA sequence that doesn’t encode protein actually does. (I distanced my book from the term early on: “Said one speaker at a genomics conference, ‘Anyone who still thinks that introns have no function, please volunteer to have them removed, so we can see what they do.’ He had no takers.”) I’ve never, ever heard a scientist call any DNA junk. Only those with mutations in the arrogance gene would term something garbage just because we can’t figure out what the heck it does.

Of course I’ve made mistakes too. Paramount among them was the mention of the adeptness of a certain Korean researcher in manipulating human embryos to obtain stem cells. I yanked that out fast when his adeptness at faking data was revealed. And I’d already mentioned ENCODE in the edition that is now gestating. But I’m spending this glorious Father’s Day, well, rewriting the textbook to knit these new results into the appropriate chapters. I suspect further changes lie ahead. ENCODE chose it’s representative 1% from 44 well-studied regions of the genome. But imagine describing a large lecture class from a specifically-chosen 1% of the students. Or the planet. Or anything. (Note to media: “well-studied”. Scientific advances are not overnight breakthroughs.)

The media will undoubtedly jump on the unexpectedness of the results too, playing it as a fault, of scientists flip-flopping, when in actuality, changing hypotheses to fit new data is the very essence of science. There is, after all, no such thing as “scientific proof”, despite the pervasiveness of the term. There’s only scientific evidence, and the more the better -- even if it turns long-accepted ideas upside down – like now.

I can’t wait for the next chapter.

-Contributing editor Ricki Lewis

The ENCODE Project Consortium, 2007. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447:799-816

Genome Research, 17(6), the entire June 2007 issue. http://www.genome.org/current.shtml

Gilbert, A. 1978. Why genes in pieces? Nature 271:501.

Lewis, R. Human Genetics: Concepts and Applications, McGraw-Hill Higher Education, 2007.

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