Scientists and Philosophers Find That ‘Gene’ Has a Multitude of Meanings
I owe an apology to my genes. For years I offhandedly blamed them for certain personal defects conventionally associated with one’s hereditary starter pack — my Graves’ autoimmune disease, for example, or my hair, which looks like the fibers left behind on the rim of an aspirin bottle after the cotton ball has been removed, only wispier.
David Corcoran, a science editor, explores some of the topics addressed in this week’s Science Times.
Now it turns out that genes, per se, are simply too feeble to accept responsibility for much of anything. By the traditional definition, genes are those lineups of DNA letters that serve as instructions for piecing together the body’s proteins, and, I’m sorry, but the closer we look, the less instructive they seem, less a “blueprint for life” than one of those disappointing two-page Basic Setup booklets that comes with your computer, tells you where to plug it in and then directs you to a Web site for more information.
Scientists have learned that the canonical “genes” account for an embarrassingly tiny part of the human genome: maybe 1 percent of the three billion paired subunits of DNA that are stuffed into nearly every cell of the body qualify as indisputable protein codes. Scientists are also learning that many of the gene-free regions of our DNA are far more loquacious than previously believed, far more willing to express themselves in ways that have nothing to do with protein manufacture.
In fact, I can’t even make the easy linguistic transition from blaming my genes to blaming my whole DNA, because it’s not just about DNA anymore. It’s also about DNA’s chemical cousin RNA, doing complicated things it wasn’t supposed to do. Not long ago, RNA was seen as a bureaucrat, the middle molecule between a gene and a protein, as exemplified by the tidy aphorism, “DNA makes RNA makes protein.” Now we find cases of short clips of RNA acting like DNA, transmitting genetic secrets to the next generation directly, without bothering to ask permission. We find cases of RNA acting like a protein, catalyzing chemical reactions, pushing other molecules around or tearing them down. RNA is like the vice presidency: it’s executive, it’s legislative, it’s furtive.furtive Show phonetics
(of people) behaving secretly so that other people do not notice them, or (of actions) done secretly and often quickly so that people do not notice:
I saw him cast a furtive glance at the woman at the table to his right.
He made one or two furtive phone calls.
There was something furtive about his behaviour and I immediately felt suspicious.
furtively Show phonetics
As she turned away I saw him sniff furtively under his arm.
For many scientists, the increasingly baroque portrait of the genome that their latest research has revealed, along with the muddying of molecular categories, is to be expected. “It’s the normal process of doing science,” said Jonathan R. Beckwith of Harvard Medical School. “You start off simple and you develop complexity.” Nor are researchers disturbed by any linguistic turbulence that may arise, any confusion over what they mean when they talk about genes. “Geneticists happily abuse ‘gene’ to mean many things in many settings,” said Eric S. Lander of the Broad Institute. “This can be a source of enormous consternation to onlookers who want to understand the conversation, but geneticists aren’t bothered.”
In Dr. Lander’s view, the “kluges upon kluges” are an occupational hazard. “We’re trying to parse an incredibly complex system,” he said. “It’s like the U.S. economy. What are your functional units? Employees and employers? Consumers and producers? What if you’re a freelancer with multiple employers? Where do farmers’ markets and eBay map onto your taxonomy?”
“You shouldn’t be worried about the fact that you have to layer on other things as you go along,” he said. “You can never capture something like an economy, a genome or an ecosystem with one model or one taxonomy — it all depends on the questions you want to ask.”
Dr. Lander added: “You have to be able to say, this is Tuesday’s simplification; Wednesday’s may be different, because incredible progress has been made by those simplifications.”
For other researchers, though, the parlance of molecular biology is desperately in need of an overhaul, starting with our folksy friend, gene. “The language is historical baggage,” said Evelyn Fox Keller, a science historian and professor emeritus at M.I.T. “It comes from the expectation that if we could find the fundamental units that make stuff happen, if we could find the atoms of biology, then we would understand the process.”
“But the notion of the gene as the atom of biology is very mistaken,” said Dr. Keller, author of “The Century of the Gene” and other books. “DNA does not come equipped with genes. It comes with sequences that are acted on in certain ways by cells. Before you have cells you don’t have genes. We have to get away from the underlying assumption of the particulate units of inheritance that we seem so attached to.”
Dr. Keller is a big fan of the double helix considered both in toto and in situ — in its native cellular setting. “DNA is an enormously powerful resource, the most brilliant invention in evolutionary history,” she said. “It is a far richer and more interesting molecule than we could have imagined when we first started studying it.”
Still, she said, “it doesn’t do anything by itself.” It is a profoundly relational molecule, she said, and it has meaning only in the context of the cell. To focus endlessly on genes, she said, keeps us stuck in a linear, unidirectional and two-dimensional view of life, in which instructions are read out and dutifully followed.
“What makes DNA a living molecule is the dynamics of it, and a dynamic vocabulary would be helpful,” she said. “I talk about trying to verb biology.” And to renoun it as well. Writing last year in the journal PloS One, Dr. Keller and David Harel of the Weizmann Institute of Science suggested as an alternative to gene the word dene, which they said could be used to connote any DNA sequence that plays a role in the cell. So far, Dr. Keller admits, it has yet to catch on.
Complex as our genome is, it obviously can be comprehended: our cells do it every day. Yet as the physician and essayist Lewis Thomas once noted, his liver was much smarter than he was, and he would rather be asked to pilot a 747 jet 40,000 feet over Denver than to assume control of his liver. “Nothing would save me or my liver, if I were in charge,” he wrote.
In a similar vein, we may never understand the workings of our cells and genomes as comfortably and cockily as we understand the artifacts of our own design. “We have evolved to solve problems,” Dr. Keller said. “Those do not include an understanding of the operation of our own systems — that doesn’t have much evolutionary advantage.” It’s quite possible, she said, that biology is “irreducibly complex,” and not entirely accessible to rational analysis. Which is not to say we’re anywhere near being stymied, she said: “Our biology is stretching our minds. It’s another loop in the evolutionary process.”
And if canonical genes are too thin a gruel to explain yourself to yourself, you can always reach for the stalwart of scapegoats. Blame it all on your mother, who surely loved you too much or too little or in all the wrong ways.