2002 : WHAT IS YOUR QUESTION? ... WHY?

John McCarthy and I are from different generations (in the semester before McCarthy invented Lisp, he taught my dad FORTRAN, using punch cards on an old IBM) but our questions are nearly the same. McCarthy asks "how are behaviors encoded in DNA"?

Until recently, we were not in a position to answer this question. Few people would have even had the nerve to ask it. Many thought that most of the brain's basic organization arose in response to the environment. But we know that the mind of a newborn is far from a blank slate. As soon as they are born, babies can imitate facial gestures, connect what they hear with what they see, tell the difference between Dutch and Japanese, and distinguish between a picture of a scrambled face and a picture of a normal face. Nativists like Steven Pinker and Stanislas Dehaene suggest that infants are born with a language instinct and a "number sense". Since the function of our minds comes from the structure of our brains, these findings suggest that the microcircuitry of the brain is innate, largely wired up before birth. The plan for that wiring must come in part from the genes.

The DNA does not, however, provide a literal blueprint of a newborn's mind. We have only around 35,000 genes, but tens of billions of neurons. How does a relatively small set of genes combine to build a complex brain? As Richard Dawkins has put it, the DNA is more like a recipe than a blueprint. The genome doesn't provide a picture of a finished product, instead it provides a set of instructions for assembling an embryo. Those instructions govern basic developmental processes such as cell division and cell migration; it has long been known that such processes are essential to building bodies, and it now is becoming increasingly clear that the same processes shape our brains and minds as well.

There is, however, no master chef. In place of a central executive, the body relies on communication between cells, and communication between genes. Although the power of any one gene working on its own is small, the power of sets of genes working together is enormous. To take one example, Swiss biologist Walter Gehring has shown that the gene pax-6 controls eye development in a wide range of animals, from fruit flies to mice. Pax-6 is like any other gene in that it gives instructions for building one protein, but unlike the genes for building structural proteins like keratin and collagen because the protein that pax-6 builds serves as a signal to other genes, which in turn build proteins that serve as signals to still other genes. Pax-6 is thus a "master control gene" that launches an enormous cascade, a cascade of 2,500 genes working together to build an eye. Humans that lack it lack irises, flies that lack it lack eyes altogether. The cascade launched by pax-6 is so potent that when Gehring triggered it artificially on a fruit fly's antenna, the fly grew an extra eye, right there on its antenna. As scientists begin to work out the cascades of genes that build the brain, we will finally come to understand the role of the genes in shaping the mind.

Response to Paul Davies' reply to John McCarthy

It is hard indeed to imagine that nature would endow an organism with anything as detailed as The Cambridge Star Atlas. A typical bird probably has fewer than 50,000 genes, but, as Carl Sagan famously noted, there are billions and billions of stars.

Of course, you don't need to know all the stars to navigate. Every well trained sailor knows that Polaris marks North. A northern-hemisphere dwelling bird known as the Indigo Bunting knows something even more subtle - it doesn't just look for the brightest star (which could be lousy strategy on a cloudy night); instead it looks for how the stars rotate.

Cornell ecologist Stephen Emlen proved this experimentally, by raising buntings in a planetarium. One set of birds never got to see any stars, a second set saw the normal pattern of stars, and a third group saw a sneaky set of stars, in which everything rotated not around Polaris, but around Betelgeuse. The poor birds who didn't see any stars oriented themselves randomly (making it clear that they really did depend on the stars rather than a built-in compass). The birds who saw normal skies oriented themselves normally, and the ones who saw skies that rotated around Betelgeuse oriented themselves precisely as if they thought that Betelgeuse marked North. The birds weren't relying on specific sets of stars, they were relying on the stars' center of rotation.

You won't find the constellations in an indigo bunting's DNA, but you would find in their DNA the instructions for building a biological computer, one that can interpret the stars, taking the skies as its input and producing an estimated direction as its output. Just how the DNA can wire up such biological computers is my vote for the most important scientific question of the 21st century.