The Gene: An Intimate History - Siddhartha Mukherjee Page 0,72

outside, and the general parameters of the measurements ascertained, the model builders could begin the most exacting phase of model building. At first, Watson tried to jam the two helices together, with the A on one strand matched with an A on the other—like bases paired with like. But the helix bulged and thinned inelegantly, like the Michelin Man in a wet suit. Watson tried to massage the model into shape, but it wouldn’t fit. By the next morning, it had to be abandoned.

Sometime on the morning of February 28, 1953, Watson, still playing with cardboard cutouts in the shape of the bases, began to wonder if the interior of the helix contained mutually opposing bases that were unlike each other. What if A was paired with the T, and C with the G? “Suddenly I became aware that an adenine thymine pair (A→T) was identical in shape to a guanine cytosine pair (G→C) . . . no fudging was required to make the two types of base pairs identical in shape.”

He realized that the base pairs could now easily be stacked atop each other, facing inward into the center of the helix. And the importance of Chargaff’s rules became obvious in retrospect—A and T, and G and C, had to be present in identical amounts because they were always complementary: they were the two mutually opposing teeth in the zipper. The most important biological objects had to come in pairs. Watson could hardly wait for Crick to walk into the office. “Upon his arrival, Francis did not get halfway through the door before I let loose that the answer to everything was in our hands.”

One look at the opposing bases convinced Crick. The precise details of the model still needed to be worked out—the A:T and G:C pairs still needed to be placed inside the skeleton of the helix—but the nature of the breakthrough was clear. The solution was so beautiful that it could not possibly be wrong. As Watson recalled, Crick “winged into the Eagle to tell everyone within the hearing distance that we had found the secret of life.”

Like Pythagoras’s triangle, like the cave paintings at Lascaux, like the Pyramids in Giza, like the image of a fragile blue planet seen from outer space, the double helix of DNA is an iconic image, etched permanently into human history and memory. I rarely reproduce biological diagrams in text—the mind’s eye is usually richer in detail. But sometimes one must break rules for exceptions:

A schematic of the double-helical structure of DNA, showing a single helix (left) and its paired double helix (right). Note the complementarity of bases: A is paired with T, and G with C. The winding “backbone” of DNA is made of a chain of sugars and phosphates.

The helix contains two intertwined strands of DNA. It is “right-handed”—twisting upward as if driven by a right-handed screw. Across the molecule, it measures twenty-three angstroms—one-thousandth of one-thousandth of a millimeter. One million helices stacked side by side would fit in this letter: o. The biologist John Sulston wrote, “We see it as a rather stubby double helix, for they seldom show its other striking feature: it is immensely long and thin. In every cell in your body, you have two meters of the stuff; if we were to draw a scaled-up picture of it with the DNA as thick as sewing thread, that cell’s worth would be about 200 kilometers long.”

Each strand of DNA, recall, is a long sequence of “bases”—A, T, G, and C. The bases are linked together by the sugar-phosphate backbone. The backbone twists on the outside, forming a spiral. The bases face in, like treads in a circular staircase. The opposite strand contains the opposing bases: A matched with T and G matched with C. Thus, both strands contain the same information—except in a complementary sense: each is a “reflection,” or echo, of the other (the more appropriate analogy is a yin-and-yang structure). Molecular forces between the A:T and G:C pairs lock the two strands together, as in a zipper. A double helix of DNA can thus be envisioned as a code written with four alphabets—ATGCCCTACGGGCCCATCG . . .—forever entwined with its mirror-image code.

“To see,” the poet Paul Valéry once wrote, “is to forget the name of the things that one sees.” To see DNA is to forget its name or its chemical formula. Like the simplest of human tools—hammer, scythe, bellows, ladder, scissors—the function of the molecule can be entirely comprehended from its structure.