The Gene: An Intimate History - Siddhartha Mukherjee Page 0,65

biophysicist might add—if not molecules of matter?

This description of physiology—as the exquisite matching of form and function, down to the molecular level—dates back to Aristotle. For Aristotle, living organisms were nothing more than exquisite assemblages of machines. Medieval biology had departed from that tradition, conjuring up “vital” forces and mystical fluids that were somehow unique to life—a last-minute deus ex machina to explain the mysterious workings of living organisms (and justify the existence of the deus). But biophysicists were intent on restoring a rigidly mechanistic description to biology. Living physiology should be explicable in terms of physics, biophysicists argued—forces, motions, actions, motors, engines, levers, pulleys, clasps. The laws that drove Newton’s apples to the ground should also apply to the growth of the apple tree. Invoking special vital forces or inventing mystical fluids to explain life was unnecessary. Biology was physics. Machina en deus.

Wilkins’s pet project at King’s was solving the three-dimensional structure of DNA. If DNA was truly the gene carrier, he reasoned, then its structure should illuminate the nature of the gene. Just as the terrifying economy of evolution had stretched the length of the giraffe’s neck and perfected the four-armed saddle clasp of hemoglobin, that same economy should have generated a DNA molecule whose form was exquisitely matched to its function. The gene molecule had to somehow look like a gene molecule.

To decipher the structure of DNA, Wilkins had decided to corral a set of biophysical techniques invented in nearby Cambridge—crystallography and X-ray diffraction. To understand the basic outline of this technique, imagine trying to deduce the shape of a minute three-dimensional object—a cube, say. You cannot “see” this cube nor feel its edges—but it shares the one property that all physical objects must possess: it generates shadows. Imagine that you can shine light at the cube from various angles and record the shadows that are formed. Placed directly in front of the light, a cube casts a square shadow. Illuminated obliquely, it forms a diamond. Move the light source again, and the shadow is a trapezoid. The process is almost absurdly laborious—like sculpting a face out of a million silhouettes—but it works: piece by piece, a set of two-dimensional images can be transmuted into a three-dimensional form.

X-ray diffraction arises out of analogous principles—the “shadows” are actually the scatters of X-rays generated by a crystal—except to illuminate molecules and generate scatters in the molecular world, one needs the most powerful source of light: X-rays. And there’s a subtler problem: molecules generally refuse to sit still for their portraits. In liquid or gas form, molecules whiz dizzily in space, moving randomly, like particles of dust. Shine light on a million moving cubes and you only get a hazy, moving shadow, a molecular version of television static. The only solution to the problem is ingenious: transform a molecule from a solution to a crystal—and its atoms are instantly locked into position. Now the shadows become regular; the lattices generate ordered and readable silhouettes. By shining X-rays at a crystal, a physicist can decipher its structure in three-dimensional space. At Caltech, two physical chemists, Linus Pauling and Robert Corey, had used this technique to solve the structures of several protein fragments—a feat that would win Pauling the Nobel Prize in 1954.

This, precisely, is what Wilkins hoped to do with DNA. Shining X-rays on DNA did not require much novelty or expertise. Wilkins found an X-ray diffraction machine in the chemistry department and housed it—“in solitary splendor”—in a lead-lined room under the embankment wing, just below the level of the neighboring river Thames. He had all the crucial material for his experiment. Now his main challenge was to make DNA sit still.

Wilkins was plowing methodically through his work in the early 1950s when he was interrupted by an unwelcome force. In the winter of 1950, the head of the Biophysics Unit, J. T. Randall, recruited an additional young scientist to work on crystallography. Randall was patrician, a small, genteel, cricket-loving dandy who nonetheless ran his unit with Napoleonic authority. The new recruit, Rosalind Franklin, had just finished studying coal crystals in Paris. In January 1951, she came up to London to visit Randall.

Wilkins was away on vacation with his fiancée—a decision he would later regret. It is not clear how much Randall had anticipated future collisions when he suggested a project to Franklin. “Wilkins has already found that fibers of [DNA] give remarkably good diagrams,” he told her. Perhaps Franklin would consider studying the diffraction patterns of these fibers and deduce