The Gene: An Intimate History - Siddhartha Mukherjee Page 0,64

physicist from New Zealand, Maurice Wilkins. The son of a country doctor, Wilkins had studied physics at Cambridge in the 1930s. The gritty frontier of New Zealand—far away and upside down—had already produced a force that had turned twentieth-century physics on its head: Ernest Rutherford, another young man who had traveled to Cambridge on scholarship in 1895, and torn through atomic physics like a neutron beam on the loose. In a blaze of unrivaled experimental frenzy, Rutherford had deduced the properties of radioactivity, built a convincing conceptual model of the atom, shredded the atom into its constituent subatomic pieces, and launched the new frontier of subatomic physics. In 1919, Rutherford had become the first scientist to achieve the medieval fantasy of chemical transmutation: by bombarding nitrogen with radioactivity, he had converted it into oxygen. Even elements, Rutherford had proved, were not particularly elemental. The atom—the fundamental unit of matter—was actually made of even more fundamental units of matter: electrons, protons, and neutrons.

Wilkins had followed in Rutherford’s wake, studying atomic physics and radiation. He had moved to Berkeley in the 1940s, briefly joining scientists to separate and purify isotopes for the Manhattan Project. But on returning to England, Wilkins—following the trend among many physicists—had edged away from physics toward biology. He had read Schrödinger’s What Is Life? and become instantly entranced. The gene—the fundamental unit of heredity—must also be made of subunits, he reasoned, and the structure of DNA should illuminate these subunits. Here was a chance for a physicist to solve the most seductive mystery of biology. In 1946, Wilkins was appointed assistant director of the new Biophysics Unit at King’s College in London.

Biophysics. Even that odd word, the mishmash of two disciplines, was a sign of new times. The nineteenth-century realization that the living cell was no more than a bag of interconnected chemical reactions had launched a powerful discipline fusing biology and chemistry—biochemistry. “Life . . . is a chemical incident,” Paul Ehrlich, the chemist, had once said, and biochemists, true to form, had begun to break open cells and characterize the constituent “living chemicals” into classes and functions. Sugars provided energy. Fats stored it. Proteins enabled chemical reactions, speeding and controlling the pace of biochemical processes, thereby acting as the switchboards of the biological world.

But how did proteins make physiological reactions possible? Hemoglobin, the oxygen carrier in blood, for instance, performs one of the simplest and yet most vital reactions in physiology. When exposed to high levels of oxygen, hemoglobin binds oxygen. Relocated to a site with low oxygen levels, it willingly releases the bound oxygen. This property allows hemoglobin to shuttle oxygen from the lung to the heart and the brain. But what feature of hemoglobin allows it to act as such an effective molecular shuttle?

The answer lies in the structure of the molecule. Hemoglobin A, the most intensively studied version of the molecule, is shaped like a four-leaf clover. Two of its “leaves” are formed by a protein called alpha-globin; the other two are created by a related protein, beta-globin.II Each of these leaves clasps, at its center, an iron-containing chemical named heme that can bind oxygen—a reaction distantly akin to a controlled form of rusting. Once all the oxygen molecules have been loaded onto heme, the four leaves of hemoglobin tighten around the oxygen like a saddle clasp. When unloading oxygen, the same saddle-clasp mechanism loosens. The unbinding of one molecule of oxygen coordinately relaxes all the other clasps, like the crucial pin-piece pulled out from a child’s puzzle. The four leaves of the clover now twist open, and hemoglobin yields its cargo of oxygen. The controlled binding and unbinding of iron and oxygen—the cyclical rusting and unrusting of blood—allows effective oxygen delivery into tissues. Hemoglobin allows blood to carry seventyfold more oxygen than what could be dissolved in liquid blood alone. The body plans of vertebrates depend on this property: if hemoglobin’s capacity to deliver oxygen to distant sites was disrupted, our bodies would be forced to be small and cold. We might wake up and find ourselves transformed into insects.

It is the form of hemoglobin, then, that permits its function. The physical structure of the molecule enables its chemical nature, the chemical nature enables its physiological function, and its physiology ultimately permits its biological activity. The complex workings of living beings can be perceived in terms of these layers: physics enabling chemistry, and chemistry enabling physiology. To Schrödinger’s “What is life?” a biochemist might answer, “If not chemicals.” And what are chemicals—a