The Gene: An Intimate History - Siddhartha Mukherjee Page 0,51

simplicity, but distrust it,” Alfred North Whitehead, the mathematician and philosopher, once advised his students. Dobzhansky had sought simplicity—but he had also issued a strident moral warning against the oversimplification of the logic of genetics. Buried in textbooks and scientific papers, these insights would be ignored by powerful political forces that would soon embark on the most perverse forms of human genetic manipulations.

Transformation

If you prefer an “academic life” as a retreat from reality, do not go into biology. This field is for a man or woman who wishes to get even closer to life.

—Hermann Muller

We do deny that . . . geneticists will see genes under the microscope. . . . The hereditary basis does not lie in some special self-reproducing substance.

—Trofim Lysenko

The reconciliation between genetics and evolution was termed the Modern Synthesis or, grandly, the Grand Synthesis. But even as geneticists celebrated the synthesis of heredity, evolution, and natural selection, the material nature of the gene remained an unsolved puzzle. Genes had been described as “particles of heredity,” but that description carried no information about what that “particle” was in a chemical or physical sense. Morgan had visualized genes as “beads on a string,” but even Morgan had no idea what his description meant in material form. What were the “beads” made of? And what was the nature of the “string”?

In part, the material composition of the gene had defied identification because biologists had never intercepted genes in their chemical form. Throughout the biological world, genes generally travel vertically—i.e., from parents to children, or from parent cells to daughter cells. The vertical transmission of mutations had allowed Mendel and Morgan to study the action of a gene by analyzing patterns of heredity (e.g., the movement of the white-eyed trait from parent flies to their offspring). But the problem with studying vertical transformation is that the gene never leaves the living organism or cell. When a cell divides, its genetic material divides within it and is partitioned to its daughters. Throughout the process, genes remain biologically visible, but chemically impenetrable—shuttered within the black box of the cell.

Rarely, though, genetic material can cross from one organism to another—not between parent and child, but between two unrelated strangers. This horizontal exchange of genes is called transformation. Even the word signals our astonishment: humans are accustomed to transmitting genetic information only through reproduction—but during transformation, one organism seems to metamorphose into another, like Daphne growing twigs (or rather, the movement of genes transforms the attributes of one organism into the attributes of another; in the genetic version of the fantasy, twig-growing genes must somehow enter Daphne’s genome and enable the ability to extrude bark, wood, xylem, and phloem out of human skin).

Transformation almost never occurs in mammals. But bacteria, which live on the rough edges of the biological world, can exchange genes horizontally (to fathom the strangeness of the event, imagine two friends, one blue eyed and one brown eyed, who go out for an evening stroll—and return with altered eye colors, having casually exchanged genes). The moment of genetic exchange is particularly strange and wonderful. Caught in transit between two organisms, a gene exists momentarily as a pure chemical. A chemist seeking to understand the gene has no more opportune moment to capture the chemical nature of the gene.

Transformation was discovered by an English bacteriologist named Frederick Griffith. In the early 1920s, Griffith, a medical officer at the British Ministry of Health, began to investigate a bacterium named Streptococcus pneumoniae or pneumococcus. The Spanish flu of 1918 had raged through the continent, killing nearly 20 million men and women worldwide and ranking among the deadliest natural disasters in history. Victims of the flu often developed a secondary pneumonia caused by pneumococcus—an illness so rapid and fatal that doctors had termed it the “captain of the men of death.” Pneumococcal pneumonia after influenza infection—the epidemic within the epidemic—was of such concern that the ministry had deployed teams of scientists to study the bacterium and develop a vaccine against it.

Griffith approached the problem by focusing on the microbe: Why was pneumococcus so fatal to animals? Following work performed in Germany by others, he discovered that the bacterium came in two strains. A “smooth” strain possessed a slippery, sugary coat on the cell surface and could escape the immune system with newtlike deftness. The “rough” strain, which lacked this sugary coat, was more susceptible to immune attack. A mouse injected with the smooth strain thus died rapidly of pneumonia. In contrast, mice inoculated with the