- Correcting the Blueprint of Life: An Historical Account of the Discovery of DNA Repair Mechanisms
Errol Friedberg has offered a first history of research on DNA repair, an impressive genealogy of the current field from the perspective of one of its participants. He recounts key experiments and important new insights from the 1940s to the 1980s, taking care to preserve the researchers’ own memories and views on scientific turning points. Individual contributions and biographies figure far more significantly in his account than do broader conceptual and institutional developments. Historians of medicine and biology will note the stunning lack of references to any secondary literature beyond Horace Judson’s The Eighth Day of Creation: Makers of the Revolution in Biology (1979) and a biography of Max Delbrück—but biologists, not historians, are the principal audience for this book.
The chapters are organized around the different modes of error correction, including enzymatic photoreactivation, excision repair, mismatched base replacement, and, most recently, SOS repair. Friedberg shows how initially peripheral research on the recovery from mutagenesis in the 1940s grew to be central to investigations of gene replication and recombination in the 1960s. The perception of DNA repair as a “hot” area of molecular biology reached its apogee in 1994 when the SOS enzymes were collectively chosen as Science magazine’s “Molecule of the Year.”
Although research on DNA repair can be traced to a few decisive experiments at the end of 1948, the origin story remains complex at two levels. First, the phenomenon of photoreactivation (light-induced recovery) of UV-irradiated cultures was codiscovered by Albert Kelner (in bacteria) and Renato Dulbecco (in phage). Dulbecco’s thesis adviser, Salvador Luria, received personal communications of Kelner’s observations before Dulbecco’s critical experiment. Friedberg handles the priority dispute with sensitivity, recognizing the disadvantages Kelner faced at the time in having neither firm job prospects nor a powerful mentor such as Luria. Second, even when the demonstrations of photoreactivation were published, they did not induce researchers to investigate the mechanisms of DNA damage and repair. Biologists were still uncertain about the chemical target of ultraviolet radiation, assessing the damage vaguely in terms of nuclear function. Friedberg attributes their delay in focusing specifically on DNA to the vestiges of a protein view of heredity, which continued to hold sway until the 1950s.
Once DNA repair had been labeled as such and researchers were working to understand its mechanisms, radiation geneticists and photobiologists were well positioned (and well funded by the Atomic Energy Commission) to identify the nature of DNA lesions and the pathways for their repair. Friedberg comments, “The field of DNA repair was born at last and the baby was not at all unattractive to the family of molecular biologists!” (p. 53). However, neither was the field dominated by workers from molecular centers such as Caltech and Cambridge [End Page 541] University: key contributions came from Oak Ridge and Brookhaven National Laboratories, and subsequently from the “Texas mafia,” as a network of important centers for DNA came to be known. The mechanisms of DNA repair turned out to be more varied and complex than anyone in the 1950s might have imagined (the same could be said of the mechanisms for gene expression); their elucidation required two decades of intensive and competitive biochemical investigation, and it established countless scientific careers. Friedberg’s comprehensive survey points to several individuals who merit fuller historical treatment—for instance, two DNA repair pioneers who were women, Evelyn Witkin and Jane Setlow. The generosity of some of the early repair researchers (particularly Witkin) toward younger colleagues reveals a more altruistic side of the scientific enterprise than that presented in many accounts of recent biology, even though important priority disputes also occurred among repair researchers.
Friedberg restricts his account to the linear scientific developments associated with the emerging field of DNA repair, but even his title suggests the role of a broader historical current. How did the conceptual shift of the 1950s...