Natural Obsessions: The Search for the Oncogene (review)

BOOK REVIEWS Natural Obsessions: The Search for the Oncogene. By Natalie Angier. Boston: Houghton Mifflin, 1988. Pp. 394. $19.95. The late Sir Peter Medawar once wrote that every scientific paper is a fraud. By that he meant that the story of a scientific discovery as told in a scientific publication is distorted and that it does not provide genuine insight into the nature of scientific progress. Obviously, for the sake of clarity and brevity, a logical account is preferable to a historical representation, and avoids confusing the reader with anecdotes. Yet this pragmatical imperative leads to a deceiving Hineininterpretierung of the facts. For example, it assigns little credit to the role of serendipity or to the synergistic effects of collaboration, and it fails to reveal extensive modifications of an original hypothesis caused by unanticipated results. Occasionally books are written that give a behind-the-scenes view ofa scientific breakthrough or the life of an eminent scientist—Jim Watson's legendary Double Helix immediately comes to mind. Natalie Angier, an experienced science writer, has added another book to this category. Natural Obsessions is not an adults-only book; it is a blunt and delightful chronicle of the discovery of the oncogene (as the subtitle fortunately points out). Angier has done extensive fieldwork for her book, spending 7 months in the lab of Robert Weinberg at the Whitehead Institute at MIT. Weinberg has made pioneering contributions to the oncogene field, for which he is "as lavishly decorated as the Joint Chiefs of Staff" (p. 11). The dissection of the genetic basis of cancer occurred in the aftermath of Nixon's War on Cancer. Much of cancer biology was then merely phenomenology , ajungle of descriptions that failed to distinguish conclusively between cause and effect. Weinberg reasoned that cancer-causing genes might be identified by trying to confer the cancer phenotype on normal cells through the newly developed technique of transfection, with which DNA from a malignant cell would be introduced into a normal cell. This reductionist approach was inspired by his profound belief in the simplicity of nature and by a wish to let light shine in the biochemical black box of the malignant cell. Starting with this transfection scheme in 1978, the Weinberg group was able to isolate a cellular oncogene in 1982 from a human bladder carcinoma. Much to their surprise, the oncogene turned out to be the cellular version of Ha-ras, a retroviral oncogene that had been known for years. Before that, it was generally believed that the cellular precursors of oncogenes (or proto-oncogenes) were a different class of genes from the oncogenes of cancer-causing retroviruses. A second surprise came with Permission to reprint a book review printed in this section may be obtained only from the author. Perspectives in Biology and Medicine, 32, 4 · Summer 1989 \ 613 the discovery that the oncogenic version differed in only a single nucleotide from the proto-oncogene. Weinberg's serial transformation assay provided a first real glimpse of the genetic basis of cancer and was in fact a variation of the very technique used in 1944 by Avery, MacLeod, and McCarthy to prove that the genetic material is made up of DNA and not proteins. The assay quickly became a widely used method to isolate many other cellular oncogenes. Again, intelligent application of a simple technique to test a simple idea had resulted in a scientific breakthrough . Back in the early 1970s, Alfred Knudson proposed that retinoblastoma, a childhood eye cancer, was caused by the functional inactivation of the two copies of a recessive tumor suppressor gene. This seminal hypothesis has been brought to the genetic level again by the Weinberg group and led to the cloning of the first tumor suppressor gene in 1986, in collaboration with Ted Dryja. Tumor suppressor genes (also called recessive cancer genes or antioncogenes) have added a new dimension to cancer biology. The action of oncogenes and antioncogenes can be regarded as the yin and the yang of tumorigenesis. The identification of the retinoblastoma gene occurred during Natalie Angler 's stay at the Weinberg lab. She has captured these events as an interested eyewitness, while she has reconstructed the history of the unveiling...