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Cancer by Default

Alan Packer

The Society of Cells: Cancer and Control of Cell Proliferation. C. Sonnenschein and A. M. Soto. 154 pp. Bios/Springer-Verlag, 1999. $34.95.

With the War on Cancer approaching the length of the Thirty Years War and billions of taxpayer dollars having been spent since it began, it is not unreasonable to ask why the overall morbidity and mortality associated with cancer has not declined appreciably in the United States. Most scientists and observers of the cancer research efforts of the past quarter century seem to have concluded that this investment of time and money has been amply rewarded with spectacular advances in the basic understanding of the molecular origins of carcinogenesis.

On the evidence of The Society of Cells, it is safe to say that C. Sonnenschein and A. M. Soto are rather unimpressed with this entire research program and its premises. Sonnenschein and Soto, physician-scientists at Tufts University School of Medicine, argue that the prevailing paradigm of cancer research is based on three fundamentally flawed views of the basic biology of cancer.

Their first proposal is that the default state of cells is proliferation rather than quiescence and that the key to understanding how cellular proliferation is controlled is to identify inhibitors of this default state.

The second, which is echoed in many quarters, is that too much of today's cancer research is in the reductionist tradition and ignores the properties of tissues that emerge once we lift our sights from a gene-centered view of how cells and organisms operate.

Finally, Sonnenschein and Soto suggest that, contrary to the prevailing view, genetic mutations are, at best, indirectly involved in carcinogenesis. Rather, the disruption of tissue organization is the causal factor in transforming a normal cell into a cancerous one.

That cells proliferate rather than enter a quiescent state given the proper nutritive environment is based on both evolutionary common sense and sound technical arguments. After all, the authors note, bacterial and plant cells behave in just such a manner when placed in culture, and there is no compelling reason to believe that this longstanding strategy for living has been overturned in animal cells.

On this point, Sonnenschein and Soto do an excellent job of elucidating the ways in which the opposite assumption (quiescence as the default state) has defined much of the work on cellular proliferation and carcinogenesis over the past few decades, on very little evidence.

Other areas of their argument, however, seem more problematic. Although some of the criticisms of a gene-centered approach to cancer are sound and interesting, there is now an immense literature—largely generated in the past 15 years—linking mutations in specific genes to overall cancer susceptibility or to the development of specific cancers. In support of their view that this is not the case, Sonnenschein and Soto review the literature in a selective manner, emphasizing animal studies that raise doubts about the molecular genetic origins of cancer while ignoring those that support it.

Does more attention need to be paid to the ways in which perturbations of cell-cell signaling and tissue organization contribute to the development of cancer? Certainly. But there is every reason to believe these events can be traced back to DNA damage and genetic mutations. Filling in these pathways is the task at hand not only for cancer researchers but for biologists in general.

In the epilogue to their book, Sonnenschein and Soto quote the eminent biologist John Tyler Bonner: "What is utterly baffling to me is why one cannot be a reductionist and a holist at the same time." The Society of Cells is certainly a provocative critique of the current program of cancer research—one that attempts to move the field away from an ultrareductionist view. At times, however, it ignores Bonner's sensible question and moves too far in the other direction.—Alan I. Packer, Genetics and Development, Columbia University College of Physicians and Surgeons

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