Category Archives: One Renegade Cell by Robert A. Weinberg

Cancer-Causing Mutations Can Occur By Chance as Millions of Cells Divide

“When the DNA double helix was first revealed by Watson and Crick in 1953, its structure seemed perfect and robust, well-designed to resist most of the disruptive influences that might be present inside living cells. For example, the bases in the double helix are turned inward and thus are not very susceptible to direct attack by chemical mutagens. Moreover, the linkages between adjacent bases were found to be resistant to cleavage by alkaline ions that arise continually in the cell.

“But while the double helix itself is relatively resistant to chemical attack, the process of maintaining a cell’s genetic integrity has a weak link. The vulnerability derives from the need to replicate the cell’s genome each time the cell goes through the process of growth and division. The resulting duplicate copies of the genome enable the mother cell to endow each of its daughters with a genome precisely equivalent to the one that it carries itself.

“This process of DNA replication has flaws. On occasion, a cell will miscopy a sequence of its DNA prior to cell division, and as a consequence, one of its daughters will receive a slightly miscopied genome, in effect a mutated one. Even the best-functioning cells will occasionally miscopy one in a million (or ten million) bases during each cycle of DNA replication. Hence, cell growth and division create vulnerability mutation.

“This imperfection suggested another way cancer formation might be accelerated. Agents that promote cell growth will indirectly create mutations simply because they force cells to replicate their DNA. More DNA copying means more inadvertent copying mistakes, hence more mistakes.”

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Testing DNA Function Through Gene Transfer

“By 1979, another strategy for searching for elusive tumor oncogenes came online. This new approach did not depend on the knowledge gained about retroviruses. It was an independent strategy made possible by the experimental technique of gene transfer. Simply put, gene transfer made it possible to extract DNA (and thus genes) from one cell and introduce these genes into a second cell. The genes introduced into the recipient cell might cause it to take on new traits or behaviors. Such a response would indicate that the information specifying the newly displayed trait was present in the donor cell (from which the DNA had been prepared) and that this information could be conveyed to a recipient cell by the transfer of DNA molecules.” (p. 38)

Cancer Growth Is Orchestrated at the Cell Level, Not By a Central Process

“How are human tissues put together from single cells? The description above might suggest the involvement of master builders who oversee crews of workers, directing them in the detailed construction of normal and malignant tissues. In reality, there are no overseers forcing throngs of cells to line up and assemble themselves into normal or cancerous tissues. Architectural complexity in living tissue comes from the bricks themselves, the individual cells. Control is exercised from the bottom up…The cells forming a tumor are all lineal descendants of a single progenitor, a distant ancestor that lived many years before the tumor mass became apparent.” (p. 1-2)