In a paper, he called “among my most important work since the double helix,” James D. Watson. Ph.D., posited a theory that links cancer progression in late stages of the disease to the presence of antioxidants.
The paper was published today in Open Biology, a journal of Great Britain’s Royal Society. According to the DNA co-discoverer and chancellor emeritus of Cold Spring Harbor Laboratory, reactive oxygen species (ROS) pose a dichotomy: They play a positive role in mediating the killing of stressed cells during apoptosis. But when no such cells exist, however, ROS’s are constantly being neutralized by antioxidative proteins, causing irreversible damage to DNA and RNA among key nucleic acid molecules and proteins.
“Unless we can find ways of reducing antioxidant levels, late-stage cancer 10 years from now will be as incurable as it is today,” Dr. Watson said in a statement. “Although mortality from many cancers has been steadily falling, particularly those of the blood [i.e., leukemias], the more important statistic may be that so many epithelial cancers (carcinomas) and effectively all mesenchymal cancers (sarcomas) remain largely incurable.”
So much, he adds, for consuming higher levels of antioxidants found in fruits: “Blueberries best be eaten because they taste good, not because their consumption will lead to less cancer,” Dr. Watson wrote.
Dr. Watson has long theorized on cancer and cancer policy. In 2009, writing in The New York Times, he restated his call for concentrating federal cancer spending on basic research rather than clinical centers. Two years later, in the journal Cancer Discovery, Dr. Watson suggested that more effective anticancer drug targets may be found through RNAi technologies designed to pinpoint key regulatory and metabolic weaknesses of “always-on” cancer cells, rather than through reversal of “always-on” signals.
In his latest paper, Dr. Watson theorized that the cell-killing ability of current anticancer therapies—from radiation to Taxol and other chemotherapeutic agents—occurs mainly due to the induction of apoptosis by ROS. This, he wrote, would explain why cancers that resist chemotherapy also equally resist ionizing radiotherapy: Both depend upon a ROS-mediated cell-killing mechanism.
High levels of ROS-destroying antioxidants, Dr. Watson added, accounts for cancer cells largely driven by mutant proteins being among the hardest to produce a response via treatment. He cited recent research showing up-regulation of the gene transcription factor Nrf2—which controls the synthesis of antioxidants—both when cells proliferate as well as when such oncogenes as RAS, MYC, and RAF are active.
“This makes sense,” Dr. Watson concluded, “because we want antioxidants present when DNA functions to make more of itself.”