Despite his fame as co-discoverer—along with Francis Crick, PhD—of the double-helix structure of deoxyribonucleic acid (DNA) in 1953, that accomplishment is not what James Dewey Watson, PhD, came to talk about during a recent presentation he gave at the World Science Festival in New York. Instead, Dr. Watson wanted to expand on his theory of curing cancer and why the search for a cure is taking so long, which he details in a recent paper in the online journal, Open Biology.1
“Even though we will soon have comprehensive views of how most cancers arise and function at the genetic and biochemical level, their ‘curing’ seems now to many seasoned scientists an even more daunting objective than when the ‘War on Cancer’ was started by President Nixon in December 1971,” wrote Dr. Watson. “We now have no general of influence, much less power … leading our country’s War on Cancer.”
Key Role of Antioxidants
Dr. Watson’s hypothesis links cancer progression to the presence of antioxidants and contends that antioxidant levels within cancer cells correspond with treatment resistance. His theory focuses on reactive oxygen species, a group of oxidizing molecules that are naturally occurring in cells at low levels, but which are directly or indirectly generated in abundance by most types of cancer therapy, including radiation and chemotherapy, and block key steps in the cell cycle. As malignant cells go through a transformation from epithelial to mesenchymal, “they almost inevitably possess much-heightened amounts of antioxidants that effectively block otherwise highly effective oxidative therapies,” wrote Dr. Watson.
The reason cancer cells largely driven by mutant RAS and Myc proteins are so difficult to cure, explained Dr. Watson, may be due to their high levels of antioxidants, keeping in check otherwise potentially cell-lethal reactive oxygen species. What we most need now are drugs that inhibit the antioxidative molecules that likely make late-stage malignancies so incurable, he said.
A Meeting of Minds
Dr. Watson’s interest in cancer and tumor viruses dates back nearly 6 decades to his tenure as Professor in the Biology Department at Harvard University, where he lectured on how cancer might be induced by DNA tumor viruses.
Born in Chicago in 1928, a year before the start of the Great Depression, books and learning were central parts of his early childhood. Although his father, businessman James D. Watson, managed to find work during those years, a reduced salary plunged the family into poverty. Still, whatever spare money there was, said Dr. Watson, went to pay for books.
Dr. Watson’s early scientific interest was in natural history and the study of ornithology, a result of his father’s—and later his—fascination with bird-watching. At 15, Dr. Watson’s mother, Jean, helped her son apply for a scholarship in an advanced placement program at the University of Chicago’s Hutchins College. He then completed the University’s 4-year program, receiving a Bachelor of Science degree in zoology in 1947. By then, Dr. Watson wanted to study genes. He enrolled in a graduate program at Indiana University and wrote his thesis on x-ray inactivation of bacteriophage, which piqued his interest in DNA.
In 1951, Dr. Watson went to work at the Cavendish Physics Laboratory of Cambridge University in England, where he met Francis Crick. “We were made for each other,” said Dr. Watson. Their collaboration on building hypothetical three-dimensional models of DNA led to their discovery of the double helix in 1953, when Dr. Watson was just 24.
Soon thereafter, Dr. Watson left England to become a Senior Research Fellow in Biology at the California Institute of Technology, where he studied x-ray diffraction of RNA, and 3 years later he joined the staff at Harvard University, where he stayed until 1976. It was during his time at Harvard that Dr. Watson wrote the textbook Molecular Biology of the Gene,2 which raised the question of how a virus might have the capacity to turn on the cell cycle, and has become one of the most widely used textbooks on biology.
Pursuing the Origins of Cancer
In 1962, Drs. Crick and Watson received the Nobel Prize in Physiology or Medicine for their discovery of the structure of DNA and later shared several other awards, including the Lasker Award and the Research Corporation Prize.
Six years later, Dr. Watson was named Director of Cold Spring Harbor Laboratory of Quantitative Biology (which later became simply Cold Spring Harbor Laboratory) in New York. Having first spent time at the Laboratory while a graduate student in 1948, and returning again in 1953 to give the first public presentation of the DNA double helix, the move was a sort of a homecoming for him. When he cut ties with Harvard in 1976, Dr. Watson had already been director of Cold Spring Harbor Laboratory for 8 years.
Dr. Watson changed the focus of the Laboratory’s research from microbial genetics to the study of cancer, with the hiring of molecular biologist Joseph Sambrook, PhD, from the Salk Institute. Dr. Sambrook launched a Tumor Virus Group, which is still in place today. Under Dr. Watson’s leadership, Cold Spring Harbor Laboratory has been transformed into one of the world’s premier research facilities in cancer, neurobiology, and basic molecular genetics.
From 1988 to 1992, while still Director of Cold Spring Harbor Laboratory, Dr. Watson was named the first Director of the Human Genome Project at the National Institutes of Health. He later became President and then Chancellor of Cold Spring Harbor Laboratory and is currently Chancellor Emeritus.
Obstacle to Curing Cancer
Dr. Watson credits his accomplishments with an insatiable curiosity and the ability to surround himself with intelligent people. “I knew I wasn’t a genius,” he insisted. “I like meeting bright people and I don’t do anything that is not important.”
At 85, Dr. Watson remains actively engaged in his two passions, playing tennis and finding a cure for cancer, although he admits, the latter goal remains elusive.
“The biggest obstacle to moving forward effectively toward a true war against cancer may, in fact, come from the inherently conservative nature of today’s cancer research establishments,” wrote Dr. Watson. ■
References
1. Watson J: Oxidants, antioxidants and the current incurability of metastatic cancers. Open Biology. January 9, 2013. Available at http://rsob.royalsocietypublishing.org. Accessed July 5, 2013.
2. Watson JD: Molecular Biology of the Gene. New York, W.A. Benjamin, Inc, 1965.
