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Pioneer Scientists: Jack Fowler and Alfred Knudson

21 March 2017: Sir Isaac Newton stated, "If I have seen further, it is by standing on the shoulders of giants.” Two prominent scientists who significantly altered my scientific career died this past year – John Francis (Jack) Fowler and Alfred George Knudson, Jr.

I received my BS in 1970 from the University of Wisconsin (UW) in Nuclear Engineering. I transitioned from the physical to the biological sciences as a graduate student at the UW under the mentorship of Kelly Hardenbrook Clifton. My shift from nuclear engineering to a radiobiology was assisted greatly by Jack Fowler’s pioneering research in tumor oxygenation and the mathematical modeling of the interaction of radiation with normal and malignant tissues during fractionated radiation therapy. Later when I was at Duke University, I invited Dr. Fowler to give an Alpha/Beta Model Workshop and a Lecture on Radiation Fractionation to describe how to maximize the therapeutic effects of radiation in the treatment of cancer.

Alfred Knudson, a physician and cancer geneticist, is widely known for his two-hit hypothesis to explain the incidence of hereditary and nonhereditary forms of retinoblastomas (Knudson PNAS 68: 820-823, 1971). This innovative conceptual framework on how to view the genesis of cancer ultimately led to the identification of the retinoblastoma tumor suppressor gene, RB1 (Friend et al. Nature 223: 643-646, 1986).

Our lab subsequently used the Knudson two-hit hypothesis of tumorigenesis to provide the first evidence that the Insulin like Growth Factor 2 Receptor (IGF2R) also functions as a tumor suppressor (De Souza et al. Nat. Genet.). Since IGF2R is imprinted (i.e. one copy of the gene silenced by DNA methylation), this finding thrusted me into the rapidly growing research field of epigenetics. Interestingly, I had the honor of finally meeting Dr. Knudson almost a decade later in Stockholm, Sweden at the 2004 Nobel Symposium on epigenetics entitled, Epigenetic Reprogramming in Development and Disease. I will greatly miss these pioneering scientists upon whose shoulders I stood.