Alfred Knudson

Alfred Knudson proposed the two-hit hypothesis of cancer in 1971, demonstrating that retinoblastoma and other hereditary cancers require inactivation of both copies of a tumor suppressor gene, which became the foundational concept for identifying hereditary cancer risk and enabling genetic cancer prevention. His theoretical framework predicted the existence of tumor suppressor genes before they were molecularly identified and enabled genetic counseling and preventive interventions for hereditary cancer syndromes. His work is the intellectual foundation of all genetic cancer risk assessment and prevention.