The article by Alfred G. Knudson, Jr. explores the hypothesis that retinoblastoma, a type of cancer, is caused by two mutational events. In the dominantly inherited form, one mutation is inherited from germinal cells, and the second occurs in somatic cells. In the nonhereditary form, both mutations occur in somatic cells. The second mutation typically results in an average of three retinoblastomas per individual inheriting the first mutation. Using Poisson statistics, the mean number of tumors (three) explains the observed distribution of cases, including those with no tumor, unilateral tumors, and bilateral tumors. The mutation rates for the first and second mutations are estimated to be 1.5-10% and 2-7%, respectively. The data support the idea that cancer can arise through multiple stages, each involving somatic mutations. The study also discusses the distribution of retinoblastoma cases by type and laterality, and the relationship between mutation rates in hereditary and nonhereditary forms. The findings align with current theories on the mutational origin of cancer, suggesting that retinoblastoma can be caused by two mutations, each occurring at a rate of about \(2 \times 10^{-4}\) per year.The article by Alfred G. Knudson, Jr. explores the hypothesis that retinoblastoma, a type of cancer, is caused by two mutational events. In the dominantly inherited form, one mutation is inherited from germinal cells, and the second occurs in somatic cells. In the nonhereditary form, both mutations occur in somatic cells. The second mutation typically results in an average of three retinoblastomas per individual inheriting the first mutation. Using Poisson statistics, the mean number of tumors (three) explains the observed distribution of cases, including those with no tumor, unilateral tumors, and bilateral tumors. The mutation rates for the first and second mutations are estimated to be 1.5-10% and 2-7%, respectively. The data support the idea that cancer can arise through multiple stages, each involving somatic mutations. The study also discusses the distribution of retinoblastoma cases by type and laterality, and the relationship between mutation rates in hereditary and nonhereditary forms. The findings align with current theories on the mutational origin of cancer, suggesting that retinoblastoma can be caused by two mutations, each occurring at a rate of about \(2 \times 10^{-4}\) per year.