Alfred G. Knudson, Jr. was a man ahead of his time when he proposed the "two-hit" hypothesis for cancer in 1971. In those days, it was generally accepted that cancer was usually a sporadic event, but in the cases that appeared to be familial, it was believed that the disease was a dominantly inherited trait that would inevitably lead to expression of the disease. By studying families with retinoblastoma, a cancer of the retina of the eye, Knudson noticed that there was a significant difference between patients with respect to the numbers of tumors present. A check of the records revealed that all the patients with multiple tumors had other family members with retinoblastoma whereas those patients with only one tumor had no family history of the disease.

To try to explain the discrepancy, Knudson used a mathematical model and hypothesized that retinoblastoma was actually a recessive disorder that...