Johannes Müller (1838): Cancer tissue is built up by cancer cells. Placed the cancer cell in the center of the oncological interest.
Rudolf Virchow (1855-1863): Extended his aphorism—Omnis cellula a cellula—to cancer.
Theodor Boveri (1914): Somatic mutation theory of cancer: Malignant neoplasms develop from a single cell that acquired a certain abnormality in its chromosome.
Dulbecco and Sachs (1960-1961): Neoplastic transformation of mouse and hamster cells by DNA viruses; viral DNA is permanently integrated into the cellular DNA.
Howard Temin (1960-1964): Provirus hypothesis: The RNA of a tumor virus acts as template for synthesis of DNA and is integrated into the cell genome as a provirus. It can serve as a template for progeny RNA viruses and can lead to malignant transformation in progeny cells.
Berwald and Sachs (1965): Neoplastic transformation of mammalian embryo cells in cell culture by carcinogenic chemicals.
Huebner and Todaro (1969): Viral oncogene hypothesis: Cells of vertebrates have viral genes that they transmit vertically to progeny cells. These can be activated by carcinogenes, irradiation, or aging and lead to cancer.
Martin, Vogt, and Duesberg (1970-1973): Investigated first viral oncogene src with src-deletion mutants.
Bruce Ames (1973-1975): Identified mutagens in salmonella assay; correlation between mutagenic and carcinogenic properties in chemicals: Carcinogens cause cancer through their ability to mutate genes. (Weinberg: this will “become the credo of our religion.”)
Michael Bishop and Harold Varmus (1976): Viral oncogene src is not a true viral gene but a normal cellular gene. It controls cell division and growth. Normal cells carry potential cancer genes—proto-oncogenes—that can be activated to oncogenes.
Robert Weinberg, Geoffrey Cooper, and others (1981): Activated oncogenes from cancer cells transferred into NIH 3T3 mouse fibroblasts induce their malignant transformation.
Weinberg, Barbacid, and Wigler (1982): Human ras oncogene is activated by point mutation.
Sporn, Roberts, and Todaro (1980-1985): Cancer cells produce and respond to their own growth factors (autocrine secretion).
Cavenee, White (1983): Discovered tumor suppressor gene in retinoblastoma.
