Why all the chickens?

Chickens have played a central role in cancer research. The first tumor viruses were discovered by Bang and Ellerman in the early 1900s as "filterable agents" (i.e. things that were smaller than bacteria) that caused lymphomas in chickens. Shortly thereafter Rous discovered a virus in chickens which caused solid tumors called sarcomas. Both of these viruses were shown to have RNA rather than DNA as their genetic material and therefore became known as "RNA tumor viruses". In the late 1950s Temin and Rubin showed that such viruses could be quantitatively studied in cell culture-- Rous sarcoma virus could cause cancer-like foci of "transformation" in a dish of normal chicken cells. Because transformation was stably inherited in infected cells, Temin proposed that RNA tumor viruses converted their genomes into DNA and integrated into the cellular DNA. This heretical proposal went against the "central dogma" of molecular biology that "DNA makes RNA makes protein". However, Temin was eventually proven right when his own lab and David Baltimore independently demonstrated the existence of a viral enzyme called reverse transcriptase that could convert RNA into DNA. Because of this "backwards" flow of information, these viruses then became known as "retroviruses". Evidence from several laboratories in the 1970s demonstrated that Rous sarcoma virus had an "extra" gene which was not required for viral growth, but was required for oncogenic transformation. Such genes became known as "viral oncogenes". Perhaps the biggest surprise came in the mid-1970s when Stehelin, Varmus, Bishop, and Vogt demonstrated that the viral oncogene of Rous sarcoma virus (v-Src) had actually been captured from a normal cellular "proto-oncogene" (c-Src). Furthermore, a closely related gene was also found in humans. Other viral oncogenes of cellular origin were then identified including v-Myb of the avian myeloblastosis virus. In the 1980's it was shown that these cellular "proto-oncogenes" could be converted to active oncogenes by various means including chemical mutagenesis, viral insertional mutagenesis, gene amplification, and chromosomal rearrangement. In particular, a number of these genes were found to be consistently activated in specific types of human cancer. Such genes are therefore the targets of intensive research for improving the diagnosis and treatment of human malignancies.

Varmus, H.E., and Levine, A.J. 1983.  Readings in Tumor Virology, Cold Spring Harbor Laboratory Press, NY. A useful collection of classic papers in tumor virology up until the early 1980s.

Varmus, H.E. 1990. "Retroviruses and oncogenes. I." Bioscience Reports, 10: 413-30. A personal account of the work that led to the discovery of cellular proto-oncogenes and a Nobel Prize for Bishop and Varmus.

Bishop, J. M. 1995. "Cancer: the rise of the genetic paradigm." Genes and Development, 9:1309-15. A vivid overview of the history and major concepts of oncogenes and tumor suppressor genes.

Cooper, G.M. 1995. Oncogenes, 2nd ed., Jones and Bartlett Publ, Sudbury, MA. A readable, book-length review of the field of oncogenes and tumor suppressor genes.

Cooper, G.M., Temin, R.G., and Sugden, B. 1995. The DNA Provirus: Howard Temin's Scientific Legacy, ASM Press, Washington, DC. A tribute to Temin and his influence on retrovirology.

R.A. Weinberg. 1996. Racing to the Beginning of the Road, Harmony Books, NY.  A very readable personal perspective on the history of oncogenes and tumor suppressor gene research. 

Coffin, J.M., Hughes, S.H., and Varmus, H.E. 1997. Retroviruses, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY. The New Testament. A revision of the classic "blue bible" (RNA Tumor Viruses) with a greater emphasis on virology and a lesser emphasis on oncogenes.

Weinberg RA. 2007. The Biology of Cancer, Garland Scientific.  A comprehensive textbook on modern cancer biology.