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Until the late fifties, Rous sarcoma virus had been shown to cause tumors only in live chickens. Temin, working closely with Harry Rubin, wanted to study how the virus converted normal cells into cancer cells. To do this, they needed a vastly simplified system—a system free of chickens and tumors, and analogous to bacteria in a petri dish. And so Temin imagined creating cancer in a petri dish. In 1958, in his seventh year in Dulbecco’s lab, Temin succeeded. He added Rous sarcoma virus to a layer of normal cells in a petri dish. The infection of the cells incited them to grow uncontrollably, forcing them to form tiny distorted heaps containing hundreds of cells that Temin called foci (the plural of focus). The foci, Temin reasoned, represented cancer distilled into its essential, elemental form: cells growing uncontrollably, unstoppably—pathological mitosis. It was the sheer, driving power of Temin’s imagination that allowed him to look at a tiny heap of cells and reimagine that heap as the essence of the diffuse systemic disease that kills humans. But Temin believed that the cell, and its interaction with the virus, had all the biological components necessary to drive the malignant process. The ghost was out of the organism.

Temin could now use his cancer-in-a-dish to perform experiments that would have been nearly impossible using whole animals. One of his first experiments with this system, performed in 1959, produced an unexpected result. Normally, viruses infect cells, produce more viruses, and infect more cells, but they do not directly affect the genetic makeup, the DNA, of the cell. Influenza virus, for instance, infects lung cells and produces more influenza virus, but it does not leave a permanent fingerprint in our genes; when the virus goes away, our DNA is left untouched. But Rous’s virus behaved differently. Rous sarcoma virus, having infected the cells, had physically attached itself to the cell’s DNA and thereby altered the cell’s genetic makeup, its genome. “The virus, in some structural as well as functional sense, becomes part of the genome of the cell,” Temin wrote.*

This observation—that a DNA copy of a virus’s genes could structurally attach itself to a cell’s genes—intrigued Temin and Dulbecco. But it raised an even more intriguing conceptual problem. In viruses, genes are sometimes carried in their intermediary RNA form. Certain viruses have dispensed with the original DNA copy of genes and keep their genome in the RNA form, which is directly translated into viral proteins once the virus infects a cell.

Temin knew from work performed by other researchers that Rous sarcoma virus is one such RNA virus. But if the virus genes started as RNA, then how could a copy of its genes convert into DNA? The central dogma of molecular biology forbade such a transition. Biological information, the dogma proposed, only travels down a one-way street from DNA to RNA to proteins. How on earth, Temin wondered, could RNA turn around acrobatically and make a DNA copy of itself, driving the wrong way down the one-way street of biological information?

Temin made a leap of faith; if the data did not fit the dogma, then the dogma—not the data—needed to be changed. He postulated that Rous sarcoma virus carried a special property, a property unprecedented in any other living organism: it could convert RNA back into DNA. In normal cells, the conversion of DNA into RNA is called transcription. The virus (or the infected cell) therefore had to possess the reverse capacity: reverse transcription.

Excerpted from pages 351-352 of ‘The Emperor of All Maladies: A biography of Cancer’ by Siddharth Mukherjee