Recorded: 03 Jun 2016
By 1982 we discovered that a Ras oncogene could convert a normal cell into a cancer cell – in fact it soon became clear that things were more complicated than that. First of all the Ras oncogene differed from the normal corresponding gene by a single base change. And secondly, the so called normal cells we were working with were not normal at all – they were mouse cells that were slightly precancerous and were just tipped over the edge through the introduction of the Ras oncogene. There might have been a fleeting period of weeks when I might have thought that a single point mutation, a single nucleotide change in a normal Ras gene would create a cancer cell. But that seemed to me absurd, because cancer development was known already to take many years and decades and ostensibly multiple steps in a complex Darwin-like evolution. And so by 1983 we discovered that if you put the Ras oncogene into a fully normal cell rather than do a slightly abnormal cell – the fully normal cell would not respond and that led to the realization in 1983 by Hartmut Land and Louis Parada that one needed to put two oncogenes into the cell at the same time. They would collaborate with one another, they would conspire, and that created the conceptual paradigm, at least in my mind, that the process of cancer formation involved the successive mutation of multiple genes – not just a single gene. In other words, it wouldn’t be the case that simply mutating a single gene in a single cell in one of our tissues could create a cancer on its own. But that on its own didn’t solve the whole problem. Because as we learned soon after, if you took a normal human cell and put in those two collaborating oncogenes – the human cell would just sit there and smile and not do anything and that already led by the mid-1980s to the realization that it was very difficult to transform human cells from normal to cancerous in contrast to mouse cells. And so that, that question remained unanswered – why it was so difficult – for a number of years.
Robert "Bob" Weinberg is Daniel K. Ludwig Professor for Cancer Research and director of the Ludwig Cancer Center at MIT, an American Cancer Society Research Professor, and is a founding member of the Whitehead Institute for Biomedical Research.
In 1982 he was one of the scientists to discover the first human oncogene, Ras, which causes normal cells to form tumors, and his lab also isolated the first known tumor suppressor gene, Rb.
He co-authored with Douglas Hanahan the landmark "Hallmarks of Cancer" paper in 2000, which laid out the six requirements for a healthy cell to become cancerous.