Recorded: 03 Jun 2016
And in about 1996/97 a new postdoc came to the lab who wanted to work on the enzyme telomerase and telomerase is a gene which extends the ends of chromosomes. It was implicated, I’ll be it in a not very convincing way in immortalizing cells – that is converting cells with a limited number of replicated doublings into cells whose progeny could proliferate forever. The process of cell immortalization. And this man – his name was Christopher Counter, came as a new postdoc and said ‘I want to work on telomerase.’ And I said to him ‘Well, telomerase is a very interesting problem – nobody in this lab works on telomerase, but I can’t let you work on telomerase because it is my role, my holy duty as your mentor to force you to work on something different than you worked on as a graduate student. You already worked on telomerase. You should be working on something else to broaden your perspective.’ And he said ‘Well that’s very good advice.’ And over the next week, proceeded to recruit another post doc Matthew Meyerson so that they could work together on telomerase – which indeed they did. And they isolated the yeast telomerase gene, sequences from Tom Cech’s laboratory and they were able to isolate the human telomerase gene and that seemed to be in fact maybe a missing ingredient in the cocktail of genes that was required in aggregate to collaborate to force a normal human cell to grow like a cancer cell. And therefore in 1999, Bill Hahn who is actually at this symposium here at Cold Spring Harbor, he showed that a cocktail of five genes was required in order to convert a normal human cell into a cancer cell. As opposed to two genes for a rodent cell – like a mouse or a rat normal cell going into a cancerous state and why our cells are so much more resistant to transformation is complicated. We still don’t understand all of the reasons. But one of the reasons is that our cells lack enough telomerase to empower them to grow indefinitely. Still, that was from my lab very useful because it meant that we could begin to generate a whole series of genetically defined human cancer cells. Well, one can say its easy to get human cancer cells, you just isolate them from a patient’s tumor and you sequence it and you know exactly what it is that’s causing the cancer cell to grow abnormally. But in truth, if you take the DNA of a human cancer patient’s cells and you sequence it – you see there’s hundreds and thousands of changes in the genome in the genes of the cancer cell. And it’s not always obvious which of those changes are relevant for creating cancer and which are irrelevant and just distractions. On the contrary, if one put in a defined set of genes, one could really create genetically defined human cancer cells with a precise causes of the cancerous growth of the cells could be defined with precision and accuracy and in a robust fashion.
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.