2017-10-04

Glycolysis, cancer and metabolomics

Born in 1928, American molecular biologist James Watson is best known for jointly discovering the structure of DNA, for which he shared the 1962 Nobel Prize in Physiology or Medicine. His long career has also seen him launch the Human Genome Project. [Listeners: Martin Raff and Walter Gratzer]

TRANSCRIPT: But everybody's now excited by glycolysis. There appeared several articles in the 'New York Times', one by Gina Kolata had written this article which certainly I didn't want which said I said cancer would be cured in two years. You know, it was a sort of survey of where are we going in cancer research and if you’d read the articles you'll just have a feeling that the only thing we can be sure of is that the drugs are more expensive, but that you'll still die. So you'll take drugs which might give you six months more life, cost a lot of money, but the grim fate still will hit you. And so I decided to write an article which I entitled 'Cure Cancer Today, Not Tomorrow,' saying that maybe we finally, with understanding the Warburg Effect, actually know everything that's wrong in cancer or we will soon know it because there's now big cancer genome projects in which we're just sequencing cancers and finding out exactly what's wrong with them. So we'll know all the sort of genetic causes, so all the things we'll want to inhibit and we'll see if anything new that can't be, you know, it's not apoptosis, it's not telomerase, so on. I would say the odds are at least 50% we finally have the big picture. Three years ago we didn't because Bob Weinberg in his very good book, the 'Biology of Cancer', you know, some 700 well illustrated pages. If you look in the index, there's not one reference to Warburg, glycolysis, or lactic acid, which I did have in the second edition of 'Molecular Biology of the Gene'. I had increased glycolysis. So in 1970, I started, but then I lost faith in it and in the third edition of 'Molecular Biology of the Gene', Warburg and glycolysis was gone. I was, you know, happy writing, there was more material on tumor viruses and I wasn't thinking glycolysis at all. But the, you know, basic intermediary metabolism of cancer cells is very different from that of non-proliferating cells. So the article came out and a few scientists wrote me saying, you know, they liked it, but the people who really liked it were sort of intelligent outsiders who had read the series of articles about cancer and could only, you know, regret having read them 'cause it just leaves you sort of in despair as to where we're going despite spending all this money. So they liked the idea that I actually said it was important who President Obama appoints as the new head of the Cancer Institute. We actually need a general who believes he knows how to cure it and just tries and isn't really worried by a lot of people saying it's, oh, we need ten more years of knowledge, which is easy to say because then you don't fail, you're bound to get more knowledge. So – and - so I was in a major cancer institute recently and to my amazement, the director had just never heard of glycolysis. So, you know, the molecular biologists don't think biochemistry. And so the cancer field is now controlled by molecular biologists. You know, whereas, you know, when I was a boy, molecular biologists didn't exist and the big people that everyone respected were the good biochemists, starting with Warburg. And so you read a lot about how DNA is made and transcription and all that and, you know, the krebs cycle. I never learned it. There are a couple of places where if it’s interfered with it does cause cancer, it fits into a rational explanation. So I think anyone working on cancer ought to really know, think metabolism and this new field of metabolomics, where you try and describe all the small molecules present in a cell and quantitate them. How much glucose is there, or you know, how much of the glycolytic intermediates, what might be limiting? Just to get a feeling of the flow of cellular building blocks, how much, how you can stop them, which, you know, uses mass spec. It's sort of expensive biochemistry in its infancy, but - and I was told, I said, how many small molecules are there in the cell? And I think on the most complete metabolic chart, you get about 300. But they said there's 1200, so lots of pathways we probably don't know exist. And you know, just like, you know, now we have the human genome, there are lots and lots of proteins whose function has not been described. I think half the proteins' functions haven't been described, unknown. So you know, if I were, you know, doing a PhD, I'd do it metabolomics, you know, if you wanted to be a biochemist because you're likely to get a good job afterward, 'cause everyone will see the need for it.

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