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Question: What does your research consist of on a day-to-day basis?

Michael Wigler: Our lab studies the genome of organisms and also the genome of cancer cells.  And we work on two kinds of problems: the evolution and outcome of cancers, and also on genetic disorders of a spontaneous sort, that is, non-heritable genetic disorders.  And those are two very—it sounds like two very different things, but they’re related by our methodology, which is genomic analysis.

What we do is called difference analysis, for example, if we’re looking at a cancer, we’ll want to see where that cancer has mutated relative to the genome of the person who gave rise to that cancer.  That’s differential genomic analysis.  And it tells us where the cancer has mutated.  And from the types of mutations, the number of mutations, we can infer a lot about cancer etiology. 

Question: Is biology becoming a more quantitative than qualitative science?

Michael Wigler: Well, biology has always been influenced strongly by quantitative types.  Many physicists in the late ‘30s, early ‘40s, ‘50s, came into biology, strongly influenced it.  There was a period, I would say, from the time I was a graduate student in the mid-‘70s until the mid- to late-‘90s, where it was not particularly quantitative, and that was largely because of the revolution in recombinant DNA.  So, really all you needed to be a good biologist was a good sense of logic and a good imagination.  And mathematical and statistical skills weren’t really that necessary for much of biology.  And I was in that group actually.  I had studied earlier on as a mathematician but I used almost none of those mathematical tools when doing biological research.  Of course, the logic comes in handy, but the tools were not very valuable.  There was no place for them because the kind of data that we were getting was very individual data and I actually had a rule of thumb. I actually disliked statistics early on in my life and I felt that if I needed to do statistics to see what I was observing, then I wasn’t really observing anything. 

But that changed with the advent of the sequencing of the human genome.  That changed everything.  And the development of new high throughput methods of extracting data, it forced biologists to reconsider the value of statistics and mathematics in the analysis of their subject.  So, a number of biologists moved in that direction.  Not a lot, but quite a number did.  And I was one of those who moved in that direction.

Question: How has the sequencing of the genome “changed everything”?

Michael Wigler: You know, we are so close, historically, to that period, and the data that’s coming out of that effort is still being generated.  I think it’s very hard for any of us to really judge the impact that it has had.  It was a huge revolution in terms of the kinds of experiments one can conceive of doing.  The only thing comparable in my lifetime was the recombinant DNA revolution which changed entirely the kinds of experiments people did.  

Since sequencing methods are changing so fast, the cost of sequencing has dropped enormously.  And with each drop in the cost, it changes entirely how you think of attacking the problem.  So, in a few years from now we’ll be in a position to have DNA sequence of a very high quality for a million people and know the medical history of these million people.  And there’ll be—I don’t even think our computers are yet to a stage where they will be able to handle data of that type and the kind of analysis tools that will be needed to analyze that haven’t been developed yet.  So, we’re in a really a strange point in the history of biology where things are changing so rapidly, we can’t quite see the shape of the future yet.

Recorded April 12, 2010

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