Sequencing the Genome “Changed Everything”

Question: What does your research consist\r\n of on a day-to-day\r\nbasis?


Michael Wigler: Our lab studies the genome \r\nof organisms and\r\nalso the genome of cancer cells. \r\nAnd we work on two kinds of problems: the evolution and outcome \r\nof\r\ncancers, and also on genetic disorders of a spontaneous sort, that is,\r\nnon-heritable genetic disorders. \r\nAnd those are two very—it sounds like two very different things, \r\nbut\r\nthey’re related by our methodology, which is genomic analysis.


What we do is called difference analysis, for \r\nexample, if\r\nwe’re looking at a cancer, we’ll want to see where that cancer has \r\nmutated\r\nrelative to the genome of the person who gave rise to that cancer.  That’s differential genomic\r\nanalysis.  And it tells us where\r\nthe cancer has mutated.  And from\r\nthe types of mutations, the number of mutations, we can infer a lot \r\nabout\r\ncancer etiology. 


Question: Is biology becoming a more \r\nquantitative than\r\nqualitative science?


Michael Wigler: Well, biology has always \r\nbeen influenced\r\nstrongly by quantitative types. \r\nMany physicists in the late ‘30s, early ‘40s, ‘50s, came into \r\nbiology,\r\nstrongly influenced it.  There was\r\na period, I would say, from the time I was a graduate student in the \r\nmid-‘70s\r\nuntil the mid- to late-‘90s, where it was not particularly quantitative,\r\n and that was\r\nlargely because of the revolution in recombinant DNA.  So,\r\n really all you needed to be a good biologist was a good\r\nsense of logic and a good imagination. \r\nAnd mathematical and statistical skills weren’t really that \r\nnecessary\r\nfor much of biology.  And I was in\r\nthat group actually.  I had studied\r\nearlier on as a mathematician but I used almost none of those \r\nmathematical\r\ntools when doing biological research. \r\nOf course, the logic comes in handy, but the tools were not very\r\nvaluable.  There was no place for\r\nthem because the kind of data that we were getting was very individual \r\ndata and\r\nI actually had a rule of thumb. I actually disliked statistics early on \r\nin my\r\nlife and I felt that if I needed to do statistics to see what I was \r\nobserving,\r\nthen I wasn’t really observing anything. 


But that changed with the advent of the sequencing \r\nof the\r\nhuman genome.  That changed\r\neverything.  And the development of\r\nnew high throughput methods of extracting data, it forced biologists to\r\nreconsider the value of statistics and mathematics in the analysis of \r\ntheir\r\nsubject.  So, a number of\r\nbiologists moved in that direction. \r\nNot a lot, but quite a number did. \r\nAnd I was one of those who moved in that direction.


Question: How has the sequencing of the \r\ngenome “changed\r\neverything”?


Michael Wigler: You know, we are so close, \r\nhistorically, to\r\nthat period, and the data that’s coming out of that effort is still \r\nbeing\r\ngenerated.  I think it’s very hard\r\nfor any of us to really judge the impact that it has had. \r\n It was a huge revolution in terms of\r\nthe kinds of experiments one can conceive of doing.  The\r\n only thing comparable in my lifetime was the recombinant\r\nDNA revolution which changed entirely the kinds of experiments people \r\ndid.  


Since sequencing methods are changing so fast, the \r\ncost of\r\nsequencing has dropped enormously. \r\nAnd with each drop in the cost, it changes entirely how you think\r\n of\r\nattacking the problem.  So, in a\r\nfew years from now we’ll be in a position to have DNA sequence of a very\r\n high\r\nquality for a million people and know the medical history of these \r\nmillion\r\npeople.  And there’ll be—I don’t\r\neven think our computers are yet to a stage where they will be able to \r\nhandle\r\ndata of that type and the kind of analysis tools that will be needed to \r\nanalyze\r\nthat haven’t been developed yet. \r\nSo, we’re in a really a strange point in the history of biology \r\nwhere\r\nthings are changing so rapidly, we can’t quite see the shape of the \r\nfuture\r\nyet.

Recorded April 12, 2010

The revolution sparked by the Human Genome Project will soon produce more genetic information than our computers can currently handle.

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