16 - The Michigan Daily - Friday, September 22, 2000 FRIDAY Focus 1 d one oft ose5 io anno nCedt tat t .a genome was Imostcomplete4y se uCe ac i ne was On Cam wnt Ts pas icnd auture Cere iat he cnivesis_ orkatt .i _heut.eofe.c re;re t te nveritS Francis Collins, director of the Nation al Human Genome Research Institute, began his interest in genetics as an undergraduate student at the University of Vir- ginia, where he received his bachelor's degree in chemistry. Collins went on to receive his PhD. in physical chemistry at Yale University. Following his graduation from Yale, Collins enrolled in medical school at the University of North Carolina, where he entered the field of medical genetics. Collins began working at the University in 1984 as a research team leader. His team successfully identified the genes for cystic fibrosis, neurofibromatosis and Hunt- ington's Disease, a fatal brain disordr. In 1993, Collins accepted the position of director at the research institute, second only to James Watson, the co-dis- coverer of the geo- yshape of * n M ,DNA - the double helix C o 11 i n s now leads the Human Genome Project, which aims to map human DNA by 2005. Last June, Collins joined President Bill Clinton in announcing to the world that human DNA was 85 percent sequenced. The Michigan Daily: Has any of the work you did here at the University been able to aid you in what you're doing now? Francis Collins: Oh yeah. When I was here, my research lab was focused on trying to find specific genes that are responsible for certain genetic disorders. A lot of my work in the 1980s was trying to find the Cystic Fibrosis gene which we finally succeeded at in 1989, right over there in the (Medical Science Research Building) research complex of the Medical School. That was incredibly difficult to do because we didn't have any of the research tools. We didn't have a sequence, we didn't have maps, we didn't have anything. Every time you tried to do something it was like feeling your way in the dark. It was a very strong motivator to get interested in the idea of having the whole human genome figured out once and for all. In fact, I applied for, and received one of the first genome center grants in 1990 when the genome project was starting. I was one of the people who was setting up the research program to get the job done. After being here for three years running that center, the chance came up to go and direct the whole enterprise at NIH. It was pretty hard to decide to do that because I was pretty happy here, but after a while I decided it was too good to pass up. TMD: What are your goals for the National Center for Human Genome Research, since you are only the second director, behind James Watson? FC: Well, the Genome Institute -it's now an institute, it started out as a center. It's called the National Human Genome Research Institute. Over the course of the past 10 years we have gone through a detailed process of scientific analysis and consultation with the scientific community about what our goals ought to be, so it's not just I decide one day, 'Okay I think we should do this and tomorrow we'll do that.' We have a series of five-year plans that enu- merate with a fair amount of specificity what we should be trying to do and while the sequencing of the genome has got all the attention, there are seven other goals that we're working on right now that are equally important if we're going to understand what this script is telling us about human biology. That includes things like understanding the variations that make us all different from each other, understanding how it is that these genes direct proteins because that's what they do and how do we begin to understand how those proteins function. We need better computational methods to deal with this massive amount of data that's being pro- duced. That's also part of our work, is to develop those computer methods. And the whole ethical, legal and social issues compo- nent is part in parson of our research agenda. We don't think that should be left to chance or for somebody else to deal with. That's part of our responsibility too. TMD: Why did you, from the National Human Genome Institute, and J. Craig Venter, CEO of Celera Genomics, announce that the human genome was approximately 85 percent sequenced instead of waiting until it was complete? FC: We had set a milestone a year and a half before, that we were going to try to achieve this draft coverage of 90 percent of the sequence by a certain date, mainly June of 2000. People were very interested in that and were watching our progress on a daily basis because of course we were putting it up on the Web, so it was hardly a secret. When it got to the point when it was pretty clear we were going to make that deadline, a lot of folks felt this was an occasion to try "I think I have to gain some , Francis Collins, director of the National Human Genome Research Institute, speaks outside the Rackham Building on Monday after addressing the School of Public Health's annual symposium. way to try to understand the natural world. It allows you to do experiments and ask rigorous questions and get vigor- ous answers. But I think most of us have a sense there maybe is a little more to the world than the mechanical parts, that sci- ence is appropriately organized to inves- tigate and that gets more into the spiritual realm. I have no examples to report of circumstances where what I know as a rigorous scientist has collided with what I believe as a person of faith. I find them actually quite delightful to integrate, and being a scientist who's exploring the anotier bi o l o gica nature of m increased career in me, in degree of pub- lic interest. The couple of them, President of the United States know what they has been very interested in this project for Head of the a long time. Specifically, he --- wanted to be involved in some sort of announcement. So, we decided that was a rea- sonable thing to do. Although. I'm actually going to be more excited about these papers we're working on right now that describes what it is that we found in the sequence. The announcement in June was more sort of a odometer moment where you say you've went past a certain point. But it was pretty exciting. it was a defined moment in history where you can say "Okay, we've got most of it." And to finish it, to actually get to 100 percent will take the better of'the next two and a half years. The last part is always the hardest. It's the part that didn't come through easily, so you're going to have to develop some new ways of getting your hands on it. Getting to 90 percent, much of that got done in the six or nine months before June of 2000, the last instances will take us a lot longer. TMD: When is the projected outcome that you will be done? FC: We're aiming to have finished all of the human chromosomes in a highly accu- rate form with no gaps by April 25, 2003, the 50th anniversary of the publication of the double helix. And if we can do it sooner, we'll do that too. TMD: During our research, we found that you're pretty religious. How do you balance your religious beliefs and your scientific work? - FC: I actually find it easy to balance, and quite comfortable to have both a sci- entific worldview and a religious world- view coexisting within me. Science is the raybe a but I don't y are." - Francis Collins National Human Genome Research Institute human beings is also an experience that makes you appreciate the amazing nature of the whole biological world. So, I think actually TMD: The University has been plan- ning an extensive Life Sciences Institute for some time now. What do you think is important for the University to do to cre- ate the best program possible? FC: Well I think it's terrific that they've identified this as a very high priority for this very strong and vigorous University. I would say they need to bring in the best people. This is a strong University and they should have a good chance to reach the top people in the fields. They should set this up in a fashion where it's very inter-disciplinary because genomics is a combination of biology with computer science with engineering with automation experts, with medicine. It's not one of those things you go off in a corner and do by yourself. It's a very team-oriented multi- disciplinary enterprise. For a successful genomic research program you want to have strength in all those areas. Take particularly the field of computational biology where you have folks who are equally at home writing a program in some computer language and understanding the intricacies of how mito- chondria work. You want those people particu- larly well represented. If I was starting right now with graduate studies, that's the field I'd go into. Certainly this Life Sciences Initiative has identified that as an area of worth. TMD: What do you think a Life Sci- ences Initiative can accomplish that sepa- rate University programs in fields like biology and chemistry can not accomplish on its own? FC: Well, as I said, genomics has much of its promise tied up in the need to be interactive between disciplines. You're going to see genomics flourish in individual departments. Not only do you need people with different perspectives on science sitting in the same room trying to tackle problems - the chemist, the physicist, the engineer, the biolo- gist, the com- 0 0 there's a terrible myth or rumor out there that if you're going to be a rigorous sci- entist, you have to put your faith on the shelf and if you're going to be a person of faith, science is dangerous. Those are not true, and there are a lot of biologists who feel the same way. TMD: What comes after the entire genome is sequenced? FC: Well, we have to figure out what it means. We have a 3 billion letter textbook which we can't understand, written in a funny alphabet with only four letters, a lot of' which seems to be filler, but we're not quite sure. And it's going to take us decades to really unravel the significance of what all these letters are trying to tell us. There are some parts we under- stand better than others. If you really look at what we know, it's enormously dwarfed by what we don't. So, there's going to be lots of fantas- tic science to be done. Occasion- ally students "I think most of us have a sense there maybe is a little more to the world than the mechanical parts .that gets into the spiritual realm. " - Francis Collins Head of the National Genome Research Institute puter scientist - - but you also need core facili- ties that no sin- gle investigator can easily put together. A lot of it is very tee h n olo g y based. Why do you need an ini- tiative instead of just more of the same? To pull *I come up to me and say 'I've missed out. I want to understand biology and it's all been done.' Well no, we have lots of opportunities for terrific careers in biological science. A lot of the things that were very limiting have been sort of pulled away because now you have this database you can start to work with. Science is going to be done very dif- ferently now in terms of understanding human biology, but it can be done more powerfully and you get a lot more answers to a lot more questions. TMD: Where do you see the life sci- ences heading in the next few years? FC: Life sciences are many in number and very interactive with each other. Some are going to be more immediately affected by this than others, but I think it's fair to say there is no life science that won't be touched by the enonme p nroiect in the 'minAr vears I wAid people together around common scientific questions, and also to allow them to collect resources, like how the technology can answer those questions. TMD: Do you plan on remaining linked to the University? FC: Oh gosh, I don't know. They've been very kind to let me stay on here in my profes- sor-on-leave capacity, which doesn't cost them anything. It's nice to have the connection. I have another connection in that my wife is on the faculty here and it's a reason to come back to Ann Arbor fairly often. My daughter is here as a social worker. So there's lots of connec- tions with Ann Arbor. I have no idea what I'm going to do after I get to the point of no longer being the right person to run the genome pro- ject. And I don't know when that will be. I hope I'll know it before everyone else has fig- ured it out. That's my worst nightmare, to sort nf hana on while evervone elsie i svine .. ;', ., e .'e t, : .w '. ad {: ,. i:, . v .. .ln I J }':. . ... s . . 3',Y.y: Ra u". I