Eric Lander Interview (page: 5 / 9) Founding Director, Broad Institute	Print Interview

How would you explain -- to someone who doesn't know what a genome is -- what makes this project so exciting? Let's start with genes themselves. Why are genes so important?

Get the Flash Player to see this video. Eric Lander: Genes code for all the protein components of the body. Basically, genes are the information storage of heredity. The human being has a total of 100,000 genes, give or take, and that sum total of all the genetic information is called the "genome." If we can completely understand the structure of the human genome, then we have a complete component list of all of the proteins that the body makes. In a sense, that goal, the Human Genome Project, is very much akin to the revolution in chemistry that happened in the period of about 1869 to 1889, when all of matter was described in terms of a finite list, a finite chart that captured its properties. That changed the face of chemistry, because it meant that matter was predictable, through only a finite number of elements. Biology now is getting its own periodic table. In the 21st Century, we will know that the human body is composed of some set of 100,000 proteins, and all biological programs will start from that list. If you want to understand any particular thing, you've got to understand it in terms of those components. There aren't any more components to go look for, at least at the level of proteins. So the effect on biology in the next century will be much like the effect on chemistry in this century. For chemists, the predictability of matter gave rise to industries, the chemical industry. The mysteries of the periodic table, and why there were rows and columns of elements, gave rise to some of the deepest theories of this century, quantum mechanics. I think so, too, understanding the component list of the human body, the human genome, will give rise to both very practical consequences and very theoretical consequences. The students looking back, 20 years from now, will not be able to imagine what it was like to practice biology without these tools. Indeed, they'll assume they were always there. They will look back to this earlier period with a romantic notion, like 19th Century African explorers going off into the jungle with their machetes, searching for a gene and sometimes coming back triumphant with a gene in hand, and sometimes never being heard from again. But that romantic picture of exploring the deepest, darkest continent of biology will be replaced by a Landsat image with accuracy down to the single DNA letter. It will be a very different world, and it will be hard to imagine what anything was like before it.

[ Key to Success ] Vision

It seems like we're about to come over a hump, like the crest of a hill, and the view from the top will be very different from what we can see now.

Eric Lander: It will. That's not to trivialize in any sense the work that has to come. In some sense, the description of genomes is just the start. All it does is it lays out the 100,000 components on the surface of the table. It doesn't tell us how they act. It doesn't tell us their roles. It doesn't tell us the circuits they build. It doesn't tell us the variation in the population. In some sense, it will be seen not as the culmination that the media today wants to associate with the Genome Project, but as barely the start. Indeed, I don't view the sequencing of the human genome as itself a goal. I view it as the starting line, not the finish line in any particular race.

But these are the next frontiers, aren't they?

Get the Flash Player to see this video. Eric Lander: The next frontiers are to understand how organisms work from a global perspective. Up to now, we've been trying to study processes like cancer one gene at a time. We have the problem of the blind man and the elephant. Some cancer researcher is feeling the trunk and describing the elephant to be one thing, and someone is back at the tail feeling it to be something else, and others are down at the hard toenails, and they're all describing the same elephant, because we don't have a global picture of all the components. It sounds like we're talking of very different things. The exciting thing to me is that in the next decades ahead, we're going to be able to take any medical process, any cellular process, and describe it in terms of the activity of all 100,000 genes simultaneously. We'll step back and we'll see patterns, we'll see continents emerge that were completely unclear when we were down on the ground.

You've already done significant work in the area of cancer, hypertension and diabetes. Can you tell us a little bit about where this is going?

Get the Flash Player to see this video. Eric Lander: Much of the work of the 20th Century human genetics has been understanding the basis of relatively rare genetic diseases -- cloning genes for simple Mendelian traits, traits that show simple transmission through families. It has been tremendously important, but in point of fact, it's not the majority of burden of disease. Most of the diseases that affect people are common genetic diseases which are polygenic in origin. Much of my own research interest, much of what my lab has worked on, is the tools to dissect polygenic diseases. Genes where there are multiple components, working together with environment. But it has got to be said this is still in its infancy. The tools to dissect polygenic traits really are just beginning to get going. We have some examples of them, and we can point to examples in cancer, for example, a modifier gene in cancer, where there's a particular genetic mutation that causes an intestinal cancer. It exists both in the human and in the mouse. And in the mouse, we learned that if you move that mutation from one strain to another by breeding, some strains don't die of that cancer -- in fact, get very few polyps in their intestine -- and others do. So there are modifier genes that can change the course of this cancer, and that's a polygenic interaction. A much subtler interaction. So in that particular case, we've been able to identify what that gene is, and it begins to point us to the pathways that may be involved.

There are a few more examples like that, but I think this is the work of the 21st Century. To tease apart the much more textured, much more complicated picture of the common genetic diseases. If there was any one problem I would say my scientific career revolves around, it's that problem of trying to tease apart complex disease. But I say "revolves around," rather than just "focuses on," because to answer a question like that, one has to build tools, apply them and test them, and then build new tools. So much of my career swings back and forth between building new methods, testing them, building new methods, testing them. One hopes we can verge, in the next couple of decades, on a set of general and powerful tools that will let us do it for any disease. There are some ideas out there of how that could happen.

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