TR: Apparently, Celera and the Human Genome Project are still negotiating a joint publication of the genome data. What has your role been in these discussions?
LANDER: Oh, I talk to everybody in the community. This is a public service project and I think it would serve the world well for everyone to be talking. I find the racing and the acrimony to be kind of silly and I don’t see why everyone isn’t managing to work together in mature ways. What is the benefit of a field in which everybody talks to each other? Progress is made much more quickly. That has always been the case in science.
TR: What does it mean for the genome project to be finished?
LANDER: The truth is that the human genome is going to have all kinds of nasty little bits that are hard to fill in at the end: the middles of chromosomes, called the centromeres, the ends of chromosomes, called the telomeres, and so on. This is not like the transcontinental railroad, where at some point someone is going to nail in the golden spike, and then and only then can you go cross-country. There is no golden nucleotide to be nailed into the double helix at the end.
What’s important is that every bit of the DNA railroad is already being used today. As of this month, more than 85 percent of the human genome is freely available on the Web. So the notion that biology will be suddenly transformed when we cross a specific finish line is wrong. The point is that biology has already been transformed. The race is over in the sense that everyone is taking the human genome for granted. That is the achievement right now.
TR: What are the next big opportunities in genomics?
LANDER: Well, let’s start with the basic research question, which is how do you use the information in a genome to figure out how physiology really works. The genome is a very elaborate program, and we don’t know how to read it. It’s as if we have some ancient computer code that was written three billion years ago and now we are trying to figure out what it does. I think what biologists are going to be doing for the next decade is figuring out the circuitry of the genome by monitoring how the 50,000 to 100,000 genes are turned on and off and how all the proteins come on and off in the cell.
A lot of technology is going to be needed to do that, so I also think that detector technology [such as gene chips] is going to be a driving force of genomics in the future. I see a real merger of physics, chemistry, biology and computer science to be able to build these detectors and interpret their results.
TR: How will that affect the creation of new drugs?
LANDER: It was noted about 10 years ago that in order to maintain the valuation of the pharmaceutical industry it would be necessary for the typical pharmaceutical firm to bring to market three new drugs each year. In fact, most companies bring to market one new drug a year, at most. So there is a huge productivity gap. And the reason for that is that making a new drug is not an act of engineering. It’s an act of art mixed with a lot of luck.
When you make a new drug you often have no idea whether the target you have chosen is valid, and no way to know whether your drug will be non-toxic or if it will be absorbed and metabolized by a human in the right way. Right now the only way to find out those answers is to pay hundreds of millions of dollars to test the drug in human clinical trials.
Imagine what would happen if one could reverse that by using technologies that had high predictive capability and could be deployed early in the process. That would mean when you go to do your clinical trial, there would be a very high probability of success, compared to the current low probability. Well, that would have a huge impact on the number of drugs that one can develop. That is what the industry sees as the promise of genomics and of biotechnology. When people look back 30 years from now, they are going to be looking back from a pharmaceutical industry that is an engineering industry. And they are going to marvel that anything at all got done in the 20th century.