TR: I found it interesting that a genomics research center chose as its director a chemist.
SCHULTZ: It is strange. On the other hand, it’s strange that an organic chemist/biological chemist started a materials science company [Symyx] too. But I think that it’s less strange now that I’m here. Because what genomics, the gene sequence, and all these tools are making possible is an understanding of biology at a molecular level. And as soon as you’re talking about something at a molecular level, it’s chemistry. A chemist is also not a bad choice in the sense that all these tools bridge biology, chemistry, physics, engineering and computation-and a chemist is a scientific jack-of-all-trades. However, it does mean that I’ve spent a lot of my time learning a lot of cell biology over the last year-let’s put it that way.
TR: You’ve been involved in a couple of very successful startup companies. Any future plans?
SCHULTZ: I was a founding scientist at Affymax, then I was a founder of Symyx. Now we’re forming a third company, which we’re spinning out of the institute. Some of the structural genomics tools we’re developing here will be the basis for the startup.
TR: What’s its name?
SCHULTZ: I think it’s going to be called Syrrx. I have good luck with companies that end with an X.
TR: Structural genomics, as opposed to functional genomics?
SCHULTZ: Right. Structural genomics involves the determination of the three-dimensional structures of proteins on a genome-wide scale. The idea we’re pursuing at the institute is to carry out high-throughput protein structure determination and then virtual docking of small molecules to identify compounds that bind and modulate the activity of these proteins. If you can input 200,000 or 400,000 compounds in a computer, and actually dock in silico this entire library of molecules against a particular protein structure, one could, in theory, virtually identify leads for new drugs. We’re developing these new technologies at the institute, but we don’t have the resources to commit 100 people just to structural genomics. With the startup, we can put together the resources necessary to really exploit the technology.
TR: Ten years from now, what kind of research will we be talking about?
SCHULTZ: In 10 years, we won’t be talking about the functions of individual proteins or individual cells but about the functions of networks-how collections of proteins in the cell, and collections of cells in the immune system or in the brain, function together. It’s like in information science-it’s not the individual bit, it’s the integrated circuit. In biology it’s going to be pathways and networks.
TR: And what will that increased understanding of pathways and networks mean in terms of developing therapeutics?
SCHULTZ: For instance, if you want therapeutics for cognition, it may not be good enough to understand the function of an individual protein or even an individual cell; you have to understand how those cells work together. Memory is not associated with one neuron. It’s associated with a network. Once we begin to understand pathways and networks, in theory we can make therapeutics that modulate activities that rationally affect the properties of the entire network. We should become a lot more effective in the development in therapeutic agents.
TR: And gain the ability to take on different types of functions?
SCHULTZ: Exactly. The immune system is another example. If you begin to understand how all the different cells work together in asthma, inflammation or organ rejection, you can become a lot more sophisticated in the development of therapeutics. The same thing is true in cancer. Most of the drugs we use to kill cancer today do so by basically targeting rapidly dividing cells. That’s not a very sophisticated approach. As you begin to better understand how cancer cells are different from a normal cell, you should be able to develop more selective drugs.
TR: I take it from what you say that there’s still a long way to go in understanding these bio-networks.
SCHULTZ: It’s a difficult problem because you have to figure out the function of individual proteins before you can figure out how they work together. If you look at a car and want to understand how it works, you look at the cylinders, the pistons, the valves, the spark plugs-and once you understand what each of those does, then you can begin to see how they all work together. It’s the same thing here. You have to look at the functions of the individual proteins in a cell, and then you can start to understand how they work together.
TR: At this point, it’s still pretty much looking at…
SCHULTZ: …the spark plugs. And the problem is that we don’t even have the whole list of the parts. We’re still collecting the list of all the parts, while we’re trying to figure what they do individually. The next level is to figure out how all the parts work together. That’s the analogy to the cell. And then you go from the individual cell-there are billions of neurons in the brain-to understand how all those cells work together to make an organ. The goal is to understand life at a molecular level. And if that’s the goal, chemists will have to play a key role.