TR: Hence the Novartis Research Foundation’s interest in funding the institute.
SCHULTZ: Exactly. I think that Paul Herrling [head of research at Novartis] realized there needed to be a place that brought together many of these tools and focused them on the opportunity created by the genome sequence. There weren’t such places in either the academic world or industrial world. We’re somewhere between university and biotech-pharmaceutical research. This is really an experiment. And the reason that the Novartis Research Foundation is willing to support us is their realization that there’s a very thin line between basic research and new opportunities for the development of therapeutics.
TR: You’ve been involved in startup companies and academia, and now you’re associated with a large pharmaceutical company. What are the tradeoffs of each in terms of the innovation process?
SCHULTZ: I retain my “academic” hat at the Scripps Research Institute. But the problem with academia is it’s very hard to focus resources like one can do in industry. On the other hand, companies sooner or later tend to become very product-focused because they have shareholders wanting value. At this institute we have the opportunity to have our cake and eat it too. As we make discoveries or develop tools that have commercial value we can pass on those discoveries through the foundation to Novartis and they can use them to develop drugs; if Novartis isn’t interested, we can spin off startups that can develop and apply the technology at a high level. The institute is free to continue developing new tools and making new discoveries. You just can’t do that in academia. You can’t focus resources like that because it’s a democracy and everyone has a vote.
TR: What are some of the specific technologies that you’re focusing your resources on?
SCHULTZ: We’re developing a range of tools and applying them to the discovery of new biology at the molecular, cellular and organism level. For example, at the molecular level we’re analyzing what genes get selectively expressed during fertilization, aging, learning or in neurodegenerative disease and cancer. At the same time, we’re setting up high-throughput screens for molecules that affect function at the cellular level, for example, the differentiation of stem cells into various cell types and the entry of viruses into cells. We’re also carrying out discovery at the level of the whole organism. For example, we’re setting up a mouse screen in which we’re going to randomly mutate a large number of genes in the mouse genome and carry out high-throughput phenotypic screens. One can screen for fat mice, thin mice, smart mice, dumb mice, mice that are pain-insensitive-or even long-lived mice. One can examine thousands of mutant mice for interesting phenotypes and then use the genomic tools that we and others are developing to map and clone the interesting gene mutations.
TR: You’ve done pioneering work in a number of areas. A few that come to mind are catalytic antibodies and combinatorial chemistry for finding new materials. Is there a common theme in your work?
SCHULTZ: I’m a chemist and am interested in molecules and molecular functions-what molecules do and how that is related to their structures. Chemistry is moving from a focus on the structures of molecules to a focus on the functions of molecules. And if you’re interested in molecular function, you should understand that nature has already solved the problem of making a remarkable array of functional molecules. For example, nature solved the problem of molecular recognition with the immune system and antibodies (a major line of defense against pathogens). Instead of making one antibody, and testing one antibody at a time for its ability to bind to a foreign molecule, it makes billions at a time and tests them all. That’s a combinatorial approach. We’ve taken that idea and used it to search for interesting new catalysts. We’ve even taken that strategy and applied it to making libraries of materials and searching for novel optical, magnetic and electronic materials. I think there’s basically a limitless opportunity in the periodic table. The underlying theme is how you do experiments thousands at a time and analyze the data thousands at a time.