 The NIH Molecular Libraries Initiative was started in 2003 as a translational initiative after the Human Genome Project, and it really had two purposes. One was to determine the function and biological and therapeutic potential of all human genes using small molecule compounds to study those functions. The other was explicitly therapeutic intent, which was to provide starting points for the development of new therapeutics for human disease. The way the Molecular Libraries program was operationalized was on the principle that there are common mechanisms which underlie many different diseases, and as we're taught in kindergarten, the knee bone is connected to the leg bone, which is connected to the hip bone, but much of science is done in a quite silo-driven way, where one person will work on the knee bone, one person will work on the hip bone, one person will work on the leg bone, but this organization, because it's funded by the common fund, is able to look on all of those bones simultaneously in a much more holistic way. So we have people, collaborators coming to us, who have different interests in aging, environmental toxicology, in cancer, in development, for instance, in rare diseases, and in many cases they are all interested in the same biological pathway, but that same pathway is involved in many different diseases. Now under a normal circumstance, it would be very difficult for one lab to work on a project with those many different disease or biological implications, but here, because the organization was built to be trans-NIH, to be something which is agnostic to the disease, and in fact looking for cross-cutting mechanisms, we're able to leapfrog many of the problems. What we started with this initiative was a completely new model of creating a pre-competitive space, so-called, for this kind of science to happen. Previously, this kind of science had only happened at this scale and at this level of sophistication within biotech and pharmaceutical companies, and we sought to and now have now done a project to bring the best of the technologies, the lessons, the team-driven, deliverable-driven culture from the best pharmaceutical companies into the academic domain and set those technologies and those people loose on the many targets and many diseases that simply can't be worked on easily in the private sector due to poor return on investment. In order to do this, we've had to set up a number of really cutting-edge innovative centers, one of which is here, where we're sitting at the NIH Chemical Genomics Center to develop what we call an assay, which is a testing system which allows us to test well above 100,000 compounds in a day as a starting point for the kind of work that we do. So the robotics that is required gives us the start of the chemical material which might eventually become a drug. So what do I mean by that? We develop an assay. That assay is a testing system which allows us to test currently 400,000 different compounds in seven different concentrations in a little less than a week. Now in order for a person to do that would require constant work seven days a week, eight hours a day for 12 years, and we do that in five days. Now what that allows us to do is to take the new gene or the new protein or the new pathway in a cell or a cellular phenotype, so-called, that is something that a cell does that's abnormal, which is representative of the disease. We put those cells in each one of the wells of this plate, which is a 1,536 well plate, which can contain 1,536 different experiments. I'll give you one example that we're working on right now as a matter of fact. There's a project that was brought to us by an investigator at Illinois State University, David Williams, who's now at Rush University in Chicago, who came to us with an enzyme that he thought was involved in a very prevalent parasitic disease known as schistosomiasis. It affects about 280 million people worldwide, and he came to us with this idea that this novel enzyme that he had discovered, if inhibited, could safely kill the worms without hurting the individual who has the infection. And so working with him over the course of two years, we developed these just such compounds and were able to prove, in fact, that his hypothesis was right, that in worms in a dish or in an animal model of those diseases, of that disease schistosomiasis, that these compounds actually do cure those mice. And then as an example of the kind of leapfrogging I'm talking about, through our various connections, through David's connections and ours, we identified an investigator, Michael Capello, at Yale, who works on a completely different disorder known as hookworm infection. It's another parasite, and it turns out the variants of these compounds, these very same compounds, also work in hookworm. Hookworm is another tremendously prevalent disease, affects about a half a billion people worldwide, and they haven't really been thought of as being related before, but here we have one set of compounds that may actually be curative of both disorders. One issue is that it's a collaboration, it's a multifaceted collaboration between biologists and chemists and informatics, scientists and engineers here, in a very tight collaboration with academic investigators all over the world who are working in a network of investigation to look across targets, across diseases, to try to identify these keys into these various locks that will work not only for one disease, but for multiple diseases.