Dr. Austin: 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 were 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, and one person will work on the leg bone. But this organization, because
its 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, and cancer, and 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, were 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 have now done a project to bring the best of the technologies,
the lessons, the team-driven, deliverable-driven culture from the best biopharmaceutical companies
into the academic domain and set those technologies and those people loose on the many targets
and many diseases that simply cant be worked on easily in the private sector due to poor
return on investment. In order to do this, weve had to set up a number of really cutting-edge,
innovative centers, one of which is here, where were 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 a hundred thousand 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? When 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 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 thats 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
has -- which can contain 1,536 different experiments. Ill give you one example that were working
on right now, as a matter of fact. Theres 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
Im talking about, through our various connections, through Davids connections and ours, we identified
an investigator, Michael Cappello at Yale, who works on a completely different disorder
known as hookworm infection, so another parasite, and it turns out that 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 havent really been thought
of as being related before, but here we have one set of compounds that may actually be
curative of both disorders. The important issue is that its a collaboration. Its a multifaceted
collaboration between biologists and chemists and informatics of scientists and engineers
here and 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.