Nonprofit and for-profit R&D need to take a good look at one another. What one has, the other lacks. Scientists searching
for drugs for neglected diseases typically work in open, collaborative systems and share information, but they lack the resources
to heavily invest in large-scale clinical trials. On the other hand, when profits are at stake and competition is fierce,
Big Pharma researchers very often plug in to their well-financed vacuum—even though the answers may not be found there.
Scientists from the two worlds of research have a lot to learn from one another. But this time, nonprofit R&D execs are leading
the charge. They are showing Big Pharma how to collaborate for the greater good, starting with drug safety, and in the process,
rewriting the rules for research and development everywhere.
Mindful of this, Novartis, with Paul Herrling at its helm, is fighting to make all areas of R&D more efficient by advocating
collaboration and communication. With Novartis, Herrling helped start the SNP Consortium, the first major collaboration between
prominent research institutions and pharma companies. Throughout his career, he has been able to bring together important
R&D players. When Sandoz Pharmaceuticals merged with Ciba-Geigy to form Novartis in 1996, he led the companies' integration
and developed a new research model that had car engineers working side by side with biologists.
When we caught up with Herrling—who in addition to his day job at Novartis is a professor at the University of Basel, Switzerland—he
gave us a lesson in R&D (there was even a pop quiz). Herrling explained how the Novartis Institute for Tropical Diseases (NITD)
is reaching out to other companies and utilizing the newest technologies to research neglected diseases. Research institutions,
pharmas, and agencies: Pick up your pencils and start taking notes.
Do you think neglected disease sets the standard in terms of efficiency? Or is it kind of behind the pack?
If you are talking about neglected diseases in the developing world, like malaria and TB, then clearly we are on a major catch
up. For example, the last tuberculosis drug that was put on the market was some 30 years ago. Of course, the reason nobody
has worked in TB is that you can't make any money—and drug companies are commercial organizations. We have to get a return
on our research investment.
Currently, there is only a handful of companies doing clinical research in neglected diseases, and Novartis' Singapore Institute
is the most consistent. We've applied the most modern drug-discovery technology to find new drugs for diseases like TB and
What new techniques are you using in this area?
We only recently have the complete sequence of the genome of pathological organisms like TB and malaria. That means we can
now apply all the tools of genomics to find characterized targets.
Up until now, drugs for TB were found by throwing a compound at bug cultures to see which ones died, with no attention to
targets or mechanism of action. The only questions were, Does it kill the bugs and does it have acceptable side effects? That's
much simpler than tweaking a subtle biological mechanism within the human body.
It turns out, however, that TB is a highly sophisticated organism that has maneuvered itself into a corner of evolution. Its
specialty is to survive only in people, so it has evolved many mechanisms that allow it to do so. And one of the most perplexing
and difficult—in terms of developing treatments—is that TB mycobacteria have learned, when they encounter negative conditions,
to stop dividing and hide in the tissue. And they can stay there and then grow again after 50 years.
So now we are trying to understand how they do this. Just to give you an example, when they stop dividing and hide, they shut
off a significant part of their metabolism. Most of the machinery being used for cell division, for instance, is turned off
to save energy, which means that antibiotics don't work anymore because they specifically address growth mechanisms.