So, as reader CalProf asked in a comment the other day, what should academic scientists who want to help discover drugs be doing?
As a first approximation, I'd say not drug discovery. That sounds a bit strange, I know, but there are some good reasons behind it. Modern drug discovery takes a lot of resources, from several rather widely separated fields, and it's not easy to bring all the necessary people together in an academic environment. You need med-chemists to make the compounds, pharmacologists and molecular biologiss to develop and run the primary and secondary assays, in vivo people to dose and evaluate effects in the animal models (which they'll also need to develop, in many cases), toxicologists, formulation chemists, computer modelers, scale-up chemists. . .and it's a great help to have people in each of these departments who've done this kind of thing many times and know all the obvious pitfalls. It's a lot easier to organize this as a company where everyone is hired to do their specialty, rather than try to run it with whatever post-docs and grad students you have handy.
But that doesn't mean that academia can't play a big role. They already do, of course, in doing much of the basic biochemical research that leads to new drug targets. Unraveling which protein interacts with which in some important cellular process is as basic as it comes, and most of the time that won't lead to drug one - but once in a while those experiments will set the entire industry off on a chase.
Another place where some academic thinking could come in very useful would be in attacking the important pharmaceutical processes that we don't understand: things like pharmacokinetics, oral availability, human versus animal toxicology, and (lots of) better disease models. The inefficiencies in these areas caused by our lack of knowledge are costing everyone billions of dollars - any improvement at all would be good news. Of course, it's not like the industry hasn't taken a crack at them, too (after all, there are those billions of dollars out there to be rescued from the bonfire). But we really need every approach we can get, and some fresh thinking would be welcome.
Want some more in that vein? Better ways to dose large proteins. New formulations, so that insoluble gunk like Taxol could be given in a dosing vehicle that doesn't occasionally give people anaphylactic shock. Some hope of predicting blood-brain barrier penetration. More understanding of active transport of drug-size molecules, and how it varies between species and among different cell types. Make no mistake, these are hard problems. But whoever can make real progress on them will get plenty of recognition, plenty of funding, and will be a flat-out benefactor of humanity to boot.