If somebody were to start reading up on the exploits of current day pharmaceutical companies, one might get the impression that the industry got blindsided by calamities such as patent cliffs and the end of the blockbuster model, failed entirely to prepare for it, and lashed out incompetently in various disastrous, knee-jerk ways. But that’s not how it looked from my vantagepoint.

My career intersected with pharma in 2001, when I managed to combine my software development skills with my formal science background in an industry context, i.e. a real job. Pharmaceutical companies provided the demand for the things that I wanted to do, and so I got busy helping out with the supply.

One of the things I remember very acutely from that time, when the pharmaceutical industry was riding a massive boom-wave, is the warning signs about the drug pipelines not being sufficiently well stocked to keep the engine fueled indefinitely. Influential people inside the industry saw the problems coming a decade or so before it hit the proverbial fan, and there was rather a lot of effort invested in trying to avert it.

From my perspective – software – it certainly looked like the large pharma companies were not sparing any expense to solve their future problems preemptively and with an impressive amount of foresight for giant companies. They funded all kinds of long shot technologies: every wacky idea in computer-aided drug design you can imagine, electronic lab notebooks, high throughput screening, combinatorial chemistry, throwing money at academics, throwing money at contract research organisations, throwing money into the emerging economies, and who knows what else. I personally benefitted from that, because if big pharma hadn’t been so open minded, I’m not sure how I would have been able to build cool things all day and collect a paycheque.

But we all know how it worked out in the end: it didn’t. The patent cliff hit, the pipelines remained understocked, and the industry degenerated into an M&A frenzy, closures, layoffs, outsourcing, lobbying and various other flavours of desperation. It seems unlikely that the crisis is over, but sooner or later the industry will find some kind of “new normal”, and I for one would really like to be able to peer into the future to see what that looks like. Will it be a global patchwork of thousands of small companies, or just half a dozen consolidated remnants holding out in the major R&D hubs, or maybe private industry will just give up on trying to make a buck and hand it over to government. As long as there are people, there will be a demand for drugs, but there are a lot of different forms that the underlying economic infrastructure could mutate into.

For what it’s worth, I find it hard to believe that the “blockbuster model” will ever make a comeback. That was just a one-off, not unlike the age of cheap hydrocarbon energy. Back in the day, when I was trying to decide what kind of a scientist to become, the big three – biology, chemistry and physics – were all in the running. Physics got crossed out because there’s too much calculus and not enough pictures, and biology for the opposite reason: a living organism is for many practical purposes infinitely complicated. If we can’t model the gravitational attraction of 3 spherical objects, then the amount of voodoo required to predict cause & effect in a human body is way more than I’m comfortable with. The notion of inserting a single kind of molecule into an incomprehensibly complex machine and fixing some inherent problem belongs in the miracle category: the fact that the number of favourable results is greater than zero is quite amazing. I struggle with my inherent skepticism every time I resort to taking an aspirin to help out with a hangover.

And yet we’ve been conditioned to believe that there will be a steady stream of these, and that every year a new batch of miracles will be produced, and done so in a way that can be made predictable (with sufficient investment), and very profitable. We do have to entertain the possibility that the low hanging fruit really has been plucked. There might be a few more aspirins out there, hiding away in the false negatives of HTS data, or in the genomes of deep sea monsters, but the persistence and serendipity needed to find them may not fit any reasonable business model.

On the other hand, the other half of the story involves killing things that aren’t supposed to be there: bacteria, viruses and parasites, whether in the form of antidotes or vaccinations. The idea of designing a drug to break a complex machine is a difference in kind to designing a drug to fix one. The catch is that it has to break just one kind, and have no effect on other kinds, but that still sounds like a more attainable goal. And with so many tropical diseases that have been neglected for too long, and increasing resistance of diseases we read about in history books, there should be plenty of action in that space.