After a multiyear run, I’m sorry to announce that this will be my last column for Contract Pharma. I would probably be unnerved to see the entire stack of them that I’ve written over the years, and for all I know, I’d be unnerved to have to read them all as well (!) But it’s been fun. I’ve enjoyed having a platform to vent my opinions, of which I seem to have no shortage, bring up questions (ditto), and every so often spend an entire column on nothing more than inside jokes about the industry.

We don’t have a shortage of those, either. I think that any field that’s as intrinsically hard as drug discovery and development is going to pick up a lot of dark humor; it’s a bit like how jokes seemed to flourish in the old Soviet Union. “Under capitalism, man exploits his fellow man. Under communism, it’s the exact opposite!” You need that sort of thing as an outlet, and to try to keep your perspective.

So, do I have any different perspective now than when I started writing this column? Looking back, I think that I can see a few trends. From a med-chem standpoint I used to be a bit more hard-headed about drug structures. Funny-looking things got crossed right off the list, if I had my way about it, but since then I’ve come to wonder about the criteria I’ve used for “funny-looking”. Any ten medicinal chemists, it has become clear, will have very different ideas about what’s worth keeping and what isn’t, and it’s harder than you’d think—or harder than I thought—to say which of them are right. I’m a lot more willing to let the numbers speak for themselves these days.

That said, my thinking has also evolved about those few compounds that all ten random medicinal chemists might agree on as troublesome. Most of the time, they’re right. If you can get that many ornery chemists to agree on anything, there’s probably something to it. There really are bad compounds out there, you know—some things just can’t be drugs. The list is shorter than I would have made it ten or fifteen years ago, but that doesn’t mean that there’s no list at all. Some classes of compounds have such a high probability of wasting your time and effort that you’re better off not even starting with them. Overall, I think that I’ve gotten rid of my middle ground in this area: most everything gets a chance to prove itself, but a shorter list must be thrown away immediately before anyone has a chance to get excited about it.

A few thoughts about other areas: I liked phenotypic screening years ago, and I still do, although I’ve come to realize that a bad phenotypic screen is (1) a lot easier to set up than a good one and (2) truly the worst of both worlds. The only problem, then, is recognizing when you’re in the middle of a bad phenotypic screening campaign. Formulations, it seems to me, is an area that looks to be in no danger of running out of new ideas, which is a good thing, because some of the compounds we’re turning out are going to need all the help we can get. About toxicology, my opinions have not changed much—it scared me then, and it scares me now, because we’re not a lot closer to being able to predict anything. Data rule in this business, and nowhere more than tox testing. If you dropped every drug candidate that might have a toxicity problem, you’d have to drop them all. The only thing to do is spend the time and money and go out and run the tests.

What about the whole direction of the industry? My pundit binoculars aren’t any better than they were—no one’s are. I’ve complained about every big pharma merger over the last twenty years, because none of them made very much sense to me, and I’ll continue to complain when Pfizer buys someone else. Or two other big companies combine into one really big mediocre one with more problems than ever. The only thing that I’m pretty sure of is that the current model can’t go on forever. Too much of the industry’s profitability has been coming from the ability to raise prices every year, and I am absolutely sure that this is not a viable long-term strategy. Meanwhile, the cost to find and develop drugs is rising merrily along as well. These two lines are heading across each other’s paths like misdirected trains. But what comes next, that’s what I don’t know. I’m fond of quoting Herbert Stein, Nixon’s old economic advisor, who used to say, “If something can’t go on, then it won’t.” I think that’s what we’re looking at here.

But at the same time, I can find a lot of things to be excited about. I doubt my own career encompasses any five-year period like the most recent one when it comes to completely new treatment mechanisms showing promise. For all of our problems, we can still discover things in this industry, and still amaze ourselves and others with how well new ideas can work. There are some extraordinary things going on right now, and more look to be coming, and that’s worth keeping in mind when gloomy thoughts intrude. There really are a lot of great things out there waiting to be found, and we never really know where the next ones are coming from.

And that, in the end, is what research has done for me, and done to me. I’m totally unfit by now for any kind of job where I would know what’s going to happen next. Being the first to try something, the first to find something out, even if it’s just a minor thing like a new NMR spectrum or another salt form, has become second nature. Everything else, by comparison, seems like working at the sawmill. If you like this sort of thing, and I do, then nothing else really compares. For all the craziness, all the dead ends and projects that didn’t pan out, I still feel like I’m getting away with something and getting paid for doing it.

For that matter, I also feel as if I’m getting away with something when I get paid to throw out my own opinions and prejudices on paper. I really have enjoyed doing that here at Contract Pharma. It’s a good thing that I have other outlets for opinion-spouting, because that’s become second nature over the years, too. I’d like to thank the editors here, and the readers out there, for letting me do it!