I enjoyed this Twitter thread very much from “Bob the Grumpy Med Chemist”. It leads off with a document that pops up periodically on the internet, a guide to sabotage that was put out by the OSS (precursor to the CIA) during the second World War. Along with practical suggestions about how to literally gum up the works in factories and motor pools, it has a famous (infamous) section for middle managers and the like on how to slow an organization down and make it less productive. The typical reaction is “Jeez, that’s where I work already”, and that’s understandable – the list magnifies and clarifies every sort of bad organizational behavior. Bob has updated it for medicinal chemists, with things like:
“The basic nitrogen might help solubility, but we might not get into the cell. I also worry about hERG”
“Well we could add an acid to help with hERG liabilities, but I worry about glucuronidation”
“With that heterocycle, I really worry about aldehyde oxidase. I’ve seen a lot of projects die because of it”
“Let’s return to the discussion about which metabolism assay is best. Do we think this is the right order to run the assays in?”
And more! A lot of us will read these and shuffle our feet a bit in embarrassment, because I think that pretty much any experienced medicinal chemist will have said such things at one point or another. But it’s very important that you watch yourself to make sure that these aren’t the only kinds of things you ever say. It’s not that “Hey, we need to watch out for X” is always a useless suggestion, far from it. But medicinal chemistry has so many obstacles, so many unknowns, and has such a correspondingly small number of projects that truly go “all the way” that there’s a nearly endless list of things that you might want to watch out for.
So if you’re that person who sits over by the wall in the conference room and comes up with reasons why this idea, that idea, and those ideas over there aren’t going to work, then you should re-evaluate your approach to your work and your place in the organization. Sure, you’re right most of the time – maybe damn near all of the time – but what good does that do anyone? You could write an app for your phone that would just say “I don’t think that’s going to work” every time you hit a button, and it would be just as correct and do just as much for everyone. Most things don’t work. You’re far better off if you can jump in when you see something interesting that you have some reason to believe has a better chance than usual, and especially if it has a better chance than the other people around the table might realize.
Think up ways to run key experiments, and think up ways to make those as direct and feasible as you can. Clarify what you’re expecting when any of these get run – help people to think through what the consequences of the most likely outcomes might be, and if the answer is basically the same for all of them, re-think whether you should be running the experiment at all. See if you can identify the biggest risk factors in what you’re doing – both the immediate stuff and the big picture – but instead of just pointing those out, keep quiet for a bit while you try to think about how to mitigate them, and bring those up together. Try to get a good balance between asking questions and dispensing your own wisdom: even if your wisdom really is the goods, you’ll often have a better chance getting it across if people think their own way up to it rather than just having it rain down on them. In general, don’t think up ways to talk yourself or others out of interesting-and-easy experiments. Sure, you can spread yourself too thin and noodle away time with too much of that stuff, but many people and projects make the opposite mistake and miss out on getting some useful experimental truths because they’re focusing too hard.
These suggestions are especially directed towards experienced research scientists, because as you go on in the drug discovery business you will have seen your ideas shot down in more ways than you can even count. That will give you a rich storehouse of failure modes, perhaps too rich. An occupational disease of longtime pharma researchers is grumpy seen-it-all-beforeness, and your challenge is to be able to use your own experience without devolving into that. The reasons for working on this are not entirely altruistic, either. Sure, your colleagues will be better off if you’re not a perpetual predictor of failure, but you yourself will be able to stay employed a lot longer if you aren’t, either. Talk is cheap, and talk about how nothing’s gonna work is cheaper still. No one needs to pay you to provide it!
The post How Not to Be That Chemist first appeared on In the Pipeline.
