Longtime medicinal chemist Mark Murcko has a Perspective article out in J. Med. Chem. on “What Makes a Great Medicinal Chemist“. As he makes clear from the beginning, if you’ve been doing this stuff for a while, you’ve likely heard many of these recommendations before. But it’s useful for people starting out, and it’s also useful for organization to think about what they’re encouraging (and what they’re not!)
There are several characteristics common to good scientists in general – paraphrasing, we have: (1) intellectual curiosity, (2) ability to focus on the problem at hand, (3) pragmatic approach to problem-solving, (4) respect for data, (5) attention to detail, (6) sense of urgency, (7) awareness of other work in the field, (8) openness to new technologies (once they’ve proved their utility!), (9) willingness to challenge assumptions and ditch old ones, (10) enjoyment of their work, (11) awareness of the limits of their knowledge, (12) resiliency, (13) effective at communication, (14) working well with team members (there are exceptions!), (15) not constantly seeking credit, and (16) looking for mentors early on, and serving as one later.
Past that, he has traits that are more specific to medicinal chemists: (17) never losing sight of the final drug profile, (18) the ability to come up with unusual structural ideas when needed, (19) attention to more than just potency, (20) three-dimensional thinking, (21) awareness of the need for different chemical series/scaffolds, (22) awareness of the competition, but not being scared of IP space, (23) never giving on validated targets, since they’re rare, (24) a deep understanding of biology, (25) decisiveness about what the next steps in a project should be, (26) being unafraid of tough chemistry (in a good cause), (27) a willingness to repurpose anything (in a good cause), and (28) awareness of the history of the field and its current state.
That’s quite a list! And it should be clear at the outset that you’re not going to find people – or not too many – who have all those qualities turned up to 11. But they’re all useful and important, and it’s worth looking over them to see what your strengths are (and especially what you might need to shore up a bit).
A few comments on specific items: I think that (3), (9), and (27) are aspects of the same approach to applied research – that is, a willingness to go with what works, even if it isn’t your idea, even if it disproves your favorite assumptions, even if it seems weird or even if it seems obvious or old. Things that work, that really work, are the ace cards in the deck. Solid experimental evidence brushes aside feelings, theories, and assumptions (quality 4 above ), and you have to be ready to come to terms with it and figure out where it’s telling you to go next (quality 25). A corollary is that if you’re running experiments whose results are not going to be solid or important enough for you to base such decisions on, then why? We’ve all sat in meetings where someone outlines an experiment that (if it works) means the project goes on as planned. But if it doesn’t work? Then. . .the project goes on as planned anyway. It’s hard to see how that’s not, at some level, a waste of effort.
This also has a connection with (11), knowing what you don’t know. There are mistakes at both ends of the scale (there always are), and in this case it’s being too tentative or being too confident. Chemists, in my experience, are more prone to the latter, the mistake the Greeks called hubris. Anyone who’s honest with themselves about biomedical research has to admit that most of the time, about most things, we can only aspire to the level of actually knowing jack diddley. What really causes Alzheimer’s? What are the specific neuronal processes involved in consciousness? What’s the specific molecular process you’d need to hit to stop multiple sclerosis or lupus? On a more immediate level, why does Compound Series A get into cells while Compound Series B doesn’t? What do I need to do to the lead compound to make it about two times more potent at the target? Or about ten times less potent at that other target it’s hitting? What other targets is the thing hitting, anyway? And so on. Decision-making under these conditions is. . .nontrivial.
That’s why many of the desirable qualities above can in fact work against each other, if taken to extremes or misapplied. Attention to detail is important – but not to the point where you become unable to make a call because you can think of bad consequences every way you turn. Ability to focus is important, but not if it leads to glossing over key experimental data that are trying to tell you something. Mistakes at both ends of the scale!
(24), understanding of biology, deserves some comment. My feeling is that not many people from other fields tend to know much about organic or medicinal chemistry, nor do they seem particularly eager to learn. So we chemists have a real advantage, knowing this stuff already, but you can’t rest on that advantage, either. The point is to start from there and go learn about the other stuff. You can be useful as a chemist (at an entry-level position) without knowing much about the biology involved – just bang out compounds. But you cannot be really good at the job with that approach, nor (as time goes on) will you continue to be as valuable to your employer – or any other employer. The chemistry is just a starting point.
One quality worth noting is (12), resilience. A constant feature of drug research is that most things, most of the time, don’t work that well. Your ideas about improving the compounds? By golly, here come the assay data, and it’s back to the bench we go. You have to be ready for your best ideas, your biggest bolts of inspiration, to land in a tangled heap over and over. It takes getting used to, and some personality types are just not suited to it. Longterm med-chemists exhibit survivorship bias; they’re the ones who have been able to deal, but not everyone can.
I’ve been focusing on individual behavior, but as mentioned above, there’s something to be said about organizations, too. Managers of all types should think about whether their labs, departments, or companies are providing a good home for these behaviors or not. Be honest. I’m not talking about wall posters, e-mail newsletters, or “State of the Company” speeches. Your mission statement might say that you’re committed to innovation or something, but talk is as cheap as it’s ever been. For employees looking at their own management, my advice is always this: don’t pay so much attention to what they say, but rather watch what they do. Don’t read the slogans on the intranet pages – pay attention and watch what behaviors your company actually rewards.
If they’re valuing the sorts of things on Murcko’s list, that’s good news. But if they’re not, they may be rewarding some less worthwhile behaviors, like delivering on deadline even if it means delivering crap, whacking people on the head for coming up with inconvenient data or ideas, advancing projects based more on who proposed them than intrinsic merit, etc. There’s a whole Devil’s Dictionary/Screwtape Letters list of things that good medicinal chemists and scientists don’t do, and you need to be alert to their presence, too. The devil finds work for idle hands, and for empty heads, too.