Now, this is a column that I’m not sure is needed. You’ll see what I mean in a moment; there seem to be plenty of people who have already taken its lessons to heart and live these principles daily. But for those of you who don’t know all the details, I present Four Ways to Ruin Your Drug Discovery Project:

1. Chase Potency
If you’re just going to rely on one technique to send your entire effort off the rails, pick this one. It’s been tested in every therapeutic area and in pretty much every company in the industry, and it rarely fails to fail. Did you get a sub-hundred-nanomolar compound out of your screening effort? Good for you! Does it look like several bricks held together with roofing compound? Who cares, right? No, you’ve got a hot one on your hands, and if you want to head for the edge of the cliff at top speed, you’ll run with it. Formulations, pharmacokinetics, metabolism, toxicity — those are either A) going to be other people’s problems, or B) going to be a problem well after you’ve delivered a candidate and checked off the goal on your form. (We’ll get back to that goals form in just a bit, never fear).

The beauty of this technique is that it can be applied to any chemical series, at any point where you still don’t have enough potency. Of course, it’s especially useful when the biologists think that what’s really needed to get good activity in the cell assays is for the darn chemists to deliver a picomolar compound, but you can hit this button any time you wish. Just start hanging big lumps of carbon off any available atoms in your current lead series. Hydrophobic interactions never give up, and you’re bound to stumble across something that’ll drive your all-important numbers down for you. An extra biphenyl? A fluoronapthyl amide? A couple of good old-fashioned t-butyl groups, the kind that make your compound look like an antioxidant added to maintain freshness? The world is yours. The bulky, greasy part of it, anyway.

2. Live By the Numbers
To be fair, this one has potential to ruin an entire company, not just a simple drug discovery project. It’s that strong. What you want to do is measure everything — yep, even things that reasonable people might not think are measurable — because (as is well known) what can be measured can be managed.

You might, for example, be one of those people who finds it hard to rate and evaluate R&D scientists, because of all those messy variables: what kind of project they’re on, what sort of optimization they’ve been asked to do, the whims of the Structure-Activity Relationship and the assays and the animal models. Clarity is at hand! Rank-order people by the number of reactions they run and the number of compounds they turn in. Or by the potency of those compounds — that way, you work in Technique Number One above at the same time.

After all, that’s what you’re after, right? Lots of potent compounds? You’ll be amazed at the jump in productivity after word gets out that a person’s share of the departmental bonus pool depends on how many new molecules he turns in. You might also be amazed at how much palladium catalyst and how much amide-coupling reagent the department starts running through, but omelets and eggs, omelets and eggs . . .

Don’t stop with your people — keep on counting. Set strict numbers for how many projects the organization is going to start each year, and (especially) how many are going to finish up by recommending a clinical candidate! (And just how else would you finish a project, hmmm?) Make sure that everyone knows that if they don’t make their numbers, well, people can be found who will. The results will be magical, keeping in mind that magic traditionally comes in two color schemes. A long, steady row of checked-off boxes is the almost guaranteed result, and if that’s not reason enough to look back with satisfaction, well, what is?

3. You Do Not Have Problems; Other People Have Problems
I mentioned this in passing above, but this is actually an entire way of life. What you have to do is be ready to define your work, which as we saw under Technique Number Two really means, “your measurable, checkboxable goals,” in such a way that your apparent problems aren’t yours any more. It’s like having a portable disintegrator; just aim and fire. Does your compound have bad solubility? We call that a formulation problem, chief, and there’s a department that lives for such things. Trouble making enough of the stuff for anyone to figure out what it might dissolve in? That right there is a problem for the scale-up group; they’re paid to work out those kinks.

Remember, you are not here at work to make the lives of others easier. You are here to make your part of the process as pristine and unimpeachable as possible. If that part ends up being rather smaller than it used to be, well, at least it’s tidy.

4. Take Refuge in Process
No, not the process chemistry department. You don’t want to go there; they have too many actual problems to solve that they can’t offload onto anyone else. What I mean is Process with a capital P. Rules, procedures, flow charts — you know.

Why do you want to dive into that stuff? Because it provides cover. If everyone has worked out the Perfect Way that Things Should be Done, and signed off on it, uploaded it onto the department web site and printed it spiral-bound, well, that’s safety, right in front of you. If something goes wrong, it’s clearly not your fault, as long as you did it the way that it was supposed to be done. People in large companies have known this for a long time; there are folks who have spent their entire careers hiding in these weeds.

Whenever someone questions the way that things are going in your area, respond by showing them how closely you’ve been adhering to the departmental scriptures. And that’s the right word, because when an organization really embraces this world view, it’s a theological event. Your bonus and your position will not, henceforth, be saved by good works, but by faith. Antinomianism never really went away; it went into a Powerpoint presentation.

There, those four doses of wisdom should be enough to coat any organization with the managerial equivalent of tetrodotoxin. Depending on how strong your research culture is, you may not even need all of them, but if you’ve been reasonably productive, you may have to empty all four spray cans to guarantee results. The interesting thing is, the place won’t just fall over with its legs waving in the air. It’ll keep on going, and to an outside observer, it might look much as it did before — maybe even more efficient and professional, if said observer doesn’t look too closely.

No, the R&D will keep marching right on, and whether it will find the cliff, the gulch, or the tar pit first, no one can say.