I had some e-mail from a graduate student in a good lab the other day, and I thought the questions raised were worth a blog post. He wrote:
One thing which stands out to me is your enthusiasm for chemistry,
after having been in pharma for a while. This is something which I am
afraid I might lose getting out of academics. I actually was strongly
leaning academically until recently. It just seems the chemical problems you
would be presented in industry are very vanilla....the problem is I
really don't have a good grasp on what these are (especially in drug
Then I imagined in drug discovery, you can use any chemistry you want,
so the "cutting edge" (i.e. new organometallic transformations with way
too much expensive catalyst) is still very relevant. I guess I'm just
curious how you stay as passionate about the science as you are. Do you
see this/has this changed since you started in industry? As you move up
the ranks and further from the bench does chemistry get less and less
These are definitely worth asking. My reply was:
?As for the enthusiasm part, I may be a little bit odd, but not all that much. There are still plenty of people who enjoy what they're doing.
But part of it is realizing that chemistry is a means to an end in the drug business, not an end in itself. People are enthusiastic about finding something that works as a drug - that's why we don't mind mundane reactions as much, because those give you a lot more shots at making a drug than something that needs 2 days to set up. Of course, if you do nothing but (say) make sulfonamides all day, every day, you'll go nuts. But things vary too much for that to be a problem (most of the time). There's always another new structure idea that you have to figure out how to realize, another new core to work on, etc.
And the chemistry problems are just as knotty as you'd get in academia - how do I set these stereocenters, how do I do this reaction selectively so I can avoid a protecting group, etc. Sometimes they're on a different wavelength as well: How can I make this stuff in fewer steps? How can I avoid that evil mercury reagent? How do I get this stuff to form the right polymorph? How can I get to an intermediate that'll let me sit back and crank out a few analogs, instead of making everything from the ground up?
But, as I said, chemistry is means to an end. And the non-chemical problems are a lot harder: how do I get these compounds to have higher blood levels? (Next question - why are they so low now? Do they not get in through the gut, or are they getting whacked by the liver, or are they partitioning into some other tissue, or getting hosed out extra fast by the kidneys?) Why does this compound work, but the one without a methyl group kill the rats? (I've had that exact situation - truth be told, we never did completely figure out what was going on. . .) Why does this thing work so much better in mice than rats, and which one is going to be more predictive of humans - if either? And so on.
So, in a way, the chemistry problems take up less of your time the further on you go. Biology and development problems pick up the slack, and then some."
I'd be interested in hearing other takes on these, and I'm sure my correspondent would, too. Any industrial readers care to add some details?