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August 12, 2004
A Week in the Life
I have a weird job. I feel safe in saying that, not least because I'm supposed to discover a drug that can be sold to sick customers, and I haven't even come close to doing that in fifteen years of work. (No, it's not just me.) Another thing that makes me sure that my line of work is abnormal is that nothing I've ever worked on has ever quite gone the way I thought it was going to.
For instance: we make a compound, and it works in the first assay - it binds tightly to the protein target. Then it works in living cells, so we make more of it and we put it into mice. And it works there - not wonderfully, not really good enough yet, but enough to show that we're on the right track. So we go back and start changing the structure of the compound and making new analogs, which is the whole point of a medicinal chemist's job. You try to find something better.
Change a group over on this side of the molecule: dead. OK, be that way, we'll change it the other way around. . .well, the activity is back to where we started, but no better. Hmm - try this part over on the other side of the ring. Hey, it works! Ten times as active as the first compound! Let's put it into cells! And. . .nothing. Dead. Corn starch would be more active. No way to find out why. Back to the drawing board.
OK, let's try doing this change at the same time as we switch this part over here (keep in mind, this stuff doesn't happen instantaneously, these are days or weeks spent the lab for each of these bolts of inspiration). . .hey! Back to great activity! Time for the cell assay again. . .this time it works. Make more of it, put it into that mouse assay, and - nothing. Nothing at all. Exactly the same as giving them club soda. Now what?
I'm not exaggerating. I fully expect some of my med-chem colleagues from around the industry to back me up in the comments section below: this is what our days and weeks look like around here. This is why I roll my eyes when I come across moonbat conspiracy theories about how the drug companies have all these secret cures that we're sitting on, see. . .hah. Secret cures, my colon. Some days we go home unsure if we're capable of boiling an egg.
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