Look, I'm just a biochemist. Part 1

"Most of the time, I work in a little glass jar and lead a very uneventful life. I drive a Volvo, a beige one. But what I'm dealing with here is one of the most deadly substances the earth has ever known, so what say you cut me some FRIGGIN' SLACK?"

Dr. Stanley Goodspeed's outburst to John Mason sent my friend, a medicinal chemist, and I into noisy guffaws which attracted the attention of the surrounding Cantabrigians on that rainy summer night. After a martini each, we weren't too discriminating and simply wanted entertainment so we chose to see The Rock at the Fresh Pond Cinemas. The movie turned out to be a pretty good thriller, and Sean Connery, always a favorite of mine, as Mason chewed up the scenes. But it was Stanley Goodspeed's (Nicholas Cage) lines quoted above which stuck with me. The first sentence is my motto.

Look, I'm just a biochemist. Most of the time, I live an uneventful life and am probably the most boring woman on earth. I don't drive a beige Volvo. I drive a red MiniCooper S. And I hope to Christ's holy amorphous image on Crixivan capsules that I am not working with the deadliest substances the earth has ever known although with the rep the drug biz has, you'd think I did. Seriously. These days I feel like I might as well be working for Big Tobacco. It's practically synonymous with Big Pharma, right? We bench monkeys don't control the devils in marketing so what say you cut us some FRIGGIN' SLACK? Whew. OK, that is a topic for another screed.

A couple of weeks back in response to my whinging about some colleagues, my SciBlog colleague, Abel Pharmboy, asked how graduate student biologists could be better prepared for biochemical issues in the corporate sphere:

...there are skills that may make one a Natl Acad of Sci academician but not a great leader in pharma. Conversely, there are skills not well-appreciated or valued in academia that are absolutely essential in pharma. Derek Lowe covers some of these things at In the Pipeline but I would love to learn your insights on what can be done in academia to better prepare scientists for a career in pharma. For example, how could those "biologists who are otherwise quite talented with things cellular, pharmacological and organismal" be better prepared for the biochemical rigor necessary to launch a HTS campaign? Or, is it better to have a team of experts in their narrow respective fields who have the sense to call upon one another for advice and, gasp, consultation?

(bold type - Doc Bushwell)

With regard to the overarching question, how does a scientist prepare for a career in the drug biz, there are some things that can be acquired in grad schools and post-docs, but much of it is learned on the job. Hopefully, I can provide what amounts to insight in a series of haphazard rambling hoots and scratches of entries. But for now, I will address the issue of Why Biochemists Are Important.

First, if biochemical rigor is necessary, then by all means get a biochemist to do the job. That means a biochemist, and not a biologist who has only used canned assays out of a kit purchased from Invitrogen or a similar vendor. A biochemist is a scientist who has characterized enzymes and receptors from scratch. The biochemist understands protein chemistry, reaction kinetics, ligand binding models, has a passable knowledge of biophysics, and knows his or her organic chemistry, even if s/he isn't pushing electrons around on hood sashes while tending to a Mitsunobu reaction. A biochemist skeptically looks at an assay "which was always done this way" and questions why each and every reagent is in the mix, picks it apart to see if it works well, and if not, whips up a matrix of buffers, salt, reducing agents, etc., to optimize the conditions. Then the biochemist sets to analysis of the response of the assay to activity and the parameters for ligand binding (substrates for enzymes) .

Biochemists in big and small pharma do lots of other neat things, and robust assay development is just one part of what we do. Although I have provided troubleshooting for assays in my time, most of my work focuses on mechanism. Anyway, if there are not enough of us to go around, then acting as said team of experts who are available for consult can work, too. However, nothing beats hands-on work. My own bias leans toward a core group of biochemists who work with biologists and chemists, but then I have been hopelessly corrupted by my stint in a structure-based drug design company where such a core group was the operating, and successful, model.

Now how can a biologist be better trained to deal with biochemical assays? If said biologist is a grad student, then a rotation in a card carrying enzymologist's lab would be quite useful. If such a critter isn't around (we card carrying enzymologists are not all that plentiful a species), then a detailed exercise in a grad level or upperclassman undergrad lab course would be quite good. By detailed, I mean a 3 week long assignment in which an "unknown" enzyme, preferably bisubstrate, is characterized at some level, sort of analogous to the determinations of unknowns in general or elementary organic chemistry lab classes.

Next..."For a biologist, you sure know a lot about structure-activity relationships!"

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