Sunday, October 25, 2009

Culture gap: synthetic chemists and learning biology

I started responding to this comment:
Now that you have invested so long to transform in to a 'chemicalbiologist', would you mind suggesting some quick tips from your journey for the people ho want to take the same path? Are there any books or some crash courses etc?
And got so in depth that I decided to make it a post of its own. So here are my thoughts about where to start to develop better flexibility as a synthetic chemist who wants to work on bilogical problems.

The best crash course I got was weekly lab meetings in a lively, rigorous yeast genetics/molecular biology/kinase signaling lab (one of my postdoc labs). I started out so clueless that I felt like I was on Mars for the first year and a half or so. But because the people in that lab were so open and helpful, and the PI is an engaged, active teacher, they helped me learn the "language" of biology-type ways of thinking and data/information representation.

It's that language that you really need as a chemist moving into biology. And by "language," I mean more than just terminology (although that is a big part of it). It's also a change in visualization of information and getting better at logic puzzles. Imagine a multi-step synthesis with a blank at step 2, where 4-5 possibilities (which you have assumed based on either mechanism or other times people have done similar things) could fit in there to result in the product (or mixture thereof). In biology, you have to come up with ways to test *which* of those possibilities comes from the retrosynthetic direction (for which you are only postulating a route) and will result in the product(s).

In all of this you also have to accept that: a) your only measurement techniques are indirect, i.e. you usually can't just analyze the structures with some direct spectroscopic technique and figure out what they are; and b) your assumptions might be wrong. So you have to do lots of control experiments where you also assume some certain set of reagents should DEFINITELY give the products, and some other set should DEFINITELY NOT. That gives you yet another indirect way to make you feel more comfortable with your assumptions. The hardest part for many chemists is having to be okay with indirect information. The second hardest part is having to remember that if your "result" gives you something analogous to "75% yield of the product," you still have to think a lot about WHAT molecules/interactions are represented in that other 25%. You can't just purify it away and pretend it didn't exist.

Getting used to reading gel electrophoresis/Western blot (antibody detection) data, as well as biological "cartoon" format (where you mostly worry about conceptual connections, and not so much molecular mechanism and byproducts etc.), are some great ways to start. But you'll probably need a coach to guide you through it and translate how the experiments work and what the results mean. Finding friendly, sharp biologists (whether faculty, postdoc or grad student--it doesn't pay to be snobby about this, sometimes the trainees are gonna be WAY better at teaching you! Just make sure to credit them or repay them somehow!) can be the difference between this working vs. not working.

4 comments:

Anonymous said...

Thanks, Arlenna.

It is mainly due the training gap, I guess. Gone are those 'Woodward days' where people would go mad after a molecule and make it for making sake. True that it would develop novel chemistry so on so forth, and other medchems could use it for some other purpose. However, it is not practical and feasible in the contemporary time where the research in many areas is increasingly getting interdisciplinary with Biology. I feel only organic synthesis is left behind, and no wonder that NIH is trying to establish the relevance. I think having some training in biology at some level (as you had in postdoc)is necessary. One way to do this is to offer more 'biology' related (if not pure biology) courses at graduate level, and design research problems to have an all-round training than just forgetting after making the molecule.

Thanks once again for your time and for the helpful discussions.

Arlenna said...

Yes, I agree about making sure organic chemists get trained into biology as they go so they don't have to jump in the deep end on their own when they go to try to find funding for their own labs. I am trying to do that by opening my lab's biology-focused weekly journal clubs (where we rip apart papers and learn how to interpret figures) to the org chem grad students in our dept. So far a couple of them are interested, hopefully it will help them.

Also though, don't forget that you can still get funding from other sources like NSF, which might be especially appropriate for certain types of molecule route/methodology development that just don't fit easily into an NIH-related motivation.

Ambivalent Academic said...

Cool - I like how you've illustrated the difference not just in data collection but in how biologists and chemists *think* about their evidence and represent their data. I'm pretty far removed from chemistry (the OChem course I took in college was my last exposure and that's buried deep in the "trauma" vault of my memory), so it's easy to forget that the point of view can be so different.

This really got me thinking about the assumptions that we make about our respective fields and our perspective informs the types of questions we ask. We take for granted that "all scientists" tend to think about these things just like we do because, obviously, that's the "right" way to do it. But of course individual experience is not objective reality, even when we're talking about empirically-based pursuits.

Great post Arlenna!!

PS - thanks for the links about gas cylinders/regulators. I brought this up with macho dude and he did not deign to read the references, but assured me that yes, teflon washers are bad...but teflon tape is good. Whatever, I tried. If he wants to change the tanks twice as often as necessary, he is welcome to as far as I'm concerned.

Anonymous said...

How many such postdoc mentors do we have who has their (best) interest in the mentoring and teaching the postdocs? Nice to see you attribute your success to your mentor and training!