Thinking about notebooks made me remember how important it is to keep track of WHAT YOU DID rather than what you realize or think you realize was the best way later on. Also about the importance of not being afraid to try things that you don't know how to do, because then you don't know NOT to do the things that could make them actually work in a new way.
My own two stories of this from my Ph.D. work:
- I needed to make bioreductive metal complexes of a drug I was working on. Everybody in the literature had been using Co(III) and it was not working very well for various reasons. I thought, "hell, why cobalt? I'm just gonna try whatever metal salts I can find in the cupboard" because I knew next to nothing about inorganic chemistry. Lo and behold, copper (II) not only made beautiful crystals (that showed via crystal structure just how perfect copper was for this compound) but also even had the intended biological effect. It was only because I was like, "Huh. Why not try it," that I went from mediocre Ph.D. progress to actual interesting advance that solved a problem people in the area had thought intractable for about 5 years.
- One of the starting materials we needed for the compounds we worked on was a real pain in the ass to make. The reagents were nasty, the yield was bad, but the literature procedure was more straightforward than some and at least gave us SOMETHING. I toiled away at making it again and again for about two years, always having to make more because it would run out. Once I got an undergrad, I assigned him to churn out a few batches of this stuff. Whaddaya know but that guy gets 80% yield to my 30%! I was like, "DUDE what did you do that I did not do?" He couldn't find anything, we combed through his notebook, nothing. Finally I have him walk me through him setting up the reaction, he goes to add the catalyst, and uses a 5 ml syringe. Me: "Why are you using a 5 ml syringe to add 0.5 ml?" Him: "0.5 ml?......I was adding 5 ml......." This is why you should write EVERYTHING DOWNNNN especially when you first start and your detail muscles are not developed yet. Once we figured that out, everything in our lives went so much better, all because he screwed up and did it wrong in a good way (and I was able to extract out from him what the hell he did).
Another awesome story I was told by an eminent chemical biologist who will soon be my colleague: as a post-doc, she had been working and working on this idea that her PI had about something (that is now one of the classics of chemical biology). It hadn't been straightforward, and the molecular biologists in the lab (she was a synthetic chemist) were having all kinds of trouble with the assays. One day, one of them had to sacrifice an animal and use some particular parts, so she asked for just one organ to see if she could do anything with it. They gave her this organ, she put it on ice, and was like "Hmmm... now what do I do with this thing?" As a chemist having no idea how one normally processes an organ for its proteins, she just picked ye olde random (and not common) procedure from some random paper. Lo and behold, something very exciting was seen in the Western blot and her PI was super pumped. The biologists in the lab all made fun of her procedure and tried to do it more "normal" ways, but nobody else could make it work. Another lo and behold: the way she randomly picked as an inexperienced (but unafraid) chemist processed that organ was THE ONLY WAY to get this experiment to work. They subsequently figured out the mechanism for why and thusly learned more about the biology and the chemistry of the system.
This is one of the things I love about chemical biLOLogy--you get to screw around with stuff that you know is based on molecules, and so it should make SOME sense, and it doesn't matter at all if you understand what you are doing at the time. You can learn it as you go along, and the chemist's molecularly mechanistic perspective helps you go back and dissect your dumb luck to find the places you pinned the right tail on the wrong donkey spleen (or vice versa).