Outsmarting our instruments

I'm a graduate student in a lab that seemingly has an instrument for everything. Peptide synthesizer? We've got it. Liquid-handling instrument for 96-well plates? No problem. You name it, we've got a robot that can do it. The convenience and efficiency can't be beat. But when I first joined the lab, I feared that these tools would make grad students like me obsolete. I thought the single quality that defined a great scientist was perfect experimental technique, and that scientists are essentially supposed to function as living, breathing instruments. Gradually, though, I accepted that these instruments had better experimental technique than I ever could master, and that I had better rethink what it really means to be a scientist. ![Figure][1] ILLUSTRATION: ROBERT NEUBECKER My misconceptions, and my anxiety around them, arose during my undergraduate training. I excelled at homework assignments and exams, but I often struggled in the lab. In my freshman-year chemistry lab, for example, we were supposed to determine the concentration of a hydrochloric acid solution by meticulously adding sodium hydroxide until the clear liquid turned pink—a standard acid-base titration. When done correctly, it's beautiful. At first, you're just combining two colorless solutions. Then, each drop of sodium hydroxide creates an ethereal swirl of pink that gradually dissipates as the solution becomes clear again. Finally, with just one more drop of sodium hydroxide, the solution blinks from clear to all-over pink. But my hands weren't steady enough to precisely dispense the sodium hydroxide. I shot right past the endpoint, turning the contents of my beaker an embarrassingly vivid magenta. As I looked around the lab at the sea of perfectly pale pink beakers achieved by students with better reflexes, I began to doubt whether I was cut out to be a scientist. No one, I thought, would care that I could predict the product of a reaction if I couldn't successfully run it in the lab. Even so, I continued with my chemistry major, driven by my passion for the material and positive feedback about my performance in the lecture components of my classes. I was also fortunate to have a professor who told me that the best predictor of success was whether I could master the concepts—which I could—and that, with practice, my experimental technique would not be an insurmountable barrier. She also insisted that grad school was the right option for me. I wasn't entirely convinced. But I had hoped to pursue a Ph.D. ever since I started my undergrad degree, so I decided to give it a try. There, I slowly came to understand what my mentor meant: Being a scientist is much more about creativity than about what we can do with our hands. This really started to sink in during my second year, when I adapted an experimental protocol for use in living cells. I needed to design a molecule that would be able to cross a cell membrane and then come up with a way to synthesize it. There's no instrument for that. I dusted off my old medicinal chemistry notebook, compiled a list of potential structures, searched the literature, and homed in on my target. I did eventually have to do the experiments, including synthesizing the molecule—which required several attempts, many helpful tips from a senior graduate student, and countless absorbent spill pads. But ultimately, I got the off-white powder I needed, and I managed to improve my experimental technique along the way. Only then did I turn to the state-of-the-art instruments at my disposal, which I had come to appreciate as tools to support my work rather than things to strive to emulate. Now, whenever I am faced with a challenging experimental task and feel that freshman-year doubt in my scientific prowess begin to creep in, I think of Alexander Fleming. A technically great scientist would have thrown out a moldy bacteria culture to prevent contamination. But as a truly great scientist, he took the time to consider the phenomenon—and used it to invent penicillin. And I bet Sir Alexander wasn't great at titrations either. [1]: pending:yes