I first began to consider structural biology seriously during the summer before my final academic year in college. The fatal moment occurred when I was reading a description of enzymes used in detergents: there was a brief passage about how a group of biochemists modified the enzymes based on their structures to greatly improve their activity in the harsh conditions of a washing machine. To my impressionable undergraduate brain, this was an epiphany: a sudden realization that scientists can have complete engineering control over these nanometer sized organic devices as long as their structures are known. Fantasies of designing Maxwell's Demon-like protein complexes to perform alchemic impossibilities flooded my fevered imagination. The entire enterprise opened before me like certain medieval triptychs filled with spiritual grandeur, precious craftsmanship bound in an artificed world complete unto itself with its own symbolic language, bizarre logic and rules of beauty. Prior to this, I had only the briefest and most indirect experiences with the subject: a few smeary ribbon diagrams from biochemistry texts that I skipped over and a large bronze ball-and-stick representation of polymerase in front of the department that reminded me of an ugly sponge. There was also that passage in A Clockwork Orange which had given me an awful impression of crystallography as something hugely esoteric, weak, unmanly, useless and perhaps a sorry metaphor for being conventional:
"There was a doddery starry schoolmaster type veck, glasses on and his rot open to the cold nochy air. He had books under his arm and a crappy umbrella and was coming round the corner from the Public Biblio, which not many lewdies used these days. You never really saw many of the older bourgeois type out after nightfall those days...And then Pete skvatted these three books from him and handed them round real skorry...The one I had was called 'Elementary Crystallography', so I opened it up and said: "Excellent, really first-class," keeping turning the pages. Then I said in a very shocked type goloss: "But what is this here? What is this filthy slovo? I blush to look at this word. You disappoint me, brother, you do really... 'The Rhombohedral System'. The starry prof type began to creech..."
However, in a few moments of dreaming and fantasy, I came to see that roughed up "starry schoolmaster" as a hero of our times.
Another event that pushed me towards structural biology was a poster presentation I had to give about my undergraduate research to a panel of professors from the department. One of them was a much celebrated biochemist whose husband and partner in science won the Nobel prize a few years later. I mention her because while the other professors gave my work much deserved perfunctory glances, she latched onto my poster and questioned me relentlessly about something that felt very trivial: she wanted to know how I knew the protein on the cell I was studying was really that protein. Iteratively, she dismissed the usual explanations from monoclonal antibody binding to molecular weight determination. Feeling lost, I ended up concluding that short of a structure, I really would never know for certain since the protein's identity is wrapped up in its three dimensional conformation. Her reply was a simple: "Yes".
When all this happened, I was living in the cramped attic of a dilapidated clapboard house near the university. It was about a fifteen minute walk to the laboratory where I spent most of my time performing cell motility assays and doomed protein interaction fishing experiments. Work was a quiet affair as the laboratory was mostly empty. The PI was rarely there and the only person who I saw daily was my immediate supervisor, a post-doc from South America. Money was a huge issue as the PI was not able to secure any funding. It was only a matter of time (a year) before the lab was finally shut down after a long and somewhat illustrious history going back to the 70s. In retrospect, finishing my undergraduate training in a lab that dies just weeks after graduation ceremony seems like a bad omen. Instead of a happy, secure pathway, a largely uncertain and stormy ocean confronted me. However, I was very idealistic about research and instead of pursuing a much more practical profession (physician), I decided to enter graduate school to become a "scientist". My parents, especially my father, were dismayed. To them, this was comparable to me running away to join the circus. Indeed, from then on, they have always given me this sadly amused look as if I were the most lugubrious clown; more sad than amused because it is their own son who is doomed to walk this pathless direction.
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