Cell and molecular biology is a bit of a dark art. The way we perform our experiments has been passed down from generation to generation in sacred texts known as “protocols”. Like any recipe used and abused by generations of creative people, the methods and materials are continually refined as people try slightly different conditions, either in the hopes of improving the result or (let’s be honest) finding a shortcut allowing them to escape to their local pub before closing time.
Protocols used to be on paper (stained, torn, smeared, possibly slightly radioactive) – photocopies of photocopies with layers of marginalia successively enshrined – but are increasingly electronic. Either way, they represent an astonishing living record of scientific processes in action. They also unwittingly betray a little bit about the researcher who first composed them. One of my favorite bits from a protocol about isolating genomic DNA from Drosophila, written originally by a wonderful Chinese PhD student in our lab, starts off like this:
1. Put flies in tube.
2. Kill with stick.
I was thinking about protocols the other day when trying out a new method for culturing cells derived from the human retina. Cultured retinal cells, not surprisingly, don’t have all the characteristics of their tissue of origin, even when you genetically engineer them with some key genes. But someone recently discovered, and published, that if you add a smidgeon of sodium pyruvate in a slightly different formulation of standard culture media, the cells start to transform just a little bit closer to what they should be. Sure enough, a few days after adding the humble salt, my cells began to take on a telltale graininess: dark pigments, expressed by cells fooled into thinking they should prepare to absorb light.
“Look, they’re making eye contact,” quipped one of my colleagues as he peered down the microscope.
I am often astonished by the weirdly arbitrary nature of the procedures that have stood the test of time, and wonder how they came about. For example, when you want to zap DNA into a bacterium to make more copies, you perform a simple but very precise protocol that includes a heat shock of exactly 42 degrees Celsius for exactly 45 seconds. Who was the first person to ever work that out, and how many iterations did this molecular biology pioneer attempt before stumbling onto the perfect formula? And is it too late for me to buy him or her a drink?
I don’t know about you, but sometimes it all seems rather eye-of-newt and tongue-of-bat.