I suppose I should preface this with a “part one” because, due to this being my honours year, it’s likely that I will regularly and often use this to rant about my science while being educational and fun because hey, that’s our shtick.
I’m still at the very beginning of my honours year and am going through that process, most dreaded by undergraduates, of experimental design. I’ve realized how little practical knowledge I have of DNA (example: do I know how to extract it from cells? NO.) (the link is to instructions on how to extract DNA from a kiwifruit using rum and detergent) and realized my vague resentment for anything I have to google and then trawl through pages of useless results to try and find the one thing that might explain the thing that I can’t remember I’m looking up.
All of this gives me a large amount of respect for people who used to do science in the 90s, and even before.
Let me take you back in time, to a generic “this is quite a while ago, you can tell from the fashion” time. It was a time of large hair, wonderful suits, and probably higher rates of smoking although I’m not looking up the statistics, it’s not relevant.
Polymerase Chain Reaction, for example, is a pretty common genetics methodology. It’s basically a DNA photocopier; you get DNA, throw it in a buffer with some primers, and put it in this machine (in my lab, they all have Greek names) and three hours later, voila. Bundles of DNA of the same area that you can sequence, run on a gel, clone into something, eat it (don’t eat it, you’re not allowed to eat it and it would taste gross).
So these days we can do PCR whenever necessary, no sweat, let’s just photocopy up some DNA.
Before PCR machines came about though, the process was more like some monks hand-copying and illuminating religious texts. Time-consuming, stressful, and involving a lot of laborious twiddly bits. This is because, before our sweet machines that make everything lovely, each stage had to be done in a water bath. So, in order to do 30 cycles of PCR, you had to manually move your DNA from a 95 degree bath to a 65 degree bath to a 72 degree bath 30 times. Not only that, you had to time every step, to make sure you were leaving long enough for the denaturation, annealing, and extension, otherwise your PCR wouldn’t work and you’d have to do that ALL AGAIN.
The lack of beautiful technology in the olden days makes it quite impressive that they got any science done at all. Then again, the structure of DNA was only discovered in 1953, so it’s also quite impressive that we’ve got this far.
BACK TO STORY TIME. While my reaction to a lot of problems in genetics now is “sequence it up a bunch then do some protein work”, back in the day they couldn’t do that. Many of the first mutations were discovered using things like Restriction Fragment Length Polymorphisms (RFLP) – here, I’ll show you:
Before we could sequence everything, disease genes had to be found via linkage, which basically meant hoping like anything there was an RFLP co-inherited with your disease. It’s the old-school method of a bunch of things we can now do by handing them to the sequencing gurus – DNA fingerprinting (like they do on CSI), paternity testing, genetic mapping, finding a locus for a disease, and looking at animal diversity in zoology.
Despite the fact that it’s time has largely passed, RFLP (and manual PCR), and those that did it, deserve our respect. They were determined scientists, using something so cumbersome and time-consuming to find even the smallest bits of information, and they laid the groundwork for the science we can now do today at the press of a button.