As someone who is currently writing their thesis, I have a major piece of advice for PhD students embarking on their studies…
Never underestimate the power of a thorough literature review!
Always, always, always read as much as you can about the field of research you are working in. Especially if there are numerous inconsistencies and unresolved controversies surrounding the expression/function of proteins/receptors and the pharmacology of their ligands. I’m specifically talking about the field of cannabinoid research and its relatives.
I carried out one of my early experiments* under strict instructions from my project manager and supervisor. Their rationale at the time sounded ok to me: look at the effects of drug A in the presence of drug B, which happens to be a selective antagonist for receptor X. My knowledge of the literature at the time (which was quite substantial, with over 100 references for the literature review I wrote 9 months after starting the PhD) concurred that this seemed like a legitimate thing to do: If drug B, which has no effect on its own, blocks the effects of drug A, then drug A must bind to receptor X.
Recently however, while doing a bit of extra research on the drugs I used**, I came across a few research articles (written by one of the most famous scientists in the field) that described both drug A and drug B to be inverse agonists of receptor X. Basically, that means both drugs should produce an effect by themselves. The same effect. At the same receptor.
Great. How on earth am I supposed to explain that in my thesis, let alone in my viva?
Luckily, my trump card was the fact that neither drug did the same thing when applied individually, which kinda goes against the ‘inverse agonists at the same receptor’ theory. Also, drug A appeared to be antagonised by drug B afterall. To top it all off, I found more research articles with evidence to suggest that not only do drug A and B bind to receptor X, but they also bind to receptor Y!
Hurrah for the inexplicable and frustrating weirdness of cannabinoid research!
Seriously though, do lots of reading. Read the reviews written by the most famous and respected scientists. Read the original articles that they refer to. Read articles about similar research conducted at other laboratories. Even read the letters and commentaries on these articles written by other scientists in the same field – they might dispute the findings, or highlight problem areas. Even attending conferences can open your eyes to what other scientists really think.
However, try to stay open minded as science is subject to fashion and popularity. Established scientists can denounce the results of perfectly good work just because it challenges the dogma. But sometimes it can take a fresh pair of eyes and a different way of thinking to make real progress.
Never make the excuse that you don’t have enough time to read research papers. There is always time to read papers. Your supervisors/advisors may be an expert in a particular field of research, but you are the expert in your PhD. Try to make sure that every experiment is properly thought through because you don’t want to be struggling to find reasons and explanations when it comes to your thesis/viva. Saying ‘My supervisor told me to do it’ is simply not good enough.
*This was supposed to be a simple control experiment to show what the majority of the literature has already described. My ‘proper’ experiments involved trying to figure out how drug C works.
**Drug A and drug C are similar, but there’s so much more written about drug A that I use this to help me interpret what drug C does.