The Slump

You know that all-to-familiar time during your research when absolutely nothing will work?  I've been going through this for about the last month, and it has worn on me extensively.  It has gotten to the point where even a simple plasmid mini prep won't work.  I'll check my antibiotics, use fresh media, make brand new compentent cells, but when it comes to the simplest of all, I cannot perform a mini prep.  I've determined that it is not a problem with the kit my lab uses because I'm not able to isolate any plasmids even using the "old school" methods of phenol-chloroform extraction.

In the past, I've gone through periods like this when I'll have a bad week, but it's never been this bad before.  Every time it happens, it makes me wonder how so much could go wrong.  After all, it is science, and we're supposed to have a method to our madness (emphasis on supposed to).  How can it be that a simple process that I was able to perform only a couple months ago has completely escaped me now?  Especially at a time when I need it to work the most...

Through my (admittedly limited) experience, I've found that there are only a few ways to drag myself from the pit of desperation:

1) Start several experiments and hope that one of them works.  This is my method of choice, mostly because I like to multi-task in the lab.  The important thing for me to remember is to make sure that none of these experiments are high-priority (I don't need these results right now with this experiment) and that at least one of them will work.  It never hurts to have a confidence booster, in my opinion.

2) Stop. While I find it hard to do, sometimes it just helps to stop and do nothing for a short period of time.  Usually this makes me feel even less productive and more depressed, leading to a vicious cycle.  I've found it can be beneficial sometimes, though, to just take a coffee break and stop worrying.

3) Read. Diving into the literature can never hurt, and reading can really take your mind off the sucky things that are going on in the lab.  I like to read reviews particularly when I'm stuck experimentally because it's less intense and allows me to relax a tad.  Reading more hardcore papers can also make you feel like your problems in the lab are quite insignificant compared to the 736 Western blots required for that awesome Nature paper.

4) Start over.  Like really start over.  New media, new cells, new antibiotics, new reagents, new pipet tips, new underwear, new music.  I find it's easier for me to pick up mistakes when I have to start over from the beginning.

5) Swallow your pride and ask for help.  Sure, a mini prep is a ridiculously simple task that a trained monkey (probably even a zebrafish) could do with one hand.  Still, it never hurts to ask for help and advice because there are probably people across the hall that have run into the same problem.  Even if not, it's nice to complain to others as a catharsis.

And that's where I'm stuck.  A month later and my mini preps still won't work.  I've tried all of my tips from above, and nothing seems to work.  All seems like it should be just dandy with a *%$! mini prep, but, alas, it is not.  As with all other times in the lab, I will plod along until one day, my ability to isolate plasmid DNA will magically reappear.  Until then, I will continue to complain about it... because that's what I do.

Post-slump update: My minipreps are all in working order again after I finally figured out that the media was an old formulation and didn't support plasmid replication for some reason unknown to me.  Lesson learned, I guess.  There is still hope for me!