Walking Backwards, Blindfolded (Crying)

During my last few chaotic weeks of mysterious experimental hiccups, I found it really hard to leave work in the evening with anything on my mind other than failure. To leave a day of work unfulfilled, with the weight of wasted time and energy, is never a great feeling. But, if you’re emotionally intelligent and in control, it’s somewhat possible to talk yourself down from a mountain of negativity. Usually, there are lessons hidden in our mistakes and ‘wasted time’. Usually, a rest and a new day can do wonders to shake those feelings of guilt.

In the instance of research however, we can go through really long periods of (perceived) failure and wasted time. Not only can it take a long time to progress forward, but you tend get very frequent reminders of just how stagnant you/ your work/ your progress is along the way. Each day brings new mysteries to be placed between you and your goals.

For example: you have samples for which you want to collect data for using an experimental method. You might think that Step 1 of this progress would be:

1. Collect data for your samples using an experimental method.

You dive in with all good intentions, before quickly realising that Step 1 is actually:

1. Read everything you can get your hands on about the experimental method.

Then, you think you’re ready. Back to the lab, let’s run the protocol. Ooops. Those results can’t be accurate. Maybe you were wrong…

1. Correct experimental method so as to control for numerable variables.

As you start to tweak the protocols for your specific needs, you realise that maybe you need to make changes to the work flow BEFORE this experimental method can even be performed. For example, the way you collect or store or prepare your samples…

Before you know it, you are weeks into a project and you haven’t even carried out the Step 1 which you thought was the Step 1 back when this whole nightmare began. Far from moving forwards, you’re walking backwards, as you keep illuminating just how much work actually needs to be done before you can reach your original goal. And every day brings more ideas and mysteries that need to be consulted; despite all the work performed, your workload is actually GROWING. Even though you might achieve something in a day: answer a question, shed some light, perform one step of a hundred step protocol; it feels as though you have achieved nothing, or at least nothing worth feeling good about. When even success feels like failure, it’s not a great place to be as far as mental health is concerned.

My supervisor often tells us (her four students) off for comparing ourselves to each other.

I suppose the same goes for comparing our actual successes to our target successes. It’s a waste of time and it’s really an invalid process to go through. Sometimes, those original targets were envisioned many months, many papers, many experiments ago, before the scale of the task at hand was truly understood. While it’s great to have targets for your research, sometimes unanticipated mysteries of science can get in the way of achieving them. The only thing you can do is give these mysteries the space and time and energy they need: and stop beating yourself up about it (it’s really not your fault).

 

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Dependence Tightrope

I recently overheard a research horror story, so terrifying it may even be worthy of campfires and marshmallows. For now, I guess, we will have to make do without. Feel free to use your imagination though. *hiss, crackle, etc.*

A friend of mine has been working with some clinical samples for about a year now, along with a few others who have been involved for two to three years. One of their main hypotheses regards a group of proteins which should be present in a particular cell type within said sample. After a lot of struggling with nailing down gene expression, let alone protein quantification, they went back to square one to check their collection and storage methods. Lo and behold; the methods the group had been using had rendered their cells of interest inaccessible. The clinical samples they had been gathering over a period of years were worthless for testing their hypothesis.

Now, whose fault all of this is, is debatable. Shouldn’t the supervisor have known better? Shouldn’t the students have double checked? Either way, the horror story demonstrates the extreme skinniness of the line between trusting and questioning your supervisor.

While a good student does as their told, doesn’t a good scientist “question everything”? While this probably shouldn’t be taken too literally (have you ever tried talking while brushing your teeth?!), a PhD student who never ventures beyond the face value of their supervisor’s advice probably isn’t destined for a highly successful career in science. Whether the advice is sound or not, assessing its value is all part and process of doing a PhD (…and, probably: life).

As a naturally inquisitive but also dubious and pessimistic individual, I have literally given myself nightmares about what would happen if my supervisor turned out to be wrong. I am ALWAYS asking questions (most of which start with, “What if…?”), and I can assure you that it’s not good for your well-being. I am constantly left wondering which circumstances are appropriate for me to doubt my supervisor’s advice.

I suppose all I can hope for is that: learning when to ask questions and when to Shut Up  And Get On With It is just one of the many skills that I will develop in the process of obtaining my PhD.

Project Verification

Although my supervisor and I are already set on a project theme/ idea, I’ve spent a lot of time this year brainstorming for new project ideas, the results which I been subconsciously storing into a sort of ‘worst case scenario’ back-up category.

I believed that I needed these back-up ideas, in the instance that we were unable to verify the observation upon which the main project theme was based. Specifically, we had spotted an isoform behaving differently to its wildtype counterpart in response to drug treatment of various cell lines. However, this observation was made using microarray data. For those of you who are unaware of gene expression studies, microarray data is a fickle thing, and has to be verified by more specific methods before anyone can get too excited about it.

I had made the assumption that, because we work in a cancer research lab, it would be improper for us to do protein/ gene characterisation studies unless they were part of a very specific question which had arisen from our “cancer-based” experiments. Hence all the brainstorming. I thought there was a chance the isoform studies could potentially be unsuitable. This is despite the fact(s) that:

i) the gene is significant in a major cell survival pathway,

ii) it has been implicated for a role in prognostics for a number of cancers,

iii) current drug trials targetting the gene are ongoing with mixed success

and iv) the gene is so well characterised and implicated in cancer, that you can read about in just about any generic cancer genetics review paper…

…yet the isoform is nowhere to be seen in the literature. It is obvious that this poses a window of opportunity for research. It hasn’t been studied before, yet due to the significance of the wildtype protein, its likely that the isoform has some interesting stories to tell too.

I think my supervisor was confused about why I seemed so unsure about the significance of the project, and why I kept on asking about alternative project ideas. It wasn’t until a conversation (where I told her about my apparent misconceptions) this week that she reassured me that, even if the microarray data can’t be confirmed (which is apparently far less likely than I thought), the gene/ protein characterisation studies can still go ahead, and are still perfectly relevant to cancer research- for all the reasons listed above.

This was a massive relief, and I am finally able to settle myself somewhat calmly into the knowledge that my project was ‘OK’.

P.S. I have a stinking cold, sorry if this post is a bit all over the place. Hey, at least I’m sticking to my own deadlines 🙂