A happy ending – just the way I like them.
Can I go collapse now?
Summer has slipped away from London, as it seems to do every year around this time – the air has an autumnal coolness and raindrops patter against lab windows. We Londoners work around this, as we do around so many other inconveniences, picking blackberries between cloudbursts or catching a quick, chilly swim in the Hampstead Mixed Ponds after work.
It’s a false autumn, and no doubt hotter weather is around the corner, but such seasonal mimicry still evokes deeply rooted, atavistic feelings of transition in me. I myself at am a turning point. Not five minutes ago I clicked the shiny ‘submit’ button on my revised manuscript, after having addressed all the referees’ criticisms to the best of my ability.
This means that, hopefully soon, there will be nothing between me and the need to start writing for independent funding. Over the past months, as I’ve worked hard on experiments to finish the paper, I’ve been snatching background reading whenever I could. And I have a rough idea how I want to structure my proposed project. But what I’ve lacked is the luxury of time and a cleared desk to truly do it justice. Until now.
For me, the biggest challenge will be trying to fit some loose ends into the main project. I have a few exciting lines of research I’m working on now that I’d love to carry on with alongside, but I need to work them into the bigger picture of the new project. Fortunately I have a knack for narrative, so I look forward to this aspect. Such a refreshing contrast, too, from working on a revised manuscript, where you dwell on every last little excruciating detail from the past until it all blurs together into a page full of random pixels.
So bring on the future, and all those wonderful biological questions that remain to be answered!
Greetings, Earthlings: just emerging from my self-imposed laboratory exile for a quick update. I do still exist, and my radio silence can be explained by the fact that I’m in the home stretch of my resubmission. For those of you who’ve lost the plot, I’m referring to my big screen paper, which I sent to an excellent cell biology journal some time ago. After three largely positive referees, and a heart-warmingly encouraging editorial letter about returning paper with just One More Experiment appended, I am almost at the end.
As explained previously, just to cover my bases, the Experiment soon morphed into several, a Gold Standard and a few Backups. Much to my bewilderment, the Experiments, both Gold and otherwise, have exceeded my expectations and are, quite frankly, eating out of my hand. I’m currently in the process of doing the final Gold replicate, putting the finishing touches to the manuscript, and supervising a lovely summer student who fell onto my head at probably the worst possible time, but – what the heck. She’s smart and enthusiastic and has managed to master the art of opening a 15 mL Falcon tube with a finger and thumb and yet somehow managing to keep the cap a safe distance away from the tube neck during extreme tissue culture. Who could ask for more?
In sum, this is not going to be the insightful blog post of your dreams. Instead, I leave you with the following tantalizing picture as a place-holder – one of the images from one of my backup experiments, expressing a construct I received recently.
Isn’t she a beaut?
I’ve been pondering the theoretical maximum number of simultaneous cell biological experiments that one person can do without losing it. I’ve also been testing the theory on a practical basis – on myself.
And I can safely report that, by all accounts, I now have the answer: Twelve. Plus or minus two (around p <.01, if I ever have the time to actually calculate the stats). Very soon, two months will have elapsed since a journal gave me a three-month deadline to answer one biological question and include its favorable answer in a revised manuscript. Two months: they’ve melted away. It’s not an overstatement to say that I’ve been running myself into the ground, having come up with four different ways to answer the question and pursuing all of them at the same time to hedge my bets. I have to dash around the lab with a diary and three timers to keep track of all the many ongoing experiments and their various time-points. Just yesterday afternoon alone, I had to replate some cells and fix them at various times afterwards; set up and monitor a timelapse video acquisition; zap DNA into some cultures that had already been depleted by RNA interference; spend three hours on the confocal microscope photobleaching and acquiring images for FRET analysis; analyze and record the last seven experiments that had just come down; and lyse cells for a Western blot. Along the way I accumulated a number of slides and lysates that I didn’t had time to process further, which are currently queuing up in the fridge and freezer.
It’s got so I’m lucky if I have time to burn my tongue on half a cup of coffee somewhere in the middle of all this, and I arrive home with a brain and body that feels pummelled. Nevertheless, I’ve been enjoying the turbo-gunner mode – probably because I know an end is in sight. I’d forgotten the seductive buzz of being the first one in, or the last one out, or stopping by on the weekend, all of which bring back memories of grad school and my five years of non-stop 80-hour weeks, when the body was younger and the dreams were still untainted by disillusion.
But that’s not what I wanted to blog about. I actually wanted to encapsulate my happiness about performing a procedure that, for no good reason, I’ve fallen in love with. Of all the things I have to do to meet my goal, I am most pleased with the Rac assay: a classic, old-school biochemistry technique in which you experimentally manipulate your cells according to your hypothesis, and then lyse them and pull down activated Rac (a small GTPase that orchestrates many events upstream of actin cytoskeletal rearrangements). With this, I can ask the question, is Rac activated or not when my gene is knocked down? This is the crux of the question that the journal editor posed to me.
The assay is notoriously fussy and is spoken about in hushed whispers of dread by those in the known. It relies on a protein partner called PAK, coupled to beads, which can bind to Rac only in its ephemeral GTP-bound state, and centrifugation, which bring the beads down while the inactive Rac washes away. Ephemeral is a bit of an understatement – the fragility of Rac’s active state forms the foundation of urban lab legend. I’ve done it once so far, with success, and am looking forward to my favorite part of the assay in a few hours’ time: harvesting the cell lysates. Yes, I know this might seem banal, but I adore mashing up cells and scraping their ice-cold, gelatinous innards with a plastic windshield-wiper-like paddle into a tidy tube for processing. I can’t really tell you why, but of all the manipulations I do, this is what most makes me Feel Like A Scientist. I like it so much that I even immortalized the procedure in my first novel, Experimental Heart.
I’m sure all scientists can single out one technique that most makes them Feel Like A Scientist, that gives them that fuzzy-focus, CSI Moment.
What’s yours?
The plot thickens.
For those of you who have been dangling in urgent uncertainty, I can report that the vibration problem in our incubator has not gone away. I thought I’d get around it by using smaller, non-round vessels, such as the 8-well chamber slide in the front of this image:
But alas, the phenomenon persists. Very oddly, in these small, square-shaped wells, I don’t get concentric circles, but long lines of cells, rather like a string of old ladies queuing for a bus shelter in the provinces:
We’ll leave aside the rather ironic fact that several people in our lab are spending lots of time and money trying to force cells to grow in lines using cutting-edge micropattern contact printing – this outcome is not desirable in my own experiments. As anyone who studies the cytoskeleton knows, outside forces can have big effects on internal actin and microtubule configurations, so the last thing I need is something that forces my cells to change shape in the wild-type situation. Will the scourge never end?
On the other hand, closer to home, I can happily report that Richard has solved my pressing microwave popcorn mystery. The solution? Elevating the bag onto an upturned pyrex casserole dish – which apparently aligns the bulk of the popcorn kernels more closely to where the microwaves are bouncing back – completely and reproducibly sorts out the problem and yields a full bag of salty goodness.
If running a scientific project is like cooking, then my usual modus operandi in the lab is to prepare a lavish, many-course meal. The meal, in this analogy, is the overarching goal of what I want to understand, and each course is one independent angle on that question. Such a multitasking approach is useful: you get to try out different competing theories, which can answer your question faster, and if something crashes – say you burn the casserole – you can still keep the project afloat with more promising routes and extra helpings of dessert.
My multitasking tendencies got more extreme during my experience as a team leader in a Dutch biotech company – when you have a group of people working for you, it’s so easy to expand your menu. My challenge in returning to science as a re-entry fellow was to adapt to being a lone-wolf chef once again. Although it’s been hard at times, I’ve managed to run my project in the manner to which I’ve grown accustomed, while at the same time keeping it manageable for my one pair of hands.
In the past month, however, I’ve had to change my approach completely. My big screen paper came back from an excellent cell biology journal with three positive reviews, but after a bit of back-and-forthing with the editor, I was charged with performing just one final experiment to flesh out the mechanism a bit more. And I was given three months in which to do it.
Never has my career depended so much on the outcome of one single experiment. Applications for independent fellowships are coming up this autumn, and though I have a good shot at them, I have a feeling that this paper will be what makes or breaks the acceptability of my track record, which will be an important component. So a successful experiment will land the paper into a safe and well-regarded home in time for the deadlines, which will facilitate my applications; in turn, success at winning a fellowship will allow me to stay in science as an independent researcher. Failure, though: I almost don’t want to think about the reverse. No timely paper, no fellowship, no position. In that event, it’s time to do yet another post-doc to try to consolidate my chances – or to finally surrender gracefully to the inevitable and leave research altogether.
So my laboratory life has narrowed down to an incredibly focused point, and I have to say I’m enjoying myself immensely. One key experiment: what could bring more lucidity to my life? It’s like trying to boil the perfect egg. Everything else is on hold as I grapple with the best way to deliver. The editor referred to the experiment as “straightforward”; well, yes and no. There are two ways to do it, neither of which are up and running in our lab: a classic biochemical approach, and a new-fangled strategy involving Förster Resonance Energy Transfer microscopy (FRET). Naturally I’ve called in all my connections and received advice – the old-fashioned biochemists, horrified, tell me to avoid FRET like the plague, while my imaging-savvy colleagues would rather put out their own eyes with a Gilson P1000 than spend all day in a cold room pulling down elusive proteins so fragile, urban myth goes, that if you so much as hold a tube at its base instead of by its lid for a few seconds, the game is up.
Typical me, I’ve decided to pursue both in parallel. Each technique is challenging and interesting, and equally useful to have under my belt for the future. And clearly, doing both will maximize my chances of success.
One month into the three-month period, and I’ve had some modest success with the FRET, though I’m not sure it’s sensitive enough to reveal my phenomenon clearly enough. And it’s gruelling work: preparing the cells and capturing the images is easy, but analyzing the data is painstaking and slow, one cell at a time with dozens of analysis steps in the pipeline. For example, I managed to look at four today, and I’ll require many dozens; rainbow-hot images of phtotobleached cells are seared into my retina and haunt my sleep. Meanwhile the reagents for the biochemical assay have arrived from America, and I’m going to set up a few pilots next week. It’s more sensitive, and I’ve always had biochemical green thumbs, but I’m worried that my process will be too localized in the cell to show up in a mass population of lysed cellular proteins.
So the game is still all to play for, and the stakes are incredibly high. I should be worried and stressed, but instead, I’m upbeat, ruthlessly efficient and buzzing on adrenalin.
It’s going to be the best damned egg you’ve ever eaten.
Crop circles are so last century. In our lab, HeLa cell circles are all the rage:
The tissue culture incubator is currently plagued – not with aliens, but a random vibration or resonance that causes our cells to sporadically seed in perfect concentric circles. As a biologist, I haven’t the foggiest what sort of vibration or energy could cause these amazing patterns – I leave that sort of thing in the capable hands of the mysterious physicist and mathematician types who drift in and out of our lab, collaborating with my colleagues on building virtual cancers and online epithelial layers and God knows what else. (For all I know, they’re busy crafting the perfect virtual post-doc, one voxel at a time, who can pipette 24/7 without sleep, social life or access to a vending machine carbon source.)
But for us real-life biologists, such vibrations can have serious consequences. The cells within the circles are confluent, when we’d rather have them in growing exponentially without neighbors – but that’s the least of our worries. Apparently vibrations strong enough to disturb the seeding pattern can wreak havoc on the biochemical processes within. The boss even offered up a few doom-and-gloom anecdotes about the time he was a post-doc and the entire lab’s experiments went into free fall when a new lift was installed next door.
To me, all of this is just a more visible-than-usual reminder of the unavoidable fact that it is impossible for any experiment to ever be replicated with the precise conditions of the previous. If you run three identical Western blot experiments, you’ll get slightly varying band intensities. If you read about an experiment in a paper and try to reproduce it, it doesn’t always work. Apparently the most trivial-seeming things can have strong effects – such as the pH of the water mains used to feed the Milli-Q water polishing machines. Minute changes of temperature and humidity – air-co in Texas versus a sultry summer London lab – are bound to stretch the boundaries of what scientists like to call STP: standard temperature and pressure. I once had a colleague in grad school whose experiments failed miserably for years until the one fateful evening she decided to stretch her legs and took her bacterial tubes along for the ride; the corridor was several degrees cooler than the lab and the rest was history – and a mighty fine Nature paper if I recall correctly.
But I don’t see this as a bad thing. Instead, I find it infinitely reassuring. When you open up that next issue of Cell and see three back-to-back papers from three different labs all reporting the same general finding, you can be sure that the phenomenon under consideration must be remarkably robust. People often complain that science is wasteful, that having a dozen labs working on the same thing is inefficient and nonsensical. But it’s not until you see the same results half a dozen different ways that you truly know you’re onto something.
So bring on those HeLa circles. My knockdowns still worked, so I know my biology is strong enough to withstand vibrations, aliens and whatever other subtle variations the environment might throw up.
Nasty referees, however, are another matter.
Whenever you stick your head above the parapet and express a strong opinion in a high-profile venue, it’s almost inevitable that you’ll receive a large number of emails in response. Most of the follow-up I receive tends to be from people in the same position who recognize and share the sentiments expressed, writing to share their gratitude. But – probably of more interest – a smaller percentage of respondents are those who disagree and want to tell me why. (An even tinier fraction are from a certain sort of person eager to explain their revolutionary ideas about quantum uncertainty, string theory or government conspiracies, but these we can classify under ‘entertainment’ and swiftly move on.)
Some of the naysayers make excellent points that make me think, and the best of these cause me to shift my position slightly to accommodate the new perspective. The most effective of these are those who have gathered thoughtful evidence, usually in the form of official surveys from reputable establishments such as Ipsos MORI, or peer-reviewed data.
But these people are in the minority. Usually what I get is anecdotal evidence.
It is, I suspect, a very strong tendency of human nature to generalize one’s own personal experience into a broader worldview. Such an approach is, after all, entirely natural – we filter our whole universe through personal sensation and, though we can be influenced by outside opinion and evidence, the most intimate and immediate impressions are those we gather ourselves. If those two perspectives happen to clash, it’s understandable that many would prefer to place more value on their own. Indeed, part of basic scientific training is to teach people to rally against these natural tendencies in favor of objective, measurable outcomes.
A few months back I wrote a piece for Nature about women scientists being under-represented as pundits, in which I speculated that this might be related to detailed empirical observations I’d made over 20 years of conference attendance: in a gender-balanced audience, far fewer women tended to ask questions at lectures. (As an example, I’ve recently returned from the British Societies for Cell Biology and Developmental Biology annual joint meeting in Canterbury, and of the first eight talks I attended [seven male speakers and one female], out of a total of 24 questions, only 3 were posed by females; the audience was roughly 50:50.)
Anecdotal evidence is especially insidious when it derives from highly isolated environments that buck the trend. For example, one response I received was from a man from a British institution who wrote that, because more than fifty per cent of professors in his institute were women, there was clearly no problem with women in science. Leaving aside the fact that my piece was not discussing the professional representation of female scientists, it’s a perplexing extrapolation for someone to make: perhaps he was unaware of the stats overall. But when I pointed out that only about 9% of UK professorships in science and mathematics were held by women, it didn’t change his opinion. In this case, hard data could not sway personal experience – not even that of a scientist who should know better.
Another response I received was from a woman – let’s call her Mary – who was frustrated by the fact that no one was willing to admit that the real story about gender skewing in science was down to the fact that women were not as mentally capable of doing science as men. We’ll leave aside for the moment the fact that (a) my piece had nothing to do with the gender basis of scientific aptitude, and (b) I was speaking about a phenomenon that occurred in a gender-balanced population – the life sciences, where numbers are close to equal as far as the pool available to give opinions. In this case, Mary’s opinions had been formed by talking to other like-minded women, but (it seemed to me) more significantly on the basis of the view of her father, a highly respected engineer who used to teach post-grad trainees in a leading industrial equipment company.
According to Mary, her father ultimately came to the conclusion that, despite their degree in engineering, the women he was charged with training just didn’t have the right sort of brain for designing equipment. So this view helped shape Mary’s conviction that women are underrepresented in engineering not because they are intimidated, but because they simply lack the basic mental skills. In her email, she implied that the phenomenon held true in the scientific research sphere as well as in engineering.
And here’s where both the scientist and novelist in me started to feel intensely curious about this man and his group of female apprentices. I began trying to fill in the gaps with the limited information to hand. Of course one possible explanation for his observations was that women in general just aren’t as apt at design of industrial equipment – or that this group of women in particular were not. But it wasn’t difficult to hypothesize other scenarios. I was guessing that these subjects were children in the 1950s, plus or minus a decade. What was the upbringing of these women like? Were they given Lego, toy trucks and Scalextrics to play with, to help hone any innate aptitude during their formative years, or were they rather showered with dolls and tea sets? What was the parental reaction if any of the girls tried to play with their brother’s toys? When they expressed an interest in becoming engineers, did their parents and teachers give them support, or did they react badly? During their studies, were they taken as seriously as their male counterparts and given the same opportunities; did they have the same level of confidence as a result?
That’s just the cohort of women to consider. What about the male trainers of women trying to be engineers in that era, such as Mary’s father? Were they a big believer that women belonged in the field? Did they do their best to make these women feel welcome? Did they treat their female students as seriously and respectfully as the male students? Or did they have a private opinion that the girls just weren’t up for the job at hand, and did this become a self-fulfilling prophecy? It is well documented (see here for a nice summary) that a phenomenon called ‘stereotype threat’ can cause women to do worse on math exams than men if they’re reminded beforehand that they’re not supposed to be as good at it – an effect which disappears when they are not prepped. Also, there are plenty of peer-reviewed studies (as always, elegantly outlined in Virginia Valian’s book Why So Slow) showing that women and men with otherwise equal qualifications and talents are not perceived to be equal; were engineer trainers of the day susceptible to that extremely common and unfortunate bias? And of course, this was one company in one physical location, many years ago: is it really possible to extrapolate to the entire, present-day world on the basis of this man’s subjective experience, no matter how respectable? And finally, most importantly, can we extrapolate from engineering to every other scientific disciple to conclude, as Mary had, that women are just not cut out to be scientists and should instead focus their efforts on endeavors more appropriate to their innate skills, such as nursing?
For me, as a scientist – female or otherwise – , the answer is obviously ‘of course not’. We don’t have enough information to draw a reliable conclusion one way or the other about the women under her father’s care. The best we can do is look to the peer-reviewed literature, which despite many attempts over the years, to my knowledge still fails to show that the innate differences in scientific aptitude between the sexes is larger than the variation within them (see for example summaries by Spelke and Hyde – please do send me any contrary studies, as I’m genuinely interested).
I could, of course, counter her arguments with anecdotal evidence of my own. In the 21 years since starting my PhD, I have never noticed a gender-based difference in scientific aptitude among the many hundreds of scientific colleagues I’ve encountered in labs around the world. I’ve never noticed that the male students I’ve supervised have had a better grasp, or the female professors who’ve mentored me have had an inferior one. Of the thousands of scientific papers I’ve devoured over these two decades, there has been no tendency for the best ones to be authored by men, or the weak ones by women. Sitting through thousands of research talks and group meetings, I haven’t noticed that the men on average produce better research data or come up with more insightful experimental designs or hypotheses than their female counterparts. All I have noticed is variation from individual to individual: some people are brilliant scientists, some are weak, and the rest fall into a long continuum in between.
I could counter her arguments this way. But I won’t – because it’s not scientific.
But what, then, is the best way to help people think beyond the merely anecdotal ? Do we reply with statistics and citations and hope to sway minds that way? Can better education that emphasizes critical thinking and objective measurements help to counter our natural tendencies to believe what we think we see and to prize this view above all others? Or will personal experience always reign supreme?
—
Note added later: I should note that anecdotal, or personal experience, is a powerful persuasive tool and I don’t advocate avoiding it for rhetorical purposes. Ironically, my op-eds in Nature have contained such items, largely because the editor encourages their use (and references are not normal for that format).
Some late nights in the lab, that vending machine chocolate bar just can’t fill the snack hole that only a truly grueling experiment can induce. You need something hot, salty and preferably dripping with fat.
It’s no surprise, then, that microwave popcorn is the scientist’s best friend. It ticks all the boxes: flat-pack construction for easy storage, non-perishable at room temp, cooks in only five minutes and – unlike sweets – doesn’t hit your stomach too hard when it’s running on empty. During graduate school, microwave popcorn undoubtedly kept me from certain starvation. Its only downside, as far as I can see, is its tendency to radiate a mouth-watering aroma all over the institute in a matter of seconds such that, by the time it’s finished popping, you might have acquired a few hopeful onlookers (typically malnourished PhD students). I find that an apologetic smile and a “Sorry, I haven’t eaten for twelve hours and this is my dinner” is enough to disband the hyenas.
I’ve been popping microwave corn for about 25 years now, probably on hundreds of different machines. I’ve popped them in cheap set-ups in the common rooms of university accommodations, in Soviet era contraptions passed from student to student in group houses, in all the various flats I’ve lived and institutes where I’ve worked in several countries. And I’ve tried all the major brands of corn. Despite the wide variation of conditions, the general recipe has remained surprisingly constant: put the bag inside, set the microwave on ‘high’ for five minutes, and press ‘start’. Sometimes between about 3.5 to 5 minutes, depending on the machine, the pops will slow to about a second apart, and then you know you’ve reached the point of diminishing returns: all of the kernels haven’t popped, but if you leave it longer, the popped corn will start to dry out and scorch. Usually you’re left with about 20 to 30 unpopped kernels after an average session.
When we moved into my new house last year, we ordered a very swanky Panasonic microwave/oven combo from John Lewis. It was easily the nicest and most expensive microwave I’ve ever had access to. We’d had it a few days and I’d used it for a few basic operations – reheating coffee, defrosting meat and the like. Nothing fancy, but everything seemed to work fine.
And then, I tried to pop some corn. The corn didn’t even start popping until after 4 minutes, and after the bell dinged at 5, only about a quarter of the kernels had popped. The bag was very hot, though. Perplexed, I put the bag back in for another 5 minutes and ended up with about 50% yield. I wrote it off as a fluke, but a few days later, I chose a bag from a new box and set the timer for ten minutes. The dynamics were similar, as was the result. The corn was a brand I’d been using for the past few years on two very different microwaves, so I knew it wasn’t likely to be the product. But the oven seemed otherwise fine, and I’d feel ridiculous taking it back for an exchange on the basis of “suboptimal popcorn performance” – the complaint was just too niche. So in true British fashion I decided to live with it.
And then one day, a few months later, I produced a perfect bag of corn after five minutes.
What had changed? I remembered that a few minutes before I’d made the corn, I’d heated up some hot water in a mug for a minute or two. Could it be that the microwave somehow had to be pre-heated or primed for optimal corn performance?
Dear reader, I did the experiment the following evening. And it seemed to work: half a mug of water for two minutes on high was enough to prime the oven to pop a bag of corn to about 80-90% of its usual yield after about 6 minutes. Not perfect, but definitely getting there.
The funny thing is, it doesn’t always work, and it fails more often than it succeeds. I think there are two important variables: exactly how much water you have in the mug, and how long after the mug run finishes before you introduce the bag of popcorn. My downfall up until now has been improper documentation, so these impressions are only anecdotal. But from now on, I’m determined to do things scientifically: to use the same mug and systematically vary amounts of water heated for the exact same amount of time; and to systematically vary the time between mug heating and bag introduction. I already know that straightaway is too quick, and five minutes is too long. So I’m hopeful to have the formula nailed over the next month or so.
In the meantime, if anyone out there can diagnose what’s wrong with my addled Panasonic based on the meager data to hand, I’d love to hear all of your theories.
Even the darkest tunnels tend to have lights at the end of them. In the past fortnight, not only have I submitted my big screen paper – the culmination of four years of work – to a very reputable cell biology journal, but said journal has actually decided to send the manuscript out for review.
I have mixed feelings about having passed muster: if it had been rejected outright, I could have submitted it to a less demanding journal that would be more likely to accept it as-is. In getting my foot in the door, I could very well be setting myself up for a protracted siege. Nevertheless, there is nothing quite like the feeling of reprieve when a paper is off your desk, for better or for worse. It’s not just the sense of wide-eyed hope, undiminished yet by sour criticisms and unreasonable demands. It’s something more fundamental: regardless of the outcome, you are guaranteed at least a few weeks of peace.
The boss is urging me to dive into experiments that the referees “are definitely going to want”. But I am not so sure: my track record of predicting the whims of referees is abysmal. Although I’ve only dealt with eleven papers as a first author, I handled hundreds as an editor and it never ceases to amaze me what the peer review process asks for – or fails to, in many cases. I’m more inclined to do a few experiments that I’d planned to do anyway, whose outcome could bolster my case should the need arise. Even if unasked for, good data can often be proffered to the editorial shrine in a sort of bartering process – “We didn’t do that extra rescue experiment, but check out these sexy Q-PCRs!” And if all else fails, I’d rather withdraw the paper and submit it somewhere else than commit to half a year or more of referee placation. Ordinarily I’d be fully committed to the glorious battle, but I no longer have the luxury of time: if my paper is not in press in time for autumn fellowship deadlines, my entire career plan could be scuppered.
There are more important reasons why I’m resisting rushing down suggested experimental paths – why I’m taking the time to weigh up options and make the right decision. One of the ideas is only tangentially related to the paper and would involve a complex and expensive fishing-exercise technique. Although it sounds easy on paper, my experience with complex and expensive techniques tells me that nothing is as easy as it sounds; even when you outsource the main activities, you can still face weeks if not months of pilot experiments to get the conditions right, and when your list of hundreds of hits comes back with nothing but a probability score to tell you what’s important, you’ll likely might need yet more time to verify the trend, let alone make sense of it in a biological context.
But the truth is that I have only nine months remaining. Not only do I need to save time to do the experiments that the referees will actually ask, but I also have to come up with a research plan for the future, write grants to fund it and, ideally, generate some preliminary data to make these plans look feasible. Seen in this light, nine months is nothing. It might be different if the complex and expensive technique were in the area that I’d like to focus on in future. But it isn’t: it’s analyzing a cellular process in which I have little interest, and it’s not going to play a role in my future proposal, at least as far as I can see right now. My preference is to spend my time pursuing angles that are transferable to the next step, either topically or with regard to the techniques employed.
There is something even more fundamental here. In the past four years I have been trying to scrabble back to the apex of my career, to the time when I ran a group and presided over an independently conceived set of projects. Since returning to the lab, it’s almost as if I have relived my entire scientific training period in compressed fast-motion, from fumbling student to tentative new post-doc to confident senior post-doc, poised on the edge of regaining my lost independence for the first time since 2001. Now more than even, it’s time for me to chart my own path through the uncertain waves and – very soon now – cut myself adrift.