In which I skate on thin ice

Britain’s recent deep freeze has got me thinking about ice. One could hardly think of anything else during the worst of it, when negotiating one’s way to the Tube was a delicate balancing act on the un-gritted pavements. (Note to my American readership: Britian doesn’t stockpile enough grit to keep all roads and pavements clear, and there is no law that residents must shovel the walk bordering their property. Hence: mayhem.) I found it scientifically interesting that the financial men in suits, who flock each morning to Canada Water station on their daily pilgrimage to Canary Wharf, were the worst affected; something about the slick soles of their buffed Italian leather shoes, perhaps. Ice is a great leveller: it doesn’t matter how tightly you clutch your Prada briefcase – you’re going to look as ridiculous as the next person with your mincing and skidding.

But ice isn’t all bad. Personally, I’ve been waiting for six years for the ponds in Russia Dock Woodland to freeze over so I could skate. And at last the day arrived. It was the first morning with temperatures above zero degrees centigrade in nearly a fortnight and the air was fresh with that almost imperceptible mildness your skin can detect when the switch flips.

I’m not an idiot: I wasn’t about to take my life into my hands like the person who left a long, extensive trail of footprints one late (and, one can only assume by the act itself, along with its meandering trajectory) drunken night along the virgin expanse of Greenland Dock.

This vast body of water – deep enough for ocean-going liners in its day – had been frozen over for about two weeks at that point, but the ice was friable with trapped air and couldn’t have been more that a few inches thick, to judge by the cross-section revealed when some kind soul bashed out a large oval by the Moby Dick for the terns, seagulls, swans, coots, grebes, cormorants and ducks that call the Dock their year-long home. Such a foolhardy act surely qualifies this (dare I guess) gentleman for the At-Risk Survivor category of The Darwin Awards.

No, I chose my pond carefully – just three feet deep at the center, therefore braving only the possibility of wet trousers and a bit of humiliation. It was supremely wonderful to skate in a meadow, despite pretty difficult going – the surface was knobbly and the ice encased twigs, leaves and even a few exploded bulrush heads: where’s that Zamboni when you need it?


photo credit: rpg

Forward movement and backwards crossover maneuvers were fine, but there was something odd about the consistency of the ice that made it almost impossible to do anything requiring a friction-mediated launch, like a waltz jump or forward spin. Could it be that with the temperature above freezing, the blades of my skates were melting the ice, but the water could not re-freeze behind them? Or perhaps the ice was simply not hard enough for my toe picks to acquire the right purchase?

Looking into it later, the slipperiness of ice is a lot more complicated than I thought. Apparently physicists and chemists have shown that the surface of ice has a “quasi-fluid layer” that makes it slippery even when ice skates, shoes or hockey pucks are not applying pressure: in other words, ice is slippery even when we’re not around to play on it. (Forests and trees, anyone?)

I do in some ways sympathize with the urge to trespass upon more dangerous ice: there is a painfully strong allure to an unblemished sheet of gleaming platinum blue stretching in all directions. It’s the sort of pull the ancient Asian race that decided to brace the Bering ice bridge and colonize America might have felt. Maybe it’s just a step in human evolution but, amongst my fellow Rotherhithe residents at least, the urge to throw stuff onto it seems even stronger. There was only one set of footprints on Greenland Dock, but a veritable menagerie of hurled objects: bricks, cans, life rings, bags, bottles, traffic cones, even a Tesco’s shopping trolley.


It’s Southwark Council’s fault for paving the local roads in easily prisable bricks

But it’s all over now. It’s raining in London, and all of the snow has melted away.


A snow-cadaver in Bloomsbury, yesterday.

The only ice left in town is the stuff I had to scrape yesterday afternoon before departmental cocktails, from the third-floor -80 freezer: a rotating chore that I loathe.

Meanwhile, out in slightly cooler Zone 2, the ice of Greenland Dock this morning was just a fragile, puddled shell with many incursions of open water for the birds to enjoy. A few of the bricks are hanging in there, half-canted like the Titanic in progress, but I also noticed a number of suspiciously brick-shaped holes. I am happy to see the water again, full of motion and shards of reflected light. I know spring is a long time away, but there are glimmers of it in the air now and it fills me with a secret glow of happiness.

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In which it has all happened

Sometimes I feel as if my career is trapped in a bubble of time. While all the scientists around me flow purposely along the classical linear progression from neophyte to tenured lab head, I float in a recursive pattern somewhat above and removed from the brisk conveyor belt sliding past below, bobbling against the ceiling like a helium balloon whose string has slipped through someone’s idealistic fingers. And this time-bubble plays tricks: when I look into the faces around me, I can see myself in every one. I am the pale-faced PhD student the morning after an all-nighter; I am the new post-doc flush with her first publishable results and the boss’s admiration, and the seasoned one with many more results, not quite as celebrated. There I am, too, defected to industry and running a team of my own. I am the last researcher standing at a start-up company that takes a full year to finally die; seven leaving parties in three weeks and no one left for my own. I am on the dole in a strange land, not knowing when my professional life will restart. I am the senior fellow doing the rounds of job interviews, short-listed but never quite chosen. I am the science journalist, the editor, the journal manager. And I am also the mature post-doc, older than the lab head who hired her, coming back to square one amongst colleagues young enough to be her own offspring.

But the bubble of time is out of time, so I can also recognize myself in stages I have not yet and may never reach. So there I am setting up an academic lab of my own, drinking champagne at the success of my first program grant application, chairing my first session at a major symposium, speaking at my inaugural professorial lecture. At the same time, I am also washed out of research, returned to publishing. And I am cast away from science-related fields altogether, doing something terribly clever and fulfilling and never looking back. And I am cast away from science-related fields altogether, doing something terribly clever and fulfilling but suffering from terrible longing and regret at what might have been.

It’s the occupational hazard of a novelist, seeing all possible outcomes simultaneously. And recently, circumstances have imbued my career path with a particular stark clarity. This month marks a milestone; in precisely two years my career re-entry fellowship will come to an end. Thus far since returning to science, I have published two review articles and will submit a second-author paper in the next few days. In addition, I am a minor co-author on another. In the next few months I’ll be writing up my screen paper as a first author – it will get into a solid journal, but nothing splashy. I envision another first-author paper from my timelapse screen and possibly one or two more from following up interesting hits that have emerged from this gene discovery program. Trapped in my own time, now, there is no telling whether those later works will end up as top-tier publications. And I suspect that this factor is what will most dictate my success or failure in remaining in academia – which most days I am fairly sure is the most favourable outcome for my talents and temperament. I can work as hard as I like, but if the biology turns out to be uninteresting, there is nothing I can do about it.

I am trying not to let the future frighten me. I have a large number of authorships in my CV even though my path has been indirect. But if a research career doesn’t pan out, I have a good history of employment, a great deal of outside experience, and I do not doubt that I will be able to find work. But there is still a sort of terror in the unknown, even if you don’t believe you will come to harm. I cannot sustain terror for long, but it dogs me now like a shadow, flickering into life whenever the weather changes.

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In which I seek patterns

I spent most of 2009 in the lab engaged in visual pattern recognition – the scientific equivalent of one of these things is not like the other (or, for the Brits amongst you, the odd one out round). In the initial triage stage of my RNAi morphology screen, which went on for months, I sat in front of my computer and flashed quartets of images before me in rapid suggestion, asking myself simply, which of these is normal, and which deviate?

Recently my father emailed me an etching of my London neighborhood, Rotherhithe, as envisioned by James Whistler (1834–1903). In the picture, two men sit relaxed on a quayside with the boats and river behind them, and I was captivated by how familiar the scene looked. Like me, Whistler was an American ex-pat in London, making the image doubly significant. I was immediately inspired to try to track down the precise site featured by the artist using solely what I could see in the picture – no cheating on the internet unless I was stumped.


Rotherhithe (Originally published as Wapping), 1860.

Unknown even to some Londoners, who as a rule tend to shun the La Rive Gauche, Rotherhithe is a leafy, beautiful place steeped in history. Situated in the Docklands on the south bank of the river opposite the Isle of Dogs and Wapping, in the old days it was a village on the outskirts of London, a port in its own right since the 12th century. Many of the old warehouses have been converted to flats, and there’s a beautiful old pub called The Mayflower where, apparently, our Founding American Fathers paused for a quick pint. The area is also memorialized in Elvis Costello’s haunting waltz tune, “New Amsterdam”. In fact, when I moved back to London from Amsterdam in 2003, I opened up the A-to-Z and tried to find a place that would remind me of my Dutch flat in the Hemonykwartier of the Pijp. Homing in on canals and docks, I made this place my new home.

I thought it would be easy to track down the scene; after all, the artist had incorporated what looked to be highly diagnostic curvature in the river beyond. Of course many of the waterfront buildings would have changed, but there was no hiding that sexy bend. Nevertheless, I failed miserably on my first outing: there simply was no place anywhere between Deptford and London Bridge where the Thames had that exact curve. I emailed my Dad in despair, opining that Whistler must have conjured the scene from his head with no precise view in mind.

It was then that my father wrote back sheepishly and told me the image he’d ripped from the internet had been displayed in the wrong orientation – flipped 180 degrees around the y axis.

Back on track! So that sketchy dome in the far right corner suddenly resolved itself as St Paul’s Cathedral, and all clicked into place. Along with my neighbor Richard and one of his daughters as reinforcements, I set off by bike on a frigid sunny afternoon armed only with a printout of the etching, correctly oriented this time, slowly working upriver from Nelson Dock Pier. Soon it was clear that, as expected, Whistler had created his work right in the heart of Rotherhithe. It looked very much to us as if the artist had been standing on the back terrace of the Mayflower itself; we were initially flummoxed by Tower Bridge, conspicuously absent from the Whistler composition, until Richard thought to whip out his iPhone and confirm that it hadn’t been built until 1886.

It didn’t seem precisely right – if the scene were part of my screen, I’d have scored it as a mild phenotype. But it was getting late: spatters of cold rain were coming down and we all felt we deserved a session at the pub to warm up. It turns out we were a thousand feet shy of the real target: the riverside balcony of the Angel Inn on Bermondsey Wall. Sounds like a good excuse to take a walk, on this long, lazy holiday week, have a nice pint and try to capture the definitive photograph once and for all.

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In which priorities clash

The famous cancer researcher leaned against the podium, smiling as she fielded questions. For the last hour, she had thrilled us with a truly stellar keynote lecture containing a pleasing mix of historical context and cutting-edge results, and now the audience was showing their appreciation with a slough of thought-provoking queries. Always easygoing, the speaker now seemed entirely relaxed in the aftermath of a job well done. In that mood, it is probably no surprise that she was feeling expansive.

“Do you have any idea,” asked a man in the back row, inevitably, “of the mechanism of action?”

The audience was silent in anticipation. The cancer researcher paused, a conspiratorial twitch to her mouth as she seemed to weigh up options. And then, leaning forward slightly, she said, “Don’t tell my post-doc I told you, but we’re pretty sure it’s down to…” – and she then proceeded to expand a little bit on the biology, not giving everything away, but certainly leading us all in the right direction.

As we filed out of the room towards the reception drinks afterwards, those words kept ringing in my head: Don’t tell my post-doc. I couldn’t help picturing this person, giving him a backstory. On the young end of scale, I speculated, maybe coming up to the end of his fellowship funding. For the past two and a half years he’d slaved over his work, trying to tease out the secret that made his protein orchestrate such intriguing behavior in cells. He’d been to two meetings so far, but both times had decided that to reveal the fact that the switch was governed by that particular mode was too easy to follow up; he didn’t like keeping such interesting news under wraps, but he only had two papers from his PhD, so he needed a really big one to even hope to compete for a career-development fellowship next year.

And a few days before when his boss was preparing her talk, they’d talked it though again and had decided that she wouldn’t mention the mechanism – after all, the field was absolutely saturated (4000 new papers published a year, the cancer research had told us in her introduction) and many of the best and brightest would be in the audience. No, they’d wait until the paper was submitted before spilling the beans.

I imagined how the post-docs might feel when his labmates returned from the meeting with the news that his secret was now out. I’ve been there myself, so it wasn’t difficult: disappointment and anxiety in equal measure. Perhaps he might even have second thoughts about that Christmas break he’d decided to treat himself to.

Now this is obviously all speculative, my novelist’s brain on overtime: I have no idea if the data really were that crucial or whether there had been any sort of pact in this particular case. But I do know these sorts of mini-betrayals happen all the time. Lab heads – especially tenured, well-established ones – have everything to gain by openness, but pretty much nothing to lose. They can afford to see the benefits of sharing information and can participate in the often joyful process of unfettered communication. Most crucially, they can weather the odd scoop. But to the young first author behind the nascent data point, it is another story. One lost paper, these days, can be the catalyst that transforms an up-and-coming researchers into a failure.

I believe that it is very difficult for lab heads to remember this in the heat of the moment, when they are riding the wave of a stimulating meeting and secure in their immutable place in the scientific community. But until the system for rewards and promotions in biological sciences changes, there will always be a clash of priorities.

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In which we go a little cycle-pathic

For most normal people, a Sunday afternoon in London might find you down the pub having a lovely roast dinner, a lukewarm pint and a chat about the torrential winter rains or the rugby. But not us geeks: we’ve got standards to maintain. It’s not just a Monday-through-Friday, nine-to-five job – neither rain nor snow, nor sleet nor dark of night shall stay these quirky obsessives from the swift completion of their appointed rounds.

This past Sunday, Eva, Richard and I were sitting around my Docklands flat. Eva, on a flying visit from Toronto, had just about dried off from her swim from the Tube station and was getting her strength back with a bowl of pasta. I was trying to hold up my end of the conversation while finishing up an opinion piece for Nature, and Richard was mixing things up a bit by fiddling with his iPhone instead of his laptop. Plans were afoot for interviewing Eva for a LabLit podcast down at the local watering hole later about something suitably sci-lit geeky.

I’m not sure who brought up the topic first, but Eva mentioned she’d like to do some sightseeing in Cambridge, and Richard told us about the BRCA2 Cycle Path, part of the National Route over a mile between Addenbrooke’s Hospital and Great Shelford. As a public engagement exercise, the path had been painted in 2007 with about 10,000 stripes of four different colors, each representing a nucleotide base and collectively spelling out the entirety of the gene BRCA2. Residing on chromosome 13 and associated with breast cancer in mutated form, BRCA2 was sequenced at the nearby Wellcome Trust Sanger Institute, who sponsored its enshrinement on pavement.

Now, this is old news (which R. has blogged about here and here). What I want to talk about now is how a random trio of geeks, in their natural habitat, handled this conversational turn.

What exactly, we wondered first off, was meant by ‘gene’? Richard googled up a photo of the start of the cycle path, and we gathered round the screen:

Green, red, yellow, blue, blue, red, green, red, red, yellow, yellow…

Eva and I reckoned that the logical choice for the designers would be the beginning of the coding sequence; therefore the first codon would be methionine, making green an A, red a T and yellow a G (and blue, C by default). I voiced my doubts straight away: most Kozak consensus sequences place a G after the initial ATG, and that didn’t fit the pattern. Plus the size of the protein would be monstrous: ten thousand base-pairs /3 bases per codon = 3.6k amino acids x 110 daltons/aa = 396 kD – a huge protein. This cheered up Richard considerably: due to his background, he is quite mRNA-ocentric, forever going through life biased towards consideration of untranslated regions.

Abandoning my Nature piece, I navigated into the NCBI Entrez website and pulled out a representative messenger RNA sequence; the protein was indeed that huge, but I failed after only a cursory scan to see a start codon that matched the pattern (and was too lazy to put some welly into it). Eva pointed out that there were 4! (4x3x2x1 = 24) possibilities matching colors to bases, so searching for all the permutations by hand just might be too much hard work even for geeks on a Sunday. Richard transcribed the first 20 stripe colors from the photo and performed a Blast search on the assumption that the first stripe was an A, but didn’t get any hits in BRCA2. When Eva suggested he try all 24 possibilities, Richard briefly considered, then abandoned, writing a Perl script to do it for him. Instead, he had a search through Entrez, pulled up another mRNA sequence and searched for the presumed starting-with-ATG string, not by eye but with Apple-F, until he found an ATGCCTATTGG that matched the cycle path colors.

Another job successfully completed – but a geek’s work is never done. Borrowing just a little from Jane Austin, if anyone has any other cycle paths that need decoding, please send them on, for we are quite at leisure.

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In which I pimp my data

I sat down the other day to prepare a figure for a paper I’m co-authoring, confident I’d have it dispatched in a matter of minutes.

You can see where this is going already, can’t you?

It was a relatively clean Western blot result – a black band on a grey background, and no other offending pixels. The sort of biochemical result that is so unambiguous and clean that you don’t bother getting more than two or three exposures when you’re in the darkroom – especially when you’ve been busy flirting with that mysterious stranger with the New Zealand accent. After I scanned the X-ray film into a tif file, I could see that it certainly wasn’t perfect – the film we’ve been using tends to come out quite dark, so I knew I’d have to fiddle with some settings in Photoshop to make it publication quality. But I didn’t really expect it to be a problem.


Pure, unadulterated biochemical genius*

A few hours later, I was stumped. To make a long story short, what looked beautiful on screen looked like a dog’s breakfast when printed out; and what looked decent on a printout looked awful on my computer. I tried Levels, I tried Curves, I tried Desaturation; I tried sacrificing a vial of virgin Drosophila to the Photoshop gods. Despite the unambiguity of the result, making the band stand out cosmetically in both formats seemed impossible. And I think it’s important for a figure to look good both ways; after all, a referee might look at your images on screen, or print them out. There is really no way to tell how your data might be consumed. And superficial appearances, unfortunately, are often more important than substance.


Photoshop is evil

This wasn’t the first time I’d hit a wall in image presentation. A few days previously, I’d had a similar problem trying to print out a rough result for my lab notebook. This had been a three-color confocal montage from the Leica SP5, processed through ImageJ, adjusted in Photoshop and mocked up in Illustrator. Heart-stoppingly beautiful images on-screen – but they were almost invisible on the printout, as if my cells were being viewed through a thick smog. Various postdocs gave me various bits of advice – adjust the Levels; convert to CYMK; pull the legs off of virgin Drosophila while reciting the alphabet backwards. I was told various bits of conflicting lore: for example, using Levels and Curves isn’t formally cheating, but adjusting the Brightness/Contrast is. And vice versa. After an entire day of this, I gave up, and the murky, uninformative printout in my notebook contains a scribbled caption that says, rather defensively, “this looks a lot better in the electronic version, but it seems that actin is decreased on over-expression of the gene”. No future archivist will ever believe it, though: the rare case of a thousand words being worth a picture.

At that point, I started to try to remember the last time I’d mocked up a data figure for publication. Why didn’t I seem to know any of the Photoshop tricks? It was only then I realized that I’d actually never done it before. When I was publishing in Leiden, I had a team of people working for me, and they did all the image processing for our papers. And before that, as a post-doc in London, none of my figures required this sort of manipulation, being mostly graphs and regular photographic images of cell cultures under phase contrast. Even more previously, as a graduate student, you took your blots and gels, mocked up with glued labels, down to the friendly guys in the Photography department and casually suggested that they might consider downplaying this or that particular background band when they were committing your data to old-fashioned 8×10 glossies.

It was at that point, with sinking heart, that I realized I might actually have to take a Photoshop course.

Oh dear God, no.

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In which science gets a bit more sexy than it might have wanted to

I don’t know about you, but I think today’s dramatic unmasking of scientist Brooke Magnanti as the mysterious call-girl Belle de Jour, blogger and titillating tell-all author, has just done wonders for the reputation of scientists. What could be more humanizing than the oldest profession?

Dr Magnanti, who in the Sunday Times’ glamour shots bears more than a passing resemblance to Paris Hilton, is reported in the paper’s exclusive to be “a respected specialist in developmental neurotoxicology and cancer epidemiology in a hospital research group in Bristol”. To make a long story short, she was broke after writing her thesis and decided that becoming a £300 per hour London call girl was a good a way as any to ease the pain.

There has been a bit of predictable tut-tutting about today’s revelation– but I wasn’t really that surprised. First of all, I have first-hand experience with how broke and destitute a graduate student can become. And second, science is a profession populated by human beings, and Magnanti’s decision seems like a perfectly human one. Maybe it’s just my liberal arts education, or my four-year stint in Amsterdam, but I can’t see anything morally incorrect about the good doctor’s money-making scheme, provided it was carried out, as she claims, without her or anyone else being exploited.

I was also gratified to find out that Belle de Jour was the genuine article – many journalists having decided that only a man could have written something so smutty. Good on her. But my main reaction on hearing the news was excitement: surely this unveiling would help to shatter the tedious stereotypes suffered by our entire profession. It may be a sad indictment of our times, but this one instance of raciness might do more than a hundred well-meaning “public engagement” exercises to show people that researchers are just as good – or bad – as anyone else.

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In which things develop

Some of my happiest moments have happened in the dark.

I have a thing for darkrooms. Perhaps it was a bias promoted in early childhood; my father is an artist and during my formative years he was in the process of transforming from a lithographer and painter into a purveyor of older forms of photography. The smell of fix and developer used to waft out of the basement of our house in Ohio when he was puttering around, and to me these essences are associated with comfort. What could be more magical to a child than images slowly appearing underwater in a tray of smelly witch’s brew? One of my earliest memories is seeing a row of wet transparent rectangles hanging by my mother’s clothespins from a line spun across the darkroom area, bathed in a red glow – the safest sort of light I can imagine.

I didn’t do a lot of dark room work myself until I was in my final year of university. I was taking photographs of plant cell spreads and karyotypes and was trying to get that perfect exposure under a vast, rickety camera contraption. If you asked me to operate one now, I’d have no idea, but I have a strong memory of having to wave my hand over the things I was shooting in order to ‘dodge’ the best exposure, and of mixing up all the developing solutions myself, just like my Dad used to do. (Why didn’t we send these off to be printed professionally? I have no idea.)

In graduate school and beyond, I practically lived in darkrooms. I remember the first time I felt comfortable enough to march right in to a place and unpack my film without a safelight – that amazing proficiency you eventually command with performing tasks blind. The sounds take over: the rippling noise of a film as you shake it out of its heavy foil bag, the snick of scissors clipping the corner for orientation, the beeping and hot breath of the X-OMAT machine. They may have automated the process, but the solutions – decanting through stained tubing into the sink – still smelt exactly the same.

In my department we had only normal doors, so going to develop your film was a solitary experience, though proceeded by a cheerful queue of people down the corridor, clutching their metal cassettes and film boxes as they speculated about how disastrous or glorious their results would be that day. About halfway through my graduate stint, Enhanced Chemical Luminescence suddenly hit the scene and there used to be a lot of tension between people like me doing radioactive Southern blots and sequencing gels (in and out in a jiffy) and those who were so paranoid and unfamiliar with the new technology that they insisted on mixing their reactions in the dark – thereby making the rest of us fret in the queue outside for much longer. I remember the first time someone showed an ECL-generated film at a lab meeting, and we marvelled at the exposure time scribbled on its top: “2 sec”.

It wasn’t until my first post-doc at the Cancer Research UK that I encountered the rotating-barrel door of a modern multi-use darkroom – what a brilliant idea. Rolling into the red-lit room (another characteristic sound, like the rumbling of a train) was a revelation: four people stood inside, calmly working in tandem – at least, I eventually worked out that there were people there as my eyes adjusted to the light. I soon determined that the composition of people in a darkroom determines how chatty they are, and the introduction of a new person can catalyze either gossip or silence. I’m not ashamed to admit that I sometimes conducted social experiments on my own colleagues. Something about the darkness changes the way we interact; it’s like being in a lift, but somehow nowhere near as awkward because no one can see your face.

Above all, darkrooms have been the scene of a thousand little personal scientific dramas. Nearly every major result I ever gathered culminated in that tense, two minute moment waiting for the finished film to emerge from its slot and fall noisily onto the plastic surface of the X-OMAT machine. I’ll describe the most exciting moment of all another time, but even the trivial controls and pilots have all engendered that same heart-pounding attack of mixed emotions: anticipation, fear, longing, wild confidence and crushing pessimism.

Recently I’ve been happy to find myself in a biochemical phase in my lab work. Cell biology is intriguing and can result in beautiful images, but somehow a scientific result doesn’t seem real until you see the bands on a Western blot. The people in my institute aren’t that chatty in the dark, I’ve found, but yesterday evening I shared the room with a congenial man with a New Zealand accent who was quite willing to pass the time. (In that quirky way of large institutions with few darkrooms and an itinerant population of students and post-docs, I actually have no idea who he is and would probably not recognize him if I passed him in the corridor today – the red reflection on his shaved head wasn’t exactly diagnostic.) In addition to talking about the weather, discussing a controversial program about the genetics of race and intelligence he’d watched on telly the night before, and opining that the more pessimistic you feel, the more likely you are to have a good film result – so not true! –, this unknown man also taught me an incredibly useful lesson: you don’t have to wait until the machine beeps to feed in the next film!

“Just stick it in on the opposite side and away you go,” he told me, gallantly demonstrating with his own film when I proved too nervous to try it out myself. I needed empirical evidence, you see. When the next guy rolled into the room (a taciturn specimen who killed the chatty atmosphere in a microsecond), he asked if the machine had beeped yet and Dr Kiwi let me tell him the good news.

It’s nice to know that after forty-something years in darkrooms I still have something to learn.

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In which I think small and see red

In my life as a scientist, I am continually struck by the modest miracle of the microscopic writ large. I think about this every time I streak a solution of invisible bacteria onto a Petri plate and come in the next morning to a sea of pale colonies scattered across the agar surface. Or when I amplify DNA from a clear droplet of liquid in the PCR machine and end up with a string of violent pink bands bristling on the gel under UV. Yesterday, my benchmate and I were marvelling at yet another manifestation of the tiny made tangible: E.coli transformed with a man-made DNA plasmid encoding a fluorescent tag called mCherry, so bright that after overnight growth, the bugs glow ruby red even by daylight:

The color became more intense after she spun the bacteria down in a centrifuge:

And, true to the laws of color mixing, when I miniprepped the DNA for her as a favor, the blue tracking dye turned a lovely shade of lavender:

It’s little observations like these that add a dash of wonder to my everyday lab experiences. But I was thinking this morning as I walked across the Quad, leaves fluttering down around me in the crisp air, that nature is the master of crafting invisible components into a gloriously omnipresent whole. The ochre and scarlet of autumn leaves are just conglomerates of microscopic pigment molecules; the blades of grass are mere chains of microscopic proteins. Even the mould that stubbornly sprouts up in the interstices of my bathroom tiles between bleach attacks is just another manifestation.

But nature does this so effortlessly. And we have become so divorced from the natural world that repeating its tricks in the lab seems like something original and clever.

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In which I react

A good scientist is never off-duty, which is perhaps why researchers throughout history have experimented on themselves. The 18th century anatomist John Hunter is said to have tested the infectious nature of gonorrhea by applying a patient’s pus to his own pertinent organ. In the 19th century, James Young Simpson proved that chloroform is an excellent anesthesia by knocking himself out, along with two unlucky assistants. And as recently as 1982, Barry Marshall could truly be said to have earned his eventual Nobel Prize for proving that ulcers are caused by Helicobacter pylori bacteria – after drinking a lovely cloudy solution of the microscopic culprits.

The other day, I was having lunch with my friend Daniel Glaser at the champagne bar in St Pancras International station. The item that most tempted me on the menu was a risotto with mussels, although I hesitated ordering at first. I tend to avoid shellfish, mostly because having a PhD in Microbiology indoctrinates you with a deep-seated squeamishness about all things Salmonella-related. But a few weeks previously, I’d decided to face my silly fears and had downed a gorgeous seafood pasta at Paradiso. It didn’t give me food poisoning, but almost immediately after finishing my lips started tingling, my eyes began to water and I developed mild respiratory problems that lasted a few days. After googling a bit, I decided it had probably been a mild allergic reaction – apparently quite common in adults, even if they’d never reacted as children – but I didn’t know which had been to blame, the prawns or the mussels.

So here I was, presented with a good experimental opportunity. If I ate the risotto and didn’t react, it was likely to have been the prawns that had troubled me earlier. But if I succumbed to the allergy, I’d know it was time to kiss mussels goodbye forever.

“Go for it,” Daniel advised, reasoning that knowledge was power and it would be good to know one way or the other. It was easy for him to say. Scientific curiosity notwithstanding, I was marginally less enthusiastic: the respiratory symptoms had made it difficult to sleep last time, and I wasn’t thrilled about going through all that again so soon. Also, food allergies can be dangerously capricious: hives one day and anaphylaxis the next.

“Don’t worry,” he added quickly. “I trained as a paramedic in the Israeli army.”

Reassuring.

I’m sure you know where this is going. Dear reader, I ate that risotto. And about a minute after finishing, I experienced the same symptoms – plus a few new ones.

“It’s unlikely to be psychosomatic,” Dan said helpfully, when – a bit of iPhonery later – it turned out the added extras also fit. “You wouldn’t make up symptoms you weren’t expecting.” Then his eyes narrowed. “Actually, we could have designed this experiment a lot better.”

As I coughed discreetly into my serviette, he outlined a plan designed to reproduce the day’s results and delve further into the important question of whether I had to eat the actual mussel or whether sauce containing mussels would be enough.

“You need to go to Marks and Spencers and buy all the permutations as ready-meals!” he said. “Then you draw a matrix and test all the possibilities. Of course you’d have to take a few days in between if you’d reacted, just to clear your system…and maybe you could try it with and without a prophylactic dose of antihistamines…oh, that’s a lot more permutations…”

I don’t think I’ll be eating shellfish again, experimentally or otherwise. I can report that prompt intake of over-the-counter antihistamines does seem to alleviate a food allergy – the symptoms were milder and only lasted few hours. Of course I can’t really prove it, but I like to think that in a parallel universe there was a control me, miserable and coughing into her pillow later that night.

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