Over the past few weeks, I’ve stepped in to help a colleague in need. I can’t go into any details, but let’s just say that owing to an astonishingly pedantic visa renewal technicality, a particular country’s immigration policy has necessitated the precipitous (but hopefully temporary) departure of one of our post-docs. He’s due back at the end of July to start a sabbatical position in another lab, on a very tight schedule. And he needs three new DNA plasmids to be ready on his return – buffed, polished and fully verified.

I quite like the thought of being a Cloner For Hire – blow into town with the tumbleweed, step into the bar and, over the sudden silence of the piano’s cessation, drawl slowly, “I hear someone here needs a GFP-tagged point mutant?”

As one, the hushed crowd turns to stare at the post-doc slumped over his whiskey in the corner.

It made sense to ask me. This particular colleague has done a lot on my project and will be a co-author on the paper I’m finishing up now. And he’s offered to stick me on his paper, which is right neighborly. But more importantly, I’m the only one in the lab besides him who really does much molecular cloning – all the geneticists just muck around making their male flies do naughty things with virgins. But I’m old school, and it when it comes to subcloning, I tend to have a green thumb. (You can see where this is going already, can’t you?)

A few hours before hitting Heathrow, the post-doc presented me with a beautiful yellow plastic freezer box containing everything I might possibly need to finish making his three constructs – he’d even crafted little machine-printed labels for the tubes. He was a third of the way through two constructs, though he did mumble something about not everything “quite working” (a comment which would haunt me later). The strategies were pretty complicated – long-range PCR, intermediate subclones – hey, even a three-way ligation! But nothing I hadn’t seen before. I like a challenge. And it was heart-warming – he’d also stocked the yellow box with aliquots of everything I might possibly need on the adventure – ligases, buffers, nucleoside triphosphates, X-Gal, obscenely expensive turbo-polymerases. It was as pleasurable as receiving a picnic hamper from Fortnum and Mason.

Despite this promising start, it all started to go wrong surprisingly quickly. The tube that was supposed to contain half a milligram of gel-purified PCR product was, in fact, entirely devoid of DNA. The vector that was supposed to contain only one EcoRI restriction site appeared to actually have two. Another vector seemed to be contaminated with a smaller plasmid. Undaunted, I made half a liter of LB broth spiked with ampicillin and told my benchmate grimly, “I will finish these clones before the broth runs out. Mark my words.”

When it became clear I’d have to start all over and venture into the post-doc’s personal boxes to find new stocks of plasmids and primers, and into his notebooks to cross-reference them, it was then that it truly hit me how difficult it is to carry on a project after someone else has gone. For in the privacy of one’s boxes, things can get very chaotic very quickly. We all do it: how many of us are guilty of filing away rows of minipreps or ligations that are only numbered, convinced we’ll remember what they are by where they are sitting in the box? It is so easy to cut corners on record-keeping when night is falling, when your timer is alerting you about your other experiment, when you’re late for lab meeting. It’s made me start thinking seriously about barcodes – should I be worried?

Anyway, the post-doc had pretty good handwriting, but he never put dates and it wasn’t always easy to tell exactly what sort of animal was lurking in the tubes – Fragments? Digests? PCR products? Miniprep DNA? I found at least three tubes that seemed to represent the vector I needed, but none of them looked quite right.

“This one is labelled ‘miniprep DNA’, but it’s a liquid at -20,” I told my benchmate, sticking the tube under her nose. “Does it smell like alcohol to you?”

“No,” she said slowly. “Actually, it smells like nectarines.”

“That was from my lunch, silly. How can we work out if it’s alcohol?”

“Color a bit with some dye and see if it floats on water?” she suggested.

“Good idea. Or – hey! Maybe we should try to set it on fire!”

And so forth. The LB/amp broth currently stands at 350 mL, and I’ve just retransformed every starting plasmid into bacteria from scratch, so at least I know what I’m working with.

But the clock is ticking.

I have always been fascinated by the untold narrative behind the precise dryness of scientific papers. So much is unsaid: the surges of triumph, the stupid mistakes, the bitter failures that litter the road to any accepted manuscript. Chronology is often tweaked, too: one of the few falsehoods formally permitted in scientific papers is the “Next, we decided to…” transition conceit that often describes as sequential those activities that were anything but, in real life.

So I was very excited when I became involved in ‘Strange Encounters’, a series of essays to be aired on BBC Radio 3 which ask scientists to describe a famous eureka moment in their field as if they were actually in the room. The producer was looking for a dramatic, novelistic style, and he was keen to avoid all the usual clichés – Watson and Crick’s helix, say, or Fleming’s Petri plate.

After some discussion, I was given the green light to imagine a critical day in the life of Peyton Rous. Working in the Rockefeller, Rous reported the first example of an RNA tumor virus in 1911 and inadvertently ushered in the era of modern cancer genetics. There wasn’t a lot on the web aside from his Nobel Prize biography, so I realized I was going to have to try to imagine his big moment through the distorted, minimalist lens of his seminal papers. And my deadline – 2000 words for a 15-minute broadcast – was in four days!

Kudos to J Ex Med for having digitized all of their back content; the two key papers, A transmissible avian neoplasm and A sarcoma of the fowl transmissible by an agent separable from the tumor cells, were available in pdf. I wasn’t, to be honest, expecting to learn very much about what had really happened from these, though. From most papers, you can’t even tell what year a discovery was actually made, let alone what time of year, or day. Would it be snowing outside of Peyton’s lab window, or a blazing summer day?

But fortunately, I discovered that they just don’t write ’em like they used to. For good old Peyton had lavished a world of attention into the minute details of his discovery, which is visually arresting and reads at times like a diary:

OCT. 1, 1909. The fowl bearing the growth is a strong, young hen. The mass is situated on the right breast…It is irregularly spherical in shape, firm, smooth, well-defined, and projects sharply from the breast contour.

He didn’t attempt to gloss over the less admirable moments:

DEC. 12. 1909. Following operation on the nodule it grew rapidly and to-day measured 5.3 by 4 by 3.5 centimeters, when it was again cut into…Hemorrhage was so profuse…that the fowl was killed.

And the paper, unlike today’s, is jam-packed with negative results:

JAN. 27, 1910. The chickens were reinoculated, this time into the left breast, with material from second generation B.
MAY, 1910. All are still without signs of tumor.

And plenty of poetic drama, too:

Soon the whole of the inoculated breast is occupied by a bulging, rounded, firm growth (figure 5); and the host rapidly emaciates, becomes cold, somnolent, and dies.

Although Rous’s penchant for applying caveats sounds thoroughly modern:

The first tendency will be to regard the self-perpetuating agent active in this sarcoma of the fowl as a minute parasitic organism. Analogy with several infectious diseases of man…gives support to this view of the findings, and at present work is being directed to its experimental verification. But an agency of another sort is not out of the question. … For the moment we have not adopted either hypothesis.

And sometimes, the old-fashioned language made me laugh. To my delight, I discovered that scientists in Rous’s day did not ‘centrifuge’ samples, but rather ‘centrifugalized’ them – which sounds rather like something George W. Bush might have said.

I didn’t even have to imagine how his hens looked, because he’d supplied a large photograph of his barred Plymouth Rock subjects (though I did consult Henry about the general behavior of chickens). But of course, I did have to invent nearly everything else. For the purposes of drama, I made him a closer friend to his bacteriologist colleague Oswald Avery than he may actually have been in real life. The crucial moment I wanted to describe was not diarized in the second paper, so I guessed that it might have been May, the year before publication. I had to flesh out his personality, his dreams, his ambitions and his actions from my own mind, and I know the result cannot be even close to accurate. I also experienced a revelation that left a tinge of melancholy, still remaining: it is remarkable how thoroughly even important details are lost once someone dies. For example, I wanted him to think about his girlfriend at one point, but though I knew the name of his eventual wife, history remains silent on when they met – and even when they married. And this is a person who won the Nobel – what hope for the rest of us to leave behind many traces?

You can hear me tell the whole story of Peyton Rous’s big moment with destiny as he encounters Rous Sarcoma Virus – it’s this coming Wednesday, 24 June on BBC Radio 3 at 23:00. (And tune in every night this week, same time and channel, for four other tales across a spectrum of scientific discoveries.)

It’s Friday in many parts of the world, so I feel compelled to report the results of a very important experiment just performed by Rohn and colleagues. I don’t know about your institute, but our building manager occasionally distributes freebies from sales reps and asks people to provide feedback. This information is in turn transmitted to the folks responsible for stocking our in-house shop with various basic consumable goods.

Normally I don’t feel I have time to troubleshoot yet another brand of microfuge tube or pipette tip, but today one of the post-docs – after a celebratory lunch with friends – decided it might be fun to have a thorough crack at new type of glove that had been distributed complete with its own helpful quantitative questionnaire:

OK, it was a pretty slow day at the bench, and the monthly departmental cocktail session was a mere hour away.

My colleague got into the spirit by persuading us to wear a normal glove (“Control”) on our left hands and a test glove (“Sample 1”) on our right. Glove fit was pretty self-explanatory, as was comfort during use. Tactile sensitivity proved a bit more amorphous, but I can report faithfully that my iPhone touch screen preferred the Control glove…hands down, as it were. Grip, we decided, would be satisfactorily covered by applying the famous ‘wet glass beaker test’. But how to assess the more illusive qualities of durability and strength?

There was only one thing for it: the application of excessive stretch strain and tortional forces. We even designed an informative readout – the fingers snapping off – and used it to come up with quantitative scale called LF (the ‘Leprosy Factor’). Sadly, the interlopers were resoundingly trounced by the Control gloves in nearly every category – which is a pity, because their color was unusually beautiful, the lavender of a summer evening sky just cooling to dusk, and they would have been easier to coordinate with my wardrobe than the ugly dark purple ones.

Well, I guess you have to have your priorities straight.

OK, I admit it: Gravity’s Rainbow was even less popular a choice for Fiction Lab than I could ever have imagined.

Book clubs, I am reliably and belatedly informed, are supposed to be about good clean fun, fairly easy reads and stimulating conversations amongst friends over a few drinks. Note to self: your average book club aficionado is not going to be too keen on a book with nine hundred pages of dense wording, disturbing sex, rampant paranoia, minimal plotting and maximum weirdness.

To celebrate our first year in existence, I had foolishly decided that Fiction Lab, my monthly book salon for scientific novels at London’s Royal Institution, was ready to take on something more challenging. After all, thanks to my sabbatical in Germany, we had a two month break to read something a bit longer than usual, and a certain Nature Network denizen had seemed unusually enthusiastic about this particular Thomas Pynchon classic. (Please note I am not apportioning blame – she did also warn me that it was not ‘book club material’). Add to that just the tiniest masochistic streak, and the fact that about a dozen people over the past two decades have kept nagging me to read it – well, I couldn’t help myself.

Gravity’s Rainbow is billed as an epic postmodern novel. Published in 1973, it’s loosely based around clandestine rocket technology development activities undertaken the German military in World War II. Several scientific themes are interwoven: mathematics, physics, the natural world, behavioral psychology, sexuality and of course, rocket science. Of historical note, the novel almost won the Pulitzer Prize in 1974, but a majority of the judging panel overturned the main jury’s decision on the grounds that the book was “unreadable, turgid, overwritten and obscene”. Despite this, Gravity’s Rainbow won the US National Book Award in 1974; it has also inspired much scholarly scrutiny and debate and is considered by many to be his best work, and by some to be the greatest American novel of all time.

I started the book with plenty of time (in electronic form, on my Sony Reader – almost half a stone lighter than the paperback version), but was scuppered by the sheer beauty of the work. You simply cannot read Gravity’s Rainbow quickly; I found it breathtakingly lovely, erudite, bittersweet, romantic, funny and sad, and to race through it at a normal pace would be an unforgivable crime. When it became clear that I was only going to make it half way, I stopped altogether, rather than rush through and ruin the experience – I plan to finish it off at a leisurely pace over the next few months.

To their credit, everyone showed up on the night, but only two people had finished it. It inspired the most polarized response we’ve ever had – people literally either loved it or hated it – but to be honest, most fell in the latter camp.

For July’s meeting, we’ve chosen the perfect antidote for a Pynchon overdose: The Embalmer’s Book of Recipes by Anne Lingard. Set in Cumbria’s Lake District, the shifting mosaic of the narrative – we’re told – explores life, love and prejudice through three very different women: Ruth, a taxidermist; Madeleine, a widowed sheep-farmer; and, Lisa, an achondroplastic mathematician. As Lisa is drawn into the group it becomes clear that the other women have strange secrets: Ruth’s essays on embalming have an increasingly dark theme. This is billed as a story about harsh decisions: eugenics in the post-genomic age; the politics of marginalizing people and communities; the desperate responses to Foot & Mouth Disease; and the illogicality of human love.

The author, Ann Lingard, is a former parasitologist, a passionate proponent of getting more science into literature, and the founder of SciTalk. And she’s graciously agreed to travel down from deepest Cumbria on the night to discuss her book with the group. So it should be an entertaining evening: do join us if you can on Monday 6 July at 7 PM at the Royal Institution.

Scientific methodology seems to come in distinct phases for me. One month I’m knee-deep in biochemistry; the next it’s all confocal microscopy on cells, or annotating images onscreen. This is part of what I love about research: the familiarity of the manipulations coupled with the variety that keeps everything fresh.

Cloning panache Sometimes it’s cool to be old-skool

This week, it’s become clear that I’m moving into a distinct cloning phase. Of DNA, as opposed to of animals (or of an army of evil minions – although they might prove useful for analyzing my 20,000 movies.)

Now, this is pretty familiar territory – I spent almost my entire PhD stint cloning constructs. Things were pretty primitive back in the early Nineties. There was only one sort of Taq polymerase, and you purified DNA using phenol, or on cesium chloride cushions if you were really fussy. You made your own competent cells. You extracted fragments from gels using low-melting agarose. You sequenced your final product by hand – with radioactive 35-S. If you had something really huge to clone, like a retroviral genome, you had to clone it using lambda phage – oy vey, was that a pain. If it was small, you used M13 phage. (For my younger readers, imagine a tape cassette – this sort of palm-sized plastic thingie that could store about an hour of music. Cassette tapes are to MP3 players as M13 or lamda cloning is to the current methodology.)

In the meantime, some things have changed. And not all progress is unwelcome. Yesterday I made a construct using the Gateway system – I don’t like to give excessive airtime to product placement, but this nifty system does away with the classic cut-and-paste ligation in favor of a snazzy recombination job on vanishingly small amounts of starting material. (This means you can usually clone directly from your collaborator’s miserly gift of 0.0001 microliters of DNA without having to amplify first: bonus.)

“How many colonies should I pick for the minipreps?” I asked one of the youngsters in the lab. “Six? Twelve? Twenty-four?”

“How many?” He blinked at me, uncomprehending. “Just one. They’ve all got the insert, all in the right orientation. Otherwise they wouldn’t grow.”

Nice. I can live with that.

But other things, reassuringly, haven’t changed. In fact, my knowledge seems a sort of forgotten, retro-chic dark art that is coming in extremely handy amongst the younger lab denizens when their turbo-charged, kit-driven cloning doesn’t work the first time. Some of the tips I’ve passed on (to frank adoration) include using the Klenow fragment to help finish off the ends of PCR product, for when that swanky new brand of Taq gets too lazy to complete the restriction tail you’ve engineered in; ethidium bromide spot plates, handy for quantitating tiny amounts of insert and vector when the molar ratios really matter, as for three-way ligations; the concept of low-energy hand-held UV illumination that doesn’t damage your DNA fragments while you’re cutting them out. These are all things that I would have thought I’d long forgotten, but which seem to have become ingrained when I wasn’t looking. It is almost as if, after returning to the lab after my career break, I had to go through that distressing one-year period of almost complete lab amnesia before being able to retrieve all the stuff in long-term storage.

Kids these days? They just don’t understand.

I think there must be a gene for it: the innate ability to think about biological cause-and-effect as an abstract pathway instead of as concrete machinery. Classical geneticists do it effortlessly. Their vocabulary is old and rich: synthetic lethal; partial rescue; incomplete penetrance. And these phrases evoke a time when biology was all smooth and wrinkled peapods, ochre- or amber-eyed fruit flies, striped petunias.

In the minds of true geneticists, genes enhance and suppress, and exert their effects upstream and downstream of other genes. And thought processes are unsullied by the need to picture what the gene products are actually doing. Proteins binding, proteins being modified, proteins translocating to the nucleus – it can all be irrelevant, if you just let it wash over you. Of course many geneticists nowadays can and do care about proteins, but they still retain this enviably breezy grasp of the almost ghostly conceptual scaffold that can be placed around them.

If there is a gene for the geneticist mindset, then I am surely a homozygous null mutant. Of course certain thought experiments are easy. In the following example,

A –> B –> C –> Effect

it’s pretty straightforward: A activates B which activates C which leads to a perceptible manifestation. These could be a chain reaction of kinases, say, leading to the onset of mitosis. Knock out B and mitosis no longer occurs: but knock out B while simultaneously adding a dose of exogenous C and mitosis is rescued. If you hadn’t already known that this pathway unfolded in that order, an epistasis experiment like this could help you to sort it out.

It all gets a bit sticky when your hypothesized pathway is more complicated, as in

A –| B –| C –> D –| Effect

that is, when your players are inhibiting as well as activating. And when you start knocking down multiple genes at once to get a feel for the order, it begins to seem, qualitatively, like one of those drunken sentences: “It isn’t that I don’t not dislike you, but…”

Fortunately, it’s nothing that an intense session with pen, paper, salted cashews and a few cocktails down at Henry’s Bar with a good friend can’t clear up. After a few Cosmopolitans, this genetics thing is doddle.

Remember the days when at the end of a postdoctoral stint, you could copy all of your files – documents, spreadsheets, presentations, data images and email – onto a couple of 5¼ inch floppy diskettes and sashay out of the lab, secure in the knowledge that you’d backed up everything you needed? (As your age decreases from mine, substitute for 5¼ floppies in the following order: 3½ inch floppies, ZIP disks, JAZZ disks, optical mini-disks, CDs, DVDs and 2 GB hard-drives. Please chime in if I’ve forgotten any of the formats – the mid-Nineties are a bit of a blur.)

Quite a handful When the data start to wear you down.

When I was preparing for my sabbatical in Germany, I did a rough calculation to work out how much hard-drive space I’d need to bring my data back home with me. It went something like this:

(384 spots/chip) x (8 chips/library) x (40 time points) x (2 fluorescent channels/spot) x (3 Mb/image) x (3 replicates) = 2,211,840 Mb or approximately 2.2 terabytes

Given the assumption that in addition to three perfect replicates, I’d also generate a number of suboptimal videos that I’d still like to keep, I reckoned that a couple of 2 Tb hard-drives ought to do it. When I went and asked one of the local university IT guys for some advice on reliable drive models, I got the classic half-weary, half-suspicious IT counter-question:

“Why do you need that much space?”

I explained to him that I was doing a high-throughput image screen, and I’d calculated exactly how much room I needed for the entire experiment.

“You can’t possibly need that much,” I was told sagely. “That’s more space than your entire institute is allocated on the backup server.”

Well, quite. When I saw this person on my return and told him about my successful results, a look of panic flashed over his face. “Well, you can’t back up your experiment here,” he said, as if I’d just proposed infecting him with a virulent strain of ebola virus.

So what’s a girl to do? The hard-drives are things of beauty: brushed steel, reassuringly solid, reputable brand name, almost silent (unlike their first-generation counterparts, which sounded as if they were about to ask Air Traffic Control for permission to taxi down the runway). But rumors abound of unexpected corruptions, inexplicable failures, soured sectors and rotten RAIDS. Will two copies be enough? And what about after publication? Do I save all the original tifs, or only the final avi video formats? Will any self-respecting journal want to lug around all this supplemental data for me in perpetuity?

Answers to the usual place.

It’s a sunny holiday weekend, and a young woman’s thoughts turn to murder.

Gastropod murder, in particular. I’ve been doing a lot of gardening over the past few weeks, and it’s all-out war. In addition to the usual complement of perennial herbs, I’ve got about forty potato plants and a dozen tomato seedlings going. The slugs and snails leave both of these species well alone, presumably because the Solanum alkaloids in the leaves are not to their liking.

Chives 1, Snails nil One application of Metaldehyde takes out the entire local population

But I’ve had miserable failures over the past few years with nearly everything else. Possibly the biggest bloodbath was the time I planted out twenty runner bean plants, each reared indoors to the height of about three feet, and in the morning found the razed stubs of their bare stalks plastered against the ground in quivering pools of ectoplasm. But there have also been decimated swathes of lettuce and rocket, chives, peppers, Lobelia, marigolds, and a devastatingly beautiful orange dahlia (I actually cried when that one went). I haven’t even been able to grow one of the most robust, fast-growing weeds in creation: the common mint.

When we bought our house we found a green bottle of slug pellets under the kitchen sink, but I had always been reluctant to use pesticides because we have a cat. And I thought things were looking up: this spring, the gastropod population seemed have been culled by the colder-than-usual winter. One afternoon, I threw caution to the wind and planted a lovely chive, but as night fell, I came out to find the thing half-digested by snails.

That was it. I found the bottle of Metaldehyde pellets and showered the remains with bright blue confetti. And in the morning, it was like the Somme. I left the corpses where they were as a warning to their fellows; I’m happy to report that the chive fully recovered, and our cat is alive and well. I’ve used the pellets sparing elsewhere with similar success and it’s given me the courage to try runner beans and strawberries again this year.

Although there are websites suggesting that slug pellets aren’t as environmentally unfriendly as the organic crusaders would want us to believe, I still feel vaguely guilty using the stuff. So I thought I’d give equal time to a contraption that Nev came up with, which we reserved for that enticing of all snail delicacies, the bean. And all you need are two saucers, a brick and salt pellets:

The only potential problem I can see with this design is that if any of the grass gets too long, or they work out how to abseil down from the nearby lilac bush, the game will be up. But I’ll keep you posted when the seedlings sprout.

I am back in London after nearly a month away in Germany, and it is an incredible relief to be home. In my absence, the UK Parliament imploded, my seed potatoes sprouted into healthy plants, swine flu came and (possibly) went, and – God, who could have possibly seen this coming? – Jordan and Peter split up. Had it really only been a month?

I never thought I would be so happy to be back in my own messy, chaotic lab. After all, the equipment in the German institute was shiner, cleaner and more reliable; everything was organized just so to a remarkable degree of efficiency. The stainless steel surfaces gleamed, the robots purred, the Speed-vac thrummed, everything was put back exactly where I had left it the previous time: pipettors and haemocytometer in the first drawer, Petri dishes and tubes in the second drawer, calculator in the bottom drawer, tissue culture medium in a neat row in the refrigerator. The shuttle arrived at the hotel every morning at 8:15 sharp, and I was usually on the 19:20 back home if all went well (except the one night, near midnight, when I braved the Wilde Schweinen and took the shortcut through the woods with a torch). A regimented meal from the hotel restaurant (rotating amongst about eight dishes and three wines) and in bed by ten: even the weekends had their routine, with the run through the forest to the labs and back, all at the appointed time to keep the schedule true.

And after a few pilots and bedding in, every day in the lab I did exactly the same thing. High through-put protocols make robots out of humans: process 96-well mother plates; rearray onto chips; seed cells onto chips; split cells to the desired confluency for the next day’s seeding; image the chips that were seeded previously; set up the thousands of files to compress overnight: a vast staggered pipeline that would tolerate no breaks. As one of the technicians told me, this sort of routine should be conducted with the serenity and thoughtfulness of a Japanese Tea Ceremony, and in truth I did sometimes enter into an altered state of consciousness. In little snatches of time between lab activities, it was project management and damage control: fiddle with spreadsheets to tweak the schedule to take into account yet another failure in microscope performance and – as gigabytes of data started pouring in – battle with slow servers to try to get a snapshot impression of whether a run was of sufficient quality to call it a true replicate, or whether I had to schedule in a replacement run.

The goal was three replicate timelapse imaging series of eight chips, each containing 384 siRNA spots. In theory this could have been completed in eight days; in practice I managed 2.5 replicates about an hour before I had to catch my flight home. Don’t get me wrong: what I have is amazing: nearly 20,000 movies of cells expressing fluorescent actin and DNA probes growing on a slide over a 24-hour period in the absence of one gene product out of a set of almost 600 key genes of interest. And, dear reader, they are beautiful. Picking a film almost at random for my farewell talk at the institute, I discovered something fascinating that had been wholly unapparent in my snapshot fixed screen with the same RNA and similar cells. And that was just scratching the surface of the nearly 3.5 terabytes of data I generated. It will take months, if not years, to get to the bottom of it all – hopefully less if I can get some decent automated image analysis up and running.

But that’s not what I wanted to talk about today. Today, I wanted to talk about how it felt to be back in my own lab, on my own time, wholly and utterly – not just low through-put, but no through-put. Having some sense of what the sabbatical would be like, before I left, as a special treat on my return, I’d set up a little experiment. A bespoke experiment, if you will, complete with one variable of interest, one hypothesis and designed to be informative no matter what the outcome. One of the post-docs obligingly fixed the transfection for me in my absence, and I returned to a multiwell plate full of just twenty glass slides, patiently waiting to be stained and lovingly viewed – their answer, just a few hours around the corner.

It felt wonderful.

Have you ever overhead a conversation that infuriated you so much that you had to physically restrain yourself from butting in?

The other day, I was sitting on the morning shuttle bus that ferries people from the ISG Hotel to the laboratories of EMBL. Normally it is sparsely occupied by visiting scientists like myself, but occasionally EMBL hosts a conference and the little vehicle becomes anchovy-packed with delegates. I was staring at the green leafiness of the woods, hypnotized by lack of sleep and the way the sunlight shafted golden through its canopy, when the loud conversation of the men in the seat behind me finally permeated my concentration.

“So then after all this – three rounds of review – they rejected our paper,” the first man said. “If they didn’t want it, why did they string us along for so long?”

Now, this guy was American: West Coast, late fifties. I’m American myself, so I’m allowed to say that he deployed that particular tone not uncommon amongst a certain generation of American males in the biomedical sciences – smug, arrogant, over-confident, reckoning themselves a science celebrity whose reputation alone should be enough to vouchsafe their work.

The second man asked what the referee comments had been like, and reading between the lines of the first man’s indignant description, I gleaned that the data were highly controversial and he hadn’t provided the extraordinary evidence required to back up an extraordinary claim.

“But these Nature editors,” the first man said. “They’re just glorified secretaries nowadays.”

The second man, bless him, did at least attempt a defense: “They’re scientists, aren’t they?”

“Yeah, like back in the Stone Age. Whatever. They’re completely out of touch with the field, and overwhelmed by manuscripts. And this puts them at the whim of the experts they rely on to make the decisions. Even if those experts have a political agenda (note another hallmark of this type of American scientist: the conspiracy theorist angle), they can’t go against them. It’s totally different when you have real scientists on your editorial board.”

I wisely held my tongue as my blood pressure rose, but I did glance back and memorize the first man’s face, just in case I ever ran into him again. In the meantime, because I used to be an editor, and because some of my best friends are (literally) Nature editors, I hereby present the apologia that I barely repressed during the rest of the bus ride.

Myth 1: Editorial staff are scientifically out of touch

Imagine you are an editor at a prominent journal like Nature . You spend every working hour seeing the top manuscripts in your field, months and sometimes years before they are published. When you are not seeing all this privileged information that normal researchers in the field know nothing about, you are attending the conferences that matter – and not just the talks and poster sessions. You are also working the bars and after-parties, gathering intelligence, hearing the latest rumors and being receptive at a time when scientists, after a few drinks, often say a lot more than they intend to. Now imagine you’ve been doing this for many years. Who do you think knows more about the field, both in breadth as well as depth: the editor, or the scientist who spends most of his time thinking about his one particular little niche of a problem? Who do you think is better placed to decide how a discovery in this niche stacks up against the broader picture of all the rest of the data coming in?

Myth 2: Editors are too stupid or uninformed about the politics of a field to notice when referees aren’t being straight.

Believe it or not, maneuvering and manipulation are blatantly obvious and, because the editor has been involved socially with all the personalities, they already know that Dr X hates Professor Y and take this into account when choosing peer reviewers and, if necessary, when interpreting their vitriol. Good editorial practice is a triumph of data over personal feelings: it’s the same ethos that would induce me to accept the first man’s paper if it were worthy – even if I did think he was a jerk.

Myth 3: Editors dare not overturn a referee decision

Anyone who’s ever compared a manuscript decision letter with the referee reports knows that this is simply not true. And just because the editor agrees with the referee who wants to reject a paper over the word of the referee who did not does not mean the negative referee somehow overpowered the poor editor into taking his side.

Myth 4: Bench scientists make better editors than professional editorial staff

As someone who has worked with journals employing both modes – professional editors, and academic editorial boards – I know that this common assertion is definitely not true in all cases. Of course there are many highly skilled scientist editors out there, but I’d like to focus on those who aren’t. Not a few academic board members are, how shall we phrase it, reaching the end of their career cycle: if not outright retired, they are often nearly there. Some are no longer performing cutting-edge research and have become fixed in their ways; some don’t attend many meetings, so are not up on the latest new theories. Many seem to be unaware of the basic tenets of the editorial credo, which is not to take an author’s word for anything. For example, I ran across a revised manuscript that one of the board members was about to accept. I remembered that there had been a contentious issue with one of the referees and was curious how it had been resolved by the author.

“They said in their rebuttal letter they addressed it,” the board member told me.

“Did they do it well?” I asked.

Silence down the phone. And when I flipped through the revised manuscript personally, I saw that the authors – as many do – had simply lied. Yes, they had fiddled with a few words in the offending sentence, but had not addressed the underlying concern with new experimental data as requested, even though their breezy rebuttal letter certainly implied that they had.

Professional editors are less likely to side automatically with authors precisely because they are not peers. They are trained to be incredibly skeptical of claims. They spend all day plying and honing their professional skills, not a few snatched moments here and there between the stresses, strains and distractions of a research career. This perception that only practicing scientists make effective editors is completely missing the point that certain editorial skills are different from the skills you need to be a good scientist – and it is not something one is automatically good at. It is an entirely different profession requiring talents that do not completely overlap.

“So what finally happened to the manuscript?” the second man asked once his colleague’s diatribe had trickled out.

“Oh, we send it off to our old standby, where at least it will get a fair hearing.”

And what I really wanted to say then was, if Nature editoral staff are so bad, then the journal’s quality would certainly reflect this. So why did you so desperately want to have your paper published there in the first place?