Mind the Gap

The tricky thing about history is that it can only be pinned down in retrospect. For this reason, it is often difficult to tell when something significant has actually happened. Few witnessing the assassination of Archduke Franz Ferdinand in 1914, for example, would have predicted that it would lead to a devastating four-year conflict and the deaths of over 15 million people worldwide. But things have a way of leading from one to another, and it is impossible to predict whether a local instability will collapse in on itself, or instead escalate beyond recognition.

Scientists, I think, are trained to be sceptical about major events in general, and the coverage of these events in the media in particular. Thus far the typical responses of my learned colleagues to the news of possible pandemic influenza have ranged from shrugs of disinterest to humorous quips, but very few feel that it will come to anything much. It is almost as if magnitude of the press response has reinforced their suspicion that nothing could possibly be as bad as advertised.

So, are we witnessing another SARS fizzle-out, or the birth of a devastating plague that will be recorded in textbooks for millennia to come? I can almost see it inscribed: In 2009, the first year of the Second Great Depression, the Swine Flu Epidemic wiped out a third of the earth’s population.

This is not to say that I am panicking. Not at all. My biggest concern at the moment is that there will be a lock-down on travel just for precautionary reasons and I will not be able to come home from my sabbatical. I consider this highly unlikely, but with the lag-time of incubation periods, I also think that it is too soon to dismiss this concern as ‘overreaction’.

So, where was I when I heard about the 2009 Swine Flu Epidemic?

I was alone in a tissue culture suite early on Saturday morning at the Advanced Light Microscopy Facility of the European Molecular Biology Laboratories in Heidelberg. Sun was streaming through the window, and my cells were looking particularly healthy. I was pleasantly tired from the run through the forest from my hotel: my hands were still damp from exertion, so I recall that it was difficult to get my nitrile gloves on. The radio was set to the TC station of local choice, 99.9 FM, the sort of platform that plays the same Top-40 hits over and over with the occasional pause for a barrage of largely unintelligibly German banter. It is certainly not a venue for serious news of any sort.

Which is why, after about the fourth repetition of a spate of exposition, I started to pick out the few words I did recognize: Mexico. Schweinen. Gezondheid. I had already put two and two together by the time the DJ finally pronounced the term that confirmed my suspicions: Influenza. A quick check on the BBC website solidified my knowledge.

On the run back to the hotel, I particularly remember that the morning air had an unusual quality of lucidity; the greenness of the leaves, the smell of ferns and the sound of water spilling over stones reminded me of the transience of life on this planet, and how little we are in control of anything.

Day Three in the lab at Heidelberg, and the pace is brisk and relentless. After a few minor set-backs, we are now knee deep into rearraying my siRNA library onto glass chips, which will take a good chunk of several kindly people’s time and about five days in total. In parallel, I am wrestling with the machine-readable spreadsheet that the microscope will need to label the 884,736 eventual timelapse images in a manner that will make assembling, and annotating analyzing the movies possible.

Breathing space A hideaway for precious downtime

Meanwhile, back on the biological front, we’re doing pilots on my beautiful new cell line to optimize image acquisition. They are rather lofty creatures, with layers of actin structures in various planes, from the basal adhesions to the dorsal microvilli – which slice will give the most information? There are decisions to be made too about time resolution – I am only here for three more weeks, and we must perform three replicates to make any future automated analysis meaningful. But even though I have two microscopes at my disposal which can in theory image four chips per scope, there are only so many spots that the hardware can visit per second. In other words, the spirit may be willing, but the stage and turret are weak.

The lab is crowded at the moment – great technology lures in lots of visitors, and after a homeless day perching on a lab stool, I’ve been given a lovely makeshift berth in a small room with a rather noisy office-mate:

Meet Robbie, the VersArray chipwriter robot. She makes a lot of noise and her moods go up and down, but she’s got great pins.

It’s only fitting I share with her, since she’s working so hard to print my siRNAs. And I’ve got a good view out the window – when the cottonwood fluff is actually sparse enough to see through.

There will be more to report soon, but for now I leave you with today’s hard-earned words of wisdom:

A watched Speed-Vac never lyophilizes.

I have just arrived in Heidelberg for my month-long sabbatical at the European Molecular Biology Laboratory, following up on the groundwork I laid when I was last here in February 2008. Although London is not far away as the Airbus flies, I am worn out from the day’s travelling and happy to be settled into the Transit-appartement on the top floor of the ISG Hotel, just down the road from the Labs. I find myself in a four-room penthouse surrounded by roof terraces. From the Bauhaus-inspired living area, I can see the wooded mountainside looming upward, and from the bedroom window, there is a good view of the vineyards and the wide, flat valley stretching out below into the sunset. The air is warm and stirs the net curtains, and I can smell lilac and hear the singing of nearly familiar birds.

These rooms seem extravagant, but the EMBL got me a good deal and assured me it was the most cost-effective way to be accommodated at this time of the month for the length I needed. I’ve bought some groceries from the local shopping plaza, where the baker remembered me and managed to charm me into buying cumin bread even though – typical American – I was after white. I’ve unpacked and had a simple but satisfying meal in the restaurant, along with a glass of excellent Spätburgunder. The waitress, too, remembers me, and seems happy to see me back.

As trips go, then, this is more than usually comfortable. I know the neighborhood and have worked with the lab before; it’s a tranquil setting and I anticipate getting a lot of writing done in my free evenings, going for long runs on the steep paths that snake around the mountain, so convoluted that you can never go the same way twice. I am looking forward to performing my big timelapse screen, and am suffused with nervous buzz I often get just before a major experiment.

But I have to confess something that, years ago as a green PhD student, I would never have dreamed of: I am weary of travel.

The itinerant existence is often touted as one of the rare perks of the profession. In my day, I have taken full advantage, having performed research stints in three countries and attended meetings in many dozens of exotic locations all over the world. When I was younger, I thrilled to these adventures and was always pining for the next one. I loved the rituals of airlines and the monkey-puzzle of foreign metro systems, trams, trains and buses. I loved that feeling when you open a hotel door and discover exactly what sort of room is on the other side. I loved meeting new people, bonding in that instant way of youth with students and post-docs from all walks of life. Things seemed less heavy then: we were all going to become lab heads, we were all going to be friends for life. Now, of course, I know better. And hand in hand, after wandering the earth for more years that I ever thought I would, I have a deep appreciation for the value of a stable home.

I have no doubt that travel is good for scientists, even ageing ones. It stimulates new ideas and keeps the thought processes from ossifying into conservatism. It forces you out of your comfort zone and ensures that you never become complacent in your routines. And though I am enjoying sitting in front of the laptop in solitude, drinking Fenchel tea and nibbling vollkorn biscuits in this spotless expanse, there is a little ache in my heart for the apple trees and cow parsley I’ve left behind, whose blooms will be faded by the time I get home.

When I was an undergraduate starting out on my Biology major, I didn’t have any preconceived notions about what branch of the life sciences I might ultimately favor. Oberlin College offered only a liberal arts degree in Biology – not only was it impossible to specialize further, but students were encouraged to explore the whole spectrum of biology from Anatomy to Zoology (and required to take many credits outside of the sciences altogether, for which I am still grateful).

Although I enjoyed my ‘macro’ courses in population genetics, evolution, ecology, botany and the like, I quickly fell in love with the molecular world. Working my way through classes with names such as Molecular Genetics, Genetics, Molecular Biology, Microbiology, Immunology, Virology and Biochemistry, at first I just saw them as complementary studies that both overlapped and differed in interesting ways. It was my parents, though, who caused me to question the nomenclature of the various subdisciplines of biology: they wanted to know, simply enough, what I was, so they could tell their neighbors and friends what their daughter was shaping up to be.

When they first asked, I told them that I wanted to be a molecular geneticist. This was probably because at the time, I was embroiled in a course by the same name and humming with the history of the Phage Group, the lac operon and everything that happened afterwards. The following year, I decided I was a molecular biologist, for equally opportunistic reasons. But ultimately the term virologist won out. Although I studied viruses in graduate school, it was in a department called Microbiology. I abandoned viruses in my first post-doc, and so suddenly found myself in need of a new name: cell biologist seemed the most appropriate for the cancer cell signalling I was investigating, although I didn’t do a lot with whole, intact cells. Later when I went back to viruses, I was doing more biochemistry than anything else, so all pretence at classification slipped away.

Somewhere during this ten-year span, something very intriguing was happening with the nomenclature of biological subdisciplines. In earlier days, there wasn’t much mixing. Biochemists studied proteins, often in isolation from cells; cell biologists did the reverse. Molecular biologists performed a lot of cloning, studying how proteins interacted with nucleic acid to turn genes on and off. Geneticists used model organisms to study processes with only scanty reference to the fact that proteins were actually carrying things out: genes were ‘upstream’ or ‘downstream’, they ‘enhanced’ or ‘suppressed’ – but when I listened to geneticists giving seminars, it seemed they had little interest in what their gene products were actually doing in cells – questions about binding partners, localization, even predicted structures and domains, were often greeted with a disinterested shrug.

But at some point, the boundaries started to blur: disciplines had become tools and techniques, almost without anyone noticing. Geneticists were isolating proteins from their animals, and cloning constructs to make transgenics; cell biologists were using the methods of biochemistry to get a handle on how signalling influenced physical forms, or making a knockout mouse to discover the consequences of their pet gene’s absence in vivo, or dabbling in computational biology or bioinformatics to gain added insights. Soon, no self-respecting biologist wouldn’t be mixing the methods of most of the previous inviolate subdisciplines, matching technique to objective instead of forcing objectives into a limited set of traditional techniques.

And when that happened, all the old names went out the window. Biochemistry used to be synonymous with enzyme kinetics; now it’s also a suite of techniques that everyone does: Western blot, immunoprecipitation, proteomics, kinase assays. Molecular biology is just a plasmid workhorse, a means to another end. I have noticed that, hand in hand with these changes, academic departments have been discreetly changing their names. Descriptive terms like Anatomy and Embryology have been phased out. Some departments attempted to deal with the blurring of boundaries by merging discipline names: Cell and Molecular Biology; Biochemistry and Cell Biology; Cell and Developmental Biology; Structural Biology and Biophysics – you can find all the permutations, uneasily shoulder-to-shoulder and not quite sure exactly what they stand for. As the following promotional blurb from UCL’s Department of Biochemistry and Molecular Biology demonstrates, any pretence at true compartmentalization seems to have been lost:

The structural biology of proteins and enzymes to the mechanism of amphibian limb regeneration; from the regulation of transcription of genes involved in drug metabolism to the uncovering of gene function in Mycobacterium tuberculosis; from understanding the signalling of insulin receptors to the computer analysis of whole genomes sequences, this department provides an exciting venue in which to realise the promise of these important goals.

I still don’t know what to call myself. When pressed, I usually mumble cell biologist, but it never feels quite right – especially as I infinitely prefer biochemistry.

I always associate Easter with the resurrection of flowering life. Although the holiday is early this year, our garden and woods are already full of birdsong and blossoms – cherry and apple, sloe and hawthorn, cowslips and coltsfoot.

Sadly, this spring will not bring back from the dead one of my favorite back garden inhabitants: a tall, woody shrub that perished over the winter, victim of a split trunk caused by its own burgeoning weight. I’ve spent many sultry summer afternoons basking in the shade of its deep-green leaves and star-like purple flowers, and was traumatized when spring did not bring new shoots emerging from its barren trunk. Only yesterday, we admitted defeat and cut it down (much to the disappointment of our neighbor peering over the fence, who loved it just as much as we did).

Rest in pieces

I wish I could tell you what it was, but I have never been able to find anyone who knows. It’s not native to Ohio, or I would have had to memorize its appearance and Latin names in my extensive undergraduate botany courses. Neither could I identify it with my Gray’s Manual of Botany, a doorstop-sized dichotomous key that will eventually lead you to identify any species – if you’re willing to count bud scars, inspect pollen shape and dissect the ovaries of flowers under a microscope.

Blooms, in happier times

The tree in the foreground on the right, last summer_

I was wondering if anyone out there could help me? I’d like to buy a replacement, and a positive ID would really help. Have a look at the pictures: it’s a woody shrub with ovate leaves, tree-like and prone to growing two or three meters tall. The purple flowers have five petals and an orange center, resembling the Solanaceae (the family that contains deadly nightshade and tomatoes), but nothing looked promising in that section of Gray’s so I’m suspecting it’s something else.

In the meantime, I hope you all have a relaxing Easter/Passover/long weekend, however you define it.

My London home is often a temporary resting spot for itinerant scientists and literary types, and this past week it has been graced with the presence of a certain house-hunting Nature Network denizen. Although the search for an abode can often be a hellish, stressful affair, Richard seems to be coping well:

Please keep your hats with you at all times when traveling on London Underground

The fine spring weather we’ve been having probably contributed to the air of good cheer, as did the frequent rest stops around the public houses of Rotherhithe where, apparently, the libations are superior to their Antipodal counterparts:

A pint of bitter at the Ship and Whale, Saturday

After having found a lovely four-bed house near the Thames (I’ll let the man himself tell you more), Richard gamely followed me around London to various sci-lit events. On Monday at Fiction Lab, there was a big turnout at the RI for the discussion of my novel Experimental Heart:

Book signing after the event, Monday

We’ve recorded the session for LabLit.com’s first podcast, so I won’t say any more at present except that it was an enjoyable and vigorous discussion. We’re just waiting for our composer to finish the jingle, and hope to have the podcast available sometime next week!

On Tuesday it was back to the RI for a discussion on The Science in Science Fiction. I was pleasantly described to see a diverse turnout of about 120 people keen to learn more about how science fiction writers have influenced real-life science and technological events. My favorite example, from panelist Mark Brake, is that apparently South Korea has become the first country to adapt the Three Laws of Robotics as a prelude to their goal to have a robot in every home by 2020.

Overall, I have found Richard to be thoroughly house-trained. He brings you coffee in the morning, uses the bread machine without looking at the recipe book, cooks a mean fajita and even cleans up afterwards. Every home should have one of him, too.

Do scientists get less effective as they get older? The urban myth would have us believe that creativity is a thing of youth – physicists and mathematicians in particular are said to be past it by the time they reach my age (forty-something, since you ask). In reality, there isn’t much evidence for this stance. The whole issue was just summarized in a great blog post from Oxford’s Future of Humanity Institute, and Malcolm Gladwell recently explored the idea that genius may not be entirely the domain of the young.

Seeing is believing But what happens when you can’t?

As a mature post-doc, I find myself in the interesting position of being able to analyze first-hand the effects of age on the process of doing science, both mentally and physically. We’re a fairly small sample size, 40+-year-old researchers; most people my age who haven’t left science altogether have already become group leaders, so they’re no longer full-time at the bench. Clearly there are a lot of advantages to being older and wiser, but I’ve come up with four main drawbacks that might make molecular biology better suited to younger folks:

1. Old habits die hard. People tend to get more conservative as they age. You’ve all heard me speaking reverently of procedures and machinations that are no longer in vogue, such as platinum loops and, as I grow older, I take more pleasure in performing manipulations that I learned long ago. All of my labmates, for example, buy expensive pre-cast SDS-PAGE gels, but when my project moved into the biochemical realm, I rooted around in the abandoned detritus of Alan Hall’s decamped kingdom until I found a complete Mini-Protean III set, then lovingly polished it up, replaced a few missing parts and put it back into commission. This is not because I am adverse to new technology – indeed, I consider myself an early adapter (I was using an MP3 player in Amsterdam months before I spotted another one), and I’ve had no problems at all getting up to speed with all the new tech and software that confronted me when I returned to the lab after my four-year break. No, this is a deeper issue: it is something to do with familiarity, with trust, with loyalty, with ritual, with nostalgia. Am I wasting my time pouring my own gels? Possibly. Do I care? Not really. Am saving the lab a lot of money? You bet.

2. Paranoia, big destroya. I’ve always been a bit obsessive in the lab, but I fear it’s getting worse with the passing years. When I transfer my proteins to filters for Western blots, I feel a strange reluctance to throw away the spent gel afterwards, in case it turns out not to have worked. When I transfer supernatants to fresh tubes, I look worryingly at the old pellets before forcing myself to throw them away – unless I give into the temptation to stash them in a freezer box “just in case”. I can’t decide if this is age-induced paranoia or simply healthy caution.

3. Senior moments. Do not underestimate the importance of memory in being an effective scientist. When I was a Ph.D. student, I could proudly recite the restriction enzyme cleavage sites of most of the major cutters; only the other day, I forgot the name of the enzyme that makes blunt ends (the Klenow fragment) and had to look it up. All of those sectors in my brain seem to have been over-written by hard living; I think if it were not for Google, I’d be done for.

4. Dwindling vision. No, I’m not talking about my ability to come up with amazing theories. I’m talking about my deteriorating eyesight. Until you start losing your close vision, you don’t appreciate how important it is to be able to see in the lab. Looking for pellets in the bottom of a centrifuge tube is the worst – if it’s something clear like DNA or protein, and the tube is white or clear, I really struggle. Today when I poured a protein gel, I had a hard time seeing that thin line that forms when the bottom portion is polymerized. I can imagine the day when I’m going to have to start wearing my glasses instead of contact lenses, just so I can put them on top of my head and position my eyes a few centimeters from the thing I need to see. (As someone with appalling myopia, I can tell you that it becomes a great advantage when you age: you suddenly have microscopic vision up close, which I reckon could come in seriously handy in the lab.)

On balance, I think I’m not ready to hang up my Pipetteman just yet: I’m more efficient and confident in the lab than I ever was as a callow youth, and age has also brought the perspective that shelters me from the more negatives aspects of science. A few hours ago the confocal microscope crashed and I lost two hours’ worth of hard-won images; as a student, I probably would have cried, but today, I just laughed, booked another session for next week and joined the rest of the institute for Friday cocktails.

It’s only science, after all.

There are many who believe that science fiction is more than just a source of entertainment: it can actually change the world. If you’ve ever wondered just how inspirational science fiction has been and continues to be to the real life perceptions and practices of science in our society, then I suspect you will be interested in ‘The Science in Science Fiction,’ an event I’ll be chairing at London’s Royal Institution on 7 April.

Taking place in the historic Faraday Lecture Threatre, the event features speakers Mark Brake and Neil Hook of the University of Glamorgan in Wales. Brake, a prolific writer and broadcaster, founded a degree program on the historical interplay between space, science and culture (which sounds a lot more fun than the undergraduate coursework I took!) and holds a Chair in science communication at the university. He’s also a founding member of NASA’s Astrobiology Institute Communication Group, and is on record as saying that we’ll only settle the life on Mars debate by visiting the surface with a shovel.

His colleague Neil Hook is Associate Lecturer in Science Fiction and an Anglican priest in the Welsh mountains. His research focuses on 17th and 18th century science fiction, which he writes and lectures on internationally. He has said that he spends his academic life reminding people that science fiction is fun and shouldn’t be taken seriously and his parish work reminding people that God is fun and should be taken seriously.

The pair have also recently published a book together on this topic: FutureWorld: Where Science Fiction Becomes Science.

So do join us on 7 April: the discussion promises to be thought-provoking as well as fun, and I’m sure there will be time for a few drinks afterwards!

___________________________________________________________
‘The Science in Science Fiction’
The Royal Institution, 21 Albemarle Street, London, W1S 4BS
Tuesday 7 April 2009
7.00pm-8.30 pm
Tickets cost £8, £6 concessions, £4 Ri members
(I still haven’t worked out how to display a url that contains ampersands on NN, so here’s the raw code for the event: http://www.rigb.org/contentControl?action=displayContent&id=3025)

Novels about scientists going about their profession are rare, and over the past five years I’ve been busy trying to find them all, both hard-core lab lit (where what scientists do is central to the plot and the science isn’t watered down to homeopathic quantities) as well as ‘lab lit lite’ (where a scientist is a central character but readers are not shown a great deal of what they do – something a step above Ross from Friends but nothing too obtrusive). We are also interested in books marketed as science fiction that have exceptionally realistic and central scientist characters, and of course plays, films and TV dramas or series.

We’ve been keeping a curated list over at LabLit and at the moment, there are only about a hundred books on it. I assembled half of this list almost single-handedly after months of trawling through bookshops, Amazon and Google – you can read an account of my adventures in doing this here. After LabLit.com took off, the rest of the books on the list were the result of suggestions sent to the editorial inbox from our readership all over the world.

Although the SF section of the list is almost certainly not comprehensive (because our readers tend to focus more on mainstream fiction when they nominate – please feel free to rectify this deficiency), I am starting to feel that the non-SF novel section has reached equilibrium. It’s been months since anyone has nominated anything new, except for foreign language examples (which my readers are still sorting through). And this is not just because interest in nominations has waned – I think Ian McEwan’s Saturday has been suggested about forty times. (Great book, but the protagonist is a neurosurgeon, not a scientist. One day if I ever have the time and energy, I’d love to add a new section to the List that highlights books with interesting science in them, even if they don’t contain scientists.)

Nevertheless, there have still been surprises. The most interesting suggestions recently have come from the older generation at the institute where I work, who have got wind of my quest and have noticed things on their bookshelves gathering dust. I heard about Trouble with Lichen this way, when one of the lab heads came round one afternoon with a 1969 paperback edition, its torn cover taped up and its brittle pages almost orange with age.

Classic SF Author of Day of the Triffids dabbles with feminism and biochemistry

Just the other day, another lab head brought me the most amazing specimen: a first edition of a novel I’d never heard of called Gloryhits by the respected scientists Mark Noble and Bob Stickgold. The hardback was signed by Noble, who apparently worked here back in the Seventies when the book was published. (I didn’t even need to look at the copyright to work out the decade: just check out the glorious hair on the woman scientist on the cover!)

Retro-chic Bioweapons are always a popular lab lit theme

I haven’t started reading yet, but from flipping through it, it certainly looks like one of those rare examples of hard-core lab lit – most of the action takes place in labs and there is a lot of science being bandied about. From the sleeve blurb, we learn that the scientist protagonist couple conceive after an acid trip (those were the days, eh?) and then everything goes horribly wrong when it turns out the military is involved: “those with their fingers on the pulse of life have twisted DNA into a weapon of death and given one young couple less than nine months to stop an experiment that could destroy their world”.

Scientists meddling with things they were never meant to know and losing control of their experiments is one of the oldest memes in the book, but if it’s good, clean entertainment, I won’t quibble!

With springtime weather filling London with the scent of flowers and friskiness, it’s never been a more auspicious time to jump onto the Geek Chic wagon. And what better way to attract the attention of that sexy post-doc down the corridor than to flaunt your Renaissance Scientist credentials?

Fiction Lab, a book group dedicated to lab lit novels at the Royal Institution, is here to help you cultivate that aura. But it’s not for the faint of heart. Although all are welcome and we have new faces every month, the group has evolved a core of diverse and entertaining regulars who can trash the most beautifully written story with the surgical precision of a nano-scalpel. When we have occasionally had authors stop by to join in the discussion, words have not been minced.

March’s book, The Behaviour of Moths by Poppy Adams, raised the hackles of a number of the group due to its unreliable first-person scientist narrator, although others, myself included, enjoyed the feeling of not knowing, even by the end, if her account was actually trustworthy. On balance, though, it is probably a good thing that Ms Adams’ agency didn’t deign to respond to our invitation to lay into her in person.

These same regulars have been nagging me for some time to put my own novel, Experimental Heart, under the knife. And, because resistance is futile, I have finally given in. If you want to join in the spectacle, please read the book and scrub in for 7 PM on Monday, 6 April. After doling out the usual preliminaries and introductions, I’ll retire meekly to the bar, out of earshot with a stiff drink, while everyone else lets rip under the firm grip of guest chair Stephen Curry. Later, I’ll join in on the wrap-up discussion.

I’m not as nervous at the prospect as I thought I’d be, now that’s it’s decided. This may be because I was pummelled by so many rejections on the long road to publication that I have long since learned not take criticisms personally – in fact, I actually crave any tips that might help me improve. Also, being hard at work on my third novel, the first invariably suffers by comparison – you can only write a first novel once, and there are things I would do differently now. Most of all, I’m keen to see what a group of people specializing in scientific novels for the past year make of what is, in many way, a type specimen of hard-core lab lit – especially as most of the group are not scientists.

There’s only one way to find out. Do join us!