Mind the Gap

It is a grey, rainy bank holiday weekend here in London so my news is appropriately frivolous. If you inspect the image below, you will see that my local Tesco supermarket in Surrey Quays shopping center is carrying an own-brand of pet food with a startlingly familiar look:

Double-take Cleverly misguided marketing mimicry, or coincidence?

My alert spy (a scientist who doesn’t want to be named for fear of becoming embroiled in any legal crossfire) snapped this image on his mobile phone camera yesterday in the pet food aisle, and reports that there is both a feline and canine version of the “JustNature” product.

I know it has to be a coincidence, because what sort of package designer could possibly think (no offense, Matt and Corie) that the NPG brand would hold any subconscious sway over ordinary British pet owners? Nevertheless, having received the subversive message myself, I am now wondering what the food’s impact factor is, and whether I really ought to ditch the Purina Felix in favor of the top-tier grub.

When I returned to the lab last year, I wasn’t just changing fields of expertise: I was encountering a whole new way of doing science. Instead of tinkering on one gene or pathway, I found myself thrown headlong into the world of high through-put genomic screens – a world that came bundled with a lot of technologies I had never before encountered. (A nice chap from Nature Protocols interviewed me about my experiences; if you’re interested, scroll down to the section called ‘My First Robot’.)

And your point is? User-friendly dialogue boxes are probably the least of a developer’s worries

All of this shiny kit, from aerodynamically automated microscope stages to zealously zippy liquid handling robots, is of course powered by software. When you buy a brand new piece of basic lab equipment – a PCR machine, say – from a reputable supplier, you know that its software interface is going to work precisely as advertised. You grow to trust the reliability of the machinery in your lab; your own manual endeavors may be imperfect, but at least the kit is not going to screw up your experiment. What you learn very quickly, however, is that new technology breeds new software, and new software is inherently buggy. Developers – who are more often than not colleagues, or coders hired by equipment companies to facilitate the needs of a few valued customers – don’t have the time to test every last ramification of their code or to make the experience corporate-smooth, so it is left to the user to work out the ways and means of these often surprisingly finicky beasts.

I had my first intensive experience with this at the EMBL in Heidelberg this past February, where I was learning how to do high-throughput timelapse videomicroscopy RNAi screens. The patient and skilled technician who was assigned to help me out was a dab hand at setting up these screens, but she employed an almost a superstitious approach to achieving this without perturbing the whole system, which had been designed by Leica engineers especially for their facility and was very much a work in progress. “You see, it doesn’t like it if you do things out of order, even though you are supposed to be able to,” she whispered, as if the software might overhear and take offense. Deviate even one iota from a scripted task, she warned, just one errant click on the desktop or a too-long pause between steps, and the software would produce a floridly incomprehensible dialogue box (usually involving 25-digit numerals) and crash out the entire system, microscope and all. I recall one day when the software resisted even the sizeable charms of the technician and we banged our heads against the wall for eight solid hours trying to persuade the system to do its job.

Closer to home, I am privileged to be able to work with a home-made database and associated programmes designed to help me store, compare and analyze all my phenotypic data. And it is marvelous. But it is a primitive affair, I must confess. The other day, while agonizing over a hierarchical clustering session, I encountered the oddest dialogue box I had ever seen (see image above). I had no idea what I did to cause it or what it meant, but I sent the screen grab to Richard and it seemed to cheer him up, so it must have been of some use.

You’ll be happy to know I’ve since worked out how to cluster my phenotypes, but the pressing question still remains: who the hell is Alok, and what did I say about his stub that caused so much offense?

For those of you who’ve been away on holiday and are struggling with your first few days back at the bench, I feel your pain, brothers and sisters. It is a truth universally acknowledged that in the wind-down to significant time off, the tendency is to postpone the most painful analyses and manipulations until your return – during which they fester, accumulate gravitas and loom like the world’s largest activation energy barrier to pummel you into submission on your return.

If only I had reserved a few of those light tasks I had taken such pleasure crossing off my list on that frenetic final day in the lab: mindless mini-preps, lazy ligations, a spot of breezy biochemistry. As it was, this afternoon found me mired in front of a computer screen, confronted with a mammoth set of dense hierarchical phenotypic clustering results. As the microarray-style matrix began to slide into a blur of crimson, green and black amid the post-lunch somnolence, I only wished I had a petite PCR or dozy digest to divert my brain’s compass away from vacation mode towards the more productive poles of the scientific method.

Rogue genes A gripping noir tale science and passion

For those of you who’d like to ease back into science in a more civilized fashion, I can heartily recommend the novel Mendel’s Dwarf by Simon Mawer, which is the book choice for our next Fiction Lab at the Royal Institution this coming Monday evening. First published eleven years ago, this little gem is a lab lit classic about an achondroplastic geneticist who studies his own disorder. Dark, erudite, poetic, sexy and extremely funny, this story is guaranteed to get your neurons back to full firing capacity.

If any of you live in the London area and fancy coming along on Monday, you’d best get your skates on. Like nearly all of the millions of novels published any time after the old classics but before a few years ago – that sad, gaping literary wormhole – it is nearly impossible to find in any bookstore. But there are still a few used copies available for quick dispatch in the United Kingdom on the Amazon marketplace, and it’s a speedy and entertaining read. I will leave you with this excerpt:

I pipetted a drop of glutinous fluid onto a slide and lowered the coverslip with consummate care. … I peered, adjusted the diaphragm, turned the nosepiece to the big lens. It locked into place.

One million million spermatozoa, all of them alive. Small exclamations of blind and culpable intent! Interrogation marks asking what absurd question? A thousands periods, each bearing its potent, muddled message…They shimmered and shook, nosing towards God knows what dimly perceived ovum, and I knew, oh I knew that of every thousand that I saw within that brilliant circle of light, five hundred carried the command for height, for normality, for happiness and contentment; and five hundred bore the curse.

But which?

Was that an epiphany? Was that the moment when something, someone – the bleak and austere muse of science – spoke to me?

Having just touched down in London from SciFoo 2008, I stare, tinged with jetlag, at the blank page and wonder how anyone could adequately summarize a get-together so bizarrely wonderful.

Spoiled for choice Dueling, self-organized sessions at the Googleplex in Mountain View, California

I participated in sessions on the possibility of using Massively Multiplayer Online Games as a sort of giant geeky cluster processor for scientific research projects, and saw a flying car (or ‘roadable aircraft’, as the CEO of Terrafugia, who looks about ten years old, prefers to call it). I watched the Pope’s astronomer defend Vatican-inspired cosmological research, talked about Descartes and Maxwell with one of my favorite authors, Neal Stephenson, and – after a day’s session had pummeled my brain into submission – laughed non-stop through an hour of science-inspired stand-up comedy. I watched a rather dry presentation about databases for mega-data devolve into a philosophical argument about whether Craig Venter is a ‘real’ scientist for gathering large datasets and seeing correlations without posing a hypothesis. In fact, later there was an entire session brainstorming how the traditional scientific method might evolve and be tweaked for better effect in the future. I saw an earnest neurologist and an evo-devo maven debate the deeper implications of a dancing cockatoo and glib gerontologists positing how we might extend our lifespans through multiple targeted interventions. I ate lunch with carbon sequestration specialists and Google engineers, sat in the hotel hot tub with futurists and solid-state physicists, skived off talks in the bright Silicon Valley sunshine with statisticians, professors of risk and macroeconomists.

Non-linear A freewheeling discussion of public engagement, LabLit and why Everything is the Media’s Fault (check out a certain someone’s fetching five o’clock shadow)

The chaotic nature of the entire event was equally evident in the session I helped organize with SF novelist John Gilbey and pseudoscience basher Ben Goldacre called ‘Seducing the Public with Science. (Ben wanted to call it ‘Pimping Science’ or ‘Seducing the Pubic’ but was gently overruled.) Someone spontaneously decided to summarize the unfolding discussion on the white board and, as you can see from the figure above, what it lacked in coherence it made up for in raw enthusiasm.

The only drawback was that the Googleplex’s impressive array of free snacks did not include Cheetos or indeed much in the way of the faux cheese-based snack food which is so imperative to fuel my intellectual thought processes. Fortunately, there was a goodly amount of evening booze and a critical mass of Brits to help deploy it liberally. (And yes, both Matt and Cameron managed to look adorable with hangovers. What’s their secret?)

The scientific method, it seems, isn’t just a professional ethos. It’s a way of life.

I thought about this today as I was fly fishing up a tricky stretch of Chalk Creek, an icy, milky-green stream that cascades downward through the pine forests and aspen groves of the San Isabel National Forest in the Colorado Rockies. A fresh breeze funneled down the creek bed, tempering the heat of the morning and foreshadowing the usual afternoon rainstorm. Besides the roar of the water, all I could hear was the scolding of chickadees and the aerial battles of hummingbirds overhead. The far bank, lush with moss and ferns and dappled with sunlight, overhung a murky indigo pool where, I imagined, the largest trout remained immune to my arts. The gravel bank under my feet, meanwhile, was festooned with a tangle of saplings, shrubs and overhanging branches that seemed specially designed to ensnare the angler’s line.

Small fry magnet? The Royal Coachman (out of the box) and friends

I’d been having great luck with one particular kind of fly, the Royal Coachman. But with it, I seemed only to be able to land small trout in the neighborhood of six to seven inches long: beautiful creatures, glistening olive green with scarlet spots, but hardly the stuff of campfire legend. While some consider small trout to be the tastiest, I only killed one on our first evening, poached over the fire in white wine and garlic as a sort of arrival ritual. I had decided not to kill one again until I’d bagged something over ten inches long.

As I worked my way up the bank, I began entertain two disparate hypotheses:

1. The stream was currently overpopulated with small trout, so these were the ones I was most likely to catch

or

2. Only the indiscriminate small fish were interested in the Royal Coachman, and the larger ones would prefer to strike on some other fly.

I decided to try to test these hypotheses, so I sat on a fallen stump in the dusky sunshine, cut off the Coachman and tied on something completely: an Elk Caddis Brown. But as I tightened on and waterproofed the new fly, it occurred to me that the experiment was flawed from the beginning. In the ten minutes since I’d caught something small with the Coachman, the sun had shifted in the trees and set a different part of the water in shadow, the temperature had increased – hundreds if not thousands of microscopic variables had altered. If I caught a big trout now, I’d never know if it was down to the new fly. How far this situation seemed from the regulated, air-conditioned world in my lab.

Or was it? I considered a hypothetical row of twenty-four Eppendorf tubes, each filled with the same substance and treated in batch. Could these tests really be considered to be exactly comparable? I might have pipetted more carefully into the first few tubes but grown more lax and cavalier by the end of the row, or a 37-degree heat block might not provide the exact incubation temperature in each of its wells, or there might be variability in the composition of the mass-produced plastic tubes. We might think we are being careful, but it is probably impossible to treat a control in the same way as an experimental sample. On further reflection, I decided that this wasn’t such a bad thing. If general lab conditions really are so variable, it must be a particularly robust biological phenomenon that can provide reproducible results on different days or when performed by different people. That we can learn anything in the face of our chaotic environment is something to be proud of.

Now you’ll have to excuse me. After having blown into this dusty cowboy town to refuel on supplies and file this report, it’s time to get back to the more important business of fishing, reading, swimming, napping, hiking, eating, gold panning – and trying not to think too much about science.

Sometimes even the most innocuous events can have serious consequences. In a recent post, Henry related a lab nightmare of Hieronymus Boschian proportions which, on waking, made him thank Dawkins that he was no longer a practicing scientist. This, in turn, reminded me of why I decided to abandon a successful and lucrative career in science publishing to return to the lab. I’ve already discussed some of the core reasons for this volte-face, but up until now, I haven’t actually revealed the decisive inconsequential moments that catalyzed the whole affair.

I have a dream: BenchKote is compulsory for those ‘CSI moments’

The first two stimuli were dreams, a vivid pair in as many weeks. In the first, I was standing just outside the lab where I did my first post-doc, over ten years ago in Lincoln’s Inn Fields. Inside the brightly lit, familiar room, my former colleagues scurried around, unaware of my presence as gels were loaded, centrifuges were set spinning, fridges and freezers were opened and slammed shut. I stepped forward eagerly to join them, only to find that an invisible membrane, flexible but strong, was physically blocking my path through the door. Try as I might, I could not breach this barrier and gain access. I awoke in a cold sweat.

In the second, I had returned to science and was working in an unspecified lab in the middle of the night. As dawn arrived, a fresh spring breeze blew through the open windows and I felt a surge of joy, acutely aware, in the dream, of how fortunate it was that I had been given a second chance. This time, consciousness greeted me with a shower of disappointment that none of it was actually real.

A few nights later, I was watching a random episode of CSI: Miami. The episode cut to one of those stock sequences they feature every week: cue trendy music and atmospheric lighting as the camera cuts to various scenes of a CSI agent in the lab, performing some crucial experimental manipulation that will crack the case. These sequences are always rather dreamlike: the person is thoughtful, focused, almost euphoric as bits of fiber or cloth or shrapnel from the cadaver are tweezed into Eppendorf tubes and their residues run through the mass spec or HPLC or PCR machine. We see the furrowed brow, the careful movements of hand and forcep and tube; nothing is hurried, nothing is sloppy. There is almost a beauty in the act.

At that moment, I experienced a sharp pang. Which is actually rather ludicrous, because I never used to research like that. Nobody does, right? But clearly, dear reader, my subconscious was desperately trying to tell me something – and the rest is history.

More than a year on, reunited with my lost profession, I am as reckless and messy in the lab as I ever was. Except occasionally. Occasionally, I get a CSI Moment. A hushed, fuzzy focus falls over the lab and I suddenly view my experimental manipulations as a beloved ritual. I am, in short, back in those dreams, not ever taking for granted the fact that I managed to wrest them into reality.

It happened today, actually, a CSI Moment. In honor of it, I ceremoniously snipped off a length of BenchKote to transform my work space into a pure white sacred zone, and then my robot and I performed a high throughput immunofluorescence assay in perfect serenity. No matter that I didn’t have the sexy lights and music, and that the space beyond the BenchKote was a thinly-veiled disaster area.

For that brief snippet in time, I was at one with my science.

When I think back to what influenced me most to become a scientist, I have never been able to pinpoint a precise moment. Like many children, I captured moths and fireflies in jam jars, played around with chemistry sets, polished rocks, pressed flowers and ferns between pages, looked at pond water under my father’s microscope and at the moons of Jupiter through his telescope. I was addicted to a series of stories about a teenaged boy who used science to solve problems, though I could relate more to his female side-kick, who always struck me as the more sensible of the two. I had a series of very good teachers, and I enjoyed all my science classes.

But until very recently, I had forgotten completely about the Science Fairs – until I was asked to judge one.

Not easy being green An experiment to test the effect of chlorine on hair

My friend Alom Shaha is an amazing guy: not only is he a freelance science filmmaker, but he’s also a part-time physics teacher at the Camden School for Girls. It transpires that the official UK science curriculum is so heartbreakingly easy that his students had finished it weeks earlier with both hands tied behind their backs and were filling in the remaining year with more adventurous, creative endeavors, including the school’s first ever Science Fair. When I met up with Alom and his pupils on the fateful afternoon, I found them out in the sunny grounds, learning about the physics of bubble blowing. In addition to the novelty of hearing Alom called variously called ‘Sir’ and ‘Mr Shaha’ by a chorus of winningly enthusiastic girls, I bore witness to a few bubbles that definitely seemed to violate the laws of physics, and got to enjoy a genuine English school dinner. (Disappointingly, there wasn’t a Turkey Twizzler in sight – after all the Jamie Oliver-inspired media hype, I’d been dead keen to try them on the grounds that any snack food condemned by the Daily Mail must surely be delicious.)

“We don’t really know how to do Science Fairs,” Alom confessed as he ushered me into the room. “It’s a Yank thing, isn’t it?”

He needn’t have worried: I was totally impressed. The projects touched on topics ranging from the aerodynamics of flight, the pharmacology of caffeine and the putative danger of lead in our lipsticks to whether chocolate is addictive (yes) and which soft drink is the worst for your teeth (Ribena, since you ask). Never mind that the methodology was a bit rough: for example, the kids responsible for the latter project thought it was perfectly fine to substitute eggshells for tooth enamel because they “read on the internet that they were similar”. And a group studying whether branding affected consumer choice hadn’t considered that it might be misleading to compare Pepsi to Coke disguised with a Pepsi label, because Coke and Pepsi might not taste the same, and two variables were being changed instead of one. But the look of intense concentration on their faces when I explained this, and their dawning comprehension, was a revelation: this is why people teach.

And no science fair would be complete without at least one baking soda and vinegar volcano, which erupted three times during the course of the hour to cheers and applause. A few no-shows were especially disappointing: for example, the question of whether a melon can grow from a seed in your stomach will probably remain forever unanswered.

Frothy Mind the Gap heartily applauds this old science fair staple

But what I and the other three judges found most interesting was the fact the projects split clearly into two camps: those that were merely descriptive and literature-research based (“What is acid rain?”) and those that actually tested a hypothesis (“Do different kinds of music affect heart-rate differently?”). We judges especially favored those that sought to answer a question, but even as I felt strongly that this should be the case, I couldn’t help remembering my own long ago blue-ribbon effort: a diorama of the solar system made out of paper mâché. It was only much later that I must have learned that science wasn’t actually about demonstrating what was already known to be there, but was about adding some new knowledge to the world.

Some of these kids, clearly, were well on their way.

At the end of this week I am taking the Life in the UK citizenship test as part of my bid to secure indefinite leave to remain in the United Kingdom. So I spent much of this weekend cramming from the official book. Although many of the facts and figures were pretty basic (“On Christmas, people usually spend the day at home and eat a special meal, which often includes turkey”, or “Libraries are places that encourage children to read”), I did find a surprising amount that was new to me.

Testing times It had a beginning, a middle and an end, but not much of a narrative arc

In my previous post on this topic, a number of people expressed curiosity about the required content of the exam. So by popular demand, herewith just a few of the more exotic specimens – feel free to play along at home.

– Although Northern Ireland is part of the UK, the term “Great Britain” does not refer to Northern Ireland, as opposed to the term “British”, which does includes the Northern Irish. The term “Briton”, however, is usually only used to refer to Brits abroad, especially by the press.

– Oliver Cromwell was a serious badass. In 1649, he had Charles the First executed and England was governed without a monarchy for nine years. And here I was thinking that New Model Army was just a great band. (Disclaimer: I have no doubt I learned about all of this at one point, but blame my apoptotic neurons, not my god fearin’ American education.)

– Almost three quarters of British women with school-aged children are in paid work.

– It is illegal to be drunk in public. (Anyone who frequents the streets and public transport after eleven might be as surprised as I was to find this out.)

– Hereditary peers no longer have the automatic right to attend the House of Lords, though they are allowed to elect a few of their number to represent them.

– Blind people still have to pay 50% of the TV license! (I’m sorry, but this strikes me as seriously unfair. Is the dialogue of most British television programs really that sparkling?)

– 45% of all the ethnic minorities in the UK reside in London. (8% of all British are non-white, according to the last census, which was taken in 2005; half of this fraction is of Asian descent).

– In England, refusal to have children is grounds for divorce.

– Men are entitled to two weeks of paid paternity leave regardless of how long they have worked for a company, whereas although women are entitled to 26 weeks of maternity leave, they are not entitled by to be paid for any of it! (What’s going on there?)

– Children are specifically not allowed to deliver milk or work behind the counter of a chip shop.

And finally, it’s not in the book, but I feel I should memorize the lyrics to the national anthem before I show up in Great Portland Street with my £35 on Friday. After all, it doesn’t seem right to just mumble “God save our gracious queen” line after line like most of my British mates.

I was chatting with Richard the other day about his pet protein ZRANB2. Something about the name rang a bell, and sure enough I found that one of its orthologues was present in my own cell morphology screen. I was interested to see that we called the same gene ZNF265 instead, so Richard tootled around and discovered that this gene’s ‘official’ symbol was ZNF265 according to OMIM, but ZRANB2 according to NCBI Entrez and HGNC.

Sweeter than pancakes iHOP is one of several useful genomics resources

Most genes have a bewildering array of synonyms, of course, but in this day and age, you would hope that the genomics community would have settled on one unique one. In short, Richard and I shouldn’t have had to stop to disambiguate before delving into the really interesting questions, and this was the third such hitch I’d experienced in the past month. I’ve been using the superlative iHOP (Information Hyperlinked over Proteins) as my one-stop genomics shop (a site which, incidentally, falls firmly into the ZNF265 camp), so I emailed the person in charge, Robert Hoffman, to see if he could shed any light.

Robert, who turns out to be a lovely chap, told me that the HGNC is the ultimate authority; they curate and publish the latest names, and other organizations pick them up. “Of course,” he pointed out, “this does not mean that other people will understand you better if you use the official HGNC name, because many continue using the names the are used to.” So why didn’t iHOP call Richard’s gene by the HGNC appellation, ZRANB2? He confessed that this information is updated on iHOP only twice a year because it takes a long time for people to take up the trend, and meanwhile the NCBI ID number is more critical. NCBI, he notes, is quicker to respond to any changes in HGNC nomenclature.

So, I’ve duly bookmarked the HGNC website, but I still think there is a big problem out there. If any of you are in the gene discovery business, you’ll know that when you start getting interested in a new gene, it’s a nightmare to find a consensus nucleotide sequence in GenBank. I am not wholly innocent in this entire affair, as I single-handedly deposited about sixty different sequences for the feline leukemia virus envelope gene into GenBank during grad school, a veritable menagerie of subtle and esoteric polymorphisms. If you want to find out the common or garden FeLV env sequence in this mess, good luck to you. Associated with each gene name are not just polymorphic sequences, but truncations, splice variants, fusion proteins and the like. The FeLV community recognizes at least two ‘type species’ of the virus – FeLV-A/Glasgow and FeLV-61E – but this information is not, as far as I can see, linked to any of the GenBank entries. And it’s the same story for any gene you look up – which of the hundreds of entries, or sometimes thousands, is the ‘right’ one?

And the next step is even more disheartening. Looking up your new gene of interest in PubMed is not an easy way to grasp a coherent idea of what’s been published in the literature. Abstracts are littered with synonyms (and some pairs of different genes have the same synonym), but there is no unique gene identifier, as far as I can see, associated with the abstracts. I have no doubt that text miners are hard at work at this problem, but I haven’t seen anything helpful recently. And when you start being interested in homologues in other species, things start to get even murkier.

I realize that my gripes are probably naïve and possibly reflect ignorance of the state of play, but I suspect I am not alone. Maybe a good first step would be for journals to enforce the use of the NCBI ID number (or some other approved unique identifier) in all abstracts that mention a gene name, and for PubMed to add them retrospectively to their older abstracts.

Hell hath no fury like the temperament of a bureaucrat designing immigration forms. I cannot think of anything other than a vengeful spirit, possibly brought on by a thwarted love affair, that could have led anyone to compose the sentence I’ve put I boldface below:

“Since [first entering the UK] have you had any absences from the UK? If yes, give the dates of and reason(s) for the absences in the spaces below. List all absences, however short, including all of 3 months or more.”

(I have yet to find anyone who can tell me, grammatically or otherwise, whether I am actually meant to try to list my forty or so absences of less than three months in the eight small spaces provided.)

Having lived continuously in the United Kingdom for nearly five years, my visa is due to expire in October. So I am in the process of applying for Indefinite Leave to Remain via the ominously-acronymed, multi-pagéd SET⁰ application. Not only do I have to complete fields packed with sentences as abstruse as the above specimen, provide originals of hundreds of documents (such as every payslip I have ever received here) and surrender £750, but I must prove my allegiance to this fair land by passing the infamous ‘Life in the UK’ Test. (I’ve trialled some of the sample questions on my British colleagues and have determined that most of them would probably fail it outright.)

Why, you might ask, is an American putting herself through all this? The short answer is that I am weary of travel and anxious to put down roots. And Britain has come to feel more like home than anywhere else I’ve ever lived, the US included. When I resided in Amsterdam, it was London I felt homesick for. I travel quite a bit, but whenever I land at Heathrow, Gatwick, Luton or Stansted, I feel a little flutter of happiness in my heart that my journey has ended in this place above all others.

One of the hallmarks of the scientific profession is, of course, its transient nature. When you are younger this feature is exciting, and there is no doubt that I have benefited from experiencing so many other cultures at close range. But gradually, the lack of a solid foundation starts to take its toll. You begin to suspect that your soul has been spread a bit too thin. Sometimes, walking down a familiar-seeming street, I’ve had to suddenly stop in my tracks and actively remember what city I’m in. I’ve done research now in three different countries, and I have lived in eighteen different residences since leaving home in 1986. But even when you’re ensconced in one laboratory for a good few years, people come and go around you in a bewildering blur. I have lost track of the number of times I’ve met a new colleague and shared a instant jolt of connection with them, only to see a flyer for their leaving party put up a week later. The pang of loss, it seems, gets worse with age.

Although settling down won’t stop everyone else from leaving, at least you are a stationary object and the relative velocity feels a bit dampened. Some friends will still slip through your fingers, but I fervently hope that given time, I can eventually accumulate a small community of warmth and stability around me.

Of course no one knows what the future will bring. Maybe the winds will change and I’ll be blown off again one day like dandelion fluff on the breeze. But for now, I am feeling the pull of solid British soil beneath my feet.