All the better to eat you

Folk- and fairy-tales are the bedrock of culture.  By telling these stories to the smallest people of our community, often by the oldest member, we transmit cultural norms and ethical positions.  They tie us to the past and help to ensure that we behave properly, or at least normally, in the future.  The structure of these tales is often ritualised: you must knock three times before the door opens; you must stay in the wilderness for 40 days or seven years; girls and boys behave in stereotypical ways.  Marina Warner famously published her analysis of these structures From the Beast to the Blonde in 1994.  It was an investigation of the meaning in fairy tales and showed that some of them reveal the darkest edges of our true selves.

The wonderful, eclectic PLOS-One has recently published a neat cross-disciplinary study on Little Red Riding Hood.  The data are firmly from the Arts Block - comparing variants of folk-tales from different parts of the world to see whether they have common elements and then to classify them on the basis of the extent of similarity. This is apparently a standard methodology.  Jamie Tehrani from Durham University has used a scientific technique (phylogenetic trees) to quantify the amount of similarity and display the data so that more similar tales are closer on the page:

The diagram shows that there appear to be three clades (related by descent sub-sets) of stories. ATU 123 is "The Wolf and the Kids" while ATU 333 is "Little Red Riding Hood".  Tehrani's hypothesis is that the East Asian variant is not, as previously suggested, a primitive ancestral story from which LRRR and TW&TK are derived by divergence, but rather a more modern amalgam of the two older stories.  Evolutionist call that horizontal transfer and it's really important particularly in bacterial evolution whereby a pathogen can acquire a handy set of antibiotic resistance genes fully developed and already evolved by another totally unrelated species,  Pretty cool I think, although I'm not 100% convinced by the statistical arguments.

It reminded me of another analysis of tales by evolutionary science tools.  It's hard to credit that The phylogeny of The Canterbury Tales was published 16 years ago, because I can still remember the details and cite it often as an excellent example of a bridge between the Two Cultures of CP Snow.  It's also hard to credit that Chaucer wrote his tales down almost exactly 100 years before it was printed by William Caxton in 1478.  Before that manuscripts were just that - things that were written/copied by hand. What Barbrook, Howe, Blake & Robinson did for their short-but-sweet 1998 letter to Nature was to transcribe 850 lines of Chaucer's Wife of Bath's Tale from 58 medieval copies in The Canterbury Tales. They then aligned all the texts to highlight the accumulating differences as quill-pen copies were made of copies. That is a very powerful metaphor for what we think happens with DNA mutations.  The process of making an exact copy of DNA is very reliable: about 20 errors per person (or 3 billion base-pair genome) per generation.  Copying manuscripts is much less reliable and BHBR found numerous differences in their dataset.

The arts-science cross-over added-value came from the fact that we evolutionary biologists have software for tracking and making sense of small changes in the sequence of letters, so BHBR were able to lash their mss into a computer and generate the pattern of relationships illustrated on the left. The key result from their analysis is that several manuscripts (marked O in red) appears to spring from the very centre of the tree, which we may suppose is the missing original in Chaucer's own fair hand.  "However, most of them have been ignored by scholars" as BHBR say.  Why is that?  Because the world of scholarship acquires its own dynamic.  Like the Talmud which evolved as a series of commentaries on commentaries on commentaries on the Holy Book, a large fraction of science develops by critiquing the work of other scientists rather than observing the natural world itself with fresh eyes.  It seems they have similar issues with self-referential vortices in The Arts.  Self-referential vortices sounds sciencey, no?  It means that academics have a tendency to spin round and round until the disappear up their own backsides. 

42

It is Douglas Adams' birthday today. He would have been 62 except that he died 13 years ago at an absurdly young 49.  He is still remembered and his words are cherished and repeated by thousands of people because they were clever, insightful and funny. They can also seem, particularly condensed into a list of quotes, tiresomely disengaged and cynical. There are a couple of people who introduce me (this is my char-lady's aunt's cousin) to their friends as the man whose brother collaborated with Adams on a couple of books. This is ever so slightly annoying because my words are clever, insightful and funny in their own right but don't seem to be Going Viral any time soon.  But today, it's not about me, but about DNA.
For your diary, Towel Day is 25th May.  A place for Hitchhiker fans to hang out.  And some words from The Great Man:

• Humans think they are smarter than dolphins because we build cars and buildings and start wars, etc., and all that dolphins do is swim in the water, eat fish, and play around. Dolphins believe that they are smarter for exactly the same reasons.
• If you try and take a cat apart to see how it works, the first thing you have on your hands is a nonworking cat. 
• It'd be like a bunch of rivers, the Amazon and the Mississippi and the Congo asking how the Atlantic Ocean might affect them… and the answer is, of course, that they won't be rivers anymore, just currents in the ocean.
• All opinions are not equal. Some are a very great deal more robust, sophisticated and well supported in logic and argument than others.
• I love deadlines. I love the whooshing noise they make as they go by.
• A common mistake that people make when trying to design something completely foolproof is to underestimate the ingenuity of complete fools.
• There is a theory which states that if ever anybody discovers exactly what the Universe is for and why it is here, it will instantly disappear and be replaced by something even more bizarre and inexplicable. There is another theory which states that this has already happened.
• Space is big. You just won't believe how vastly,hugely,mind-bogglingly big it is. I mean, you may think it's a long way down the road to the chemist's, but that's just peanuts to space.
• Life, the universe and everything.
• Don't panic.

So long and thanks for all the fish!

analfabeto beats illiterate

We're been living with an eSpanish these last couple of months.  A few days ago, Barça was playing Real Valladolid in La Liga BBVA (that's soccer) at the same time as Ireland was playing Italy in the Six Nations Rugby.  Poor La Manch' was a bit conflicted: he wanted to go down to the local watering-hole and root for Ireland but he is a  Barça fan, so wanted to see his team getting trounced by the Lads from Leon.  If I'd gone with him, I'm sure he'd have opted for Rugby in a crowd in spite of having close to zero knowledge of the game. But I'm too much of a sofa-guy to cross the street to watch team sports.  There is a certain amount of good-natured rivalry here on the farm: my country is more corrupt than yours; our banking crisis is worse; our youth unemployment is crippling whereas yours is merely shameful; our weather is definitely crap; your chaps can't even play rugby.

La Manch' claimed that Spanish people never read books, while the Irish houses he's been in all have shelves of them. I asked him to show me the data for his unsupported assertion and he came up with some statistics showing that:

• Spaniards read books for only 5 hours per week (half that for India and China)
• Only 53% of Spaniards qualify as 'readers' compared to 80% in Sweden
• Spaniards only read 1.7 books on holiday compared to 2.6 in Britain
• Literacy is 99% in Ireland vs 97.7% in Spain

I cannot find a source for the relevant "average number of books bought per country per capita per annum". You may, and we all should, take these statistics with a shovel of salt. Maybe there are better quality or more newspapers in Spain and these make up the difference in book reading.  The last one is about as credible as the "fact" that 99% of Albanians regularly turned out to vote for the ruthless Enver Hoxha during his 40 years of red tyranny.  99% literacy in Ireland might be possible if you define literacy as the ability to a) recognise 26 different letters and b) sign a cheque with your name.  Functional literacy requires you, for example, to read the instructions on a bottle of medicine before dosing your sick child.  Getting that wrong could hazard your evolutionary future.  I've known a couple of farming neighbours who, when they owe me money, invite me to fill in the cheque for them to sign it,  I reckon they'd have trouble filling in some of the forms they get from the EU and the Department of Agriculture.  The shocking spelling and poor syntax that I get from many of my students at The Institute is a different level of inability - even the dyslexic ones can read a lab manual and an exam script; whatever they achieve towards answering the questions correctly.

The levels of adult illiteracy in Ireland is among the highest in Europe.  18 months ago, the government was set to reduce the number of illiterate adults from half a million to 300,000 by the end of 2016.  A Programme for International Student Assessment (PISA) study in 2010 found that 23% of Irish males are functionally illiterate, while 18% are significantly handicapped by their inability to read.  Successive governments have been complacent in the repetition of the tired old mantra that Ireland has the best education and that the multinationals which queue to set up their tech companies in the Republic do so because of the highly educated work-force.  When the Morrison Visa program allocated 16,000 work visas for Irish people in the early 1990s, my old boss in Boston put it quite graphically: "If I have an Irish lad on a building site and tell him that this piece of timber has to be sawn into three pieces of equal length, I can be sure that he'll be able to do it.  I have no such confidence in the average American high-school graduate".

That may be true at the top end of the labour market, but I think you'll find that many of the multilingual operatives in the many Irish-based call-centres are not Irish born or Irish educated. The multinationals may be tapping an educated work-force but few of them have green passports. It's much more likely that Apple, Google LinkedIn are here because we let them finagle their way out of most of the tiny amount of corporation tax that they should pay the Revenue Commissioners. If illiteracy is this bad in Ireland, I'll have to hope that people in Spain are choosing to read fewer books over the holidays because they prefer partying rather than that they cannot read books at all.

Clostridium damned difficult

Clostridium difficile was being written up again last week in Nature.  It's an awkward sort of a microbe: difficult to diagnose, difficult to culture in the lab, and a serious killer to boot.  Ordinary folk don't even know how to pronounce the specific name:  a ploddy diffiseel ? a pedantically sounded final e diffisilé ? a florid italinate diffeechilley?  Most of us, including wikipedia, give up and call it C-diff.  It's interesting because it is somewhat opposite to Marshall and Warren's H.pylori, which can be cleared up pretty damned quick with a short course of antibiotics.  Gonorrhoea used to be similarly amenable to treatment until we squandered our augmentin on pigs and as growth promoters in chicken.

C-diff on the other hand usually springs up to kill after a short course of antibiotics has shifted the balance of power in the gut to allow this minor (<2%) player in our intestinal flora to foment its revolutionary take-over.  C-diff is indicated by a watery diarrhoea with a distinctive odour, fever, and a recent course in antibiotics. It is a classic iatrogenic (doctor induced) nosocomial (hospital acquired) infection, far more common in places for healthcare than in the outside world and often induced by medications which suppress acid production in the stomach (hello Tagamet). It makes you think that having a gastric pH not far off that of car-battery acid might not be primarily about digesting food but rather for digesting pathogens before they get access to the goodies further down the tube.  And once you've got C-diff in spades, it's really hard to shake off because it is resistant to so many of the antibiotics - that's presumably why it is triggered by a course of these drugs administered for something else.

In teaching Food and Fermentation Microbiology this last year (great fun!!), I've tried to encourage the students to use their noses, which can be pretty accurate diagnosticians.  You know how domestic trash has a really distinctive smell which is different from toilets which is different from pig-slurry. After 5 days without a fridge during the last power-cut, my sour-dough starter developed a worrying smell of acetone with overtones of esters (pineapple, pear-drops, hint of jasmine to a better nose than mine).  It was still full of oomph for raising bread but the product was very sour.  So I'm still dithering about throwing it out and getting fresh start from a neighbour.  Needless to say (the young of today - harrrumph) the students refused to engage and skittered about the room squeaking girlishly holding their noses - some literally.  I'm sorry to use "girlishly" but you know what I mean and the boys were worse than the women.

But as with so much in our scientific world there is a three-letter acronym (TLA) in the wings which is showing great promise for forcing Cthulhu-diff back into the cellar and shutting the trap-door on it: not to wipe it out entirely but to allow the other denizens of the dark to keep it under control.  FMT is faecal microbiota transplantion and it works on the old principal "Eat shit, a trillion horse flies can't be wrong".  Of course, science tries to make it more sciencey than that and to make it more uniform and reliable but the idea is to deliver an aliquot of microbes from a healthy gut into the intestine which is infested with C-diff: by nasal tube or from the other end by enema or colonoscope.  This is rather humbling: the intestinal flora is comprised of about 200 trillion cells from maybe 10,000 different species, and we have less idea about how they function and interact than we do about the animals than cavort and copulate and kill on the plains of the Serengeti.  Despite not knowing how it works, we now cannot deny that work it does. A year ago the first randomised controlled trial of this therapy was wrapped up early because those receiving FMT were twice as likely to have their symptoms resolved and it was deemed unethical to continue giving the crappy no-crap option when the crap option was clearly better.

The FDA is now scrabbling to get its regulatory act together to allow this therapy before C-diff kills its annual quota of 14,000 US citizens and a pro-rata equivalent of Europeans.  BUT we don't want to repeat the errors of the Blood Transfusion Board which developed and delivered a new therapy for hemophilia which, because it was badly thought through, contrived to infect 300 misfortunate bleeders with HIV.  So regulation is probably a Good Thing if only because it might "reduce the demand for risky at-home procedures" (!?).  Also because we know so little about how the human intestinal flora works, we want to be careful that we don't leap from the C-diff frying pan into the, as yet unknown/unnamed, C-death fire.  The whole story is freely available at Nature.

Living Willing

There aren't many advantages to living 40km from your place of work without any available public transport.  One is that it is not 130km from work,  Another is that it gives an opportunity to listen to the car radio and catch up on events outside the county.  For a family without television and which doesn't 'take' any newspapers, this is a lifeline to the rest of humanity.  I tend to listen to Newstalk-FM in the morning as Ivan Yates and Chris Donoghue slag each other off and get opinionated about events.  They read the newspapers and the press-releases for copy and often interview somebody to give them a chance to be famous for fifteen minutes.  A Living Will a.k.a Advanced Health Care Directive is a document that endeavours to clarify your options and opinions concerning 'end of life issues".  Such documents have, at the moment, no legal standing in Ireland.  They are in the news because there is a movement to clarify the status of such clarifying papers.

I used to think such matters were easy.  I've already asked Dau.II, who can be a cold-blooded pragmatist, at the appropriate time, to hold a pillow over my wizened face until my heels stop drumming on the bed.  She, like Barkis, is willing, but there are two problems a) the appropriate time and b) the necessity to involve a confederate.  We are absurdly caught up with the sanctity of life in Ireland, so that "It is a criminal offence to aid, abet, encourage or procure the suicide of another person." Dau.II would probably get banged up in chokey for helping to off her father, as the case of Marie Fleming made clear; although in The End she died before needing help from her husband..  A lot of this was explained on Newstalk last week by Patricia T. Rickard-Clarke, the Law Reform Commissioner, who made clear that you can refuse certain interventions much more easily/legally/acceptably than you can request others.

But what was more interesting was to be forced to think a bit about when and under what circumstances fully-cognisant me could imagine severely-impaired me welcoming quietus. This conversation was helped along a lot by a PDF that was generated a few years ago by the Irish Council for Bioethics (of all people!), but which doesn't appear to be on-line anymore.  A committee can work very well at such tasks because the anecdotes and experience of the several individuals on the committee come together as a wide context than a single lifetime can encompass and thus become data.  The following list from that PDF is prefixed by "I do/don't want":

• cardio-pulmonary resuscitation (CPR) 
• artificial ventilation
• artificial feeding by tube or drip
• antibiotics
• blood or blood products
• kidney dialysis
• surgery or invasive diagnostic tests
• any new treatment without discussion with my Healthcare Proxy (HP).

I can happily refuse all of these, but you might know a case of, say, dialysis where this allows someone to live on with dignity and minimised discomfort for months or years. For example, CPR, from what I hear, can easily break a rib, especially if weak from, say, osteoporosis; and has a negligible chance of working.  You may want to trade a broken rib and exquisitely painful breathing for a few more days of life. I don't. You are strongly recommended to discuss your wishes with your GP, s/he's more likely to be beside the bedside at the relevant time.  But also, you are recommended to designate in writing, and talk deeply with, a person (Healthcare Proxy - HP) who will make the decisions on your behalf when you are no longer capable of doing so. I written about the end of my friend-and-mentor Lynn Margulis whose daughter, as HP, had to fight for the right of her mother to die.

It's also important to sort out a will (I give my second best tea-pot to Cousin Maria) as soon as you have any assets at all, but we are all agreed that you can't take that with you when you go.  So it is more important for self-interest to make sure your last days/weeks above ground are the best that you can hope for. Me, and it's all about me, I don't want to finish up neglected in the corner of a ward as the puddle of my own leakings ferments into open sores.

Start(l)ing in science

International Women's Day today, so it would be remiss if The Blob didn't acknowledge it.  There are 3,500,000,000 women walking the planet and I know nothing about most of them.  That's partly because I've never been to Brazil where a lot (100ish million) of them live, but mainly its because they come from another planet. Or rather, their use and experience of our planet is very different from mine as a man.  Mervyn Peake tried to articulate this Ignorance Of The Other in Titus Alone:

I am clueless about Women but I've met a few extraordinary women in a life in science.  The first meeting hasn't always been auspicious.

About 18 years ago, the newly appointed Director (and sole employee) of the Irish National Centre for BioInformatics was approached by his Head of Department.  HoD had a problem: two young women had done extraordinarily well on their exams at the end of second year in college. It was really important to him that they did not end up completing their degree in The Other Department. So we must make Our Department look more interesting, dynamic and attractive than the (absurd, posturing, second-rate) rivals across the car-park.  I agreed,with a sinking feeling, to take on one of these women for six weeks that summer and pay her out of a slush fund that I had squirrelled away. HoD took on the other. I think, like Best and Clark, they may have drawn straws.

When "my" intern turned up on the first Monday it turned out that she knew nothing about computers, next to nothing about biological sequences (sinking feeling plummets) . . . but she seemed willing to learn and capable of hard work (feeling gets hint of buoyancy).  My grand plan was to write a Manual for Bioinformatics, to make my job as a facilitator of database access and teacher of molecular sequence evolution easier.  To populate the pages, I needed examples from the Universe of Sequences that would best illustrate the techniques Joe Boffin would be likely to need in his research. For starters I needed a pair of Goldiloxian sequences that were similar enough to be alignable but not so similar that the alignment was trivial and uninformative.  Not addressing this problem was getting to be a full-time job for me.  So, speaking  v e r y   c l e a r l y  I explained the big picture, showed how to explore the universe of sequences and gave her a pile of reading to get started.  Believing I had give the Intern a week's work, I disappeared back into my burrow to Direct myself in the manifold tasks of starting up a National Centre.

In the early afternoon of the first day, the Intern came back having completed all the tasks I'd given her that morning as well as having a break for lunch.  It was clear that I, in my Human Resources hat, had seriously underestimated the available personnel.  It went on like that for four weeks.  I'd set out a doughty task-list; Intern would ask a couple of telling questions, go away to fulfill the stated tasks and then proceed to extend and embellish them.  At the end of the month, she had not only found all the worked examples, she had also written the Manual although I think it was the first time she'd ever used a word-processor.  For some reason I was absurdly impressed that each chapter title appeared in a shadowed box - it made it look so very professional. I was exhausted and had nothing left for her to do, so I lent her to a colleague. Within a week she had solved an intractable software problem that had baffled a lab-full of post-graduate and post-doctoral researchers. That Intern was Aoife McLysaght who went on to become a geneticist,  researcher, communicator, broadcaster, activist, teacher and a great role-model for young women in science. это день матери в России: Эта женщина является матерью тоже. I have no idea where the energy comes from, but I've encountered something similar before. 

Back in August 1996, did we give her the last week off?  I hope so, she deserved a holiday with pay.   The Manual we she wrote inevitably came to be called As Easy as ABC or Aoife's Bioinformatics Course and I put in a lot of train miles hawking it and the associated training course round the Island.  Later I put in a lot of air-miles taking it abroad and ran the five day course for which it was the backbone in Norway, Finland, Turkey and South Africa.  Her contribution thus helped some hundreds of bio-scientists make a better fist of understanding the evolutionary context of their research.  Clearly I owe her a lot too.

Bonnets off!

Enterprising Students 2014

Almost 365 days since the 2013 Student Enterprise Awards, the foyer at The Institute was awash with young capitalists again.  Just like last year, I was tied up in classes the whole afternoon, so didn't get round to talking to all the youthful entrepreneurs.  Heck, I didn't get to talk to more than a dozen different groups before they were being told to pack up and go home.   Rupert Sheldrake holds a fringe-science concept of morphogenetic fields - where ideas propagate across an as yet undefined aether (woowah video).  This is a scientifically testable idea so it's silly to just cry nonsense and close down the shutters.  Sheldrake thinks that it may be easier to solve The Times Crossword late in the afternoon after two rounds of commuters have struggled with the clues.  He also thinks that after sheep in New Zealand have learned to negotiate cattle-grids by taking a bit of a run and getting across them with a parachute roll, it may be more likely for Scottish sheep to develop the same trick for accessing greener pastures.

Last year, at least two enterprises were producing smoothies, this year three companies were producing cup-cakes.  Smoothies nowhere to be seen - soooo last year y'know.  What's all that about?  Something in the Sheldrake air?  A new cookie series on RTE?  Industrial espionage in school uniforms?  Or Friendface social media?  All the cup-cakes looked gorgeous: like orchids - totally artificial, quite over-decorated, hard to believe really.  One of the three groups, which should have been called Boys who Bake Buns, but wasn't, had my vote for producing gluten-free and diabetic-friendly cup-cakes.  The Boys and I agreed that their product looked great but tasted like saw-dust.  Nevertheless the sense of including those with medical conditions in the latest food-fad seemed like a Good Thing to do.

Next door, a couple of girls were producing bouquets . . . made of candies & chocolates.  My good old friend P from graduate school loves to give people flowers - birthdays, graduations, communions, bar-mitzvars.  She was once asked to do the florals for a friend's wedding and, being temporarily car-less, went to the florist  in the wheels (that's a synecdoche) of a fellow-student.  On the way back to venue, the driver asked "Don't you find it a little strange that we celebrate these events by cutting off the reproductive parts of plants?".  It gave her pause!  Meanwhile back at The Institute, I launched into the bouquet girls " Yar yar roar roar, what's wrong with flowers? I think this is a terrible idea, we have an epidemic of Obes . . ." when I realised that one of the teenage partners was twice as big as the other ". . . ahem, my girls have terrible trouble with their teeth: always at the dentist."  I admitted that their sweetie-bouquets looked very nice and moved quickly on with a red face.

33 years ago this week, Clive Sinclair launched the ZX81: a personal computer selling at an unbelievably low £69.95 or $250.  Immediately other people battened onto the BASIC concept and made comfortable money selling peripherals, carry-cases, Sinclair magazines, and ZX81 games on cassette. Shortly after Crocs, the shoes that aren't water-proof, launched in 2002, Sheri Schmelzer started designing and selling little decorative studs that filled some of the holes. A year later the parent company bought out Jibbitz for $20million  That's called an exit strategy and how capitalism works.  Another thing in the Sheldrake this week seemed to be "dang, where did I put my hair-clips?".  There were two teenage solutions to this distressing conundrum.  One groups bought some nice picture-frames, stuck in a nice back-ground and then glued on a horizontal median strip in a different colour.  The strip was about as wide as a hair-grip is long.  So if you remember to clip the grips onto the frame, then you'll know where to find them next-time.  The other group were selling a piece of colored card on which a magnetic strip had been glued.  Stick the card on the wall as a magnetic store for your hair-clips. That's also how capitalism works - find an unfulfilled need (or create one through advertising) then make and sell a solution. I can see a new sport sweeping the country, a bit like darts - you lie on your bed and fire hair-grips at the card and count how many stick. Let's call it klipnominations. You could do it through Friendface другособа and issue challenges to your facefriends in Ukraine.  You might need "волосся-кліп" and "магніт" in your communications.