Sunday 30 November 2014

Outing of sport

A couple of days ago, I suggested you read a longform about an athlete and her quest to unearth the causes of her medical problem(s) by research. In my rush to get copy out and because I'd gone on too long already, I didn't draw attention to a quote that gave me a ding of empathy. But my pal Russ was also caught by it and so I share here for those who don't follow all my links and read everything with care-and-attention. "It wasn’t that she was much of a competitor, exactly—passing someone in a race felt more deflating than energizing. Mostly Kim just wanted to be moving".  Here is an athlete, who has devoted her entire life to running, abseiling, kayaking to edge of endurance, who doesn't care about winning. Cripes, if I'd known you could participate without caring about who won, I'd have done better at sports . . . maybe.

Then metafilter pointed us at a Marxist deconstruction of Strictly Come Dancing by Alexei Sayle.  Sayle's key beef with Strictly it that conflates art with sport in a way that degrades the former and all who participate (dancers, judges, viewers).  This was expressed with passion and integrity way down in the comments "The real problem of Strictly is to mix art (which is meant to be collaborative and transcendent) with sport (point scoring, judge pleasing). That's why I hate ballroom competetions. It's also why I hate singing contests, arts prizes, literary prizes and that whole nauseating caper. Art is not sport - every time you mix the two (and rhythmic gymnastics and diving come into this category) you get a mess.  And I'll also thank Sayle for naming the seepiness of RG: "the disturbing Olympic event of rhythmic gymnastics (can anybody explain why it is only little girls in tight costumes who perform this “sport”?)". I'll add that to boxing as a spectator sport that will be banned when I become President.  Incidentally, Katie Taylor just won the World Boxing Championship in her class for the 5th time in 10 years and was fulsomely tribbed on her return home by our current President Michael D. Higgins who momentarily parked his life-time commitment to human rights and human dignity.

I have written about running your heart out as a way of achieving transcendence; not forgetting Derartu Tulu's instinctive kindness being bigger than winning. Maybe the longer you run, the less you are competing with other and more competing with yourself.  This all started an ear-worm nagging: "dance like there's nobody watching" and I had to track that down . . . to Quote Investigator.  It is according to QI much bowdlerised but:
You’ve got to sing like you don’t need the money
Love like you’ll never get hurt
You’ve got to dance like nobody’s watchin’
It’s gotta come from the heart if you want it to work
comes from 1989 and song-writers Susanna Clark and Richard Leigh who have this to say: "For some reason, people have a great deal of trouble attributing this lyric to its creators: Susanna Clark and Richard Leigh. The reason you can not find any printed or recorded support for these assertions dating back any earlier than our song, is because they don’t exist. In other words, as disappointing as it may be to learn for those who use our work without permission, the lyric is not in the public domain, but actually a relatively new work “made up” by a couple of hard-working songwriters." Harrumph indeed!

Sylacauga 1954

It's exactly 60 years ago today that a grapefruit-sized meteorite came crackling through the Alabama sky, penetrated the roof of a wood-frame house in Sylacauga, bounced off the wireless and whacked Ann Hodges on the hip.  Luckily she was dozing on the couch, covered in a quilts, so the only damage she sustained was a massive haematoma. Then again, if she'd been in the kitchen peeling potatoes, the rock would have missed her altogether.  When her husband Eugene returned home from work, not only was there no dinner, but he had to fight his way indoors through a hoard of rubber-neckers.  A local geologist came round from the quarry where he was working and pronounced that the rock came from outer space but many people chose to believe that it came from they communiss from Russia. And everyone wanted a piece of the action. The local police called The Feds and a USAF helicopter landed and took the meteorite away for analysis. The Hodges's landlady Birdie Guy claimed the rock as having fallen through her property and a couple of lawyers turned up to help themselves to a client and some folding money. Eugene and Ann refused a cash offer from The Smithsonian but by the time the Air Force had returned the rock and they were ready to accept the Smithsonian's derisory amount, the Smithsonian (and everyone else) had gone off the boil and the offer was no longer on the table.  A couple of years later the meteorite was donated to the Alabama Museum of Natural History in Tuscaloosa. Not many winners there.

But the following day a local black farmer called Julius Kempis McKinney was carting a load of firewood home when his mules [you couldn't make this up] baulked at a black rock in the dirt road.  That night the hullabaloo in Sylacauga caught up with McKinney and he went back to collect the other fragment of meteorite. After confiding his tale to the local post-man, McKinney was able to sell his meteorite to an attorney (another lawyer!), who sold it on to the Smithsonian where it is on display to this day. The McKinneys were quietly able to buy a car, a new house and some additional land with the proceeds. My information is sketchy and may be incorrect in its details because it happened long ago in a world without web-cams or twitter.  In contrast, the Chelyabinsk meteorite which exploded over Siberia a couple of years ago was at least 100x bigger and sold for about $30/g.  That would realise Mr McKinney about $55,000 if it happened today . . . and if the price held pro rata for larger pieces. You can buy a modest detached home with a small yard in Sylacauga today for $35,000.

Saturday 29 November 2014

Charcot Marie Tooth

You notice something new about yourself, or you wake up feeling crap for the seventh morning in a row and you go to see your doctor.  If s/he's any good and over the age of 30, s/he'll have seen a lot of sick people: 10 or 15 an hour for days on end since last Christmas and beyond. Each patient has been sick in their own special way but some have been sick with similar symptoms. Alert medicos ask if there might be an identical underlying cause to the same disease in each of several different persons.  If nobody has noticed the connexion before, the doctor gets to write up a hypothesis about cause and effect and often the disease becomes an eponym named after the discoverer.  Why just the other day I was talking about the causes of Down Syndrome. Sometimes the discovery doesn't get to be associated with the chap who makes it: neither William McBride nor Widikund Lenz got to name the developmental tragedy caused by the drug thalidomide. Some of these syndromes have such evocative names that you have to find out more, not only about the causes and symptoms, but also about the combination of events that perked someone up with "That's curious, I've seen that, or read about it, before".  One of those is Charcot-Marie-Tooth disease aka CMT which is a curious grab-bag of neuropathies that was first noticed by Jean-Martin Chacot and his assistant Pierre Marie in their paper "Sur une forme particulière d'atrophie musculaire progressive, souvent familiale débutant par les pieds et les jambes et atteignant plus tard les mains".  Coincidentally in the same year 1886 across the Channel an English neurologist Howard Henry Tooth was publishing his MD thesis on the same disease, describing particulière d'atrophie musculaire as a progressive muscular atrophy.

CMT is so diverse in its causes and symptoms that it is a bit like 'cancer' which only the most superficial assessment could call _a_ disease.  CMT is degenerative in that those with the wrong combination of genes start off fine and, as they turn into adults, start to decline from the outside in.  Initial symptoms include 'dropped foot', hammer-toes, and muscle-wasting in the lower leg.  Weakness and loss of feeling in the legs then starts to manifest in the hands and forearms and the doctor can put a label CMT on the condition. That's about all s/he can do because currently the disease is incurable. In times past, they would have lumped it in with muscular dystrophy; and quite possibly some doctors (less down with the medical hood) are still doing that. Which leads to the small-world observation that Charcot studied under the great French neurologist Guillaume-Benjamin-Amand Duchenne de Boulogne after whom Duchenne Muscular Dystrophy DMD is named. It is common enough in adults at 1:2500 but defects in many different genes can trigger symptoms, and many of these oddities are exceedingly rare.  70% of cases are caused by a duplication of part of chromosome 17 which puts the gene PMP22 out of whack, but about 40 other genes are known to be involved.  It shows just how complex and interconnected normal development and neuro-muscular control is.  Each of these 40 genes has to be switched on within a narrow range of tolerance for you and me to walk normally and yell out when we stub our toes.

Charcot stood astride (1825-1893) late 19th century medicine in a quite monumental way.  He held court in the Pitié-Salpêtrière Hospital in Paris and lots of younger giants were educated and inspired by him, including Sigmund "It's a cigar" Freud; Joseph "Reflex" Babinski [R]; William "Free Willy" James; Alfred "IQ test" Binet; Georges Gilles "fuckit-fuckit-fuckit" de la Tourette. I mentioned Charcot last year, partly because it was his birthday (as it is again today) but mainly because I was on about another of his students Theodor Escherich who makes the spelling of eponymous E. coli scho damned difficult for anglophones.

I was going to get round to tribbing Charcot in due course but CMT surfaced in my corner of the blogosphere just two days ago in a remarkable long-form article about a workaday athlete call Kim Goodsell.  Goodsell could have been a doctor like her brother, but she dropped out of medical school and lived the free life of a rover in the wilderness, coming back to civilisation periodically to make a bit of entrepreneurial money to feed her running-in-the-outback habit. In her 40s, her feet stopped working to command and she picked up a diagnosis of CMT.  Strangely, she had earlier been diagnosed with a heart arrhythmia which would have stopped the fell-running gallop of a less determined person. She couldn't believe that she had been dealt two crap cards from the deck of life and flung herself into an amateur research project to find the roots of her condition(s).  It was a long time since she'd been in medical school and she's forgotten all the jargon and in the interim new dictionaries of terms and techniques had been invented.  She needed to get her head round all this information and integrate it. Her journey through the darker reaches of PubMed in search of enlightenment was a bit like Simone George applying her lawyerly training to find a cure for her man.  What, by dogged perseverence, Kim Goodsell eventually worked out was that a defect in her copy of the gene LMNA was the likely cause of both of her conditions. It didn't make a cure more likely, but it made her feel that she wasn't taking this thing lying down. But in the process she really pissed off some of her consultants who couldn't see beyond the comfortable confines of their own specialty. 150 years ago Charcot said "In the last analysis, we see only what we are ready to see, what we have been taught to see. We eliminate and ignore everything that is not a part of our prejudices".

Friday 28 November 2014

Cobber, stick to your last

We were just about halfway through a microbiology laboratory session yesterday afternoon when the lights went out and the lab fridge started beeping in an annoyingly persistent way. It was a power cut, and as people's smartphones started to light up it was revealed that the outage involved the whole Institute . . . and the school next door . . . the whole town . . . a village 15 km down the road. The class was in the business of performing a spore-stain on bacteria originally isolated from soil.  The protocol requires smearing the bacteria on a glass slide, adding a virulent green stain and then bringing it to the boil, cooling it down, rinsing the slide and 'counter-staining' with another dye.  It takes about 10 minutes of tricking about and then you can view your preparation under a microscope to see if your sample is capable of producing a spore to weather hard times or if it just pegs out and dies. There are few things that give a beginning scientist more satisfaction than a really good microscopic preparation that a) s/he has made and b) looks intrinsically pretty. In the prep above you can see that most of the bacteria are stained a uniform pink but that some of them have a greeny-blue blob inside them - that blob is the spore and its location (end, centred, off-centre as here) and size is diagnostic for the species.  The power-cut occurred just as the staining process was ending and before we needed the microscopes to see the results.  Students being people, when the electricity failed and their microscopes became unavailable, most of them started to gather their traps together for an early departure.  But three of them stayed to finish the task, dry off the microscope slide and leave it with me for viewing the following week.  I congratulated them on their commitment because I'd been in a similar position myself when I was their age 40 years ago.

In my case, we'd been in a practical session trying to observe polytene chromosomes in the salivary glands of the larvae of Drosophila melanogaster, the fruit-fly which has made such a contribution to the science of genetics over the last 100+ years. The larvae are the maggoty flightless juveniles which cruise over rotting apples gobbing out digestive juices in their saliva and sucking it all down to grow strong enough to pupate and get reborn as an adult fly.  They need to make a lot of digestive enzymes to deal with this food-source, and enzymes are proteins which are made from genes located on the chromosomes. One way to beef up the enzyme supply is to double and double and double the DNA of each chromosome strand until it is a great thick braid made of maybe 1024x copies of each DNA thread and clearly visible under a microscope. I have included a picture of these objects which can be stained a pretty mix of dark and pale pink.  The pattern of dark and pale is absolutely reproducible and diagnostic of the species of fruit-fly and the region of each chromosome. Tracking the changes in these microscopic 'banding patterns' to match gross changes in the colour and shape and hairiness of the eyes, wings and body of different flies helped nail down the fact that chromosomes did indeed contain the hereditary material about 50 years before Crick and Watson worked out the structure of DNA. Barbara McClintock made similar contributions matching chromosomal anomalies with oddities in the shape and colour of maize (Zea mays) kernels.

ANNyway, in 1975 we were tasked to follow in the footsteps of Calvin "polytene" Bridges by pulling the heads of Drosophila larvae in such a way as to expose the salivary glands and their giant chromosomes. Essentially the same process is carried a million times a day as forests chickens are eviscerated for Kentucky Fried, except that each larva is about 4mm long. In other words it was eye-crossing work that required some dexterity and a lot of application until you worked out what amount of pull applied to what part of the head would do the trick. We had a lot of larvae to practice on, but it also required patience and repetition and muscle-memory and none of this could be learned from being told or from reading a book. After nearly an hour of (very) trying <BARrinnnnnngggg!!> an alarm went off and we were all told to evacuate the building because of a bomb threat.  This was less than 300 days after one of the 17th May 1974 Dublin car-bombs had been detonated less than 300m from the place where I was working. so I should have used that as an excuse to finish for the day and go home.  But I didn't, I stuck at it, in the empty building, no longer distracted by the sighs and curses of my neighbours, and about 15 minutes later pulled like Goldilocks and the diminutive salivary glands plooked out on the slide ready for staining. Staining was easy enough and I was the only one in that year's class who succeeded in seeing freshly prepared polytene chromosomes. They looked gorgeous. In my not notably auspicious career in science, that was one of my proudest moments.  See, I'm still talking about it 40 years on.

Thursday 27 November 2014

Reasons to be cheerful Part 27/11

привітання Ukraine, Bonjour La Belle France.  It's Thanksgiving in America. The painting on the left is Norman Rockwell's Freedom from Want which was inspired by a State of the Union address to Congress, in January 1941, by President FD Roosevelt.  Roosevelt identified Four Freedoms that needed to be achieved for a better world. "The third is freedom from want—which, translated into world terms, means economic understandings which will secure to every nation a healthy peacetime life for its inhabitants—everywhere in the world".  On the right is one of dozens of parodies of the painting - not all of them so nostalgic or insular. I hope you have enough to eat . . . but not too much.  Every year at this time, I try to reflect on the many reasons I have to be cheerful.  It's a little easier here in Ireland where Thanksgiving with turkey and all the trimmings [T+T+ttttt] is being celebrated elsewhere:  I don't feel obliged to invite Daft Auntie May and her disagreeable husband to dinner.  Cue Ian Dury:
"A bit of grin and bear it, a bit of come and share it
you're welcome we can spare it ... yellow socks"

Wednesday 26 November 2014

Counting chromosomes

At The Institute, I affect shock-and-amazement when young scientists seem to have no idea how many chromosomes they have in each of the 100 trillion cells in their body. Does nobody else teach them the fundamentals?  Is it not part of the curriculum in Irish secondary schools?  I shouldn't be too hard on them because, when I was born, everyone was certain-sure that we humans had the same number as the great apes: chimpanzees (Pan troglodytes), bonobos (Pan paniscus) and gorillas (Gorilla gorilla) at 2N = 48. But in December 1955, Joe Hin Tjio, an Indonesian cytogeneticist working with Albert Levan in at University of Lund in Sweden, invented a new technique for puffing up cells so that the individual chromosomes could be more easily separated, identified and counted.  He made out only 2N=46 chromosomes and published his revolutionary finding in record time - it was published (in print, on paper, having been peer-reviewed) in a record breaking 35 days.  Everyone now agrees that 46 is the normal number for humans and almost all of us have that count.  But for 50 years before that everyone was wrong. I should, and do, cut our poor students some slack if they don't know what the correct number is either.

I should, for folk who are legitimately a bit weak-at-the-ould-genetics, explain this 2N= notation. All mammals [there are some Muntiacus muntjak exceptions] have so many pairs of chromosomes, one lot inherited from their mother and a matching set from their father.  The single "haploid" set is what travels briefly as sperm or egg before the full "diploid" set is formed at fertilisation.  Another way of describing our chromosome content is to count off 22 pairs of regular "autosomes" but give special place to the last two: XX for girls and XY for boys.  For convenience and to ensure we're all talking about the same thing, we number the chromosomes from 1 (longest) to 22 (shortest). The Y chromosome is tiny but the X is one of our biggest, so these sex-chromosomes don't fit the pattern and aren't included in the numbered list.  Actually <pedantry alert> chromosome 21 is shorter than 22 but the early cytogeneticists looked at the two teeny similar sized blobs down the microscope and made a mistake about which was bigger. The differences between our chromosomes and those of our nearest relatives the apes are numerous but include the fact that our chromosome 2 is represented by two half-pint chromosomes in the apes [see L and above: a single human chr.2 on the left with the equivalent pairs for chimp, gorilla and orang].  Thus part of the process of becoming human involved clagging together two chromosomes in a massive genetic engineering experiment that seems to have worked.
Most of us know a bit about chromosome 21 because it is responsible for The Down's aka Down Syndrome, DS or trisomy-21 if there is an extra copy of this the shortest chromosome. Over all, about 1 in every 1000 live births is Down Syndrome with the frequency increasing steeply [your last pregnancy before menopause is about 30x more likely to have a Down's outcome than when you were in your early 20s] among older parents especially older mothers.  With the increasing age of mothers in the Western world, you might think that the frequency of this syndrome would be increasing but in fact it was 2x as common 50-60 years ago.  The discrepancy is probably best explained by prenatal diagnosis and selective abortion. Not in Ireland of course, we don't allow that sort of sin here; we make people ship off to England to get sorted.  Down's is interesting also for the insight it gives into the location of genes that cause a variety of other diseases and syndromes. These include congenital heart defects (50% of all DS), while leukaemia is 30x more common in DS than in the general population and more or less 100% of DS develop Alzheimer symptoms over the age of 35.  About half of DS show a single fold/crease in the skin of the palm where the 'heart' line and the 'head' line fuse into a single crease.  This used to be called a simian crease because our great ape cousins are meant to have this arrangement.  But about 10% of the reg'lar human population also have a simian crease on one or both palms.  Presumably genes associated with Alzheimer's are located on chromosome 21 and having extra copies disrupts some delicate balance.

Other trisomies are found, but their prognosis is much worse than for Down's. Trisomy 18 aka Edward's syndrome occurs at a rate of 1:6000 live births and has an average survival time after birth of less that 2 weeks. 80% of Trisomy 13 or Patau syndrome die before their 1st birthday and are even rarer at birth: 1:10,000 to 1:20,000. When I was learning genetics in college 40 years ago, we had a whole course on this sort of thing; there was much less to cover in the subject in those innocent pre-genome days and the course was still four years long. You might ask, as I did in 1975, why these three anomalies in the count of chromosomes survive to term while others don't: why do we 'never' see children with trisomy 22, 20, 19, 17, 16, 15, 14 ?  It turns out that mere length of the chromosome is a rather crude measure of their functionality.  A better one might be counting the number genes - because some chromosomes are much more gene-dense than others. In terms of (gene count) rather than length, the shortest chromosomes are . . . Y (45); 21 (225); 18 (268); 13 (318).  When I was being paid to analyse the human genome just after if was delivered into the public domain we noted wildly different gene-densities in similarly sized chr19 (24 genes/Mb) and chr18 (4 genes/Mb), and didn't know quite what to do with that information. Now I appreciate one of the consequences of the anomaly and see how the human genome sequencing project shines a handy lamp on the crude tools we had back when I was a student of genetics.

Tuesday 25 November 2014

Journal club to beat you with

Lots of academic institutions have a periodical Journal Club, when people can get round a table and go through a scientific paper with a fine tooth comb to hone their critical faculties and inform themselves about some new progression in their field.  It is great mental exercise and, by flagging the defects in somebody else's work, we can resolve not to make similar mistakes in our own.  And, more positively, we can recognise really good, apparently unflawed, papers and strive to be as good.  I've run and participated in these things for the last ###ty years and almost always found it half-an-hour well spent. I'm in a minority on this; most other people put JC way down their list of priorities.  In my last job, the Principal Investigators and senior post-doctoral researchers would come if a) one of their students was presenting and b) they didn't need more urgently to write a grant proposal, redraft a paper, slog through the monthly accounts, prepare a lecture, go shopping or stare at the ceiling.

This term - bummer! - our journal club has been scheduled for the same time as my second Human Physiology lecture, so I've been unable to attend.  But this last week to accommodate a graduate student from the government institute on the other side of town, the JC was shifted to lunchtime on Friday and I could go. Oh joy!  My HoD had been asked by the regular organiser (who had to be elsewhere) to chair the session, so I wasn't the only salaryman there.  But we were collectively very thin on the ground: two lecturing staff, two presenters and . . . five other people: from a community of perhaps 30 post-grads; 30 lecturers; and 20 from the government institute!  Thge numbers suggest that 90% of our community believes they are too busy to turn up.  But honestly, if you're too busy to go to journal club or the local series of visiting speakers then you really need to take some time out to go to journal club or the local series of visiting speakers!  Why?
  • you might learn something new
  • you're taking your mind out for a run
  • you're showing respect for the presenters
    • and support: many graduate students find this really hard
  • you're respecting the organiser
  • you're participating in the community
  • you're doing something different
When I was a lad in the Genetics Department of TCD way back in the last century, the then Professor of Genetics hosted a monthly symposium on a midweek evening in the Winter.  A vaguely-genetics speaker would be invited: from the Guinness brewery or a chap who had just returned from collecting potatoes in South America or a silviculturist who was breeding trees. Three of the undergraduate students would be told off with a modest handful of cash to cook a meal for thirty that could be eaten off a lap-balanced plate. Everyone turned up to those meetings, and it wasn't because of my chili con carne. 15 years later, after working in Rotterdam, Boston and Newcastle upon Tyne, I was back in my alma mater.  Symposia were a thing of the past - altogether tooo Aristotelian; but there was a weekly seminar series scheduled towards the end of the working day at 5pm.  Afterwards everyone was invited round the corner to the boozer: speaker, faculty, students, post-docs, the cat. That was the symposium (from συμπίνειν - drinking together) and the craic was often mighty and not just because the alcohol lowered our standards.  But the academic staff who went out for a jar after work all grew up  and got married and were rushing home for diapers and telly rather than collegial discourse, so the weekly seminar series was shifted to the middle of the day. It made experiments more difficult to schedule but did ensure the working day finished shortly after 5pm.  This sort of compromise doesn't encourage young scientists to work all the hours god sends the way I did when I was starting out. harrrumph!

Monday 24 November 2014

3,200.040 years BC

Forty years ago this morning 24 Nov 1974, Don Johanson wrote in his diary that he was "feeling really lucky".  A few hours later, he found a few fragments of the fossil hominid that he was looking for. He was on an expedition with two French anthropologists, Maurice Taieb and Yves Coppens, looking for 'the missing link' - fossil evidence of transitional forms between modern humans and the great apes our nearest living relatives.  At the end of the day, sitting round the camp-fire with the Beatles "Lucy in the Sky with Diamonds" playing again (there was a limited repertoire available in the middle of an Ethiopian desert), someone suggested that the fossils fragments should be named Lucy - and by breakfast the next morning it was so.  Some people claim that, as Lennon was cranked up on LSD when he wrote the song, so drugs had been taken the night our renote ancestor was discovered.  Even after weeks of intensive work in widening circles round the original find, only 40% of the skeleton was recovered and only a couple of fragments of skull.  The picture L from Patrick Clarkin, shows what we know in pink with the rest 'reconstructed' and filled in. The first bits Johansen found were crucially bits of the knee, which showed that his fossil was knock-kneed rather than bow-legged like apes, which can and do walk upright but it's a hirple for them but normal for us and for Lucy.  The other piece of crucial information was the date, which we now agree to be about 3.2 million years ago.  That came from the analysis of the relative amounts of potassium and argon (it's the radio-active decay, stupid) in nearby volcanic rocks.  There is a key leap of faith required because volcanic rocks don't have fossils, and sedimentary rocks don't have the K/Ar clock. A bit of stitch and match is required.

Lucy (AL-288-1 officially) was only 110cm tall but probably a female (the pelvis has a couple of different possible re-constructions) and definitely an adult from the complete ossification of the epiphyses of the bones and the eruption of, and wear to, the third molars aka wisdom teeth.  The skull fragments show that she was small brained like other apes and the knees show that she walked upright, so it settled a debate about brain early or bipedal early. I like this very much because I buy into the idea that the hand drove the brain.  Freeing the hand from any constraint for locomotion means that it can start sewing, flint-knapping, spear-crafting and designing fish-hooks; not to mention make jewellery and other fripperies to impress the opposite sex. It needs an ever bigger brain to cope with these ever multiplying artifacts (bangles to Saturn V rocket, say): we are Homo faber, in the coinage of Hannah Arendt, of banality of evil fame.

As it happens, I met Johanson, about ten years after Lucy changed his life entirely, when he was the guest of my friend-and-mentor Lynn Margulis at BU when I was still in graduate school.  I had just completed a catalogue of hominid teeth, including Lucy's, with another of my friend-and-mentors called Ben Blumenberg.  On the back of cranking some hundreds of tooth metrics through a mainframe computer to generate comparative statistics we said something profound about the human condition - I can't remember what it was though.  Johanson was charming and I didn't bore him too much before fading into the background and leaving him to talk to a real evolutionist like Margulis.  I haven't been there, but I've talked to the T-shirt.

Sunday 23 November 2014

Even the goddamn rice

Bangladesh doesn't really have a bad press in The West (and I don't mean [West] Pakistan which used to exercise braggart rights over their Bengali co-religionists) it's rather that they have no press at all.  160 million people are effectively invisible to us here in Ireland. It's tough out there boxed in by India and exposed to the sea.  I've indicated how two of the great rivers from the Himalaya, Ganges and Brahmaputra, control the destiny of this densely populated country, not least by killing about 6000 citizens each year in floods.  While they wait for the end in the next big climate-change induced storm surge, the people must live and in order to live they must have food and water.  I've written recently about the terrible no-good-option deal they have with water&arsenic or water&dysenteric.  Turns out that the food is not much better for them.

Although it is the North of the subcontinent, Bangladesh is primarily a rice economy.  They get through 34m tons of it every year compared to only 4m tons of wheat.  It is possible to grow rice in a field and depend on the rain to satisfy its thirst for water, but yields are better for varieties that are grown in paddies.  The 30 October 2014 issue of Nature has an amazing supplement on rice which I've been reading with great interest. It turns out that rice is rather good at concentrating any arsenic that might be present in the water, and we've seen that there's a lot of that about in Bangladesh.  When rice is grown under water in paddies, the soil turns anaerobic and that tends to solubilise the arsenic so it can be more readily be taken up by the plant. Upland rice cultivation in 'dry' soil watered by rain can reduce the arsenic concentration by 30x, so clearly that is one option, but Bangladesh is rich in flat alluvial soils ideal for paddy rice and has limited hectares of suitable upland soils. Once inside, the arsenic tends to accumulate in some tissues more that others and one of those tissues is the seed-husk of brown rice. One way to reduce the intake of arsenic by humans is therefore to mill off the husk and eat white rice which has 10x less arsenic than brown rice, but the husk is full of niacin which in economies on the edge is a vitamin in chronic short supply.

Another solution hinges on the observation that some of the thousands of varieties and strains of rice accumulate much less arsenic than others.  Simple but extensive and comprehensive genetic experiments suggest that the arsenic-clearing trait might be a single gene.  They have no idea yet where the gene lies or how it works but the hunt is on.  Another nifty and elegant option is to encourage bacteria to create the gas tri-methyl-arsine from soil arsenic although that is unlikely to scale up any time soon as a way of detoxifying the soil.  Another microbial solution is to encourage the growth of bacteria that coat the rice roots with a layer of iron salts that inhibits the uptake of arsenic by the plants. That also has limited efficacy at the moment. Science has all these cards to shuffle in a deck of cause and effect that has dealt Bangladesh a poor hand; surely there is a workable solution.

Saturday 22 November 2014


Peter Greiß was a mid-19th century organic chemist from Germany who left for England to work with Hofmann at the (UK) Royal College of Chemistry.  He married an Engländerin, chamnged his name to Griess, refused a good offer to return to the fatherland with a position BASF and worked for the Allsopp's brewery until he died. He's buried in Burton-on-Trent, England's brewing Mecca. BASF BLOB BOOM.  His lifetime's work with nitrites, diazonium salts and other nitrogen rich organic compounds made it inevitable that he would contribute to our understanding of nitroglycerine and TNT trinitrotoluene. Those years were exciting for chemists and in the course of that century science went from knowing very little to knowing a lot about how chemicals interact and how we can tilt reaction processes to favour desirable outcomes.

The Griess test for the presence of nitrates and nitrites is named for him because he invented it in 1858. The previous paragraph and a previous Blob shows that nitro-containing compounds lean towards flammability, not to say explosiveness, because of the excess oxygens that are embedded in the molecule and so don't need to be found from the surrounding air when things blow up.  If you use caustic soda - NaOH - you can strip off the nitro parts of unexploded TNT or nitroglycerine (the active part of dynamite) and then carry out the following two reactions.  First add sulphonamide to make a diazonium salt with a rather reactive N=N side-chain.
If you then add N-alpha-naphthyl-ethylenediamine and it turns pink, then you must have had some nitro groups in the original sample . . . and those nitro groups must have come from an explosive material.
All this stuff about nitroglycerine and the Griess test is because sometime in the small hours of 22 November 1974, a government appointed forensic scientist was swabbing the hands and fingernails of six Irishmen who had just been arrested in the port of Heysham.  The police were certain-sure that they had nabbed the fleeing perpetrators of the Birmingham pub bombings which had ripped through some scores of people the night before and killed 21 of them. While the boffin was taking the swabs and analysing them to produce one plank of the evidence, the police were extracting confessions from the arrested men. One problem with the Griess test is one of false positives: nitroglycerine will give a pink colour but so will a raft of other common-or-garden substances including detergents used to wash the vials for carrying out the test and lots of stuff (shoe-polish, cleaners) you probably have under your kitchen sink. The analysis hinges critically on the strength of the NaOH used at the very beginning of the test: too weak and it cannot possibly strip off nitro groups; too strong and it will find them everywhere - there is no middle ground, and the Griess test is only useful as an preliminary indicator rather then evidence in itself.

At the trial the following year the judge summed up the evidence thus ". . . if Dr Black [the defense counsel] is right, the Griess test was not worth carrying out... Do you think that Dr Skuse [the govt forensic scientist] has been wasting most of his professional time? It is a matter entirely for you".  As is enshrined in the justice system in these islands, the judge will have made up his mind at this stage in the trial and can phrase his summing up in such a way as to tilt the opinion of the jurors so that - surprise! - they come to agree with the judge.  At the appeal years later the judges had this to say "if the trial judge had known what we know, he would have excluded Dr Skuse's evidence as valueless".  I'm not going to beat up on Dr Skuse here, having had a go at him five months ago, but before you make up your mind you could, with advantage read Beverley Schurr's long essay summarising and dissecting the whole sorry story.  Of course, it's not the whole story, but it's more comprehensive and balanced than the original convictions.

Friday 21 November 2014

Man behaving well

I wrote yesterday about two soldiers from yesteryear who managed to save their own skins and in the process allow the men under their command to be slaughtered.  I suggested that you and I should utter only a qualified tsk!  I was only aware of the Siege of Godesberg because of a restless rambling through the murky parts of the interweb. Today it's an antidote to yesterday's story that I came across at about the same time but on completely different threads and also involved an officer and his men.

I wrote in June about the extraordinary situation in which my father found himself at the beginning of WWII - in charge of a fast, dangerous and expensive piece of kit at the age of 22. More importantly he was responsible for the lives and welfare of 12 men under his command in their motor torpedo boat. At the same age, the extent of my other-person responsibilities was a half-share in an infant child.  As I look round the students at The Institute, I sometimes wonder how well any of them would fare if required to step up to the plate of either of those sorts of responsibility.  Across the water Jeremy John Durham Ashdown, Baron Ashdown of Norton-sub-Hamdon GCMG, KBE, PC was born in 1941 at about the time my father crashing his piece of government property into Dover Beach. Ashdown was born in India, but his soldier father retired to Donaghadee in N.Ireland after he was demobbed in 1945. Ashdown Jr, went to school in England and earned the nick-name "Paddy" because he couldn't shake his Nordie accent. In due course, like his father and mine, he joined the services and did 15 years as a Royal Marine Commando.  He acquired a knighthood, a life-peerage, and a couple of honorary degrees for his work in politics and diplomacy and he plans to mastermind the Liberal Democrats strategy in the next UK general election. But I don't want to write about him now, it is rather his father who is to be recognised. You may be sure that this man and his actions would never have come to general notice except for the success or celebrity of his son.

ANNyway, in 1940, Captain John Ashdown, Paddy's father, was serving in the Royal Indian Army Service Corps.  He was ordered to take his platoon of Indian soldiers and their mule-train to France to fetch and carry for the British Expeditionary Force.  They were, along with hundreds and thousands of servicemen in the BEF, entirely wrong-footed by the German advance into France.  In the chaos of the retreat to Dunkirk, Captain Ashdown was ordered to cut loose from his mules and their dusky minders and get himself and other British officers with all haste to the coast for embarkation to England. He could not find it in himself to obey such an order, so he abandonned the mules, formed his men into line and marched them with dispatch to Dunkirk where they all secured space on the last ship to leave the wharf before it was bombed to buggery.  Apparently he was court-martialled but in those desperate times he was cut some slack and the case was thrown out.  Even in the army, which functions only because men are relentlessly trained to obey orders until they will consciously put their lives in extreme peril, some men can't park their native sense of do what is right.

The Indians finished up in North Wales of all places, which caused a bit of a stir because they had never seen such exotica as turbans and chapattis in the valleys.  The Indians and the Welsh children got on pretty well because neither group could speak English every well.  That's a happy ending.

Thursday 20 November 2014

Men behaving badly

I originally called these column-inches Science Matters as a declaration of belief (because it does!) with a subtle acknowledgement of the other meaning of matter as 'stuff' which enabled me to rabbit on about whatever appeared uppermost in my 'mind' when I sat down to write my daily piece.  One thing that exercises me in a groundswell or background sort of way is trying to work out how to Do The Right Thing - how to live properly. Researching this dawn-of-man conundrum allows me to surf widely over the wireless airwaves (well at least as far as Newstalk-FM) and the blogosphere (front page of Wikipedia and a handful of blogonsolidaters like Metafilter and 3quarksdaily) . . . I haven't got all day to do this sort of stuff so some of the cuts are short.

Today's Featured Article on Wikipedia a couple of days ago was about the Siege of Godesburg: one of the opening events of the Cologne War in 1583. This was a ghastly prelude to the 1618-1648 Thirty Years' War which consumed Central Europe in a bloody mess of clashing antlers and murdered peasants as protestant and catholic magnates jostled for principle and principality.  In the middle of the previous century at the Peace of Augsburg (1555) the principle of cuius regio, eius religio [the locally established religion was to be that of the top gun - be that king, knight, bishop or castle] had been established. With the protestant reformation sweeping through the continent, particularly in the chillier Northern half, everyone recognised that it was easier to assign territory to one side or the other and so the catchy and memorable Latin tag was adopted as a rule of thumb in the hope of a peaceful way forward.  The ecclesiastical reservation was an exception to this rule: if the local ruler was a prince of the church, he was not entitled to change the religion of the local people on the whim of changing his own set of religious beliefs.

In 1582 Archbishop Gebhard Truchsess von Waldburg, the Prince-elector of Cologne (a catholic) fell in love with Canoness Agnes von Mansfeld-Eisleben (a protestant) and she with him.  Being more beautiful she managed to convert him to her faith, and her brothers insisted that they get married.  So far, so romantic; but Gebhard, rather than resigning his see in accordance with the reservation, attempted to turn his Cologne into a secular princedom with himself and Agnes in charge. The Chapter (lesser members of the ecclesiastical hierarchy) were having none of this and elected another archbishop Ernst of Bavaria . . . and so the Cologne War began.

Schloss Godesberg [seen R towering over the town of the same name on a recent sunny day] was a key fortress in the principality, on the road between Bonn the territorial capital and Cologne the economic powerhouse.  It was built on the top of a natural eminence and had over the centuries been fortified and garrisoned. Gebhard the Calvinist installed Oberstleutnant Felix Buchner with Eduard Sudermann, Captain of the Guard, as his second and a force of 180 "Dutch" [and hence Protestant] mercenaries to defend the strategic stronghold.  In November 1583, forces loyal to Ernst the Catholic laid siege to the castle. The religious differences added an extra bit of needle to the conflict. [your mother is a hamster etc.] The castle seemed to be more or less impregnable to normal cannonade and the besiegers eventually decided to dig a hole in the side of the mountain, fill it with 700kg of gunpowder and blow it up.  The explosion sheared off one face of the hill and carried away that side of the fortifications but the defenders retreated to the central keep and continued to defy the assault.  The Bavarian troops had been at this palaver for a solid and wintery month and were severely pissed off, especially as they had gained access to the castle after the explosion by worming up through the shit-hole. Buchner entered negotiations with his opposite number for free passage for himself, his wife and Sudermann his lieutenant.  These were concluded with difficulty and the losing officers, together with some catholic hostages, were escorted off-site by the winning officers through a mob of truculent and whiffy soldiery.  Everyone else, who were after all only Dutch mercenaries and their dependents were hunted down and slaughtered . . . it took the rest of the night to find and kill everyone.

Clearly from the high moral ground, looking back 400+ years from your sofa, Buchner and Sudermann were not behaving in the tradition of officers and gentlemen.  But before you get altogether too judgmental, ask what you would have done in the circumstances.

Wednesday 19 November 2014

Nate Silver Signal Noise

I don't know if it's The Blob, old age, a full teaching schedule or the misplacing of my glasses but I don't read books like I used to.  From about the age of 13, when I learned to read, I've been ploughing through 2 to 4 books a week.  This is nothing to Dau.I who knocks off a book-a-day and has done since she learned to read in the month after her sixth birthday.  But it's a habit that has been quite abruptly shaken loose over the last couple of years. During that time, I'd pick up a book and almost immediately fall into a slobbery doze; and when I woke a short while later I'd have to start that section again.  It was much easier to write 600 words than read them.

Nevertheless in 2014 I have struggled through The Signal and the Noise: The Art and Science of Prediction by Nate Silver.  It has taken me about 10 months which is a pathetic 2 pages a day.  Part of the problem is that the 450 pages of text are printed in a mean minuscule font that requires bright lights and extra levels of concentration to get into the run of it.  Despite this, I was never tempted to fire the book out of the window: I knew I was getting gold and it was worth sticking at the project. What Silver does is apply mathematics, experience and probability to a number of problems which hinge on telling the future.  How good are we at forecasting:
  • the weather (really rather good over the next 4 or 5 days)
  • determining when earthquakes will happen (really no better than guesswork)
  • who will win this Saturday's sport's fixture (fair if you work hard at having a good model)
  • rise and fall in the stock market (hopeless unless you are trading inside)
He has the best explanation of how the currently trendy Bayesian statistics work in the real world, so I'm grateful for that alone.  Bayesian stats require you to do something that is, on the narrow face of it, a bit unscientific: you are required to have a punt at what you think the outcome of a test or experiment will be, rather than like Darwin "I worked on true Baconian principles, and without any theory collected facts".  The results of the test are used to modify your 'priors' to come closer to the truth. It's mathematically very simple and quite powerful in its predictive power - IF you are good at guesstimating what the likelihoods of several related events are.  I think we can get much better at these estimates if we practice making them.

Typical of the book is an analysis of just how unexpected the tragedy of 9/11 was and the answer is: well actually could/should have been expected. In 2002 Donald Rumsfeld was pilloried for his WTF? oracular statement "there are known knowns; there are things we know we know. We also know there are known unknowns; that is to say we know there are some things we do not know. But there are also unknown unknowns -- the ones we don't know we don't know."  But the idea of unknown unknowns is key to making sense of a complex and potentially violent world.  It's the core, and indeed the title, of Nassim Taleb's 2007 book The Black Swan. A lot of people, who should have done better to protect US citizens, stoutly maintained that the 9/11 attacks were unknown-unknowns - so far beyond imaginings in scope that they couldn't (nobody could) have predicted such a Series of Unfortunate Events. Nate Silver shows in two graphs that this is a wretched excuse for dereliction of duty.  That's why the American tax-payer pays the big bucks to the TLAs (three-letter acronyms) NSA, CIA, FBI: so that they have some big ideas and deliver big solutions.  Here's the first one which indicates that, in 30 years, we have had one several-thousand-killer event in the catalogue of terrist attacks against NATO countries.  It's way out there on the bottom right:
Xeroxed straight out of S&N, so a little skew.  On the following page, Silver plots "# of attacks killing this many people" vs "# of fatalities" just as above except on a log scale for both axes. Extrapolating the now straightish line down and to the right, it shows that an attack taking out 2500 people, far from being unimaginable, was to be expected about once every 80 years. Or a lot more likely than a Richter 8.2 earthquake in California.

The most readable chapter tells how, in his 20s, Silver dropped out of a well paid job as an economic consultant for KPMG and made a modest fortune at poker. He got good at it because he worked really hard for several years getting to know when to fold and when to hold. This skill hinges in part on knowing the basic probabilities but the money lies in getting to predict what other players will do given a particular hand.  I've picked up on the language to this extent: when I'm in class getting the students to think about what the outcome of an experiment, I'll say something like "I lay €5 on the test-tube turning pink".  If I was unscrupulous and needed money, I'd actually slap folding money down on the bench-top, because my knowledge of biology (the priors) having been in the game for 4 decades is much more extensive than theirs who haven't yet served for four years.

I won't drop any more spoilers but urge you to lay hints among your loved ones to get you S&N for Christmas . . . and also suggest that a magnifying glass would be handy too. While waiting, you might check out Silver's blog FiveThirtyEight which is heavy on politics [538 is the number of seats in the US Electoral College] but has thoughtful essays on scientific and other issues.

Tuesday 18 November 2014

Bangladesh - a watery place

Bangladesh is the 11th most densely populated country in the world, but all those ahead of it in the list are micronations like Macau and Monaco where people are stacked like cord-wood - each person in either of those places is allotted less than 50 sq.m. each (our humble home has a foot print 60sq.m shared by two people . . . but we've got a garden and a landscape of fields).  Singapore and Hong Kong have some millions of people but are rather limited in extend as are less populous Gibraltar, Vatican City, Bahrain, Malta, Bermuda and Sint Maarten.  But Bangladesh is a big place AND it is home to teeming millions of people.  The only countries that come close to this level of extensive population density are Taiwan and S. Korea which have less than half as many people per  Other densities per Ukraine 75, Ireland 65; Kazakhstan 6; Nigeria 190.

Just after independence, in 1950, East Pakistan had a modest 40 million people aboard, that has since increased by a factor of 4x so that today there 160 million Bangladeshis.  Tomorrow there will be 160,009,000 and the day after 160,018,000 - the clock is ticking. Bangladesh is actually doing better at controlling its population than a lot of other third world countries: Venezuela, Kenya, Tanzania, Zimbabwe and Zambia all have higher rates of increase.  But the climate change prognosis is not good for the country because pretty huge wet prairies of the country are made up of the delta of the Brahmaputra and Ganges rivers.  90% of the people of Bangladesh live a few metres above the high water mark.  "Pakistan" - Muslim rump of India that didn't trust the Hindu minority to see them square in an independent India - was created in 1947 from the two chunks of the Raj where the followers of The Prophet lived.  East Pakistan grew increasingly unhappy about paying taxes to Islamabad and not getting a fair share of the money back - a bit like Ireland before independence. Things came to a head in the aftermath of a devastating storm surge driven by a cyclone on 12th November 1970.  The low lying areas of the delta were washed away and half a million people drowned.  Islamabad was seen to be slow in responding to this natural disaster but quick to send in the military when the local people objected. The soldiers from the West killed somewhere between 30,000 and 3 million Bengalis in a turmoil of ethnic cleansing. There was a disconcerting amount of intellectual cleansing as well with academics, doctors, writers and other intellectuals being driven to the killing fields. With help from the Indian Army, the Bengalis eventually won their war of independence but it took a year of bloody mayhem. A sad and inauspicious birth for the nation.

As the population exploded during the 60s and 70s, access to clean water was increasingly compromised.  The rate of childhood dysentery and diarrhoea was getting to unacceptably high levels, even for the Third World. UNICEF recommended sinking boreholes to tap the ground water rather than the coliform-rich soup that passed for drinking water on the surface, and somehow funding was found to make this happen across width swathes of the country. The rate of dehydrating-to-death among children fell in a gratifyingly direct manner.  Unfortunately the rate of acute and chronic arsenic poisoning increased in a similarly direct way. In 2000, a WHO report, finding that between 35 and 75 million people (about half the then population of Bangladesh) were affected, named this "largest mass poisoning of a population in history". The sub-surface geology of Bangladesh is notably rich in this element which is quite soluble in water.  The proposed solution was to sink even deeper bore-holes to tap older sub-sub-surface bedrock that is depleted in arsenic and other heavy metals. But, in large measure, the well of money had run dry.  Death by arsenic is slower than death by enteric so, in the grossly unfair scale of things by which life in the Third World is weighed, the Bengalis are better off.

The plain people of Ireland are currently in a state of self-righteous indignation claiming that clean drinking water is an Inalienable Right that shall be delivered to their kitchen tap for free.  After their first-born dies of cholera or dysentery or falls into the final coma of acute arsenic poisoning, they might re-evaluate how much they are be prepared to pay for what falls from the sky but is rather difficult to pick up.

Monday 17 November 2014

one step at a time

A month ago we killed had killed some of our ram-lambs for the chops that they bear and now have our freezer brimful of meat. Yesterday being sunny, I dropped a bagful [1 whole lamb, in butchered chunks, less the head and skin but including kidneys, liver and lights] down to one of our friends / customers, and paused for a cup of tea.  We fell to talking about students, ex and current and wished that some of them were less caught up in their future/career because it can get in the way of getting there. Look at me; I've been 40 years in science and still don't know what I want to do when I grow up. It's been easier for me than for some other people because I realised a long time ago that a lot of the goals we set ourselves have rewards [a fast car, foreign holidays, promotion, a bigger house than the Murphys'] that mean nothing when you achieve them. You don't need a million dollars to do nothing.  One of the problems is that the traditional career-path [BSc 3-4 years; PhD 3-4 years; Post-doc researcher 3-4 years; Principal Investigator with own lab 30-40 years] has all gone to hell in a bucket not least because in a steady state over those 30 years a PI might supervise 30 graduate students and only one can inherit the mantle. The excess PhDs have to seek other ways of making their PhD training work for them and their employers.  It takes them a while to realise that these other opportunities are not a step down but finding a better fit for their own skin.

One of the events that I caught during Science Week at The Institute was a panel show in which our students who were also sports stars were interviewed about the pattern and process of getting to the top of their profession. These students, who play for their county and in some cases for their country, somehow fit in a gruelling training schedule in the evenings and every weekend as well keeping their lab-books up to date, writing assignments and swotting for quizzes and exams.  Now I am religiously unsporty but I respect anyone who will work at their craft.  One of the panel was a slight young woman who is the European champion at one of those martial arts which is hard for me to distinguish from assault and battery.  The interviewer, acknowledging that in class she was almost painfully shy, asked how she could switch from mousy quiet to being out there and literally in the face of someone else. Ms Handstrike said that, when she steps into the ring, she becomes a different person.  It's not even a conscious transition any more after so many years of training and being. I could relate to that because it's very similar to what some actors and especially comedians say: it's like shrugging yourself into a overcoat of shape-shift as the curtain rises. Lecturing is just like acting except there is more scope for ad-libbed lines and I try so that we all get a laugh out of it occasionally.

After a small pause and before she handed the microphone on to the next chap MsH. said "It's okay to lose . . . you can learn something if you lose . . . if you care less about winning the wins are more likely to come".  (!) I was enchanted that this not particularly articulate, rather shy, young woman could offer something so profound and self-revealing to a room full of her peers. If you just stand up intending to do the best you can - or perhaps a little bit more - then you aren't intimidated by the size or reputation of your opponent.

That's the advice we should give to our students: one step at a time but make every step count in and of itself.  Don't do grim or boring things in order to achieve some more distant goal. Do the best you can, and try to do it better each time. Give it socks to your current position and the next position will open to you.  You may find, like me, that you've skipped from short-term contract to shorter-term contract for 35 years and had a [mostly] great time putting one foot in front of the other. Or as Thoreau put it  “I went to the woods because I wished to live deliberately, to front only the essential facts of life, and see if I could not learn what it had to teach, and not, when I came to die, discover that I had not lived." If that's a bit woolly, try Aldous Huxley  "It is a bit embarrassing to have been concerned with the human problem all one's life and find at the end that one has no more to offer by way of advice than "try to be a little kinder."

Sunday 16 November 2014

Wife-beaters and axe-murderers

My pal P in Boston alerted me to a new study out of Finland which investigated the genetic basis of violent crime. Genetic association studies in humans need to be approached with your crap-detector switched to maximum red alert.  Every few years some 'science' journalist will report that some boffins have discovered the gene 'for' homosexuality which has the dimmer members of the reactionary public sharpening their pitch-forks and looking for a tinder-box for their torches.  As the commentary in the Economist [always good for sensible analysis] says, this all sets off a whoop whoop genetic determinism alert.  This is the touchy concept that you can be damned by your genetic heritage and is triggered when anyone suggests that people who have a Y chromosome or have a really good tan are different from those who lack these attributes.  Even when there is no suggestion that possessors or lackers are better or worse than the other lot, it still gets liberal people exercised. Men can't multitask, women can't read maps are not too edgy, but don't even mention intelligence or athletic ability or crime statistics.

The group led by Jan Tiihonen work out of the Karolinska Institutet in Sweden but their data came from prisoners in Finland. They identified variants in two genes MAOA & CDH13 which were far more common in perps who were in chokey for violent crimes. These genes were at normal frequency in ordinary shop-lifting, car-thieving, handbag-snatching criminals. MAOA codes for a protein Monamine Oxidase A whose task is to breakdown some classes of neurotransmitters after they have delivered their load. If the MAOAs are less efficient because of the mutation then the neurotransmitter will hang around for another round of transmission and particular neurons will continue to fire off. This is not the first time MAOA has been identified in this context.  Another previously named gene is HTR2B which codes for the receptor that recognises the neurotransmitter serotonin, and then implements a firing cycle.  You can imagine that another way in which neurons can continue to fire is because of changes in sensitivity receptor-side rather than excess on the supply-side.

But while the Karolinska team found no statistical signal for HTR2B in their cohort of violent Finns, they identified another player in the game CDH13 which is a cadherin, a class of proteins which stick out of cells and promote adhesion between them.  The Economist claims that CDH13 is involved in axon development but wikipedia makes no mention of this.  Tiihonen identified the variant CDH13 by doing a genome-wide association study - searching through all the genes looking for those that were positively associated with their cohort of beserkers.  There are ethical, philosophical, statistical and mathematical problems with such studies but that hasn't stopped me from using the technique myself.  The main problem is one of multiple testing: with 23,000 protein coding genes, all of which can have some sort of variability between normal you and your fighting mad cousin Lenny, you're bound to find one or two which are associated with whatever you're interested in.  Association does not necessarily identify a cause.

But the more serious civil libertarian issue is the false positives. Before you advocate testing for MAOA status at birth and tattooing the result on each forehead reflect on this. For every low-activity MAOA-possessing axe-murderer in jail, in Finland or in your own country, there are thousands of folks out there on the street who also have a low-activity MAOA but have no intention of beating anyone up. An earlier study in New Zealand, went the extra mile and did a painstaking psychological history for each case as well as the high-tech lab work.  They found that the Kiwi violent offenders, not only carried the MAOA variant but also had experienced an abusive upbringing. As ever, it's in the interaction terms: genes may be important but they don't act in a vacuum - the environment also plays its part.  It's more difficult to think about complex grey-scale situations than to call things black (you) and white (me, of course).

Saturday 15 November 2014

Holcomb Syndrome

Bill Bryson must have sold a million copies of his various books, but his best, funniest and most insightful is his first The Lost Continent in which he goes on a gigantic figure of eight road trip across the Continental US from Des Moines, Iowa where he grew up and back again via both coasts and a chunk of territory in between.  One of the most telling anecdotes is when he steams into Holcomb, Kansas for a bit of gristly rubber-necking.  Holcomb was where a whole family of stalwart citizens were murdered In Cold Blood by two deluded hoods looking for a non-existent stash of folding money which they couldn't be bothered to earn.  It was written up with patchy attention to the truth by Truman Capote with help from his pal Harper "Mockingbird" Lee.  Capote's book was a sensation at the time and sold thousands of copies. Yet when Bryson rocked up thirty years later and asks some of the local youths about The Event of their small town, none of them seem a) interested or b) to know anything substantive about it.  Later, Bryson compared notes with the high-school track coach, a man about his own age and they agree that a) in their day, they were more fully engaged b) the generation down didn't/couldn't read books and just didn't give a monkey's about their cultural-historical-geographical milieu.  "We agreed that this was, you know, weird".  I mention this, because today is the 55th anniversary of that nihilistic atrocity.

Eeeee, when I were a student, I was up for anything that was on offer that seemed to be interesting or challenging or a bit different.  I'm not saying I was a great student: a lot of the standard curriculum was uninspiring and occasionally tedious but the extras could be very good indeed.  When we were junior ticks in 1st or 2nd year, my pal Cliona and I signed up for a series of evening seminars on the philosophy of science  and learned a heckuva a lot about our craft even though we were lowly apprentices - not even yet foot-soldiers. Over the subsequent 40 years in science, I've made it a firm rule to go to any optional talks and seminars if at all possible, because you never know when you'll be surprised.

As I mentioned earlier today, we are up to 75mph at The Institute this last week running a slew of extra Science Week events for our own students and the local school children.  My Head of Department was up to 110, making things happen, including a whole morning of interviews at the Institute as outside broadcasts from the local radio station, a bang-and-stinks show for primary school children and a dozen other events.  Me, I was up to 90, making happen a showing of Ross Whitaker's film Unbreakable on the Monday as well as inviting Ireland's most cited scientist on Friday.  But the rest of our community seemed to take it all with a good dollop of 'meh', hence my calculation that on average 'we' were only up to 75. I thought that the interest in the film, at least, would be mega and arranged for it to be shown in a room with 250 seats. When I rushed over from another class with the DVD, I found the room occupied by three (3) students.  Eventually 30 people dibbled in and settled down to watch the film; 20% of whom were teaching staff.  That's out of a population of nearly 5000. That's a bit disappointing, I find. It was the same at the end of the week. I had booked a room and a time when our third (N=38) and fourth (N=32) year biologists had a scheduled class and arranged for the lecturers to bring both classes to the one room to hear The Great Man speak. I needn't have worried about the room having sufficient capacity, because it was much less than half full and only a dozen or so of the target audience thought such an event was more important than getting an earlier bus home, or writing up their lab books, or finding a quiet place to eat a Mars bar.
Afterwards, we agreed that this was, you know, weird

Cites seeing

I've had a bumbly sort of career in science (so far! it's not over till the fat Blobby sings).  Not stellar but not without faults.  From my perspective, the major problem has been 'finish', I've had a few (3) good ideas, I've worked really hard to develop projects but I've often-and-often fallen at the last hurdle: having solved the problem to my own satisfaction, I go off the boil and move on to the Next Big Thing rather than sitting down, writing it all up and getting it published.  I wrote a while back about how the landscape of publication is skewed by the process of science - there are far too many papers adding warts to the portrait of some Important Idea while other equally important ideas are barely sketched out.

But there's no point in carrying out some research, however diligently, if nobody reads or cares about the result. That's a waste of some graduate student's time and intellectual energy and a waste of tax-payers' money.  [Except insofar as the student gotten some training in benchwork, statistics, critical thinking, interpersonal relationships, or ExCel].  How do we know which of the papers are wasting space?  We ask whether some other scientist has referenced the work in a paper of their own.  Such an acknowledgement is called a citation and 50 years ago last month Eugene Garfield started to collect, index and distribute these citations.  Nature, Europe's scientific journal of reference, has just reviewed progress in the field. And produced its own mountain of data.  According to their records, 57 million scientific papers have been published since the beginning of time, millions since WWII, rather fewer at the beginning when Cuvier, Darwin, Kepler and Newton started working on the foundations. 45% of those papers (25.3 million) have sunk without trace, nobody else having found a single thing of value in the effort - heck, not even the authors of the paper in their own subsequent work.  The only positive thing about this sorry state of affairs is that 'papers' are increasingly published only on-line, so only electrons are being wasted rather than trees.  You can look up your scientific cousin (use lastname initials) to see how big a cheese she is.  My own contribution has been bumbly enough with some reasonably referenced material: my 'top' paper, on the nematode worm Caenorhabditis elegans, having garnered 253 citations.The rest of my opus dribbles off with 198, 197, 184, 136, 115, 109, 103, 97, 92 . . . 32, 29, 23, 19, 10, 10, 7, 7, 5, 5 and then disappears into the grass.  If you tally it all up, my citation count is about 2300: mid-range, not entirely worthless, not very exciting.

This last week at The Institute, we've been going great guns for Science Week. As part of this jamboree I invited a far more successful scientist down from Dublin to talk to our students.  Des Higgins, who has had a walk-on part on The Blob before, was asked to talk about The Joy of Molecular Evolution. The title implied that what we both do is as exciting as ...Sex ...Cooking ...the Lord is My Strength or ...Painting which is the order Google offers for completion of The Joy of...  I asked Des a couple of months ago and in the interim Nature published its analysis of exciteing papers (geddit?). This revealed that Professor Higgins is by far and away Ireland's most cited scientist! This is almost all on the back of the discovery and development of a handy and effective method of aligning biological sequences.  Since he had the kaCHING! idea in 1987, he has written a program for carrying out this key infrastructural task and over the last 20+ years developed it to crest the tsunami of sequence data that has flooded our world. Each development required an additional paper to explain how it worked and how the new material was implemented.  The most useful of these ClustalW was published 20 years ago next week on 22 Nov 1994. In the intervening two decades it has gathered an astonishing 48000 citations - on its own dwarfing by 20x my lifetime's work and making it the 10th most cited paper of all time. Reports on other stages in the development - Clustal1-4, ClustalV, ClustalX, ClustalΩ - have boosted this total to something more that 115,000 cites for this one Big Idea.

Hats off, it's a huge achievement indicating a HUGE contribution to the field . . . and also an indication of how huge the field of bioinformatics and molecular evolution has become. But, as Des pointed out in his talk, citations accrue more to successful techniques than to paradigm shifting ideas. Crick and Watson's description of the structure of DNA, which started this whole gallop of in 1953, has only been cited a tad over 10,000 times. Nirenberg and Matthaei [Blob-trib], who started working out how the genetic code worked in 1961 have been acknowledged only 1700 times.  Now, if only more people would read The Blob, I wouldn't feel I was wasting my time . . . not to mention all the electrons.

Friday 14 November 2014

Our Maude

At last, a year after being tribbed in The Blob, County Kerry's most famous naturalist, Maude Delap, has been given her own Wiki-page. She features in today's New Content section. You first heard it here.  Bonnets off!

Crumbs! Berlin exclaves

I wrote a short piece about the end of the Iron Curtain and the Berlin Wall on 9th November to recognize the 25th anniversary of the opening of the border between East and West Berlin.  As might be expected, in researching the back-story I fell down an interweb rabbit-hole and finished up in . . . Steinstücken a few streets of territory that was part of West Berlin but isolated from the rest of Stadtgemeinde Zehlenberg, its borough/municipality, by a 1 km wide section of woods that was part of the DDR. 200 people lived in this island of Capitalism and it was hard enough for them as they had to go through a tedious rigmarole at two border-crossings [W-E then E-W] to go shopping or to visit friends and relations.  It was not the largest of a dozen similar exclaves that surrounded the beleaguered state of West Berlin but it was the only one which housed permanent residents.  All these patches of land were the result of following legal niceties; blowing the dust off deeds to document land-tenure over the previous 700 years.  After WWII, Germany and Austria were carved up into zones of occupation by the victors: France, UK, USA and USSR all awarded themselves chunks of the conquered territory and Berlin, as the capital of the Third Reich, was separately partitioned.  It was more or less the same as we saw in Baarle, but with the added frisson of the Cold War: if you were seen to back-down you lost face. It was manlier to stick to your guns.

On 18 October 1951, a police squadron from DDR were ordered to occupy Steinstücken but backed down and backed out after four days of objections from the 200ish local residents who paid their taxes elsewhere. The US forces, which were still nominally in charge of that part of West Berlin, added their diplomatic weight to the protest.  The great powers were rather less active in their condemnation of India's annexation / liberation / decolonialisation of Goa in December 1961.  This despite the fact that 1.4 million Goans were not asked for their opinion and 30 of them were killed in the invasion. When the Cold War cranked up a notch with the building of the wall and the Berlin Airlift, 3 (three) US servicemen were stationed in Steinstücken to defend it in the event of another attempted invasion. Posturing on the other side meant that they were not allowed to drive or walk to their battle-station but had to be brought in and out and serviced by helicopter. That went on for ten years! Ten minutes a day of helicopter fun at $100 a pop at today's prices over ten years is $365,000 of tax-money. But that's mohnkuchen compared to the costs of keeping the troika of soldiers in place which was well north of $3.65 million in today's money.

In 1971, the situation of the Berlin exclaves was regularised, by agreement and a lot of hard cash. For DM4 million [about €2million] West Berlin bought a corridor of land to connect Steinstücken with its own town-hall.  The Berlin Wall was extended on either side leaving a strip 1000m x 20m totalling 2.3 ha.  That's €90 per sq.m! Two of the other exclaves continued in a limbo of legal correctness but personal faff until 1988. Fichtewiese (3.5 ha) and Erlengrund (0.5 ha) were almost adjacent and used by allotment clubs whose members had to be accompanied by a member of the border patrol every time they wanted to thin out their turnips or stake up their peas. In 1988, they were connected to the mainland when the DDR ceded just enough territory to round out the border. The other bits were uninhabited fields or wasteland: Falkenhagener Wiese 45ha; Wüste Mark 22ha; Laszinswiesen 13ha; Große Kuhlake 8ha; Nuthewiesen 3.5ha; Finkenkrug 3.5ha; Böttcherberg 0.3 ha were all ceded to the DDR either in 1971 or in the go-round-again in 1988.  Quite apart from the fact that these territories were part of either Spandau or Zehlenberg municipality and then ceded to Schönwalde, Falkensee or Potsdam, they were owned by people some of whom needed access to farm them.  Their inconvenience tends to be overlooked. Aw shucks, it only lasted from 1961 to 1989: what's thirty years between enemies? It's a generation is what it is.