Tay-Sachs is a terrible degenerative disease that starts to affect children just as they start to crawl and finishes them off before they are ready for primary school. I mention it in passing early on in my course about Human Physiology because it is to do with a dysfunction in lyzosomes which are little blobs (membrane-bound vesicles, indeed) inside most of the cells of your body which act as waste-processing factories. One of these clean-up processes requires an enzyme called hexosaminidase A which breaks down fatty molecules called gangliosides. In the developing brain there is an enormous amount of metabolic activity: neurons are made, novel connections are set up and there is a huge amount of turn over of the bit-and-bobs that make up the cells. If you can't break down the gangliosides they accumulate and eventually destroy the function of the neurons in which they build up.. You can't break down the gangliosides if you have inherited two defective copies of the gene for Hexosaminidase A: one from each of your parents. If you have one blitzed copy and one functional copy of the gene then you're fine and there are a lot of these "carriers" out there.
Of course it depends what you mean by "a lot"; there are about 1 million carriers in the USA out of a total population of 300 million, so if you pick you partner at random and you are yourself a carrier there is a 1:300 chance that any of your children will be affected. The odds are still stacked in your favour because 3 out of 4 of your offspring will not develop the dread disease. You could, of course, be unlucky and have four affected children in a row. If you don't know what your Tay-Sachs status is, the odds are better still = 1/300 * 1/300 * 1/4 = 1:360,000 lives births in the USA develop this infantile Tay-Sachs.
But some groups in the great melting pot are much more likely to have children with Tay-Sachs because the frequency of carriers is much higher: by accident; by cultural endogamy [a tendency to fall for the girl next door]; or good old inbreeding. Incest, they say, is the game the whole family can play. Notably, the Ashkenazim have higher frequencies of Tay-Sachs carriers [1/30], as do some groups of Québécois and their cousins the Cajuns of Louisiana and even Irish-Americans. Here the odds of having a T-S child = 1/30 * 1/30 * 1/4 = 1:3,600 or a hundred times more likely than in the general population. Despite the manifest increase in social capital from such schemes as The Jack and Jill Foundation, it is a hard road to care for a deeply handicapped child and most people would prefer to avoid that cross.
The Ashkenazim have developed a clever system for minimising the chances of their community bringing Tay-Sachs children into this world. Dor Yeshorim (דור ישרים) - "upright generation" aka Committee for Prevention of Jewish Genetic Diseases was set up a generation ago in the 1980s by a rabbi in NYC. One of the neat things about the scheme is that it is anonymous and so can't be used to hike up your health insurance premiums or deny employment. On a regular basis, Dor Yeshorim goes to Jewish schools and takes DNA samples in exchange for a docket containing a PIN code. The DNA is processed to identify carriers, not only of Tay-Sachs, but also Cystic Fibrosis and maybe a dozen other potentialy damaging genetic traits but these data stay on the computer until a Jewish boy and a Jewish girl think they might take the plunge together. In some of those communities, they practice a system of arranged marriages called Shidduch (שִׁדּוּךְ) in which the families get together and decide that Moshe and Rebecca might be a good match. Over a few meetings the eager elders gradually fade discretely into the back-ground and the boy and girl get to talk to each other and start to imagine what living together might entail. At some stage (earlier the better), they submit their PIN numbers to Dor Yeshorim and the computer says Yes or less likely No. This cunning plan has been remarkably effective in reducing the incidence of the disease in that community but has had no effect whatsoever on the prevalence of carriers in the population.
Tuesday 31 March 2015
Monday 30 March 2015
Near naked tottie
On Saturday 10 days ago, I caught the final 15 minutes of the Ireland vs Wales Rugby International. My father-t-law Pat was conflicted because he is Cardiff-Irish but it was, for him, a win-win situation either way. Wales beat [23-16] but did not trounce the Irish. It seems fairly straight forward: each country fields a team of fit, strong, agile, skillful young(ish) men to do symbolic battle on our behalf. It's good, in my book, because it celebrates diversity: it is hard to find "Citius - Altius - Fortius" all three in one man, so the teams are complementary and mutually supportive. And despite the concerns of neurologists about contact sport encephalopathy CSE, it's surely better to have Our Boys heaving against each other in a scrum than heaving spears and rocks at each other until somebody loses an eye. There is a Machiavellian argument to be made against wall-to-wall broadcasting of professional sports every week-end afternoon - surely it would be better to get the citizenry off the sofa at home and shedding some pounds on a local sports field.
There are other sports where the lines are a lot more blurry. Less about Citius/Altius/Fortius and more about Sexius/Scantius/Exploitius. In another of my tirades against boxing, I mentioned Alexei Sayle's throwaway critique of rhythmic gymnastics, suggesting that it was more like pole-dancing [Saddius] than pole-vaulting [Altius]. So you don't have to, I've trawled through youtube to find a short example of a Ukrainian young-wan Viktoriia Mazur cavorting with a ball. She can do amazing things with a whip too. But if it was only about her dexterity and fitness she'd be doing her perf in track-suit, wouldn't she?
But what's floating my boat today is a related issue in the world of professional music. I like a bit of classical music and where better to find it than on youtube. If it was just about the music we'd either have a) sound only youtube files or b) concentrate on the hands of, say, Yuja Wang as they go blurry from one end of the keyboard to the other [L]. When the top male pianists perform in public they are still dressed up like 19thC waiters in black and white; but when top female pianists appear on stage they are undressed in something gorgeous and off the shoulder - so that they can get the necessary freedom of movement (hmmmmmm?) - not as stripped down for action as Ms Mazur but nevertheless it's not just about the music here, is it? To give you a head-start in getting to see fit young-wans pounding the keyboard, I've done some research:
All different, gorgeous all . . . and the music is good too. A celebration of diversity if ever there was one. I did look for youtubes of overweight female pianists, with acne and glasses, but they don't seem to win any competitions. I'm not sure how to test this hypothesis but I don't think that symmetry assorts genetically with musical ability. Do you think that the judges of musical competitions are disproportionately heavy with older men?
There are other sports where the lines are a lot more blurry. Less about Citius/Altius/Fortius and more about Sexius/Scantius/Exploitius. In another of my tirades against boxing, I mentioned Alexei Sayle's throwaway critique of rhythmic gymnastics, suggesting that it was more like pole-dancing [Saddius] than pole-vaulting [Altius]. So you don't have to, I've trawled through youtube to find a short example of a Ukrainian young-wan Viktoriia Mazur cavorting with a ball. She can do amazing things with a whip too. But if it was only about her dexterity and fitness she'd be doing her perf in track-suit, wouldn't she?
But what's floating my boat today is a related issue in the world of professional music. I like a bit of classical music and where better to find it than on youtube. If it was just about the music we'd either have a) sound only youtube files or b) concentrate on the hands of, say, Yuja Wang as they go blurry from one end of the keyboard to the other [L]. When the top male pianists perform in public they are still dressed up like 19thC waiters in black and white; but when top female pianists appear on stage they are undressed in something gorgeous and off the shoulder - so that they can get the necessary freedom of movement (hmmmmmm?) - not as stripped down for action as Ms Mazur but nevertheless it's not just about the music here, is it? To give you a head-start in getting to see fit young-wans pounding the keyboard, I've done some research:
All different, gorgeous all . . . and the music is good too. A celebration of diversity if ever there was one. I did look for youtubes of overweight female pianists, with acne and glasses, but they don't seem to win any competitions. I'm not sure how to test this hypothesis but I don't think that symmetry assorts genetically with musical ability. Do you think that the judges of musical competitions are disproportionately heavy with older men?
Sunday 29 March 2015
Variation and lots of it
It's m'mother's birthday today! 95! Born in 1920 - not before the First War but as a consequence of it. Her contribution to science has been immeasurable: just think that without her, there would be no Blob! Turns out she shares a birthday with a much younger chap called Dick Lewontin (b. 29 Mar 1929) whose impact on my field, evolutionary biology, has been far greater than mine. I'll give you one example today, it would tax your patience if I was to summarise all his contributions which include The Genetic Basis of Evolutionary Change which in its day (publ. 1974) was the definitive textbook. In 1953, Crick and Watson worked out the structure of DNA, which could be recognised as the birth of molecular biology. In 1966, however, two papers burst of the scene that made us question everything that we knew about the way evolution worked. Lewontin and Jack Hubby published their findings on variation in the fruit-fly Drosophila pseudoobscura and Harry Harris published another paper showing very similar levels of variability in Homo sapiens.
What Lewontin and Hubby did was isolate proteins from a number of different flies, treat them in a scientific protocol of their own divising, load each sample into a little hole at the top of a slab of gel and apply a strong electric current [don't try this at home. kids] to sort them by their electric charge. Some amino acids have positive charge, some negative and most are neutral. What they saw was really surprising: about a third of the proteins they investigated showed a pattern similar to that illustrated [L ripped from their original paper]. Each column represents an individual fly, some of which have 'fast' proteins, some 'slow' and some, called heterozygotes, have both varieties. What does it matter?
It matters because the evolutionary gospel at the time was that Nature had been honed to a high level of perfection by millions of years of evolution. Yes yes, of course there were exceptions, but almost all the exceptions were identified as "inborn errors of metabolism" such as phenylketonuria PKU, a disease which is tested for with the heel-prick test in all Western newborns. We could accomodate such disease states in our worldview because, although they had effects that were bad for the propagation of the species, they were rare. If 1:1200 babies are born with CF, and 1:10,000 have PKU, we are losing an insignificant fraction of the next generation. But if a large proportion of the genes are 'deleterious' [bad!], the algebra suggests that we'd need to produce offspring like cod - which drop a million eggs at a sitting - to have a reasonable chance of having any humans (or fruitflies) in the next generation. Suppose that 1:1000 children carry gene-variant X which means that they don't survive to have children of their own; that means that 0.999 of the population do survive to breed. If the 'genetic load' in the population is two such duff genes, then only 0.999^2 of each generation = 0.998 survive. But it is an exponential equation: 0.999^10 = 0.99; 0.999^100 = 0.90 (losing 1 in ten of all children born - before the ravages of infection, train-crashes and tsunamis have an impact); 0.999^1000 and 2/3 of the children don't make it. Harris's data suggested that about 7,000 of our 23,000 genes are variable.
SO, the holy writ of then current evolutionary theory must be wrong! Lewontin & Hubby and Harris forced us to re-appreciate our view of genetic variabilty. There was a bitter rear-guard action by the 'selectionists' who held to the old view but by the end of the 1970s the 'neutralists' had won the war. I was for years a naive pan-selectionist because my mind is so inert it takes a tock on the head with a bloody big hammer to change it. But now I have joined everyone on the good ship neutralism and it shakes down well with my wider world-view. There is a lot of variation out there; we are all different and we should celebrate it rather than labelling 'different' as 'worse'.
What Lewontin and Hubby did was isolate proteins from a number of different flies, treat them in a scientific protocol of their own divising, load each sample into a little hole at the top of a slab of gel and apply a strong electric current [don't try this at home. kids] to sort them by their electric charge. Some amino acids have positive charge, some negative and most are neutral. What they saw was really surprising: about a third of the proteins they investigated showed a pattern similar to that illustrated [L ripped from their original paper]. Each column represents an individual fly, some of which have 'fast' proteins, some 'slow' and some, called heterozygotes, have both varieties. What does it matter?
It matters because the evolutionary gospel at the time was that Nature had been honed to a high level of perfection by millions of years of evolution. Yes yes, of course there were exceptions, but almost all the exceptions were identified as "inborn errors of metabolism" such as phenylketonuria PKU, a disease which is tested for with the heel-prick test in all Western newborns. We could accomodate such disease states in our worldview because, although they had effects that were bad for the propagation of the species, they were rare. If 1:1200 babies are born with CF, and 1:10,000 have PKU, we are losing an insignificant fraction of the next generation. But if a large proportion of the genes are 'deleterious' [bad!], the algebra suggests that we'd need to produce offspring like cod - which drop a million eggs at a sitting - to have a reasonable chance of having any humans (or fruitflies) in the next generation. Suppose that 1:1000 children carry gene-variant X which means that they don't survive to have children of their own; that means that 0.999 of the population do survive to breed. If the 'genetic load' in the population is two such duff genes, then only 0.999^2 of each generation = 0.998 survive. But it is an exponential equation: 0.999^10 = 0.99; 0.999^100 = 0.90 (losing 1 in ten of all children born - before the ravages of infection, train-crashes and tsunamis have an impact); 0.999^1000 and 2/3 of the children don't make it. Harris's data suggested that about 7,000 of our 23,000 genes are variable.
SO, the holy writ of then current evolutionary theory must be wrong! Lewontin & Hubby and Harris forced us to re-appreciate our view of genetic variabilty. There was a bitter rear-guard action by the 'selectionists' who held to the old view but by the end of the 1970s the 'neutralists' had won the war. I was for years a naive pan-selectionist because my mind is so inert it takes a tock on the head with a bloody big hammer to change it. But now I have joined everyone on the good ship neutralism and it shakes down well with my wider world-view. There is a lot of variation out there; we are all different and we should celebrate it rather than labelling 'different' as 'worse'.
Saturday 28 March 2015
On the bread watch
Something tastey for the weekend, Sir? At the end of January, I did a piece on gastromovies: youtube and vimeo clips about the making of food. I liked them a lot and didn't get any negative feedback, rétroaction négative, or even негативний зворотний зв'язок from my extensive readership, so I'm going to offer another set of gastroclips ( and I don't mean bariatric surgery) here and now. I didn't, I hasten to add, get any positive feedback on the movies either!
- How to make bread
- Definitive and defined Roman pizza
- Down the Roman road Forno Campo de'Fiori
- Saveur. French boulangerie in SW England
- Charcoal sandwich. Baking for hard-chaws
- Happy clappy Catalan croissants at Forn can Curtichs
- Same place - less butter: still smells good
Friday 27 March 2015
Hold me down
Freda, a pal o' mine, has been blogging recently about the 'need' and undesirability of applying physical restraint to those in "care and treatment settings". The question hinges on what carers should do when faced with an angry and aggressive person in their care a) to protect themselves b) to protect others in the vicinity and c) to protect the angry one - and not necessarily in that order! One thing that all the pundits agree on is that you should be right leery about applying physical restraint because a) it might be counter-productive b) it might be fatal. The latter is especially true if the perp is restrained in a face-down position as shown by the death of Eric Garner in Staten Island NY, NY. last July. It's interesting to see that carers are being advised to use 'de-escalation techniques', where, using a set of tried-and-tested protocols, you attempt to talk someone down from their heights of frustration. You can just hear the soft >!splot!< as the experienced carers throw their eyes at the ceiling. They just don't have time for dealing with a crisis in that manner. You might think that this is an recent issue from the relentless reduction of staffing in our institutions so the tax-payer has more to spend on electronic entertainment and foreign holidays.
But the problem goes back at least 40 years, when the Irish health service was, by today's standards, quite extravagantly staffed. In 1977, my pal Mac, then a medical student, blagged me a job as a stand-by medical orderly in the hospital in which The Boy was born. I used to be assigned, at no notice, to the male medical ward to act as the runner for the qualified nursing staff. Male medical was a mix of diabetics and demented, many of the latter still in an acute ward because no accommodation could be found outside [no change there in the succeeding generations]. One of my regular tasks coming on for night shift was to tie one old buffer to the cot-sides with bandages. As a navy-brat, I knew better knots than the woman who was instructing me. The chap had his cot-sides up because he was in the habit of wandering about the ward at night looking for his cat; he was being restrained because the cot-sides were only an obstacle in his quest and he had fallen to the floor some nights previously when trying to get over the fence. Accident report form, extra work, "not having that again", restraint - as easy as 1 - 2 - 3. The irony of using bandages for the task was not lost on me.
But there could be another way, that may not impact on the caring staff's busy schedule and may lead to a sustainable solution. I should add that the alternative to such draconian-Victorian restraint is to use drugs to achieve chemical restraint although this also is deprecated . . . and unsustainably more expensive than tying people down. Freda's post is called What if "Restraint" was not an option? but she looks into the possibility of What if "Restraint" was no longer necessary? . . . because we had looked more holistically at the problem and made some policy changes. Recognising the root of the angry outburst might be a simmering frustration and dealing with the causes of the frustration might have start up costs but just might be cheaper in the long run. What causes frustration in Institutions? Boredom; lack of access to fresh air; failure to recognise the individual; failure to recognise a change in circumstances (bereavement for example); failure to recognise a tooth-ache; really crappy food.
It can't be beyond the wit of woman to sort out some of these at an institutional level - that's why they pay the tiers of management the big bucks after all - without significantly impinging the efforts of the coal-face workers. Change, any change, even change ultimately for the better, causes anxiety and anxiety breeds inertia. To management it must seem that the primary role of trades unions is to block any change at all, but maybe those cot-sides can be taken down as an indication of trust.
But the problem goes back at least 40 years, when the Irish health service was, by today's standards, quite extravagantly staffed. In 1977, my pal Mac, then a medical student, blagged me a job as a stand-by medical orderly in the hospital in which The Boy was born. I used to be assigned, at no notice, to the male medical ward to act as the runner for the qualified nursing staff. Male medical was a mix of diabetics and demented, many of the latter still in an acute ward because no accommodation could be found outside [no change there in the succeeding generations]. One of my regular tasks coming on for night shift was to tie one old buffer to the cot-sides with bandages. As a navy-brat, I knew better knots than the woman who was instructing me. The chap had his cot-sides up because he was in the habit of wandering about the ward at night looking for his cat; he was being restrained because the cot-sides were only an obstacle in his quest and he had fallen to the floor some nights previously when trying to get over the fence. Accident report form, extra work, "not having that again", restraint - as easy as 1 - 2 - 3. The irony of using bandages for the task was not lost on me.
But there could be another way, that may not impact on the caring staff's busy schedule and may lead to a sustainable solution. I should add that the alternative to such draconian-Victorian restraint is to use drugs to achieve chemical restraint although this also is deprecated . . . and unsustainably more expensive than tying people down. Freda's post is called What if "Restraint" was not an option? but she looks into the possibility of What if "Restraint" was no longer necessary? . . . because we had looked more holistically at the problem and made some policy changes. Recognising the root of the angry outburst might be a simmering frustration and dealing with the causes of the frustration might have start up costs but just might be cheaper in the long run. What causes frustration in Institutions? Boredom; lack of access to fresh air; failure to recognise the individual; failure to recognise a change in circumstances (bereavement for example); failure to recognise a tooth-ache; really crappy food.
It can't be beyond the wit of woman to sort out some of these at an institutional level - that's why they pay the tiers of management the big bucks after all - without significantly impinging the efforts of the coal-face workers. Change, any change, even change ultimately for the better, causes anxiety and anxiety breeds inertia. To management it must seem that the primary role of trades unions is to block any change at all, but maybe those cot-sides can be taken down as an indication of trust.
Thursday 26 March 2015
Travel[ling] books
A while back, I was drawing attention to the Cheekpoint Book Exchange, which unaccountably hasn't yet featured in the Russianside blog. That oversight is probably an example of familiarity blindness - you just can't see the extraordinary if it is right under your nose on a daily basis. The current Western economic model privileges growth over all other economic indicators, as if there is no limit to available resources. I really think it would be better for the planet if J.K. Rowling and her publishers had chopped down fewer trees to print millions of copies of Harry Potter and the Infinite Papermill. I don't want to stop children reading about Potter and fantasising about flying on broom-sticks, that's all good fun and mostly harmless.
Mais revenons nous a nos livres. We had friends to lunch on the brilliant sunny Saturday last. Back in the day, when he was very young, the chap had been a trainee padre to the Mersey Missions to Seamen. He's spent most of his life in theatre, and being a priest is not so very different. One of the services which the Missions provided were book-bags: a canvas dunny sack with a draw-string top that was filled with reading matter and topped with an invemtory. While there were limits to what sort of books went into the sack - the Missions were firmly in the Anglican Christian tradition - it was by no means only bibles and religious tracts. The Merchant Marine covered the globe and these bags could be exchanged in Rangoon or Buenos Aires as easily as in Liverpool. Those books were well-travelled and well-used before they fell apart entirely. Books are for reading - they are just a fire-hazard sitting on a shelf.
- What to do? Get more readers for each printed copy.
- How do we do it? Open more libraries.
Mais revenons nous a nos livres. We had friends to lunch on the brilliant sunny Saturday last. Back in the day, when he was very young, the chap had been a trainee padre to the Mersey Missions to Seamen. He's spent most of his life in theatre, and being a priest is not so very different. One of the services which the Missions provided were book-bags: a canvas dunny sack with a draw-string top that was filled with reading matter and topped with an invemtory. While there were limits to what sort of books went into the sack - the Missions were firmly in the Anglican Christian tradition - it was by no means only bibles and religious tracts. The Merchant Marine covered the globe and these bags could be exchanged in Rangoon or Buenos Aires as easily as in Liverpool. Those books were well-travelled and well-used before they fell apart entirely. Books are for reading - they are just a fire-hazard sitting on a shelf.
Wednesday 25 March 2015
Trace elements
A few weeks ago I tasked my final year Environmental Chemists to find out the relative concentration of ‘trace elements’ in a) the Earth’s crust b) the human body and put the results together as a poster. Last year’s EnvChems did something similar with detergents in November 2013. Trace elements were defined as being present in the body at concentrations so low that you'd have difficulty believing that they were essential. If we are 70% water (or is it 90%?), it is clear that we have a lot of Hydrogen and Oxygen about our person, for example. Other elements are present in lesser amounts but some are too 'obvious' to be worth discussing - Carbon in carbohydrates, Calcium in bones etc. Here's a diagram which identifies the elements which are known or suspected to be of vital importance in human physiology. The paler the highlight the less required - but not the less important!
As there are twelve in the class, with me making up the full coven, I listed out F, Zn, Si, As, Cu, I, Br, Se, Cr, Mn, Co, Mo, V and invited The Lads to chose one each. I asked everyone to deliver
It was a collective project for a group that apparently doesn't hang out together outside of class, so I was happy enough with the results. I would have done it out a bit different, but then my peculiar obsessions are not everybody's and I backed off and let them tell it like they saw it. I suggested, for example, that the references should be trimmed by url.ie or tinyurl.com but the final poster came out with a clatter of these informationless tokens tucked into the bottom right-hand corner. It was surely better to write them as: F http://url.ie/yxfx; Mo http://url.ie/yxfy; etc.
In any case, I sent out a calling-all-cars e-mail to staff and post-graduate students which included the sentence:
"The poster is now on the wall outside the molecular biology lab so that biologists can learn something as they come out."
One of my colleagues was quick to point out that "as they come out" could be taken as the process by which people declare their BLTness. Ooops, open mouth . . . insert foot, that's me. I shall spend the rest of the week worrying about being hauled before a Dignity At Work Tribunal to ask why I am singling out people of a particular orientation for attention.
As there are twelve in the class, with me making up the full coven, I listed out F, Zn, Si, As, Cu, I, Br, Se, Cr, Mn, Co, Mo, V and invited The Lads to chose one each. I asked everyone to deliver
- the two abundances in
- % or ppm for earth data
- g, mg, or μg per 70kg human
- a few notes on what that element did for us
- 'something interesting to say about their element.
It was a collective project for a group that apparently doesn't hang out together outside of class, so I was happy enough with the results. I would have done it out a bit different, but then my peculiar obsessions are not everybody's and I backed off and let them tell it like they saw it. I suggested, for example, that the references should be trimmed by url.ie or tinyurl.com but the final poster came out with a clatter of these informationless tokens tucked into the bottom right-hand corner. It was surely better to write them as: F http://url.ie/yxfx; Mo http://url.ie/yxfy; etc.
In any case, I sent out a calling-all-cars e-mail to staff and post-graduate students which included the sentence:
"The poster is now on the wall outside the molecular biology lab so that biologists can learn something as they come out."
One of my colleagues was quick to point out that "as they come out" could be taken as the process by which people declare their BLTness. Ooops, open mouth . . . insert foot, that's me. I shall spend the rest of the week worrying about being hauled before a Dignity At Work Tribunal to ask why I am singling out people of a particular orientation for attention.
Tuesday 24 March 2015
World TB Day
Mycobacterium tuberculosis is one of the biggest infectious killers of people, the other billboard causes of death are malaria and infectious diarrhoea but these are caused by a variety of different bugs. Deaths from malaria are usually caused by a protozoa parasite Plasmodium falciparum but only because its relatives P. vivax, P. ovale, P. knowlesi and P. malariae cause a milder form of the disease which merely debilitates (makes you feel crap) and destroys economies by lost or inefficient work-days. Destroying economies may well mean that the bread-winner is laid low so that the children starve. Infectious diarrhoea is caused by a much wider variety of agents notably rotavirus which kills half a million children every year. An equal number dehydrate themselves to death from bacteria such as Vibrio cholerae, Campylobacter and Escherichia and also protozoans like Giardia lamblia, Entamoeba histolytica and Cryptosporidium parva. The old name for infectious diarrhoea is The Flux or the Bloody Flux which is what happens.
Tuberculosis, is also called consumption romantically associated with dying poets, or phthisis which is more awkward to spell and is a major health problem in the third world although its incidence is increasing among the dispossessed of the West. World TB Day is the WHO's way of raising awareness and has been running for the last 20 years, each year having a theme which emphasises one aspect of the disease, its treatment or control. They picked 24th March to remember an extraordinary piece of scientific theatre delivered in Berlin on that day in 1882 by Robert Koch [R nursing a worrying headache]. Koch is famous in science and microbiology for Koch's Postulates which tie particular disease to a particular microbe which becomes the first step in treatment and cure. If you don't know the cause, you can just mop up the mess, try to make thye patient comfortable and wait. This is all that Florence Nightingale was able to achieve in the 1860s. Koch changed all that. His raree show that day brought his lab to the lecture theatre, as he took his audience through the evidence that a particular rod-shaped bacillus, for which he had invented a specific microscopic staining protocol, caused a spongy destruction of the lung in mammals. For this he won the Nobel Prize in 1905. Paul "magic bullet" Ehrlich (Nobel 1908) maintained "I hold that evening to be the most important experience of my scientific life." and reported that at the end of Koch's tour-de-force the audience was stunned into silence - no amount of applause would suffice and Koch had already answered all their questions in his presentation.
If you think that TB is a serious enough problem now, and it is, you should reflect on the fact with which Koch started his lecture - in the 1880s one in every seven people was infected with Mycobacterium. And also think long and hard about how we use antibiotics because many strains of the bacillus are resistant to everything we have to throw at it. There was no cease upon the midnight with no pain when Keats was hacking up bloody sputum as he composed his Ode to a Nightingale:
Tuberculosis, is also called consumption romantically associated with dying poets, or phthisis which is more awkward to spell and is a major health problem in the third world although its incidence is increasing among the dispossessed of the West. World TB Day is the WHO's way of raising awareness and has been running for the last 20 years, each year having a theme which emphasises one aspect of the disease, its treatment or control. They picked 24th March to remember an extraordinary piece of scientific theatre delivered in Berlin on that day in 1882 by Robert Koch [R nursing a worrying headache]. Koch is famous in science and microbiology for Koch's Postulates which tie particular disease to a particular microbe which becomes the first step in treatment and cure. If you don't know the cause, you can just mop up the mess, try to make thye patient comfortable and wait. This is all that Florence Nightingale was able to achieve in the 1860s. Koch changed all that. His raree show that day brought his lab to the lecture theatre, as he took his audience through the evidence that a particular rod-shaped bacillus, for which he had invented a specific microscopic staining protocol, caused a spongy destruction of the lung in mammals. For this he won the Nobel Prize in 1905. Paul "magic bullet" Ehrlich (Nobel 1908) maintained "I hold that evening to be the most important experience of my scientific life." and reported that at the end of Koch's tour-de-force the audience was stunned into silence - no amount of applause would suffice and Koch had already answered all their questions in his presentation.
If you think that TB is a serious enough problem now, and it is, you should reflect on the fact with which Koch started his lecture - in the 1880s one in every seven people was infected with Mycobacterium. And also think long and hard about how we use antibiotics because many strains of the bacillus are resistant to everything we have to throw at it. There was no cease upon the midnight with no pain when Keats was hacking up bloody sputum as he composed his Ode to a Nightingale:
Darkling I listen; and for many a time
I have been half in love with easeful Death,
Call'd him soft names in many a musèd rhyme,
To take into the air my quiet breath;
Now more than ever seems it rich to die,
To cease upon the midnight with no pain . . .
I have been half in love with easeful Death,
Call'd him soft names in many a musèd rhyme,
To take into the air my quiet breath;
Now more than ever seems it rich to die,
To cease upon the midnight with no pain . . .
Monday 23 March 2015
A small pair of hands
I was in my mid-thirties before I really appreciated that there was a whole other class of scientists who were what I have called a Good Pair of Hands. I was working back to back, and a long way outside my comfort zone, with a woman who really understood what she was doing, rather than following the protocol like me. Such people are not as rare as hen's teeth, but we recognise Barbara "A Feeling for the Organism" McClintock as being extraordinary because she was rare enough. You need a particular cast to your mind to imagine yourself coursing about at molecular size and appreciate what's actually happening in the test-tube.
You could say that one of the prized attributes of a veterinary surgeon, as with midwives, is a small pair of hands. Often enough a vet will have to shove an emerging head back up the uterus and then untangle a mess of legs and a couple of heads before guiding them out in an orderly fashion rather than an unseemly scrum for the exit. In a different world, veterinary science could, like midwifery, have become an exclusive domain for women. There was, for example, a brief window of time when women were pre-eminent in the world of software and computer programming until the men realised that software was a lot more sexy than wiring, transistors and diodes.
When Aleen Cust was born in Cordangan, Co Tipperary in 1868 being a vet was the exclusive domain of men, but that was all the girl wanted to do and after the death of her father, she was staked by her guardian to attend Vet School in Edinburgh. She aced all the courses, won the gold medal for Zoology, but was refused entry into the qualifying exams for membership of the Royal College of Veterinary Surgeons (RCVS). She returned to Ireland as the assistant of a charismatic chap called William Augustine Byrne who was an MRCVS. On dit que they were lovers in Edinburgh, and had two children (!) but in Co Roscommon, they were recognised rather as being a good pair of vets: she at least as competent as he. When he died in 1910, she took over as sole proprietor of the practice. She couldn't call herself Vet, but the farmers and gentry clearly valued her expertise and preferred to call her than the 'qualified' male vets in the district. Galway County Council, for example, were keen to appoint her as a Veterinary Inspector; the RCVS objected so she was appointed [Veterinary] Inspector and carried on working. She jacked it all in when WWI broke out and arrived in Abbeville to work with the thousands of horses that were milling about behind the trenches waiting for the Big Push and a gallop to Berlin.
In 1919 the British Government passed the Sex Disqualification (Removal) Act 1919 and that tipped the balance in the RCVS, which had been split on the possibility of women being capable of knowing the difference between Strangles and Glanders, or recognising a case of acorn poisoning. The Royal Society took another 25 years to accept women as equals, but in 1922, Aleen Cust applied for the diploma that she had qualified for in 1897, was put through a brief oral examination, and was presented with her MRCVS by the President of the College in December of that year. She was the first woman to achieve this distinction.
You could say that one of the prized attributes of a veterinary surgeon, as with midwives, is a small pair of hands. Often enough a vet will have to shove an emerging head back up the uterus and then untangle a mess of legs and a couple of heads before guiding them out in an orderly fashion rather than an unseemly scrum for the exit. In a different world, veterinary science could, like midwifery, have become an exclusive domain for women. There was, for example, a brief window of time when women were pre-eminent in the world of software and computer programming until the men realised that software was a lot more sexy than wiring, transistors and diodes.
When Aleen Cust was born in Cordangan, Co Tipperary in 1868 being a vet was the exclusive domain of men, but that was all the girl wanted to do and after the death of her father, she was staked by her guardian to attend Vet School in Edinburgh. She aced all the courses, won the gold medal for Zoology, but was refused entry into the qualifying exams for membership of the Royal College of Veterinary Surgeons (RCVS). She returned to Ireland as the assistant of a charismatic chap called William Augustine Byrne who was an MRCVS. On dit que they were lovers in Edinburgh, and had two children (!) but in Co Roscommon, they were recognised rather as being a good pair of vets: she at least as competent as he. When he died in 1910, she took over as sole proprietor of the practice. She couldn't call herself Vet, but the farmers and gentry clearly valued her expertise and preferred to call her than the 'qualified' male vets in the district. Galway County Council, for example, were keen to appoint her as a Veterinary Inspector; the RCVS objected so she was appointed [Veterinary] Inspector and carried on working. She jacked it all in when WWI broke out and arrived in Abbeville to work with the thousands of horses that were milling about behind the trenches waiting for the Big Push and a gallop to Berlin.
In 1919 the British Government passed the Sex Disqualification (Removal) Act 1919 and that tipped the balance in the RCVS, which had been split on the possibility of women being capable of knowing the difference between Strangles and Glanders, or recognising a case of acorn poisoning. The Royal Society took another 25 years to accept women as equals, but in 1922, Aleen Cust applied for the diploma that she had qualified for in 1897, was put through a brief oral examination, and was presented with her MRCVS by the President of the College in December of that year. She was the first woman to achieve this distinction.
Sunday 22 March 2015
Douce France
Friday 20/Mar/15 was International Day of Happiness. Who decides these things? What are they thinking? Can't I just be happy on my own, without having to sign some daft petition protesting the fact that, today, I am happy, and being happy along with a billion Indians. I was too busy on Friday to pay any heed, without indeed being aware that it was IDoH, but I was pretty happy anyway. I cut away from work early and as I drove home in the late afternoon I heard two chaps on the radio discussing a list of Officially Happy songs with the imprimatur of Ban Ki Moon, Sec. Gen. of the UN. You may be sure that a random farmer in Andhra Pradesh would pick something other than Three Little Birds, by Bob Marley and the Wailers, no matter how popular that might be in Jamaica.
I did think briefly about what kind of a list I'd put together for Happy Songs but realised quickly that it would be personal to me - songs that were associated in my 'mind' with happy events. It could be something as indirect as the song that was playing on the wireless when I heard that I'd got the job in The Institute. But I'll use this as an opportunity to trib Charles Trenet, who was born in 1913 and lived into the following century. Unless you're French and older than 50, it's quite possible that you've never heard of him, but he was huge in the 1930s and 40s as Le Fou Chantant, the Singing Loon. It's less likely that you've never heard him. He wrote all his own songs, of which there were hundreds and wasn't adverse to other people giving them a lash as well.
His most famous song in the Anglophone world is possibly La Mer, which has featured in several films including Tinker Tailor Soldier Spy and The Diving Bell and the Butterfly. It was blown up out of all proportion to wrap up the infinitely annoying Mr Bean's Holiday. Despite now being associated in my mind with Mr Bean, I really like that song, it gives a lift to the spirit that can be mistaken for happiness. And my French isn't good enough to follow all the words. Then there is Boum, which RTE played early on St Patrick's Day for no particular reason, and that put me in a good mood for day. Apparently it featured in the Bond movie Skyfall, which I haven't seen.
I'm also rather fond of Douce France both the song, which was composed in 1943 in the midst of German occupation, and the country. The song has become an alternative to the Marseillaise in some quarters for its nostalgic evocation of traditional rural France. Not everyone likes the blood-thirsty lyrics of La Revolution. Follow your Trenet-nose through youtube, you'll be happier for it. The occupation was a difficult time for France and its inhabitants: it was easy to put a food wrong in the delicate pas-de-deux between feeding your children and collaborating. With 20/20 revisionist hindsight it was particularly easy to point the finger at people who had survived and make them culpable for not dying pour la gloire de la France. Trenet came in for his share of that, because he demonstrably continued to work on the stage during the early 1940s and German soldiers were undoubtedly in the audience at the time. He was accused of anti-semitism because he complained too loudly about being labelled as Jewish. He was also grassed up by Maurice "Sank 'eaven for liddle girls" Chevalier, whose stage career also continued in Paris throughout the war, for being a homosexual. But it wasn't until the 1960s that Trenet was actually convicted of 'corrupting the morals".
Trenet experienced a revival in the 1980s when the French government got frightened by the cultural imperialism of America and the English language. They instituted quotas on the wireless to ensure that at least some French lyrics got airplay. Trenet, having written more than 1,000 different songs was inevitably on the wireless a lot because there was only so much Charles Aznavour the public can take; and if you listen to Birkin and Gainsbourg coming and going between their kidneys more than once a week you'll either overheat or leak.
But let's finish on an upbeat note with y'a d'la joie.
I did think briefly about what kind of a list I'd put together for Happy Songs but realised quickly that it would be personal to me - songs that were associated in my 'mind' with happy events. It could be something as indirect as the song that was playing on the wireless when I heard that I'd got the job in The Institute. But I'll use this as an opportunity to trib Charles Trenet, who was born in 1913 and lived into the following century. Unless you're French and older than 50, it's quite possible that you've never heard of him, but he was huge in the 1930s and 40s as Le Fou Chantant, the Singing Loon. It's less likely that you've never heard him. He wrote all his own songs, of which there were hundreds and wasn't adverse to other people giving them a lash as well.
His most famous song in the Anglophone world is possibly La Mer, which has featured in several films including Tinker Tailor Soldier Spy and The Diving Bell and the Butterfly. It was blown up out of all proportion to wrap up the infinitely annoying Mr Bean's Holiday. Despite now being associated in my mind with Mr Bean, I really like that song, it gives a lift to the spirit that can be mistaken for happiness. And my French isn't good enough to follow all the words. Then there is Boum, which RTE played early on St Patrick's Day for no particular reason, and that put me in a good mood for day. Apparently it featured in the Bond movie Skyfall, which I haven't seen.
I'm also rather fond of Douce France both the song, which was composed in 1943 in the midst of German occupation, and the country. The song has become an alternative to the Marseillaise in some quarters for its nostalgic evocation of traditional rural France. Not everyone likes the blood-thirsty lyrics of La Revolution. Follow your Trenet-nose through youtube, you'll be happier for it. The occupation was a difficult time for France and its inhabitants: it was easy to put a food wrong in the delicate pas-de-deux between feeding your children and collaborating. With 20/20 revisionist hindsight it was particularly easy to point the finger at people who had survived and make them culpable for not dying pour la gloire de la France. Trenet came in for his share of that, because he demonstrably continued to work on the stage during the early 1940s and German soldiers were undoubtedly in the audience at the time. He was accused of anti-semitism because he complained too loudly about being labelled as Jewish. He was also grassed up by Maurice "Sank 'eaven for liddle girls" Chevalier, whose stage career also continued in Paris throughout the war, for being a homosexual. But it wasn't until the 1960s that Trenet was actually convicted of 'corrupting the morals".
Trenet experienced a revival in the 1980s when the French government got frightened by the cultural imperialism of America and the English language. They instituted quotas on the wireless to ensure that at least some French lyrics got airplay. Trenet, having written more than 1,000 different songs was inevitably on the wireless a lot because there was only so much Charles Aznavour the public can take; and if you listen to Birkin and Gainsbourg coming and going between their kidneys more than once a week you'll either overheat or leak.
But let's finish on an upbeat note with y'a d'la joie.
Saturday 21 March 2015
WrIT runs not large
The Irish Times puts itself about as The Newspaper of Record . . . for the whole island. The Rebels might take this with a pinch of salt in Cork where they have their own newspaper The [Cork] Examiner which made the transition to national newspaper by dropping 'Cork' from the masthead with similar aspirations to that of The [Manchester] Guardian across the water. Likewise you might think that The North would find little of interest in the coverage in the Irish Times which can be embarrassingly parochial. Devoting a two page spread to a tutorial on how 18 y.o.s should act to have the best chance of passing Geography (or whatever) in their school Leaving Certificate may sell papers to anxious parents but hardly enhances the paper's facade of gravitas and (inter)national authority. The issue reporting the results of the worthy IT Cat Survey was filled up with small-small news items. WhoTF cares, for example, who wins the FAI Schools Senior Cup final between Coláiste Eanna, Rathfarnham and St Joe's Galway [CE won 4-3 on penalties after a 3-3 draw]. That's what you get in the local rag, not in a Newspaper of Record. I still have a handful of notices clipped from the Irish Times for parts I played in amateur dramatics when at TCD in the 1970s "Bob Scientist was credible as the Second Student in Georg Büchner's Woyzeck" - note not incredible. I care(d) about that and so does The First Student but nobody else gives-a-damn.
Now I have data to prick these pretensions and see just how far the writ of the IT runs. You don't want to take this from the IT sales or circulation figures: solicitors' offices across the country may 'take' the Times to impress their clients but only use it to line the cat-litter tray at home. Who said cat? Wasn't he on about cats a couple of days ago? He was, and indeed that is the source of my far-is-the-writ data. The survey of cat coat colour launched by the IT in January was fired into the public domain last week with a slab of data which I have started to analyse. To respond to this survey you needed a) to have a cat or an interest in cats b) to take the Times or know someone who reads it and knows of your interest in cats. It seems that the intersection between those two sets is much larger [N=10,000] than those who give-a-damn about a soccer match between two high schools. One of the purposes of the survey was to get geographical data - a report of the county of provenance - and cross-reference that with the genetic information. For the following analysis I'm going to ignore the genetics and report on the number of cats recorded in each county. To establish a baseline rate, I've also gone to the CSO to get human population for each county. Data incommmming!:
You can abstract from this that Dublin is grossly bigger in population than the other counties: 28% of the people squeeze into the second smallest county. I've highlighted in blue(-shirt) the two highest points on the cat/pop column - Dublin and Wicklow - which have reported a disproportionately large number of cats.
I don't accept that the people of Greater Dublin love cats more than us shit-kickers down the country, it is much more likely that more people read the Times in the capital than elsewhere. Almost all the other counties are, in contrast to the folks of Lake Woebegone, below average; from a low of 0.46 in Monaghan to a handful of regions G, KE, LH, MH where the rate-of-return is just above the average. I think it's handy to graph the data [L. above] to show a) that there is a solid trend/correlation between human population and cats reported, b) it identifies just how much of an outlier Wicklow WW is. I put a lot of effort in The Institute to get more data for Co Carlow, but that had no discernible effect. I've trimmed the graph to exclude Dublin which is such an outlier that it would clump everything else in the bottom left-hand corner. The graph also identifies the counties - Donegal, Tipperary and Limerick - which are most obviously below the line. Traditionally, the Irish Times is the paper of the Protestant Ascendancy and I think a case could be made that its writ runs out beyond the Pale but not very far.
The clearest element of this analysis is that there is effectively no interest in the Irish Times north of the border. The rate of cat reporting [i.e. Times readers] from the six counties of "Norn Iron" [data L] is down in the grass even compared to the well-below average shrubs on the landscape like Monaghan and Donegal. I've highlighted the relevant data in orange but that's just a tease. I reckon the Irish Times is on a lose-lose in the North: the Protestants think it is run by a bunch of yahoos who seceded from the United Kingdom 100 years ago; while the Catholics know it is run by Protestants.
Now I have data to prick these pretensions and see just how far the writ of the IT runs. You don't want to take this from the IT sales or circulation figures: solicitors' offices across the country may 'take' the Times to impress their clients but only use it to line the cat-litter tray at home. Who said cat? Wasn't he on about cats a couple of days ago? He was, and indeed that is the source of my far-is-the-writ data. The survey of cat coat colour launched by the IT in January was fired into the public domain last week with a slab of data which I have started to analyse. To respond to this survey you needed a) to have a cat or an interest in cats b) to take the Times or know someone who reads it and knows of your interest in cats. It seems that the intersection between those two sets is much larger [N=10,000] than those who give-a-damn about a soccer match between two high schools. One of the purposes of the survey was to get geographical data - a report of the county of provenance - and cross-reference that with the genetic information. For the following analysis I'm going to ignore the genetics and report on the number of cats recorded in each county. To establish a baseline rate, I've also gone to the CSO to get human population for each county. Data incommmming!:
You can abstract from this that Dublin is grossly bigger in population than the other counties: 28% of the people squeeze into the second smallest county. I've highlighted in blue(-shirt) the two highest points on the cat/pop column - Dublin and Wicklow - which have reported a disproportionately large number of cats.
I don't accept that the people of Greater Dublin love cats more than us shit-kickers down the country, it is much more likely that more people read the Times in the capital than elsewhere. Almost all the other counties are, in contrast to the folks of Lake Woebegone, below average; from a low of 0.46 in Monaghan to a handful of regions G, KE, LH, MH where the rate-of-return is just above the average. I think it's handy to graph the data [L. above] to show a) that there is a solid trend/correlation between human population and cats reported, b) it identifies just how much of an outlier Wicklow WW is. I put a lot of effort in The Institute to get more data for Co Carlow, but that had no discernible effect. I've trimmed the graph to exclude Dublin which is such an outlier that it would clump everything else in the bottom left-hand corner. The graph also identifies the counties - Donegal, Tipperary and Limerick - which are most obviously below the line. Traditionally, the Irish Times is the paper of the Protestant Ascendancy and I think a case could be made that its writ runs out beyond the Pale but not very far.
The clearest element of this analysis is that there is effectively no interest in the Irish Times north of the border. The rate of cat reporting [i.e. Times readers] from the six counties of "Norn Iron" [data L] is down in the grass even compared to the well-below average shrubs on the landscape like Monaghan and Donegal. I've highlighted the relevant data in orange but that's just a tease. I reckon the Irish Times is on a lose-lose in the North: the Protestants think it is run by a bunch of yahoos who seceded from the United Kingdom 100 years ago; while the Catholics know it is run by Protestants.
Friday 20 March 2015
Michaelis-[Menten] Kinetics
"Michaelis-[Menten] Kinetics" is an biochemical in-joke because this piece has its concentration on [Menten]. If you've done undergraduate biochemistry, the graph on the left may give you the heebie-jeebies. It shows how, in an idealised, primary colour way, you can calculate Km, the Michaelis constant for a biochemical reaction. The constant depends on so many variables - the temperature, the pH, the enzyme, the substrate, their relative concentration - that it can only be calculated with reliability in certain cases, under strict conditions that bear no relationship to the roiling tumult of interfering molecules that is the inside of a cell. It is an example of reductionist science and it is always presented to students as a practical exercise to be completed in the next three hours while the sun is shining on the lawn outside. I suspect it has done more to turn students to other fields than any other experiment. One thing to blame is that, in the desire to get good figures, so that a graph may be drawn, so that the unknown parameters may be calculated, the students are not asked to critically evaluate the assumptions that underlie the theory. Who to blame? Certainly not Michaelis or Menten who did the pioneering work on the biochemistry of the breakdown of the di-saccharide sucrose into its constituent glucose and fructose. Their work was published as Michaelis L. & Menten ML. (1913) "Die Kinetik der Invertinwirkung" in Biochemische Zeitschrift 49: 335–369. The enzyme they used is called invertase because the substrate sucrose rotates light to the right while the products fructose and glucose give light a slight leftwards twist. Glucose on its own will rotate light to the right, which is why it is often called dextrose in food product lists to disguise the fact that the manufacturers are horsing in more sugar. According to Joe Felsenstein in a comment, the standard for the the M-M equation was in fact derived by Briggs and JBS Haldane (is there no end to his talents?) in 1925, and the fundamentals were discovered much earlier by Victor Henri but not widely published or properly understood. You can read a very interesting dialogue of war-stories about the youth-of-today and the giants of the past in the comment thread cited just above.
It turns out that Menten ML, is Maud Menten [L] a pioneer in biochemistry and pediatrics who happens to be a woman and Canadian and a lot easier on the eye than her !@&!! equation. It's her birthday [1879] today! Don't feel obliged to lift a glass of high-fructose corn syrup in her memory, but by all means raise a glass of something mildly alcoholic (and better for you that HFCS). She was born in Ontario, took an Arts degree at U. Toronto before she realised that she was an extraordinarily good pair of hands and she qualified with a MB (1907) and an MD (1911). Between her two medical degrees she spent a couple of years at the Rockefeller Institute working with Simon Flexner, who also hosted Alice Hamilton a few years earlier. An essay critically investigating Maud;'s many degrees.
Although Maud Menten was a brilliant bench scientist, as you can tell from the intensity with which she stares at the small conical flask [L], she had many other talents: she was an accomplished painter, could play the clarinet, work an astronomical telescope, make tasty scones and shortbread, yomp up a mountain and speak at least five languages. She couldn't drive a car, however, or rather she shouldn't have been allowed on the road; so she agreeably had feet of clay. I can't find anybody who has a bad word to say of her - except for the driving and even there she never killed anyone. And plenty who were willing to give her tribs [4m40s movie] including getting inducted into the Canadian Medical Hall of Fame - which makes her seem like a baseball star but I can find no evidence that she added second-baseman to her long list of accomplishments. Writing about women like MM from the perspective of now, makes her achievements seem much less than they are. In 1913, we didn't know for sure what enzymes were, let alone how they were made, women hadn't got the vote anywhere except New Zealand, we were still 40 years adrift from knowing what was the structure of DNA or the alpha helix of proteins. She had to work twice as hard (and she was notorious for putting in 18 hour days) as a man to get where she did - eventually full Professor at U Pittsburg - and twice as hard as us moderns to make the fundamental discoveries that we all now take for granted. Bonnets definitely off!
It turns out that Menten ML, is Maud Menten [L] a pioneer in biochemistry and pediatrics who happens to be a woman and Canadian and a lot easier on the eye than her !@&!! equation. It's her birthday [1879] today! Don't feel obliged to lift a glass of high-fructose corn syrup in her memory, but by all means raise a glass of something mildly alcoholic (and better for you that HFCS). She was born in Ontario, took an Arts degree at U. Toronto before she realised that she was an extraordinarily good pair of hands and she qualified with a MB (1907) and an MD (1911). Between her two medical degrees she spent a couple of years at the Rockefeller Institute working with Simon Flexner, who also hosted Alice Hamilton a few years earlier. An essay critically investigating Maud;'s many degrees.
Although Maud Menten was a brilliant bench scientist, as you can tell from the intensity with which she stares at the small conical flask [L], she had many other talents: she was an accomplished painter, could play the clarinet, work an astronomical telescope, make tasty scones and shortbread, yomp up a mountain and speak at least five languages. She couldn't drive a car, however, or rather she shouldn't have been allowed on the road; so she agreeably had feet of clay. I can't find anybody who has a bad word to say of her - except for the driving and even there she never killed anyone. And plenty who were willing to give her tribs [4m40s movie] including getting inducted into the Canadian Medical Hall of Fame - which makes her seem like a baseball star but I can find no evidence that she added second-baseman to her long list of accomplishments. Writing about women like MM from the perspective of now, makes her achievements seem much less than they are. In 1913, we didn't know for sure what enzymes were, let alone how they were made, women hadn't got the vote anywhere except New Zealand, we were still 40 years adrift from knowing what was the structure of DNA or the alpha helix of proteins. She had to work twice as hard (and she was notorious for putting in 18 hour days) as a man to get where she did - eventually full Professor at U Pittsburg - and twice as hard as us moderns to make the fundamental discoveries that we all now take for granted. Bonnets definitely off!
Thursday 19 March 2015
Blue skies come to earth
I was up mad early yesterday morning and fielded an e-mail from my old gaffer, sent late the previous night, looking for a recent reference for one of her brighter students, who was asking some on-the-button questions that predicts a bright and shining future in science. Looking to me, with my two week event horizon, for that sort of thing is a bit of an ask but I can still do research so I went looking. It turned out to be a paper that we had talked about a couple of years ago. It showed that the work I had pursued twenty years ago as quintessential pure science which had no earthly 'use' in a curing-cancer or feeding-the-millions sort of way, turned out after a lapse of two decades to be really important in biotechnology. Score 1 for funding blue-skies research. Then, as I left for work, I heard about a letter signed by 900 Irish Scientists which urged the government to start funding less obvious projects and open a seam of support for pure, blue-skies, higher risk research. I worked myself into a lather about that because I felt that I had been disrespected by not being asked to sign too. But it was for sure a blue-sky day.
When we came back to Ireland in 1990, I secured a job doing a particular/peculiar class of research involving the analysis of DNA and protein sequences. You may like to have a quick refresher of how the genetic code works. It was interesting and intellectually challenging and hinged on the fact that genes of low-to-mid-range expression used 'codons' (the DNA triplets that code for particular amino acids in proteins) more or less indiscriminately while highly expressed genes use a biased subset of codons and you can use this to infer the expression level of an unknown gene. Almost all microbes had such an expression pattern but each species used its own characteristic subset of codons in its highly expressed genes. It was canny enough in its day, the data was patchy before mega-genome sequencing kicked in ten years later. You had to work hard and read a lot to make sense of the data and find the signal in amongst the noise. But we helped set the ground-rules for the field of synonymous codon usage research. I've had three good ideas in 40 years of science, and one of them came out of that project. I'm not making any such bigging-me-up claims for my 30-years-ago research on domestic cat genetics that came back to the spotlight for 15 minutes on Tuesday.
I hasten to say that I was too thick to appreciate at the time how this codonuseless usage knowledge could be mobilised for anything more than honing my crap-detector and generating some papers that were cited a few dozen to about 200 times by other scientists. The average paper is cited less than once and 45% of all papers are published and never referred to again . . . by anyone: so we had some modest impact on science. But in October 2013, a paper was published in Nature showing that if you want to make some useful product (insulin, say, or in this case an enzyme that will efficiently degrade chitin for better health) using current biotechnological techniques you'd better pay attention to codon usage. In particular you should modify your gene of interest so that it looks as much as possible like a highly expressed gene of the carrier species that will be grown in a 10,000 lt vat and generate kilos of your Amazing Therapeutic Protein. If you just lash in the human gene, as it is found in nature, it won't get fast-tracked by the expression vector, and may not work at all. As I say, I didn't have any of the key insights that got this paper published in Europe's premier science journal, but it is fair to say that they stood on the shoulders of our 'useless' research from the end of the last century. I might say "I have done the state some service", as I prepare to exit stage right.
When we came back to Ireland in 1990, I secured a job doing a particular/peculiar class of research involving the analysis of DNA and protein sequences. You may like to have a quick refresher of how the genetic code works. It was interesting and intellectually challenging and hinged on the fact that genes of low-to-mid-range expression used 'codons' (the DNA triplets that code for particular amino acids in proteins) more or less indiscriminately while highly expressed genes use a biased subset of codons and you can use this to infer the expression level of an unknown gene. Almost all microbes had such an expression pattern but each species used its own characteristic subset of codons in its highly expressed genes. It was canny enough in its day, the data was patchy before mega-genome sequencing kicked in ten years later. You had to work hard and read a lot to make sense of the data and find the signal in amongst the noise. But we helped set the ground-rules for the field of synonymous codon usage research. I've had three good ideas in 40 years of science, and one of them came out of that project. I'm not making any such bigging-me-up claims for my 30-years-ago research on domestic cat genetics that came back to the spotlight for 15 minutes on Tuesday.
I hasten to say that I was too thick to appreciate at the time how this codon
Wednesday 18 March 2015
The science of the dispossessed
A letter in the Irish Times this morning signed by 900+ Irish & Diaspora scientists petitions the government, now that we are emerging from the recession, to re-think how they fund science. The last decade has seen a funding policy of short-term precisely-focused goals with a high likelihood of benefitting the economy. It is probably true that the real big break-throughs in science are generated about 50/50 in a) applied, commercially obvious areas and b) blue-skies, tenured, follow-my-passion research. Principal Investigators PIs, who have dependent researchers will show a tendency to follow the money to keep a cherished post-doc on the team and in funds. I think the maths indicate that, by privileging certain fields, you will lower the average quality of research in that area as less qualified and less fundamentally interested PIs start sucking at the teat-that-gives. What may have been, by some objective criteria, a fleet flag-ship in Irish science, becomes a laden ferry-boat dragging through the water.
The signatories of the IT Letter are chaps and women who would be shocked if they were shown to have treated a whole cohort of Irish scientists as not worth inviting to join the angry-at-being-dispossessed-club. As you do, I scanned the list of signatories to the letter looking for my friends-and-relations. They are all there, but none of them sent the letter to me to see if I'd like to sign. I presume that was a case of Bystander Effect - "Ach sure, someone will have asked Bob" because I cannot believe that they think I am no longer a scientist. But it's systemic: there are no signatures from Institutes of Technology except from Dublin IT [N=13], MIT [N=3] the US one, not Mayo and Cal Tech [N=2]. That suggests that nobody in the University sector knows anybody in the IT sector well enough, or has sufficient respect for their thoughts on the matter, to ask. There are lots of possible takes on that, but one is that, while you can rebrand ITs as Technological Universities, The Real Universities are not going to invite TUs to join the Senior Common Room, which is where all the strategic decisions are made. The TUs will have to bunk into the Sergeant's Mess, waiting for orders. I shall use this as an opportunity to cultivate my feminine side, because women in science have always had to suffer this sort of exclusive nonsense.
As you didn't ask, I'm all for blue-skies research because that is more exciting, if also higher risk, than the sort of project that Ireland Inc wants to push forward. It's like the choice you have when betting on the roulette wheel
The signatories of the IT Letter are chaps and women who would be shocked if they were shown to have treated a whole cohort of Irish scientists as not worth inviting to join the angry-at-being-dispossessed-club. As you do, I scanned the list of signatories to the letter looking for my friends-and-relations. They are all there, but none of them sent the letter to me to see if I'd like to sign. I presume that was a case of Bystander Effect - "Ach sure, someone will have asked Bob" because I cannot believe that they think I am no longer a scientist. But it's systemic: there are no signatures from Institutes of Technology except from Dublin IT [N=13], MIT [N=3] the US one, not Mayo and Cal Tech [N=2]. That suggests that nobody in the University sector knows anybody in the IT sector well enough, or has sufficient respect for their thoughts on the matter, to ask. There are lots of possible takes on that, but one is that, while you can rebrand ITs as Technological Universities, The Real Universities are not going to invite TUs to join the Senior Common Room, which is where all the strategic decisions are made. The TUs will have to bunk into the Sergeant's Mess, waiting for orders. I shall use this as an opportunity to cultivate my feminine side, because women in science have always had to suffer this sort of exclusive nonsense.
As you didn't ask, I'm all for blue-skies research because that is more exciting, if also higher risk, than the sort of project that Ireland Inc wants to push forward. It's like the choice you have when betting on the roulette wheel
- pair/impair
[government policy: good chance of making an incremental step] - lucky 19
[blue-sky: lots of duds but one spectacular triumph] - some intermediate neither/nor strategy like betting on {1-12}
Student Enterprise 2015
We have been here before in 2013 and 2014 but not quite here because you can't bathe in the same river twice. Enterprise moves on in waves and the bri'nt idea of 2013 is Old Hat for Fogies two years later. Last Thursday afternoon, there were some beginning-businesses in the catering trade but they are dropping off the radar in favour of other themes. Though they be a bit retro, I liked two girls from Gaelcholáiste Cheatharlach who are floating their cookie company Blas ['taste'] in the local farmer's markets and by word-of-mouth. They sell sacks of crumble-topping (400g €2.50), brownie mix with added chocolate (€3) and rolls of cookie-dough (€3). That should work. Across the aisle was a chap who was, to my initial confusion, running two businesses Skool Cookies and Zapp. I must have looked particularly dense because he patiently explained that "Skool" hinted at Kool as in trendy and hip. Every night he piles flour, sugar, butter and chocolate chips into the oven and every break-time at school he flogs 3 generous rounds of calories in a paper bag for €1. I told him that he was under-pricing himself because a standard candy bar was at least 2x 33c but he nay-said me by pointing out the competition in the market. His bottom line is that he has sold €2500 worth of product over the last several months, bought a serious computer to develop Zapp his Android app, and still had €250 left over for product development.
Another product I liked for its understated aesthetic sense was Memory Catcher which captures a young woman's skill at water-colours and adds a personalised touch into a white frame. The artist paints a branch of cherry-blossom Prunus cerrulata, with or without a life-sized blue-tit Cyanistes caeruleus. Her hench-team then ask the client for significant dates, events or people, prints these out on white paper hearts and hangs them off the branch with embroidery thread. The whole thing retails for €25 and would be good value if they could crank up some details of the quality. But they were adamant that pink hearts or purple framing-mat would definitely not be the thing. And although it looks hand-painted, in fact your cherry branch is colour photocopied from an original; which is fair enough for the price.
This year's trend seems to be the apotheosis of capitalism [as in Hail Capitalism, I'll sit on my arse and watch the money pile up]. In the old days, teenagers would create something handy and/or mundane with their own hands, using their creative powers to create, manufacture and market the product; and also keep tabs on the margin, profit-and-loss and unit costs. Weird stuff maybe: gluten-free muffins and purple cookies; bird-tables and boot-removers; painted stones and woven bracelets; cardigans for infants and kneelers for the elderly. There's something wrong with teenagers starting off as middlemen and acting as a mere clearing house for stuff. Two enterprises last Thursday had essentially the same business model. There is a regular growny-uppy company, with a shed and some machinery in an industrial park somewhere, that prints T-shirts and another that embroiders a name on the outside of sport shorts. Now there are two school-based companies whose contribution to the market is to elbow their way between the manufacturer and the customer and turn a profit by so doing. Here's a handy idea: when we were young and at very expensive schools, we used to have Cash's name-tapes on the inside collar or waistband of all our clothes. Mine were black, the sister's were green: just our names in 3mm high letters: discrete, like, on the inside. Nowadays you wear clothing that makes you look like an advertising hoarding, but if I want to put a name on my kit, and I have the internet, I can find a source. I cannot imagine why I would need four teenagers help me here. There's barely case for one teenager. "So you do the embroidery?" No. "You have a transfer printer and iron the design onto the T-shirt?" Er, no. "What would you say you do here?". There's a helluva lot of this niche parasitism on the interweb: if you try to find, say, a dentist in, say, Tramore, you'll get lots of strikes to sites that seem to be less able to to run a Google search than me but affect to be providing a consolidation service.
I'm glad I talked to the cookie-makers first, I wouldn't have stayed to talk to people if they wereall just getting in the way providing a service with no goods. As it was, I caught a full dozen small 'companies' and had an adult conversation with each one - in a couple of cases having to fend off their teachers to do so. That was good fun. informative and interesting - a good way to wrap up a heavy day's teaching.
Another product I liked for its understated aesthetic sense was Memory Catcher which captures a young woman's skill at water-colours and adds a personalised touch into a white frame. The artist paints a branch of cherry-blossom Prunus cerrulata, with or without a life-sized blue-tit Cyanistes caeruleus. Her hench-team then ask the client for significant dates, events or people, prints these out on white paper hearts and hangs them off the branch with embroidery thread. The whole thing retails for €25 and would be good value if they could crank up some details of the quality. But they were adamant that pink hearts or purple framing-mat would definitely not be the thing. And although it looks hand-painted, in fact your cherry branch is colour photocopied from an original; which is fair enough for the price.
This year's trend seems to be the apotheosis of capitalism [as in Hail Capitalism, I'll sit on my arse and watch the money pile up]. In the old days, teenagers would create something handy and/or mundane with their own hands, using their creative powers to create, manufacture and market the product; and also keep tabs on the margin, profit-and-loss and unit costs. Weird stuff maybe: gluten-free muffins and purple cookies; bird-tables and boot-removers; painted stones and woven bracelets; cardigans for infants and kneelers for the elderly. There's something wrong with teenagers starting off as middlemen and acting as a mere clearing house for stuff. Two enterprises last Thursday had essentially the same business model. There is a regular growny-uppy company, with a shed and some machinery in an industrial park somewhere, that prints T-shirts and another that embroiders a name on the outside of sport shorts. Now there are two school-based companies whose contribution to the market is to elbow their way between the manufacturer and the customer and turn a profit by so doing. Here's a handy idea: when we were young and at very expensive schools, we used to have Cash's name-tapes on the inside collar or waistband of all our clothes. Mine were black, the sister's were green: just our names in 3mm high letters: discrete, like, on the inside. Nowadays you wear clothing that makes you look like an advertising hoarding, but if I want to put a name on my kit, and I have the internet, I can find a source. I cannot imagine why I would need four teenagers help me here. There's barely case for one teenager. "So you do the embroidery?" No. "You have a transfer printer and iron the design onto the T-shirt?" Er, no. "What would you say you do here?". There's a helluva lot of this niche parasitism on the interweb: if you try to find, say, a dentist in, say, Tramore, you'll get lots of strikes to sites that seem to be less able to to run a Google search than me but affect to be providing a consolidation service.
I'm glad I talked to the cookie-makers first, I wouldn't have stayed to talk to people if they were
Tuesday 17 March 2015
Lá Fhéile Pádraig
'Tis St Patrick's Day, to be sure and begorrah. Half the Irish Cabinet is in America viewing parades and quaffing tankards of green beer and taking selfies wearing leprechaun hats. All good fun and mostly harmless - indeed the argument is made that such antics, paid for by the hard-pressed Irish tax-payer, benefit the economy. It is little known in Kiev, but St Patrick's Day is celebrated with gustoin one of the Leeward Islands [L]. Montserrat was named after Santa María de Montserrat by Kris Colon as he passed by on his second voyage to the New World. It was acquired by the Brits and used for a while as a dumping ground for Irish indentured servants aka slaves who have been taken in rebellion and transported . . . and not only by Cromwell. They were known as redlegs, which is probably a fair description because the Irish tend not to tan very well. On St Patrick's Day 1768, there was an, ultimately unsuccessful, rebellion by the enslaved which is one of the reasons why the day is still celebrated, with a wild mix of steel-bands and shamrocks. That is as much authentico as rolling out a Samba School in Dublin. The weirdest aspect of this history is that the Irish accent has been retained while the redlegs have been absorbed by generations of miscegenation <huzzah> so that the locals have been known as the Black Irish, although you may be sure to be sure that designation is streng verboten nowadays.
When I saw the map, I noticed the red dotted line and "Exclusion Zone" I assumed that the Southern half of the island was used as a artillery testing zone like Cape Wrath and chunks of Northern Dartmoor in the UK. But it is not military but natural explosives that people are being protected from. In July 1995, the long dormant volcano in the Soufriere Hills started rumbling and dumped 12 m of mud into the island's capital Plymouth [crappy movie]. It's still rumbling on with periodic drama as everything that volcanoes are capable of is thrown out - ash venting <coff coff>; pyroclastic flow; the more dramatic pyroclastic surge that can travel up hill; vulcanian explosions >!BOOM!<. Nobody died when Soufriere surprised everyone: it wasn't catastrophically abrupt like Pompeii. But half the island lost their homes, plantations and farms, and their jobs. More than half of them, given rights of settlement in the UK, chose to leave for the cold islands of the coast of Europe, where they presumably experienced both "no Irish Need apply" when they spoke on the telephone and the usual cold-shoulder when their black faces appeared in person. But enough of that negativity, today everyone is having a party back home in Montserrat.
When I saw the map, I noticed the red dotted line and "Exclusion Zone" I assumed that the Southern half of the island was used as a artillery testing zone like Cape Wrath and chunks of Northern Dartmoor in the UK. But it is not military but natural explosives that people are being protected from. In July 1995, the long dormant volcano in the Soufriere Hills started rumbling and dumped 12 m of mud into the island's capital Plymouth [crappy movie]. It's still rumbling on with periodic drama as everything that volcanoes are capable of is thrown out - ash venting <coff coff>; pyroclastic flow; the more dramatic pyroclastic surge that can travel up hill; vulcanian explosions >!BOOM!<. Nobody died when Soufriere surprised everyone: it wasn't catastrophically abrupt like Pompeii. But half the island lost their homes, plantations and farms, and their jobs. More than half of them, given rights of settlement in the UK, chose to leave for the cold islands of the coast of Europe, where they presumably experienced both "no Irish Need apply" when they spoke on the telephone and the usual cold-shoulder when their black faces appeared in person. But enough of that negativity, today everyone is having a party back home in Montserrat.
Cata data
I'm sure you're all dying to hear the results of the Irish Times Cat Genetics Survey that was launched at the end of January. 30 years ago, I did that sort of thing for a living and wrote a PhD thesis on the cats of New England and the Canadian Maritime Provinces with a special focus on polydactyl cats. From more than two years of field-work, I had the relevant information on about 10,000 cats from New York to Newfoundland. The plain people of Ireland, mobilised and empowered by the Irish Times have delivered another 10,000 cats into the mill for analysis. That's an important proof of principle - if the topic is engaging then people will engage.
But is the data any good? How would we know? A couple of weeks ago, when Dick Ahlstrom, the IT's science correspondent, sent me a fat Excel data-sheet with 10,000+ cats from all over Ireland, I gave a little moan of pleasure and did a first pass analysis as a quality control QC check. Last Thursday, he reported the results, which finishes up with an unintelligible statement by a so-called expert called Lloyd. What he was trying to say was that the dataset has failed a key QC test. I'll see if I can explain.
It hinges on the fact that, in mammals, sex is determined by the presence of XY chromosomes [males] or XX chromosomes [females] in the fertilised egg. Not to outrageously simplify reality, if you have a Y chromosome then SRY, one of the very few genes on the diminutive Y, will program the cells of the "primordial gonadal ridge" to develop into testes which over the next several months migrate down and almost out. If you have XX, these cells migrate less far and become ovaries. The X chromosome is about 5% of the whole genome and has many genes including those that cause haemophilia [previously], one form of muscular dystrophy [previously] and red-green colour-blindness . . . and in cats the gene variant that causes orange fur to develop. Having two copies of all these (and hundreds more) genes in females would have an impact on the delicate business of development which requires balancing the effects of many genes. That the 'dosage' of genes is important is indicated by the suite of symptoms shown in Down Syndrome where there is an extra Chr21. Early in pregnancy, in each and every cell of the fetus, one of the X chromosomes is switched off: it could be either the X inherited from the mother or the paternal X and this 'decision' is made at random; girls thus have one functional copy of all those genes just like boys. If a kitten has inherited 'orange' from her mother and 'non-orange' from her father she will grow up tortoiseshell with their fur having random blobs of the two colours [Above R: cutiness factor 8.5]. Clearly male kittens can be either orange or not, because they only have one X chromosome . . . unless they have Klinefelter's syndrome, XXY, in which case you'd expect them to have rather small testes and a suite of other abnormalities . . . but who'd looking? Lesson on sex-linkage aka inheritance of genes carried on the X.
Klienfelter's occurs in about 1:1000 live births but not all Klinefelter cats are going to be torties because that requires the additional condition of having parents of opposite colours. Let's say that we expect 2/10,000 tortoiseshell males in our dataset. How many are reported? 244!! The data:
It's clear that John and Mary O'Phobail needed better instruction on what 'tortoiseshell' looks like, possibly by showing them pictures [above R]. A standard way of dealing with that anomaly is to exclude 'equivocal data' and assume the rest of the observations are sound. On that basis we conclude that the frequency of Orange in male cats in Ireland in 2015 is 950/(950+3050) = 0.24. This is much higher than any of the previous values calculated by trained geneticists 40 years ago which range from 0.03 in Waterford to 0.17 in Donegal with Dublin, Dundalk, Limerick and Galway intermediate. We can probably conclude that The Crowd doesn't really know what geneticists mean by 'orange' and have included a bunch of sandy tabbies in their N=950. At this stage I should give up but I did persist in seeing if the female data was consistent with that from males. It sort of is, but here there is a disconcerting and statistically significant under-reporting of tortoiseshell in females.
Even the sex-ratio [F: 4786; M: 4244] is a bit squiffy with an excess of females far outside the statistical expectation of 1:1 ratio unless you're dealing with human centenarians where antient grannies are far more common than old grandfathers. You could hypothesise that the cats reported, with their excess of females, include a disproportionate number of [grossly obese, coddled, indoor-only] aged female cats like the blob that shares my outlaws' home. But I don't believe it; it's more likely that folks just don't know how to sex a cat [lift the tail, folks]. My one escapade in writing a computer program in COBOL was a contract from The Cat Fancy Association of America to see if they could detect fraudulent pedigrees from the genetic data declared for sire-dam-offspring trios. A pilot study revealed a 7% error rate! That showed me that professional cat-breeders hadn't a clue about genetics and couldn't look with sufficient care at their own cats to see what colour they were. In summary, we cannot, with 20/20 hindsight, expect to generate reliable data from owners' reports without a bit more training in the difficult cases.
BUT, I think we we can assume that the errors are systematic. It would be a stretch to imagine that punters in Carlow were better at cat genetic diagnosis than their city cousins in Cork, so we can probably go forward to establish relative frequencies of the genetic variants, county by county, across the country. There's a BT Young Scientist's project in there, and I have comparative data on hundreds of sites across the World. Go to!
But is the data any good? How would we know? A couple of weeks ago, when Dick Ahlstrom, the IT's science correspondent, sent me a fat Excel data-sheet with 10,000+ cats from all over Ireland, I gave a little moan of pleasure and did a first pass analysis as a quality control QC check. Last Thursday, he reported the results, which finishes up with an unintelligible statement by a so-called expert called Lloyd. What he was trying to say was that the dataset has failed a key QC test. I'll see if I can explain.
It hinges on the fact that, in mammals, sex is determined by the presence of XY chromosomes [males] or XX chromosomes [females] in the fertilised egg. Not to outrageously simplify reality, if you have a Y chromosome then SRY, one of the very few genes on the diminutive Y, will program the cells of the "primordial gonadal ridge" to develop into testes which over the next several months migrate down and almost out. If you have XX, these cells migrate less far and become ovaries. The X chromosome is about 5% of the whole genome and has many genes including those that cause haemophilia [previously], one form of muscular dystrophy [previously] and red-green colour-blindness . . . and in cats the gene variant that causes orange fur to develop. Having two copies of all these (and hundreds more) genes in females would have an impact on the delicate business of development which requires balancing the effects of many genes. That the 'dosage' of genes is important is indicated by the suite of symptoms shown in Down Syndrome where there is an extra Chr21. Early in pregnancy, in each and every cell of the fetus, one of the X chromosomes is switched off: it could be either the X inherited from the mother or the paternal X and this 'decision' is made at random; girls thus have one functional copy of all those genes just like boys. If a kitten has inherited 'orange' from her mother and 'non-orange' from her father she will grow up tortoiseshell with their fur having random blobs of the two colours [Above R: cutiness factor 8.5]. Clearly male kittens can be either orange or not, because they only have one X chromosome . . . unless they have Klinefelter's syndrome, XXY, in which case you'd expect them to have rather small testes and a suite of other abnormalities . . . but who'd looking? Lesson on sex-linkage aka inheritance of genes carried on the X.
Klienfelter's occurs in about 1:1000 live births but not all Klinefelter cats are going to be torties because that requires the additional condition of having parents of opposite colours. Let's say that we expect 2/10,000 tortoiseshell males in our dataset. How many are reported? 244!! The data:
It's clear that John and Mary O'Phobail needed better instruction on what 'tortoiseshell' looks like, possibly by showing them pictures [above R]. A standard way of dealing with that anomaly is to exclude 'equivocal data' and assume the rest of the observations are sound. On that basis we conclude that the frequency of Orange in male cats in Ireland in 2015 is 950/(950+3050) = 0.24. This is much higher than any of the previous values calculated by trained geneticists 40 years ago which range from 0.03 in Waterford to 0.17 in Donegal with Dublin, Dundalk, Limerick and Galway intermediate. We can probably conclude that The Crowd doesn't really know what geneticists mean by 'orange' and have included a bunch of sandy tabbies in their N=950. At this stage I should give up but I did persist in seeing if the female data was consistent with that from males. It sort of is, but here there is a disconcerting and statistically significant under-reporting of tortoiseshell in females.
Even the sex-ratio [F: 4786; M: 4244] is a bit squiffy with an excess of females far outside the statistical expectation of 1:1 ratio unless you're dealing with human centenarians where antient grannies are far more common than old grandfathers. You could hypothesise that the cats reported, with their excess of females, include a disproportionate number of [grossly obese, coddled, indoor-only] aged female cats like the blob that shares my outlaws' home. But I don't believe it; it's more likely that folks just don't know how to sex a cat [lift the tail, folks]. My one escapade in writing a computer program in COBOL was a contract from The Cat Fancy Association of America to see if they could detect fraudulent pedigrees from the genetic data declared for sire-dam-offspring trios. A pilot study revealed a 7% error rate! That showed me that professional cat-breeders hadn't a clue about genetics and couldn't look with sufficient care at their own cats to see what colour they were. In summary, we cannot, with 20/20 hindsight, expect to generate reliable data from owners' reports without a bit more training in the difficult cases.
BUT, I think we we can assume that the errors are systematic. It would be a stretch to imagine that punters in Carlow were better at cat genetic diagnosis than their city cousins in Cork, so we can probably go forward to establish relative frequencies of the genetic variants, county by county, across the country. There's a BT Young Scientist's project in there, and I have comparative data on hundreds of sites across the World. Go to!
Monday 16 March 2015
Blueprint
Anna Children was born on 16th March 1799 and she was tribbed with today's Google-doodle. I need to have this information thrust under my nose because I've never heard of this pioneering botanist and photographer and I think we should. She was there at the beginning and she moved in privileged circles - her father was a scientific polymath/dabbler who was at one time Secretary to the Royal Society but Anna was born 100 years too early to be dubbed FRS herself. The father John George Children should be given more credit because, after a home-lab conflagration >!whooomph!< he recommended the use of safety-goggles. Anna was a family friend of William Henry Fox Talbot and Sir William Herschel, whom we've met before discovering planets with his sister Caroline. Talbot and his oppo Louis Daguerre in France were independently developing the technology and techniques (different!) of photography in the late 1830s standing on the shoulders of chemists of the previous generation. Their discoveries and tastes dictated the way in which photography became available. It could have gone in different directions using different chemical reactions but it worked and that put a damper on blue-skies research to discover other Ways of Seeing. William Herschel invented a totally novel chemical technique for recording fine detail. He required the process as an early form of backup, so that his notes and diagrams could be recorded indelibly. The chemistry involves mixing 8% potassium ferricyanide and 20% ferric ammonium citrate and slapping it on an absorbent material - usually paper or cloth. On exposure to light the iron is reduced to form a complex called Iron(II,III) hexacyanoferrate(II,III) aka ferric ferrocyanide aka Prussian Blue, an insoluble blue dye.
The advantages of this cheap and cheerful process were immediately recognised by technologists, engineers and architects and gave us the word blueprint - as a fundamental and accurately reproduced template. It exercised the adopters of the alternative silver-based process in ways out of all proportion to the issue at hand. Why not have a landscape with a blue tinge? Why did the monochrome have to be black? Very interesting essay on the photographic angle.
Anna had by now married a well-heeled merchant called John Atkins and was developing a passion for botany in particular for the architectural divergences within the Algae. She found that she couldn't easily record sufficient detail time-efficiently and used Herschel's cyanotype process to accumulate a huge archive of images. These were published in a severely limited edition, which has now acquired significant value for its rarity . . . as well as for its record of the diversity of botanic life. There is a dilemma here: I was taught that you had to draw specimens because the details were only visible to the trained human eye. Effectively this meant that we drew but we also interpreted the specimen and to do that we had to have a hypothesis about what we were seeing. Looking at the cells of an onion skin, we knew there were nuclei so we drew nuclei and duly labelled them as such from the margin of the drawing. The problem was that we also knew there were mitochondria in the cells and so we would be tempted to draw them too . . . although at 1μm they were beyond the resolution of the optical microscopes that we were using. Drawing thus tilts the object so it shines a little brighter than it really is - to the detriment of object[ive] truth. This is one of the reasons why I welcome the smart-phone into my introductory biology labs - it gives an extra 4x magnification but it also is accurate. I also regret the arrival of this technology because it can be used to bypass the brain altogether.
Anna Atkins wasn't having any of that - she wanted an accurate record, she wanted it fast and she didn't give a tuppenny damn if it was blue. Brilliant!
The advantages of this cheap and cheerful process were immediately recognised by technologists, engineers and architects and gave us the word blueprint - as a fundamental and accurately reproduced template. It exercised the adopters of the alternative silver-based process in ways out of all proportion to the issue at hand. Why not have a landscape with a blue tinge? Why did the monochrome have to be black? Very interesting essay on the photographic angle.
Anna had by now married a well-heeled merchant called John Atkins and was developing a passion for botany in particular for the architectural divergences within the Algae. She found that she couldn't easily record sufficient detail time-efficiently and used Herschel's cyanotype process to accumulate a huge archive of images. These were published in a severely limited edition, which has now acquired significant value for its rarity . . . as well as for its record of the diversity of botanic life. There is a dilemma here: I was taught that you had to draw specimens because the details were only visible to the trained human eye. Effectively this meant that we drew but we also interpreted the specimen and to do that we had to have a hypothesis about what we were seeing. Looking at the cells of an onion skin, we knew there were nuclei so we drew nuclei and duly labelled them as such from the margin of the drawing. The problem was that we also knew there were mitochondria in the cells and so we would be tempted to draw them too . . . although at 1μm they were beyond the resolution of the optical microscopes that we were using. Drawing thus tilts the object so it shines a little brighter than it really is - to the detriment of object[ive] truth. This is one of the reasons why I welcome the smart-phone into my introductory biology labs - it gives an extra 4x magnification but it also is accurate. I also regret the arrival of this technology because it can be used to bypass the brain altogether.
Anna Atkins wasn't having any of that - she wanted an accurate record, she wanted it fast and she didn't give a tuppenny damn if it was blue. Brilliant!
Sunday 15 March 2015
Ripablik blong Vanuatu
As we sit safe in our houses in Kilkenny and Clonmel [or indeed Kiev] today, with a bit of frost or a light drizzle, we might reflect on how fortunate we are in the weather. Vanuatu has been in the news briefly (until the next multiple fatality on Irish roads) because Pam the most ferocious storm ever recorded (anywhere?) has just roared across the archipelago with winds records at 250km/h. Some are claiming that Cyclone Zoe, which gave the region a bad drubbing in 2002, was worse. 250km/h should require an extension on the Beaufort Scale which lumps every breeze higher than 120km/h as Force 12 = Hurricane. The map of the island ripablik [L.] is coloured pink to identify areas where you must take precautions against malaria - which is the whole country; so it's not just tropical storms, earthquakes and tsunamis the people of Vanuatu need to concern themselves about. Before the Republic was established in 1980, the country was a French/British condominium which allowed missionaries of many Christian denominations to come and convert the locals. But the number of languages far outstrips the numbers of sects: Vanuatu has the highest concentration of languages per capita, anywhere in the world,: there are only about 250,000 people (about as many as the city of Cork) but they speak somewhere around 125 different languages, spread unevenly across 65 inhabited islands. It's as if the villages of Ferns and Cloyne, as well as absurdly having their own bishop, also each spoke it's own unique language. I'm guessing that half of these languages are on their last generation of existence. Because you might have to buy a bicycle in the capital, almost everyone in Vanuatu speaks a pidgin called bislama [formerly bêche-de-mer] most of whose vocabulary is derived from English but whose grammar is typical of other Melanesian languages. Richard Feynman has a famous story of sitting behind two chaps on a plane to Brazil and hearing enough to think that he was eavesdropping on a Portuguese conversation, but one that was not quite right. It turned out that they were speaking Ladino, the Sephardic equivalent of the Yiddish spoken by the Ashkenazim on Northern Europe. It's like that with bislama, listen to this propaganda from the .vu government: yumi = us; solwata = the sea; bata nus = snot; nambawan = best; sel blong fingga = fingernail etc.etc. Written down it could be Latin or Athabascan but if you sound out the words their meaning often becomes clear. And don't get me started on Tok Pisin, the equivalent glue that holds the 3,000 language-speakers of New Guinea together in a single nation. In some sense, pidgins can be thought of as a reduced instruction set: a vocabulary limited set of words [N=~5000] with which you can explain any concept at all without jargon; a bit like Globish. If you're old enough you may remember Let Stalk Strine by Affabeck Lauder ca. 1965 - a guide to the weird pidgin they speak in Australia.
Saturday 14 March 2015
Gobsmacked
Earlier this week Irish Social Media and regular media, were having the vapours about a dramatic example of racism in Ireland. A mind-your-own-business Spanish tourist was sitting in a St*"!*cks in Dublin, when a drunken yob hucked a lunger and spat in his face, shouted "Foreigners" and swept out of the cafe. According to the reports, everyone in the cafe was gobsmacked and didn't stir to apprehend the perp. Actually, of course, only one man in the place was smacked by gob: the rest were just having an attack of bystander effect. As the drunk left the premises, it is reported that a beer bottle fell from his his pocket and smashed on the ground - a telling metaphor for his condition: would it count as pathetic fallacy? It is certainly pathetic journalism because it avoids the difficult bits: we can all now suck our teeth and tsk-tsk because we would none of us be guilty of such a flagrant breach of good manners and so by extension we are not racist. Hmmm? Not the teensy tiniest bit racist?
I've written before about, say, bus-drivers being clever enough to note the colour of a passenger's skin but too dense and benighted in their ethics to ignore it. If you have a black person in front of you, you can casually ignore them, or pause before serving them, or find a reason why their kettle just cannot be fixed. But how do you work it out from an e-mail?
It's the surname stupid! The EU optimistically claims that there are 140,000 speakers of Irish in Ireland and some of them have gone back to an ancient parchment deed and brought to life an exotic and largely romantic version of their ordinary surname. See if you can guess what Ceallacháin, Ní Dhulchaointigh, Muimhneacháin, and Seoighe were two generations ago when (being) Irish was distinctly unsexy. I don't know of any case where the Irish version has fewer letters than the terse English equivalent - Churchill, famous for his use of Anglo-Saxon terms recommended "Broadly speaking, the short words are the best, and the old words best of all." He got a Nobel Prize for Literature [1953], so he must be correct; although to give Churchill the Nobel Prize was a decision somewhere on the spectrum of bonkers to deeply unimaginative.
Nobody is going to refuse to interview Ms Seoighe, not least because she is symmetrical, but if a CV comes in from Ms Al Malaawi, or Mr Rakotodramananana, it must be easy to imagine trouble with English, let alone trouble with clients or office-mates, and put it to one side. One of my mature students, a charming PakistanIrish addition to multicultural Ireland used to be manager of a section of fast-food franchises - he was told by his boss not to employ "any blacks" because Irish people didn't like to be served by such people.
I'm getting all cross about this because I teach at The Institute and this last year, I've had an intense six hours every week with about half final year project students. One thing that distinguishes an Institute degree from a University degree is that the former requires a minimum of 12 weeks in a work placement. That's a good thing, I reckon: we try to deliver a "good pair of hands" into the work-force rather than someone who has succeeded entirely in their head. A couple of my final cohort have been getting antsy about finding an internship this Summer and have asked me for help. At the next class I had a straw poll of all the students [N=16] which revealed the data in the table above-left [N=4 missing data]. All but one of the white (including the Russian) folks have secured their position while none of the dusky brigade have (including a Malaysian). It's a small enough sample but Fisher's exact test shows that it is statistically significant, so unlikely to be due to random bad luck.
In Environmental Chemistry, in discussion of water pollution we recognise point sources and diffuse sources. The former are much easier to deal with: if all the fish go belly-up downstream from the cheese factory, it is a racing certainty that someone has left the whey-discharge tap open all night and the EPA can prosecute. But nitrate run-off into Irish waters? That's an unavoidable part of the human condition in the modern farming world, everyone is guilty and it is therefore futile to point fingers. It's like that with the social pollution of racism: we can, if we have moral courage and dare risk a biffing, run after the gobber described above and point out the errors of his ways. Or, more likely, we can feel ashamed that we didn't act quick enough to do so.
It is much more difficult to recognise our own casual racism and do something about that.
I've written before about, say, bus-drivers being clever enough to note the colour of a passenger's skin but too dense and benighted in their ethics to ignore it. If you have a black person in front of you, you can casually ignore them, or pause before serving them, or find a reason why their kettle just cannot be fixed. But how do you work it out from an e-mail?
It's the surname stupid! The EU optimistically claims that there are 140,000 speakers of Irish in Ireland and some of them have gone back to an ancient parchment deed and brought to life an exotic and largely romantic version of their ordinary surname. See if you can guess what Ceallacháin, Ní Dhulchaointigh, Muimhneacháin, and Seoighe were two generations ago when (being) Irish was distinctly unsexy. I don't know of any case where the Irish version has fewer letters than the terse English equivalent - Churchill, famous for his use of Anglo-Saxon terms recommended "Broadly speaking, the short words are the best, and the old words best of all." He got a Nobel Prize for Literature [1953], so he must be correct; although to give Churchill the Nobel Prize was a decision somewhere on the spectrum of bonkers to deeply unimaginative.
Nobody is going to refuse to interview Ms Seoighe, not least because she is symmetrical, but if a CV comes in from Ms Al Malaawi, or Mr Rakotodramananana, it must be easy to imagine trouble with English, let alone trouble with clients or office-mates, and put it to one side. One of my mature students, a charming PakistanIrish addition to multicultural Ireland used to be manager of a section of fast-food franchises - he was told by his boss not to employ "any blacks" because Irish people didn't like to be served by such people.
I'm getting all cross about this because I teach at The Institute and this last year, I've had an intense six hours every week with about half final year project students. One thing that distinguishes an Institute degree from a University degree is that the former requires a minimum of 12 weeks in a work placement. That's a good thing, I reckon: we try to deliver a "good pair of hands" into the work-force rather than someone who has succeeded entirely in their head. A couple of my final cohort have been getting antsy about finding an internship this Summer and have asked me for help. At the next class I had a straw poll of all the students [N=16] which revealed the data in the table above-left [N=4 missing data]. All but one of the white (including the Russian) folks have secured their position while none of the dusky brigade have (including a Malaysian). It's a small enough sample but Fisher's exact test shows that it is statistically significant, so unlikely to be due to random bad luck.
In Environmental Chemistry, in discussion of water pollution we recognise point sources and diffuse sources. The former are much easier to deal with: if all the fish go belly-up downstream from the cheese factory, it is a racing certainty that someone has left the whey-discharge tap open all night and the EPA can prosecute. But nitrate run-off into Irish waters? That's an unavoidable part of the human condition in the modern farming world, everyone is guilty and it is therefore futile to point fingers. It's like that with the social pollution of racism: we can, if we have moral courage and dare risk a biffing, run after the gobber described above and point out the errors of his ways. Or, more likely, we can feel ashamed that we didn't act quick enough to do so.
It is much more difficult to recognise our own casual racism and do something about that.
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