Friday, 18 December 2015

Suffer the children?

Yes they do!  It's a biblical reference ye heathens: Matt 19 v14.  Like Thich Nhat Hanh prefers to do his walking meditation with kids rather than with neurotic adults, so Jesus wanted kids to hear the message rather than being hustled out of the way by officious disciples.  I have a sorry tale to tell today about the commodification of children. It's only 80 years since the Lebensborn programme was launched 12 December 1935 in NSDAP Germany. One of the key legs of their racial purity nonsense was that the master race should be encouraged to have more children, so that eventually only Aryans were left.  In my book it's nonsense because cultural, genetic and linguistic diversity is what we should be aiming for: life is so much more interesting that way. Lebensborn = fount-of-life was initially a social welfare organisation which set up maternity centres and after-care services to support [some approved sorts of ] women, both married and unwed, to raise their children safely in a world at war. I don't think we have a good leg to stand on in complaining about the exclusivity of the programme. Catholics still get better access to education here and richer women certainly get better access to post-delivery maternity care. The current flap in Ireland is that agnostic parents are 'abusing the sacrament' by getting their children baptised to improve their chances of a place in the better local schools. Almost all schools are almost entirely paid for by me-the-tax-payer but Catholic boards of governors act as gatekeepers for pupils.

Later on the ethics of the Lebensborn programme took a plunge downwards when it started to process children, or whatever parentage who looked a good fit for the master-race. Most of the records were destroyed in the maelstrom of 1945, so we can only estimate how many children were forcibly separated from the parents and taken away to be raised as Aryans. Poland and Norway seem to have been more actively trawled because of the higher frequency of the blonde and blue-eyed preferred stereotype. But no part of the conquered territories was immune. In Norway after the war, as in other parts of Europe, those suspected of 'collaboration' with German soldiers were scapegoated and so were their children. It must take a disagreeable amount of priggish self-righteousness, not to say want of intellect, that could mete out punishment on kids for the sins of their parents.

Tsk! Tsk! we say as we judge the doings of folk back in the 1930s and 40s.  But we've very recently had a sorry record of cultural [white, catholic, patriarchal] imperialism in Ireland and have very recently allowed state institutions [Gardai, Social Sevices] to knee-jerk racial stereotyping to seize blond and blue-eyed children who were a poor external match for their parents. The press and their readership had a fit of the self-righteous vapours over those [temporary] kidnappings of children by the Irish state.  But that, if I might make so bold, is a useless, if not positively damaging, response.  We should rather look at ourselves and try to see the unconsidered certainties that blight our day-to-day actions and interactions. We had a good example of that at the end of last week: most commentators who were old enough to have adult children, and so brought up in an earlier era, were of the opinion that a no harm would come to a child who was occasionally given a slap by its loving parents. As Senator Jillian Van Turnhout responded "and no good came of such an action either".

Thursday, 17 December 2015

voluminous nonsense

I had a good time Monday and Tuesday of this week teaching a section of the TCD MSc in Immunology.  There were so many students on the MSc, and the material was so new to them that I asked if the management would rise to a Teaching Fellow to help field the questions in the practical sessions.  I wouldn't have asked if I didn't have an Effective in mind: a young graduate of The Institute who did a stonking good final year research project with me and is now building that into a MSc by research in the Comparative Immunlogy group in Trinity. That turned out to be a good idea: by having to explain things, Ilaina the TF got to understand them better herself and also learned a lot of stuff that hadn't been necessary to pick up yet in her nascent post-graduate career. Meanwhile, back at the day job . . .

At The Institute, I teach a weird and wonderful set of subjects, few of which are what I was trained to do.  That's what makes the job so interesting although it was a teeny bit stressful when I started work three years ago: being 2 weeks or even 2 days ahead of the students in mastering the syllabus. I've had two sections of 1st Year QM remedial maths quantitative methods this term and the end of last week was time for their Xmas Exams. I do have standards, but I also want to get them over the line. Many of them have ingrained Math Anxiety and have probably had crap teachers who are at the edge of the competence (a bit like me teaching Environmental Chemistry). Nevertheless they want to do science and I don't want to hold them back with stuff that may well become easier when they use it for things that matter: their own experiments for example. I've long been a fan of Edward MacNeil's Mathsemantics, which book hinges on the observation that even quite handy number-wonks go all to pieces when the problem is embedded in a sentence and/or you have to define your units and/or you have to have an order-of-magnitude clue about what the answer should be.

In a metric world, one of the weirder units of measurement is a bale of 4-inch solids, which consists of 44 (?!) concrete blocks 100mm x 215mm x 450mm.  Why 44?  It's not because the molecular weight of carbon-dioxide is 44? And to point out that I get 44 flapjacks out of a swissroll tin is to suggest that these popular cookies are like door-stops. No, the answer is apparently that, because the density of concrete is about 2.35g/cu.cm, then 44 blocks weighs about 1 metric ton: it's convenient for loading trucks.

So I thought, I'd pop a question in tne QM exam, for the boys, like:
Q. What is the volume of 44 (100mm x 215mm x 450mm) concrete blocks in scientific notation and SI units [cu.m]? A. 0.426 cu.m. or 4.26 X 10-1
Only one student got it right, having converted it, correctly, to 0.1m x 0.215m x 0.45m x 44.  Another was wrong wrong-almost-right at 4.257 X 101. The majority of the students plonked for 4.257 * 108. On the assumption that mm are essentially the same as m.  A minority view had 4.257 * 105 as the answer; under the mistaken impression that if
1mm is the 1/1000th part of 1m so
1cu.m is 1000x the size of 1cu.mm; when in reality it is 1000 x 1000 x 1000 times bigger.

Whatever about the maths, the thing that distresses me is that 425,000,000 cu.m. is about the volume of the entire domestic housing stock of the Republic of Ireland ! How could you write that down as an answer for the volume of half-a-hundred blocks; which wouldn't even make a garden shed large enough to shelter a lawn-mower.  What to do? Throw the kids out of the classroom!  Stop them doing pages of Victorian sum-copy exercises and make them measure timber and mix concrete and order up enough plywood to make a play-house in the garden. They'll soon get the measurements right if the first version of their play-house hasn't sufficient plywood for the roof. You can't invite your dolls to tea if the sandwiches get all wet from the rain.

Wednesday, 16 December 2015

Sexiest Protein Competition

Pubmed is a database of the scientific literature. A key element of science is endeavouring not to unwittingly reinvent the wheel by doing an experiment that someone has already carried out. Replicating another group's experiments by design is another matter and carried out less frequently than might be desirable. So before you launch your research project you should read the scientific papers that have appeared on the subject. This will stop you getting a red face from being seen to copy someone else's work as if your contribution was totally novel. Reading will also fill in the gaps in your knowledge, give you inspiration and food for thought and help you see places where you and your students can usefully make a contribution. But b'gob you cannot read every paper ever written: there are 26.7 million papers indexed in PubMed, with 1.15 million which came out this year.
You had better learn how to use Pubmed effectively so that a) you get to read, or at least scan, all the papers of interest b) you don't have to trudge through lots of irrelevant off-topic material to locate the jewels. Years ago, I wrote a manual called Better PubMed, and I've updated it periodically. At the end it points out some of the hilarious blunders that lurk in this all-compassing database like a number of papers which include both psuedogene AND pseudogene in the same Abstract.  You can't do anything about that but you can find
  • papers published out of Institutions in Waterford: waterford [AD]
  • the couple of papers published by Dr Mouse ignoring the couple of million papers published about The Mouse Mus musculus: mouse [AU]
  • papers published by Dr S Bob: Bob S [AU]
  • papers published in the noughties: 2000:2009 [PDAT]
I've been on about PubMed before insofar as it exposes a pernicious HarryPotterism at the heart of science. Aled Edwards in Canada has made a devastating analysis of this funding-fondling problem.  Scientists don't study what's important, so much as they study what other scientists are working on.  Some areas, some genes, some proteins 'get legs' and sweep all before them, leaving a lot of orphan genes weeping for lack of attention in the corners. How to encourage students on, say, a Masters of Imm course to find out how to use PubMed effectively?  Why, run a competition, of course! offering a small bag of Werther's Original butter candies.  I asked them all to bring to class the name of an immune Protein-of-Interest on which they would be carrying out their molecular evolutionary analyses.

The first step in any research project is to discover what the competition is doing . . . by reading the literature . . . using PubMed to open the door to these data. I suggested that we could look into the hypothesis that some proteins/genes were more "sexy" [as in hot current trendy] than others.
Q. How to measure that?
A. Count the number of publications about Protein "P"; then count the number that have appeared since, say, Jan 2014. Divide the latter by the former  et voila! you have a Sexy Quotient.

Protein PubMed Recent Sexy Qt Protein PubMed Recent Sexy Qt
NLRP3 2173 1024 0.47 CD47 870 157 0.18
IL28B 1249 462 0.37 CTLA4 5647 882 0.16
CD3g 39 12 0.31 ERBB2 22375 2691 0.12
NFKBIA 212 64 0.30 CD56 7874 941 0.12
IL8 2586 712 0.28 p53 78696 9351 0.12
NFKB1 781 195 0.25 iKba 69 8 0.12
MyD88 5031 1239 0.25 CCR5 8208 871 0.11
STAT3 14356 3518 0.25 CD154 7209 584 0.08
TLR4 13752 3345 0.24 EBAG9 164 8 0.05
RAG1 1417 273 0.19 recA 6351 260 0.04
I've sorted the chosen proteins by hotness, and there turns out to be an order of magnitude in the difference between Princess and Cinderella. Why might this make a difference? You can see that some widely cited proteins, like TLR4 and STAT3 are really going off the boil, while NLRP3 and IL28B are on the up-and-up.  If you have a choice, I suggest you are going to pull down more grant money and find it easier to publish in Nature if you devote your time to Sexy Proteins than tired old dowager proteins. 

Tuesday, 15 December 2015

Bigger than a bread-box?

This week, Mon/14 and Tues/15, I'm up in Dublin doing a couple of honest days' work teaching for the TCD MSc in Immunology. Because I spent a decade working in a Comparative Immunology lab, I know some of the language and some of the key concepts but I wouldn't call me an Immunologist. You may call me an evolutionary biologist if you want, though, and I've been trying to transmit that angle, that way of thinking, to these smart young immunologists.  It's quite intense, 2 hours theory in the morning, 3 hours on the interweb in the afternoon using an unfamiliar toolkit to answer some immunological questions. I can't expect, in two busy days, to cover all the information I've internalised during two decades immersed in the field of bioinformatics and molecular evolution. But if they learn one or two things that are new-and-interesting, and maybe later use some parts of the manual which I've written for the course, then I feel it will have been worth talking myself hoarse.

As in a lot of my courses/modules I started them off with a pre-quiz so that they would have a bench-mark to compare against the new things they will learn over the next couple of days. In 2013, I asked that class to put in order of size: a molecule, a macromolecule, a cellular organelle, a cell and a tissue. That turned out to be easy for almost all the Msc students - although it's eye-watering hard for my first year students at The Institute. This year, I thought I'd quantify the question, to further emphasis the relative size of the objects immunologists talk about quite casually - mostly various proteins and various cells - as if everyone is intimately familiar with them.  It's my belief that many scientists compartmentalise their knowledge - ecology is out there in the Serengeti; biochemistry is here on the side-table; genetics and evolution have nothing to do with biochemistry; drug actions have nothing to do with the intestinal flora . . . aNNyway, here's the question:
Q. If this room [5m x 7m x 3m]  was a T-cell [a vital part of the immune response to pathogenic attack]; how big would the T-cell receptor TCR [a key protein embedded in the cell membrane of the T-cell] be?

If you know, or can calculate/guesstimate this ratio, you'll know how many copies of the TCR there are likely to be. You'll also be able to hazard a guess about the number of copies there are of CCR5, another T-cell membrane protein that opens the door for HIV to infect and ultimately kill T-cells. The cartoon [L from Nature Immunology so it has some authority] suggests a ratio of about 1:100. My answer based on a larger classroom in The Institute and some assumptions about the size of the cell was
A. a sultana.

My assumptions were a bit off because a T-cell is a bit smaller at ~15μm than an average cell in diameter. A typical protein is about 7nm across.  So in that room with that cell specified, the answer is more likely to be
A. a grain of rice
But I was a bit nearer than the other people in the room who variously offered:
a raisin; a stapler / a computer mouse; the paper-bin [twice]; a chair seat not the whole chair / 50cm / 10% / a chair; 20% / the door [twice] / the [small] white-board; half the diameter; the office next door; no idea [tsk tsk: damn and blast you have to commit!].  That's a lot of variability, and I think we're all exaggerating.

Why does it matter? Because the scale difference between biochemistry and cell-biology is so enormous that it's impossible to fit in a textbook diagram: if you show a cell at a reasonable size on an A5 page, then the cell's proteins would each be a single pixel wide.  It's like trying make a scale model of the solar system where those attempting the problem say things like "Jupiter is a chestnut, more than a city block from its nearest neighbor in space!" We, all, need to integrate knowledge from across disciplines: specialization is for insects!

Monday, 14 December 2015

Smack!

Ireland took another step away from being a medieval theocracy last week by starting the implementation of new law forbidding anyone, including parents, to hit a child.  It's one of those things for which our adult grandchildren will look at us closely and wonder what kind of people we were in those days when whacking children for real or imagined misdeeds was widely accepted.  One of my earliest solid memories is a conversation at the school gate in the year I turned 8. I rather smugly confessed that I'd been in school for nearly a whole year and hadn't been beaten by any of the teachers. I should have stopped my gob, because in the last two weeks of that school year I was hit with a stick no less than 4 times . . . I was seven, I was struck, with a stick, by an adult, who was in charge of my education.  It was typical of that time and place that boys used to have a session in boxing after lunch one day each week.  Hitting other people was thus institutionalised; but assymetrically: children were not allowed under any circumstances to strike out at an adult - that would be disrespectful.

The weird thing is that if asked baldly "Is it okay to batter/bludgeon/beat a child?" a majority of adults will say "NO!".  Asked if it is okay to smack or slap a naughty child, the unequivocal No! is likely to get a little wobbly. Is it all in the language? Under English Common Law, which we inherited at the foundation of the state in 1922, it was deemed okay for a parent or guardian to use "reasonable and moderate chastisement" to discipline a child in their care.  Indeed this phrase was enshrined in the 1908 Children Act.  But the problem is that one person's reasonable chastisement of an annoying little pillock who won't listen when asked to stop; is someone else's assault on the person and dignity of one much smaller than you. Senator Jillian van Turnhout was interviewed on the wireless that evening.  She claimed that the new legislation was really just tidying up loose ends by repealing the relevant section of the 1908 Act but also by explicitly scotching the common law defense. She also pointed out that there were no sanctions if you were caught giving young Maisie a whack: and that omission was deliberate.  The current change was just to make it easier to prosecute when a gross violation of a child's rights and dignity had been perpetrated.  There is, now, no excuse (Maisie being lippy; The Da being drunk; The Mammy being worn to ribbons by sleep deficit) for striking a child.  That's great in my book because it will make it really difficult to sustain boxing in youth clubs and elsewhere.

One thing about The Law is that's its requirements are, in some sense. what the majority want or believe to be necessary to maintain a happy society. Writing "thou shalt not strike any child" into the statute books brings that idea into everyone's consciousness.  It's like a lot of inconvenient intrusions into our freedom: wearing seat-belts and not consuming alcohol while driving a car; not smoking cigarettes in aeroplanes and pubs; not burning rubbish in suburbia on Saturday morning; picking up dog-shit; paying for clean water.  Once you break the old habit and embrace the new, oftentimes you wonder why you (and we all) put up with the other nonsense for so long.

Our sense of smug satisfaction of occupying the high moral ground in the world (like when we put a charge on disposable plasic bags aor banned smoking in pubs)  lasted until Sunday.  Marian Finucane on her RTE1 chat-show was all over the victory of Irish Cage-Fighter Conor McGregor. Whatever you think about boxing with its rules of not hitting below the belt mixed martial arts competitions run by the UFC Ultimate Fighting Championship are another level of brutality. McGregor finished off his Brazilian opponent José Aldo in 13 seconds with a few extra blows while Aldo lay befuddled on the floor. Because he was Irish, it was considered worthy of widespread media coverage: not only on RTE. Will our diminutive President welcome McGregor back to the country with the same razzmatazz granted to boxer Katie Taylor?  Will nobody learn from Primo Carnera's 1933 victory over Ernie Schaaf which left Schaaf in a coma from which he never woke up?

Sunday, 13 December 2015

Sunday sausage 131215

Last Thursday it was the Annual Works Christmas Dinner and I voluntarily went out to dinner, in a restaurant, with colleagues from work. I won't say it's the thing above all that I would rather do in the evening but it was pleasant enough.  Everyone ate too much and when it came time for dessert there were some groans round the table.  I suggested that complainers could make room by doing a Kobayashi shake: a little shimmy of the torso perfected by Takeru Kobayashi the world's most well-known competitive eater. This injection was met with blank stares - my experience of popular culture is clearly different from theirs. Kobayashi has recently been toppled from his hill-of-beans by an up-and-coming young feller from California called Matt Stonie who won this year's Coney Island hot-dog eating contest despite being a slight 54kg 175cm young chap.  He has to be seen to be believed:
That calls for a song or four to lighten the load:

Lunacy

A while back I wrote about the Harry Potter aspects of the moon-landings: everyone over a certain age knows that Neil Armstrong was the first man to walk on the face of the moon. To the nearest whole number nobody among 100 people could name the last man on the moon.  It was Eugene "Gene" Cernan, the commander of the Apollo 17 mission which touched down on 11th December 1972. You can see him here [R] throwing up dust as he does wheelies about the lunar surface in the Lunar Rover. There were many aspects of the mission that exemplified the throw-away society that was, and is, riding our planet to a dusty and depleted desert. It took 50 tons of Saturn V rocket and fuel to deliver 5 tons of material to the moon.  At each stage in the process, bits were discarded so that the moon is now littered with 180 tons of space trash.  It's a bit like the approaches to Mt Everest, or the Camino de Santiago: someone else will pick up my discarded packaging.

The Lunar Rover program was budgetted at $38,000,000, but forced by politicians to have a declared budget of $17,000,000. Cost over-runs led to the final cost of deploying 3 throw-away vehicles to the moon being . . . $38,000,000.  Obviously, they had to be engineered under the constraint of a declared max-weight and still be functional to transport the men and material and bring back lunar rock samples to the landing module. Cernan brushed against the fender of one of the wheels while getting it ready for use . . . and ripped off a chunk of it. The first trip was thus carried out in a fog of moon-dust. Something similar had occurred on the Apollo 16 mission, so a roll of duct-tape was available on-board. They also had some stiffish paper lunar surface maps.  Guided by bodgers and engineers back at mission control, Cernan was able to construct a replacement fender-extension to keep the dust down on the second day's excursion. I like that story very much: using 50c's worth duct-tape and a bit of cardboard to fix a $10m luxury people-and-clutter carrier. Except that the duct tape was probably sold to NASA a Space Duct Tape - a snip at $5,000.  It's like that in science: the glassware you buy in a hardware store is sold with a 10x markup through a medical supply catalogue.  It's like that with weddings: book a table for a Works' Outing and it will cost €X, book it for John and Mary's wedding and the cost is €3X and the quality and menu choice is worse.

Cernan and his "Lunar Module Pilot" Harrison H Schmidt, launched back towards home on the 13th December 1972.  Schmidt, a geologist, was the only scientist to go to the moon and back - the rest were pilots. Apollo XVIII had already been cancelled by the money-people. Nobody has been back for 43 years. In 1994, Cernan became Rád Bieleho dvojkríža a Grand Officer of the Order of the White Double Cross [see R] having been bestowed this honour by the Republic of Slovakia "for the outstanding spread of good reputation of Slovakia abroad" ie because of his Slovak ancestry and out-of-this-world achievements. Slovaks live in Slovenská republika so you can see why the rest of us confuse it with Slovenia Republika Slovenija an entirely different place with a less interesting flag. But that's politics, here we are removing our Dan Dare space-helmets to Gene Cernan - no better man!