Ignorant not stupid

I had French lessons for ten years in school in England, where it was the standard foreign language. It didn't do me much good when I went to spend Easter in Paris when I as 16. The poor Parisians were at a loss to interpret my mangling of their language as to accent, syntax and vocabulary. With the wannabe sophistication of Hemingway or Becket, I went into a bar and asked for a tasse cup of red wine. But that's another story. One of the early exercises,  at about the age of 8, in mastering a foreign language was learning how to tell the time in French. One of my classmates did not, at that age, know how to tell the time in English. I guess I remember that because it was so exceptional. I imagine we later seized on the poor fellow and mocked him unmercifully before flushing his head down the toilet.

It's a case of the Curse of Knowledge, where you can't imagine what it's like not to know something. It was one of the reasons why American Blacks did so poorly at Early IQ tests: they were asked to make judgement calls about stuff that was completely alien to their culture. The [white] chaps who devised the questions could not even see that there was an issue because they were so locked into the own cultural milieu that much of it became an invisible backdrop. To poor blacks, these obvious-to-all-thinking-bourgoise allusions just caused bafflement. I've written before about how some salient points of the language I use, although English, are incomprehensible to the kids at The Institute. I try to modify my words to maximise communication without patronising anyone.

I was reminded of these cultural deficits last week in Research Methods class.  I'm giving them an exam this week and had hunted out some example of data for them to analyse for the mock exam, The mock exam is a way of coaching them in the key concepts, so that nobody is totally at sea for the end of term assessment. You can check out the dataset which is the weights of the US rowing squad at one of the Olympics. I picked it because it deals with sporty things and so seemed sensible for both my Strength & Conditioning and Sports Rehab classes. On top of that, Ireland had a rare medal win at the Rio Olympics by a pair of rowers from Skibbereen Co. Cork who went viral with their laconic humor. One of the boys in the class is a rare Dubliner, proudly working class and city-bred.  "What's a cox?" the Dub asked. I replied.  "s/he's the small one at the back of the boat who steers because all the big chaps are progressing with their backs to the direction of travel"  . . . I used to be one of them myself as part of my very expensive education. "Why are they facing backwards?". I stopped there; the young feller had never imagined, let alone seen, rowing in action, it seemed hopeless to proceed with explanation.

Another question to ask about the rowers is whether, statistically, the light-weight "LW" rowers weigh significantly less than the others. To make the problem 'easier' I marked out two columns of data marked 'Open' and 'LW'. "What's 'Open' ?" asked one woman. My 'Socratic' answer started "You know what Open is in golf or tennis? The US Open? Rory McIlroy? It means unrestricted, how might that apply to rowing weights?"To each rhetorical question, I could only see mounting confusion. So I paused and said "You're a credit to your parents with your politeness. I know you want me to shut up and just tell you what Open means in this context and here I am rambling off in two different directions neither of which relates to boats. I am sorry, I'll try not to do it again.". Then I realised that I had used the term 'cox' in my question, whereas the dataset used 'coxswain' and this internal inconsistency would be wholly opaque and grossly unfair to people who, because of their cultural heritage, are ignorant of rowing as Ulysses' land-locked Scythians:

carry your well-planed oar until you come

to a race of people who know nothing of the sea,

whose food is never seasoned with salt, strangers all

to ships with their crimson prows and long slim oar

The Odyssey

Baltic Ace

The North Sea is not the Med. Even at the height of Summer, bathers emerge from a swim blue and teeth-chattering. Nevertheless one may be often warmer in the sea at 10^oC than exposed to a whipping wind and horizontal snow above the surface. At 10^oC nevertheless you are only going to survive for 60 or 90 minutes before the remarkably high specific heat of water sucks the warmth from your very core and kills you.

I written before about a disaster in a RoRo - Roll-on, Roll-off - car ferry; the Herald of Free Enterprise that sank dramatically in 1987 while leaving Zeebrugge. The design flaw in RoRo ships is the free-surface of the car decks. Water weighs in at a tonne per cu.m., and even a small depth of water inside will weigh heavy if the surface area is large. A car ferry might be 150m long and 25m in the beam: so a cm of water on the deck - not enough to reach your shoe-uppers - could weigh 40 tonnes.  Which is not so much if the deadweight tonnage [DWT=carrying capacity] is 7,000 tonnes. But, with no transverse or longitudinal bulkhead to compartmentalise the slopping water, this bulk will travel without impediment to the lowest side of the deck and increase any list to port or starboard. This may well allow the ingress of yet more water. It took less than 2 minutes to sink the Herald and 193 people lost their lives and everyone on board lost something material or psychological. If you're on the bridge in charge of one of these things, you want to be extra vigilant because a collision which holes the side is going to be bigger, wetter, problem than for normal ships.

Zeebrugge is a busy port and the tracks towards it criss-cross with tracks into other ports notably Ostend / Oostende and Anvers /Antwerpen / Antwerp. on 5th December 2012, the MV Baltic Ace, a vehicle shuttle, was taking a load of Mitsubishi cars from the port to Kotka in Finland. At 1615hrs hey dropped the pilot and headed North for the Skagerrak. As they picked up speed they noted a number of other vessels in the seaway, it was dark but ships have lights and the night was clear. Coming South heading for Antwerp was a container ship Corvus J and the two officers of the watch made radio contact with each other.

There are strict rules of priority at sea that predate new-fangled things like wireless and radar. The latest version is International Regulations for Preventing Collisions at Sea 1972 aka COLREGs. Sailing vessels of whatever size have priority over motor vessels . . . because sailing-ships are  more difficult to manoeuvre.If two powered vessels are crossing each other's track then the vessel which has the other on it's starboard side must give way. That's entirely arbitrary, but if everyone agrees to that convention then both ships know what their responsibilities are. The corollary is that the stand-on vessel must keep its initial direction and speed - again so that there's no doubt about who is doing what. It's so simple that a child of six could understand it and indeed my nautical father dinned it into us at that age as "If to starboard red appear, 'tis your duty to keep clear" Red is the light on the left side of the ship as in the other bit of relevant doggerel "No more red port left in the bottle".

Foolishly-in-hindsight, he two Officers of the Watch came to an accommodation by VHF radio - a relaxation of the strict COLREG rules that would allow them both to get to their destinations at full power and on schedule. It didn't help that, although both OoWs were Polish, they communicated in nautical English. Their maverick approach to convention resulted in a disaster with the Corvus J whanging into the starboard side of the Baltic Ace, holing her, flooding the lower car deck with water and causing her to sink within 15 minutes of the collision. 11 out the Baltic Ace's crew of 24 seamen died in the aftermath and the Corvus J stove it her bow [see damage R] as it did it acted the tin-opener. It's all in the report by the Bahamas Maritime Authority.  As the Corvus J blundered about in the dark she ran down one of the lifeboats but was able to pluck to safety the only passenger on board.  The last survivor, the 4th engineer, was pulled from the sea after 2hrs immersion. Even with a survival suit that is at the outer limit of what is physiologically possible at 8-10^oC.

The salvage was paid for by the insurers, authorised by the Dutch Rijkwaterstaat and carried out by Boskalis. They couldn't leave the hulk on the sea floor in such a busy shipping and fishing area of the North Sea. Not least, there were half a million litres of fuel oil on board. You really should check out the salvage video. Neat, efficient and a lot cleaner than, say, the British government which dumped thousands of tons of munitions into the North Sea after WWI, when people didn't know any better, and WWII when they did. Or as in Bari 1943 where The Man pretended to know nothing about the cargo on a sinking ship.

Thrill spectator sports 041216

In The news: Magnus Carlsen has just defended his World Chess Champ title. Here's some back-story whc shows that Carlsen, apart from being off the normal scale at chess is not a 1-dimensional geek.

• Thrills of chess, with expert commentary
• Advice from the master

Also in the news, which may not have filtered across La Manche to France, was the death of English actor Andrew Sachs. He guyed a hapless, bullied waiter who 'came from Barcelona' and had washed up in Fawlty Towers, the BBC sit-com from the 1970s.

• I know nothing
• Que?
• Burro .ne. butter

If you want more, and there is mucho, you're on your own. You know it's funny, because of the roaring laughter-track, to make a comic buffoon of a Spaniard and, by extension, all of Spain. Although I guess Magdrileños shrug and say It's not us, it's the Catalans that are being mocked. What's not to laugh about wheeling out such stereotypes and applying them to blacks, muslims and jews?  Is it because they don't have a sense of humor?  As late as 1978, it was acceptable to dress chaps up in white flairs and black-face to sing songs with white girls in hot-pants:

• Black and White Minstrel Show [<miscegenation alert> and don't look it you lived through the 70s: too embarrassing]

Here's Werner Herzog [prev] doing the "By Gad Sir, I've lost my leg" about a mere flesh wound. Well 'ard that Herzog.

On the BBC last night a travel company, decides to get the staff DNA tested to shake up their sense of identity /certainty. I hope the HR department and the Union, if any, are awake to potential ethical issues.  On a related issue are dopplegangers: distant people who are not identical twins separated at birth but who have the same face. We could ask if they are broadly similar as to their genetic heritage or if their faces are just thrown together at random.

Castle Rackrent

Caisleán cíos forlán

The price of a roof is being much discussed in the media and at coffee-breaks across the country this weather. The Central Bank has reduced the requirement for a deposit on a mortgaged property from 20% to 10% and the government has brought in a needlessly complicated scheme to subsidise 1st time buyers. The 20% deposit was designed to stop home 'owners' going bankrupt in a negative equity trap that caught 50,000 people at the top of the Celtic Tiger boom in 2006-2008. In 2009 there was much talk of ghost-estates where speculative builders had started 100s of homes in peculiar places in the hope of turning them into profit. Now we have a gross insufficiency of housing stock and consequent inflation of both rental costs and house/apartment prices - especially in Dublin.  It can't all be put down to the 200,000 extra Poles and Balts Witamy chłopców! that Ireland has acquired since 2000 or the fact that every IT multinational megacorp has opened its European headquarters in Dublin. We returned to Ireland in 1990 having, along with half the population, spent the 1980s depression abroad.

We found an old farmhouse out near the airport to rent which was a) enormous b) inconveniently remote from my place of work and c) cheap at £180/mo. The landlord, who had grown up in the farm but built a warmer, drier and easier-to-clean bungalow when he got married, was renting out the home-place since his parents had died 5-6 years previously. Each year, a couple or a family would come and view the place in the Summer, fall in love with the ideal of rural bliss and sign a 1 year lease. They would then endure a Winter with no central heating, whistling drafts, rattling windows, leaking roof, and a kilometer to the nearest bus-stop . . . and go live somewhere else. We stayed there for six years; Dau.I then Dau.II were born there; we wore hats in bed at night; consumed prodigious quantities of solid fuel; it was grand altogether. I cycled to work - a round trip of 24km - and clocked up a round the World total of 40,000km before my non-fatal RTA turned the bike into a pretzel.. After about three years, the landlord said he'd have to put up the rent . . . to £200/mo and we had to suck that up. We stayed there for another 3 years until . . .

It's 20 years since we moved from that almost-rural down to the real country and raised 2 girls on a 7 hectare micro-farm. The raising two daughters worked out rather well, the farming was much more of a joke and certainly not a way of making a living. So I continued to hold down a job in Dublin, which put shoes on the girls' feet and food on the table. I looked around to find a room in Dublin where I could spend M-Tu-We-Th nights and the only sensible thing that turned up was a 1-bed apartment in salubrious Dublin 4 which would set me back £320/mo. That was still cheaper than commuting to Dublin from home; quite apart from the gruelling amount of time spent in bus and car. Our farrrmlet is 20km from the nearest bus-stop. The Dublin pad was remarkably civilised and grown up and we would often spend the weekend in Dublin. I walked to work - a round trip of 8km. After 3 years, as the Celtic Tiger started to roar, the landlord raised the rent by 28%, I cut down my hours to 4 days a week and it was no longer sensible or affordable to have my own place in Dublin. This may surprise European readers but there is no rent-control in Ireland. It is entirely driven by supply-and-demand, nature red in tooth and claw 19thC capitalism.

I wasn't homeless for long but threw in my lot with a couple of long-haired botanists, with a long-haired cat, for the three days a week I was up in town. I hardly saw them because I'd be late 'home' and up early, but it was gezellig and hygga, and a round trip of 12km. My share of the rent was a little less than I'd been paying in Dublin 4 but I had to share a bathroom and front-door and snores, so it was on balance a step down in the world. Apart from anything else it was in Dublin 6, very much lower in Monopoly board terms than Dublin 4. In the small-small world that is Ireland, it turned out that our landlord was a landlady who was the teacher in a secondary school very close to our farrrrm. After I'd been there about 18 months, the landlady announced that the rent was going up 40%! We three sat down and had a full and frank discussion about whether this was fair [not!], possible to support [reluctantly yes] and signed up for another year at the grossly increased rent. As that term drew to a close, the landlady announced that we were to be evicted: she was about to retire and wanted to cash in her chips for her pension. I was outraged, not on my own behalf because I had a home, but on behalf of the senior tenant who had been there for 11 years paying his rent regular-as-the-clock and walking to work round the corner. It was his home and he was being thrown out on the street because the building was somebody else's investment.

My life moved on, I went on pilgrimage and slept in a great variety of unprivate and uncomfortable places and the sky didn't fall. When I came back to work in Dublin I was down to 3 days a week and built up a wide experience of hostels in Dublin city centre where you could have you pick of bed&breakfast for €12/night. After a few weeks of that, I was at a Chinese New Year celebration and was sat between a pair of short-haired molecular evolutionists who made me an offer in these terms.
"This is ridiculous, a man of your seniority sleeping with a miscellaneous crew of Australian back-packers and Polish Gastarbeiter. You could be a professor, if you weren't such a lazy-arse; and quite frankly you're letting the side down. If you pay us whatever you're paying these berluddy hostels, you can have our box room in Marino".  I though about it overnight and accepted their offer the next day. Every morning I was there, I'd get up bright and early and put €20 on top of the TV before leaving for work. That went on for a tuthree years, we spent at least one night a week in the pub drinking far more than I had the capacity for until . . . we were evicted. The landlady was retiring from a life-time in Baltimore and she intended to live in her own house. We moved round the corner to another place owned by an Irish physicist who was working in JPL in California, until after a couple of years the landlord came home to be married and we were evicted again. Our menage broke up as one of the lads got married himself and I went back to hostels.

That's it, I don't think this sorry tale of rent-hikes and evictions is extraordinary over the last 20 years of boom and bust in Ireland. A typical rent for a 2-bed Dublin apartment with a kitchen the size of a shoe-box and bathroom with no window was £500 = €625 in 1996 and is now €1,800. You may be assured that wages have not gone increased by a factor of 2.75x over the same time scale.

I heard that the high-school teacher landlady died a few weeks ago.  She didn't live long on the money she raised by depriving a fellow man of his home. What's the point? You can't take it with you so you might as well be kind while you're still above ground. If we lived in a socialist paradise such as imagined by Padraig Pearse and his fellow revolutionaries of 1916, we wouldn't be allowed to think of domestic housing stock as a commodity or an investment. The fact that we do allow, and indeed encourage, that attitude results in the fact that 25% of Dublin's rental market is owned by anonymous foreign corporations who can't get a better return on capital elsewhere.

It was Andrew Carnegie's birthday 25-Nov-1835 and wordaday popped up this quote "Surplus wealth is a sacred trust which its possessor is bound to administer in his lifetime for the good of the community".

H-bomb

A is for Atom bomb, two of which have been used in anger; one for Hiroshima and one for Nagasaki. Actually 'used in anger' overstates the case because the US military applied a rather cold-blooded cost-benefit utilitarian analysis in terms of the cost vs American lives saved.  Laurens van der Post, guru to royalty, who was a prisoner of war of the Japanese at the time, makes the argument that having an explosion brighter than 1000 suns resonated powerfully with the Japanese and their government and brought about their capitulation. The [rising] sun features on the national flag and is deeply embedded in the national identity. Within a few years, A-bombs, nuclear fission bombs, were seen as piffling and under-powered as Teller and others pushed for the development of the H-bomb, the hydrogen fusion bomb. We may be thankful that, despite 1000s of tests, no H-bomb has been gone off in a theatre of war.  But that depends of what you mean by H-bomb, because a shipload of H-bombs went off on 2nd December 1943 in the harbour in Bari.

The liberty ship SS John Harvey had arrived in harbour several days before hand with a cargo of munitions for the US Army, which was fighting its way up the Italian peninsula. The John Harvey's deadly cargo included 2000 M47A1 bombs filled with 1-Chloro-2-[(2-chloroethyl)sulfanyl]ethane aka (ClCH₂CH₂)₂S aka mustard gas aka mustard agent H [structure R looking like a colourful plastic toy sulphur, chlorine]. It was one of the chemicals developed in WWI to kill and disable enemy troops in a particularly unpleasant way. It is a blistering agent which, if it doesn't kill by destroying the wet surface of the lungs, also has cytotoxic effects damaging DNA to cause mutation and cancer. The same strategic wonks who authorised the use of the Hiroshima and Nagasaki bombs were concerned at the likelihood that the Germans would use chemical warfare as the war turned in the Allies' favour. In their assessment, the US needed to be in a position to retaliate in unkind.

But if the threat of retaliation is to have any effect, the other side have to know or suspect that the capability and the will are there. Au contraire, the shipping of hundreds of H-bombs was kept a strict secret; probably because the Allies were trying to adopt the high moral ground in their prosecution of the war. When the SS John Harvey arrived in Bari, there was a huge backlog in the unloading schedule, but her Captain didn't feel able to demand priority at the dockside and so waited his turn in the harbour. On 2nd December, the Luftwaffe launched an air attack that caught the harbour defensive on the hop and sank 17 ships including the John Harvey.  Because of 'security' hundreds of soldiers, sailors and civilians didn't get proper treatment for the weird lesions they presented with. Although the US military dispatched Dr Stewart Alexander, who 'happened' to have some expertise in the diagnosis and treatment of mustard gas, to Bari, he was unable to obtain official confirmation of John Harvey's cargo. The victim were collateral damage on the high moral ground. There is a suggestion that a similar cargo is lying on the bottom of the Thames estuary.

It's the kind of event that colours a rational analysis of Gulf War Syndrome 50 years later. GWS is a statistically significant excess of miscellaneous chronic symptoms among soldiers who were deployed to Kuwait in 1990-1991; compared to soldiers who served elsewhere. The Veteran's Administration has exclude a bunch of head-line possible causes including " . . . depleted uranium, anthrax vaccine, fuels, solvents, sand and particulates, infectious diseases, and chemical agent resistant coating". But 25 years on, nobody is 'fessing up to what caused "Gulf War Veterans’ Medically Unexplained Illnesses" as the VA prefers to call it. The current generation of squaddies would like to know before the next big escapade of the military-industrial complex. "Do we need weapons to fight wars? Or do we need wars to create markets for weapons? -Arundhati Roy"

Will The Man never learn?

Speak, Memory

Golly me, it's almost the end of term. I've been prepping up my classes for their  Xmas exam - test - quiz. We had a big discussion in one of my classes at the beginning of the year about what to call these [goddamned] assessments. Clearly we don't want the poor petals to feel overcome with anxiety and weak at the knees about the inevitable requirement that me-the-teacher has to find out what, if anything, they know. Everyone in the room had baggage about the word exam, and test was not much better, so I've made them fade into the background. Quiz is also a quite stressful word for many but some have had fun at table quizzes, so that's the least bad option. Today in Human Physiology we have a quiz on blood, blood-pressure and the circulatory system, so last week I was able to wheel out my perf on The Art of Memory as The Palace of Pressure, with a certain degree of hilarity at my antics.  That's the point! If I turn a cartwheel - without breaking my osteoporotic wrists - to suggest turn-over of red blood cells on their 100 day life-cycle then that might embed the concept in their noddles. They would remember it for longer still, of course, if I did break a wrist and they had to call [meemo meemo meemo] the para-medics.

For the last five years, all the 1st Year students at The Institute have had to sit through an hour a week of "Communications", where one of our more enthusiastic lecturers talks about conveying ideas effectively: written, verbal, small-group, seminar and executive summary etc. If the medium is the message, and it is, this is hopeless.  "And today we/I will talk about small group work  and powerpoint presentation . . . don't anybody ask any questions we have a lot to get through". This year, as part of the new Five Year Plan, we agreed to hive off Communications into each of the several modules when and as appropriate. So I could, with justification, tick the Comms box by billing the Memory Palace as a generic method of retaining the structure and content of an oral presentation.

In F&F last week, I picking on a couple of students to be ALO, autoclave liaison officer.  I'm working through the class to fulfill this key role and keeping tabs of who has won the election. I hope that everyone will get to do it at least twice and thereby feel competent and safe in their use of this potentially dangerous bit of kit. We've had two non-fatal accidents with autoclaves in the last 18 months. One of the ALOs said that he was terrified of autoclaves because I'd told him a story about my mother getting injured by one two years ago when he was still a wet behind the ears 1st Year. I hadn't, I'd told a story about a friend of my mother where the only victim was a kitchen ceiling. A salutary bit of trepidation in dealing with potentially dangerous equipment is a good thing but not so much fear that you can't use it. Why, if we took that attitude, we'd definitely not sit into a car. We then had a discussion about the difference between being ironic [which I often am] and being sarcastic [which I never intend] because I hope I have enough respect for difference in outlook and knowledge.

It's not the first time this recall of previous dramatic story has happened. Two years ago, the management foolishly asked me to take a lab section in the Molecular Biology module. I say foolishly because I am a danger to myself and others in the laboratory. But there was a positive outcome: because I knew nothing, the kids had to step up to the plate and actually learn how to carry out protocols and interpret results because the adult-in-the-room was no use to them. It didn't always work: this was the class that hadn't a clue about quantities. ANNyway, I was explaining the operation of a gel-reader in my own inimitable [be thankful that there is only one me explaining stuff on the deg of my comfort zone] way. One of the students perked up and said
"That's like the story you told us in Biochemistry last year".
"Quite possibly, Natalie, but it might be better if you could remember what you need to know about using these instruments, rather than cluttering up your head with my off-centre stories."

One of the key concepts in constructing the aids to memory is to use images that are off-colour, frightening or hilarious. I do my best.

footnote: 'Speak, Memory' is the title of  Влади́мир Влади́мирович Набо́ков Vladimir Nabokov's 1951 autobiography. There is a LOT more to Nabokov than Lolita, which elbowed his other works aside like Harry Potter and sold 50 million copies. You could do worse than read Ada, The Eye or Pale Fire which I hoovered up when I was a teenager. Here's a fragment from Speak, Memory - I love the image of the girl's arm waiting for the nut-cracker. And another chunk of Nabokov via the Guardian.

Orkambi - the state says No

Cystic fibrosis is a medical disorder inherited in an autosomal recessive manner. Autosomal means that CF is equally common in boys and girls. This is in contrast to the common forms of haemophilia [prev] where boys are more likely to have the condition because the relevant gene is carried on the X-chromosome. Girls have an extra X which can carry a normal gene and so compensate for the error on the other one. That is why some of Queen Victoria's sons and grandsons were bleeders but none of the princesses were. Recessive means that you need to inherit two duff copies of the gene to actually get the disease. That's interesting because it shows that so long as you have some active genes, even if only half the normal amount, you'll be grand, if not completely without symptoms.

That's the genetics; the maths indicate that, as about 1 Irish child in 1500 is born with CF, about 1 person in every 19 or 20 is a carrier of the disease. Carriers can also be found in other N European countries but Ireland takes the biscuit for the highest rate. If two carriers get [it] together, then 1/4 of their children will have CF; half will be carriers like their parents; and 1/4 will be clear. You could roll the dice twice and finish up with both kids affected. Why this works. As with Tay-Sachs, you can get yourself tested at the National Children's Hospital to see if you are a carrier.  It's not worth it to check everyone but if your partner or you come from a family with CF running through it, it might be a good idea. One of the problems with the genetics and the testing is that there are several different ways in which the gene can be banjaxed. It helps to explain what the normal gene does.

We are tunnelled with mucus membranes: lungs, nose, sweat glands, vagina, vas deferens, gut . . . oh, and don't forget the pancreas. Wherever the body meets 'the outside' it tends to be wet and managing the degree of dampness is a key to keeping alighting microbes under control. One way to manage the lubrication of the mucus is to fit up epithelial cells with a channel that transports chloride ions across the cell membrane. Water will follow the chloride to equilibrate the concentration on either side of the membrane by a process called osmosis; as with cake-batter, more water = more runny.

This chloride channel is a bit of a mouthful: cystic fibrosis transmembrane-conductance regulator or CFTR to its friends. The R=regulator indicates that, as well as acting as a chloride channel, CFTR also controls the activity of other channels which shunt sodium about to balance the charge as well as the degree of dilution - sodium is Na⁺; chloride is Cl^-.

The gene is in the nucleus of each cell, the CFTR channel [R] is, or should be, in the membrane, and getting the one to the other requires a few steps.

• The gene [DNA] needs to be translated into a full-length protein
• the protein needs to be trafficked to the membrane
• then it needs to open up for business and start moving chloride. 

If any of these steps fails, then the mucus gets thick and gloopy and tastes salty if you lick it. These are the primary symptoms of cystic fibrosis. Bacteria love this thick protein-rich mucus and the immune system has to work overtime to keep on top of the extra opportunistic pathogens. If it gets overwhelmed, the lungs fill up with fluid and people can die. People with CF are in and out of hospital all the time, often for an aggressive course of antibiotics to help combat the latest invasion. Children with CF need physiotherapy to help move the mucus and bronchodilators to keep the compromised lungs open. If all else fails, and your insurance can afford it, a lung transplant can be carried out.  There's got to be a better way and the multinational pharmaceutical industry is on the case.

The problem is that there are at least 1000 mutations documented in CFTR which cause some degree of failure in the chloride channel. It's possible that you or I have a mutation in our CFTR gene that has so little effect that it will never be flagged unless Our Great Leader decides to sequence everyone's genome for our own good. T334W and T338I are flagged as 'mild', T334W means that 334th amino acid in the protein sequence, normally Threonine T has been replaced by Tryptophan W according to the conventional protein codes. By far the commonest mutation, responsible for about 75% of CF patients, is deltaF508 a deletion of a single amino acid at position 508. This is nothing to do with the channel itself [the hanks of 12 sausages shown embedded in the membrane at the top of the cartoon R]. deltaF508 rather has delivery problems because the absence of F508 makes the folding of the protein go wonk. The word on the street is that if you could ever get a deltaF508-CFTR inserted in the membrane it will function just fine.

A few years ago Vertex Pharma, a Boston based rational drug design company, launched a drug targetted at a particular CFTR mutation G551D - production=complete; a delivery=fine; channel=blocked mutation - called ivacaftor aka Kalydeco. The ball park figure for the cost of bringing a new drug to market (through a forest of trials, a blizzard of paperwork and multiple false-starts) is $1billion. The maths on G551D is that they make up about 4% of the USA's 30,000 CF sufferers. Those 1,000 people are being asked to pay $300,000/yr for the treatment. Vertex may start to show a profit on this revenue stream in the 5-10 years while the drug is still protected by patent. Obviously not every person with G551D will have health insurance or have multimillionaire parents. But this loss is offset by the market abroad. The drug makes you better than you were before because it allows a little chloride leakage but it's a long way from a cure.

A couple of years later Vertex went after deltaF508 with a different drug they called lumacaftor [who dreams up these wholly unmemorable tongue-mangling names? clearly not the marketing department] which was supposedly a chaperone which massaged the CFTR into something approaching normal shape. That prevents it being degraded and also help traffic some of the molecules to cell surface.  You've got to reflect on the fact that the drug has to get from the gut into the blood-stream and thereby course round the body to the various epithelia. then it has to cross the cell-membrane to do its massage trick inside. lumacaftor is being marketed only in combo with ivacaftor under the name Orkambi.  They can market it all they like in Ireland but the National Centre for Pharmacoeconomics NCPE has done the sums and advised against reimbursing the cost from the public purse.

Why? The spoil-sports! Well it's because the cost:benefit ratio doesn't stack up. Sorry to be so utilitarian about it. Possibly because there are more deltaF508s that G551Ds, the cost per year's treatment is 'only' €160,000. But, by one objective measure of lung function, the average Orkambi improvement compared to placebo is about 3%. The other measure preferred by NCPE and their other country equivalents is the QALY [multiprevs on The Blob]. The spokesman from the NCPE was on the radio Monday morning being blunt about matters financial; comparing the cost of supplying 700 people with this one, 97% ineffective, drug to the cost of building the new, and long promised, National Children's Hospital. That evening RTE gave a platform to a chap [the singular of data is anecdote] with CF who had responded extremely well to Orkambi. They quoted a tweet from the Health Minister who wants in an open letter to reassure CF Ireland that the analysis put out by the NCPE is "not the end" which suggests that objective, cost-benefit, QALY based decision-making can be massaged or discarded if it is politically expedient. He has instructed his Department to haggle with Vertex tp bring the price down. NCPE reckons €30,000 /year is the cost-benefit tipping point. But the pay-back time for the company on that price will be 25 years rather than 5 and the drug will be long off patent before the risk-taking venture capitalists have been paid back.

The chair of the NCPE only made his comparisons within the health service. But Ireland Inc. is brimful with blighted lives all of which could be made better with money

• ghetto-estates 
• educational deficits, in the ghettos
• job prospects, ditto
• access to low-quality 'recreational' drugs, ditto
• suicides attempted and 'successful'
• years lost commuting in cars
• homeless people
• homeless people with addiction issues
• asylum-seekers lost in red-tape for a decade
• under-funded science
• Arts, Culture and the Gaeltacht
• exorbitant rents 
• in crappy houses
• insufficient speech therapists
• obesity, fitness, food quality
• bachelor farmers
• sewage on beaches

Our Great Leader should be able to juggle the numbers rationally, so that the finite benefit of what tax-dollars buy accrues to the greatest number of citizens and no child is left wholly behind.