Thursday 31 January 2019

Davy Jones

I spend quite a bit of time mulling over End of Life Issues intubation - nursing homes - DNR - funerals - disposal of remains. I hope not too dismally.  In any case, I was much taken with a link on TYWKIWIDBI about drilling 5cm air-holes in coffins . . . so that they sink smartly and don't go all Bob the Casket and drift ashore.

Cue Master & Commander soundtrack.  The EPA in the US has some restrictions on the practice but basically asserts that everyone has the right to be buried at sea - not just Pat the Salt. So long as
  • the launch is 3 nautical miles = 3,000 fathoms = 5.5 km from the low-tide mark
  • no wreaths esp. plastic wreaths
  • no tombstones, mausoleums
  • casket to be weighted (no lead!!) and bound with six (6) bands of stainless steel, chain or natural fibre rope, holes drilled in the top and both ends [see pic R]
  • The event is reported to the local office of the EPA within 30 days.
I can't imagine what the EPA is going to do with the information on the Burial at Sea form, except file it. You may be sure I was hopping from one foot to the other until I could find out what the score in in Irish territorial waters because burial at sea sounds like a cheap and cheerful option . . . unless a force 6 gale blows up as the mourners leave harbour. It turns out that there are no regulations (yet) about the practice - only guidelines.  A couple of years ago a woman was sea-buried but reappeared on the beach many months later and caused work for the Gardai and the state pathologist - who found this body has been post-mortemed before. Nobody wants that sort of hassle so let's all resolve to do it properly. As far as possible by following The Guidelines:
  • 50 miles off the coast!
  • No embalming and no MDF cheapo coffins
    • no oak mahogany or iroku either - they last too long
    • holes drilled prior
    • robust for launch impact >!kersploosh!< and indeed impact >!baDONG!< on sea-bed several minutes later
  • 100 kg extra weight - steel chain recommended
    • No lead Pb, copper Cu or Zinc Zn
The 50 mile exclusion zone indicates a weekend trip at least - bring plenty of rum and ship's biscuit.

Wednesday 30 January 2019

Crispr: the craic is mighty

Someone who loves me and thinks I spend too much time bloggin' and not enough reading gave me a copy of A Crack in Creation by Jennifer Doudna and Sam Sternberg. Doudna is in line for getting a Nobel Prize for her invention of a gene-editing technology called CRISPR-Cas9. Sternberg was her graduate student, is now a professor at Columbia U, and can tell a story better than most scientists. He's not exactly a ghost writer because he gets full author credit. But you get the feeling that when publishers hunted down Doudna to write a popular science book about her journey, she turned to her most literate friend and brought him on board. After a few style-and-substance quirks that had me fling the book to the other end of the sofa in a pet, I settled down and read it through to the end without skipping much. I'm a scientist; I've known about CRISPR for half a decade; I know it is important; I know it is ethically controversial; I know that there are fortunes to be made; but I couldn't have explained how it works. To be honest, I'm not now better able to explain it after reading this book.

That is partly because the methodological explanation is at the start when I was aggravated by the stylistic yo-yo of alternating between over-simplifying the easy stuff and making unwarranted Curse of Knowledge assumptions about the trickier concepts. The Curse of Knowledge is when you've learned something (hard) it is impossible to unthink that knowledge to understand how an absolute beginner approaches the problem. I'll give you an unscientific example: on p232 "linkages between class and genetics would ineluctably grow from one generation to the next". In a popular book relentlessly or unavoidably would do just fine; ineluctably is a college-boy word. Next page exacerbate is used rather than worsen. I'm a college-boy - I've had to edit my fancy vocabulary [herbivore - salient - indelible] so my students know wtf I'm on about.

If you want to know how CRISPR works you could do worse than listen to Paul Anderson a high-school teacher from Bozeman Montana as he explains the system. I use his channel in my Human Physiology classes - his animations are better than I can do with words and static pictures. MIT, an institution with $ignificant $kin in the CRI$PR-CA$ game (and load$a money for propaganda), has produced their own video with fancier graphics than Bozeman's but gaping holes in their story. MIT don't trouble to explain that CRISPR is an acronym [clustered regularly interspaced short palindromic repeats] but tell us <yawn> that A pairs with T and C pairs with G. Every word in [clustered regularly interspaced short palindromic repeats] is a key clue to how the system works and what is its potential. No surprise that Jennifer Doudna was invited to address TED-Global in London in 2015, her technical explanation isn't as good as the high-school teachers perhaps because she's too close to it. WIRED's Biologist Explains One Concept in 5 Levels of Difficulty isn't what it says on the tin (he's hopeless with the easy stuff and seems to know less than the experts) but advances the discussion in useful directions. One could wish that youtube presenters would consider not-Anglophone watchers and Enunciate Clearly: problem not pro'm; ability not abil'y. tsk!

If a 7 minute video is tl;dw for you, you can skip to the fact that this technique has the potential to precisely remedy the genetic damage that causes cystic fibrosis or retinitis pigmentosum or thalassaemia <etc.> and leave all the other genes unchanged. Parents who bonk bonk love each other very much but are carriers for one of these diseases can have children "of their own blood" but no chance of developing the disease that dogged their ancestors. You'd have to be a hard-hearted god-botherer to be against such tilting of Fortune's table IF the precision and reliability of the edit could be guaranteed.

But what about cosmetic changes [getting rid of all those Irish freckles] or smoothing out natural variability so that everyone has faster reflexes, nobody is on the autistic spectrum. If you can change such factors reliably and cheaply (which is a probability) then people who don't or can't or won't avail of the opportunity to change themselves and their children may get excluded. Me, I'd rather cherish and support The Different because diversity is intrinsically interesting: when conditions change [think End of World issues like carbon footprint] then maybe slower more deliberative folks will be an asset while the rest of us run around like headless chickens. We need to think about these ethical issues because genetic editing is at the gate and a lot of rich people have invested a chunk of their money in the technology and want a return of their investment.

Did someone mention money? In her book, Jennifer Doudna [L above] absolutely avoids talking about the Patent Law dispute her Institution, UC Berkeley, [and her pal and co-inventor Emmanuelle Charpentier [R above] of the Helmholtz Centre for Infection Research in Braunschweig, Germany] is fighting with Feng Zhang [sandwiched above], the Broad Institute and its parents Harvard and MIT. Berkeley & Co. want exclusive use and licencing of the whole field. Broad & Co. hold that their boy was the first to make a usable product out of CRISPR . . . perhaps while Doudna was agonising about the ethical issues and holding workshops to discuss them. The US Law is currently supporting the case from The East Coast while the Europeans are favouring The Californians - perhaps because Emmanuelle Charpentier is Euro-french. That split decision will play havoc with the development of CRISPR-tech because drug-companies work best in a Global Village - bigger population and a uniform playing field = more profits. I hope Doudna, and indeed the other two, makes a fortune out of these ideas and that they share it with all the people who inched the idea along the way. And watch the Nobel space!

Tuesday 29 January 2019

Trust Axis

Week 3, term 2 ✓.  25% of my hours this term are on the remedial maths axis. That's not to say that all the people in the room need help because their math-anxiety is overwhelming: some appear to be both competent and curious about the edges of my competence in, say, MS-Excel. I can usually amuse such students if I ask them to plot a pair of unlikely variables against each other and maybe calculate a correlation coefficient. In class on Friday, I looked over the shoulder of my willing-and-able Magyar-Irish student, to see a map of early 20thC Central Europe! It was a long way [110 years and 2,000km!] from the class assignment, but he said he was making a pie-chart of the ethnic diversity in the Austro-Hungarian Empire prior to Sarajevo 1914. Well, that's at least as valuable a question as my madey-uppy dataset of Iron and Zinc concentrations. His graph [R] was particularly interesting to his Polish-Irish neighbour who hadn't previously appreciated that 5 million Poles had sworn fealty to Erzherzog Franz-Joseph the Last. Imagine how interesting it must have been living in Vienna or Budapest in 1910 - so many languages, so many cuisines, such a variety of dress and dance and song. Hark! the strains of the contemporary march "Die Bosniaken kommen".

Voices off: Don't mention the Axis! That's the next War. Sorry, lads, I've started on Axis [look at the post heading f'chrissake] but a very different beast altogether. If you've been reading The Blob since it was born 6 years ago then a) you are in a very small set b) you might be forgiven for thinking that The Institute has but one teacher - by the name of Bob. That is not true of course but reads that way because of an early policy decision to preserve [a thinly veiled] anonymity and therefore allow me considerable freedom to tell it like it is. Thus The Blob has reported on events in my classrooms and labs; on visiting speakers and other public events; on some of the absurdities of management; on what I read in the papers . . . but decided I wasn't going say anything negative about my teaching colleagues or the secretarial staff or the technicians. There have been times when I've been disposed to write about these people because they had really annoyed me, disrespected the students, or failed spectacularly to do their job: but I've held fire. De collega nil nisi bonum, eh?

In October last year I had a "difference of opinion" with two of the other lecturers about the conduct of final year research projects. It was quite surprising to hear this first coming at me by scuttlebutt through intermediaries and very surprising when it came up and was minuted in a Faculty Meeting a few days later. But it didn't surprise me that one of the youngsters had chosen a Jacques Bonhomme open-forum approach while the other had preferred a tittle-tattle SoS snark of snake route. Each fellow was naturally behaving to type. Predictably these events caused a mild shit-storm of indignation - who would be next for trial by innuendo??  There was a bit of an enquiry as to whether there was any substance in the allegations: if there is going to be bad-mouthing in the scientific community, then it would be scientific to have the allegations both fact-checked and evidence based. Last week we had the next Faculty Meeting, when I was expecting the issue to be put to bed. But it never happened. That was partly because a far bigger management shit-storm blew up which took a lot of deliberation to decide about. But it was also because I didn't feel righteous enough about the disagreement to insist on another difficult discussion eating into everyone's dinner hour.

When I got home in the evening The Beloved and I talked over the non-event and I said something about being spineless nice to people because I liked to be liked. I had for example dropped in on Jacques B, whom I like and respect, the evening before the meeting to say "I just wanted to reassure you that I don't intend to get all shouty tomorrow". He had apologised (twice) and I didn't want the poor chap to lose sleep worrying about an Ordeal by Faculty let alone the far more frightening jihad by Baobab al Antiquam. TB said that, in her life, she found it easier to take adverse comment if it came from someone she trusted. That sounded a little redundant to me because I thought that 'trust' and 'like' were essentially the same; while she seemed to be claiming that they were on orthogonal [independent, at right angles as L] axes. If they are really independent, I said, we should be able to fill the bottom-right and top-left corners: people whom we trusted but didn't like much and/or people we liked but didn't trust. YMMV but I was scabbling to find examples.

For about 10 years I was the father of teenage girls, who were thankfully triple-M monogamous and minimally moody through the walking-out process. A couple of weeks ago, I was talking with another father-of-girls and asked "Is D still going with that Most Unsuitable Bloke From Enniscorthy MUBFE?" Apparently not, he'd been dumped a while ago (and good riddance). I then asked The Dad if any of the parade of dated lads were liked by the parents  - even if they were considered to be unsuitable for their daughters. Didn't get a coherent answer to that one but it seems possible:- young feller who is polite, helpful, deferential and funny but also feckless, spendthrift, and far too frequently drunk. People are complex and interesting because they are multi-dimensional.

Monday 28 January 2019

A medical first in Ireland

In this months issue of the Irish Medical Journal IMJ, three doctors from Tallaght Hospital record a peculiar case of self-abuse. Young chap had presented himself to hospital because his arm was all swollen, painful, red and hot - tumor, dolor, rubor and calor - the four classic symptoms of inflammation. The patient revealed that, to cure a back-ache, he had elected to inject his own semen intravenously every month for a year and a half. A comprehensive search of the medical literature revealed that no similar case had been reported since records began. A bit like the Darwin Awards for people who have offed themselves in extravagantly silly ways [examples], such stories get quite a bit of traction. I felt I had to share it with you even at the risk that several readers might try a copy-cat self-treatment for a real or imagined illness. Semen is, after all, free and readily available [to chaps anyway] and in all sorts of metaphorical ways is deemed to be 'potent'.

Searching the medical literature through Pubmed is an essential part of medico-scientific research: you need to know if anyone has been there before - they might have a helpful remedy. The current investigation reminds me of my training set of pubmed search terms which included "vacuum cleaner injury". Don't go there if you're squeamish and don't read Deadspin's 2018 Year in Review list of objects retrieved from people's orifices. Don't compare and contrast 2017's list: same picture different inventory.

This report is only vaguely related [even in my 'mind'] to the widely misunderstood tale about Irish poet laureate WB Yeats and his monkey-gland potency injections - which probably never happened. In that story, I used Yeats as part of the back-story on experiments where youthful blood is injected to old veins in an attempt to live forever. This treatment has gone commercial at least partly because blood-transfusion falls under medical regulators' categorization "generally recognised as safe" GRAS. Ambrosia Inc. will sell to Patriarchs 2 litres of young blood delivered for $8,000. It's not clear how that $8K is divvied up among the donor, management, share-holders and lawyers.

Sunday 27 January 2019

Hello LO

L is for list

Saturday 26 January 2019

Driving Miss Ursula

I occasionally scan 3quarksdaily to see whaaaaat's happenin'? on the liberal arts front. A tuthree days ago I was pointed to a delightful essay in Granta in which Alison Smith gives a very personal tribute to Ursula le Guin. In 1988, when Alison was 18 and Ursula about 40 years older, the famous writer came to visit Rochester NY and the young student was assigned to be her gopher-chauffeur for the week. Alison had been a huge fan of Ursula's books since she was a bookish sub-teen but didn't get gushy and completed her minder's assignment with discretion, honesty and empathy. My reading is that the author found her company far more congenial than that of the English Faculty, who covered their awe of the famous write with a layer of bluff blokey bravado that must have been tedious if not oppressive. By the end of the week young Alison had been transformed by the respect and kindness of the older woman into someone with ambition, confidence and a, probably misplaced, fascination with French culture. She was also determined to be a writer, rather than having pretensions to being an author. To this end she started writing, more and with more regularity [ahem - like myself], until now 30 years later she is scrabbling some sort of a living from her craft. You should read the memoir. If you have a bookish, possibly gay, teenager / twenty-something about your household then you should be sure to make a copy for them. Ursula le Guin died this time last year - I've written my own tributes.

About 15 years ago, The Beloved TB came out . . . and embraced the practice of the Vietnamese peacenik and Dharma teacher, Thích Nhất Hạnh. After being exiled from his native land during the Vietnam War, TNH started a community in the Dordogne Valley in SW France called Village des Pruniers / Plum Village. Round about the time that I went on my transformative pilgrimage to and from Santiago de Compostella, TB went to Plum Village for a week of meditation and silence and underwent her own transformation.
We subsequently fixed up a telephone booth in the yard at home to facilitate our emergency clothing changes before flying off to rescue sheep caught in wire fences. In 2006, we took Dau.I and Dau.II to Plum Village for the Summer Retreat because it was billed as For Workers in the Neurosciences. I've written about how a succession of contingent accidents found me addressing 1,000 participants about Mindfulness in Medicine. I was famous for five-and-a-half minutes [me and Onnie were so taken with the theatre that we ran over by 30 seconds].

In 2011, Plum Village announced that, as their retreats were getting flooded by Irish citizens in need of mindfulness, Mohammad TNH would proceed to the mountain four green fields of Ireland . . . and could somebody local make that happen? That somebody materialised as a small committee of dedicated TNH fans including The Beloved. It was like having to organise part of the World tour of a middle ranking rock band [with fewer drums and guitars, but more bells and saffron. . . and no drugs or alcohol]; because Hissonour announced that his party would include at least 50 monastics from Plum Village. The Itinerary settled down to a) Filling the Dublin Convention Centre with 2,000 bodies for an evening talk; b) Filling the Killarney Convention Centre for a three-day retreat for 800 people; c) Addressing the Norn Iron Assembly at Stormont. A succession of contingent accidents found me as the designated driver of the Popemobile a rented 7-seater people carrier. With my grey hair, dismal-Eeyore demeanour and dressed in my interview-wedding-funeral suit with a sober tie, I looked the part. A peaked cap would have degenerated the costume into parody, so I skipped that.

Very respectful I was too:  not speaking unless addressed, not restlessly searching for soccer commentary on the radio, doing my best to go easy on the gear-changes. There was one dicey moment on the way up to Stormont [R] when I missed a turn in suburban Belfast and did a quick-thinking U-turn neeeeooooww across two lanes of oncoming traffic. The monk sitting in the passenger seat turned a whiter shade of pale but the VIPs in the back seats were in a state of satori - they didn't yelp! anyway. The following day we headed back to Dublin. TNH elected to sit in the front seat to see a bit of the countryside; his team of attendants sat in the back singing Vietnamese pop songs and generally larking about - because the Stormont gig had gone rather well and we were all relaxing. TNH was quietly amused by a sign on the Gormanston toll-booth:
 Arrive Alive 
and when we finally pulled into the place they were staying in Dublin that evening, he put his hand on my arm and said "Arrive Alive" with a little nod of appreciation. Maybe he'd been more alert than I thought when I did the two-wheeled U-ie the day before.

Friday 25 January 2019

Chunder rice

Being hospitable folk with a few drops of Irish blood, we always cook for the unexpected guest. D'ye remember the old instructions for making a pot of tea: "a spoon of tea for every person round the table and one for the pot" . . . that resulted in tea the colour of tomato soup and able to strip the skin off your palate? . . . not to mention strip the enamel off a tin plate. There is always something left-over in a small pot in the fridge: half a cup of rice; a portion of caldo verde for lunch tomorrow; the last two boiled potatoes; a corner of lasagna. As we gave up on microwave ovens some years ago, these bits and pieces require some ingenuity to make palatable - and safe.

At The Institute, we're in the middle of Yr3 Food & Fermentation Microbiology, this week we're hoping to isolate Gram-positive spore-formers. That would be Clostridium spp. and Bacillus spp. F&F is an introduction to microbes that are either a) essential for the making of some foods - Lactic Acid Bacteria LABs mainly or b) bacteria associated with food spoilage. Clostridium [botulinum] - [tetani] - [difficile] and Bacillus [anthracis] are in a third category c) microbes that will kill ya or make you give at both ends.  Most years, I remember to tell the students about the problems with eating re-heated rice - it's the Bacillus cereus silly. That's relevant in this context because these bacteria, when confronted with adverse circumstances - drying out; boiling water; 70% alcohol; caustic soda - can curl up into a ball and wait it out.  This "spore" is remarkably robust to external insult and can be remarkably long-lived. One of the concerns with the melting of Siberian permafrost is that it will wake up Bacillus anthracis spores which have been in limbo for hundreds of years and release a pestilence of anthrax through any caribou and people who get downwind.

But, I add, nonchalant-like I've been eating re-heated rice on a weekly basis for 4 or 5 decades and I've never had to talk to the porcelain telephone.  Nor has anyone in my family. B. cereus is a natural inhabitant in soil and on vegetation and appears to have a particular preference for rice. You boil it up and that kills almost all the bacteria but some of the B. cereus start the sporulation process and hunker down to wait. A hour later, the temperature is waaay down and the bugs start to wake up again. If you slam them in the fridge at 4oC that will put a stop to their gallop by slowing their cell division but it won't kill them. Every time they are left at room temperature for 30 minutes they double their numbers. Leave them over-night on the counter and they will have increased 2^20 = 1 million-fold.

Here's an interesting but tragic story of an adverse event: A Student Ate 5 Day Old Pasta For Lunch. This Is How His Liver Shut Down. Title says it all: poor fellow died of acute liver failure from the toxins produced by B. cereus but made his prognosis much worse by topping off his fizzy pasta with a generous slug of aspirin [it's the Reye's Syndrome silly]. via MeFi where lots of on-topic discussion and commentary.

You know the Aussie for vomit = Chunder?  supposedly shortened from Watch under! A list of synonyms seems like a bowlful of funny perhaps because they sound the part - barf, hurl, chuck, boke, ralph, hork, puke, spew, heave, yark, york . . . and the phrases: whistle beef; technicolour yawn; russian salad [L]; woof cookies; bark at the ants.

Thursday 24 January 2019

Helping yourself

Earlier this month I was a bit jaundiced / skeptical about finding a cure for alkaptonuria. It may work out for Nick Sireau and his boys but nitisinone is not a cure: it just transfers the molecular rubbish to another place. You don't get the dark-skin, joint-pain and eye-damage but you get "elevated tyrosine levels, thrombocytopenia, leukopenia, conjunctivitis, corneal opacity, keratitis, photophobia, eye pain, blepharitis, cataracts, granulocytopenia, epistaxis, pruritus, exfoliative dermatitis, dry skin, maculopapular rash, alopecia, bloated abdomen, dark urine, abdominal pain, feeling of tiredness or weakness, headache, light-colored stools, loss of appetite, weight loss, vomiting, and yellow-colored eyes or skin . . . instead. I have been critical of fantastically expensive, marginally effective drugs getting pushed by politics, instead of being refused licence by accountants. Parent's lonely fight to save compromised child is A Story which a hungry free-lancer can write up for the Grauniad, the NYT, or the Sligo Champion. Search keywords: quest, desperate, fight, tireless, crusade, tragic, diagnosis, genetics.

A week ago, a variation on the theme popped up on MeFi [comments informed and wide-ranging] and I followed through to Wired for one of my 3 free reads there this month. The hook here is that, although there is a cute toddler, it is the girl's mother who is trying to save herself from a late-onset, rapidly degenerative brain disease called fatal familial insomnia FFI. Sonia Vallabh and Eric Minikel [looking right sciency L - NPR source], who knew bugger-all science before Sonia's fateful diagnosis, went back to college and eventually got to be lead authors on a massive paper in Science Translational Medicine which compared the genome sequences of thousands of people with prion diseases and thousands of unaffected controls. They also set up a company (Sonia was a lawyer) Prion Alliance as a vehicle for gathering slabs of money for The Cause.

Prions have featured semi-incognito on The Blob as Kuru; they are also involved in Mad Cow Disease [aka bovine spongiform encephalopathy BSE], scrapie is sheep and the human equivalent variant Creuzfeldt-Jacob Disease CJD. It is news to me but FFI is another prion disease triggered by a different mutation in the PrP [Prion Protein] gene.

The PrP gene is found in all mammals and may have an essential function in copper transport, and/or something to do with synapse health between neurons and/or some association with circadian rhythms and the sleep/wake cycle. Bad things happen when the protein derived from the PrP gene flips to a 3-D structure that a) cannot flip back to normal structure and b) cannot be broken down by clean-up enzymes or undone. It then accumulates in lumps, especially in the brain, causing a cascade of unpleasant neurological events to occur: incontinence, blindness, loss of speech, loss of swallow, twitching, dizziness ataxia, insomnia. Death follows about a year after first symptoms.

It is believed that the flip to the indigestible form of the protein can be induced by contact with another copy the misfolded protein . . . acquired through the diet by eating meat from a Mad Cow or through blood transfusion from someone who has eaten some of that meat and is now in limbo waiting for symptoms to appear. The Irish blood transfusion service IBTS refuses donations from anyone who lived in the UK during the 80s when variant CJD and BSE were being revealed in that country. BSE was spread through the sketchy agri-practice of feeding cattle a protein-rich feed . . . made from ground up cow-parts. The same intensive cattle-rearing practice was going on in other European countries at the same time but the French authorities, for example, didn't look very hard for BSE and so found no cases. French blood is thus acceptable to the IBTS but not mine or that of any of the thousands of Irish people who lived in England in the 80s because there was no work in Ireland. Shamefully, only 4% of adults in Ireland are blood donors and I think the IBTS really needs to do a risk assessment on excluding me and The Boy and The Beloved and three of her siblings.

One of the interesting fall-outs of the scientific community acquire two smart committed grown ups to do research in FFI, is that Sonia and Eric came with a different tool-kit, different expectations and different ways of thinking. They were a real asset in lab meetings because of this intellectual flexibility which provided alternative viewpoints; perhaps especially in response to "that's impossible".

Wednesday 23 January 2019

Where there's muck, there's brass

Have I told you about fatbergs? I have, begodde! We were down for lunch on the Wexford Coast on Sunday and very nice it was too. It was sharp and sunny outside with the Kerragh Islands on the horizon black beyond a greeny sea. I was glad we could sit beside a roaring log-fire rather than garnering virtue [and yet more plastic buoys, rope and fish-boxes that I really have a use for] with a walk along the beach. As householders myne hoste and I were comparing notes about storm damage and house-keeping. It seems that a few months ago, their foul-water pipe backed-up from a sclerotic clot of congealed fat. They hadn't been as obsessively careful as us about washing greasy plates and pans in the kitchen sink and the residue had come back to bite them. For a variety of reasons, he elected to clear the pipe chemically rather than mechanically and dumped a load of hot sodium hydroxide / caustic soda / lye / NaOH down the kitchen sink and left the room. It was okay in this sense - that the water started to flow again. But he hasn't done a colonoscopy yet to estimate when he should buy the next packet of NaOH. Basically what's happening down there is that the Na+ and the fat are making soap which, as you know is water soluble. If you could get a really good marketing team in place, you could do this on an industrial scale with matter from fta-clogged pipes and sell the soap under a brand-name like Flush!. Well it's a better name than Enema - the soap that cleans the darkest places.

The after-lunch chat shifted slightly from cleaning out fatbergs to monetizing them - but not as soap but rather as bio-diesel. Argent Energy from the English Midlands is actively scavenging fat-bergs, and heating them in a huge vat - remember that these slug-like tangles can weigh in at 10 tonnes or more. The wet-wipes, sanitary towels, hair, dental-floss and nappies (who would throw a diaper down the t'ilet? What were they thinking?) all sink to the bottom or float to the top and the now liquid grease can be run out of a spigot at the base of the vat. Like pressing olives, you could have first run extra virgin diesel and them squeeeeze the mass until it yields the last drop of discoloured goop.  When the hot liquid cools, I'm guessing that like chicken stock, the fat floats to the top and the water-soluble proteinaceous soup sinks. I was making soupe aux choux over the weekend, for example, and the liquid cooked out from the belly of pork cooled into a rich brown gelatinous stock covered by a layer of pure pork fat.

The Argent plant in Ellesmere Port near Liverpool can recover 25%-40% by weight of oil from fatberg and has a production capacity of nearly 100,000 tonnes of the good stuff each year. Previous to their enterprise, fatbergs were a hazardous, noxious waste product that was burned or land-filled. Now it's getting a second lease of life in a repurposed form before it goes up to make carbon footprint in the sky.  Argent has a regular order of 30 tonnes a week from one [large] sewage treatment plant in Birmingham. There are 9,000 such places in Britain.  I hope it works out for all parties.

Tuesday 22 January 2019


When I was learning genetics in the 1970s, it wasn't quite possible that an ambitious graduate would know ALL there was to know in the field; but it was surely a lot simpler and less extensive back then. The half dozen standard text-books all re-hashed the same war stories to illustrate the most exciting or the most fundamental aspects of genetics. One well-worn story was about resistance to malaria effected by being a carrier for the haemoglobin variant that causes sickle-cell anaemia. That revelation was largely the work of a single medical geneticist called Tony Allison. Another of the paragons was Archibald Garrod [R as a suited Edwardian walrus] an English physician who pioneered the field of inborn errors of metabolism. We would call them genetic diseases now. The deal is that:
  1. people are clearly not well; 
  2. their adverse symptoms make a distinct syndrome which can be recognised in other patients
  3. some of those other patients are relatives of the first case. The disease runs in families, to the extent that, in some cases, you could find distant cousins by their shared medical peculiarities.
What is remarkable about Garrod is that he worked out the genetics of Alkaptonuria and published it in 1902. This was barely a year after Carl Correns, Hugo de Vries, and Erich von Tschermak-Seysenegg rediscovered Mendel's laws of inheritance. Effectively, when Garrod started his investigations, there was no useful knowledge of Genetics, so he was working blind. Alkaptonuria is rare, distinctive and peculiar. The most obvious early symptom is that patient's pee turns black in the piss-pot which must be disconcerting  when first noticed. As these symptoms kick in before weaning, it is the parents who are distressed. Garrod didn't know what the biochemical cause was, but he mapped out pedigrees and proved that it was inherited as an autosomal recessive. That phrase means that the disease is a) as common in boys as girls b) it requires both parents to carry the defective gene. Years later, it was established that the black stuff was homogentisic acid; a metabolic breakdown product of the amino acids tyrosine and phenylalanine. It gets peed out because a key enzyme in its metabolic pathway, homogentisic acid 1,2-dioxygenase, is missing or defective. There is no cure and the disease is progressive: the homogentisic acid can't all be forced through the kidney tubules, so the toxin accumulates in the joints, under the skin,around the heart valves and in the eyes. It's a bit like gout, therefore, where uric acid crystals accumulate in joints. Longevity is not affected but quality of life definitely goes downhill and modern treatments involve hip and knee replacements when these joints become too painful to use. Phenylketonuria PKU is another inborn errors of metabolism from the same aromatic amino acid degradation pathway. That condition is identified within hours of birth with a heel-prick test to yield a few spots of blood on fiche of blotting paper.

Being of historical interest and colorful is not sufficient to trigger a Blob on alkaptonuria but a four page article in last week's Nature adds sufficient weight. A father’s fight to help his sons - and fix clinical trials - Nick Sireau’s quest to give his sons weedkiller could help thousands struggling with rare genetic conditions. That about sums up the sensational aspects of the essay. The problem is that nobody should want to 'fix clinical trials' unless it is the share-holders and sales-force of the pharmaceutical company which is marketing the therapy. Mr Sireau's boys were born with alkaptonuria and he was determined to find a cure, preferably before the lads grew up and started to show the worst of the symptoms - typically in their 30s.

There is a cure, of sorts, but because alkaptonuria is so rare it is hard to get sufficient numbers to carry out a clinical trial of its efficacy. Nitisinone [structure L] also interferes with the correct function of the tyrosine degradation pathway but one enzyme upstream as shown in the metabolic pathway [above L]. Under this drug's regime there is no accumulation for homogentisic acid because there is no accumulation of its immediate precursor. This means that other tyrosine degradation products, from further up the chair, do accumulate. Although the diet can be restricted to minimise the intake of tyrosine and phenylalanine, and that helps also.  The pathway, as we now understand it, shows just how complicated things can be to keep things turning over and keep essential nutrients like tyrosine and phenylalanine in homeostatic balance - so that they are present in just right Goldiloxian amounts. And for most of us, most of the time, it all works nicely, but disable any one of the multiple steps and the whole elaborate pipeline is banjaxed.

Nitinisone costs about $50,000 or $60,000 per person per year and they've done the figures on using it to treat Type I Tyrosinaemia a disease caused by a defect in the same pathway as alkaptonuria and PKU. Mr Sireau believes that it will have positive effects for his chaps but there is no good evidence that it makes the adverse symptoms measurably better. The US Food and Drug Administration FDA won't allow the drug to be marketed without that sort of positive benefit data. Nobody should be allowed to pay so much for something that doesn't work. Especially, this should be stopped if somebody else is picking up the bill. It seems that Sireau's advocacy group has blagged the European authorities to accept a less standard of 'success'. If, under treatment, the concentration of homogentisic acid falls significantly then that will be enough - it will be what is called a surrogate marker.  We-the-tax-payer will then start paying for the drug regardless of whether the 'real' adverse symptoms like pain, joint flexibility, heart dysfunction, eye disease improve. If it don't work; don't pay for it. It's better to grimace and bear it without treatment than to grimace just as much and be out of pocket. I dunno, I'm not certain about the ethics or economics here: you read the Nature piece and decide where you want your share $50,000 allocated. Trolleys? More nurses? Pay-hike for nurses? Mental health? New children's hospital? OR "I'll keep my share of tax-dollars, thanks very much, less tax will mean I can build my much desired (and to be admired) gazebo in the back garden"

A final grimace and bear it irony. Archibald Garrod had three sons. They all joined the army in WWI and they were all killed: Thomas 10th May 1915; Alfred 20th Jan 1916; Basil  4th Feb 1919 (Spanish 'flu). No amount of money could save them.

Monday 21 January 2019

I demand to have some booze

New Year's Day I was looking through our Christmas Hamper from Baskets Galore. As with the rest of Christmas fare, I scanned the sell-by dates and started on those goodies most nearly gorn-beyond.
 4 Luxury Mince Pies    with Brandy  (05 Jan 19) had to go down the hatch first. With the  Brandy   and all, I was careful not consume any of them if I was planning to drive.

But what is this? The declared ingredients:
Pastry (Butter (Milk), Flour (Wheat flour, Calcium, Iron, Niacin, Thiamin)), Sugar, Water)
Mince filling: (50%) (Apple, Sugar, Waxy Maize Starch, Water, Dextrose, Preservative [E202, E260], Mixed Spice (Coriander, Cinnamon, Ginger, Cloves), Caramel, (Glucose syrup), Dark Vine Fruit, Mixed Peel, Vegetable Suet (Non Hydrogenated Oils (Palm and Sunflower)
(Wheat flour, Calcium, Iron, Niacin, Thiamin))
contain a lot of sugar (Sugar, Sugar, Dextrose, Glucose Syrup) but not even a sniff of Brandy. E202 is potassium sorbate and E260 is acetic acid - neither being ethanol let alone brandy. Altrhough acetic acid [=vinegar] is a natural oxidation product of ethanol.

I demand to have some booze! [Withnail alert]
I've written, more in sorrow than in anger, to Baskets Galore and Ditty's Home Bakery, but after a full working week no answer is forthcoming.

I was on about the ToC of (unboozed) mince pies a little over a year ago

Sunday 20 January 2019

Sunday Miscellany 20 Jan 19

This A is for 'Orses, B is for bogwit trope can be constraining and I'm accumulating a bunch of other interesting-to-me links so I'll dump them out here-and-now before I go to Mass.

Saturday 19 January 2019

Gutted for Giertz

Damn damn damn!
I wrote about The Queen of the Shitty Robots last May. That would be Simone Giertz, college drop-out who came back to make amazeballs contributions to The Public Understanding of Science. She's a hoot and her robots are the antidote to hubris - ya gotta love her. The tragedy struck when she put up an episode of her youtube channel to explain that she had a brain tumour (called Brian, because ridicule helps) but that surgery and therapy were in the offing and we'd see her later. Now it transpires that her tumor has bounced back, sooner than expected; and more distracting medical hell will have to endured. It is hard to see any good in this news because I am not Dr Pangloss who on learning that he had contracted syphilis said "Not at all, it was a thing unavoidable, a necessary ingredient in the best of worlds; for if Columbus had not caught in an island in America this disease, which contaminates the source of generation, and frequently impedes propagation itself, and is evidently opposed to the great end of nature, we should have had neither chocolate nor cochineal." I quote this from Candide this because a brain tumor is somehow the worst fate imaginable for a creative thinker.

I cannot, right now, bear to watch Giertz breaking the bad news.  My helpless rage might find some solace with MeFi commenter CynicalKnight. "I hate that a fun person is going like this. I'm going to my workshop to smash something with a hammer." I'll try that as soon as it is light tomorrow.

So you miss nothing, here's Pangloss in Voltaire's French:
Point du tout, répliqua ce grand homme; c’était une chose indispensable dans le meilleur des mondes, un ingrédient nécessaire; car si Colomb n’avait pas attrapé dans une île de l’Amérique cette maladie qui empoisonne la source de la génération, qui souvent même empêche la génération, et qui est évidemment l’opposé du grand but de la nature, nous n’aurions ni le chocolat ni la cochenille.

Linguistic shift

I mine A-Word-a-Day for quotations for the kitchen calendar and to keep my finger on the pulse of the quirkier aspects of the English language. This week they were floating a handful of adjectives with the challenge to re-coin them into nouns. It's a rather artificial conceit because very few neologisms invented by earnest wordsmiths, actually stick in the language. While vibrant new usage floats up from the ghettos and gets adopted by everyone. "Ooops, my bad" - do you use that phrase? It's an excellent recent example of recent adj-noun shift. AWAD uses "fat": noting that it was an adjective for 500 years before becoming a synonym for lard in the 1300s.

My contribution to the trope:
"Well I'm happy out! The Gaelic Athletic Association GAA in Ireland attracts fierce local loyalties. Each county plays in a strip of one, two or three colours and has acquired a nick-name, often from some real or supposed historical fact. One monnicker for Wexford is the Yellowbellies supposedly because Caesar Colclough, a 19thC magnate and a distant ancestor in my horse-riding protestant family, sent a team of hurlers to England wearing a distinguishing yellow sash. They comprehensively beat a team from Cornwall and the cry "Up the Yella'bellies" resounds down the years. Next time I'm watching a match in Innovate Wexford Park I'll try "Up the Xanthic" and hope I don't get tonked with a rolled up copy of The Enniscorthy Guardian."

In the interests of completeness, I have tabulated a list of the 26 counties and their nick-names:
Carlow Scallion Eaters Longford Slashers
Cavan Breffni Louth Wee County
Clare The Banner Co Mayo Westerners
Cork The Rebel Co Meath The Royals
Donegal Herring-gutters Monaghan The Farney
Dublin The Jacks King's Co Biffos
Galway The Tribesmen Roscommon Sheep-stealers
Kerry The Kingdom Sligo Yeats Co
Kildare Lilywhites Tipperary Premier Co
Kilkenny The Cats Waterford The Déise
Queen's Co O'Moore Co Westmeath The Lakemen
Leitrim The Wild Rose Wexford The Model Co
Limerick The Treaty Co Wicklow The Garden Co
Some of these are clearly a bit pejorative, but even so will have been adopted with pride by the inhabitants. Like artists like Derain and Matisse who were damned as Les Fauves and rather liked the epithet. Actually some of these nicknames are new to me, but then again I've never watched a GAA match in Co. Louth.

Friday 18 January 2019

Mary Oliver gone

Mary Oliver died yesterday of cancer but of 'a good age' having been born in 1935. She was an unpretentious poet of the natural world.  She shared her observations with a sensitivity to how the words sounded, and worked to make those words be an echo of the true voice of the world in which she chose to immerse herself.
"the world offers itself to your imagination / calls to you like the wild geese, harsh and exciting" . . . In Blackwater Woods.
The Journey
One day you finally knew
what you had to do, and began,
though the voices around you
kept shouting
their bad advice--
though the whole house
began to tremble
and you felt the old tug
at your ankles.
"Mend my life!"
each voice cried.
But you didn't stop.
You knew what you had to do,
though the wind pried
with its stiff fingers
at the very foundations,
though their melancholy
was terrible.
It was already late
enough, and a wild night,
and the road full of fallen
branches and stones.
But little by little,
as you left their voices behind,
the stars began to burn
through the sheets of clouds,
and there was a new voice
which you slowly
recognized as your own,
that kept you company
as you strode deeper and deeper
into the world,
determined to do
the only thing you could do--
determined to save
the only life you could save.

Thursday 17 January 2019

Fast now live forever

Because I was a perfectly ghastly person in a previous life, The Fates have made me convenor of the Wexford Science Café, which meets of the 3rd Tuesday of most months in The Sky and the Ground on South Main Street, Wexford [all welcome!]. It's been running for 4 years now and has featured many times on The Blob, because, well, Science Matters. "Running" would not be be the best verb to describe WSC's progress because convening a schedule of speakers is more like pushing a bus uphill. But enough of this passive-aggressive moaning, we've just had a Third Tuesday and nearly a dozen people turned up and everyone contributed to the discussion. So that's clearly a success.

We had on the table a May 2018 paper [see R under the watchful elbow of His Blobbiness] about the relationships among: periodic fasting, fatty acid oxidation, intestinal health and longevity. Here's the Executive Summary from the MIT Press Office. Of course as an impoverished independent scientist, you may be sure I wasn't going to shell out $31.50 to Elsevier to read the whole paper; but SciHub delivered. The discussion made us briefly Famous on Twitter. It is prolly a coincidence that Luke O'Neill was talking about aging on Newstalk FM the very next day. Calico, the company being admired by O'Neill, has a string of prestige papers on senescence. We've met their CSO, David Botstein before. The model organism for longevity is the naked mole rat Spalax ehrenbergi. They're right small but they live for more than 30 years. It may be to do with caloric restriction. Seemingly Spalax finds itself without food periodically and the hypothesis is that drives its long life.

Me, I'm a fan of the Harry "BIG" Secombe diet "You can each as much of whatever you like . . . so long as you don't swallow." I spent more than half my adult life toting around about 10kg of extra lard under my jumper. When I started working at The Institute six years ago, all I ate between breakfast [two small slices of toast] and supper was a modest cheese-and-nothing sandwich made on home-made sourdough bread. There's a canteen at work: cooked breakfast; cappuccinos; packed sambos; muffins, cookies; massive plates of meat-and-two-veg; dessert; candy-bars are all available. But I'm too mean, and frankly, too busy at work to go for any of those things - unless it's a free dinner with a visiting speaker. That didn't make much difference to my [over-]weight because when I got home, I'd have m'dinner and then graze through the bread-basket and cookie-jar. For the last couple of years, I do this far less often, indeed I metaphorically or actually brush my teeth immediately after supper most days. Consequence is that I'm down to a little less than my 18-to-30 weight. It's a real bind after Xmas - not only is that far too much cookies and calories in circulation BUT I see half price stollen in Aldi and 6 mince-pies for 45c. That makes them cheaper than potatoes, so it's hard to say No.

We spent some time at WexSciCaf talking about the 5/2 diet because that accords with the caloric restriction hypothesis. Deal is that you can eat around you for 5 days so long as you go cold turkey eat nothing for the next 2 days. That would be far too much for most Westerners so the advocates of 5/2 allow you 500Kcal a day on the off days. That's possible surely:

  • Breakfast:
    • 2 slices toast = 140 Kcal
    • 10g butter =70 Kcal
    • Total = 210 Kcal
  • Lunch
    • 2 slices bread = 140 Kcal
    • 20g cheese = 80Kcal
    • lettuce = zero
    • Total = 240 Kcal
  • Evening: 
    • 2 satsumas = 50 Kcal
  • Total Total 500 Kcal.

Another potentially beneficial regime is to have breakfast . . . in the old style where we used to not eat for 12 hours before the first meal of the day. The absence of food for that amount of time each and every night might trigger a spike of fatty acid oxidation which will turn over the stem cells, renew the cells lining the gut and make us live longer.

These diets have another thing going for them: they must be hard to monetize. Megacorp will surely find it difficult to make a product out of eating nothing. A few years ago my in-laws inherited an indoor cat from one of their descendants. This creature was fat, and it got fatter under the care of two indulgent pensioners. When it sat waiting for food, it looked like a heap of extruded ice-cream. They took it to the vet for a check-over and that charlatan sold them a €20 = 4kg bag of Cat's Slimming Pellets! Vastly more expensive than regular cat food, it seemed to work by being repellent to eat. I offered to buy them a 25kg bag of sheep muesli at €8.95 but my PhD was trumped by the Vet's B.Vet.Med.

Wednesday 16 January 2019

Misogyny in the lab

Last week, I was doing some research on comparing recruitment videos in the Irish Institutes of Technology. A couple of days later, I was in class with my proposed New Irish film star and mentioned that I'd put in a word for him with The Suits if/when the next propaganda vehicle was to be made. One of his Old Irish friends whipped out his smart-phone and found the whiter-than-white video that had triggered my investigations.
"What did you think?", I asked.
"It was okay", he replied
"Did you see any black kids in the film?"
"Fakk ?!?"
He was a little rueful that, even in the year after he'd left school, he'd become part of the Patriarchy with all the privilege and selective blindness that comes with the position. We didn't even begin to discuss the second class citizen position of women in the film. The  Star , on the other hand, said that he'd noticed the discrepancy (of course) but for him also it was almost invisible because he'd been putting up with that shit his whole life [I paraphrase: he is far to well-spoken and mild-mannered to talk like a low-life]. Later on I shared the video with one of my teaching colleagues - he white and in his 30s and (of course?). For him also I had to point out the absence of blacks and the discrepancy in gender.

Being unable to properly see minorities and women could be classed as a sin of omission. There's a much murkier class of sin (of commission) in the world of science which has been exposed in an essay Surely, You're a Creep Mr Feynman by Leila McNeill in The Baffler. Now I am an admitted fan of Richard Feynman [multibloboprev] and his book Surely, You're joking Mr Feynman. Indeed, a few weeks ago I brought my old kindle to life and this weekend I was re-reading with enjoyment a couple of anecdotes from Feynman's memoirs. It is an indication of how Patriarchal I really am, that Feynman's reminiscence of his treatment of women struck me as bouncy and direct, if vulgar, rather than abusive. I don't believe that many of his interactions with students or younger women, or indeed any women, ended in tears - like those of one successful scientist I know. But it's pretty clear that Feynman got more women to bed because of the confidence that glitters from men who are at the top of their game. And it looks like he started to believe that he deserved these trappings of success and had a tendency to get foot-stampy if things didn't work out for him just like he wanted with the opposite sex. McNeill is quite hacked off that, for his fans, and they are many, Feynman is almost beyond criticism because his charisma blinds us all.

I looked for a picture of the great man and found an odd twist to the story which more or less backs her position [patriarchy locks shields to protect Feynman's rep] up. In 2014, XY science blogger Ashutosh Jogalekar posted a piece critical of Feynman's attitude to women. The very next day: the text of this post was replaced with the following statement: "The text of this post has been removed because it did not meet Scientific American's quality standards."  At some indeterminate time thereafter it was re-instated by the editors of Scientific American. Poor fellows, they must have been in an ethical turmoil to chop the article and then change their minds. I've read the post, but am too Patriarchal / insensitive to see what aspects of it required censorship. The censorship aspect, rather than the misogyny, might remind you of Rupert Sheldrake's cleansing from TED.

One of the threads which Leila McNeill pursues through her "outburst" is the idea that we shouldn't attempt to separate the science from the scientists. Being a genius is no excuse for being a Dick. She suggests that because science has this aura of the pursuit of objective truth, then scientists are excused seepy behaviour, because the science is pedestalled as some sort of Platonic ideal independent of those who contribute bricks to the edifice. But I think this aspect of her broadside is misplaced. Nobody who is in the game and has the least amount of sensitivity thinks that science is objective. Scientists I know really cherish their hypotheses, and tend to design experiments which confirm rather than challenge. Their credit, their status, their very livelihood depend of their ideas being right and that colours every analysis and interpretation of data.

And I certainly don't think that examples of arrogance, misogyny and bullying are more prevalent in science than in Hollywood, Bollywood, Wall Street, or Tibet. Every group or community I have had dealings with has had its share of Patriarchs throwing shapes because their sense of self[-importance] depends upon grinding some other poor bastard in the dirt.

Tuesday 15 January 2019

Tree down

When we stopped bloggin' about it last week, our mighty Monterey cypress Cupressus macrocarpa had been shorn of all its top hamper and was but the backbone of its former wide-spreading self. It was another day's work to remove another 3m from the top to simplify the gestalt. As I worked to tidy up the fallen debris, I took time to reflect on how feeble people are until they tool up with chain-saw, axe and wedges and become Homo faber, the maker, and/or Homo destructor the destroyer of the natural world. One misplaced tonk with my splitting maul and I'd be off the Effectives List for the day with a burst finger, sprained wrist or massive bruise on my shin. All of which I have sustained in the past in similar circumstances. But tool use is part of the human condition and examples in the rest of the animal kingdom are few, far between and pathetic compared to using a hammer and nails; let alone constructing the Golden Gate Bridge or the Channel Tunnel. Until you're up close on a building site it is hard to imagine the relative size of people and their creations.

Check out the bottom part of the rebuilt Oroville [multiblovoprev] spillway. The 4x4 parked [R] in the middle of the concrete can fit 6 or 8 people and one of their hands is a single pixel at this scale. Those hands [and $1 billion] made this massive structure. With the macrocarpa trunk now reduced to about 3m of vertical biodiversity aka beetle hotel it is ready for its next role - tree-house. Peadar the tree-climber suggested that we leave a good length on the lowest limb of the tree to serve as a natural brace for the said house. It has to be at least 2m x 2m interior floor area, excluding balconies with sea-view; because it is my determination to force the grand-children to join Swiss Family Robinson and sleep up there as much as possible.  I think also that a helical staircase going round the trunk is the obvious way to sort out access. There is a helluva lot of fire-wood: