Bloody covid

A couple of weeks ago, my KK correspondent G sent me a story in The Jerusalem Post about ABO blood groups and differential response to Covid-19. I was in the midst of a Covid moratorium so didn't follow it up. I did pause to reflect on why G was scanning the Jerusalem Post: surely if you live in the SunnySouthEast everything you need to know can be met by perusing the Munster Express?

The JPost is referring to a study in NEJM which has taken a blood sample from ~1600 people in the Spanish and Italian epicentres of early Covid-19 meltdown. At some stage in every patient's treatment bloods were taken and while they were routine checking for creatinine, serum albumin and alkaline phosphatase they also had to check ABO blood groups in case anyone needed a transfusion. I've written about ABO blood groups before in the context of priority - paternity - geography - history - disease association.  But my [slightly delayed] response was ooooo data and I scooted off to the NEJM to download Supplementary Appendix 8 which contains the raw counts and %s for ABO in various geographic and medical-severity bins.

The first thing to note is that Spain and Italy are not the same population wrt ABO blood groups and so, strictly speaking, the data from the two agglomerations should not be pooled. This fact was brought up to the top of my 'mind' because one of the tables in Appendix 8 has gathered a bunch of Basque ABO data as a control. Whoa, lads! The Basques are the Martians of Europe, even more so than the Magyars: their language is not proto-Indo-European PIE and their blood groups look like a sore thumb (mostly Rhesus diffs it must be said). As a side-swipe, note the different colours on the map [R] for Lombardy and NE Spain where most of the Covid-sick in the study came from.

I scraped the pooled ABO / Covid-serious cases / Disease free controls from Appendix 8:

Which tells us a) that there are a lot of data here b) that the number of hospitalised cases is about equal in the two countries (although quite uneven in among the several participating hospitals) c) that sick people include more GpA people and fewer GpO people than you'd expect if they were a random selection of the population based on the controls. Because the paper didn't do this, I checked for ABO heterogeneity between total ES controls and total IT controls with a simple Chi.Sq test. The base-line differences are highly significant (Chi.Sq = 27; df 3; p < 0.001) with their being more A alleles in Spain and fewer B. Which is grand because we effectively have two different parallel experiments which both reveal the same skew: you are about 50% more likely to finish up on a ventilator if you are blood group A and a third less likely to do so if you are Group O. This is the odds ratio OR: [explained] (a/c)/(b/d)  = 1.54 for Italy (it's 1.31 for Spain) where

• a = ++ number of ventilated As = 388
• b = +- number of unsick As = 451
• c = -+ number of ventilated (AB+B+O) = 43 + 91 + 313
• d = -- number of unsick (AB+B+O) = 50 + 163 + 591

You can do similar calcs with O vs ~O / sick vs well. What are you / me / we meant to do with that information? My correspondent G was jubilant that she was Group O. I'm Group A but I'm not really concerned although the odds look stacked against us the (elite) A-team.  There are far more people with Group A who are uninfected, asymptomatic or who have copped a dose and had mild to moderate symptoms because that's the ~80% in the Covid-19 world. The 20% who get real sick and the 1% who die (or have such a crappy experience that death is wished for) are disproportionately A, yes, but they are far more obese, diabetic, have cardio-vascular issues or are over 80 years old. I am none of those.  Ed Cara at Gizmodo has covered the story with extra input from front-liners “It’s a big headline, but scientifically, if one of my colleagues in the emergency room were to call me up and say, ‘Hey, we were about to intubate somebody, but then we noticed their blood group was O. Should we still do it?’ I’d be like, ‘You’re crazy. You’re just absolutely crazy,’” Gehrie said.

And remember that it takes two to tango: before you get a chance of a go on a ventilator, you have to first catch SARS-CoVi2. Me? I rarely go shopping; I wear a mask in LIDL; I wash my hands afterwards; I don't suck face with young wans in discos; etc etc. I don't think G should take fewer risks than me because her red blood cells each carry a really small titanium Captain America shield.

It's a bit like my analysis is Statins. They have demonstrable, statistically significant effect on lowering cholesterol and so will prevent heart attacks. But the number needed to treat NNT for statins is more than 100! 100 people have to be taking statins for 1 to not have a coronary infarction. Statins have wild side-effects in some people and will cost you (or the beneficent HSE) a chunk of money. You'd be better off changing your diet, getting off your couch, de-stressing and being more socially engaged. But these take effort, statins just need a small glass of water.
On Covid-19, you can't change your blood group but you'd be spiffin' bonkers to think
I R O, I R OK, I can share spittle with randomers

Might have been

<Guest Blog Alert> [never done this before]
I wrote recently about my exercise-induced arse-ma; which put the kibosh on my prospects with the loneliness of the long-distance runner. It struck a nerve with my correspondent [recent] G who wrote about her own lack of wind so eloquently that I'm posting it here (with her permission):

Exercise-induced asthma - the bane of my life and only recently diagnosed by an occupational therapist of all people. When I was 15 and gasping for air after a couple of minutes on the trampoline double and triple somersaulting, my PE teacher used to make cracks about me giving up the cigarettes (a few years before I took them up). This made a huge impression on me in terms of unfairness and amazingly one of these incidents was memorialised in a poem by a schoolfriend forty years later. 

When playing hockey, if a game was very defensive and as a left back I had to be on the move continuously then I'd see things like the far corner of the hockey pitch lift up and roll itself towards me. Charles Bonnet Syndrome [prev] or purely oxygen deprivation? When I told the PE teacher, she suggested for the first time that I give up smoking - at 12, in a convent - FFS! She had to be on drugs to think that! 100 yards sprint was no bother to me, the fastest in the school, till I'd finished it... but the three rounds of the hockey pitch after dinner every day, that the couchiest potatoes in school found easy, never happened for me. I could never finish one round... a long and short side and I'd hit my wall with no running through it. Courtney Dauwalter is a better woman than me.

Five years ago, before the chance discussion with the OT, I was determined to take a crack at running in the dark instead of standing on sidelines and started running, using a Couch to 5K app. By the time I'd repeated six weeks of Week 1 without any visible difference in my fitness, I muttered curses and let the weather get the better of me and ceased my running endeavours. It has been a constant wonderment to me how one of my friends can get out there and do 5K cold from the couch without wanting to die during or after it. 

How did a woman fresh out of a four year PE teacher training course in Thomond College which presumably contained both sports physiology and psychology modules fail to see that the most active sporty girl in the entire school wasn't a smoker but had a real health problem? She never put together that, while I excelled at all sports, that basketball, netball, tennis: any sport requiring stamina were washouts for me after very promising oxygen-loaded starts. 

What could have been! Such tiny things to mould a character and change a life. The Blob sometimes hits a nerve [ouch].

[coulda beena contenda]

G's nearly on her pension now but, in her youth, people who knew the field talked up her potential as an Olympic gymnast. But that dream would have required getting many ducks in a row, and for network and exteernal support, G hadn't even a feather, let alone one full duck.

“Strange friend,” I said, “here is no cause to mourn.” 

 “None,” said that other, “save the undone years, 

 The hopelessness . . . Strange Meeting Wilfred Owen

Caisleán na Cailleach

Who shall be saved? That's today's question. It is a truism to say that slaps can be delivered to the head of any one of us - Henry V took an arrow in the face; Terry Pratchett's cortex emptied out; Phineas Gage's was briefly filled with an iron bar - but you'll respond better to life's tonks if you have money or connexions. How the dispossessed are treated is a measure of how civilized a society is. 

It's not enough to aspire to cherishing all the children; elected governments have to allocate resources to ensure that the difficult cases get dealt with. From 2000 Kathy Sinnott took the Dept Education to courtS to vindicate the Constitutional right of her disabled son Jamie to have "free appropriate primary education based on need". Jamie got to vote before he got his rights!  It's pretty clear that, in the 1916 proclamation, Padraig Pearse was cherishing all the children metaphorically not just the subadults. No grown-up nation should allow its citizens to sleep in cars, or in tents, or in at whim B&B accommodation. But that's where we're at. This last Winter there were 15,000 people homeless in Ireland a third of which were children. Not good enough.

Relying on private citizens to make homes available for those who don't have one might have worked sorta in the past. So long as you weren't black, an unmarried couple or <oof> with child. In 1975, with a newborn at foot, as students, we were able to rent a seafront property in Dun Laoghaire. The rent was about 2.5x that of the 2m x 2.5m x 3m shithole bedsit The Beloved and I had shared with a family of mice the previous year. I'm sure, the demeanour of patriarchy (and the accent) got us that room with a view of the sea. Through the noughties, I found that private rentiers could raise rents arbitrarily and evict tenants with impunity. It is only by being born at peak boomer and being lucky in the breaks, that we bought the farm 30 years ago and had a home for which we owned the keys. My correspondent G after 10 years in the private rental sector with her extended family, finally got a Council House in 2022.

I am relieved . . . happy . . . delirah to add my correspondent M to the list of those who have washed up ashore after years at sea in Dublin's rental sector. Whom shall we thank? Maybe Ned Guinness (1847-1927) [R, in his patriarchal prime] whose family had made a fortune in booze. At one time he was the richest man in all of Ireland. Having more money than anyone was capable of spending on racehorses and champagne, he allocated part of his patrimony to The Iveagh Trust [if you're reading from Baluchistan, don't bother clicking that bloatware link but get the gist from Wikipedia]. Still tl;? it's a provider of affordable housing in Dublin. They run a 200 bed homeless men's hostel, built the Iveagh Public Baths and the Iveagh Covered Market, and . . . a home for The Old. M is six weeks older than me and little bit more crocked up. After 50 years buffeted by the winds of change in private rental sector, M obtained the key to a teeny tiny apartment owned by The Iveagh and moves in Today!

All bets would have been off, if she hadn't been old.

Community wheelbarrow

Beau Miles is an eponysterical running - vlogger - fixer from Oz. Me, I can only run if its downhill, but I'd be happy with being called a Fixer . . . because bricoleur is maybe too French pretentious? Anyhow, Beau was jogging with a pal when the latter tripped over a rock in the middle of the trail and buggered his ankle. Beau quixotically undertook to take wheel-barrow and crowbar back to the spot to remove the folk-felling obstacle . . . it's only 14 km! Go Beau! 

I have some form on removing obstacles from the road. It really doesn't take much a) time b) effort. But a sort of madness overtakes most car drivers - insulating them from The Others out there struggling through life's journeys.

On a related matter, my correspondent G is moving house. They've been in their current place for nearly a decade, it was almost Hobson's choice because, even in those post-crash days, it was hard to find a place to rent that could take multigeneration family and a shouty dog and was approaching affordability and was within the city limits. But how is where you make it and it's a wrench to have to leave . . . because the Irish Constitution privileges the rights of property or the rights of people. I've been struck with the shitty end of that stick in the 00s . . . yes even Patriarchal me. Finally, probably because of the imminent eviction, G has moved to the top of the the local council housing list. I am sure there are compassionate and caring people who work in the housing office; but the system is quite unbending and capricious in its bureaucratic requirements. Nothing can be removed or added to the front garden without permission, for example.

The  back/side yard is fair game, it seems. Whatevs, I was [t]asked to start the removal of a clatter of raised "flower" beds which a previous tenant had built over the concrete slab in  the far corner of the yard. After removing the rotten remains of a rabbit hutch and a raffle of crushed flower pots and plastic sacks, I was left with a tonne of cleanish soil and pebbles which had to go somewhere else. It seemed an outrage to add this to the dumpster which is ordered for next weekend; so I took it home to our farrrm.  Even a tonne of clean soil disappears when you have 7 hectares of a patrimony. Every time we came home from the New Gaff, I filled the trunk with feed-sacks full of earth but without a clear idea of exactly where this bounty was to be dumped.

But the answer was immediately apparent on arrival. Our yard was pancake flat when we moved but that was only because the vendors had contracted John Nolan the Digger to bury the many heaps of farmyard manure, broken buckets and generalised midden. Over the following 25 years, the FYM has fermented and de-gassed, causing a buckety landscape of subsidence. It has been on my mind to scrape a couple of front-loader bucketsful of soil from a corner of one of the fields and use that to build up the cavities. Less so, now because [L] I've been able to top up the most egregious fox-holes / buffalo-wallows. Arra, I should have been a dentist!

Lasso them microdogies

My correspondent G continues to scour through the interwebs looking for Blobocopy. I tell 'er she should start 'er own effin' blog but she's too busy scouring the interwebs. She did though submit The Blob's one-and-only guest blog [cw: asthma] in 2019. The latest alert concerned the discovery of a novel source of potent antibiotics in a Canadian soil sample. This happens occasionally as in the discovery of Eleftheria terrae ten years ago or more to the point discovery of Teixobactin - a chemical from that novel microbe that kills pathogens like MRSA. Back in my 2015 report, I bet that Teixobactin would give its discoverers a Nobel gong within ten years. But they haven't even got a production schedule sorted [there are technical hurdles] let alone FDA approval. Science is Hard.

Gerry Wright [L,L] has been on this line of research for at least ten years but Manoj Jangra [L.R] only came to the lab as a post-doc a tuthree years ago. He is holding [yea! 3-D printers!] a model of their novel antibiotic. If you squint, the molecule looks like a lasso = lariat hence "lariocidin". Their discovery is important because lariocidin nobbles other bacteria in a novel way - by interfering with the bacterial ribosome and preventing protein synthesis. 

When bacteria become resistant to antibiotics, researchers tend to modify [add a bell, drop a whistle] the antibiotic chemically, so that the bacteria no longer recognise the cause of their own demise. But that tends to buy only a few years until the bacteria develop their own modification in the arms-race. It is hoped that, by presenting a completely new method of attack, the effective life of lariocidin (and its inevitable derivatives) will be longer. And lariocidin's structure is radically different from existing antibiotics, so that will pose an extra challenge for the target pathogens. On the safety-side, bacterial ribosomes are functionally equivalent [make proteins] but structurally different from mammalian ribosomes; so there is not going to be cross-toxicity to both pathogen and patient.

Seems that the soil sample from which the lariocidin-producing Paenibacillus was isolated came from the garden of one of the lab techs in Wright's lab at McMasters U. But that's the easy bit, it only needs a trowel. I assured G that her garden was full of bacteria killing each other but even the a silver plated trowel isn't going to get her a Nobel. Wright sensibly enlisted the help of a team from University of Illinois Chicago UIC, who provided complementary expertise.

Wright seems to have a thing about Paenibacillus: in 2016 he was scrabbling about in the bowels of the New Mexico earth to find an ecosystem uncontaminated by humans. There they uncovered Paenibacillus sp LC321whose genome held a number of potential target antibiotics. One of the nice threads in that tale is that Wright heard about these New Mexico caves by going to a lecture by Hazel Barton, an Akron U spelunking microbiologist.  Note to self: always go to lunchtime seminars! Like me at Aled Edwards' giving side-eye to same-old same-old research funding.

Microdogies? It's a Rawhide reference. Dogie: an orphan calf.

Troy

A couple of days ago, I was on about Troy and Avoirdupois and Metric units in the context of gold prices.  It's hard to drag people into the uniform and mathematically simple world of the Metric system.  When we lived in the Netherlands it was normal to hear people in the market asking for een pond van kaas when they wanted 500g.  It was six or eight generations since NL had officially adopted the Système International (SI) created by French revolutionaries nearly 200 years before.  It's nearly twenty years since they changed all the roadsigns in Ireland to km, and more than that since they started selling petrol in litres, but you still hear car-buffs talking of how many miles per gallon their wheels do for them.  All my students at The Institute are happy to give their weight in stones and their height in feet and inches.  They've never learned anything but SI in school, but 80% of them couldn't tell their weight in kilos without a calculator.  And, of course, the births of babies are reported in pounds and ounces.

Troy measures may be derived from the city of Troyes in France. A Troy ounce is 480 grains 31.1g, whereas an Avoirdupois ounce is 437.5 grains 28.3g.  The grain, nominally the weight of one wheat-seed, in both cases is the same at 15.43 to the gram. To (over)compensate, there are 16 AvdP oz in a pound (lb) - 7000 grains, but only 12 Troy ounces in that pound 5760 grains.  As I said in the last post, Troy measures are only used for gold, silver and gems.

Matter a damn, you say?  It can matter to the tune of $125million if you mix your measures and don't pay attention and don't communicate properly with your partners and traders.  The most famous case was NASA's cunning plan to measure the weather on Mars.  It seemed a bit premature to add a bunch of Martian data to the stream when we were/are so long from knowing how Earth weather works.  But they made their case to Congress and launched the Mars Climate Orbiter MCO in late 1998.  The spacecraft never achieved stable orbit round the red planet when it arrived there 10 months later but rather took a figgairy to plunge straight at the surface and burn up in the atmosphere.  Whooomph!

The physics and engineering required to drop a man to a precise spot on the moon is so complex you need rocket-scientists to make it happen. NASA missions are extra complex because they have to share out the contents of the pork barrel among the clients of their paymasters in the US Congress.  As I blogged about before, they also have to be relentlessly optimistic and play down the risks or they'd never get any support.  In the case of the MCO, one set of directional control software was programmed to deal with measures in the US-friendly pound-force while an interacting piece of code written by another company assumed (we're all scientists and engineers here) that the data would be in newtons - the SI units.  Even before the destination was reached, the MCO appeared to be behaving a bit lively:  weaving left and right like a drunk trying to walk a straight line for the cops.  Even with that information nobody back in Houston realised what the problem was.  If they had they might have been able to modify the code to read:
THRUST = THRUST/4.448
even
THRUST = THRUST/4.5
would probably have saved the day.  They didn't make that mistake again.  But several other missions went wrong before NASA finally (Jan 2004) landed a vehicle on the Martian surface that worked.  Indeed the Spirit Rover was so well engineered that it lasted 6 years longer than its expected 90 day shelf life.  It wasn't NASA's fault that Spirit drove into a patch of soft sand and couldn't get out again. Three weeks later, a sister vehicle Opportunity landed on the other side of Mars and she's still going; as is Curiosty which started work in August 2012.  For most of us, including pretty much everyone in RTE except their canny and redoubtable new science correspondent Will Goodbody, its as if these marvels of engineering chutzpah didn't exist.  But they show us what science can achieve - we're not just primates any more.

Lay off the bitchin': it's discouraging

Further musings on BTYS [prev; prevlier]: I'm usually aware of the BT Young Scientist BTYS competition as it come around every year in early January. When our girls were of the equivalent age we even went up to the show a couple of times. But the timing is awkward for me as it coincides with the end of the first week back teaching at The Institute. Usually, therefore, BTYS surfaces in my mind around New Year and then sinks into oblivion without me knowing who won or what the sexy projects had been (the two are not always the same). A friend of mine was a BTYS judge for several years, so I know something of the efforts the system puts in place to ensure that the winners deserve the ballyhoo. There are lots of subsidiary prizes too, so lots of good kids get a bit of a boost and hopefully are encouraged to stay on in science when they leave school.

This year's Winner Winner was Simon Meehan [L holding his active principle] of Coláiste Choilm, Ballincollig, Co Cork; with a microbiological project "Investigation of the antimicrobial effects of both aerial and root parts of selected plants against Staphylococcus aureus".  That gave me a frisson of interest because briefly in my butterfly life as a scientist, I'd also made a contribution to devising a novel therapy against MRSA = methicillin-resistant Staphylococcus aureus. MRSA is what kills you if you go to hospital for a hip-replacement. It's not really a problem outside of hospital - 30% of us have some MRSA up our noses without it being the least bother. Our immune system and the other bacterial actors on the surface of our nasal epithelium keep the bad boys at bay. Back in 2005 and 2007 we found that certain anti-microbial peptides AMPs, which we had discovered in the chicken genome, were particularly effective at killing some pathogenic bacteria. With a rush of blood to the head we thought about setting up a campus company which would design novel AMPs - effective against MRSA, cholera and whatever you're having yourself. One of our post-grads was notably ambitious and enterprising in the pursuit of science, fortune and fame. One of the consultant surgeons in the hospital, where all the research was going on, was approached for the first tranche of VC. We started to casually use corporate-speak about burn-rate, low-hanging fruit, and paradigm shift. Then it all went pear-shaped. Our Young Turk went to work with another research group, the consultant went back to his theatre saving lives directly and the vision about  retiring on our money at 40 fizzled out in a bath of dull reality.

I would have missed Simon Meehan's story entire if my correspondent G [prev, prevlier] hadn't sent me a link from boards.ie.  You often get interesting discussions, insights and straight-dope info on boards.ie but the only qualification for contributing is that you have an internet connexion.  The tenor of the commentary about young Meehan is that about 10 years ago his mother Brigid Lucey, a scientist (now in CIT then at Cork University Hospital) and a student at Cork IT Susan O'Shea  investigated the MRSA-killing power of certain wild-flower extracts. The implication being that the son is just a sock-puppet for his Mum.

In general rather than in this particula, at least as relevant as the parent is the science teacher. During the 43 years the competition has been running, 4 schools have won twice and 2 schools have won thrice. No fair! the begrudgers complain: there are nearly 800 secondary school in the country, why don't they get a chance? Because the quality of the mentoring, the passion in their science department and/or the spare capacity and commitment of their teaching staff is wanting. Let's hear it for the teachers and the ethos at Abbey Grammar School, Newry; Coláiste Mhuire, Dublin Kinsale Community School; Scoil Mhuire Gan Smál, Blarney; St Finian’s College, Mullingar; Synge Street CBS, Dublin.

I find prima facie that the sock-puppet theory of BTYS success is both unlikely and unfair. Every year about 60,000 kids sit their Junior Certificate, that is more or less every 15/16 y.o. in the country. Only a few hundred of those kids start doing a Young Scientist project on top of their school work. The rest don't: they have enough on their plate with hormones, school, drink, sports, helping on the farm, sex, tricking about with their smart-phones, sex, worrying about being bullied, bullying smaller people, counting their Friendface friends, sex, recovering from the binge drinking session last Friday, volunteering with St. John's Ambulance, more drink, instagraming another picture of themselves or their parts in the hope of getting more sex.

Why does one teenager have an interest in science while another goes swimming?
Because they click with their science-teacher [_];
because their pals are also doing sciency things [_];
because they have a relative who does science [_];
because of that documentary they saw on the TV [_];
because they read Feynman's book [_];
because they 'are good at it' [_];
Tick all that apply. If a kid ticks none-of-the-above then s/he is most unlikely to win the BTYS . . . because s/he never got into the traps at the beginning of the race. But even if you tick ALL the boxes, you need additional toolkit else to be successful.

• You need to Do The Work - nobody won a prize without data
• You need to analyse the results - nobody aged 15 knows enough statistics to design the experiments and apply the correct tests to determine if they are interesting; so you almost certainly need help, guidance or discussion on this. My experience in the local competition is that statistical knowledge is close to nil.
• You need to continue through the dark tea-time of the soul when nothing is going right: when your trial plants get eaten by your brother's rabbit; when it rains every day in July; when you spill coffee on your (unbackedup) laptop; when you find fungus all over your Petri-dishes.
• You need to present the data presentably: deciding what details are left on the cutting room floor; deciding that Helvetica looks better on your poster than [default] Calibri; deciding how to best graph the results [not a bar chart!!]; deciding which picture will catch a judge's eye.
• You need to defend your results, your experimental design and your methodology, when grilled by the judges

Who had the original idea is the least of it and it was aNNyway almost certainly only part of an idea which grew through discussion and preliminary results and changes in direction when the original concept met reality on the ground. I've written with some hilarity at the thought that ideas spring fully-formed from the head of Zeus. The begrudgers on boards.ie should just zip it unless they have some better evidence that young Meehan didn't do the work. And sitting on your fat arse on the sofa busily typing one-liners on boards.ie doesn't really give you locus standi as a referee of scientific ethics.

Orange is not the only . . . compost

🍊 Dan Janzen is now one of the grand old men of ecological science. He first loomed over my horizon shortly after I rocked up to graduate school in Boston. That same year Janzen published a paper in the Ann Rev Ecol & Syst entitled How to be a Fig. My attention was probably drawn to this overview of Ficus ecology by Pete August who was then completing his PhD with Tom "Batman" Kunz on How to be a fruitbat. Every fig that you eat is filled with egg-cases and a dead female wasp who has parasitized the fruit to lay her eggs and propagate her species. Without her pollinating invasion, no fruit. Without bats to eat the ripe figs - and shit out the seeds on the branches of a distant tree, there would be few new fig trees. And don't forget that the tree which hosts the fig-seedling will eventually get strangled in place soon after the fig roots have reached the ground and no longer need support. [bloboprev] It was stories like that which blew my sheltered European Ivory Tower mind: the diversity and inter-connectedness of the natural world were almost too complicated to comprehend.

🍊 Dan Janzen coursed over my horizon again in the middle of last week when my correspondent and independent researcher G [multiprev] flagged up a more recent research project which Janzen had started at the end  of the last century. With his wife Winnie Hallwachs, Janzen had been instrumental in creating the  Area de Conservación Guanacaste ACG in Costa Rica where they had been doing much of their field work. The ACG was an almost pathetic too little too late project to save a fragment of the old growth tropical forest which used to cover swathes of Central America. Stout Cortez and his conquistadors started the destruction of the alternative reality which was the New World in their rapacious looting for gold and god. Colonialism and capital had finished the job. 

🍊 The thing is that tropical forests are abundant but nutrient depleted. If a single tree falls, its resources are captured and recycled back to the community by an active army of beetles, termites and fungi. If an entrepreneur clear fells the trees to supply the market for hardwood cabinets for Japanese salarymen, then the recyclers are coincidentally done to death and the biomass is shipped abroad. There is little carbon left to sustain regrowth. In one sense, the timber is typically a windfall once-off bonus payment for the new owners of the land who plan to grow beef for hamburger or citrus for the morning OJ of the plain people of America.

🍊Janzen and the ACG struck an unlikely deal with Del Oro, one of the fruit-growing megacorps which had been responsible for replacing a great tract of mind-bogglingly diverse old growth forest with a neat monoculture of orange trees for the juice market. In exchange for a tract of still-a-forest which they owned, Del Oro would be permitted to dump their waste skin and squeeze-dried pith in part of the degraded once-upon-a-forest. Del Oro accountants considered that the exchange would be a nett gain for their share-holders, the papers were signed, and truckloads of bright orange garbage were shipped to the designated area. But within a year of the start, the scheme was brought up all standing by a spiteful law-suit by a rival juice company. TicoFruit fought their case, that Del Oro had "defiled a national park", up to the Supreme Court of Costa Rica; and won.The last truckload of 12,000 tonnes of skins was shipped before the cease-and-desist order was applied; and Del Oro and ACG walked away from the project.

🍊Fast forward 15 years. Tim Treuer, a graduate student from Princeton, had completed “It was so completely overgrown with trees and vines that I couldn’t even see the 7-foot-long sign with bright yellow lettering marking the site that was only a few feet from the road,is course work but needed a project on which to attach his thesis. He fell to talking with Janzen, who had a faculty position in the school, and it was agreed that the pile of orange skins in Costa Rica could bare looking at again. Treuer went South to scope the situation and couldn't even find the site. “It was so completely overgrown with trees and vines that I couldn’t even see the 7-foot-long sign with bright yellow lettering marking the site that was only a few feet from the road". They upped a drone to capture the bird's eye view [L]. The side of the road which had been buried in orange skins was clearly different - and "better" - from the unremediated forest which had gotten only a whiff of decaying orange . . . and a blizzard to fruit-flies and fungal spores. The back of my envelope indicates that ½ a tonne of peel waste was deposited on every sq.m. Treuer et al. did plenty of science: measuring the height and girth of trees; counting species; comparing transects. But the picture is the executive summary.

🌳 In 15 years our 0.4 hectare forestette, with scarcely a single orange peel, has done well for carbon uptake and up-growth. Several of the trees, especially larch Larix europeaus, are now taller than our 2 storey home and as thick in the butt as my thigh. We've been talking with Sean the Forester [not the same as Seán the tree-surgeon!] about thinning in the tail end of this winter.

N🍊pe! It is not okay for you to take your organic-rich old mattress and drop it into a secluded culvert up in the hills: to increase the biodiversity and recycle nutrients, like.

Is the mouse a good model?

A few years ago I was embarrassed to admit that I'd never heard of the 4th biggest city in China. [Ans: Tianjin 天津市 - it is near Beijing in the NE of the People's  Republic]. The 3rd biggest city in PRC, after Shanghai and Beijing is Chongqing 重庆市. Now I had heard of Chungking because it was the Capital in Exile in WWII after the Japanese sacked Nanking and occupied Beijing and much of the N of the country. Note the last character 市 is the same for both cities: it means city! Our ignorance of China is immense: the population of Chongqing alone exceeds that of the island of Ireland: could we take the trouble to find out more?

That opportunity was provided last week at the end of a 3 week Summer Programme at The Institute for students of Southwest University (SWU 西南大学) in Chongqing. I was 'volunteered' for 6 contact hours to play some computational-biology games.  They paid me, but not enough to create a whole new course, so I modified part of a comparative immunology module I developed a few years ago. The question I put to the students was

"Is the mouse a good model organism for developing 

a novel therapeutic against such-a-disease".  

One pharmaceutical research avenue which has been fruitful is the development of monoclonal antibodies specific for key molecules in immunological / inflammatrory response pathways. Monoclonal antibodies MABs are amazingly specific in seeking out rogue actors which get over-excited in  a particular disease. What I know about normal human physiology, after teaching it for 7 years, is that the whole system is a set of checks and balances; disease is when this delicate, multiply redundant, complex of interactions goes AWOL. MABs are given dork-dopey names , mostly ending in -mab so that Google-savvy patients don't be bothering their doctors to try the latest me-too drug they read about in Hello magazine.

The standard protocol for a new drug prospect is to build on our increasing knowldge about the molecular fundamentals of a disease and ask . . . if we could put a damper on MAPK then it wouldn't be able to gee-up STAT3 and the whole over-heated system would cool off. MegaPharm is only interested in drugs that will make them a load of money, but they have to ensure that a) they do indeed work in the way intended and b) they are safe to use: that their side-effects are not too damaging. The usual thing is to try out the prototype drugs on a couple of hundred lab mice Mus musculus, and then do some statistics to see whether the idea might be a runner.  If none of the mice get the screaming abdabs [technical term] and enough of them get better, then it's time for the first human trial.

In 2014, I wrote about the most famous case where that next step went horribly wrong with a test of TGN1412 which seemed in mice to counteract the effects of CD28. It was a salutary reminder that mice and men are similar, yes, but also different. Nobody died in that first human trial but several of the human guinea-pigs were badly roughed over and won't ever properly recover.

That gave me the bones of a hypothesis to test with the boys and girls from Chongqing. Let them compare a list of drug targets to see how similar those molecules were in Mus musculus and Homo sapiens. TGN1412 was to be a treatment for Rheumatoid Arthritis. My correspondent G who is pain-wracked by RA has been taken off Infliximab because her condition is no longer responsive to having her TNFα tricked about; so she would welcome a novel therapy to help her get out of bed in the morning. But TGN1412 and multiple organ failure is a bridge too far even for her.

The kids from Chongqing were invited to choose one molecule from a list that had been used as a target for a named monoclonal antibody. Starting with Infliximab and ending with TGN1412:

They were then requested-and-required to use the Blast server at NCBI to find the homologous [equivalent] gene in mouse and see just how similar they were. I show above the target-list and, in the last column, the answer for the class. The specific hypothesis under test was that CD28, the TGN1412 target, would be noticably more different mouse-vs-human. And the answer is . . . No!  I emphasised that nothing like this analysis had ever been carried out before since science began in the 17thC: the kids from Chongqing were pushing the Frontier of Science.
Here's some more detail on IL13 one of the crappier comparisons. At 59% identical, you might think that IL13 is missing in mouse and P20109 is something else entirely. But a reciprocal best hit analysis shows that the two sequences are indeed orthologous and probably have the same structure and function in both species.
IL13 Mouse P20109 Query vs Human P35225 Sbjct
Expect 2e-40 Identities 76/130(59%) Positives 93/130(71%) Gaps 8/130(6%)
Query  6  TAVLALACLGGLAAPGPVPRSVSLPLTLKELIEELSNITQDQ-TPLCNGSMVWSVDLAAG 64
          T V+AL CLGG A+PGPVP S +L    +ELIEEL NITQ+Q  PLCNGSMVWS++L AG
Sbjct  20 TTVIALTCLGGFASPGPVPPSTAL----RELIEELVNITQNQKAPLCNGSMVWSINLTAG 75

Query  65 GFCVALDSLTNISNCNAIYRTQRILHGLCNRK-APTTVSSL--PDTKIEVAHFITKLLSY 121
           +C AL+SL N+S C+AI +TQR+L G C  K +    SSL   DTKIEVA F+  LL +
Sbjct  76 MYCAALESLINVSGCSAIEKTQRMLSGFCPHKVSAGQFSSLHVRDTKIEVAQFVKDLLLH 135

Query 122 TKQLFRHGPF 131
           K+LFR G F
Sbjct 136 LKKLFREGRF 145
The fundamental problem is more complex than 22 undergraduates from China can solve in 90 minutes; but we probably knew that. I still think it's an empowering exercise.

De Mother of De Bride

When my correspondent G got married on a Summer Bank Holiday weekend 30 years ago in Carbally Co Waterford, the family rowed in to do the catering. Ham and salmon; potato salad; green ditto; hummus bi tahini; cake and ice-cream. Monstrous portions, lovely weather, tipsy aunts, riotous children: a great wedding. Despite the absence of any form of mean-spirited portion control, there was still rations of food the following day. The left-overs were laid out on trestle tables in the farm-yard and we all nibbled our way through mighty hang-overs to a state where we could face another dhrink. The toilets backed up from the septic tank and had to be rodded out. The following following day, it was the same: folk were still trenchering through an apparently undiminished food mountain making sandwiches from cold cuts. Then I turned over a slice of ham to reveal (m'eyes were better then) a couple of neat rows of blowfly Lucilla sericata eggs. Quiet word with the chatelaine [no point in frightening the horses] and the rest of the spread was quickly and discreetly condemned to the bin. No harm done.

It is an ill wind that blowflies nobody any good! Lucilla sericata does get a bad press because it flits between the kitchen and midden with sticky feet - without even getting as far as laying eggs. But it has a useful side as well; as was brought home to me by some of our Pharmacy Technician students. They had been formed into groups, each  to do a small independent research project, summarise their findings in a poster and present it all at an academic meeting later in the year. There's €250 riding on the best poster from The Institute and more prizes at the national meeting. The Faculty from the PT course were each assigned to mentor a poster-group and mine elected to write about the uses of leeches and blowfly larvae in wound debridement. Most PTs choose to work in community pharmacies but others go for work in a hospital pharmacy where they deal almost exclusively with medical professionals rather than anxious parents and dithery ancients. One of the jobs of a hospital pharmacy is to feed the leeches Hirudo medicinalis! These lads are closely related to the earthworms that rummage through my compost heap but they depend on a blood meal rather than deco posibg vegetation. You can pick up leeches if you wade through the water where they live - which was all over Europe and much of West Asia.

They are in hospital pharmacies for their saliva which is a rich stew of anti-coagulants: to stimulate the blood flow y'know. If the surgeon clamps a couple on after a microsurgical finger re-attachment, then these secrations keep the blood circulating in the area and promote healing. Very retro, not to say medieval, but they are in some circumstances the best tool in the box.

In the bed next to Jimmy with accident chopping kindling, old Mrs Doohickey is nursing some weeping sores on her lower legs: her diabetes doesn't help but the primary cause is an antibiotic resistant tuberculosis infection. Because she's old and quite crocked up (the diet of cigarettes and  biscuits doesn't help) her immune system just isn't clearing up the wound. The nurses have to change the dressings twice a day and the smell is funky. Part of the problem is that the resident bacteria are working away underneath a thick biofilm of dead and dying cells - both Mrs D.'s and her spongers' and what's left of her immune system is overwhelmed. Bring on the dancing blowfly larvae! These aren't on the inventory of the Pharmacy but can be ordered up from a convenient supplier. The larvae come cleaned! so that they don't make things worse by adding more microbes to the soup. It is also required that they are applied to the gaping wound under a maggot-proof dressing - nobody wants t'buggers crawling out between the sheets and dropping to the floor like a scene from the Great Escape. Amazingly, the larvae = maggots prefer the soupy elements of the lesion and eat everything back to sound tissue which is then able to start the healing process. Surgeons are taught debridement in med school - cleaning up ragged wounds so that the can be sewn up but the scalpel or more usually a curette is a rough bludgeon compared the delicate rasp of the larva's mouth-parts.

• What about The Mother in the title? 
• Where do you suppose the eggs come from which hatch into larvae and debride the mess? 
• Do you always answer a question with a question?

I bet you're glad I didn't include pictures of suppurating sores. Instead I slapped in some nice thumbnails of a Spotted Wood Breacfhéileacán Coille Pararge aegeria, a handsome and still reasonably common Irish butterfly.

I R Borrred

 I'm an institutional[ized] kinda guy; that's why I've been happy working at The Institute these last several year. The day, the week, the term, the timetable is so busy that I have little time to be idle at my desk waiting for the next event. I have been in other academic posts where I was expected to adult-up and be responsible for running my own day, week, term, timetable. I didn't cope well and it was the least productive time for which I got paid a salary. In the late 1990s, I told one of my colleagues that I was a really good post-doc[toral] researcher: I was hard-working, dogged, not stupid, dependable and painstaking but I wasn't interested / capable of running my own lab. Part of that was a reluctance to be responsible for the health, welfare and success of people under my care.

Interestingly, that same colleague believed my patter and a tuthree years later hired me to work in his new edge-cutting multi-million €$£ research lab. The was he explained this eccentric decision was that he wanted at least one known quant in the multinational mix whom he hired to push the frontiers of science. In more or less the same month [the Celtic Tiger was starting to leak science-bucks], I was hired to work in another lab to supervise a post-graduate student whose project was at the interface between computational biology [me] and innate immunity [The Gaffer]. In the hiring interview she said that the student welfare/thriving buck stopped with her - she de Gaffer - and that I should just concentrate on wrastling the genomes into submission. Working in two different fields in two different labs at the same time was - tiring, energising, creative and interesting. There was a surprising amount of cross-over and complementarity.

My correspondent G sent me an article from the New Yorker about the science of boredom. I found it difficult to relate to because I'm never rarely bored . . . nowadays. But I guess I'd y-a-w-n be all over it with a dull of recognition, if it was 1988 and I was gazing out of the window waiting for lunchtime. It's worth reading, even if you're not prone to being bored yourself. It will give you insight into the Lives of Others who are less well set up for amusing themselves [Ennui by Walter Sickert L]. As a few experimental psychologists are involved, there are some nifty ways to induce boredom:

• read numbers out of the telephone directory
• watch a film of two guys s l o w l y hanging laundry
• transcribing the reference list of a technical research article

The outcomes seem to require measuring the consumption of junk-food as a consequence of being bored. The take home seems to be that you'll likely be bored if what you are doing is a) monotonous AND b) of no interest / value. Playing Grand Theft Auto is of no interest / value but it would be a peculiar person who was bored by the proxy-mayhem. Contrariwise, I am quite happy tallying up pages of data or repetitetitetitetitively making thumbnail pictures of our incoming students. It's monotonous but when you're in the zone, the time passes and each page is box ticked. There's a lot of that in science: carrying out a protocol reliably, repetitively to acquire data to test a hypothesis is an important part of the process.

What's your boredom threshold? You can measure it if you have the patience to answer 28 [twenty-eight!] not very interesting questions. I found
You don’t get bored easily.Well I knew that; I have The Blob to put to bed each and every day. But the case would be altered 32 years ago. BBC: why boredom is good for you. Grauniad: why it's good to be bored.

Legless in Gaza

My correspondent / source G ordered me to watch No Limits a documentary by John Zaritsky about Thalidomiders. I've had a peek at Thalidomide before, largely to give tribs to Frances Kelsey who, as the newest hire at the FDA, stalled drug company Richardson-Merrell from marketing the devil's spit-balls in the USA. The few [N = 17] US cases of Thalidomide-induced damage seem to have come from freebies given out in handfuls by Merrell as pre-sale promotion for the new wonder-drug. Merrell was interested in the distribution rights because Thalidomide had been so profitable for Grünenthal, the German parent company that held all the intellectual property.

Although I knew the story, there were numerous details which had escaped my notice (or slipped my memory since, as likely).

The Nazi connexion. Otto Ambros was appointed Chairman of the Grünenthal Board. We've met him before as one of the developers of the nerve gas Sarin, when he worked for IG "slave-labour" Farben in WWII. Dr. Heinrich Mückter was Grünenthal's Head of Research and claimed a tidy royalty for each packet of Thalidomide sold. During the war Herr Dr. Mückter had worked im Osten, doing experiments, without informed consent, to develop a typhus vaccine on Polish civilians and the inhabitants of the Krakow ghetto.

The off-switch statistics. There was a very high rate of perinatal mortality among victims of Thalidomide-induced dysmelia. It is true that there was were a number of still-births associated with the drug; and presumably a, hard to guesstimate, number of spontaneous abortions and miscarriages. But it is alleged that many full-term babies, without the full complement of limbs, were left in the delivery room by their mothers and taken care of by doctors and nurses who couldn't imagine that a limbless child could live longer than a few days or weeks, let alone a full and active life as an emergency physician; a motivational speaker; or a film director.

The film No Limits is about what it says on the tin No Limits and so has a black [those Nazis, callous doctors and unimaginative midwives, corrupt officials, company lawyers] and  white  [Kelsey, survivors-who-have-done-well, Widikund Lenz, William McBride] view of the people involved. Those who have been bullied; who haven't found love; who have a crap self image; whose general health is getting worse with age; whose life has not been a bowl of cherries; they have no parts - not even walk-on parts - in the film. Nevertheless, hats off to the following people, who survived the drug induced insult to normal development and went on to live their best life: with a little help from parents, foster parents, teachers, spouses, their own kids . . . and indomitable spirit, of course:

Jan Schulte-Hillen

Moni Eisenberg

Louise Mason

Lynette Rowe

Niko von Glasow

Paul Murphy

Eileen Cronin

Alvin Law

But don't accept my take on it, watch the film yourself, it's only 80 minutes long.

. . . Promise was that I

Should Israel from Philistian yoke deliver!

Ask for this great Deliverer now, and find him

Eyeless in Gaza, at the mill with slaves,

Himself in bonds under Philistian yoke.

Samson Agonistes, John Milton

Looks great, not true

For many evolutionary biologists, Darwin's second big idea was not about the origin of coral reefs, but rather an explanation of such peculiarities of the natural world as the tails of peacocks Pavo cristatus. My correspondent G was kind enough to send me the cartoon [R] about 30 years ago: clearly it has been difficult for me to shake the image from my strutting patriarchal mind.  Darwin reckoned that sexual dimorphism " . . . depends not on the struggle for existence, but on the struggle between males for possession of females . . ." even if the attributes which attract females make the males potentially attractive to a wider variety of more voracious predators. It's hard to escape from a fox if you can barely get airborne. It's not just peacocks: deer with an inconvenient coat-rack attached to their heads; monkeys with absurdly rainbow-bright bottoms. We can tell things about the behaviour of animals even if the only specimens are in the Dead Zoo. We've documented on The Blob that human males are bigger than females: bigger feet, bigger upper-body, bigger beard. The irresistible conclusion is that blokes strut and throw shapes and that girls pay attention to their antics. But . . . competition for mates is not as important a drive in us as it is in gorillas with their big heads, sagittal crest, mighty brows and 2x M v F weight differential.

Another take on the over-blown extension of sexual attractants (feathers, horns etc.), which was first proposed by Amotz Zihavi in 1975, but popularised  Richard "God-hater" Dawkins is that the 'extras' are not so much about run-away selection for these attributes. The handicap hypothesis rather says, basically, look at me girls, I got a ton of feathers and a bright-pink head and I can still fly and haven't been swatted by a hawk; I must be well fit, fancy a shag?

You can make all these observations, add your opinions about why these peculiar traits have evolved and convince yourself that you've explained <tick, done that> that aspect of the natural world. By convincing an editor and two referees you can secure another publication against your ambition for tenure at Harvard. How much more convincing this Just-So story would be if you could artificially manipulate the world and show that your changes made a difference in the mating game. In the 1980s Nancy Burley noted that the coloured bands put on the legs of the birds = zebra finch Taeniopygia guttata [L half an ounce 12g each of super-cuteness] she was studying appeared to have such an effect. Red leg bands appeared to enhance the attractiveness and the reproductive success of male finches, while pale green bands were a total bust in sexual politics. Further studies appeared to support this hypothesis and soon enough these now iconic ideas worked their way into text-books of Ecology and Evolution. It seemed to show that sexual preference was lurking just beneath the surface and can hook on to whatever small difference can be detected by the opposite sex. Those small-small differences will get more distinct and enhanced if more offspring come to the odd-ones. When data is consonant with theory it is just more easy to get it published. I told a story of a gamma-male chimpanzee who upped his pay-grade by using a kerosene-drum to act bigger than his god-given muscles.

The pendulum bounced about as scientists tried to replicate these findings, some getting supporting data and some, like Aurelie Seguin, Wolfgang Forstmeier in 2012 finding no effect. Forstmeier was at it again in March of this year, doing a comprehensive review of the field and doing a meta-analysis of all the published data. It's the sort of idea which is hard to kill - because theory and observation collide - and having shown that leg-bands are irrelevant in zebra finch, there will be hold-outs claiming the effect in one of the other 8,000 species of bird. Not much different from the ding-dong battles about whether vultures detected dinner by smell or vision - the answer being both, because there is more than one species of vulture.

If you're really interested in the issues of bias, special pleading and uncritical thinking, you could do worse than read the summary of Forstmeier's jihad and its context by Yao-Hua Law in The Scientist.

Mind and change

The second week of November is Science Week. It was a bit piano last year, what with Coronarama but The Powers that Science are trying for a bigger splash this year. A national, multi-venue, several day festival needs a good bit of forward planning. [spoiler] Wexford Science Café has decided on a theme of Metanoia - allowing your certainties to be toppled by evidence. This is particularly on point because of the bunkers, barricades and tribalism which has been cemented by The Virus. I think the formal question put to participants will be "What have you changed your mind about since Wuhan?". The participants in the WSC gig in Science Week will mostly be, well, scientists.

Meeeeee! I cried, without really having a clue about whether I had changed my fossilized thought-cycles about anything since March last year. I find myself notably prone to availability error: I {gab | blob} happily on [and on] about what is uppermost in my 'mind' so I had a couple of ideas available which could be worked into a five minute piece-to-camera.  But my original idea, about the ethics of keeping small animals in homes, was bit edgy for pet-loving Ireland. So it was erasers out, and back to the tabula raza to think about my recent mind-changing experiences.

A tuthree weeks ago, when I was on the hill scything bracken with my neighbours and was getting talked at by one of them about the pernicious dockens Rumex obtusifolius & R. crispus which were taking over his pastures. This man is scientifically ignorant but not stupid and his solution was to spray the whole field with a dicot specific herbicide like by 2,4-dichlorophenoxyacetic acid aka 2,4-D [branded Trimec; I've blobbed about how this selective chemical works]. But, he said in his stream of consciousness, it will kill all the clover and I know that clover is, well, A Good Thing.  This same man used to say kidding-not-kidding that with modern farming if it couldn't be done from a tractor seat, it wouldn't be done at all. I turned away back to The Work and pondered how and whether a different view of docks could turn them into an asset. That's a well-trodden path of ponder since farming stopped turning stock into species-diverse meadows and embraced monocultures of Lolium perenne - perennial rye-grass - which tests have shown will get sheep and cattle up to market weight quicker than any other species . . . especially if you lurry on the nitrates. Docks are weeds because they are successful when all the other dicots have been done to death.

The very next day I heard Catherine "Sheepish" Friend talking about composting bracken and wool as a replacement for peat-based compost. Now that was a change of view-point about my previous six days of work trying to make bracken disappear rather than having sheep disappear into banks of bracken far higher than their woolly backs. I sort of knew that the old people used to harvest bracken as an available winter bedding which was thrifty but labour intensive. But this was a whole other view of the value of ferns. And right now the value >!for shame!< of a shorn fleece is about the same as a Mars bar and much less than a latte. As proof of principle, I went down to a field more convenient than The Hill and cut a generous sheaf of bracken [L] to add to the compost. Need some industrial espionage [or indeed some original scientific research] to determine the exact proportions of ferns to fleece.

Another option for surplus fleece is as packing for boggy walk-ways in Co Leitrim. [via G my KK correspondent]

Like Baldwin's of The Déise who started making ice-cream on the farm because it was tooo depressing to see their milk sold for half-nothing and turned into milk-powder. You can add value to things if you are creative and work hard on the marketing. Paddy and Joyce O’Keeffe, pioneers in the dairy-biz and founders of Tipperary Organic Ice Cream [prev] retired in 2008.