corona codona

In my butterfly life flit flit flitting from one bright scientific blossom to the next, I spent far too much time on the flitting and not enough time actually finishing the task on any one flower. I'm sorry if that's far too graphic an image of a grizzle-bearded silver-back helping out in the fertilisation of angiosperms. But in the early 1990s I was locked into a lab for 10+ hours a day trying to make sense of synonymous codon usage SCU, a field which was then both obscure and select and of no earthly use to anybody. I was locked into SCU because I got a bit obsessive and started to make contributions that were a) published and b) noticed in that small community and success became its own reward. SCU is the study of which triplets of DNA are used to encode for amino acids in the process of translation. GGU GGC GGA GGG all code for glycine and you'd expect [null hypothesis, we say] that each of these codons is used with rough equality. But they ain't, in many species GGU is used much more frequently than you'd expect by chance. And the other amino acids have similar distortions from random codon usage. As we got better at doing these analyses we became proprietal about doing the analysis right [i.e. like we did it] and on at least one occasion we savaged a group who intruded on the territory with a half-cocked analysis of SCU in Aspergillus nidulans.

My [and others] cerebral ponderings and analysis showed that for many microbes, there was a characteristic set of 'optimal codons' which were preferentially used, especially in genes which were in high demand. Decades later, these pioneering studies turned out to be essential for the efficient use of biotechnology in biomedical research. If you want a vat Bacillus subtilis to make a lot of human insulin in a useful example of genetic engineering; then you'll get more if you modify the human gene to incorporate many B. subtilis optimal codons. I was moderately chuffed by this vindication, although I had long before flit flit flitted off to an entirely unrelated field of research.

Because I'd moved off and away from SCU, I missed the contribution of Peking U Med School Wei Ji's team to the field  [PMID] in which they used SCU to identify a couple of snakes as probable intermediate hosts for the currently scarey Corona virus 2019-nCoV.  My pal Des "Whales" Higgins had to draw my attention to the paper; or rather its rebuttal. Now that snake connexion could be an important insight. If we know the source of a new virus that has leapt the species barrier, then we can carry out appropriate remedial action. You don't want to go slaughtering millions of  innocent chickens. Condemning chickens was appropriate in Hong Kong most recently in 2011 [NYT]. There, then, a single carcass positive for H5N1 bird 'flu precipitated the slaughter of 10,000 ready-to-eat chickens in an attempt to create a cordon sanitaire round the site of infection. In the same jurisdiction in 1997, 1.4 million birds were killed and incinerated rather than barbecued and eaten. H5N1 is the harbinger of doom: of 573 cases identified by WHO 2003-2001 336 died - nearly 60%. 60% mortality was the worst that the black death [bloboprev] could achieve in the 1340s.

IF it's snakes that Corona virus 2019-nCoV has escaped from, then a very different policy should be implemented - bounties [bloboprev] on snake heads, for example. But it just ain't so. Back in the early 90s one of the Effectives in our SCU lab was a canny chiel from Dundee whom we called Bobbo. I think he was studenting in Dublin partly because his granny lived in Ballyhale, Co Kilkenny. He had a brilliant early coup identifying a case of mix-and-match among HIV strains. It was /is going to be much harder to find a molecular therapy against HIV, if its RNA wouldn't stay in one place. That wasn't luck except in the sense that hard work and smart thinking makes you lucky. We now call him <respeck!> Professor David Robertson Head of Viral Genomics and Bioinformatics at Glasgow U.

Robertson, who has been immersed in the evolution and recombination of viral genomes from 25+ years, doesn't acccept the conclusions of Ji et al. but points rather to bats as the most likely reservoir / vector for the current Wuhan outbreak. Lancet paper by Lu et al. rushed out says 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China. Two days after Robertson, Kristian Andersen rowed in with more data and a different analysis but the same conclusion:
a) don't worry about snakes
b) don't eat bats - no matter how nicely they are presented in the bush-meat markets in China

The smell of death

My dog's got no nose!

How does he smell?

Terrible!

We're wrapping up the academic year at The Institute and I had to schedule an extra session for my 1st Year Cell Biology class. In the regular class they had been finding bacteria on their hands and on the lab bench and fewer bacteria after the hands had been washed and the counter-top swabbed down with alcohol. Classic case vs control science. We had a brief discussion about the fact that there were clearly different sorts of bacteria out there and on the petri-dish: that one is 2mm across and yellow, this one is twice the size and powdery-pink. One of the kids was paying attention but, suddenly and disconcertingly, she whipped the lid off one petri-dish and sniffed the surface.  That was such a surprise, because most students have a fit of the vapours if they smell aNNything. You have a career ahead of you as a wine-taster, I quipped.  If you do it often enough (two or three trials in plenty) you can distinguish Escherichia coli [sweet with a hint of vomit], Bacillus subtilis [a whiff of socks and ammonia], Streptomyces [wet earth after rain] and Pseudomonas aeruginosa [grapes and corn-chips]

The brilliant polymathic Richard Feynman had a party trick in which he'd leave the room after asking one person in the group to pick a book off the shelf and leave it on the table. Feynman was reliably able to sniff the hands of all the people and the book and identify the perp.  He maintained that, although bloodhounds are really good at following specific scents in a welter of conflicting signal, humans are not so bad themselves.  We don't have as many olfactory receptors as dogs but its only about 20% fewer rather than half the quantity.  Being a wine- or tea-taster is trainable but a genetic predisposition helps.

Because things always come in Threes, last week's Futureproof on the wireless, was talking about smelling rats. They were interviewing Haylee Ellis [L with rat] from APOPO, a Belgian NGO, that works in the Third World. APOPO is an acronym: Anti-Persoonsmijnen Ontmijnende Product Ontwikkeling or Anti-Personnel Landmines Removal Product Development for those who can't manage de Vlaamse taal. Clearing mines is clearly a Good Thing, much better than developing psychotechnical fix for people who have lost a leg because the mine wasn't cleared. I talked before about bio-degradable land-mines as a partial solution and an ethical maelstrom. Why do ALL the personnel at APOPO have rats on their shoulders? Because the giant aftrican pouched rat Cricetomus ansorgei is their bread and butter.  Bert Weetjens, the founder of APOPO, had pet rats when he was a boy and was impressed by the acuity of their sense of smell and their trainability. He had the idea that they might be used, like dogs, to recognise the smell of TNT and scurry about a blighted landscape pausing over buried mines and waiting for a foody reward. They are cheaper on the upkeep than dogs and also lighter (1-1.5kg), so they are very unlikely to go up with a boom in the course of their work. The alternative to sniffing the things out is to use a metal detector, but this turns up false positives (coins, nails etc.) and puts a human operative directly at risk,  A single rat can sweep 200 sq.m in 20 minutes as opposed to a punitive 4 days with a metal detector.  The monstrous effectiveness of land-mines is that they are invisible and can deny territory by mere suspicion: only 3% of suspected mine-fields actually have any mines.  For every mine detected, the clearers have to carefully cover a helluva lot of territory finding nothing. You need a special sort of patience and dedication to do that work, quite apart from the danger-money.

They want to be careful not to let these diminutive work-horses escape as you schlep them all over the world to clean up the aftermath of bitter internecine feuds. C.gambianus is an invasive species in Florida, because like the lionfish Pterois volitans off shore, some imbecile released their pet rat into the wild. It is probably implicated in the introduction of monkeypox to the USA where it is now endemic in prairie-dogs Cynomys spp. I guess that's especially important for Cambodia where APOPO has operations; less so in Angola, Mozambique and Zimbabwe where the mine-rat is already present naturally.

Someone in APOPO then had the brilliant idea to have their rats sniff out Mycobacterium tuberculosis the causative agent of TB. TB, along with malaria and HIV/AIDS still kills an astonishing number of poor black people every year and early diagnosis is important for successful treatment. This is traditionally carried out by microscopic examination of a sputum sample. There is a likelihood of a false negative, especially if the concentration is low. But M. tuberculosis gives off a distinctive odour [beer, some say, or tar], which even people can smell if the disease is far enough developed. Cricetomus ansorgei can be trained to pick up minute quantities of the distinctive volatile molecules and pause over vials containing infected samples.

How clever is that?

Damned clever!

Dark Brew

I was on about Irish soda bread the other day and "Dark Brew" might, in that context, bring Guinness to mind but I'm going further afield than Dublin today.  The far side of the world indeed, to talk about Soy Sauce. In my youth soy sauce was utterly foreign.  I went to a Chinese restaurant about half a dozen times before I was 18, but we never had soy sauce at home where the only available added flavorings were salt, pepper and mustard; and maybe an ancient tub of curry powder.  Only recently, I've taken to adding soy sauce to a wide variety of food to give things a bit of colour and flavour. What flavour?  Umami! which, in my soy-free youth, hadn't been discovered as the fifth taste after salt sweet sour and bitter. The flavour umami depends a lot on the presence of glutamate, the salt of glutamic acid [D, glu] one of the 20 amino acid building blocks of proteins.  You will have met it, maybe in excess, as mono-sodium glutamate MSG in the Chinese restaurants we all go to more often nowadays.  Soy sauce is loaded with glutamate because it is, like bread and beer, a fermentation product. Unlike the yeasty staples of the Western world, soy sauce depends on a different species of fungus called Aspergillus oryzae or possibly A. sojae.

The ingredients of beer and bread, even without Reinheitsgebot purity regulations are really simple but in the East, the Aspergillus molds are given a more complex cocktail to work on, consisting of cooked soya beans Glycine max, [roasted] wheat Triticum aestivum (occasional barley Hordeum vulgare) and some sort of brine.   Often the fermenting brew is more complex too, including some lactic acid bacteria LABs, some regular yeast and, in some parts of the world including Korea, some Bacillus subtilis.  The brine must be there to inhibit the growth of other microbes, because LABs are often quite salt-tolerant. All these species will have a complex variety of genes and their enzymatic products which have been selected over hundreds of years to give a product that is a) safe to consume and b) tasty.  As a new-comer to soy-sauce eating, I just go to the Asia Market and buy 750ml of Pearl River Bridge Light Soy Sauce which is manufactured in Southern China and shipped over the whole world, it is tasty but also cheap.

Cheap suggests that it is made in a chemical process rather than by slow fermentation. If you want something that is rich in glutamate for the umami kick, you can get there really quickly by adding a protease [or even 1M caustic soda NaOH] to a mash of soya beans which will break down the proteins into their component amino acids, some of which will be glutamate.  We carry out a similar chemical attack in Ireland to make soda bread (as I am doing even at this moment to warm the kitchen) rather than a slower fermentative process with yeast that will have time to develop some subtlety of flavour.  In all manufacturing process, but perhaps particularly in the food industry, time is money, and less time is more profit. The several new start-ups in Ireland making various high-alcohol beverages need to be heavily capitalised because their first batch of product is required to sit on a shelf (supposedly developing wonderful flavour) for several years before it can be sold as "Irish Whiskey".

A feel-good story is circulating in the East and now on the blogosphere about a soy sauce company that was destroyed in the Fukushima tsunami and has now after four years started selling the same old product which they are rebranding as Yagisawa 'Miracle' Soy sauce. The current CEO, Michihiro Kono [L with a bottle of the miracle], is the ninth generation of this family firm that has been producing soy sauce for more than 200 years.  One of the things that people learned the hard way in Hurricane Sandy and in the 2011 tsunami is the importance of maintaining back-ups.  Kono-san's whole factory, including his precious and meticulously maintained microbiological stock strains, was filled to the brim with a salty, oily sludge from which nothing could be recovered. But he had left some vials of these stocks with a local university medical school, where they were pursuing some woo-wah theory about the anti-carcinogenic properties of the soy sauce or its ingredients.  The laboratory was similarly inundated and its contents swept away but one of their workers providentially found the carton of Yagisawa material safe-and-well some distance away.

Like Irish Whiskey, Yagisawa is a quality product that must sit tight for 2 years before being sold, and it has only started selling in the last few months, but sales are recovering well with a different direct-to-consumer marketing strategy it looks like new markets will open up. They are supplying one toney Parisian restaurant. It is particularly feel-good because the company kept all its surviving staff (one died in the waves) on the payroll when they had nothing to sell and contributed in all sorts of ways to the local community in the wake of the disaster.  Maybe you'd like to support it, too?  A crowd-funding site raised $1.5million to getting the company back on its feet. More deets. Same deets. More.

Agent BG GRAS

My youtube feed is bloody woeful; same ould same ould shite that I might have clicked-in-error months ago. What I really want is a random selection of peculiarities that I've never 'eard of. I have been to The History Guy - a USian feller with a bow-tie and clear diction - before but not this year, so I was interested to look-see what he had to say about Johnson Atoll a US government owned "bird-sanctuary" and weapons-testing facility in the middle of the Pacific. As well as poorly fore-thought, poorly controlled, nuclear debacles [Blue Gill Prime 25 June 1962], the site was also used for bio-weapons testing.

Project SHAD Shipboard Hazard and Defense investigated the dispersal of biological agents about the same size - 1-5μm -  as, say Bacillus anthracis a pathogen which we've encountered before on Gruinard Anthrax Island. The first step is to investigate the best way of dispersing / targeting such an agent so that it rains down on the Soviets [Bad Guys R] while minimizing collateral damage to USMC / USN personnel [White hats]. It was as if the multiple own goals (which proved that the wind is fickle mistress) in WWI had never happened. 

The apple falleth not far from the tree! The mad boffins lit upon Bacillus globigii which is close enough [exactly the same 2μm size anyway] to B. anthracis and has the advantage of forming black colonies when spread on Petri dishes. The central conceit of SHAD was to expose USN ships to "Agent BG" delivered in a variety of SciFi vehicles and then swap down the surfaces afterwards to see how far and fast the bacteria had travelled. "In Project SHAD, B. globigii was one of the simulants for biological warfare agents. It was used to determine characteristics such as the behavior of biological aerosols such as downwind travel, dispersion, penetration, and the tenacity of its presence after washing equipment" Bacillus globigii is now known as B. atrophaeus but some [lumpers!] taxonomists think it squeezes nicely in the spectrum of Bacillus subtilis - a genetic and bio-fermentation work-horse which we've met before.

If this sounds suspiciously close to the USN raining Serratia marcescens down on San Francisco in Operation Sea-Spray, that's because it was the same operatives ringing the changes on the bacteriological colour spectrum. That exposure turned out to be fatal to at least one US citizen who didn't sign an informed consent form! Almost all the participants in the SHAD shenanigans were also oblivious to the fact that they were guinea-pigs in an experiment. The biowarfare folks, seemed to have given "Agent BG" a GRAS [generally recognised as safe] designation without, like, actually carrying out some studies to test that assumption. And it turned out that this blasé certainty was quite unjustified although it took 30 years for the Feds to admit this. Most healthy adults will successfully resist the assault - so there wasn't a rush to the infirmary aboard the ships involved in SHAD - but Bacillus globigii has been identified in infections from prostheses and catheters as well as ingested food. The black colonies of B. globigii is not the Black Death but it's not completely harmless either.

Nosocomial nose? The noes have it!

Joy! Sometimes the headlines write themselves. Regular readers will know that I lurk-a-lot at Metafilter a site which allows a community of interested and interesting people to post once a day about what is floating their boat. Not everything there floats mine, but there is enough overlap that I check in most days in my restless search for Blob-copy. A MeFi post about I recognized your foul stench [It's a Star Wars ref] just cries to be clicked.

I've been interested academically in the evolution of olfactory receptors and am curious about the refusal of my students to use theirs. Pretty much anything that smells in the lab (or the previous inhabitants of a lecture theatre) will have them elaborately fanning their faces and throwing open windows. Young people don't like silage or slurry [or even know the difference]; they don't like Escherichia coli; Bacillus subtilis; Streptomyces or Pseudomonas aeruginosa - none of them or old bones. Limburger? No thanks! In my human physiology course I tell the students that, before they had pee-sticks, doctors used to diagnose diabetes by dipping their finger in a urine sample and tasting it - sweet indicates a problem, because are kidneys are really good at recovering circulating glucose. EEeeuuww, the students shriek. They must be terrible cooks if they are so unwilling to taste, taste, taste.

The MeFi post is more or less about a commercial product called Liquid Ass which 'smells like butt-crack' and has a ready market among fart frat boys even at $13/bottle. Ho ho "I sprayed a small stream of it in my buddy's office and it ruined his entire day!" etc. But there is a minority demand for the product among those who are training nurses, first-responders and battlefield triage medics. Best get the disgust [prev] under control in class before you have to deal with it at the coal-face. As so often on MeFi, the comments are often as rich as the original post. I now know far more than I need  about fisting, for example. And a list from Slarty Bartfast of various hospital smells that knock Liquid Ass into the ha'penny place: yeasty body odour; bloody stool; necrosis and gangrene. And others that are less unpleasant: electrocautery [bloboprev]; amniotic fluid, strep throat

But, given my previous short list of the smell of different species of bacteria; and my ongoing interest in the well-known potentially deadly nosocomial [hospital-acquired] pathogen Clostridium difficile, I was delighted to find the comment by ericales "I've found C. diff to have a very recognizable odor." Yes, yes, but what is that smell? I googled and found lots of nurses certain that they were 100% precise and 100% accurate and no need for the path lab in detecting a C.diff infection by the whiff: moldy like stale bread...tinged with a little skunk; outhouse during 3 months of 110+ degree temperature days; rotten chicken meat smell, (like when you smell that chicken and go..."no way..can't make this tonight!) mixed with baby diaper sweet smell, mixed with old blood smell [which in turn smells like I have nickels in my mouth]; road kill on a 100 degree day mixed with silent but deadly flatus.

But it just ain't true, because when you put normal nurses, even the confident ones, in a proper scientifically controlled double-blind experiment, it turns out that they are piss-poor in matching the smell to real C.diff samples. But you might have know that already from the lack of agreement about what C.diff actually smells like.

Similar proteins

Proteins are made of amino acids stuck together in long chains which come curling out of ribosomes in an order dictated ultimately by the DNA in the genes on the chromosomes in the nucleus of every cell which makes new proteins -- which is all cells that
are still alive. I've spent the last 30 years trying to make sense of those sequences: usually comparing them by alignment. Here's part of the sequence of insulin for pigs and humans:
SP|P01315|INS_PIG   PQAGAVELGGGL--GGLQALALEGPPQKRGIVEQCCTSICSLYQLENYCN 108 SP|P01308|INS_HUMAN LQVGQVELGGGPGAGSLQPLALEGSLQKRGIVEQCCTSICSLYQLENYCN 110
                     *.* ******   *.** *****  ************************
Notes:
[Each of the 20 amino acids found in proteins has a unique 1-letter code. And a more readable 3-letter code too]
{For the first half of the 20thC, diabetics were injected with insulin extracted from thousands of pig pancreases and it worked just fine.}

You can see that the sequences, and therefore by inference, their 3-D structures, are very similar but with several significant differences: the human version has two extra amino acids GA for starters.  If the final functioning protein is in 3 dimensions, then the linear sequence, as it appears from the ribosomes, or as represented on paper and on screen as above, can be thought of as a 1-D object. In between, biochemists talk about the secondary structure, which is comprised of the intermediate building blocks or structural elements: α-helices; β-sheets; turns; ω-loops.

How similar do protein sequences have to be for us to believe that a) they have a common ancestor and b) they therefore have a similar structure and function? If you line up any pair of sequences, some of the letters will match because there are only 20 amino acids to play with. Like when I align the opening words of the first two paragraphs above:
Proteins are made of aminoacids
You can see that the sequences
3/30 = 10% of the letters appear in the same position in these random unrelated sequences. Molecular evolutionists talk about the twilight zone when ~15-20% of the amino acids are identical between two sequences. More than 20% identity and you can be reasonably confident is assigning similar function and inferring the same 3-dimensional structure. In the twilight zone you really need some independent information to make that call. You might naively think that the random probability is 5% = 1/20 because there are 20 amino acids to play with. But because you're allowed to insert gaps in one sequence [to accommodate the extra GA in the insulin above, for example] and because some amino acids eg LAG and more common than others eg HWC:

the biologically meaningful / statistically significant cut-off (and the Twilight Zone) are pitched higher than 5% at just under 20%. To be continued . . . as gene location becomes the added value independent information to match barely detectable similarities between genes in two different species.

Years ago, in the late 90s, I wrote some code to deconstruct protein sequences as if they had been hydrolysed by 1M NaOH [that's caustic soda to cooks] into a soup of their component amino acids. This might be though of as a protein's 0-dimensional structure. My program also tallied up and counted the frequency of each of the 20 amino acids. Tricking about with a test dataset, I noticed that this string of 20 numbers had quite high predictive value: the AA frequencies of Bacillus subtilis recA could predictably fish out the recA in Escherichia coli etc. I got sufficiently excited about this that I presented it as my contribution to the weekly internal lunchtime research seminar. Ken Wolfe, not yet my boss, but usually the smartest chap in the room, said he'd noticed this several years earlier but hadn't though it worth publishing. My abiding problem as a scientist is that I lack the stamina to get results, even interesting results, down on paper and through the publication process. I am thus glad to be able to publish this executive summary in The Journal of Blob Studies - they will take anything.
  Part II.

Darwin's last days

Darwinday today as it was last year and indeed for me every previous year back to 1982 the centenary of Charles Darwin's death. Events that year gave some traction to the canonisation of St Darwin of Downe which is pursued with quite evangelical vigour by some who 'believe' in evolution. When I worked at Evolution Central in a couple of Genetics Departments, I used to bring donuts in to work as a sort of agnostic host. My fellow believers were happy to glom down a donut on Der Tag but generally forgot about the great man for the rest of the year. The trouble is that, to be successful in science, you need to specialise and focus on one area of expertise - like cyanogenesis in plants fr'instance - rather than flitting from one thing to the other as the fancy takes you. I was never a very successful scientist because I was always starting something new before I'd wrapped up and published the previous project. That butterfly mind makes me a successful, or at least prolific, blogger.

As Robert Heinlein said specialization is for insects: you can't understand, let alone explain, evolution unless you know some biogeography, some embryology & development, some taxonomy and comparative anatomy, some geology . . . and some genetics helps too. If you have spent the last 20 years studying mutations in the upstream control control region of a single gene in Bacillus subtilis, you're not going to do well in a TV debate with an intelligent designist.

The final year honours course I taught in Newcastle was a whistle-stop tour marshalling the evidence for evolution a) as Darwin knew it and b) as subsequent developments, like Mendelian genetics, had added to and fleshed out that evidence. Even back then I filled out the Evolution course with nifty anecdotes about mutilated bears and Slijper's goat, rather than sticking strictly to genetics. I was driven to develop, write and deliver that course because one of our students, a biblical fundamentalist [Plymouth Bretheren?] asked me to recommend a book on evolution that she could present at her church's monthly book club. I was completely wrong-footed by this request because, although I could think of a few books, I couldn't there and then convince this young wan that evolution was a better explanation of the marvellous diversity of life than God's Grandeur. And this was just a couple of years after I'd taken BI504-Evolution sitting at the feet of Lynn Margulis in graduate school. Shame on me!

If you ask most biology students - those in the bible-belt of the USA possible exceptions - if they believe in evolution they will say Yes, of course without the least blush of shame that 'belief' is a disturbingly religious word. Furthermore, because they have neither read the Origin of Species, nor taken BI504 or my Evolution from primeval soup to hominid nuts course they are not qualified to assert such a belief because they don't have a coherent bank of evidence to back that belief. Same goes for almost all the teachers of biology in school and college.  Today, in honour of Darwin's birthday you might resolve to read The Origin - you won't be disappointed and you will be blizzarded by quirky facts. If you're French, and that's currently more than half my readers, you might pick up Thomas Glick's The Comparative Reception of Darwin for less than $10. I was lent a copy by Lynn Margulis in the 1980s. That shows that Darwin had a different impact on thinking people on the Continent than in insular Britain where they made Darwin FRS, FLS, FGS and FZS and knighted three of his sons . . . which?:

On dit que Darwin spent 20 years not writing the Origin of Species because he was conflicted by religious doubts and was only goaded into committing his thoughts to paper to avoid being scooped by Alfred Russell Wallace in 1858. That is peculiar because all his children grew up to be agnostics and felt that they had taken that position from listening to their Papa. Nearly 100 years ago a peculiar story was put about that Darwin had a sort of death-bed conversion and invited a bible thumper called Lady Hope to preach to his servants and tenants in the summer house at Downe. The idea of this evangelical busybody pitching up in Darwin's bedroom in the last year of his life to hear his confession has the ring of augmented truth. It's the kind of thing my Great Aunt Lily would have done. That dreadnought lady had a habit of ringing the doorbell of whatever grand house she was passing and insisting on viewing the staircase or the Adam fireplace in the main bedroom. The fact that all Darwin's children [the seven who survived to adulthood are shown above] were adamant that the meeting with Lady Hope had never taken place doesn't fully allay suspicion.

Chargaff rules, ok

The dogs in the street know the story of the discovery of the structure of DNA.  Daring and iconoclastic model-makers Francis Crick and Jim Watson finally cracked the problem in 1953; signing off their classic Nature paper with a laconic understatement "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material." The dogs also know that the boys had pulled a fast one on Rosalind Franklin whose key and revealing X-ray crystallographic data was shown to them by her boss (or not her boss, they couldn't agree on the matter and were too British to talk it out) Maurice Wilkins. Wilkins was a personal old-boy-network friend of  Crick who is claimed by scientific chauvinists in New Zealand (where he was born) and Ireland (where his people were buried). Franklin did not get a share of the Nobel Prize because she was dead by the time the Nobel committee got round to recognising that the DNA coup was indeed a) correct and b) ground-breaking. Crick, Watson and Wilkins split the loot three ways.  The youngest of them and the only survivor was in Dublin a couple of weeks ago.  So far, so grossly simplified in the telling.

But Crick and Watson's insight depended on another crucial piece of evidence that had been carefully worked out earlier by Erwin Chargaff. In 1950 he had noted that the ratios of the four bases A, T, C, G in DNA varied according to source: Mycobacterium tuberculosis has a %G+C of about 65% while Bacillus subtilis has a %G+C = 40%.  That was interesting and unexpected under then current theories of DNA structure and function. Chargaff's other (and more revealing) Rule says that the ratio of pyrimidine bases (C & T) to purine bases (A & G) is always 1:1 regardless of source.  In particular he noted that %A = %T and %G = %C.  But it does seem to have escaped his notice that this information offered the crucial insight that A paired with T and C paired with G on opposite strands of the double helix.  Some more detail of who ripped what from whom is found in a Nature Education piece by Leslie Pray.

Chargaff must have been kicking himself when the true meaning of his finding was revealed by Crick and Watson just three years later. Not least because he had a very poor opinion of Crick and Watson as knowledgeable scientists "The [first] impression, one 35 years old, the looks of a fading racing tout, something out of Hogarth's The Rake's Progress, Cruickshank, Daumier; an incessant falsetto with occasional nuggets glittering in the turbid stream of prattle. The other, quite undeveloped at twenty-three, a grin more sly than sheepish; saving little, nothing of consequence." And his description of what they actually knew was even less flattering: "So far as I could make out, they wanted, unencumbered by any knowledge of the chemistry involved, to fit DNA into a helix. The main reason seemed to be Pauling's alpha-helix model of a protein....I told them all I knew. If they had heard before about the pairing rules, they concealed it. But as they did not seem to know much about anything, I was not unduly surprised." After the hullabaloo of the Nobel Prize his opinion was more polished / poetic: "That...such giant shadows are cast by such pygmies only shows how late in the day it has become".  Ouch! But Chargaff had a bit of  a reputation for not holding back to spare someone's feelings: "Erwin Chargaff, had written "an exceedingly sarcastic letter" in assessing his findings" . . . about Arthur Kornberg's Nobel prize winning work on the enzyme that makes copies of DNA.

It's Chargaff's birthday (11th August 1905) today, I think a bitter lemon cake and a glass of vinegar might be appropriate. But I can't help thinking that, of all the DNA principals, Erwin Chargaff would have been the most interesting to have dinner with.