Thursday 13 February 2020

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

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