Monday, June 21, 2021

mRNA therapies coming soon

One of the major changes brought about by the Covid-19 pandemic is that it lifted medical applications of RNA out of obscurity and to global stardom. Just imagine, trying to promote an mRNA in a lipid nanovesicle as a therapeutic in December 2019. You would have had to work very hard to persuade people that it's probably safe and might actually work. Now you can just point to the mindboggling fact that hundreds of millions of people have received vaccines based on this principle - within six months.

Given that all the experts in the field are currently either busy developing new products or already counting their billions, I went through the back catalogue of RNA therapeutics that were in development before Covid happened, on the assumption that these will now find it much easier to find funding and get approval and actually reach the market.

My feature on those other, non-Covid medical applications of RNA is out now:

The renaissance of RNA therapies

Current Biology Volume 31, issue 12, pages R763-R765, June 21, 2021

access to full text and PDF download
This is currently on open access as part of the general Covid-19 info policy from Cell Press. Should that change, it will become open access again one year after publication

Any problems with the link above, try the:

Magic link for free access
(first seven weeks only)

mRNA researcher at the German company BioNTech, which in collaboration with Pfizer brought the first mRNA vaccine to regulatory approval. The company also develops treatments for cancer and other diseases based on mRNA. (Photo: © BioNTech SE 2021, all rights reserved.)

Saturday, June 19, 2021

sous le kiosque a musique

Ce qu'on peut rigoler
Par les beaux soirs d'été
Sous le kiosque à musique
On entend l'orphéon
Les tambours les clairons
La fanfare et la clique

I'm regularly using Oxford's only bandstand this plague year summer, both for chamber music and for folk sessions, so I am often reminded of one of my favourite French songs, an ancient one from the 1930s, which gently mocks the culture of widespread amateur / semi-professional music making for which these structures were built. I'm loving all the attention-grabbing flourishes and fanfares in the melody which are obviously a parody of the type of light music you might have heard at a bandstand on a summer evening in the early 20th century. Now that this culture has gone the way of the dinosaurs (along with the ophicleide mentioned in the text) and bandstands are mostly silent, I wonder what the authors of the song might have to say about it.

I've known the song since forever in the version performed by Georges Brassens (1921-1981) in a radio programme dedicated to the popular music of his youth: Georges Brassens chante les chansons de sa jeunesse (also available as CD).

Looking it up right now, there seems to be a general block in place forbidding users in the UK to access this recording. If you're outside the UK, you may be lucky to be able to listen to it on Soundcloud here.

I never knew the original version, only now I unearthed this one from jazz band leader Ray Ventura (1908-1979) which I'm assuming must be the version Brassens heard in his youth.

The only modern cover I've found is this one, which looks like a music teacher made it for kids, but it does have rolling lyrics, so if you want to learn the song it's a good resource (there are also chords provided here). According to this video, the composer is Marc Lanjean, and the lyrics are by Maurice Vandair.

Lyrics are also here (wrongly attributed to Brassens).

I've poked the very amazing Pomplamoose via twitter, I think they should definitely cover this.

Not our local bandstand, but one I saw at Romsey on a day trip earlier this year.

There is also a lovely flickr group called Bandstands Worldwide where you'll find some amazing structures (loving this one in Hove) as well as the occasional contribution from me.

Friday, June 11, 2021

Neumühl 1923

A mysterious photo from my inlaw family - there is no memory of anybody in the family ever having played a musical instrument, but then there is also this photo with the name of a great-uncle on the back (Friedrich Kosmowsky, sometimes also spelled Kosmowski), and the place name Neumühl, which is now a district of Duisburg. Several of Friedrich's relatives came to nearby Hamborn in 1922. To add to the confusion there was also a place called Neumühl in the area of Eastern Prussia where they came from (Kreis Wehlau), also very close those who didn't move west in 1922. This one is now part of Kostromino in the district of Kaliningrad. It could be either - although given that the Hamborn relatives didn't know anything about musical adventures, I am inclined to think they happened in Eastern Prussia.

Tuesday, June 08, 2021

brother Klundt

Nearly seven years ago, I wrote up what I knew about the descendents of my ancestors Johannes Klundt and Eva Hust, who had emigrated to the Black Sea (today’s Ukraine) with their youngest children, while the oldest son, Johann Jacob Klundt (1782-1853; my four-times-great-grandfather) stayed in Germany.

The post has created a lot of interest (as well as inspiring a master dissertation from the young historian in the family) and most recently, two readers have been able to fill me in on the descendants of the youngest son, Georg Michael Klundt (1805-after 1866), about whom I knew nothing back then. It turns out his son became famous as a founder of the Baptist community in Bulgaria, but let’s start from the beginning again, from the migrating couple, and the new village of Rohrbach where they settled.

I found the historic report of school master Fritschle (an English translation available here) who taught at the village school in 1848 and wrote a detailed account of its history with its ups and downs. It started in 1809 with 26 families, and another 69 families arrived in 1810. Another arrival of five families brought the number to 100 families with 475 individuals. There were numerous Fritschle individuals among the settler families, so the schoolmaster definitely came from within that community, but I don't know his first name and haven't been able to identify him in the databases.

Fritschle noted that this happened under the authority of the governor “Rischileu”. I recently learned from Neal Ascherson's excellent book Black Sea that the city of Odessa, founded around the same time, was essentially run by French nobility that escaped the French Revolution. So this governor was Armand-Emmanuel Sophie Septimanie de Vignerot du Plessis, the 5th Duke of Richelieu and Fronsac (1766 –1822) who later returned to France to serve in the restored monarchy.

In 1810, my relatives at Rohrbach accounted for two households with nine individuals:

Founder family: Johannes Klundt, 51; Eva Katharina Hust, 48; Eva Catharina, 18; Heinrich, 13; Johann Michael, 9; Georg Michael, 5.

First generation family: Wilhelm Klundt, 25; Ottilia Golum, ca. 22; Jakob, 3

Fritschle notes that the Russian government paid for a stone-built house for every family. All other necessities such as farming equipment, seeds, animals and food were provided on a credit basis.

According to Fritschle, the colony failed to thrive in the first 18 years, because the colonists were lacking the relevant skills and/or work ethic, and for most of the time, the village didn’t have a pastor to instil the fear of God in its residents. Pastorn Elias Hübner was appointed in 1812, but died after less than two years in the job.

In 1824, the pastor Johannes Bonekemper (1795-1857) was appointed as pastor for both Rohrbach and the neighbouring colony of Worms (7km away). Bonekemper was of Reformed protestant faith, but was also tasked with offering Lutheran services. Also, from 1826, a new schoolmaster arrived, Wilhelm Eberhard, who taught until 1843 and is credited with a change of culture.

Bonekemper spread the “Erbauungsstunde” idea (a daily hour of spiritual recollection) around the Southern parts of Russia, creating what became the “Stundist” movement. A more extensive account of his role in the Reformed faith is here, scroll down to the subheading "Life in Russia". By 1847, the spiritual fervour of Bonekemper's followers got out of hand to an extent that authorities persuaded him to move on which he did in 1848. Schoolmaster Fritschle, by contrast, created the impression that Bonekemper resigned voluntarily and praised the spiritual renewal he achieved: "The blessings of his 24-years' work with us will long be remembered." Bonekemper was intending to emigrate to the USA, but didn't make it.

In the early 1840s, seven families from Rohrbach, including Georg Michael Klundt and his wife Elisabeth Feiock (* 1817 Rohrbach) moved to the new colony Neu-Danzig and took the stundist idea there. They had married in 1836 and had three children, including Margaretha (1837), Jakob (1839) and Barbara (1841). They may have had additional children in Neu Danzig, possibly including Beatha Klundt.

By 1840, the founder couple Johannes Klundt and Eva Hust had died, but all their children had families, with up to eight children. In stark contrast to the school master's moans about the colony’s initial lack of economic success, this family was thriving rather nicely, as judged by survival rates. Not counting the descendants they left behind in Germany, the founders had at least 19 grandchildren, and 22 great-grandchildren.

In 1864, the Klundts in Neu Danzig became Baptists, which was a growing but illegal faith in Russia. In 1866, Jakob and his young family fled to Katalui, in the Danube delta, which was then a German colony under Osman rule, now known as Cataloi, Romania. This wider area on the West Coast of the Black Sea is called Dobruja, and the German settlers were known as the Dobrujan Germans. Georg Michael followed them and died there after 1866. The above-mentioned Beatha Klundt and her husband Johann Wilhelm Graf also moved there. Their first three children were born in Neu-Danzig in 1862-1865, but the fourth was born in Cataloi in 1867.

Jakob started a Baptist community in Katalui, which appears to have been so successful that he was hired by the British and Foreign Bible Society as a Bible colporteur for Bulgaria and part of Macedonia and Albania in 1872. For eight years he worked and traveled from Albania, but dangers and difficulties he faced there led him to move his base to Bulgaria.

From 1880 and for the rest of his life his base was in Lompalanka, now Lom, Bulgaria, and any history of Baptism in Bulgaria includes his biography (see eg here) and sometimes even a portrait (see below). His name in Bulgarian looks like this: яковъ клундтъ (in case anybody wants to dive into Bulgarian sources). Accounts mention his wife Regina as an active participant in the Baptist community, but don’t mention his descendants by name. He did have a son in law who later took over his role as pastor in Lom, so at least one daughter survived. We believe that no sons survived to adult age.

Jakob died on March 28, 1921, in Kazanlak, Bulgaria, where he was staying with his son in law (the obituary does not mention his daughter at this point, not sure if she was still alive).

Of Jakob’s sisters, we know nothing about Margaretha beyond her date of birth, but his younger sister Barbara married Philipp Krause and had five children. Only Barbara Krause (* 1864 in the Black Sea colony of Worms) survived to adulthood, she married Johann Brandner, emigrated to South Dakota (as many other descendants in her generation did too) and had 14 children.

Portrait of Jakob Klundt which appeared with his obituary in The EVANGELIST, Organ of the Evangelical Baptist Union of Bulgaria, editor: Rev. V. Tachtadjieff, Tchirpan.

Special thanks to Mihai, whose comment under the original Klundt Clan post already contained a lot of information about Jakob Klundt and set further investigations and contacts rolling.

Monday, June 07, 2021

giraffe genomes

I tend to write about species that are underappreciated, eg because they are living underground or in the deep sea or because they are invisibly small. Every once in a while, however, I also cover the big beasts that everybody knows from their local zoo or wildlife park. So this week it's the debut appearance in my writing of the mighty giraffe. I had noticed a paper on its collective behaviour, as well as one on genomics explaining its extreme adaptations, and then it turned out Current Biology had another one in the pipeline with more giraffe genomes.

So here goes, the questions you were asking on your first visit to a zoo, can finally be answered:

Survival of the tallest

Current Biology Volume 31, Issue 11, 07 June 2021, Pages R697-R699

Restricted access to full text and PDF download
(will become open access again one year after publication)

Magic link for free access
(first seven weeks only)

Giraffe mothers with calves are more often seen near human settlements, presumably due to the lower risk of predation from lions and hyenas. (Photo: 12019/Pixabay.)

Thursday, June 03, 2021

delta rising

It is fairly obvious now that the delta variant (formerly known as B.1.617.2, first identified in India) is out of control in the UK, as the week-on-week increase in case numbers has been accelerating dramatically over the last 10 days.

Week-on-week rise in new cases, last 12 days, according to the govt. data site:
24.5. + 17.0 %
25.5. + 18.0 %
26.5. + 18.0 %
27.5. + 20.5 %
28.5. + 24.0 %
29.5. + 23.3 %
30.5. + 26.8 %
31.5. + 28.8 %
1.6. + 31.9 %
2.6. + 34.7 %
3.6. + 38.9 %

To unpack those data: any positive percentage means new cases in the last seven days are higher than they were in the previous seven days. A constant percentage means an exponential rise, but at around 20% per week, it would only double in four weeks or so, so if the figure stayed at 20% it would be nothing to panic about.

What really worries me is that the percentages are increasing, and even this increase seems to be getting faster. From Tue to Wed it was 4.2 percentage points more, a jump of a size we haven't seen recently. The likely explanation is that it started in a few clusters, but as these clusters haven't been containe, it's gaining more and more territory to spread in. If this trend holds up we will end up with a doubling time well under a week before the month is out, and then we're in trouble. Even if many of the most vulnerable people are vaccinated, the extra risks that they are likely to take because they feel safe after being vaccinated may well compensate part of the gain. The other part may be wiped out by the Delta variant being more agressive than the original version. Early data suggests it may well be, see today's report in the Guardian.

Hospital admissions are also on the way up, while deaths have just begun to rise again after Monday's minimum of 43 deaths in the last 7 days. Today this fitgure is 54. As cases have been rising for more than two weeks now, I am guessing that this was the turning point and deaths are also creeping up again.

I really don't think the lifting of all regulations can go ahead on June 21 as scheduled, and if it does we're bound to have a rather murderous summer which could rival the previous waves not just in cases but even in hospitalisations and deaths. There are always people unprotected, and an epidemic running out of control will eventually find them.

The other big covid news in the UK is that Portugal has been removed from the green list, which means people returning from there are not exempt from quarantine. This is of course a distraction. As we have a Variant of Concern spreading out of control in the UK, nobody should have been allowed to travel to Portugal in the first place, especially not those footballers who could have just sas well played their game in Wembley.

Update 6.6.: the last three days have continued the trend shown above. If anything, the percentages are rising faster ...
4.6. + 39.8 %
5.6. + 46.2 %
6.6. + 49.0 %

Meanwhile, clusters of Delta are also beginning to pop up in France ...

Tuesday, June 01, 2021

jigging into summer

Plague Year(s) Bach Project, 16th month

As I write this, it is becoming clear that the govt. has lost control over the spread of Covid for the third time, so if they continue to eff up things like this, I'm still in with a chance to get through a considerable part of the Bach suites.

In May, I memorised what was missing from the Courante in G, and promoted it to metronome work - although it's rhythmically very simple, it still needs speeding up considerably. It's a running dance, and I'm still sleepwalking. I also consolidated the minuets in D major and D minor to an extent that I can play them as a unit as they are meant to be played.

In June, I am aiming to memorise the second half of the Gigue in D minor, and also do more park "performances" (if people around politely ignore me that's good enough). May was very rainy, so not much luck with playing cello in the park, but at least the Wednesdays were ok for Cowley Orchestra, which in very much reduced formation played some chamber music on three evenings this month. And accidental audiences were very appreciative - many will not have seen any actual humans playing actual musical instruments in more than a year!

So after 15 months with 420 practice days, 12 movements studied, and 424 bars memorised, my list now looks like this:

1) movements I've studied for a month, then put aside for now
1.1. Prelude
1.2 Allemande

2) movements memorised in a significant part
2.6 Gigue (1/2)
3.4 Sarabande (1/3)

3) movements memorised in their entirety
1.3 Courante
2.4 Sarabande
2.5 Minuet I&II
3.6. Gigue

4) movements memorised and synchronised with metronome
1.4 Sarabande

5) movements recorded on video and also performed in public
1.5 Minuet I&II- VIDEO
1.6 Gigue
(ooops, need to upload the video, watch this space!) 3.5 Bourree I&II - VIDEO

Sunday, May 30, 2021

new wave

So here we go again, the UK govt is making the same mistakes with the new variant first identified in India (B.1.617.2) as it did with the original Covid and then with the Kent variant (B.1.1.7) - play down the problem, let it spread, and only act when people die in their hundreds.

As the Death Eaters are going to deny it later, here's what we know today, 3 weeks before the planned end of all restrictions. B.1.617.2 is spreading exponentially in England. So far, this rise has been masked in the overall stats by the decline of the Kent variant, but now that B.1.617.2 is the dominant version, it is beginning to dominate the stats, and those stats are pointing upwards, at up to 30% increase week on week. I reckon that figure will still get worse as the variant spreads to places as yet unaffected. Follow Christina Pagel on twitter for the latest warnings. Also this analysis by David Spiegelhalter and Anthony Masters which just came out in the Observer today.

I hear the AZ vaccine which is predominantly used here, protects to 60%, so we have still 40% of the original risk. So if with B.1.617.2 as compared to the original strain, and all other things being equal, we're 2.5 times more likely to get infected, this cancels out, and we're just as screwed as we were last year with no vaccine. [Update: numbers corrected 1.6. - in the original version I stated wrongly that it would only take a 1.6 fold increase in infection risk. Still quite realistic possibility that this will happen, eg it's 60% more contagious than the Kent variant, which was 60% more contagious than the original strain, 1.6 squared is 2.56.]

Meanwhile, two English football clubs played the champions league final at Porto, Portugal, yesterday, and English fans were allowed to travel there and spread the the new variant a bit more. Spain is also welcoming tourists from the UK in June. Both countries will come to regret this before the summer is out. As Champions League games played a significant part in spreading the original Covid around Europe (First Valencia fans travelling to Covid-infested Italy, then Madrid fans travelling to Liverpool as Spain was preparing for lockdown), I really don't understand why these things are still allowed to happen.

So even though we're fully vaxxed now, we're still stuck on Mutant Island for the foreseeable future ...

street scene from the first pandemic summer, own photo.

PS: Today's figures from the govt website just in:

22474 new cases in the last 7 days, that's 4755 more than the previous week, up 26.8% in a week. 60 deaths in seven days, up 18 or 42.9%. Hospital admissions up 23% week on week.

If you ask me, don't plan anything for June 21 onwards that you wouldn't be comfortable with right now, or better still live by the rules we had before May 17th. The third wave is happening.

Friday, May 28, 2021

in praise of amateur music making

Some thoughts on

Play it again: An amateur against the impossible
Alan Rusbridger
Vintage paperback 2014

Reading Alan Rusbridger’s piano-centred memoir ten years after the events is perfect timing for me, as I am almost exactly ten years younger than him, so, right now, I can relate to his 2011 persona quite well. In fact, like him, I have also launched a crazy musical project at the age of 56 (ie last year, in response to the covid crisis), and like him I am considering writing a book related to it. However, my professional life doesn’t involve steering the Guardian through some of the most adventurous times in its 200 year history, so there the similarities end.

But even if you’re not 56 and seeking crazy music challenges, you might enjoy his memoir, eg as a celebration of amateur music making. This hobby has declined steeply with the advent of recorded music, as many of the pianists Rusbridger interviewed have discussed. Until the 19th century, if you wanted music at your wedding, in your salon, or just for your enjoyment after work, you would have to pay a musician to play it, or play it yourself. And many people did. To the extent that, as one interviewee remarked, a composer’s success in the 19th century was decided in private music rooms more than in the concert venues.

Since recorded music became ubiquitous, this motivation disappeared, and fewer people played. Those who played professionally had access to recordings of the best performers to compare themselves to, which drove up standards and opened a chasm between them and the remaining amateurs, where a continuous spectrum of standards had existed before. Which leads us to the somewhat deplorable state of the world where Rusbridger fears ridicule from fellow editors in chief for his musical hobby, whereas playing golf or tennis would count as a perfectly reasonable pastime for the editor in chief of a major media outlet.

The crazy challenge he took on, for no other reason than being impressed by a performance from a fellow amateur, was Chopin’s ballade in G minor, op 23. The score is included in the book, complete with markings from Rusbridger and his four piano teachers, the whole battlefield. A nice touch, and yes, to this non-pianist the piece does look quite scary. It lasts around nine minutes when played by professionals (see eg Olga Scheps here).

Other things happening in his musical life during the time include some chamber music – he also plays clarinet and appears to have many musical friends – building a music shed and buying a piano for it, and endless discussions with numerous pianists up to and including the stellar Alfred Brendel and Daniel Barenboim. I sometimes had the impression that he spent more time talking about the piano than actually practicing it.

Then there was the day job, which at that time involved dealing with Julian Assange and publishing the original WikiLeaks files together with Der Spiegel and the New York Times, and then the peak of the phone hacking affair, culminating in the revelation that the News of the World had (among thousands of others) also hacked the phone of murdered teenager Milly Dowler – a Guardian scoop that forced Rupert Murdoch to close the News of the World. (This story is also told from a different perspective in Tom Watson’s excellent book Dial M for Murdoch.)

So, never a dull moment, but I’m glad now that I’m more in control of my work-music balance than he was. He has since then retired from the Guardian post and become principal at Lady Margaret Hall, Oxford, in fact less than 1 km away from my place. I trust he has a lot more time for practice and playing now.

Wednesday, May 26, 2021

replicating the RNA world

I'm really excited about recent progress in the field of recreating the RNA world. The very small bunch of people pursuing this is now tantalisingly close to having an RNA molecule that can replicate itself or other RNAs of the same size. Once they achieve this, I naively imagine, they could just let the magic molecule loose in their in vitro RNA world scenario and watch it evolving all by itself, re-enacting the origin of life. I wrote a feature about this for Current Biology last autumn, but since then Peter Unrau's group has made another step forward in mimicking modern aspects of gene regulation on the the RNA World stage, in a move that also improves processivity, i.e. the replicating ribozyme staying on the template for as long as it takes. So, my new feature, taking this step into account, is now out in C&I:

Spark of life

Chemistry & Industry Volume 85, Issue 5, May 2021 Pages 26-29

access via:

Wiley Online Library (paywalled)

SCI - appears to be on open access right now

Loving the carnivorous plant closeup on the cover - nothing to do with my feature, but with a feature on plant peptides.

PS The previous issue (No. 4) includes my review of the book Stem cells: From hype to hope on page 37)

Monday, May 24, 2021

a different kind of plague

With the pandemic and everything else going on, a different kind of plague has received very little attention, although it also causes devastation in several countries, the locust outbreak in East Africa and the Middle East.

Following a suggestion from the editorial team at Current Biology, I have looked into the fascinating science of why and how solitary insects turn into devastating swarms. While surveillance and early intervention can stop it from happening, there's no way of putting the genie back in the bottle, which is why insecticides are being applied at a massive scale. I find this a bit frustrating, as it would be both amazing and useful if chemical ecologists could come up with a pheromone that switches the swarm back into solitary animals that disperse and avoid each other. Might be useful for humans, too on occasions when they become a nuisance. (Oh, and I forgot to mention in the feature, the periodical cicadas now emerging in North America are unrelated, they are true bugs, while the locusts are grasshoppers. Will have to do a separate feature on cicadas some other time.)

My feature is out now:

How locusts become a plague

Current Biology Volume 31, Issue 10, 24 May 2021, Pages R459-R461

Restricted access to full text and PDF download
(will become open access again one year after publication)

Magic link for free access
(first seven weeks only)

Locusts, while harmless as solitary individuals, are among the worst pests known to mankind once they become gregarious. (Photo: christels/Pixabay.) NB while this image was labeled as "desert locust" on pixabay, I am told it may show a different species of grasshopper. So for illustration purposes only, don't use the picture as a field guide.

Sunday, May 23, 2021

quartet times three

I kept saying we only have two photos of the string quartet in which our family cello Heinrich and his eponymous owner participated, but I was wrong, I've rediscovered a third. To avoid confusion, I'll reunite the three here (they also appear in my flickr album "family history").

This is the one I rediscovered most recently,

this is the classic group portrait, dated April 1927,

... and here is the quartet in action.

I only realised last year that, zooming in on the sheet music in the last picture, one can read that they are playing BRAHMS. He only published three string quartets, so that narrows it down dramatically.

All photos were taken by my grandfather Richard, who was the only child of the cellist and a keen photographer.

I'm still none the wiser re. who the other three musicians were, see my search appeal here.

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