Moral Directions

This cryptic clue

Right, second right, then a left.  (5)

was set by 'Punk' inThe Independent (a daily UK newspaper), The solution depends on a frequently-used abbreviation of the synonym 'moment' for 'second'.

Covid-19: Who passes it on?

In tracking the course of an epidemic, the R-number - the average number of infections caused by an infectious individual - is a crucial parameter in understanding the spread of a disease. Although less talked about, the dispersion rate is important too. The following cumulative frequency chart, which is taken from a large-scale study of covid-19 track-and-trace data in India, shows that 71% of infected individuals did not pass their infection on to anyone else; a further 19% accounted for 40% of the directly-transmitted infections, while the remaining 10%, the so-called 'superspreaders', were responsible for a full 60% of the transmitted cases.

Small proportion responsible for most infections

The above diagram, published in The Economist, uses data from a paper by Ramanan Laxminarayan of Princeton University and eight co-authors that analyses information from test-and-trace records in Andhra Pradesh & Tamil Nadu between March and August 2020. Their data involved 84,965 infected individuals and 575,071 of their known contacts who subsequently tested positive for covid-19. 

Slippery Surfaces

The obvious interpretation of a good cryptic crossword clue, taken at face value, should have nothing to do with the answer; in fact, the 'surface meaning' should deliberately lead you astray. This is in contrast to the non-cryptic kind where the solution is a synonym for the clue. Here are two good examples of such clever deception: 

Founder of business in Kentucky  (4 letters starting with S) by Tim Morey in The Week

Left-wingers, for instance, spouting Marxist doctrine (3 letters starting with I) by Jumbo in The Times

In one case the defining verb masquerades as a noun. In the other, what could be the defining noun is a key part of the word-play. 

Corrupting the Coronavirus Code

Inoculating with live attenuated (weakened) versions of deadly viruses has been a successful approach to eradicating viral disease. Two striking examples are: 

• The variola virus that causes smallpox.  Before smallpox was completely eradicated in 1977, an estimated 50 million cases worldwide led to 2 million deaths each year and left many survivors crippled and disfigured.
• The poliovirus that causes the sometimes-crippling disease of poliomyelitis. Protection is given with one or two doses of a vaccine delivered orally on a sugar lump. Through a concerted international campaign, the 350,000 annual cases of polio recorded worldwide in 1988 has been reduced to 179 cases in 2019, thanks to widespread inoculation with both the live attenuated and the inactivated versions of the virus.

More than 150 different vaccines are now being developed around the world to combat the coronavirus SARS-CoV-2 that causes the severe respiratory disease Covid-19. A number of different immunological approaches are being tried, including several that use live attenuated viruses (LAV). Codagenix is a US company working on this approach in collaboration with with Serum Institute of India, a large-scale manufacturer of vaccines. A novel feature of their approach is the use of synthetic biology to weaken the virus strain. Whereas the process of creating LAVs previously took years to develop — requiring a patient search for naturally-occurring mutations in millions of generations of the virus hosted in animals — modern editing techniques can directly rebuild the virus genome in a matter of weeks in such a way that its replication mechanism is seriously impaired and its ability to cause bodily harm removed. Here are some of the advantages of Codagenix’s LAV approach:

• The vaccine can be administered via inexpensive nose drops. Its production scales up easily and no injections or refrigeration are required.
• A recipient’s body encounters and reacts to the entire virus rather than a just surface feature, thereby stimulating not just antibodies but also T-cells and other specialised forms of immunity that give longer-lasting and broader protection.
• The 3-letter words (codons) in the virus’s genome that specify its building blocks (amino acids) are replaced by suboptimal versions that can slow its speed of replication by a factor of 1000 and thus give the immune system more time to respond and marshal its forces to defeat the viral invasion.
• The attenuated form of the live poliovirus has only a small number of mutations and very occasionally (just once in 750,000 times) it reverts to its wild form and causes paralysis. But over 250 mutations have been introduced into Codagenix’s attenuated coronavirus so there is no chance of it mutating back to its original form. 

URGENT APPEAL: Covid-19 Symptom Study

With Covid-19 cases surging again in the UK, please download the Covid-19 Symptom Study app to your mobile phone. It takes a minute to make your daily symptom report and gives the King's College (London) team up-to-date information about new cases of coronavirus across the country; it also tells you about the current situation in your local area. 

Over four million have already signed up, but more are needed to increase the accuracy of the data, It is a quick download from the Apple and Android app stores.

Musings on a plague year in Stratford upon Avon

When in disgrace with fortune and men’s eyes,

I all alone beweep my outcast state,

During an outbreak of the bubonic plague in 1592, when London theatres were closed for 6 months, Shakespeare used the time to write two long narrative poems and quite possibly this Sonnet XXIX.

And trouble deaf heaven with my bootless cries,

And look upon myself and curse my fate,

Could those be the words of man fed up with lockdown? Shakespeare’s whole life was overshadowed by the plague. A few months after he was born in April 1564, a serious outbreak swept through England and killed nearly a quarter of the people of Stratford upon Avon. The plague was again rife in the 1590s and Shakespeare’s only son Hamnet died in 1596 aged 11; the cause of his death was not recorded but the plague was not ruled out. The plague returned in force to London in 1603 and again in July 1606 when theatres, including Shakespeare’s Globe, were once more closed; in fact, London playhouses were intermittently closed for 78 months of the following decade (60% of the time). A preacher at that time thought that “The cause of plagues is sin, and the cause of sin is plays”; fortunately we now know better: if was fleas, not sin. Theatre-goers today, perhaps, should take heart from the fact that Shakespeare’s company managed to keep the show on the road throughout those troubled times. 

Wishing me like to one more rich in hope,

Featured like him, like him with friends possessed,

He certainly sounds as though he’s “got the hump” as my mother used to say, although during  her low moments she was more like a nervous sheep than a camel. The currrent pandemic is so widespread across the world, afflicting “all conditions of men and women”, that it is hard to think  with envy of anyone “more rich in hope”. Perhaps our son who now lives in London might wish he were back in New Zealand again, or I can feel grateful for another son who lives in Japan’s northern island of Hokkaido and has not seen a single case of covid-19 in his coastal town of Shiranuka.

Desiring this man’s art and that man’s scope,

With what I most enjoy contented least;

Among the diversions of my years of retirement, I have noticed recent changes in “what I most enjoy”. For example, I have stopped drinking and watching films. Living alone since the pandemic began has made me realise these are social activities and no longer so satisfying in my outcast state. All my life I have struggled for inspiration with the tricky art of watercolour, but the muse has lately completely deserted me. My small local group of fellow greying artists has started meeting again (in the garden, of course) but now seem to gas as much as draw. I have enjoyed Zooming or WhatsApping to stay in touch and have dug up old friends from home and abroad, I have also enjoyed keeping this blog alive with commentary on the pandemic and cryptic crossword clues. I get a weekly Mindbender for the Quarantined from the New York Museum of Mathematics and spend hours writing small programs to search for solutions; off and on I append a new paragraph to my memoir (for family consumption only, I hasten to add).

Yet in these thoughts myself almost despising,

Haply I think on thee, and then my state,

Aha, at last, a welcome change of mood, a happy memory, a ray of light to banish his gloom. Begone dull care! There have been better days and there will be again. Put way introspection and melancholy, stay “Looking on the bright side” as my old maths teacher called his memoir.

Like to the lark at break of day arising

From sullen earth sings hymns at heaven’s gate;

Praise be the Lord! Heaven is not entirely deaf to his bootless cries; the lark has interceded.

For thy sweet love remembered such wealth brings

       That then I scorn to change my state with kings.

Yes, I can relate to that. For the past three months my wife has been locked away in Penzance, without a pirate in sight as far as I know. But we will soon be braving public transport to meet up in London to celebrate four family birthdays. Things are not so bad after all, for me, and even for Stratford. Sure, the RSC is closed, but they have been streaming their past productions, and their cast of actors, hopefully only temporally out of work, have been reading Shakespeare’s sonnets. Anthony Sher reads Sonnet XXIX and this reminds me that only a year ago I watched him and John Kani give an outstanding performance of Kani’s moving South African play, Kunene and the King. They will be back, the RSC will return, and then I shall scorn to change my state with kings.

The Hammers

During my early childhood in Derbyshire I was an enthusiastic follower of the local soccer team, Derby County ("The Rams") and was very proud when they won the Football Association Cup in 1946, beating Charlton Athletic 4-1 after extra time.   Much later in life, when I moved to the Midlands, I occasionally went to watch Coventry City ("The Sky Blues"), but they fell on hard times, dropping two leagues below the Premier, and I lost interest in the game. (These days I confine my watching to brief random TV broadcasts while standing in the queue at my local fish and chip shop.) 

I had therefore not been aware that the Premier League Club, West Ham United ("The Hammers"), had forsaken their 100-year-old home at the Boleyn Ground in Upton Park in favour of the London Stadium, built originally for the 2012 Olympic Games in the Stratford district of east London, until I saw this brilliant crossword clue (due to Russell Henwood in his puzzle in The Telegraph  on July 10th):

 The new stadium designed for West Ham United, perhaps? (7, first letter A).

T for Thymus!

After answering questions about my age, health and lifestyle for a covid-19 mortality calculator on this UK website, I was given a 1-in-20 risk of becoming infected and a 1-18 risk of dying if infected. It has become well-established that the risk of succumbing to a bout of covid rises dramatically with age, from essentially zero for the under-20s up to around 6% for reasonably healthy over-80-year-olds like me. The reasons for this disparity are not fully understood, but a decline in the effectiveness of the human immune system with advancing years is likely to be a significant factor. To give a readable account of the amazing complexity of this system is well beyond my knowledge and the scope of a short post, but I have managed to isolate one important component relevant to these statistics, namely the role of the T-cells

The Enemy

Pathogens are microbes that invade your body and make you ill. They include bacteria, viruses, pollen and fungi. A bacterium is a single cell organism that can independently reproduce in your body and may sometimes cause damage. In contrast, a virus, which  is much smaller, can only replicate by entering one of your cells and taking over a normal cell function to make copies of itself.

An antigen is a small part of a pathogen, typically a specific protein on its surface, that is used by your immune system to identify, track down and destroy the invading microbe. You could think of it as a banner advertising the pathogen’s presence to your immune system.

Your Defences

T-cells have many important functions in the human immune system:

• They kill your own infected cells that have been hijacked by a virus to replicate itself
• They activate other immune cells that directly attack the invading virus or other pathogen
• They regulate the overall immune response, and
• They store memories of earlier infections in order to mount a pre-emptive strike if one of them tries to re-infect you. 

T-cells begin life as a type of stem cell made in your bone marrow. From there they are carried in our blood stream to other organs, in particular to the thymus, a small gland located in the upper chest behind the sternum and in front of the heart. There they undergo a selection process which many don’t survive. Those that do then circulate round the body’s peripheral lymph-organs ready to be activated when they encounter a specific antigen. Once activated, the T cells will proliferate and differentiate into effector T-cells, which further diversify into T-cells with a variety of different functions; among these are cytotoxic T-cells whose main function is to kill your virally-infected cells but which can also kill tumorous cells and cells invaded by bacteria.

The thymus continues to grow after birth and reaches maximum size and activity around puberty. Thereafter it decreases in size and function and continues to atrophy until old age, eventually  turning to fat and becoming very hard to detect even under a microscope. Surely SARS-Cov2 exploits this decline in our once-vigilant defences.

Special K

"Superspreaders" is a name given to individuals infected with the novel coronavirus who pass it on to a very large number of their contacts. Many examples have been reported. For instance 29-year-old man infected 101 people after visiting several nightclubs in Seoul, South Korea; a singer unwittingly infected 52 fellow singers at a choir practice in Mount Vernon in Washington State in early March. Most of these multiple transmissions have taken place in crowded, poorly-ventilated places where the spreader was expelling plenty of virus-laden breath, say by singing or talking loudly over background noise. 

We have heard much about the statistical parameter R, called the epidemic reproduction number; it is the average number of contacts an infected person will pass the virus on to. For the coronavirus SARS-Cov-2 in a fully-susceptible population, the value of R lies between 2 and 3 in urban settings. As a proportion of the population becomes immune and social restrictions reduce the number of contacts, the value of R declines, and when it falls below 1, the epidemic will start to retreat. There is another parameter epidemiologists use called K. The value of K represents the level of individual variation in R. When K is small (less than 1), there will be wide variation in the number of people one infected person will infect; in particular, there will be more so-called superspreaders. In the early stages of the outbreak of covid-19 the value of K was between 0.1 and 0.5 which meant that 10-20% of those infected probably generated about 80% of the transmissions. An increase in the value of K, to above 5 say, will reflect the fact that the number of transmissions generated by most individuals will be close to the value of R.

Imagine a group of 200 individuals in a large population and divide them into  say 50 who are shielded and at no risk, and the other 150 who are moving out of lockdown as now. Assume that the number of active infections has significantly fallen and that the reproduction number is just below 1. Just as it was at the initial outbreak, the value of K will be small and the risk of the return of superspreaders high; it will only need one or two of them among the 150 to send the R-number soaring. This is why an effective test-and-trace system is so important at this stage, to catch the potential superspreaders before they have a chance to set off a second wave.

Production of Mighty Marmite marred

An unlikely casualty of the pandemic is the supply of that famous metaphor love-it-or-hate-it Marmite, which now only available in small jars, A key ingredient is dead yeast cells, which are a healthy by-product from brewing beer, and with pints no longer being pulled in the pubs, the supply has dwindled.

Up close and dangerous

One metre or two? That is a question exercising politicians right now. Halving the current social distancing guideline of two metres would make a huge difference to the viability of the hospitality industry, which has taken a big hit during the lockdown.

Two metres is already not safe. The risk depends on many contingencies. Let’s assume your face is two metres from the face of someone already infected with the virus. Whether you catch it will depend on:

• How long you spend with them
• How infectious they are
• How many water droplets and aerosols they are expelling; in particular whether they cough or sneeze in your direction
• Whether you are facing each other and which way the air currents are moving
• Whether one or both of you are wearing masks

The transmission risk will be proportional to the time you are exposed. Evidence suggests there is a wide variation in individual infectiousness. It is higher if your contact is breathing heavily, speaking loudly or singing. It depends on what stage of infection they are at and how heavy their ‘viral load’ is. It will be much worse if you are in a crowded space with poor ventilation, such as a pub or night-club.

A recent meta-study - a study of studies - suggests that using one metre instead of two for your social distancing will double the risk of contagion, but that’s just an average and the confidence margins are wide. The real risk depends on the detailed circumstances of your encounter and these override the simplistic calculations derived from the meta-study.

Two More Free National Theatre Productions on YouTube

The Deep Blue Sea

Terence Rattigan’s devastating masterpiece contains one of the greatest female roles in contemporary drama, played by Helen McCrory.

Streaming from 7pm on 9 July, until 7pm on 16 July.

Find out more

Amadeus

Lucian Msamati plays Salieri in Peter Shaffer’s iconic play, directed by Michael Longhurst with live orchestral accompaniment by Southbank Sinfonia.

Streaming from 7pm Thursday 16 July until 23 July.

Find out more

Covid Analysis Apps

The Covid Symptom Tracker described below now has nearly 4 million contributors. Scientists at King's College London are using it to identify (i) high-risk areas in the UK, (ii) who is most at risk, by better understanding symptoms linked to underlying health conditions and (iii) how fast the virus is spreading in your area. The more people who join, the more useful the data. Your daily report takes only 15 seconds - tap, tap, tap! Please sign up if you have not already done so.

Another app that is gathering covid-related research data has longer term goals. It is called Covidence UK and is led by Queen Mary London in a consortium of 6 Higher Education Institutions from England, Scotland and Northern Ireland.

                          

People aged 16 years or older, from all parts of the UK and from all walks of life, are invited to sign up and fill in an online questionnaire with details about their lifestyle and health.

Participants will then be contacted every month to check if they have developed any symptoms of coronavirus disease, and to ask some follow-up questions about participants' more general health and social circumstances.

The data they collect will be analysed in order to:

• advance understanding of risk factors for coronavirus disease among UK adults
• find out how quickly people recover from coronavirus disease and whether there are any long-term complications of this illness
• evaluate the impact of coronavirus disease on the physical, mental and economic wellbeing of the UK population
• establish a platform for future research on coronavirus disease in the UK.

Curly Sceptic (anag, 7,5)

1. A reminder that ‘social distancing’ needs to be policed

            Deal with some backsliding males in a group (8)

by first-prize winner, Jane Ainsworth, in The Telegraph monthly clueing competition.

2. Another reminder, this time of the change of leadership in the British Labour party:

            Bad mistake, error ousting old Labour leader (4,7)

from a Paul Bringloe crossword in The Telegraph.

3. And finally this double definition, which has nothing to do with the cladding on New England houses:

Old boarding (7.2)

A ‘double definition’ means that the solution is synonymous with both ‘old’ and ‘boarding’.

Safe Bet

Take three dice A, B and C and change the numbers on two faces of each as follows:

A: 1, 1, 3, 5, 5, 6       B: 2, 3, 3, 4, 4, 5      C: 1, 2, 2, 4, 6, 6

Find someone who enjoys a wager, ask them to choose a die. Then choose your die to be the one to the right of theirs in the sequence ABCA. Bet them a pound that if you both roll different numbers, your roll will higher than theirs. After 100 rolls you can expect to be around six pounds up on average! (For more information see the Wikipedia article Nontransitive Dice.)

Update: Since posting the above, I have written a short program to simulate the game. The average profit over a 1000 games of 100 rolls each was £6.76 per game, reasonably close to the theoretical figure of £6.25. Averaged over 100,000 games the simulation's predicted profit per game was even closer at six pounds and 24.84 pence. But be warned, there were significant deviations from the mean, with the 100-roll games occasionally showing a negative profit!

Jude the Obscure

This is the title of the last of Thomas Hardy’s twelve or so published novels, depending how you count them. He also published many short stories and volumes of verse, and regarded himself principally as a poet. Among the major themes in his writing is a sense of loss for the old traditions and the devaluation of the rural ways of life as many moved from the countryside to the towns and cities. In Jude the Obscure, Hardy offers a biting critique of the rigidity of the law and social attitudes on marriage and the obstacles to social mobility due to poor education and snobbery. Jude went to a village primary school and learnt to read and write (as did I), but after that he was on his own. He was ambitious, nevertheless, and knew that a key to bettering himself was a knowledge of the Classics (see previous post), an insurmountable hurdle devised by the higher social classes to ensure their offspring didn’t end up working down a mine. Jude had his sights on Oxford (called “Christminster” in the novel) and was able to purchase cheap or second-hand editions of the books he needed, from Latin primers to Anglican tracts. He kept these books by his bedside and dreamt of joining the “great thinkers” while burning the midnight oil in private study even after a long day’s labour as a stonemason. But when he arrived in Oxford, his only way into the colleges was to repair their crumbling masonry. When Jude writes a letter to five heads of college, only one bothers to reply, and his curt advice that Jude should be content to stick to his trade.

I read the novel only recently for a book group and confess that I was disappointed in it. Having admired Hardy over the years and having been prepared to put up with the pessimistic endings to many of his stories, I felt this one verged on the melodramatic and that Jude’s decline into obscurity offered too bleak a vision of the future. In personal terms I have been better treated in life than Jude. I got a decent education, including some Latin, despite the bookless social class I was born into. Moreover, no-fault divorce became British law earlier this year. Hardy might be smiling quietly to himself in his tomb in Westminster Abbey that his hope for a fairer world has come to pass. Jude got some vicious critical reviews and Hardy never wrote another novel. In a postscript to the original preface, written 16 years later, he indicated that he had been creatively wounded by the hostility of the response to what one critic called "the most indecent book ever written". But I have a suspicion that perhaps Hardy felt he had written himself out and was secretly happy to call it a day.

Classical, Classics and Class

The word “class” has an interesting etymology, as I learnt recently from Edith Hall in an episode of Start the Week on BBC Radio 4 (on 25th May). The Latin word “classicum” meant, among other things, a war-trumpet or a military trumpet call - the word also had nautical associations - and it was used, so legend has it, by Servius Tullius. the sixth king of Rome, to announce roll-calls of Roman citizens in their separate groups according to their social status and wealth for voting and taxation purposes. So the word “class” became associated with Rome’s six taxation ‘classes’, especially with the highest class. Modern usage the word can mean a teaching group (as in ‘‘ top of the class’), a social stratum (as in ‘working class’), or a quality of distinction (as in ‘class act’); ‘class’ also has technical meanings in taxonomy and mathematics. While ‘classification’ retains just the division-into-categories meaning, the words ‘classical’ and ‘classic’ have overtones of something of quality with a gilded past, although when applied to music, ‘classical’ has a narrower meaning. Finally, the word “Classics’ has come to mean the study of the languages, literature and history of ancient Rome and Greece as well the wider culture of their associated civilizations, which flourished during the last six centuries BCE and beyond. In more recent British history the acquisition of a ‘classical education’, typically involving 8 years of swotting up Greek and Latin, was the unique passport to wealth and the power, and separated the ruling class from the hoi polloi. But more about that in my next post.

Cummings Comes Clean?

The Prime Minister's chief advisor, Domenic Cummings, gave an hour-long press conference in the garden of 10 Downing Street yesterday afternoon (25th May). He answered many of the questions that Johnson had failed to answer the day before (see my previous post). Some were convinced by Cummings's defence of his actions, especially the Cabinet Ministers, but many were not, including 40 MPs of the governing Conservative Party. This afternoon a retired police chief was bold enough to advise the Government that "When you have dug yourself in a hole, you should stop digging." My view is that Cummings made a serious error of judgement when he took the risk of blatantly breaking the spirit of the official advice to stay at home and not to travel, especially if there is a suspected case of covid in your family. Through that error, and its subsequent failure to acknowledge it, the Government has squandered much political capital; the story continues to run and to distract it from the vital task of keeping Covid-19 under control as it moves to restore Britain's economic and social well-being.

Cummings not going

The British Prime Minister, Boris Johnson, has shown us a way to save our country many £billions, money which would certainly come in useful at this time of astronomical borrowing by his Government. His solution would render the whole legal system superfluous: the judiciary could be pensioned off, the lawyers sent on permanent unpaid furlough. There would be no further need for courts, juries (already under threat during lock-down), clerks, bailiffs, chambers, or any of the elaborate paraphernalia of the law. It might bring temporary hardship to the makers of barristers’ wigs but the more enterprising among them could surely find new openings with the closure of barbers shops by offering wigs to cover the shaven pates of the general public. Who needs hair-dressers anyway?

On 27-28th March Johnson’s main political advisor, Domenic Cummings. (mentioned in an earlier post on this blog), travelled with his wife and 4-year-old son from London to his parents’ home near Durham in north-east England, a journey of some 250 miles. This act appears to have broken the Government's lock-down rules to stay at home and self-isolate if a family member (e.g. his wife, the journalist Mary Wakefield in this case) has coronavirus symptoms. Cummings’s excuse was their need to find child care in case they both fell sick. Since this story broke in The Guardian newspaper, Cummings has been under heavy fire with calls for his head from his many opponents -- you can’t be a radical reformer of the British political system without making enemies.

Yesterday afternoon the Prime Minister appeared on TV to defend his right-hand man against charges that he broke the lockdown laws. During the broadcast Johnson told his now less-than-admiring public that he had spoken to Cummings and had come to the unequivocal conclusion that Cummings had acted “responsibly, legally and with integrity” by ignoring the rules, while the overwhelming majority of his viewers had made significant, even heroic, sacrifices by following them. There are many unanswered questions surrounding Cummings’s movements during the lock-down -- nineteen of them according to Amy Jones in the Daily Telegraph, a broadsheet that usually supports conservative administrations -- and Johnson patently failed to answer any of them. He simply pronounced the defendant innocent by personal diktat. There was no need to investigate further, no need to hear the allegations or cross-question the witnesses, no need to examine the evidence or invoke the law. Johnson’s version of summary justice could certainly help to deal with the backlog of 46,000 criminal cases presently awaiting trial. He just needs to have a quick chat with the defendants and pronounce them guilty as charged or, in the case of his friends, innocent and set them free. Silence in court and no legal fees!

Pandemic Progress

Congratulations to South Korea and New Zealand. They appear to have the virus SARS-CoV-2 firmly under control, with days when new cases are in single digits, often zero. They are smallish countries that were well prepared, have trust in their political leadership and respect for scientific evidence, as well as social discipline and a sense of national purpose. That's one kind of progress.

Meanwhile the virus itself makes its relentless progress through Europe, Russia, the USA, and increasingly through the poorer countries in Africa and South America. The United Kingdom, where I live, has not been doing well, with over 28,000 deaths by 5th May. We made a slow start, with poor supplies of protective equipment and little testing capacity. Care homes have been particularly poorly served with many covid deaths not included in the official figures.

This must be a particularly hard time for right-thinking people. For those who scorn science and believe in intelligent design, this must present a real philosophical challenge when they are constantly confronted with epidemiological evidence and the value genetic analysis, not to mention the fact that SARS-CoV-2 is constantly mutating and evolving. Speaking truth to power is also tough when those in power regard imparting unpalatable information as an act of disloyalty. When safe and effective vaccines are available, there will be further uncomfortable decisions for those who believe vaccination is a wicked government conspiracy. 

Today the UK Government announced a trial launch of its track-and-trace mobile phone app. This pilot is restricted initially to the approximately 140,000 inhabitants of the Isle of Wight, which sits close to south coast of the English mainland and was once a favoured holiday resort for Queen Victoria. As predicted in an earlier post, this app has been developed by the NHSX digital team and will be centrally managed. As such, there are already criticisms of its weak privacy safeguards and the questionable background of some recently-hired team members. This contrasts with the app being developed jointly by Apple and Google in the USA, which operates locally and has more stringent protection against the misuse of the information gathered. To be really effective it will need to be adopted by at least 50% of the population. Since it cannot be made mandatory, it seems an ambitious aspiration that so many will be prepared to sacrifice their privacy for the sake of the greater good. I hope to be proved wrong.

Cryptic Diversions

The first cryptic crossword clue is taken from the novel A Week in December by Sebastian Faulks:

          Butcher has ox tongue (5)

The second comes from one of Tim Morey's recent puzzles in The Week:

          It can be shuffled (7)

And these two are winning entries in a clueing contest devised by The Telegraph's puzzles editor, Chris Lancaster:

          Play this for 14 or more (8)

          Bird's very large eggs withheld from Putin's comrade (7)

The first two involve anagrams flagged up by the words "butcher" and "shuffled", the second being in &lit format. The third needs lateral thinking and some knowledge of a well-known board game. The final clue is a combination of charade and deletion and calls for some erudition: an abbreviation used by purveyors of large clothing, the Latin word for "eggs". and the Russian word for "comrade".

Covid Vaccine Update

The Oxford team mentioned in the Front-runners post below have started clinical trials and plan to test 6,000 people by the end of May.They are also preparing for large scale production in case their vaccine proves effective.

Epidemics Animated

Grant Sanderson's YouTube Channel 3Blue1Brown has the most wonderful animations of things mathematical, full of insight and thoughtful intelligence. He has devoted  a recent video to a striking visual simulation of how models predict the transmission of disease in epidemics. If you would like to understand better what our Government means by the phrase "guided by the science" in their daily briefings, click on this link.  It's essential viewing and I strongly recommend it  (and it contains no equations, I promise).

More Shakespeare streamed

Royal Shakespeare Company, Stratford upon Avon

CULTURE IN QUARANTINE

We have partnered with the BBC to bring six of our shows to television audiences through BBC iPlayer and BBC4.

Macbeth (2018), directed by Polly Findlay with Christopher Eccleston and Niamh Cusack

Hamlet (2016), directed by Simon Godwin with Paapa Essiedu

Romeo and Juliet (2018), directed by our Deputy Artistic Director Erica Whyman

Much Ado About Nothing (Love's Labour's Won) (2014), directed by Christopher Luscombe

Othello (2015), directed by Iqbal Khan with Hugh Quarshie and Lucian Msamati

The Merchant of Venice (2015), directed by Polly Findlay

FIND OUT MORE

WATCH ON IPLAYER

Reducing the DOTS for Infectious Diseases

To measure of how fast an infectious disease is spreading, you need to know the Reproduction Number. This is the average number of people someone with the disease will infect during the course of their illness. 

• If the reproduction rate is bigger than 1 the disease will spread, and the larger it is, the faster it will spread
• If the reproduction rate is less than 1, the disease will die out, and the smaller it is, the quicker it will disappear.

The value of the reproduction rate is determined by four quantities, the DOTS:

Duration. The number of days someone with the disease is infectious

Opportunity. The average number of close contacts a typical person has each day.

Transmission, The proportion of contacts that lead to the infection being passed on.

Susceptibility. The proportion of the population without immunity.

Reducing any of these four numbers will slow the spread of the pathogen. If the reproduction rate stays below 1,  the disease will eventually go away.

How can we reduce the DOTS for the novel coronavirus?

• We can’t change the duration of SARS-CoV-2 because that is an intrinsic property of the disease when it is allowed to run its course without intervention, and we have no proven treatment at the moment.
• At the beginning of the outbreak, the susceptibility was 100% because no one had had covid-19 before, and we can’t actively change it until we get a safe and effective vaccine. However, it is expected that people who have recovered from the disease will have antibodies produced by their immune systems, which should afford them some protection against reinfection; but at what level and for how long is still unknown.

That leaves opportunity and transmission.

• We can make a big reduction on the opportunity by keeping people at home and quarantining those that show symptoms or have underlying health problems. The experience in Wuhan strikingly showed this: before the outbreak the average daily number of contacts was 15. This number dropped to 2 during the strict lockdown and the reproduction rate fell to 0.6. Consequently the disease died out.
• Social distancing also has a big effect on reducing the transmission rate. Washing hands and surfaces, covering mouth and nose with a tissue when coughing and sneezing, and probably wearing masks also help to minimise it.

Other issues that need to be taken into account are: silent spreaders (those with no symptoms who are nevertheless passing on the infection in all innocence); super-spreaders (those with a high viral load who, because of their work or lifestyle, have very many contacts); the different immune responses of men and women, young and old; genetic mutations of the virus, which have already been identified and used to show the convoluted journeys different strains have made around the world.

Readers seeking more of the details behind this post might be interested in the timely book The Rules of Contagion by Adam Kucharski, published on February 13th. He must either have had inside information or a good fortune-teller.

Frontrunners in the Race for a Coronavirus Vaccine

Two early candidates for vaccines to protect against Covid-19 are already undergoing animal trials on ferrets at the Australian Centre for Disease Preparedness, a high security laboratory in Geelong, Victoria. They both employ innovative approaches that depend only on knowing the genetic code of the novel corona virus (SARS-CoV-2), and this was published by Chinese scientists in early January. The fact they didn’t need quantities of the actual virus gave them a head start.  These two candidates were chosen by the Coalition for Epidemic Preparedness Innovations (CEPI), who are funding the Australian work and had already set up the pipeline before the covid-19 outbreak  began. The two teams leading the charge are:

The Oxford University Vaccine Group and Oxford's Jenner Institute are using a harmless non-replicating chimpanzee adenovirus to carry the genetic code for a protein found on the surface of the coronavirus (see picture).

Immune responses from other coronavirus studies suggest that these club-shaped spikes are a good target for a vaccine. After vaccination, the adenovirus enters our cells and starts to produce the surface-spike protein of the coronavirus, which then primes our immune systems to attack the coronavirus if it later infects our bodies. (Chimpanzee adenoviral vectors are a very well-studied vaccine type and have been used safely on thousands of subjects, from new-born babies to 90-year-olds, in vaccines targeting over 10 different diseases.)

Inovio is an American bio-technology firm specialising in DNA-based immunotherapy. The human cell has many amazing functions and in particular is a protein factory for making and maintaining our body parts. Their vaccine magically inserts a piece of the coronavirus DNA directly into the human cells in such a way that it can borrow the cell’s machinery to make the viral protein that will prepare the immune system to destroy any invasion by the actual virus before it can take hold. This is a completely novel approach and has not be used in a vaccine before.

Why Ferrets? In 2003, when a different coronavirus (SARS) struck, a team at the Scripps Research Institute in Florida discovered that it was getting into human cells by targeting a specific receptor called ACE2 on certain cells in the lining of the lungs and in other vital organs. It turns out these receptors in ferrets’ lungs are very similar to those in humans and make the ferret an ideal ‘guinea-pig’ to study the progression of covid-19 and the effectiveness of the vaccine. The first cohorts of ferrets were infected and separately inoculated in March and preliminary results should be available by the end of April. Another group of ferrets will receive a second booster dose of the vaccine before being infected. A full assessment of the trials will be made available to the two teams in the UK and the USA by mid-July. Meanwhile, both teams have started the first phase of clinical trials on humans.

Clinical trials. These typically have three phases:

Phase 1. A small group (around 40--50)  of brave people are shielded from exposure to the virus and injected with the vaccine to see if it has harmful effects. This is a safety test, not a test of efficacy. 

Phase 2. A much larger group of people from the general population who would be naturally exposed to the virus are divided into two groups. One half are injected with the vaccine, the other half with water; neither those carrying out the trial nor those participating know which group they belong to (a so-called double-blind trial). After a sufficient time elapses for exposure to have occurred, the levels of infection from the two groups are compared. Ideally the trials should be continued for a much longer time to find out how long immunity, if any, is conferred by the vaccine.

Phase 3. When the safety and the efficacy has been confirmed, the programme of large scale vaccinations is rolled out.

This project is a striking example of the power of international cooperation. If Inovio is successful, it could even go a small way to making America Great again!

Updates

1. CEPI receives its funding from philanthropic (e.g.Gates Foundation), institutional (e.g. Wellcome Trust) and international sources (Japan, Norway, Germany, Australia, Belgium and Canada). In March 2020, the British government pledged £210m. specifically to focus on a SARS-CoV-2 vaccine, making Britain CEPI's largest individual donor.

2. Ferrets now have a rival species for testing. When a Hong Kong team recently infected 8 hamsters with SARS-CoV-2, high levels of the virus were found in the hamsters’ lungs and intestines, tissues studded with the virus’ target  protein: angiotensin-converting enzyme 2 (ACE2). 

3. Two of the world's largest vaccine manufacturers, GlaxoSmithKline and Sanofi, are joining forces to develop a new vaccine to prevent Covid-19.