Blog Reset - from Business to Personal

 

I finally closed Milton Contact Ltd in March, leaving just a legacy website www.miltoncontact.com. 

I have retired and this blog will reflect my personal interest and activities, which range from microscopy to museum volunteering to getting to grips with gluten free cooking!

GB-DE Rail sectors on track in London this week

Trains ready at Kings Cross (2020)

This time, a trip to London was quite an adventure, in this Covid era! I was off to Belgrave Square to spend two days chairing an event between a delegation of German companies in the rail sector, with a combined annual turnover of over a billion pounds, and GB representatives of key organisations, companies, and government departments. 

The event had been planned and implemented by Europartnerships, on behalf of the BMWi, the German Federal Ministry for Economic Affairs and Energy and the ministry's program "Mittelstand Global", which supports exporting German SMEs.

Day one, Hendrik, Stefan, Johann, Stuart, Robert, Yannik and Thomas, representing the seven participation companies (see links at bottom of article), were the audience to a range of presentations. Although their companies already had global business presences, including the GB, Covid and Brexit meant that it was important to get up to speed with the current situation vis a vis  GB-DE trade.

Some of the points that struck me personally follow.

Topics covered were:

• The excellent support available by their own BMWi through export development initiatives and portal IXPOS. One of the reasons for the success of German businesses abroad is the integrated assistance provided to SMEs, from theri local regions upwards to the federal level.
• Different distrubution channels and important cultural factors (how to understand us Brits), presented by the German Chamber of Commerce in the United Kingdom - AHK. (Do accept the invitation to go to the pub after meetings!). Perhaps the most worrying part of the presentation is that our (UK) importance for the German market (the 4th largest gloal economy), in terms of imports has rapidly declined down from 5th to 11th place and still sinking.
• The UKs decline in trade with Germany was also repeated in figures shown by the GTAI (Germany Trade and Invest) and was coupled with uncertainty about the GB reorientation post brexit. That said, the UK was still the 5th largest economy, expected to have strong growth in the coming years, and therefore a major partner to seek out.
• The Department for Transport gave us an update on Rail in the UK, showing that in terms of passenger miles, the UK was outperforming our neighbours - and that this was coupled with an exemplary safety record, including only 10 fatalities on the whole network in 2020-21. HS2 and the planned investment in the eastern parts of the North were in progress and a major organisatory change, in the formation of Great British Railways, was imminent.
• The Department for International Trade gave a very positive presentation on the opportunities and support for companies based in the UK. This was complemented by a useful list of project opportunities and places to look out for forthcoming contracts, as well as contacts for our German delegates to get in touch with at the DIT.
• With the UK being the birthplace of the rail sector, it is no surprise that one of the key membership organisations, the RIA (Rail Industry Association) has a 145 year history, a substantive membership of relevant companies in the sector, of which more than 60% are SMEs. As influencers of policy and public affairs, they also provide a comprehensive program of events and support, as well as encouraging innovation and providing trade missions overseas themselves.
• I suppose we all anticipated an opportunity for a nap during the presentation on Tax law peculiarities in the UK, by the speaker from Blick Rothenberg. Instead, the consequences of Brexit had us gripped by their impact on the import and export of goods across the new border with Great Britain. Theoretically The EU–UK Trade and Cooperation Agreement (TCA) allows for more than 99% of trade between us to go on without tariffs, if the goods are made more than 70% in the EU. Unfortunately, the sticking point for complex items is that the supplier has to do considerable checks to assess the percentage of non-EU items in multi component items or complex equipment and confirm it is below the 30% level to comply. More fundamentally, all your accompanying paperwork has to be in order, otherwise your goods get stuck in the Customs quagmire. Audience tip: if importing goods from EU to UK, get your UK recipient to sort out the paperwork and carriage. I was already aware of the risk of double taxation, by both the sender and recipient country from another as goods transferred across borders. This was another detailed presentation and emphasised the importance of getting the right advice to avoid pitfalls in trade.
• The talk by Entreprenör covered the assistance in setting up a copany in the UK (much simpler than in Germany but with public transparancy re accounts and personell information held at Companies House. One of the new hazards to look out for was that an audit may be required based on the size of the worldwide group.
• Day 1 ended with a very informative talk on Transport for London (TFL) and Cross Rail, which shone a light on the recovery after the initial covid Epidemic.
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Millstone phallus comes to Godmanchester Museum

 

Godmanchester Millstone with Phallus held by Curator Kate Hadley (courtesy of Godmanchester Museum)

I left the preparations for the reinstated annual Hall End BBQ for a quick dash up the A14 for a very important date. Godmanchester Museum was celebrating its re-opening with a major event, the display of the new exhibit, part of a Roman millstone emblazoned with a phallus (Saturday 31st July 2021). This is a very rare item indeed - only four are known of amongst the tens of thousands of Roman millstone fragments found to date in Britain. 

My small involvement with this stone began with a phone call taken by my wife Jane, from the Godmanchester Museum's curator Kate Hadley, who wanted the stone photographed. 

"Kate called, saying that she was holding a p....s you might be interested in!" was the message.  How could I resist! Kate and I spent an afternoon in June trying to get the best lighting and positioning of the stone to reveal its true magnificence.

By the time I arrived, a crowd had already gathered for the Godmanchester Museum opening and  David Stokes, Chairman of the museum, began the proceedings at 2:30 pm.

David Stokes, Chairman of the Godmanchester Museum, opening proceedings

Interested crowd at the opening of the Godmanchester Museum

He was followed by Claire Hardy, Director of the Norris Museum, who had generously brought along their rare example of another Roman millstone fragment with a phallus, from the Norris collection, (partner to another fragment held at the Norris showing engraved curves).

Claire Hardy, Director of the Norris Museum, and their phallus millstone

Godmanchester Mayor Councillor Clifford Thomas and Philip Saunders, Chairman of the Huntingdonshire Local History Society

The Godmanchester millstone fragment had been found in a posthole at Offord Hill house, during the excavations prior to the new A14 build. Archaeologist Ruth Shaffrey, realised its significance when when was conducting a routine catalogueing of the finds. She had been researching Roman millstones and was a specialist in ancient worked stone. It was thanks to Quentin Carrol, Historic Environment Assistant Director and Archaeologist, Cambridgeshire County Council, that the remarkable millstone was made available to its nearest hometown museum.

Ruth Shaffrey, Archaeological Worked Stone Specialist, with the Godmanchester millstone phallus (courtesy of Godmanchester Museum)

It was great to hear from Ruth about the origins and possible significance of the millstone. This is what I recall from her talk.

During Roman times, millstones were made using stone excavated from the Millstone grit from the Peak District/Yorkshire. The Godmanchester and Norris millstones were of a medium size and probably animal driven, whilst larger ones could be water powered.

In a typical Roman bakery, the counter would be in the central part of the room, the millstone at one end of the room and the ovens at the other. Customers would therefore have quite likely seen the magnificent carved stones displayed in action. 

The millstone had obviously broken at some time and was later used as a quernstone for hand grinding of grain in its own right.  It was also used as a sharpening tool for blades. It finally ended up in a filled-in post hole, where it was finally discovered in the A14 dig.

Millstones with carvings upon them are rare and would most likely have been commissioned by a wealthy baker or merchant. Whilst the use of a phallus might seem unusual to the modern eye, it was a familiar emblem in Roman times and used both in domestic and other settings, including as jewellery and even being worn by children (https://imperiumromanum.pl/en/curiosities/phallus-symbol-in-roman-and-greek-world/). It is thought that it was a lucky symbol as well as the usual possible links to fertility that we would associate it with.

Much like anvils, millstones were themselves seen as important objects, imbued with symbolism, as they were closely linked to grain, harvests and the production of food. To have an object like a millstone, that is already highly symbolic, and then to have it engraved with another important symbol was therefore unusual, hence their rarity.

Ruth also revealed that our region was regarded as one of the granaries of Britain and that more millstones and fragments had been discovered here than in the rest of the UK.

After a walk around the exhibition afterwards and purchase of one of the magnificent postcards of the millstone, I left Ruth to enjoy her specially made Roman vegetarian meal. It had been prepared by local Godmanchester Roman cookery expert, Sosia Juncina. It was back to Milton for our own annual BBQ and street party!

Lewis Woolnough - a life under the microscope (Obituary)

Memories by Chris Thomas. 06 May 2021

I always knew it was Lewis, as soon as I heard his “Hello Chris” on the phone. A quiet yet warm voice that shone with light of his positive yet reserved nature.

Of course I had met and occasionally chatted to him at  meetings of the Quekett Microscopical Club, but it was really when he approached me about re-issuing his book ‘Understanding and Using the Stereomicroscope’ that I came to know him better.

Lewis was above all an open, positive but self deprecating person. Yet in his quiet way, it soon became apparent that appeared ever so slightly unhappy with the way an old first version of his book had been produced and presented. For those of us who got to know Lewis well, this was so uncharacteristic of his usual unflappable outlook, that the small hints of dissatisfaction spoke volumes about his feelings on the matter. I might therefore have had some initial reservations on embarking on the project of producing the book in a way that he wanted.

Such fears were soon dispelled as I found that here was someone with a deep shared interest in helping and instructing others. What really struck a chord with me was his constructive and cooperative approach to transferring his knowledge to an audience starting out in microscopy. No didactic lecturing, here was a friend who would take you through right from the beginning to proficiency in using the stereomicroscope.

I really enjoyed debating certain points with him, as he or I would try to persuade the other to our viewpoint, each of us microscopy experts in our own right. There was a steely core of certainty about what his objectives were underlying that calm smiling exterior, combined with a flexibility of mind that allowed compromise where it would ultimately benefit the book. We worked well as a team and I looked forward to his company, despite our different personalities. 

We were able to combine his text and quirky black and white illustrations with many colour photos, include colour coded sections for easy reference and even introduce stereoscopic images. The result was the new first edition, published in 2010 by the Quekett Microscopical Club – which was recognised as a useful handbook, not only for novices but also those already familiar with stereomicroscopy. It is now out of print.

Milton Contact Ltd published the second edition of his book with added material in 2018.

The second edition of Understanding and Using the Stereomicroscope

Digital printing also allowed smaller print runs, in the hundreds rather than thousands. When a batch was close to running out, we simply ordered another small print run to tide him over. There are several retailers still selling the book, Brunel Microscopes and Northern Bee Books being examples. The Quekett also purchased copies use at special events and for the Arkwright Scholarship course on microscopy that it runs annually. Individuals also ordered copies directly from Lewis, with many copies going abroad.

Such was the feeling of success from the relationship that I was inspired to write and publish ‘Understanding and using the light microscope’ with Lewis’ assistance, input and co-authorship. We had great fun hiring a photographic studio for an afternoon, roping in my student daughter for age and gender balance. We produced nine instructional videos accompanying the book. Lewis was such an excellent teacher that we basically agreed a topic for each video, an outline of the content and then just let the camera roll as all three of us turned these into real life lessons on using the light microscope. We did have to do several takes on certain parts sometimes but it went remarkably smoothly, with great fun had all round. 

Other fond memories I have are of meeting Lewis and Janet in their home, having a lunch or a tea in the kitchen overlooking their large garden. Lewis and I would then ensconce ourselves in the study to pore over microscopes, samples and generally talk of things microscopical. At the end of the day, Lewis would always safely wave me out onto the road from his drive as a large hedge on the right obscured the view and I feared for my safety.

Whilst I could always find my way to Lewis, I invariably had trouble finding the route to the nearby Village Hall in Bradfield St George, where Lewis was involved in the organisation of the annual East of England Microscopy meeting in Autumn. I must have found at least three different routes to get there and exit over the years, seemingly finally coming to the venue almost by chance!

Lewis was also the turn to person when it came to meeting the relatives of other microscopists and helping them find good homes for their microscopes, slides and occasional hazardous stains and solvents!

Lewis was also there with constructive advice and support when I contemplated and finally joined the new Quekett Committee.  

From our occasional conversations this year, I learnt almost as an aside of Lewis’ illness, and hearing of his hospitalisation and passing away, I felt the loss of a decade’s long companion and like minded person in microscopy, as well as the an author.

But Lewis is still there within me, the shared memories, laughter, debates and interests. I’m pleased that I can tread in his footsteps by taking on the first part of the Quekett’s Arkwright Scholarship course, aiming to continue his aim of making microscopy education fun, interesting and interactive.

The searchable Cambridge Open Studios 2019 guide

 A searchable version of the Cambridge Open Studios guide for 2019 is now available to view as an eBook on the internet archive, or to search directly on this page in the window below. (For a full leafable version, click on the link below the book)

COVID-19 deaths per 100,000 population increase with freedom and level of democracy by February 2021

 SUMMARY

There appears to be a trend towards a greater number of deaths from COVID-19 per 100,000 population with increasing freedom and level of democracy. The results below were obtained by plotting COVID-19 deaths per 100,000 population against four different categories of freedom and democracy for 171 countries, where possible. 

The COVID-19 data used was published by Johns Hopkin University of Medicine at https://coronavirus.jhu.edu/data/mortality on the 5th February 2021.

Four indices of freedom or democracy for the same countries were obtained from the Wikipedia ‘ List of freedom indices’ available at https://en.wikipedia.org/wiki/List_of_freedom_indices. They covered data gathered from 2018 to 2020 and were:

1. Freedom in the World
2. Index of Economic Freedom
3. Press Freedom Index
4. Democracy Index

RESULTS

All four indices appeared to show a positive correlation between COVID-19 deaths per 100,000 population and increasing freedom or democracy. Some of the differences appear to be significant.

The data is skewed and not normally distributed. Data can also cover quite a range from low to high values of COVID-19 deaths per 100,000 population for each freedom or democracy category within in each chart

THE CHARTS

The charts below show both a distribution of each countries value for a given freedom or democracy index as blue dots, and the data described in the form of boxplots.

Figure 1. Deaths per 100K population for countries identified as free, Partly free and Not free.

Figure 2. Deaths per 100K population for countries identified with Economic freedom, categories Free, Mostly free, Moderately free, Moderately unfree and Repressed.

Figure 3. Deaths per 100K population for countries identified with press Freedom categories Good, Satisfactory. Some problems, Difficult and Very serious.

Figure 4. Deaths per 100K population for countries identified withcategories of Democracy: Full deomocracy, Flawed democracy, Hybrid regime and Authoritarian regime.

THE TABLES

The data for the box plots is summarised in the charts below. The red boxes in the tables of percentage differences between any two sets of data within an analysis suggest the data is significant.

Table 1. Data used for figure 1 on Freedom in the World

Table 2. Data used for figure 2 on Economic freedmom

Table 3. Data used for figure 3 on Press Freedom

Table 4. Data used for figure 4 on Democracy index

The full spreadsheets with all the raw data and calculation are available from the author on request.

CONCLUSIONS

I simply visualise the correlation between increase in COVID-19 deaths per 100,000 population with increases in freedom and democracy. It requires a more detailed analysis of the way different countries experienced and tackled their epidemics, to identify which factors might be responsible for these trends.

Areas to consider could include:

• Acceptable balance of increase risk of deaths per 100,000 population against temporary maintenance or loss of freedoms
• Ability to take action in the face of a growing epidemic.
• Impact of differing political and economic viewpoints on speed of decision making process.
• Local factors that impact on public willingness to accept decisions relating to the epidemic.

Chris Thomas, 08 February 2021

Ann Hales-Tooke, née Petre 1926 - 2020: My inspiration to become a publisher

 

There are some special people in your life who change your future direction in a totally unexpected way. Ann Hales-Tooke, née Petre, was the person who set me onto the path to publishing back in 2005. 

Her son Hugh called me to let me know that she had passed away peacefully in her sleep on the 6th November 2020.

Before I go into my personal story, here is an insight to her life.

Ann Petre was born in 1926 at Langley Hall Farm, Norfolk, coming from a family that included aviation pioneers and WWI heroes, and lived through some of the most tumultuous decades of the 20th Century. An independently minded and active person, she followed a varied path in life, rich in experiences. 

Ann gained an Oxford degree in Modern Greats in 1947, took on various administrative jobs and work in an agricultural firm near Cambridge, leading to her marriage and to her raising three sons there. Interest in early child development and freelance writing led to her involvement with the movement to liberalise the care of children in hospital. She wrote two books on the subject and became a Governor of the United Cambridge Hospitals in 1970. In 1977, after gaining a P.G.C.E. (Postgraduate Certificate in Education), she worked in primary and special schools specialising in the teaching of sign language. For this she was awarded a Research Associateship in 1984, at the Institute of Education. She trained as a psychodynamic counsellor with the Cambridgeshire Consultancy in Counselling. She gained BACP (British Association for Counselling and Psychotherapy) accreditation and taught counselling for a number of years for the university.

Ann also exhibited as an accomplished artist at the Tavistock Foundation and with the Cambridge Open Studios for the fourteen years. 

Le Trepied Dolmen

All this was unbeknown to me when she first approached me as a fellow member of Cambridge Open Studios in 2005. 

Ann had recently travelled to many Bronze Age sites to make paintings of ancient sacred places. She asked for my help in photographing the paintings so that she could make cards for her art sales at Cambridge Open Studios and the important Christmas market.

It was while we were meeting to go over the images in readiness to have them printed that Ann uttered a question that was to change the direction of my work.

"Chris, I've been writing my memoirs since my 50s. I'd like to get them published next year in time for my 80th Birthday. Can you help?"

Not knowing much about publishing but good at research, I went away to find out how she could achieve her ambition.

I returned with the news that she would probably have to find a book agent who would then target the main publishing houses. The likelihood of success was small as she would be competing against thousands of others, of which only a very small number would be successful. 

However, since desktop self publishing was now possible, and she was comfortable using Word, I suggested she could produce and publish the book herself.

"I can't do this on my own - could you help me?" was Ann's fateful reply.

A networking colleague, Julie Buck, put me in touch with an Irish publisher, based in Spain, who helped authors self publish. David Cronin of Moyhill Publishing was happy to help, letting us do the layout of the book and cover and dealing with the book registration, publishing and finding a suitable printer.

Completing the final version of the illustrated manuscript and the cover was an exciting period for both Ann and me. The printed books came a bit later than Ann's birthday, arriving in July 2006, but we were both happy with the end result that was "Journey into Solitude".

It was at this point that Ann also revealed her experience of promoting herself - presumably gained from Cambridge Open Studios. She planned a big book launch and signing session and  began busily corresponding with friends and family to ensure a full house. As her book included an element of her journey in faith, its loss and then regaining faith, Ann also successfully place her book in the SPCK bookshop in Cambridge. As I would tell future authors, "producing the book is the easy part, selling you have to work at".

I was proud to be at the bustling launch party that went well, including food and readings by Ann.

Journey into Solitude was simply an interesting project for me at the time. That is, until it prompted others to come and ask for my publishing services. Gaining confidence, and with David Cronin's good will, I took on the full role of publisher for local authors. Now that I'm semi retired, it is my main activity with over 50 books published. All because of Ann's fateful question "I can't do this on my own - could you help me?"

The success of "Journey into Solitude" inspired Ann to venture into historical fiction. 

At the time, she lived in Priory Road, close to the ruins of the Cellarer's Chequer, part of the Barnwell Priory which was dissolved by King Henry VIII in 1539. 

Ann made the priory the focus of a story of a murder at Stourbridge Fair in 1534, the suicide of the Manager of a Homeless project hounded in 1990, the loss of a new-born baby and the painful end of Margaret Clifton, local visionary and artist.  The story lines touched on the question, "does the Evil that men do live after them, but the Good redeem itself in many ways?"

Ann's son, Hugh Hales-Tooke, reprised his role as cover photographer. His beautiful photo, taken with infrared film had graced 'Journey into Solitude'. For 'The Lost Priory', 83 year old Ann was game to be photographed by Hugh as the ghostly figure outside the Cellarer's Chequer. 

Barnwell Priory was closely associated with the ancient Stourbridge Fair, outside Cambridge. Ann invited us (my wife Jane and I) to attend a revival event outside the Leper's Chapel, as she had a stand there. 

It was another example of her sense of fun and willingness to go out and meet people to share her art and, of course, her books.

Our final collaboration came at the end of 2016, when Ann tackled the history of the Petre family prior to and during the first World War, in her book "The Family That Flew".

1914 was a key year for Ann's family, the Tor Bryan Petres. There were seven offspring. Four sons fighting - three sons flying and the fourth, an aviation pioneer, already dead. The book vividly protrays the tragedy and sacrifice, fortitude and hopefulness in the face of loss, through photographs, letters and memories. 

The story begins in the Victorian era with the family influenced by the deep spirituality of Ann's grandmother, Elise Sibeth. It portrays the excitement of aviation in the Edwardian years and something of the sadness and horrors of WWI.

The seven siblings, Ann's aunts and uncles, mirrored their times. The eldest, Mary, the family ‘carer’, was imprisoned by Edwardian mores. They all shared a passion for flight that led to the untimely deaths of Edward and Jack. Henry went on to found the Royal Australian Air Force. Sybil, the youngest, enjoyed more freedom as an ambulance driver and considerable artist.

The book was also the story of Tor Bryan, Ingatestone, a unique Arts and Crafts House, built in 1850 by Ann's grandfather and destroyed by developers a hundred years later. In Ann's mind, the demise of the house mirrored the lives, and deaths, of its occupants.

At 90, Ann had thrown herself fully into the project and the burden of bringing the story to paper would occasionally weigh heavily upon her mind. Illness too interrupted her progress. Then she would recover, regroup and progress. Despite the minor hurdles, we started working together in August and managed to get the final draft of the book to the printers by the beginning of January 2017.

Extract from the press release: "The Author, Ann Petre, (married name Ann Hales-Tooke), aged 90, is launching ‘The Family That Flew’, to an expected audience of 50 guests, at St Andrews Church Hall, Chesterton, on Saturday 21st January, 2017, at 2:30pm."

Yet again, Ann, with the help of friends, organised a launch party with tea and cakes, book signings and readings. Her children and grandchildren were involved and it was a memorable day! The photos below reflect how I will remember her.

All throughout the time between books, we stayed in sporadic contact and I was happy to help with other matters as they arose. As the first author I ever worked with, a fellow artist, and the initiator of my change in direction, Ann has always had a special place in my heart that went beyond the purely transactional. 

Ann, thinking about you passing does make me melancholy and regret losing a friend. But this is balanced by the positive memories of our working together over the 15 years, the shared cups of tea and biscuits - and your smile when all the hard work was done or a hurdle overcome.

It has been a privelege to be a part of your life, Ann. Thank you.

Chris Thomas 16.11.2020

The 1967 Be-Ro Home Recipes Cookery Book

Sitting on our small bookshelf in the kitchen is the most used and referred to cookery book of our home, 'Be-Ro Home Recipes: For Self Raising and Plain Flour'. It was bought by Jane who sent off for the book whilst still at primary school in the late sixties. Her 1967 edition cost a princely shilling and sixpence in old money. It is the first book she goes to when wanting to look up cake and biscuit recipes. It is the book that Jane first refers me to when I am looking for a recipe to do with flour and pastry. First produced in 1925, the book had already gone through multiple print runs and editions, and was entering its 31st million by 1967. 

The 1967 Be-Ro Home Recipes Cook Book

That should have placed it in the list of top one hundred best selling books, on a par with Gone with the Wind, Nineteen Eighty Four and The Great Gatsby! https://en.wikipedia.org/wiki/List_of_best-selling_books#List_of_best-selling_regularly_updated_books.

Much to my delight and surprise, Be-Ro products and, more importantly, the Be-Ro book , still exist and you can order a copy of the 41st edition here from https://www.be-ro.co.uk/ at a mere £2.99. Naturally, I had to get Jane a copy!

Our 1967 book is now suffering from the wear and tear of such loving attention for more than half a century and I resolved to ensure that we had a digital copy we could use. Using my photographic and computer skills, I prepared a readable PDF version. 

This little DL shaped book with 84 pages packed with information and recipies is a historic gem that deserves to be shared. The layout and images may appear dated but ingredients and instructions are clear and as relevant and tasty today as then. As a former scientist, my only gripe is that I have to get used to imperial measures. Fortunately, my kitchen scales can switch from grams and kilograms to pounds and ounces! The new 41st edition is both metric and imperial and also has useful conversion charts for temperatures and weights.

With the permission of Premier Foods, the parent company of Be-Ro, I have made the 1967 book available to all by uploading it to the Internet Archive - free to read and access for non-commercial use. you can find it here:

https://archive.org/details/be-ro-Home-Recipes-1967/mode/2up 

My favorite recipe is Cheese Scones on page 7 in the 1967 edition and page 9 in the most recent 41st edition. My only change - I use butter instead of margerine.

Last chance to capture Comet Neowise

Jupiter (top centre) and Saturn (top right)

Half past midnight, I stuck my head out of the front door and checked. Had the cloud cover broken for the promised hour? There were gaps where the stars glinted through, so I put on a jacket, grabbed the tripod and camera and wandered down Fen Road.

Beyond the last street lights, I entered the dark tunnel of trees and hedges, came out into the open at the level crossing and continued down the winding road till I reached the small bridge over the creek.

There was a clear view across the fields. To the South, Jupiter and Saturn were visible between the broken clouds and I took my first photographs of them to settle in. As the cloud cleared and I zoomed in with my 55-300 mm lens, I could see Jupiter sporting two moons to one side.

Saturn and Jupiter with two moons close by

Facing North and aiming for between the Big Dipper and the trees on the horizon, I started hunting for, and found, Comet Neowise. It was invisible to my naked eye but it could be seen even with the 55 mm lens.

First sight of Comet Neowise

Zooming in was a problem. I had to find a distant light, zoom in and refocus, then go back to where I thought the comet was. I could only find it my taking several pictures as I scanned the horizon.

Zooming in on Comet Neowise

The core of the comet definitely had a green tinge, hinting at the cyanogen gas being emitted and ionised by the sun's solar radiation.

After an hour, I suddenly noticed the cold, packed up and mady my way home. A lone figure loomed out of the darkness, followed by jogging little green lights that turned out to be the luminous collar of his dog. We chatted and then went our separate ways in the silent village night.

As I made myslef a cup of hot chocolate, I could see the clouds scurrying in again and counted myself lucky to have had this last window to see the comet before it disappeared on its 4000 to 6600 year journey out and back again through the solar system. https://en.wikipedia.org/wiki/C/2020_F3_(NEOWISE).

Daily COVID-19 charts of USA, UK and selected EU countries

UPDATED 28-06-2021

This post is charting the progress after the first coronavirus peak in Europe. 

The toughest rules to try and contain the Coronavirus epidemic in the UK are now being relaxed. A faster spreading variant of the virus from India, named delta, has been spreading in parts of the UK, however, the vaccine appears to give protection. The hope is that this time, it might still be possible to relax rules fully in June. Travel from the UK to some countries is possible again, with the NHS app providing a Covid Vaccination Passport.

Cumulative global cases to date pass the 180 million mark at 180,817,269. Cumulative global deaths due to COVID-19 to date: 3,923,238.

The first two charts are key to showing whether countries have managed to gain control over the COVID-19 epidemic. What we all want to see is that the number of new cases per day is decreasing. The day to day data varies quite a bit. To even out the curve to see the underlying trend, I plot the  average of the values for the 7 days including the most recent day.

Figure 1. shows the USA data which appeared to have passed its fifth peak, declined to less than 10,000 new cases per day and continues to be decreasing further. The USA is compared to the daily cases for Russia, France, the UK, Italy, Germany and Belgium, which all  have passed their most recent peaks. The UK was later in reaching its peak of daily cases, at roughly the same time at the US then declined to be lower even than Belgium. However in the past weeks, daily new cases have been rising again in the UK, predominantly in unvaccinated younger people. At present, UK deaths do not appear to be following suit.

There is a new concern about the so-called delta variant of SARS CoV 2 B.1.617.2, which appears to be more transmissable and has become the dominant strain in UK. The current vaccines do seem to be effective against the strain after two jabs.

Figure 1.  Following a long decline after the first coronavirus peak, there has been a second peak and and then a third peak. The USA  and the EU countries are now past their most recent peak.

Figure 1.  Following a long decline after the first coronavirus peak, there has been a second peak and and then a third peak. The USA  and the EU countries are now past their most recent peak.

The current strategy is to identify hot spots and damp them down by reinforcing the total lockdowns, track and trace, and concentrated vaccinations until the coronavirus levels decline. 

Figures 3 appears to suggest that the increase in the number of global cases is slowing down. The reassuring feature is that the death rate has decreased from a peak of 7% in April 2020 to 2.2% at the most recent date, or 2.3% of the cases infected 28 days ago.

Figure 3. Global cumulative cases of COVID 19 and deaths by Covid over time.

The cumulative figures below reflect the rise, slowdown and new rise and slowdown in cases seen in many countries. Most remarkable is the UK curve, which showed the impact of the hard lockdown and vaccination in reducing the rise in daily cases. However, the new delta strain which has become dominant in the UK is resulting in a new rapid increase in daily cases, which fortunately does not seem to be matched by an increase in hospital cases.

Figure 4. Cumulative cases of Covid-19 for the USA and selected European countries.

Figure 5. Cumulative COVID-19 cases in the UK and selected European countries.

For information on COVID-19 gleaned during the first COVID-19 peak -see post "State of Covid-19, caused by the SARS-CoV2 virus, on 16th May 2020" available here http://www.miltoncontact-blog.com/2020/02/should-i-worry-about-covid-19-wuhan.html. 

USA figures are from their CDC (Centre for Disease Control), occasionally from the Worldometer when not. 

UK figures from UK Department of Health and Social Care and Public Health England, Global and other EU data from WHO situation reports.

What could I find out with a Wuhan COVID-19 coronavirus sequence?

When I heard on the news that the sequence of the new Wuhan COVID-19 coronavirus had been made public, the nerd in me was awoken. It triggered memories of when I used to work with plant viruses two decades ago. Would I still be able to find out more about the virus using some of the methods I would have used back then? Would I be able to understand how the up-to-date and vastly more experienced teams in animal and human virology might approach the problem? Could I explain it to others who don’t work with viruses?

If you are simply looking for general information on the current COVID-19 epidemic, have a look at my earlier post here http://www.miltoncontact-blog.com/2020/02/should-i-worry-about-wuhan-2019-ncov.html. This includes up to date charts and tables on the progress of the epidemic using data from the WHO situation reports.

For my adventure with the Covid-19 sequence, read on.

Finding the Wuhan COVID-19 sequence

One of the great early benefits of the internet was the setting up of DNA databases accessible to all scientists, via The European Molecular Biology Laboratory (EMBL), a molecular biology research institution supported by 27 member states - https://www.embl.org/. This database is currently held by the EBI, the European Bioinformatics Institute, whose centre is based in Hinxton, just outside of Cambridge.

My first step was to see if I could find and download the 2019 nCoV (COVID-19) sequence, using the European Nucleotide Sequence Browser that I found at https://www.ebi.ac.uk/ena/browser/home. In the last week of January, I found a sequence of "A novel coronavirus associated with a respiratory disease in Wuhan of Hubei province, China" provided by F. Wu and a further 18 co-workers. It had been submitted on 05-JAN-2020 by the Shanghai Public Health Clinical Center & School of Public Health, Fudan University, Shanghai, China and entered into the database on 13-JAN-2020. Its entry number on the EBI database is MN908947.

Note that if you search now, you will pick up a different set of 7 later sequences under the accession number MN988668: The first two are from "RNA based mNGS approach identifies a novel human coronavirus from two individual pneumonia cases in 2019 Wuhan outbreak"; Emerg Microbes Infect :0(2019) by Chen Land others, submitted 23-JAN-2020, State Key Laboratory of Virology, Wuhan University, Bayi Road, Wuchang District, Wuhan, Hubei 430072, P.R. China. These cover the first two sequences.

There are 5 further sequences from US laboratories from isolates of the virus from US patients in Arizona, California and Illinois, also from around the end of January.

Update 24 February 2020: 24 different COVID-19 sequences were available, from the US, Japan, China and Italy

The virus sequence is given as 29,881 nucleotides

Are there differences between the eight COVID-19 sequences?

I downloaded all the sequences and combined them into a merged file using the software SeqVerter, part of a downloaded freeware called GenStudio Pro. I then uploaded the merged file to Clustal Omega, an EBI program that compares multiple sequences online. After a cup of tea and a scone (with jam), the result appeared on the screen.

They were all 100% identical – the three Chinese and the 5 five different US isolates.

Short section showing sequence identity over the eight available 2019 nCoV (COVID-19) sequences

From a disease point of view, this was ‘good’ news. It showed that from the beginning of the outbreak in China to the first cases in the US, the virus had not mutated into a different strain.

From an old virologist’s point of view, this was quite an unusual result. Why? Well, virus RNA is replicated with a far higher error rate than DNA. The rate is 1 in 10,000 nucleotides. The virus RNA is almost 30,000 nucleotides long. So every time the virus reproduces, I would expect two to three differences to be introduced. When you get millions of virus particles made during an infection, the sequences are actually a spread of mutations that average out around a consensus sequence. An RNA virus is thus not a species as such, but technically a quasispecies. This hold true for another coronavirus disease, MERS (Middle East Respiratory Syndrom), as explained in Mandary et a; (2019) “Impact of RNA Virus Evolution on Quasispecies Formation and Virulence” https://www.researchgate.net/publication/335938867_Impact_of_RNA_Virus_Evolution_on_Quasispecies_Formation_and_Virulence.

I would expect it to be true for the COVID-19.

Diseases like polio, for example, took advantage of these spread of mutations. After infecting a body and causing mild symptoms, a few viruses were able to break through the blood brain barrier and cause the more severe paralysis. This spread of mutations is also what might make it possible for a virus to jump species and infect a host it does not normally reproduce in.

When I did sequencing more than 20 years ago, we had to clone virus fragments and then sequence each clone. We would have seen the different sequence mutations and would have had to sequence a number of clones to get the average quasispecies sequence.

Modern virus sequencing gets around the individual cloning by using NGS, next generation sequencing https://bitesizebio.com/21193/a-beginners-guide-to-next-generation-sequencing-ngs-technology/. The viral RNA, with its whole population of different sequences is extracted, amplified and sequenced. The sequence obtained is the most average sequence, the quasi-species sequence (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3708773/pdf/1471-2164-14-444.pdf).

Update 24 February 2020: A news report stated that there were now sufficient sequences of COVID-19 for researchers to determine how the disease might be migrating into different countries. 

I therefore had a go myself,  generating a first phylogenetic tree. Here are the results I obtained with Clustal with unedited sequences straight from the EBA. 

I do not claim that these results are definitive linkages of relationship or origin at this point. 

24 February 2019: Phylogenetic tree showing possible relationships using unedited COVID-19 sequences from the EBA.

Tentative questions from my data. Are there really two major families of the virus? Are the Japanese and the Italian strains closely related?

A more comprehensive chart created by researchers can be found at the global flu initiative GISAID at https://www.gisaid.org/.

What is the closest relative to the COVID-19?

The beauty of having a public sequence database is that you can take a new sequence, like COVID-19, and use it to see if you find similar sequences amongst the millions already there. I did this online at EBI, using the nucleotide similarity search, Fasta. It was limited to finding 50 related sequences.

I had the results displayed as a “Phylogenetic tree cladogram”, a branching pattern showing the degree of similarity between the different sequences.

My first phylogenetic tree using 2019 nCoV (Wuhan Seafood Market, COVID-19) against the EBI nucleotide database

The tree showed that the closest similarity of the COVID-19 (Wuhan Seafood Market) coronavirus was to Bat SARS-like viruses, and more distantly to other SARS viruses. Those simply called SARS are human isolates. There was a SARS epidemic, which also originated in China, back in 2002, which was finally brought under control in 2004. SARS stands for Severe Acute Respiratory Syndrome. It killed almost one in ten of people infected.

It is interesting how many patent sequences were also picked up. Presumably from companies and organisations that wanted to provide detection and possibly treatment products against SARS.

I wanted a different display to put the COVID-19 in a wider context. I therefore downloaded a number of species specific Coronavirus sequences that I found by searching the European Nucleotide Sequence Browser for coronavirus. I also removed all the patent sequences from the original set found. The new set of data was uploaded for analysis.

The new phylogenetic tree is shown below. I’ve left the accession numbers in to make to make it easier for future work. I also stretched the tree horizontally from the original, to make the branching clearer and coloured different groups for interpretation.

My second phylogenetic tree from using the results from the first search, minus the patent sequences, plus 15 other coronaviruses from different animals

The different human SARS (simply called SARS) sequences in dark red divide into two groups. One has similarities to Civet SARS (in orange), the other has links that reach to Bat SARS strains (orange). The Wuhan COVID-19, marked in bold red, is more closely related to the Bat SARS. The MERS, Middle Eastern Respiratory Syndrome (dark red), was first identified in Saudi Arabia in 2012. It seems to be more lethal than SARS, with about 36% of individuals diagnosed with the disease dying from it. However, it does not seem to spread easily and there have been around 2000 cases recorded in the period 2012 to 2017. My and the professional advice is – keep away from sick camels.

The remaining animal coronaviruses marked in black cover a range from pig to human to rat. The human coronavirus OC43 is one of a number of viruses that cause the common cold.

Using the COVID-19 sequence to find a vaccine

Companies and organisations around the world, including the US and Porton Down in the UK, are now racing to develop a vaccine. One company in the news recently hoping to get to human trials in the Summer.

Where would I begin?

A search for antigenic regions in SARS on Google, after the last SARS outbreak, will find a number of publications. Researchers use blood serum from people who are ill with, or have just recovered from SARS and see if their sera cross react with any of the virus’s proteins (are they antigenic). If they do, they probably contain useful antibodies.

A paper I particularly liked studied the SARS spike protein. The spike protein sits on the outside of the virus capsule. It interacts with the human cells during infection and plays a part in the absorption of the virus into the cell. The spike protein has two domains (stretches), S1 and S2. S1 is not very antigenic, but S2 is. Hong Zhang et al (2004) used a strain of the human SARS called BJ01 (accession no. AY278488). They created 12 different overlapping fragments of the S2 domain of the spike protein. They labelled them F1 to F13. They looked at which of these fragments were bound by antibodies in sera from 15 different SARS patients. (published as “Identification of an Antigenic Determinant on the S2 Domain of the Severe Acute Respiratory Syndrome Coronavirus Spike Glycoprotein Capable of Inducing Neutralizing Antibodies” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC421668/). 

The fragments F3 and F9 in SARS turned out to be antigenic, i.e., the patients’ sera reacted with them. Proteins are made up of chains of amino-acids. F3 stretched from the amino acid Arginine at position 797 in the spike protein to amino acid Proline at position 844. F9 stretched from amino-acid Leucine at position 1045 to Aspartic acid at 1109.

Using a single letter code for each amino acid, the sequences of F3 and F9 are:

F3=RSFIEDLLFNKVTLADAGFMKQYGECLGDINARDLICAQKFNGLTVLP

F9=LHVTYVPSQERNFTTAPAICHEGKAYFPREGVFVFNGTSWFITQRNFFSPQIITTDNTFVSGNCD

First I compared how similar the human SARS BJ01, a Bat SARS, a MERS and a human coronavirus spike proteins were to that of COVID-19 (labelled 2019 nCoV). I did this in pairs using the alignment program in GenStudioPro. The results are shown in the figure below. You can get a good first impression how well sequences match by looking for how much of the aligned protein sequences is coloured darkly, indicating a 100% match.

Pairs of alignments between COVID-19 (2019 nCoV) and human SARS BJ01, a Bat SAR, a MERS and human coronavirus OC43. The locations of the antigenic fragments F3 and F9 from human SARS BJ01 are marked in red bars. The dark colours in the aligned sequences show a 100% match.

Just from the colour patterns alone, you can see that the spike protein of COVID-19 is very similar to both the human and the bat SARS sequences. There is much less matching between 2019 nCoV and the MERS or human coronavirus OC43.

I then looked more closely at the similarities between the F3 and F9 antigenic fragments from human coronavirus OC43 and a variety of sequences. I always included the F3 or F9 fragment, the human coronavirus OC43 sequence from which it was derived, and the COVID-19 sequence.

Looking at similarities to the F3 antigen from human SARS BJ01 with COVID-19  (2019 nCoV) and Bat SARS, a MERS and human coronavirus OC43. Differences just in the COVID-19 (2019 nCoV) are highlighted in red. Differences in the other sequences are highlighted in orange.

Looking at similarities to the F9 antigen from human SARS BJ01 with COVID-19 (2019 nCoV) and Bat SARS, a MERS and human coronavirus OC43. Differences just in the COVID-10 (2019 nCoV) are highlighted in red. Differences in the other sequences are highlighted in orange.

COVID-19 shows three differences in amino acids from F3, marked in red and a further three differences from Bat SARS marked in orange. Compared to F9, COVID-19 shows 9 differences marked in red, as well as a further three differences from Bat SARS.

The question I might try to answer in experimental trials would be, if I changed the F3 and the F9 sequences to match those of COVID-19, would these changes give me antigens that could generate antibodies, and therefore help create potential vaccines against the current COVID-19 outbreak?

Other approaches

The answer to my question might actually be no. Remember earlier on we learnt that an RNA virus like COVID-19 is likely to be a quasispecies. It is not one definite sequence but a population of viruses with an average around the published sequence. The altered F3 and F9 based vaccines would only affect those viruses in the population with exactly these changes. Those with a different mutation might slip through.

Vaccines made with live attenuated viruses are often the most effective and can be made by using such a mixed population found in a quasispecies virus. The other strategy could well be to create an attenuated version of the COVID-19. By being weakened in some functions so it did not cause disease, it might still being able to induce the same antibodies against the native and more dangerous virus and so create an effective vaccine. The availability of the consensus viral sequence and existing information on related SARS viruses might make this work easier.

Conclusion

I hope this gives an insight on what can be done if you have available sequences for a new disease like COVID-19. But do remember, I am just an outsider, 20 years behind the times, who used to work with plant viruses, which are very different to animal and human viruses.
It is reassuring to know, as the disease continues its growth and spread, that vastly more experienced research teams in public labs and private companies are racing to generate an effective vaccine.
They are likely to do so at a pace that I would have found unbelievable when I was working in my field.