Monday 16 November 2020

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

Monday 24 August 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!

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 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: 

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.

Thursday 23 July 2020

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.

Sunday 17 May 2020

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

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.

Wednesday 5 February 2020

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 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 - 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 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”

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 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 (

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

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” 

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:



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.


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.

Monday 3 February 2020

State of Covid-19, caused by the SARS-CoV2 virus, on 16th May 2020

Photo: CDC/C.S. Goldsmith -

Updated 16 May 2020 15:30
data as of 15 May April 2020 

COVID-19 still affects many people in Europe and the US. The disease could be with us for the next few months and possibly into next year.

  • Most of the hardest hit European countries and the USA are seeing the results of their varied lockdowns. 
  • The number of new COVID-19 cases per day appears to have reached its peak in many of them, begun to decline in some such as France and Germany and recently, the USA
  • At last, the number of new cases in the UK begins to show a decline.
  • Russia is a latecomer to infection and is just reaching its peak.
  • The controls are being loosened slightly in some countries. Everyone is on the alert for any negative impact of lesser restrictions. 
  • Most countries are ramping up testing for track and trace as a tool of combating the progress of the disease, possibly with the help of apps.
  • Several preliminary trials of potential vaccines are being tested globally. 
  • Testing/screening
    • PCR is still the most accurate method of testing for coronavirus infection, but takes time and expertise. 
    • There is a new fast single step DNA test awaiting approval, which uses CRISPR technology. It might even be possible to conduct this one at home.
    • Faster antigen based tests against the virus are being evaluated to identify COVID-19 infection in greater numbers. 
    • Screens for virus specific antibodies are also being evaluated to identify those who have recovered and to see if they have a longer lasting immunity.

This article covers:

  • What is the COVID-19 coronavirus? Symptoms and risks.
  • The spread of COVID-19 in Charts
  • Will I be infected?
  • How can I protect myself?
  • What nations and the international community can do
  • So, should I be concerned?

What is the COVID-19 coronavirus? Symptoms and risks.

COVID-19, is the disease caused by SARS CoV 2, formerly known as the Wuhan 2019 nCoV by the WHO (World Health Organisation). This is a new coronavirus that began in the Chinese city of Wuhan and originated in bats.

Symptoms can include fever, sore throat, dry cough, fatigue and breathing difficulties. A recent report suggests digestive problems can by symptomatic in nearly half of admitted patients. There are lots of different coronaviruses infecting humans and animals. Some of the colds you had in the past were probably caused by a human coronavirus.

This COVID-19 appears to be mild in most cases. However, those with pre-existing health problems and the elderly are more likely to be severely affected.  In severe cases it can cause a viral pneumonia and cause death. See below for more information.

Further results show that men and persons from black, Asian and other minority groups (BAME) are more likely to be adversely affected by COVID-19. Social (poverty and and differences in family groupings) appear to be important here.

COVID-19 is different from flu and the common cold in that it affects the lower respiratory tract rather than the upper. A recent publication suggest that digestive issues often arise before the other symptoms. See the comparison of symptoms below. The colours indicate likelihood from red = most likely to white = not likely:

Table 1. Comparison of symptoms between COVID-19, Flu and the common cold. Collated from various medical sources. Includes recent article on gastric problems in the American Journal of Gastroenterology.

COVID-19 seems to be at least as infectious as flu, with an average rate of one person infecting between 2 to 4 people, with suggestions tending towards the higher figure. One person with Rubella infects 5 to 7 people and one with measles, 12 - 18 people.

If you are fit and healthy, the COVID-19 disease is much less likely to be severe. You are at much greater risk if you have a compromised immune system or are affected by other illnesses. As with many diseases, the over 60s are more vulnerable.

Current estimates are that the death rate from COVID-19 from global figures has risen from  5%, or 1 in 20 on average to 6.9%. However, it is higher for figures given by some countries. For example, Italy has a mortality figure of about 13%, the UK also has a figure of 13%. This may be the result of insufficient testing, such as only testing admissions to hospital.

For comparison, Measles kills 1 in 500, a previous coronavirus – SARS - killed  almost 1 in 10. Seasonal  flu usually has a death rate one tenth that of COVID-19. 

Detailed figures on mortality rates for COVID-19 are now available based on 44,672 cases from the Chinese Centre for Disease Control and Prevention (figure 2). Age is an important factor. How healthy you are also has a significant effect.

Figure 2. Mortality rate  with age for COVID-19 based on on 44,672 cases from the Chinese Centre for Disease Control and Prevention. I have deliberately set the vertical axis to 100% to avoid  over-emphasising the figures.

Figure  3. The effect of  pre-existing conditions on deaths by COVID-19. I have deliberately set the vertical axis to 100% to avoid  over-emphasising the figures.

A preliminary Chinese study ( looking at ABO blood groups in COVID-19 patients suggested that blood group A was associated with a slightly higher risk for acquiring COVID-19 (about 1.2 x above average) compared with non-A blood groups, whereas blood group O was associated with a slightly lower lower risk (0.67 x of average) for the infection compared with non-O blood groups. The results still need to be validated by others.

The spread of COVID-19 in Charts

By the 15 May:
  • Europe is still the centre of the pandemic but the US has overtaken all countries in number of COVID-19 cases
  • The rest of the world is still showing a linear increase at about 70,000 new cases per day. However some countries appear to have passed the peak
  • 215 countries and territories have cases of COVID-19 recorded now. For all daily data from the WHO, see
I have limited my monitoring to countries with historic high cases of COVID-19 (China, Iran, South Korea) as well as Japan, Australia, and European countries with more than 1,000 cases. Of the countries I am monitoring:
  • Eight countries have 1000 -2,000 cases:  Bosnia and Herzegovinia, Bulgaria, Estonia, Iceland,  Lithuania, North Macedonia, Slovenia, Slovakia.
  • Twelve countries  have more than 2000 - 11000 cases: Armenia, Australia, Croatia, Czechia, Denmark, Finland, Greece, Hungary, Luxembourg, Norway, Republic of Moldova,  Serbia.
  • Eleven countries have 10,000 to 50,000 COVID-19 cases - Austria, Ireland, Japan, The Netherlands, Poland, Portugal, Romania, South Korea, Sweden, SwitzerlandUkraine.
  • Ten countries have more than 50,000 cases of COVID-19: Belgium, China, France, Germany,  Iran, Italy, Russia, Spain, the United Kingdom, the USA.

I use the data from the WHO Situation Reports, which reflect figures that lag about 12-24 hours behind the final figures on any date. They are at least consistent and allow trends to be observed over time. US figures have been obtained from the CDC or the Worldometer when CDC unavailable at Weekends, and UK figures from Public Health England. (UK counts now include the results from the expanded testing from the beginning of May.)

By the morning of 15 May, 2020, more than 4,338,658 total cases of COVID-19 had been reported worldwide.

Figure 4 below shows that after the leveling off of cases in China by the 16th February, cases in the rest of the world began, and still are, increasing (figures 4 and 5) but the rate of increase is linear, not exponential (figure 4 & 5,) at a rate of half a million cases per week.   The number of deaths to date globally is 297,119 (figure 4 and 5). There is still a daily increase.

The  top scoring locations are USA and a number of European countries, who account for most of all  cases (figures 6,7, 8 and 9).  Cases in the USA exceed those of other countries more five and a half times.

Some European countries and the USA have now implemented measures to relax their strict lock-down measures. The number of new cases in European countries is beginning to slow down, judging by data from the past few weeks (figures 6 and 7).  

Figure 4. Total counts of global accumulated COVID-19 cases and recorded deaths over time

Figure 5.  Same data as figure 4 but as a logarithmic plot  (base 2) of global cases of COVID-19 and global deaths. Horizontal lines for values increasing 2 fold.

I have introduced two new charts which show the number of new cases per day (figures 6 and 7). Daily figures do vary a lot, so I have used an average of the previous 7 days for each day which smooths the curve. The climb to a peak, leveling off and decline is seen much more easily.

It looks as if Spain and Italy have reached the peak and are on the decline. Germany and France also appear to be past their peak.  The UK at last shows a similar trend though the sign of decline in new cases is only just appearing. USA values are so high, they merit their own graph (figure 6) but appear to have reached a peak at 32,000 new cases per day are declining slowly.  

Figure 06. The number of new COVID-19 cases in the USA per day, Seven day average. 

The dates of the peaks of new cases per day are interesting: Italy 26th March; Spain 31st March; Germany, France and Iran by the 2nd-4th April, USA 10-14th April; the UK 13th - 16th April. Among lower scoring countries, Austria and Switzerland peaked at almost the same time. Belgium and The Netherlands show a similar pattern of reaching a peak at about the same time and then plateauing off without a significant decline for more than a fortnight afterwards.

Figure 07. The number of new COVID-19 cases in countries other than the USA per day, Seven day average. Note the 10 fold differences in scales in these two figures.

The following graphs show the cumulative number of COVID-19 cases over time for selected countries. USA has had five and half times as many cases than any other country so is shown separately in some of the charts. Russia is showing a late rapid increase in cases but has reached its peak.

Figure 8.Ten countries have more than 50,000 total cases of COVID-19: Belgium,  China, France, Germany,  Iran, Italy, Russia, Spain, the United Kingdom, the USA. The graphs is also shown without the US as the values in the US are more than five times higher than any other country.

Figure 9. The same data as figure 8 but using a logarithmic plot (base 2 ). Horizontal lines for values increasing 2 fold. Ten countries have more than 50,000 cases of COVID-19: Belgium, China, France, Germany,  Iran, Italy, Russia, Spain, the United Kingdom, the USA.
Most countries with 10,000 plus cases out of their exponential growth phase as seen in figures 8 and 9,  showing a slow down in the number of new cases over the past few weeks (figures 10 & 11). 

Figure 10.Eleven countries have 10,000 to 50,000 COVID-19 cases to date - Austria, Ireland,  Japan, The Netherlands,  Poland, Portugal, South Korea,  Romania, Sweden, Switzerland., Ukraine.

Figure 11.Logarithmic plot, base 2. Eleven countries have 10,000 to 50,000 COVID-19 cases to date - Austria,  Ireland,  Japan, The Netherlands,  Poland, Portugal, South Korea,  Romania, Sweden, Switzerland., Ukraine.

Taking the UK as an example, the rate of increase of new cases is slowing down. Figure 12 below shows that the time taken for a ten fold increase in cases in the UK has come down from ten-fold every 7 days to two-fold every 46 days and declining. Hopefully the rate will continue to slow down.

Figure 12. Graph showing the change in the rate at which new cases arise in the UK. The rate of increase in COVID-19 cases, based on the last 7 days, is about two fold every 46 days and declining.

Table 3. Showing data for countries  with more than 10,000 cases of COVID-19

Public Health England map and charts of COVID-19 across the UK

COVID 19 Symptom tracker for the UK
Note that this suggests more than twice as many cases as given by figures from tests done so far.

Will I be infected?

Information was that you have to be within 2 meters of someone. The consensus is that the main route of infection to avoid is - touching surfaces contaminated by the virus and then touching your mouth or eyes. Even when you do, this does not mean that you will always become ill (see 'How can I protect myself' below) as you have to receive a certain dose of virus for successful infection.

  • The virus is possibly shed into the air by an infected person. 
  • The virus can even be spread by people who are not displaying obvious symptoms like fever or a cough. 
  • The highest shedding of virus occurs just before the onset of symptoms and then declines.
  • Your risk of infection is dramatically reduced the further away you are from ill people. 

However, it is possible that a significant percentage of the population will be infected eventually.

What does the virus COVID-19 do?

The COVID-19 coronavirus infects the cells lining the airways of the body, the epithelial cells.  In severe cases it seems to progress to the lungs, causing pneumonia.

The virus has a complex protein capsule that contains the virus genes. The virus genes are on a single strand of RNA – not DNA. This strand is 29903 bases (units) long. Numerrous isolates of the virus have been sequenced and their sequences made publically available for all scientists - see

On contact with one of your epithelial cells, the cell is triggered to take up the virus. Inside the cell, the virus hijacks your cell’s own functions to make copies of its single RNA strand. The genes encoded on the virus RNA are translated into a range of virus proteins by the cell. New virus particles are then assembled within the cell. They are then either exported by the cell or released when the cell dies. Neighbouring cells are then infected.   If the conditions are right, the virus begins to spread along your airways.

COVID-19 can be symptomless in some people for between 5 to 12 days. If they appear, the symptoms you may get range from fever, sore throat, dry cough, fatigue and breathing difficulties. A recent paper in the American Journal of Gastroenterology suggests that digestive problems may be an early indicator of COVID-19 in nearly 49% of cases, in advance of other symptoms.

They are in part due to the virus affecting/killing cells but also due to your body going into overdrive to try to fight the virus infection (often described as a cytokine storm). How ill you are is a balance between virus multiplication and how fast and effectively your body defence works. There is more information below in the next section on how you can protect yourself.

How can I protect myself?

Your choices NOW affect how many cases the NHS has to deal with in 14 days.

There is no vaccine for COVD-19 yet – but with the full sequence of the virus available, work is in progress to provide a vaccine in the next months. Therefore isolation and quarantine remain the most effective means to prevent the spread of the disease. Things you can do are:

  • Keeping healthy by eating and sleeping well, exercising*
  • Avoiding locations and people with the illness
  • Hand-washing
  • Use hand sanitisers
  • Good personal hygiene generally
  • Use the new tracking and trace app when it is on general release
*Keeping healthy is a great prophylactic as it means that your immune system is in best condition. Our bodies are actually geared to be alert to any foreign invaders and illnesses and the incoming virus does not have it all its own way.

Get the COVID Symptom Tracker app

You can join in with research on the progress of COVID 19 in the UK by downloading the COVID Symprom tracker app from

Disinfecting smooth surfaces:

You can use:
  • 70% or stronger alcohol to wipe surfaces (preferred - effective and leaves no residue)
  • Thin bleach or diluted thick bleach
  • Soapy water.
Remember to wear rubber gloves. Wipe with paper towels you can throw away. AND WASH YOUR HANDS AFTERWARDS.

Clothing/ cloth articles
  • Wash in washing machine with your usual detergent.
  • WASH YOUR HANDS AFTER placing possibly contaminated clothes into washing machine.

Possible UV inactivation of CoV SARS 2

Hospitals and laboratories often use special flow cabinets with UV lights to sterilise surfaces. From the publications I looked at, RNA viruses in aerosols are quite resistant to UV exposure, requiring times of half an hour or more with shortwave UV (about 254 nm). For those wanting to pursue this further, the following may be of interest.

Your body - your best defender!

If a cell in your body is overcome by an infection and dies, this triggers other chemical signals which alert a variety of white blood cells. Some, called macrophages, come to absorb the invading foreign viruses and take the information back to T-cells. The T-cells in turn use this information to help create killer T-cells and antibodies. There are also memory cells that will remember the antibodies required to fight any future infections by the same strain of virus.

Some of my neutrophils from a cold,
photographed at over 1000x magnification
using anoptral contrast

In the meantime, a whole army of another type of white cell, neutrophils, invade the infected area and gobble up all the debris of damaged cells and the viruses they come across. When you have pus from a spot, or your runny nose produces the thick white stuff, or you cough up thick phlegm - that is mostly made up of these short lived neutrophils that have gorged themselves on what is infecting you.

Incoming coronaviruses also trigger the production of interferons within the cell and initiate other yet unknown responses. These seem to slow down virus action. In turn, viruses continually evolve to overcome the cell’s defences. (

In chemotherapy and radiotherapy, these immune systems are weakened, hence you become more susceptible to infections taking over. So take extra care.

What nations and the international community can do

Countries and the World Health Organisation have plans and structures in place to trigger action when diseases are spreading. The WHO had expressed its opinion that this was still a controllable pandemic and that a shift from containment to mitigation would be wrong and dangerous.

UK Response

PM Boris Johnson acknowledged that this was "the worst public health crisis for a generation".

  • The UK is trying containment by restrictions on movement and will be introducing track and trace in the near future. 
  • The UK is ramping up testing for all critical care workers (hospitals, care homes, emergency services, including police, teachers etc.).
  • Individuals with a fever or cough must self isolate for seven days. Families with one infected person need to self isolate for 14 days to ensure everyone is in the clear. 
  • Schools and non-critical businesses have been closed from the weekend of  21st March, exceptions are for critical care workers and essential functions to keep the country running. 
  • People over 70 and those with pre-existing health conditions have been told to self isolate for the foreseeable future. 
  • Travel locally and abroad is strongly discouraged
  • The NHS has survived the current peak and people with symptoms are no longer required to call NHS 111. They are instead directly to look for information on the NHS website and 111 online.

Latest Documents from the UK Government accessible here: 

The plan

The aim is to slow down the rate of infection so that the peak in hospital cases is lower and spread, so that the NHS can cope.

Even after the virus has been brought under some degree of control, the virus and some degree of control measures are with us for the foreseeable future - possibly more than one year.

The number of tests for infection is to be dramatically increased to determine which key workers are affected and which individuals can work in critical posts. The UK is still lagging behind in testing compared to a number of other developed countries.

In the near future, testing to see who has been infected and recovered will be possible. This will most likely be by using mass produced antibody kits, similar to pregnancy tests. Knowing someone has recovered and is resistant to the virus will give reassurance that they can return to work without being at risk to themselves and others.

Ultimately, the country needs to gain a significant proportion of the population that is resistant to the virus. This "herd immunity" (see below) can be obtained both by recovery from being infected and from vaccination.

Vaccines are being developed and tests have begun both in animal and small scale human studies. It could take a year or more before a vaccine is generally available.

Herd Immunity and Vaccination

Herd immunity by recovery is a real effect with a number of diseases. Governments around the world expect that a significant percentage of the population will be infected over the coming year. The hope is that recovered individuals will be immune.

Note of caution, immunity to existing corona-viruses, such as those causing the common cold, disappears quickly. We do not yet know if we gain immunity after infection with the SARS CoV2 and how long the immunity will last.

Natural herd immunity occurs when a significant proportion of the population has been infected and survived. The survivors are resistant to the illness and, if their numbers are high enough, it becomes more and more difficult for the disease to find uninfected persons. The progress of an epidemic slows or can even peter out if herd immunity is high enough.

With the current  estimate of an average rate of one person infecting between 2 to 4 people for COVID-19, this could mean that 50% to 80% of the population would have to go through infection to achieve full herd immunity against COVID-19 (based on figures in

However, it could be that the UK is hoping that a lower figure of herd immunity may reduce the level of general infection in the population, if not achieving outright cessation of the epidemic.

In the meantime, vaccine development, testing and then mass production will be undertaken as fast as possible to provide our protection in future years. The first safety trials of some vaccines have already started. Earliest prospects for a possible vaccine in low numbers suggested for end of year. Realistically we might have to wait till 2021.

Other countries' responses

As Europe was the new focus of the pandemic, the US and other countries stopped people from European countries (including the UK and Ireland) entering.

Within Europe, France, Germany, The UK and Spain had joined Italy and also introduced more control measures, promoting self isolation, banning public gatherings and restricting movement within and between countries. Now the controls are being relaxed gradually. The aim is to allow more and more freedom but to a level that we do not have another sudden flash of cases and allows the health systems cope at a reasonable level.

The USA had implemented more testing and stringent control measures to try and limit the escalating crisis in its states. However, there is very strong pressure to relax controls and get the economy going again and different states are opening up to varying degrees, often contradicting the recommended scientific tests. The balance between scientific modelling and advice and political decision making is beginning to lean towards the latter. So far this has worked OK as new cases continue to decline.

The differing responses of countries to the coronavirus epidemic have in effect been a global experiment whose results will reveal best strategies for future epidemics. The same is now true for the rate of relaxation of controls in different countries - it is the next global experiment.

The general global practice with new diseases prior to COVID-19

Every year, new strains of influenza arise naturally by mutation as the virus adapts to us changing humans. Rather than letting a large proportion of the world’s population become ill (letting many people die) with the survivors therefore gaining resistance to the newest strain, we humans are proactive. Up and coming new strains of viruses are identified and vaccines produced so that by the time the disease arrives in your part of the world, you are protected in advance and do not get ill, or only have mild symptoms

With totally new viruses, like the COVID-19 coronavirus, there is no immediate vaccine defence. It is therefore vital that a country keeps tabs on new illnesses that arise. They need to have plans in place to deal with the isolation of infected people. They also need to provide care whilst patients go through the illness, to mitigate symptoms until they get well.

Until we have a vaccine, severe cases may be helped by giving them antibodies from people who have recovered from the disease. This method was used against diphtheria in the early 1900's in Alaska, though the antibody serum was actually derived from horses. I do not know if this is currently being pursued. Cloned antibodies might be an alternative solution.

Update 08/03/2020 re using antibodies from people who have recovered: first reports in news that Germany and USA looking to use plasma from recovered patient for serious cases. 

Update 20/04/2020: Plasma treatment (using antibodies from people who have recovered) being trialed in the UK, including Addenbrookes, Cambridge.

In this interconnected world, nations also have a responsibility to alert the WHO early about upcoming diseases. This time round, full marks for the Chinese response, because we were made aware of the issue earlier than in the past. The world was able to start monitoring for carriers of the illness and put in place travel restrictions.

Despite the WHO advice to act quickly and decisively, most countries underestimated the speed at which the COVID-19 spread in the population and held back from mass testing and tracing whilst numbers were still low. Now, outbreaks such as those in the USA and most of western Europe are now challenging us with a significant number of deaths and stretched healthcare systems.

Information, documents and guidance from the WHO, the UK and US.

The UK and WHO have the following information on responses to epidemics and the teams and mechanisms in place. They can be found in public documents such as:

So, should I be concerned?

Yes. COVID-19 is still affecting many people in Europe and the US.  The disease could be with us for the next few months and possibly into the coming years.

The hard containment measures have slowed down the number of new infections in a number of countries. Relaxation of restrictions is gradually being introduced but with an eye being kept on the effect on virus reproduction in the population.

Look out for public advice from the authorities dealing with the outbreak. The following advice is practical not just in this instance but to minimise your risk of getting ill from any disease that is circulating:
  • Keep healthy by eating and sleeping well and exercising
  • Avoiding locations and people with the illness
  • Regular hand-washing
  • Use of hand sanitisers where there might be a risk in public
  • Note, the use of masks is best for protecting others from you when you are ill rather than protecting you from others.
If you have returned from a region seriously affected by COVID-19, or met an individual who has subsequently succumbed to the illness, and begin to experience chest and cough symptoms, stay at home and look online at NHS 111 in the UK This ensures that you get the right response and treatment and do not accidentally spread the disease further, endangering people in public places, doctors surgeries or hospital reception.

I have also been looking at some of the more technical aspects of the virus genome sequence in the article "What could I find out with a Wuhan COVID-19 coronavirus sequence?" here