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Covid-19: A Primer On DNA, RNA, and SARS-CoV-2 January 13, 2021

Posted by mwidlake in biology, COVID-19, science.
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<<—- Long term hopeful, short term worried

<<– The new Covid-19 B.1.1.7 variant & threat to the health services

I want to explain a few things about SARS-CoV-2 (the virus that causes Covid-19) and the vaccines that are being rolled out in both the UK and the world. To do so I first need to explain about DNA, RNA, proteins and what is called the central dogma of molecular biology, which is what this post is about. The central dogma is the core – the absolute fundamental key thing of life, of our biology. It is the biological equivalent of what quantum mechanics is to physics.

Thankfully, it is far simpler to understand the basics of the central dogma of molecular biology than the basics of quantum mechanics. It is also a well established concept, I was taught it last century at university and it has not changed much in the 32 years or so, though we better understand so much more of the details and ramifications now (6).

Central Dogma Of Molecular Biology

Basically the Central Dogma is that DNA makes RNA and RNA makes protein – and information does not flow backwards. I’ll try and explain that in steps, but before that I want to give a quick reminder about DNA, which most of you probably remember from school, and protein/polypeptides. Sorry, but it’s necessary. Skip to “The Core Of Biology” if you already know all about these.

DNA and Proteins

DNA molecule – from Yourgenome.org

All living organism contain and are controlled by DNA – Deoxyribonucleic Acid. This is the helical, double-stranded molecule whose structure was worked out by Watson, Crick, and Rosalind Franklin. In all organisms (except bacteria & archaea – together known as prokaryotes) the DNA is held in the nucleus of the cell (1). The whole genome is in every normal cell in an organism (be it a plant, fungus, moss, animal, you. Everything alive that is not bacteria/archaea is a eukaryote – which means the cell has a nucleus). There are some exceptions – such as red blood cells that lack a nucleus, or sex cells that carry one half of the normal amount of DNA for a given species.

The DNA directs all of the biochemistry of an organism (2). Everything. It defines the structure of the proteins we are made of, how the proteins go together, the layers and parts of our organs, the overall plan of our bodies, and the hormones, chemicals, and free-moving cells that go around our bodies like red and white blood cells. We still don’t know how some of this control is done but as DNA changes (mutations) affect all of these things, we know the DNA is basically the instruction book to both make an organism and to keep it functioning.

The DNA of an organism contains (amongst other things) it’s genes. Genes are the instructions for making all of our proteins and we say the genes are “expressed” when the genes are activated and make the proteins. And they do this all the time, at great rates, churning out vast quantities of proteins in each and every cell.

I say proteins but that is not *quite* right. Proteins are made of polypeptides, and polypeptides are made up of amino acids. As an analogy, proteins are paragraphs, polypeptides are sentences, sentences are made of letters which are the amino acids.

In the vast majority of organisms there are 20 different amino acids available to “spell out” all polypeptides. Genes have instructions to make chains of amino acids, called polypeptides. A protein may be a polypeptide, but it might also be made of several polypeptides or polypeptides that have been chemically modified after being initially made. I make this point as below, and in some of the links, polypeptides and amino acids are referenced and general scientific literature can be a bit muddled between polypeptides and proteins. For now, just think of proteins as really complex polypeptides. (3)

DNA consists of four letters as you probably know. Adenine, Cytosine, Guanine, and Thymine. In the double helix the two strands are “inverse mirror images” of each other and the letters pair up – A with T and C with G. So a short strand of DNA might be something like the below and, as indicated, the two halves can be split and, via the pairing of the letters, perfectly copied:

 

Double stranded DNA can be split and (perfectly) duplicated

 

The DNA is unzipped and split (by an enzyme called Helicase) and then DNA Polymerase can come along and add in the missing letters and you end up with two perfect copies. Usually. In my example, to the right, there is a mistake,  – a C has been added in where an A should be. This mistake is an example of a mutation.

However, that is not part of the Central Dogma. Although DNA duplication is vital (after all, every cell needs a full copy of the organism’s genome so the DNA needs to be replicated each time the cell divides). The main function of DNA is to pour out instructions for the creation of polypeptides

Central Dogma by Brownfield 5 on slideshare

The Core of all Biology

All the complexity of what our cells do and how our biochemistry works is via genes being expressed.  I’m not going to even attempt to describe how gene expression is controlled. It’s incredibly complex, it’s an area of understanding that has advanced hugely since I was taught the basics in my degree 32 years ago, and science still does not really understand a lot of it. But it’s the expression of these genes that allow are cells to do what they do, from growing hair, muscles, and making white blood cells to producing the enzymes that digest our food and control our bodies. All cells express thousands of genes all the time, at different levels of expression, and they do this by producing Messenger RNA, known simply as mRNA.

RNA, or Ribonucleic Acid, is (as the name implies) structurally very similar to DNA. It is single stranded, not double stranded like our genomic DNA, and the Thymine is replaced with a very similar chemical called Uracil.

Transcription

When a gene is expressed the relevant piece of DNA is “unzipped” and an enzyme called RNA Polymerase walks along the DNA and creates a complementary (meaning A becomes U, T become A, C becomes G and G becomes C) RNA copy of the DNA, as is shown in the diagram to the right. This is called transcription and it produces something called pre-mRNA. This is itself then processed by by other enzymes which cut out parts of the RNA that represent “Introns” – bits of DNA in the gene that are not to be used. This bit is not shown on the diagram. It is one of the complexities of our DNA that was poorly understood before the Human Genome Project and is still rarely explained. In a complex organism like a mammal or plant or fish, a single gene can produce a range of proteins depending on how this pre-mRNA is processed.

The diagram below shows how the double-stranded DNA is “unzipped” and the RNA polymerase reads one strand of the DNA and produces an RNA strand based on it.

RNA Polymerase, from BC Opentextbooks

The final mRNA consists of three main parts. The first part, at what is called the 5 prime (or 5′) end is a cap that allows the mRNA to be recognised and grabbed by the Ribosomes (see later) and transcribed. Then comes the RNA equivalent of the DNA gene for the protein. At the other end, the 3 prime (or 3′) end, a string of As is added (100-200 of them normally), the poly-A tail. We will see why later.

Pre-mRNA to mRNA from Wikipedia

This mature mRNA is then transported out of the nucleus of the cell and out into the body of the cell, into the cytoplasm. The mRNA may hold markers to say where specifically in the cell it is to go but that’s a detail I won’t go into. This seems to be very important to complex organisms like ourselves, that the DNA sits in the nucleus, mRNA is produced and this is quickly passed out of the nucleus to be processed elsewhere in the cell.

Translation

So we now have an mRNA molecule in the cell ready to be translated, i.e. used to make a polypeptide. In the cell there are thousands and thousands of very complex molecules called “Ribosomes”. A ribosome is actually made of two parts, both of which are themselves made out of RNA, not protein. These ribosomes clamp onto the cap of the mRNA, one part on one side, the other on the opposite side, the mRNA in the middle. The cap is a special starter molecule and the first part of the mRNA, which does not code for a polypeptide but controls how easily the Ribosome attaches to the mRNA. The attached ribosome will then “read” the mRNA, working down the string of letters and creating a polypeptide that is described by the RNA sequence.

Special intermediate molecules are used to translate the RNA to an amino acid. These are the tRNA molecules shown in the diagram below. As a ribosome walks along the mRNA is reads small chunks of the mRNA, finds a tRNA that complements the mRNA and temporarily binds it to the mRNA. At the other end of the tRNA is a specific amino acid and this bonds to the growing polypeptide/protein.

Ribosome translating mRNA – from sites.google.com

Many ribosomes can be walking along a single mRNA molecule  at a time, creating more than one copy of the polypeptide. When a Ribosome gets to the end of the mRNA, to the poly-a tail, it drops off (4) and it will (or at least may) snip off the very end of the poly-a tail. So it shortens the tail. This tail protects the mRNA molecule from being destroyed by the cell so, as it shortens then the mRNA becomes more likely to be destroyed. Why is this important? Well, the cell needs to produce different polypeptides at different concentrations at different times. The poly-a tail is a key part of how the cell controls how long an mRNA molecule last for, creating polypeptides. The longer the tail, the longer the mRNA lasts. The mRNA can’t be allowed to hang about in the cell producing polypeptide for ever. Once it’s tail is gone it is destroyed. Thus for a polypeptide to be constantly produced, the genes in the nucleus need to keep producing the mRNA for it.

As you can appreciate, changes to the 5′ cap can change how quickly (and often) a ribosome latches onto an mRNA molecule, the length of the poly-a tail can control how long the mRNA lasts and so how much polypeptide that one mRNA molecule creates, and the nucleus has overall control over when and how much mRNA is produced. These processes allow constant control and change to how a particular gene is expressed.

I’ve said about the RNA being read and converted into a polypeptide. How does this work? The diagram above and the tRNA give clues to this.

How Codons translate to amino acids

As I said earlier, there are four letters of the RNA alphabet – A,C,G, and U – and a polypeptide is like a sentence. There are 20 types of amino acids that are strung together to make our polypeptides. Our genes are written in sets of 3 letters, called codons. You can think of them as a gene “word”. You can see this with the tRNA molecules in the diagram, at one end they have three RNA letters, and the other end the specific amino acid that those three RNA letters translate to.

A codon, such as UCA, codes for an amino acid called serine (or Ser). GCU codes for alanine (Ala). With 4 letters and a “word” being 3 letters long, there are 64 combinations of A,C,G, & U possible. You can see all 64 of these combinations in the table to the left. So how do the 64 possible codons map to 20 amino acids? Well, some codons have a special meaning.

3 – UAA, UAG, & UGA – are stop codons. They mean “this polypeptide is finished, ribosome stop reading”. One codon is special, AUG. This either means “start reading here” (note, there have to be other sequences in the RNA near it to make it mean this) or amino acid methionine (Met).

As for the others, well several codons mean the same amino acid, as you can see in the table to the left (5). Generally the first two letter in the codon define which amino acid the codon is for (anything starting GU is for valine, Val) but for some the third letter is the deciding factor.

Ribosomes thus start at a special AUG codon on the mRNA and then read three letters at a time and for each one, for each codon, the specific amino acid is added to the growing chain – via the tRNA molecules. The chain can be thousands of amino acids long or just a handful. The chain grows until a stop codon is reached. The longest polypeptide is titin, which is between 27,000-35,000 amino acids long (due to those “introns” I mentioned, sometimes some are cut out, sometimes not) and makes muscle elastic.

That’s it. That is how our DNA, our genes, make all the things that build and control our bodies. Of course, there is an incredible amount of complexity that arises from that central process, like how do the proteins control the inclusion of calcium to make our bones, grab iron and put it in our blood, and stuff all that fat in our cells. But it is all controlled and mediated through polypeptides, through proteins and enzymes.

If you want to see a large version of the Central Dogma diagram you can click here:

->ci350poster-141201170705-conversion-gate02

 

mRNA vaccines.

I won’t go into too many details here, but you may know that a couple of the Covid-19 vaccines are mRNA based. These vaccines are millions of mRNA molecules packaged up into little balls of fat (also called lipid). These mRNA molecules are all the same and are the instructions to produce the spike protein of Covid-19, the bit the virus uses to attach our cells and that the immune system is good at identifying and attacks. This is the Moderna and Pfizer vaccines

The vaccines are ONLY for the spike protein, not the rest of the virus, so the vaccines cannot give you Covid-19. But what the mRNA does do is get into your cells and your cell ribosomes latch on to the mRNA and make the spike protein. The mRNA molecules is not exactly like the one produced by the virus, it is modified to be more stable and last in the cell longer, with for example a longer poly-A tail. The longer it last, the more spike protein is produced. The vaccine mRNA is engineered to produce as much spike protein as possible.

Your body sees this spike protein, it knows it is “foreign” to your body and learns to attack it. Then, if you are infected by the real virus, your body will already know to attack the spike protein and either you do not get ill or you get less ill. Fantastic, isn’t it? I love science and I especially love biology and medicine. Even just 50 years ago this virus would have had to run it’s natural course through us and kill maybe like Spanish ‘flu did, but now we understand so much better what is going on and we can now do something about it. I say “we”, I mean biomedical scientists.

Previous vaccines have relied on getting a modified or damaged version of the whole virus into your body, or modifying another virus that is harmless so that it produces mRNA for exact copies of parts of the dangerous virus. These are hard things to do. The Oxford vaccine is a modified virus (a chimpanzee adenovirus, chosen I believe because it can infect us but does no harm and does not spread in humans).

Advances in handling mRNA, creating it, and understanding how to make it work in our cells, have allowed scientists to create mRNA vaccines which are simpler, more efficient, easy to create or modify , and more targeted than traditional vaccines. Only part of the virus is made and nothing else, so there is no danger whatsoever of the vaccine causing the disease, or a modified version of the disease. Further, if the virus alters (something that is a current worry) then modifying an mRNA vaccine is theoretically very easy and quick. Testing the new version would be necessary and would take months (regulatory bodies allowing – they might let a modified version be fast-tracked, my wife is an expert in pharmacovigilance and she thinks it could be done) , but it means mutations to SARS-CoV-2 can be handled relatively quickly if the need arises. This could be vitally important.

This work has not all been done since Covid-19 appeared about a year ago, it is based on several years of work on MERS, SARS and other viruses. So on the one hand these mRNA vaccines are a new technology, but they are new since 4 or 5 years ago and great advances in how to create them have been made in the last year.

 

Implications of the Central Dogma

Some things follow on from the above that are fundamental to SARS-CoV-2 and vaccines. I’ll touch on them here and expand on them in further posts, as this is a lot in one go.

Mutations and Open Reading Frame

In my previous post on the new variant of SARS-CoV-2 I mention mutations. At the start of this post I mentioned the copying of DNA/RNA and how mistakes can be made, in particular a single letter changing to another. When a single letter of the genome gets changed, this is called a Single Nucleotide Polymorphism or SNP. If that letter is the first one in a codon in a gene, it is almost certainly going to have an impact. It will change the amino acid inserted at that point in the polypeptide. If you look at the codon table earlier it is possible to change the first letter A to C and still get Arginine. Other than that, altering that first letter in the codon alters the polypeptide. Other SNPs can have no effect – changing GUU to GUC still makes valine. Of course, any SNP that creates a stop codon is going to have a potentially massive effect.

SNPs that cause no change to the polypeptide are called synonymous. As they make no difference to the organism, they occur and get passed to the next generation of the organism and all their offspring. We can use these synonymous SNPs to track the lineage of organisms and they are used to track the lineage of SARS-CoV-2. This allows us to, for example, track how the virus has spread geographically. I say us, I mean phylogenetic scientists.

Those SNPs that change the polypeptide sequence are more likely to change something about the biology of the organism. If the change is negative (for example it reduces the efficiency of an enzyme) the organism and it’s descendants will be at a disadvantage and the change will be selected out. If it gives the organism an advantage, it and it’s descendants will do better than those without the change and will take over in the population. This is true of the new variant B.1.1.7 – is better at spreading, it is taking over. Many SNPs that change one amino acid have very little positive or negative effect on the virus. (I don’t know what it is like on modern genetics degree courses but in my day lecturers would almost come to blows over how much effect a single mutation would need to have to be significant, and how much evolution of DNA was just mathematical, accidental drift, and how much was through selection pressure.)

Other, rarer mutations can be deletions and insertions. Extra letters get added or removed. Now, if the number of letters added/removed is 1, 2, 4, 5 or any number that is not divisible by 3, the impact is huge. Why? Well, a gene has something called it’s Open Reading Frame. Codons are always 3 letter long, staring at the ALU that initiates the mRNA being read. That reading frame of 3 letters per word has to be preserved through the whole gene. If you shift all the letters along by anything other than a multiple of 3, everything after that change becomes very different – and usually garbage.

An insertion or deletion of a non-multiple of 3 letters will not be significant if it occurs in DNA/RNA that does not code for something, but if it is in a gene it is 99.9837% (2) of the time a disaster for that gene, destroying the function of that polypeptide it producers. SARS-Cov-2 is an RNA virus and such viruses are almost all functional gene. Thus deletions or insertions that do not preserve the reading frame are rare (but do occur) in SARS-Cov-2 and other viruses.

Variant B.1.1.7 has 3 deletion mutations in it but they all preserve the reading frame. They drop 1,2, or 3 amino acids out of the polypeptides they code for. But the rest of the polypeptide is preserved. One particular deletion, in the spike protein removing amino acids 69 and 70, stops one of the standard PCR tests from detecting RNA fragments of SARS-CoV-2. I’ll revisit this topic in another post, but because it stops one of the standard PCR tests from working, that can be used in many situations for tracking this variant. Don’t worry, PCR tests for SARS-CoV-2 use 2 or 3 RNA sites to identify the virus, so it is still detected. However, the failure of one of the “channels” has turned out to be a boon for tracking this nasty variant.

Single Direction Of Information.

Under the central dogma you will see that information flows from DNA in the cell nucleus, to mRNA that leaves the nucleus and goes into the cell cytoplasm, and this is translated into polypeptides. It does not go the other way.

Nothing I know of in biology can take a polypeptide, let alone a mature protein, and generate RNA from it. Nothing. Humans can make a stab at it, we can look at the amino acid sequence of a protein and design an mRNA strand that might sort-of work but it’s hellishly difficult as organisms like terrestrial plants and vertebrates have complex post-processing of many polypeptides. Biology cannot do it.

There is nothing that takes mRNA and pulls it back into the cell nucleus and shoves it into our DNA. Nothing natural can do this that I am aware of. A couple of people on a social media forum full of biology experts that I mentioned this post on have voiced possibilities, but nothing concrete yet has been forthcoming (and it would be fascinating to learn about if they do, I’m always looking to learn).

Some of you may have heard of retroviruses such as HIV (the virus that causes AIDS). They can do something that sounds similar – but it is not. They can reverse transcribe their own RNA, i.e. create a DNA copy of their RNA using a reverse transcriptase enzyme, and insert it into the host DNA using an integrase enzyme. The retrovirus has the RNA genes for these two proteins in it’s genome, it brings it’s tools with it. They get into the nucleus of the host cell and use their own tools to insert their own genome into the host, along with control DNA so that the viral DNA can be expressed. What it does NOT do (as far as I know and this is possible where I am wrong) is grab random mRNA from around it and insert it into the DNA of the host. Remember, mRNA is exported out of the nucleus. It’s not there in the nucleus, at least not for long. Also, even if a retrovirus was to insert mRNA into the host’s DNA, it would be doing so without promoter sequences and all the stuff needed to get a gene to be expressed.

I make this point as some people on social media have claimed the mRNA in Covid-19 vaccines could get into your DNA. No, it can’t. It won’t. Anyone claiming this does happen does not understand the central dogma of molecular biology. Either that or they could be in line for a Nobel Prize in biology.

Firstly, the vaccine does not get into the nucleus. Second, there is no biological process native to vertebrates to do the insertion of mRNA into DNA. Third, even if by some chance a virus like HIV was present, and by some miracle some of that mRNA for the vaccine got into the nucleus, HIV is inserting a copy it’s own DNA, not random mRNA hanging around. Finally, even if a miracle on a miracle occurred and the mRNA from the vaccine was inserted into your DNA – there would be nothing to cause it to be expressed. It would just sit there doing absolutely nothing.

What Retroviruses can do is insert into a DNA genome, then when it is expressed it can occasionally pick up DNA from around where it inserted into the genome, which is transcribed and included into the RNA for the virus. If this modified virus then infects another organism and takes that original host DNA (as an RNA copy) with it, it can then insert that picked-up DNA into the new host. It’s very rare, it can happen. But no reverse reading of mRNA was involved.

Basically, the idea of mRNA from a vaccine getting into your genome is damned close to impossible given the current understanding of molecular biology.

Viruses

I’ll finish with some information on viruses.

Viruses are weird. There is an ongoing debate (and has been for over 35 years, as it was a topic of discussion during my degree) whether viruses are alive. Viruses can’t do anything without a cell and it’s machinery to make proteins from DNA/RNA. They can’t move themselves, they get moved about by mechanical processes (in droplets of liquid, floating in water, blown around in the air, transferred via fluids in real living things…). They don’t grow, they do not respond to stimuli (all other life from bacteria up do). They do nothing. A virus consists of just a few things:

  • A string of genetic material, either double stranded DNA similar to what is in us, single stranded DNA or RNA (usually single stranded but occasionally double stranded). SARS-CoV-2 is a single stranded RNA virus.
  • A protein coat, called a capsid, encapsulating the genetic material, keeping it protected and whole. This might be a simple, uniform coat or something more complex made of many proteins. SARS-CoV-2 has a capsid made of several proteins including the famous “spike” protein, which sticks out of the capsid and is what latches onto the ACE2 proteins on our cell walls and allows the virus to get into the host cell.
  • Protein(s) within the capsid, binding to and protecting the genetic material. SARS-CoV-2 has this.
  • A virus may have an outer lipid (fat) layer, usually derived from the lipid layer of the host cell it infected. SARS-CoV-2 does not have this.

I think of viruses as very, very complex poisons and not alive. Others think of it as alive.

If you want to know more about the structure of SARS-CoV-2 this paper on the structure of the virus on the NCBI site is very good but quite technical.

The genetic material for a standard virus (like SARS-Cov-2) codes for a load or mRNAs that usurp the polypeptide making machinery of the host cells. i.e., they use the second half of the central dogma. Once the virus gets into a host cell, the mRNA is released and it hijacks our own cell’s ribosomes. It makes new proteins to make the virus shell and proteins to coat the RNA of the virus. It creates an RNA Polymerase enzyme to replicate it’s own genetic code and, in the case of coronaviruses like SARS-CoV-2 (and other types of virus) it produces a “checking enzyme” to make sure the RNA copies accurately.

This last point is very interesting. All organisms mutate but RNA viruses are the fastest mutating thing we know of. But SARS-CoV-2 mutates slowly for an RNA virus as it has a check enzyme. That’s one thing to be very thankful for. Influenza is an RNA virus that does not have a checking enzyme, which is part of why it changes so quickly and we need a new vaccine for it each year.

All these bits of the virus then self-assemble into thousands of new copies of the virus, burst the host cell and go and infect other cells in the organism. Some are ejected from the host organism in droplets coughed out or similar mechanical processes and infect other hosts.

That’s pretty much all that a virus does.

Notes

1) I said all our DNA is in the nucleus and controls everything. This is not quite true and I am sure some of you know that. We also have DNA in our mitochondria, the organelles in our cells providing us with energy at a biochemical level. Mitochondria look a little like bacterial cells living within our cells and some scientists think this is where they originally came from. It is suggested that a very early Eukaryotic cell absorbed and made a symbiotic relationship with a bacterial cell that was very good at making ATP (the unit of energy in most biology). This was so successful that the organism that did that out-competed all other Eukaryotic life and took over. And, over time the absorbed bacteria became simplified and specialised as the mitochondria. As a result, mitochondria have their own DNA. As do chloroplasts in plants.

2) There is really only one hard, absolute rule in biology. There is an exception to every absolute rule. See 1! Forgive me if I don’t cover all the exceptions in the rest of this post, but what I sat here is true 99.9837% of the time. And treat all percentages in documents with scepticism, many are made up.

3) The distinction between amino acids and peptides has always annoyed me. If “Amino acid” is the term for the building blocks of proteins should not a chain of amino acids be a “polyamino” or something? No, we have peptides/polypeptides.  A peptide has to be 2 or more amino acids as it is named after the bond between the two amino acids. A Peptide bond. Strictly speaking a peptide of between 2 and 20 amino acids is called an oligopeptide, and above that is a polypeptide. It’s just messy.

4) The ribosome may not drop off the mRNA. If the poly-A tail and the mRNA cap are intact, they my bind together to form a loop that allows most of the ribosomes to simply circle around the whole mRNA and make more polypeptide more efficiently. This might help curtail the activity of the mRNA more quickly as, when the poly-A tail or the cap are degraded (as there is some mechanism to degrade the cap too), then the loop is broken and Ribosomes can no longer cycle around. I don’t know the details.

5) The codon to amino acid mapping is very nearly universal. Almost all organism use the same mapping and it is one of the proofs that all life on this planet is related. However, there are some exceptions (as there always are in biology). If you want to nerd out on it look at this Wikipedia page on alternative codon translation tables.

6) The basics of the central dogma of molecular biology has been known for over 50 years. Here’s the start of the chapter on it from my 33 year old  “Genes 3” by Benjamin Lewin. Looking back at this book, which I pretty much knew cover to cover back then, I realise how much knowledge has leaked out my head.

This is the central dogma in my genetics undergraduate text book from 1988

 

Covid-19: The New Variant and the NHS December 29, 2020

Posted by mwidlake in COVID-19, ethics, rant, science.
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<<- Long term hopeful, short term worried

As I said in my blog post a couple of days ago, I’m very concerned about the new variant of SARS-CoV-2 that has been spreading through the UK and is now being found in countries all over the world. My main concern is that this could be what pushes our health services beyond the limit of what they can stretch to and, as a result deaths will jump up – and not just from Covid-19.

New Variant Impact

In my last post I highlighted the new variant of SARS-CoV-2 that is more infections (spreads more easily), but said that there was little evidence that it was any more fatal. Understanding what was going on was hampered at that point as we had hit the festive period and, with the best will in the world, everyone needs a break at some point. New data on hospital admissions, virus sequencing, case numbers were all missing or affected. Scientists studying aspects of Covid-19 were reminding themselves what their partners, kids, and pets looked like after what must have been a heavy year. Now the new information is coming out, as is the analysis by relevant experts.

There is a paper detailing this new variant by Public Health England which was published on 28/12/20. Much of the below is derived from that, but is backed up from many tweets and bits of evidence from the scientific community.

This new variant is know by a few names:

  • VOC 202012/01 – Variant of Concern identified in 2020 month 12, number 1
  • B.1.1.7 – the phylogenetic name of the variant (I think!)
  • 20B/501Y.V1 or simply 501Y.V1 – the identifier given by Nextstrain

B.1.1.7 has many mutations from the original SAR-CoV-2 virus (this STAT article states 17 mutations, the tracking page I mention below lists 17 SNP mutations, this overview by the CDC on VOC 201212/01 lists 20 SNPs and 3 deletions and seems to be the best source of information on this. I’ll explain all the mutations better in a later post) . Mutation is not unusual, viruses change all the time. Each time a virus is copied (and that is how viruses like coronaviruses reproduce, there is no sex, they are identical clones of their only parent) the RNA is copied and occasional mistakes are made and thus changes, mutations, happen. The most common change is a Single Nucleotide Polymorphism, or SNP. One letter of the 30,000 in the viral genome changes.

A single SNP change to the SARS-CoV-2 RNA does not seem to be enough to change the virus into a significantly more infective version (or more lethal, or more likely to infect children, or change it’s behaviour in a way to make it more dangerous). If it did, we would have seen this already – the virus has been so successful in spreading in humans and thus reproducing and so those SNPS occurring, that most individual SNP mutations that are possible will have happened by now (there is evidence for minor change by them though, but that’s for another time). It is going to be a combination of two or more changes I think that has altered the transmissibility.

B.1.1.7 has several changes to the gene that creates the spike protein.

The paper from Public Health England I reference reviews the data that was initially presented to the UK government (on around the 19th December I presume) and resulted in their initial analysis of the 21st, which this paper links to.  This review considers the degree to which the new strain transmits more easily and possible reasons why. It can  be summed up as saying:

  • This new variant is indeed spreading faster.
  • it is becoming the most dominant strain in all the areas it is in.
  • It’s ability to spread to others (secondary attack rate) is increased by about 55%.
  • It is not spreading faster as it is more successful in re-infecting people who have already had Covid-19.
  • There is no evidence it results in more hospital stays or is more fatal.

I’m not sure the evidence is yet firm that this new variant does not also increase the severity of the illness a little as there are too few cases to go on, but it does not like there can be a huge increase. Usual caveat, I’m no epidemiologist.

I’ve also looked at a paper by Nick Davies’ team at the London School of Hygiene and Tropical Medicine.

They considered 4 possible methods by which the new variant (they use the VOC202012/01 name) could be causing the rapid spread of the new variant

  • A) Increased Transmissibility
  • B) avoids current immunity
  • C) Children being more susceptible
  • D) shorter viral generation time

As you can see from the graphs, the model based on (A) Increased Transmissibility fitted the date better than anything else.

You may be aware of the new variant in South Africa that is also more transmissible. This is not the same as B.1.1.7, for example, it does not have the 69/70 deletion mentioned in Public Health England paper that is used as a proxy to identify B.1.1.7 in the UK population (again, more information later on the details of the new mutation). So this deletion either is not key to the increased transmission or else there are two methods by which the transmissibility can be increased (now, that’s a worrying thought).

There has been a lot of other analysis and commentary from the scientific community to back up the hypothesis that B.1.1.7 spreads 50%-55% faster.

Why Is 50% Faster Spread So Significant?

Why is this significant? Wouldn’t 50% more lethal be more of a worry?

No. The reason an epidemic is so scary and has such an impact is down to exponential growth. To use an extreme example such as exists before a new disease is recognised and steps taken to control it, If 1 person infects 2 people who infect 4, 8,16,32… Ten duplications later and you are at 1,024 infected people. If each person infects 3 then it goes 1 person, 3, 9,27, 81…ten tripling’s is 59,049. If you know how many people each infected person will infect (the R number) and how long it takes for an exposed person to themselves become infectious, then you can calculate how quickly the disease will spread and grow. So the transmissibility is key.

Adam Kucharski put it better than I can (if you are on twitter and you are interested in Covid-19 science, if you are not already following Adam then I highly recommend you do, and then follow some of the people he follows). This is how he explained it:

Here in the UK the number of cases and, more importantly, hospital admissions have been shooting up. You cannot compare case from the spring to now as testing now is orders of magnitude improved compared to the shambles back in April. But hospital beds occupied is a very powerful metric and can be compared. Up to a point.

I showed a graph in my last post about how many people are ill in hospital with Covid-19, going up to 24th December. The below is the graph up until the 28th December. We still don’t have data for Wales, Northern Ireland, and Scotland beyond the 22nd December – but England on it’s own ( 20,426) is not far off matching the UK peak of 21,683 back on 12th April. If we optimistically only add on 1,727 for Wales, 1,045 for Scotland, and 451 for Northern Ireland (their figures for the 22nd) we are at 23,649. I’m seeing a lot of stuff on social media and the BBC news about hospitals running out of capacity, cancelling routine work, calling staff in from holiday (and remember, this is staff who have nearly all been pulling extra and double shifts for 9 months already). We suspect are approaching 100% hospital capacity for the NHS.

Patients in hospital with Covid-19 across the UK, 28/12/20

Update, 30/12/20 – we now have the Welsh & Northern Irish data to 28/12, Scotland & England to the 29th . The UK total for the 28/12 is 23,771 (slightly above my optimistic lower threshold of 23,649, as is to be expected. Northern Ireland shows a modest increase that could just be random variation, all three other nations show an increase.

Patients in hospital with Covid-19 across the UK, 29/12/20

 

 

 

100% Hospital Capacity is a Really, Really Bad Thing

I said that hospital beds occupied is a powerful metric up to a point. Why up to a point? At some point that metric stops increasing so fast or even at all – but not because of a lack of patients to treat, but because you are running out of capacity in your hospitals.

I’m sorry, I’m going to go on a bit of a rant here. The below is why I get so vexed at people saying “I need to go on holiday” or “I must have my nails painted” or decide it’s OK if they have a party or that we don’t need a lockdown.

If you get Covid-19 and are badly affected, you may well need supplemental oxygen. You may also need treating for various blood clotting conditions, or to stop your immune system over-reacting, and several other things. That can only be done in hospital. If it is done, most people treated survive (though some of course still sadly die). If you are not treated, you will die. As some of you know, I had personal experience of this late last year when influenza type A and pneumonia landed me in intensive care for a week, on very powerful CPAP ventilators. If I had not had that treatment, I would not be typing this (or anything). So we can (and do) treat and save many people with compromised breathing and the other things that come with Covid-19. Until we run out of trained hospital staff. It’s not beds per se that are the issue, or ventilators, or really any equipment. It is people who have the skills to run that equipment, monitor you, keep you ticking over and otherwise not-dead whilst supporting the broken parts of your body until they heal. Once the capacity of the health service is exceeded, they have to pick who dies. And of course, we do not just have Covid-19, hospitals are dealing with all the other sick patients we always have – car accidents, cancer, influenza, septicaemia, heart attacks…

I’ve seen the stuff by some people about how “only” 377 or so healthy, young people have died of Covid-19. Part of me can’t be bothered explaining to them why they are selfish, clueless idiots right now but what I can say is if we run out of hospital staff capacity, you can be as young and fit and bloody callous as you like but you will die if you need oxygen treatment and do not get it.

I’ve seen some tweets by people who say things like “well, just get more nurses and doctors”. I checked, they are not made in a factory. Training to be a nurse is not like going on a week-long course to learn to use a chainsaw. Doctors and nurses and radiologists and lab staff (and all the others people forget about who are vital to the NHS) are trained for many years. Being an ICU doctor or nurse is particularly technical and needs months or years of training ON TOP of being a standard doctor or nurse.

The UK was desperately short of all NHS clinical staff before Covid-19. One of my closest friends organises the lab rotas for a very large hospital and she never has enough people to fill the rotas. She has to beg and hassle people to do more than their fair share of weekend and night shifts. They constantly have not just one or two but a dozen or more open positions for staff. I’m not getting political here but there was a crisis in care long before the pandemic.

If you see figures saying ICU capacity is at 90% you would probably naturally think “well, they still have 10% spare, it’s fine”. It’s not. One of my first jobs was writing bed management software for hospital systems and teaching hospital staff how to use the software. The software was a god-send for them. A hospital bed is not just a bed. It’s a type of bed, and there are several types in hospitals. Some are for children, most are for adults, some are powered to help move the patient about, some are specialist for ICU (such as being able to pass air around incapacitated patients to reduce bed sores)… And beds move. For my spell in ICU I was initially admitted to A&E and held in a storage room as there was no spare capacity. They brought a suitable bed to me and squeezed it into the storage room. About 12 hours later, 6 or 7 nurses took the bed with me and a shit load of equipment through the hospital to the ward.

You have to know who is in which bed, the consultant & specialty treating them. For very, very good reasons, the specialist or someone in their group needs to approve a lot of what is done to you in a hospital. To administer a drug to a patient you have to find the bed they are in and you have no time to go wandering around the ward as you have 101 other things to do. The same is true of feeding the patient. You have to track when a patient moves (either with their bed or moving from one bed to another) and you need to know where you can move them to, so you need to know what beds are spare or, more likely, probably going to come spare. I worked on another part of the hospital system, “notify patient as dead”. It was horribly complex, lots of stuff has to happen when a patient dies, for example some lab tests get cancelled, others get created. The bed is noted as empty pending a deep clean. Sometimes, heartless though it sounds, the staff need to know when a bed is likely to become available via that route.

The people in charge of beds need to know ASAP when a bed is free so they can try and do all the juggling above that I mentioned. The fewer spare beds they have the harder it gets to make use of the few spare ones you still have and move people around efficiently. Or even inefficiently.

When I moved out of ICU it was a rush job. Someone needed one of the very most critical ICU beds (yes, there are tiers to what we non-medics think of as ICU), they felt able to move another person into my intermediate dependency bed as they were improving – IF they could get me out of it and into the Respiratory Medicine ward. Which they did, at about midnight. The sticking point was I needed to be isolated to I could not give someone with COPD influenza and finish them off. Another complication. It being night there were fewer staff so only 2 people could be spared to move me. Admittedly, less equipment came with me but half of it (including a heavy oxygen cylinder) was on the bed with me, I had hold of something on wheels, the 2 nurses somehow corralled the bed and other equipment.

The point I am making is that the closer a hospital gets to 100% capacity, the harder all that juggling becomes, and you actually end up having to move patients to other hospitals – and moving a sick patient to a different hospital is generally not in the best interest of the moved patient – or discharge patients who could really benefit from being there longer (but don’t need it as much as the person who is dying that they can’t find a bed for).

I’ve only ranted about beds. I have no idea how they keep track of other equipment, plan who is allocated to do what, how to cover for say a member of staff going ill, a major road traffic accident when all ICU is full…

If we do not see some sort of miraculous downturn in hospital admissions (and all indicators are against this happening) I’m expecting the UK to be in full national lockdown in a week, kids returning to schools cancelled. If we hit 100% hospital capacity and are not in a strict lockdown, then our government will have failed us in this crisis once more.

Even more distressingly, we may see avoidable deaths.

 

 

Communicating on Covid-19 Again December 27, 2020

Posted by mwidlake in COVID-19.
Tags: ,
4 comments

New Variant & impact on NHS->>

<<- Start of Original Post beginning in March 

After quite a break, I’ve decided to return to converting my notes & thoughts on Covid-19 and SARS-CoV-2 into blog posts again, but I’m going to do so in a slightly different format. Why am I returning to blogging on the topic? Well, people do still keep asking me what is going on and I’ve mostly been answering on Twitter or Facebook (or in person on the rare occasions I meet people!), but I don’t feel Twitter and Facebook are particularly good forums for explaining things. And writing it down in a way I feel someone with a little bit of scientific understanding can understand helps me understand and, more importantly, makes me check the scientific output to try and make sure I am right.

As for the different format, I’m going to do shorter, less comprehensive posts. This is because when I did this last spring/early summer I would spend a week doing a post that I thought would take a day and, by the end of the week, some things were changing and the post was just too loooooong.  If you feel something is missing from my future posts or you have any question a post prompts, please ask. If I can I will try and answer, or at least point you in the direction of a scientist or similar expert saying something about it.

On the subject of expertise, as anyone who has followed my blog knows I am a computer person (I specialise in the performance of Oracle databases). As ever I am going to stress that I am not an epidemiologist, not a virologist, and I have no medical qualifications. I have never been a working scientist (closest I got was I did a summer as a volunteer in a genetics lab before my final year at university, I mutated moss). What I do do is look at the output of scientists who communicate on Covid-19. I only listen to scientific and medical output. I do look at what the UK government says but I don’t see their briefings as a reliable source. This is not due to conspiracy theory, it’s more that (a) the UK government does not have a good back history of actually ‘Following The Science’ as they keep claiming (b) their job is not to explain stuff, it’s to get the population to do what they want them to do and yet remain as popular as they can (c) when a minister or one of the experts on the public briefings do explain something, they have to keep it simple and short.   

Given I am not an expert, why do I think I can explain to you what is going on? Well, I have an ancient degree in genetics & zoology and I’ve maintained an interest in science all my adult life. I’ve worked (developing computer systems) in or alongside the UK NHS for 7 years, in biological academia (mostly ‘the human genome project’) for 7 years, so I have a lot of experience in communicating with medics and scientists. For the last 15 years I have presented at conferences (and I get good speaker scores), written articles, done the odd webinar, and produced this blog. So I have experience of communicating what I do know to an audience.

If you want a refresher on Covid-19 (what it is, what it does to you) there are endless resources out there, but This summary I wrote back in March is still mostly relevant and it is interesting to see the predictions I made and which were right and wrong. Spoiler, I’m pretty good at saying how things will go for a few weeks (as are millions of others), I’m not so good beyond that, so I’m leaving that to the epidemiologists!

I’m hoping to put out my first real posts on the current situation on Covid-19 in the UK over the next couple of days, but I wanted to mention what is really concerning me and what helped prompt me to dig back into the scientific details again.

Long term – I’m really hopeful.

One thing I was wrong about was how long it would take to create a vaccine that was safe and gave good protection. I’ve never been happier to be wrong!

It’s a testament to the long hours and days of work of thousands of scientists, the worldwide sharing of information between scientific groups, the funding made available to them by governments & charitable bodies, and the efforts of the regulators & pharmacovigilance experts working to ensure Due Diligence in compressed timescales – i.e. that the vaccines are proven safe.

We have three vaccines in the West that are approved or close to being approved over a growing number of countries – 

  • BioNTech/Pfizer and Moderna/NIAID that use the new mRNA-based methodology. They need to be kept very cold (minus 70C and minus 20C respectively) but are approximately 95% effective,
  • The Oxford University/AstraZeneca vaccine which is a more traditional vaccine that uses a modified, harmless adenovirus and is less effective (work still being done on how effective: 60-90%?) but does not need to be frozen and so is much, much easier to transport.

Many more vaccines are still in development. Having a set of vaccines will be a real boon as, for example, the Oxford/AZ one will be a lot easier to administer in warm countries lacking in ultracold-chain facilities, but where such infrastructure is present, we can use the more effective vaccines.

Gary Myers corrected  my information on how cold the two mRNA vaccines need to be kept and pointed me to this article by NPR

Nine months ago I would have been overjoyed for a single vaccine that was 75% effective by the summer of 2021, so to have three by the end of the year and more on the way is fantastic.

But it is a massive logistical effort to roll these vaccines out and the impact on the spread of Covid-19 and our lives will evolve over the next 12 months. For the whole globe we are looking at 2 years probably and I am sure there will be bumps along the way, such as one of the vaccines proving to be not very long lasting so re-vaccination is needed for some.

One thing I want to point out is that there have been over 1/2 a million 5 million people inoculated (wow, that’s shot up so quickly) to date with very, very few contraindications (things going wrong) reported. I am not aware of any life-threatening reactions to the vaccines to date but they protect the vast majority of people from a life-threatening disease.

You can track world numbers for vaccinations at this “ourworldindata” site. I have not looked at it much myself yet but it certainly seems to give you the key information.  

Short term – I am very worried

I was already concerned that world figures for cases & deaths continue to rise, the figures in the UK are constantly going up, and yet more and more people seem to be wanting to believe there is no problem. And now we have new variants of Covid-19 that spread more easily, both in the  UK and across the globe.

In summary, as some of you will be aware, we have a new, more contagious, variant of SARS-CoV-2 in the UK, which is most prevalent in the South of England. It appears to spread a lot more efficiently than other versions and it has worried the scientific community. For once, the UK government actually responded very quickly to this change and they “cancelled Christmas”, put the South East and London effectively into lockdown and soon after announced many other areas would go into the new Tier 4 the day after Christmas. (To be clear, many scientists had already called for the proposed relaxation of social distancing for 5 days over Christmas to be abandoned and replaced with tighter controls, based only on the growing case figures – which Boris Johnson and his cabinet seemed set to ignore).

With the new information about the new, more virulent variant of SARS-CoV-2, many countries have stopped flights to/from the UK or brought in stricter checks and/or rules on isolating people arriving from the UK. France closed their border with the UK preventing (amongst other things) any lorry freight (as people drive the lorries). This island became pretty much isolated (and people started worrying about getting fresh salad, which tells you a lot about some people’s priorities).

Cases of C-19 in UK Regions since August

It seems some people think these national and international restrictions were brought in simply because the number of cases of Covid-19 in the UK were escalating quickly, but it was this new variant that has mostly worried other countries.

The graph is from an excellent twitter thread by Christina Pagel, based on official UK government figures. It shows how the last UK lockdown had the intended effect of suppressing Covid-19 in most areas, reducing the number of people affected by the disease (unlike the regional tier approach which had struggled to really reduce transmission). However, look at the black East of England, orange London and green South East lines. The lockdown had less effect there and by the end of lockdown cases were rising in these areas. Why? It could have been more testing being done (so you see more cases) or people ignoring the rules, or something else. It turns out it was something else, this new variant. Correlation is not causation, but the percentage of people with the new variant of SARS-CoV-2 is much, much higher in these areas. Lap tests have shown the new variant latches onto ACE2 proteins, it’s door into our cells, more efficiently.

At the moment there is no evidence that this new variant is any more deadly or makes people sicker, or that it means the vaccines that are currently being rolled out will not work against it, but time and more study will tell.

C-19 patients in English hospital 14/12. It will increase.

So why is this new variant a worry? Because if this new variant is spreading more easily (and the figure quoted by the media is “70% faster” but I’ll dig into that in a later post) it means the number of people who are ill will double much more quickly – and we are in real danger of flooding the NHS with ill people. All along, since this new disease reared its head, the overwhelming of healthcare systems has been the main worry, much more than the actual raw number of people it will kill and harm. That is what all that talk about flattening the curve was about in March & April, spread the people getting sick over a longer period so at no point do you run out of hospital capacity. The more infectious version of Covid-19 is pushing up the curve, and threatens to do so very significantly.

The graph to the left is for hospital beds occupied by Covid-19 patients as of Christmas Eve – the latest day we have figures for as I type. They are only just below the April high. In Wales, for which we only have figures up to the 22nd December, bed occupancy greatly exceeds the spring high. I am sure that if we have not already exceeded the previous national high for hospital bed occupancy UK-wide then we will in a very few days and it will get worse, as people catching the disease over the last week or two get admitted. Cases precede hospital admissions precede number of deaths.

The new variant is most common in the South East, East and London areas of the UK, but it is present across the whole of the UK. (In Wales there appears to be slightly different more-contagious version of SARS-CoV-2 but again for a later post.)

Here in the UK we are in for a rough ride and the government is going to have to bring in more restrictions to try and keep this new variant under control. 

New Variant across the world

What about across the world? Well this new variant is already present in many countries. It might have originated in the UK, it might not, this is still being investigated. The reason we do not know for sure is that the UK sequences a lot more SARS-CoV-2 samples than other countries, so they might not have spotted what we did. Again, I plan to expand on this in a later post.

The new varient, B.1.1.7, has been seen now in France, Netherlands, Singapore, Italy, Israel, Denmark, Australia. The list will grow daily.

I’m afraid the genie is out the bottle and, much as we saw with the original spread of Covid-19, with international travel and it having got out before we could close borders on it, it is probably inevitable that this new variant will take over in all countries where SAR-CoV-2 is spreading.

In South Africa there is yet another more virulent strain, with some of the same mutations the new UK strain has, which seems to have arisen independently. I have no idea why more than one highly virulent strain has occurred in relatively close temporal proximity (same time) in different locations, it is probably just bad luck. Genetic mutation is random and directionless (well, with a few odd exceptions that as far as I know do not apply here). This other new strain is known as B.1.351

Both variants can be tracked at this site, which is where the image to the left is from. Updates are a little slow at the moment due to the time of year but, even with it being Chistmas, the people behind the site have added more information. Scientists, nothing stops them for long.

I think we are at a crucial point:

  • Vaccines are on their way and that is brilliant.
  • World wide we were already struggling to keep the Covid-19 situation from getting worse.
  • The new variant(s) are increasing the spread rate, possibly significantly.

Despite my reputation for it this year, I don’t like being all doom & gloom, but I feel right now like I did at the end of February/start of March. Very anxious about how this is going to play out for so many people, especially those who (for whatever reason) have decided Covid-19 is being blown out of all proportion or is not going to impact them.

I cancelled Christmas before the government did, it was not wise to go see my mother and brother, even though we all keep ourselves fairly isolated and take all the proper precautions. I think no matter what, for the next 6 months until the vaccines are making more of a difference (and by this I mean reducing the stress on the NHS by protecting those most likely to get critically ill, as opposed to herd immunity), I’m going to be a hermit, read books, sort out the garden, and keep watching what the scientists say.

I think Christina Pagel summed it up perfectly:

Sourdough – Creating The “Starter” December 18, 2020

Posted by mwidlake in Baking, off-topic, Private Life.
Tags: ,
1 comment so far

A couple of people have asked me to describe how I create the Sourdough bread that I often tweet about baking. It’s too much for a Facebook post, and waaaay too much for a twitter thread, so I’m putting it here on my blog. This is part one – you need something called a “Sourdough Starter” to make sourdough bread, this is how I create my starter. Part two will describe making an actual loaf of sourdough.

Nothing much beats a sandwich made with home made sourdough

I know this is seriously off-topic for a blog that is supposed to mostly considers Oracle tech & performance, working in Oracle/I.T, and thoughts on IT management & how people work, but let’s face it – the more semi-retired I get the more this blog is becoming somewhere I simply share “stuff”. However, there is a bit of a link. Over the last few years baking bread has been taken up by a surprising number of people in the Oracle Presenting sphere (and this pre-dates the craze for making your own bread that came with Covid-19). One presenter, Jože Senegačnik, even wins national awards for his bread in Slovenia.

What is Sourdough?

Sourdough is a rustic type of bread, usually white, with a dark, thick crust and usually more flavour than a standard loaf of white bread. I know I am biased, but the sourdough bread I make is about the nicest bread I have ever eaten (with perhaps the exception of the bread of some of my other baking friends). It is certainly nicer than your average loaf and better than “normal” bread I have made at home.

Sourdough bread has an open texture (lots of holes), so it is quite light and, at the centre, soft. Sometimes the bread has large voids in it. If you buy sourdough in a shop or it is part of a meal in a cafe/restaurant (it’s almost always the bread used in posh cafes with your smashed avocado and free range egg for breakfast) it seems to me that the posher the place, the larger the voids. Sometimes a slice of sourdough toast can be more void than bread. It does not need the large voids and, in my opinion, they are detrimental to the bread. You can’t make a sandwich or put anything on the bread without the contents falling through the big holes! It’s fine with soup & stews I suppose, where you are dipping chunks in liquid.

Sourdough is a type of wheat-based bread where instead of using dried yeast or fresh yeast that comes in blocks that look like soft cheese, you use an active, growing “porridge” of yeast. This is a fairly thick mixture of strong bread flour and water, with the yeast growing in it, slowly consuming the flour to produce more yeast.

big voids to lose your topping through…

This “porridge” is called the Starter, and you add it to a mixture of more bread flour, water, and a little salt, to make your bread dough for baking. The starter smells quite strongly, distinctly sour, and I suspect (but am not sure) that sourdough bread is named more for the smell of the starter than the final loaf, which only has a hint of the smell if any at all.

The bread itself also has a distinctive tang to it, not as marked as the smell of the starter mixture, but it is a key part of the flavour.

The crust is an important part of a sourdough loaf. It tends to be thicker, stronger, and (when fresh), well… crustier than normal bread.

The key to it all is the starter, so how do you create and keep your starter?

 

 

The Jar

You need a sealable jar to hold your starter. I use a Kilner jar, as pictured, but a very large jam jar will probably be fine. The jar needs to be able to hold well over a pint/half litre. My jar can hold a litre, which is large enough to generate enough sourdough starter for a good sized loaf but not so large it won’t fit in my fridge (which is important).

Once you have your jar, make sure you have:

  • a packet of white strong bread flour.
  • either some grapes or apples or, if you can manage it, some starter from a friend.
  • at least a week before you want an actual loaf of your own sourdough bread.

I would recommend you use white bread flour as brown or wholemeal (or even seeded) not only provides bits in your mixture where yeast cells would struggle to get to (so might make it more likely for your starter to get infected and “go off”) but as you add quite a bit of starter to the final dough, it’s always going to be partially wholemeal or brown if that is what your starter is based on, no matter what you want.

It has to be strong bread flour. Strong bread flour has a higher percentage of protein, gluten, in it. This is vital to support the texture of bread. Cake is lighter than bread and normal flour that you make cakes out of has less gluten in it.

Sterilise your jar before you use it. Either wash it in really hot water or, preferably, but it in an oven at about 120C for 20, 30 minutes. Let it cool to room temperature before you use it though. You want to sterilise it as the idea is to get a yeast colony growing in the jar that will out-compete bacteria and not-yeast fungi and keep the mixture clean and edible and not poisonous. To begin with there will not be a lot of yeast cells and any bacteria or fungus present could make the mixture bad before the yeast takes hold.

Making the starter

This just needs a little more mixing

Put about 300 grams of the strong white bread flour in the jar and add about 300ml of water, stirring it. you might want to add the water in two or three parts, mixing it well as you go but don’t stir it for minutes. You will hopefully end up with a smooth mixture that is a bit thicker than porridge/wallpaper paste/pesto. Now add a little more water until it *is* the consistency of porridge. Thin enough that it would pour, thickly, but thick enough so that a spoon stuck in it will probably stay in place. Don’t forget to take the spoon out…

Now the tricky bit. Getting the yeast in it. Don’t use baker’s yeast or brewer’s yeast or anything you would buy to make a normal loaf of bread, you want something slower growing and, if possible, local. In some places, at least in the UK, you might have enough yeast in the air to get it going, especially if you live in the countryside near orchards. Leave the jar with the lid open for a few hours and then shut it. A more reliable way to get the yeast is to take the skin off a couple of grapes, preferably ones you have had in the house a few days, or some peel (just a couple of stripes) from an apple, either a locally grown one or one that’s been hanging about in the fruit bowl a few days (but is not rotten!!!). The peel from fruits like this are covered in many yeasts. Use only the peel, not the pulp of the fruit. Chop the peel into little bits and throw it in the mixture and stir.

The yeasts on the skin will get it all going

If you are lucky enough to know someone who already makes sourdough who is local (in which case, why are you reading this?!? Go have a cup of tea with them or a glass of wine and get them to show you how to do all this – relevant covid-19 restrictions allowing of course) then get some off them, about 30ml will be more than enough. I got some from a local bakery a couple of years back who specialised in sourdough. You can even use dried out sourdough, as I did once. I’ll put the little story of that in another post.

The advantage of using some existing starter mix is that it gets going quicker and you an be pretty sure it will work. Getting your starter fully active from scratch using peel or the air can take weeks, a dollop of starter in it’s prime will get you a fully active new starter in days. I swap the jar I keep my starter in every few months, as they can get a bit gungy & crusty, I make the bread/water porridge and chuck in about 200ml of my existing mixture – usually what is left when I am making a loaf. I can use the “new” starter created in this way in a couple of days.

Shut the jar. If you were lucky enough to use existing starter, keep it out at cool room temperature if you are making a loaf in a day or two. Otherwise put it in the fridge.

If you really are starting from fresh, with peel, put the jar somewhere that is “cool room temperature”, that is about 16-18C, not near a radiator or source of heat, not somewhere cold. Hopefully, in a few days you will see little bubbles in the mixture. That means the yeast is growing and releasing carbon dioxide! After about 5 days, whether you see little bubbles or not, take out about a third of the mixture and discard, replace with the same volume of flour/water mix that you removed, give it all a good stir and seal the jar again. Do so again in another 5 days. If you do not see any bubbles by now, it has probably failed. Discard and start again.

A starter in it’s prime, a day after being fed

If the mixture develops any colour other than pale cream/oatmeal (so if it goes green or purple or pink or grey) you now have a jar of poison. Bacteria or fungus have won and out-competed the yeast. If there are spots of grey or other colour on the surface, or fluffy spots, again it is poison. Throw the contents away, sterilise the jar, try again.

Once you have a pale cream/maybe very slightly oatmeal coloured gloop that bubbles a bit you have your starter. Well done. You now have a new pet in your life.

Looking After The Starter

Once you have created the starter you have actually created a living colony – and you have to feed and care for it. If the yeast runs out of food it will go dormant and that opens the door to bacteria or moulds getting a foothold and growing. You have to keep the yeast active and reproducing. To do this you feed it.

Professional bakers who are making a lot of sourdough bread are constantly taking out part of the starter mixture and using it in the dough. An 800 gram loaf will use between 150 and 250 grams of starter depending on how they make the dough. This is replaced with the same volume of flour/water mixture they take out. You can do this yourself, if you are going to make a new loaf every few days you can keep the starter at room temperature and replace what you take out with flour/water mix. The yeast in the remaining starter quickly works through the added mix and new yeast cells grow.

If you are going to make a loaf once a week you can extend this process by putting the starter in the fridge. You take the starter out the fridge a day before you are going to use it. This is so it warms up and becomes more active. If you have space in the jar, you might want to add a bit of extra flour/water mix for the yeast’s breakfast (about 100 grams flour) when you take it out the fridge – I do. You take out about a third of the starter when you make the loaf the next day and replace it with flour/water mix. I leave my jar out for a few hours/overnight after this to let it get going and then you put it back in the fridge.

If you keep your starter for more than a week in the fridge, or 3 or 4 days at room temperature, without using it, you have to feed it. Take out a third of the mixture and discard, replace with water/flour mix that you stir into the starter. So long as you regularly feed the starter it will last pretty much forever, but of course you are simply throwing away flour all the time.

If you are a bad starter owner and you forget about it, it won’t be happy. A layer of fluid will separate out at the top of the mixture and it will go grey. Grey is bad. If this happens, if the fluid and only the very surface of the starter are a light grey, no fluff, you can pour off the fluid and the top third of the starter, feed it, and it might be OK. I’ve brought back starters from grey gloom a few times. However, the starter won’t make a good loaf again until you have fed it a couple of times. If the grey comes back straight away, you best put the poor thing down.

If your starter or anything in the jar goes pink, orange, purple, green, or fluffy, you have let the yeast get too weak and you have grown something new. It might be useful to a microbiologist, it could even contain a new antibiotic unknown to man, but it is far, far more likely to be poison. Throw it away, start again.

When you feed the starter, make sure there is space for it to expand. I keep my jar about half full. When I feed it, the contents expand with the CO2 and then subside. If the jar is too full, there is no space to expand. Also, I suspect my jar leaks every so slightly so no pressure builds up. If your jar is totally sealed you might have issues with it spraying out when you open it. Let me know if you do, photographs of the mess would be appreciated.

The more regularly you use the starter, the better will be the bread you make. When I’ve kept my starter out of the fridge for a week or two and either made a loaf or simply fed the starter every 3 or 4 days, it gets more active and the dough rises more readily when I make a loaf. If I leave the mixture in the fridge for a month, only occasionally feeding it, the first loaf I make from it struggles to rise.

Starters Vary

I’ve occasionally had two starters running at the same time. I once had my home-grown starter and also one seeded from some starter given to me by Jože. I’ve also had a starter that was initiated from a sample from a local baker’s, as I have said, and I’ve created a new starter from scratch when I already had one going. The bread made from different starters have slightly different tastes. And the one I got from Jože was more active than my home grown one. I have to say, I did not notice much difference between the two home grown starters I had. I am sure this is down to a difference in the actual yeasts in the mixture (or not, in the case of my two home-grown ones).

Hmmmmm…. Tasty

I discussed this with a fellow Oracle Presenter Baker and we decided it was highly likely that the actual yeasts in there not only vary with where the seed material came from but also how you keep it. If you keep it in the fridge, yeasts that are more tolerant of cold conditions will survive better, keep the starter at room temperature and those yeasts that reproduce faster in warmer conditions will take over.

Whatever, a loaf of sourdough bread you make from your own starter is a real treat. I’ll describe my baking process in the next post.

 

Friday Philosophy – My First Foray Into I.T November 13, 2020

Posted by mwidlake in ethics, Friday Philosophy, humour, Perceptions, Private Life.
Tags: , , , ,
1 comment so far

This is the first ever computer I used. The actual one. It is a Sinclair ZX Spectrum 48K. It was at the heart of a long, terrible family feud, the source of much angst, anger, and even fist fights. Blood was spilt over this machine. Literally!

Picture of a Spectrum home computer

The actual first computer I ever used

Anyone who lived in the UK in the early 1980’s and is currently about half a century old will recognise this box with the grey, rubber (sometimes called “dead flesh”) keyboard. It was the model that came out after the Sinclair ZX81, which is itself a classic of early computers, and sometimes the ZX Spectrum was called the ZX82. The Spectrum could put colour on the screen (up to 8 different colours at a time!), had a resolution of 256*192 pixels, the Z80A ran at 3.5MHz, and it could make a sound. A beep basically (from a wide variation from too few hertz to hear to too many hertz to hear, and of any duration – but it was still just a beep)

The Spectrum was initially a rival in the UK for the Commodore VIC 20, BBC Micro, Atari 400 and, later, the Commodore 64 (C64). They all had their advantages, the Spectrum’s was it was cheap! Even the more expensive 48K version (as opposed to the basic 16K) was cheaper than most rivals. It even tried to make out it was superior to it’s rivals as it was simpler and had fewer chips inside it. The Spectrum and the C64 were probably the most common home computers in the UK. They might not have been the best but they ended up having a huge number of games you could play on them, and that’s what counted.

The Spectrum was the first computer in the Widlake household. My dad agreed to buy it for my older brother Simon, who made a strong argument that it was an educational tool – and the early advertising material for the machine made a lot of it’s suitability as a such, with lots of worthy software for doing graphs and learning computer languages. About the only game available for it on release was chess. Dad was of the opinion Simon was the genius in the family – he was going to go to University! (At the time no one in the family had ever gone into higher education, only about 5% of people in the U.K. did then. As it turned out, all three of us kids went into higher education). So Dad felt it was worth spending the money, as he felt computers were going to become something. He wasn’t wrong.

But before Dad agreed to get Simon the Spectrum, he made Simon agree it was something the whole family was to have access to, he was to share it with myself and Steve, the eldest. Simon agreed.

Spectrum with games and tape recorder

The spectrum needed a tape record and a TV to be used

So the Spectrum arrived. Back then, home computers almost never came with everything needed to use them. The Spectrum, like several rival computers, needed a cassette tape record to save and load programs from tapes, and a TV on which to show the image. Simon had his own tape recorder and he was of the strong opinion that, except when Dad wanted to watch the news, he could use the family TV whenever he wanted, as he was a genius. He quickly lost the TV argument, the last thing our parents wanted was to lose the power of distraction that the TV provided for the other two kids. Steve did not watch a lot of TV but as he wanted nothing to do with the computer, it would have been really unfair on him.

But Simon had a back-up plan. I had a portable TV and Simon was older & bigger than me. So he took possession of my TV. I complained to the court of Mum & Dad but the Tyrant justified his acquisition of the resource on the grounds that he was going to have to share his Spectrum with me – so it was only fair?!? “Yes” I agreed, but only when I was not using MY TV for MY watching of what ever (probably crap) I was wanting to watch. The court came down on the side of the Tyrant, but with caveat of the plaintive. Tyrant could use the TV when Plaintive was not watching it. It turned out that the reality of the situation was that Simon was still bigger than me and to my considerable surprise “I didn’t want to watch anything” whenever Simon wanted to use his – err, sorry, “our” Spectrum.

The next blow to the plans of bigger brother was that it turned out his tape deck (the one in the picture) was crap. Most games would fail to load from it. But my tape recorder worked fine… So, yes, you guessed it, another possession of mine was now to be treated as his – sorry, “our” – possession, still on the basis of shared access to the Spectrum.

So Simon used my stuff as and when he wanted, but did he share?

Sinclair User Magazine

Well, sort of. Those of us of the correct vintage who got into early home computers would buy magazines like (in our case) “Your Spectrum” or “Sinclair User”. Inside there would be long code listings of programs. Simon “let me” read the text of the code out to him to help him type it in more easily. Or, if he was in a really good mood, he would let me type the code in on my own – whilst he was doing something else (like seeing his friends or picking on the cat). I was not allowed to play it until he got back. Yeah, like I paid any attention to THAT rule…

These games you typed in often had bugs in, especially if they had a lot of code. And, to give him his due, Simon was really good at finding and fixing the bugs. Once there was a flight simulator in the magazine, spread over a couple of issues. I think it later got developed further and become “Psion Flight Simulator”. But the version in the magazine did not work properly. Simon found and fixed the bugs and even got them published in a later copy of the magazine. It taught us both that software could be wrong and that it could be fixed. I did fix some of the games myself (sometimes Under Orders from the Tyrant, who was out setting light to papers in people’s front doors or something…)

But I was not allowed to play with the computer myself without permission, and certainly not if he was out. Apparently I was old enough to enter code for him unattended but not to load up “Meteor Alert” or “Ant Attack” and have fun. You’d think from this I was about 8 or 10, but I was actually about 14 and more than old enough to recognise hypocrisy and injustice. I would say that’s what older siblings are primarily for, to teach you about these philosophies. Not by saying “this is something you should not do, oh younger brother of mine” but by amply demonstrating for real what it feels like to be on the receiving end of such bullying treatment. But my oldest brother felt no need to deliver such life lessons, so I could be wrong.

Simon would let me play “with him”. This usually took the form of him playing the game and, once he lost, letting me play until I lost – and then we would swap again. Sounds fair? Not really, as a lot of the time he would be playing on his own and I was not invited. He would be using “our” TV and “our” tape recorder but it was still His computer and he was not letting me join in. So given my lack of practice and that I was younger and not so good at computer games as him, when he did let me join in his go would last 20 minutes and mine would last 2 minutes. Basically, he liked to be beating someone. I was better than him at a couple of games, one being “Attic Attack”, as I had learned the layout. We never played Attic Attack. Oh, he did play Attic Attack. He played it on his own, trying to get better…

I could beat the Tyrant at Attic Attack

After about a year things came to a head. Simon was never going to play fair, in his mind it really was his Spectrum and also now his TV and tape recorder. After all, as he kept telling me, his computer was the more expensive item. Only, it was less expensive than my contribution combined. I started playing on the Spectrum when he was not in, as far as I was concerned I’d put more into this pot that he had and I was not going to accept this shit. As you can guess, this did not go down well with him when he found out and the Tyrant did what all bullying, older brothers did and he physically asserted his authority. He’d hit me. I was not really pleased about that, so when he’d go out and I would absolutely play on it out of spite (and also to keep my edge in Attic Attack) – and it would repeat. One time he made my nose bleed – and it dripped on the computer. That was, of course, my fault…

It was now warfare. I banned him from using my equipment. Which he ignored of course. I went to the court of Mum & Dad, but not only was Simon “the genius” but he was, back in reality, a lying & manipulative sod and he made out he was sharing and I was being a spoilt child and I was told I had to share as he was (!!!!). So I took things into my own hands – and I started hiding the cables to my tape recorder and taking the plug off my TV. He tried to work around it, one day I came home from friends to find he had plugged the Spectrum into the family TV and he’d got hold of a spare power cable for the tape recorder and he was using it, despite me banning him from it. I went nuts. I demanded my stuff back and an apology or something or let me play too and he was having none of it. So I tried to take my tape recorded back and he tried to stop me, but I was so mad I got hold of it (I think I was finally getting strong enough to fight back a bit) and, shouting something like “and you used it to load that games, so I’m taking THAT as well!” I kicked the power plug out the Spectrum. Game gone, no tape player to load one up, games afternoon with his friends was over and there was nothing he could do about it. He went BERZERK, trying to wrench the tape drive back off me but I was so furious I held my own and I think I even kicked his computer again. He was straight off to Mum saying I was trying to break his computer. And this time, the Court of Mum & Dad finally realised Simon was being a little shit. He could not deny he had used my things, even though I had told him he could not, and he could not claim I started it or acted unfairly or attacked him first (his usual stance), as his mates backed me up. Yeah, his mates dobbed him in it!

This led to a full judicial review and this time the voice of the Plaintive was heard (after all, I had witnesses and I must have been pretty mad at him to be taking the plug off my TV!). Simon was told to play fairly or else… have his precious Spectrum removed.

Amstrad CPC 464

This was my Amstrad, I bought it, Simon was not using it.

After that, it got a bit more equal. I did get some time on the Spectrum myself (though I did sometimes have to get enforcement from the judiciary) and I did not just play games, I had typed in a lot of programs for Simon and fixed a few of them, so I slowly learnt how to program. I wrote a couple of my own simple games and put in stuff from magazines I wanted to try but Simon had no interest in.

But it never did really completely end. He could no longer stop me using the Spectrum. But if I was using it and Simon decided he wanted it, he would just bully me, or tell dad I was stopping him “learning” (I am not so sure what you learn from playing “Jet Set Willy”). That Spectrum came, for me, to represent what a selfish, lying, bullying, devious shit my older brother was. I swore one day it would be mine.

Then I got my own computer, an Amstrad CPC464, which I bought with my own money I earnt from months of back-breaking fruit-picking work (Simon was “too good” to do manual labour, so he had no money). It had not been bought by Mum and Dad, it was in no way a shared resource, it was totally mine. And guess what I said to him when he asked (well, demanded) to use it?

Yes, he could Fuck Right Off.

And I was now strong enough that it would be a more equal fight if he tried his old tricks (manual labour will do that for you), so he decided against that. He could keep his crappy Spectrum.

Well, the Spectrum is now mine. I picked it up from Mum’s house this week. Simon passed away many years ago, so it’s been sitting in a drawer for almost 2 decades. Well, being a Friday Philosophy I guess I should now tell you what the Spectrum now means to me, the healing process, what we can learn from this?

Well, I can.

Simon was always a bullying, nasty, selfish, self serving sod and he got no better as he got older. So there.

And the Spectrum is now *mine*!

But I don’t have a TV to plug it into and I know already – that tape drive won’t load games…

Friday Philosophy – Is The Problem The Small Things? August 7, 2020

Posted by mwidlake in ethics, Friday Philosophy, off-topic, rant, User Groups.
Tags: , ,
4 comments

Something has been bothering me for a while. In fact, I’d go as far as to say it’s been depressing me. It’s you. Well, many of you.

Well, it’s not MY problem!

What do I mean? Well I’ll give you an example. A week or so ago I went out in the car to get some shopping. A few minutes into the journey, as I go around a gentle bend, I see there is a car coming towards me – on my side of the road. I had to brake to give it space to get back over and I see it has swerved to avoid a branch in the road. As you can see in the picture, it’s not a huge branch, it covers less than one lane. I’m past it now so I go on to the shops and get my stuff.

30 minutes later I’m coming back. And I’m thinking to myself “I bet that branch is still there.” And it is. I can see it from maybe 300 meters back. The two cars in front of me barely slow down and they swerve past it. An oncoming vehicle that *I* can see coming, let alone the two cars in front of me, has to slow down for the swervers like I did. That slight bend means you get a much better warning of the obstacle from the side of the road it is on and as it is on your side, it’s really your responsibility so slow or even briefly stop, but the people in front of me just went for it. They did not care.

I did not swerve. I slowed down. And I put on my hazard lights, and stopped about 20 meters back from the branch. I double checked that no car has appeared behind me and I got out the car. In 20 seconds (including taking the snap), I’ve moved the branch off the road with no danger at all and I’m back to my car.

I know, you would have done the same.

Only no. No, you would not have.

Some of you would like to think you would have stopped and moved the obstacle.

I suspect most of you would claim, if asked, that you would have stopped and moved the branch.

And of course all of you would have slowed to avoid inconveniencing others.

But reality shows that nearly all of you would not.

As I left the scene, I was wondering how many people would have passed that branch in that 30 minutes I knew for sure this small branch had been an obstacle on the road. I’m going to let people going the other way off, as they would have to do a u-turn to come back to it, so how many people would have had to swerve past it?I know that road well, it would have been hmm, 4 or 5 cars a minute going past in one direction – certainly more than 3 cars, less than 10. So well over a hundred drivers would have seen that branch from a distance, most would have been able to safely slow and stop – and yet not one of them had. I have no idea how long the branch had been there, it was not too beaten up so maybe not long, but it could have been a couple of hours. It was easy to avoid – especially if you swerved with little concern for any on-coming traffic…

It turns out I’m the one in a hundred.

Are you thinking “well, it’s not my job to move branches of a road!”

So who’s job is it? And if you could label it as someone’s job (let’s go for someone in the “highways agency”) how do they get to know it needs doing? I don’t know about you but I see dozens of highways agency maintenance people on every journey I do, just cruising around looking for things that need doing. {sarcasm}.

When was the last time you saw something that needed doing in a public place and took the time to think about who should be told, try to contact them, get told to contact someone else, find out it’s not their job but are asked to ring Dave, who you do ring and he says thanks (before making a note to think about it, whilst probably muttering “this is not my job, I’ve got major roadworks to look after”). Hell, it’s easier to stop and move the branch.

Generally in life, in so many situations, I am constantly wondering why someone has not done X (or has done Y). Why don’t you reach for the jar in the shop the old lady can’t quite reach? Why don’t you hold the door? Why did you drop that litter when the bin is JUST THERE! That person  in front of you buying a parking ticket can’t find 10p in their purse to make the correct change? You have loads of 10p pieces… some in your hand already.

This is what is depressing me. Even though nearly everyone likes to think they are the nice person who will do a little for the common good, the reality is that most people won’t when it comes to it – but most people think we all should, and you tell yourselves you do the little things. You are telling yourself now, aren’t you? You are trying to think of the little things you have done for the common good. If you can think of a half dozen in the last month then you really are one of the good guys/gals. If you can only come up with a few…and actually most of them were ages ago… well, sorry but you are the problem.

The strange thing is that, having just insulted you all, as a group you lot are much more likely to be in the 1% than normal. Even though out of the general public not even 1 in 100 people would put in a little effort to move that branch, out of the people reading this, I’d say 10% would. Because I spend a lot of time in the Oracle user community, packed with people who give up their time, knowledge, even their holidays, to speak at conferences, help organise meetings, answer on forums, write blogs, answer questions on twitter, and all that stuff. Many of you reading this are active members of the User Community doing not just small things but often large things for the community. That’s why the community works.

To the rest of you, instead of liking to think you would move the branch or claiming you would (as everyone wants to be thought of as the nice guy/gal) just occasionally move the branch. Or pick that piece of litter up. Or do something small that cost you so little but it just would be nice if someone did it.

No one will thank you.

But you will know you did it. And you are becoming no longer part of the problem but part of the solution. I’m not asking you to give 10% of your salary to charity or give up an important part of your life, just do a bit of the small stuff.

If more of us do it, we will have a better world. If someone had moved that branch soon after it fell, I would not have had to  avoid some swerving dickhead, and the person I saw later would have not had to avoid people who could not even be bothered to slow down or stop briefly. And, in the worst case, that needless accident need not have happened. It really is as simple as spending 1 minute moving a branch.

Don’t be part of the problem, be part of the solution. It’s really, really, really easy.

 

COVID-19: The Current Situation in the UK and June. May 30, 2020

Posted by mwidlake in COVID-19, Perceptions, Private Life, rant, science.
Tags: , , , ,
7 comments

I’ve not said anything about Covid-19 for much longer than I expected, but really it has been a case of watching the coming peak come and go, pretty much following the pattern of Italy, Spain, Belgium and France. I plan to do a post soon which pulls together the current scientific position, but for now I wanted to record where we are and where my gut feeling (based as ever on reliable scientific sources and not so much on what the daily government updates would like us to think) says we will be in a month or so.

The number of UK recorded deaths where C-19 was present, and detected cases

We’ve not done very well in the UK. If you are based in the UK you may not be aware of the fact that most of Europe think we have,as a nation, been idiots – failing to learn from other countries, late to lock-down, lock-down was not strict enough, too early to open up, our PPE fiasco… I can’t say I can disagree with them. We have one of the highest deaths-per-million-population rates in Europe, exceeded only by Spain and Belgium. But it could have been worse. A lot worse.

I’m truly relieved my predictions in my last post were (for once) too pessimistic. I misjudged when the peak in deaths would be by over a week – it was 9 days earlier than I thought, happening around the 11th April. As a result of coming sooner, the peak was lower than my little model predicted. Even allowing for that, the increase in number of deaths did not mirror the increase in cases (I used the cases pattern as my template for deaths). I think this is because the UK finally started ramping up it’s testing rate. The more testing you do, the more of the real cases you detect, so some of the increase in cases was simply better testing and not continuing spreading. That’s what happens when the source of your metrics changes, your model loses accuracy.

Deaths are directly related to real case numbers, it does not actually matter how many cases you detect. This is part of why case numbers are a much poorer metric for epidemics, whereas deaths are better. The best metric is a random, large sample for those who have had the disease – but we still do not have reliable, large-scale antibody or similar tests to tell us this.

If you look at the actual figures and compare to what I predicted for the peak of deaths, I seem to have been pretty accurate. I said 1,200 to 1,500 around the 20th April and the peak was 1,172 in the 21st April. But I was predicting hospital deaths only. Up until 29th April this was the number reported each day but since then the daily number of deaths reported included community (mostly care home) deaths. The previous figures were altered to reflect this and the graphs to the right are based on these updated figures. Hospital deaths seem to have peaked at 980 on the 11th April, so I was wrong.

I think it is crucial in science and technology (and actually, just in general) that you be honest when you are wrong – even if (like in this case) I could made a fallacious claim to have hit the nail on the head.

The bottom line is, we are well past the first peak and it did not overwhelm the NHS. It got really close and our issues with personal protective equipment was a scandal and must have resulted in more illness and some avoidable deaths to our front-line NHS staff. But, apparently, saying so is Political.

All in all we followed the pattern of European counties that were impacted by Covid-19 before us and implemented similar country-wide lock-downs.

One difference between us and other European countries that have been hit hard is our tail of cases is thicker and longer. We have not been as rigorous in our lock-down as those other countries (e.g we did not have to have written permission to leave or enter an area and children were not utterly forbidden from leaving home, which are just two examples how our lock-down was softer). I know it might not feel like it, but we were not.

What really concerns me is that we are easing lock-down measures so soon in the UK. Our daily new case rate and number of deaths are both still really quite high. The figures always drop over the weekend, especially Sunday and Monday (due to the numbers reported being for the day before). Over the last 3 days (Wed to Fri) we averaged 1998 new cases and 371 deaths per day. If you think Covid-19 has gone away, every single day there are 371 families who sadly know different.

I understand that the economy is important, that unless things are being manufactured, services provided, money earned and spent, that a large part of our society is not functioning. Maybe I don’t really appreciate how important it is as economics has always looked more like a dark art based on greed than anything logical, but some people feel getting back to normal business is critical and the long-term impact of not doing so is potentially as serious as Covid-19.

I also know that not being able to go to places, eat out, have a drink in the pub, meet up with friends in a building or in more than small numbers is frustrating. For many, not seeing your family and loved ones who are not in your home is very upsetting.

I’m sure that parents are desperate for kids to go back to school (partly for education and partly as it turns out kids are a lot of work), couples need a bit of time apart, people are missing their jobs. Nearly all of us have never had to spend so much time with a very small number of other people.

But I’m also sure that what we don’t want is in 4-8 weeks to have to go into the same level of lock-down as we spent most of this spring in. And the next lock-down may be even more draconian as there is a difference now to where we were at the second week of March when we should have locked down first.

SARS-Cov-2 is now endemic and prevalent across the UK. It is everywhere.

At the start of an epidemic the disease is growing in a small number of places, so usually (such as was the case with MERS and SARS) you can contain it by strong isolation and tracking efforts in those areas it occurs, as most of the population are not exposed. This is why you cannot contain seasonal ‘flu epidemics by isolating people, it does not work if it is wide-spread enough. ‘Flu simply flows through the population and it does in some years kill a lot of people.

With Covid-19 right now, If our R(e) – the effective reproduction number – goes above 1 anywhere across the UK, Covid-19 cases will rapidly increase in that area. And with restrictions being lifted across the whole UK and in England especially, I am privately convinced the disease will burst fourth again in many, many places and it is going to go very wrong again. I think the government is being utterly disingenuous about the impact of opening up schools and my friends who are teachers and medics have no doubt this is a significantly more dangerous step than it is being sold as. It might be the right move, but lying about it’s potential impact is not helpful long-term.

Not only are we relaxing social distancing steps too early, but I feel the government has utterly bolloxed up (technical term meaning “done a jolly poor job of”) the messaging. As examples:

  • The very clear “Stay at Home” became the vacuous “Stay Alert”, which no one seems to be able to clearly define and every one seems to have a different interpretation of.
  • We were given contradicting and non-nonsensical rules such as you could see one family member from outside your household in the park, but you could have people come and view your house. So if you want to see your mum & dad at the same time, put your house up for sale and have them view it.
  • Parts of the UK (Wales, Northern Ireland, Scotland) have said they were not consulted on changes, they do not agree with them, and they are doing their own thing. That’s not confusing to people is it?
  • The whole Cummings affair. Dominic Cummings did break the rules, he acted like a selfish idiot, he lied about what he did, he had pathetically stupid excuses (“I drove my child around in a car to test my eyesight” which shows he either does not care at all for other people’s safety or has too low an IQ to be allowed out on his own). The issue is not that one arrogant, self-important person decided the rules do not apply to him. It is that the government fail to understand that not sanctioning him is being interpreted by many to mean they can make up their own minds about which rules apply to them and which they can ignore. Continuing to say “look, get over it” is simply coming across as telling us all to bugger off.

To help steer us through this crisis, we really needed a government with both the mandate to introduce new rules and also the acceptance by most of the population of those rules, and at least acquiescence from the majority to put up with limitations placed upon us. What we have now is a not just the hard-core “we won’t be told what to do” people that would always be a negative factor in limiting the spread of a disease, but a large number of angry, confused, worried people across the country. Almost everyone I personally know in the UK feel angry, confused, worried, and mostly with a progressively declining respect for the government and their advice.

I know I’m not very good at understanding people, it does not come naturally to me. If someone does not think like I do, I can have a devil of a job working out why. But I’m pretty sure that here in the UK a lot of people are going to start saying “to hell with the lock-down rules, everyone else is ignoring them and I’ve not seen anyone die in front of me…”

I went to see my Mum this week. I had to drive 100+ miles to do it. Unlike in Dominic’s case, it’s allowed now and I have no Covid-19 symptoms. I took a mask, I took my own food, we sat in her garden (I got sunburn, so Covid-19 might not get me but skin cancer might). I assured myself she was OK and that her tech will keep working so we can stay in touch. And I felt a little naughty doing it.

But I made a conscious decision to do it now – as I think SARS-CoV-2 is about at it’s lowest prevalence in our population right now (end of May 2020) than it is going to be for months. Admissions and deaths are going down and I expect at least deaths to continue to do so for another week or two. Personally I am deeply worried that in 4 weeks time new cases, hospital admissions, and deaths will be going up again. I don’t want them to be but I’ll be (very happily) surprised if they don’t go up  – what we see in cases & deaths at any point in time is based on the level of spread one or two weeks ago respectively. I suspect that as I type our R(e) number is going up and will exceed 1 this week.

If you don’t agree with me, just keep an eye on what the scientists are saying. Some are already making noises of anxiety as an article on the BBC is already saying today. Scientists tend to make cautious statements such as “we do not think this is wise” or “we feel there is a danger in this choice of action”. It’s a normal person’s equivalent of screaming “Are you bloody idiots?!?”.  Once again, the experts are saying we should do one thing and the government are doing another. It’s not gone too well to ignore the scientists so far.

There is a T-shirt you can get at the moment, which I really must order a dozen of.

“All disaster movies start with someone ignoring a scientist”.

 

 

Friday Philosophy: The Intersecting Worlds Around Oracle April 24, 2020

Posted by mwidlake in conference, Friday Philosophy, humour, User Groups.
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5 comments

Some of you may have noticed something about the Oracle Community: How certain other aspects of human nature, factors, and outside activities are unusually common.  An abiding love of the works of Douglas Adams (If you have never read “The Hitch Hikers Guide To The Galaxy” you should question if you are right for this community – and if you have read it/seen the series/watched the film and disliked it, I’m afraid you have to leave now); Lego was probably an important part of your childhood (and quite possibly your adulthood, though some “project” this fixation on to their kids). A lot of the most talented people, especially presenters, are called “Martin” or similar :-}.

Three Different Worlds Meet

There are two other groups of people that are large within the Oracle community and that I fit into.

  1. Oracle people who have a thing about cats. A positive thing, not those weird people who don’t like cats. It seems to me a lot of people in the Oracle community are happy to serve our feline overlords. This can polarise the community though, so introduce the topic of cats carefully. If the other person mentions how evil or unfriendly cats are, put them on The List Of The Damned and move on to something else.
  2. Making bread, especially of the sourdough variety. This is a growing passion I’ve noticed (quite literally, given the careful tendering of starter mixtures and also expanding waistlines). It seems to be especially common with technical Oracle people. More often than not, when I get together with a flange of Oracle Professionals (or is it a whoop or a herd?) the topic of baking bread will come up. Unlike technical topics, such as what is the fastest way to get a count of all the rows in a table, baking topics are rarely contentious and lead to fights. If you want to put spelt wheat in you mix, that’s just fine.

Mrs Widlake and I were talking about this last night (one of the problems with all this social isolation business is that Mrs Widlake is being forced to spend a lot of time with me – after 27 years of marriage idle conversation was already a challenge for us and now with over a month together all the time, we are getting desperate for topics). She asked how many of my Oracle friends liked both cats AND baking bread?

It struck me that it seemed to be very, very few. Unusually few. I think this is something that needs to be investigated.  This pattern would suggest that bread makers are cat haters. But in my non-Oracle world, this is not the case. The best people are, of course,  Ailurophiles and many of my feline-fixated friends are also bakers of bread. Just not in the Oracle world.

What makes Oracle people so weird?

Does anyone have any ideas? And have you noticed any other common areas of interest (excluding computers of course, that’s just obvious)?

A few that spring to mind are:

  • Terry Pratchett and the Discworld
  • Running
  • Weird science
  • XKCD
  • The Far Side
  • Star bloody Wars.

Let me know. Or don’t.

And for all of you who don’t like cats…

Meow

COVID-19: The Coming Peak in the UK & Beyond. April 9, 2020

Posted by mwidlake in biology, COVID-19, off-topic, science.
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9 comments

<<<<<<Introduction to Covid-19
<<<< Why we had to go into lock-down
<< What we could do to help ease social distancing

The UK government is now talking more in it’s daily briefings about what will come “next”, that is after we have seen the number of diagnosed cases & deaths continue to grow, plateau, and then fall. It will plateau & fall, so long as we all keep staying at home and limiting our social interactions. If we do not, we risk the virus spreading out of control again.

When Will the Peak Be?

My estimates so Do Not Trust At All

First of all, there will be two peaks. First the number of new cases a day will peak and then, about 8 days later, the number of deaths per day will peak. This is because of the average gap between being diagnosed in hospital and succumbing, for those unfortunate enough to do so.

The number of deaths a day looks to me like it will peak around April 20th, at somewhere between 1,200 and 1,500 a day (see below why I think tracking deaths is more reliable than case numbers and why case numbers are a poor metric). We will know that peak is coming as, if the lock-down measures have worked as intend, their effect will result in a plateauing and then drop in new cases during next week ( April 12th-18th). We might be seeing that plateauing already. Deaths will plateau (stay steady) for maybe a longer period than cases due to the fact that the gap between diagnosis and recovery or death is variable. That period will be something like April; 20-27th

If we follow the same “curve” as Italy and Spain,  the number of new cases will slowly start dropping but not as sharply as early models indicated. Deaths will also drop, about 8-10 days later. What happens then I have no idea really, it depends on how well the current social distancing measures work and if people continue to stick to them as spring progresses and people want to escape confinement.

A disproportionate number of deaths in this peak will be from our health services and critical works – people working in shops, bus drivers, refuse collectors, GP’s, teachers – because they are the most exposed. The care industry workers and lower paid people in our society will be hardest hit, which seems monumentally unfair.

The plan of pretty much all national governments so far is the same:

  • Isolation of all people who are non-key workers
  • Slow the spread
  • Expand the respiratory Intensive Care capabilities of the health services as much as possible
  • Look after as many of the wave of people already infected & becoming ill as possible

As I’ve covered in prior blogs, if the government’s measures work we are then we are left “sleeping with the tiger”. The virus is in our population, it will be slowly spreading still, and when social isolation measures relax there is a real risk of the illness and deaths exploding again because most of us are not immune. This is know by all epidemiologists studying this, it is a situation that China, Italy, Spain, and most other countries will face.

The big question is – what comes after the peak?

I’m going to cover three four things:

  1. Why we cannot go on “Cases” the number most often graphed and discussed. We have to go on deaths, and even then there are some confusing factors.
  2. Why the Infection Fatality Rate is key – and we do not know that yet
  3. A “test” or “vaccine” is not a black and white thing, it’s grey, and especially for a Vaccine, it is not coming soon.
  4. How we might manage the period between either a reliable vaccine or herd immunity. Both currently look like at least 18-24 months away.

Why Case Numbers Cannot Be Relied On.

Case Numbers do not tell you as much as you may think

Case numbers (the number of people who have been confirmed as having Covid-19) are the most commonly reported figures, many of us track if things are getting better or worse by them. But they are a very poor indicator really and they certainly cannot be used to compare between countries.

First of all, how are the diagnoses being made? Most countries are using the WHO-approved test or a very similar one, called a PCR test. I won’t go into the details here, I’ll put them in the section of the post on testing, but the test is accurate if done in a laboratory. Why in a lab? because any cross-contamination can give a false positive and if the sample or test chemicals are not kept/handled correctly, can give a false negative.

Not all countries are using just PCR tests. China made some diagnoses based only on symptoms. I’m not sure if other countries are making diagnoses from symptoms only and including them in official figures.

More significantly is who is being tested. In the UK the test was originally only being done on seriously ill patients in hospital. It is now being done on a few NHS staff and certain key people (like Boris Johnson!). In South Korea and Germany, many, many more people were tested, so there will be more cases identified. Add on to that the number of tests a country can do.

In the UK are testing rates have been very poor

In the UK we were limited to a pitifully small number of tests per day, less than 6,000 until March 17th and we only reached 10,000 test a day at the start of April. You cannot detect cases in people you have not tested.

Case numbers will also vary from country to country based on the country’s population! The UK is going to have a lot more cases than Denmark as we have over 10 times as many people.

The final confusion is that even in a single country, what counts as a day for reporting can vary and it can take time for information to be recorded. The UK sees a drop of cases against the prevailing trend on Sunday and Monday. As the cases are for the prior day and it seems like the data is not being as well processed at weekend.

Estimations of how many people really have Covid-19 at any time, as opposed to validated Case numbers, vary wildly. In the UK I doubt we are detecting even 1/3 of cases.

So, all in all, Case Rates are pretty poor as an indicator of how many people are really ill.

Infection Fatality Rate and Tracking Deaths Not Cases.

As I mentioned in my previous post last week, what we really need to know is the Infection Fatality Rate (IFR). This is the percentage of infected people who die. It is not the same as the Case Fatality Rate (CFR), which is the percentage of known cases that die. As the number of known cases is such an unreliable number (see above!) then of course the CFR is going to be rubbish. This is a large part of why the CFR varies so wildly from country to country. France has a CFR of 8.7%, almost as bad as the UK at 10.4%. The US has a CFR of 2.9% (but they will catch up).

As I also covered last week, we cannot calculate the IFR until we know the number of people who have been infected. For that we need a reliable antibody test and one does not exist yet. Yes, they are being sold, but the reliability is poor. Last I knew the UK NHS had reviewed several candidates and none were reliable enough to use.

Scientist have suggested many Infection Fatality rates. I feel 0.5% is a fair estimate. It is vital we know this number with some accuracy as if we have an Infection Fatality Rate we can flip the coin and calculate the number of people who have been infected from the number of people who have died.

IFR * deaths =  number immune

You can go from a graph like the example one I show (either from a model or, after the peak, from real figures) and as you have the number who died (say 20,000 to keep it simple) and the IFR of 0.5% you know that 4 million people (minus the 20,000 who died) had the disease and are now immune.

Of course, once we have a reliable antibody test we can verify the exact value for Infection Fatality Rate and the percentage of the population now immune.  But we only need that information from one country and it can be used, with minor modifications for population age and capacity of the health services, to estimate how many people are immune and thus how many are still at risk from Covid-19. In my example, about 62.5 million people in the UK would still be susceptible to Covid-19. Which is why this will be far from over after this initial peak.

There is one huge caveat in respect of the IFR. If in the UK the NHS is over-run, we will have extra deaths. People who would have survived with treatment die as too many people needed treatment at the same time. This is the whole “flattening the curve” argument, we have to protect the NHS from being over-run to limit this extra, avoidable deaths. In effect the IFR is elevated due to the limitations of the health system.

Countries which do have a poor health service or other aspects of their society that block them from the health service (cultural bias, fear of crippling debt) or more likely to have an elevated IFR, as are countries that allow Covid-19 to run unchecked through their population.

There is another aspect to the IFR and measuring progress of Covid-19 via the death rate. The number of deaths is a more reliable measure. I know that sounds callous, but as we have seen, the Case Number is totally reliant on how you do your testing and there needs to be a huge testing capacity to keep up. Deaths are simpler:

  • There are fewer deaths so fewer tests are needed (to confirm SARS-CoV-2 was present in the deceased, if not already tested).
  • Deaths have to be recorded in a timely manner.
  • Deaths are noticed. There are going to be people who are seriously ill and would be tested if they went to hospital but don’t, they get better and it is not recorded. They are “invisible”. Dead people invariably get noticed.
  • A country that wants to hide the active level of Covid-19 can do so by not testing, under-testing, or not reporting honestly on the tests. It’s not impossible, but it’s hard to cover up a significant increase in the number of deaths.

I stress that is is not a perfect indicator though. There is no clear distinction made as to whether the patient dies of some other illness but SARS-CoV-2 was present; whether the patient was likely to die “soon” anyway – again due to other illnesses; patients who die outside hospitals are not counted in the UK daily figures yet. (If you follow me on Twitter you will have possibly seen me querying the figures last Monday – and people pointing out the reason!)

Reported deaths will also suffer from spikes and dips due to how the reporting is done. The UK and some other countries I checked (France, Italy, Spain) show a dip in all figures, against trend, on Sunday or Monday (or both).

There is a really nice article on all of this this by New Scientist which is itself partly based on this paper by the lancet that gives an IFR of 0.66%

There is also a whole plethora of graphs and information on ourworldindata.org/coronavirus , as well as text explaining in more detail what I have said here. It is well worth a look and you can change which countries appear on the graphs.

 

Test are Not Black And White

There has been a lot of talk in the UK and elsewhere (including the USA), about not doing enough testing. On the other hand their is a constant stream of media reports about quick home tests, both for if you have Covid-19 or have antibodies to SARS-CoV-2 and so are immune. So what is the reality?

A test is only any good if it is reliable as used. For something like a deadly pandemic, it needs to be really reliable. Let me explain why.

Let’s say a company is selling an antibody test and someone uses it, it says they are immune,  and they stop self-isolating. But the test is 75% accurate. 75% sounds good, yes? No. it means 1 in 4 people who take that test and it says they are immune are not –  and they have now gone out, spread the disease to their aunt Mary and she dies. Plus infecting a large number of people and keeping the whole sorry mess going.

{Update – as a friend reminded me, when you are testing for an “unlikely” event, which being immune to C-19 is right now, even a 95% accurate test will give far more false positives than real positives across the whole population – I’ll try and do another blog to explain why}.

And that is if they take the test properly – companies are most likely to give you the best, under-ideal-conditions accuracy rate as they want to sell more kits than Sproggins Pharma selling a similar kit which they claim is 73% accurate.

If you are reading this, you are probably the sort of person who will read the instructions, follow them carefully, not put the swab down on a table,  not let the dog chew it.  And you note the bit on reliability. Most won’t. They will do the test quickly, it says they are immune and they will believe it, especially if the quoted reliability rate is high.

Any home test that can be used by the public has to be both very reliable (less then 5% false positives) and utterly idiot-proof. I’m really concerned that countries that put money first will allow companies to sell tests that do not meet these criteria and it will make the situation a lot, lot worse. It might even result in the pandemic running out of control.

Test For Being Infected – PCR test

PCR stands for Polymerase Chain Reaction. The WHO-approved test for Covid-19 is a PCR test and has been fully described since the end of January. You can even download the details of the test and methods from the WHO page I link to.

A PCR test is a genetic test. A primer is added to the sample to be tested and that primer latches on to a very specific DNA or RNA sequence. A biochemical reaction is then used, called a Polymerase Chain Reaction, to make copies of that DNA/RNA, doubling the number in the sample. These steps are repeated 30 to 40 times to make millions of copies of DNA/RNA. With an old-style PCR test you would then need to run the processed sample through a second process to detect it, like a Southern Blot – you get a square of gel with black lines on it. The PCR test for COVID-19 should be a real-time PCR test. With this the new copies made are attached to a florescent dye so that it can be easily detected as soon as there are enough copies in the sample, say after 30 iterations not the full 40, saving time.

If the original sample contains even just a few pieces of the DNA/RNA you are testing for, you will detect it. The process takes a few hours.

The RNA of the SARS-CoV-2 virus was sequenced (read) back in January and the WHO identified sequences that were unique to the virus, and these are used to make the primers. As I understand it most countries use the WHO identified primers but the USA had some “discussions” between commercial companies over which primers they thought should be used. I won’t suggest there was an element of these commercial companies looking to make a fortune from this, i’m sure it was all about identifying an even more unique RNA sequence to target.

The test has to be done in laboratory conditions. Because the test is so sensitive any cross contamination can give a false positive. e.g the sample taken from a patient was done by someone with COVID-19 themselves or there was SARS-Cov-2 virus in the air from another nearby patient. If a swab is used to get a sample from the back of the throat, it has to be put into a sealed tube as soon as it is used.

If the sample to be tested has not been looked after properly (kept cool, not kept for too long etc) or the chemicals for running the test are similarly not kept in a laboratory environment, you may fail to detect the RNA – a false negative.

Finally, the virus RNA has to be there to be detected. A patient early in their illness may not be shedding virus at a high enough level for the swab to pick up some of it. Once a patient’s own immune system has wiped out the virus (or almost wiped it out) again the swap may not have any or enough virus in it to be detected.

Done right a PCR test is a powerful, incredibly reliable (over 99%) diagnostic tool and is used for detecting many viral diseases, including HIV, Influenza, and MERS.

How a simple yes/no infected test might work

You can probably now understand why creating a PCR test for Covid-19 that can be used at home or in the ward and gives a result in minutes is a bit of a challenge.

Some companies are trying to create a different sort of test. These depend on creating a chemical that will bind to the virus itself, probably one of the viral surface proteins. That chemical or part of it will then react with something else, a marker chemical, to give a visible change, much like a pregnancy test. You put the sample in a well or spot where the detecting chemical is. Fluid is then dragged along the strip carrying the thing to be detected (the virus in this case) and the detecting chemical. Any detecting chemical that did not bind will be left behind. When the fluid goes past the marker chemical, if there is enough detecting chemical, it will change colour. Neat!

Best I know at time of writing, no one has come up with such a test that was reliable. I’m pretty sure someone will, in a few weeks or months. It should be accurate but no where near as sensitive as a PCR test. I must stress, to actually be of use in handling Covid-19 as a nation, the rate of false positive would need to be very low. False negative, though not good for the individual, is nothing like as big a problem in containing the pandemic).

Antibody Test

An Antibody test will show if you have had Covid-19. It will not show if you currently have it, or at least not until the very late stages. This is because it is testing for the natural ability for your immune system, via antibodies, to recognise and attack the SARS-Cov-2 virus.

We desperately need an antibody test as it will allow us to identify people who have had the disease and are now immune. This is vital for 2 reasons:

  1. Someone who is immune does not need to be restricted by social distancing. See my prior post on why this is vital and how we might identify such people.
  2. We can find out how many people have had the disease and compare it to the number of people who have died of the disease and get that very useful Infection Fatality Rate.

Unfortunately, making an antibody test is not easy. Some are in trials and I think the UK government have tried some –  and none have proven trustworthy.

An antibody test is simply not simple. What you need to do is design something that an antibody reacts against, so let me just describe something about antibodies. Before I go any further, I must make it very, very, very clear that of all the biological things I have touched on so far, antibody technology is something my academic background hardly touched on and most of what I know comes from popular science magazines and a few discussions with real experts last year when my work life touched that area.

Your body creates antibodies when it detects something to fight, an invader in our tissues. This is usually a viral or bacterial infection. It also includes cells that “are not our own”, which is why we reject organ transplants unless they are both “matched” to us and we take drugs to dial down our immune response. Our antibodies recognise bits of the invader, in the case of viruses that is (usually) proteins that are in the coat, the outer layer, of viruses. Usually it’s the key proteins, the ones that give them access to our cells. Our immune cells learn to recognise these proteins and attack anything with them on it.

Anyone infected with SARS-Cov-2 who survives (which is, thankfully, most of us) now have antibodies that recognise the virus. There is no guarantee that what Dave’s immune system recognises SATS-CoV-2 by is what Shanti’s immune system does. It will be a bit of the virus, but not necessarily the same bit!

So an antibody test has to include proteins or fragments of proteins that most human immune systems that recognise SARS-Cov-2 will recognise. And as that will potentially vary from person to person…. Oh dear. Thus a good antibody test probably needs to have several proteins or protein fragments in it to work. This is why it is complex.

Again, the tests will come but the first ones will almost certainly not be specific/reliable enough to really trust.

 

Vaccine

The bad news? Despite all the media hype and suggestions in government announcements of creating a vaccination in 18 months (maybe sooner), it is very unlikely. Sorry. It is very, very unlikely. Don’t get me wrong, I would love us to have one right now, or in a month, or even in 6 months. But unless there is a medical miracle, we won’t and by suggesting to everyone that we might, I think the powers that be are storing up a lot of anger, frustration and other issues

A vaccine needs to do something similar to the Antibody test. It needs to contain something that either is part of the virus or looks like part of it. This is usually:

  • An inactivated version of the virus
  • a fragment of the virus
  • One of the key proteins on the virus
  • Rarely, a related virus that is much less harmful (for example cowpox for smallpox vaccine).

The vaccine is administered and the person creates antibodies to it. Now, when the person is exposed to the real virus, the immune system is ready to attack it. Neat!

Influenza Vaccine is often less than 50% effective

Creating vaccines is a long process. You need to come up with something that is safe to administer, prompts our immune systems to create the antibodies, and the antibody reliably attack the virus the vaccine is for – and nothing else! (Occasionally a new vaccine is found to prompt some people’s immune system to attack other things – like the healthy, useful protein the virus actually attacks). And you have to produce a LOT of that thing if you are going to administer it to a large number of people, such as most of the UK population.

The vaccine has to work on most people as you need 60-70% of people to be immune to SAR-CoV-2 get herd immunity from Covid-19 – the higher the better. The influenza vaccine is often much less effective than 50%, especially in older people.

You are giving the vaccine to healthy people and to lots and lots of them. It has to be really, really, really safe. If it seriously harms 1 in a thousand people (which might sound reasonable at first glance, for treating something as bad as Covid-19) – well, that is almost as bad as Covid-19 itself. You would be harming hundreds of thousands of people.

With a drug you use to treat the ill, you can afford for it to be less safe – as you are only giving it to people who are ill (so a smaller number) and they have more to lose. The risk/reward balance is more likely to be positive for a drug. Even if a drug for a life-threatening illness harms 5% of people but cures 50%, it is worth (with informed consent) using it.

We have never, ever created a vaccine in 18 months before. I’m struggling to get a scientific reference as searches are swamped with talk pieces (like this one!) on why it will take a long time. However, this video by an American doctor  Zubin Damnia who does social media about medical matters explains better than I can and this history of vaccines makes it clear at the top it often takes 10 years.

The bottom line is, much though I want to be wrong, the often stated aim of having a suitable vaccine in 18 months or less will need a medical miracle and a huge amount of work.

After The Peak And With No Vaccine – How Do We Cope?

After the peak, most people are still at risk from Covid-19. As I said earlier, if the Infection Fatality Rate is 0.5% then for each person who died there will be 200 people who are now immune, so if there are 20,000 deaths that is 4 million people immune. 6

If there is no vaccine then we have, I think, four options:

  1. Continue social isolation measures as they are to keep the virus from spreading.
  2. Relax isolation a little and let cases creep up but held as steady rate, but within the capacity of the NHS.
  3. Relax isolation quite a bit, monitor number of admissions to ICU (or something similar) and re-impose strict social isolation at  the current level if things start getting worse.
  4. Relax isolation a lot and massively increase testing and case tracking – copying the South Korea/Singapore approach.

Option 1 to hold us all in isolation is, I think, untenable. People will stop doing it and the impact on our economy must be massive. The impact on our society will also be massive, especially if this continues into the next academic year.

I don’t think we can manage option 4 in the UK yet.

So I think we will see an attempt at option 2, relaxing some social isolation rules (such as allowing restaurants to open and small gatherings) but then option 3, tightening social isolation if numbers of new cases start to build.

Option 4 could become a reality in a few months, especially if we can get people to use mobile phone apps to track movements and aid identifying the contacts of people who become ill,  but not everyone has a mobile phone and I think a good percentage of people will not agree to be tracked.

At present, without a vaccine, we will be living with some sort of social until we reach herd immunity, with at the very least 60% of us immune. How long will that take? 60% of the UK population is 40.5 million people. That equates to 202,500 deaths from Covid-19 to get there (remember, see the bit on IFR above).

This current peak of Covid-19 will last about 3 months, from the start of March to the end of May. It remains to be seen if we exceed the NHS expanded capacity. If we allow 20,000 deaths a peak with 4 million people becoming immune each peak, that’s 10 peaks, so 2.5 years.

A better option could well be to aim for a steady rate of new cases and deaths from Covid-19, say 1000 a week. At that rate herd immunity will take just over 200 weeks, 4 years. If we allow 4000 deaths a week than we could be there in a year, but our NHS would have to be handling the many, many thousands of ill patients that would entail.

Of course, in reality, our treatment of Covid-19 patients will get better over time, so fewer people will die from it, but it will still be a horrible thing to go through. And, if we DO get a vaccine sooner rather than later, many of those people will have died needlessly.

So, as you can see, we are in this for a long while.

The expanded health services, better knowledge of what social movement restrictions work, improved testing (including home testing), even my idea of cards for those immune, would all make life easier, it is not all doom and gloom. But I just wish all of what I have put here was being discussed and shared with people (preferably in a shorter form than this blog!) in a clear and constant message. I think if more people understood where we are and what is likely to to happen (or not), we will save ourselves a lot of issues weeks/months/even years down the line.

I honestly don’t know what the answer is – I don’t think anyone does. Which is why all of this talk about an “exit strategy” results in lots of hand waving and no clear plan.

As ever, if you think I’ve got something wrong, you know of a good academic source covering this, or you simply have a comment – let me know.

Friday Philosophy – Concentrating and Keeping Calm. April 3, 2020

Posted by mwidlake in biology, COVID-19, Friday Philosophy, Perceptions, Private Life, science.
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I was talking with a friend this week (via a webcam of course) about how he had been looking & looking at some misbehaving code for days. His team mates had looked too. It was not working and logically it should work. None of them could work it out. The problem turned out to be a small but obvious mistake.

My guesses for UK cases & deaths. Do Not Trust

This of course happens to us all occasionally, but we both agreed that, at the moment, we have the attention spans of a goldfish and are as easily distracted as a dog in squirrel country. I asked around a few other friends and it seems pretty much universal. All of us are making cups of tea and then taking the milk into the lounge & putting the cup of tea in the fridge. Or walking into the kitchen and asking who got the bread out to make lunch. It was you. The cat is wondering why I open the pouch of cat food and then leave it on the worktop and go do my email for 20 minutes. She’s getting annoyed.

Why are we all failing to function? Because we are all worried. This is one of the things anxiety does to us.

The whole COVID-19 thing is stressful – the feeling of being trapped inside, concern for friends and family, the ever growing numbers of infected & dying. I actually think if you are not at all worried then you are either:

  • Not understanding the situation
  • In denial
  • A total sociopath
  • Someone who should not be allowed out alone
  • Have reached a level of Zen calm usually only attainable by old oriental masters/mistresses

I’m by my nature often in camp 3 above, but even I am worried about this and I know it is making me tetchy and less able to focus. I’m struggling to keep my mind on things. Except on COVID-19. I tend to handle things I find unnerving by studying them and I probably spend about 3 or 4 hours a day looking at the latest information and scientific output on COVID-19. However, I note more things to “look at later” than I actually look at, as I am trying to manage my stress.

After an hour I make myself get up, go trim some roses, play a computer game, read a book. Anything to distract me. I’ve even started talking to the other person in the house and my wife is finding that particularly annoying. Sue seems easily annoyed and quite distracted at the moment. I wonder why?

Another way I cope is I talk with people about topics that are causing me stress. If I can’t talk, I write. Thus I wrote this Friday Philosophy – think of yourself as my counsellor.

I’ve seen a lot of social media “memes” about how long ago the 1st of March feels like, when we first started worrying about this. It seems like months ago, yes? To me it seems like a year. I started worrying about this a good while before the 1st March. I think the worry started about early/mid-February. Why? Because I’m a genius of course. {Note, this is called British self-deprecating sarcasm – I’m not a genius!}. No, the reason I picked up on all of this early was that chance primed me to.

I have a background in biology and some of the job roles I have held over my career have been in healthcare and the biological sciences. One role last year was working with a small biotech company working on immunology. So I take an interest in this sort of thing, it’s “my bag”. I was also pretty ill in December with Influenza (and yes, it WAS influenza, type A – I am not “the first case of COVID-19 in the UK”). So I was convalescing at home and took a specific interest in a new illness spreading through China that was influenza-like… And was worrying the hell out of the Chinese authorities who were coming down on it in a way we have not seen before, even with SARS and MERS.

My play spreadsheet.  I should leave this to the experts really

I have to confess, I initially suspected (wrongly, I hasten to add) that this new disease had escaped from a lab. The way it spread, that it seemed to be ‘flu-like, the rapid response by the authorities. I don’t doubt research into modifying diseases goes on – by the UK, China, USA, the Vatican, by every country with a biotech industry. I know we have the tools to directly mess with genomes, I did it myself, crudely, 30 years ago and I know people now who do it now, with considerable accuracy, for medical and other altruistic reasons. However, genetically engineering an organism leaves traces and when COVID-19 was sequenced there was no sign of this and it could be tracked to similar, previously known samples. I might even know some of the people who sequenced it and checked. But, anyway, that suspicion also made me watch.

The rate of spread in Wuhan was as shocking as the authority’s response and then through February the scientific analyses started appearing. The R(0) number (infection rate) and the high case fatality rate were both high. I’m not an epidemiologist but I had been taught the basics of it and I knew what was coming. No, that’s not right, I suspected what was coming, and I was worried. It was when the number of countries with cases started to increase that I felt I knew what was coming. By the end of February I was sure that unless something huge happened to change it, 2-3% of people, everywhere, would be killed. This was going to be like Spanish ‘flu only quicker (as we all travel so much). I became “The Voice Of Doom”.

On 2nd March I recommended to our CEO that UKOUG cancelled our Ireland event (people & organisations were pulling out so it was making it financially untenable anyway, but my major concern was that this was going to explode in the population). Thankfully the rest of the board agreed. I created my tracking spreadsheet about the 5th March. So far it’s been depressingly good at predicting where we are about a week in advance, and not bad for 10 days. I leave it to the experts for anything beyond that. All so depressing so far.

But Something Huge has happened. Governments did take it seriously. Well, most of them. And those who took it seriously soonest and hardest have fared best. The social lock-downs and preparation work that is going on in the UK is going to reduce the impact down dramatically and, more importantly, give us time to try and find solutions. But it still worries me. And I think they could have done it sooner. But most of the world is taking this very seriously – as it is very serious.

Part of me wants to keep watching how COVID-19 develops, and maybe writing more articles on it. I’ve had some really nice feedback on the first two and I want to do a post on where we might go in the coming months and why. But part of me wants to stop as it is making me very anxious and I’m sick of losing my cups of tea, or being stared at hard by the cat, and the wife asking me what the hell am I doing with the spanner and tin of peas.

I can’t easily listen to the government announcements each day as it is obvious, if you look at the scientific data and what medical professionals are saying, that they are simply not being candid. It’s all “we can beat this in the next few weeks” and “we will get you testing kits this month that are utterly reliable” despite the fact that’s going to need a scientific miracle to do that, let alone develop a reliable vaccine. I understand we need to keep positive but I think bullshitting the population now is only going to make telling them anything they will believe in 2 months even harder. In 6 months time when there is still no reliable vaccine and so many people have been wrongly diagnosed and the first few countries have had this rip through them almost uncontrolled, the lack of candid honesty will come back to roost. I worry about that a lot.

So I’m worried and I’m worried I’m going to be worried for months and months and months.

But for now I’m going to go for my daily (local) walk along a path I know will be almost empty of people and relax.

 

* Note, the graph and the spreadsheet are just “decoration”. They are my wild guesses on what may happen and have no reliability at all. Just saying