Covid-19 was genetically-engineered

A Covid-19 blog post for the non-expert

Germ warfareThe story that Covid-19 is a genetically-engineered virus from a Wuhan laboratory has gone viral across the internet (dated pun intended). President Trump implied it, and the Daily Express ran a 10th March headline, “Coronavirus may have been genetically engineered for the efficient spreading in the human population, a bombshell new study has claimed.” The article was withdrawn soon after.

The title of this post is deliberately provocative, and it may attract conspiracy theorists, so I’ll say up front, there is no evidence whatsoever SARS-CoV-2, the causative virus for Covid-19, was genetically engineered in China, or anywhere else. Instead, everything points towards completely natural origins which Charles Darwin would recognise (and probably say, “I told you so”). If you’re not a conspiracy theorist and you want to know why I’m confident this is the case, read on.

Everyone has heard of Covid-19 (caused by SARS-CoV-2),  Middle East Acute Respiratory Syndrome (caused by MERS-CoV) and Severe Respirator Syndrome (caused by SARS-CoV). These are well known because the infection spread across multiple countries but there have been four other, less infective and therefore less well known outbreaks, HKU1, NL63, OC43 and 229E. In all seven cases, the coronavirus jumped from an animal species into human. How do we know this? It goes back to the genetic code and Darwinian evolution.

The molecular structure of DNA comprises bases called purines and pyrimidines pointingDNA inwards from a double helical backbone of phosphate and deoxyribose sugar. There are two purines called adenine and guanine and two pyrimidines called thymine and cytosine. The DNA molecule is constructed somewhat like a child’s magnetic building kit, where north and south poles of magnets stick together to make a cube or a pyramid, or other similar shape. The child soon discovers that although north and south poles stick together, north-north or south-south poles repel. They can’t build their pyramid from magnets joined with like-poles, no matter how hard they try. Like north and south poles of magnets, bases of DNA can only join pyrimidine to purine, never pyrimidine to pyrimidine or purine to purine. In fact, they are more specific than that, because adenine (A) always bonds to thymine (T) and guanine (G) always bonds to cytosine (C). The sequence of A-T and G-C in DNA forms the genetic code, and is collectively known as the genome. It encodes for all the processes of life that makes everything from viruses to you and me. (There are some great animations on DNA and its function here).

How does a sequence of A-T and G-C go to make the complexity of all life? The DNA helix unwinds and makes ribonucleic acid (RNA) from the A, T, G, C template. RNA is like DNA except it has ribose instead of deoxyribose, and instead of thymine it has another base called uracil. Putting aside the complexities of the three types of RNA (messenger – mRNA, transfer – tRNA and ribosomal – rRNA) the molecule translates the A,T, G,C code into a series of amino acids. Each amino acid is coded by a sequence of 3 bases, GGT, for example, codes for the amino acid, glycine. By joining together long strings of amino acids, we make proteins and proteins control all the biochemistry of life. To quote from a previous blog post:

“Proteins are hugely complex molecules made from strings of up to 20 distinct types of amino acids. Some proteins contain hundreds or even thousands of individual amino acids; the muscular protein, titin has 30,000 of them. The long strings of amino acids fold like tangled pieces of string but unlike string, the tangles are very precise. Proteins have molecular grooves and pockets where specific biochemical reactions take place. The grooves and pockets are analogous to spanners and wrenches in a biochemical tool kit, each fitting a particular sized nut or bolt in building the machinery of life.”

Coronaviruses take a shortcut that leaves out DNA, and goes directly to RNA, but it’s still the sequence of bases which codes for viral existence. It takes over the genetic machinery of mammalian cells, mostly human lung cells in the case of SARS-CoV-2, to make viral proteins, which builds lots of new viruses. The human cells are destroyed in the process, giving us the symptoms of Covid-19. If you wanted to engineer a coronavirus pandemic, then you would have to start with its RNA and it’s the same genetic sequence that tells us SARS-CoV-2 was made by mother nature herself.

Coronaviruses jump from one species to another, making them so called zoonotic viruses, but this isn’t that uncommon. In fact perhaps three quarters of all viruses are zoonotic, or at least transmitted through a vector, such as mosquitoes. SARS-CoV-2 most probably started out in horseshoe bats, based on a 96% identical RNA sequence to the RaTG13 virus endemic in that species. There is also a related RNA sequence in SARS-CoV-2 implicating the scaly anteater, called a pangolin, as an intermediary species before infecting humans. The origins of SARS-CoV-2 are written right there in its genetic code but we have to be careful because there’s much we don’t know about viruses carried by the thousands of mammalian species across the world. We do know that the vast majority of species-hops, result in a cul-de-sac for the virus and it’s only extremely rarely that a virus jumps into humans and then is able to transmit human to human. It seems however, a mutation in RaTG13 to SARS-CoV-2 is one of those rare cases.

But what about the 4% difference in RNA between RaTG13 and SARS-CoV-2, where did that come from? The genome of RaTG13 changed for the same reason the genome alters in any organism. Random changes as imperfections in the RNA→protein process arise as mutations. Some mutations are fatal and the organism dies, and some give it a small advantage so it perpetuates through the generations. Once a chance mutation in RaTG13 RNA gave it the advantage of human to human transmission – it then thrived giving us Covid-19. This random mutation, followed by biological selection is what defines Darwinian evolution. It’s happening all the time, it’s just we don’t see it until there’s a pandemic.

Not all parts of any genome are equally susceptible to mutation and one notable region of the SARS-CoV-2 RNA is particularly prone to variation. This is the region which codes for the so-called spike protein that recognises a receptor on the mammalian cell enabling it to enter that cell and infect it. It’s this variable region of RNA in coronaviruses generally that gives them their nasty species-hopping talent. From analysis of the RNA sequence, all seven coronavirus outbreaks likely originated from other mammalian species through variations in RNA coding for spike proteins. By looking at the RNA sequence in this variable region we know, both MERS-CoV and SARS-CoV, like SARS-CoV-2, most likely originated in bats, while the milder HKU1 coronavirus originated in mice and OC43 likely came from cattle. Scientists have identified precise changes in RaTG13 RNA and the corresponding amino acid sequence alterations in the spike protein which transformed it to SARS-CoV-2, enabling it to latch onto a human cell-surface protein called ACE leading to infection (I blogged about ACE previously). From the rate of coronavirus mutation, we can estimate this mutation probably occurred sometime in the last 40 to 70-years. There’s nothing unusual in the way RaTG13 mutated to SARS-CoV-2 and, indeed, it’s exactly what you would expect it to do, given the right opportunity as humankind expands into previously uninhabited ecosystems.

Worryingly, the mutation which gave us SARS-CoV-2 does not optimise the spike protein’s infectivity and so Covid-19 is actually a milder disease than nature might have given us. Even more worryingly, a variant was recently identified where another change in the variable spike protein region has increased SARS-CoV-2’s potency. The trouble is, a single error in copying the virus’s 30,000 base pairs in the RNA code can result in replacement of one amino acid in the protein for another, thereby changing the protein’s functionality. Where GGT codes for glycine, for example, just one changed base to GCT now codes for the amino acid alanine.

The problem with all conspiracy theories, be it genetically engineered SARS-CoV-2, or fake moon landings, they use a simple lie to hide the complex truth. As soon as you get below the surface, conspiracy theories lack detail and rely instead on the idea of vast networks of people, all somehow holding on to the dastardly secret. Like all the world’s virologists and molecular geneticists conspiring to keep genetically engineered SARS-CoV-2 from the unknowing public. And the fact I’ve just explained the natural process by which SARS-CoV-2 arose, just makes me part of the conspiracy. I’d like to explain more, but I’m scheduled to attend an illuminati meeting in Atlantis, so I’ll see you next time.

Murder and Atoms

Richard Hill and fellow hikers were walking in the Yorkshire Dales, about an hour’s drive from where I live, when they stopped to take a photograph. He stood by a stream near to the Sell Gill Holes caves in Pen-y-ghent but didn’t notice, just behind him, was the face-down body of a half-naked woman. They were two kilometres from the nearest road and the body had likely been dumped on higher ground one to two weeks earlier, before being washed down by torrential rain over the previous 24-hours.  It was the decomposing body of a 25-35 year old woman wearing green Marks and Spencer jeans, socks and a wedding ring. This was back in 2002 and an E-fit picture and police enquiries made at that time turned up nothing. Oddly, no one meeting her description had been reported missing anywhere in the country.

Locals affectionately called her the Lady of the Hills, they gave her a funeral and buried her in the village cemetery. The case went cold, until the new forensic technique of stable isotope analysis arrived on the scene. 

The chemical elements listed in the periodic table are defined by the number of protons in their nucleus, one for hydrogen, two for helium, and so on until the 92 protons of uranium. Although atoms of any given element always have the same number of protons, they can have different numbers of another sub-atomic particle, the neutron. All hydrogen atoms for example, have one proton but one in 6,250 also has a single neutron and about one hydrogen atom in a quintillion has two neutrons. This subclass of elements, defined by the number of neutrons, are called isotopes. Those hydrogen atoms with one proton are an isotope of hydrogen called protium. Those atoms with one proton and one neutron are an isotope of hydrogen called deuterium. Those atoms with one proton and two neutrons are an isotope of hydrogen called tritium. And as the atom packs in more neutrons, so its mass increases, protium with a mass of one, deuterium with a mass of two and tritium with a mass of three. Chemists identify which isotope is which from its atomic mass, including it as a superscripted prefix to the elemental symbol, such as, 1H for protium, 2H for deuterium and 3H for tritium. The periodic table, that we are all familiar with, lists only the elements themselves but behind each of the elemental boxes is a plethora of isotopes.

The chemistry and reactivity of isotopes of the same element are almost identical, prompting their discoverer, Frederick Soddy, to say “put colloquially, their atoms have identical outsides but different insides.” The neutron does have some effect on the behaviour of the isotope and they separate out slightly under the right conditions. Take a spoonful of water from the Arctic or Mid-Pacific ocean and the isotopes of oxygen and hydrogen will be slightly different. Water with lighter isotopes is the first to evaporate, leaving behind seas enriched with heavier isotopes in warmer climes. Pour a glass of water from your tap and the blend of 1H216O, 1H217O, 1H218O, 2H216O, 2H217O and 2H218O depends upon where on planet Earth your tap resides. Similar effects can be seen with all the isotopes to differing degrees, and as those isotopes are taken up into the body, they leave an atomic trail of breadcrumbs as to where you’ve been. Isotopes incorporated in tooth enamel is locked in for life and so reveal where you were raised as a child. Isotopes in hair reflect more recent travels.

The forensic scientist and author of a 2010 book on forensic isotope analysis, Wolfram Meir-Augenstein of Robert Gordon University in Aberdeen, arranged to have hair, teeth and bone from the Lady of the Hills analysed for isotopes of carbon (13C), oxygen (18O), hydrogen (2H) and nitrogen (15N). Those in her hair matched proportions found in North Lancashire or South Cumbria and given the rate of hair growth she must have lived close to those areas in the time immediately leading up to her death. Isotopes in teeth and bone however, indicated she was from Thailand. Was she a so called Thai bride? 

Enquiries in Thailand eventually identified her as Lamduan Armitage new Seekanya, who had married in Thailand and then moved to Portsmouth, Rugby and then to Preston in Lancashire consistent with isotope analysis of her hair. DNA comparisons with family members in Thailand confirmed her identity last year.

As with so many other cold cases, her killer has not been identified. Police have said her husband, who lives in Western Kanchanabur, Thailand, is not a suspect but the Thai Examiner expressed frustration with the investigation. The British Newspaper The Sun, is campaigning to bring the culprit, whoever that may be, to justice. 

Isotopes can only go so far but without them it’s unlikely the women buried in the Yorkshire Dales would have ever been identified. And that has to count for a lot. I hope this blog post becomes out of date quickly, and this cold case can indeed be closed.

Education through adversity

A different sort of pandemic blog post, and a rather personal one.

There are problems reopening schools, universities are going virtual and post-graduates are struggling to complete. Education is having a hard time, and many students are rightly concerned about the impact this will have on their careers. If I was in this situation, I’d be worried as well – but I want to tell my personal story because it might offer a glimmer of encouragement, at least I sincerely hope so.

I come from a very working class background. Although not so uncommon for the time, I was raised in a house without a bathroom and with an outside toilet. The bath, as it was, was in the kitchen and filled from the sole hot water tap in the house only on a Sunday night. This might sound like the start of a “Four Yorkshireman Sketch” but I tell you this because it wasn’t just the material things of life that were in short supply but an attitude to life more generally. Seen as something for other people, education was “not for the likes of us” and the only book in my home was a Bible. I failed my eleven-plus and went to a terrible secondary modern school in South East London where the highlight of the curriculum was football. My family made me leave school at sixteen with a few CSEs,* whereupon I became an apprentice plumber at the now long-gone gasworks on the Old Kent Road. It was on the number-53 bus journey to and from work, where I read my first book, the Kraken Wakes, by John Wyndham. Something inside me made me curious and, determined to get an education, I took every opportunity I could. Oddly, my lucky break was being made redundant and I ended up getting a job at the gas-appliance testing laboratory, also on the Old Kent Road. Scientist there were all too happy to show me how to calculate the efficiency of gas-appliances, which I could soon do for myself, giving me a step up in the world. One of my unofficial teachers wore leg braces because of childhood polio. That puts the times into perspective.

I went to night school to get qualifications for University but it’s a tough route and since that time I have nothing but admiration for those who choose a part-time education. I was doing well until one Saturday morning the motorbike I was riding collided with a delivery van. Smashed up very badly, I was lucky to survive. In and out of hospital for nearly three-years, somehow I kept the education going and eventually found myself an undergraduate at the ripe old age of twenty six. When I graduated, then married with one child, I managed to ignore my mother who constantly berating me to “get a proper job”, and I embarked on a PhD. This opened doors completely invisible to me in those early days. The journey took me to three adjunct professorships, some amazing experiences and, sadly, osteoarthritis from the motorcycle accident. Even so, my journey hasn’t ended and I’m still learning new things. Having been bitten by the bug of curiosity, I can never be cured of an insatiable desire for knowledge. It will stay with me until I am no more.

I’m recounting this mini-autobiography because although I’m sure there will be many students despairing for their future, if you are determined, if you have a drive for education, if that curiosity is overwhelming, you will make it in the end. It might take longer, it might be harder, but you’ll look back and be proud of an achievement through adversity. Take it from someone who’s been there, and if I can do it, believe me anyone can. Stick with it and it’ll be worth it, I promise.

* A top-grade Certificate of Secondary Education (CSE) was equivalent to a mid-grade O-level. They were replaced in 1987 with the GCSE (General Certificate of Secondary Education).

A sober look at dexamethasone

A Covid-19 blog post for the non-expert

It stared with a 16th June 2020 press release  from the University of Oxford “Low-cost dexamethasone reduce death by up to one third in hospitalised patients with severe respiratory complications of COVID-19” – which triggered the equivalent of a media cytokine storm (pun explained shortly).

I do not want, for one moment, to dowse good news when it comes to Covid-19, but medical science is progressing during the crisis by press release and so I think it worth taking a step back to understand at the time of writing, the clinical trial is unpublished and not peer reviewed. Trawl through the media, newspapers and websites, and you’ll find pretty much a rejigging of what’s in the Oxford press release. A few newspapers, such as the Guardian, took the trouble to add some interviews but overall there was no explanation of what dexamethasone is, or what it does. So I thought I’d try to address that question in this blog post.

I once attended a lecture by Sir Martin Rees, the Astronomer Royal here in the UK, who said Astronomy was a simple subject. Many in the audience expressed surprise by this but he explained he thought real complexity was in biochemistry where there were so many interactions between molecules, membranes, cells and different tissues of the body. We might one day be able to understand the Universe’s beginnings and perhaps even how it will end, but he doubted if we would ever fully understand the multifariousness nature of biochemistry. Looking at the action of dexamethasone, I think, Martin Rees is right.

The immune system is complicated – beyond Martin Rees’s astronomy complicated. There’s probably more that scientists don’t understand about the immune system than they do. It’s evolved because there’s a whole world out there intent on killing you, one way or another, and the immune system is the ultimate defending army. A key part of the immune defence is inflammation, which is difficult to precisely define in immunological terms but in a nutshell, it’s a response against an irritant, anything from a splinter to a deadly virus, or indeed in some people, nutshells. Symptoms are erythema (redness), raised temperature, swelling and pain, which in the case of a splinter are external. Inflammation can also occur internally, such as with nut allergy for example, in which case it might become life-threatening.

Inflammation results in an increase in blood flow and an influx of a wide range immune system cells, commonly called white cells. Many of these cells were identified before their action was understood and so were named after their reaction to different stains under the microscope. And so you get, for example, basophils, neutrophils and eosinophils (eosin is a pink-red dye) as well as cells types, not named after microscopic dyes, such as mast cells, monocytes and macrophages. These cells come piling into the affray, like the proverbial Fifth Cavalry in a western movie to the sound of a bugle. Infected cells, of course, don’t have a bugle, instead they communicate with the immune system through small proteins called cytokines. There are around 80 known cytokines, including interferons, interleukins and TNF. TNF stands for tumour necrosis factor (although disregard the tumour part in the current context) and it’s one of the first cytokines produced to open surrounding capillaries to increase blood flow to allow more white cells in.

This plethora of cells and cytokines, together with other factors of the immune response such as a cascade of proteins called complement and, of course, antibodies, all react with each other making the complexity of the universe look trivial. Usually this biochemical and cellular mêlée is pretty good at seeing off infection and the inflammatory response plays an important role in that process. Don’t get the idea it’s all completely chaotic because the entire operation is controlled – or regulated in biochemistry-speak, chiefly through a structure in the cytoplasm called the “inflammasome”. Sometimes however, it all gets out of control, like a scrap between two schoolboys turning into a full scale riot. The communication proteins, the cytokines, go mad, attracting more immune cells, releasing more cytokine. It’s like the schoolboy fight going viral on social media, inviting anyone who wants a scrap from miles around. This has attained the name, cytokine storm and although it doesn’t have a precise definition, it became notorious in the 2006 clinal trial with TGN1412, which went horribly wrong. The term cytokine storm (or cytokine storm syndrome) actually originated earlier from a 1993 paper concerning adverse effects of organ transplants (1).

Now enter dexamethasone. In some cases, infection with SARS-CoV-2, the causative virus of Covid-19, sends the inflammatory response into overdrive, and that is the ultimate cause of fatality. Dexamethasone is a synthetic steroid of the type produced in the cortex (outer layer) of the adrenal gland, located just above the kidneys, and hence is called a corticosteroid. Corticosteroids find receptors in cells which initiate a chain of events involving RNA and DNA, down-regulating protein synthesis, damping down production of cytokinins and calming the inflammatory response like switching off social media in the middle of our metaphorical riot. Dexamethasone comprises a molecular skeleton common to all steroids, but with a fluorine atom added. It is a very potent anti-inflammatory drug, being around 25-times more potent than cortisol, for example. (Cortisol is more associated with the “fight-or-flight” response but it also has a role in moderating inflammation and is used as a hydrocortisone cream to treat eczema and dermatitis).

Dexamethasone is a well-establish drug used to treat a wide range of inflammatory disease including allergic responses, arthritis, lupus and some breathing disorders. In many ways it’s not surprising it helps in cases of severe SARS-CoV-2-induced inflammation and so unlike hydroxychloroquine, promoted so heavily at one point, it does seem to hold a lot of promise.

It is not however, an anti-viral, it does not inhibit infection, it is not a prophylactic, but it may save lives and for that some celebration is justified.

(1) Ferrara, J. L., Abhyankar, S. and Gilliland, D. G. (1993) Cytokine storm of graft-versus-host disease: a critical effector role for interleukin-1. Transplant. Proc. 25 1216–1217

Has the scientific method been suspended?

There’s a scene in the Netflix series Space Force when Chief Scientist Dr. Adrian Mallory asks, “why do you distrust scientists?” To which General Naird angrily replies, “you scientists say don’t eat carbs one day and only eat carbs the next”. One of the scientists in the room interjects, saying, “because of the sample sizes and long time period, day-to-day science is by nature an imprecise…” Naird cuts in with a frustrated, “shut up, shut up…”

I’ve heard the criticism that science is fickle all too often and you’d certainly get that impression if your sole source of science news was from the daily press. The two philosophies, that of the press and that of science are diametrically opposite. The general press want the sensational, here and now, while science is considered and unhurried. That’s not to say science isn’t competitive and there’s often a rush to publish, but one paper very rarely initiates a scientific consensus. Science works from accumulated information over time and a consensus will only form once there’s a body of consilient evidence all pointing in the same direction. The general press however, are all too happy to pick out a single publication and present it as an uncritical headline.

One of the best examples of science through press release remains how Stanley Pons and Martin Fleischmann announced cold fusion in 1989. Amidst a media storm, scientists across the globe tried to reproduce their results based on scant information and even committed the same sin of announcing positive data through their own press releases. It all ended badly, when those claiming to confirm cold fusion found artefacts in their measurements and there was a rush, not to publish, but to retract. 

Publishing a single peer reviewed paper will not convince scientists of its truth, as evidenced by Andrew Wakefield’s 1998 press briefing and subsequent paper in the Lancet, that there’s a link between the MMR vaccine and autism. This incident did unquestionable harm to medical science’s reputation and the slow retraction and enquiry did nothing to help. Nevertheless, science moved along in the meantime, albeit with its own snail-like pace, with many studies finding no evidence of any MMR and autism link. The Daily Mail however, was still publishing MMR anecdote in 2003 while ignoring the growing body of scientific studies. Wakefield was eventually struck off by the General Medical Council in 2010.

The cold fusion and MMR cases illustrates all too well the difference between scientists, who are human, fallible and sometimes dishonest, and the objective scientific method. I’ve heard the Wakefield case, and other similar instances, given as reasons why we should distrust scientific opinion. I’ve even heard the argument they are reasons to distrust scientific opinion on anthropogenic climate change.  This is a false equivalence, of course, because unlike Wakefield, consilient evidence for climate change has been building since the first paper linking carbon dioxide to temperature back in 1896 (1) and it’s no longer an opinion but as close to scientific fact as you can get. 

Having said all that, we are living in unusual times, with a viral pandemic taking many thousands of lives. We have suspended the process of scientific consensus at times, with announcements as pre-prints or press releases ahead of peer-reviewed publications, and even retractions after the event. Although our government mantra has been, “we’re following the science,” what they really mean is they are following scientific advice and although the advice comes from of the best in their field, it’s not the same thing as following the science. This might seem pedantic, and a moot point of philosophy, but it really isn’t.  Complaints from the scientific community are numerous that the advice, and basis for that advice, is not transparent and unavailable for wider review. The extreme urgency of the situation undoubtedly pushes aside the usual scientific conservatism, which is of course understandable and sometimes on the spot decisions are necessary, without time to weigh up all expert feedback. But they do this at peril, “because of the sample sizes and long time period, day to day science is by nature an imprecise…” and the public interrupts, “shut up, shut up..” 

(1) Svante, A. 1886. “On the influence of carbonic acid in the air upon the temperature on the ground.” Philosophical Magazine and Journal of Science.

Broken Clock Fallacy

I had a terrible bout of flu in November. In fact, my wife said she’d never known me so ill. I had a fever that went up and down, aching joints, a prolonged dry cough and found it hard to breath when laying down at night. I have an oxometer which occasionally dipped below 90% accompanied by light-headedness bordering on delirium. Do the symptoms sound familiar?

I’ve spoken to a number of people who had a similar illness around the same time and there are now suggestions Covid-19 reached the UK earlier than first reported. I understand why some think this, and the possibility that my November illness was Covid-19 had crossed my mind. Furthermore, if I was a betting man, I’d put money on several people reading this blog thinking the same thing. There is however, a major problem with this assertion because there’s no evidence for it. It’s more likely November and December experienced another flu-like outbreak, certainly unpleasant but not on the scale of Covid-19.

I shouldn’t be too certain however, because if there’s one thing we know about this virus, it’s there’s a lot we don’t know about this virus. As time goes by, and our knowledge grows, the arrival of Covid-19 to the UK at the end of 2019 cannot be ruled out entirely. If this happens, there will be those shouting, “I knew it all along,” and “I told you so.”  And then we get into another problem, that of the logical fallacy.

Logical fallacies have some great names such as, there’s no such thing as a Scotsman, Texas sharpshooter and the nirvana fallacy to name just three. If you’re interested, then you’ll find a lot of them here. The fallacy covering the, “I told you so,” if Covid-19 did arrive early, is called the broken clock. Those making the claim had no basis or evidence for it at all, but can claim they were right after the event on the basis even a broken clock is right twice a day. Fallacy spotting can be fun, but also very frustrating at times. 

A scientific tightrope

The two most senior scientific advisors to the UK, Sir Patrick Vallance (Chief Scientific Advisor) and Professor Chris Whitty (Chief Medical Officer) have come into a lot of criticism recently for failing to say what they really believe regarding the Government’s response to the Covid-19 outbreak. As Civil Servants they are meant to be impartial and have steadfastly refused to be drawn into the politics. Some think this is a good thing, others not so much 

I thought I would recount an episode of my own career, which was not as pivotal to national safety by any means but tells a story of how a scientists can become conflicted between honesty and loyalty.

I ended my commercial days as the Chief Scientific Officer of a blue-chip company based in York, UK and Maryland USA. It was my job to give scientific advice on the commercial direction of the company and I helped Business Development present scientific options to potential clients. I needed diplomacy in that job and walking the tightrope between intellectual honesty and the company’s commercial goals was a tricky balancing act. I did it as best I could, although one person in Business Development (who I now consider a good friend) once said I suffered from “wise guy Tourettes”.

There was an occasion however, where the company started to sell a particular option which I believed was not viable. In fact I emailed the CEO explaining my concerns, and received the curt response, “solutions not problems.” It was a tough time because I was expected – indeed instructed – to sell this option even though I knew it wasn’t possible to deliver. I refused to do so, but dodged the inevitable bullet until one day I was on the podium at a conference in the USA, where the CEO presented this non-viable option to the audience. The participants, all experienced scientists, were skeptical and one asked me directly if I agreed. I decided the time had come and said, “no I don’t”. As you can imagine there were repercussions and I was prepared to lose my job. As it happened, other events interceded and I got away with it and this particular option was never actually sold.

This experience makes me empathise with Vallance and Whitty because their tightrope is a lot tighter than mine ever was. I recognise their careful responses to certain questions as the sort of bullet dodging answers I gave. The impact of one of them breaking ranks and defying the government however, would be much more far-reaching than me losing my job and so I understand how they continue to walk that tightrope.  There might come a time however, where scientific integrity overbalances and they have to take a stand. Perhaps the government going against SAGE’s advice to open schools might be one of those times, who knows?

Is Covid-19 over… no it’s not!

In this blog I try to keep to the science I know, and If I don’t have enough expertise, I reach out to those who do. I declare therefore, I am wandering into fresh territory in this post and, at least in part, it’s my opinion – although I believe backed up with the facts. I know others might disagree with the opinions – and that’s fine, but I hope the facts stand for themselves.

I’ve seen comments on social media declaring the Covid-19 lockdown is over and we can get back to “normal”. I’m witnessing pubs opening and people gathering in my local area and a distinct relaxation of social distancing. I find this disturbing because we are not out of the Covid-19 crisis yet and the scientific experts are warning of the likelihood of a second wave.

The claim from government, up to now, has been they are following the scientific advice. If this was true, then coming out of lockdown now is certainly not following scientific advice. The independent SAGE report on re-opening schools explicitly says,

“…. The most recent estimates for the UK are that R is between 0.7-1, meaning that all scenarios modelled by SAGE are at risk of pushing R above 1. The school reopening scenario chosen by the government is not one of those modelled by SAGE making the potential impact of reopening even more uncertain. Robust testing systems are not in place everywhere. Additionally, public adherence to social distancing is influenced by trust in the government and its messaging. This trust is increasingly strained. We therefore believe that by going ahead with a general school reopening from 1st June, the government is not following the advice of its SAGE group and is risking a new surge in cases of COVID19 in some communities.”

There are those who point out the economic damage of a prolonged lockdown and I understand that. The problem of course is how do governments and their advisors balance the risk of Covid-19 fatalities with economic damage. That’s a hard question and not one that I would want to tackle. The UK however, has an appalling record of Covid-19 fatalities. The current statistics show the UK is one of the worst hit countries, certainly in Europe and, depending how you cut the statistics, also in the world.

If this situation is because the country was late to enter lockdown, then we will not compensate by coming out too early. And what I fear most is that given the polarised politics of today, the government will try to shift blame towards scientists. If this happens, then just remember the words of the SAGE report,

“… the government is not following the advice of its SAGE group and is risking a new surge in cases of COVID19 in some communities.”

Covid-19 vaccine pessimism

Another blog on Covid-19 for the non-expert


I’ve seen claims on social media and in the press saying a vaccine for Covid-19 may never arrive. The Telegraph, and The Guardian are two examples.

The three most commonly quoted reasons I’ve seen for vaccine pessimism are: (1) vaccines take many years to make, the mumps vaccine took four years. (2) We still don’t have an effective vaccine against HIV and (3) we still don’t have any vaccines against SARS and MERS.

All three points are correct but only superficially, and so let’s look under the surface and put the claims into more detailed context.

Scientists isolated the mumps virus in 1945 and the first vaccine appeared in 1948, although its effectiveness was short term. The Jeryl Lynn vaccine was launched in 1967 in the United States and entered routine use in 1977. The mumps vaccine therefore took between three years or 22-years to develop, depending upon how you look at it. The problem with comparing Covid-19 to mumps however, is the year the first mumps vaccine appeared, 1967, was 53-years ago. At that time there was only one way to make a vaccine and that was from the virus itself. It was necessary to isolate the virus, then inactivate it so it remained potent to the immune system but non-pathogenic (known as an attenuated vaccine). Things have come a very long way since 1967. Nowadays we no longer need the virus itself, but only its genetic sequence (RNA in the case of Covid-19).

Covid-19 was first reported in December 2019, and by February 2020 the 26,000 – 32,000 RNA code sequence of SARS-COV-2 (the Covid-19 virus) went round the world via the internet. Genetic sequencing and the internet were both science fiction in 1967; in fact the structure of DNA was only elucidated 14-years before. Vaccine development today is another world, and comparing a Covid-19 vaccine to one for mumps is like saying electric cars are impossible because there weren’t any in the 1960s.

HIV was first identified as the causative virus for AIDS in 1984 and despite some trials, no effective vaccine has emerged. HIV however, is an entirely different virus and if SARS-CoV-2 was anything like HIV, few scientists would be optimistic of ever getting a vaccine. HIV attacks the immune system, the very thing a vaccine stimulates in the fight against infection. HIV also mutates rapidly, and it’s ability to mutate appears to be built into its very biochemistry because a key enzyme in its reproduction (reverse transcriptase) cannot translate its genetic code accurately. This has led to over 60 strains of HIV virus world-wide. SARS-CoV-2 is far more stable and all evidence suggests it does not attack the immune system. Comparing HIV and SARS-CoV-2 regarding a vaccine is like saying I can’t rid my lawn of dandelions because I can’t eliminate Japanese knotweed.

There was an outbreak of SARs in 2003 and MERS in 2012. The reason why no vaccine has emerged for these viruses is less technical than for HIV – no one has really tried. There was an initial effort and there are vaccine candidates, but it soon became clear that neither of these diseases turned out to be the deadly pandemics they were first thought to be. They were successfully contained and haven’t been seen for several years.

By far the biggest difference between attempts at a Covid-19 vaccine and any other are the enormous international collaborative efforts currently taking place. There are an estimated 100 Covid-19 vaccines somewhere in development as well as other possible treatments such as a range of drugs, both established and new, including antibody-type treatments which proved successful against Ebola. (Remdesivir was aimed at Ebola but was succeeded by antibody-type drugs. Remdesivir is now being tested against Covid-19). At the leading edge of fresh approaches is research into RNAi. (Richard Jorgensen discovered RNAi, after he became curious about patches of colour on petunia petals. His investigations led to the discovery of a whole new branch of genetics and won him the Nobel Prize in 2006).

We have to be realistic about the possibility and timing of a vaccine, or other treatment, and it may turn out no such vaccine emerges, or if it does, it might be years away. The honest answer is we don’t know but I do believe there are reasons to be optimistic. The Jenner for example are entering Phase II and III trials after promising phase I results. But in the meantime, if a more pessimistic climate arises, then at least let’s make sure it’s for the right reasons and not some spurious comparisons.

Covid-19 – warnings ignored

I’ve heard it said, we have not experienced a pandemic since the Spanish flu of 1918 so how could anyone predict Covid-19? Just about everything in that statement is wrong.

Everyone has heard of Spanish flu, but how many have heard of the 1957 flu pandemic, or the one in 1968? We see an annual upsurge of influenza every year which on average kills about half a million people worldwide. The United States sees about 20,000 deaths a year and Europe(1) about 70,000 due to influenza. Spanish flu was far more deadly, killing an estimated 17 million to 50 million people – and possibly many more. It was by far the worst flu pandemic in over a hundred years, but it wasn’t unique. The 1957 flu pandemic, also known as Asian flu, was first identified in Singapore in February of that year. It rapidly spread around the world and resulted in about one to two million deaths. Here in the UK it killed an estimated 30,000 people, making it comparable with the death rate of Covid-19. The 1968 flu outbreak was first identified in Hong Kong and killed around a million people worldwide.

It’s difficult – and potentially misleading – to classify influenza viral potency by simply comparing death rates because there are many confounding factors, such as modern vaccines for seasonal flu, susceptibility and age of the fatalities, the proportion of survivors left with lasting medical conditions and the measures taken to stem the rate of infection. They took very few measures to prevent the spread of Spanish flu and in 1918, there were no flu vaccines of any kind. In 1957, the UK were very slow to react, eliciting outrage from scientists such as John McDonald at the Public Health Laboratory Service (later to become director of the Epidemiological Research Laboratory and then chair of the Department of Epidemiology and Health at McGill University in Montreal). He wrote to the Royal College of General Practitioners, “Although we have had 30 years to prepare for what should be done in the event of an influenza pandemic, we have all been rushing around trying to improvise. We can only hope that at the end it may be possible to construct an adequate explanation of what happened.”

The 1968 flu pandemic was a little different in that it was more contagious than previous outbreaks, and the morbidity rate in younger people was higher. There was yet another influenza pandemic in 2003 (SARS) and then MERS in 2012, both of which fizzled out before they became major pandemics. In the historical context of flu outbreaks therefore, the idea Covid-19 came “out of the blue” and no one could have predicted it, seems ridiculous. Scientists have in fact been warning for years that a viral pandemic wasn’t just likely but inevitable. Papers have been published in the scientific literature including the most prestigious journal Nature in 1997, there were reports from the World Heath Organisation, the United States Federal Emergency Management Agency report 2019 and the UK’s Exercise Cygnus in 2016 to give just a minimal number of examples.

Despite this, in the main, warnings were ignored and the collective governments of the world were caught with their pants down. The warnings of John McDonald’s letter have been repeated and instead of having a well-prepared plan, the world just tried to improvise. Some countries improvised more than others, and some became the proverbial headless chickens. And realise when Covid-19 is over, the next pandemic is just as inevitable. The scientific outcry of 1957 have been largely ignored, and so let’s hope we don’t make the same mistake again. The German philosopher Friedrich Hegal wrote, “we learn from history that we do not learn from history”. Regarding viral pandemics, so far Hegal has been proven right. Let’s hope in the future he’s proven wrong.

1 – As defined by the WHO European area