Spanish Flu, and what it teaches us about social distancing

First of all, hi there to all my readers! I’m sorry I haven’t written anything in a while. Things have been intense with the day job – any teachers reading this will know that working from home and delivering remote learning is actually a lot more labour intensive than face-to-face teaching. Like so many other people, I’ve also been finding social distancing tough. I’ve been asked how I cope with it, and the simple answer is, because I know that I have to. In this article I will be looking at the 1918-19 Spanish Influenza pandemic, and explaining the lessons we can learn from it about social distancing.

It’s inevitable that parallels will be drawn between the situation now, and the Spanish Flu pandemic. This time 100 years ago, the world was reeling from a devastating global pandemic that had killed more people than the preceding four years of war.

It has been suggested that Chinese labourers brought the disease to Europe

The origins of Spanish flu have been hotly debated. There is speculation that the virus originated in China, and was brought to Europe by Chinese labourers working for the British and French armies – a theory that has been seized upon by conspiracy theorists looking for evidence of sinister Chinese involvement in the current pandemic.

Those studying Spanish flu, particularly epidemiologists, have a wealth of data to work with. It was the first global pandemic to occur in an age where there was good record keeping in both military and civillian hospitals.

The initial outbreak was probably Fort Riley in Kansas

Detailed studies of records kept by the US Army have actually narrowed down the origin of the disease to the state of Kansas, and the US Army training camp at Fort Riley. The evidence strongly supports the theory that the disease jumped directly from birds into humans, with ‘patient zero’ being a farm worker from a poultry farm who caught the disease just before enlisting in the US Army.

Wartime conditions were almost ideal for spreading the virus. After the first cases were reported, the illness spread rapidly through Fort Riley; movement of troops ensured that it spread rapidly to other camps and into the civilian population. Troops with the illness were sent overseas to fight, meaning that the disease very quickly spread to England and to continental Europe. It is ironic that the entry of the USA into the war, which was instrumental in bringing it to an end, also ensured that the Spanish flu outbreak became a pandemic.

Nurses in a military hospital treating a patient with Spanish Flu

I won’t dwell here on the disease itself and its effects. If you want to know more, I thoroughly recommend Lyn McDonald’s book ‘The Roses of No Man’s Land’ which contains harrowing first-hand accounts from doctors, nurses and others, of the effects of the illness in crowded military hospitals, camps and troopships.

Spanish flu spread rapidly on troopships such as the RMS Olympic (sister ship to the Titanic)

What I find interesting, and highly relevant, about the Spanish flu pandemic, are the lessons we can learn about social distancing. Wartime conditions meant that social distancing simply wasn’t possible – in fact, the opposite was the case with people crammed together in hospitals, training camps, troopships and, of course, the trenches themselves.

King Alfonso XIII of Spain became seriously ill but survived

Another, more pernicious factor that contributed to the spread of the disease was lack of public information. Basically, the public were not told about the illness for fear that it would damage morale in the critical final months of the First World War. People who could have practiced social distancing didn’t, for the simple reason that they did not realise there was any need to. The pandemic got its name because in neutral Spain, there were no restrictions on the press; they were even free to report when King Alfonso XIII became seriously ill. This led to a misconception that Spain was particularly hard hit.

Not only was social distancing not practised, the British government actually discouraged authorities from putting measures in place to limit the spread of the infection. Medical officers in large cities were discouraged from closing schools, churches, cinemas, theatres, dance-halls etc.; again, out of fears that this would damage morale.

Dr James Niven, medical officer for Manchester during the pandemic

One man who went against this was Dr James Niven, medical officer for Manchester. Against direct advice from the government, he closed schools and entertainment venues, and distributed posters and leaflets giving information about the illness and advice on how to protect against infection (mainly, ‘wash your hands’ – sound familiar?). Niven insisted on quarantine for those who were sick, gave regular interviews to the Manchester Guardian to keep the public informed, and took measures to deal with delays in funerals.

As a result, the rate of infection in Manchester was lower than in other large cities with similar population densities. The death rate among those infected was also lower, because medical services were now overwhelmed as they were elsewhere. High tech devices such as ventilators were not available in those days, but high quality medical care, particularly intensive nursing, could make all the difference between surviving or dying from the illness.

One of Niven’s posters informing the people of Manchester about the Spanish Flu

I’ve no doubt that during the Spanish flu pandemic, there were those living in Manchester who resented the restrictions. Why were their cinemas closed when those in other cities remained open? No doubt, too, there were those who regarded Niven’s information campaign as exaggerated or scare-mongering. I also am in no doubt that if I went back in time to 1918 and had to live in a large city in the UK, I would choose Manchester with its social distancing.

In my next post I will be discussing the differences between oxygen therapy, continuous positive air pressure (CPAP) and ventilation; and the role they all have to play in helping people survive COVID-19. Stay well and safe, everyone.

Social distancing: Why it’s important, and why we find it so difficult

Social distancing has been in the news a lot in the last few days here in the UK, mainly because we Brits seem to be very bad at it! Friends in countries that are locked-down, like France and Spain, are telling me how shocked and horrified they are by scenes this weekend of crowds flocking to parks, beaches and beauty spots. The UK government is threatening lock-down unless we start to take things seriously. In this post, I will discuss why social distancing is important, and some possible reasons why we are finding it so difficult.

Exponential growth curve for hypothetical ‘Virus X’.

Why do we need social isolation? Let’s think about how disease spreads. A person gets infected with a disease, we’ll call it Virus X. That first person to be infected is called Patient Zero. On the first day, Patient Zero infects two other people. On the second day, they each infect two more, and so on. After a week, we have 256 patients.

If each patient infects 5 people a day, then after one week there will be 78125 people with the disease. If each infected person passes the virus on to 10 people, then after a week there will be 1 million with the disease. You get the picture. This process is called exponential growth and is shown on the right. If the shape of that curve is familiar, it’s because you have probably seen it on graphs showing the number of cases of COVID-19 in the UK, like the one below.

Cases of COVID-19 in the UK. In blue, you can see a classic exponential growth curve.
Comparing the spread of ‘Virus X’ with and without social distancing.

How does social distancing help? Basically, unless an infected person is in close contact with someone else, they can’t spread the virus. Exponential growth will still occur, because there will always be some in the population who cannot practice social distancing, i.e. key workers. But the rate of exponential growth will be much slower. This is known as ‘flattening the curve’ and is shown on the left.

An additional consideration is that although discoveries about COVID-19 are being made at an unprecedented rate, there is still a lot that we don’t understand. When you get an infection, it will be several days before you start to show symptoms; this is called the incubation period and varies between different pathogens. When the level of the pathogen in your body drops below a certain level, your symptoms will go away; but you are not yet fully clear of the infection.

A few people have asked me why this pandemic is so different from the 2009 Swine Flu pandemic. With Swine Flu, we were dealing with a new strain of a very well understood virus. In particular, it is known that influenza viruses can only be passed on to other people by patients who are symptomatic. During the incubation and recovery periods, patients cannot pass the virus on except under exceptional circumstances. This meant that only those who were actually ill needed to be isolated. In addition, it is known that patients who recover from influenza viruses will then be immune to the disease.

With COVID-19, the incubation period is up to 14 days, and we still don’t know at what point patients become infections. We also don’t know how long it takes for recovered patients to cease to be infectious, and whether people who have recovered have immunity. We need to know whether immunity develops; how strong it is; and how long it lasts.

Look at the two diagrams below, showing the spread of the hypothetical Virus X through a population. On the left is the situation on Day 1, on the right is the situation after one week. The top diagram shows a population that is not practising social distancing, the bottom diagram shows a population that is. Speaks for itself, doesn’t it?

So, why is social distancing so difficult? Especially for us Brits, who historically have a reputation for doing as we are told. One reason is that we are having to break habits that have become ingrained over many years. Take this scenario: you are in a queue at the supermarket. The person in front of you moves forward, what do you do? You move forward too, to close the gap. This is not neccessarily deliberate, it’s a habit, and changing habits requires conscious thought. The good news is that it doesn’t take long for new habits to develop. I went shopping today (because I needed to, I hasten to add), and everyone was keeping their distance in the queue without needing to be reminded.

Another reason is people are used to freedom of movement. It’s a sunny spring weekend, the kids have been stuck in the car, let’s go to the beach because social distancing means no one else will be there. Unfortunately, hundreds of other people have had the same idea, and when you get there, it’s heaving. Do you have the strength of mind to turn the car round and tell the kids we aren’t going to the beach after all?

Recent panic buying is not helping either. Those of us who have continued to shop sensibly and responsibly have found that due to panic buying, we have had to visit multiple shops to get the basics. I’m trying to practise sensible social distancing due to my asthma, but it’s difficult when you have to visit 3 different shops to find toothpaste! Thankfully things seem to be settling down a bit. This morning I went to a local supermarket and was able to pretty much get my normal weekly shop, much to my relief!

Possibly the biggest barrier to social distancing, though, is the fact that we are primates, and by and large, primates are social animals. Our brains are not wired for isolation and I know I am not alone in worrying about how this will affect my mental health. However, there is a lot we can do to combat this.

The good news is that we live in an age where technology has made it easier than ever to keep in contact with friends and loved ones. So take advantage of Facebook, Zoom, WhatsApp, Skype and everything else that’s out there. Reconnect with people you’ve lost touch with. Share memories of good times! And keep remembering, social distancing isn’t forever; and the better we are at it, the less time it’s likely to last.

In the next couple of days I will be posting some ideas about simple experiments you can do at home to engage children with science while they aren’t at school, so watch this space! As always, if you have specific questions or concerns you’d like me to address, let me know. Stay safe and well, everyone.

Drugs to treat COVID-19: how close are we?

Donald Trump has been in disagreement this week with top scientists by claiming that the anti-malarial drug chloroquine should be adopted immediately for treating patients with COVID-19, and even given as a prophylaxis. In this blog I will explore the challenges facing scientists working to develop drugs to treat COVID-19 and discuss recent advances, including chloroquine.

What are the challenges in designing anti-viral drugs? After all, there are a lot of antibiotics out there that work for a whole range of different bacterial infections. Let’s look at the structure of a bacterium, shown below.

Compared with a virus, the structure of a bacterium, shown below, is highly complex. Bacteria carry out a huge number of chemical reactions and process. They release energy through respiration; they make proteins; they replicate their DNA in order to reproduce. And that’s just for starters; there are many, many more processes going on. Viruses, by contrast, can’t do any of these things without infecting a cell and using its organelles.

Structure of a bacterium. There are many different processes which can be targeted by antibiotics.

With bacteria, inhibiting or blocking even one of these reactions or processes can be enough to kill it. All chemical reactions in living organisms are controlled by enzymes, which are a type of protein. Each protein controls one, specific reaction. Disable the enzyme, and you stop the reaction.

For example, penicillin works by disabling the enzyme that bacteria use to maintain and repair their cell walls. The cell wall disintegrates, and the bacterium dies. Baytril, an antibiotic widely used in veterinary medicine, interferes with the replication of DNA, meaning that the bacterium can’t reproduce.

So, why are viruses harder to fight? The answer lies in the fact that viruses are so simple, meaning there are far fewer reactions and processes for drugs to target. One virus that is treated very successfully with drugs is HIV. So, why can’t some of the drugs used to treat HIV be adapted to use against COVID-19? By virus standards, HIV is quite complex. It’s a type of virus called a retrovirus, which has a more complicated reproductive cycle than other viruses. To put it simply, most of the drugs used to treat HIV are blocking or inhibiting processes that just don’t happen in COVID-19. Two HIV drugs, lopinavir and ritonavir, have shown some promise in treating COVID-19.

The structure of a virus is much simpler than that of a bacterium.

One of the most promising potential treatments is a drug called favipiravir. It’s a drug being developed in Japan, specifically to treat RNA viruses, and COVID-19 is an RNA virus. Originally developed as a treatment for influenza, trials have been carried out in China on 340 patients who had tested positive for COVID-19. It was found that the drug significantly shortened the time taken for patients to test negative, and that respiratory symptoms and lung function improved as well.

Why then, is favipiravir not being adopted immediately? The answer is that it has only been licensed to treat influenza. This means that extensive clinical trials must take place before it can be licensed for COVID-19 to ensure that it is safe and effective.

What about chloroquine? Chloroquine is an old drug, it’s been used for over 80 years to treat malaria, which is a disease caused by a parasite carried by mosquitos. It has been known for a while that chloroquine has antiviral activity. It basically prevents viruses from sticking to the membranes of cells, meaning they cannot enter and infect them.

So far, the evidence supporting chloroquine is anecdotal – this means it does not meet the standard to be considered reliable. Some doctors in China and South Korea have given it to patients with COVID-19 and seen improvements; and in France, 24 patients were given a similar drug, hydroxycloroquine, and showed improvements.

Chloroquine shows promise in treating COVID-19, but a lot more research is needed.

These were small scale experiments and not carried out under the controlled conditions of a clinical trial. As a result though, 6 properly designed clinical trials are getting underway around the world to test whether chloroquine or hydroxychloroquine are safe and effective against COVID-19.

If either chloroquine or hydroxychloroquine do turn out to be effective, it would be a major breakthrough. Because both have been used for many years in treating malaria, they are already known to be safe. They are also safe to take during pregnancy; there are concerns that favipiravir may have adverse effects on a developing foetus. Both drugs are cheap, and facilities to manufacture them in large amounts are already up and running.

There are downsides. The side effects of chloroquine or hydroxychloroquine are pretty unpleasant, mainly nausea and diarrhoea. In rare cases chloroquine can cause blindness. An important consideration too is their use in treating malaria. Drug resistance in malaria is a big concern to those involved in treating it.

The risk of malaria developing resistance to chloroquine and hydroxychloroquine must be carefully evaluated.

There are already a number of strains of malaria that are resistant to both chloroquine or hydroxychloroquine. The risk malaria resistance must be evaluated before using them to treat COVID-19 in places where malaria is active. For example, it’s now malaria season in southern Africa and malaria will be active until around the end of April. In India, malaria season begins in May.

In terms of drug development, there is a lot to be optimistic about. It may well be that an effective treatment is developed before a vaccine. Certainly, many scientists are now beginning to talk about a timescale of months, rather than years, for developing an effective treatment. I will keep you all up to date about advances as they occur, meanwhile, stay safe and well!

COVID-19 and pets: facts and fiction

I’m not in full-blown isolation yet but I am practising pretty stringent social distancing. At times like this, the companionship of our pets is more important than ever, particularly for those like me who live alone. I’ve seen a few posts about animals and COVID-19, and as usual, there’s rather more scaremongering than factual information. In this blog, I am going to address four issues. Can domestic pets catch/ spread COVID-19; is it safe to take a pet to the vet; what precautions should pet owners be taking; and is hand-sanitiser toxic to pets.

First, can our pets catch COVID-19? The answer is, no. Coronaviruses are zoonotic, which means they can spread from humans to animals. However, this requires large numbers of humans and animals to be crowded together, as was the case in Wuhan. The current advice from the WHO is that there is no evidence at all that pets can catch COVID-19.

As a ferret owner myself, I am aware that there is a lot of worry in the ferret community because ferrets can catch flu from humans. Also, the fact that ferrets were initially used in vaccine testing has got people worried. The reasons ferrets were initially thought to be a good choice for vaccine testing were that they are generally quite susceptible to respiratory infections; and they can catch the coronavirus that causes Severe Acute Respiratory Syndrome (SARS).

However, ferrets were very quickly rejected for vaccine testing. It was found that if deliberately infected with the virus, they showed no symptoms. Not only that, but within a few hours, they were testing negative for the virus.

The one thing I would say to ferret owners is that the early symptoms of COVID-19, which ferrets can’t catch, are very similar to those of flu, which they can. With the focus so much on COVID-19 we sometimes forget that all the normal colds and flu that circulate at this time of year are still doing the rounds. So if you get a sore throat, fever and dry cough, it would be prudent to avoid contact with your ferrets until you know what you actually have.

What about dogs? It is known that dogs can be susceptible to coronaviruses. They can catch three specific strains: Type 1 & 2 canine coronavirus, both of which cause diarrhea; and Canine respiratory coronavirus’ that causes kennel cough. There is no evidence that they can catch the COVID-19 strain. A single dog in Hong Kong has tested positive for the virus but did not get any symptoms. Actually, to say that there is no evidence to suggest that dogs can catch COVID-19 isn’t quite correct; it would be more accurate to say and there is plenty of evidence that they CAN’T – there has been extensive testing of dogs in China and Hong Kong.

Cats can also catch one, very specific coronavirus; Feline Infectious Peritonitis. Again, there is absolutely no evidence to suggest that they can catch COVID-19. There is also no evidence to suggest that humans could spread the virus to other pets such as rodents, reptiles and birds.

So to the second question: can pets spread COVID-19? In theory, yes. There is evidence that the virus can survive for short periods outside a host. However, survival is most likely in droplets on smooth, non-porous surfaces. Animal fur does not fit this description. In theory, if you have COVID-19 and cough all over your cat, then someone else puts their face in the cat’s fur, there’s a small risk of transferring viable virus. But if you have COVID-19 self isolation means that should not be happening!

Beenie boys love to get mucky! But that doesn’t mean they are spreading COVID-19.

Another thing to consider is how clean most animals keep themselves. If you cough all over your cat, I guarantee they will gallop off and have a jolly good wash, only pausing now and again to give you their best ‘you humans are absolutely disgusting’ glare. Ferrets are also very clean, with the possible exception of beenie boys but I don’t think poo-surfing is going to spread the virus ;). Dogs aren’t quite as meticulous but again, short of actually coughing on them, they are not going to harbour the virus on their coats.

Basically if you have a pet and are ill, self-isolating or in a vulnerable group, the overwhelming advice is that it’s fine to be around your pet, but practice good hygiene such as regular hand-washing. Also clean food bowls, water bowls, litter trays etc. regularly – which we should all be doing anyway.

So, it it safe to take your pet to the vet? There are two things to consider here: your pet’s safety, and that of yourself and the vet staff. As far as your pet goes, the vet’s surgery is a perfectly safe environment, and if he or she needs treatment, they absolutely MUST be seen by a vet! I’ll talk later about sensible contingency plans for those with pets.

If you are self-isolating, you definitely should not take your pet to the vet yourself, for your own safety and that of the veterinary staff. If you are vulnerable but not in full-blown isolation, it’s not so clear-cut but consider things like how easy it is to practice social isolation in the waiting room or consulting rooms. I do know that in every veterinary practice I’ve ever used, they are absolutely scrupulous about hygiene, and you can bet they will have stepped this up.

You may find in the coming weeks that your vet may cancel or postpone routine, non-urgent procedures. This is to minimise the risk to staff and ensure that if they have staff members going off sick, they still have the capacity to provide care for your pets. You can also be 100% confident before postponing any procedure, your vet will have carried out thorough checks to make sure that doing so will not adversely affect your pet’s health.

Dogs need exercise and it’s important to plan for who will walk them if you can’t

If you have pets, it’s sensible to have a contingency plan for what will happen to them if you become ill or have to self-isolate. This is particularly important for those living alone. I’ve installed a key safe on my property and three good friends have the combination. I have people lined up who would deliver pet supplies, and who would also help out if, for example, I had to go into hospital. Which I have no intention of happening! Dogs will need to be walked no matter what, so dog owners also need to ensure you have someone lined up to walk the dog if you can’t.

So, is it safe for you to take a pet to the vet whose owner is ill or self-isolating? Absolutely yes. Cats, ferrets and small animals will be in carriers. My plan would be that when the person collecting the pet arrives, I would put the pet carrier outside my front door then go back in and shut the door; the person collecting can then come and get the carrier. Wear disposable gloves and wipe the carrier down. On returning the pet, repeat in reverse. With dogs, which are probably on a lead, think about how you could hand the lead over to someone else while maintaining isolation. Planning ahead is the key here!

Finally, what about hand sanitiser? The rumour is that it contains ethylene glycol, which is toxic, and that if your pet licks your hand after you’ve used it, they will be poisoned. Not true. Hand sanitisers contain ethanol, or in some cases propanol. Which is toxic in large doses, but your pet would have to ingest a heck of a lot of it! In the ferret community we’ve used hand sanitiser for years at shows, with no ill effects whatsoever.

If you want further information, the PDSA website is fantastic:

It only remains for me to thank those whose photographs appear in this blog: Milo (drooly tabby and white cat); Beezy (ginger ninja cat); Crooks (handsome dark polecat ferret); Wookie (mucky beenie ferret – he’d just been up the chimney! No longer with us but would be very proud to have been chosen as an example of a messy beenie boy); Tess (angora diva ferret whose pic I didn’t need but she insisted); and Ebony (greyhound who’s sadly no longer with us, but who adored the beach!)

COVID-19 and ibuprofen – what are the facts?

Hi everyone, there’s been a bit of scaremongering out there (surely not??) about ibuprofen making the symptoms of COVID-19 worse. In this post, I will give you the facts, and the latest advice from the World Health Organisation (WHO).

It started with a Tweet on 14th March by French health minister Olivier Veran, stating that anti-inflammatories such as ibuprofen could aggravate the symptoms of COVID-19, and that the symptoms of COVID-19 should only be treated with paracetamol.

Ibuprofen is on of a group of drugs known as non-steroidal anti-inflammatory drugs or NSAIDs. Other examples include aspirin and naproxen. M. Veran claimed that ‘serious adverse events’ had been reported in COVID-19 patients being treated with NSAIDs and that their use should be banned. No details were given about these supposed ‘adverse events’ at the time.

On 17th March, the French state-owned news service, Agence France-Presse, stated that this was based on evidence published in the medical journal The Lancet on March 11th. I’ve read the article and trust me, it makes absolutely NO mention of ibuprofen or any other NSAIDs. It’s actually about increased risk of complications from COVID-19 in patients with a combination of diabetes and hypertension (high blood pressure) who are being treated with a specific class of drugs that are not remotely related to ibuprofen or any other NSAIDs.

Following M. Veran’s tweet, the WHO did the sensible thing and advised against the use of ibuprofen to treat COVID-19 until they could clarify the situation. After a full investigation and analysis of all the available evidence, on March 18th both the WHO and the European Medicines Agency (EMA) issued statements saying that there was no evidence of a link between ibuprofen and worsening of COVID-19 symptoms; and that there was no recommendation against taking ibuprofen or other NSAIDs.

So, is there a risk? NSAIDs are known to trigger or worsen the symptoms of asthma in some people. If your asthma is triggered by NSAIDs, you will already know not to take them. I know that for me, the NSAID diclofenac is one of my triggers. Ibuprofen is fine, so are aspirin and naproxen, but to be on the safe side, I try to avoid using them for longer than 2-3 days.

So, there is no reason not to use ibuprofen or any other NSAID to treat symptoms of COVID-19, provided you read all the information and follow the instructions on the pack. Personally, if I am unwell, I prefer to use paracetamol, which relieves pain but is not anti-inflammatory. But that is because inflammation is an important part of how your immune system fights infection so if possible, I prefer to let it do its stuff!

A final note. If you are being prescribed ibuprofen or any other NSAID for a long-term medical condition and you are worried, don’t stop taking it but do consult your doctor for advice. Later today, an update on progress in the search for an anti-viral drug to treat COVID-19. Watch this space!

How scientists study new viruses: crystallography

In the fourth post in my series on how scientists study viruses, I am going to talk about crystallography. Crystallography involves shining a beam of X-rays through a crystal. By looking at how the X-rays pass through the crystal, scientists can actually generate a detailed picture of the structure of a molecule and how the atoms are arranged.

So, how does it work? Think of the waves you see in the ocean. They are straight lines, more or less, like the picture on the left. Now think of what happens when you throw a stone into a pond. The waves spread out in a circle from where the stone hit the water, as in the picture on the right.


Now, let’s look at what happens when a straight wave is forced through a narrow gap. It spreads out in a half-circle. This is called diffraction and is shown in the diagram on the right. What does this have to do with studying viruses? It’s to do with the fact that X-rays behave like waves.

Basically, if you shine X-rays through a crystal, tiny gaps between the atoms act like the narrow gap in the diagram and make the waves spread out into circles. These then meet waves emerging from other gaps, causing an interference pattern. You can see an interference pattern for yourself by dropping two stones into water close together, and watching what happens when the waves meet. By analysing the interference patterns when X-rays pass through a crystal, scientists can work out the arrangements of the atoms.

Dorothy Crowfoot Hodgkin with models of (L-R) penicillin; insulin; vitamin B12. In the frame is the first structure she solved: cholesterol.

One of the most important scientists in the development of X-ray crystallography was Dorothy Crowfoot Hodgkin. She solved the structures of cholesterol and penicillin, and in 1956 she found the structure of vitamin B12, for which she was awarded the Nobel Prize in 1964. However, she is best known for solving the structure of insulin in 1969.

The basic principals of crystallography are no different today to what they were in 1914 when the first crystal structure (table salt) was solved. What has revolutionised crystallography is the development of computers.

To get from measurements of interference patterns to a molecular structure requires some truly horrendous maths – one of the few bits of my chemistry degree that I really didn’t enjoy at all! It took Dorothy Hodgkin 30 years to solve the structure of insulin, and insulin is a comparatively simple molecule. Modern computer processing means that scientists can determine the structures of very complex molecules, like the spike protein on the surface of COVID-19, relatively quickly.

Modern X-ray crystallography equipment at the University of Strathclyde

So, how are scientists using crystallography to study COVID-19? They are using it to determine the chemical structures of molecules that make up the virus. The most important of these is possibly the spike protein. This is on the surface of the virus, and the virus uses it to attach itself to the surface of a human cell. An important part of how your immune system fights the virus is by making antibodies which are exactly the right shape to attach to the spike protein.

X-ray crystal structure of the COVID-19 spike protein

Scientists have been able to isolate the spike protein and grow a pure crystal; they have then used crystallography to solve the structure. Knowing the exact structure of the spike protein will help those developing vaccines and anti-viral drugs to combat COVID-19. Also, scientists can monitor how the spike protein changes when the virus mutates; this knowledge will help to make sure that any vaccine will continue to work if there are mutations.

The structures of other important molecules in the virus have also been solved, including an enzyme called protease. Enzymes are substances that control chemical reactions; protease controls the production of the proteins needed to make new viruses. By solving the structure, scientists have identified how it could be stopped from working. As a result, a team in Shanghai are investigating 30 (yes, 30!) molecules that could be used to treat COVID-19. And that’s just one of hundreds of teams around the world.

Structure of COVID-19 protease enzyme. This shows how a potential drug molecule (in green) could bind to the enzyme and stop it working.

I hope this has been interesting/ helpful. As a scientist myself, I am in awe of what has been achieved in such a small time, and how much we now know about the virus. There is actually plenty of good news out there, if you know where to look for it, and you can be sure that I will keep you updated of new discoveries as and when they happen. In fact, I’ve just found out that some drug trials in China are showing real promise, so watch out for a post about that later today.

How scientists study new viruses: microscopy.

Early microscope made by Italian scientist Galileo

Confession time here: microscopes are one of my favourite things, ever! I love investigating things with a microscope and could happily spend hours messing about with one. The strangest experiment I ever did was to get a friend’s cat to lick a microscope slide so we could see what was in her mouth. In this post, I will talk about how scientists use the latest in microscope technology to study viruses.

The use of lenses to make objects look bigger dates back to the 13th century. It’s not certain who actually invented the microscope; but they started to appear in the mid 17th century. Italian scientist Galileo Galilei played an important part, using his knowledge of telescopes to improve on earlier inventions.

Typical optical microscope used in schools and laboratories

If you’ve used a microscope at school, it will have been an optical microscope, also sometimes called a light microscope. If you haven’t used one yet, you will do this in Year 7 and trust me, it’s amazing! Optical microscopes work by shining a light through a sample, and using a combination of lenses to magnify the image. Often, a stain is used – for example, methylene blue to stain animal/ human cells; or iodine for plant cells. Sometimes a combination is used – for example, Wright’s stain, used to examine blood, is a mixture of methylene blue which stains white blood cells, and a different stain for red blood cells.

Human cheek cells, stained with methylene blue and seen under an optical microscope
Onion cells, stained using iodine

Optical microscopes have some limitations. The first is magnification. Mitochondria (the organelles of a cell that release energy) are the smallest things that can be seen with a standard optical microscope. Advanced computer processing does allow smaller objects to be observed; but this is very specialised, and still doesn’t produce the magnification needed to see viruses.

The second limitation of an optical microscope is that the images are two-dimensional – in other words, everything appears to be flat. Cells, like the ones seen above, are not flat but are three-dimensional. Being able to study cells, viruses and bacteria in 3-D is very important if we want to properly understand their structure. So, instead of optical microscopes, scientists studying COVID-19 and other viruses will be using electron microscopes.

An electron microscope

Optical microscopes work by shining light through a sample. Electron microscopes use a beam of electrons instead of light. This has two advantages. First, you can achieve much greater magnification and resolution (resolution is how detailed and clear an image is); second, an electron microscope can give 3-D images. The disadvantages are that they are expensive; they are not portable; and some samples require very specialised preparation.

Preparing a sample for SEM. This often involves coating the sample with a thin layer of gold or silver.

So, how will scientists be using microscopes to study the virus? There are two types of electron microscopy: scanning electron microscopy (SEM) and transmission electron microscopy (TEM). They can both do different things but broadly speaking, SEM is used to study objects in 3-D and TEM in 2-D.

SEM is particularly useful for scientists studying the structure of the virus, and how the virus attaches to the surfaces of human cells. TEM is very useful for studying how the virus behaves inside infected cells. Some pictures are shown below.

SEM image showing COVID-19 viruses (orange) on the surface of a human cell. The colours are added by computer, to make the image easier to see.
Another SEM image of COVID-19 (in yellow) on the surface of a human cell. Again, colours are added by computer.
TEM image of COVID 19. You can clearly see the spikes that give the virus its name – ‘corona’ means ‘crown’.
TEM showing COVID-19 particles on the surface of, and inside, a human cell.
Another TEM showing COVID-19 particles attaching to and entering human cells.

I hope you have found this interesting! In my next post, I will explain the technique scientists use to study proteins and other molecules on the surface of the virus: crystallography.

Jenner had it easy: the challenges of developing a COVID-19 vaccine

One of the most frequently asked questions at the moment is how long it will take to develop an effective vaccine for coronavirus COVID-19. An effective and safe vaccine would undoubtedly be the best way to halt the spread of the virus. There’s some excellent news on that front – the first human testing of a vaccine began in the US earlier this week. This is an incredible achievement to have got to human testing within such a short time! In this post I’ll explain some of the challenges facing vaccine developers, and some of the amazing leaps forward that have been made in recent weeks.

A Chinese child is variolated by nasal insufflation

Edward Jenner is credited with the discovery of vaccination, but in fact, a crude (and highly risky) form of immunisation against smallpox, called variolation, had been in existence for centuries. Variolation dates back to 10th century China, and the earliest form involved taking a powder made of crushed smallpox scabs and then blowing it up children’s noses with a tube – a practice called nasal insufflation. Yes, revolting I know! In Sudan, mothers of babies with smallpox would sell the scabs to other mothers who would rub them on the skin of their children.

By the time Jenner made his discoveries, variolation had been common practice in England for around 80 years and usually involved making a cut or scratch on the arm and introducing pus taken from infected patients. Yes, still revolting! The problem with variolation is that it involved deliberately infecting someone with a dangerous disease. The idea was that variolation gave a much milder illness, and after recovery, the variolated person was immune. The risk was kept to a minimum by ensuring that the material used in variolation was taken only from patients with mild illness; nevertheless, a small but significant proportion of those variolated would get the full-blown disease, leading to disfigurement or even death.

Edward Jenner innoculated 8 year-old James Phipps with cowpox, then deliberately infected him with smallpox

I won’t go into Jenner’s story in detail here, as it is covered in plenty of other places. In short, Jenner discovered that innoculating someone with cowpox, which is a similar virus to smallpox but a very mild illness, gave immunity to smallpox.

Early vaccines were developed basically using trial and error. A major breakthrough was made by Louis Pasteur, who discovered that bacteria and viruses could be artificially weakened, and that the weakened strains induced immunity with either mild symptoms or no symptoms. Pasteur’s arch-rival Robert Koch pioneered the use of dead pathogens (bacteria and viruses) as vaccines; later, the discovery of antibodies enabled better understanding of how vaccines work.

There have been cases where a vaccine has been developed and produced very rapidly. In 1957, a new strain of influenza emerged which had the potential to become a global pandemic. In 9 days, American microbiologist Maurice Hilleman had isolated the new virus, allowing development of a vaccine and saving many thousands of lives.

Maurice Hillman saved many lives by developing a vaccine for the 1957 Hong Kong flu pandemic

This begs the question, why can’t a COVID-19 vaccine be developed that quickly? After all, the virus has been isolated and its genome sequenced. A major difference is that Hilleman was working with a virus that was already well understood – it was simply a new strain. Vaccinations for flu use either dead virus (adults) or live, weakened virus (children). The manufacturing process basically involves growing the required strain in chicken eggs. It’s reliable and can be used for any strain of flu once the virus has been isolated.

A second point is that in 1957, regulatory processes were nothing like as strict as they are now. Hilleman’s Hong Kong flu vaccine did not have to go through the extensive stages of development, testing and approval that a modern vaccine is subjected to before it reaches clinical use. Even so, for a well-understood virus like flu, a vaccine can make it into clinical use relatively quickly. In April 2009, the first cases of a new strain of H1N1 swine flu were reported; by November a vaccine was in clinical use.

So, what are the challenges of developing a vaccine from scratch? Vaccines make use of antigens. These are proteins on the surface of a pathogen that signal the immune system to attack it. As part of the immune response, antibodies will be made to match the antigen. Your immune system then ‘remembers’ how to make those antibodies, so that if you encounter the pathogen again, you can fight it off before symptoms develop.

A major challenge is identifying which type of vaccine will be most effective. Inactivated vaccines use a dead pathogen; the pathogen is killed by heat, radiation or chemical treatment, then introduced into the body to provoke an immune response. Attenuated vaccines use a weakened form of the pathogen. They are highly effective but cannot be given to people with compromised immune systems. Protein sub-unit vaccines use either a protein from the surface of a virus, or the virus envelope with the DNA or RNA removed. DNA or RNA vaccines use part of the virus’ DNA/ RNA; cells in the body take this up and make proteins that mimic those that the virus produces; provoking an immune response.

BCG is an attenuated vaccine – it uses a weaker form of the bacterium that causes TB.

It’s also important to make sure a vaccine is resilient to small mutations of the virus. This is especially important because COVID-19 is an RNA virus and they mutate much more easily and often than DNA viruses – see my post about how viruses change. These mutations are very small, and modern vaccine developers have the tools to create vaccines that will still be effective if the virus undergoes small changes.

A COVID-19 vaccine will need to be 3 things: safe, effective and resilient to minor mutations of the virus. Vaccine development has two stages: pre-clinical and clinical. In the pre-clinical phase, scientists study the virus and its antigens; they test it in test tubes and on animal models; and they develop the manufacturing process. In the clinical phase, there are a series of carefully structured and monitored trials.

So, where are we with COVID-19? A major development is that scientists have determined the structure of the spike protein on the surface of the virus, which acts as an antigen. More about how this was done, and why it’s important, in a separate post.

A computer model of the structure of the COVID-19 spike protein

In brief, studying the structure of the spike protein in detail will help vaccine developers create that mutation resilience I talked about earlier, because they can ensure that a vaccine will still be effective if there are changes to the spike protein. In addition, now the spike protein has been fully characterised, it’s possible to manufacture it artificially and also manufacture artificial antibodies; scientists can use both of these in vaccine research, which is easier and safer than using the actual virus.

Another important tool is genome sequencing, which I explained in an earlier post. Again, in brief, scientists all over the world are sequencing the genome of the virus and entering results into a massive international database. This allows them to track changes in the RNA of the virus, which is also very important in ensuring that a vaccine is resilient to minor changes.

Earlier this week, a vaccine in the USA entered what is known as Phase I clinical trials – this is when the vaccine is tested on a small number of carefully selected, healthy volunteers to assess safety and immune response. If those are successful, Phase II trials will begin; these involve a larger group of volunteers who will be vaccinated and then deliberately infected with the vaccine. Phase III would be a large scale trial involving hundreds of volunteers in multiple locations to test whether the vaccine is safe and effective across the population as a whole. If that is successful, the manufacturers can apply for a license and the vaccine can be adopted for clinical use.

I will stress here, only a small proportion of Phase I trials progress to Phase II. However, to have a vaccine in Phase 1 trials this quickly (within about 3 months of the virus appearing) is amazing progress. I’m keeping a very close eye on vaccine development and will keep you all updated, so watch this space!

How do scientists study new viruses? Genome sequencing

In the second in a series of posts explaining how scientists study new viruses, I will talk about genome sequencing. Thanks again to 9-year-old Chloe for asking about how new viruses are studied.

If you’ve read my post ‘What is a virus?’, you may remember that a virus consists of a protective envelope, and inside that envelope is a strand of either DNA or RNA. DNA and RNA are molecules that store information in the form of a code. This code contains all the instructions that the virus needs for reproducing, and is called the genome. All living organisms also have a genome, including each of us.

Believe it or not, the code that makes up the genome only has four letters. In DNA these letters are C, G, A and T; in RNA they are C, G, A and U. Each letter represents a chemical called a base: A is adenine; T is thymine; G is guanine; C is cytosine and U is uracil. In the genome, the letters are arranged in groups of 3, called triplets. I won’t go into the maths, but there are 64 possible triplets.

Part of a DNA molecule. It forms a spiral called the double-helix, joined across the middle by bases. Here, purple represents thymine (T), orange is adenine (A), yellow is guanine (G) and green is cytosine (C)
RNA is a single strand. It’s shorter and less stable than DNA, and thymine (T) has been replaced by uracil (U) which is coloured red.

DNA and RNA contain the instructions for making proteins. Proteins are long molecules made up of chemicals called amino acids. There are 20 amino acids, and DNA and RNA have the instructions for which amino acids to join in which order to make a specific protein – this works because each amino acid is matched to a specific triplet. There are 64 possible triplets and only 20 amino acids. Several amino acids match more than one triplet. There are a few unused triplets which do not match any amino acid – these are called non-coding triplets and they are used to create spaces between instructions for different proteins.

Genomes are unique. When a new virus appears, its genome will be different to anything else, because it’s alterations to the genome that have made the virus change. Genome sequencing basically involves reading a genome and finding out the combinations of letters making up the code. This isn’t easy. The first full genome to be sequenced was a bacterium,and it had over 1,800,000 bases. Sequencing the human genome took 13 years!

Viruses are a lot simpler than bacteria with fewer bases – COVID-19 has around 30,000. That’s still a lot, but improvements in technology mean that when a new virus appears, it’s genome can be sequenced fairly rapidly. Within weeks of the first cases appearing, Chinese scientists had sequenced the virus’ genome using samples taken from patients.

Why is genome sequencing important? Although the genome of COVID-19 is unique, it has similarities to other strains of coronavirus. By comparing the genome of COVID-19 to other strains, scientists can get important information about where the virus came from and how it has changed to affect humans. In the case of COVID-19, they found that the virus is most likely to have come from bats or snakes; epidemiologists (see an earlier post) were able to use this information to confirm their theory that the virus originated in a livestock market in Wuhan, China.

The study of COVID-19’s genome is a world-wide project. In every country where cases appear, scientists are sequencing the genome and adding their findings to a massive international computer database. As recently as 13th March, scientists from the University of Sheffield published the genome sequence of the virus from the first patients in the UK. Collecting and analysing this information from across the world means that scientists can monitor how the virus is changing as it spreads, and it provides vital information for those working on vaccines and treatments. Monitoring minute changes in the genome also provides important information which epidemiologists can use in studying how the virus is spreading.

Something to be reassured about with COVID-19 is that scientists are making discoveries about the virus at an incredible rate. I’d hazard a guess that if this virus had appeared even 10-15 years ago, it would have taken scientists several years to discover what has been discovered in a few months. As a scientist myself I am literally in awe of what has been achieved in such a short time. I hope you found that interesting. My next post in this series will look at how microscopes are being used to study the virus.

Why gargling with vinegar will NOT cure you of coronavirus!

Hot on the heels of panic buying, we are starting to see people posting about supposed ‘cures’ for COVID-19 that some mysterious ‘they’ are not telling us about for ‘their’ own sinister reasons. Folks, this is reality, not the X-Files (I know, showing my age). Seriously, I’ve seen the image below posted on Facebook by several people in the last 24 hours (minus the red X – that’s my addition!). In this post I am going to explain why it’s incorrect, and why anyone who shares or follows it is NOT saving someone, but is putting themselves and others at risk.

The reason this is incorrect lies in the way viruses reproduce. As explained in my earlier post, ‘What is a virus?’, viruses consist of a strand of genetic material (RNA in the case of COVID-19) inside a protective envelope. In order to reproduce, they have to get inside a cell, hijack its organelles, then destroy the cell membrane to release the new virus particles. The image below shows this. It’s for an influenza virus, but all viruses work the same way.

When you have a sore throat from COVID-19 (or any other virus), it’s because the virus is invading the epithelial cells that line the throat, and using them to reproduce. A combination of damage to the lining of the throat, and inflammation from your immune response, is what gives you a sore throat.

Gargling with warm water and salt/ vinegar may destroy some of the free virus particles, or wash them away. What it won’t do is affect cells infected with the virus. Any viruses that are already inside cells will be completely unaffected because they are protected by the cell membrane; they will be busy reproducing away like crazy. As soon as you stop gargling, viruses leaving infected cells will once again go on to affect other cells.

So why might gargling and drinking plenty of water make a sore throat feel better or even disappear? If the lining of the throat becomes dry, it makes the soreness worse, so drinking plenty of water will prevent drying out. Gargling warm salt water to soothe a sore throat is nothing new, it’s a tried and tested remedy. I can remember my granny making me do this during childhood bouts of tonsillitis and it really does help. You can also use bicarbonate of soda. So, hydration and gargling will soothe a sore throat, as will throat lozenges, or in fact any boiled sweet because they generate production of saliva.

Please though, take it from me, the advice in the picture at the top of the post will NOT cure you of COVID-19 infection. Posts like this are extremely dangerous for two reasons. First, they may make people think they are cured, so they are unprepared when more serious symptoms appear. But the biggest danger is someone might believe they are cured and go out and about, potentially spreading the virus.

The take-home message from this post is, if you want information about how to treat COVID-19, PLEASE get it from a reputable source. In the UK, your first port of call should be the NHS; there is plenty of advice available online. If you have a health condition, charities and support organisations have specific, up to date advice – personally, I check Asthma UK daily for updates. Whatever you do, DON’T follow advice from random, unaccredited sources on social media. And if you see something like the post I’ve been talking about here, please, PLEASE do not re-post or share it! If you’ve found this post useful though, please do share.

A footnote. Vinegar or salt water may not kill cells infected with the virus, but your immune system will. There are two types of white blood cell that do just that. Natural killer cells (NKCs) and killer T-cells. So alongside good hygiene, the best thing you can do to protect yourself is make sure that you are fit and well, so that your immune system is as strong as possible. Good diet, enough sleep and plenty of exercise are important in maintaining a strong immune system. Looking after your mental health is also vital, as there is a strong link between mental health and your immune system. In the list below there is a link to advice from Mind on taking care of your mental health which I can’t recommend enough, it has some fantastic advice 😀

Some good sources of reliable information: – This is a brilliant resource for anyone who has mental health issues; and excellent advice for taking care of your mental health generally. – Epecific advice for those with diabetes. – A FAQ developed by a number of cancer charities for those living with cancer. – Excellent advice from Marie Curie for those dealing with a terminal illness. – Great advice for those with asthma. – Advice aimed at older people.