How do scientists study new viruses? Epidemiology

If there is anything to be thankful for about the COVID-19 outbreak, it’s that it is happening at a time when scientists have more tools than ever available to study new diseases. Doctors and scientists studying the virus have already made discoveries that even as recently as 15 – 20 years ago would probably have taken several years. Chloe, who is 9, has asked me to explain how scientists study new viruses. Four of the most important methods are epidemiology, genome sequencing, microscopy and crystallography, and in this post I will explain about epidemiology.

Victorian cartoon showing the conditions in big cities that allowed cholera to spread.

Epidemiology is the science of how a disease spreads. It may not sound that interesting but it’s one of the oldest methods of studying disease. The science of epidemiology started in 1854, and was the result of an outbreak of cholera. Cholera is an infection of the intestines that is caused by bacteria. It causes severe diarhea and vomiting, and left untreated it frequently results in death. Cholera bacteria are spread when faeces (as in poo) from infected people get into a water supply, and other people drink the water.

John Snow, the doctor who investigated how cholera spreads.

In the 1850s, cholera was a major problem in big cities because of overcrowding and poor living conditions. Poor people were crowded together in slums and did not have clean water or proper sewage systems – ideal conditions for cholera to spread. In 1854 there was a large outbreak of cholera in London, and it was centred on Broad Street in Soho, and the surrounding areas. A doctor named John Snow used a map to mark where cases were located, and noticed that they were all occurring in houses that used the same water pump, located in Broad Street. John Snow realised that cholera was being spread by water from the pump, and had the handle removed.

Dr John Snow’s map of the 1854 cholera outbreak. Houses were there was cholera are shown in black, and the Broad Street pump is circled in red.
The Broad Street pump, with the handle removed. It’s actually a replica.

Snow’s investigations did not stop there. He started looking at cholera cases for the whole of London, and realised that the majority were occuring in areas supplied by two water companies, both taking their water from the River Thames and supplying it to households without any attempt to clean it. Parts of London that were supplied by companies that got their water from clean sources, and filtered it before supplying it to households, had far fewer cases of cholera.

In 1858, engineer Joseph Bazalgette began work on a system of sewers and pumping stations to prevent sewage from running through the streets or being dumped in cesspools underneath houses. As a result, cholera was completely eliminated from London’s water system. The spread of other diseases such as thyphus and thyphoid decreased dramatically.

So, how will will scientists be using epidemiology to study COVID-19? In the first few days and weeks after the virus appeared, scientists in China used epidemiology to investigate whether the victims had anything in common. Just as John Snow was able to link the 1854 cholera outbreak to the Broad Street pump, Chinese epidemiologists were able to link COVID-19 to a livestock market in Wuhan. This led them to realise that the virus had originated in animals sold at the market, which is really important information for other scientists studying it.

Map showing cases of COVID-19 in China and surrounding countries on January 23rd 2020

Once the virus started spreading more widely, epidemiologists will be looking at where the virus appears and how quickly it spreads. Epidemiologists working for organisations like the World Health Organisation (WHO) are constantly monitoring the spread of the virus. This provides important information about how the virus is spreading. It also allows scientists to evaluate how well measures to prevent or slow down the spread are working; they can then use this information to advise governments on what they should do to try and slow down the spread of the virus in their own country.

I hope this has been useful. If you want to see the latest map from the WHO, you can find it by following this link:

https://bit.ly/2TMWEn4

How do viruses change?

In this post I will try to answer three questions that are related to each other. How do new viruses evolve, how do viruses spread from animals to humans, and can viruses change when they start to spread.

In my last post, I talked about how viruses contain a strand of DNA or RNA which holds all the information needed to make new copies of the virus. When a virus reproduces, part of the process is making a new copy of either the RNA or the DNA.

DNA, which stores information.

If you’ve ever had to copy something out, you’ll know that from time-to-time, you make a mistake. The same thing can happen when new copies of the virus’ DNA or RNA are made. These mistakes are called replication errors. The altered DNA or RNA can still be used to make new viruses, but they will be different – this is called a mutation.

Replication errors do not produce completely new viruses. Instead, they produce new versions of the original virus – these are called strains. Viruses which store their information as RNA have more replication errors than those with DNA. There are two reasons for this. RNA is designed to store information for shorter periods of time, so it is less stable than DNA. Also, remember, the virus is using the organelles of a cell to copy itself. The organelles in a cell are designed to copy DNA, not RNA. They have all sorts of safety mechanisms to prevent replication errors when copying DNA, but these won’t work for RNA. The common cold is caused by RNA viruses, this is why there are so many different strains of it.

Flu is also caused by an RNA virus. As well as replication errors, flu viruses can do something called re-assortment. Basically, if two different strains of flu infect the same person or animal, they can mix their RNA together and then recombining it, giving a new strain which is very different to the old ones. The most recent example of this was swine flu in 2009.

So, what about coronavirus COVID-19? It’s an RNA virus, so whenever it reproduces there may be replication errors. Most replication errors actually cause changes that make viruses weaker, and these strains die out very quickly. Very occasionally a replication error will give a new strain that survives.

So, is COVID-19 a completely new virus? The answer is no, and this relates to the second question, which is about how viruses spread from animals into humans. If you’ve read my post about how viruses work, you’ll know that they invade cells and take them over in order to make new viruses. The first step in this is to stick onto the surface of a cell.

Spikes on the virus must match exactly with receptors on a cell.

The envelope of a virus is covered in proteins, called spikes, which it uses to attach itself to a cell. These proteins will attach to proteins on the cell surface called receptors. For this to happen, the shape of the spike has to match up with the receptor – like a key fitting into a lock, or two jigsaw puzzle pieces fitting together. If the key, or the puzzle piece, is even slightly the wrong shape, it won’t fit.

There are a lot of viruses that affect animals but which humans can’t catch – this is because the spikes are the wrong shape to attach to human cells. Every so often though, a mutation will occur which alters the shape of the spikes, so that they can attach to human cells. Humans can now catch the new strain of the virus.

COVID-19 spread from animals when a mutation changed the shape of the spikes so they now match receptors on human cells.

So, how did this happen with COVID-19? Viruses are more likely to cross from animals into humans if there is a lot of contact between them. Wuhan, in China, where the virus was first seen, has a large market where live animals are sold. The city is also very overcrowded, so it’s easy for viruses to spread. Scientists think that the virus spread to humans from animals being sold in the market. They aren’t sure which animal, but coronaviruses are common in bats, and in an animal called a pangolin – both of those were on sale in Wuhan.

The final question is, do viruses change when they start to spread? The answer is, yes. The more a virus spreads, the more it reproduces, so the more opportunity for replication errors. With a virus like flu, there is also more chance of the same person or animal being infected by two different strains, leading to re-assortment. So, how will COVID-19 change as it spreads? The answer is that any changes are likely to be very small, because they will be due to replication errors – coronaviruses can’t undergo re-assortment like flu viruses do. Changes are likely to be very minor and will not alter how the virus affects humans. Scientists working on a vaccine will also be making sure that it will still work if there are changes to the virus.

I hope you have found that useful! In my next post, I will be looking at how scientists study new viruses and find out how they work.