Combatting COVID-19: An Interview with Virologist George Lomonosoff

Last Thursday, I interviewed virologist George Lomonosoff, an expert in the use of plants to express and produce therapeutic molecules for vaccines and diagnostic tests. We talked about the current crisis, the search for a vaccine, and his laboratory’s work to produce reliable coronavirus testing kits. In a few places, I’ve added notes to explain a couple of scientific terms and add context; you’ll see those [in blue].

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LSM:  So, tell me a little bit about yourself and what you do.

george-lomonossoff-2016GL: My name’s George Lomonosoff. I’m a virologist working at the John Innes Centre, although I’m actually working from home at the moment, so I’ve been working strange hours- I’ve been doing some media work, appearing on talk radio at odd hours, things like that.

Our work has been focussed on using plants as bioreactors to produce things like viral coat proteins [the proteins on the outsides of viruses, which your immune system recognises; they’re used in vaccines]. Traditionally, industrial processes to make  therapeutic molecules have often used big vats, which we jokingly refer to as GBSTs (Great Big Steel Things). When you use these processes to make vaccines, you have to keep equipment sterile, and there’s always a risk of the product becoming contaminated.

And these ‘GBSTs’ can be used to mass-produce vaccines?

Yes, that’s right. And if you use a plant as a bioreactor, the cells of the plant will produce the useful proteins for you, and  the environment is naturally sterile throughout the process- you can purify the product at the end. And there’s less risk of contamination with another nasty virus because plant viruses don’t affect animal cells.

What are you working on at the moment?

We’re working on producing more reliable coronavirus tests. What we’re making is something called in-tube positive controls. [In a normal viral test, if a virus is present, a process known as PCR amplifies a section of the virus’ genes, making lots of copies of it. The genes are found in a molecule called RNA]. What we’re doing is making a control RNA molecule, and placing it inside a plant virus coat so it’s more stable.

So, when you take a throat swab from someone, you can add a little bit of the control RNA into the same tube, and that checks that the test is working correctly! If you do the PCR reaction, you might or might not be able to detect the virus, but you should always be able to amplify the RNA in the control. If you can do that, it means that the reaction is valid, and everything’s worked, but there’s no coronavirus present. If you can’t, that means the test hasn’t worked. The advantage of that means that you don’t get false negatives- if you know the reaction hasn’t worked, you just have to do the test again.

You’ve been working from home. So… how does that work?

There’s a lot of designing of experiments that can be done from home. We can do a lot online, we can order the reagents and plan the process online. Eventually, we will need to do some laboratory work, some people in my group will be doing that, and the lab work might include me at some stage. But we’re trying to reduce the number of people in the lab to the minimum at any one time.

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A lot of reports are suggesting that a vaccine will take at least 18 months to develop. What steps are in that process? Why does it take 18 months to develop?

Well, first you start off by identifying and isolating an antigen [a protein which the immune system can respond to] on the virus. And then you prepare something which you think might work, and what you’ve got is a vaccine candidate. Then you need to trial the vaccine at very low doses, to make sure nobody has any nasty side effects, and see how people’s bodies respond to the vaccine.

After that you can start the main stage of trials, and there are really two ways you can do this. So one option is to give a large group, maybe a thousand people, the vaccine, and you say, go out into the community and see how many of you get the disease, compared to a control group (basically just the rest of the population).

And that’s inevitably a slow process.

It’s a very slow process. Especially if you’ve got a lockdown! They may not even come into contact with people, because of social distancing. And then you have to work out what dose of the vaccine to give. So that’s all tricky.

But if you have a delivered infection, where you actively infect people with the virus, you need a control group who are willing to be infected with the virus without the vaccine. So, who’s going to volunteer for that? It’s not like giving somebody a common cold or the flu, there is a significant mortality rate. It’s low in younger people, but you’re likely see a certain reluctance to be in the control group.

Then, of course, even if that’s all hunky-dory and works really well, you then have to find a way of producing, not a thousand, but a hundred million doses! Of course, ultimately you’ll want to produce billions of doses. You need to find production facilities, purification facilities, and then finally you need distribution as well. Is it stable? Does it need to be refrigerated for travel? What’s the best method to apply it- a jab, inhalation, or something else?

So those are all the steps. What’s happened in the last twenty or thirty years is that the first stage, producing a vaccine candidate, has become much, much faster.

When you put it like that, eighteen months seems miraculously fast.

Yes! Having said that, new flu vaccines can be made in nine months for each outbreak of seasonal flu [different strains of Influenza A and B are common each winter]. But the extra speed comes from the fact that they have so much data to rely on, the equipment and systems are all in place, they know exactly what dose to use. We have no previous data on COVID-19.

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SARS was also a type of coronavirus, right? Why has this outbreak unfolded so differently from the SARS epidemic?

It had a greater mortality rate. So basically, a good virus ‘doesn’t want’ to kill the host, it wants to make you asymptomatic for as long as possible so you can travel around the world and pass it on. SARS was too serious. It debilitated people very quickly. It was deeply unfortunate for those communities, but it stayed very local. The mildness actually helps the spread of the virus.

Is there a sort of inverse relationship between the mortality rate and how quickly the virus is transmitted then?

Between the mortality rate and the spread of the virus, yes. An example of this was Ebola, which had a very high mortality rate, but proved to be easier to contain. Also, Ebola required direct contact with the body or bodily fluids of infected patients, while COVID-19 can be spread through the air. So that also makes the transmission of the virus easier.

What lessons should we take away from how the pandemic has been handled so far?

Simply, speed is of the essence. You need to take action as quickly as possible to prevent the spread of the virus. Also, global co-operation is really important. There were a few weeks in which the Chinese government tried to somewhat keep this out of the news. And that just doesn’t help anybody in the long run. It’s really important that people are open about what’s happening so we can get a lead on the virus.

We’ll see about social distancing, if that’s effective. Only time will tell, really. We’ve had different approaches in different countries, and we’ll see which ended up being best- going for the more stringent lockdown, like South Korea, which does seem to have been pretty effective- or the more gradual approach adopted by the UK. South Korea’s quite a good comparison because the population numbers are similar, its economic development is similar too.

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I lived in Japan for a while, so I’ve been following the news there. Japan has had a very atypical pattern of infection, right? Do you have any insight into what might have happened there?

Well, there’s a lot of concern in Japan at the moment that the virus is really going to take hold. It seems to have been fairly effectively dealt with in the people coming into the country. I think it’s been restricted a bit by the measures they’ve taken [closing schools, suspending some flights, limiting large gatherings and advising people to stay home at the weekends], but there’s a lot of concern in Tokyo. We’re about to see whether it’s been effective.

Bars and restaurants are still open there, though.

They may regret that, but we’ll see. The progress of the infection has been rather slow.

In some countries, authorities may be underreporting cases. In Russia, for example- you know, with an enormous border with China- it seems almost impossible to have so few cases. Maybe in many cases they’re not calling it COVID-19, they’re calling it ‘winter pneumonia’. If you don’t test people, you won’t know. Some countries are in denial, like Bolsonaro in Brazil, and some countries are underdeveloped and don’t have the resources for testing, particularly in parts of sub-Saharan Africa.

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There’s been a lot of fake news surrounding COVID-19. What are some common misconceptions you’ve heard about the disease, which you’d really like to correct?

People say that it’s a bioweapon, created in a lab. If you’re in China, you say it was created in America, and if you’re in America, you say it was created in China. Actually, we can quite easily trace its origins from the group of coronaviruses, which are well-known. They’re zoonotic diseases, which means they affect animals, so you have this huge reservoir for infection.

Which animals in particular? We haven’t heard so much of this in the media.

Well, this particular coronavirus is thought to have developed from a bat virus. Bats are very good at transmitting viruses like coronavirus: of course, they’re quite mobile. We have this theory that it might have come from a market in Wuhan- it’s not a bad theory, but we don’t really know that. We can do things to reduce the risk of transmission, but you can never really eliminate it.

Other things- there’s been a confusion about whether to use antibacterial handwash. Well, coronaviruses aren’t bacteria, but antibacterial handwash which contains a lot of alcohol will inactivate the virus as well. It’s different from antibiotics, which are ineffective against viruses.

Finally, it’s not just a disease of elderly people. It’s true, older people and people with underlying conditions do usually have worse symptoms. But you can be unlucky, and have complications. What’s more, if you are asymptomatic [carry the virus but don’t get sick], you can still spread the virus to other people.

You’ve been working in virology during a pandemic. It must have been stressful! What do you do to relax?

Well, it’s certainly tiring. It’s curious. I’ve done a few appearances before, but what I’ve never done with anything like this intensity is all the media work. I do enjoy it, but it’s quite new for me, responding and talking to members of the public about the outbreak. The other day I was on a radio programme with (the journalist) Julia Hartley-Brewer, and she was asking why Prince Charles was tested for coronavirus when lots of other people haven’t been tested. And I was thinking, well, I don’t know! I don’t have access to his medical records, I can’t really speculate on this.

I don’t really get much time to switch off at the moment. I really do need to keep up with the news, and then I get asked a lot of questions. Normally I like watching the football, but of course there isn’t any football on at the moment! Yesterday we got our daily exercise, going for a nice walk in the park with my daughter and baby grandson. Our garden is beautiful too, so that helps.

George, it’s been a pleasure speaking to you. I hope you get some time to relax later in the year!

COVID 19

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