In this interview, Volker Thiel, Professor in Veterinary Virology at the University of Bern and since May 2020 full member of the NCCR RNA & Disease reflects on the implication of the Corona viruses on his career, on the society, and on the relationship between science and the public.
After your studies, PhD and postdoc in Würzburg, you became a PI in St. Gallen. How was it for you to get your first PI position?
That was in 2003 and everybody told me that Coronaviruses are not really interesting and I should consider researching a virus family causing more severe human disease. It was hard to find something but luckily, they were interested in hiring me in St. Gallen and a grant application for my position to work on Coronaviruses was funded soon after. Just a week after the grant application's approval, it was discovered that a Coronavirus causes SARS. My boss in St. Gallen told me later that at that time, he feared that I would go elsewhere because suddenly Coronaviruses became interesting.
“It is impressive how the scientific community reacts to the current pandemic.”
I assume that the increased interest in Coronaviruses was advantageous to you in terms of grants and publications but also resulted in increased competition?
Indeed, we can also see that right now: It is impressive how the scientific community reacts to the current pandemic. There are so many excellent studies that are being published almost daily. The competition is huge, but we have some advantages as we already have systems running in the lab and as we worked with Coronaviruses before.
Do you see this pandemic as a chance for your career?
To some extent, yes. It certainly helps that our research is interesting to a broader community now. But it will not last forever and you still have to deliver. I hope that it will make a difference for the young researchers in my lab and help advance their careers.
What was a key discovery moment in your career?
There are several such moments but one I remember very well: When I was still in Würzburg, I was trying to establish a reverse genetics system for Coronaviruses. I tried to clone the entire genome and reconstruct the virus from the cloned DNA to build a system that allows you to modify the virus. This was our main goal for many years, but it was very challenging at that time. One of my favorite moments as a scientist was when I saw the first plaque arising from what I had cloned. This was then the basis for my future work.
“One of my favorite moments as a scientist was when I saw the first plaque arising from what I had cloned. This was then the basis for my future work.”
At that time, it took you years and today you can do it within weeks?
Yes, it took me essentially my entire PhD and a year after to complete it. Back then, it was quite difficult to sequence 30 kilobases. Only Sanger sequencing was available: in the beginning, we performed radioactive sequencing and then switched to capillary sequencing. You had to do about a hundred sequencing runs and purify your reactions. It took two or three days and a lot of money to sequence an entire virus genome.
What drives you in your career?
Curiosity. To see this new virus and figure out how it works. My main interest is the replication complex of Coronaviruses. Before I retire, I would like to see its structure or the replication complex synthesizing RNA in real-time. However, the techniques for that are not there yet.
According to an essay in the Horizons magazine, you think that "writing a doctorate should be a normal job". Can you elaborate?
It is at the same time normal and not normal. It should be normal in terms of working conditions and work-life balance. PhD students often suffer when experiments do not go as planned and then they put themselves under pressure. As a PI, you have the responsibility to watch out for this and see how you can help remove the pressure. You should not allow people to work day and night for a long time until they get exhausted. That is what I mean by not normal. Of course, you should not stop PhD students because they usually like to work on their project and often they do more than they formally would need to through their own motivation. It is important to give them their freedom. In this sense, it is not a normal job.
What general advice do you give to young researchers?
Do what your curiosity in science drives you into. And just do it.
“Everybody is aware that if we mess this up, we get into trouble. We must have the necessary safety precautions in place and I believe that this is granted at least in the developed world.”
What were the biggest changes you witnessed in virology or science in general during your career?
The current work on the new Coronavirus is a good example: many people enter the field and bring with them all these new technologies. All sorts of "omics", for instance, where you as a "simple scientist" do not understand in detail anymore what they are doing. It is often a black box. You have to deal with massive datasets and you have to think more globally. So, it is a different kind of work nowadays. The times are gone when you have a small little project on a simple mRNA and try to do your simple experiment. It is a bit sad because that is how I grew up. I think that having these novel technologies is a big change in science.
What do we currently know about the origins of SARS-CoV-2?
It is quite clear that there are similar viruses in bats. However, it is not clear how the virus transmitted from bats to humans – whether there was an intermediate host in between or not. So far, we have not yet found this exact virus in bats but only its close relatives that are too distantly related to be the virus that was transmitted.
Would you discard the idea that SARS-CoV-2 escaped from a lab?
I would certainly discard the thesis that SARS-CoV-2 was created in a lab. I also do not think that it escaped from a lab. From what I know, the Wuhan lab was not working with live SARS viruses. Research with SARS-CoV was not allowed in China because there was a lab accident in 2004. They became cautious regarding permissions for experiments with viruses.
Why are MERS-CoV, SARS-CoV and SARS-CoV-2 so much more virulent for humans compared to other Coronaviruses?
SARS-CoV and MERS seem not to be well adapted to humans. This is often the case when viruses transmit from animals to humans. They are suddenly in a new host, on which they depend for replication and transmission. They have to adapt and optimize every mechanism that is needed to survive. What makes SARS-CoV and MERS-CoV dangerous in humans is that, for some reason, they induce a lot of inflammation, which results in severe disease and even lethal infections.
In the case of MERS-CoV, the original hosts, the camels, do not really suffer from severe disease when infected.
Exactly, MERS-CoV just causes a common cold in camels. While for humans, a MERS-CoV infection can cause lethal disease, for camels, it is just a "childhood disease", which they get during the first two years of their life and only causes a running nose.
Why could the spread of SARS-CoV-2 not be stopped earlier like SARS-CoV and MERS?
I think one of the main reason are the asymptomatic carriers. We know that MERS-CoV is not transmitting very well from human to human. SARS-CoV transmitted reasonably well but only when people were already having symptoms. It was relatively easy to isolate these persons and stop the chains of transmission. But with SARS-CoV-2, you do not know that you are infectious because in the beginning you do not have symptoms.
“Nobody could really anticipate that this virus is so causing so much trouble.”
Do you think that it is realistic to find a vaccine against SARS-2 that is protective without compromises on safety within a very short time?
There are some basic rules and requirements for vaccines. Everybody is aware that if we mess this up, we get into trouble. We must have the necessary safety precautions in place and I believe that this is granted at least in the developed world. People are now willing to speed up the development and they are very careful not to weaken the safety.
Based on the current knowledge regarding the mutation rate, do you expect that new vaccines will need to be developed regularly, like for Influenza?
The mutation rate of SARS-CoV-2 is not comparable to what we see with Influenza. The virus is quite stable so far. In contrast to Influenza, there are not many different strains for which the antigenicity is different and would require adapted vaccines. That is not something we expect for this new Coronavirus.
Would it help to stop SARS-CoV-2 if technologies were developed that enable testing at home?
Yes, this is under discussion. It has been proposed that if we have a cheap test, we could test ourselves by spitting on the test stripe every morning before we drink our coffee. The test should be fast and give a result within as little as 10 minutes. If you get a negative result, you go to work. If the test is positive, then you stay home and consult with your doctor. Such tests do exist already, either based on isothermal amplification or simple antigen detection. They are not as sensitive as the PCR assay but are sensitive enough to detect people that have high virus loads.
Now we have talked about diagnostics and vaccines. How fast do you think there will be new drugs available?
I do not know. Millions of compounds are being screened, but developing a new drug will take several years. If a drug can be repurposed, then we may have it very soon.
Why was there no antiviral drug developed against SARS-CoV or MERS-CoV that could now be applied to treat SARS-CoV-2?
Many people worked for a long time on drugs for Coronaviruses with different approaches, for instance, by purifying the polymerase or protease and subsequently performing binding and inhibition studies. This resulted in discovering some compounds, but they were never further developed into a product because there was no market. SARS-CoV was luckily eliminated from the human population after it had infected only a few thousand humans and for MERS-CoV, there were and are not that many cases.
When did you realize that the new Coronavirus also poses a threat in Europe?
At the beginning of this year, when it became clear that what was first known as “pneumonia of unknown origin” is caused by a Coronavirus, we got, of course, very interested. However, at that time, we did not think that a pandemic could emerge from this virus. We saw that there was this outbreak on a market in Wuhan but the first announcements claimed that the virus was not transmitting between humans. It took one or two weeks, or even longer until it became clear that there must be human-to-human transmission to explain all these cases. It took quite a while until we realized that this is a massive outbreak. Even then, we did not think it would cause a pandemic given the experience of how SARS-CoV and MERS-CoV were contained. It became clear mid or end of February that this virus is different.
“It became clear mid or end of February that this virus is different.”
How should the world have reacted differently to contain the virus earlier?
In the first two months, I think not too much went wrong because, as I just mentioned, nobody could really anticipate that this virus is causing so much trouble. After we realized this - I think this was in late February and in March - many countries reacted very well and took immediate measures to reduce the cases. But what went wrong is – this is now a bit political – that some countries did not take the virus seriously in the beginning. Now that they realize the severity, they try to make it too political. I think that this is not a matter of any political dimension. It is something that should go beyond parties and personal interests. It should unite people rather than putting them apart.
In research with highly pathogenic viruses, there is always the danger that you create something more dangerous, especially using reverse genetics systems or propagation experiments. How do you deal with that?
That is a serious discussion in the field, not only for Coronaviruses. There were experiments with Influenza viruses a couple of years ago where Influenza viruses were created that transmitted better between ferrets. These "gain of function" experiments were very much criticized. But we also learned a lot from these experiments, for example, which regions in certain genes to look at when assessing the risk of a new strain.
Are you in favor that these findings are published – in contrast to people who say that this information should not be publicly disseminated because of the risk of being misused?
I judge the potential that these findings are misused as relatively low because not many people have the ability to work with these viruses. Also, the previously mentioned Influenza experiments showed that these strains transmitted better, but at the same time, they lost much of their pathogenicity. It is almost impossible to create intentionally a highly transmissible virus that is also highly pathogenic.
Regarding the Covid-19 pandemic, do you think that the preprint server system was beneficial to accelerate the battle against the disease or did it more harm than good?
This is hard to say. There are several factors to consider: On the one hand, especially in the beginning, the press jumped on everything with a fancy title, often lacking the background to judge the merits of certain preprints and publications. On the other hand, the scientific community soon realized that there are better and worse papers. Interestingly, if you have the right network on Twitter, you can filter out most of the publications that are not that good and get the excellent papers.
“[The pandemic] is something that should go beyond parties and personal interests. It should unite people rather than putting them apart.”
Do you think that the government should build an infrastructure to be better prepared for a crisis, even if there is no profit to be made?
There are so many viruses and bacteria that it is impossible to have a vaccine or a drug for every pathogen. In Switzerland and other countries, there are good funding systems, such as the SNSF, that do not select research on the most dangerous viruses and bacteria. They provide funds for basic research and this lays the foundation that we can count on. For many years, there was good basic research on Coronaviruses that taught us a lot about the basic principles of this virus family. This knowledge can then be translated into applied research if there is the need for it. Of course, there are some viruses or bacteria that we know are dangerous. For example, the West Nile virus might come to Central Europe very soon. There are some things we can anticipate and we can prepare for it before the disease reaches us. However, in other cases, such as in the case of this new Coronavirus, it was impossible to predict the event and, thus, it is impossible to prepare for everything. Regarding antibiotic-resistant bacteria, the numbers and the disease-burden is growing for a long time. Yet, there are not many antibiotics in development as it seems that companies cannot make enough profit.
Why can new life-saving antibiotics not be priced at the same level as some other new therapy?
That is a difficult question. People are used to getting into action only when there is a danger. For a long time, and still nowadays, a couple of antibiotics work. We live in a world for 50 to 70 years, where particularly in Europe we did not have any of these wide-spread deadly infectious diseases. We were not really confronted with any of these diseases, and as long as we do not suffer, I fear that we will not do anything in that direction.
You said that there are now more of these outbreaks of infectious diseases; why is that?
One general reason is that we are just too many people on this planet and we go more and more into areas in the wild where humans are usually not. So we get more and more in contact with wild animals that can carry viruses that are infectious to humans. And the other aspect is that we are globalized. Once there is a virus in the human population, it can quickly spread because we are so much connected not only locally but internationally.
On the peak of the first wave, you were interviewed on a live prime-time broadcast. How did it feel sitting in that TV studio and knowing that an afraid nation is hanging on your lips?
That reminded me of when I was a young student and had my first presentation at a big conference. I was a little nervous, but at some point, you just go there. Then you are in this bubble and do not think what others might see or think. That is my strategy to do that.
Have you experienced any difficulties with the media?
Yes, one difficulty is that sometimes your quotes will be taken out of context. When I received the interviews for approval, it was sometimes very annoying to see what they made out of what you said. And I often had the feeling that this occurred not due to a lack of knowledge but to make the story spicier.
Did people from the public reach out to you and were the reactions positive or negative?
Not a lot, but quite some. There were different reactions, and for the most, they were very positive. But some people deny that viruses exist and think you are cheating and not telling the truth.
Do you reply to them?
I try not to answer because of my experience back in 2012 with MERS. I once answered and this resulted in a big mess because they do not stop and keep arguing. You send emails back and forth and it does not bring anything in the end. You cannot convince them and they will not accept that you have another opinion.
“This feeling that you are restricted to this country, to your local area sometimes- that is what I will remember most.”
How do you think this whole pandemic will change the relationship between science and the public?
Overall, I hope that it will change positively. It is interesting that many more people now know a little bit about virology. I also think that the public got an idea what science can tell you and what it cannot tell you - they got a feeling of where there is solid information, where it ends and where speculation starts.
Is there an image from this period that you will never forget?
What I will never forget again is that suddenly we were again confronted with border controls. We were used to crossing borders essentially all over Europe. And now, suddenly, you could not simply leave the country without having a reasonable explanation. This feeling that you are restricted to a country, to your local area sometimes- that is what I will remember most.
What does it mean to you to be part of the NCCR RNA & Disease? Where do you benefit from being part of the network?
In my past and current work, I have always been interested in RNA because we work with an RNA virus. We studied different mechanisms on the RNA level. Already as an associated member, I enjoyed the spectrum of methods and approaches that are present in the NCCR. It is a very broad group of people that do different things in different ways, but it all centers around RNA. That was and still is very interesting for me.
Volker Thiel obtained his PhD from the University of Würzburg, Germany, in 1998, where he also conducted his postdoctoral research. In 2003, he moved to Switzerland and joined the Institute of Immunobiology in St. Gallen as a group leader. Since 2014, he is Professor in Veterinary Virology at the Vetsuisse Faculty of the University of Bern and head of Virology at the Institute of Virology and Immunology in Mittelhäusern. He serves as a member of the Swiss National COVID-19 Science Task Force.
Interview: Dominik Theler / Veronika Herzog
Interview conducted on July 28, 2020.