Tell us a little about yourself.

Originally from Lugano, Switzerland, I studied in Geneva and Heidelberg, before working in Zurich and at Yale. I started my virology group back in Switzerland before moving to the Mayo Clinic, where I’ve been for more than 20 years now.

This shows you how much young scientists move around. I had a lab meeting on Friday by Zoom with three researchers who will be joining the lab, one in Brazil, one in Germany, and the third in India. A lab meeting across four continents and four time zones! At the beginning of your career, you move around, and then when you establish a lab, you stay put and people come to you.

What do you do in your spare time?

When I was in Zurich I used to do orienteering, which is running in the forest with a map and a compass. Here in Minnesota I mainly cross-country ski in winter and cycle in summer. We are close to Canada, and Winter is cold and sunny. So, if it’s not very windy, we’re outside.

Why did you move to the Mayo Clinic?

The clinic had a vision, not only to study viruses as pathogens, but to use viruses to treat cancer. That was very interesting to me because it would allow, has allowed, me to continue my fundamental research on viruses but also to develop genetically modified viruses to treat cancer. That basically sums up what we do. We take the individual pieces of viruses and modify them, then exchange the new piece for the old one in the viral genome. We then infect animals with these genetically modified viruses to understand how they cause disease. We also develop genetically modified viruses that target certain types of cancer, and test them in animal models. Some of these new viruses advance to clinical trials in humans.

And is there a particular virus that you use as a basis?

The measles virus. Everybody has their specialty, and we know quite a bit about the biology of the measles virus and can predict what will work differently if we change the virus in a certain way. We test that experimentally.

Could you describe your lab?

There are six to ten people in the lab; half post-doctoral researchers, and some technicians and students. The lab is pretty much as those in the movies. There are benches, and on these there are centrifuges and gel apparats. People wear safety glasses, white coats, and gloves.

Something which really facilitates our work is making viruses that carry a fluorescent protein that we can use to follow the virus spread in cells, both in the petri dish and in an animal. We can infect a ferret with canine distemper virus (similar to measles), and see where the virus replicates. We learn a lot with this process; finding a needle in a haystack because the needle lights up.

Your lab primarily focused on measles, and now you work on SARS-CoV-2. How has the transition been?

The lab re-deployed on SARS-CoV-2 at the beginning of this year but now we’re back to 50-50, so half our activities are on measles again. In January I had a bit of a Deja vu moment: in 2003, when the first “severe acute respiratory syndrome” (SARS) virus appeared on the horizon, people in the lab were excited, and we made antibodies against it. But by the time these reagents were ready, the virus was basically under control. In January, I was really wondering whether this time it would be big.

Yes, and there was no way you could have known what was going to happen.

Right. But people in the lab were very excited. It was a coronavirus, an RNA-type virus with an envelope, like the measles virus, so we knew how to deal with it. We had many experimental systems in place that were applicable to the new virus. When at the end of January it became clear that SARS-CoV-2 was a serious public health threat, we began to collect and make reagents to study it. Some students really wanted to immediately start working on it. By March, when the clinic completely closed except for work on the new virus, and then there was a lockdown, everything had switched to SARS-CoV-2 research. We were allowed to continue working because we were preparing the clinic to react to this public health emergency. So, the virus came to us rather than the other way around.

How much did the switch change the protocols in the lab?

There were not so many changes in the lab. We had to rededicate a chemical hood for viral RNA extraction procedures, but it was easy for us because the viruses, measles and SARS-CoV-2, are similar. On the other hand, we introduced shifts to minimize contacts, started always wearing a mask, and moved meetings, journal clubs, seminar series and every academic or administrative meeting on virtual communication systems.

Could you explain how these viruses are so similar?

Both are respiratory viruses that affect the same cells, so we already had the cells in which the virus grows. And then both measles and SARS-CoV-2 have an envelope layer, and have RNA (not DNA) as genetic material, which allows them to adapt quickly to new hosts. So, the main characteristics of the viruses are all the same. We can use the same techniques to study both viruses.

And you also have your previous experience with SARS in 2003.

Yes. It’s kind of funny, but we took some antibodies that we made in 2003 against the envelope protein of SARS (the “spike”), and we hadn’t used for 17 years, out of frozen conditions. We checked them against SARS-CoV-2. Since SARS and SARS-CoV-2 are very similar viruses, these reagents work.

How have you been affected by money and time constraints?

The American system reacts very quickly. It was scary and instructive. To ensure that the institution remained financially accountable, at some point staff salaries were reduced and some internal research grants were frozen. On the other hand, funds were quickly made available for targeted SARS-CoV-2 research. When this happened, we had preliminary data, and a grant already drafted, so we got over the critical phase without too much turbulence. Now the financial situation is much better, and our salaries have been restored. We are submitting grants to continue working on SARS-CoV-2.

What’s the main activity in the lab right now?

We have a very productive collaboration with cardiologists. The virus can cause problems with the heart. Some of these problems are due to immune cells infiltrating the heart, but we discovered that the virus is able to fuse the heart cells and cause arrhythmia, causing the rhythm of the heart to change, which can be lethal. So that’s one line of research, on how the virus causes disease in a way that differs from a classical respiratory tract infection (*).

Another branch of research follows the variability of the virus, and whether it adapts to different organs.

Whether it can learn to attack different organs?

Well, it adapts. All RNA viruses have an inbuilt system for changing rapidly. In each genome that they replicate, they introduce a handful of changes. Most of these changes, or mutations, have a neutral or negative effect in their standard environment, but if the virus gets to another environment (another organ), some of the mutations can have a favourable effect. The viruses with these mutations replicate preferentially, and so they rapidly adapt to the new tissue environment. This is something that we had explored and characterized for the measles virus. You would assume it would be similar for SARS-CoV-2 because it replicates initially in the lungs, but then makes problems elsewhere. Some of these problems are due to an over-reactive immune system, but not all of them. Sometimes, it’s really the virus getting to replicate beyond the lungs.

What’s the most rewarding part of your work?

Probably the fact that I get to educate and shape other scientists. At the beginning of your career as a scientist, you want to make discoveries, publish in top journals. You want to put your name on something relevant and memorable. But later, it’s more rewarding to see how people who have trained with you develop, get in positions of responsibility, and do good work. I’m in regular communication with at least half of my former group members.

Which myth about SARS-CoV-2, or viruses in general, would you love to debunk?

There is one thing that’s just not getting to the public. There is a simple explanation as to why the hospitalization rate for SARS-CoV-2 is much lower than the infection rate. The concept of lethal dose. The point I’m driving at is that it’s really important to minimize the amount of virus that you receive when you are infected. And this can be done through using masks.

Masks do not block 100% of the virus, but even if they block 50%, when you and another person are wearing masks, the infectious dose will be one quarter of that exchanged between people who aren’t wearing masks. And if you’re wearing masks that are 80% tight, the infectious dose is 25 times lower.

This is where the lethal dose comes in. The first things we do when we establish an animal model of a disease is to give a lot of virus to the host. Then we lower the dose by a factor of ten, and perhaps only 80 or 90% of the animals die. If we give 100 times less virus, only 10 or 20% of the animals die, and if we go 1000 times lower no animal dies. That is a simple experiment that has been done for many viruses in different hosts. There is every reason to think that the same happens with SARS-CoV-2 in humans. And some people don’t get it. I mean, everything that you do to get less virus at the beginning will help you, could take you from a lethal dose to a severe infection dose, or to an asymptomatic infection.

It’s true, this really hasn’t been discussed in the media.

Sometimes, I speak with my neighbours about this. And I tell them this, but then they say, “But why is this not discussed?” and I don’t know. I really don’t know.

Many thanks to Dr. Roberto Cattaneo for talking to us.

(*) We attach here a recent publication from Dr. Cattaneo’s lab (preprint under review at a Nature Research journal) about the effects of SARS-CoV-2 on cardiomyocytes: 

https://www.researchsquare.com/article/rs-95587/v1