After two years living with the pandemic, everyone considers themselves to be an amateur virologist these days. What’s been your experience as an actual virologist during Covid-19?
I always say: “Will the real virologist please stand up!” It’s been an incredible couple of years to work in virology. On the one hand, people understand a little more about what we do. On the other, we had one of the first Covid-19 patients in the Netherlands come into Amsterdam UMC/AMC, and it’s just got busier ever since. It’s been a lot of hard work for everyone involved, with seemingly never-ending shifts, and we’ve needed to keep a constant eye on what’s going on in the hospital to supply test results round the clock in order to keep the clinical care up and running. I’m extremely proud of all my colleagues during this difficult time.
Your research is primarily about using human organoid technology to treat viruses – has that been used in research relating to Covid-19 as well?
In some respects, yes it has. I actually have a research student who’s looking at how organoids are used in Covid-19 research. So far, they’ve been used for antiviral research and to look at how the virus causes disease in different organs. For instance, human airway models are being used to test antiviral drugs against SARS-CoV-2: the virus that causes the disease Covid-19. These airway models give scientists a better idea of how effective the drugs are, but also whether they might be toxic to humans. In the past, we’ve seen lots of animal testing in the virology field, but it’s also a space in which there’s plenty of scope for replacing parts of the testing process with human models. For antiviral testing in general, companies are interested in having these new models as part of their portfolio.
What about vaccines – can they be tested using human organoids?
Not yet – at the moment, legally you can’t make a vaccine without animal research. Almost all of the vaccines available on the market at the moment, from polio to Covid-19, were tested on animals. But I believe we can and should change that. If we can put people on the moon, why can’t we make a model that will test the safety of vaccines?
A lot of animal testing doesn’t yield particularly good results. For example, in 2007, a vaccine against HIV that was tested on monkeys failed spectacularly. Meanwhile, we can treat all sorts of tumours in mice but can’t find a way to treat (or prevent) cancer. There has to be a better way.
How are you using human organoid technology in your main field of research, human picornaviruses?
First of all, let’s look at which viruses we’re talking about: polio is a well-known picornavirus, which in itself is almost extinct, but it has plenty of cousins out there for which there are currently no vaccines. The common cold is another picornavirus – one that it would be extremely beneficial to be able to treat effectively. As a group, picornaviruses are very intriguing because there are so many different variations and they can cause a lot of diseases, especially in children. The basic questions we’re trying to answer are: why does this child get sick but not that child? Why do children experience severe disease with this virus, but not adults? Our goal is to fight these viruses so that we can stop losing children to them. That doesn’t mean we work directly on drugs themselves, but we work on the mechanism by which the virus enters the body.
For example, our consortium GUTVIBRATIONS is building a model that brings human organoids and the immune system together: we can use it to look at how a virus that comes into the body via the gut then enters the brain. Are there characteristics in the virus or in the host that mean some viruses enter the brain and others don’t?
How does all this contribute to animal-free research?
Many virologists study systematic infections in animals, and traditionally virology has always relied heavily on animal research because you cannot infect a human deliberately. But I’m excited about the idea of building models that replicate human infection more closely. We don’t need animals for this – we need organoids. We started to build organoids in 2014, and now we have a whole lab with lots of different individual organoids and more complex organoid systems. We build organoids involving the airway and the gut as they’re the most important sites of entry. And we use brain organoids as the brain is an important end target for picornaviruses – it’s often the site of the most severe infection.
What’s your motivation for animal-free research?
I’m a doctor – I like working in the lab and researching questions that relate to human disease. My first experiences were in thinking about the human context – it simply didn’t occur to me to use animals. Of course, I have had to use animal-based products during some parts of my career – but I’ve managed to avoid using animal models in the lab. I felt a lot of resistance to working with animals, but it’s only recently that I’ve started to talk about it.
When I joined Amsterdam UMC/AMC, the patients – specifically, growing their human cells – were the starting point, not animals. In the meantime, my team was in contact with Stichting Proefdiervrij (the Dutch Society for the Replacement of Animal Testing) as they wanted to start a dialogue. If I’m honest, I was a little scared of engaging with animal-right activists, but now I have a very different perspective. There’s plenty of room for discussion, for innovation and for collaboration.
What does the future of innovation in animal-free research look like?
Innovation happens by believing you can do something, but also by collaborating with others in different fields. We’re already collaborating with tissue engineering companies, with immunology specialists, with animal-rights organisations… I feel like we’ll soon be collaborating with computer modelling and artificial intelligence specialists as well. When I look at what’s happening in the organoid field, it’s like reading a sci-fi novel. The sky’s the limit!
Where can people go to find more information?
There are two great resources for information about human-derived organoid technologies:
- OrganoVIR is a network of public and private experts and talented early-stage researchers, who team up to lead innovation in the field of organoids for virology. Their mission is to transform the virology landscape and establish human organoids as superior models for virus research.
- GUTVIBRATIONS is a multidisciplinary international consortium of European partners from the fields of academia and industry that are developing a next-generation gut-brain axis organ-on-chip. This multi-organ system will simulate the human body and provides an animal-free solution for modelling human diseases and pre-clinical drug development.
Follow Katja on Twitter @K3Wolthers and LinkedIn.
Interview by Vicky Hampton, December 2021