Translating science in more ways than one: an interview with Frances Balkwill

Frances Balkwill was born near London and carried out her undergraduate training in Bristol. She began her graduate studies in the Department of Medical Oncology at St Bartholomew’s Hospital, where she later returned as a principal investigator in the Barts Cancer Institute, and is currently Lead of the Centre for Cancer and Inflammation. Her post at Barts and a dedication to communicating science to children led her to take on the additional role of Director of a unique interactive science centre known as Centre of the Cell, which opened its doors to the public in September 2009. The Centre is located within the Blizard Building, which also houses laboratories of the Institute of Cell and Molecular Science at Barts and the London School of Medicine and Dentistry.

How did your time as a graduate student influence your path into translational cancer research?

I initially wanted to study medicine. I ended up changing my mind, but I think that’s why I’ve always wanted to do translational science – I’ve always been interested in the real disease, and I really always wanted to work with cancer patients. I went to do a PhD with Gordon Hamilton-Fairley at Barts, who was the first specialist medical oncologist in the UK. He was a wonderful man, but he was killed by the IRA in a dreadful accident, while walking his dog, during the time I was a student. After Gordon died, I was taken on by a second supervisor, the Professor of Pathology at Barts, but he died of heart attack 6 months later. So, I never really had a PhD supervisor, although Professor Tim Oliver helped me towards the end. It was a strange time.

My training was translational right from the start. Gordon actually interviewed me for my PhD in the leukaemia clinic. As a student, I used to go onto the ward and take blood from the leukaemia patients, and hold their hand as they had bone marrow taken from the iliac crest. So, the translational emphasis was really immediate, and I’ve never strayed away from wanting to study the whole cancer, for better or for worse.

These days, a main focus of your research is on developing anti-cancer agents that block certain cytokines, chemokines or chemokine receptors. What is it about these types of molecules that makes them good targets?

Chemokines and cytokines are downstream druggable targets of oncogenes. For example, Ras induces IL-6, Myc induces various chemokines and IL-1, and mutation of VHL stabilises TNF mRNA. Targeting these molecules is a way of interrupting the conversation between the malignant cells and the other cells in the tumour. Also – although this is still unclear – chemokines appear to control the movement of both malignant and accessory cells in and out of a tumour. There’s no doubt that there is a great deal of inappropriate expression of inflammatory mediators and inflammatory transcription factors, even in the early stages of cancer. This is all part of setting up a ‘rogue organ’.

You’ve collaborated extensively with industry in bringing some of these anti-cancer agents to clinical trials. What’s involved in bringing a new idea to that level?

You need to convince a pharmaceutical or biotech company that you’ve got a good idea. A lot of it is about being in the right place at the right time, and having a good story. Sometimes, a company comes to us with an antibody or a small molecule and asks if we’ll do the preclinical trials. Other times, we’ll go to them. Once you get a track record of working successfully with companies, it’s easier – companies start to come to you.

What do you see as the major hurdles we’re currently facing in translating new anti-cancer therapies to the clinic?

One big barrier is the difficulty in getting patient samples. This was extremely difficult in our last clinical trial on ovarian cancer, but it’s not trivial to take samples when you’ve got patients who are very sick. Although that aspect is incredibly difficult, I do believe that’s the only way to investigate the hypotheses.

Another problem with the type of work that I do is that we don’t have that many good models of the human tumour. If we want to develop a therapy for ovarian cancer based on anti-human IL-6, how do we model that in a mouse? We can transplant human tumour xenografts intraperitoneally, but this isn’t ideal. We should also use 3D models in parallel, because a lot of the things we’re interested in only work on human cells. Genetic mouse models are fantastic, but they are incredibly expensive and time consuming.

If you could go back to the bench, what would be your first priority?

I’d work on trying to grow cancer cells and other cells properly, in a proper microenvironment, with the proper mechanical properties. The tumour microenvironment is probably not a ‘moving target’ like the malignant cells, so it may be a more realistic drug target. But the problem is that the microenvironment is more ‘normal’ than the malignant cells, so it could be more difficult to target specifically. Also, some people have shown that if you inhibit one cell type in the microenvironment, the tumour can bring in another cell type to accomplish the same task: for example, if you inhibit macrophages, the cancer might be able to bring in immature neutrophils to fulfil the same function. So, it might not be enough to obliterate one cell type in the microenvironment, because the malignant cells can adapt, and perhaps even become more invasive as a result.

In addition to working in cancer research, you’ve written several children’s books about science.

Yes, 13 of them!

That’s not something many scientists do – what gave you the idea to write for children?

It was when my own children were young. I had spent a lot of time looking down the microscope at cells, and I thought they were really gorgeous, and I wanted to show my kids. I went to a bookshop, as I thought there was bound to be lots of good body books and science books – but the science was quite disappointing, and there really wasn’t anything on cells. So, through various ways, I got to know a graphic designer who was a very talented cartoonist. He didn’t know anything about science, but he was interested in science. That worked really well because I couldn’t draw, but I could write and I knew how things should look, so it was a very good partnership. I also edited some other books. Doing this kind of thing really feeds your science: to try to explain immunology or genetics or cell biology in just 3000 words at a level a child will grasp is an amazing challenge.

When we were looking to get the first book published, we had loads of rejections before approaching HarperCollins. I phoned up on a rainy day and somehow got put through to the Senior Editor of children’s non-fiction. We bonded on the phone immediately, and she said I should come and see her. It just happened that they were looking for new ideas. They phoned up 3 days after the initial meeting and said, “We want four books”, which was just incredible! We later won the Science Book Prize, and the books were translated into lots of languages, all of which was very encouraging.

Even now, amazing stories crop up about how these books have influenced readers. Just a couple of weeks ago, I got an email from a Chinese postdoc who is interested in coming to work with me because she’s pursuing a dual career in research and science communication. I asked her how she found out about what I do, and it turned out that her supervisor in China had a copy of one of my books, ‘Cells Are Us’, in his office, that he’d picked up in Germany!

Your passion for communicating science to children is now realised in your capacity of Director of Centre of the Cell. How did the Centre come to be?

When I came to Barts, they were planning to build a new research building that would bring together various different buildings and research sections on the Whitechapel campus. Mike Curtis, who is now Director of the new building [the Blizard Institute], had mentioned as long ago as 1997 that he wanted there to be a public space in the new building. After I’d joined, I asked the University if they wanted me to take responsibility for it. We decided to call it Centre of the Cell. The physical Centre has been open since September 2009, and the website was launched in 2007.

It was a real struggle to find the £4 million we needed to fund the Centre. The university was fantastic, in that they gave us the shell, and made a major financial contribution with lots of ‘in-kind’ support as well. We wanted to do something that was more than just space for exhibitions – we wanted to do something that would knock your socks off. So, I encouraged the designers of the Centre not to think about the money, but just to dream about what they’d like to do. The design was a challenge because it’s a small space – only 80 square meters. As it turned out, that’s been an advantage, because the Centre is really immersive. What would have been a vast gallery in a science museum is concentrated, which gives it a great theatricality and a real buzz. And it’s been amazing to see what happens when you stick something like Centre of the Cell in the middle of a working laboratory: it triggers all kinds of ideas. About 120 or 150 of our scientists are now involved.

The aim of the Centre is not just to stimulate the next generation of biomedical scientists, doctors and health professionals, but also to promote scientific literacy. The top-level message of Centre of the Cell is: “Your body is made of millions of cells, and when you’re ill, your cells have gone wrong. People here and all over the world are trying to find ways to put cells right”. We’re soon going to expand this to add something like: “There are ways that you can look after your cells”, because the 1-year survival rate for cancer in East London is the worst in Europe, and we don’t know why. We don’t know whether it’s a matter of education, whether people don’t come to the doctor in time – it may be more complex than that. Science education may be a way of reaching people. It’s the kind of thing that’s really challenging and interesting to do.

How is the Centre funded now?

We currently run the Centre as a charity. We have wonderful core support from the University and medical school, trusts and foundations, businesses and banks. But the way we’ll survive in the long term is by cloning around the world, by building new centres in other cities. Very few children’s science centres or museums around the world have cell biology and biomedicine content, which is really the core of modern biomedical science. So, that’s our future.

Excerpts from this interview can be heard in the podcast associated with DMM Vol. 4, Issue 3 at http://www.biologists.com/DMM/podcasts/index.html. DMM greatly appreciates Professor Balkwill’s willingness to share her unique thoughts and experiences. Professor Balkwill was interviewed by Sarah Allan, Scientific Editor for DMM. This piece has been edited and condensed with approval from the interviewee.