For the next stop on our virtual tour around the UK meeting the directors of our research centres and institutes, we speak with Professor Ian Tomlinson, who heads up the Cancer Research UK Edinburgh Centre.
When geneticist and clinician researcher Professor Ian Tomlinson took over as director of our Cancer Research UK Edinburgh Centre in January 2020, little did he, or any of us, know that just a couple of months later he’d be steering the centre and its 100+ staff through a global pandemic and seeing cuts to research funding. “You can imagine the challenges involved in the reduction in funding, which was unfortunately necessary,” Ian says. “But we managed to steady things fairly quickly and we’ve been able to carry on as best we can.”
This seems a modest summary of the centre’s recent impact. In just a few of their latest studies, Edinburgh researchers have shown how severe brain cancer evades an immune system attack by using signals normally found in immune cells, published findings that will help doctors better predict treatment response in people with ovarian cancer and helped to optimise treatment for older or frailer cancer patients, for whom standard chemotherapy isn’t possible.
It all points to the centre’s clear commitment to translational research – whereby lab discoveries are translated into treatments and techniques for tangible patient benefit. Indeed, since its inception in 1979, the centre has grown into a major hub for research into developing more effective cancer treatments and reducing the negative side-effects of anti-cancer drugs. It’s also home to our Cancer Research UK Brain Tumour Centre of Excellence, a collaboration between the centre and University College London, and is integrated with the Edinburgh Experimental Cancer Medicine Centre and the Host and Tumour Profiling Unit, where tissue from patient samples is studied in extraordinary detail using the latest sequencing and imaging techniques. Having so much combined scientific and technological expertise in one place makes Edinburgh perfectly positioned to carry out the whole gamut of research, from discovery science – studying the basic biology of human health and disease – to clinical trials of new treatments.
A model career
Ian’s approach to the directorship and plans for the centre draw from an illustrious career that saw him elected to the Royal Society in 2019. He is perhaps best known for his work on cancer-causing genes, especially inherited genetic variants that predispose a person to cancer. And his work extends to the identification of disease mechanisms in model systems and cancer evolution. Over the years, Ian has developed models that describe and explain how cancers grow owing to changes in their DNA. One of these is the ‘just right model’, also known as the ‘Goldilocks model’. “I prefer the latter,” Ian says, “but ‘just right’ is the one that stuck.” The model dictates that the evolution of certain types of cancer relies on genetic mutations that don’t “completely mess things up” and kill cells, but rather influence the behaviour of a healthy cell just the right amount to compel it to do cancer’s bidding.
Researchers could use this model to develop treatments that, instead of trying to reverse cancer’s influence on the cell, could nudge the cell to the brink, causing it to pull its own self-destruct switch – a process known as apoptosis. Using the Goldilocks metaphor, Ian explains: “We could push things so that the porridge is too hot, as opposed to making it cold again. And because only the cells that have the mutation would be capable of being pushed too far, it could be highly targeted.”
Connecting the dots
Prior to this, Ian led work that identified and characterised genes that increase cancer risk. Although many of these genes predispose a person to bowel cancer, a particularly interesting development was finding a link between a type of smooth benign tumour deep within the skin – in the muscles that make your hairs stand on end – and kidney cancer. Working both as a clinical cancer geneticist and a cancer researcher, Ian was meeting patients who had these smooth muscle tumours and he soon realised that they ran in families. Ian and his team found that the families commonly had a mutation within a gene involved in energy production. “Perhaps counterintuitively, when energy production is blocked in your muscle cells and some kidney cells, you get a build-up of molecules that normally go on to form the energy supply for the body’s cells,” Ian explains. “You’d think that this would stop cells from dividing and forming a tumour, but in fact these molecules inhibit critical enzymes that are involved in restraining tumour growth, and therefore you get these smooth muscle and kidney tumours.”
Thanks to Ian’s astute connecting of the dots, families showing these symptoms are now being monitored to reduce their risk of cancer, and the conditions are known among healthcare professionals to help them identify people who are predisposed to the disease. “Bringing our findings into clinical practice is one of the most satisfying things about doing this sort of work,” he says.
A focus on prevention
Ian’s clinical background continues to influence his approach and the work he’s most eager to develop during his tenure. “I feel strongly that we should try as hard as we can to prevent common cancers from happening in the first place,” he explains. “I’ve seen patients die very young from cancers that could have been prevented. For some bowel cancers, for example, we’re now in a situation where, in theory, we could prevent almost all of them. Of course, in practical terms, it’s more complicated.” And while whole-population screening programmes exist for bowel, breast and cervical cancers, Ian thinks there are opportunities to screen for other cancer types. “In Scotland, there’s a high incidence of several cancers that are sometimes associated with so-called ‘lifestyle’ factors. We could screen some patients to detect tumours before they’re malignant or find cancers early, before they’ve spread,” he says. One important example is mesothelioma – a type of lung cancer largely associated with exposure to asbestos. “We have a large group of people with this disease here in Scotland. By working with our colleagues in Glasgow, we’d really like to see how we can make a difference in this area within the next five years.”
Another of the centre’s current focuses is the immune response to cancer. Treatments based on re-activating this response are now used widely to treat some cancer types. “One related, intriguing question is whether the body launches an anti-cancer immune response on a benign tumour that may grow into cancer,” Ian points out. “If the answer is yes, then there’s potential to intervene at that very early stage, before it turns into cancer, and give the immune system a boost.”
Training tomorrow’s leaders
Ian is just as committed to educating and training the next generation of science leaders as he is to current research. “We must ensure the infrastructure is there for people who, through a combination of ability and real enthusiasm for their work, will become great scientists,” he says, while also acknowledging that despite providing an optimal environment for junior researchers to make the ‘next big discovery’, there is a large degree of luck involved. “There’s no denying it – that forms a big part of science. Things can go wrong for no good reason. But if someone is enthusiastic and bright, that’s a good start.”
Central to it all, Ian says, is continued investment in the centre’s research, fuelled by the generosity of supporters. “Clearly, we would not survive without people donating,” he says. “Cancer Research UK will always be our main funder, and it’s that core funding that gives us the stability to be inventive and try new things. And because Cancer Research UK has endorsed the work we’re doing, we do better science and can work with groups at other great institutes in the UK and elsewhere. Putting that badge on is so important, even before you consider the money and what that enables.”
“Because of all that,” Ian says, “philanthropy is priceless.”
Beyond the bench…
Home is… in between Edinburgh city centre and the Western General Hospital, where I work.
In my downtime… I’ve always liked playing sport, particularly hockey. The fact that I haven’t been able to play due to the restrictions is a great sadness for me, but I am currently struggling to re-learn golf after a 20-year gap. I’ve also discovered, partly out of necessity, the pleasures of long-distance walking.
If I weren’t a scientist… I don’t know what else I’d be. I like the autonomy of science and I really enjoy finding out new things. I can’t think of any other profession that would give me that combination. That said, if I were lucky enough, I could envisage being an author of some kind.