David Crosby is Head of Prevention and Early Detection Research at Cancer Research UK (CRUK): the world’s largest independent cancer research organisation. It is the world’s second largest non-commercial funder of cancer research, after the US government. David began life as a baby, before becoming a pharmacologist via a PhD studying cell signalling in platelets. With this, he went into academia and spent time lecturing in clinical pharmacology. He then moved into industry, identifying and evaluating new clinical development opportunities for Linde Gas Therapeutics: the world’s largest medical gases company.
David then moved into the public sector, joining the Medical Research Council: the UK’s government research funding agency. Here he oversaw various key scientific themes and research funding programmes (including inflammation, cardiovascular and respiratory research). Latterly, he led the MRC-NIHR Methodology Research Programme, together with the MRC’s strategic delivery plan and its investments in experimental medicine. David is now developing and implementing a new strategy and programme of research investments at CRUK. These aim to accelerate progress towards earlier detection and prevention of cancer, through an integrated multidisciplinary approach, driven by equitable improvements in health outcomes.
When or where do you get your best ideas?
While I am out running – it’s pretty much the only time that I’m not mentally engaged in something. I’m usually either in front of the computer, in a meeting talking to people or getting kicked in by my kids: I’m doing something the whole time and never have time where I’m just sitting with no immediate activity.
Whereas when I’m out running, I just have music on and I run and I think.
Which failure or failures changed you the most, if any?
I recall a time when I was working at the MRC: I was doing a big project in systems biology and was attempting to get the board of MRC to think about the project in a different and more ambitious way.
Whenever you’re trying to pitch something to the powers that be, there’s a balance between telling them exactly what they should do, what you want them to do and endorse, and giving them space to think of ideas and create.
For example, if you tell people in power: “You should do this,” people can react negatively. It can rub them up the wrong way. It can come across as you giving them orders. It can sound like you’re telling them something they should maybe already know, and in a sense asking them “why haven’t you already done this?” That can raise antibodies. The opposite is you paint a picture of a broad area, while outlining some challenges and trying to give them the space to independently conclude what should be done. But the danger with this is that you run the risk of basically not asking them to do anything.
Back at the MRC when I was pitching my idea, I painted a broad canvas, giving them space to input. It did not work. It crashed and burned. They were interested: they read the paper and thought it was a fascinating area. They had a lovely philosophical chat about it for an hour and got absolutely nowhere. We ended up with no real recommendation, no real sense of direction.
It was definitely a failure, and it has certainly changed the way I approach things since.
I now pitch things better, engage people’s imaginations, and give them space to think and generate ideas. I do this while still maintaining direction and presenting clear options (including the one I may wish to subtly nudge them towards!).
What’s the best piece of advice in work, or life, that you’ve been given?
The best piece of advice I’ve been given is sometimes it’s best not to have an answer to every question.
My inclination, whenever I’m talking about something in my area of expertise, if somebody asks me a question or highlights a potential issue, is to respond with an answer. I’ve usually got an answer and I’m seldom ever stumped. I will want to explain why the thing that they are saying is a problem isn’t in fact a problem, and I will give an explanation for that. That is my instinct.
A previous boss of mine said: sometimes answering every question this way is the wrong thing to do. If you’re being questioned on something by a more senior person, this is usually as they think they’ve seen a flaw in what you’re doing or saying. Dismissing their thinking therefore often does not land well. A better approach is to say: “Ah, brilliant, that’s a great thought you’ve just expressed. That is something we need to be very careful with and really think properly about. We’ll take that on board, it might really affect the way we do things going forwards.” And of course often those senior people are right!
What are you inspired most by?
Persistence in the face of adversity.
People that take knocks and keep on going, people who have disasters before them personally or professionally, yet in spite of this manage to keep themselves together and deal with their horrendous circumstances and persist and succeed nonetheless.
What is an event that changed your life?
There have been plenty, I’m sure. However, the most significant was when my mother died of colorectal cancer. It was a late diagnosis and she was young, only in her early 40s. I was 16.
I was interested in science already, but I think it definitely cemented in me the desire to try and help to do something. I knew science and biomedical research had the power to help and to save lives. I wanted to be part of that and contribute.
I think it is no coincidence that I have ended working in cancer prevention and early detection. I feel that the most impact will be achieved through prevention and early detection: at the point when you can still help people. You’re not fighting cancer diagnosed at a late stage, when the disease has already become intractable.
What’s the next big thing in cancer research? What is the next game changer?
One of the most interesting things happening right now, and that will change the way we think about and try and deal with cancer, is the discovery of increasing numbers of what appear to be cancer-causing mutations in perfectly normal tissue. The immediate lesson from this is that cancer is more complicated than we initially thought.
The reigning paradigm of cancer until now has been of a disease caused by mutation. If you get a mutation in the wrong gene in the wrong place, then bang: cancer. While that is still a fundamental part of the picture and you don’t get cancer without it, it is not the whole picture.
We’re seeing work in a number of centres, where they’re looking at healthy-looking, phenotypically normal epithelial tissue riddled with cancer driver mutations. In skin, eyelids, the oesophagus. And yet, even with these mutations, there are no actual cancer lesions.
Why is that? What is the immunological mechanism that means cells can continue operating as normal despite having those driver mutations? What’s the tipping point that then flips those cells from normal (but mutated) into pre-cancerous or cancerous?
The more we unpack that biology, the more opportunities that’s going to give us for early detection and early intervention. This is the concept that the Americans call ‘interception of disease’, where you are able to spot risk and spot cells that have gone a bit wrong. Cells that are possibly on a trajectory towards cancer but aren’t yet cancer.
If you can remove those cells, it should prevent any potential development into cancerous from ever happening. Understanding the biology behind this will enable us to determine who is at risk and who we need to offer intervention to.
How far down the road you think that is – that we really start to understand this?
I think we’re at the start of a journey. These insights have only been emerging over the last five years or so and the increasing pace of knowledge acquisition is tremendous. But we’ve got a way to go.
That said, what is happening now is really encouraging. Even with the knowledge we do have, strategies are already being developed to try and intercept cancer early. For example, in high-risk groups with inherited germline mutations (pre-dispositions to cancer), efforts are being made to develop preventative vaccines.
If you have pre-cancerous or early cancerous cells, often they express neoantigens on the surface. These neoantigens are proteins, but are different to healthy proteins. You can vaccinate against them, meaning that the immune system can then patrol for (and destroy) the pre-cancerous or early cancerous cells before they ever get anywhere near being a clinically apparent cancer.
This is happening now and we’re only going to get better at things like that. It’s very cool.
What’s your favourite paper that you’ve published in the last five years?
I am really proud of a paper that we published two years ago: Early detection of cancer. It’s a review of early detection work in the journal Science.
Myself and colleagues at CRUK convened a gang of world-leading researchers across the space of early detection. Subject areas ranged from biology, to technology innovation, to imaging, to clinical trials, to population science.
Our aim was to give a true picture of what the whole field looks like right now. Where are the innovations happening and what does the future look like? What are the barriers to getting to that future, where are the challenges and where does the field need to concentrate its efforts?
It was an attempt to plant the flag and say to the wider world: if we get it right, we’re going to save lives on a really big scale. It was a massive effort by the authors and my colleague Alexis Webb at CRUK, whom I’d like to give a shout out to.
It has been pretty well-received, and well-cited. Hopefully we planted a few seeds in people’s minds.
Which book has greatly influenced your life?
‘Made to Stick’ by Chip and Dan Heath
It’s written by two brothers and gives advice on how to communicate ideas. How to make your ideas stick in people’s heads and be memorable and influential.
They dissect lots of real-life examples of how people have effectively communicated ideas that have changed behaviour. For example, Apple: how they came to dominate the mobile phone markets early. Or how a particular airline came to dominate the low-cost travel scene in the US.
It’s absolute gold and it’s massively useful. It’s totally implementable and it’s very much informed the way that I communicate. Everyone can learn from it, but particularly if you’re ever in a scenario where you’re pitching something – for example convincing your boss to do something, or convincing a panel to fund your project.. the list goes on!
If you could have a gigantic billboard anywhere, with anything on it, what would it say and why?
Something along the lines of: “It’s OK: go for it”
I spend a lot of time saying this to my family and colleagues. It is easy to be buried under anxiety and problems, and to become paralysed through a fear of difficulty and complexity. But it’s okay. Just go for it. Don’t worry about it. Don’t get caught up in anxiety and problems.
What are bad recommendations you hear in your profession or area of expertise?
Anything that sounds like “it needs to be perfect.”
There is no such thing. Nothing is perfect: everything has flaws. It’s impossible to predict every eventuality. I plan and I’m careful and considered, but whatever it is, at a certain point you’ve got to stop working on it and just shoot. Just press the button and do it and hope for the best. Whether it’s work, or at home.
Sometimes I write songs or do drawings for the kids and there’s always a temptation to endlessly tinker and improve. Whatever the thing is that you’re working on, you could work on it forever. So, whether it’s your next paper, your next grant submission, a song, a drawing, you could keep tweaking and tweaking and tweaking.
I often see people paralysed trying to make things perfect and tearing themselves to bits. It’s self-destructive.
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The views expressed are those of the author. Posting of the blog does not signify that the Cancer Prevention Group endorses those views or opinions.
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