Talking sci-novs and cancer with Dr Robin Hesketh

Dr Robin Hesketh sat down to write a novel about cancer – and coined the term sci-nov – but just where do you start?

Dr Robin Hesketh didn’t want to write a just another book about cancer – his aim was to write something for a general reader, but rather than focus on the ‘battling against the odds’ stories of sufferers, Robin wanted to tackle the story from another perspective – where the science and the scientists that do it make the story.

The result was Betrayed by Nature: The War on Cancer. We spoke to Robin to find out exactly what a sci-nov is, and to discover how he approached writing science as a story.

Tell us about Betrayed by Nature: The War on Cancer. I’d wanted to write this book for at least 20 years because the life of cells and molecules – the things that make all living organisms – is just such a wonderful subject. I figured that there must be lots of people who would say they don’t know much science and would love to have someone take them by the hand and lead them into this marvellous world. So the book is really for anyone who’s curious about how they work. But of course, once you’ve got the hang of how things work normally you can’t resist going on to look at what can go wrong – perhaps the most extreme example being what sets cancers off and helps them to develop.

Why do you describe this book as a sci-nov? I conceived it as a novel, although it’s about biology, because it’s for non-scientists so, first and foremost, it’s got to be an enjoyable read – something you don’t want to put down and that gets you enthused to go on and find out more – so it has to be a story where the biology is made fairly easy to follow. It’s also a good idea to have a liberal sprinkling of, if not rib-ticklers, at least allusions and tales that will make folk smile.

Science and especially biology is phenomenal: it’s what we are and just as plants and animals are beautiful, amazing, astonishing in their complexity and staggering in their variety, so too are the molecules that make them. That’s really what this ‘novel’ is about and the aim is to leave the reader not only fascinated by science but with the realisation that it can be, and often is, fun – yes, even cancer!

How did you approach it – just how do you write a novel about cancer? In one way it was easy because it’s more Shakespearean drama than Agatha Christie whodunit. So the historical background was ready and waiting: a pageant of a vast citizen army whose encounters with cancer have been recorded since the time of the ancient Egyptians. The cast with speaking parts was pre-assembled too – the principal players, kings and queens if you like, who have played leading roles as physicians and in unveiling the science. But the real stars are of the microscopic variety – and they speak through their actions rather than their words. These are the molecules that make us – proteins – the machines of life that breathe (or at least flex) and talk to each other (i.e. move around, bump into each other, change shape, and make things happen). In their ranks there are thousands of supporting roles – a sort of chorus – but many are important in cancer as messengers, signallers, regulators – and there’s even the odd murderer in there. As I said, these are almost always proteins but some small molecules and the odd steroid have cameo roles.

We also have a script, of course, in the form of our genetic code, enshrined in the sequence of DNA – a set of instructions for life that can, however, become disastrously corrupted – as can happen to coded messages in every setting from parlour games to the battlefield. And when something goes wrong with the script (i.e. it gets mutated), good guys can turn into knaves and rogues that upset the works. It’s more Richard the Second than Macbeth in that the destructive factors are mostly (though not entirely) beyond the control of the individual – but it’s a plot with far more twists and turns than even Immortal Will could have dreamed up.

So writing the novel didn’t need invention – the challenge was to weave all this into a story – to find the best analogies, anecdotes, metaphors and models to portray just how extraordinary living systems are and how cancers are created through yet more levels of complexity. It was easy in another sense too: for all its complications, at heart cancer is pretty simple to understand: damaged DNA (i.e. mutations) makes abnormal proteins that in turn give rise to cells making more of themselves in an uncontrolled way.

That does make cancer sound very simple: is it really that easy? No! Of course cancer is jolly complicated or it wouldn’t be killing nearly eight million people a year – a figure that’s set to almost double by 2030. But the simple description that DNA mutations change proteins and cause abnormal cell growth is fine. The trouble comes from the plurals in that sentence: the fact that cancers aren’t caused by single mutations (like, say, cystic fibrosis or many other heritable diseases). They’re driven by combinations of events and, to all intents and purposes, there’s an infinite number of these. The model I sometimes use is of a bus rolling along a flat road at, say, 10 mph – but this bus has no engine. So how come it gets moving in the first place and then keeps going? Well, obviously, it’s being pushed but to get a bus trundling you need ten or a dozen strong men. Each of these represents a key ‘driver’ (or ‘pusher’) mutation and different cancers have their own group of drivers. So the message of the bus model is that cancers are driven by groups of critical mutations – and treating them with drugs is difficult because you need to knock out several to have a significant effect.

What have you learned through writing Betrayed by Nature? First, my respect for the wondrous piece of evolution that is the English language is greater than ever – and the total immersion of trying to shape it to my ends in explaining biology is a continuing joy. I’ve also learned an awful lot of science, particularly from having to think through basic concepts when trying to come up with clear explanations – the aim being, as Einstein said, to make everything as simple as possible but not simpler. But I’ve also learned to look at science, and especially cancer, from a broader viewpoint than you tend to have working every day in a research lab. So I now follow reports in the newspapers and on the BBC more carefully than I did and try to see them as a non-scientist would – which has had the effect of making me much more sympathetic when people get irritated with boffins and their utterances (or reported utterances) of the “Another Great Cancer Breakthough” variety. I’ve also been very lucky in that Betrayed by Nature has already brought me into contact with some amazing people, particularly several dealing with cancer in themselves. To hear from them that they enjoyed the book and found it helpful has been one of the great experiences of my life and a wonderful vindication of my motives for writing it.

What would you say is the most important part of Betrayed by Nature? As I’ve said, I’d hope readers enjoy gaining a sense of the wonder of biology and a desire to find out more. From a practical point of view, the story covers some of the most dramatic events in scientific history – from the discovery of DNA as the material of heredity to the Human Genome Project that produced the first complete DNA sequence in 2003. After that BbN moves to the present with the breath-taking events that are taking us into a new era of personalised medicine in which treatment will be designed on the basis of the specific mutational profile of an individual cancer – and that is going have an impact on the lives of all of us.

You're a senior lecturer in the Department of Biochemistry at the University of Cambridge – what do you do here? To be really accurate, I’ve recently retired but the department is kindly letting me continue doing experiments aimed to develop ways to stop tumours growing – though gradually letting me off teaching and sitting on committees. But it’s worth a further word of explanation about just what people who have teaching positions in major research departments do, because I think most outside that world have absolutely no idea.

Those who hold lectureships generally run their own research group and, as even the smallest is likely to have an annual budget of several million, raising money and administering a group is almost a full-time job on its own. In addition many will try to continue to have a ‘hands-on’ involvement doing experiments. Their second job is to teach, which includes not only lecturing but running practical and tutorial sessions, to all of which may be added (in Cambridge) college supervising if they hold a fellowship. A third component is the inevitable administration that can cover everything from designing lecture courses to the dreaded ‘elf & safety’ and will also include, almost every year, being an examiner in one of the half dozen or so Tripos courses to which the Department of Biochemistry contributes.

So I’m very lucky now as I get to do the just good bits – which means that I have time to concentrate on giving public talks on biology and cancer – a great challenge but hugely enjoyable. And there’s the next book – as well as the blog!!

• Palgrave has given us two copies of Betrayed by Nature to give away. To win, just send your name, address and organisation/ institution to phil.prime@laboratorynews.co.ukby 28th September.And if you can’t wait that long, get a 30% discount plus free P&P by visiting www.palgrave.com and entering WLABNEWS30 at the checkout. (Available until 31st October 2012.)