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Professor Allan Bradley – a decade at Sanger

15 Jun, 2010
Professor Allan Bradley

Professor Allan Bradley

Earlier this year, Professor Allan Bradley stepped down as Director of the Wellcome Trust Sanger Institute after ten years in charge. In an interview with Mun-Keat Looi he reflects on the great changes and achievements in that time.

Reclining in a garden chair on a sunny day in Cambridge, Professor Allan Bradley looks like a satisfied man. As Director of the Sanger Institute, he oversaw some of the milestones in genomic research over the past decade: the completion of the Human Genome Project and the first published genome sequences for mouse, malaria and cancer, to name just a few.

His tenure began at a time of uncertainty, albeit full of the promise of the genomics age. Bradley took the reins from Sir John Sulston in 2000, just as the Human Genome Project reached its peak. But with the announcement of the draft sequence, there were questions about what the Institute would do next.

“The question was: how does an institute which, essentially, had just one project evolve a more holistic approach?” says Bradley. “How do you add an academic dimension to a place that has been focused on the achievement of one major technical goal for so long?”

The ten-year plan

His first unenviable task was to set out a new strategic plan for the Sanger Institute. Bradley’s goal was to diversify its interests, essentially to transform it from a centre that sequences biology to one focused on the biology of sequences. Yet in the year 2000, the Institute had neither the infrastructure nor personnel to do the science it aspired to.

“What we set out was essentially a ten-year programme,” he says. “We needed the first five years of funding to build the physical infrastructure – animal labs for mouse work, containment units for pathogen work, IT capacity – as well as to expand our intellectual capital by recruiting scientific leaders in a few areas.”

Not every project worked out, of course. Schizosaccharomyces pombe and Caenorhabditis elegans programmes, although successful, were dropped as model organisms in favour of focusing on mouse and zebrafish. And while proteomics still holds a lot of promise as a field of study, it has yet to bloom as a high-throughput experimental discipline the way the researchers envisaged.

Bradley likens the first five years of the programme to “growing a tree and then pruning it back”.

“My philosophy is that it’s important to try things. They don’t always work, but that’s the nature of science. If it always works you’re not really pushing the boundaries of what can be achieved.”

World leaders

The key was diversifying, but with focus. Sanger remains associated with many big international projects, but what is important, says Bradley, is not just being involved, but leading projects and shaping them.

“The large-scale nature of Sanger’s projects is a historical feature of the way the Institute operates – managerial experience, organisation, bringing lots of people to bear on a common objective. What we’ve been able to do is replicate that in other projects.”

He cites the International Cancer Genome Consortium as a prime example. For many years this was solely a Sanger endeavour led by Professor Mike Stratton, Dr Andy Futreal and Dr Richard Wooster. Their vision and hard work founded the field of cancer genomics, which inspired a community of cancer researchers to emulate their approach all over the world. This has led to the formation of the Consortium, which aims to sequence the genomes from 25 000 cancer samples and create a free resource that will help cancer researchers worldwide.

Another key element in the Sanger strategy has been investing in young scientists in key areas, who would eventually become world leaders in their fields.

“Some of our greatest successes have been in identifying young people and watching them grow to international stature as a scientist,” says Bradley.

He highlights Dr Matt Hurles as an example. Hurles took on the Copy Number Variation Project at the Sanger Institute, helping to establish a major new area of study in a form of variation in the human genome that wasn’t fully appreciated at the time.

As Bradley says: “It shows that if you put decent resources in the hands of the right person, you can achieve a lot.”

The international nature of the Institute’s collaborations and its global reputation has led to a diversity of people from many different countries and many different backgrounds. The Institute boasts postdocs from 20-30 countries and students from twice that.

“The fact that people want to come here – be it 55-year-old professors on sabbatical or 18-year-olds on work experience – is very satisfying,” says Bradley.

“You know that over the years, you are fostering a way of thinking about genomics and high-throughput biology, and that people are taking that knowledge and experience to apply elsewhere. They wouldn’t have that opportunity in any other place in Europe.”

The Institute’s outreach programme, which offers teaching resources, school visits and student work placements among other activities, is also a source of great pride for Bradley.

“It’s a real testament to the impact that the Institute has in terms of societal value of the science,” he says. “We’re talking about inspiring the next generation of scientists. It’s not a big investment but this sort of activity has the potential to be very significant over the coming generations.”

Leading from the front

The Sanger Institute is now a hub of international science with strong programmes in human genetics, informatics, pathogen genetics and model organisms. It’s a far cry from 2000, or even 2006, when the Institute was mainly known for its sequencing work.

“Sanger today is regarded as an outward-looking organisation, far more so than it was a decade ago,” says Bradley, “We’re proud that people look at what we’re doing, access our data and resources, and in many cases work directly with us to achieve their scientific objectives.”

Having stepped down as Director, he will now concentrate on his research, though stepping back into the white coat shouldn’t be too hard considering he’s kept a laboratory throughout his time as Director.

“I felt strongly that I should have a lab and maintain my stature as an independent scientist,” he says. “Moreover, I wanted my lab to equal or exceed the very best in the Institute. It’s about setting academic standards and leading from the front.”

Bradley’s lab specialises in mouse genetics, for which he is well known. He has a new start-up company in mind, based on translation work developed by his lab, and is looking forward to getting stuck into the science again.

The Sanger Institute has made him more ambitious, he says, setting goals beyond what he once thought possible. “When I came here, my experience was of ‘one person, one project’ labs. Seeing what can be achieved with groups of people, and how the data, informatics and pipelines can be handled, has been profoundly influential. You don’t realise what the possibilities are until you get here and see you could do things 10 000 times faster and more efficiently.”

He’s excited about the new opportunities in genomics: induced pluripotent stem cells, new insertional mutagenesis techniques, further discoveries about gene function. I ask him whether people have been too quick to jump on the genomics bandwagon and whether that has contributed to the sense of disappointment some feel about the clinical applications of the field. But he disagrees.

“You have to remember that even though the draft sequence of the human genome was published in 2000, the gold standard sequence wasn’t finished for several years after. So, really, it hasn’t been that long since the human genome was sequenced.”

And while acknowledging that we still have a lot to learn, he points out how much we do know about human variation and how that influences disease susceptibility. We’ve also learned much about the function of genes from model organisms and variation in different pathogens. All of this will lead to fundamental changes in healthcare, he argues.

“I see opportunities that are greater today than ten years ago,” he says. “I’m more excited by science now than I have ever been.”

A decade of discovery

2001: Draft human genome sequence published

2002: Mouse genome sequence published, malaria genome sequence published, BRAF cancer gene discovery

2004: Gold standard human genome sequence achieved, UK MRSA genome decoded

2006: CNV project publishes first findings, C. difficile genome sequence published

2007: Researchers use mouse knockouts to uncover the critical role of microRNAs in the immune system

2008: International Cancer Genome Consortium Established

2009: Pig genome sequence published, Schistosoma mansoni parasite genome published, first cancer genomes published

Image credit: Wellcome Images
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