Edinburgh scientists opening the door to brave new world of DNA discoveries

Professor Mark Blaxter in his lab

Professor Mark Blaxter in his lab

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A row of old wooden cupboards line a 
corridor in Edinburgh University’s Department of Zoology, labels helpfully stuck to the doors to explain what’s lurking inside.

They make Professor Mark Blaxter grin as he goes by. “Look at this one,” he smiles, pointing to a yellowing label, the words hammered out years ago on a typewriter. “‘Giraffe’. And that one – ‘llama’, ‘camel’. This makes me laugh – ‘horses’. That’s horses, plural.”

The cupboards are so small it is impossible they could hold more than a few lab coats, never mind horses, plural. Instead, the specimens are rather deflated examples minus bones, unlike the unfortunately overstuffed platypus next door which has been so hugely overfilled that it looks as if he’s overdosed on Big Mac meals.

Through a door are rows of old wooden workbenches – once packed with students, now banned from use because cracks in the wood could apparently harbour all manner of nasties – surrounded by rows of glass cabinets with long dead moths, crabs, birds and butterflies, precious samples brought from far-flung places for Edinburgh scientists to research. Scientists like the young zoology student Mark Blaxter.

Yet if his eye was caught by the dazzling colours of the butterfly collection back then, there’s no way he could have dreamed that in years to come he would run a team of researchers attempting to unravel the secrets of butterflies’ brilliantly patterned wings, or contemplate that he would be at the forefront of genetics breakthroughs with the potential to change our lives.

But that’s exactly what he and his colleagues are doing – and doing it just up the stairs from zoology rooms which would still be familiar to Charles Darwin, below right, but using technology which seems to belong to science fiction.

In Room 3.53 of The GenePool, three machines – looking not unlike photocopiers – buzz away as they produce the most startling array of data which just a few years ago would have made even Prof Blaxter’s mind boggle. It is this information which has the potential to dramatically impact our lives.

In just 48 hours, two of these £400,000 machines can unravel the complexities of ten individuals’ DNA, sifting through the six billion bases that create each person’s individual blueprint.

It’s an astonishing process which ten years ago would have cost £3 billion and years to achieve. Now, thanks to the non-stop march of technology, it costs just a fraction of that, opening the door to a future where every one of us could have our own DNA map.

Last week, Edinburgh University researchers took a giant leap closer to that when it emerged that the biggest genomics organisation in the world, China’s BGI, is to forge a new link with scientists at Prof Blaxter’s GenePool facility within the School of Biological Sciences, along with colleagues at The Roslin Institute and the Wellcome Trust Clinical Research Facility at the Western General Hospital.

Eventually, predicts lab director Prof Blaxter, these machines could churn out the genetic code of every baby born in Edinburgh – indeed, Scotland – helping pinpoint future illnesses, determine which medicines are most appropriate for them to take and mapping out the future for lives just days old or, incredibly, even before birth.

“We can sequence DNA from a mother even before her baby is born, which is exciting because if there are worries over the health of a foetus and we need to look after it before it appears, then we can,” he explains. “Eventually, most of the babies born at the ERI, for example, will have their genome mapped. It will be cheap enough to do.

“Say you have colon cancer. There are a number of genes which could be affected and whatever one it is affects what drugs you get. You need 50 genes to test for colon cancer anyway, so it’s almost cheaper to just sequence the whole genome.

“It’s going to be part of standard clinical practice very soon.”

While it’s easy to see the benefits of producing an individual’s genetic code in a bid to treat a certain condition, providing us all with a genetic map may raise serious ethical questions – particularly if it reveals other health issues.

“It has huge ethical complications,” says Prof Blaxter, who is a professor of evolutionary genomics. “Someone could go to hospital because they have stubbed their toe and you do their genome and find they have a gene that means they’ll have something more serious in the future.

“Or they come in with colon cancer and you discover that they are very likely to have very early onset Alzheimer’s. What do you do?

“What if an insurance company gets it, decides you are going to die at 46 and won’t give you insurance? Then there’s the issue that the state can track wherever you are because they have got the gene sequence from a hair follicle.”

He prefers to think the information contained within our DNA can be used to help, say, individuals destined for heart disease to plot better exercise and diet regimes. He adds: “If you know your metabolism can’t do something well but can do something else very well, then focus on that.”

Tempting as it may be for the father-of-three to run his own DNA through the machines to find out what could be in store, he shrugs and says he’s never even considered it.

Instead, he’d rather find out the genetic 
blueprint of, say, a miniscule worm that causes misery to millions in third world countries and discover a vaccine to protect potential victims.

“There are neglected diseases that affect a lot of people but they don’t have much money to buy drugs. Take elephantiasis, it affects the legs,” he says. “It is caused by nemotod – roundworms – and affects around 30 million people but there is no vaccine.

“For the drug company, there’s no reason for them to develop the drugs,” he adds, selecting a petri dish and slotting it under a microscope to show a dozen tiny creatures wriggling on its surface. “Suddenly we can offer a genetic approach.”

Unlocking the secrets of a tiny insect’s genetic make-up or, as in a recent case, of a particular species of exotic butterfly can change the way science thinks about evolution forever.

“We had two butterflies, different species but the same complicated wing pattern,” he explains. “These butterflies are perfect examples of Darwin’s theory of evolution by natural selection. They had developed markings which advertised themselves as being nasty and unpalatable, and the birds had learned not to eat them.

“It’s a leap of faith for biologists to state that these two wing patterns evolved to become like each other. But mating between species provides a sterile offspring. Some people have spent their entire research lives trying to figure it all out and now we have an answer.”

Four years ago in a worldwide project, a male Postman butterfly’s genetic printout was analysed until a 150-year-old riddle was solved.

“When you compare their genomes, you find the colour pattern genes are more similar than you would expect even by the wildest of chances, a one in a billion billion billion chance.

“The guy who did that element of it was too excited to speak. Our jaws dropped. This had to be a big change, an exchange of genes, and it had to be in the recent past.

“Two of these butterflies mated, one of the offspring carried the colour pattern gene and was able to mate with others in its species. Suddenly, two butterflies were like each other. It was shocking because species are not meant to do that.”

And, says Prof Blaxter, it raises a whole raft of questions about our own genetic make-up. “It suggests that there’s this pattern of sharing of genes between species that could be more common than we thought and might be a very important part of the evolution process,” he smiles.

“If it happened to butterflies, could it be 
happening in lots of places?”

MEAN MACHINES

THE human genome of 23 chromosomes is estimated to be around 3.2 billion base pairs long and contain up to 25,000 genes.

Ten years ago, it cost £3 billion to sequence the human genome and required the world’s largest computer. But today’s powerful sequencing computers have shrunk to the size of photocopiers, and a challenge that previously took years can be rattled out in hours.

“Sequencing has become about a 100,000 times cheaper,” says Professor Mark Blaxter, whose Blaxter Lab houses the School of Biological Services Sequencing Service.

“I sequenced 3000 letters of a genome of a small parasite that causes a nasty disease in India for my PhD. Cutting edge at the time, it took three years to do. The machines we use today can sequence 300 billion bases in ten days. It’s now cheap, accessible and there are all sorts of possibilities with this technology.”

The lab has two large machines which can sequence the genetic make-up of ten people every two days, plus a smaller one working at a slightly slower pace.

However, the link with the world’s biggest genomics organisation, China-based BGI, means the likelihood of fresh investment and more equipment at the laboratory.