Archives for June 2010

If the sequencing of a single human genome - the complete genetic blueprint for an individual person - was an astonishing achievement, a breakthough to rival the first landing on the moon, then what price 10,000 genomes?

Ten years, almost to the day (the actual anniversary is on Saturday), after British and American scientists "flopped over the finish line" clutching the first 3 billion letter draft of a single DNA code, the Wellcome Trust is launching a project to sequence 10,000 human genomes over 3 years.

The project, known as UK10K, is expected to reveal many of the rare genetic variations that give rise to disease. It will involve the sequencing of the genetic codes of 4,000 healthy volunteers, and another 6,000 who are known to suffer serious medical conditions including neuro-developmental disorders, congenital heart disease and obesity.

The hope is that by comparing the genetic codes of so many individuals, researchers will be able to tease out the subtle variations - the individual genetic mutations - that give rise to disease.

The project has been made possible by astonishing advances in the speed - and corresponding fall in cost - of genetic sequencing. If Moore's Law dictates that computing power doubles every 18 months, then gene sequencing technology is well ahead of the curve, doubling every year.

"The pace of technological change is extraordinary," says Dr Richard Durbin, who will lead the project. "It took a decade to unravel a single genetic code. Now we can study the genome sequences of 10,000 people in three years".

Speaking on the programme this morning the two scientists who lead the original project to sequence the human genome, Sir John Sulston and Professor Francis Collins, said medical science was rapidly approaching a tipping point where genetic insights would start to transform patient care. Within five years genome sequencing would be commonplace - a basic part of everyone's medical records that would inform decisions about lifestyle, and which drugs would be appropriate for them and at what dose.

"We've really arrived at a revolution here," says professor Francis Collins. "It's coming gradually, not overnight, but it is transforming our understanding of biology and medicine".

Pollinating insects - like honeybees, bumblebees, hoverflies and moths - are the unsung heroes of global agriculture.

Their busy comings and goings help to fertilise a third of all the crops grown around the world, and provide an economic service to UK farmers (pollinating commercial crops like oil seed rape and soft fruits like raspberries and tomatoes) worth £440 million a year.

Without them we will be hard pushed to feed a global population set to reach nine billion by 2050.

And that's a problem, because pollinating insects are in steep decline.

Of the 25 species of bumblebee native to the British Isles three have recently gone extinct and others are increasingly rare. Honeybee populations have crashed (mostly as a result of disease), and there has been a 75% decline in butterfly species since the 1970's.

Speaking on the programme this morning Professor Andrew Watkinson described the decline in insect pollinators as "catastrophic", but said there was no obvious single cause, or cure.

"There are a range of potential issues here. We know that wild flower populations have declined significantly since the 1930's, and that agricultural land use patterns have changed. Habitats have been destroyed, pesticide use has increased, and pollinators have also faced problems with disease. So there are a range of problems that we need to address".

In a bid to get to grips with the problem the Government is to fund a series of nine research projects through the Insect Pollinators Initiative, that will look at everything from the causes of insect decline to potential treatments for disease.

The studies include research into the Varroa mite, which has devastated honeybee populations, and the impact of the cocktail of pesticides and agricultural chemicals in use in modern farming.

"It's imperative that we get to the bottom of what's causing these declines," Prof Watkinson says, "so that we can ensure food security and also maintain biodiversity in the countryside."

"Today we are learning the language in which God created Life."

When President Bill Clinton unveiled the first draft of the human genome - the complete genetic blueprint for an individual person - in a live transatlantic celebration, you could be forgiven for thinking hyperbole was going out of fashion.

Hailed as a breakthrough to rival the discovery of DNA itself, the achievement would revolutionise health care, paving the way for cures to our most intractable diseases, and launch a new era of personalised medicine.

Given the tools available at the time the unravelling of the genetic code - mapping out the three billion chemical letters of all the genes present in every one of the hundred billion cells in the human body - was an astonishing achievement. The culmination of a decade of hard work by hundreds of researchers and computer scientists both here and in the United States.

"We flopped over the line in June 2000 pretty much exhausted," recalls professor Mike Stratton, now the director of the Wellcome Trust's Sanger Institute, where the UK effort to sequence the human genome was focused. "Just doing that, just getting to that milestone, was a massive enterprise".

But it was also just a start. Many of the scientists involved - if not the politicians - understood that it would take years more hard work, and a massive increase in the power and speed of gene sequencing, to realise the dream of a revolution in health care outcomes.

That's because the real benefit of this "complete parts list" for all 21,000 genes in the human body, comes from comparing it with other genomes. Only then can scientists begin to tease out the subtle differences - the individual genetic mutations - that give rise to disease.

Standing somewhat incongruously, like an oversized 1950's washing machine, in the Atrium of the Wellcome Trust's Sanger Institute just outside Cambridge, is one of the robotic sequencing machines that did so much of that ground breaking early work.

But while the ABI 3700 could sequence 96 snippets of DNA at a time, ten years on it's already little more than a museum piece. Humming continuously in the Institute's main sequencing hall the latest generation of sequencing machines can process an entire human genome in a fraction of the time.

"The initial human genome sequence took many many years," Says the head of gene sequencing at the Sanger Institute, professor Julian Parkhill. "One of these machines will generate a whole human sequence in a matter of weeks. At the moment we're sequencing hundreds of individual humans and planning to sequence thousands more over the next few years".

One area of medical research that has been transformed by the lessons of the human genome project is cancer.

Because all cancers result from mutations in the DNA of individual cells, having a reference blueprint has allowed scientists like professor Mike Stratton to begin to hunt down the variants that give rise to disease.

"These abnormal cancer genes are the achilles heel of the cancer. They provide us with our first stop as drug targets. So that's an illustrative and optimistic and positive way in which we can use the human genome to find new ways to treat human disease".

To date only a handful of the genetic mutations that give rise to disease have been identified. But, even after ten years, it's still early days. As the computing power of sequencing increases - and costs fall - it should be possible to tailor specific drug regimes to individual patients - the much heralded era of personalised medicine.

The post-genomic revolution has only just begun.

The UK is rightly proud of its record in biomedical research, punching above its weight in terms of investment, and second only to the United States in the number of academic papers published in scientific journals.

The question is how to maintain and enhance that leadership position in the face of fierce competition from emerging economies like China and India.

Dubbed a "cathedral for science" the UK Centre for Medical Research and Innovation (UKCMRI) is one answer to that challenge.

The Institute is the brainchild of the Medical Research Council, the Wellcome Trust, Cancer Research UK and University College London, who are joining forces to create this huge new hub for research and cementing the UK's position at the forefront of international science for years to come.

The vision includes space for more than 1,250 scientists, and brings biologists together with chemists, physicists and computer scientists under one roof to tackle the underlying causes of some of our most pressing health care problems.

According to Sir Paul Nurse, the Nobel Prize winning biologist who chairs the consortium's scientific planning committee, "The UKCMRI will provide the critical mass, support and unique environment to tackle difficult research questions."

At an initial cost to the Government of £250 million the UKCMRI had been considered vulnerable to the Treasury axe. When the project was signed off by Gordon Brown shortly after the last budget that money was due to be paid in a lump sum up front.

Earlier this month a spokesman for the Department of Business Innovation and Skills confirmed the project would go ahead, but that the funding would now be staggered over a five year period. It means the project will get just £17 million this year.

In the circumstances the MRC's chief executive, Sir Leszek Borysiewicz, said it was the best the consortium could hope for.

"The Medical Reasearch Council understands the need for budget savings in the current economic climate. We are satisfied that the Government is fully committed to UKCMRI".

Take a look at this picture - a tale of two potatoes.

The one on the left is a standard Desiree potato - very good for roasting and chips, but sadly somewhat prone to fungal infection.

The sorry looking excuse for a spud on the right is a wild relative of the Desiree which is actually poisonous to eat, but does have one highly desirable characteristic: It's developed a natural resistance to the fungal infections that cause late blight.

You can see where this is going, and if scientists at the John Innes Centre near Norwich had managed to cross these two by conventional plant breeding - producing a potato with all the culinary qualities of the Desiree, but with the added benefit of hardy resiliance - it would be hailed as some sort of super spud.

But that's not quite what has happened. The researchers, led by Professor Jonathan Jones, have managed to cross the potatoes, but they did it by genetic modification - isolating the genes that confer blight resistance from two species of wild potatoes, and inserting them into the genome of a conventional Desiree variety.

The results - in the shape of 300 genetically modified potato plants - are being sown on an experimental plot behind the Sainsbury Laboratory at the John Innes Centre today.

"It's really very simple," says Professor Jones, "We identified a gene for late blight resistance in a wild potato from South America, and used biotechnology to sieve-out that gene from the 30,000 other genes in the plant, and then transfer it to the cultivated potato variety".

The stakes are high. Late blight is the disease that caused the Irish potato famine, and on average UK farmers spend between £30m and £50m a year spraying crops up to 15 times with chemical fungicides. If the trial goes well, Professor Jones says, it could lead to the development of new varieties that wouldn't need all those expensive treatments.

It's a sign of the times that as the plants go in the ground a 15ft wire fence bristling with CCTV cameras is also being erected around the trial plot. Previous GM crop trials have been targeted by environmental campaigners who claim the risks associated with genetically modified foods are simply too high.

Speaking on the programme this morning Friends of the Earth's Kirtana Chandrasekaran said the real reason why GM crops had not taken off in the UK was because they offered no benefit to consumers, issues around food safety remained unresolved, and similar advances could be achieved through conventional plant breeding at a fraction of the cost.