Gene revolution just a dream

Robert Matthews

• Last Updated: November 22. 2009 12:22AM UAE / November 21. 2009 8:22PM GMT

A scientist studies a DNA sequencing autoradiogram made during research associated with a genome project. Science Photo Library

It has taken an Icelandic company more than a decade and millions of dollars to do it, but last week it proved that dreams of a gene-based revolution in medicine remain precisely that: dreams.

The demonstration came not in a scientific paper, but in the form of a bankruptcy filing in a US court. It had been lodged by DeCode Genetics, a Reykjavik-based company formed in 1996 on a wave of excitement about the potential for genetic research to lead to cures for cancer and heart disease.

Founded by Kari Stefansson, a charismatic medical researcher at Harvard University, DeCode set out to find the genes behind these common killer diseases, discover their function and then design drugs that put right whatever was going wrong.

Even in those gung-ho times, geneticists knew this was going to be a bit of a challenge. Up until then, only the genetic causes of relatively simple but uncommon inherited disorders like cystic fibrosis had been identified. Diseases like cancer were already known to have somewhat more complex genetic roots. But DeCode’s strategy for identifying the relevant genes within the human genome was brilliantly simple. As an Icelander, Prof Stefansson knew that his fellow countrymen made the ideal target for a programme of mass genetic screening. Their isolation has given Icelanders a uniquely homogeneous genetic background, while a national obsession with genealogy means that family ties can be traced back hundreds of years. Better still, Iceland has a first-rate healthcare system, with medical records dating back to 1915.

To exploit this golden opportunity, all that was required was for blood samples to be collected from every Icelander. DeCode could begin correlating genes with insights from family trees and medical records, and come up with targets which drug companies could exploit.

As a strategy, it seemed perfect. Everyone seemed to win: Iceland would be the first to benefit from any drugs that were found, and then the rest of the world – while DeCode and its investors made a truck-load of money.

But almost immediately, the perfect strategy went awry. In a move that crossed the line between confidence and arrogance, DeCode struck a deal with the Icelandic government whereby all Icelanders were presumed to have given their legal consent to have their blood analysed. Only those who specifically objected to taking part would be left out of the programme. This provoked a storm of protest from doctors and privacy campaigners who argued that presumed consent strayed too far from the long-standing tradition by which doctors actively seek consent.

A legal challenge was mounted against DeCode’s plans, and it ended up abandoning its national DNA database. Convinced that its basic aims were sound, however, the company ploughed on with its quest for disease-linked genes, using DNA provided by tens of thousand of volunteers.

But as the years rolled by, a more fundamental problem with DeCode’s strategy began to emerge. Despite having the world’s best data set for the job, the company’s scientists struggled to find what they sought. They found that the genetic influences on disease were far more subtle than the cheerleaders for gene-based medicine had led them to believe.

After years of effort, the company turned its genetic findings into DG-031, a drug designed to protect vulnerable patients from stroke and heart attack. The drug got as far as clinical trials in humans but these were halted in 2006, when it failed to show consistent efficacy.

With money beginning to run out, the company turned to that other “great white hope” of 21st century medicine, genetic screening. As a revenue stream, this seemed promising: hardly a day goes by without the media reporting that a new gene has been linked to increased risk of some or other disease. DeCode offered to screen people for the presence of these genes, but found itself in competition with many other companies in a relatively small market.

Finally, last week, the company threw in the towel. In its 13 years of existence, it racked up debts of more than US$300 million (Dh1.1 billion), never made a profit and failed to produce a single effective drug.

For those with eyes to see, the writing had been on the wall since at least June 2000, when the British prime minister Tony Blair and the US president Bill Clinton trumpeted the completion of the “genetic blueprint” of humans.

While rightly hailed as a huge scientific achievement, the cataloguing of the human genome has failed to live up to the hype. Indeed, it has largely served to deflate it. Take its most basic finding: that humans have around 23,000 genes. This is a far smaller number than geneticists expected, given the complexity of the human organism.

A further blow to simplistic ideas about genes came when researchers finished cataloguing the genomes of other organisms. They found, for example, that rice has more than twice as many genes as humans, while just 300 genes separate humans from mice.

The central message of these findings is that, however they work, genes don’t work in simple ways. Only if genes interact with each other in incredibly subtle ways can a difference of just 1 per cent lead to creatures as different as a man and a mouse.

It’s a conclusion that has become ever more obvious as the years go by. Researchers have found a host of influences on genes, with environment and inheritance affecting how they are expressed. At the same time, many of the supposed “links” between genes and diseases have proved to be nothing but statistical quirks, as illusory as DeCode’s profits.

The harsh reality is that, with few exceptions, attempts to turn genetic insights into treatments for major diseases have failed. Billions have been spent by the world’s pharmaceutical industry in return for precious little.

And yet, despite the litany of failure, some scientists seem convinced they will one day succeed. Last week, one medical geneticist responded to the collapse of DeCode by telling The New York Times: “It would be a mistake to draw any connection between the medical promise of the human genome and the success of a specific company and business model.”

Three hundred million dollars says he’s wrong.


Robert Matthews is Visiting Reader in Science at Aston University, Birmingham, England