March 30, 2010 / 5:08 AM / 9 years ago

SPECIAL REPORT-Fast machines, genes and the future of medicine


One part of the hunt starts in a nondescript building in west London, where volunteers line up to reveal their innermost secrets. While many have given blood before, this time they are donating their DNA and medical records, both past and future, to a vast experiment that will track them to the grave.

It sounds Orwellian. Yet volunteers checking into UK Biobank — backed by the government and the Wellcome Trust — are keen to participate in something that might help their children or grandchildren.

This age group, 40 to 69 years, has been chosen because the volunteers won’t keep researchers waiting too long before developing interesting conditions such as cancer, arthritis, diabetes, heart disease and dementia.

So far some 450,000 Britons have signed up, consenting to have their DNA sequenced and their health tracked, anonymously, through the National Health Service.

The target of 500,000 should be reached around July, by which time the project’s giant freezer facility in northern England will have the equivalent of two road tankers worth of frozen blood samples.

Principal investigator Dr. Rory Collins says it is only by doing such large-scale sampling that scientists can uncover how lifestyle factors interact with a long list of rare genetic variants to cause common diseases.

“If you are looking for the effect of lots and lots of different genetic variants that are producing modest effects and they’re interacting with a lot of non-genetic factors, then you need to be able to do studies that are very, very big,” he said. “It’s only just now that the technology allows those experiments to be done.”

China, Sweden and other countries have also set up biobanks but the British one is the most comprehensive in terms of the number of factors studied. Organizers hope it will go beyond what earlier biobanks produced — like one in Iceland that helped create gene-hunting firm Decode Genetics.

Working out of a glass-and-steel building on the outskirts of Reykjavik, Decode’s scientists have peppered the scientific literature with reports on common DNA variants linked to schizophrenia, cancer and other diseases by trawling the country’s genetic heritage, which has changed little since the Vikings arrived more than 1,000 years ago.

Understanding a few of the pieces of the gene puzzle, however, was not enough to shore up Decode’s ailing business and the former Nasdaq-listed company filed for bankruptcy protection last November. It re-emerged as a private business in January.

Decode was one of a number of biotech start-ups that rode the first wave of genomics, offering the technological tools needed to understand the links between genes and diseases. Many fell by the wayside after just a couple of years — but not all.

Human Genome Sciences Inc HGSI.O is one that finally looks set for prime time. Its shares have skyrocketed since last year, when it reported unexpectedly strong data from a trial of its experimental lupus drug Benlysta.

Last March the company was trading as low as 45 cents; now its shares hover around $30. If approved, the drug, which is being developed in partnership with GlaxoSmithKline Plc (GSK.L), would be the first new treatment for lupus, a serious immune system disease, in more than 50 years.

But such winners are rare and investors remain wary of biotech drug developers over-selling the promise of genomics, given the fact that new medicines face a risky, 10 to 15-year path to market.

In fact, the past decade has turned out to be the worst in the history of the drugs industry, with a dearth of new medicines and an unprecedented cliff of patent expiries.

“There is no question that people have felt that they got their fingers burnt and the enthusiasm has decreased a great deal,” said Glaxo’s head of genetics Lon Cardon.

The problem for drug developers and investors is that greater knowledge has brought with it greater complexity, frustrating early hopes for relatively simple fixes to complex diseases.

Yet Cardon, too, now sees a turning point, driven by cheaper, faster sequencing and clear advances in one key disease area — cancer.


For many cancer patients, a major fear is that their surgeon missed something and their cancer will grow back. The only way to tell now is to wait until tumors are big enough to be spotted by imaging machines.

That could soon change. A gene-based test that can search a patient’s blood for tiny bits of DNA shed from tumors may soon give doctors an early warning that they may have missed something.

“That’s only become possible through the advent of so-called next-generation sequencing technology,” said Dr. Bert Vogelstein of Johns Hopkins University in Baltimore and the Howard Hughes Medical Institute, who is developing the blood test.

The test takes advantage of rapid advances in the technology to sequence whole genomes. The latest machines from companies like Illumina Inc (ILMN.O) and Life Technologies Corp (LIFE.O) can map out a patient’s whole DNA code in just a few weeks for as little as $5,000, a far cry from 13 years and $3 billion it took Collins and his international collaborators to get the first human genome.

Vogelstein said the rapidly falling cost of genome sequencing means the blood test could be affordable enough to be on the market within two years. Before long, all cancer patients could have their tumors sequenced routinely to find the genetic defects that cause them to grow.

“Cancer is maybe the best disease to cut our teeth on,” said Yale Medical School geneticist Richard Lifton. “The reason for that is we know that cancer is largely a disease in changes of DNA sequence.”

Matthew Meyerson of the Dana-Farber Cancer Institute and the Broad Institute of Harvard and the Massachusetts Institute of Technology said he is impressed by the pace of change. “The first cancer gene sequence was reported in 2008. There were probably 100 done last year. Maybe there will be many hundreds or even 1,000 this year,” he said.

Lifton predicts that within the next two years, scientists will have the genetic sequence of every major human cancer. “Many of these will identify new genes that we had not previously known about with a role in cancer,” he said. “Some of these will turn out to be incredibly important new drug targets.”

Or new tests, as Collins suggests. “If you’ve just discovered the molecular basis of a rare disease, you can turn it into a (test),” he said.

A new industry is just emerging to help them get there — and its smart kit is bowling over scientists.

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