Third-generation 'single-molecule' technology has been used for the first time to read a human genome sequence. Professor Stephen Quake, from Stanford University, California, US, is only the eighth person whose genome has been published since the first breakthroughs were made in 2000. When this latest generation of technology is perfected the hope is that it will bring us one step closer to ‘the $1,000 genome' that will open the door to personalised medical treatments based on an individual's unique genetic makeup. Details of the research were published in the journal Nature Biotechnology.
When the Human Genome Project commenced in 1990 the cost of reading a person's entire DNA code (around 3 billion letters spread over 20,000 to 25,000 genes) was estimated to be $3 billion. Ten years later the first draft human genome sequences were deciphered for considerably less than that – Craig Venter's genome cost $10 million and James Watson's cost about $1 million. Even so, this is still considerably more than the $48,000 that Quake claims it cost to use the new method to successfully read about 90 percent of his genome (about 2.5 billion base pairs).
Quake sequenced his DNA using a machine called a Heliscope (produced by Helicos BioSciences of Cambridge, Massachusetts, US). What gives the machine a right to claim ‘third-generation' status is the fact that it directly analyses single molecules of DNA rather than small samples that have to be amplified. This means that a small team of only three people was needed to carry out the work, and the hope is that it technology such as this will usher in a new era of faster, cheaper and more accurate DNA sequencing. 'This is the first demonstration that you don't need a genome centre to sequence a human genome. It's really democratising the fruits of the genome revolution and saying that anybody can play in this game,' proclaimed Quake in Stanford University's press release.
Helicos CEO Steve Lombardi stated that Quake's paper is 'the first large statement from someone other than the company that the technology works. That's a really important thing for us.' However, Quake cannot be considered an entirely impartial observer (he co-founded Helicos, a company which he consults for and holds shares in) which may explain why unaffiliated observers have been a little more critical of some of his paper's claims.
Firstly, the Heliscope machine costs upwards of $750,000, it is required to be mounted on a slab of granite to ensure microscope stability, and because of its huge weight structural reinforcements often need to be made before it can be installed. The quoted price tag of $48,000 clearly overlooks these significant initial costs as well as the inevitable and substantial deprecation costs involved. A second issue is that the Heliscope only covered 90 per cent of the genome and the error rate given in Quake's paper is much higher than current proven 'second-generation' methods which can be just as affordable – for example, Illumina based in San Diego, California, US, already offer genome sequencing to the private individual for a little under $50,000.
While the Quake genome is an important step forward, and the error rate and price will fall in the future, it seems that third generation technology (such as the Heliscope and its rivals being developed by Oxford Nanopore, UK, and Pacific BioSciences, US) is not ready to go head-to-head with the second generation technology just yet.