In the future, your doctor might map your whole genome as a routine diagnostic test. Helicos BioSciences, a five-year-old biotech company in Cambridge, MA, has set out to make that happen in the not-too-distant future—by developing an extremely powerful gene-sequencing technology.
The instrument is the size of a refrigerator. A 3,000-pound refrigerator, built on a steel and granite frame, filled with precision mechanic and optics and advanced electronics, with a list price of $1.35 million. Stan Lapidus, the companhy’s founder and CEO, points to different parts of the machinery—the optical system with its solid-state laser, the plastic tubing that handles the chemicals used in the analysis, the glass flow cell for the samples. With these innards, he says, Helicos’ brand-new DNA sequencing machine is capable of doing what used to take months in just a few days or even hours, and at a fraction of the cost. And all it needs to do the analysis is one single molecule of DNA.
“We hope that this instrument will change the paradigm in life science measurement, which has always been based on measuring many molecules,” says Lapidus. That’s a bold statement, coming from a company that only shipped its first commercial instrument to a customer in March. In a press release about that milestone, Helicos also said that it was a significant step toward the “$1000 genome,” that is, the ability to map one person’s total DNA for a just a thousand bucks. (Spurring the development of such sequencing abilities is also is the aim of the $10 million Archon X Prize for Genomics, which is led by Xconomist Marc Hodosh.) Compare that to the billions of dollars spent when the publicly funded Human Genome Project raced against Craig Venter’s Celera to be first in mapping just one human genome.
At that time, in the late nineties, both teams mainly relied on a technology called Sanger sequencing after its inventor, two-time Nobel laureate Fredrick Sanger. Even today the Sanger method is regarded as the “gold standard” in DNA mapping, against which every other technology is matched. It also shares one attribute with gold—it’s expensive. Sanger sequencing takes a lot of sample preparation involving with methods like molecular cloning and polymerase chain reaction, PCR, and the throughput is relatively slow. So, if you are in a hurry, you will need to spend a lot on instrumentation, chemistry, and people. (In its efforts to beat the Human Genome Project, Celera had 300 automatic gene sequencers and a staff of 500 at its center in Rockville, MD, working for about one year to read three billion letters of genetic code as a first draft of the human genome.)
In contrast, one single Helicos instrument reads 25 to 90 million letters per hour by first chopping up the DNA molecule in very small pieces, and then sequencing many millions of the pieces simultaneously—skipping the DNA-copying steps that earlier techniques required. Afterwards, the information is pieced together by a massive amount of computing.
To demonstrate that its technology really works, Helicos has sequenced the whole genome of a virus from a single DNA molecule. The results were published in Science a couple of weeks ago. But the big expected market is not mapping the genomes of virus, bacteria, plants, or animals. It is in mapping your DNA and mine. Whole genome sequencing might become a major diagnostic method, used to pinpoint significant risks for a number of diseases.
“We now know that many diseases are caused mainly by changes in genetics. Diabetes, stroke, cancer are all diseases of the DNA,” says Lapidus. “It might be that you sequence the whole genome of a person just once and then just look at changes in certain regions. Or maybe you will do the whole genome several times in a person life, we will see.”
Lapidus has a background in diagnosis. He is the founder of two very successful bioscience companies, Cytyc and Exact Sciences. The former was sold to Hologic of Bedford, MA, for more than $6 billion.
Helicos is not alone in trying to develop radically faster and less expensive sequencing methods. The phrase “next generation sequencing” has been coined to describe a number of methods that all, Helicos’s included, use a massively parallel approach. Three competitors, Roche, Illumina, and Applied Biosystems have already sold next-generation sequencing instruments.
Roche got its technology in early 2007, when it bought 454 Systems, which in turn had licensed major parts of its technology from Swedish Biotage. Just a few months earlier, Illumina had acquired Solexa and its technology. Applied Biosystems, ABI, is the market leader when it comes to the classic Sanger sequencing method, but has also developed a next-generation sequencing technology of its own called Solid. At the moment it is unclear if one of these companies will dominate the market or if their technologies will coexist in different niches.
