Rapid Genome Sequencing Predicted by Mid-2009

Surprise announcement that California firm is about to achieve a $1,000 human genome sequence

CEO SUMMARY: In the same way that the Human Genome Project was disrupted by the entry of C. Craig Venter and Perkin-Elmer in what was then a 15-year, $3 billion project, now Complete Genetics of Mountain View, California, is disrupting the race to the $1,000 human genome sequence. Developments in this field are moving at rocket speed and the resulting new technologies and instrument systems may give laboratory medicine new clinical assays that are disruptive in their own right.

TALK ABOUT DISRUPTIVE TECHNOLOGY! The race to achieve the $1,000 genome was transformed earlier this month when Complete Genomics, Inc., of Mountain View, California, publicly predicted that it would achieve this goal, possibly as early as the spring of next year.

In accomplishing the feat of sequencing the entire human genome for a cost of $1,000, Complete Genomics will instantly transform the field of genetic medicine. Not only is its gene sequencing technology disruptive, but its business plan appears equally disruptive.

That’s because Complete Genomics does not plan to sell gene sequencing instrument systems. Rather, it will create a global network of gene sequencing centers and will sell gene sequencing services to pharmaceutical firms and researchers. Its first gene sequencing center will cost $75 million and will be located in Mountain View, California. The company predicts this 32,000 square foot center will produce 1,000 human genomes during 2009 and as many as 20,000 human genomes in 2010.

“We are setting out to completely change the economics of human gene sequencing so that we can do diagnostic quality human genome sequencing at a medically affordable price,” stated Clifford Reid, Complete Genomics’ President and CEO, during an interview with Bio-IT World. “Essentially, [we’ll] transform this genome sequencing world from a scientific and research endeavor into a pharmaceutical and medical endeavor.”

This statement of intent is clear and unambiguous. Complete Genetics believes its technology and its business plan will immediately propel genetic medicine to a higher level of knowledge. It expects the availability of high numbers of human genomes, produced at reasonable cost, will unlock a host of medical breakthroughs that can quickly be adapted into clinical practice.

Implications For Lab Testing

For pathology and laboratory medicine, the implications of Complete Genomics’ technology and business plan are many and profound. Experts observe that, having complete genomes for a large number of humans sharing the same disease will make it possible to identify all the genetic variations that contribute to individual diseases.

Once that knowledge becomes available, new diagnostic assays will be developed that look at thousands—and possibly tens of thousands—of biomarkers that must be present in certain combinations to confirm specific diseases.

THE DARK REPORT observes that an explosion of knowledge is expected to result from the study of thousands of complete genomes of people afflicted with the same disease. This is likely to trigger a flood of new lab tests. The majority of these will involve analysis of DNA, RNA, and proteomics. For that reason, the role of the molecular laboratory will steadily expand as clinicians apply the diagnostic knowledge generated by these laboratory tests to patient care.

Global Genome Sequencing

After construction of its first gene sequencing center in California, Complete Genomics intends to build 10 similar centers in the United States and abroad during the next five years. These will be developed in partnerships with selected organizations and foreign governments.

Complete Genomics’ strategy is to offer its technology via a service model—not by selling instrument systems. It considers itself to be a “wholesaler of human genomes.” It will price a genome sequence at $5,000 when it opens its sequencing center.

Reid believes the service model has a ready market, particularly among pharmaceutical companies. Not only do they already spend billions on research and clinical trials, but they recognize how outsourcing to the right supplier can both accelerate results and save money.

“The pharmaceutical market has declared very clearly they don’t want to buy instruments,” continued Reid in his Bio-IT World interview. “They want to buy services, so that they get the data that enables them to do the discovery and development work, without having to own and operate a large-scale genome sequencing center.”

Another factor in selecting the service model is the sheer volume of data generated by genome sequencing. This issue is already well-known to pathologists and scientists operating molecular laboratories and offering molecular testing to clinicians. Reid observed that new sequencing technologies “generate a breathtaking amount of data. Simply selling 10 or 20 instruments to a company doesn’t solve the problem. You then have to be able to manage huge volumes of data. We are putting in a Google-style data center to manage the data.”

Outsourcing By Pharma

According to Reid, in its service model, Complete Genomics will “offload [users] from the operational burden of running all those sequencers; the computational burden of running all those assemblies; and from the capital purchase burden, having to build up these huge genome centers they haven’t started building to generate the volumes of data we’re talking about. By providing this outsource service, they get access to the data so they can do the science.”

Reid indicates that first customers for this service will probably be pharmaceutical companies wanting to study cancer and mental illness. There is a strong genetic component in both categories of diseases. Further, because of the prohibitive cost of using today’s generation of sequencers to generate the full genome of the hundreds of people participating in research studies and clinical trials, Reid is confident that he has ready-made customers for his genome-sequence service. “The pharma guys are pretty much sitting on the sidelines, waiting for guys like us to come along,” he noted.

With the public announcement of its accomplishment in sequencing a human genome for just $4,000 this summer, Complete Genomics intends to leapfrog the competition in the race to achieve the $1,000 genome sequence. However, the speed of technology and the numerous competitors in this race make it unwise to make Complete Genomics the odds-on favorite to finish first.

Moreover, this unfolding story has immense consequences for pathologists and the entire laboratory medicine profession, for at least four reasons. First, DNA sequencing technologies and instrument systems to perform this function are improving at what seems to be an exponential rate. Consider, for a moment, what this means.

Uses In Clinical Testing

The multiple technologies under development by a variety of companies to per- form human genome sequencing are likely to find useful applications in clinical diagnostics, particularly where smaller sequences of DNA need to be sequenced and studied. Thus, one likely outcome from the collective efforts to achieve a $1,000 human genome is for these technologies to find uses for smaller scale DNA sequencing that supports molecular testing for clinical purposes.

Second, the speed with which the cost to sequence the human genome has fallen reinforces an expectation that this technology will be both robust enough for clinical lab tests and cheap enough to be affordable for health plans and labs that perform such tests.

Third, as researchers during the next 36 to 48 months gain access to the complete genomes of hundreds of people with the same diseases, pathologists and lab directors should expect a myriad of new biomarkers to result from this research. That could trigger disruptive forces within laboratory medicine in as few as five years.

Tidal Wave Of Data To Come

Fourth, genome sequencing generates huge amounts of data. That means lab directors and pathologists will need more robust software and hardware to accommodate what is likely to be an exponential growth in the number of molecular assays offered by hospitals and independent laboratories.

That creates an opportunity for information technology vendors. Clinical laboratories are likely to be voracious buyers of software and systems that do a good job of collecting, storing, and manipulating the data generated by genome sequencing and related molecular assays.

Who’s in the Race to the $1,000 Genome? Several Companies Have Promising Approaches

SEVERAL COMPANIES ARE RACING TO BE FIRST to sequence the human genome for $1,000. It is widely acknowledged that, until the cost falls to $1,000 or less, progress in genetic medicine will be slow.

Some of the main contestants are Applied Biosciences, Inc. (ABI); Illumina, Inc.; 454 Life Sciences (a division of Roche), and Pacific Biosciences. Now Complete Genomics must be added to this list. Helicos BioSciences Corporation and Intelligent Bio-Systems, Inc. are two other companies which have thrown their hats in the ring and declared that their respective technologies will produce the $1,000 genome sequence. Additional companies working in this field are NABsys, Inc. and VisiGen Biotechnologies, Inc.

One stimulus to this race is the “Archon X Prize for Genomics.” (www.xprize.org) Anyone who can sequence 100 genomes in ten days will win $10 million plus bragging rights. The X Prize for Genomics believes that the ability to sequence 100 genomes in 10 days represents the technology threshold that will enable an explosion of research and new knowledge about the human genome.

Another stimulus is a program offered by the National Human Genome Research
Institute (NHGRI), part of the National Institutes of Health (NIH). In recent years, it has awarded millions of dollars of grants under its “Revolutionary Genome Sequencing Technologies” program. Also called “$1,000 genome grants,” the NHGRI’s grants are intended to speed development of sequencing technologies that will accelerate the use of genomics in medical research and health care.

Claims made by the different companies demonstrate the potential of various technologies to reduce both the time and the cost required to sequence the human genome. Intelligent BioSystems, for instance, has stated its plans to have, by year-end, a system that requires only 24 hours and $5,000 to sequence a full human genome.

However, that impressive prediction is about to be surpassed. At its press conference on October 6, Complete Genomics stated it had sequenced a genome in July that required four days and was completed at a cost of $10,000. Complete Genomics has also made the public prediction that its technology can eventually drop the cost of sequencing the human genome down to just $100.


First Genome Sequence Was Achieved for $4,000

WHEN THE FIRST COMPLETE HUMAN GENOME was sequenced this July using Complete Genomic’s disruptive technology, it only cost $4,000. That cost will fall to $1,000 and includes instruments, material, labor, and overhead.

“This [genome] ran four instruments for one week,” explained Clifford Reid, President and CEO of Complete Genomics in an interview with Bio-IT World. “This is a 28 instrument-day experiment. By the launch of our product in Q2 [of 2009], it will be a four instrument-day experiment.”

Bio-IT World described the experiment as “the genome coverage was 22-fold from 67 gigabases (Gb) of mapped reads.” Concordance with the HapMap was slightly more than 98%. Reid boasted that the speed of his company’s instrument “is about 10 times as fast as ABI [Applied Bioscience, Inc.] and Illumina.”

The technology used in the Complete Genomics’ system was developed using work done by Rade Drmanac, Ph.D., who has been involved in DNA sequencing from its earliest days. He was sequencing-by-hybridization using a ligation strategy and gridded arrays of up to one billion “nano-balls.” Drmanac is now Chief Science Officer at Complete Genomics.

Drmanac’s work in biochemistry was married to Clifford Reid’s experience in computing to develop the sequencing system at Complete Sciences. Reid, a Ph.D., was using MIT’s OpenCourseWare (OCW) in 2004 to do self-study on biology, genetics, and molecular biology. Reid became intrigued by the confluence of biology and computation in systems biology. It caused Reid to seek out Drmanac to discuss his ideas on how to blend the two fields of science. As a result of these discussions, Reid and Drmanac launched Complete Genomics in 2006.


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