Over the Horizon: A Moore‘s Law for Genetics

Nanofluidic arrays made by BioNanomatrix could make it possible to sequence an individual genome for $100.  Credit: BioNanomatrix


60 to 90

The number of days it takes to get a genome sequenced by Illumina’s service, which costs $48,000. The first human genome sequence took 13 years.


MIT Technology Review, March/April 2010, by Courtney Humphries  —  Sequencing the first human genome cost $3 billion–and it wasn’t actually the genome of a single individual but a composite “everyman” assembled from the DNA of several volunteers. If personalized medicine is to reach its full potential, doctors and researchers need the ability to study an individual’s genome without spending an astronomical sum. Fortunately, sequencing costs have plummeted in the last few years, and now the race is on to see who can deliver the first $1,000 genome–cheap enough to put the cost of sequencing all of an individual’s DNA on a par with many routine medical tests.

Interpreting genomic information is still a very difficult task and we have limited knowledge of how genetic variation affects health. But people will still want to get sequenced, suggests George Church, a geneticist at Harvard Medical School and a pioneer in sequencing technology: he says there are 1,500 genes that are considered “medically predictive” and for whose effects mitigating action is possible. A once-in-a-lifetime test could reveal, for example, whether someone couldn’t metabolize a particular drug or should pay careful attention to diet and exercise because of a propensity for heart disease. The $1,000 barrier is expected to be broken in the next year or two, with even cheaper sequencing to follow.

“The key thing that’s driving all of the next-generation sequencing is miniaturization,” says Church. Just as miniaturization steadily decreased the price of computer chips, genome sequencing is getting cheaper as working components are shrunk down and packed more densely together.

Advances include using microfluidics to reduce the volume of chemicals needed for analysis, which saves money because reagents are responsible for a large fraction of sequencing cost. In addition, some companies, such as BioNanomatrix, are developing tiny nanofluidic devices that force molecules along channels about 50 nanometers wide. The company says that using such channels could bring the price of sequencing down to $100 per genome–though it will probably be at least five years before that happens.

Complete Genomics is building a facility full of automated sequencing instruments like this one.  Credit: Jen Siska




778 megabytes

The size of one human genome, stored in a standard format that uses two bits to specify each base in the DNA sequence. The human genome contains about three billion base pairs.

MIT Technology Review, March/April 2010, by Lauren Gravitz  —  Companies are struggling to make it fast, affordable, and profitable to sequence individuals’ genomes–a tall order considering that until late 2008, fewer than 10 human genomes had been sequenced, and those at considerable expense. Four-year-old startup Complete Genomics, based in Mountain View, CA, thinks it has cracked the problem. It demonstrated its technology by sequencing what it claims were more than 50 genomes in 2009. Now it is scaling up its facility to sequence, it says, as many as 5,000 individual genomes in 2010, with 10,000 genomes a year thereafter, at $1,500 to $5,000 each.

The key to the company’s technology is the ability to analyze more than a billion amplified particles of DNA on a single microscope slide. Putting so much information on a single array reduces the number of slides and the amount of expensive reagent required to sequence a genome, and it speeds up digital imaging. Rather than selling its sequencing technology in the form of machines, reagents, and software, as its competitors do, Complete Genomics sells sequencing as a service, taking orders from researchers who FedEx samples to the company–eight genomes minimum, no maximum. “That’s a very easy business to scale up quite rapidly,” says CEO Clifford Reid.

For now, the company is taking advantage of the pent-up demand for sequencing among researchers, who have already placed orders ranging from tens to hundreds of genomes. After the initial research rush passes, Complete Genomics hopes to enter consumer and medical markets. The continuing drop in prices leads some experts to predict that soon the genome of every newborn will be sequenced at birth. That’s more than four million genomes per year in the United States alone. And most oncology researchers believe that sequencing the DNA of a patient’s tumor will one day be the key to effective treatment. Because every cancer seems to have its own set of mutations, its entire genome will be sequenced as if it were a person.

Given the potential demand, Reid is bullish. He says, “We expect to open 10 sequencing centers around the world that, collectively, will have the ability to sequence one million genomes over the next five years.”

Digital sequencing systems can capture vast amounts of genetic data, but interpretation has been difficult.  Credit: Monty Rakusen/getty images



The number of genes that could be linked to autism, according to a computational analysis conducted by Columbia University researchers. The analysis also suggested 21 genes that could be implicated in bipolar disorder and 25 in schizophrenia.


MIT Technology Review, March/April 2010, by Emily Singer  —  The personalized-medicine industry aims to convert information about an individual’s genome into useful diagnostic tests and targeted drug treatments. Companies that deal with gathering the information–sequencing genomes and identifying genetic variations–have made impressive technical advances that have dramatically reduced the cost of analyzing DNA (see “Faster Tools to Scrutinize the Genome“). Now the biggest challenge lies in interpreting the huge volume of genetic data being generated. Studies have identified thousands of candidates for genes underlying common diseases, for example, but it’s not clear how to make that information medically useful.

The problem is going to get worse before it gets better. Most genetic variation discovered to date accounts for a fairly small percentage of the overall risk of disease. Countless genetic variations are still hidden in our genomes. As scientists begin to uncover the remaining genetic culprits, they will need to develop ways to interpret what those variations mean for individual health. “The field urgently needs a breakthrough in the way we analyze such data, or we will end up with a collection of data … unable to predict anything,” wrote Serge Koscielny, a researcher at the National Institute of Health and Medical Research in Villejuif, France, in the journal Science Translational Medicine in January.

Efforts to find solutions are just beginning. Personal-genomics companies such as 23andMe and Navigenics have developed their own algorithms for combining different genetic risk factors into a predictive risk score. And Knome, a personal-sequencing startup based in Cambridge, MA, is taking this strategy one step further by developing software to analyze entire genome sequences. But it will be impossible to develop effective analysis methods–or weigh their predictive power–without large databases that pair individuals’ genome sequences with their medical records.

Genetic tests and therapeutics also face an economic challenge: who will pay for them? Insurance companies will not cover these diagnostics unless they are proved to be both effective–accurately spotting whether a person will respond to a drug, for example–and cost-effective. Insurers would be motivated to pay for tests that could rule out an expensive cancer treatment as unlikely to work. But with drugs that are inexpensive in the first place, the financial case for such testing is less obvious.

If scientists succeed in developing tests that can accurately predict an individual’s risk of disease years or decades in advance of symptoms, the problem of who pays will become even trickier–especially in the United States, where people change insurance plans every three to four years on average. Pharmacy benefits managers such as Medco and CVS Caremark, which provide prescription-drug coverage to many Americans on behalf of employers and insurers, are starting to take the lead in judging the economic value of personalized medicine (see “Sequencing Companies Dominate Investment“).

Company: Affymetrix
Revenues: $327.1 million

Innovation: A pioneer in commercializing DNA microarrays, which allow for large-scale analysis of genetic samples, the company has made acquisitions that will let it analyze proteins and other biomarkers.

Company: Amgen
Revenues: $14.6 billion

Innovation: Its drug for colorectal cancer comes with a recommendation that patients be genetically screened to see if they would benefit from it.

Company: AstraZeneca
Revenues: $32.8 billion

Innovation: Has moved aggressively into personalized therapeutics; its drug olaparib is now being tested in cancer patients with specific genetic mutations.

Company: Celera Genomics
Revenues: $138.7 million

Innovation: Is trying to broaden the reach of personalized medicine into cardiac health.

Company: Celldex Therapeutics
Revenues: $7.5 million

Innovation: Is developing technology for protein analysis, which is critical for translating genetic data into therapeutically valuable knowledge.

Company: GlaxoSmithKline
Revenues: $45.8 billion

Innovation: Tackling the diseases of aging

Company: Helicos Biosciences
Revenues: $0.8 million

Innovation: Has set its sights on developing technology that can sequence a human genome in a day, at a cost of $1,000.

Company: Life Technologies
Revenues: $3.3 billion

Innovation: Created from the merger of Applied Biosystems and Invitrogen in 2008. Applied Biosystems’ machines were instrumental in completing the Human Genome Project; it is now developing a range of next-generation sequencing instruments.

Company: Medtronic
Revenues: $14.6 billion

Innovation: Stimulating the brain

Company: Roche
Revenues: $47.9 billion

Innovation: It acquired 454 Life Sciences, which develops DNA sequencing machines, including a desktop sequencer suitable for rapid sequencing of small genomes or portions of a human genome.

Company: BioNanomatrix
Funding Raised: $5.1 million
Battelle Ventures, Ben Franklin Technology Partners, KT Venture Group, 21Ventures

Innovation: The nanochannel technology it’s developing could be used to sequence single DNA molecules without reassembling many small sequences into a genome.

Company: Complete Genomics
Funding Raised: $91 million 
Enterprise Partners, OVP Venture Partners, Prospect Venture Partners, Highland Capital Management, Genentech

Innovation: Sequencing human genomes to order

Company: Generation Health
Funding Raised: Not disclosed
CVS Caremark, Highland Capital Partners

Innovation: Manages health benefits related to personalized medicine for insurance companies. As DNA testing becomes more common, this type of company will be increasingly important.

Company: Integrated Diagnostics
Funding Raised: $30 million
InterWest Partners, Wellcome Trust, Dievini Hopp BioTech Holding

Innovation: Is developing diagnostic products based on genetic and protein analyses to look at tens to hundreds of disease markers simultaneously.

Company: Knome
Funding Raised: Not disclosed
Privately funded

Innovation: Will sequence and analyze the complete genome of any individual for $68,500.

Company: Metabolon
Funding Raised: $30 million
Syngenta Ventures, Sevin Rosen Funds, Aurora Funds

Innovation: Analyzes an array of metabolic markers to diagnose diseases or reactions to drugs.

Company: Navigenics
Funding Raised: Over $40 million
Procter and Gamble, Kleiner Perkins Caufield and Byers, Mohr Davidow Ventures

Innovation: Offers genetic testing directly to consumers and encourages doctors to incorporate testing into their practice.

Company: Pacific Biosciences
Funding Raised: $266 million
Wellcome Trust, Mohr Davidow Ventures, Kleiner Perkins Caufield and Byers, Alloy Ventures

Innovation: Accurate sequencing in real time

Company: Proventys
Funding Raised: Not disclosed
Burrill and Company

Innovation: Is developing software that will help doctors use genetic testing and clinical data to make prognoses and determine treatments.

Company: 23andMe
Funding Raised: Not disclosed
Google, Genentech, New Enterprise Associates

Innovation: Sells genetic testing directly to consumers; results include information about ancestry and about the subject’s sensitivity to a range of drugs.

By MIT Technology Review, Editors


  • Drug
    Atomoxetine HCI (Strattera)

ADHD treatment

The Gene Factor
Patients with a mutation in the CYP2D6 gene are at risk of suffering serious liver damage.

  • Drug
    Clopidogrel (Plavix)

Prevents heart attacks by inhibiting blood clots

The Gene Factor
A variation of the CYP2C19 gene interferes with the way the drug is metabolized, rendering it ineffective.

  • Drug
    Cetuximab (Erbitux) and Panitumumab (Vectibix)

Colorectal cancer drug

The Gene Factor
The drugs work only in people whose tumors have a normal KRAS gene.

  • Drug
    Gefitinib (Iressa)

Lung cancer drug

The Gene Factor
Works best on people whose tumors have a mutation in the EGFR gene.

  • Drug
    Irinotecan (Camptosar)

Colorectal cancer drug

The Gene Factor
People with a genetic variant suffer side effects because they have fewer liver enzymes to break down the drug.

  • Drug
    Tamoxifen (Nolvadex)

Breast cancer drug

The Gene Factor
Variations in the CYP2D6 gene can make a person metabolize the drug too quickly or not at all.

  • Drug
    Warfarin (Coumadin)

Blood thinner

The Gene Factor
In patients with either or both of two genetic variations, the drug can cause excessive bleeding rather than help prevent blood clots. Genetic testing can reveal the right dose.

By MIT Technology Review, Editors

  • Company
    Mountain View, CA

Technology and Cost
Microarrays that test for genetic variations
$399 to $499

You get information about …
Ancestry, disease risk, carrier status, and sensitivity to particular drugs

  • Company
    deCode Genetics
    Reykjavik, Iceland

Technology and Cost
Microarrays that test for genetic variations
$195 to $985

You get information about …
Ancestry and genetic susceptibility to diseases such as various cancers

  • Company
    DNA Direct
    San Francisco, CA

Technology and Cost
Varies by subcontractor
$175 to $3,456

You get information about …
Risk for more than a dozen conditions, including cystic fibrosis and breast cancer

  • Company
    Cambridge, MA

Technology and Cost
Complete genome sequencing

You get information about …
Your entire genome sequence (analysis by a team of scientists is included)

  • Company
    Redwood Shores, CA

Technology and Cost
Microarrays that test for genetic variations

You get information about …
Genetic predisposition to dozens of diseases, including Alzheimer’s, type 2 diabetes, and various cancers

  • Company
    Pathway Genomics
    San Diego, CA

Technology and Cost
Multiple platforms to test for genetic variations
$199 to $399

You get information about …
Risks for up to 90 conditions; information on ancestry, carrier status, and drug sensitivities



The approximate cost of genetic testing to predict a patient’s response to the commonly prescribed blood thinner warfarin.

MIT Technology Review, March/April 2010, by Lauren Gravitz  —  The market for personalized medicine is growing: according to ­PricewaterhouseCoopers, the core market will reach $42 billion by 2015. However, that growth is not uniform. Some areas, such as genomic sequencing, are surging ahead; others, such as translating genetic data into clinically useful information, languish.

In this environment, startups developing sequencing technologies, such as Pacific Biosciences, Illumina, and Complete Genomics, have attracted sustained investor interest as they race to create ever cheaper ways to decode DNA (see “Faster Tools to Scrutinize the Genome“). In their most recent rounds of venture funding last summer, Pacific Biosciences and Complete Genomics received $68 million and $45 million, respectively.

Diagnostic technologies, too, are moving at a rapid pace. Startups from Boston to Silicon Valley have been pinning down disease-related genetic markers and creating many new tests that are already in the clinic or on their way. As these companies grow and bring more tests to market, large diagnostics companies are likely to acquire them, says venture capitalist Brook Byers of Kleiner Perkins Caufield and Byers.

One of the biggest undeveloped areas in personalized medicine, however, is the information technology needed to analyze and store the huge quantity of genetic data that is starting to pour forth (see “Drowning in Data“). Of the few bioinformatics companies working to digest the data, Proventys, based in Newton, MA, is among the furthest along. Its technology combines biomarkers and other information to make risk predictions about diseases.

Meanwhile, pharmaceutical companies are responding to the nascent market for personalized therapeutics in different ways. Pfizer, for example, is collaborating with existing biotech companies to develop drugs and diagnostics based on genetic testing. AstraZeneca recently announced a partnership with the Danish diagnostics company Dako, the first of many alliances it plans in a strategy for bringing genetic tests to market. Novartis is taking a different tack, dedicating a large portion of its own resources to developing personalized medicine.

In the United States, benefit management companies, which act as middlemen between patients and insurers or employers, are aggressively moving into the market. One of the largest, Medco, has established a personalized-medicine group to recommend which genetic tests insurers should pay for. In February it acquired DNA Direct, a firm that specializes in analyzing genetic diagnostics, to aid in this effort. One of its largest competitors, CVS Caremark, increased its stake in a similar company, Generation Health, last December. Because such companies serve millions of people, they will play a critical role in making genetic tests broadly available and educating doctors about the benefits of offering such tests to their patients.

A machine for DNA sequencing was invented by Leroy Hood and his colleagues at Caltech. In 1992, Hood and several others were granted U.S. patent 5,171,534 for an “Automated DNA Sequencing Technique.” Replacing slow and expensive manual methods, this is one of the most important pieces of intellectual property in biotechnology; explore this interactive analysis by IPVision of the patent’s impact on the innovation landscape. http://www.technologyreview.com/biomedicine/24593/page2/

By MIT Technology Review, Editors

Finding ways to analyze large amounts of genetic data and extract information related to diseases that involve multiple genes.

  • Project: Cancer Biology and Genetics Program
    Sloan-Kettering Institute

Testing a microfluidic chip that will measure differences in how genes are expressed in tumors.

  • Project: Coriell Personalized Medicine Collaborative
    Coriell Institute for Medical Research

Enrolling 100,000 participants in a research study to measure how genetic information can improve health.

Developing a genetic test that will identify patients at risk of sudden cardiac death who should receive an implantable defibrillator.

An EU-funded consortium seeking to standardize genetic testing and establish guidelines for doctors and patients.

An American-Japanese scientific alliance studying pharmacogenomics across a broad array of medical conditions, including depression, AIDS, and asthma.

  • Project: Pharmacogenomics Knowledge Base
    Stanford University Medical Center and others

An international consortium building a database detailing the influence of genetic variations on drug reactions.

Investigating whether using genetic tests to determine a patient’s sensitivity to certain drugs is more cost-effective than choosing drugs that are less affected by genetic variations.

  • Project: The 1000 Genomes Project
    Wellcome Trust Sanger Institute, Beijing Genomics Institute Shenzen, National Human Genome Research Institute

Sequencing the genomes of about 1,200 people around the world to create a database of biomedically relevant genetic variation.

  • Project: The Cancer Genome Atlas
    National Cancer Institute, National Human Genome Research Institute

Sequencing thousands of samples from over 20 types of tumors to understand the genetic changes that underlie these cancers.

Cheap DNA Sequencing Will Drive a Revolution in Health Care

Credit: Leonard Lessin / Photo Researchers, Inc.

MIT Technology Review, March/April 2010, by Stephen Cass  —    The dream of personalized medicine was one of the driving forces behind the 13-year, $3 billion Human Genome Project. Researchers hoped that once the genetic blueprint was revealed, they could create DNA tests to gauge individuals’ risk for conditions like diabetes and cancer, allowing for targeted screening or preëmptive intervention. Genetic information would help doctors select the right drugs to treat disease in a given patient. Such advances would dramatically improve medicine and simultaneously lower costs by eliminating pointless treatments and reducing adverse drug reactions.

Delivering on these promises has been an uphill struggle. Some diseases, like Huntington’s, are caused by mutations in a single gene. But for the most part, when our risk of developing a given condition depends on multiple genes, identifying them is difficult. Even when the genes linked to a condition are identified, using that knowledge to select treatments has proved tough (see “Drowning in Data“). We now have the 1.0 version of personalized medicine, in which relatively simple genetic tests can provide information on whether one patient will benefit from a certain cancer drug or how big a dose of blood thinner another should receive. But there are signs that personalized medicine will soon get more sophisticated. Ever cheaper genetic sequencing means that researchers are getting more and more genomic information, from which they can tease out subtle genetic variations that explain why two otherwise similar people can have very different medical destinies. Within the next few years, it will become cheaper to have your genome sequenced than to get an MRI (see “A Moore’s Law for Genetics“). Figuring out how to use that information to improve your medical care is personalized medicine’s next great challenge.

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