All about the base

THE project to understand the human genome has long promised to revolutionise the way that diseases are diagnosed, drugs are designed and even the way that medicine is practised. An ability to interpret human genetic information holds the promise of doing everything from predicting which drugs will work on a particular patient to identifying a person’s predisposition to develop diseases.

Genomic information is already transforming some medical practices. Sequencing has changed the way that fetuses are screened for Down’s syndrome, from a risky invasive test to one where abnormalities in fetal DNA can be picked up from blood drawn from the mother. In time this sort of method will extend to other genetic disorders and other medical applications. One area of promise is treating some types of cancer. Using blood tests to detect genetic changes in tumours could allow doctors to discover more quickly when drugs are no longer effective. This is so promising that there is already speculation that performing such “liquid” biopsies could be a $11 billion business by 2022.

Realising the vast potential of genomic medicine is a commercial project as well as a scientific one. It relies on a small but growing group of companies that are vying to produce data more cheaply, analyse them more quickly, store them securely and then to translate them all into useful information.

These tasks have proved harder than expected. As genome data have started to be collected and sifted, nuggets of genetic gold are emerging. Yet creating and using this torrent of information is an endeavour of enormous scale and complexity. Each human genome comprises about a hundred gigabytes of data. The amount gathered is doubling every seven months; by 2025 it could require more storage capacity than for every YouTube video on the planet, or for all the information astronomers have drawn from the heavens.

One firm in particular has been at the heart of this nascent genomic-data industry. Illumina, based in San Diego, is the main provider of the machines that sequence genetic information. Its dominance, and its role in reducing costs (see chart), has led to comparisons with Intel’s grip on chipmaking. It controls 70% of a market worth $3.3 billion in 2015, according to Research and Markets, a research firm. As its customers, now mainly researchers, expand to include medical practitioners, that market could grow to between $12 billion and $20 billion by 2020.

Illumina’s continued dominance is by no means assured. Pacific Biosciences, based in Menlo Park, California, has developed a machine that does a similar job. It is selling well because it is better at some jobs than Illumina’s machines. Thermo Fisher, of Waltham, Massachusetts, is another rival; its machine should appeal to clinics because it is easier to operate and more efficient at targeting those sequences that are likely to be of most interest.

Pore man, rich man

New technologies threaten both Illumina and its current competitors. Oxford Nanopore, a small British company, has pioneered a new method of sequencing. It passes DNA through tiny holes, whose changing electrical resistance is recorded as different molecular “letters”, or bases, pass by. Existing methods tag the four letters of DNA with a different marker and then read the sequence of tags.

Using pores is not yet as accurate as using markers, but is allowing sequencing machines to be built that are small, portable and quicker at reading data. That would eventually allow for new services such as diagnostics in the field and on-the-spot testing for infections. Although it is unclear whether the technology can compete in the business of sequencing entire human genomes, the British minnow does seem to pose a threat. In February Illumina filed two lawsuits against the company for patent infringement.

Once sequenced, genetic data are the raw materials for other business ventures. One flourishing area of activity lies in making sense of it all. Craig Venter, a pioneer of genomics and boss of Human Longevity Inc (HLI), also in San Diego, is assembling the largest and most comprehensive database of genomic and clinical data in order to hunt through it for targets for new drugs.

Understanding the genetic basis of a disease or disorder can be critical in identifying therapies that will fix these problems. With this in mind HLI recently signed a ten-year deal reportedly worth hundreds of millions of dollars with AstraZeneca, a British drug company, to sequence half a million genomes. The potential to find targets for drugs is such that Mr Venter thinks HLI might one day transform itself into a pharmaceutical company.

The race to identify promising targets is likely to encourage more of these partnerships as drugmakers try to get their hands on data that will help them improve their drug pipelines. Indeed, in another deal ten companies, including AbbVie, Biogen, Roche, Takeda and GSK, have partnered with Genomics England, a company set up by the British government to sequence the genomes of 100,000 patients.

Genome data have to be stored as well as analysed. That relies on cloud-computing firms. Mr Venter says his company pays Amazon $1m a month for computing and storage. This is not yet a big business, but it is growing. According to one estimate, cloud-computing firms could charge $1 billion a year by 2018 as the quantities of digital information continue to grow. Firms including Amazon and Google are jostling to become the platform of choice for managing genome sequences.

One way to attract business is for the cloud firms also to offer tools to make sense of the data. In February Microsoft announced a collaboration with Spiral Genetics, which has developed methods for managing and analysing genome sequences. In May Huawei launched China Precision Medicine Cloud which, by including tools from Wuxi NextCODE, an analytics firm, allows thousands of complete human genomes to be analysed in one go. Plenty of other companies are offering ways of slicing and dicing data in the cloud, including DNAnexus, Seven Bridges and Illumina’s BaseSpace.

As genetic testing becomes ever cheaper, it will open up new opportunities. Invitae, based in San Francisco, is already trying to set itself up as the Amazon of genome sequencing by making the process of ordering medical-grade tests so easy and cheap that testing for genetically inherited diseases becomes as simple as ordering books online. Other applications stretch beyond medicine. Genome sequencing could be used to check if food is safe to eat, for example, or to clamp down on the illegal trade in wildlife or to monitor the spread of antibiotic resistance.

But profits are not guaranteed to flow quickly. Health-care providers and governments are an obvious source of sales, but they are notoriously slow to spend their money on new forms of testing. And the business of direct-to-consumer genetic testing relies on convincing individuals that such tests are worthwhile and regulators that they are safe and accurate. Genomics has long blended huge promise and practical difficulties. That won’t change.