Technology

Seven Billion Genomes

Why wouldn’t we sequence everybody?

Last August, Facebook passed a major milestone when 1 billion people logged into the social networking site in 24 hours. That’s an extraordinary statistic, considering Mark Zuckerberg only created Facebook 11 years ago, in 2004.

This reminded me of a recent report from UBS Financial Services on the future of life science tools and diagnostics companies. The author, UBS analyst Jon Groberg, estimated that 229,000 people had had their genomes sequenced by the end of 2014. Groberg highlighted this rapid progress by cheekily comparing the number of humans sequenced to the total population of the U.S. (316 million) and the world (7 billion).

So, that still leaves a considerable gap before we cross the one-million person threshold, let alone Facebook’s headline-grabbing number. But 229,000 genomes sequenced is, nevertheless, a remarkable number, given that the dominant sequencing technology on the market (Illumina) has been commercially available for less than a decade. But, as readers of Genome are well aware, the cost of sequencing a human genome is now hovering just above the $1,000 mark. As the price has plummeted in recent years, the number of people sequenced — including sick children, cancer patients, clinical trial participants, personal wellness pioneers, and genome project volunteers — has exploded.

Illumina has established a virtual monopoly on high-throughput genome sequencing since acquiring British biotech Solexa in 2006. Competitors such as Thermo Fisher Scientific’s Ion Torrent, an ingenious benchtop sequencer that has many fans and niche applications, and Complete Genomics may have to be content with niche markets in cancer or the clinic. The Illumina HiSeq X Ten, introduced in early 2014, is now installed at institutions around the world. Illumina touts that this machine delivers the $1,000 genome. (Some caveats: This cost excludes analysis, overheads, and compute time).

Many think that the technology that might unseat Illumina’s dominance one day is nanopore sequencing. Oxford Nanopore’s smartphone-size minION sequencer has attracted most of the attention. It’s capable of reading the sequence of a single strand of DNA as it snakes through a hollow bacterial protein (the nanopore) by interpreting real-time fluctuations in the electric current. This device could revolutionize countless diagnostic and field applications — it’s already being used successfully to sequence Ebola samples in Africa. But it’s a long road to match the prodigious throughput of the Illumina fleet, and who knows what the San Diego firm is cooking up. Another nanopore hopeful worth watching is Genia, which was acquired by the diagnostics powerhouse Roche in 2014.

As the cost of sequencing edges closer to $1,000, the question changes from why should we sequence everybody to why wouldn’t we sequence everyone?

Harvard Medical School geneticist George Church launched the Personal Genome Project 10 years ago with an essay in Scientific American entitled “Genomes for All.” Church remains a staunch proponent of genome sequencing. “We want 7 billion people” sequenced, he says, but a key to getting anywhere close to that goal will be ensuring that the experience of the first 250,000 is smooth, with no unexpected consequences. “In order to get to that, the first billion will have to have a pleasant journey,” he says.

In a commentary a couple of years ago in The BMJ (formerly the British Medical Journal), Sir John Burn, a leading British medical geneticist, made the case for comprehensive genome sequencing, stating that “only by analyzing sequence data and phenotypes across large patient populations will we understand which bits of genetic information are clinically relevant.” The U.K. has spun out a company from the National Health Service called Genomics England, which is conducting a 100,000 Genomes Project focusing on extracting diagnostic data on cancer and rare diseases.

President Obama trumped that effort by making a one-million person biobank the focal point of his Precision Medicine Initiative, first announced in his 2015 State of the Union address. Building a large national biobank of genotyped individuals is hardly new, however. The notion of sequencing an entire country came from the most unlikely of places. About seven years ago, the Faroe Islands launched the FarGen Project, aiming to sequence all 50,000 inhabitants of their tiny, windswept islands in the North Sea between Scotland and Iceland, to improve the country’s public health system.

The Faroes are, to some extent, emulating the work of Icelandic firm deCODE Genetics. Acquired by Amgen in 2012, deCODE scientists have spent the past 15 years gathering genomic data on roughly a third of the country’s 320,000 residents. In a recent paper in Nature Genetics, deCODE presented the complete genome sequence of over 104,000 people on the island. One of the tantalizing results is that deCODE can now pinpoint some 2,000 Icelanders who carry a serious mutation in the BRCA2 gene. This raises a host of medical and ethical issues around notifying these carriers, as they are at an increased risk of breast and ovarian cancer in women or prostate cancer in men.

Indeed, we’re seeing genome sequencing ramping up sharply in the private sector. Craig Venter says his latest biotech company, Human Longevity, can sequence 40,000 genomes a year and confidently believes it will account for one million genomes by 2020. Google (or should I say, Alphabet?) has funded a biotech called Calico, spearheaded by an impressive lineup of former Genentech executives, to study the genetics of life span. Meanwhile, Lee Hood, the father of automated DNA sequencing, recently founded a personal wellness company called Arivale, which will offer individuals genome analysis and much more, including monitoring of blood biomarkers and the gut microbiome, for an annual $2,000 maintenance fee (see “Alternate Route,” page 36).

Regeneron Pharmaceuticals has launched its own major genome sequencing initiative with Geisinger Health System, focusing on 100,000 volunteers. Increasingly, the boundaries between genetics and drug discovery are blurring. Earlier this year, Richard Scheller, the executive vice president of research and early development at Genentech, joined 23andMe. Just a few months before that, David Altshuler, a leading geneticist and the deputy director of the Broad Institute, moved to Vertex Pharmaceuticals.

Curiously, as the number of people sequenced soars, the ranks of the unsequenced contain some surprising names. Two years ago, Broad Institute director Eric Lander, who has had a hand in sequencing more genomes than just about any other scientist, told Reddit that he hadn’t had his genome sequenced because he hadn’t had any medical necessity to do so. “If I did have a medical reason, I’d do it in a heartbeat,” he said. “But not ’til then.”