2014's Turning Points in Genomics

January 7, 2015

By Aaron Krol 

January 7, 2015 | From the $1,000 genome to the $1,000 sequencer, the field of genomics has had a big year for small numbers. Not since the advent of next-generation sequencing in the mid-2000s have so many tipping points felt so palpable: the CRISPR revolution in gene engineering alongside new paradigms for clinical and consumer genetics, all in the context of an unprecedented gush of data. As the new year begins, we’re looking back on six of our most popular stories of 2014 that together encapsulate the year in genomics — along with some quick commentary on how each story has developed since.

January 15: What You Need to Know About Illumina’s New Sequencers 

The launch of Illumina’s HiSeq X instrument provided an exciting, even cathartic start to 2014 — after years of anticipation, someone finally stood up to claim the mantle of the $1,000 genome. People can and will continue to pick nits off that figure (once you factor in energy costs and a decent hourly rate for the technicians, you’ve almost certainly passed the $1,000 mark), but there’s no doubt that for institutions reading whole human genomes at scale, sequencing has never been faster or cheaper. Since January, we’ve seen the release of some raw HiSeq X data that reveals it’s very similar to the well-loved HiSeq 2500, and over a dozen new customers have bought a $10 million HiSeq X Ten system — including Craig Venter’s outside-the-box (and well into low earth orbit) Human Longevity, Inc., which scooped up two. So far, most users seem to be struggling to get enough samples to keep their instruments humming along at full capacity. The new sequencer will likely have a bigger practical impact in 2015, as early adopters get up to scale and, if Illumina President Francis de Souza’s prediction holds, we can expect to see over 400,000 whole human genomes sequenced within the year.

January 29: Gene Therapy’s Next Generation 

Excitement about CRISPR has only grown since the founders of Editas Medicine spoke to us at the beginning of 2014, introducing the first company to bring this revolutionary gene editing technology to bear on human disease. Editas didn’t have the field of CRISPR-based gene therapies to itself for long: it was joined in April by a European counterpart, CRISPR Therapeutics, and in November by latecomer Intellia Therapeutics, which has made up for lost time with a big development deal with pharma giant Novartis. Next comes the long slog to building a safe vector, choosing therapeutic areas, and starting up clinical trials, during which there will be plenty of speculation but only occasional drips of data about how CRISPR is progressing as a human therapy. Nonetheless, the three players in this area have already found some surprising drama in a tangled patent dispute that could take months or years to sort out. Editas inked key licensing deals early on, but there’s reason to think the most foundational patent — claiming the use of CRISPR inside eukaryotic cells — could be struck down as invalid. Meanwhile, Jennifer Doudna, one of the co-discoverers of the CRISPR mechanism and a scientific founder of Editas, has already parted with the company and has her own corporate links to Intellia. We can only hope that none of this slows down the progress of CRISPR drugs, which have unprecedented promise in fighting cancers, viruses, and rare genetic disorders at the most fundamental level, the genome itself.

March 24: 23andMe Pursues Health Research in the Shadow of the FDA 

23andMe has had a wild ride. An upstart trying to democratize DNA, a passionate advocate for personalized healthcare — and perhaps a bit early to market with a product that was heavy on the health claims but not quite willing to own up to the inherent uncertainties in our genomes. It’s safe to say that the FDA crackdown on 23andMe’s health reports signaled big changes to consumer genetics in the U.S. In 2014, companies like BaseHealth, LifeMap Solutions, and Coriell Life Sciences sprung up to fill the void, all of them promising a more holistic, physician-friendly approach to genomic health. At the same time, 23andMe deserves huge credit for soldiering on, pursuing big new research initiatives into human health, continuing to attract users with its DNA ancestry service, and making a quick shift in its regulatory strategy. With the help of newly-hired chief legal and regulatory officer Kathy Hibbs, an industry veteran, the company has taken baby steps to restoring its full health service by submitting a single test for a rare genetic disease to the FDA. It’s a gesture of good will, and a canny way to familiarize the agency with its scientific approach. The fact that 23andMe has also gone on to offer its health reports in Canada and the UK, where regulators may prove more lenient, only shows that the contradictions at the heart of this genetic pioneer have not yet been settled.

April 17: As Genetics Moves to the Clinic, Pathogenic Variants Still Subject to Doubt and Debate 

Is it being brutally honest or just a spoilsport to say that genomics has singularly failed to live up to the medical promises made during the heady days of the Human Genome Project? Pharmacogenetic tests go unused, neurological disease is still a genetic black box, and using the genome to predict cancer, heart disease or diabetes is sure to attract the full weight of the FDA — and for good reason. Highly targeted cancer drugs are one hopeful sign for the future, as is the coming wave of biologic drugs and steady inching of gene therapy toward the clinic. But if there’s one medical field that’s almost there, it must be rare disease, where whole exome explorations are pushing the diagnosis rate near 50% at the leading centers. So it’s sad to see something as mundane and petty as data sharing standing in the way of universal access to these advances. Let 2015 be the year we all take projects like ClinGen and VariantWire seriously, and make sure information on the variants that cause human disease is open to the public eye. Today’s hospital labs have access to an FDA-cleared next-generation sequencer; it would be a crime for genetic data to be stuck in the days before AMP v. Myriad.

June 30: The Hunt for a New Human Reference Genome  

Twenty years ago, scientists were grateful to sequence a single gene. Ten years ago, a new species’ genome was still a headline event. By five years ago you needed to talk about thousands of genomes to raise anyone’s eyebrows, and today’s geneticists can afford to be downright picky about sequence quality. Nothing exemplifies this trend from more sequencing to better sequencing like the platinum genome, a project to cover every last base of a single set of human chromosomes, telomeres not spared, with each structural variant in order and intact. In fact, despite Illumina’s big January announcement, 2014 could be looked at as the Year of PacBio, when the smaller company proved there was room in the market for a pricier instrument that won’t flinch at high GC coverage, large indels, or de novo assembly. The shift in emphasis could also be good news for BioNano, whose Irys system does nothing but resolve large structural variation. The platinum genome is still not complete, but we did get a glimpse in November of a PacBio-only sequence that fills big gaps in the reference and reveals thousands of previously unknown variants.

December 22: Nanopore Sequencing Is Here to Stay 

2014 was the year that genomics’ most prominent piece of vaporware became its most tantalizing piece of hardware. You may still have your doubts about Oxford Nanopore’s MinION, but the geek-out factor is undeniable. It runs on a laptop, fits in a fanny pack, and is out there right now generating 100-kilobase reads. The early access MinION is not without its problems, but they’re no longer the sorts of problems that call the whole enterprise of nanopore sequencing into question. So let’s take a minute to wonder what happens if, this year, Oxford Nanopore gets its error rate and manufacturing problems under control, and releases not just the MinION but the high-throughput PromethION as well. Three years ago, Clive Brown told us that “too many companies try to compete on one differentiator, and they often fall short. We’ve tried to compete on every differentiator.” So what if the company with the cheapest instrument, the longest reads, and the easiest sample prep also gave lots of data at high accuracy? Is genomics headed out of the lab and into the living room? A lot of very promising startups in this field have fallen short at the finish line, and I won’t try to predict the future. But if you’d like to see someone else have a go…