274
Remember the year 2012, when all we could hear from the smartphone industry was the on-going litigation between Apple and Samsung. Well, after a recent move from Illumina, the world’s largest next generation sequencing instrument provider, we can expect 2016 to be a similar year of litigation in the genomics industry. Except that unlike Apple’s opponent Samsung, who were busy selling smartphones around the world, Illumina’s opponent is a young company based in UK, Oxford Nanopore Technologies just venturing out in the real world. To understand, why Illumina would take such a step, we first need to go back in time, where all this began.
 |
| The Human Genome Project was an ambitious project taken up by the National Human Genome Research Institute (NHGRI) and funded by the National Institute of Health (NIH) |
Back in 2003, with the then available method of sequencing (Sanger Sequencing), it took the researchers 13 years and $2.7 billion to publish the Human Genome. At this rate, sequencing would be the luxury of just a few people on the planet and would eventually die. To harness the potential of the genetics and make the genome “the transformative textbook of medicine” as Francis Collins, the then director of NHGRI called it, sequencing had to be cheaper and affordable for all. Sanger Sequencing had its own limitations and therefore, there was a need for a cheaper, better, faster method of sequencing. But this was not some late realization that had struck after the HGP was completed.
Companies were already work on the next generation of sequencing (NGS) technology and as early as 2005, 454 Life Science launched its 454 sequencing platform, which was closely followed by Solexa that launched its Genome Analyzer in 2006 and AgenCourt that launched SOLiD (Sequencing by Oligo Ligation Detection) the same year. Larger companies like Roche and Applied Biosystems were quick to harp on the potential of these companies and bought out the companies, 454 and AgenCourt along with their technologies. Illumina, that was looking at its BeadArray Technology to offer genotyping services using microarrays, bought off Solexa to get into the NGS arena. (Source: http://www.hindawi.com/journals/bmri/2012/251364/)
 |
| A quick comparison of the different types of sequencing platforms 454 is now owned by Roche, SOLiD by Thermo Scientific and Solexa by Illumina. |
The years that followed brought out iterations of these technologies, promising longer reads, faster turn around, reduction in costs etc. Illumina, however, were quick to realise that costing was the single largest factor that would determine the adoption of this new technology and therefore, since 2009, has been constantly reducing their prices for complete genome sequencing from $48000 to $19,500 a year later and then reducing it to $4000 per individual while testing their Hi Seq machines. This dramatic decrease in pricing even forced the X Prize organizers to cancel their Genomics X Prize, a first in their history, where the goal of the prize was outpaced by innovation. With their HiSeq X machines (cost of $10 million each), which is 10 Hi Seq sequencers in a single behemoth unit, Illumina claims to sequence genomes for $1000 (Just that the machine is capable of sequence genomes of about 50 people a day and is busy convincing governments to do so).
 |
| HiSeq X Ten, the behemoth sequencer! |
But the smartest company of 2014, as suggested by MIT Technology Review, did not put all its eggs in one basket. Apart from the high end sequencers, Illumina also has a range of bench top sequencers called MiniSeq that at approx.. $50,000 are affordable for regular sized labs. Apart from its popular sequencing technology, it has also invested its efforts in non-invasive prenatal testing and aims to be the one stop solution for the genomics needs of a family. Illumina, which also promotes, other sequencing technologies (at least 6 others) that it owns, in 2009 tied up with UK based company, Oxford Nanopore Technologies to further develop the nanopore sequencing technique that held potential to reduce sequencing costs further.
Just like the mobile giants, Apple and Samsung, who were collaborators once upon a time, the relationship ended in 2013 on a bitter note after Oxford Nanopore Technologies revealed their plan of going to the market with nanopore sequencing technology but on their own range of instruments. By this time, Illumina was already controlling 70% of the market share with its sequencers and with products like HiSeq X in the pipeline, there seemed to be little to worry about. Nevertheless, they pursued their interest in nanopore sequencing separately and later that year also licensed a version of nanopore sequencing from University of Alabama at Birmingham (UAB) (will come back to this later).
Oxford Nanopore were yet to even hand out their prototypes to their early adopters and Illumina were probably confident that they would have their newly owned nanopore technology products ready before the British company would reach out to the markets. Delays due to technical glitches hit Oxford Nanopore’s prospects even further and the prototypes were further delayed but in April of 2014, selected researchers got their hands on the first MinION sequencers, which changed the story entirely.
 |
| True to its name, the MinION sequencer, from Oxford Nanopore Technologies! |
These USB stick like devices were given away for an early adopter’s price of $1000 and later that year, publications begun to pour out, which had used MinION as its sequencing platform. The portability of the device was is largest USP and as researchers were able to use this simple sequencers on the field to track the spread of Ebola in Guinea and a nosocomial infection of Salmonella in the UK. These success stories were hailed across the world and suddenly, the bench top sequencer of Illumina, started to look like a gigantic unnecessity. Why bother using an externally powered hard disk drive, when you can use a USB powered flash drive.
MinION’s strength does not lie only in its small size. Along with the fact, it lowers sequencing costs further than what Illumina currently offers, the MinION is capable of reading long sequences of DNA that has never been achieved before (>5000 bp) and sequence detection is done in real time and lets the researcher access the sequencing data in real time as opposed to the 11-24 hour wait on Illumina’s machines. If MinION’s capabilities were not good enough, Oxford Nanopore is now promoting, what we can call, its flagship product, PromethION, a benchtop sequencer, which packs the power of 48 MinIONs that the user can choose to use individually or altogether and a direct competitor to the MiSeq machines that are Illumina’s popular product.
Coming back to the present, Illumina has now filed a case of patent infringement on part of Oxford Nanopore Technologies and accuses them of stealing ideas from the patent they hold (the one they licensed from UAB in 2013). The basis of the complaint is that Illumina strongly believes that the nanopore used in MinION and PromethION match those derived from Mycobacterium smegmatis. What MinION uses to carry out its sequencing is a secret held very closely by Oxford Nanopore but Illumina are certain that it is some derivative of M.smegmatis.
 |
| Representation of how a nanopore works and gives out sequencing data. |
On the basis of this conjecture, Illumina have requested the Court of California to stop the import of equipment made by Oxford Nanopore on US soil. Interestingly, they also claim that if a void, is created in the area of genomic services as a result of this ban, Illumina and other sequencing providers (Roche, who are planning to close down their sequencing business, Applied Biosystems, who are now part of Thermo Scientific and boast of ION torrent sequencers, based on SOLiD technology and Pacific Biosciences, whose latest sequencers is bigger and more expensive than llumina’s ) will be able to address it.
 |
| With their revolutionary technology, these guys are looking to sequence genomes of 300 dead people. Why? Read this blog post to know. |
Taking into consideration that Illumina has recently attacked their biggest clients BGI before they took over Complete Genomics, who also boast of a revolutionary sequencing technology , it is no surprise, that Illumina are fighting this legal battle, purely because Oxford Nanopore Technologies is a potential competitor now. Oxford Nanopore do not have regular customers but are valued at $1.4 billion dollars not very far from the Illumina, who have worked over a decade to reach this far. It, therefore, seems that this litigation is only to put a cog in the wheel and slow the progress of Oxford Nanopore. Illumina are probably working on a nanopore sequencer and its nearing completion and would like it be available along with the PromethION, so that they do not lose market share. Probably, the story is much worse. Illumina have nothing in the pipeline in terms of a nanopore sequencer but just a HiSeq 50 or 100 and as always, the MinION is ruining their best laid plans.
While Oxford Nanopore have not said much about how they are going to react to this litigation, they too have multiple patents relating to this technology, some of which precede the patent that Illumina is fighting with. A countersuit might be on the cards and we will probably see, the two companies slug it out in the courts rather than in the market, where the real challenge is.
We have to just wait and see, how this battle takes shape, but researchers around the world want just one confirmation. Like Apple and Samsung did, keep rolling out new products every year and bringing down costs of genome sequencing. A $100 genome anyone?
Reference:
Reference:
Liu, L., Li, Y., Li, S., Hu, N., He, Y., Pong, R., Lin, D., Lu, L., & Law, M. (2012). Comparison of Next-Generation Sequencing Systems Journal of Biomedicine and Biotechnology, 2012, 1-11 DOI: 10.1155/2012/251364
