Illumina Concedes on Long Reads, Buys PacBio

Theral Timpson

At 1:02 pm today, there was a tremor in the world of genomics as it was announced that the two leaders in the field of sequencing have become one company. Goliath has opted to pick David up and put him on his shoulders. Upon first reaction, I'd say three things. 1. High quality long reads are the future of sequencing. Disrupting a standard carried for years in the drive toward the $1,000 genome of quantity over quality, PacBio stepped in and raised the bar for the technology of DNA sequencing. As Evan Eichler of UW put it to me in an interview once, "when long reads are just twice the price of short reads, short reads are dead."


2. Why now? Roche had a major deal with PacBio which ended this past year. Were the Illumina folks in the hallway when the Roche people closed the door and headed to the airport? This is Illumina’s biggest purchase ever, but they have the money. Did it take this long for Illumina to recognize the value of PacBio's long reads? Is PacBio facing some limitations with their technology, made more urgent with Oxford Nanopore appearing closer in the rearview mirror?


3. Is this good for science and medicine? Since Mike Hunkapillar took over at PacBio, the company has slowly and methodically built up the business based on this niche of high quality long reads. I remember the first interview I did with Mike back in 2014. I brought up Illumina. He quickly said, “oh you mean short reads...” He said it so diminishingly as he sat there at his desk in his plain red shirt looking down at the floor, then directly back up at me. At the time Illumina seemed absolutely unstoppable. And PacBio’s stock was at its lowest. Their instruments were way behind schedule, not doing what they were supposed to do, and having a terrible problem with errors.


My first reaction was, what a cocky guy. My second reaction was, what are short reads? It was the first I’d heard of the distinction. PacBio then went around the world educating one scientist after the other on the possibilities of their long read technology. And they demonstrated that their errors were random, and that with deep enough sequencing, the error rate could potentially be not a problem at all. Then scientists came to PacBio educating them on the possibilities of their long read technology. At that time we had a bioinformatician on the program by the name of Gene Myers, the same guy who worked for Craig Venter in the Celera days and wrote the Blast algorithm. Gene said he loved the PacBio long reads and was getting 100% accuracy! This was not what I was hearing from the critics of PacBio down in San Diego. It was painstaking work for PacBio when the whole world was buying up Illumina machines without a second thought. Soon scientists were collaborating with PacBio on very new and innovative projects such as exploring areas of the genome that had never been characterized, going back to the days of the Human Genome Project. A whole new field of structural variation blossomed and began to have meaningful impact on cancer and neurodegenerative disease. The folks at PacBio were having fun. There has been an atmosphere over there akin to a university institute. They have published and co-published thousands of papers. It’s been a unique company. Now let's move south. Illumina is more than just a company today. They are an ecosystem. I was just in San Diego at the Jay Flatley Innovation Center. Up here in the Bay Area they set up the world’s first genomics incubator. They got FDA approval of the first clinical next gen sequencing diagnostic test. Illumina is an ethos, and that ethos is boldness. They have kept an aggressive timeline in coming out with new products, and they have conquered new markets. They spun out a company called Grail for heaven's sake. It’s mission? To detect cancer before we have it. Illumina has also driven personal genomics. Years ago they began offering to sequence anyone's genome. They spun out the direct-to-consumer company, Helix. It seems DNA just can't replicate itself fast enough for this bold company. Here's my question: Will that boldness nurture or knock over PacBio’s methodical scientific collaboration laboratory? We’ve talked about the elephant in the room. And the monkey. We must mention the mouse. This year Oxford Nanopore, who Illumina divested it’s shares of a couple years ago, sequenced a whole human genome on their pocket sized synthesizer. The read lengths were much longer than PacBio’s read lengths. The scientists I listen to tell me that in the coming head-to head between PacBio and Nanopore, PacBio had nowhere to go with their technology, that Nanopore wins out on throughput and, already, on price. Is this a surrender on PacBio's part? Will Illumina be able to take the Sequel and advance it? And will we soon hear that Illumina will be buying Nanopore? Remember that Illumina's current technology, the tech that made them who they are was picked up in a buyout. That was Clive Brown's technology, who is the technologist at Oxford Nanopore. He already lost one instrument to Illumina, and I've heard he’s sworn never again. As I write this, I can't help but see that the engine of Illumina's boldness has been built on the assumption that gathering all this data about all the DNA in our whole world will mean a whole lot to a whole lot of people. (I'll never forget one bioinformatician on a panel in a very chic setting in San Francisco one night saying, "we're just sequencing for sequencing sake!") Some of it is very important. BRCA data mean a lot to many. New structural variants can mean a lot to some patients. Understanding how life works will go into our biology text books. Don't get me wrong. But the pace of sequencing should somewhat match the pace of our making sense of the data, the pace of our understanding. PacBio and their scientific partners have been pretty good at that.