Eight Lessons from John Stuelpnagel (Illumina)
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John Stuelpnagel co-founded Illumina in 1998 as its first CEO. Trained as a biochemist, Stuelpnagel started working on CW Group (Larry Bock’s firm) after getting his MBA at UCLA. While working as a VC, he identified a unique invention out of David Walt’s Lab at Tufts: combining microwell arrays with beads attached to different DNA sequences to enable single nucleotide polymorphisms (SNP) detection. Stuelpnagel was a driving force to build Illumina around what work became their BeadArray platform. This technology quickly became the standard for genome-wide association studies (GWAS), along with Affymetrix, and set the company up to dominate next-generation sequencing - part acquiring Solexa and part out-executing Roche and Thermo. Stuelpnagel is still a leader in the field as chairman of companies like 10X Genomics, Inscripta, and Element Biosciences as well as sitting on the board of Encoded Therapeutics and Adaptive Biotechnologies. His relationship with Bryan Roberts at Venrock, Illumina was actually Roberts’ first VC investment, is one of the greatest case studies of investor-founder symbiosis: Stuelpnagel handles the weekly meetings and Roberts the board meetings.
1.“We’re in the midst of a historical revolution, a biological revolution. This is the century of biology. We’re going to gain mastery over life, and it will have implications over everything we do.”
2. Roberts talking about Stuelpnagel: “He quickly figured out that if Illumina was successful, it would need more than the world’s supply of oligonucleotides. He went out and he found somebody who was, at a very early stage, working on novel oligonucleotide synthesis technology, and bought it. He brought it into Illumina, got it working, licensed it out to the oligo manufacturers, brought the price of oligos down by like 90% and dramatically increased supply. “Imagine if you woke up one day and said, ‘Oh, this Illumina thing is awesome. It totally works. And we can only sell twelve of them a year because there’s not enough oligos in the world.’”
Illumina’s business model rapidly evolved in the early days and this was driven by the quality of the founding team and thinking. The company is one of the canonical case studies of commoditizing your complement in life sciences.
3. “People [companies] are apprehensive about Illumina and worried about if, and when, they might choose to compete against them” With this business model, Illumina is always on the search for new suppliers and possibly applications to commoditize to increase demand for their sequencing devices and consumables.
4.“Genomics has been mostly—and I hope I don’t offend the audience—a passive science. We’re limited by our cohort sets that we can put together. I think the next level of biological discovery is going to be where you can actively perturb the system—it’s called a cell—and then ask what kind of phenotype did we generate.” In combination with cheaper-and-cheaper sequencing, driven by Illumina among others, the next step is to invent new tools to modify biological systems to connect genomics to a phenotype.
5.“In my view, gene editing is where DNA sequencing was shortly before the advent of next-generation sequencing. Researchers desperately need a scale transformation that will allow gene editing efforts to be as useful and as informative as possible. I believe that Inscripta will make that transformation possible.” To achieve this vision of connecting genes with their corresponding phenotypes, gene editing needs to become as accessible as gene sequencing.
6.“Where we are today is mostly doing those edits in a one-off way. It’s not unlike where we were in the early and mid-1990s with DNA analysis technology … before genomics technologies took over, arrays and next-generation sequencing. That was the scale that changed the pace of discovery. I think the same thing will play out in gene editing. Single edits will help us predict certain things, but we’re only as good as our ability to predict, and we’re limited by our knowledge of biology. And all of that’s going to mean that we’re only going to explore small spaces of the complexity. To me, we need to provide the genomics-level tools to genome editing.”
7.“I see the same opportunity now in gene writing that I did in gene reading.”
8. “I think the ability to both read and write and to have those in a virtuous cycle is really going to be critical to accelerating learning. What we’re doing with gene editing is designing and creating literally new organisms, and then phenotypically testing them [using] genomics data sets. … So I see, actually, a combining of traditional genomics, traditional gene reading, with this new field of gene writing.” John is helping achieve this vision through Inscripta.