An Illumina Sequencer In The Year 2000?

Summary: With appropriate investment we could have had Illumina-style sequencing six years earlier.

Keith recently posted an excellent article over on this blog, discussing Illumina’s moats… This prompted me to dig some more into the history of Illumina sequencing…

This in turn led me to an amazing article containing an interview with Pascal Mayer. Pascal Mayer and Manteia provided one of the fundamental technologies required to enable Illumina style sequencing: bridge amplification. The approach had also been pursued by Mosaic Technologies, but Manteia took the execution significantly further. To the point that it was clearly practical for sequencing.

The article makes it clear that Manteia lost out due to lack of financial support. Overall based on statements in the article I’d estimate that Manteia, and the projects leading to it’s foundation probably received less than $8M USD in funding.

Compare this to Helicos (2004, total $77M). Or more recently Ultima (2016 - $600M).

The story makes it clear that access to capital was at least as important as a fundamental technological advantage (and IP)… Almost everybody has something to complain about:

• Mosaic could complain that they were the first to have the fundamental insight (and patent) into bridge amplification.

• Manteia could complain that they didn’t get the investor support they needed on a clearly very promising approach.

• Solexa could complain that they were forced to into $600M exit rather than bring given the capital to scale the technology in the UK.

• Illumina could complain that they don’t get the credit they should for executing on the acquired technology.

These complaints are all or a lesser or greater extent well founded. And at this point ancient history

Stepping outside of this, I think it’s interesting to think about the broader dynamics.

And regarding the “broader dynamics” my initial reaction was:

All roads lead to Rome

All these pieces of technology flowed to companies with ever greater access to capital. Until they finally ended up in our modern Bio/technological Rome: The US west coast.

But It’s Fun To Speculate

In my (somewhat limited) experience, investors often do very little in the way of effective technical due diligence. The Manteia story should make the reasons why somewhat obvious. It often doesn’t matter how good the technology is. What matters more is how much access to capital to you have.

It’s no good investing $1M in Manteia in 2000 if nobody else is going to invest, no matter how good the technology is.

The result is that I suspect investors find themselves considering the question: “can this attract next round investors, or can I help this attract next round investors”. More than “does this technology have fundamental value”.

In a different world capital we’d perhaps figure out a way to direct capital more effectively. By 1997 there was sufficient technology evidence in bridge amplification to support an investment of $100M USD (in my view). With sufficient funds in place (and the right team) I suspect development could have been accelerated toward a working sequencing platform in a few years¹.

However in the world we do live in it takes time for these technological advances to make their way to Rome and then finally be distributed to the rest of the biotechnological empire²…

Of course, the Mosaic-Manteia-Illumina story has led to attempts to buck this trend. And no doubt one day the empire will fall… but probably not today.

1. It doesn’t seem to me that there was anything external that you’d need to wait around for. Camera’s of course have improved, but I don’t think these advancements were required to enable a working platform. Same on the optics front (lasers etc.) though it would be fun to dig into this further. In terms of nucleotides, you could have developed reversible terminators, or you could have built a platform with an unterminated chemistry which would have been or value. In any case it seems likely that $100M and a good team would have been sufficient to solve these problems. Perhaps even in time to make significant contributions to the human genome project.

2. Of course, this whole article is somewhat hyperbolic. It’s perfectly possible to create biotech companies outside of the US. But it’s not easy, and often these companies end up being acquired by US entities in part because they have much greater access to capital. This in turn draws more talent to the US, which makes development of new approaches and execution in the US (right now I imagine particularly in the west coast, but of course there’s a strong east coast biotech scene as well) easier.