Posted May 21, 2020

The race to sequence the human genome set the bar for what engineering in biology could do.  Thirty years ago, this race started with the audacious goal of understanding the blueprint of humanity––sequencing the entire human genome, completed roughly twenty years ago. As important as that was, the intervening two decades have brought an even more impressive engineering feat: the exponential decrease in the cost of sequencing (“Flatley’s law,” analogous to Moore’s law in computer chips), from billions, to millions, to thousands, and now finally hundreds of dollars per human genome. This massive feat of engineering in bio is what allows us to rapidly sequence SARS-CoV-2, and beyond that, to start opening and begin “reading” the giant book of all of human biology.

But unfortunately, the human genome––our blueprints of life––are not enough, in fact falling far short of what we need to truly understand biology and disease. Just the way the house you live in likely varies quite a bit from its original blueprint, we too are defined not just by our genes, but by which genes get used and how: i.e., by the proteins. The human genome project is, in fact, only a warm up—to the ultimate goal of decoding the human proteome

This is the audacious goal that Nautilus Biotechnology has set: to win the race to quantify the human proteome, and at single molecule precision. It will be a feat of technology in the world of bio that will be just as fundamental a leap forward, and with just as massive consequences, as sequencing the human genome. 

And history appears to be playing out in a similar fashion. How do we use technology to make major leaps? Do we use it to push forward from the same directions as before, just a little “harder”? No—the best way to achieve that is to take out a clean sheet of paper and rethink the problem with new tools and frameworks from the very beginning, designing a completely new approach that avoids all the challenges and pitfalls of current approaches. The original, brute force approach to sequencing the human genome eventually gave way to more clever approaches, utilizing combinations of both biological and computational advances. By bringing computation to the very heart of how sequencing was done, major advances followed, directly leading to the methods employed today. 

By embracing both computation and biological measurement methods, and taking advantage of the major rapid advances in computational methods over the last twenty years––in particular, advances in machine learning—Nautilus is rethinking the approach from the ground up, instilling an engineering approach that will bring an analogous exponential decrease in cost for decades to come. 

This is what will transform this technology from a critical tool for researchers and drug designers to potentially even a daily part of our healthcare lives, allowing us to “unlock” the human proteome the same way we have unlocked the human genome, with all that brings. By directly measuring the level of all of the proteins in a cell, we can finally directly understand what biology is doing in intricate detail, and in particular in outlier situations, where rare events are telling, yielding novel drug targets, as well as novel assays for drug performance in complex phenotypic and animal model screens. A detailed reading of biology like this—with the potential to make routine information that is currently unobtainable—will naturally yield new diagnostic approaches to detect disease and direct therapeutic interventions. It will one day impact just as many areas in biology and medicine as genomic information touches: from how we investigate the biology of disease to—eventually—the standard of care in many diseases. 

To architect such a dramatic breakthrough, one needs a very special team. Nautilus is led by an unmatched pair of founders: Sujal Patel’s deep experience in tech and execution, as former co-founder and CEO of Isilon Systems; matched only by Parag Mallick’s creativity and brilliance in both the theory and practice of biology plus computer science, as a professor at Stanford focused on proteomics and biomarker discovery, and former director of Clinical Proteomics at Cedars-Sinai Medical Center. We are thrilled to support and invest in Nautilus Biotechnology, from having led the Series A and joining the board to supporting through the Series B and company launch. We look forward to supporting Nautilus as they bring this new technology to market, in order to fundamentally advance our understanding of human biology—and transform our ability to improve healthcare.