The octant was the dominant tool for maritime navigation in the 18th century because it enabled sailors to chart an accurate course, even in pitching and rolling seas. Like seafaring, drug discovery is, at its core, exploratory. The primary objective in traditional drug discovery is to identify molecules that have a beneficial effect on biological processes. But it remains largely a process of trial and error—and success is dependent on tools that enable navigation through the unknown and unpredictable waters of biological complexity.
What if we could engineer biology to create tools that guide us to the safest and most successful routes? Octant is pioneering the use of synthetic biology as a tool for drug discovery. Synthetic biology, the ability to engineer or program cells and organisms, is typically associated with the biomanufacture of products like alternative fuels, materials and foods. But Octant has instead used it to engineer human cell lines that act as “real-time” reporters for what is happening inside the cell, providing precise and complete readouts of the complex interactions and effects that drug molecules have within a living cell. In other words, if you expose these engineered cells to a drug, the cells “tell” you exactly how the drug impacted it and which pathways were modulated.
This approach has the potential to systematically create exhaustive maps of drug targets that reveal novel treatments for our most intractable diseases. Imagine being able to recapitulate decades of knowledge about a therapeutic area in just a few experiments. Or enabling a single research scientist to generate orders of magnitude more high-resolution data versus traditional screening approaches. This is the untapped potential of using synthetic biology to help us discover new medicines: it allows us to interrogate biology at an unprecedented scale. Octant plans to use its technology to tackle complex and underserved diseases like neurological disorders, cardiovascular disease, and metabolic conditions like obesity by going after important but challenging drug targets known as G protein-coupled receptors, or GPCRs. The future of treating these common diseases will include drugs that simultaneously alter the activity of multiple cellular pathways, and Octant’s approach will allow these multifactorial diseases to be targeted with unparalleled precision.
Why don’t these tools already exist? Novel tools are forged by a new generation of toolmakers. Sean Eddy, a professor of mathematics and bioinformatics at Harvard coined the term “antedisciplinary science” to describe “the science that precedes the organization of new disciplines, the Wild West frontier stage that comes before the law arrives…People who gravitate to the unexplored frontiers tend to be self-selected as people who don’t like disciplines—or discipline, for that matter.” Octant CEO Sri Kosuri is an antedisciplinarian. He’s one of the leading synthetic biologists in the world. He holds degrees from UC Berkeley and MIT, a postdoctoral fellowship in George Church’s lab at Harvard, and a tenured professorship at UCLA. But he’s not prone to taking the traditional path.
When Sri realized that his technology could have a broader reach if incubated inside a startup, he shuttered his academic lab to launch Octant with co-founder Ramsey Homsany, a technology executive who had early and impactful stints at Google and Dropbox. Together they have assembled a team of antedisciplinary scientists with native expertise in synthetic biology, genomics, computer science, and have built a company with a fiercely creative, independent and outspoken (counter)culture. When they developed a simple, low-cost, scalable plasmid sequencing workflow (codename: OCTOPUS), they released it to the world. When they realized that a portion of their platform could be repurposed to help with COVID-19 detection efforts, they quickly developed a novel testing protocol dubbed SwabSeq and made it freely available, code and all. Throughout this pandemic, Sri has been a vocal advocate for mobilization and collaboration in order to meet the moment.
There is so much uncharted water when it comes to our understanding of disease, but if we can engineer biology to have cells tell us precisely what is happening inside them, how far might we see into the horizon? Just as the original octant guided sailors to safe harbors, Octant is on course to lead us to hidden treasures in our fight against society’s most burdensome diseases.