This month marks one year since we openly released a diagnostic method for SARS-CoV-2 detection called SwabSeq. Today, and every day, thousands of people from healthcare workers to students at many universities are being tested using the method. It’s been a remarkable learning experience. This blog post explores a few lessons we’ve learned over the past year.
A. NO REALLY, THIS TIME IT IS DIFFERENT
This is the year the promise of synthetic biology in healthcare finally arrived. And the future promises to be even more different. The production and deployment of multiple new vaccines and diagnostics using a range of novel technologies in under a year post-emergence of the virus in humans is truly remarkable. The development and remixing of new technologies to read, interpret, write, edit, and distribute biology at scale powered rapid responses against biological threats on timescales approaching nature’s ability to produce them. While these trends have been discussed and debated by many, it took the emergency of the pandemic to pull the future forward and put these new approaches to the ultimate test, and synthetic biology passed with flying colors.
B. BIOTECH CAN NOW MOVE FAST WITH SMALL TEAMS TO ACCOMPLISH EXTRAORDINARY THINGS
The largest testing providers such as LabCorp and Quest (not to mention the CDC), hit major roadblocks in trying to scale testing. The largest vaccine makers prior to the pandemic, GSK, Merck, and Sanofi, were largely pessimistic that a vaccine would be a fast answer. Some of the biggest success stories, such as Curative, Broad and BGI in testing, and Moderna & BioNTech in vaccines had never conducted a single clinical test or produced an approved vaccine.
There are a few trends that have come together to upend what was previously thought realistically possible:
Our understanding of biology has crossed a new threshold at the molecular level. We can consume genetic information, and put it into context of engineering approaches that let us intervene, at much faster timescales and higher confidence than ever before. For example, it was remarkable how fast Moderna, BioNTech, and J&J deployed rational approaches to express the necessary proteins in a locked state after gaining access to the first SARS-Cov-2 genome sequence. It required rapid understanding of the genomic sequences being produced, the informatics and structural biology to understand the proteins and their potential function, molecular engineering insights to know that we could potentially lock those proteins in a useful state, and knowledge of our own immune systems to know such an approach might work. It happened, in some cases, within days.
Biotechnologies and infrastructure improvements have enabled new levels of biological information gathering, sharing, and collaborating. The technological improvements over the last decade in biology have been remarkable. The 10,000-fold drop in sequencing costs from 2007-17 enabled (1) sequencing the genome to enable vaccine development, (2) use of sequencing as a pure measurement and barcoding technology to scale testing, (3) a means to track the virus and its evolution in real time, and to better understand the factors at play in studying our own responses. Recent progress in synthetic biology, nanoparticle engineering, nucleic acid production, viral vector engineering, technologies to scale production, automation and computational approaches enabled teams to quickly incorporate others’ information and rapidly prototype ideas and solutions. Standardization of information formats and new forms of early sharing (preprints, sequencing datasets, open code, and shareable licensing) enabled teams to share and consume each other’s data much more quickly, leading to a tep change improvement in development times.
Cross-disciplinary individuals and small teams can think and work across fields, which has enabled more and varied experimentation and prototyping. The above two trends have empowered small teams to do more with less capital and less permission. There is now a larger ecosystem of smaller nimble companies taking varied and different approaches fueled with new classes of capital and partnership models. For example, because of the maturation of genomics, it no longer requires a sequencing center to sequence a viral genome in the field. Nor does it require a big pharmaceutical company to engineer new locked protein states. Similarly at Octant, we were able to repurpose the DNA-barcoding approach we developed for drug discovery, to run large COVID testing facilities without the need for rooms full of liquid handling robots. This is possible because we have teams of cross-disciplinary scientists and engineers remixing improvements in sequencing, genomics, computation, and synthetic biology to use biology’s own advantages to improve our technologies.
C. PLACING MORE, ORTHOGONAL BETS IN BIOLOGY SHOULD BE A MORAL, BUSINESS, AND SOCIETAL IMPERATIVE
If the pandemic reminded us of anything, it’s that human health is centrally important and deserves our time, attention, innovation, and capital more than ever. What is more important and urgent? We lost >3 million lives this year to COVID-19, and we lost tens of millions more on diseases we should be working on solutions for. These issues should demand attention from a greater portion of our best and brightest people, our policy choices, and our capital. Anything less is a misallocation of our industriousness as a society.
Given the consequences are so high, the cost of new projects is dropping, and the diversity of the ecosystem to work on these problems is flourishing, it’s important for more investors and companies across more sectors to start taking more differentiated bets in biology. Early during the pandemic, we talked with some very big providers that could have easily accelerated COVID testing progress for minute fractions of what they were losing in revenue due to the pandemic. Most of these providers gravitated towards scaling qPCR testing like everyone else, and often failed to foresee shared failure modes. When the health of entire societies is at stake, we must encourage placing secondary and tertiary bets on our largest problems. The cost to do so is minimal relative to the consequences of failure. Similarly, there continues to be a herd mentality in the treatment of human diseases. Despite the above great advances in technology, so many companies chase the same dozen or so bets in the same dozen or so indications. The biotech ecosystem and possibilities have sufficiently evolved such that we should be diversifying the problems and solutions we invest in. There are new possibilities, and like the COVID vaccines, there now exists the possibility for outsized positive outcomes along many new routes.
Octant Scientists Erin Thompson and Jimin Park working on SwabSeq R&D
D. IF YOU DON’T DO IT, WHO WILL?
I am encouraged that we are entering a new period where those that feel like they can make a difference have increased ability to make it happen. We were a 20-person drug discovery company who had no business trying to launch a diagnostic. But we knew that if we didn’t make SwabSeq happen, no one else would have. Low cost and routine asymptomatic testing for people like UCLA healthcare workers and Caltech students wouldn’t have happened. Similarly, the bets that Octant is taking in the diagnosis and treatment of serious diseases are bets nobody else is taking, but we think they will work, and like SwabSeq, they will save lives. I frequently talk to professors and trainees, given my history as a professor, about their ideas. They’re often conflicted about whether to leave the safety of their academic posts, and take the plunge or not. I always tell them one thing: If you have a vision that can help people, and you really believe it can work, go make it happen. There is not some broader committee that is going to decide this is a good idea and make it happen for you. A new age of biology has arrived. There is no better time for us to build the next generation of therapies for patients than now. The founders, companies and ideas that will make the biggest differences in people's lives will likely look and feel different than what's in vogue at the moment. The world is counting on it.