Biohub’s success inspires CZI to extend and expand support through 2031, replicate our model in new CZ Biohub Network

In their 2021 Annual Letter, released today, Chan Zuckerberg Initiative (CZI) co-founders and co-CEOs Dr. Priscilla Chan and Mark Zuckerberg announced that they are doubling down on their commitment to accelerating biomedical science and advancing human health with an ambitious new effort to observe, measure, and analyze any biological process throughout the human body — across spatial scales and in real time.

Beyond expanding support for its own science and science technology programs to achieve these goals, CZI made two other announcements of great importance to those of us at CZ Biohub.

First, our operations will be expanded and extended through 2031, which will allow us to continue taking on the large and complex scientific challenges that are the cornerstone of our work. This new commitment will enrich our efforts in both infectious disease and quantitative cell science by building up our pathogen early-detection efforts in the U.S. and abroad, and by creating new technology platforms, foundational datasets, and pipelines for cell biology at scale.

Second, building off the successes and lessons learned from our work at CZ Biohub over the past five years, CZI Science announced the formation of a new Chan Zuckerberg Biohub Network, which will replicate the Biohub model in different locations and give other universities and institutions the opportunity to join us in pursuing grand scientific challenges on 15-year time horizons.

Just as we have in the Bay Area, these new Biohubs will take on grand scientific challenges in areas such as imaging, artificial intelligence (AI), infectious disease research, cell biology, and neuroscience, while building new technologies and tools to tackle them.

Up to now, we have had shared leadership of CZ Biohub as co-presidents, but in 2022, Steve will change roles, moving to CZI to lead the new CZ Biohub Network initiative; Joe will assume sole leadership of the Bay Area CZ Biohub as president.

A successful model

Both of these announcements are a direct reflection of how valuable our work is and how well everyone at CZ Biohub has done that work. These are achievements we are very proud of. It seems fitting, then, to take this opportunity to reflect on what we have accomplished over these past five years, accomplishments that inspired CZI to extend their support for us and to also give others the chance to work within the model we’ve found so productive and successful here in the Bay Area.

When we sat down in 2016 to help found a new philanthropically funded nonprofit research institute, established with a $600 million pledge from CZI, we wanted to empower Bay Area scientists to pursue their boldest, most innovative ideas. We decided to bring scientists from different fields together and give them support to launch projects that might be difficult to support through conventional funding sources. Specifically, we sought new ways to bolster the tremendous scientific talent of three powerhouse universities — Stanford, UC Berkeley, and UCSF — to further a central goal of the concurrently established CZI Science: to cure, prevent, or manage all human disease by the end of the century.

In designing the Biohub we borrowed the best aspects of other philanthropically funded science organizations that we had the privilege to be a part of earlier in our careers. That led to our Investigator Program, a self-nominated competition for discretionary, no-strings funding intended to support the best early-career and established researchers at our partner universities. We then launched a series of projects that required intercampus teamwork, in areas such the microbiome, early animal evolution, and cardiovascular disease.

Complementing this effort, we built intramural teams within the Biohub itself, again primarily composed of early-career scientists, to pursue large projects that wouldn’t naturally happen in a university setting. To help power these projects, we built technology development platforms to drive scientific discovery at scale. 

Our criteria for success began with a simple thought experiment that we called “the deletion test.” The test starts with deleting the Biohub: imagining a branch of the multiverse in which it never existed. Would the projects taken on by the Biohub and our Investigators have been done anyway? Or did the Biohub make possible things that would not have happened otherwise? 

We’re the new kid on the block, and as we celebrate our fifth birthday, we’re just getting started. But when we look at what has been accomplished so far, our experiment shows promising preliminary ­­­results.

Coming together

Consider our Quantitative Cell Science initiative. The “Tabula” projects aim to map every cell type in organisms ranging from flies to lab mice to lemurs, and even human beings. The whole-organism atlases the Tabula projects create move us closer to understanding how diseases arise at a cellular level and how they impact us. These are huge undertakings that require a deep dive into how cells use their genome — their RNA transcriptomes, their proteomes, their interactomes. This is important work, at a scale beyond the scope of a single lab or even a single university.

That’s why we assembled a broad, interdisciplinary consortium of diverse experts for these Tabula projects. A recent paper on our human cell map, Tabula Sapiens, listed more than 160 authors. Some are geneticists or cell biologists. Others are surgeons, engineers, data scientists, or experts on specific organs and tissues.

This kind of collaboration happens when people are genuinely excited to work together on a project that matters. Our researchers tell us that, funding aside, what they most appreciate about CZ Biohub is the connection and community it provides. From our twice-a-month Biohub gatherings for Investigators to the meetings we’ve offered online during the pandemic, we bring people together and watch them play — not to compete with other scientific institutions, but to be true partners.

The researchers we recruit to work inside the Biohub, generally just starting their careers, are offered a non-traditional path. They  work at the bench and run small groups, but don’t have teaching or fundraising responsibilities.

In addition, our support for faculty recruitment bolsters our partner universities. In addition to the 97 existing university faculty that we supported through our Investigator competitions, in our first five years we also helped support the recruitment of 16 new faculty members to our partner universities via a university-nominated Investigator program; more than half of these are women and more than a third are Black, Hispanic, or people of color.

Engaging a broader range of communities in science is critical — it widens and deepens our ways of thinking, driving better scientific outcomes. Over the next five years, we have committed to help diversify the faculty of the universities by creating 21 new slots in the university-nominated Investigator program, each of which contributes $1 million to the startup package of a new faculty member. While the second 5-year phase of this program is just starting, it has already led to the recruitment of ten additional faculty, all of whom are Black, Hispanic, or people of color, and seven of whom are women.

Inventing the future of the life sciences

Every research institution has its own strengths. Some are dedicated to basic science. Others focus on global public health. We believe in the power of technology to drive scientific discovery. The chief ingredient in our “special sauce” is building new tools that drive science, since the future of research and improving human health both depend on such technological advancement.

For the Tabula projects, for example, that meant spending years prior to the founding of the Biohub developing the microfluidic technologies that enable single-cell genomics. We then challenged the Biohub team to figure out how to deploy that technology at an unprecedented scale in order to create the Tabula cell atlases.

We’re also developing inexpensive microscopes, intended for use in less-developed countries, that use advanced AI to spot malaria parasites in blood samples. We’re backing software for visualizing multidimensional biological data, and new imaging technologies that track how living creatures develop from single cells to adult organisms, in exquisite detail. The discoveries by our scientists have led to many patents. We have helped spin out a set of companies to develop these inventions, some of which have already launched their first clinical trials.

It is core to our work that advancements made possible by the Biohub embrace the spirit of open science. With this ethos in mind, everyone who collaborates with us agrees to post their work to a preprint server, such as bioRxiv, at the same time they submit to a peer-reviewed journal. We believe that this will accelerate scientific progress. The publication process can introduce significant delays (we’ve investigated this, and found that six to 18 months is typical) that thwart collaboration.

While it may be too early to fully measure the impact of our open-science policy, we can share one story. Our first preprint from the Tabula Muris project, which brought together more than a dozen labs to map 20 organs and tissues in the laboratory mouse using single-cell techniques, was downloaded more than 8,000 times before it finally appeared in a journal. By that time, the data had already driven at least two other published projects.

Meeting the COVID Challenge

But our unique model isn’t suited only to long-term scientific projects. It also affords us a nimbleness that allows us to turn on a dime in response to societal needs.

From the very beginning, our Infectious Disease initiative has been a major focus of the Biohub, which served us well when the COVID-19 pandemic emerged In the midst of our first five years. Early in the pandemic, in January 2020, CZ Biohub helped researchers in Cambodia to sequence the SARS-CoV-2 genome when the virus first emerged in that country. When COVID broke out in the United States, the Biohub, working with local regulators, was able to repurpose its special combination of technology and automation expertise at astonishing speed.

We set up a CLIA-certified lab for diagnostic testing in just eight days. Soon, COVID testing through this facility was available to all 58 counties in California at no cost. Drawing on the relationships we’d been building in California and across the world, our infectious disease experts had an immediate impact by providing rigorous clinical testing to the most vulnerable populations in California — including incarcerated persons, those in skilled nursing facilities, and patients at safety-net clinics — at a time when commercial testing was unavailable.

This effort was powered by a small but powerful army of 175 graduate students and postdocs, and we taught other institutions how to do the same. Along with our colleagues at CZI, we coordinated with public health departments to track and sequence the virus, and to monitor the evolution of new variants.

This work was possible because of our prior efforts, in close partnership with the CZI’s science and technology teams, to make genomic tools more widely accessible. One of these tools, CZ ID (formerly IDSeq), a hypothesis-free global software platform, helped identify pathogens in metagenomic sequencing data. Another, previously known as Aspen, and now called CZ GEN EPI, empowered local public health agencies to do genomic epidemiology on their own.

To speed research on vaccines and antibody treatments, the CZ Biohub Protein Science group, in collaboration with our Bioengineering Platform, put into place automated systems for purifying SARS-CoV-2 spike protein, which we then provided to labs around the world. Out in the field, our Rapid Response Team tracked down sources of infections, saving lives. Simultaneously, the CZ Biohub’s Infectious Disease teams led a collaboration to screen host factors using CRISPR, identifying potential therapeutic targets that affect coronavirus infection and replication.

Biohub scientists and Investigators are now intensely studying the newly emerged Omicron variant of SARS-CoV-2 to gauge its infectiousness and the effectiveness of current vaccines against this variant.

We’re building on all this COVID-related work to prepare for possible future pandemics. We’re strengthening and refining a soup-to-nuts pipeline for identifying pathogens; monitoring their spread; revealing mechanisms of infection; and informing the development of tests, vaccines, and treatments. That’s much easier to do at a place like CZ Biohub, with its stable funding and continuity, outside the confines of the usual grant-making process.

The road ahead

We’ve blown out five candles, and we’re just getting up on our feet. Has everything been a success? Not really. We tried, for instance, to create a fully instrumented set of equipment at the Biohub that would enable a “self-writing lab notebook.” This proved difficult to coordinate and, for the moment, remains a dream.

But as we’ve learned to run, we’ve begun to integrate all our efforts to date: to align, for instance, our cell biology and infectious disease expertise to better understand the cellular and molecular effects of infection. We’re proud to see that our human microbiome project achieved significant follow-on funding, and we’re preparing to fund the next cohort of Investigators at our partner universities, each of whom will each receive $1 million in research funding over the next five years.

Throughout, we’ve kept our eye on passing the deletion test, by supporting work that wouldn’t have happened without our unique approach and its real impact. As more independent research institutes appear, we hope to serve as a model, even as we continue to iterate and refine our approach.

The CZ Biohub may be small, but we’ve been scrappy and always punched above our weight. Maybe that’s because we set out to do things that are bigger than anyone can do alone. We believe that a rising tide floats all boats, from the scientists and institutions we support to the health of people everywhere.

Now, as we begin a new chapter, both in the Bay Area and at new Biohubs yet to be imagined, we can’t wait to see what comes next.

Steve Quake & Joe DeRisi