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The Making of the Biohub

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The Making of the Biohub news feature Sundry Photography / Alamy Stock Photo. The making of the Biohub The Chan Zuckerberg Biohub is both an institute and an academic network devoted to accelerating research via cutting edge technologies and open science. Its focus on single-cell analysis and infectious disease has placed it front and center in the pandemic. Laura DeFrancesco global pandemic is something Joe Before long, the virus had arrived on The pivot on a dime was possible DeRisi has been preparing for his his doorstep in San Francisco, California, because the Biohub is funded by the Aentire career. What he didn’t expect and DeRisi and his colleagues pivoted to Chan Zuckerberg Initiative (CZI) — a was that the viral scourge would ravage so throw their considerable technological philanthropy set up by pediatrician Priscilla close to home. DeRisi was in the process of expertise and infrastructure at it. They Chan and tech titan Mark Zuckerberg to standing up sequencing technology to help set up a COVID-19 testing lab and leverage technology, community-based researchers in ten low- to middle-income recruited several hundred skilled volunteer solutions and collaboration to accelerate countries detect known, emerging or novel researchers from around the Bay Area. education, justice, opportunity and pathogens. In early January, during a visit to With the help of California governor Gavin science. Together with Steve Quake of one such station in Phnom Penh, Cambodia, Newsom, as well as the administrators at Stanford University, DeRisi is co-president his cloud-based IDseq tool, developed for their sister institution the University of of CZI Science’s Biohub, the first major scanning metagenomics data, sequenced California, San Francisco (UCSF), collaboration to come out of CZI’s Science the first full length COVID-19 genome in the necessary permits were acquired initiative. The Biohub is an experiment country — in a few days, rather than the and a fully functional and accredited combining the complementary strengths weeks it usually takes when samples are sent clinical lab was launched — this time in of three Californian academic institutions: away for analysis. just eight days. Stanford, UCSF and UC Berkeley. The Chan 1116 NATURE BIOTECHNOLOGY | VOL 38 | OctobER 2020 | 1116–1120 | www.nature.com/naturebiotechnology news feature disparate areas of biological science, meet twice a month to share their findings and discover areas of common interest that they might not otherwise be aware of. Catherine Blish, a Stanford immunologist and Biohub investigator since 2017, says the environment of sharing has been more important than the money. “The investigator meetings are a fantastic opportunity to learn about new approaches, new ways of applying old approaches, and generally stretch the boundaries of what seems possible. Dozens of new collaborations have developed based on lunchtime conversations at these meetings,” she says. A recent Nature Medicine paper from Blish’s lab illustrates the value proposition. “Through Biohub connections, we were able to share the data in a readily accessible portal, well before our paper was accepted, so that investigators throughout the world could use it to test hypotheses.” With DeRisi and Quake at the helm, Leading the charge: Biohub co-presidents Joe DeRisi of UCSF and Steven Quake of Stanford University Chan and Zuckerberg had the perfect pair were instrumental in designing the Biohub before taking the helm. Credit: Tyler Mallory, Chan to head such a project. With a background Zuckerberg Biohub in physics, Quake has developed numerous enabling life science technologies, which have been the foundation for over a dozen Zuckerberg Biohub’s core principles of science does. One question Chan asked of startups. DeRisi built an early version of enabling technology, collaboration and open all the consultants was how can science be a cDNA microarrayer while a graduate science are what enabled its turbocharged accelerated. By distilling down the answers, student in Pat Brown’s lab at Stanford, a response to the pandemic. CZI came up with an answer: “giving technology that transformed the field of researchers the tools and technologies they gene expression profiling in the nineties. What is the Biohub? need to do their best work,” she says. His other inventions include the Virochip, In 2015, Priscilla Chan and Mark Chan also wanted “to change the a microarray containing probes for Zuckerberg pledged 99% of their wealth incentive structure away from tenure or all known viruses, and more recently derived from Facebook shares over their publishing papers, allowing researchers IDseq, a cloud-based tool for analyzing lifetimes to launch CZI. The initiative to go deep on an issue.” Thus, the Biohub next-generation sequence data. IDseq takes on numerous scientific as well as instituted an extramural program with delivers to sequencing labs around the globe societal issues, among them prison reform, roughly a third of its funds to support the considerable computing power required the homeless problem in the Bay Area, and research considered too risky to receive to fish for pathogens in metagenomics data. equity gaps in remote learning. In 2016, the federal funding (Fig. 1). To foster “A lot of those places were hamstrung by couple announced they were expanding collaborations, their grantees, who work in the inability to analyze the data or even CZI to include science, and as part of that announcement, they pledged $3 billion over ten years to support science and technology that would make it possible to cure, prevent or manage all diseases by the end of the century. After broad consultations in the scientific community, the couple made the first major investment of CZI Science, with $600 million in Funding research Building shared technology for risky, exciting CZ Biohub Technology platforms available to endowment over 10 years, to form the new ideas investigator platform Bay Area scientists Chan Zuckerberg Biohub. “Folks from program development across the board were willing to talk with us, share ideas, share where they think there is an unmet need,” Chan says. Chan is a CZ Biohub scientist/pediatrician herself and takes research the lead on science issues. Infectious Disease Initiative Cell Atlas But it’s not all Chan. Zuckerberg’s Undertaking major initiatives fingerprints can also be seen in the emphasis to solve big problems on developing technologies that cut across fields, as opposed to focusing on particular diseases as much of other philanthropic Fig. 1 | Chan Zuckerberg Biohub’s work. Source: Chan Zuckerberg Biohub. NATURE BIOTECHNOLOGY | VOL 38 | OctobER 2020 | 1116–1120 | www.nature.com/naturebiotechnology 1117 news feature Box 1 | Open science on steroids One point of commonality between data sharing across disciplines, such as as a preprint when they submit for CZI founders and co-presidents is a ASAPbio, protocols.io and the Essential peer review. Surprisingly, to Quake, commitment to open science. In 2017 Chan Open Source Sofware for Science initiative. everyone agreed. “I thought we’d get and Zuckerberg donated an undisclosed Both Quake and DeRisi are vocal pushback, but we didn’t. Amazingly, sum to the preprint server bioRxiv, along advocates for open science. Quake said everyone agreed to do it. We hit the with technical support to develop better that when he and Joe were brought into the zeitgeist right.” tools for creating machine-readable and discussion on ways of accelerating science, Quake is clear that preprints remain searchable platforms for manuscripts. they decided that the most practical way to primarily a means of rapid communication Again in 2020, as the pandemic put stress do that was to eliminate publication delay. among the research community. He on preprint servers — which went from Using a back-of-the-envelope calculation, generally doesn’t speak with the press about publishing a few percent of Ebola and Quake estimates that getting rid of research fndings until they are associated Zika virus pandemic-related manuscripts publication delays could speed up scientifc with a later peer-reviewed publication. “It’s in 2014–2015 to publishing fully half of discovery by fvefold. “If you think of there for experts and we’re not out there COVID-19 manuscripts, more than 18,000 one discovery depending on the next, the pounding the drum,” he says. He thinks as of August — the couple supported the earlier people know what their colleagues excessive media attention to preprints medical preprint server medRxiv with a are doing the faster they can beneft from will recede once the pandemic is over. $2 million donation. Tis is only one part that.” So they made it a rule that everyone “In normal times, science is not front- of CZI’s Open Science initiative, which they fund has to publish all their work — page news. We go unnoticed except supports various platforms that facilitate not just the work that the Biohub funds — by the experts, he says.” participate in this sort of thing. So that Brain Initiative from the NIH, started under Foundation dipped into the Biohub’s Tabula really led to this concept of IDseq, to bridge the Obama administration. She helped Sapiens lung atlas to verify an observation the compute and storage barrier and make design the program that, since its inception they made — that COVID-19 infection metagenomics sequencing accessible to in 2013, has invested almost a billion dollars affects surfactant-producing cells in the low- and middle-income countries where in research funding for neurotechnology lung. (Surfactants make breathing easy the infectious disease burden is the heaviest,” tools to map brain circuitry. In 2016, by reducing surface tension at the air– DeRisi says. Bargmann was brought on as head of science liquid interface of alveoli.) This relates at CZI, and in that role she works closely to ongoing Gates-supported projects to Reaching out with DeRisi, Quake and others to define develop therapies for premature infants, The CZ Biohub now employs 100 priorities and foster collaborations between many of whom suffer from deficiencies in scientists, engineers, data scientists and the various arms of the CZI.
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