Chan Zuckerberg Biohub to Foster High-Risk Technology Development

NEW YORK (GenomeWeb) – The Chan Zuckerberg Biohub today announced its first cohort of investigators funded to pursue high-risk scientific exploration focused on medical research and technology development.

The Bay Area Biohub is funded largely by a $600 million gift from Priscilla Chan and Mark Zuckerberg, co-president Stephen Quake said in an interview during a visit to New York yesterday.

A third of that amount will go to fund "the riskiest, most exciting ideas" of chosen investigators affiliated with collaborating institutions — namely, University of California, San Francisco, UC Berkeley, and Stanford University — while the remaining two thirds will fund a brick-and-mortar research program and two initial main research projects at the Biohub.

One project, called the Infectious Disease Initiative, aims to develop technologies and treatments for infectious diseases around the world, as well as prevention and emerging threat response methods. It will be based in part on co-president Joe DiRisi's metagenomics-based approach to diagnostics.

A second project, a collaboration with the Human Cell Atlas Initiative, will use single-cell genomics and cell-tagging technologies to create an atlas of all the cells in the human body, and the Biohub will be hosting a conference later this month at Stanford related to this project.

The so-called Investigator program has now committed $50 million to support the first cohort of researchers. The 47 individuals will be provided with five years of unrestricted gifts, "to work on their riskiest, most exciting idea," Quake said. Tenured faculty will receive $300,000 per year, while junior investigators will get half that. "We're trying to make the amount large enough so they can work on one thing, but not so large that they can run their whole lab off of it," Quake said.

Among the investigators is Adam Abate, whose single-cell digital sequencing research was also recently funded by the National Human Genome Research Institute. Others of note are: Jillian Banfield, whose research has expanded the tree of life; Carlos Bustamente, who studies population genetics; Will Greenleaf, who recently repurposed the Illumina GAIIx instrument for use as a massively parallel RNA array; bioinformatician Young Song; Catharine Bish, who recently found a correlation between immune cell diversity and infection risk; Katharine Pollard, who helped develop a computational method to quantify bacterial species and strain-level genomic variation; low-cost diagnostics developer Manu Prakash; and Matthew Porteus, who developed a method to use CRISPR/Cas9 to modify T cells.

"We're betting on the investigators to invent the future, and so it is a very broad portfolio of fields and ideas, from neuroscience to implantables, genomics, microscopy and imaging, and novel therapeutics" Quake said.

Meanwhile, the internal programs are more technology- and platform-focused and aim to get things that are already working to be more broadly used in science. "These are technologies that we helped develop, that we feel are mature, and are ready to have a huge impact on science right now," he said.

A collaboration agreement with the universities will also enable researchers at the Biohub to use facilities at the three universities, and vice versa, Quake said.

Quake noted that he and DiRisi "have had philanthropy impact our research at crucial moments," via Packard fellowships and affiliation with the Howard Hughes Medical Institute, and that they aim to expand that phenomenon into a larger-scale, systemic model. Funding this many high-risk projects with philanthropy at once may in fact be a precedent, Quake said.

For the Infectious Disease Initiative and Cell Atlas, the Biohub plans to hire group leaders, "Creating kind of an alternate career path for people who want to do science without getting on the university treadmill of writing grants and teaching," Quake said. Each of the projects will have five new hires. The Biohub has already staffed the head of the ID initiative with Peter Kim, an investigator who was most recently at Merck, as well as one of four group leaders who was recruited out of Novartis, he said. For the Cell Atlas, the two group leaders already recruited are Spyros Darmanis, a postdoc in the Quake lab at Stanford, and Manuel Lionetti, a postdoc in the lab of Jonathan Weissman at UCSF.

Quake also noted that CRISPR technology will be used "pretty broadly" across the projects. The Biohub has recruited the CSO from Caribou Biosciences, Andy May, to lead a genome engineering team, Quake said, and there will be a CRISPR core available to "make sure the latest CRISPR tools and approaches are available to faculty at the three universities as well as our internal groups."

The Biohub facilities will also house a novel optical microscopy facility, high-performance computing and data science, and a single-cell genomics and other genomics facility. The Biohub is also slated to get one of the first NovaSeq sequencing platforms from Illumina, Quake added.

A number of these tools and technologies will also be made available to researchers in the Bay Area at the three universities and Biohub staff, which Quake says will hopefully accelerate research.

"These are people that are going to succeed," he said. "It's just the way they're wired."

The Biohub is also expecting to partner with industry. "Our focus is on the front-end, early technology development and basic science," Quake said, adding, "To see these inventions and discoveries have an impact on human health, they're going to have to be translated by other organizations, most of them probably in industry." The Biohub will thus have an active licensing program, with the Biohub and the universities holding joint intellectual property and sharing royalties from licensing.

The investment in high-risk research could theoretically lead to a higher failure rate. Although the researchers in the Investigators program can each work on their riskiest project, Quake noted that Biohub is "making a bet on the person rather than the project."

"These are people that are going to succeed," he said. "It's just the way they're wired."

In terms of risk, Quake cited examples in his own career arc wherein he may have seemed like an unlikely prospect to develop genomics technology since he was an outsider to the field with his background in biophysics. Likewise, he went into non-invasive prenatal diagnostics development without a background in diagnostics or prenatal testing. Philanthropic investment can also be more flexible than funding from the National Institutes of Health, for example, "where you are funded to do what you've done before," Quake said. To further facilitate engagement among all its investigators and internal team, the Biohub will have academic meetings every other week, he said. In addition, creativity is an important aspect, and, based on their track records and proposals, the new cohort of investigators is "willing to take risks and try things that are a bit untethered from traditional funding." 

In the long run, the Biohub has not set any metrics to evaluate its successes, but rather will have a holistic assessment by an external panel of experts seven years into the 10-year commitment of support from Chan and Zuckerberg. 

The overarching goal of the Chan Zuckerberg science philanthropy is "curing, preventing or managing every disease" by the end of the century, and Quake admitted that this is an "audacious and unreasonable goal," but, quoting Bernard Shaw, "All progress depends on unreasonable people."

In addition, he said, for any big project, "It is hard to know what the ultimate impact will be ... but that is part of the charm of science." The human genome project yielded personal genome sequencing and NIPT, but those fruits would have been hard to predict at the time, for example. With the Biohub investigators, Quake said, "We're going to unleash them, set them loose, and they are going to surprise us in ways that I think will be fantastic."  

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