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MOVE FAST AND TEST THINGS

Coronavirus is putting the power of private philanthropy to the test

REUTERS/Beck Diefenbach
The Chan Zuckerberg Initiative aims to cure all diseases by the end of the century. Now Covid-19 is on the list.
Published Last updated This article is more than 2 years old.

On a rainy Saturday morning in early March, Joe DeRisi and Eric Chow were hauling a $90,000 robot down 16th Street in San Francisco’s Mission Bay neighborhood. The machine, a 150-pound cube of dull gray metal crucial for running medical tests at a high volume, was perched on a plastic cart, with scrap cardboard taped to the top to keep it dry.

The streets were eerily empty. A shelter-in-place order would soon take effect in the city, which reported its first case of Covid-19 on Jan. 31. To avoid sidewalk bumps, DeRisi and Chow rolled their cart right down the middle of the road.

Chow, who runs the University of California, San Francisco (UCSF) Center for Advanced Technology, was doing DeRisi a favor. He was loaning the machine to the UCSF biochemist, who is also a co-president of the Chan-Zuckerberg Biohub, a research facility launched in 2016 with a $600 million grant from Priscilla Chan and Mark Zuckerberg’s private philanthropy.

Under normal circumstances, the Chan Zuckerberg Initiative (CZI) would be funding projects to advance its many lofty ambitions, which include ending all disease by 2100. But in March, much of the scientific research CZI planned to support had ground to a halt. Instead, the philanthropy was scrambling to redirect some of its patrons’ wealth to confront just one virus: SARS-CoV-2.

The high-throughput robot was one of several pieces of equipment the scientists would roll off the UCSF campus, down the road—pausing whenever the cart’s wheels got stuck in the streetcar tracks running through the neighborhood—and up to the third floor of the building that houses the Biohub.

There, in a disused lab space, DeRisi, Chow, and a team of volunteers were sprinting to set up a Covid-19 testing lab to track the progression of a pandemic that had recently reached California and would go on to kill at least 4,700 people in the state in just three months. The effort to launch the lab illustrates the potential and power of private philanthropies to mobilize millions of dollars and leverage relationships to move scientific endeavors forward at lightning speed—and then change their focus just as quickly.

In some ways, CZI is not like other philanthropies. For starters, it’s organized as a limited liability corporation instead of a charitable organization, which means it has fewer transparency requirements and can spend money on lobbying and political contributions. Theoretically, it could turn a profit—although it was created for the express purpose of giving away Priscilla Chan and Mark Zuckerberg’s $45 billion, Facebook-generated fortune. It also has a focus on developing its own technologies: Biohub co-owns any patents that researchers generate while using its funding or resources, along with the scientists and their universities.

But in other ways, CZI behaves like many of its peers, such as the Gates Foundation, the Wellcome Trust, or the Li Ka Shing Foundation. It invests in a few broad areas of interest, including a $3 billion arm dedicated to science. The science wing writes grants for basic biology research—for example, supporting a project to build an atlas of every human cell—and funds medical research on rare diseases and neurodegenerative disorders. (Quartz’s editor in chief co-founded a research foundation that has received support from CZI.)

The bulk of that work was put in limbo when governments began issuing shelter-in-place orders. “All over the world, our grantees’ labs shut down,” said Marc Malandro, vice president of operations for CZI’s science wing.

Meanwhile, hundreds of requests for CZI funding began flooding in from researchers and health officials. As the pandemic evolved, they received calls for help finding ventilators, then funding to develop methods for sterilizing masks, then support for virology studies. “We realized pretty quickly that we weren’t going to be able to go through [this wave of requests], and give it its due consideration, in a time that was going to have immediate impact,” said Malandro.

Instead, CZI referred those applicants to other organizations and donated $25 million to the Therapeutics Accelerator, an effort to speed Covid-19 drug discovery launched by the Gates Foundation, Wellcome, and Mastercard in early March. Malandro says the investment was CZI’s attempt to have a big impact, quickly, outside of its usual wheelhouse. “We don’t have a program in drug discovery,” Malandro explained, “so the thought was, ‘How do we get partnered with people who know how to do this well and share our values?’”

CZI also looked for ways to pivot its existing work to deal with the virus: The team that had been working on building out the cell atlas turned its attention to funding research on how coronavirus affects individual cells, spending $750,000 on five studies to build a basic understanding of the disease. Before the pandemic, CZI had donated $2 million to fund bioRxiv, where biologists can share their research findings quickly while their papers await peer review at scientific journals. CZI says it will announce an additional $2 million investment in bioRxiv’s sister site for medical research, medRxiv, later this month.

But from the start, the bulk of CZI’s coronavirus effort centered on leveraging the expertise of Biohub head and sometime-robot toter Joe DeRisi. In 2003, DeRisi helped identify the SARS coronavirus during his work at UCSF. Since then, he and collaborators at his Biohub lab had created a pathogen-spotting tool called IDSeq, which he hoped could be deployed around the world to monitor disease outbreaks. He was halfway through deploying the system when the coronavirus pandemic disrupted his work.

In early January, DeRisi was in Phnom Penh, visiting researchers at the National Institute of Allergy and Infectious Diseases’s Laboratory of Malaria and Vector Research. The scientists had recently adopted IDSeq for their investigation into the pathogens that cause high fevers in Cambodia, and DeRisi was helping them troubleshoot the system. Three weeks after he left, IDSeq confirmed the country’s first Covid-19 diagnosis.

He watched with alarm as the new coronavirus moved faster and farther than the 2003 SARS outbreak. Even as California and the rest of the US faced severe testing shortages, the American case count began to rise. “By late February, I realized that it wasn’t going to be about having this external detection network, but instead that we were going to have the pandemic in our own backyard,” DeRisi said. “By the first week of March we knew we had to really pivot away from what we were doing before.”

At first, CZI set its sights on expanding testing capacity in the Bay Area, but the organization balked at the regulatory hurdles involved in starting a clinical lab from scratch. One of the most formidable was a California requirement that all clinical lab workers undergo a two-year certification process. “The barriers and technical difficulties and logistics of doing real clinical testing we thought, initially, were insurmountable,” DeRisi said.

But Malandro and DeRisi both said they wanted to set up a clinical lab, and not just an epidemiology research lab. They wanted to help patients.

Then DeRisi got a fortuitous call from an unfamiliar number with a Sacramento area code. (“I thought it was a telemarketer and I wasn’t going to answer,” he recalled.) When he picked up, California governor Gavin Newsom was on the line. He wanted to know what the state could do to improve its coronavirus response. DeRisi suggested loosening some of the requirements around staffing clinical labs.

Within a week, on March 12, Newsom issued an executive order suspending the state’s lab staffing regulations. Workers didn’t need a special certificate to test patient samples anymore. Under the less stringent federal rules, they just needed a relevant degree and lab experience.

“That flipped the switch for us,” DeRisi said. Work on a testing lab began immediately. Because of Biohub’s close ties to UCSF—many of its researchers are UCSF faculty members, and the campus is just two blocks away—the university and the philanthropy quickly formed a partnership. The new facility would technically be an extension of UCSF’s existing clinical testing lab, backed by Biohub funding and organizational support.

Since testing equipment was hard to come by, DeRisi texted his friend Eric Chow on Thursday, March 12 to ask if they could borrow some from idled UCSF labs. By Saturday, they were carting lab equipment down 16th street in the rain.

On March 16, San Francisco mayor London Breed issued a shelter-in-place order, and UCSF ordered any straggling scientists to shut down their research within two days. Jamin Liu, a third year bioengineering PhD student in DeRisi’s UCSF lab, went to campus that night to wrap up an experiment on living cells as best she could, working until 3am. “Obviously everyone had the same plan,” she said. “All the machines were booked up, all the times were booked, and it was a bit of a panic.”

The next morning, DeRisi asked her to join his new Covid-19 testing lab as an unpaid volunteer, joining the ranks of other UCSF researchers who had already shut down their experiments and gone to work setting up the lab. “This is the culmination of all these years of schooling and training,” Liu said, “and to be told that, ‘Hey, there’s something you have the skills for that will help lots of people’…it would have been ridiculous to say no.”

They worked to haul and install machines, set up procedures for receiving samples and reporting results, and create their own method of testing for Covid-19, borrowing pieces from existing assays developed by the CDC and other organizations.

The lab validated the accuracy of its testing method on Tuesday, March 17. To an untrained observer, the moment would not have seemed very dramatic: A laptop churned through data generated by the lab’s machines, checking to make sure there weren’t any glaring errors. But for the scientists gathered expectantly around the screen, it was euphoric.

“Everyone screamed, arms were up, and I think after that we may have broken out some whiskey bottles to celebrate,” Chow said. Usually it takes months to go from an empty lab to a validated clinical test, he explained. The team had just done it in five days.

They spent the next two days testing samples that had already been tested at the main UCSF clinical lab, to make sure they got the same results. On Friday, March 20—eight days after Newsom’s executive order—the lab returned its first independent result.

All told, CZI has invested $4 million in the testing lab—a significant sum, but one that won’t break the bank for a multibillion-dollar organization. In fact, it has relied on free labor from a few dozen volunteers and, in its early days, equipment filched from UCSF labs. (Biohub has since returned most of the borrowed machines and bought its own.) In cases like this, the value of a philanthropy is as much about the strings it can pull as the cash it can dole out.

While DeRisi says he can’t take credit for California’s new, looser restrictions on lab staffing, Malandro, the CZI science executive, said the philanthropy did lobby for the changes. “Since early on there’s been a number of different touch points with the governor up to and including Priscilla [Chan], who’s on a task force of his,” Malandro said. “We’ve been in almost direct contact with the administration since this all began.”

All that string-pulling has had a clear effect. At the end of May, DeRisi said the lab was churning out 840 free tests a day on average, with volumes surging above 1,700 samples on the busiest days. It has offered to handle testing for any county health department in California, although it works mainly with partners in the Bay Area.

One of those Bay Area healthcare providers is La Clinica, located in Oakland’s Fruitvale neighborhood, which has become a coronavirus hotspot. Its 94601 zip code had 494 active cases as of June 11, the most in Alameda County. Chief medical officer Paul Bayard said the corporate testing lab that the clinic used to depend on charged $60 per test, sometimes struggled with shortages of testing kits, and had inconsistent turnaround times that ranged as high as 12 days in one case. (“And that patient was positive,” he recalled.) After switching to the UCSF/Biohub testing lab, the tests have been free, there have been no shortages, and results consistently come back in 24-36 hours.

Free testing means La Clinica can diagnose patients without seeking payment or insurance information, which is crucial because many are undocumented, uninsured, and unwilling to seek medical care if it means filling out extensive paperwork they fear will be used against them. The clinic now plans to boost its daily testing totals from around 30 to a goal of 100. “We know we need to do more and we feel like we can do that with the UCSF testing kits,” Bayard said.

Now, though, CZI and the Biohub lab face an inflection point. Lockdown restrictions have begun to ease, and academic labs are gradually starting to reopen. The volunteers who have kept the testing lab open from 7:30am to 1am some nights will have new demands on their time as they get the opportunity to return to their stalled experiments and careers. Some volunteers, like Jamin Liu, are international students on visas and can’t afford to lose time finishing their degrees. [Read more about how the careers of young scientists are being disrupted by the pandemic here.]

In the meantime, Malandro, who runs operations for CZI’s science wing, says the philanthropy is looking to turn the lab over to UCSF. “The goal the whole time wasn’t for the Biohub to gain a diagnostic testing capability,” he said. While CZI is committed to backing the lab into July, Malandro said the organization’s larger goal is “to be able to take the positive tests and feed them into Joe [DeRisi]’s sequencing pipeline so we can start to understand the epidemiology and the spread, and how the virus mutates or not.”

The details of the handoff are still being worked out. Steve Miller, who runs UCSF’s clinical testing program, said it wasn’t yet clear if the lab would be able to continue offering tests for free or at the same volume without CZI backing.

The epidemiological work, though, is moving forward. CZI has leveraged its relationships with universities to kickstart a slew of studies: In April, it reached out to UCSF epidemiologist George Rutherford and Stanford epidemiologist Yvonne Maldonado and said it had money and testing capacity to support any project they wanted to work on. Within weeks, their proposals were approved, and CZI had pledged $13.6 million for two long-term testing studies.

One will sample a representative population in the Bay Area over nine months to monitor the spread of Covid-19, and the other will give Bay Area healthcare workers weekly PCR and antibody tests to determine whether coronavirus antibodies confer immunity. UCSF and Biohub researchers have also partnered to understand coronavirus’s unequal impacts on marginalized people.

Maldonado, who is the principal investigator on one of the studies, said philanthropies like CZI can fill a research funding gap by writing checks quicker than institutions like the US National Institutes of Health, whose bureaucracy can make it difficult to pivot. “If you apply for a grant and you’re astoundingly successful, you can get funded in nine months,” Maldonado said.

“That’s where philanthropy has made a difference here,” he said. “We’ve had the funds for a month and we’re already enrolling and testing people in the study. It has gone remarkably fast.”

This story has been updated to reflect the changed date of CZI’s announcement of its investment in medRxiv.