Priscilla Chan charts an ambitious, unglamorous course to fight disease. (Her husband is involved, too.)

SAN FRANCISCO — Dr. Priscilla Chan was just over a year out of her pediatric residency when, in 2016, she took the stage beside her spouse, Facebook founder Mark Zuckerberg, and pledged to affirmatively answer the question projected on the big screen behind them: “Can we cure all diseases in our children’s lifetime?”

It was the sort of absurdly ambitious question that would be easy to dismiss from a Silicon Valley technologist — the billionaire instantly recognizable in his gray T-shirt and jeans. But Chan, who grew up in the Boston suburbs, knew something about science. She had studied biology and worked in a neuroscience lab. She knew that the human body was more complicated than the most dizzyingly technical challenges her husband had overcome.

And yet.

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Three and a half years later, Chan, who turns 35 this month, insists that the goal she and Zuckerberg have set for themselves — to “cure, prevent, or manage all diseases” by the year 2100 — is a realistic one.

“We are serious about it,” Chan told STAT in an interview. “We think that if that’s our north star, we think it’s not impossible.”

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Today, Chan presides over the 400-person organization tasked with gradually giving away almost all of the couple’s fortune, which is currently worth about $80 billion. During a period in which her husband’s public image has been dented by a series of controversies involving privacy and disinformation, Chan has emerged as one of the most influential philanthropists in science — and as the key day-to-day decision-maker shaping an unusual approach to supporting research.

While other prominent tech billionaires have homed in on specific fields of research — Paul Allen picked the brain, Sean Parker chose cancer immunotherapy, and Bill Gates took on infectious diseases — Chan and Zuckerberg have taken a broader view. So far, they’ve focused on doling out grants for technology infrastructure and tools for basic science, an approach that might fail to generate breakthroughs on its own but that, in their view, could have wide impact.

“What I really believe in is actually making sure that the system works better,” Chan said. She added: “It’s not about one disease that’s important to me, or one specific question I want answered.”

That philosophy has meant funding a variety of projects that don’t deliver the direct payoff that can come with a drug trial or a vaccination drive. Among them: developing microscopy methods and software for imaging, building a dashboard to detect pathogens, supporting preprint manuscripts that have not yet been peer-reviewed, diversifying science journalism, and, most recently, organizing patient groups tackling rare diseases.

Critics see a goodwill tour to distract from Facebook’s sins. Fans see a thoughtful effort to build scaffolding that will prove critical to advancing science. Still other observers see a long game.

The couple’s approach “speaks to (A) how much money they have, and (B) how much time they have,” said David Callahan, founder and editor of the digital media site Inside Philanthropy.

Zuckerberg and Chan “are sitting on one of the biggest fortunes in American history,” Callahan said. “They have decades to deploy wealth to try to get toward their goal.”

Their vehicle for trying to get there is the Chan Zuckerberg Initiative, which they set up, unusually for a philanthropy, as a limited liability company, and which works on education, criminal justice reform, immigration, housing, and local issues, in addition to science. They have funded it over the past few years by selling several billion dollars of Facebook stock, and have vowed to keep it going by selling off 99% of their Facebook shares during their lifetimes. It is funded by no outside donors beyond the couple.

Zuckerberg and Chan in 2016 pledged to spend $3 billion over the next decade on CZI’s science initiative. So far, $800 million has been doled out in grants. That doesn’t include other spending, such as compensation for the roughly 100 CZI employees who work on the science initiative.

Their biggest expenditure in science to date has been for the Chan Zuckerberg Biohub, a research center in San Francisco’s Mission Bay neighborhood that brings together researchers from the Bay Area’s top three universities: UCSF, UC Berkeley, and Stanford. Another big project: supporting an international collaboration known as the Human Cell Atlas that’s working to map all the cells in the human body by funding the development of experimental methods, computational tools, and data platforms.

These are “areas that just don’t seem glamorous — but are absolutely required to move a field like this forward,” said Cori Bargmann, the Rockefeller University neurobiologist and geneticist brought in to serve as CZI’s head of science.

Zuckerberg and Chan are officially co-CEOs of CZI, and Zuckerberg comes by for things like strategy reviews and advisory board meetings. But in practice, “Priscilla’s the full-time person,” and is in the office four days a week, Bargmann said. (Chan left full-time medical practice three years ago to run CZI, but recently returned to the clinic at UCSF to practice about once a month.)

“I see this as her life’s work,” Bargmann said. “She takes it very seriously. She’s there all the time. She reads everything I send her.”

STAT asked Chan how she and Zuckerberg think differently about science, in light of their different backgrounds. Zuckerberg, she said, “thinks about it from an engineering perspective of: How do you answer unknown questions? And what are the moonshots that we can support to see or do something previously impossible?” By contrast, she said, “I spend more time really thinking about: How do we make sure that that net improves patient lives?”

When it comes to talking science with Zuckerberg, she said, “our conversations are both exciting and frustrating.”

Chan and Mark Zuckerberg attend the 2020 Breakthrough Prize Red Carpet in Mountain View, Calif.

Ian Tuttle/Getty Images for Breakthrough Prize

Zuckerberg may be the best-known CEO in America. You don’t have to be a tech news junkie to be able to recite the outlines of his biography: starting a database of profile pages in his Harvard dorm room; growing the social network into a global juggernaut; getting scolded by lawmakers on Capitol Hill over how Facebook was used to harvest user data and spread disinformation during the 2016 presidential campaign.

Chan, who has been with Zuckerberg since the beginning, has kept a much lower profile. Even today, as her role leading CZI puts her in the most visible position of her career, she has grasped on to some semblance of her own privacy.

On the phone with STAT, Chan spoke in earnest and idealistic terms. She talked about giving hope and living a life of service.

Her Facebook page — or at least the part she makes publicly available — is polished, a mix of posts that read like press releases and a dash of the personal. In one post, she wishes happy birthday to Jonas Salk, who developed the polio vaccine; in another, she shares a photo of her desk at CZI, covered with photos of the couple’s daughters, 4-year-old Max and 2-year-old August, and a tea mug inscribed with the words “Need. More. Sleep.”

Chan grew up in Quincy, Mass., a suburb of Boston. Her parents — ethnic Chinese refugees who fled Vietnam — worked long hours at a restaurant and other jobs. Chan graduated as valedictorian from her public high school and, when she enrolled at Harvard, became the first person in her family to attend college.

She met Zuckerberg in the fall of her freshman year, while waiting in line for the bathroom at a dorm party. Zuckerberg, a sophomore, had been called in to face Harvard’s disciplinary board after creating FaceMash, a hot-or-not-style website for rating students on their attractiveness that was something of a predecessor to Facebook, and he was expecting to be forced to leave school.

“In what must be one of the all-time romantic lines, I said, ‘I’m going to get kicked out in three days, so we need to go on a date quickly,’” Zuckerberg later recalled in his commencement speech to Harvard’s Class of 2017.

Zuckerberg did not get kicked out — he would leave Harvard voluntarily for Silicon Valley, at the end of that school year, as his new website, TheFacebook, was taking off — but they went on that date.

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After graduating, Chan moved west to be with Zuckerberg and teach fifth and sixth grade science at a school in San Jose. A year later, she started medical school at UCSF. The couple married in 2012, the same year Chan finished medical school and Facebook went public and reached a billion users.

When it came time for Chan to apply for residency programs where she would train as a pediatrician, she sought out, and got accepted into, a competitive program at UCSF for pediatric residents who want to help vulnerable children. The program included special training in leadership, communication, and advocacy — skills that could come in handy when giving away what was already well on its way to becoming one of history’s largest fortunes.

In the clinic with kids and their families, Chan proved to be a natural, according to her mentor, Dr. Meg McNamara, who served as her attending physician during her residency.

McNamara rattled off a few of the most memorable cases Chan saw as a resident: the preschool-aged girl with high blood lead levels, the teenager smoking too much marijuana, the pregnant woman who delivered after coming into the emergency room late at night. Chan handled each case deftly, with warmth and diligence, McNamara said.

McNamara was unsurprised when Chan decided to leave full-time medical practice to lead CZI. “I think that she recognizes the privilege that she has in her position — and also the responsibility that goes along with that.” McNamara said.

Dr. Harold Varmus, who previously directed the National Institutes of Health and the National Cancer Institute and now sits on the CZI science initiative’s advisory board, said that Chan’s medical training gives her a “level of sophistication” when it comes to overseeing CZI science’s programs.

It’s “quite unusual among funders,” he said.

“What I really believe in is actually making sure that the system works better.”

Dr. Priscilla Chan

CZI’s headquarters takes up several floors of an office building in the heart of Silicon Valley, just a 5-mile drive from the giant Facebook campus that effectively bankrolls CZI’s work.

Bargmann said there’s a strict firewall between CZI and Facebook, which itself has been building out its own health business. The two organizations don’t share code or resources, and CZI doesn’t much use the social network, other than for communications purposes.

As Facebook’s reputation has taken a hit, CZI’s science initiative hasn’t heard concerns from the scientists it works with. After all, Bargmann said, “most people don’t complain about funding.”

Still, Bargmann said, “we are quite serious about recognizing that our founders mean that we are going to be held to a higher standard than we would otherwise be held at this stage of our development.” (Among other things, CZI has invested heavily in a team devoted to privacy and security.)

CZI’s science initiative is infused with the values of Silicon Valley — in the types of grants it doles out, in who it hires, even in its structure.

Its establishment as an LLC has given it flexibility, Chan said — a flexibility that sometimes makes it look more like yet another tech company on the hunt for deals. In 2017, for example, CZI acquired Meta, the startup behind an AI-powered search engine for researchers trying to wade through scientific papers. As an LLC, CZI preserves the option to spin out Meta into an independent entity in the future, though it has not yet announced plans to do so. Were CZI a tax-exempt nonprofit, it would face a number of bureaucratic hurdles that would complicate a potential spinout.

About three-quarters of the employees who work on CZI’s science initiative are in technical roles such as software engineering, analytics, and product management. Some have been hired from companies like Microsoft and Amazon and, yes, Facebook.

The poaching can also go in the opposite direction. “There’s even sometimes a little bit of side eye between Mark and Priscilla. We just had a terrific person in our user experience group move to Instagram,” Bargmann said.

In other ways, CZI’s science initiative is charting a more open and collaborative course than is typical in Silicon Valley, where proprietary code is often fiercely guarded.

It publicly lists its grants, a level of transparency not required for an LLC. It has pledged to release software developed by it or its grantees under open-source licenses. And it strongly encourages — and sometimes requires — grantees to post their manuscripts as preprints prior to peer review.

As for Chan, she sees her job as thinking “about the meta question of CZI: How can we as an organization develop differentiated ways to give back — that’s in addition to money and resources?”

That focus on adding differentiated value is part of why CZI hasn’t gotten into funding drug trials or investing in biotech. “We feel like there’s a lot of good support, existing infrastructure, and funders in that space that are doing a great job,” Chan said.

Of course, Zuckerberg and Chan’s money isn’t going to cure any diseases — much less all of them — without getting closer to the clinic.

Dr. Eric Topol, the cardiologist and geneticist who directs the Scripps Research Translational Institute in San Diego, recently visited CZI in Silicon Valley as part of a group of researchers brought to discuss biosensors. Topol met with Zuckerberg and Chan while he was there, and says he’s impressed by a number of the projects they’ve funded so far.

Still, he said, “it’s unlikely that what they’ve done so far is going to eradicate diseases.” He added: “Even if they put every asset they have … even if you plot out 10 years, you’re still going to need more than that to even put a dent in the disease burden that we face.”

The couple hasn’t announced additional funding for CZI’s science initiative beyond the initial $3 billion commitment that will last through the middle of this decade. But, Chan said, “we have a deep commitment to this work in the long term.” She said she’s currently “pointing the team towards a lot of work and measurement and evaluation to figure out what works, what doesn’t work, what we should do more of, what we should do less of.”

Asked about the legacy she wants to leave in science and medicine, Chan gave a two-part answer. When it comes to CZI’s science initiative, she wants to bring together scientists, patients, and clinicians in a way that makes each piece of the biomedical research system “greater than the sum of its parts,” she said.

And as for her personal legacy? “One day when I retire from this job, hopefully I’ll get to go back to being in the clinic,” she said. “At the heart of it, I’m a pediatrician.”