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hen Facebook founder Mark Zuckerberg and his wife, Dr. Priscilla Chan, recently announced that they would donate shares presently worth about $45 billion to good works, they understandably looked for inspiration to the world’s undisputed philanthropy leaders — Bill and Melinda Gates, whose foundation is by far the world’s largest.

Here are some lessons the Gateses could offer on global health and life-science philanthropy, but probably won’t:

Beware of world domination

Big money can crowd out other ideas, and mega-benefactors can do harm, as well as good, when they substitute for societies in taking the lead in solving their own problems.

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Council on Foreign Relations senior fellow Laurie Garrett estimated in 2012 that the Bill & Melinda Gates Foundation underwrote 68 percent of all private giving for global health. Gates money has driven away hundreds of smaller donors, she said, because the long Gates shadow blocks the warmth of public appreciation for these others.

“More and more is decided in Seattle about what everyone else does,” Garrett said in an interview.

In 2014, Gates gave the World Health Organization $257 million, more than all nations except the United States. Excluding the nine largest national donors, Gates gave more to WHO than all remaining nations combined.

“That scares me,” Garrett said. “It means that a lot of countries are getting away with being free riders, and are not as engaged as they should be.”

Big donors also skew funding toward more narrow goals that the donors can take credit for, said William Muraskin, a professor of urban studies at Queens College in New York and author of books about global vaccination programs. For example, it’s easier to develop a vaccine for water-borne rotavirus — a developing-world killer and Gates priority — than to tackle the harder, but ultimately more effective, goal of providing poor nations with clean drinking water systems.

Don’t let your endowment subvert your goals

The Zuckerberg and Chan fortune is currently tied up in their Facebook stock. As they gradually move it out to underwrite the corporation they are creating to oversee their charity, they might consider the problems of the Gates Foundation, which has invested billions of dollars in companies whose activities work starkly against its philanthropic goals.

For example, the foundation profited from subprime lenders who victimized Seattle homeowners, while giving money to organizations fighting local housing insecurity. It made bets on Big Pharma companies that priced AIDS drugs out of reach for the developing-world victims the foundation was trying to save. It invested in chocolate makers who benefited from the labor of African child slaves.

And according to the foundation’s most recent tax filing, it profits from hundreds of millions of dollars of investments from BP, Arch Coal, Duke Energy and Anglo American, despite Gates and Zuckerberg having recently cofounded the Breakthrough Energy Coalition to combat climate change.

Temper your faith in technology

Naturally, the founder of the most successful social networking platform might look to technology to solve public health problems.

Technology titans-turned-philanthropists often assume they can revolutionize global health and life sciences the way internet companies transformed the tech landscape. Their excitement tends to wane when they encounter “problems that are not easily solved with an invention,” Garrett said.

Taking on problems that require structural and political solutions can mean stepping into the worlds of social compromise and political deal-making. It’s true that governments and United Nation agencies can suffer from crippling bureaucracy, but the opposite — overconfident, long-distance dictates for rapid change from wealthy donors — can be equally ineffective. Gates and Zuckerberg each saw this in their massive, disappointing experiments in American schools.

Public health experts around the globe tried for years to get the Gates Foundation to move beyond technical solutions for disease, such as new vaccines, and seriously address a basic problem of development and health: Vaccines let babies survive to age 5, but without fixing social and economic systems for food security and basic health services, many of those children still die young, or become orphans.

The trick for Zuckerberg will be to listen to voices that might move him out of his tech-driven comfort zone and learn much faster than the Gateses did.

Create a culture of openness and accountability

The Gates Foundation has a reputation for insularity and an abstruse process for deciding on grants. Its board consists of just the Gateses and Berkshire Hathaway CEO Warren Buffett, who has committed most of his personal fortune to the foundation. But as a nonprofit charitable foundation, its plans, grants — and by law, its tax returns, and investments — are public information.

Zuckerberg and Chan have gone in a different direction, setting up their giving vehicle as a limited liability company — with less protection from taxes, but no obligations to share any information with the public.

They’ve already heard a raft of criticism from those who suspect that the LLC might orient itself toward helping Facebook achieve even greater power. Given Zuckerberg’s reputation as a ruthless business competitor, the more opaque his giving, the more skepticism he’ll face. But if he takes a hint from Facebook — opening up and inviting feedback — fans and doubters alike will more likely become supporters, and help make the Zuckerberg-Chan pledge one of history’s most important philanthropic acts.

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