> The letter to our daughter works pretty well as comedy, e.g., “Medicine has only been a real science…” (emphasis added).

I'm not sure what the author is trying to say here. He cut out important context. The "..." was "for less than 100 years". While one might quibble with the exact number, Zuckerberg was reasonably in the ballpark.

> It also works pretty well as a dictionary example of “optimism”, with Zuckerberg imagining that a $1 billion annual budget is going to move the needle (NIH spent $31 billion in 2010, according to Wikipedia, and the drug companies keep telling us that they are spending some of their Irish dough on research)

The Gates Foundation spends about $4 billion a year, spread over many different kinds of initiatives. Their health spending is "only" about $1 billion a year, and they move the needle there. I see no reason the Zuckerbergs can't move the needle at $1 billion per year as long as they don't spend in too many disparate areas.

Here's an article from NPR that explains why it can be more effective to do charity and activism through an LLC instead of through a non-profit foundation: http://www.npr.org/2015/12/03/458276386/facebook-founder-to-...

Some excerpts:

    "A foundation itself is not allowed to do what the
    Internal Revenue Code defines as lobbying," he says.
    "If you're trying to achieve a social end through
    advocacy, you're going to find yourself very
    constrained, whereas if you're just paying it out of
    your own pocket if you're a company or an LLC, there
    are really no constraints at all, at least imposed
    by the tax code."

    In a public letter to their newborn daughter, Chan
    and Zuckerberg said about their philanthropic goals,
    "We must participate in policy and advocacy to shape
    debates."

and

    Mollie Cullinane, who runs a law firm that
    specializes in philanthropic giving, says creating
    an LLC instead of a nonprofit looks like a move by
    Chan and Zuckerberg "to get more deeply involved in
    advocacy and promotion of certain causes that other
    charities and foundations can't speak out about as
    loudly."

and

    But beyond politics, there are other ways an LLC
    will give the couple philanthropic flexibility.

    "There's a whole new area opening up, so-called
    impact investing, where you invest in a for-profit
    organization that has a social mission," Brest says.

    So the couple might invest in clean energy
    companies, for example, and could make money off
    those investments. Foundations can do some of that.
    But, Brest says, "you are freer from any
    restrictions if you simply do it through a private
    company."