Having departed Microsoft, Bill Gates will now concentrate his full and formidable attention on the Bill and Melinda Gates Foundation and the intractable problems of global health. Being Bill Gates, he plans to solve them completely and permanently. In this effort, he will be overthrowing some traditional research practices and deploying some methods learned at Microsoft in trying to solve long-standing scientific challenges. Can he do it?
I used to think that given enough money and enough top scientists, time, and a fierce persistence, we would solve these health riddles. Now I worry: Maybe not. Gates does, too, which is why he is going at these challenges in some quite different ways that may dramatically shake up the way we do science.
Consider, for instance, the AIDS vaccine effort. After an unprecedented, quarter-century scientific offensive, it has failed badly. None of more than 30 vaccines tested have worked or provided insight into what might. The most recent candidate seemed to increase the risk of HIV infection. DNA sequencing technology and its scientific offspring, genomics, have not led to a breakthrough. Today's "rational drug design" has yet to break free from the trial-and-error methods of the past. The new model, wrote a Gates-funded researcher in tuberculosis, "completely collapses beneath the complexities and peculiarities of the disease."
Meanwhile, TB is pulling away. More than 400,000 people a year contract a strain resistant to multiple antibiotics; XDR or extensively drug-resistant cases are on the rise and essentially untreatable. Malaria, even with each of 5,300 genes laid bare, is currently "setting records" for fatalities, an incredulous Gates has observed.
Gates moves into his full-time role at his foundation following a decade's invovlement with unleashing the full potenital of science and technology on global health. First, Gates ended the neglect of diseases of the developing world. "The real missing element," he said years ago, "is applying biology to the diseases of the developing world. That's where the market mechanism doesn't work." Market forces, Gates added, put curing baldness ahead of curing malaria. Some $37 billion in assets and a bit of ingenuity later, the Gates Foundation has rectified this market imperfection to an admirable degree, through public-private partnerships and by creating an artificial demand curve to entice pharmaceutical companies into the field.
Initially, when it came to the specifics of applying biology, the foundation and Gates were hands-off. In 2000, with a minuscule staff of six, the foundation picked the best organization for a given disease and issued big blocks of cash, which others carved into grants and projects. But Gates was also looking to contribute in "clever ways," as he said, "so that it's not just writing checks."
Those munificent checks bulked up global health research capacity. Next, Gates gave it direction. In 2003, he handed down an agenda at the World Economic Forum in Davos, Switzerland, in the form of Grand Challenges that identified the 14 most critical scientific obstacles to global health. Gates drew inspiration from David Hilbert, who, at the dawn of the 20th century, put forth a set of ambitious mathematics problems which he hoped "the leading mathematical spirits of coming generations" might strive to solve.
Gates' Grand Challenges dangled nearly half a billion dollars before researchers. Further enhancing the engine of innovation — and ruffling feathers in the research community — the Gates Foundation required applicants to specify milestones, timelines, and deliverables. "In no other grant," said Nobel laureate David Baltimore, who got one, "do you so precisely lay out what you expect to happen."
Gates expected breakthroughs as he handed out 43 such grants in 2005. He had practically engineered a new stage in the evolution of scientific progress, assembling the best minds in science, equipped with technology of unprecedented power, and working toward starkly-defined objectives on a schedule.
But the breakthroughs are stubbornly failing to appear. More recently, a worried Gates has hedged his bets, not only against his own Grand Challenge projects but against how science has been conducted in health research for much of the last century. Among Gates' first tasks in his new job will be sorting through grant applications for his new Grand Challenges Explorations, a search for completely new ideas in global health.
In an invitation/indictment recently appearing in the New England Journal of Medicine, the foundation faulted the research establishment for its "unchallenged dogma" and "traditional thinking," noting the failed AIDS vaccines and timid research in AIDS, malaria, and tuberculosis that has produced only "incremental innovation."
The Explorations reflect Gates' decade-long, top-to-bottom reform of global health. Gates has now bored down practically to the lab bench as, simultaneously, he arrives to take a direct hand at his foundation. He's squeezing the elements of innovation together, trying to generate and capture "transformative innovation" on a remarkable scale that recalls the discovery of vaccination itself.
In part, the Explorations are a kind of Challenges 2.0. Like do-overs, the Explorations topics re-issue a subset of the original Grand Challenges — curing AIDS, for example. All four topics relate to infectious diseases, the central front in global health, and originally believed the softest target for rapid progress when the Grand Challenges were announced in 2003.
But there's a new twist. Finding progress lacking, the Explorations cast a vote of no-confidence in "anointed experts." The foundation now wishes to hear from engineers and physicists who it believes "could have brilliant insights into a difficult biomedical problem" where biologists have not. (Biology has actually been crawling with physicists since the end of the Cold War; their methods had taken over long before.) Most radically, the Explorations application process will dispense with a cornerstone of the scientific enterprise, peer review, suspected of killing truly novel ideas.
Gates is casting about for reasons why science, bristling with 21st century technology, isn't working — and fast. But as the deep-cutting critique of the Explorations show, he is running out of reasons other than problems with the way we do science. Amid a seeming profusion of breakthroughs, the biggest obstacles are hardly budging. Gates, whose first love is science, is almost the only one who seems to have noticed something wrong, that the old ways are exhausted. Humanity's top single-combat warrior is now contending against nature and the methods we've used to subdue it.
In constructing a more effective paradigm, Gates will be dusting off some things he learned at Microsoft. One is Internet "crowdsourcing," an open call for ideas. Another is the venture capital model of funding lots of small, long-shot projects in hopes that a few will survive to become huge successes. As when he launched Microsoft's rise to world dominance by taking on a lumbering IBM, he's now tackling large institutions and their bureaucracies. Innovation lives, the foundation believes, "in the minds of people who could never navigate their way through a grant application for the National Institutes of Health." NIH, the largest funder of health research, famously declined to fund development of the DNA sequencer, arguably the most transformative technology of all ages, saying it was impossible.
Fil Randazzo of the Gates Foundation recently spoke of the Explorations as "democratizing" science, meaning there were grant opportunities for researchers who are not bigwigs running big labs. This goes to the heart of the new Gates push, and it is like inciting a revolt among the junior officers. At Microsoft, Gates was always very attentive to feedback at all levels. When Microsoft Research was blindsided by the Internet, for instance, it was the junior officers who really got the company back on track.
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