The Imaginations of Unreasonable Men (27 page)

Another facet of succeeding as a nonprofit is being competitive economically, that is, delivering your product at a price point—again, Peter Hotez’s “dollar a dose,” or Jay Keasling’s attempt to increase supply through synthetic biology so that life-saving artemisinin becomes affordable to those who need it the most.

Finally, to be effective in solving social problems, whether in hunger, education, the environment, or global health, one must compete to provide the best return on investment from a mission point of view. This requires a willingness to hold oneself accountable for measuring outcomes and communicating what you’ve measured. The business sector does this
through stock price and earnings per share. Hoffman, Alonso, and Keasling will do it through clinical trials. The goal of eradication may seem idealistic, but ultimately, it is measurable, and—as was the case with smallpox—the measurement everyone is aiming for is zero. Getting there may take a long time, but it begins with having the courage of a competitor to set a measurable goal.

Finding solutions that advance the public good takes more than the spirit of a saint, it requires the soul of a competitor. Collaboration is critical to the advancement of most scientific objectives, and progress is always built up in the foundations laid by others. Those at the center of the malaria vaccine development story are no exception, but they also approach their work with the competitive zeal of athletes who work to give themselves every possible edge. They don’t expect first-rate outcomes with second-rate inputs. They resist the reflex to depend on whatever leftover resources are available rather than seeking out the best resources available. They have a personal drive to win, they are undeterred by short-term setbacks, and they believe in the superiority of their own vision and abilities, even when no one else does.

—John Buchan,
Montrose: A History

 

 

 

T
HE THIRD ANNUAL WORLD Malaria Day, celebrated on April 25, 2010, marked a wave of optimism about the progress that had been made in reducing deaths from malaria. “A wind of change has stirred Africa and the world,” declared the executive director of Roll Back Malaria, Professor Awa Marie Coll-Seck. United Nations Special Envoy Ray Chambers, writing in the
Financial Times
about the promise of insecticide-treated bed nets, proclaimed: “Today, we know
we can achieve the goal of universal coverage of nets by the end of this year and near zero deaths from the disease by 2015.”
¹

Such optimism would have been unthinkable on the day five years earlier when I’d first walked into a cramped, makeshift lab in a Rockville, Maryland, strip mall to learn more about that “wild thing Steve Hoffman is doing.” Back then, deaths from malaria were steadily increasing. Bill Gates’s Grand Challenges Exploration Grants had yet to award a single dollar. There was little support for innovation or entrepreneurship in global health, and no such thing as a UN special envoy for Malaria.

The battle against malaria was being waged by a relative handful of obscure experts and specialists in research labs, military hospitals, and schools of public health, just as it had been for more than a hundred years. It was the classic “neglected disease”—not on the radar screen of most of the developed world or receiving much support. There were about seventy different vaccines in development, most underfunded, and none instilling confidence.

Now, less than a decade later, Hoffman was at the beginning of his clinical trials, and GlaxoSmithKline’s researchers were near the end of theirs. Bill and Melinda Gates had declared it the decade of vaccines, and billions of dollars in new funding had been committed. Jay Keasling had contracted with Sanofi-Aventis to mass-produce artemisinin. The Global Fund to Fight AIDS, Tuberculosis and Malaria was reporting the distribution of 108 million bed nets a
year. There had been striking increases in public awareness, political will, and consequently, resources, ranging from the World Bank’s increased financial commitment of $200 million to
Idol Gives Back
, the Emmy Award-winning television show on Fox that engaged celebrities to help raise $45 million for the cause from viewers.

Most important of all, there had been at least some measurable results, particularly from control strategies such as insecticide spraying and bed nets. The number of African households with at least one bed net increased from 17 percent to 31 percent between 2006 and 2008, and 9 of 45 malaria-endemic countries—including Eritrea, Swaziland, Botswana, Equatorial Guinea, and Zambia—had seen a 50 percent drop in cases, thanks to a tenfold increase in funding for malaria control since 2004.
²

Spurred on by such outcomes, other African countries in 2010 were making unprecedented efforts to achieve universal coverage, hoping to cut malaria mortality in half. For example, Congo and Nigeria, which together accounted for 36 percent of the malaria burden, were mounting the largest net-distribution campaigns in the history of malaria control.
³

No one was debating that a sense of optimism had taken hold. Whether such optimism was warranted, however, remained an open and energetically debated question. In 2009, the World Health Organization reported 243 million cases of malaria and 863,000 deaths attributed to the disease.
⁴

As a result, not all global health leaders joined in the celebration. Those with long memories had seen misplaced optimism before, sometimes with devastating consequences. Some saw the danger of becoming a victim of one’s own success looming, especially because so much of the success came from methods like using bed nets, which reinforce a narrower, not a more expansive, approach. Bed-net advocates ignore or dismiss vaccine development as a distant ideal. Vaccine developers have little interest in, and rarely advocate for, investing in medicines, a strategy they see as shortsighted compared to developing a vaccine to prevent infection in the first place. This, along with reports of emerging resistance to artemisinin and the belief that even current efforts lack sufficient breadth and ambition, have combined to produce dissenting voices.

The medical journal
The Lancet
timed its World Malaria Day editorial to emphasize that “malaria control and elimination via prevention and treatment can only go so far. The risk of serious setbacks is ever present. What is still needed is the only tool that has ever truly conquered any infectious disease: an effective and affordable vaccine. And here, the global malaria community has been too complacent.”
⁵

On the Friday before World Malaria Day, the
Wall Street Journal
led with a cautionary tale about the perils facing even the most ambitious vaccine strategies. The front-page story was not about the newly energized global effort to eradicate malaria, but instead about the decades-long struggle to conquer polio and the setbacks that organizations working in the
field of global health, including the Gates Foundation, had encountered in their strategy of massive vaccination campaigns.
⁶
The painful lessons learned may be invaluable to how we think about eradicating not only polio and malaria, but hunger and other persistent challenges as well.

The
Wall Street Journal
article documented new polio outbreaks in a number of African countries—Uganda, Mali, Ghana, Kenya—that had been believed to have stopped the disease. Over the past two decades, $8.2 billion has been spent to kill off polio, with the hope that it would soon be eradicated just as smallpox was in 1979. Bill Gates alone spent $700 million to fight polio. Success seemed close. The number of polio cases in 1988, 350,000, decreased to under 1,000 by the year 2000. But in 2009 new outbreaks brought the total back to 1,600 cases. Once polio was ended in some countries, weak health-care systems, poor sanitation, and malnutrition allowed it to return.

The
Wall Street Journal
, describing it as “one of the most controversial debates in global health,” framed the debate this way: “Is humanity better served by waging wars on individual diseases, like polio? Or is it better to pursue a broader set of health goals simultaneously—improving hygiene, expanding immunizations, providing clean drinking water—that don’t eliminate any one disease, but might improve the overall health of people in developing countries?”
⁷

Big donors usually prefer the “vertical” strategy of fighting individual diseases, and advocates are influenced by the preferences of big donors. When a more “horizontal” strategy is
pursued, focusing on a broader spectrum of health-related issues, the objectives are often less specifically defined. Dead-lines are often nonexistent, since improvements are likely to take many years longer than in vertical-style projects. And yet the horizontal strategies can be just as important as the vertical ones to long-term success. The Gates Foundation and allied organizations, the
Wall Street Journal
said, were devising a revamped plan that would represent a major rethinking of strategy acknowledging “that disease-specific wars can succeed only if they also strengthen the overall health systems in poor countries.”
⁸

It seems an obvious and commonsense insight, but it reverses decades of conventional wisdom that most of the global health community embraced, funded, and acted upon. It also underscores that very different ways of thinking and very different strategies can not only complement each other but be necessary if diseases like malaria and polio are to be drastically reduced or eradicated.

How could Gates and his colleagues have missed this before now? It’s not that they aren’t smart. Resources were not a primary constraint. Gates has an impressive track record of matching his big bank account with big ideas. No one has ever accused Microsoft’s founder of lacking vision or thinking small. But even Gates suffered a failure of imagination when it came to fighting polio. The enormous financial commitment he made to the disease-specific approach must have seemed like a leap of imagination in and of itself, perhaps the bolder course in the either/or choice described
above. But bolder still is the decision to do both, notwithstanding the pressure it creates to generate needed resources, maintain focus, and ensure the ability to measure results. It shows that those fighting diseases as intractable as polio or malaria—or taking on any other task of that size—have to ask whether even their most ambitious efforts lack vision and imagination.

Against the backdrop of the millions of lives threatened by the emerging resistance to artemisinin, and a malaria community energized by new funding to support a wide variety of creative experiments, stands the curious figure of Steve Hoffman.

Doggedly championing what is perhaps the most unconventional approach of all, Hoffman had taken on and refuted every argument—purity, safety, effectiveness, stability, feasibility—for why his vaccine could not work. When he was done, there was nothing left but an immunogen that had demonstrated more than 90 percent effectiveness, and that the FDA had approved for Phase I clinical trials as a vaccine.

Why Hoffman? What propelled him and his idea past literally thousands of others? What has brought him to the brink of success?

As is often the case, the answer lies at the intersection of the man and the moment, a combination of his personal qualities and the trends and the times in which he lives.

Hoffman’s personal qualities can be summarized in three words: imagination, entrepreneurship, and leadership. I’ve never heard Hoffman speak in such terms; he only demonstrates and embodies them. The combination of all three is occasionally seen in business or politics, but rarely in science. In Hoffman’s hands, it has proved a potent formula.

Hoffman’s hard-earned technical successes transformed the perception of his vaccine from preposterous to miraculous. More important, he had the imagination and vision to see each scientific and technological breakthrough not as an end in itself but as the means to a larger end. The time he devoted to science was more than matched by the time he spent coaxing the scientific and philanthropic community up and over Mount Improbable, that Everest-like mountain of skepticism that had prevented them from seeing a potential solution lying long dormant, but nevertheless in front of them all along.

Art instructors urge aspiring artists not to paint what they think they see or what their minds have conditioned them to see, but what they actually see in front of them. Hoffman championed a similar discipline: peeling away preconceived notions about the drawbacks of a vaccine based on live, attenuated parasites and insisting instead on a notion at the heart of all good science—that the vaccine be judged on the evidence and facts. And like Brother Thomas Bezanson, who never hesitated to break a pot that was good but not good enough, Hoffman steadfastly rejected RTS,S, which he’d even had a hand in creating, and any other vaccine
that fell short of the gold standard of nearly 100 percent protection.

The technical barriers to success were not inconsiderable. When the yield of parasites harvested per mosquito was not to scale, Hoffman and his team figured out how to increase it. When the time came to irradiate the mosquitoes so that each one received the same dose of radiation, he figured out how to do that, too. Hoffman’s wife, Kim Lee, had solved issues of purity and sterility. On and on it went, through years of tedious testing, revision, and refinement.