The Imaginations of Unreasonable Men (7 page)

Nussenzweig’s approach became known as an “attenuated sporozoite vaccine.” Sporozoite literally means animal seed and is the name for the cell form that infects a host, such as the parasite cells that eventually leave the mosquito’s salivary gland and enters a human’s liver.

The bottom line, as Hoffman explained, “is that it has always been considered clinically and logistically impractical to immunize large numbers of susceptible persons with the irradiated sporozoite vaccine, because the sporozoites must be delivered alive, either by the bite of the infected mosquito, or potentially by intravenous injection, as is done with mice.” The challenge, then, is first to make an appropriately irradiated parasite, and then to keep it frisky until it can be injected into the target population. All vaccines can be weakened by time and temperature variations. Many a parasite could perish en route from a laboratory in Maryland to a field station in Africa.

It is in this space between impractical and impossible that Hoffman has decided to bet the ranch.

Sanaria employed twenty-seven people when I first toured the facility. As we made our way through the office, every section was compartmentalized. There were double-door safeguard systems so that one door wouldn’t open until the other had been closed, to ensure that nothing could escape. A keypad code was required to enter sensitive areas, and in the chamber between the two doors was the ubiquitous blue-light
bug zapper. Protective gear was required, but Hoffman gave me the grand tour. I saw the room where the technicians peered into microscopes to dissect the salivary glands, the room where the mosquitoes were irradiated, and the room where the cultures were bred.

And then as Hoffman speculated about the potential of the vaccine, he got excited again, as he had been on the phone when I first walked in. He told me that one technician working for one hour could dissect a hundred mosquitoes, and that eight technicians working for four hours could produce enough sporozoites to fill the initial clinical trials. Four technicians working for a year could provide enough for the entire military market, and ninety technicians could produce enough for Africa.

He also explained that, to satisfy the FDA, you have to be able to make four guarantees. He summed them up this way, explaining how Sanaria is meeting each requirement:

I asked why everyone had been wrong about how many sporozoites could be extracted. “No one actually bothered to find out, including me,” he said. “I was just on the phone yesterday with Ahvie Herskowitz from the Institute for OneWorld Health. He asked me how in the world we kept getting better and better numbers. I said ‘Avi, remember the joke about how to get to Carnegie Hall? Practice, practice, practice,’” and at this he threw back his head and laughed.

As we were leaving the lab, I asked Hoffman what could stop him from succeeding. He perked up, as if in anticipation of his own answer: “Nothing! Money, of course, is always an issue. And the security of this lab. If some mosquitoes got out and a man across the street came down with malaria that would be it. I’d be dead. Finished. Just meeting the regulatory requirements to build this place was amazing.”

No one person stood out as the obvious and logical choice around which to tell this story. In fact, it was quite the opposite. There were many amazing possibilities from which to choose.

The field of global health is home to Nobel Prize- winning scientists, conquerors of disease, revered humanitarians, and unfathomably wealthy philanthropists. It boasts entrepreneurs like Craig Venter, who won the race to map the human genome, and Victoria Hale, the former Food and Drug Administration official who created the first nonprofit
pharmaceutical in order to address neglected diseases. There are leaders of large institutions like the National Institutes of Health, or the Walter Reed Army Hospital, and physicians who have opened small clinics in the most remote jungles and deserts, such as Rick Hodes, who moved to Ethiopia on behalf of the American Jewish Joint Distribution Committee and adopted more than a dozen children in need of complicated surgeries.

But I wasn’t searching for the perfect choice. Perfection eludes most of us. Imperfection is more representative. It is certainly more universal.

I sought out Steve Hoffman after becoming intrigued by the way others referred to him, particularly within the tightly knit group of doctors, research scientists, and military and diplomatic officials known as “the malaria community.” It was not what they said so much as what they left unsaid. His name invariably left an invisible but palpable tension in the air, like one of those high-energy transmission towers that can be valuable or dangerous, depending upon your point of view.

Without knowing anything else about him, I could sense that Hoffman was a complicated man, someone who challenged others’ comfort zones and vigorously protected his own, whose ideas were too radical to simply accept, but grounded in too much experience to casually dismiss.

Fifty-six years old when we first met, trim and muscular, Hoffman had the guarded and intense demeanor of a competitor watching the game clock run down before his victory
is secured. He is skilled at political positioning but lacks the politician’s gift for small talk aimed at surfacing any patch of common ground that can serve as the basis for a relationship.

He first agreed to see me after receiving a brief e-mail that I’d sent without benefit of introduction from any third party. By coincidence, we’d both graduated from the University of Pennsylvania, and his lab was in my neighborhood. Other than that we had little in common.

Once we met, though, I began to feel some vague but unarticulated kinship with Hoffman, notwithstanding the fact that our personalities were very different. We had both made the transition from long government careers to long-shot start-up enterprises. We’d both worked in institutions—the navy and the U.S. Senate—that afforded resources, prestige, and access to almost anyone or anything one might need. We’d both traded that away for the pressures and headaches, but most of all the freedom, that comes with a start-up enterprise housed in crowded, makeshift offices and financed paycheck to paycheck.

I couldn’t walk through his crowded and cluttered lab without thinking of Share Our Strength’s first days in the sub-basement of a Capitol Hill townhouse that had been converted from an electroshock therapist’s facility, complete with sound-muffling egg cartons glued to the walls. I remembered that feeling of having the kernel of a half-baked idea that the rest of the world had yet to hear about or understand, but that, once developed, tested, and refined, might prove to inspire and mobilize others.

I certainly didn’t put Hoffman’s odyssey at the center of this story because I had the foresight to be sure he would succeed. Indeed, the odds of him reaching his goal are long, if not forbidding. We won’t know the full measure of Hoffman’s success or failure, or that of any of his competitors, until the passage of time has had its way. Many years will be required for conducting and assessing clinical trials. Even if his vaccine makes it through those hurdles and a successful vaccine is put into wide use, the malaria parasite could evolve to escape defeat, as it always has in the past. There are an infinite number of variables, ranging from climate change to African infrastructure, that may have more to do with whether the vaccine works on the ground than anything Hoffman does or doesn’t do in the lab. And there are other possible breakthroughs on the horizon that could blow Hoffman’s ideas out of the water. Scientific discovery, by its very nature, stands still for no man.

But the trajectory of Hoffman’s life and career so clearly parallels and illuminates our society’s changing approach to solving social problems. He began as a doctor doing what doctors do, helping one person at a time. But as he became interested in tropical diseases like dengue fever and malaria, he came to see that the scale of the problem and the enormous number of people affected was far greater than what any one doctor could handle. It was greater even than what all the doctors in the field of tropical medicine could handle. And the problems were not just medical, they were economic and political.

When he realized it would take the resources of government to solve the problems he cared about on the massive scale on which they existed, he joined the U.S. Navy, which had the best facilities at the time, and eventually led its malaria vaccine development efforts. The goal was not just delivering good medical care, but scaling up that care so that others would have access to it. Lacking an economic market for doing so, Hoffman found a political market in the form of government. For twenty-one years, the U.S. Navy and Army offered the tools necessary to advance vaccine development.

But after a certain point, he also came to see the limitations of what could be done via government. He then became the classic entrepreneur, resigning from government, setting out into the private sector, and starting a company—a biotech company. He chose to operate at a new intersection of philanthropy and entrepreneurship that would permit him to take risks and try out innovative ideas in order to solve problems that there were no economic or political markets for solving.

The accelerated and massive investment in global health and in the eradication of diseases affecting the poorest people on the planet has been a powerful generator of ideas and strategies in the field of health care. But, like the space race of the
twentieth century, it has applications that reach beyond its own immediate field to impact other social challenges. Outside of government, the work of global health is conducted through nonprofit organizations. Generations of social-change agents in every field will be shaped by what is happening in global health today. And the catalyst for investing in global health has been the Bill and Melinda Gates Foundation. It is the modern day NASA of the global health field.

In the 1960s and 1970s, NASA-led space programs, from Mercury through Apollo, yielded thousands of spin-offs, adaptations, and alternative uses that have impacted every aspect of life. They range from kidney dialysis machines that were derived from processes to remove toxic waste to smoke detectors first used in Skylab that are now common in almost every home, from the fabrics of fire fighters’ uniforms to ear thermometers, from solar energy panels to weather forecasting and water treatment systems for developing nations. Few Americans have a direct connection to the men and women who have gone into space or the team that supported them. But no American was left untouched by the literally thousands of applications of the technologies created for space. The goals of the space race pushed the edge of the envelope of innovation and inspired some of the best minds of a generation to achieve things that reached far beyond the parameters of the space race itself.

President Kennedy was able to foresee the impact of the space race when he announced the challenge at Rice University on September 13, 1962. What he said can be instructive
as we face a new kind of challenge—a challenge to improve life on earth:

Thousands of scientists, researchers, manufacturers, computer programmers and contractors from all around the world became part of the NASA effort in the same way that the goals set by the Gates Foundation have mobilized thousands of doctors, scientists, biotech companies, labs, and universities, bringing new talent into the effort at an unprecedented pace. Global health spending will result in new medicines, vaccines, cures, and treatments for diseases and health-care practices. It has already produced new diagnostic techniques, new kinds of sterilization and purification equipment, new preservation methodologies, and an entirely new field, that of synthetic biology.

But it is also leading to the creation of innovative new financing mechanisms, such as advanced market commitments
and philanthropic collaborations between governments and foundations, and has produced the first nonprofit pharmaceutical. It is even leading to new, clean energy sources.

As the modern-day equivalent of the space race, our global health challenges will transform the nonprofit and philanthropic universe in ways far greater than anything we might have anticipated, changing the way we approach a vast number of social problems.

In June 2004, Hoffman applied for one of the grants that the Bill and Melinda Gates Foundation was making, especially designed for risk-taking projects aimed at making big breakthroughs—like solving the malaria vaccine issue. He did not get it.