Over a decade there were hundreds of such technical challenges. They related to how the vaccine would be created, handled, stored, transported, and delivered, at what temperature, in what material, in compliance with which regulations, and so on. And still there are challenges. How will such a vaccine, once manufactured, actually get to Africa and into the infants and children under five years old, the group that needs it most?
Skepticism remained, but each technical achievement became a foothold on Mount Improbable, bringing its glittering peak more clearly into view. Hoffman had seen the summit in his mind’s eye; now he had to drag and cajole the whole climbing team that straggled behind him.
The skepticism was not entirely unwarranted. Hoffman’s assault on the malaria parasite was neither obvious, at first, nor practical. It was fraught with hardship and with hurdles so steep as to be considered unimaginable, and if imagined, then so difficult, complex, expensive, and tedious as to be
unacceptable. As Hoffman along with several colleagues wrote in the journal
Human Vaccines
, the initial insight “was accompanied by an equally universal consensus that it was inconceivable to consider developing an attenuated
P. falciparum s
porozoite vaccine . . . not due to concern about the potential safety. . . . Rather, it was believed to be impossible to manufacture and administer adequate quantities of aseptic, purified, well-characterized, stable
P. falciparum
sporozoites that met regulatory and cost of goods requirements.”
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The doubters were simply holding to conventional wisdom. But for Hoffman, conventional wisdom prevailed only until weighed against the alternative: the disaster of death and destruction inherent in maintaining the status quo. Hoffman insisted, repeatedly, that his vaccine be judged that way: not on its own, but in comparison to the alternatives.
Many said the beginning of Hoffman’s Phase I clinical trial marked a critical turning point. One tropical disease expert, Michael Good, the director of the Queensland Institute of Medical Research, called the trial a “watershed event” and went on to say it was “the culmination of a remarkable translational research effort by Sanaria.” Many had believed the vaccine would not be able to meet the FDA’s rigorous requirements for safety, sterility, purity, potency, and reproducibility, but Sanaria, said former president of Merck Vaccines, Adel Mahmoud, had “been able to systematically overcome obstacle after obstacle.” Myron Levine from the University of Maryland explained that previous research
had never been translated into vaccine development “because the task was considered to be impossible.”
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These comments underscored a principal ingredient of Hoffman’s success. “Remarkable translational research effort” is scientific jargon for relentless entrepreneurship. The classic hallmark of entrepreneurship is a willingness and ability to adjust, evolve, and adapt, along the lines of Darwin’s explanation of evolution: It is not the smartest or the fastest or even the strongest that survive, but those most able to adapt.
Hoffman reminds me of one of those robotic floor sweepers or battery-operated kid’s toys that, when running into a wall, simply careens off into another direction. There’s no sign of it being worse for the wear, no matter how many times it bounces back, and eventually it has covered the entire floor.
Hoffman combines imagination and entrepreneurship with leadership, inspiration, calculation, and strategy, and especially with what the historian Richard Neustadt said characterized effective U.S. presidents, the power to persuade. Neustadt explained that the power to persuade “is more than charm or reasoned argument”; it is enabling others to see why it is in their self-interest to act in a particular way.
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Just as science, entrepreneurship, and philanthropy evolved, so, too, had Steve Hoffman—from one man with a vision to the leader of an enterprise that has attracted diverse and idealistic talent from around the world as well as funding and the increasing respect of the scientific establishment.
Hoffman’s entire enterprise was built on a slender but tantalizing experiment: In the 1990s, Hoffman and thirteen volunteers, testing Ruth Nussenzweig’s 1967 work, allowed themselves to be bitten by irradiated, weakened mosquitoes about 1,000 times to simulate a natural immunity. When later “challenged” by being exposed to and bitten by regular infected mosquitoes, thirteen of the fourteen were protected from malaria infection. There had been no injections, no lab-created formula or vaccine, only this crude compression and mimicry of nature’s own methodology. From this one set of results, from a sample size smaller than a Little League team, and an experiment tried once and never repeated, Hoffman parlayed his power to persuade into tens of millions of dollars, international attention, and ultimately FDA approval for trials.
Hoffman committed himself not just to science but to leadership in a way that embodied the prescription of Warren Bennis, University of Southern California professor of business administration, founding chairman of USC’s Leadership Institute, and author of one of the most influential leadership books of all time,
On Becoming a Leader
:
Limits, constraints and reduced expectations are the conventional prescriptions for our time. True leaders, however, are able to see beyond an anemic zeitgeist in order to sense opportunities that can employ and house a multitude.
Optimists have a sixth sense for possibilities that realists can’t or won’t see. That gives the optimist the ability to
“define reality” for others in a compelling way—which is the first task of a leader, as the author Max Dupree has observed. This is not sentimentalism: It is the essence of creative pragmatism. It is good because it works.
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For Hoffman this has been a way of thinking and a way of being more influential than any breakthrough or “Eureka moment” in the traditional sense. Hoffman didn’t have a strategy, or a formula to be replicated. Instead he had a mind-set. He came upon the vaccine the way Sherlock Holmes came upon the solution to a mystery: “When you have eliminated the impossible, whatever remains, however improbable, must be the truth.” It would be hard to have a vaccine more improbable than Sanaria’s, but it is the improbable that Hoffman is on his way to proving true.
Although it will be years before we know the final results of Sanaria’s clinical trials with certainty, and the ultimate success or failure in overcoming all of the other technical, logistical, political, and economic hurdles to eradicating malaria will remain uncertain for even longer, we at least know more about the ingredients of breakthrough thinking that bring one to the pinnacle of such success. Not everyone who makes it to the base camp of Mt. Everest makes it the rest of the way to the top. But just getting to the base camp is a Herculean task that separates the very few from the very many rest of us. Knowing how they got that far is no guarantee that one can go the whole way, but it’s not a bad place to start.
Hoffman is far from alone there. Rip Ballou, David Lanar, Pedro Alonso, Victoria Hale, and Peter Hotez have all journeyed heroically. At times they’ve collaborated and at times they’ve competed, but from each other’s successes and failures they have always learned. As a result they have not only advanced their own agendas but also the field of global health, creating hope and inspiring others to tackle problems that affect the most vulnerable and voiceless among us.
WHAT WE SEEK TO KNOW
In May 2010, the United Nations hosted a special photographic exhibit called “Malaria: Blood, Sweat and Tears.”
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The photos were taken in Cambodia, Uganda, and Nigeria. They show people who either have the disease or are engaged in fighting malaria in some way—as a community health worker, a guard at a bed-net warehouse, or a pharmacist. Each picture is compelling on its own, but when you consider the group of photos as a whole, and examine common features, you gain a better understanding of what these African people must endure, and that is what makes this photographer’s effort to bear witness so powerful.
I recognized something in one of the women in the photos. She is attractive, perhaps in her late twenties, with jet black hair and high cheek bones shining in the sun. She is wearing a colorful, flowered blouse and carrying her feverish son, with a green towel draped around his shoulders.
They are outside, with one of the lush green hillsides of Cambodia behind them, just slightly blurred.
From the way her body is angled it looks as though she may be balancing in the back of a truck. Her son’s chin is tucked between her left arm and breast, and her strong left hand presses against his back to steady him as they race toward their destination. His lower jaw is pulled slightly to the left, as if his teeth are chattering from severe chills. His eyelids are heavy, almost closed. But not her eyes. In fact, her eyes burn fiercely, not with fever but with frightened determination.
I’ve never met this woman, but I recognize her because I can see from her urgency and selflessness that she is every mother I’ve ever known. Her name is Pheap Sung. She told the photographer that, “He was sick for three days, had a very high fever. I would have sought help at a private clinic, but I did not have the money. The free clinic is a long way, but I decided I had to take him. I thought he might have malaria.”
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I doubt it would have made any difference if the clinic had been five times as far. There is no such thing as unreasonable when it comes to a mother doing what is necessary for her child. There is no such thing as too far, too much, too expensive, or too complicated. The look on her face was a plea, a look that could go right through the camera’s lens all the way across the globe to Steve Hoffman or Rip Ballou or Jay Keasling or Victoria Hale, a plea to not stop at the conventional response, to not be deterred by the unreasonable, to not accept that good is good enough, to not succumb to a failure of imagination.
The 3,000 African kids who die every day from malaria die quietly and invisibly. That’s because they die routinely, year in and year out, in numbers too large to fathom. They die in the pages of medical journals, not in our living rooms on high-definition TV. Unlike a child buried in the rubble after Haiti’s earthquake, they don’t reach the threshold for Anderson Cooper or the 82nd Airborne, or for benefit rock concerts on MTV.
This tension between the immediate and the long-term, between the personal and the abstract, is always with us. It exists in every effort to create meaningful change. The drama of tragedy always prevails over the numbing of statistics. Saving 8 million lives over ten years might get a headline—on a slow news day. The improbable rescue of one child a day from a collapsed building in Port au Prince can lead the news for weeks.
The consequence, while understandable, is a spectacular failure of imagination. When we focus on the one rather than the many, on the symptom rather than the cause, on what we can accomplish on our own rather than on what needs to be accomplished by the broader community, we neglect our greatest opportunities to do the greatest good. It is equivalent to suffering a massive stroke that leaves one seeing only what is in our direct line of sight, with no peripheral vision or sense of relationship to the larger, surrounding world.
There is no recourse to such failure of imagination but to recognize it, confront it, and struggle to overcome it as one might a crippling stutter.
It would be nice if there were a more concrete and guaranteed prescription, perhaps a handy checklist to tick through. But overcoming failures of imagination has less to do with following procedure or tapping external resources than it has to do with looking deeply and expansively within. It requires each of us to intentionally challenge our own imagination, questioning whether we have engaged it to the fullest, and especially pushing to contemplate, and react to, not only what we see but also to what we do not see.
A few years ago, the commencement speaker at a college graduation made exactly this point. The speaker, Ophelia Dahl, cofounder of Partners in Health (PIH) and daughter of the children’s book author Roald Dahl, quoted Adam Hochschild, who wrote about the importance of “drawing connections between the near and the distant.” Dahl, speaking to the women in the class of 2006 at Wellesley College, went on to explain one of the ingredients most essential to fighting for whatever might be their cause:
Linking our own lives and fates with those we can’t see will, I believe, be the key to a decent and shared future. . . .
Imagination will allow you to make the link between the near of your lives with the distant others and will lead us to realize the plethora of connections between us and the rest of the world, between our lives and that of a Haitian peasant, between us and that of a homeless drug addict, between us and those living without access to clean water or vaccinations or education, and this will surely lead to ways in which
you can influence others and perhaps improve the world along the way.
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Dahl said that being the daughter of writer Roald Dahl meant learning a lot about imagination at an early age. She implied that it had served her well in helping to envision and create Partners in Health. After all, PIH had succeeded where so many others had failed precisely because of a leap of imagination. The leap was not that highly educated doctors in Boston would volunteer to provide health care to Haitians in Haiti—though it would be fair to call that a stretch in its own right—but rather that with the support of partners from Boston, Haitians could create and deliver their own health care.
That
is where imagination really triumphed.
The photos at the UN exhibition satisfied Ophelia Dahl’s challenge to draw connections and link “our own lives and fates with those we can’t see.” I recognized Pheap Sung because it was in her face that I also finally met and recognized the mother of Alima, the young Ethiopian schoolgirl I’d befriended, whose photo still graces my bookshelf, who died of cerebral malaria before reaching the age of fourteen, and who should not have. The terror, love, and determination in the eyes of Alima’s mother could not have been much different from what I saw in the eyes of Pheap Sung.