The Imaginations of Unreasonable Men

by Bill Shore

  Each of these efforts is very different from the others, and yet there is a common thread. What they all share is the attempt to redress the shortcomings of the philanthropic marketplace—the fact that philanthropy typically is not responsive to performance in the same way that capital markets are. Other mechanisms must be developed if nonprofits are to be responsive, and so, as Gates said, we must “stretch the reach of market forces” to address social needs.

  Not every nonprofit needs to concern itself with transforming into an MDO. Many small, local efforts to expand a cultural institution, to promote better environmental practices, or to support neighbors in need could well thrive on charitable support alone. But when it comes to solving complex national and international problems, addressing root causes and not just symptoms, then some alignment with market forces designed to attract more capital is likely to be a necessity.

  VENTURE CAPITAL FOR VACCINATIONS

  To create the malaria vaccine that has long eluded tropical disease specialists, it is not enough to be an expert in infectious disease, parisitology, molecular biology, and genetic engineering, or even to have assembled the best talent in each of those fields. Nor is it enough to have access to the best laboratory and research equipment. Medical knowledge and scientific achievement represent just one aspect of what is needed.

  At an initial cost of $400 million to $500 million to bring a vaccine from laboratory discovery through clinical trials and production, vaccine development is big business. As such, it requires—in addition to scientific knowledge—expertise in corporate finance, venture capital, IPOs, engineering and manufacturing, and supply-chain management. The physicians and researchers who care about vaccines for neglected diseases and drive their development almost never have training in those disciplines. Steve Hoffman is no exception. That is what brought him, before his Gates funding came through, to the Madison Avenue office of legendary investor and philanthropist Ray Chambers on a sunny spring morning in New York City. That, and the fact that by December 2009 he was expecting to run out of money.

  Ray Chambers had made his fortune at Wesray Capital, the New York City firm where he had masterminded the leveraged buy-outs of Gibson Greeting Card and Avis Rent-A-Car in the early 1980s. He had then turned his attention to philanthropy, both in his hometown of Newark and around the world. He had a penchant for investing in for-profit activities that had a social impact, precisely because they were more sustainable as for-profits.

  It was a big week for Steve Hoffman. That night he expected to see his colleague, malaria researcher Pedro Alonso, who was in the United States for a visit from his post in Barcelona. Alonso was then the lead investigator for the clinical trials on the RTS,S vaccine. The results of the Mozambique trials were considered promising, although almost everyone in the field found them to be preliminary, at best. Nevertheless, it was the hot prospect, generating press and buzz and dollars.

  Hoffman had known Alonso for a long time, and it was clear he respected Alonso’s ability to command so much attention and support. “He’s a great medical and scientific entrepreneur,” Hoffman told me. “But I think what Pedro really wants is to test our vaccine. He knows RTS,S is a first-generation vaccine that is only partially effective. So when people ask what I think about their trials and the vaccine clinics they are setting up with the $105 million grant from Gates, I say, it’s great, because those clinics will be there for others to use later.”

  Ray Chambers, immaculate, as always, in a black suit, sat at attention, put his hands together, and listened carefully as Hoffman told him about his background in the navy and explained how he’d moved to Indonesia to work at the navy’s research lab in Jakarta. “After having the experience that many tropical disease doctors have, of having many children die in my arms, I decided to focus on development of a vaccine,” Hoffman told him.

  Hoffman described his vaccine work and spoke of being recruited by Craig Venter to work at Celera, which he thought would be of interest to Chambers. The fact that Steve had been part of the ambitious effort to map the human genome caught Ray’s attention. The discussion shifted from science to business as Hoffman explained the advice he had received to make Sanaria a for-profit enterprise. He spelled out his strategy to develop a first-world vaccine that would be available at a 95 percent discount to the developing world: “There are between 10 and 15 million travelers between the U.S., Europe, and Asia. Even with inept marketing and just a 20 percent penetration rate, a vaccine could bring in three-quarters of a billion dollars,” he said.

  The problem was that the foundations didn’t want to participate in the development of a vaccine for the developed world. They wanted their dollars to be targeted exclusively to a vaccine that would reach the infants in Africa.

  “In the entire history of vaccines there has never been a vaccine used in the developing world that was not a first-world vaccine first,” Hoffman explained. “You can’t go to Africa and meet with prime ministers and their health advisers and say, ‘We have this vaccine that is good enough for you but we’ve never put it into our own children and we’re not going to.’ That just doesn’t fly.”

  Ray Chambers offered lots of advice supporting Steve’s instinct not to give up equity, and therefore control, to a larger biotech VC firm at this early stage. He agreed that the for-profit model was the best way to bring production to scale. “This is a conversation I have with myself every day,” Chambers said. “Can I do more for the world if I keep making more money?”

  It could take $500 million to get the vaccine through licensing, but Hoffman believed that much of that amount could come through private capital, once “proof of principal” was established. He needed $2 million to $6 million in the short term, but even $1 million would be valuable, as he was spending $400,000 a month and bringing in only $200,000. The toxicology studies alone would cost $800,000. The expense resulted largely from the massive amounts of paperwork required to meet FDA documentation requirements.

  As the meeting went on, it became clear that the questions confronting Steve, the unknowns, were not about molecular biology or chemical reactions, but about financing and logistics. He was schooled in the former. The latter would have required a Stanford Business School MBA to master. How to finance a $500 million enterprise? What types of venture capital to take? How much equity to give up? What financing mechanisms were right for the various stages of production and manufacturing? When he did experiments in the lab, he could repeat them if they went bad. With financing decisions, he risked getting locked into an irreversible course, especially when it came to giving up control.

  Ray asked Steve questions about his production plans and the timing of the capital needed. Hoffman said he had enough money for a few more months, but he was determined not to allow short-term needs to compromise his ability to make decisions in the long term, or to let foundation program officers with two years of biotech “experience” decide how his vaccine should be developed.

  Ray passed along advice he’d received from a Buddhist, though it was a Latin proverb—festine lente, “hasten slowly”—and then brought in his chief investment officer, Carla Skadinsky. She had been with him for five years but before that was at Goldman Sachs for twenty years and was at Rockefeller University in between. She suggested several names of potential investors and promised to look at any materials Hoffman would send along.

  Afterward, Hoffman reflected, “Everyone in this field, whether the pharmaceuticals or the foundations, think they know best and want to do it their way, and I guess I do, too, I think I know what’s best, and I’ve come too far to walk away from that now. But it’s never easy. There’s always something, you just have to keep pushing forward.”

  On February 14, 2008, United Nations Secretary General Ban Ki-moon appointed Ray Chambers as the UN’s first special envoy for malaria. For the previous eighteen months, Ray had been the cochairman of an organization he founded called Malaria No More, which worked to raise funds and create awareness to combat t
he disease.

  I had met Ray in 1996, when he was involved in organizing what was known as the Presidents’ Summit with retired general Colin Powell. That was in the years before Powell became secretary of state for President George W. Bush, and the summit convened for three days in Philadelphia in the spring of 1996. Along with all of the living presidents, representatives of businesses and organizations announced commitments to get necessary resources to America’s poorest kids. It led to the creation of “America’s Promise,” a foundation supporting “Five Promises” to youth to help them succeed.

  Ray had been devoting himself to mobilizing commitments on behalf of kids for years, ever since leaving the leveraged buy-out industry that he had helped to create. As his passions evolved, he had already begun to support mentoring—the focus of one of the Five Promises—seeing it as the kind of silver bullet that could change children’s lives. In that spirit, he had taken up the idea of a summit of all of the living presidents and run with it. His primary purpose was to call attention to the resources children needed.

  As his interests turned from revitalizing Newark to a more national and global outlook, he had asked if I would introduce him to Jeffrey Sachs, the Columbia University professor, author, and anti-poverty advocate. That led to Ray’s embrace of the Millennium Development goals and the creation of yet another organization, called Millennium Promise. The goals are a set of eight globally endorsed objectives—such as providing universal primary education and halting the spread of HIV/AIDS—intended to address the multiple causes of extreme poverty, and Millennium Promise mobilizes both public and private partners to achieve them. Ray traveled to Africa and saw children dying of malaria, and his commitment to doing something about the disease became irreversible.

  Ray is particularly good at bootstrapping his way forward, identifying someone whose support will bring further credibility, and then parlaying a small achievement into larger ones.

  This role of UN envoy is his most public to date. Before that appointment, Ray had always worked behind the scenes. But unlike most philanthropists, he understands that big change and big results don’t come cheap. He is willing to pay to have the best people in any field be a part of what he is doing. “Belts and suspenders, Billy, belts and suspenders,” he used to rasp to me over the phone as a way of saying “spare no expense.” Ray has not only devoted a substantial portion of his personal fortune to philanthropy but personally works far harder than he has to, spending long days learning from experts and pursuing and cajoling others with a proven ability to accomplish things to join in his efforts.

  Ray’s good intentions have at times been undermined by the seduction of a too simple solution—such as increased distribution of bed nets, which, while vital to saving lives, can’t by itself end malaria. But as a man of almost unlimited imagination, he is attracted to the challenge of solving big, complex problems that intimidate others, and he brings a vision and expansive sense of what is possible to those tasks that others often lack.

  “AT WHAT POINT WILL WE TREAT IMMUNIZATION THE WAY WE TREAT UTILITIES?”

  In October 2007, the New York Times published a story in its science section describing how scientists fighting malaria were split over the best strategy for distributing insecticide-treated bed nets to help prevent the disease. The article unintentionally said as much about the state of the nonprofit sector today as it did about science, highlighting an ongoing debate about how the tools and assets of government, philanthropy, and the marketplace might complement each other to solve social problems. The Times reported:Recently, Dr. Arata Kochi, the blunt new director of the World Health Organization’s malaria program, declared that . . . the only way to get the nets to poor people . . . is to hand out millions free.

  In doing so, Dr. Kochi turned his back on an alternative long favored by the Clinton and Bush administrations—distribution by so-called social marketing, in which mosquito nets are sold through local shops at low, subsidized prices . . . with donors underwriting the losses and paying consultants to come up with brand names and advertise the nets.3

  I raised the issue the day after the article appeared during dinner in Barcelona with Pedro Alonso, one of the world’s largest and most grateful beneficiaries of American philanthropy. Tropical medicine’s equivalent of a rags-to-riches story, Alonso was to join Bill Gates in Seattle the following week to announce another milestone in saving the lives of the world’s poorest children.

  Like Hoffman, Alonso is an alumnus of the London School of Hygiene and Tropical Medicine. His primary partner in fighting malaria has been his wife, Clara, whom he met in school. They have three children. Alonso views malaria as both a cause and consequence of poverty in the most undeveloped regions of the world. Based at the University of Barcelona, where he has taught since 1992, he also leads Barcelona’s Center for International Health Research, where his efforts are part of every discussion about the need for a vaccine.

  Under the best of circumstances, vaccine development takes extraordinary amounts of money, time, patience, commitment, and luck. The few who have succeeded are like Olympic gold medal athletes who graduated summa cum laude and also happened to win the Powerball lottery. Alonso is optimistic but also realistic. Writing in 2006, he explained:One of the greatest problems with malaria, which accounts for the extreme difficulty of developing a vaccine, is that we do not yet understand how individuals develop immunity against the disease. Since . . . the end of the 19th century, it has been known that adults who survive malaria infection acquire a highly effective immunity, but the mechanisms involved and how they operate remain unknown, as is the role of indirect protective measures. . . . Thus, the only way to assess whether a vaccine is effective is by conducting clinical trials in natural conditions.4

  In 1996 Alonso built a sophisticated medical facility, the Manhica Health Research Center, in one of the most malaria-infested areas of Mozambique for this purpose. Mozambicans have an average life expectancy of just forty-eight, and there are only 800 doctors for a population of 18.9 million.5

  Alonso is credited with putting Barcelona on the map as an international center for global health research. I expected his office to be something more than the nondescript fourth-floor walkup pointed out by a bored shop employee in the lobby of a building near the fashionable shopping district of Barcelona. Nevertheless, I went up for our 4:30 appointment, and an assistant told me Alonso was in a meeting. I waited, but 4:30 came and went, as did 5:00 and 5:15. Finally he rushed into the room through a nearby door, shook my hand, said, “Sorry, I’m in a conference,” and disappeared again.

  The office looked like that of many mission-driven nonprofits, with walls sporting maps of Africa and photos of children at medical clinics in small villages. It was quiet, with most of the staff staring at computer screens. At one point Alonso came out again to take a call on his cellphone, saying only, “Sí, sí, sí, sí, Gates, sí, sí, sí, sí,” before returning behind closed doors.

  When he finally emerged an hour past our scheduled time, I guessed, accurately, that he was late for his next appointment. He asked how long I was in Barcelona and whether we might have a drink or dinner. A quick call to his wife confirmed that she could join us. He returned, said, “Well then, it’s all arranged. See you tonight.” With that, Alonso turned and the encounter was over.

  Despite the delays, I found Alonso impossible not to like. Intense but relaxed, he resembles a more sober version of Dan Ackroyd, with a young Ackroyd’s dark hair and the middle-aged Ackroyd’s girth. He speaks excellent, authoritative English in a deep resonant voice that could make him an anchorman on an English-language news network.

  An exchange program with Boston University had brought Alonso and his wife to the United States and to Boston City Hospital, where they had found mentors who steered them toward international health. Clara specializes in malaria control in pregnant women. When asked how they both ended up working on malaria, Alonso told me: “The real question is how can you not work on mala
ria? If you are interested in African health and poverty, everything depends on addressing malaria.”

  Their decades of travel to Africa, the research facilities they built, and the people they trained in Tanzania, Mozambique, and the Gambia had by 2003 created an infrastructure in African villages that the Gates Foundation found appealing and rare. Speaking of Bill and Melinda Gates, Alonso said, “They got it. Gates himself got it. They got that vaccines in Africa are not just about science and developing the product. The question is always what do you have on the ground? How do you test it? What about infrastructure?”

  The commitment of the Gates Foundation to vaccine development for malaria has included hundreds of millions of dollars to support numerous competing vaccine development efforts. More than $107 million had been initially earmarked for Alonso’s work. Hundreds of millions more dollars have gone into refining RTS,S. As lead investigator of the clinical trials for RTS,S, Pedro Alonso quickly became the public face of malaria vaccine development.

  The formidable hurdles to vaccine development usually cause the hurdlers to become fierce competitors, but Alonso seems to take a longer and more generous view. “RTS,S will likely be the first malaria vaccine to get approved,” he told me, “but it won’t be the final vaccine. They will continue to evolve and develop, and RTS,S will be a contributor to it. Actually the wild idea of Steve Hoffman may make the best vaccine, but he still has challenges to overcome.”