The Imaginations of Unreasonable Men

by Bill Shore

  THE “SPACE RACE” OF THE TWENTY-FIRST CENTURY

  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:We choose to go to the moon in this decade and do the other things, not because they are easy, but because they are hard, because that goal will serve to organize and measure the best of our energies and skills. . . .

  The growth of our science and education will be enriched by new knowledge of our universe and environment, by new techniques of learning and mapping and observation, by new tools and computers for industry, medicine, the home as well as the school. Technical institutions, such as Rice, will reap the harvest of these gains.4

  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.

  CHAPTER 5

  TROPICAL LINEAGE

  A team of researchers in Costa Rica’s Alberto Manuel Brenes Reserve have been searching for plants that might help cure the mosquito-transmitted disease known as malaria. . . .

  During their research, the team collected a total of 50 promising plants. . . . As of now, no other details have been released by the team as to why they think that these species . . . might cure (or help prevent?) malaria.

  —Levi Novey, “Potential Cure for Malaria

  Discovered in Rainforests of Costa Rica,”

  EcoLocalizer, September 18, 2008

  TROPICAL REGIONS ARE PARTICULARLY FERTILE areas for disease because of the many insects that breed and thrive there. Tropical medicine is the most dangerous and least lucrative of all medical practices. Patients live far away in jungles and near swamps. They are poorly educated, have little money for medical bills, no insurance, and barely enough food or water to survive. They are exposed to horrific diseases that often have no cure, and of which most of us have never heard.

  One of them is African trypanosomiasis, also known as sleeping sickness, which infects half a million people annually and kills 50,000. Visceral leishmaniasis, transmitted by sandflies, afflicts 1.5 million every year, giving them skin ulcers and potentially massive tissue destruction, and is 90 percent fatal if untreated. Chagas’ disease infects 16 million to 18 million people annually, mostly in Latin America. The parasite enters through broken skin, and there are often no symptoms for years, yet the disease invades organs and creates severe cardiac problems, claiming some 45,000 lives a year.

  A magnified photo of just one of the parasites that teem within human hosts would deter most Americans from ever applying for a passport.

  THE PRIESTHOOD OF TROPICAL MEDICINE

  As Donald Burke, past president of the American Society for Tropical Medicine and Hygiene, explained at the centennial meeting of the organization in 2003:It is no coincidence that our society was founded at the very moment when the USA first emerged as a global power. . . .

  After the Spanish American War of 1898, the United States suddenly found itself with a string of new possessions that almost circled the globe in the tropics, including Cuba, Puerto Rico, Hawaii, the Philippines, and various island territories in the Pacific Ocean. U.S. military personnel sent to occupy these new tropical possessions were decimated by infectious diseases.1

  Doctors who specialize in tropical medicine went through the same rigors of medical training and accumulated the same amount of medical-school debt as their colleagues who chose pediatrics, oncology, cardiology, or neurology. But when they chose different diseases, they chose different patients. As a result, they gave up the comforts of American medicine and many of its rewards.

  The diseases that plague much of the world are neglected across the entire spectrum of American health care, from medical schools to research hospitals to global pharmaceuticals. Doctors Without Borders reports that of 1,393 new medications introduced into the market between 1975 and 1999, only 13 (or about 1 percent) were for the treatment of tropical diseases.2

  Only 10 percent of global health research is devoted to diseases that account for 90 percent of the global disease burden. Meanwhile, billions of dollars are spent each year on research and development of drugs for ailments that afflict people who can pay, which include conditions such as obesity, baldness, and those associated with aging among Baby Boomer populations.3

  In 2002, Michelle Barry, another past president of the ASTMH, explained one reason why we should be concerned: “In the medical condition of the world’s poorest people we can see the incubators of political and social pathology as well as medical, and as events of the past year have pointed out, the borders of the advanced industrial countries are permeable to all three. Tropical medicine specialists are a kind of distant-early-warning system of public health. We see problems in their early stages.”4 In other words, in a world where global travel is common, those diseases are no longer so far away.

  Tropical medicine is a priesthood of sorts. Passionate true believers prize purity over profit, sometimes even over success. They may be among the last of the idealists. If there is a way to practice medicine and not make money, this is it.

  So, when a renowned leader i
n tropical disease like Steve Hoffman transitions from a lengthy career in government service to launch his own commercial business venture, it can feel, to some, almost like a betrayal. Like going over to the other side. Repudiating the path others have chosen and clung to. Selling out. For-profits are suspect. The pressure of having to make a profit has always prevented pharmaceutical companies and health-care corporations from investing in R&D and clinical trials for drugs unlikely to find a profitable commercial market.

  For-profit or not-for-profit, the odds are stacked against anyone who has enlisted in the battle against malaria. Historically malaria has proven the most difficult to conquer of all tropical diseases. The parasite transmitted by certain species of mosquitoes has proven to be remarkably resilient, mutating, adapting, and eventually growing resistant to every drug that has been designed to attack it. Hoffman himself, describing the challenge of stopping malaria, led one reporter to conclude, “It’s always a good bet to put your money on the parasite.”5

  Those who persist in developing malaria drugs and vaccines are like increasingly desperate homicide detectives on the cold-case squad, obsessed by a serial killer who has managed for years to evade, elude, and outwit them at every turn. Having pursued all the obvious leads and logical clues, they are unwilling to admit defeat, though all that remains are ever more fantastic theories and complicated scenarios. Still stymied after exhausting all of the practical ideas, what’s left are only the impractical ones.

  Sometimes, though, progress creeps along an inch or so at a time. Like good detective work, good science often comes slowly and in small steps after years of persistent, methodical legwork. Chasing down leads, eliminating hypotheses, piecing together facts, and applying instinct and judgment can take time. Good science requires patience, because it requires waiting: for tests, trials, reviews, corroborations, and approvals, and for insight, understanding, and synthesis. For children exposed to malaria, waiting often means dying. Every thirty seconds, a child under five years old dies from malaria, as the clock ticks off months and years. Scientists like Steve Hoffman race each other and race against time.

  Malaria conjures a distant place and another era. One thinks of stifling heat and humidity, fetid swamps, Africa’s thatched-roof huts, nineteenth-century explorers, khakis, medical tents, ceiling fans, bed nets, and, of course, mosquitoes. It is not only an ocean or a century that separates us from malaria. So does air conditioning, urban density, building codes, technology, sophisticated health care, and education. Malaria is about Africa, and as Americans we don’t go much to Africa. We don’t live, study, or travel there. Americans only rarely contract malaria or die from it. Most of us don’t know anyone who ever has.

  The malaria parasite is one of the oldest and most persistent of all diseases, and throughout the course of human history, the battle against it has been a losing one, each advance met and outwitted by the parasite’s ability to mutate and resist drug treatment. No more epic struggle between life and death has ever been waged on planet earth.

  It’s not surprising that Steve Hoffman, with his sterling pedigree and a track record of having made good use of it, chose the fight against malaria as his fight.

  THE “GRAND OLD DAYS” OF TROPICAL MEDICINE

  Hoffman was born and raised in a middle-class family near Asbury Park, New Jersey. His father sold paper products. He majored in political science at the University of Pennsylvania. He took off his junior year, traveled abroad, and on a visit to Jerusalem decided that he wanted to dedicate his life to helping people. He called his parents and said he was going to become a doctor. After graduating from Penn he ended up at Cornell Medical School.

  At the time, Cornell was one of only two medical schools in the country that made tropical medicine a requirement. Hoffman took the sixty-hour course in his second year of med school. At Cornell he heard lectures by the legendary Dr. Ben Kean, a renowned teacher, researcher, and practitioner of tropical medicine. (In 1979, Kean went on to wider renown as the doctor who brought the shah of Iran to the United States for medical treatment, indirectly setting off the Iranian hostage crisis and fatally complicating the presidency of Jimmy Carter.) Hoffman had the opportunity to join with other students who would gather round Kean and listen to his tales after hours. He was quick to fall under his spell. Kean believed that early hands-on experience in the tropics was the best way to stimulate careers in the specialty. He was instrumental in helping many medical students obtain these experiences. Hoffman applied for a fellowship to spend the next summer studying lactase deficiency in infants in Bogotá, Colombia. He ended up staying in South America for a year. When he returned, he was committed to a career in tropical medicine.

  In his training and commitment Hoffman descends from a distinguished lineage that covers almost the entire history of modern tropical medicine. Kean’s mentor was Francis O’Connor, his professor of tropical medicine at Columbia University’s College of Physicians and Surgeons in 1934. O’Connor was an unforgettable figure. In his autobiography, Kean describes him striding into the lecture hall:It was a breathtaking entrance. As was his custom, O’Connor wore morning clothes to class—grey pinstriped trousers and a cutaway coat. He carried a bowler hat and an ebony cane. A hundred second-year medical students swiveled from their microscopes and gaped in wonder. O’Connor, elegant, imperious, civilized, stared back, as if he were peering through his microscope at a wholly predictable, if mildly amusing species of protozoa. . . .

  And how he could teach! O’Connor drew crayon sketches for me in his quick, deft hand of all the important parasites and their complicated life cycles—“mug shots” he called them. Starting with malaria, he explained how all parasitic diseases have three things in common: they all feature a scene of the crime, the human body or the host, where the evil business is done; each involves a third-party accomplice called a vector that helps transmit the infection (in malaria, the mosquito); and all involve a cunning culprit, the parasite itself.6

  When Kean told stories to his students, he was following in his mentor’s footsteps. O’Connor had spent hours regaling Kean and his classmates about the “grand old days” of tropical medicine. The hero of his tales was the widely acknowledged father of tropical medicine, the founder in 1899 of the famed London School of Hygiene and Tropical Medicine: Sir Patrick Manson, also known as “Mosquito Manson.” It was Manson who had discovered, in China, that the mosquito was the transmitter of filarial, the parasite which causes elephantiasis, and who later suggested, but never proved, that it might also be the transmitter of malaria as well. And it was Manson who mentored Ronald Ross, a British officer in the Indian Medical Service who was the first to conclusively demonstrate that malaria parasites were transmitted by mosquitoes.

  It was a French army surgeon, however, who was the first to notice parasites in the blood of a patient with malaria. Alphonse Laveran, born in Paris in 1845, had decided to follow in the footsteps of his father and become a military doctor. In 1878 he was posted to a military hospital in what was then the French territory of Algeria. While working there, Laveran saw dark, pigmented granules in the blood he examined, and motile, flagellated bodies.

  Followers of Louis Pasteur had already suspected that “bad air” was not to blame. (The conjecture previously was that malaria was caused by mysterious “vapors,” mostly from swamps, and the name of the disease, from the Italian mala aria, literally means “bad air.”) Pasteur was convinced of a bacterial cause until Laveran wisely invited him to look through his microscope at what Laveran described as “filiform elements which move with great vivacity.”7 Pasteur was quickly convinced.

  Laveran was prolific. He wrote six hundred scientific papers and six books, and in 1907, his discovery was recognized with a Nobel Prize.

  Identifying the parasite solved one mystery, but for the next twenty years it remained unclear how the parasite found its way into humans. In 1897, Ross demonstrated that malaria parasites could be transmitted from infected patients to mosquitoes and th
en back to other humans who would become infected in turn. It was in August of that year, while dissecting the stomach tissue of an Anopheline mosquito, that Ross found parasites and proved the role of mosquitoes in transmission.

  Ross became an expert at dissecting mosquitoes, something that Steve Hoffman would eventually excel at as well, and his painstaking research took years to bear fruit. But when it did, the discovery that mosquitoes were the vector by which malaria was spread won Ross a 1902 Nobel Prize.

  In his December 12 lecture upon accepting the award, he placed the issue in broader context:Malarial fever is important, not only because of the misery which it inflicts on mankind, but because of the serious opposition which it has always given to the march of civilization in the tropics. . . . There it strikes down, not only the indigenous barbaric population, but, with still greater certainty, the pioneers of civilization, the planter, the trader, the missionary, the soldier. It is therefore the principal and gigantic ally of barbarism. No wild deserts, no savage races, no geographical difficulties have proved so inimical to civilization as this disease. We may almost say that it has held an entire continent from humanity.8

  The same words could be spoken today with the same veracity.

  Dr. Ben Kean went on to work at Gorgas Hospital in Panama, which he described as “the mecca of tropical medicine.” It is named for William Crawford Gorgas, who helped to eliminate yellow fever and reduce malaria during the building of the Panama Canal. Of the 26,000 men working on the Panama Canal in 1906, 21,000 were hospitalized for malaria at some point. Hoffman’s training would one day include numerous visits to Gorgas as well. And a trip to Ecuador while on break from medical school in December 1972. He ended up hospitalized and alone for ten days with typhoid fever, and the experience cemented his commitment to tropical medicine.