Quest for the Cure

More than a third of the world's population doesn’t have access to essential medications. Greedy drug companies, government bureaucracies, and apathy all get in the way. Some brave scientists have had enough of the high costs and red tape. They're frustrated, they're mad, and now they're finding ways to buck the system.

Dr. Peter Hotez has always been fascinated by the kind of grisly afflictions that turn most people's stomachs. As a 13-year-old, he spent hours poring over the authoritative tome Manson's Tropical Diseases, keeping it within easy reach on his nightstand. He chose to spend his career studying hookworms -- tiny, half-inch-long parasites that burrow into victims' bodies and literally suck the life out of them. By the mid-1990s, Hotez's research had reached a breakthrough: a concept for a vaccine to fight against the nasty tropical disease.

Dr. Peter Hotez has always been fascinated by the kind of grisly afflictions that turn most people’s stomachs. As a 13-year-old, he spent hours poring over the authoritative tome Manson’s Tropical Diseases, keeping it within easy reach on his nightstand. He chose to spend his career studying hookworms — tiny, half-inch-long parasites that burrow into victims’ bodies and literally suck the life out of them. By the mid-1990s, Hotez’s research had reached a breakthrough: a concept for a vaccine to fight against the nasty tropical disease.

Hotez made the rounds at pharmaceutical firms, looking for a drug company to test his vaccine. But doors slammed in his face. He talked to animal health companies, makers of flea collars and sheep disinfectants, because hookworm also infests livestock. They turned him down, too. Having exhausted the traditional options, he wondered if he had hit the end of the road. "It was pathetic," Hotez sighs. "Really discouraging." He considered moving to Iowa to become a small-town children’s doctor, leaving more than 20 years of research — and the hopes of millions of sick patients — behind.

Sadly, Hotez’s frustration wasn’t unique. Despite the fact that so-called "neglected diseases" such as hookworm affect millions of people, they have long been abandoned by modern medicine. The reason is simple: The typical victim is too poor to pay for treatment. As with any commercial entity, a pharmaceutical company is driven by the promise of profits. If a firm spends time and money developing a new drug, it hopes to reap financial rewards by selling the final product. But remove the profit motive from this engine, and it sputters to a grinding halt. One study, published in May by the medical journal The Lancet, found that just 1 percent of the 1,556 drugs developed between 1975 and 2004 were treatments for neglected diseases or tuberculosis. Sixteen years ago, an influential report from the Commission on Health Research for Development — an independent, international initiative supported by donors from 16 nations — defined the problem as the "10/90" gap: Only 10 percent of the world’s research dollars are spent on the problems that affect 90 percent of the world’s population.

For decades, it was unlikely that this desperate situation would ever be reversed. Big Pharma has to keep its shareholders happy, governments move slowly by nature, and scientific research takes years to yield positive results. Such obstacles have long stymied those looking to cure the world’s diseases. But recently, there have been signs of hope. Doctors, researchers, and entrepreneurs have begun to find creative ways to slash away red tape and find solutions where few had thought to look. It may not be a revolution, but there are a growing number of innovative, courageous, and caring mavericks who are making inroads in getting medications to those who need them most.


Obscure scourges have been quietly maiming or killing people in Asia, Africa, and Latin America since Biblical times. According to the World Health Organization (WHO), millions in the developing world suffer from neglected diseases, which include hookworm, lymphatic filariasis, and Guinea worm. They kill more than 530,000 people every year, resulting in a loss of 56.6 million years of healthy life. Another 460 million people are affected by the slightly less ignored "Big Three" — HIV, tuberculosis, and malaria — which claim 5.6 million lives each year. Every 30 seconds, it is said, malaria takes a child’s life.

Good sanitation, clean water systems, and access to basic healthcare prevent people in wealthier countries from falling victim to these ailments. Neglected diseases primarily affect people who are poor to start with, and they often deepen their poverty. Take hookworm, for example. Hookworms feed on the blood of their human hosts’ intestines, leaving infested patients debilitated and anemic, lacking energy to pay attention in school or show up for work. Although deworming drugs exist, they don’t protect patients from becoming reinfested. That leaves 740 million hookworm victims around the world trapped in a chronic cycle of poverty and infection.

Another pervasive but largely ignored disease is river blindness. It is caused by worms that can live for a decade inside a human victim, breeding thousands of tiny progeny that swarm just underneath the skin. If they infest the delicate surface of the eye, the scarring infection can lead to total loss of vision. The condition affects a whopping 17.7 million people, has blinded 270,000, and has damaged the sight of 500,000 more. Another parasite, the worm that causes schistosomiasis, infests 200 million people. It burrows its way through human skin, then gorges itself on blood before churning out thousands of eggs. But because these afflictions only hit the poorest people in the world, there’s simply no reason for companies to spend money on them.


The tragedy is that these diseases don’t have to remain neglected. Take AIDS, for example. For years, it was a deadly affliction that no one had heard of. By the end of the 1990s, drug companies had developed new medications that made it possible for many patients to live relatively long lives. But AIDS had already begun its merciless rampage around the world.

Most of the world’s AIDS patients — 9 out of every 10 of whom live in Africa, Asia, and Latin America — could not afford the expensive new medications. The disparity in aid was shocking; by the turn of the century, the United States was spending $10 billion per year to combat HIV/AIDS domestically, while the international community spent only $2 billion on the developing world. The activist community that had grown up in the West demanded that drug companies cut their prices, or at least allow drug companies in poor nations to make cheap copies of the drugs. But pharmaceutical companies wouldn’t budge, arguing that discount drugs would drive them out of business.

The messy fight hit the world stage in 1998, when a coalition of drug companies sued the South African government to prevent it from importing or selling cheap AIDS medications. The lawsuit triggered an international outcry and quickly devolved into a public relations disaster. The companies withdrew their lawsuit in 2001. "The South African court case was a watershed," says Mary Moran, a doctor and policy analyst who works at the George Institute for International Health in Sydney, Australia. "Until then, the companies could face this movement down."

Pharmaceutical companies were forced to adopt cheaper prices, donate drugs for free, or allow poor countries to make cheap generic AIDS drugs on their own. It was a taste of victory for the activists. And it woke the Western world to the fact that there were serious health problems in poor countries that were festering away with little hope of remedy.


Unfortunately, other neglected diseases haven’t managed to attract Hollywood’s attention — or, more important, Wall Street’s cash — the same way that AIDS has. But some frustrated doctors are now finding creative ways to bring modern medicine to neglected diseases. Their first challenge is to get drug companies to loosen their grip on potential treatments they already have on the shelf. It may seem counterintuitive that after investing millions of dollars to usher a new drug from test tube to pharmacy, a company would try to hide the fruits of its labor in a closet. As Dr. Richard Chaisson learned, this is life in the land of neglected diseases, where the free market works in mysterious ways.

Chaisson, a 52-year-old infectious disease researcher at Johns Hopkins University’s Bloomberg School of Public Health in Baltimore, Maryland, has studied tuberculosis (TB) for more than 20 years. For most of the modern, industrialized world, the word "tuberculosis" conjures up images of 19th-century Victorians delicately coughing blood into handkerchiefs. The disease really should not exist in the 21st century. It’s caused by bacteria, and it has been curable since the discovery of antibiotic drugs 60 years ago. But in the developing world, TB is a massive and growing problem. More than 14.5 million people are currently afflicted worldwide.

Tuberculosis also sends drug companies running for the hills. Chaisson found that out the hard way eight years ago, when one of his Johns Hopkins colleagues, Dr. William Bishai, went to an international infectious disease meeting where the German pharmaceutical giant Bayer was eagerly touting a new antibiotic, moxifloxacin, to combat pneumonia. Bishai was intrigued and asked Bayer to send him a sample of "moxi" to test in his lab at Johns Hopkins. Eager for scientists like Bishai to validate their new drug’s power, Bayer gladly agreed.

Back at the lab, Bishai dropped the moxi in a petri dish swimming with tuberculosis bacteria. He was amazed to discover that the drug cleared the bug right out of the dishes. Bishai then tested moxi in mice infected with a TB-like illness. Again, the drug wiped their lungs almost completely clean. Bishai and Chaisson began to wonder whether moxifloxacin might be the powerful wonder drug they had been looking for.

To find out, Chaisson would need to test moxifloxacin in human patients with TB. He called Bayer to pitch the idea. But the company wouldn’t answer his calls. Chaisson persisted for more than a year and a half, to no avail. "The company wouldn’t even talk to me," Chaisson says. "It was pretty clear that they just didn’t want to see this drug developed for tuberculosis." In response, Bayer says moxi has to be used in combination with other meds for TB treatment, and the company needed to be assured of the safety and efficacy of a long-term study before moving forward. But Chaisson believes that Bayer was worried that if moxi was branded as a TB drug, doctors would stop using it against more lucrative diseases such as pneumonia. And their shiny new drug would be relegated to the impoverished backwater of TB treatment.

Chaisson was undeterred. He went straight to the U.S. Food and Drug Administration (FDA), asking it to approve a study of moxifloxacin against tuberculosis. His brash action was unusual. Requests are usually made by a drug company, because the FDA requires a huge file of data on the chemistry, safety, and production of a drug before it will approve a study. And usually, only the company knows all these details, which it compiles into a document called a package insert. But Bayer had already submitted a package insert when it asked the FDA to approve moxi for pneumonia in 1998. So all Chaisson had to do was Xerox a copy, staple it to his study proposal, and submit it to the FDA. Not only did the agency approve Chaisson’s proposal, it awarded him a $1.3 million grant to conduct his trials in Brazil on a disease that kills fewer than 1,500 Americans a year.

Bayer executives were astonished by Chaisson’s tactics. Faced with his fait accompli, they were forced to backpedal. In exchange for a promise that Chaisson would give them advance warning about the trial results, Bayer not only allowed him to conduct his study, it also decided to donate the MOXI for his trials. The moxifloxacin study is now under way in Brazil, and it should be finished by the end of the year, thanks to Chaisson’s ingenuity. "It wouldn’t have happened if we hadn’t done an end run around them first," he says.

In a way, Chaisson was lucky. There already happened to be a preexisting potential treatment for TB lurking in some drug company’s warehouse. All he had to do was wrench it free. But for researchers working on the most neglected diseases, that is usually not true. There are no treatments hidden away in a corporate medicine chest. And there likely won’t be, because no drug company cares to spend money looking for them. For these diseases, scientists have to find ways to fill in the gaps by developing drugs on their own.


Six years ago, this was the situation confronting Peter Hotez. After devoting 25 years to studying hookworm, he had created a vaccine to take patients off the merry-go-round of repeated deworming treatments. He had already done the hard part; through decades of research, he had identified the most promising ingredients for the vaccine. All he needed was a company to sponsor a trial, and it would soon have a product in hand, ready to sell. But no one was interested. Such a vaccine could only be sold to poor nations, and would never make much money. It was during these bleak days that Hotez contemplated abandoning his grand idea and moving to Iowa.

But he decided to try one last-ditch attempt before calling it quits. If no company would join his quest, perhaps he could do it himself. Hotez knew that Microsoft billionaire Bill Gates had started a foundation that was supporting work in global health. He also knew that Gates had already given money to a project to find a vaccine for malaria, which, like hookworm, is a neglected disease caused by a parasite. So Hotez sent an application to the Bill & Melinda Gates Foundation, proposing, essentially, to turn his lab at George Washington University into a mini vaccine factory.

The idea was crazy. No scientist had ever done anything like it before, because academic labs simply don’t have the money or the expertise to manufacture new drugs, test them in large trials, and usher them through the paperwork maze required to earn a government stamp of approval. But, miraculously, Gates said yes. In 2000, the foundation awarded Hotez $18 million (followed by another $21.8 million last year) to the Sabin Vaccine Institute, which partnered with George Washington University to enable Hotez to create what he calls his "guaranteed money-losing company" — a vaccine maker that will never turn a profit, because that is not its goal. Hotez simply hopes to prove the hookworm vaccine works. If it does, he will hand it off to the Instituto Butantan, a biomedical research center in São Paolo, Brazil, that will make and sell it in the developing world.

So far, Hotez has managed to do what was previously thought impossible. He whipped up a batch of vaccine and tested it in 36 healthy U.S. volunteers to make sure it is safe. Now he’s taking his home-brewed meds to the streets. This fall, the next phase of the world’s first-ever clinical trials of a hookworm vaccine will begin in Brazil. Whether or not the vaccine works, the fact that it is being tested at all is a landmark event, emblematic of the shift that just may revolutionize the world of global health. In the past, doctors like Chaisson and Hotez probably would have fought the good fight for years, and lost anyway. But the long, slow shift in conscience that began with the AIDS crisis is spurring new thinking — and new financing — for neglected-disease research. And that has opened the door for projects that were unthinkable just a decade ago.


Talk to anyone who works on neglected diseases, and the conversation inevitably turns to Bill Gates, who has made global health his raison d’être in recent years. "The world is failing billions of people," he said at the World Health Assembly in Geneva last year. "Rich governments are not fighting some of the world’s deadliest diseases, because rich countries don’t have them." In just one decade, Gates has used his foundations to spend $6 billion on neglected-disease research — more than what all the world’s governments combined spent during the same time period.

The impact of this spending is undeniably huge; the foundation can already claim that it has saved millions of lives. In 1999, for example, Gates gave $325 million to start an organization called the Global Alliance for Vaccines and Immunization. The alliance vaccinates babies and children in poor countries against easily preventable diseases, such as hepatitis B, yellow fever, and polio. In just six years, Gates has given $908.5 million to the alliance, which estimates that it has averted 1.7 million future deaths from preventable diseases. The governments of the world have chipped in only a combined $791.5 million.

Gates has also invested in the types of global health research that the traditional pharmaceutical industry has shunned. Chaisson’s work on moxifloxacin, for example, will be funded in part by the Global Alliance for TB Drug Development, a group looking for new treatments, which draws money from Gates. Hotez’s hookworm vaccine trials are also Gates-funded. The foundation invests in projects that tackle a host of other global health problems, including malaria and childhood illnesses such as severe diarrhea. This spending is doing more than just aiding the quest for new cures. Public health officials, who have worked on neglected diseases for decades, credit Gates with spreading ripples of possibility throughout this previously hopeless field. And that, in turn, is coaxing some reticent donors and wary governments back to the table. "What Gates has done is shine a light on a lot of these issues," says Helene Gayle, a former Gates Foundation official who is now president of the humanitarian organization CARE. "There’s definitely a much greater focus on these problems than ever before."

Money alone, however, isn’t a complete solution. A new public-private partnership model has emerged. These new entities accept the fact that drug companies simply won’t spend their own money to find, test, and sell neglected disease treatments. So they pick up the slack by using government or private funding from organizations like the Gates Foundation to absorb the costs of clinical trials. By combining industrial expertise with the conviction and know-how of academics and activists, they hope to create a wave of new tools against diseases that affect the poor.

These partnerships are already injecting a batch of new drug candidates into what used to be an empty pipeline. According to a study released last year by Mary Moran and her colleagues, at least 63 new neglected-disease drug projects are now in progress, compared to only 13 drugs approved between 1975 and 2000. By 2010, these projects should deliver at least eight or nine new drugs to patients — almost as many as in the previous 25 years, in less than half the time. And nearly three fourths of these drugs are being developed by public-private partnerships. "There’s been a sea change since 2000," says Moran. "It’s very clear: We now have a model that is going to make new drugs against these diseases."

Moran’s study, which counted 92 public-private partnerships in neglected-disease research, found that almost all of them have one thing in common: Bill Gates. His foundation alone provides 60 percent of the funding for these groups. "The public was pressing companies to find these drugs," Moran says. "Gates provided the missing chunk of money."


One such partnership that receives assistance from Gates, the Institute for OneWorld Health, is on track to deliver the first tangible victory for the new business model. The nonprofit pharmaceutical company was started in 2000 by Dr. Victoria Hale. She had previously worked at the FDA and at the large biotechnology firm Genentech. But at the age of 37, Hale started to think about where she was going next. "I was a little too comfortable in my life, and that was unsettling," Hale says. She quit her job at Genentech and decided to devote the rest of her life to making medicines for the world’s poorest citizens.

Hale’s first project was a rescue mission. Field doctors with the aid agency Doctors Without Borders had found that an old drug called paromomycin seemed to work against the deadly disease called visceral leishmaniasis, also called black fever or kala azar. The disease strikes 500,000 people around the world each year, painfully causing their spleens and livers to swell. Like sleeping sickness, kala azar can be treated, but only by a long course of painful drugs that are losing their power against the disease.

In the 1980s, Pharmacia, the company that made paromomycin, handed over the rights to the drug to the WHO. It is rarely used in rich countries anymore, so paromomycin’s meager profits didn’t justify its production costs. The WHO was about to pull the plug on the drug in 2001, when Hale quickly organized a salvage mission, using the world’s last remaining stocks of the drug and designing a clinical trial for kala azar patients in India. In April 2005, OneWorld Health reported that the drug worked, curing more than 94 percent of patients. Paromomycin is so old that it is no longer covered by a patent. So Hale found a Hyderabad, India-based company, Gland Pharma, which could produce the drug at low cost. OneWorld Health will soon submit its formal request to the Indian government to approve the use of paromomycin for the treatment of kala azar.

The world was fortunate that paromomycin happened to work against a neglected disease. But poor patients will not always be so lucky, and that’s why Hale believes that groups like OneWorld Health will always be necessary. Somebody needs to create new types of drugs that will render neglected diseases obsolete, rather than incrementally improving on old treatments. But these innovations won’t come from commercial companies. "We know the companies cannot keep kala azar in their portfolio when they have the next big hypertension drug coming along," Hale says. "These diseases have no home, and we need to find a home for them."

Hale is already thinking about how OneWorld Health might turn itself into that kind of stable home. The foundation will probably always need philanthropy, government funding, and help from the pharmaceutical industry. But unlike some other public-private partnerships, OneWorld Health also files for patent rights on new treatments developed under its umbrella. Hale thinks it may be possible to sell some of these new treatments to middle-class patients in otherwise poor countries at a small profit. If it works, OneWorld Health could be the new prototype for a successful, sustainable neglected-disease research engine.

The question of whether these public-private partnerships will succeed has crucial implications for everyone, not just for the millions of people in poor countries who are suffering from ill health. The equity of global markets is also at stake. Groups like OneWorld Health are testing these markets. Will they be vindicated in the end? Not without help. "Governments need to start funding these things soon, [too], or else they’re going to be responsible for sending these drugs down the tubes," says Moran. It is no longer possible to say that people aren’t trying hard enough, or thinking creatively enough, to solve the problem of neglected diseases. If people like Chaisson, Hotez, and Hale are not given enough support, it will be an indictment of the system itself. Whether or not their science ends in success, it may tell us something about the world’s collective moral health as well.

Erika Check is a senior reporter at Nature.

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