A small San Francisco charity has big plans for bringing new drugs to the world

Dr. Victoria Hale's professional story started as former Genentech executive and Food and Drug Administration official. But her personal story started years ago when close friends had a 13-year-old daughter diagnosed with a deadly form of cancer. Doctors had little to offer them, so Hale began her search. Hale found hope, two of them in fact.

IMS Health estimates that the global pharmaceutical market in 2006 exceeded $260 billion dollars. We read about blockbuster drugs every day that are impacting cancer, AIDS/HIV and aging. New compounds are being discovered daily and exploration continues from the Amazon forest to the depths of the ocean. It would seem on the surface that this powerful economic juggernaut is poised to steamroll diseases across the globe.

Dr. Victoria Hale discovered that this was sadly far from the truth. Dr. Hale had already put in a stint at Genentech, but had left in 1995 to start her own regulatory consulting business. While she was consulting she visited the World Health Organization in Switzerland. There she discovered a disturbing truth: in reality there are drugs and compounds all across the world that have been shelved at some point in the research and development process. No one, it seemed, was working to develop these compounds into drugs. It was shocking. Dr. Hale discovered the same situation happening to dozens, perhaps even hundreds, of potential drugs too expensive to develop for rare conditions or for diseases typically affecting the poorest of the poor.

The repercussions are staggering. Worldwide, it is estimated that two million children under five years of age die from diarrhea annually, and that every 30 seconds an African child dies from malaria. Viseral leishmaniasis (VL), also known as black fever, afflicts 1.5 million people worldwide, killing some 500,000 people every year, according to the World Health Organization. Yet, the Western world remains largely unaware of the disease.

Dr. Hale saw the fatal affliction first hand in 2000. After her meeting with the World Health Organization she traveled to India to visit a doctor working on VL and witnessed the impact this curable disease had on poor, rural villages in India. On a global scale Dr. Hale could immediately see the problem. Although developing countries represent 80 percent of the world's population, they are responsible for only 20 percent of medicine sales. And the number of drugs that were being developed for use in the Third World paled in comparison to the number of medicines developed to combat cancer, cardiovascular disease or AIDS. Now, acutely aware of the number of neglected compounds with medicinal potential, Hale wanted to find a way to guide these would-be medicines into development, creating new life-saving drugs. She also wanted to tackle diseases that disproportionately affect the world's poor. So six years ago she and her husband, Dr. Ahvie Herskowitz of the University of California, San Francisco, founded OneWorld Health.

Hale and Herskowitz put up a total of $100,000 of their own money and signed a promissory note for $315,000. They used the ground floor of their house as offices. Both worked without pay for two years, overcoming numerous obstacles. The I.R.S. turned down Hale's request for nonprofit status three times in 10 months, suspicious that the couple's plan was a scheme to shelter pharmaceutical profits. Two weeks after convincing the I.R.S. that OneWorld Health was indeed a nonprofit organization in a profit dominated industry, Hale and Herskowitz set out to tackle black fever.

Black fever, known locally in India as kala azar, is a parasitic infection caused by tiny, biting sand flies. It can be fatal if left untreated, and has stretched from India to Nepal and Bangladesh and as far as Brazil. If the half million deaths caused each year by the disease occurred in America, black fever would rank third, behind heart disease and cancer, as a leading cause of death in the United States. Instead, black fever is a neglected disease. In the 1960s development of a promising drug called Paromomycin was all but abandoned for lack of profit potential. Paromomycin was left sitting on a corporate shelf somewhere in the United States. Hale was determined to dust off that shelf. As a result of nearly three decades of company mergers and neglect, "ownership" of Paromomycin had fallen into the hands of the World Health Organization (W.H.O.), despite the fact that the W.H.O. lacked the funding to develop the drug or conduct clinical trials. For two years, negotiations with W.H.O. to secure the necessary permission to allow OneWorld Health to develop paromomycin dragged on.

To understand the task in front of Dr. Hale, it is necessary to understand the process that billion dollar pharmaceutical companies endure to bring new drugs to market. OneWorld was tackling a production cycle with a fraction of the funding and with compounds that had been shelved for years. The development process for new drugs consists of three distinct stages: 1) Research, which includes laboratory research and screening to identify positive leads; 2) Development, which includes optimizing a drug and guiding it through clinical trials and regulatory approval; and 3) Production, which includes finding manufacturing and distribution partners.

It is a process that takes years and often several attempts at securing regulatory approval. To its advantage, OneWorld was working with compounds previously discovered and as such, was skipping most of the research stage. But they still had to work through the trials and approval processes. For instance, it took three years to get Paromomycin into Phase 4 Clinical Trials in India.

Next the manufacturing and distribution problems had to be resolved. Since OneWorld Health was not developing global drugs with a large audience, their ability to create a cost-effective network of local distributors could have been the piece that made or broke their model. Distribution typically has the added headache of working with government health ministries and non-government health organizations. All to distribute drugs Hale hoped to sell for pennies per dose. These challenges would vex even the largest pharmaceutical companies, but OneWorld Health was attempting to do this with only a fraction of the resources.

However, funding did appear. Hale's efforts and tenacity attracted the attention of-and substantial funding from-the Bill and Melinda Gates Foundation. Eventually, OneWorld Health secured approval of their VL drug from India's government. On the distribution front, OneWorld Health has given the license to Gland Pharma, an Indian drug company that has agreed to manufacture and sell the drug at cost, estimated to be approximately $10.00 (U.S.) per treatment for each infected person. Hale continues to work with the Indian government to secure final approval to distribute the drug to remote villages at the end of pothole-pocketed roads. OneWorld will not gain any income from the drug.

On the heels of Hale's groundbreaking success, pharmaceutical researchers are offering OneWorld Health a variety of compounds for consideration and possible developme nt. Equally impressive, many of these researchers are volunteering their ti me to help Hale in her efforts. At the end of the day, Hale does not bla me profit-driven drug manufacturers. Instead, she tries to work with them. She acknowledges that many in the pharmaceutical industry are in the business to ease suffering and save lives, but she understands that shareholders demand profits. It is almost certain that Hale's efforts will save millions of lives, and hopes are high that OneWorld Health's new efforts to tackle malaria and chronic diarrhea in children will be just as successful. But Hale's greatest legacy may be the creation of what many believed to be an oxymoron, a "nonprofit drug company."