PAUL EHRLICH'S DEVELOPMENT OF ARSENIC DERIVATIVES TO TREAT syphilis at the turn of the 20th century has been viewed as the dawn of the age of chemotherapy and rational drug design. 1 When Ehrlich's personal secretary, Martha Marquardt, commented on his life, she reserved her most heartfelt praise not for his brilliance as a chemist but for his mission. "Nothing on earth mattered to him except scientific research aimed to overcome suffering and disease." 1 These noble aims, however, were subject to priorities and agendas over which he had no control. English clinic staff viewed patients with syphilis as depraved sexual offenders, which adversely affected their compliance with treatment. In English colonies such as Uganda, eradicating syphilis was not a economic priority. 2,3 For these reasons, syphilis remained an explosive epidemic. Today, it is exciting to imagine the possibilities of biotechnological wonders like the human genome project, stem cells, and microarrays. But the priorities driving these efforts may be leading us astray. Michael R. Reich recently declared that the current drug development system, despite its "extraordinary research and development capacity," has led to "global inequities in health care." 4 He argued that the dependence on large profits from affluent countries created restrictively high drug prices and a penchant for developing drugs that target only the health problems of the wealthy. The solution, according to Reich, is the creation of incentives and reforms to refocus the global pharmaceutical industry on curing the most serious diseases rather than merely the most profitable ones. Articles in this issue explore how existing health management systems and technologies could be optimized "to overcome suffering and disease," often despite severe financial and logistical challenges. June Dahl argues for systematic changes to improve the medical management of pain-one of the most undertreated conditions for which highly effective drugs are readily available. Amit Etkin explains how the human genome data can be made clinically useful. Bret Ball and French Anderson outline how to overcome the major barriers that impede the application of gene therapy in the clinic. David Walton and Paul Farmer call for an end to the policies of negligence that have governed the treatment of multidrug-resistant tuberculosis in third world countries. Since Ehrlich's time, few of the principles of disease management seem to have changed. "Rational drug design" still occurs largely through a process of large-scale screening techniques, moments of serendipity, and years of targeted research. Effective use of available therapies remains hampered by physicians who fail to prescribe drugs rationally. Pathogens may evolve to evade our therapies. But, at the current rate of progress in biotechnology, we may soon have the tools with which to address most of the world's diseases. However, how will we employ these tools and would Martha Marquardt approve? ON THE COVER
