Fewer and fewer magic bullets

March 14 marked the 150th anniversary of the birth of Paul Ehrlich. A pioneer in the foundation of modern medicine, Ehrlich was a contemporary of Koch, Pasteur, Curie, Roentgen, and Lister.

Charles John Palenik, MS, PhD, MBA

March 14 marked the 150th anniversary of the birth of Paul Ehrlich. A pioneer in the foundation of modern medicine, Ehrlich was a contemporary of Koch, Pasteur, Curie, Roentgen, and Lister. He was most active during the 50 years prior to World War I. Ehrlich was a laboratory genius. He is considered to be the father of hematology, a key early immunologist, and the creator of the field of chemotherapy. It was Ehrlich who coined the term "magic bullets." He felt that special chemicals could specifically destroy pathogenic organisms or even tumor cells. Ehrlich's hope eventually became one of the central elements of clinical medical practice.

Initially, antimicrobial drugs were very successful. Even as late as 30 years ago, the thinking was that infectious diseases had been conquered. Today, however, we know that infection is the third leading cause of death in the United States and the second most common cause of death worldwide. Multiple drug-resistant microorganisms, especially bacteria, have resulted in few or even no viable treatment options for certain types of infections. New infections continue to emerge. Genetic engineering could result in pathogens with enhanced drug resistance. Such microorganisms could then be used for bioterrorism attacks.

A recent article in Clinical Infectious Diseases describes an apparent paradox — in a time of true need, the pharmaceutical industry continues to curtail research programs to find agents to combat infectious diseases. Only six of the 506 drugs currently known to be under development are antibacterial agents. Approval by the FDA of antimicrobial drugs has decreased by 56 percent over the last 20 years. The majority of the antimicrobials being developed involve anti-HIV agents, rather than those that treat bacterial infections.

Today, there are impediments to the development of any drug, especially antimicrobials. Research and development costs for FDA approval run $400 to $800 million. Also, it takes an average of eight years to bring a drug from Phase I clinical testing to a salable product. The percent of potential drugs that make it to the pharmacopoeia ("from bench to bed") is tiny.

Antimicrobials approvals declined from 1983 to 2002. Research and development work has moved downward for several decades. A review of products under development indicates this trend will not reverse soon.

Other factors influence interest in drug development. As the population ages, the number of chronic disease cases increases. Chronic medical conditions include hypercholesterolemia, diabetes, mood disorders, hypertension, dementia, and arthritis. Chronicity means consistent drug demand over extended periods of time among relatively large numbers of people.

Conversely, antimicrobial drugs generally are short-term applications. A cure means the patient no longer needs the drug. A relatively large number of antimicrobials are currently approved. Newly developed drugs must compete in a crowded marketplace. Finally, there is great pressure to limit the use of broad-spectrum antimicrobials, thus reducing the chances of emerging resistant forms. This retards new products from gaining market share. The combined effect of these factors is that a number of large pharmaceutical companies have severely curtailed or, in some cases, eliminated research into antimicrobial agents.

A continuum in the development of antimicrobial drugs is needed. A thorough and comprehensive review is required to overcome the current barriers. A similar program was completed recently concerning anticancer agents. The result was significant increases in the levels of governmental funding for cancer research and cancer treatments. Perhaps something similar could be done for antimicrobial research and development. A cooperative effort among government, academia, and industry probably will be required. Government contracts and economic incentives likely will be needed to help industry develop antibacterial agents to meet specific national needs.

There is a necessity for better antimicrobials. Emerging diseases, increased microbial resistance, and the potential for a bioterrorism attack all demand greater activity. Innovative solutions will be needed to remove the current barriers to the development of new antimicrobial drugs.

OSAP, the Organization for Safety & Asepsis Procedures, is dentistry's prime source for evidence-based information on infection control and prevention and human safety and health. Further information on antimicrobial agents and emerging diseases is available on the OSAP Web site at www.osap.org.

Dr. Charles John Palenik is an assistant director of Infection Control Research and Services at the Indiana University School of Dentistry. Dr. Palenik has authored numerous articles, book chapters, and monographs, and is the co-author of the popular Infection Control and Management of Hazardous Materials for the Dental Team. He serves on the Executive Board of OSAP, dentistry's resource for infection control and safety. Questions about this article or any infection-control issue may be directed to office@osap.org.

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