Newsroom

The looming threat of bacterial infections resistant to available antibiotics can be averted if industry, regulators, and academics work together in creative new ways, writes Weill Cornell Medical College expert Dr. Carl Nathan in a commentary in the October 21 Nature.

"Despite growing bacterial resistance to existing drugs, antibiotic development in the pharmaceutical industry is steeply declining," warns Dr. Nathan, Chairman of the Department of Microbiology and Immunology at Weill Cornell Medical College and Co-Chair of the Immunology and Microbial Pathogenesis Program at the Weill Cornell Graduate School of Medical Sciences in New York City.

The decline in development of antibiotics for infections prevalent in economically developed regions is merging with the long-standing shortage of antibiotics for infections that mostly afflict less affluent areas. In fact, Dr. Nathan argues that the two crises can best be addressed if they are considered facets of a single problem that has the same causes and potential solutions.

"Government agencies and professional societies have addressed antibiotic resistance, but little has changed," he writes. "We need new approaches."

One approach may involve working with the cooperation of, but outside the regular structure of, the pharmaceutical industry. According to Dr. Nathan, the intense pressure put on the private sector for wide profit margins means drug companies are increasingly forced to drop their traditional pursuit of antibiotic development.

To fill the gap, he supports the creation of "another kind of player on the scene: a not-for-profit drug company," focused on identifying and patenting new drugs and drug combinations overlooked by industry.

This type of non-profit initiative would license its intellectual property "gratis to any company or agency that commits to produce and distribute the resulting drugs on a basis that serves the needs of patients and society," Dr. Nathan writes.

A second innovation involves changing a regulatory system that restricts antibiotic development while encouraging widespread resistance to these drugs, according to Dr. Nathan.

The use of antibiotics in combination is key to their long-term effectiveness, so regulatory changes that encourage manufacturers to test specific drug "synergies" may be crucial, he says. Patent life should also be extended for newly minted antibiotics aimed at novel microbial targets, and "all new antibiotics should be banned from widespread administration to healthy animals," since the use of antibiotics in agriculture remains a prime source of resistance today.

Finally, Dr. Nathan believes scientists and academics must change their approach to antibiotics research. For years, he writes, efforts have focused on a very limited number of microbial targets, "producing almost nothing but variants of older antibiotics." Now, he says, "the well has gone dry."

Thanks to the recent explosion of knowledge in genetics and cellular biology, researchers now have a multitude of largely unexplored "points of vulnerability" at which to target new antibiotic drugs, Dr. Nathan points out.

Diagnostics can and must be improved, he says, and scientists must also move away from developing drugs that work against a broad spectrum of pathogens, since this encourages microbial resistance. Instead, he says, "it is medically preferable, and will preserve the utility of the drugs longer, if antibiotics are highly specific, so that each one is used less often."

"Is it hopelessly unrealistic to envision not-for-profit companies, a smart regulatory environment, and fresh scientific approaches to antibiotic development?" Dr. Nathan asks. Perhaps not: He points out that not-for-profit entities — like the Bill and Melinda Gates Foundation, and the Medicines for Malaria Venture — are already having a significant impact on new drug discovery.

In the end, he says, the search for new, effective antibiotics cannot be allowed to fail.

"All sectors of society, including the pharmaceutical industry, have a major stake in the control of infectious diseases," Dr. Nathan writes, "not only for medical reasons but also for global economic development and security."