A New Way to Discover Antibiotics?
Researchers have created a simplified platform for discovering antibiotics that may help solve the rising crisis of resistance to such helpful drugs.
In a study just published in the journal Nature, Andrew G. Myers of Harvard and colleagues describe “a platform where we assemble eight (chemical) building blocks by a simple process to make macrolide antibiotics” without using erythromycin, the original macrolide antibiotic, and the drug upon which all others in the class have been based since the early 1950s. Erythromycin, which was discovered in a soil sample from the Philippines in 1949, has been on the market as a drug since 1953.
“For 60 years, chemists have been very, very creative, finding clever ways to ‘decorate’ this molecule, making changes around its periphery to produce antibiotics that are safer, more effective, and overcome the resistance bacteria have developed,” said Myers, Amory Houghton Professor of Chemistry and Chemical Biology in Harvard’s Department of Chemistry and Chemical Biology. “That process is semisynthesis, modifying the naturally occurring substance.”
In contrast, the process described in the Nature study involves using “eight industrial chemicals, or substances derived from them,” Myers said, manipulating them in various combinations and then testing the products against panels of disease-causing bacteria. This allows for “new compounds in fewer steps than was previously possible.”
For a host of reasons, from the difficulty of developing antibiotics to the relatively low return on investment they offer, by 2013 the number of international pharmaceutical companies developing antibiotics had dwindled to four. In addition, in each five-year period from 1983 through 2007, the number of new antibiotics approved for use in the United States decreased, from 16 at the beginning of that period to only five by its end.
One thing that has complicated antibiotic development is federal agencies’ perceived reluctance to fund the research. In fact, Myers said, his new antibiotic development system would have been impossible without support from a Harvard alumnus and his wife who are interested in science, and Harvard’s Blavatnik Biomedical Accelerator.
“I was making a presentation to a group of visiting alumni interested in science, and one, Alastair Mactaggart, asked me about funding. I told him I had no funding, because at that time we didn’t, and he followed me back to my office and said, ‘This is ridiculous: We have to do something about this.’” Myers said that without the support of Mactaggart and his wife, Celine, and the Gustavus and Louise Pfeiffer Research Foundation, the new platform would not exist. “And the Blavatnik accelerator funding was also hugely important,” he added