Academia's role in antibiotic development – crucial since the dawn of the antibiotic age when Oxford University purified penicillin ahead of mass production – remains just as important today. Despite the centrality of pioneering work undertaken at universities, challenges from basic training to funding crunches have left a yawning gap in some areas, contributing to a complex web of problems slowing the arrival of new antibiotics on the market.
In the U.S., universities largely look to the NIH to fund discovery work — often employing sheer perseverance and grit to get something to a point that's ready for an IND filing, University of Notre Dame professor Shahriar Mobashery told Medical Device Daily. But even when that discovery work is productive, advancement of promising antibiotic candidates can be challenging.
"Academic groups have a lot of obstacles in front of them," said Mobashery. Against a background of flagging industry activity in antibiotic discovery and development, he said, many of the academic world's leading experts are either on the verge of retirement or have moved into other areas.
Furthermore, "universities, even well-to-do ones, are not in the business of drug discovery. They might provide infrastructure, in terms of instrumentation and physical space," Mobashery added. But ultimately, whether a compelling piece of science gets off the ground in the academic environment can come down to just one or two people convincing funding agencies or other backers to lend their support.
University of Michigan professor David Sherman has experienced the challenge of that necessity first hand. "We're discovering new antibiotics all the time," Sherman told Medical Device Daily. But moving a promising candidate to the next stage can be difficult, he said. "There's a big gap between discovery and development."
After discovering a new biofilm against Acinetobacter, a serious emerging human pathogen, he and he colleagues published an article about their findings in Nature Communications. Conversations with a European company that took an interest in the findings followed, leading to a question: Would they take the risk on investing in a promising early stage molecule? After considering the risks, the company walked away.
If the molecule is to progress, Sherman will need to be the one to move it ahead, he said. But that need creates a difficult choice – one faced in the academic space every day: Does one devote time to pursuing the academic mission of advancing knowledge, publishing papers and training students or make a significant investment of time to advance an new chemical entity in the hopes that it will one day become a drug? "We're left in this situation where NIH and other grant agencies are supporting our discovery of new molecules, but they're just sitting there and nothing is happening," he said.
Reasons for hope
Though the picture can seem bleak, Rescuing Biomedical Research, a Washington-based group focused on reforming the research enterprise to make it more efficient and equitable, sees reasons for hope. For one, young researchers today have the benefit of new technologies redefining the discovery process, director Christopher Pickett told Medical Device Daily. Furthermore, he said, with so many young scientists getting advanced degrees and then moving into areas outside of academia," there may be somebody trained in developing antimicrobials or new antibiotics. If they go into a policy position, they can affect policy that would help the government remove policies that block advances or implement policies that would facilitate advances."
Closer ties between academia and industry could also help, as evidenced by a collaboration between the University of Bonn, Northeastern University and Cambridge, Mass.-based Novobiotic Pharmaceuticals LLC. In Nature, they documented a new antibiotic called teixobactin which binds to lipid II and lipid III of bacterial cell walls for the potential treatment of gram-positive infections.
A new incubator to expand the current insufficient pipeline of antibacterial drug candidates, the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator, is also in the works. The project, proposed in 2014's the National Strategy for Combating Antibiotic Resistant Bacteria, is envisioned as a home for academic institutions and start-up companies "to explore creative, early stage research ideas that could lead to development of new antibacterial drugs or therapies."
Whether current efforts to move the most promising early stage research in academic circles to market can get the traction they'll need to achieve more than the often incremental progress made so far remains an open question. While volumes have been written about ways to push antibiotic development forward, there often seems to little economic fuel to pull it ahead as well.
"I think that, at the national level, some kind of soul searching needs to take place," said Mobashery.