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Vol. LXV, No. 18
August 30, 2013
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Lecture Launches New Natural Products Interest Group

Dr. Jon Clardy

Dr. Jon Clardy

Are you interested in the scientific aspects of natural products such as herbs, fungi and dietary supplements? If so, you may wish to check out the new NIH natural products scientific interest group.

Recently, the group held its inaugural event—a talk in Lipsett Amphitheater by Dr. Jon Clardy, the Hsien & Daisy Yen Wu professor in the department of biological chemistry and molecular pharmacology at Harvard Medical School. Clardy, an NIH grantee, is a pioneering researcher on biologically active small molecules.

Natural products have transformed our understanding of biological processes and provided many important types of therapeutic agents, he said. In recent years, though, their role in biomedical discovery research has been decreasing. However, there are ways that the field could be retooled so that it is more compatible with the current discovery environment. Among the public-health needs for these kinds of small molecules are novel antibiotics, primarily to address antibiotic resistance, and antifungals for the destructive fungal and fungal-like diseases emerging in humans, animals, plants and the ecosystem.

Clardy told stories from his laboratory illustrating ways that bacteria (a particular interest of his) interact with humans and certain insects. These interactions typically are mediated by the kinds of small molecules that are logical targets of natural-product research and are relationships of mutualism, or a two-way street of benefit to both parties.

As one example, “We’re not the only ones who do farming,” Clardy said, referring to humans. “There are animals that have been doing it as a specialized form of symbiosis much longer than we have,” such as beetles, ants and termites. In their farming, they grow and/or carry bacteria that make small molecules. These small molecules combat parasites or pathogens that attack the insect or its food supply and they can also have other functions such as antibiotic, antibacterial or antifungal. The insect uses its own sophisticated chemistry in creating these molecules and “while the names and molecules change, the strategy is consistently the same.” Since there are about 6,000 species of beetles, 200 species of ants and 300 species of termites, there are many research possibilities in this arena alone.

Clardy said, “We’re not the only ones who do farming. There are animals that have been doing it as a specialized form of symbiosis much longer than we have.”

Clardy said, “We’re not the only ones who do farming. There are animals that have been doing it as a specialized form of symbiosis much longer than we have.”

“What I find interesting,” Clardy said, “is that these ideas were not thought up by scientists, but came from small molecules and were evolutionarily selected.” The trick is to find these molecules (“the known unknowns”) and their antecedent genes or gene clusters. To do so, researchers can take advantage of the widespread genomic sequencing of bacteria.

Clardy recommended expanding use of efficient, algorithmic and systematic approaches. An advantage is that, in bacterially produced natural products, the phenotype is clear. Challenges, however, include if bacteria stop their aggressive molecular activity when removed from their host or if there is horizontal gene transfer. His other recommendations included obtaining more and better bioinformatic tools, having different skill sets on a team, working on at least a fairly large scale and using high-throughput screening.

Dr. Josephine Briggs, NCCAM director, noted, “I am delighted to have NCCAM sponsor this new scientific interest group (SIG). It will help encourage the kind of dialogue between biologists and chemists that may facilitate mutual understanding and collaboration. There is an extraordinary chemical diversity out there to be captured.”

To join the SIG, email Dr. John Williamson at williamsonjs@mail.nih.gov.


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