Modern medicine may be at home in the laboratory, but it is born of the natural world. From aspirin to rapamycin, it is the small molecules found in the herbs, microbes and wild substances that form the basis of our medicines cabinet.
Although the biopharmaceutical industry still looks to pick up promising natural molecules in partnership with research institutes once much of the legwork has been done, most big pharmaceutical companies eschew research into natural compounds, preferring rational drug discovery and computer-aided drug design.
There are many reasons behind this strategic decision, several of which are explored in this week’s feature. But for illustration, in its library of over 2 million molecules, GlaxoSmithKline has only 12,000 natural products. Meanwhile, Merck donated its entire natural product library to the Institute for Hepatitis and Viral Research in 2011 so it could focus exclusively on vaccines and synthetic compounds. Merck says that this will bring products to the market more rapidly.
Natural product experts argue that strategies devised by business minds are the reason that industry is not investing in natural compounds. If this criticism is justified it would seem industry is undervaluing the wealth of resources outside the lab. The vast libraries of random synthetic molecules have yielded a grand total of one approved drug, sorafenib, licensed for the treatment of certain liver, kidney and thyroid cancers. And even using new techniques, synthetic molecules do not have the structural complexity that can be found in natural products honed over millions of years of biological binding.
One big problem in natural products, however, is rediscovery of the same molecules from many samples. Accessing and identifying novel natural products takes some clever science and is labour intensive. Nonetheless, while industry has shied away from this challenge, with the notable exception of Novartis, academic researchers have embraced it.
NovoBiotic, a spin-off from Northeastern University, for example, has invested in technology that allows it to cultivate bacteria that couldn’t previously be grown in the laboratory (it is estimated only around 1% of bacteria have been grown in the lab). In January 2015, it identified a novel bacteria that produces a new antibiotic, teixobactin, with little detectable resistance. A big win in the fight against antimicrobial resistance.
Another natural product success story is the small Spanish pharmaceutical company, PharmaMar. It specialises in finding drugs from marine sources to treat cancer. PharmaMar’s drug, Yondelis (trabectedin), is marketed for relapsed ovarian cancer and has just been fast-tracked by the FDA for treatment of soft tissue sarcoma and the company has three more drugs in phase I, II and III clinical trials.
Perhaps it is time for industry to take heart from these small but significant successes and go and get its hands dirty once again.