Some of the world’s most used medicines were directly inspired by compounds found in nature. Morphine, for example, was first extracted from opium in a pure form in the early 1800s, and Taxol, one of the most-used cancer drugs, is based on compounds originally isolated from the bark of the Pacific yew tree. Aspirin is one of the oldest nature-inspired drugs, modifying from compounds discovered in willow tree bark.
Natural products are still crucial to drug discovery today. According to a 2012 study, up to 50% of drugs approved in the last 30 years were directly or indirectly sourced from nature. But for drug companies, the 1990s was the height of their interest in "bioprospecting," or looking in nature for potential new drug compounds.
"Most companies have greatly reduced their natural product departments, and it’s mainly because of the cost and time that it takes to do this properly," says Eduardo Esquenazi, founder of a San Diego-based startup that aims to fill this gap. "What we try to do is remove both those components, or at least reduce them greatly."
The company, called Sirenas, is focused on hunting for new drugs in the ocean, where organisms have evolved nuanced, unique chemistries for competing, communicating, and defending themselves over hundreds of millions of years of evolution. "The chemistry in the ocean—we’re just scratching the surface of understanding it," says Esquenazi.
About four times a year, Sirenas divers go out to remote locations and collect sponges, cyanobacteria, and algaes and bring them back to the lab in San Diego. They catalogue each of their compounds and screen them against different diseases, such as cancers or—now with a new grant from the Bill and Melinda Gates Foundation—neglected diseases like malaria, tuberculosis, and cryptosporidium. Using heavy data-crunching software, Sirenas mines the results and selects the best drug candidates. The last and perhaps hardest step is to then synthesize that natural molecule in the lab, a job led by Sirenas cofounder and 2013 MacArthur Foundation Fellow Phil Baran.
Sirenas partners with drug companies to triage its research and focus on the most promising compounds. The company, only founded four years ago, hasn’t licensed any of its work yet, but it has had early successes. On a trip to a salt pond in Chile’s remote Atacama desert, it found a novel antimalarial molecule that Esquenazi says "works in a completely new, very potent way." Still, it is a complicated molecule that is very costly to produce, so it’s future remains to be seen.
Only a few other companies have focused on marine-based drug discovery, the best known of which is Spain-based company PharmaMar, which harvests the ocean for cancer drugs. And Seattle Genetics has an approved biologic anticancer drug on the market made partly from a synthetic version of a marine-derived compound. Esquenazi says Sirenas is focused on harnessing the explosion of computational resources, artificial intelligence, and data mining that could allow it to make discoveries much faster than in the past.
The World Health Organization says that more than 1 billion people today suffer from one or more neglected diseases. With the $775,000 Gates Foundation grant, Sirenas will focus on finding new molecules that could offer treatments. As it is today, pharmaceutical companies tend not to pursue these drugs. With these diseases affecting the poorest nations, it’s difficult to make a profit, so nonprofits and governments step in.
[All Photos: via Sirenas]