Drugs from the Sea

Some trawl the ocean for fish, but marine bioprospectors trawl for microbes.

Matthew Braga

Matthew Braga

Frobisher Bay, Nunavut. Image: Rod Brazier/Flickr

A single gram of sediment might contain a billion bacterial cells. Each one of those cells might contain 100 molecules—and if you're lucky, one of those molecules might hold the secret to a new generation of lifesaving drug.

The chances of finding the right molecule on the right grain of sand are infinitesimally small, of course, but not impossible. About two-thirds of FDA approved antibiotics trace back to natural products such as these, and the majority of antibiotics used on humans come from molecules found in actinomycetes, a single bacterial group.

In fact, the hunt for these molecules is a whole scientific field.

"Very simplistically, if we can find new members of this group of bacteria—from, say, arctic sediment—then we may be able to isolate new natural products produced by these bacteria," said Russell Kerr, a Canada Research Chair in Marine Natural Products, and a professor at the University of Prince Edward Island. "The hope [is] that these natural products will have potential as antibiotics or anti-cancer drugs, and other applications such as nutraceuticals and cosmeceuticals."

This process is known as bioprospecting, and according to Kerr, it's one of the oldest sciences around. Bioprospectors such as Kerr are tasked with going out into the field, or sending others in their place, to collect samples of sediment, fungi and bacteria, and sifting through their spoils with the hopes of finding molecules that, hopefully, can be of some medical use. The practice isn't new—people have been going out in search of barks and leaves with medicinal properties for centuries—but our techniques have certainly improved.

"There have been very very few studies done in these remote but very pristine parts of the world," said Dr. Kerr

Kerr is no ordinary bioprospector, either. He's a marine bioprospector, a more recent vintage of bioprospecting that has emerged in recent decades as marine research, exploration, technologies, and techniques have improved. He visits oceans and lakes and wet aquatic areas, and hunts for molecules of note.

"We know much more about microbes from terrestrial habitats than we do about marine habitats, but I think it's quite clear that there is much more microbial diversity in the oceans than there is on land," Kerr told me. His speciality is the Arctic.

"There have been very very few studies done in these remote but very pristine parts of the world. So we've had some really exciting discoveries of very new bacteria and fungi from our polar samples, our samples up in Nunavut," said Kerr.

While it's tempting to think that warmer, more temperate regions would be home to far more microbial life than the harsher extremes of the Canadian North, Kerr says that's just not the case. The diversity of microbes is about the same—but their characteristics just differ. That means the types of natural products and potential medicines we can find in the Arctic might be different, too.

Marine bioprospectors collect samples about as you might expect. Divers go down to the bottom of oceans, lakes or rivers—or researchers wade into shallow waters or crouch over dampened areas—and take a few scoops. Kerr has been collecting sediment samples in Nunavut from Frobisher Bay south of Iqaluit to the northern corners of Hudson Bay, as well as areas in between, since 2010. In this case, a team of local Inuit partners from Nunavut Tunngavik Inc. (NTI), in association with Nunavut Research Institute, have been working with Kerr to send back samples from some of these sites.

If this sounds simple, well, it's really only the start of the bioprospecting process. As the "prospecting" part of the name probably implies, bioprospecting is naturally pretty risky. There's no guarantee there will be anything useful in any of the myriad scoops a researcher collects—and much more often than not, there's nothing. At Simon Fraser University in British Columbia, department of chemistry associate professor Roger Linington is trying to take some of the guesswork out of this process.

Linington, a Canada Research Chair in Chemical Biology, has been working on methods to make our analysis of sediment and ocean extracts more efficient, so that we'll have better chances of finding useful molecules, and find them more quickly, too. His process involves a combination of new screening and analytics tools his team is developing that can not only identify all the molecules in an extract, but predict which molecules might be most apt for further study.

"It's not that difficult to find new chemistry, but to find significant new chemistry is quite a lot harder," Dr. Roger Linington explained

Linington's team recently looked at all the published literature on new molecules from the past 75 years. They found that the number of discoveries has increased dramatically, from less than 100 new molecules per year in the 1950s and 1960s, to around 1,700 per year since the new millennium—and that's just molecules found within the marine bioprospecting world.

"But if you look at the novelty index of those compounds, how many of those compounds are very similar to things found before, and how many of them are really really new and interesting scaffolds, you find that the rate of novelty has decreased as the number of compounds per year being published has increased," Linington explained.

"This is, perhaps, not a surprise," he added. "But it means that, of those 1,700, quite a lot of those molecules bear strong resemblance to things already in the literature, so this sort of further highlights how important it is to have smart tools for doing the discovery part. Because it's not that difficult to find new chemistry, but to find significant new chemistry is quite a lot harder."

Indeed, while Kerr's team has had lots of promising leads in Nunavut, they haven't found anything that has been suitable enough to be turned into a pharmaceutical. That part is hard.

"You want a natural product that kills [superbugs] but isn't toxic to human cells," Kerr explained. "We get excited when we see a new molecule with great activity against one of these super bugs, but [...] quite often these molecules you find are just nasty toxins. They're toxic to bacteria, but they're also pretty toxic to us, so those get triaged pretty quickly."

But although they haven't found any pharmaceuticals, Kerr's team has had luck finding a potential cosmeceutical, which is being commercialized through Nautilus Biosciences Canada, Inc., a company that he also owns. Importantly, any revenues from the commercialization of Arctic bio-products found will be shared with the University of Prince Edward Island's Inuit partners at NTI.

"We have discovered a fungus from a sediment sample in Canada's Arctic that produces some very interesting antifungal agents that have very real applications in the personal care product industry, so cosmeceuticals," Kerr explained. "So a series of patents are being filed and licensed, and there's a very good reason to believe a product might come out of this in a year or two."

Meanwhile, the molecule hunt continues; the next big antibiotic or cancer-fighting drug could just come from the sea.