Blue Biotechnology Rises From Below

Bacteria can be killed with bleach or a biocide, but those options have their environmental drawbacks. Unilever thinks it has an effective and benign alternative in a halogenated furanone that the red seaweed Delisea pulchra generates on its exterior. Unlike traditional chemicals, the furanone doesn’t kill bacteria. Instead, it interferes with their communication, preventing them from informing one another that they should adhere to a dirty surface.

It’s an example of how novel compounds found in marine organisms can be useful when applied in the human environment. Unilever is not the only one plumbing the oceans for solutions. Companies developing all manner of drugs, functional foods, cosmetics, and specialty chemicals are interested in the fruits of oceanic organisms big and small.

Natural products chemists have been prospecting marine organisms for novel compounds for a long time, and numerous drugs and cosmetics have resulted from such efforts. For example, polysaccharides from carrageenan seaweed are widely used to thicken foods. Yondelis, a cancer drug from the Spanish firm PharmaMar, comes from a marine animal called the tunicate. Despite such activities, however, scientists have tested only a small percentage of the 1 million marine organisms and 1 billion marine microbes that the Census of Marine Life estimates are in existence.

Several industry-academia consortia have emerged in Europe with the goal of making marine, or blue, biotech more accessible. Goals include standardized tests for microbes, systems for cultivating microbes in the lab, and bioinformatics for handling large volumes of data. Consortia are also sharing the cost of collecting large numbers of organisms for testing. With such initiatives under way, many European scientists are confident the field has a bright academic and commercial future.

A key focus for PharmaSea, a consortium that emerged in 2013 with 24 partners from academia and $13 million in European Union funding, is to identify microbes containing bioactive compounds that are potential drug leads or ingredients for foods or cosmetics.

The consortium is building a library of 2,500 microbes, of which 45% will come from partners’ collections and the remainder from new samples. From these sources it aims to generate a library of 18,000 extracts, and from there several hundred novel druglike compounds. So far PharmaSea has developed two drug leads.

PharmaSea’s members are attempting to develop standardized approaches so they can share test protocols, according to Meredith Lloyd-Evans, a member of PharmaSea’s executive committee who was one of several marine biotech consortia members to speak recently at a workshop in Reims, France.

In one screening test being developed by PharmaSea members, marine-derived bioactive isolates are evaluated for their effects on zebrafish larvae using automated video analysis, Lloyd-Evans said at the Reims meeting. Of PharmaSea’s 24 partners, 18 are extracting molecules, but all have different ways of evaluating them. A standard test would reduce evaluation costs, he said.

PharmaSea and other blue biotech consortia also want to ensure that the microbes their members find can be cultivated. “A potential problem may be that you get them out of the ocean but then can’t grow them in the lab,” Lloyd-Evans said.

MaCuMBA, an EU-funded consortium of 23 partners, aims to improve the growth efficiency of marine microorganisms by applying methods such as cocultivation of interdependent organisms and high-throughput procedures that mimic natural conditions. “Of the 10⁹ different microbes in the ocean, 99% have not been cultured or are considered ‘unculturable,’ ” said Lucas J. Stal, a professor of marine microbiology at the University of Amsterdam who is a coordinator for MaCuMBA.

MaCuMBA plans to source 10,000 target organisms from the oceans, from which it will identify 2,000 industrially interesting strains.

How to handle the large volume of data being generated by MaCuMBA and other marine biotech groups is a challenge being taken by Micro B3, an initiative started in 2012 with 32 industrial and academic partners.

The partners are developing bioinformatics that integrate marine data with research on microbial biodiversity and functions. The project aims to facilitate the whole process—from sampling and data acquisition to analysis—leading to better understanding of marine ecosystems and commercial applications, said Johanna B. Wesnigk of the Environmental & Marine Project Management Agency, which manages the Micro B3 project for Jacobs University in Bremen, Germany.

As academic groups explore the ocean for the public good, companies are going there for profit. For example, Croda, a specialty chemical firm based in Goole, England, has already dipped a toe into marine biotech and begun to reel in the commercial benefits.

The firm produces a range of cosmetic ingredients based on marine organisms. One example is Venuceane, the active ingredient sold by the firm’s subsidiary Sederma for use in antiaging creams. It is derived from a strain of Thermus thermophilus, a bacterium found 2,000 meters down in the ocean near thermal vents.

Douglas Cossar, research manager for Croda Europe, sees opportunity to develop other products, such as skin-hydrating cosmetics that emulate the water retention properties of species found in marine intertidal zones. These species have evolved to survive in both direct sunlight and water.

“There are a lot of things we can look for in the marine environment that have commercial potential,” Cossar said.

But marine biotech can also be expensive. “With specialty chemicals, the market won’t bear huge costs such as it will in pharmaceuticals, so we have to go by the backdoor, if you like, by forming collaborations and by outsourcing R&D as much as possible,” Cossar cautioned.

Cost-cutting collaboration can happen outside industry as well. In 2011, the governments of the U.K. and Norway forged a pact to share their expertise and have since embarked on a series of joint development projects. Converting fishery waste rather than fossil fuels into useful products is a key driver for the partnership.

An example is a project to convert up to 7,000 tons per year of crab waste, which currently costs $95 per ton to dispose of, into useful chemical products. With funding from the U.K. and Norwegian governments, U.K.-based innovation and marketing firm Pennotec and Norwegian ingredient maker Seagarden have developed a process for converting the waste into organic acid and chitin by fermenting it along with sugars.

Other European firms are also seeking to create high-value materials from marine organisms. Jellagen, a start-up based in Pembroke Dock, Wales, is developing a process for converting jellyfish harvested in the nearby Atlantic Ocean into medical-grade collagen for bone and wound treatments. Advantages of the approach are that it is low cost and avoids health or religious concerns associated with the mammalian-sourced collagen used now.

In the spring, Jellagen secured early-stage funding of $870,000 from angel investors and the Welsh government. It recently won a $160,000 grant from the government agency Innovate UK to fund a 12-month R&D project for improving the efficiency of collagen extraction from jellyfish, said cofounder and Chief Executive Officer Andrew Mearns Spragg.

Unilever, for its part, has established a lab in Liverpool, England, to screen organisms, including those sourced from marine environments, for functionality. Neil Parry, head of biotechnology science for Unilever, hopes to see his vast company develop blue biotech innovations in ever-greater numbers as part of a corporate goal of increasing sustainability.

For the D. pulchra project, Unilever is now developing a commercial furanone synthesis so it can add the compound to its low-temperature detergents and prevent black biofilms from forming in washing machines.

Unilever is also mulling other ways that it might apply marine biotech. Furanones from D. pulchra could even be coated on toilet bowls, Parry said. In recent years, Unilever has replicated an antifreeze protein from ocean pout, a polar fish, that it uses to prevent large ice crystals from forming in its ice cream and other frozen foods. “So blue biotech is not something we are afraid of,” he said.

It will be a few years yet before companies are generating a constant stream of novel products derived from marine organisms. But the first step—creating the science infrastructure to underpin this goal—is now being taken.