Raiding the underwater medicine cabinet: the EU’s €9.5M venture into the sea

The European Union is backing research raids in remote seas, hoping to uncover micro-organisms that can be put into service as the basis of new antibiotics that are effective against drug-resistant bacteria like MRSA (Methicillin-resistant Staphylococcus aureus).

The PharmaSea research consortium, comprising of 24 institutions and commercial groups spread across 13 countries, has EU funding of €9.5 million to plumb the depths until 2016, at which point pharmaceutical companies will be invited to help co-develop and put on the road to commercialisation any compounds found.

It is hoped that this EU investment in bioprospecting will in time feed the drugs pipeline. “Microbial marine diversity has immense application potential,” says Johanna Wesnigk, project manager of a project entitled Micro B3 - which focuses on bioinformatics and biodiversity. 

Many hardy species found underwater – often in extremes of temperature and darkness - produce chemical compounds for defence or attack. Marine organisms also have means of repairing themselves and getting rid of infections. Amongst this chemical warfare, scientists are hoping to find the medicinal raw materials they need.

Anti-cancer drugs provide an exemplar here. According to the US National Cancer Institute, one per cent of samples from marine animals tested reveal anti-tumour potential, compared with 0.01% of samples of terrestrial origin. The figures for cancer drugs are impressive, with 70% owing their origin to marine organisms.

How will Pharmasea stand out from the crowd of bioprospectors? “It’s the first time it’s all been joined together, we have every single part of the biodiversity pipeline,” said chemist and project coordinator, Marcel Jaspars of Aberdeen University. The project combines researchers from areas of marine genomics, biosynthesis, chemical structure analysis and legal experts.

Ultimately, the proof of the pudding will be how attractive the research is for industry. The history of bioprospecting is one of mixed success – striking gold is never guaranteed. In the past, industry has flinched at prohibitive costs, uncertain legal and regulatory parameters and long waiting times.

Jaspars acknowledged that industry does not always rush in. “They see the whole process as slow – to counter this, we’re trying to have a very business outlook,” he said. “To make it more attractive, we need to do it faster, we need to present timelines for completion.”

This is a boon period for European blue biotechnology, Jaspars believes. “I am getting calls from envious friends when they see the funding the EU is putting up,” said Jaspars. “I’ve also had calls from people from New Zealand, Australia and China looking to join the team,” he adds.

The perils of accessing the sea

While the number of marine expeditions has been increasing in step with the development of new technologies, it remains difficult to access remote ocean trenches.

By the end of 2010, only 17 compounds had been reported from deep ocean and ocean trench environments – a testament to the difficulty in reaching them.

PharmaSea started its life in easy waters in the fjords of Norway. After some opportunistic swipes, the next stop-off is the more demanding Peru-Chile trench in the autumn. The Kermadec off New Zealand, Izu-Bonin, off Japan and the Mariana in the Western Pacific, are also due to be explored before the end of 2016. 

When the research vessel picks its spot, dive teams send a sampling device down 8,000 feet to handpick microorganisms. Samples are taken to a lab where they are cultivated and then screened.

In addition to the difficulties of retrieving organisms at such depths, there’s competition to book specialised research vessels in the first place. “There’s only a limited number on the planet and waiting times can be between 18 months and two years,” said Jaspars.

Another thing that may cause the biotech industry to pull on its reins is the uncertain and unpredictable legal and regulatory environment.

Whilst the ocean is – as the doctrine of international law goes – the “common heritage of mankind”, and under the remit of such bodies as the United Nations Convention on the Law of the Sea (UNCLOS) and the International Seabed Authority (ISA), there is no unanimous agreement as to whether there is adequate provision for “commercial marine activities” in international conventions.

In 1991, the Convention on Biological Diversity highlighted bioprospecting as an area of concern for sustainability. “Biopiracy” is an increasingly used term among conservationists who are loath to see a gold-rush on the sea’s resources.  

Jaspars plays down any fears that PharmaSea will pillage the sea’s resources. “We take small samples and then grow bacteria from those. Once we have them, we don’t need to go back and get them again,” he said. 

Amidst uncertainty, Norway is an interesting example to watch. Kjersti Lie Gabrielsen, coordinator of the national marine biobank, says her country will soon introduce regulations on permits for sampling organisms in national waters.  

“Norway is one of the first countries to look at this,” she said. “Sustaining the treasures of the sea is very important.”

Opportunities during its lifespan

PharmaSea is financed under Horizon 2020’s predecessor, the Seventh Framework Programme (FP7) for a four-year term that ends in 2016. Within the scope of the project it is hoped to have molecules in development.

“By 2016, we hope to have a couple of compounds and have completed some preliminary animal testing,” says Jaspars. Co-developing products with a pharmaceutical company from that point on would be the ideal, he adds.

While four years may not sound like much, short timeframes are not a unique problem, notes Vangelis Papathanassiou, coordinator of the Hellenic Centre for Marine Research. “The lifespan of a research project and a policymaker is different – this is the always the problem,” he says.

“The duration is short, but if results are there, it’s reasonable to think that there’ll be some option on a second edition of funding,” said MEP Maria do Céu Patrão Neves, who has been tracking the project. “They can always apply for complementary funding from the EU too,” she added.

Although the lifespan of the project is short, the EU is hoping it will spur innovation in a high-risk field.

One study puts the cost of underwater sampling per day at a little over €20,000. The cost of going from the research to commercial product phase may be in the region of €1 billion - across a waiting time of some 15 years.

Not surprisingly then, the blue biotech field is dominated by a few countries. Ninety per cent of patents originate from ten countries, eight of which are in Europe.

On the other hand, marine discovery presents many opportunities for innovation. A veritable cottage industry of specialised companies have achieved success in developing submersibles and remotely operated vehicles, helping to advance the pace of discovery. Deep Tek, a British salvage team, is active in this field and is contributing specialist rope and winch combinations to the project effort.

EU funding picture for marine research

Financial support for marine research is being steadily ramped up by the EU and to date 31 projects have received €195 million.

For Horizon 2020, there is, for the first time, a dedicated marine and maritime competition: “Marine and maritime research and the bio economy.” The first “blue growth” call for 2014-2015 is worth €145 million.

Pharmacology is not the sole blue biotech application of interest to the EU. There are projects studying the genes of marine organisms for agriculture, food, cosmetics and industrial applications too.

Outside of blue biotech, the EU is also interested in funding aquaculture, ocean energy, coastal tourism and seabed mining projects.