Who Owns the Ocean? Policy Issues Surrounding Marine Genetic Resources

The rich biological diversity in the ocean, estimated to range from 0.7 to 1.0 million eukaryotic species (Appeltans et al. 2012), with millions more prokaryotic (Curtis et al. 2002) and viral (Suttle 2013) taxa, plays a vital role in the Earth's life support system. This biological diversity has also proven to be an important source of novel genes and natural products with applications in medicine, food, materials and energy, and across a wide array of bio-based industries. With much of the biodiversity in the ocean unknown, there is a great potential for discovery of new species, genes and adaptations that will further our understanding of ocean ecosystems and their function, and also support biotechnological innovation. Nowhere is the potential for discovery greater than in the realm of the microbial ocean. An estimated 95% of ocean life by weight is microscopic. On average, there are about a million bacteria and 10 million viruses in each mL of seawater. Viruses are by far the most abundant life-forms in the ocean; stretched end to end would span about 10 million light years, or further than the nearest 60 galaxies. This universe of viruses is thought to kill about 20% of the living material in the ocean each day; consequently, viruses are of great environmental significance (Suttle 2007). Moreover, they are a rich source of unknown proteins with a wide range of functions, and harbor perhaps the greatest reservoir of largely unexplored genetic and biological diversity on Earth (Yooseph et al. 2007; Suttle 2013). Even with the enormous strides that have been made in describing the diversity of viruses in the oceans through metagenomic approaches, up to 90% of the sequences recovered remain a mystery with respect to the function of the proteins they encode. (Hurwitz and Sullivan 2013). The deep sea is by far the most poorly explored area of the oceans, and has great potential for new discoveries. Many deep sea organisms have adapted to life under extreme conditions, and thus have unusual molecular and metabolic adaptations. This is particularly true of micro-organisms at hydrothermal vents, where toxic, high temperature conditions prevail, but it is also true of microbes found in the deep seabed, the water column and polar regions. Consequently, the deep ocean is a large reservoir of untapped genetic resources, some of which are of major commercial interest (Skropeta and Wei 2014). The development of pharmaceuticals, enzymes, cosmetics and other products from marine sources is not new. In fact, back in the late 1960s, chemicals from the shallow-water sponge, Tectitethya crypta, led to the development of an anti-leukemia drug, and subsequently in the 1980s, the HIV drug AZT (azidothymidine). Similarly, the venom of the cone shell Conus magus (Fig. 1) resulted in the development of a synthetic compound used in the painkiller Prialt, or ziconotide, which is used for chronic intractable pain. Antifreeze proteins from cold-water fish and other organisms are used to improve the quality of frozen foods, such as ice cream, by inhibiting recrystallization and maintaining a smooth texture. And an enzyme extracted from a microbe from the Mid-Atlantic Ridge is currently used in the development of biofuels. These are but a few examples of the wide range of uses and applications of what in environmental policy are called “marine genetic resources” (Leary et al. 2009). Some marine species that have been the source of discovery for biotechnological innovation. (a) Conus magus, which resulted in the development of a synthetic compound used in the painkiller Prialt. (b) Alvinella pompejana. A bacteria associated with this tube worm is the source of the compound Abyssine used in cosmetic cream. (c) Ecteinascidia turbinate, which was the source of the cancer drug trabectedin. (d) Tectitethya crypta, which provided the basis for development of the HIV drug AZT. Photo credits: 1a “Conus magus 001” by Richard Parker - Conus magus. Uploaded by JoJan. Licensed under CC BY 2.0 via Commons - https://commons.wikimedia.org/wiki/File:Conus_magus_001.jpg#/media/File:Conus_magus_001.jpg; 1b “Alvinella pompejana01” by National Science Foundation (University of Delaware College of Marine Studies) - http://www.nsf.gov/od/lpa/news/press/01/pr0190.htm. Licensed under Public Domain via Commons - https://commons.wikimedia.org/wiki/File:Alvinella_pompejana01.jpg#/media/File:Alvinella_pompejana01.jpg; 1c Ecteinascidia turbinate by Sean Nash, taken on April 5, 2010. https://www.flickr.com/photos/[email protected]/4526304280; 1d Tectitethya crypta by Sven Zea, taken in Sweetings Cay, Bahamas. Image from Zea, S., Henkel, T.P., and Pawlik, J.R. 2014. The Sponge Guide: a picture guide to Caribbean sponges. 3rd Edition. Available online at www.spongeguide.org. Accessed on: 2016-03-18 While there is no universally accepted definition for “marine genetic resources,” the term implies both that they are a subset of “biological resources” as defined by the Convention on Biological Diversity (https://www.cbd.int/; CBD) and that they have actual or potential value. Because the diversity of marine organisms is high and many taxa are evolutionarily ancient compared to terrestrial species, the ratio of potentially useful natural compounds is likely higher in marine than terrestrial organisms. In turn, this implies that material sourced from the marine environment is more likely to yield previously unknown biologically active chemicals that are of particular interest in the search for new pharmaceuticals and a higher probability of commercial success (Montaser and Luesch 2011). In addition, emerging “omics” techniques are facilitating the rapid discovery and characterization of previously obscure microorganisms. The growing commercial interest in marine genetic resources is not unexpected, given the rich biological diversity in the ocean, its potential for future discovery, and the enhanced possibility of commercial success with marine-sourced materials. One way to quantify these trends is to use patenting as a proxy for commercial interest. Recent research using publicly available patent databases shows that the rate of patent applications related to marine genetic material is rapidly increasing at rates exceeding 12% yr−1, with over 5000 genes derived from marine organisms already patented (Arnaud-Haond et al. 2011). Significantly, this rate is faster than the rate of discovery of new species. Yet, access to marine genetic resources is highly uneven across nations, thus raising equity concerns. More than 90% of the patents including “marine genes,” are registered with ten developed countries with the top three countries (U.S.A., Germany and Japan) holding approximately 70% (Fig. 2). This is a pattern similar to the one observed for human and plant crop genes (Arnaud-Haond et al. 2011). Accessing marine genetic resources, in particular those found in the deep seas, requires significant financial resources and sophisticated technology relating to ships and submersibles, and advanced laboratory equipment for the processing of samples. Only developed or rapidly developing countries have access to such resources, with the result that the benefits from the exploitation of the ocean are unevenly shared among nations. In addition, further advances in research leading to further commercial success will cause an ever-widening capacity gap between developed and developing countries. The blue bars indicate the number of genes patented from marine organisms by individual countries and the red bars the number of countries and their associated patents. By far, most patents are held by a few highly developed countries, while most patent-holding counties, only have a single patent. Figures are based on data from Arnaud-Haond et al. (2011), and the figure is courtesy of Sophie Arnaud-Haond, Ifremer. Progress made in exploration of the oceans has dramatically increased our ability to exploit marine resources, much faster than the rate at which corresponding societal norms and rules about environmental and ethical issues have evolved. Much of the policy debate centers on whether developing countries have the right to share in the benefits gained from the commercial application of marine organisms. Presently the answer to this question depends on where the organism is collected. If it comes from a country's Exclusive Economic Zone, then that country has the right to share in the benefits from the discovery in accordance with the Convention on Biological Diversity (CBD) and its Nagoya Protocol, which is discussed in more detail in the next section. However, if the organism comes from the 64% of the ocean that is beyond national jurisdiction, the answer is not clear, and there is currently no formal mechanism for sharing benefits. While these areas are considered to be common property owned by all countries and their citizens, the United Nations Convention on the Law of the Sea (UNCLOS), which was adopted in 1982 and entered into force in 1994, was developed when the focus was on seabed minerals and their potential exploitation. Little was known about marine genetic resources in the deep seabed, and UNCLOS does not explicitly cover them, leading to legal ambiguity. UNCLOS, often considered to be the “constitution for the oceans,” divides marine space into a number of zones, both within and beyond the limits of national jurisdiction (Fig. 3). The areas beyond national jurisdiction are divided into (1) the “high seas,” which consist essentially of the water column beyond countries' Exclusive Economic Zones, and which are subject to the largely open access regime of freedom of the sea (conditioned by an array of duties), and (2) “the Area,” which is the seabed, ocean floor and subsoil beyond national jurisdiction, and which is subject to the regime of common heritage of mankind (with explicit duties to share the economic and other benefits from marine science or the mineral resources with humankind). These regimes will be further explained below. In areas within national jurisdiction, the CBD and its provisions, in particular the Nagoya Protocol, also apply. Under the United Nations Convention on the Law of the Sea (UNCLOS) the ocean is divided into areas within and outside of national jurisdiction. While the Nagoya Protocol applies in areas within national jurisdiction, there is no applicable mechanism for access and benefit-sharing of marine genetic resources in areas beyond national jurisdiction. (Notes: “M” = nautical mile; * The outer limit of the continental shelf could extend beyond 200M, as provided for by UNCLOS article 76. Some maritime zones included in areas within national jurisdiction are not indicated in this diagram (I.e.: Internal Waters; Archipelagic Waters; Contiguous Zone). Let us first consider the coastal waters of countries, given that this is where the source materials for the early development of pharmaceuticals, such as AZT, were found. Even today, most genetic resources for commercial development are collected from within countries' national jurisdiction, and of those, the majority are terrestrial. Commonly, resources are sourced from tropical countries with high biodiversity, which, in the marine realm, include sponges, corals, sea slugs and other organisms. The countries collecting and using these genetic resources are mainly industrialized countries with the technological capacities to transform them into commercially viable products, such as pharmaceuticals, enzymes, and cosmetics. Historically, and prior to the implementation of the CBD, some developing countries have experienced “biopiracy,” particularly in regards to terrestrial biodiversity, and remain concerned that they do not receive their fair share of benefits from products that have been developed from raw materials collected from their territories. For example, there have been numerous cases of plants used as traditional medicines in a developing country being patented by researchers or pharmaceutical companies in a technologically advanced country without permission, and sometimes knowledge, of the source country. In such cases, if a product is put on the market, it is unlikely that the source country or community will see any compensation. The proponents for benefit-sharing received a boost from the 2010 adoption of the Nagoya Protocol on Access to Genetic Resources and the Fair and Equitable Sharing of Benefits Arising from their Utilization (The Nagoya Protocol) to the Convention on Biological Diversity. The Nagoya Protocol, which entered into operation on 12 October 2014, was intended to combat biopiracy. On a basic level it aims to ensure that developing nations, including communities whose traditional knowledge may have led to the “discovery,” benefit when their plants, herbs, animals, and microorganisms are used by scientists and biotechnology companies from a different country. The benefits can range from non-monetary, such as sharing of research results, capacity building and technology transfer, to monetary, mainly in the form of a percentage of royalty payments upon commercialization. The Nagoya Protocol sets out legally binding core obligations for its Parties to take the necessary legislative, administrative or policy measures in relation to access to genetic resources, benefit-sharing and compliance. While obtaining research permits for collecting samples is already a requirement in many countries, the Nagoya Protocol takes matters further by requiring access and benefit-sharing (ABS) agreements. These agreements outline the conditions for access, and stipulate the non-monetary and monetary benefits that the provider country can expect. The binding principle of the Protocol is the requirement that all countries must act to ensure genetic resources are only used in accordance with terms established by the provider. According to Article 6 of the Nagoya Protocol, the national access measures must create legal certainty, clarity and transparency; provide fair and non-arbitrary rules and procedures; establish clear rules and procedures for prior informed consent and mutually agreed terms; provide for issuance of a permit or equivalent when access is granted; and create conditions to promote and encourage research contributing to biodiversity conservation and sustainable use. While there are still uncertainties about the practicalities relating to development of ABS agreements, and the amount of red tape they might create for scientists, it is also likely that scientists will ultimately benefit from these arrangements. ABS agreements offer a way to rebuild trust in cases where that trust has been broken or eroded by previous suspicion of biopiracy, or, for example, by the results of research never being shared with the country of origin. By laying out clear rules, both the providers and users of genetic resources know what is required, and can move forward in a constructive manner. The ABS agreements also have the potential to help narrow the capacity gap between developed and developing countries by providing for training in molecular techniques, co-authorship in journal articles, and other much needed capacity building and technology transfer assistance. The positive impact that such cooperation can have on knowledge transfer and capacity building in a developing nation can be seen in Papua New Guinea (PNG). A royalty sharing agreement between The University of British Columbia (UBC) and the University of Papua New Guinea (UPNG) led to the first ever payment of royalty milestones to a developing source country from a drug development project (Raymond Andersen, UBC pers. comm.). In this case, a cancer fighting compound isolated from a sponge led to the construction of a synthetic analogue (Taltobulin) that went into clinical trials (Fig. 4). Royalty payments were used to convert dilapidated student residences into properly equipped research laboratories for Ph.D. and M.Sc. students, and provide the infrastructure to allow UPNG faculty and students to conduct research in the area. Recently, a new drug based on a compound from a PNG sponge has also gone into clinical trials; this drug is being developed by a start-up company in which both UBC and UPNG have equity. Both institutions will receive milestone royalty payments if the drug works in phase II trials and gets approved for use. These provide excellent examples of how cooperative agreements can positively affect the development of research and training in developing countries. 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