What lies underneath: Conserving the oceans’genetic resourcesJesús M. Arrietaa,1, Sophie Arnaud-Haondb, and Carlos M. DuarteaaDepartment of Global Change Research, Institut Mediterrani d’Estudis Avançats, Consejo Superior de Investigaciones Científicas (CSIC)-Universitat de les Illes Balears (UIB), 07190 Esporles, Mallorca, Spain; and bInstitut Français de Recherche sur la Mer (IFREMER)-Department“Etude des Ecosystèmes Profonds” - DEEP, Centre de Brest, BP 70, 29280 Plouzané Cedex, France

Edited by Steven D. Gaines, University of California, Santa Barbara, CA, and accepted by the Editorial Board August 10, 2010 (received for review October29, 2009)

The marine realm represents 70% of the surface of the biosphere and contains a rich variety of organisms, including more than 34 of the 36living phyla, some of which are only found in the oceans. The number of marine species used by humans is growing at unprecedented rates,including the rapid domestication of marine species for aquaculture and the discovery of natural products and genes of medical andbiotechnological interest in marine biota. The rapid growth in the human appropriation of marine genetic resources (MGRs), with over18,000 natural products and 4,900 patents associated with genes of marine organisms, with the latter growing at 12% per year,demonstrates that the use of MGRs is no longer a vision but a growing source of biotechnological and business opportunities. Thediversification of the use of marine living resources by humans calls for an urgent revision of the goals and policies of marine protectedareas, to include the protection ofMGRs and address emerging issues like biopiracy or benefit sharing. Specific challenges are the protectionof these valuable resources in international waters, where no universally accepted legal framework exists to protect and regulate theexploitation of MGRs, and the unresolved issues on patenting components of marine life. Implementing steps toward the protection ofMGRs is essential to ensure their sustainable use and to support the flow of future findings of medical and biotechnological interest.

marine protected areas | marine reserves | natural products | gene patents | law of the sea

The protection of marine areas tomanage fisheries in a sustainablemanner has been in place forcenturies, since Polynesian cul-

tures closed areas to fishing to protectbreeding grounds and allow recovery fromoverfishing (1), but the usefulness of no-take areas was conclusively demonstratedby the recovery of fish stocks in World WarII mine fields in the North Sea closedto fisheries (2). Marine protected areas(MPAs) have since emerged as key instru-ments to protect fish stocks and other livingresources from overexploitation (3) andhave expanded to exceed 5,000 locations,covering about 0.7% of the oceans (4).The advent of biotechnology has broad-

ened human use of biological resources farbeyond food to include other valuableproducts, such as flavors, fragrances, en-zymes, and medicines. Although terrestrialplants have been used as medicines formillennia and still support the needs of80% of the world population (5), the useof marine biological resources for pur-poses other than food is now blooming.The discovery of organisms containingmolecules and genes of commercial in-terest is growing in parallel to the explo-ration of marine biodiversity. Historically,MPAs have been set up for the conserva-tion of general marine biodiversity or forthe preservation of fisheries resources (6),but the increasing use of marine speciesas sources of genetic resources calls fora reassessment of the scope of MPAs toinclude the protection of these keyemerging resources.Here, we report on the accelerating rate

of discovery of marine genetic resources

(MGRs) and the associated emergingchallenges for the shared use of the oceansand the conservation of the resources theycontain (7). We do so based on the ex-amination of patterns in the use of marineorganisms to derive natural productsand gene-associated patents, using dataderived from inventories of natural prod-ucts (SI Text) and data extracted fromGenBank (8), respectively. We then dis-cuss the need to regulate the use of theseemerging marine resources and the lead-ing role that MPAs could have in theprotection of MGRs.

Marine Biodiversity and the Ocean’sBounty of Genetic ResourcesMarine species make up about 9.7% oftotal named species (9) (Table 1), a pro-portion comparable to the share of re-search effort on biodiversity allocated tomarine systems (10) and the fraction ofmarine species among those describedeach year (9). However, the most surpris-ing discoveries in biodiversity in the pastdecades have taken place in marine sys-tems, including the discovery of a wholeecosystem based on chemosynthesis inhydrothermal vents in 1977 (11); the de-scription of a previously unnoticed meta-zoan phylum, the Loricifera, discovered in1983 (12); and the discovery in the 1980sof the marine phototrophic prokaryoteProchlorococcus, which turned out to bethe most abundant photosynthetic organ-ism on Earth (13). Recent coordinatedinternational efforts, such as the Census ofMarine Life (14) and the World Registerof Marine Species (15), are propelling thegrowth of the inventory of named marine

organisms at a rate of 0.93% per year (Fig.1A). This growth is dwarfed by a rapidincrease in the inventory of marine naturalproducts and genes of commercial interestderived from bioprospecting efforts. Thenumber of natural products describedfrom marine species is growing at a rate of4% per year (Fig. 1B and Table 1), whichis much faster than the rate of speciesdiscovery, because many species yieldmultiple natural products. Indeed, about18,000 natural products have been re-ported from marine organisms belongingto about 4,800 named species (16) sincethe initial reports in the 1950s.The growth of patents that include genes

of marine origin is even faster. The patent(PAT) division of GenBank (8) (release165) lists more than 5 million records ofDNA sequences deposited in differentpatent offices worldwide. Most of these se-quences belong to a few selected species,mainly humans, pathogens, and model or-ganisms. Although the patent inventory inGenBank is not exhaustive, the reportedsequences include DNA from 3,634 namedspecies. This register includes 4,928 non-redundant marine gene sequences derived

Author contributions: J.M.A., S.A.-H., and C.M.D. designedresearch; J.M.A. and S.A.-H. performed research; J.M.A.and S.A.-H. analyzed data; J.M.A. wrote the programs;and J.M.A., S.A.-H., and C.M.D. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission. S.D.G. is a guesteditor invited by the Editorial Board.1To whom correspondence should be addressed. E-mail:txetxu@imedea.uib-csic.es.

This article contains supporting information online atwww.pnas.org/lookup/suppl/doi:10.1073/pnas.0911897107/-/DCSupplemental.

18318–18324 | PNAS | October 26, 2010 | vol. 107 | no. 43 www.pnas.org/cgi/doi/10.1073/pnas.0911897107

from 558 distinct named marine species(Table S1). Since 1999, the number of ma-rine species with genes associated withpatents has been increasing at an impressiverate of about 12% species per year, whichis more than 10 times faster than the rateof description of marine species (Fig. 1A).This is, however, an underestimate, because

cloning and sequencing techniques allowdescription and patenting of genes of spe-cies yet to be named or even discovered.The 18,000 marine natural products

reported in Table 1 comprise about 10%of total natural products known (17),which is in good agreement with the shareof marine species in the total inventory

of named species (Table 1). In contrast,the proportion of named marine specieswith genes included in patents (28%) farexceeds the contribution of marine or-ganisms to the total inventory of namedspecies (10%) (Table 1). Wild marinespecies used as source of natural productsoutnumber by up to 18-fold those everdomesticated, while the number of spe-cies included in patent applications isgrowing almost 4 times faster than thenumber of domesticated marine species(18) (Fig. 1). Thus, appropriation ofMGRs is progressing much faster than thealready impressive rate of domesticationfor aquaculture (19).

Taxonomic Provenance of MGRsThe taxonomic origin of MGRs covers theentire breadth of the Tree of Life, fromArchaea to vertebrates (Fig. 2 and Fig. S1),in contrast to the limited taxonomic rangeof domesticated species. Although thebulk of the Earth’s metabolic diversity re-sides in prokaryotic organisms (18), natu-ral products of marine origin are almostentirely (97%) derived from eukaryoticsources. The reason for this apparentparadox is that marine natural productshave been mostly derived from large ses-sile organisms, which are easily collectedand provide relatively large amounts ofbiomass for screening of natural products.Sponges alone are the source of 38% of allreported marine natural products, fol-lowed by cnidarians (20%), tunicates(under Chordata, 20%), and red algae(Rhodophyta, 9%). However, a majorprokaryotic contribution is compatiblewith these estimates, because a significantfraction of sponge biomass, for example, iscomposed of symbiotic microbes, whichare increasingly identified as the source ofthe secondary metabolites contributing thenatural products attributed to their host(20, 21). The share of marine naturalproducts of microbial origin may expandrapidly in the future, as demonstrated bythe 600% increase in the number of ma-rine natural products of microbial originreported in 2007 relative to the averagefigure for the period 1965–2005 (22).The taxonomic provenance of the ma-

rine sequences in patents is quite different

0

200

400

6004,000

5,000120,000

140,000

160,000

domesticated

as source of gene patents

described

as source of MNP

A

numberofspecies

1980 1990 2000 20100

5,000

10,000

15,000

20,000

0

2,000

4,000

6,000

natural products described

distinct sequences patented

B

Year

Accumulatedumberofmarine

naturalproducts

Accum

ulateduniqueofgene

sequencesofmarineorigin

Fig. 1. (A) Time course of the accumulated number of marine species described (black line), those do-mesticated for food (red line), those having sequences associated with patents in GenBank (blue line), andthe total number of species reported as sources of natural products in the marine realm by 2006 (greencolumn). Note the broken scale along the y axis. (B) Accumulated number of distinct natural products(green line) and sequences associated with patents reported in GenBank (blue line) over time.

Table 1. Number of described species, species source of patents, and percentage of described species resulting in patents for marineand terrestrial environments

Described species (15, 61) Patented species (8)Percentage of described species

being a source of patents

Total Terrestrial Marine Total Terrestrial Marine Total Terrestrial Marine

Prokaryotes 7,928 7,173 755 1,619 1,401 218 20.42% 19.53% 28.87%90.48% 9.52% 86.53% 13.47%

Eukaryotes 1,800,000 1,653,045 146,955 2,019 1,679 340 0.11% 0.10% 0.23%91.84% 8.16% 83.16% 16.84%

Total 1,807,928 1,660,218 147,710 3,638 3,080 558 0.20% 0.19% 0.38%

Arrieta et al. PNAS | October 26, 2010 | vol. 107 | no. 43 | 18319

SPECIA

LFEATURE:PERSPECTIV

E

from that of marine natural products, be-cause more than a third (39%) of themarine species in the PAT division ofGenBank are prokaryotes (bacteria andArchaea), contributing 42% of the marinegenes included in patents, in contrast to theample dominance of eukaryotes among themarine species domesticated for food orused to derive natural products. Moreover,the percentage of described species beinga source of patents is much larger for pro-karyotes as compared with eukaryotes forboth terrestrial and marine organisms(Table 1). Chordates (mainly fish), mol-lusks, and cnidarians are the major eukary-otic sources of gene sequences in patents,contributing, respectively, 17%, 15%, and

9% of the marine species yielding patentedgene applications (Fig. 2 and Fig. S1).

Applications and Prospects for MGRsMarine ecosystems are particularly suitedfor bioprospecting. Our survey indicatesthat marine species are about twice as likelyto yield at least one gene in a patent thantheir terrestrial counterparts (Table 1),and it is estimated that the success rate infinding previously undescribed activechemicals in marine organisms is 500 timeshigher than that for terrestrial species (23).The applications of genes of marine

organisms patented thus far range widely,with a prevalence of applications in thepharmacology and human health (55%),

agriculture or aquaculture (26%), food(17%), or cosmetics (7%) industry and anemerging and growing number of applica-tions in the fields of ecotoxicology, bio-remediation, and biofuel production (Fig.3). Many of the patents are related to theproduction of enzymes and other reagentsfor molecular and cell biology applica-tions (29%) and to the genetic engineering(modification) of organisms (48%).Current applications of patents associ-

ated with genes of marine origin are mostlybased on a few specific properties of ma-rine organisms. About 8% of the patentsrelate to the use of polyunsaturated fattyacids, which are present in high quantityand diversity in marine organisms. Theseare components of dietary supplementsthat deliver health benefits to humans andcan alleviate a broad range of diseases (24).Another major cluster of marine patentsinvolves fluorescent proteins with appli-cations in biomedical research and celland molecular biology (25). Their impor-tance is illustrated by the 2008 Nobel Prizein Chemistry awarded to Shimomura,Chalfie, and Tsien for the discovery anddevelopment of GFPs, originally describedfrom the jellyfish Aequorea victoria. Manyof the patents are associated with genesof marine organisms inhabiting extremeenvironments, such as hydrothermal ventsand polar oceans. The adaptation of en-zymes of hydrothermal vent organisms tovery high operating ranges of temperature(>80 °C) and pressure (>100 bar) allowthe use of these “extremozymes” in thetransformation of substrates of biotech-nological interest to proceed under theharsh conditions imposed by some in-dustrial processes. Applications of ther-mophilic and barophilic (pressure-loving)enzymes include the liquefaction of starchfor biofuel production, the use of inteinsfor the safe production of toxic proteins,and the use of thermostable enzymes inmolecular biology (26). Marine organismsfrom polar areas are the source of psy-chrophilic (cold-loving) enzymes, whichpresent high activity at low temperatures.These enzymes allow processing of heat-sensitive substrates and products, such asfood, or the avoidance of expensive heatingsteps in some processes. Some applicationsof psychrophilic enzymes include the useof proteases, amylases, and lipases in theformulation of detergents active at lowtemperatures or the use of cod pepsins forthe production of caviar and descaling offish. Other applications of cold-adaptedenzymes include proteases for meat ten-derizing or for the efficient skinning ofsquid and the use of β-galactosidases for theelimination of lactose from milk (27).The blooming of marine patents and

patent applications associated with MGRsis largely a result of recent technologicaladvances in exploring the ocean and the

Archaea

Bacteria

Stramenopiles

Other protists

RhodophytaV

iridiplantaeFungi O

ther

met

azoa

Porif

era

Cnid

aria

Chorda

ta

Echinodermata

Mollusca

Arthropoda

177

1481

400

0

643 32 5

1815

0

563

116

287 16 2

19 4 0 134

4 0

211

850 48

642

1

94

356

121

301

6 4

83445 84

285739

with one or more patented DNA sequences

with one or more described natural products

domesticated

Number of described marine species

,

Fig. 2. Phylogenetic affiliation of marine species as sources of DNA sequences in patents, naturalproducts, and domesticated for food. Bar lengths correspond to the percentage of species in eachtaxonomic group relative to the total number of species for that particular use (natural products, se-quences, or domesticated). The numbers show the actual number of species.

Human

hea

lth

Genet

ic e

nginee

ring

Molecular

and ce

ll bio

logy

Agricultu

re &

aquac

ulture

Food indust

ry

Cosmet

ics

Enviro

nmen

t

Biote

chnolo

gies

Biore

med

iatio

n

Biofu

el0

20

40

60

Application

%of

pate

nts

Fig. 3. Synthesis of the uses proposed in the claims or description of 460 patents deposited at the In-ternational Patent Office and associated with genes isolated in marine organisms. Because each patentclaim can belong to several categories, the sum is larger than 100%.

18320 | www.pnas.org/cgi/doi/10.1073/pnas.0911897107 Arrieta et al.

genetic diversity it contains. Advances intechnologies for the direct observation andsampling of the deep ocean, includingthe development of submersibles and re-motely operated vehicles, opened the deepand hitherto unexplored areas in the highseas to bioprospecting. Parallel develop-ments in molecular biology, including high-throughput sequencing,metagenomics, andbioinformatics, are greatly acceleratingour capacities to explore and make use ofthe genetic resources of the ocean, evenbefore the source organisms are discoveredin some cases. The continued improvementin these technologies is facilitating the hu-man appropriation of the genetic resourcesof the oceans, which is already evident in thevery rapid growth of patents that includegenes and natural products of marineorganisms presented here (Fig. 1B).Bioprospecting of marine resources only

requires the collection of a very limitedamount of biomass for the initial geneor product discovery. Therefore, bio-prospecting does not generally involvethreats to biodiversity comparable to thelarge biomass removals involved in har-vesting of marine resources for food (28).This is especially true for gene finding,where a small amount of biomass canprovide enough DNA for endless replica-tion by cloning or PCR. However, in thecase of natural products, when a promisingdrug candidate is found, a second moresubstantial harvest may be needed to col-lect the several grams needed to test thedrug’s suitability in clinical studies. Ex-amples of these needs for large biomasscollections are the anticancer drug ectei-nascidin 743, obtained from the tunicateEcteinascidia turbinate (1 g in 1,000 kg wetweight), the cytostatic halichondrin BfromLissodendoryx sp. (300mg in 1,000 kg)(29), or the bryostatins from the bryozoanBugula neritina (1.5 g in 1,000 kg) (30).Although total synthesis of these substan-ces has been successfully demonstrated, itwas deemed economically unviable (29),resulting in the need for large collections ofwild biomass. A survey on the feasibility ofLissodendoryx sp. harvests revealed thatonly small quantities of this sponge can becollected despite its relatively good pop-ulation recovery after dredging. On theother hand, more than 12,000 kg ofB. neritina, enough to support all pre-clinical and clinical trials, were recoveredfrom docks and pilings where this foulingorganism is commonly found, with no de-tectable impact on the populations (30).These results demonstrate the need forcareful assessment of the impact of har-vesting and the capacity of the species forpostharvesting recovery before attemptinglarge biomass harvest. Although theselarge collections may be feasible at the re-search stage, successful launch of any ofthese substances as therapeutical agents

would require a few kilograms per year ofthe active principle. Matching such de-mand would require harvesting about 106–107 kg (31) of the corresponding organism,which is clearly unsustainable, given theirlimited distribution. However, commercialextraction of wild resources may be possi-ble in some instances. The pseudopterosinsfound in the Caribbean octocoral Pseu-dopterogorgia elisabethae are used in thecosmetic industry for their antiinflam-matory and analgesic properties. Largewild harvests of P. elisabethae, estimated at13–20 tons per year, have been conductedin the Bahamas for over a decade (32).The successful exploitation of these octo-corals has been made possible by a combi-nation of two factors: (i) a carefulcollection strategy that involves manuallyclipping part of the coral and allowing thecentral branches to recover for 2–3 y and(ii) regulation by means of an exportlimit set by the Bahamas Department ofMarine Resources (32).Wild harvests of marine organisms are

undesirable from a conservational point ofview because it is not always possible topredict their impact accurately. Anyway,many of these large biomass collections canbe avoided when alternative productionschemes are developed. Cost-effectivecommercial scale production in aquacul-ture has been demonstrated for E. turbi-nate, B. neritina, and several sponges (31).Moreover, a dinoflagellate symbiont ofP. elisabethae has been found to be thesource of pseudopterosin (33), and bryos-tatins have recently been attributed to anuncultured bacterial symbiont of B. ner-itina, indicating that production in simplemicrobial cultures may be possible in thefuture. Also, the limitations in the supplyof halichondrin B have been resolved bythe synthesis of simplified artificial ana-logues (34). These developments indicatethat the exploitation of scarce MGRscan be pursued in a sustainable mannerwith little impact on the populations ofthe source organism in many cases.Many potential sources of genes and

natural products become available everyyear, because the rate of discovery of pre-viously undescribedmarine species remainshigh (Fig. 1A). A complete inventory ofmarine species may require a further 250–1,000 y at current rates of discovery (9),projecting opportunities for discovery ofMGRs well into the future. The prospectfor unique findings is huge, particularlyin the microbial realm, as illustrated byrecent studies reporting 1.2 million previ-ously undescribed gene sequences usingcultivation-independent sequencing tech-niques on a single cubic meter of water fromthe Sargasso Sea (35) and 6 million pre-viously undescribed proteins and 811 dis-tinct prokaryotic ribotypes (a proxy forspecies) from a series of 45 surface seawater

samples (36). Impressive as they are, thesenumbers are likely gross underestimatesof the true potential for discoveries becausethe inclusion of rare and normally un-detected prokaryotes may increase presentestimates of marine microbial diversity byone to two orders of magnitude (37).

MPAs and the Conservation of MGRsVery little is known about the conservationstatus of most of the species used so faras sources of MGRs. The Red List ofEndangered Species of the InternationalUnion for Conservation of Nature (IUCN)(38), one of the foundations for de-termining and validating conservationpriorities, contains data about only 36 ofthe 340 marine eukaryotic species re-ported as a source of genes included inpatents, of which 10 appear as “data de-ficient,” 2 as “endangered,” 6 as “vulner-able,” and 7 as “near threatened.” Thus, 8of the 36 marine species assessed so farare threatened, and 7 of them are close toqualifying as threatened or likely to bethreatened in the near future. Althoughcurrent Red List coverage of marine spe-cies is biased toward fish and other largemetazoans, efforts are in progress to ex-pand coverage from the actual numberof 2,331 (38) to about 20,000 species by2012 (39), which will likely result in agreater number of threatened speciesamong those listed as a source of genesand natural products. Nevertheless, thedata shown here illustrate the need toidentify threats and determine conserva-tion priorities for MGRs.We are not aware of any conservation

measures ever taken to protect prokaryotes,which comprise a large share of the MGRsdescribed in this paper. The most extendedview is that microbes, in general, are notlikely to be endangered because of theirsheer numbers, fast growth, and potentialglobal dispersion (40, 41). However, somemicrobes are constrained to very particu-lar environments, which make them sensi-tive to the same threats faced by theirmilieu. Examples include symbiotic mi-crobes, which are likely to perish along withtheir hosts, or the obligate psychrophilesdwelling in Arctic Sea ice and its sur-rounding waters, which are unable to copewith warmer temperatures, and are there-fore threatened by global warming. Thus,some of the prokaryotes sourcing naturalproducts and genes of economic interestmay be confronting a much higher risk forextinction than hitherto assumed (40, 41).The exploitation of MGRs has the po-

tential to be a sustainable process de-livering considerable wealth and businessopportunities. The global market formarine biotechnology was estimated atUS $2.1 billion in 2002, increasing ata rapid 9.4% from the previous year (23).However, these practices will only be

Arrieta et al. PNAS | October 26, 2010 | vol. 107 | no. 43 | 18321

sustainable if based on sound in-ternationally accepted governance andconservation mechanisms, which are lack-ing as yet and must be urgently developed.Prospects are indeed jeopardized by theglobal deterioration of marine ecosystemsby direct and indirect human pressuresconducive to biodiversity loss (9, 38, 42)and the associated loss of potential geneticresources. The unresolved legal and ethi-cal issues associated with bioprospectingand the global protection of biologicalresources allocated beyond national juris-dictions also represent major obstacles forthe sustainable exploitation of MGRs.MGRs of economic interest are deemed

to be particularly abundant in biodiversityhot spots, such as coral reefs and seamounts, and in extreme environments, suchas polar and hydrothermal vent ecosys-tems. Unfortunately, coral reefs, seamounts, and marine polar environmentsare threatened. Coral reefs are experi-encing a steep global decline, which isforecasted to be aggravated further byclimate change and ocean acidification (43,44). Polar ecosystems experience some ofthe fastest warming rates on the planet,particularly in the Arctic (45), leading toa loss of sea ice and warming of seawaterabove the thresholds for psychrophilicorganisms, one of the reservoirs of usefulgenes. Sea mounts are facing increasingpressure by deep-sea fisheries, which islikely to result in high environmental im-pacts and extinctions (46). Little is knownabout the potential impacts of miningfor sulfide deposits rich in gold and othermetals located near hydrothermal ventecosystems, but they are likely to be severebecause these sites support the highestbiomass concentrations in the deep sea(46). Other future threats include gas ex-ploitation or mining near the summits ofsea mounts, ridges, and other areas wheresediment does not accumulate. Their dis-tribution often coincides with hot spotsof deep marine biodiversity, which are alsolocated on hard substrates, away fromthe typical deep sea soft sediment (46).Finally, projects of massive CO2 sequestra-tion in the sea floor, with pilot studies al-ready ongoing, also raise concern as apotential threat to deep sea biodiversity (47).As agreed at the World Summit on

Sustainable Development in Johannes-burg, a global network of MPAs should beeffective by 2012. There are ongoing effortsto reach an international consensus onthe scientific criteria and guidelines un-derpinning this network. Also, the Con-ference of Parties to the Convention onBiological Diversity (CBD) (48) has re-cently made a significant step towardachieving this goal by adopting scientificcriteria for identifying ecologically or bi-ologically significant marine areas in needof protection and designing representative

networks of MPAs (49). These criteriaare well suited for the protection of MGRsbecause they target, among other things,the protection of rare, vulnerable, natural,or extreme environments and diversityhotspots. MPAs with general conservationgoals are suitable for the preservation ofMGRs because they target both knownand yet to be discovered species. How-ever, there is a perception of an inherenttrade-off between conservation and othergoals, such as fisheries management,which must be addressed (6). Although nosingle MPA design is likely to providethe perfect conditions for the preservationof all species, the emerging evidence in-dicates that carefully designed MPA net-works are probably the best tool to meetboth fishery and conservation goals (6).Although the scientific aspects involved inexpanding and networking marine reservesare moving forward, the economic andgovernance structures required for theglobal protection of marine biodiversityremain ill-defined.At the present state, MPAs encompass

an area 10-fold lower than that of terres-trial protected areas (4), with most of theseareas located within economic exclusivezones (EEZs) under national jurisdictions.However, 65% of the ocean lies beyondthe EEZs, including many of the potentialhot spots for MGRs, such as sea mountsand hydrothermal vents, which are mainlydistributed in areas beyond national juris-diction, thereby lacking a global gover-nance framework to ensure their pro-tection. Regarding the international wa-ters outside the EEZs, the first article ofthe United Nations Convention on theLaw of the Sea (UNCLOS) (50) definesthe “area” as “the seabed and ocean floorand subsoil thereof, beyond the limitsof national jurisdiction,” thereby clearlydistinguishing it from the water columnreferred to as “high seas” in the areasbeyond national jurisdiction. Freedom ofthe high seas is warranted under conditionsof part VII of the Convention. Cooperationis also promoted for the conservation ofliving resources, research, and resource ex-ploitation in the high seas, with govern-ments being responsible for activities ofships carrying their country flag. Althoughmany MGRs are extracted from benthicorganisms, part XI of the UNCLOS dedi-cated to the area is clearly restricted tothe exploitation ofmineral resources, underthe management of the International Sea-bed Authority. The conservation of MGRsin the area can only be addressed by theInternational Seabed Authority under theframework of mineral exploitation, whichwill thereforemanage limited and scatteredprotection zones in the area beyond na-tional jurisdiction, such as the one beingimplemented for nodule mining in theClarion–Clipperton zone (51).

On a more global scale, the GeneralAssembly established a United Nations“Open-Ended Informal Consultative Pro-cess on Oceans and the Law of the Sea,”with an “Ad-Hoc Open-Ended InformalWorking Group” to study issues relating tothe conservation and sustainable use ofmarine biological diversity and geneticresources beyond areas of national juris-diction (52, 53). Despite the establishmentof regional fisheries management organ-izations, about two-thirds of fish stocks areeither depleted or overexploited (54);therefore, there is a growing need to establishhigh seasMPAs for theprotection offisheriesresources (55) that converges with the needfor protection of general biodiversity, in-cluding MGRs. In addition, the imple-mentation of high seas MPAs covering thewater column, the sea floor, or both, andtargeting specific environments, such as seamounts and hydrothermal vents, will benefitthe protection of MGRs in areas beyond na-tional jurisdictions. Additional regulations,such as the requirement for environmentalimpact assessment of bioprospecting activi-ties, would be desirable in some cases, par-ticularly when large biomass collections orharsh techniques like trawling are required.However, enforcing a compulsory environ-mental impact assessment would require aninternational agreement on access and own-ership of MGRs in areas beyond nationaljurisdictions, which is currently lacking.Bioprospecting technologies are vul-

nerable to biopiracy practices, whereinindividuals or corporations from techno-logically advanced countries may securethe intellectual property of resources de-rived from unique ecosystems in de-veloping countries lacking the financial andtechnological resources to compete in thisrace. Thus, MPAs may help to reducebiopiracy by implementing clear policiesregarding the use and sharing of the ben-efits generated by the resources they pro-tect. Within national EEZs, biopiracycan be addressed by specific policies ongenetic resources clearly defining theconditions for bioprospecting and accessand benefit sharing. More explicit androbust national laws may also add to theongoing efforts of the CBD toward an in-ternational regime on access and benefitsharing that should at least apply to EEZs(56). These access and benefit sharingpolicies should also accommodate otherneeds for access, such as basic academicresearch. Increasingly difficult access pro-cedures have been reported to deter basicscientific research in the terrestrial envi-ronment (57) and could also conditionbasic marine research, biasing samplingefforts toward sites beyond national juris-dictions. Limitations to basic research onbiodiversity could be detrimental, imped-ing the collection of the data that areneeded for the implementation of the pro-

18322 | www.pnas.org/cgi/doi/10.1073/pnas.0911897107 Arrieta et al.

tection goals set by the CBD (57), partic-ularly in developing countries. This sit-uation could be eased by ensuring thetransfer of knowledge and developmenttools necessary to build the capacity toconduct research on biodiversity in de-veloping countries. Fear of biopiracy couldalso be alleviated by a clear mandate todisclose the origin of patented biologicalresources, a requirement that does notexist at present. Detailed informationabout the geographical and phylogeneticorigins of MGRs would help states tosettle disputes over intellectual propertyrights after a patent claim is made.Whereas the issue of biopiracy has beenaddressed by the CBD, this conventionapplies strictly to the resources fromEEZs, excluding the area and the highseas, which are by far the largest marinespaces to be explored and exploited, andwhere very profitable genes have alreadybeen isolated (58). The unregulated ex-ploitation of MGRs in the absence of

a universally accepted legal framework forthe protection and equitable exploitationof the genetic resources of 65% of theocean represents a 21st century techno-logically sophisticated version of the“tragedy of the commons,” affecting fish-eries in international ocean waters (59).In summary, the data reported here

portray the appropriation of MGRs asa major recent development, with a hugeprospect for scientific discovery and crea-tion of wealth during the 21st century. Theunfathomable biological diversity of theoceans offers a vast repertoire of poten-tially useful biological molecules with nocomparable equivalent in terrestrial envi-ronments (60). Most importantly, whereasthe use of marine organisms for food hasoften caused major ecological damage,the appropriation of their genetic re-sources is a potentially sustainable processbut also requires conservation measures.Realization of the ample opportunitiesfor science and business in the oceanic

realm requires (i) halting the widespreadloss of marine biodiversity, for whichMPAs are key instruments, and (ii) theurgent development of international leg-islation regulating the conservation ofthese resources as well as access andbenefit sharing for the vast economic andsocial benefits still to emerge. More spe-cifically, high and deep seas MPAs must becreated and international laws explicitlyregulating the use and protection of bi-ological resources beyond EEZs must beurgently agreed on for the effective pro-tection of the vast pool of marine bio-diversity and MGRs yet to be discoveredin the in the high seas and the area.

ACKNOWLEDGMENTS. We thank Sara Teixeira fortechnical help and Joël Querrelou and Elie Jarm-ache for useful discussions. This is a contribution tothe MALASPINA 2010 project, funded by theCONSOLIDER-Ingenio 2010 program of the SpanishMinistry of Science and Technology (ReferenceCSD2008-00077).

1. Johannes RE (1978) Traditional marine conservationmethods in Oceania and their demise. Annu Rev EcolSyst 9:349–364.

2. Beverton R, Holt S (1957) On the Dynamics of ExploitedFish Populations (Chapman & Hall, London).

3. Committee on the Evaluation, Design, andMonitoringofMarineReservesandProtectedAreas intheUnitedStates,Ocean Studies Board, National Research Council (2001)Marine Protected Areas: Tools for Sustaining Ocean Eco-system (National Academy Press, Washington, DC).

4. United Nations Environment Programme (UNEP) and In-ternational Union for Conservation of Nature (IUCN).World Database on Marine Protected Areas (WDPA).Available at http://www.wdpa-marine.org/#/countries/about. Accessed October 23, 2009.

5. Cragg GM, Newman DJ (2001) Natural product drugdiscovery in the next millennium. Pharm Biol 39:8–17.

6. Gaines SD, White C, Carr MH, Palumbi SR (2010) MarineReserves Special Feature: Designing marine reserve net-works for both conservation and fisheries management.Proc Natl Acad Sci USA 107:18286–18293.

7. Marra J (2005) When will we tame the oceans? Nature436:175–176.

8. Benson DA, Karsch-Mizrachi I, Lipman DJ, Ostell J,Wheeler DL (2008) GenBank. Nucleic Acids Res 36(Database issue):D25–D30.

9. Bouchet P (2006) The Exploration of Marine Diversity:Scientific and Technological Challenges (FundaciónBBVA, Bilbao, Spain), pp 31–62 (in Spanish).

10. Hendriks IE, Duarte CM (2008) Allocation of effort andimbalances in biodiversity research. J Exp Mar Biol Ecol360:15–20.

11. Corliss JB, et al. (1979) Submarine thermal springs onthe galapagos rift. Science 203:1073–1083.

12. Kristensen R (1983) Loricifera, a new phylum withoschelminthes characters from the meiobenthos. ZZool Syst Evol 21:163–180.

13. Chisholm SW, et al. (1988) A novel free-living pro-chlorophyte occurs at high cell concentrations in theoceanic euphotic zone. Nature 334:340–343.

14. Convention of Biological Diversity (2010) Census ofMarine Life. Available at http://www.coml.org/. Ac-cessed October 24, 2009.

15. WoRMS—World Register of Marine Species. Availableat http://marinespecies.org/. AccessedOctober 24, 2009.

16. Blunt JW, et al. (2008) Marine natural products. NatProd Rep 25:35–94.

17. Dunkel M, Fullbeck M, Neumann S, Preissner R (2006)SuperNatural: A searchable database of available nat-ural compounds. Nucleic Acids Res 34 (Database issue):D678–D683.

18. Trüper HG (1992) Prokaryotes: An overview withrespect to biodiversity and environmental impor-tance. Biodivers Conserv 1:227–236.

19. Duarte CM, Marbá N, Holmer M (2007) Ecology. Rapiddomestication of marine species. Science 316:382–383.

20. Piel J (2004) Metabolites from symbiotic bacteria. NatProd Rep 21:519–538.

21. Thoms C, Schupp P (2005) Biotechnological potentialof marine sponges and their associated bacteriaas producers of new pharmaceuticals (part I). J IntBiotechnol Law 2:217–220.

22. Blunt JW, et al. (2009) Marine natural products. NatProd Rep 26:170–244.

23. Venugopal V (2008) Marine Products for Healthcare:Functional and Bioactive Nutraceutical Compoundsfrom the Ocean (CRC Boca Raton FL), 1st Ed.

24. Bergé J, Barnathan G (2005) Marine Biotechnology I(Springer, Berlin), pp 49–125.

25. Mocz G (2007) Fluorescent proteins and their use inmarine biosciences, biotechnology, and proteomics.Mar Biotechnol (NY) 9:305–328.

26. Adams MW, Perler FB, Kelly RM (1995) Extremozymes:Expanding the limits of biocatalysis. Biotechnology (NY)13:662–668.

27. Cavicchioli R, Siddiqui KS, Andrews D, Sowers KR (2002)Low-temperature extremophiles and their applica-tions. Curr Opin Biotechnol 13:253–261.

28. Hunt B, Vincent ACJ (2006) Scale and sustainability ofmarine bioprospecting for pharmaceuticals. Ambio 35:57–64.

29. Proksch P, Edrada-Ebel RA, Ebel R (2003) Drugs fromthe sea-opportunities and obstacles.Mar Drugs 1:5–17.

30. Pomponi SA (1999) The bioprocess-technological pot-ential of the sea. J Biotechnol 70:5–13.

31. Mendola D (2003) Aquaculture of three phyla ofmarine invertebrates to yield bioactive metabolites:Process developments and economics. Biomol Eng 20:441–458.

32. Goffredo S, Lasker HR (2008) An adaptive manage-ment approach to an octocoral fishery based on theBeverton-Holt model. Coral Reefs 27:751–761.

33. Newberger NC, Ranzer LK, Boehnlein JM, Kerr RG (2006)Induction of terpene biosynthesis in dinoflagellatesymbionts of Caribbean gorgonians. Phytochemistry 67:2133–2139.

34. Towle MJ, et al. (2001) In vitro and in vivo anticanceractivities of synthetic macrocyclic ketone analogues ofhalichondrin B. Cancer Res 61:1013–1021.

35. Venter JC, et al. (2004) Environmental genome shotgunsequencing of the Sargasso Sea. Science 304:66–74.

36. Yooseph S, et al. (2007) The Sorcerer II Global OceanSampling expedition: Expanding the universe of pro-tein families. PLoS Biol 5:e16.

37. Sogin ML, et al. (2006) Microbial diversity in the deepsea and the underexplored “rare biosphere.”. ProcNatl Acad Sci USA 103:12115–12120.

38. International Union for Conservation of Nature (2010)IUCN Red List of Threatened Species. Available athttp://www.iucnredlist.org/. Accessed October 25, 2009.

39. Polodoro B, et al. (2008) Status of the World’s MarineSpecies (IUCN, Gland, Switzerland).

40. Staley JT (1997) Biodiversity: Are microbial speciesthreatened? Curr Opin Biotechnol 8:340–345.

41. Weinbauer MG, Rassoulzadegan F (2007) Extinction ofmicrobes: Evidence and potential consequences. En-danger Species Res 3:205–215.

42. Jackson JBC (2008) Colloquium paper: Ecologicalextinction and evolution in the brave new ocean.Proc Natl Acad Sci USA 105 (Suppl 1):11458–11465.

43. Carpenter KE, et al. (2008) One-third of reef-buildingcorals face elevated extinction risk from climatechange and local impacts. Science 321:560–563.

44. Intergovernmental Panel on Climate Change (2007)Climate Change 2007, the IPCC Fourth AssessmentReport. Availableathttp://www.ipcc.ch/publications_and_data/publications_and_data.htm. Accessed October 25,2009.

45. ACIA (2004) Impacts of a Warming Arctic (CambridgeUniv Press, Cambridge, UK).

46. GloverAG, SmithCR (2003) Thedeep-seafloor ecosystem:Current status and prospects of anthropogenic changeby the year 2025. Environ Conserv 30:219–241.

47. Metz B, Davidson O, de Coninck HC, Loos M, Meyer LA(2005) IPCC Special Report on Carbon Dioxide Captureand Storage: Prepared by Working Group III of the In-tergovernmental Panel on Climate Change (CambridgeUniv Press, Cambridge, U.K.).

48. Convention of Biological Diversity (1993) Conventionon Biological Diversity. Available at: http://www.cbd.int/convention/convention.shtml. AccessedMarch 24, 2009.

49. Convention of Biological Diversity (2007) CBD-EBSAs:Ecologically and Biologically Significant Areas. Availableat http://www.cbd.int/doc/meetings/mar/ewbcsima-01/information/ewbcsima-01-ewsebm-01-02-en.pdf. AccessedOctober 26, 2009.

50. UnitedNations (1982)Conventionon theLawof theSea.Available at: http://www.un.org/Depts/los/convention_agreements/texts/unclos/unclos_e.pdf.

51. Smith CR, et al. (2007) Preservation Reference Areas forNodule Mining in the Clarion-Clipperton Zone: Rationaleand Recommendations to the International SeabedAuthority. Workshop to Design Marine Protected Areasfor Seamounts and the Abyssal Nodule Province in PacificHigh Seas (University of Hawaii, Manoa, HI).

52. Zewers KE (2007) Bright future for marine geneticresources, bleak future for settlement of ownership

Arrieta et al. PNAS | October 26, 2010 | vol. 107 | no. 43 | 18323

rights: Reflections on the United Nations law of the seaconsultative process on marine genetic resources. LoyU Chi Intl L Rev 5:151–176.

53. United Nations (2009)United Nations Open-Ended In-formal Consultative Process Accessed October 28, 2009Available at http://www.un.org/Depts/los/consultative_process/consultative_process.htm.

54. Cullis-Suzuki S, Pauly D (2010) Failing the high seas: Aglobal evaluation of regional fisheries managementorganizations. Mar Policy 34:1036–1042.

55. United Nations Environment Programme-World Conser-vation Monitoring Centre (2008) National and regional

networks of marine protected areas: A review of progress.Available at: http://www.unep-wcmc.org/marine/pdf/MPA%20report%20FINAL.pdf.

56. Convention on Biological Diversity (2010) Negotiations ofthe International Regime on ABS. Accessed June 14, 2010.Available at http://www.cbd.int/abs/ir/.

57. Martinez SI, Biber-Klemm S (2010) Scientists—Takeaction for access to biodiversity. Curr Opin EnvironSustain 2:27–33.

58. Vierros M, Hamon G, Leary D, Arico S, Monagle C (2007)An Update on Marine Genetic Resources: ScientificResearch, Commercial Uses and a Database on Marine

Bioprospecting (United Nations, New York) AccessedAugust 25, 2008. Available at http://www.ias.unu.edu/resource_centre/Marine%20Genetic%20Resources%20UNU-IAS%20Report.pdf.

59. Dietz T, Ostrom E, Stern PC (2003) The struggle togovern the commons. Science 302:1907–1912.

60. Newman DJ, Cragg GM (2004) Marine natural productsand related compounds in clinical and advancedpreclinical trials. J Nat Prod 67:1216–1238.

61. Euzèby J. (2009) List of prokaryotic names with standingin nomenclature. Available at http://www.bacterio.cict.fr/number.html. Accessed October 29, 2009.

18324 | www.pnas.org/cgi/doi/10.1073/pnas.0911897107 Arrieta et al.