How can a healthy ocean improve human health and enhance wellbeing on a rapidly changing planet?

The rich biodiversity of the ocean holds enormous opportunities for enhancing human health and wellbeing through providing new medicines and new biotechnologies. Our ability to realise these opportunities is, however, entirely dependent on the health of the ocean.

The biodiversity of the ocean is currently under threat. Unless humanity takes urgent action to protect this biological diversity, more marine species will be lost, the genetic and biological secrets these organisms hold will be gone forever, and their potential benefits for human health and wellbeing will never be realised.

Actions to sustainably, ethically and equitably explore, preserve, and manage marine biodiversity have high potential to yield new medicines and novel biotechnologies to the benefit of human health and wellbeing.

Benefits of marine biodiversity for human health

The ocean is home to an incredible diversity of life. Of the 42 currently recognised biological phyla (major groupings of living organisms), over 80 percent exist only in the ocean (Katona et al. 2023). These species dwell in an astonishing variety of ecosystems. The organisms that live in the ocean have evolved unique chemical, physical and behavioural adaptations that are seen nowhere else on Earth and hold enormous promise for humanity.

Marine organisms have had far more time to adapt to their environment than most terrestrial species, and thus have had more opportunity to acquire unique genetic traits and develop a wide array of metabolic and chemical adaptations (Voser et al. 2022). There is great likelihood that biotechnological remedies for a wide range of problems can be found within the traits expressed by marine organisms (Carroll et al. 2023).

Study of the distinctive features of marine life has already resulted in scientific breakthroughs, new knowledge and a range of useful products that have improved human health and wellbeing (from alternative pain medications to micronutrients that can prevent chronic diseases to super-strong composite materials) (see Rotter et al. 2021 for a comprehensive list). These advances have translated into thousands of new jobs in marine biotechnology, biomedicine and drug discovery. They have generated many millions of dollars per year in revenue; the market for marine-derived pharmaceuticals alone is currently valued at $4.1 billion and is anticipated to reach $9.1 billion by 2033 (Fact.MR 2023). Until now, these advances have primarily benefitted those living in the Global North (in particular multinational corporations), and little benefit has been returned to the low- and middle-income countries (LMICs) where many of these discoveries originated (Blasiak et al. 2018).

If new biotechnology, medical and pharmaceutical products are to continue to come from the ocean and the ocean economy is to continue to grow, we must have the wisdom and the courage to build cross-sectoral, cross-national partnerships that preserve the ocean and prioritise human health and wellbeing. These collaborations will effectively conserve and manage the rich biological diversity of the ocean and ensure the sustainable and equitable use of marine resources by all people and for future generations.

Key opportunities for human health

Medicines from the sea

An estimated 30,000 unique molecules, about 10 percent of all currently known natural products, have been discovered in marine life (including marine bacteria, fungi, fish and invertebrates) (Lindequist 2016). These materials have myriad potential applications in biomedicine and biotechnology. To date, 23 approved pharmaceutical agents have been developed from marine molecules, and an additional 33 are in clinical trials and development (Antunes et al. 2023). They have been used already for treatment of inflammation, immune system disorders, skin pathologies, infectious diseases and cancers (CHEMnetBASE n.d.; Pascual Alonso et al. 2023).

As an example of unique marine molecules, Plitidepsin (a molecule derived from the sea squirt, Aplidium albicans (Milne Edwards 1841)) has been used to treat leukaemia and lymphomas. During the COVID pandemic, it was found effective in a limited clinical trial of patients with severe COVID disease (White et al. 2021). Conotoxins (neurotoxins isolated from predatory cone snails) are the basis for the potent pain control medicine Ziconotide® (Safavi-Hemami et al. 2019). Case study 1 describes the successful development of anti-cancer medicines from marine cyanobacteria.

Tetrodotoxin is an example of a biologically active molecule derived from marine microalgae, among other organisms (Chau et al. 2011). A potent neurotoxin at high doses, tetrodotoxin in low doses is under investigation for its pain relief potential as a local anaesthetic agent and for treatment of chemotherapy-induced neuropathic pain and cancerrelated pain (Cerone and Smith 2021). It may also reduce withdrawal symptoms from opioid addiction (González-Cano et al. 2021).

In the foreseeable future, we can expect many more new medicines based on marine compounds. The economic potential of these compounds is vast, but only if there is equitable, ethical and sustainable exploration.

Marine green chemistry

Marine organisms hold great promise as a source of new catalysts that can be used in ‘green chemistry’, which seeks to harness natural catalysts (e.g. enzymes) and their processes to produce the chemical reactions currently performed by conventional ‘brown chemistry’ (the latter often based on persistent and polluting chemicals derived from fossil carbon).

Marine catalysts include the marine cellulases, which break down cellulose (e.g. wood), the most abundant organic compound on the planet. Other marine microbial enzymes have been discovered that may be able to degrade microplastics (although the toxic plastics additives are still a challenge) (Zhai et al. 2023).

These materials are of considerable interest because of their potential to generate green bioproducts with applications in medicine, energy, food chemistry and agriculture (Navvabi et al. 2022).

CASE STUDY 1. Anti-cancer medicines from marine cyanobacteria

Cyanobacteria (‘blue green algae’) are an ancient group of organisms that arose on Earth some 2 billion years ago. Some cyanobacteria are abundant producers of biologically active substances, and some predators of cyanobacteria, such as sea slugs, are able to accumulate these biologically active compounds and use them in their own defence against predators. Several cyanobacterial compounds extracted from sea slugs show great promise for the treatment of diseases such as cancer.

Source:

Authors, Seattle Genetics Inc.

DISCOVERY OF DOLASTATIN 10 AND ITS APPLICATION AS AN ANTI-CANCER MEDICINE

Dolastatin 10 (Figure CS-1.1) is a natural product originally discovered in an Indian Ocean sea slug, Dolabella auricularia (Lightfoot 1786), and produced by a marine cyanobacterium (Pettit et al. 1987; Luesch et al. 2001). Dolastatin 10 has extremely potent antitumor activity. Very limited availability in nature at first delayed its development as an anti-cancer drug, but synthesis in the laboratory has provided a large supply for continued development.

Currently six different dolastatin 10–antibody drugs are being used to treat various cancers, including lymphomas and carcinomas. A further dozen related drugs are in various stages of clinical evaluation to treat other forms of cancer.

Zero-waste industry

Products such as food supplements, fuels and nanoparticles manufactured using marine resources may generate less waste and less CO2 than those created through other manufacturing processes (Vijayan et al. 2016; Pessarrodona et al. 2023). For example, marine phytoplankton are rich sources of polyunsaturated fatty acids, especially long-chain omega-3 fatty acids (Cerone and Smith 2021). These nutritionally and economically valuable fatty acids can be harvested sustainably and can be stabilised and distributed with significantly less waste for aquacultural purposes by nanoencapsulation (Hosseini et al. 2021).

Marine microalgae have also been extensively investigated as new sources of specialty lipids, including those that can be used as energy sources (e.g. biofuels) (Maeda et al. 2018).

Biomimicry

Biomimicry is a ‘nature-based solution’ (NBS) strategy for creating new technologies based on the unique adaptations of organisms. In the context of marine biotechnology, its goal is to create ocean-inspired sustainable design solutions and environmentally friendly products. An example is an extremely strong and durable composite material with potentially multiple uses (e.g. airplanes, cars, medical devices), inspired by the helicoid layers of chitin present in the shell of the mantis shrimp (Figure 2) (Rivera et al. 2020; Xin et al. 2021).

The many uses of seaweeds

Marine seaweeds present rich opportunities for blue biotechnology. For example, Case study 2 describes the development of seaweeds into bioplastics as potentially sustainable alternatives to fossil fuel–derived plastics currently polluting the ocean (Figure 3).

Farmed seaweeds command a high value for food, cosmetic and medical purposes (Naylor et al. 2021). Marine algae are rich in essential nutrients (carotenoids, vitamins and phenolic antioxidants), and thus may help to mitigate the nutrient-poor diets of many coastal populations; these materials can be produced using socially conscious and environmentally and economically sustainable aquacultural methods, as well as through large-scale industrial production (Wells et al. 2017) (see Section 2). Large-scale seaweed production is a potential source of non-chemical agricultural fertilisers because seaweeds contain metabolites that can enhance crop growth (Nabti et al. 2017). One genus of red seaweed, Asparagopsis (Montagne 1840) is being explored as a supplement for dairy and beef cows, as it significantly reduces their methane emissions; methane from ruminant animals is responsible for approximately 15 percent of global anthropogenic greenhouse gas emissions (Roque et al. 2021; HoeghGuldberg et al. 2023).

Source:

Adapted from Xin et al. (2021).

CASE STUDY 2. Seaweeds into bioplastics

Humanity’s great and growing dependency on plastics affects not only the health of the ocean but also human health through the release of harmful synthetic chemicals and toxic pollutants at every stage of the plastic life cycle (Landrigan et al. 2023). Over 98 percent of all plastics are currently made from fossil carbon: coal, oil and gas. Global plastic production is increasing exponentially and is on track to double by 2040 and triple by 2060. Declining global demand for fossil fuels is an important driver of increasing plastic production as the fossil fuel industry pivots towards plastic production.

Bioplastics offer a transitional path to plastic reduction. Bioplastics are ‘green materials’ made with carbon-rich plant or seaweed materials that can be cultivated in a wide range of environments in many coastal regions, from the tropics to the high latitudes. Indonesia is currently a global leader in the seaweed-bioplastics industry with the recent emergence of at least two companies (EVOWARE® and Biopac®).

Bioplastics made from seaweed are potentially safer for ocean and human health than petroleum-based plastics (Figure CS-2.1). The emerging seaweed-bioplastic industry has the potential, if properly managed, to facilitate an ethical transition from harmful to environmentally friendly industrial practices (Lomartire et al. 2022).

Another approach to bioplastic production involving two French companies (ERANOVA® and Algopack®) uses two seaweed species (Ulva spp. and Sargassum spp.) that are present in huge abundance on coastal shores as a result of anthropogenic harmful practices and climate change. Harvesting them may both help resolve an emergent environmental problem and provide raw materials that replace petroleum-based plastics (Orr 2013; Orr et al. 2014).

It will be important to monitor the toxicity and the environmental fate and persistence of bioplastics to ensure that they fulfil their promise as a safer alternative to petroleum-based plastics.

Source:

Authors.

Limitations to current knowledge and future opportunities

As the ocean changes in response to human stressors and marine species are irretrievably lost, we are rapidly losing opportunities to develop knowledge of its incredible biodiversity. We have a profoundly inaccurate and incomplete understanding of the role that small bioactive compounds play in the ecology of the organisms that produce them, of how their production is controlled, and of how they might benefit humanity (Karthikeyan et al. 2022). We also have little insight into how species will adapt and potentially survive these changing conditions, which species will be lost, and which can be saved.

We have even less information concerning the DNA blueprints underlying the exceptional biodiversity of marine life. For example, only 3,300 of the 1.5 million known animal species on planet Earth, and about 220 of the approximately 27,000 known species of algae, have had the DNA of their genomes fully sequenced (Hanschen and Starkenburg 2020; Hotaling et al. 2021). There is urgent need to undertake periodic biodiversity inventories, conduct detailed biochemical investigations of adaptive traits and initiate studies of accelerated evolution, all ideally through ethical public-private partnerships. Open access to these data is essential to provide equitable, sustainable and creative development and use by all, not ownership and use by the few (Blasiak et al. 2018).

Exploration of the unanswered questions is essential if we are to be good stewards of the natural world and if we are to discover and produce adequate supplies of useful green pharmaceuticals and green chemicals to meet the needs of human society. It is not sufficient to discover new potential medicines from the ocean. We must also devise strategies to provide these medicines equitably and ethically in the amounts needed, using sustainable and costeffective methodologies.

To ensure that humanity can realise the full benefit from marine genetic resources now and in the future, we must secure sustainable access to this rich diversity of species.

A key challenge to the development of biomedical (and other marine biotechnology) products from marine organisms is the substantial time required for their development; for example, the discovery and characterisation of a potent anticancer compound from the Caribbean tunicate, Ecteinascidia turbinata (Herdman 1880), took more than 20 years of concentrated study. Since many of the most biodiverse places, such as the Malay Archipelago, are in the Global South, a further key challenge is the equitable, sustainable and ethical co-development of these products with local communities and countries.

Source:

SymbioTex n.d., with permission.

Cataloguing biodiversity and measuring biodiversity loss for adaptive and sustainable management of MPAs

Climate and other environmental change threatens the biodiversity of all life in the sea, including in biodiverse-rich areas such as many MPAs, and other areas designated as protected (Bruno et al. 2018). To ensure the effectiveness of current and future MPAs, their biodiversity must be fully characterised and high-quality monitoring data collected across both space and time (Bates et al. 2019). Adaptation strategies need to be incorporated into MPA design and management plans (including working with local communities and incorporating other effective conservation measures, or OECMs) (Gurney et al. 2021) in all ecosystems and habitat types (Wilson et al. 2020), including areas beyond national jurisdiction (Maestro et al. 2019).

Medicine discovery

Because the success rate of medicine discovery from marine life is up to four times higher than that of natural product discovery from other sources (Sigwart et al. 2021), research into the pharmaceutical properties of natural products, including medicines, from marine organisms should be intensified.

Green chemistry and zero-waste approaches

‘Green chemistry’ is nascent in its development. Bringing it to scale in industry will require investigation into the chemical processes of marine life and their ability to make bioactive compounds using enzymes.

Biorefineries utilise biomass conversion processes to produce value-added chemicals from sidestream biomass (i.e. not the main product) (Rotter et al. 2021). For instance, unused oyster shells from aquaculture facilities can be used to make building materials and biomedical scaffolds (Gheysari et al. 2019). They can also be ground up and reinjected locally into the ocean, at a small scale, to stabilise pH in aquaculture (Chilakala et al. 2019).

Transdisciplinary research and fair, sustainable development of blue biotechnologies

The innovation potential of marine resources is vast, but the realisation of this potential will require transdisciplinary international research, ranging from discovery in marine ecosystems to laboratory and industrial development to clinical and other applications (Schneider et al. 2022). To ensure that marine resources are not exploited in ways that endanger fragile ecosystems or deprive local communities and lower-income countries of resources, research in the social sciences and ethics and communication efforts to engage and involve the general public will be needed (Rotter et al. 2021).

Actions and opportunities

The challenges above can be addressed through the following five actions and opportunities.

Create governance policies to ensure sustainable use of and equitable access to ocean resources. Sustainable use of marine genetic resources in blue biotechnology will require governance policies tailored to the intricate social-ecological systems that surround the ocean. These policies must comply with ethical inter- and transdisciplinary scientific approaches, such as responsible research and innovation, and seek explicitly to protect human health and wellbeing.

Undiscovered marine genetic resources must be developed in ways that ensure fair access and equitable benefit, whether they are located in exclusive economic zones or in areas beyond national jurisdiction, consistent with the UN Agreement under the UN Convention on the Law of the Sea on the Conservation and Sustainable Use of Marine Biological Diversity of Areas beyond National Jurisdiction. These resources should not be concentrated in the hands of a small group of global corporations or nations (Blasiak et al. 2020). New collaborative policies will be needed that facilitate equitable access of LMICs to expensive equipment (e.g. research vessels), marine collections of various types, open-access scientific data (e.g. databases) and expertise.

Create and support digital DNA libraries containing the genetic blueprints for most marine life. Several national and international collaborative projects are undertaking the enormous task of developing digital knowledge of the underlying genetic blueprint for all life on the planet. As noted by the Earth BioGenome Project (n.d.), the compelling rationale for these endeavours is ‘to revolutionise our understanding of biology and evolution; to conserve, protect and restore biodiversity; [and] to create new benefits for society and human welfare.’

These coordinated and collective global efforts, such as the Earth BioGenome Project (n.d.), the International Barcode of Life Consortium (n.d.) and the Darwin Tree of Life Project (n.d.), need stable international funding by a consortium of nationstates. It is conceivable that the DNA blueprints saved by these projects could even be used to ‘resurrect’ species that go extinct.

Support ethical startup companies making equitable and sustainable marine-based biotechnology products.
To move ocean-inspired discoveries from the beach and the lab bench to the marketplace requires transdisciplinary expertise and significant capital. Government incentives and programmes are needed to support and encourage the funding of marine biotechnology start-up companies and other coordinated collective efforts that embrace ethical, equitable and sustainability policies. The amounts of these investments will be dwarfed by the societal and economic benefits procured: long-term growth potential, job creation and valuation of marine species and the environment.

Improve funding for equitable and sustainable marine medicine discovery research that connects biodiverse low-income countries with wealthy ones. Much marine life remains unstudied for its potential to yield valuable resources, especially in regions where scientific infrastructure is not well developed. Equitable and ethical international research partnerships should connect biodiversityrich regions with those having high scientific capacity, promote scientific training, build capacity, follow good stewardship practices and abide by international standards recognising the inherent rights of all countries and all their people to their genetic resources. These should receive broad financial support. Such investments have the potential to advance both the scientific development in LMICs and the attainment of the UN SDGs.

Prioritise development of marine-based processes and products that are socially relevant, economically sustainable and environmentally friendly. Assessment of the published literature by expert bodies can identify promising processes and products (e.g. new antibiotics). Impacts of such products must be considered in a balanced way, taking into full account policies, needs and negative results and unintended consequences.