Our vision is a more targeted approach to explore, identify and obtain what marine biodiversity can provide to biotechnology, medicine and disease prevention, while demonstrating the critical importance of marine biodiversity and its protection.
The ocean is the last great frontier of planetary discovery, with up to two-thirds of marine species still to be discovered. With so much still unknown, the unique diversity of the marine environment is the largest untapped source of chemical compounds and other biotechnological products including food supplements, enzymes, and biomaterials such as artificial bone from corals and silica, chitin, and collagen from sponges. With species extinction increasing at a rate unprecedented in human history (IPBES, 2019) it is critical to describe and protect marine biodiversity as soon as possible to promote a healthy and resilient ocean and to ensure conservation of these environments, as well as the provision of ecosystem services for human health into the future.
The quest for new drugs is more urgent than ever before due to the rise in antibiotic resistance(1), and marine organisms are important in providing new chemical diversity for the drug development pipeline. While more than 34,000(2) molecules of pharmaceutical or cosmetic interest have been discovered (Blunt et al., 2018) there are only 10 pharmaceutical products(3) of marine origin currently on the market, including four anti-cancer drugs and one anti-viral drug (Collins et al., 2019; Jaspars et al., 2016; Mayer, 2012). There are a further 28 drugs in clinical trials globally. There are several challenges in bringing marine-derived compounds to market, including very high costs and a time investment of approximately 20 years. The vast majority of these compounds are synthetically produced since there are major technical difficulties in sustainably supplying enough biomass from marine organisms to scale up production of target compounds, which generally exist in very small quantities in nature (Newman, 2016), although new –omics tools are opening up possibilities. While there is a tendency to focus on the discovery of new treatments for the most prevalent health conditions such as cancer and HIV, marine organisms offer unique genetic resources with potential to also treat rare diseases (Bhatia & Chugh, 2015) that typically receive limited attention (Sharma et al., 2010).
Although only small quantities of biological resources are harvested, the exploration of the ocean for new biotechnological products often involves environmental disturbance with potentially adverse effects, particularly in highly sensitive ecosystems such as coral reefs or the deep sea. Access to biological resources within exclusive economic zones (EEZs) of countries is regulated and near-shore collections typically fall under national regulations, requiring environmental impact assessments and permits, and imposing collection limits. There are however no regulations for bioprospecting in areas beyond national jurisdiction, including the majority of the deep sea. As such, it is important to use caution and to establish appropriate regulations for bioprospecting.
Biobanks, such as the European Blue Biobank(4), enable the storage of biological specimens and facilitate sustainable access to marine biodiversity. They are an important component of the biodiscovery pipeline and can be consulted as part of a bio-prospecting campaign. If used properly, these infrastructures can help reduce over-collection of the same species. Biobanks can be an approach to conserve biodiversity, but they need to be expanded to become a more comprehensive representation of marine biodiversity and to not only represent cultivatable marine organisms.
A targeted approach to biodiscovery is needed to maximize the chances of finding specific compounds of interest. This calls for improved knowledge of marine chemical and molecular ecology to enable the identification of promising sites and organisms. Sites of interest may include extreme or unique environments such as the deep sea or coral reefs, ‘blue zones’, highly stressed or polluted areas, or areas with high competition between species. Organisms to focus on include sessile species that depend on ‘chemical warfare’ for their survival, and specific organisms in which the majority of marine-derived compounds have previously been discovered (i.e. invertebrates, algae and marine microorganisms). There is a need for close collaboration between the marine science, biotechnology, medical and pharmaceutical communities to streamline the biodiscovery process and share expertise. Previous and current collaborative projects have demonstrated this can be successful e.g. FP7 and Horizon 2020 projects SPECIAL(5), BluePharmTrain(6), PharmaSea(7), MarPipe(8) and TASCMAR(9).
Interest in marine species also extends beyond compounds purely for medication and treatments. Marine biodiversity is also important in fundamental biological research, e.g. green fluorescent protein (GFP) first isolated from jellyfish is used extensively in cell and molecular research, and the molecular basis of memory was discovered in sea slugs. Marine species have specific adaptations, patterns of behaviour and lifestyles that may present beneficial applications in human health and well-being. To enable this exploration into the future, the protection of the marine environment and its biodiversity should be guaranteed. Trawling prohibitions and the protection of coral reefs and the deep sea by increasing the extent and number of marine protected areas (MPAs) are examples of positive actions that could be incentivized by the OHH community.
Biotechnology research accounted for 46% of the original research identified through the SOPHIE literature and evidence review(10). However, biotechnology research is time and resource intensive so the numbers of research articles alone are not necessarily representative of the extent to which marine compounds have been investigated. The majority of this research relates to the development of supplements and other applications for marine-derived omega-3 fatty acids.
Outstanding questions not yet fully answered by current research include:
- What are the fundamental links between healthy, biodiverse marine environments and human health?
- How can we best demonstrate the importance of preserving marine biodiversity, ecosystem functioning and ecosystem services for ensuring human health?
- Where should we look for species with a high likelihood of possessing compounds or properties of medical interest?
- How can we overcome challenges in the sustainable supply of target organisms and compounds in order to scale up production of useful products?
- What can marine biodiversity contribute to fundamental biomedical research and bioinspired applications for human health and well-being?
In order to achieve our biotechnology and medicine vision, there are three key research questions that need to be addressed:
A better understanding of marine ecosystems is needed to enable a more targeted approach to biodiscovery in the ocean. Continued research on how, why and where marine organisms produce bioactive compounds and other products will improve the identification of habitats and species that will contain products useful for human health. This should take into account threats to marine biodiversity in a holistic manner to account for ongoing and future shifts in the abundance and distribution of marine species due to both human pressures and climate- and global change.
Continued development of new technologies is needed to overcome bottlenecks in the marine biodiscovery pipeline. These include -omics technologies, culture methods, advanced screening techniques, chemical synthesis techniques, and synthetic biology approaches. Improved fundamental knowledge is needed for species from which medically relevant products originate and of the environmental conditions under which they are produced, in order to facilitate scaling up of products under controlled conditions. An interdisciplinary approach is needed, drawing on expertise from marine scientist, chemists, molecular and synthetic biologists, pharmaceutical scientists, and SMEs.
Research is needed on the unique characteristics of marine species and applications to fundamental biomedical research and bioinspired applications that sustainably benefit human health and well-being.
The research questions identified in this vision should be dealt with in parallel. The second question – of how to bring the communities together for a strategic approach – will support the more technical aspects of the other two questions, but all three are intrinsically linked and involve multiple sectors with significant innovation potential.
The links between this vision and policy are complex, as this topic spans various different policy and ethics fields.
On the health and medical side, the marine biodiscovery pipeline is by necessity heavily regulated, with safety considerations meaning that the burden of proof of a compound’s efficacy and safety is significant. The European process is concisely outlined by the European Medicines Agency (2016), and similar processes are used by the US Food and Drug Administration (FDA). Of note, environmental sustainability is an important but underemphasized aspect of this pipeline, and the marine science community could provide additional input and advice.
The marine side of this topic is less regulated in comparison. At the European level, the Marine Strategy Framework Directive(11) (MSFD) implicitly discusses biodiversity protection and the extraction of resources without harming the ecosystem, and promotes the ecosystem-based approach to management. Extraction of resources is more directly covered by the European Biodiversity Strategy(12) and the Strategic Plan for Biodiversity 2011-2020(13) (including the Aichi Biodiversity Targets), and in the EU 2030 Biodiversity Strategy which is currently under development. However, there is also competence within the Maritime Spatial Planning Directive(14), the Integrated Maritime Policy(15) and Habitats Directives(16), as well as the Blue Growth Strategy(17). What is needed from the OHH research community is to develop a wider understanding of how these policies complement each other and where there may be gaps. Scientific input will also be required to provide greater understanding of the importance of marine biodiversity to ocean health, and of the links between healthy and diversely populated marine environments and healthy humans.
Internationally, the Nagoya Protocol(18) on Access to Genetic Resources and the Fair and Equitable Sharing of Benefits Arising from their Utilization (ABS) is a supplementary agreement to the Convention on Biological Diversity(19). The EU is a signatory to ABS and hence has strict regulations to ensure compliance. Member States must in turn ensure compliance in relation to sampling for marine compounds and put in place provisions that require licenses to sample within their EEZs (Lallier et al., 2014). This should ensure fair and equal benefit from these resources. The process leading towards an international legally binding instrument under the United Nations Convention on the Law of the Sea(20) on the conservation and sustainable use of marine biological diversity of areas beyond national jurisdiction (BBNJ) began in 2014 and is still ongoing. In order to achieve the vision set out in this topic, these marine policy and governance gaps will need to be addressed, and will require OHH research community input.
The public is concerned about biodiversity loss. More than 14,000 European citizens in the SOPHIE survey(21) ranked loss of marine species as 3rd out of 16 potential threats. Marine species and wildlife protection gained most support (ranked 1st out of 16) as an area to receive more research funding in order to better understand their public health and well-being implications. Many of the bottom-up innovative initiatives(22) in the SOPHIE inventory addressed the loss of biodiversity, indicating that local stakeholders and citizens are motivated to protect biodiversity.
In terms of biotechnology specifically, citizens felt that medicines derived from marine organisms were good for the economy and for human health and well-being, and neutral for the environment. However, support for funding more research into marine biotechnology and its implication for public health and well-being was ranked 14th out of 16. This may indicate a need for greater public awareness about what marine biotechnology actually is, and where and how these compounds are and could be used. It may also indicate a prioritization of other challenges such as biodiversity conservation. This needs to be further investigated and understood.
Protection of the marine environment (including biodiversity and all marine life) was the most frequently cited priority category by participants in the citizen deliberation survey and workshop(23). Citizens also identified the need to find balance between human actions and marine protection: Without a balanced natural marine environment no benefits can follow – get back to nature, man is part of nature. However, citizens surveyed made no reference specifically to the importance of medicine from the sea or potential biotechnical benefits from marine species, etc., again suggesting that this is not yet an area widely discussed in public discourse – greater awareness-raising is required. Societal stakeholders responding to an equivalent survey did however identify marine biotechnology to advance synergies between oceans and human health as a priority area.
The SOPHIE inventory of innovative initiatives(24) showed that citizen science is a popular and feasible approach to collect data about marine biodiversity and at the same time raise awareness and enjoy marine spaces.
However, the narrative between biodiversity and health (medical/biotech benefits) is poorly developed. ‘Medicine from the sea’ and the broader category of nature-based solutions from the ocean are not well developed in mainstream media, and are therefore not in the public consciousness. As highlighted above, this indicates a need to increase awareness of the medical and other benefits that are linked to marine species and the marine environment, and what could be lost if marine biodiversity is not appropriately ‘valued’ and protected.
Within the research community, it would be beneficial for students specializing in one part of the pipeline to be more aware of how the full system works sustainably, where compounds come from, how they are scaled up for production, and how they are trialled for approval. This will require dedicated interdisciplinary courses and opportunities for interaction.