Coasts and seas for human health

Headline facts

 

 

Nutritious food

The seas around Scotland have been a source of fascination and food for centuries. For example, the middens from Skara Brae, a Neolithic settlement located on the Bay of Skaill on the west coast of Mainland, the largest island in the Orkney archipelago of Scotland, contain both shells and fish bones. In addition, since the last quarter of the 18^th Century, cod liver oil has been used for the treatment of various conditions as well as being held in high regard as being nutritionally beneficial (Bull, 1890). Since the early 1970s, there has been intense scientific interest in the health benefits of fish and fish oils stimulated by the work of Dyerberg and co-workers on the incidence of coronary heart disease in native Greenland Eskimos (e.g. Dyerberg et al., 1975). Such interested and research continues today, in the 21^st Century. Scientists continue to publish research on the benefits of consuming a ‘marine’ diet highlighting the benefits of the n-3 fatty acids, especially all-cis-5,8,11,14,17–eicosapentaenoic acid (EPA; 20:5(n-3)). (e.g. Veno et al., 2019). These n-3 (sometimes termed omega-3) fatty acids are synthesised by marine plankton and are conserved in the food chain, hence their use as trophic markers in marine systems (Madgett et al., 2019).

 

The fatty acid composition of marine lipids (Figures 1 and 2), be it as a component of the fish and shellfish eaten or as encapsulated fish oils consumed directly, is more complex than those found in many terrestrial plants and animals (McGill & Moffat, 1992). The carbon chain is generally formed of 14 to 24 carbon atoms and the carbon chain may be saturated or unsaturated. The variability is associated with:

1. Fatty acid chain lengths from 14 carbons to 24 carbon atoms with an even carbon chain length predominance
2. The degree of unsaturation ranging from saturated (no carbon-carbon double bonds) to highly unsaturated molecules containing five or six carbon-carbon double bonds as exemplified by all-cis-4,7,10,13,16,19-docosahexaenoic acid (DHA, 22:6(n-3))
3. The presence of minor amounts of odd chain length and branched fatty acids

 

 

 

It is not unusual to be able to identify over 40 fatty acids in a sample of fish lipid, the number depending, to an extent, on the thoroughness of the analysis. Any data on the fatty acid composition of fish and fish oils, and thus their relevance to the diet, should take account of the recognised variations in the natural composition within species as a result of season, sex and geographic location.

Deep-sea fish, such as those caught on the shelf edge to the west of Scotland, are subject to increasing utilisation. Such fish tend to be slower growing and longer lived than fish living in the North Sea or other shallower waters around the UK. The liver of the roundnose grenadier (Coryphaenoides rupestris; Figure 3) is lipid rich, the lipid comprising essentially of triacylglycerols. The fatty acid composition is dominated (~ 60%) by monoenoic acids including hexadecenoic acid (16:1), octadecenoic acid (18:1), eicosenoic acid (20:1) and docosenoic acid (22:1). The oil from another deep water fish, orange roughy (Hoplestethus atlanticus),comprises essentially wax esters. Wax esters are found in other plants and animals as well as the microbiological community. They have a variety of functions, such as acting as energy stores, waterproofing and echo-location (Moffat, 2009). The implications for health from this variety of fatty acids has focused, as highlighted earlier, on the n-3 fatty acids, including EPA and DHA. These fatty acids are regarded as being beneficial throughout life, even during development in utero where EPA and DHA are important for neuronal, retinal, and immune function development. However, they are essential fatty acids and must be obtained through the diet. Inclusion of oily fish such as mackerel, herring, salmon, sardines or tuna, in the diet will provide both EPA and DHA; ethyl esters of the n-3 fatty acids are also available as supplements and are currently in clinical use (Blasiak et al., 2020).

 

 

 

An opportunity for discovery

The abundance and diversity of marine life extends from the viruses to the top predators including seals and seabirds. Developed over billions of years, there is a diversity of life that is characterised in the ocean genome. Ultimately, the ocean harbours unique biodiversity that dwarfs the biodiversity found on land. Many of the eukaryote (any organism whose cells have a clearly defined nucleus) marine species remain undescribed, the proportion depending on the taxon group, while even less is known about the bacteria (prokaryotes) and viruses. These are forms of marine life, be that plants, animals, fungi, bacteria or viruses, that have evolved to live in the extremes of the heat, cold, pressure, water chemistry and darkness found in the ocean. For example, the hydrothermal vents on the Atlantic Ridge exhibit high temperature gradients (up to 400ºC or more, but the water does not boil due to the pressure) and an acidic pH. They exist where photosynthesis does not occur due to the lack of light and emit high levels of toxic elements such as sulphides or heavy metals. However, far from being devoid of life, hydrothermal vents have dense and biologically diverse communities. The organisms which thrive around the vents have distinct metabolisms based on chemosynthesis. The chemosynthetic bacteria are the basis of the vent food web. They may also be responsible for the synthesis of bioactive marine natural products: an anti-inflammatory polysaccharide isolated from a deep-sea bacterium Altermonas macleodi, which is isolated from an annelid worm collected from a hydrothermal vent in the East Pacific Rise, is the active ingredient in Abyssine®, a cosmeceutical (a cosmetic that has or is claimed to have medicinal properties). Another example is venuceane. This is derived from Thermus thermophiles (Blasiak et al., 2020a; Blasiak et al., 2020b), a bacterium found in the Gulf of California, associated with hydrothermal vents, and is a component of anti-ageing creams.

 

 

Sessile organisms lack the ability of self-locomotion and are predominantly immobile. They must be able to protect themselves from predation using a method that does not depend on being able to move. This can involve producing anti-biofilm agents such as the brominated furanones produced by the red alga Delisea pulchra, the structures of which were published in 1993 (de Nys et al., 1993). The natural furanones, a group of compounds based on a five membered ring which includes 4 carbon atoms and an oxygen atom, disable bacteria’s ability to colonise, thereby preventing the formation of the biofilm. Synthetic furanones can be used to prevent the build-up of biofilms on inanimate objects such as pipes and ship hulls. More recently, synthetic versions of the natural furanones have been found to be effective against the production of biofilms by Salmonella (Janssens et al., 2008). The sessile organisms also protect themselves using other biochemical defence mechanisms. The chemicals are often structurally unique, with no counterparts in terrestrial organisms. It has been shown in the recent past that marine invertebrates produce more antibiotic, anti-cancer, and anti-inflammatory substances than any group of terrestrial organisms. Currently, there is extensive preclinical pharmacological research on the antibacterial, antifungal, antiprotozoal, antituberculosis, antiviral, and anthelmintic activities of marine natural products (Mayer et al., 2019). A range of organisms have been investigated with respect to whether or not they contain pharmacologically active compounds (Figure 4).

 

 

Sponges, members of the phylum Porifera, are amongst the most common marine organisms to be studied (Figure 4). It should be noted that although a chemical might be isolated from, for example, a tunicate such as Ecteinascidia turbinate (Table 1), the actual chemical, in this case ecteinascidin, is produced by the bacterial symbiont Candidatus Endoecteinascidia frumentensis (Le et al., 2015). Scotland’s deep sea comprises the Faroe-Shetland Channel to the north of the Scottish mainland and the Rockall Trough and Hatton-Rockall Basin to the far west, covering an area four times bigger than the land mass of Scotland and reaching depths in excess of 2,000 m. Deep-sea sponge aggregations (Figure 5) are a feature of Scotland’s deep sea. The aggregations are principally composed of glass sponges (Hexactinellida) and giant sponges (Demospongiae), the latter sponges being a source of discodermolides which are inhibitors of tumour growth. These greatly increase habitat complexity that supports diverse biological communities (see Case study: Deep sea vulnerable marine ecosystems). To date pharmacologically active compounds have not been isolated from the sponges within the waters to the west of Scotland.

 

 

There are a number of drugs extracted from marine organisms that are currently in clinical use (Table 1). The disease area that many of these cover is cancer while ziconotide, trade name Prialt®, is a potent pain-killer used to treat severe chronic pain (Table 1). Although marine species are a good source of these compounds to provide the required quantity to treat the various conditions, there is a need for a synthetic process to be developed.

 

Table 1: Examples of drugs extracted from marine organisms that are currently in clinical use. (Modified from Blasiak et al., 2020a)

¹Halichondrin B was the lead compound. Eribulin, which is about two thirds the size of Halichondrin B, is the synthetically produced drug (Jaspers, Pers Com).

Compound (Trade name)	Original source (Current source)	Disease area
Eribulin Mesylate (Halaven®)	Halichondria okadai (sponge) (Derivative synthesised1)	Anti-cancer agent · metastatic breast cancer · liposarcoma
Cytarabine (Cytosar-U®)	Cryptotethya crypta (sponge) (Now synthesised)	Anti-cancer agent · leukaemia · non-Hodgkin’s lymphoma
Vidarabine (Vira-A®)	Cryptotethya crypta (sponge) (Now synthesised)	Anti-viral agent for Herpes simplex virus
Plitidepsin (Aplidin®)	Aplidium albicans (tunicate) (Now synthesised)	Anti-cancer agent · multiple myeloma · leukaemia · lymphoma
Ecteinascidin or Trabectidin (Yondelis®)	Ecteinascidia turbinata (sea squirt) (Semi-synthesis)	Anti-cancer agent · advanced soft tissue sarcoma · ovarian cancer that has come back
Brentuximab vedotin (Adcetris®)	Dolabella auricularia (sea slug) (Now a derivative attached to an antibody)	Anti-cancer agent · Hodgkin's lymphoma · anaplastic large cell lymphoma
Ziconotide (Prialt®)	Conus magnus (cone snail) (Ziconotide is a synthetic equivalent of the natural compound)	Potent pain-killer used to treat severe chronic pain

 

As more is discovered about the compounds from the ocean which have the potential to treat a range of disease states, it is increasingly evident that this provides a further reason for protecting the ocean and marine biodiversity, including the marine genetic diversity.

 

Health and welfare

‘The Ultimate Road Trip – The new scenic route showcasing fairy-tale castles, white sand beaches and historical ruins’ is the description of ‘North Coast 500’. Now regarded as one of the World’s iconic touring routes, it takes in the west coast of Scotland north of Applecross (Figure 6), the north coast and the east coast as far south as Inverness. There is an opportunity to explore the varying Scottish coast line, from towering cliffs, to expansive beaches, and the extensive coastal wildlife. In just a few years, this coastal route has become a popular break for many.

 

 

 

The draw of the sea has been realised for a very long time, as have the health benefits of living beside the sea. However, in more recent times, various studies have begun to evaluate these benefits. The term ‘Blue health’ is being used more regularly as well as being the title of a major pan-European research initiative investigating the links between urban blue spaces, climate and health (https://bluehealth2020.eu/). Gascon et al. (2017) reviewed human health and wellbeing in relation to outdoor blue spaces and found that, across 35 articles, there was consistent evidence of positive associations between blue space exposure and mental health and physical activity (Figure 8). Using the Health Survey for England, some 25,963 subjects were surveyed. The conclusion was that, for urban adults, coastal settings may help to reduce health inequalities. A major European project, Seas, Oceans and Public Health in Europe (SOPHIE), is underway. This project will bring together and evaluate information to help policy and decision-makers optimize the benefits of access to and enjoyment of marine and coastal environments.