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1 Living with the oceans. – A report on the state of the world's oceans

Active substances

Active substances from marine creatures

> Substances from the sea are already used as cancer drugs and painkillers, while other preparations are undergoing trials. But searching for new substances is a time-consuming business. Genetic analysis could speed up the process.

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9.1 >  Works by the ancient Greek dramatist Euripides (ca. 480 to 406 B.C.) are still being staged today. The sea is a fateful element of his tragedies, acting as both a threat and a source of life. © Bettmann/Corbis
9.1 > Works by the ancient Greek dramatist Euripides (ca. 480 to 406 B.C.) are still being staged today. The sea is a fateful element of his tragedies, acting as both a threat and a source of life.

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Source of healing since ancient times

For thousands of years people have believed in the healing power of the sea. As the Greek dramatist Euripides says in one of his plays about Iphigenia, “The sea washes away the stains and wounds of the world”. The ancient Egyptians and Greeks examined the effects of seawater on human health. They credited the sea and the substances it contained with healing properties. Marine products have for centuries been an integral part of folk medicine all around the world. For example, sea salt has traditionally been used to treat skin diseases, and algae to treat parasitic worms.
In 1867 the French doctor La Bonnardière introduced the classical thalassotherapy (seawater therapy) and climatotherapy to Europe, reinforcing people’s belief in the therapeutic properties of the sea. However, mythologizing these powers has also brought forth irrational fruit – the notion that eating turtle eggs or shark fins increases virility, for instance. Unscrupulous businesses have exploited this superstition and are contributing to the decimation of numerous animal species.

High-tech equipment seeks out promising molecules

Modern biomolecular and genetic techniques now make it possible to identify promising marine substances very rapidly. We have long known that the oceans are awash with unfamiliar bioactive substances that have healing or other beneficial properties. In many cases researchers have been able to ascertain the roles played by certain substances within the living organisms – the immune system for instance – and to explain the biochemical processes that occur. They believe that many new agents will be found in the sea and in marine organisms in future, since the oceans are home to millions of plants, animals and bacterial strains. Today there are approximately 10,000 known natural substances, most of which were isolated from marine organisms over the past 20 years. New technology such as nuclear magnetic resonance, which can be used to identify and analyse unknown molecules, even if the organism contains only a trace of them, has made the search much easier. More research is now being conducted on the ocean floor than ever before. Unmanned submersible robots are capable of diving to depths of several 1000 metres to take samples.
In spite of these advances and the enormous biodiversity in the oceans (Chapter 5), few marine substances have so far been officially approved for clinical use. A new substance must not only attack the molecules that are key to the disease process, but it must also not interact negatively with food or other medication taken at the same time. It must also be capable of manufacture on a large scale.

Active agents from the sea – perfect for people

The appeal of most of the marine substances already approved lies in their potency. They are valued because they are produced from different source materials and compounds than their land-dwelling counterparts. The special structure of the molecules and components such as bromine and chlorine apparently help to make them so effective. The substances are not normally used in their pure form. First the molecules must be chemically modified and tailored to the human metabolism. The following marine substances are either already in clinical use or show promise for the future:

9.2 >  Europe did not rediscover the benefits of the sea until the late 19th century. People living inland began to travel to the coast for rest and recuperation – as here on the East Frisian island of Norderney, off the North Sea coast of Germany. © Haeckel/Ullstein Bild
9.2 > Europe did not rediscover the benefits of the sea until the late 19th century. People living inland began to travel to the coast for rest and recuperation – as here on the East Frisian island of Norderney, off the North Sea coast of Germany.

Nucleosides

Some of the best-known natural marine products are the unusual nucleosides spongouridine and spongothymidine derived from the Caribbean sponge Cryptothetya crypta. These have been in clinical use for more than 50 years. Nucleosides are components of DNA. For a cell to divide it must first replicate the DNA in its genetic material, incorporating the nucleosides precisely into the new DNA. Nucleosides contain a sugar component, usually ribose. Spongouridine and spongothymidine, however, are arabinose-containing nucleosides. When these exogenous nucleosides are incorporated in the DNA, they inhibit the replication of genetic material, which is known as nucleic acid synthesis.
It was not long before this principle was being used to treat cancer and viruses because tumour cells divide extremely quickly, and even viruses need an active DNA synthesis in the cell to proliferate. Administering substances that interrupt the nucleic acid synthesis can greatly inhibit tumour growth. Thus the sponge nucleosides were developed into a substance for this particular purpose, a cytostatic drug. They were the basis for the synthesis of Ara-C (Cytarabine®), the first marine-derived drug approved by the U.S. Food and Drug Administration (FDA), in 1969. The virostatic agent Ara-A (Vidarabin®), which inhibits the proliferation of viruses, was approved in 1976, and is still used today to treat serious herpes simplex infections. >

9.3 > Many effective agents are derived from marine sponges. Substances from the Elephant Ear Sponge Lanthella basta inhibit tumour growth. This sponge is abundant in the waters off the coast of Australia or Indonesia.

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9.4 > Scientists first isolated prostaglandins from the coral Plexaura homomalla in the 1960s. This coral is found in the Caribbean and the western Atlantic Ocean at depths of up to 60 metres.

9.3 >  Many effective agents are derived from marine sponges. Substances from the Elephant Ear Sponge Lanthella basta inhibit tumour growth. This sponge is abundant in the waters off the coast of Australia or Indonesia. © J. W. Alker/TopicMedia<br />
9.4 > Scientists first isolated prostaglandins from the coral Plexaura homomalla in the 1960s. This coral is found in the Caribbean and the western Atlantic Ocean at depths of up to 60 metres.  © Humberg/imago

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