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WOR 1 Living with the oceans. A report on the state of the world’s oceans | 2010

Active substances

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Other cancer drugs from the deep

A number of other marine anti-tumour agents are currently under study in clinical trials. They include bryostatin extracted from the bryozoan Bugula neritina, squalamine lactate from the spiny dogfish Squalus acanthias and sorbicillactone which comes from bacteria present in sponges. Substances such as dolastatin 10 and dolastatin 15 isolated from the Dolabella auricularia snail and their progeny appear less promising. Clinical studies show that these anti-cancer agents alone are not capable of healing breast cancer or pancreatic cancer. They could conceiv- ably be effective, however, when combined with other preparations.
9.7 > Scientists have successfully extracted many active agents from organisms that live in the sea or fresh water. Some substances have already been devel­oped into drugs.
9.7 > Scientists have successfully extracted many active agents from organisms that live in the sea or fresh water. Some substances have  already been devel­oped into drugs.  © maribus

Extra Info The fight against antibiotic resistance

9.8 > Countless bacteria live in the outer cell layer, the ectoderm, of the cnidarian Hydra. Staining them shows how closely they are interwoven. Under the microscope the cell nuclei of Hydra appear blue and the bacteria red. © Bosch, Foto: Sebastian Fraune 9.8 > Countless bacteria live in the outer cell layer, the ectoderm, of the cnidarian Hydra. Staining them shows how closely they are interwoven. Under the microscope the cell nuclei of Hydra appear blue and the bacteria red.

What is the true potential of marine substances?

Many substances derived from the sea are already in commercial use as pharmaceutical drugs. Others have future potential. The following are some interesting theories and questions on the future of research into marine substances:
1. The sea provides prime candidates for new medications. But locating them and then producing them on a large scale is not easy. This, on the one hand, is because the living organisms are difficult to find in the endless expanses of the ocean, and they often occur in very limited quantities. On the other, it is impossible to keep many of these organisms under laboratory conditions for long periods, or to cultivate them. For many years the pharmaceutical industry has had automated procedures in place for analysing variations of known substances and testing their suitability as drugs. This high-output screening allows researchers to test entire catalogues of related substances very rapidly. However, the molecular structure of marine substances is often so complicated that, even after being proved effective, they cannot easily be replicated or modified. This is what makes them so difficult to locate and develop. Finding them is also an extremely time-consuming process that requires expensive equipment. The time and effort involved are usually considered too great by the industrial sector. For this reason, most marine substances have thus far been discovered, isolated and analysed by researchers at scientific institutes. Moving the substance from the laboratory to the marketplace can also prove difficult – partly because patent law can create a barrier between universities and industry. The researcher would like to publish his findings. But the industrial sector wants to keep the agent and the drug formula secret, for fear of competition. Professional articles published too soon can also obstruct patent approval. This is why the pharmaceutical industry has long overlooked the ocean as a major and important source of new drugs. But industry and academia are now collaborating in promising new ways, such as the creation of start-up ventures. During the past few years these kinds of young businesses have sparked important new initiatives in this field. A vital question will be how to fund these risky schemes, and how appealing such individual paths out of academic research are likely to be considering the overall economic situation.
2. Which organism is the actual source of the marine substance is not always clear-cut. Many substances have been isolated from invertebrates in the past. In many cases, however, these did not originate from the animal itself but from the bacteria or fungi living in or on it. Microorganisms can make up as much as 40 per cent of the biomass of sponges, many of which are also colonized by microalgae. It is crucial to know when microorganisms are the actual producers of the agent, because it is hoped that they are more easily cultivated under laboratory conditions than the sea-dwellers upon which they colonize. It was initially believed that harvesting sponges and other animals on a grand scale was possible, but it soon became clear that the species could easily be completely wiped out. The focus then shifted to breeding bacteria in the laboratory, a process which is seldom successful. In some cases researchers have achieved results, however. For instance, large quantities of sorbicillactone, a substance mentioned above, were extracted within a short time from fungal cultures derived from sponges. Nevertheless, the difficulty remains that cultivating unknown bacteria can be a time-consuming process.
9.10 > Biomolecules of water organisms such as hydramacin isolated from the Hydra polyp are often complex. This makes them difficult to reproduce in the laboratory. © maribus (after Bosch) 9.10 > Biomolecules of water organisms such as hydramacin isolated from the Hydra polyp are often complex. This makes them difficult to reproduce in the laboratory.
3. Today the search for new substances is facilitated by culture-independent methods of genetic analysis. This does away with the painstaking and complicated laboratory culture of bacteria and other organisms. For many decades expensive chemical and biochemical analyses alone were used to verify the presence of effective substances. Today, thanks to modern genetic analysis, this can be done much more quickly and easily. The latest procedures search the genetic material of marine organ- isms for conspicuous gene segments that contain the blueprint for promising enzymes. Such enzymes are the tradesmen of the metabolism, building different substances. The development of such DNA-sequencing techniques is definitely the greatest advance in substance research of recent years. Large-scale sequencing projects can now trawl through the genetic material of thousands of marine organisms within a short time, searching for promising gene segments. One example is the Global Ocean Sampling expedition by the J. Craig Venter Institute in the USA, which played a significant part in de- coding the human genome a few years ago. The focus of this institute is now turning increasingly to the sea. Its objective is to search the genetic material of marine or- ganisms for economically significant metabolic pathways. Entire habitats can be subjected to sequence analysis. Such major projects process both the organisms and the microbes growing on them at the same time. Therefore the findings can no longer be attributed to individual species, but the researchers anyway are mainly preoccupied with learning about the genetic make-up of an entire habitat within a short time, and finding out whether that location harbours any interesting substances at all. Textende
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