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what to do in marine biotechnology

  1. 1. What to do in marine biotechnology? Johannes Tramper a, *, Chris Battershill b , Willem Brandenburg c , Grant Burgess d , Russell Hill e , Esther Luiten f , Werner Mu¨ller g , Ronald Osinga h , Gregory Rorrer i , Mario Tredici j , Maria Uriz k , Phillip Wright l , Rene´ Wijffels h a Food and Bioprocess Engineering Group, Department of Food Technology, Wageningen University, P.O. Box 8129, 6700 EV Wageningen, Netherlands b Australian Institute of Marine Science, Townsville, Australia c Plant Research International, Wageningen, Netherlands d Heriot-Watt University, Edinburgh, UK e University of Maryland, Baltimore, MD, USA f Netherlands Study Center for Technology Trends, Hague, Netherlands g Johannes Gutenberg University, Mainz am Rhein, Germany h Wageningen University, Wageningen, Netherlands i Oregon State University, Corvallis, OR, USA j University of Florence, Florence, Italy k Center for Advanced Studies of Blanes, Blanes, Spain l University of Sheffield, Sheffield, UK Abstract During the symposium ‘‘Marine Biotechnology: Basics and Applications’’, held 25 FebruaryÁ/1 March, 2003 in Matalascan˜as, Spain, a special brainstorm session was organized. Two questions were addressed: 1, ‘‘What is the most desirable development in marine biotechnology’’?; 2, ‘‘What is the most spectacular development in this field in your ‘wildest’ dreams’’?The outcome of this session is reported in this paper. From the more than 250 ideas generated, concern for the environment and human health emerged as the most significant issues. # 2003 Elsevier Science B.V. All rights reserved. Keywords: Marine biotechnology; Brainstorm; Future 1. Introduction The sea is a gigantic, largely untapped reservoir of biodiversity. Careful and cautious exploitation is essen- tial in order not to damage and disturb this fragile ecosystem. The field of marine biotechnology aims to explore and utilize this biodiversity, and has great potential for beneficial outcomes for mankind. To realize this aim and potential, creative thinking and multi- and inter-disciplinary research and developments are required. At the symposium ‘‘Marine Biotechnol- ogy: Basics and Applications’’, held 25 FebruaryÁ/1 March, 2003 in Matalascan˜as, Spain, about 150 experts in the field of marine biotechnology, representing all the essential disciplines and from all over the world, presented and discussed their work. To tap this vast amount of gathered knowledge to its fullest extent, a special brainstorm session was organized. The way of brainstorming, a variant of the metaplan method, was special in the sense that it was structured to some extent, and that it required the active participation of preferably all the participants of the symposium. The aim of this session was to elicit as many new ideas as possible about developments that sooner or later can contribute to the sustainable exploitation of the biodiversity of the sea, realizing that this might even be essential to meet future requirements by mankind. After raising the ideas, they * Corresponding author. Tel.: '/31-317-48-3204; fax: '/31-317-48- 2237. E-mail address: hans.tramper@wur.nl (J. Tramper). Biomolecular Engineering 20 (2003) 467Á/471 www.elsevier.com/locate/geneanabioeng 1389-0344/03/$ - see front matter # 2003 Elsevier Science B.V. All rights reserved. doi:10.1016/S1389-0344(03)00077-7
  2. 2. were evaluated by ranking them according to the participants preferences. This session proved that a wealth of such ideas could be harvested in a very short time, and that trends can be deduced easily from the results, in particular after ranking. Besides, the pertinent meetings were interesting and fun to participate in. 2. Procedure There are many methods that aim to generate ideas in an uninhibited fashion. One such method is especially suited for groups of ideally 10Á/12 persons. In a short, speedy meeting of maximally 1 h and 30 min, the group is first confronted with one or two challenging ques- tions, and 5Á/10 min are then permitted to think about answers. Each participant then is requested to briefly explain (2Á/3 min) and sell his or her idea. In the form of keywords written in large letters, legible from a distance, on post-its, the ideas are positioned and clustered on a wall. During a short intermediate discussion, the parti- cipants can react to each other and more ideas can be gathered before everybody is asked to vote on his or her favorite idea(s) by putting one or more colored stickers on the pertinent post-it(s); each participant gets three to five such ‘‘voting stickers’’ for each question. It is interesting and fun to participate in such a brainstorm, and the results can be quite spectacular, but the success stands or falls with the way the discussion is generated and coached. Required is a convener with some seniority in the field, who has at least once participated in such a session, and who is able to keep the meeting lively and speedy. When the idea came up to organize such a brainstorm session during the symposium, a try-out was first done within the marine bioprocess-engineering group of Wageningen University. There was no doubt during the evaluation that such a session should be incorpo- rated in the conference. Two questions were formulated as the most appropriate to address: . ‘‘What is the most desirable development in marine biotechnology’’? . ‘‘What is the most spectacular development in this field in your ‘wildest’ dreams’’? Much more discussion was, however, needed before the decision could be made on how to structure the session. It was finally decided to have 12 identical parallel workshops (about 150 symposium participants were expected) all addressing the above questions, while clustering was already pre-determined by taking the sessions of the symposium, i.e. Phototrophic organisms, Heterotrophic organisms and Invertebrates, as the lead topics and further dividing these into basics and applications, the sub-title of the symposium. Also, division of the participants over the workshops was not completely random; it was made sure that in each workshop industry was represented and that national- ities and backgrounds were heterogeneous. A couple of weeks before the symposium, the conveners were chosen from the registered participants and approached with the request to undertake this task. They all said yes, but most of them indicated that they never had participated in such a brainstorm. For that reason, and to make sure that the approach was similar in all workshops, a second try-out was organized on the second evening of the symposium with the intended conveners as participants. That worked out well too, and the next evening the actual workshops, with most of the participants (about 120 of the total of 150) contributing, were held. The day after, during the poster session, the conveners sat together again and presented a summary of the results of their own workshop. It became clear that many ideas were applicable to all three classes of organisms and, therefore, a fourth category was added, that is General. The ideas from all the workshops were then combined and divided amongst these four categories. Four of the conveners volunteered to further cluster the ideas and prepare each a presentation of no more than 10 min for the final part of the brainstorm: presentation of the results in a plenary meeting with sufficient time for the participants to comment and react to it. 3. Results 3.1. General Looking at the results of all the workshops (Fig. 1), it could be observed that in general most of the ideas submitted tended to relate to environmental issues. There were also many relevant to human health and they were the ones that in general scored best. The idea that a multibillion-euro successful blockbuster drug is needed to really promote the development of marine biotechnology was raised several times. In one of the workshops an interesting philosophical discussion origi- nated. It was concluded that: . Basic and applied research cannot be easily sepa- rated. . ‘‘The spirit of biotechnological research is to APPLY it’’. Despite this, the classification ‘Basics’ and ‘Applica- tions’ is maintained in this section as it gives the best quantitative overview. Also, the two questions ad- dressed are treated separately throughout the general category. In the rest of the paper a more qualitative description is given to prevent repetitiveness. J. Tramper et al. / Biomolecular Engineering 20 (2003) 467Á/471468
  3. 3. 3.1.1. Most desirable developments Basics. More than 20 ideas fell into this category. ‘Respect for each others position in the science economy’ got the highest score, and ‘Elucidation of the cancer mechanism’ was the second best. Ex equo 3 and 4 were the ideas that ‘Real good projects should not have to worry about money’ and ‘Development of genomics and proteomics of symbionts’. A good score was also given to ‘Sustainable use of nature for human use’. Interesting ideas without votes are ‘Model systems for finding bioactive compounds’, ‘Multicultural research groups’ and ‘Independent aquaculture’. Applications. Of the 20 ideas in this class ‘Antibacterial compounds to fight multi-resistant bac- teria’ was the number one followed by the desire for an ‘Underwater taxonomic DNA-chip’. ‘Anti-HIV drugs’ and ‘Market-oriented approaches’ were next with the same number of votes and ‘Sustainable development’ having one less. Ideas relating to multicultural research groups, commercial successes and better industrial liaison and networking did not attract votes. 3.1.2. Most spectacular developments in our ‘wildest’ dreams Basics. Under this class only ten ideas could be grouped with a ‘New drug selling for more than $10 billions per year’ ranking highest. ‘Clean seas’ got one vote less, just as ‘Drugs derived from combinatorial genetics’. Again one vote less was given to the ideas ‘Super-transformation vector’ and ‘Control of climate by global voting’, obviously all in relation to marine biotechnology. Ideas without votes, but nonetheless interesting: ‘Molecular engineering basics’, ‘Fully tun- able secondary metabolism’ and ‘Believe in basic research’. Applications. Not less than 31 ideas were categorized under this class. The following table sum- marizes them. What are the most spectacular developments in the field of marine biotechnology in our ‘wildest’ dreams? Rank Score Idea 1 6 Uni-layer of antifouling cells on ship hulls 1 6 Anti-aging chemicals 1 6 Marine viagra 2 5 Peace pill 2 5 Green symbiontic fish Á/ Food and oxygen for other planets Á/ Marine production systems on ship (polycultures) Á/ Cheap, sustainable-produced food Á/ Most of the rest (20) had similar themes to the last three 3.2. Phototrophic organisms About 80 ideas were classified under the category Phototrophic organisms, which is comparable to the number found under General. An impression of the Fig. 1. Some of the results of the brainstorm. J. Tramper et al. / Biomolecular Engineering 20 (2003) 467Á/471 469
  4. 4. more or less clustered ideas with the highest ranking, provided with short comments, are given in this para- graph or in the accompanying list. 3.2.1. Most desirable developments In order to make algal production systems more competitive with heterotrophic systems, in particular more economically feasible, it is necessary either to improve the systems or to improve the organisms so that they are better adapted to production conditions. The following submitted ideas reflect this desire: . More efficient production; . More efficient photobioreactors; . Productivities of 60 g dry weight biomass per illuminated square meter per day; . Continuous systems for production of pigments, PUFA’s, proteins, polysaccharides, etc. . Production and harvesting are thus far two separate domains in research. The idea ‘Integration of produc- tion and harvesting systems’ is a plea for an integrative, multidisciplinary approach. With algae, it is possible to combine several functions/ applications. Reasonable efficient systems to produce hydrogen as energy source have already been reported. At the same time, the biomass itself can also be applied for energy generation, CO2 sequestration or other applications. Several ideas refer to this integrated utilization. Combining the latest developments in genomics, proteomics, metabolomics and combinatorial chemistry, it must be possible to find more efficient ways to generate important leads in drug discovery and devel- opment. This should be combined with efforts to scale up production for clinical trials and obviously the final application. Several of the generated ideas reflect these desired developments. Increasing the efficiency of development and produc- tion of (functional) food is suggested. From both agricultural practice and industrial micro- bial applications, it can be learned that genetically improved living organisms greatly contribute to the final performance of the production system. Thus far, this has received little attention in the applied algal world. The idea ‘Genetic improvement of micro-algal strains’ pleads for increased attention. 3.2.2. Most spectacular developments in our ‘wildest’ dreams The rather wild idea ‘Marine viagra’ (see table above) was actually brought in under this heading but really points at the need for a success story, a ‘cash cow’, in the field of marine biotechnology in general. The rest of the submitted ideas are listed below and accompanied by a short comment: . The great possibilities of changing heterotrophs into phototrophs are reflected by the idea ‘Humans with algal chloroplasts’. . Climate change urges for CO2 sequestration; at the same time something useful should be done with it. ‘CO2 sequestration makes whiskey’ stands for that. . The world has in its urban environment thousands of hectares of unused space: roofs. Making them avail- able for algal production, we use our space more efficiently and lots of applications are feasible: energy, functional food on site, etc. The idea of ‘Rooftop flat-panel photobioreactors’ aims at that. . There is already work being done on ‘Outer-space life-support systems’, but in view of (far) future perspectives, this really is one of the developments to invest in. . This similarly holds for ‘Algae giving light’, but this idea is also one of the possibilities to tackle scale-up problems of photobioreactors. . ‘Universal drug from algae’, a dream, but in view of the potential of algal production capacity, one that should become reality to some extent. . ‘Hemaglobin produced in algae’ is self-explanatory in its context. . ‘Artificially produced diatom structures’ is in view of the demand for diatomite, an obvious objective. . As we have large-scale agricultural production as opposed to horticultural production, the analogue is to have well-controlled open-pond systems to pro- duce algae in bulk for, e.g. food (or feed) protein. The idea ‘Micro-algal strains optimized for open ponds’ covers this and is at the same time a plea for the development of effective algal selection systems. . As marine algae produce lots of complex, special secondary metabolites, there is an obvious need for more efforts in understanding the relevant pathways and their biological functions. ‘Pathway understand- ing’ is the pertinent idea. 3.3. Heterotrophic organisms Heterotrophic marine microorganisms are future sources of bioactive substances, industrial enzymes, and feed for aquaculture. They are also platforms for the biological remediation of contaminants from the marine environment. The brainstorming process identi- fied three major opportunities for expanding basic research and applications of marine heterotrophic organisms. First, it is well known that most heterotrophic marine organisms are not culturable in the laboratory. There- fore, methods must be developed to isolate these ‘‘unculturable’’ marine heterotrophs from any compo- nent of the marine environment, including deep and shallow ocean waters, sediment, or even the surfaces of marine organisms such as marine invertebrates or J. Tramper et al. / Biomolecular Engineering 20 (2003) 467Á/471470
  5. 5. seaweeds. Furthermore, strategies must be developed to rapidly obtain balanced medium formulations and optimal cultivation conditions for the newly isolated marine microorganisms, in other words, as one partici- pant put it, ‘‘to tame the culturable’’. Second, efforts to identify and produce bioactive substances, industrial enzymes, and commodity chemi- cals from heterotrophic marine organisms must be stepped up. Three new tools of biotechnology*/geno- mics, proteomics, metabolomics*/together represent a powerful approach for discovering the next generation of antibiotics and anti-tumor drug candidates. These tools should also be extended to the discovery of marine extremophiles that promote industrially significant che- mical reactions (e.g. hydrolysis) at both high and low temperatures over broad pH ranges. Finally, the poten- tial of using heterotrophic organisms to produce com- mercial fatty acids (e.g. EPA) and carotenoids (e.g. astaxanthin) must be more thoroughly explored. Many of these compounds are already produced by photo- trophs, and so the possibility of turning these photo- trophs into heterotrophs may be an exciting avenue of research. Third, heterotrophic marine microorganisms are un- derutilized in aquaculture and environmental biotech- nology. For example, heterotrophic marine organisms may be an ideal food source for larvae of commercially important fish and shellfish species. The economics of commercial aquaculture processes are often limited by low survival rates, and heterotrophic feeds may address this issue. Finally, it is hoped that heterotrophic marine organisms will serve as stewards for a cleaner marine environment. For example, the use of marine micro- organisms to clean up petroleum spills in the ocean and coastline at the source of contamination was a dream shared by many of the participants. Finally, as an illustration, two ideas expressing a ‘‘dream for everyone’’: . ‘Marine biotech companies launch three new blockbuster products in the next 5 years based on marine heterotroph metabolites. . .’; . ‘Some profits go to support the marine biotech academic research community that helped to get them there’. 3.4. Invertebrates Invertebrates are in general difficult organisms to work with in many ways. This also became apparent from the brainstorm session. It was difficult to group the large number of ideas into a smaller number of clusters. Invertebrates are difficult to grow, if at all, outside their natural habitat. Invertebrate biology is still poorly understood. The relationship with their symbionts even less so. Genetic modification is clearly still a dream. Most of the ideas refer to these difficulties and can, therefore, be categorized as ‘spectacular’ or ‘wild dream’. To mention just a few: . Fast growing sponges (faster than men); . Stable (transgenic) sponge cell lines; . Expression vector system for sponges; . Invertebrate virology under extreme conditions; . Understanding of symbionts; . Invertebrate (including symbionts) genomic, proteo- mic and metabolomic technology available. One thing is clear, if a few of the many ideas come true, realization of the great potential of for instance sponges, and their associated bioactive compounds of pharmaceutical interest, will be much nearer. 4. Conclusions As one can see, the above comprises a myriad and wealth of ideas (foto), too many to even think of discussing them all, even shortly. By listing them, they at least are not lost and point in directions for research that ultimately lead to sustainable exploitation of the biodiversity of the sea. That is the least we can hope for, because they represent a vast amount of knowledge: that of all who participated! We, therefore, thank all of you for your enthusiastic contributions. From the reports of the conveners and from the many reactions, it can be concluded that the brainstorm session was successful, and interesting and fun to participate in. Finally, ‘greenness’ and ‘sustainability’ emerged as leads, as exemplified by some really ‘wild ideas’: . Use marine biotechnology to design ‘green biological toys’ for entertainment purposes, for example, a green pet or ‘living ornament’ of a marine organism genetically designed only for aesthetic purposes. . Green functional fish, i.e. fish genetically modified such that it has become phototrophic and that it produces nutraceuticals, e.g. vitamins, anti-oxidants, etc. . Green people genetically designed to live on Mars. . Green mermaid, i.e. a human being genetically modified with photosynthetic genes and genes coding for the fish tail. Well, let us be realistic and concentrate first on research and developments that lead to a sustainable exploitation of marine biodiversity! J. Tramper et al. / Biomolecular Engineering 20 (2003) 467Á/471 471