Marine biotechnology - NOPR

Indian Journal of Geo Marine Sciences Vol. 40(5), October 2011, pp.609-619

Review Article

Marine biotechnology: An approach based on components, levels and players Seshagiri Raghukumar Myko Tech Private Limited, 313, Vainguinnim Valley, Dona Paula, Goa – 403 004. [E-mail: [email protected]] Received 29 December 2009; revised 3 December 2010 Marine biotechnology may be viewed from the perspective of three issues, namely components, levels of research and the players or researchers. (1) The three components are organisms, applications and processes. Access to known organisms and the discovery of unique ones are basic requirements. Sustainable harvesting is the key for accessing marine invertebrates. An alternative is the development of cell culture methods and ecosystem conservation. Establishment of microbial culture collections of organisms difficult to access or cultivate, such as deep-sea and anaerobic microbes, obligate marine fungi and phytoplankton is an important facilitator. Extremophilic organisms from the deep-sea and cold environments are useful candidates for novel applications. Genomics and metagenomics are emerging as powerful tools in discovering useful genes. Application of organisms constitutes the second component of biotechnology. A search for candidate organisms for applications should be based on intelligent screening, while innovative applications of unique properties of organisms need to be established. The former is exemplified by novel drugs from coral reef invertebrates, marine polysaccharides and polyunsaturated fatty acids. Adhesive proteins of molluscs, biomimetics and nanolevel cell wall organization in diatoms are examples of intelligent applications. Process development and improvement for new and existing technologies are the final determinants of a technology. (2) The three levels are established, emerging and exploratory technologies. It is important to recognize this in order to decide who does what. (3) The key players are the academia and industries. Participation and collaboration of the two must be viewed in light of different levels of biotechnology. Improvement of established technologies belongs more to the realm of industries. Emerging technologies offer the best platform for their collaboration, while exploratory technologies are the domain of academic institutions. [Keywords: Marine biotechnology, Organisms, Applications, Processes, Players]

Introduction Marine biotechnology is an area of great potential and research in this area needs to be strategized to foster it. Biotechnology is the sum total of three components, namely organisms, applications and processes1 (Fig. 1). Application is central to biotechnology, but cannot exist without organisms, which constitute the basis of biotechnology. Applications may be conceived without knowing the organisms that possess the required properties. Besides, innovative applications may arise out of the discovery of interesting properties in organisms. Process development commences with the discovery of the right organism for the required application. The process is dependent on both organisms and application and cannot exist independently, since every process is designed to suit the two requisites. I shall, therefore, first consider the organisms and applications as independent entities and discuss the process subsequently. When we talk of marine biotechnology, we refer to a group of special organisms from that environment, their unique

properties that can be applied for human welfare and creation of engineering and manufacturing processes to grow these organisms or organisms containing their genes to produce targeted biochemicals. Each of the three parameters is governed by two factors, namely what we know of them and what we do not (Fig. 1). Individual and institutional policy decisions to support marine biotechnology research should tackle issues relating to organisms, applications and processes at an individual level and in toto. They should also consider the level to which the technologies have advanced, since technologies could exist in an exploratory, emerging or established phase. Since technologies foresee the participation of industry, it is further important to consider the levels at which academia and industry collaborate. Components Organisms The strategy to reap the benefits of the incredible diversity of unique organisms of the marine

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INDIAN J. MAR. SCI., VOL. 40, NO. 5, OCTOBER 2011

Fig. 1—Schematic diagram of the three components of biotechnology.

ecosystem depends on the group to which they belong, such as macro- and meiofauna, macro-and microalgae and microorganisms including bacteria, archaea, fungi and protests Table 1. Macrofauna and macroalgae Of the 34 animal phyla, 19 occur exclusively in the ocean, nine are found both in the sea and on land and only two are exclusively terrestrial2. More than 95% of the nearly 200,000 species of marine animals are distributed among nine phyla. Among these, the Cnidaria including the corals and jellyfish, the Echinodermata comprising among others sea urchins and sea cucumbers, the Porifera encompassing sponges and a few groups of Mollusca, such as the nudibranchs, are now the subject of much biotechnology research. Most of these inhabit the exotic coral reef ecosystem. Deep-sea invertebrates are yet another fascinating group. The Division of Biomedical Marine Research (DBMR) at Harbor Branch Oceanographic Institution (HBOI), Florida, USA, boasts a comprehensive collection of deepwater sponges collected using submersibles from more than 400 sites over two decades (http:// www.hboi.edu/hubs/bmr.html). Besides invertebrates, macroalgae that inhabit the intertidal and shallow subtidal regions, as well as seagrasses are important organisms in our search for drugs, nutraceuticals and industrial products. The present method of accessing larger organisms for marine biotechnology by harvesting them from their natural habitats leads to the serious issue of stock depletion. Cell culture methods3,4 and metagenomics will help in sustainable use of marine invertebrates

Table 1—Strategies to access known organisms for biotechnology research. Organisms Marine invertebrates

Strategies to Access Examples

Natural habitats; Cell line cultures; Metagenomes Macroalgae Natural habitats; Tissue culture; Metagenomes Microalgae Culture collections; Metagenomes Microorganisms Culture collections; Metagenomes

Sponges, nudibranchs, soft corals; Deep-sea organisms Green, red and brown algae Diatoms, Dinoflagellates, Thraustochytrids Actinomycetes, anaerobic microbes, deep-sea microbes, Invertebrate-associated bacteria and fungi, obligate marine fungi

and plants for research and production of important compounds. (1) Research on cell culture of invertebrates is now focusing on a few groups such as sponges and crustaceans, compared to molluscans in earlier years. The use of cellular, genomic and proteomic tools would provide us a fresh approach to improve this technique3. (2) Metagenomics, discussed below, is yet another technique to conserve marine macroorganisms in their natural environment. Rare samples like deep-sea specimens may be cryopreserved and studied later. Microorganisms Culture collections are the chief source for microorganisms. Major biotechnology companies dealing with microbial metabolites maintain large ex situ collections of cultures. A few groups of microbes have attracted special attention. The DBMR at Harbor Branch Oceanographic Institution (HBOI), USA, maintains over 16,000 marine

RAGHUKUMAR: MARINE BIOTECHNOLOGY: AN APPROACH BASED ON COMPONENTS, LEVELS AND PLAYERS

bacteria and fungi, isolated mostly from sponges, as well as marine plants, deep sea cnidarians, echinoids, bryozoans, sediments and seawater. This collection serves as their source for novel bioactive product discovery. The vast expanse of the oceanic water column houses an astounding diversity of microbes5. Among the prokaryotes, picoplanktonic photosynthetic bacteria of < 1.0 µm size play a major role in the biology of the oceans and are fascinating tools for genomic research6. Bacterial diversity includes the chemoautotrophs, as well as aerobic and anaerobic heterotrophs. Protists, comprising nanoflagellates, heterokont flagellates, microzooplanktonic protists, ciliates and dinoflagellates form the major groups of marine microbial eukaryotes5. Diatoms and dinoflagellates are the major eukaryotic phototrophs, comprising nearly 10,000 and 1,000 species respectively7.8. The evolutionarily interesting dinoflagellates probably evolved chimerically from numerous pro- and eukaryotes. Picoplanktonic, photosynthetic eukaryotes are yet another interesting group9. Wijffels4 lists a number of companies which specialize in the niche market for microalgal products. More than 500 obligate marine fungi have been described so far, mostly from mangrove ecosystems10. Many of these belong to the straminipilan fungi and are widespread in the sea. Besides, terrestrial species of fungi adapted to the marine environment (the ‘marine-derived fungi’), are physiologically distinct from their terrestrial counterparts and have yielded a variety of novel natural products. While several bacteria and fungi associated with coral reef invertebrates are easily cultured, maintained and investigated by individual workers, most are uncultured. Other interesting groups are marine actinomycetes, deep-sea bacteria and fungi, anaerobic marine bacteria and obligate marine fungi. The environments where these organisms live are not easily accessible to everyone. Besides, these organisms require special skills to culture. Culture collections would play an important role in such a case. The Center for Culture of Marine Plankton (CCMP) of the Bigelow Laboratory of Ocean Sciences, USA, originally established by the great algal physiologists Dr. Luigi Provasoli and Dr Robert R.L. Guillard, is perhaps the biggest collection of microscopic algae in the world, harbouring nearly 2,500 cultures (http://ccmp.bigelow.org/). An example from India is the National Facility for

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Marine Cyanobacteria at the Bharathidasan University, Tamil Nadu. However, only a small percentage of cyanobacteria have been successfully cultured11. Making new organisms available for biotechnology Much of the diversity of marine organisms has yet to be discovered. This has imposed a limit on our present capabilities to develop marine biotechnology. According to the baseline report of the Census of Marine Life, continental margins are rich in unicellular protists, molluscs and arthropods. More than 100,000 species of unicellular protists, worms, crustaceans and seastar kins have been reported from the deep-sea or abyssal plains at an average depth of 4 km. This is a happy hunting ground for an estimated 150,000 undescribed species. The light zone of the oceanic waters are home to tens of thousands of unicellular protists, arthropods and swimmers, while the dark zone is rich in arthropod crustaceans, fish, jellyfish and molluscs. Vents and seeps in geothermally active sites harbour more than 6,000 species of molluscs, annelids and crustaceans. It is needless to emphasize that organisms living in such exotic environments will harbour unique genes and metabolites. ‘The Great Plate Count Anomaly’, which denotes the disproproportionately low culturable numbers of bacteria (few hundreds per ml) compared to the actual numbers estimated by epifluorescence microscopy (about a million cells per ml) has demonstrated that most marine bacteria have not been cultured. Sequencing of 16SrDNA of water samples has revealed the diversity of ‘hidden bacteria’ many of which are new taxa12. Analysis of over 1000 sequences of 16S rDNA from just 14 samples of 3 corals yielded 430 distinct bacterial ribotypes, more than half of which shared 200 from fungi, mostly associated with invertebrates, have been described since 200023,24. These associations may be dietary, commensalistic or mutualistic20. Sponges harbour diverse bacteria and fungi25 and are home to ‘Poribacteria’ , a mostly uncultured group. Many of the bioactive compounds found in marine invertebrates might actually be produced by associated microorganisms. Dolastatin, an anticancer compound produced by the ‘sea hare’ (nudibranch) Dolabella auricularia is probably produced by its cyanobacterial symbionts11. Microorganisms comprise nearly 40% of the biomass of the sponge Aplysina aerophoba. The cyanobacterium Oscillatoria songelliae accounts for nearly 40% of the biomass of the sponge, Dysidea sp.11. Micromonospora from a deep-water sponge produced two alkaloids that were believed to be produced by sponges. This bacterium produces the anti-malarial manzamine, a drug which is in preclinical trials. Dietary organisms might also contribute to the production of bioactive molecules found in invertebrates. Thus, the mollusc Elysia rufescens produced the anticancer kahalide only when it fed on the alga Bryopsis20. Ascidians, a rich source of metabolites, harbour cyanobacterial symbionts belonging to Prochloron11. Marine cyanobacteria are a rich source of useful secondary metabolites, such as the tubulin-binding compounds dolastatin and curacin and various actin-binding and neurotoxic compounds11.


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Table 2—Some examples of interesting drugs discovered from marine organisms. Organism Bugula neritina (Bryozoan) The sponge Luffariella variabilis

Compound Bryostatin Manoalide

Aplidium albicans (ascodoam)

Aplidine

Ecteinascidia turbinate (Tunicate) Dolabella auricularia (nudibranch)

Ecteinascidn (ET-473) Dolastatins

Discodermia sp. Discodermolide Lynbya majuscula Curacin A derivative Micromonospora marina (Actinomycete) Thiocoraline Penicillium chrysogenum (fungus)

Sorbicillacton A

A list of some interesting and useful compounds from marine sources is presented in Table 2. Present information is also available at the website http://www.marinebiotech.org/pipeline.html4. • Marine macroalgae, a traditional source of food and medicine in coastal south-east Asian countries, are excellent targets for novel nutraceutical screening. Knowledge on edible and medicinal algae needs to be combined with in vivo and clinical studies on their health benefits26-28. • The high lipids yields of many microalgae make them a potential source for the production of biodiesel. It is possible to achieve a yield of 20,000 L of oil ha-1 year-1 with marine microalgae through application of state-of-the-art technologies4. • Straminipilan microalgae are the target for omega-3 and omega-6 polyunsataturated fatty acids (ω-3 and ω-6 PUFAs), which are important for human health and also growth and reproduction of crustaceans. Although fish oil has been the source of these PUFAs, marine microalgae are now finding use for commercial production of high value PUFAcontaining oil. The ω-3 PUFA docosahexaenoic acid (DHA) is already commercially produced by the heterotrophic thraustochytrid Schizochytrium29,30 and the heterotrophic dinoflagellate Crypthecodinium for infant and adult nutrition and aquaculture. Eicosapentaenoic acid is yet another important PUFA that is abundant in many diatoms. Intelligent applications The greatest prospect lies in innovation of new applications by exploring the unknown properties of organisms, identifying the unique ones and recognizing technologically desirable ones, a process which could be termed ‘intelligent application’.

Application Status Anticancer Clinical Phase II Analgesic and anti-inflammatory Synthetic analogues are being evaluated Acute lymphocytic leukaemia Approved in Europe; Clinical Phase II Anticancer Clinical Phase II Anticancer Candidate for combination therapy Anticancer Clinical Phase I Tubulin inhibitor, anticancer Preclinical Anticancer Advanced preclinical evaluations Anticancer Preclinical trials

Unique properties could be found by asking fundamental biological questions about organisms and their biochemical and molecular basis. An organism is the end product of its environment and its effect on evolution. One needs to understand the peculiarities of the marine environment and their potential impact on the biochemistry of marine organisms before meaningfully discussing marine biotechnology. This approach is leading to several exciting discoveries and technologies. The science of mimicking useful characteristics for technology is popularly termed ‘biomimetics’ (see the website of the University of Redding’s Special Centre for Biomimetics http://www.marinebiotech.org/biomimetics.html, for examples). • The visual system of the seastar Ophiocoma wendtii uses spherical calcite crystals on its arms to focus light onto underlying photoreceptor cells. Scientists at the Bell laboratories and Lucent Technologies believe that a further understanding of this system may lead to its application in optical computer circuitry. • The glass sponge Euplectella (Venus’ flower basket) is capable of assembling siliceous spicules containing sodium at low temperatures. This characteristic could have implications in fibre optic technology. • The remarkably strong and durable adhesion of mussels to underwater substrata has fascinated marine biologists for long. Muscle adhesive proteins (MAPs), a group of polyphenolic proteins, cure and harden in an aqueous phase. Such an adhesive can have enormous biomedical and industrial applications and has spawned interest in biological adhesives also of other invertebrates such as barnacles and polychaetes31. The biochemistry of the MAPs that


confer the adhesive property has been studied in detail. Further development in this area probably lies in recombinant technology. • Shell deposition of mollusks is being studied in order to develop synthetic bone-like composites. Of particular interest is their nacre layer. • Toxic dinoflagellate blooms have often caused havoc to fish and shellfish populations and severely endangered the health of human beings consuming them. Toxic compounds produced by them, such as saxitoxin, gonyautoxins, brevetoxins, palyoxins and diarrhetic shellfish toxins could have interesting pharmacological properties. Dinoflagellates have peculiar biosynthetic pathways. The low yield of compounds from these organisms poses a problem in obtaining sufficient material for detailed studies. Culturing and screening these organisms for various applications has been a great challenge. Their molecular biology is poorly known and will throw more light on their applications. Mysteries of their complex genome need to be unravelled8. • Diatom frustules are characterized by intricate, micro- to nano-level designs of silicate structures. Structural, chemical, genomic and engineering aspects of the diatom frustules may soon enable novel processes in nanotechnology32. • Deep-sea barotolerant and barophilic macro- and microorganisms grow under high hydrostatic pressures of the deep-sea. Research on the mechanisms by which they withstand such extreme conditions by altering their cell membrane properties and expression of genes and proteins will contribute significantly to marine biotechnology33. • Diverse organisms inhabit the extreme and perennial cold habitats of polar waters and the deepsea. Regulation of membrane fluidity, adaptations for protein synthesis under low temperatures, coldacclimation and antifreeze proteins seem to be some of the mechanisms by which these organisms thrive in cold conditions34. Cold-tolerant or psychrophilic enzymes which act at low and moderate temperatures have special applications in industry and bioremediation35. Screening organisms for applications is prolonged and risky. However, efforts are likely to yield better success if we are armed with the knowledge of potential groups of organisms for particular applications. ‘Intelligent screening’ based on this knowledge offers the best returns at the moment. However esoteric it might appear to study processes and molecular biology of organisms with

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unique properties for their own sake, these are likely to have a tremendous impact on biotechnology, if combined with innovation. As sensitive biologists observe marine organisms and experiment with them, more and more of their unique properties are likely to be discovered. Process Process development for applications from particular organisms is the final stage leading to commercialization of biotechnology. Processes need to be innovated where none exist for a given combination of organism and application. Besides, several well established commercial biotechnology processes tend to become uncompetitive or unprofitable unless the process is further improved or replaced for newer applications from the same organisms1. The development of enabling technologies such as molecular biology and bioinformatics further plays a major role in development of the technology. Process development requires participation by manufacturing and process engineers. Process Innovation Several bioactive compounds, such as ziconotide, an analgesic drug from the cone snail Conus magnus can be chemically synthesized and made economically viable. However, synthesis is not always possible with others. Therefore, simultaneous production of a high biomass of the required organism and yield of the desired compound is the final challenge in biotechnology process development. Such processes are important not only for drugs, but also for enzymes, fatty acids and other products. Processes for large-scale cultivation of organisms are crucial for supply of marine-derived drugs20. Since every organism has its own requirements for cultivation and metabolite yield, processes have to be innovated constantly to suit individual organisms. • An excellent example of process innovation is that of pharmaceutical aquaculture. The low yield of compounds in marine invertebrates is a big obstacle for economically producing important drugs. The challenge of obtaining large amounts of biomass for drug discovery and production has encouraged development of aquaculture processes for marine invertebrates22. Aquaculture of the bryozoan Bugula neritina that produces the anticancer compound bryostatin is being developed by Cal Bio Marine Technologies. Culturing of the tunicate Ecteinascidia turbinata is being attempted by Pharma Mar of Spain,

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while the University of Wageningen and Porifarma are optimizing culturing of the sponges Pseudosuberites andrewsi and Dysidea arena. The National Institute of Water and Atmospheric Research, New Zealand and the Australian Institute of Marine Sciences are developing aquaculture of Lissodendroya and other sponges that produce the antitumour compounds halichondrins and discorhabdins. The gorgonian octocoral, Pseudopterogeorgia elisabethae that produces the anti-inflammatory pseudoptericins is being grown by the State University of New York at Buffalo. A variety of innovative processes are being adopted by these companies. Yet much remains to be done in this field. • Extremophiles, such as barophiles and psychrophiles require special bioprocess engineering technologies, because of their slow growth, low cell yield and high shear sensitivity36 and require special considerations. • Improvements in photobioreactor or raceway processes will boost microalgal technology, which is still poorly developed because most industrial processes are designed to produce large biomass, but with low yields of the required biochemicals4. • Many technologies are in the danger of lapsing into oblivion or postponed indefinitely for want of suitable economic processes. Bioremediation is one area where it is often hard to translate laboratory level technologies into commercial processes. Several marine fungi are extremely efficient in decolourizing and detoxifying textile dye effluents and distillery spent wash, using the enzyme laccase37,38. However, a process is yet to be developed for this technology. Recombinant technology and heterologous expression will facilitate the production of several compounds that are either hard to synthesize, occur in minute quantities in organisms or are present in organisms that are difficult to culture. Process Improvement and Improvement of applications In the case of established processes using target organisms for specific applications, the scope for further research depends on a critical evaluation of market and competition, the possibility of further process improvement or use of the same process for novel applications. • Aquaculture is an example of a technology that has been well established in the last 30 years. The

production of shrimp and macroalgae for food and industrial products has already reached optimal levels. Further progress in shrimp aquaculture can perhaps result from process improvements such as increasing the yields, improved broodstock or disease prevention. Aquaculture technologies are being developed for ornamental fish, holothurians and lobsters. Macroalgal mariculture may get a boost through novel applications for algal products, such as drugs, the use of alginates in drug delivery systems and increased efficiency in seaweed farming methods. Processes for using macroalgae to treat polluted and effluent waters or their use to generate biofuels are other possibilities39. • A more recent technology is the production of the ω-3 PUFA, DHA, from the heterorophic marine protists, the thraustochytrids in fermentors. DHA and the cells or oil containing the PUFA are now manufactured by Martek Biosciences Inc., USA and Lonza from Switzerland for human and aquaculture applications29,30. Martek also manufactures DHA from the heterotrophic dinoflagellate Crypthecodinium coehnii for use in infant feed formulae. The market continues to expand and there is a large scope to screen for better strains, to develop novel fermentation methods to enhance DHA and formulate novel food applications. As new findings on the usefulness of DHA for human health emerge, it may be possible to develop innovative applications. Single cell oils with specific fatty acid profiles may be applied for different uses. • There is much scope to improve processes and applications for nutraceuticals40. Fish skin collagen and gelatine and fish frame protein may find novel applications. Development of microencapsulation processes for omega-3 fatty acids from marine oils would help prevent lipid oxidation in fortified foods41. Nutraceutical applications of chitin and chitosan from marine shellfish, which are well known products are yet to be fully developed42. Process development for producing chitosan oligosaccharides with different degrees of polymerization and correspondingly different nutraceutical properties is yet another area. Process development has often been ignored in biotechnology. Processes that deal with larger aquaculture organisms or with microorganisms in photobioreactors and fermentors depend on the properties of the organisms, each one having its special requirements. Greater participation of engineers will be a catalyst for process development.


Levels Biotechnology may be discussed at the three levels of established, emerging and exploratory technologies. Biotechnology using terrestrial organisms has matured into a number of processes for production of drugs,, nutraceuticals and industrial products like enzymes and chemicals. A variety of useful compounds from terrestrial organism have been produced through heterologous expression. Marine biotechnology, however, is still in its formative years. The different levels, therefore, can be clearly perceived in the case of marine biotechnology. The author’s perception of the three levels is outlined in Table 3. Established technologies are those for which organisms, their applications and process are all well known and for which industry players already exist. Prawn and macroalgal aquaculture for production of chitin, chitosan, glucosamine and a variety of polysaccharides, such as agar, carrageenan and alginate, as discussed above, is probably the best example of this level. The production of the ω-3 PUFA, DHA by thraustochytrids is yet another example. Emerging technologies are characterized by a fair amount of development in both the application and the requisite organism for that. It further means that much time has already been spent on screening a number of organisms for the required application or that sufficient background research has been carried out to understand the uniqueness and novelty of an organism that its application can be envisaged. The process, however, may have to be developed. The production of drugs and nutraceuticals from marine organisms is an example of emerging technologies. Exploratory technologies are those where an interesting organism may be known but not its application, or where an applicaton has been

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envisaged, but no suitable group of organisms for screening have been decided. Nanotechnology and biomimetics, technologies based on barophilic and psychrophilic organisms, bioremediation and metagenomics are some examples of that are in an exploratory level at the moment. Prior to investing time and funds in research and collaboration in marine biotechnology, it is important to decide whether the technology exists at the established, emerging or exploratory level. This is a prelude to academia and industry participation in marine biotechnology. Players: The academia and industry, who does what? Technologies can come into being only if they are commercially viable. They are often the end result obtained jointly by academia and industry. Quite often, neither of these players can fully develop every one of the numerous steps involved in achieving success in technology development. In their research relating to organisms, their applications and the processes, academia and industries participate at the different levels of established, emerging or exploratory technologies Table 4. Table 4—Some examples of the three levels of marine biotechnology. Established technologies Aquaculture

Emerging technologies Drugs

Marine algal polysaccharides

Pharmaculture

Exploratory technologies Nanotechnology and biomimetics Application of barophilic and psychrophilic organisms Bioremediation

Products from finfish Nutraceuticals and shellfish wastes Macroalgal extracts Value-addition to Metagenomics as fertilizers finfish and shellfish wastes

Table 3—Levels of biotechnology and the role of the academia and industry. Exploratory Technology

Established Technology

Emerging Technology

Process Property Organism Requirement

Well known Well known Well known Investment

Time frame Executing parties

2-3 years Industry

Partly or not knownPartly known Partly known 1) Process development; 2) Fine tuning 3) Molecular Biology 3-5 years 5-10 years Industries/Industries Large industries, and academia Academia

Candidate Search Not knownPartly or well known Not known Screening

Property Search Not known Not known Partly or well known Biochemistry and Molecular Biology

5-10 years Large industries / Academia

Scenario 4 Unchartered search Not known Not known Not known Unique Biodiversity discovery

Continuing Academia

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Established technologies There is little scope for the academia in the case of established technologies, research in these areas only amounting to the reinvention of a wheel. Such technologies are of no use to fresh industrial entrants either, unless the market is still open for them and there are no intellectual property encumbrances. Despite the public domain know-how in such cases, an industry with sufficient investment may take about 2 years to establish and commercialize the technology. Industries are expected to be fairly well equipped with scientific and technical expertise to develop established technologies. However, industries that do not have the scientific know how might seek the expertise of academia in the form of sponsored or turnkey projects. Yet, established technologies belong more to the domain of industries rather than academic research institutions. Emerging technologies Emerging technologies call for active participation of both the academia and the industries, unless the industry itself has a large R & D laboratory. For example, many multinational drug companies carry out large-scale, high throughput screening for drugs. However, most industries cannot afford this luxury of time and money for screening or for understanding the basic biochemistry and molecular biology of organisms. However, when these criteria are established, a medium or small scale company could then revalidate the results with the economics and market viability in view and then go ahead to develop the process. Process development is generally the forte of industries, since economising the technology through pilot scale studies and downstream processing interests those more. It might be unwise to expect or demand the development of a complete technology by an academic institution alone. Their role probably is to establish up to an extent the organisms and their applications, further revalidation and scaling-up being done by industries. Despite any form of collaboration, emerging technologies will perhaps take at least 3 years before they can be commercialized. Exploratory technologies Exploratory biotechnology research has the potential to offer major breakthroughs, even if they may last up to a decade of intensive research, the time frame and economics not being acceptable to medium- and smallscale industries. These, therefore, are the domain of the academia. For example, when novel organisms are

known but not their application, academic institutions may be encouraged to carry out detailed studies on their biochemistry and molecular biology. An innovative biotechnologist may then find an application for it. Alternatively, when an application is envisaged based on a particular property, research organizations may be encouraged to find the right group of organisms among which to search the candidate. Research on the metabolic pathway and molecular biology of the pathway of the property, aided by genomics, metagenomics and bioinformatics is an area where academic institutions need to excel. One may add ‘unchartered areas of biotechnology’ as yet another aspect, where neither the organism, nor its application is known and therefore, no process can even be envisaged. Unchartered areas are a luxury that only government funded academic research institutes can afford since one may, or may not find rewards in them. Deep-sea biology is an example. The ship time, sampling gears, collection and isolation of organisms and instruments for hyperbaric cultivation and experiments cost enormous amounts of money. Biodiversity is yet another area. Isolation and conventional, as well as molecular identification of novel organisms, understanding their unique properties, and unravelling their basic molecular biology are time-consuming. In addition, the enormous uncertainty make forays into these areas of research highly uneconomical for industries, but extremely promising for academic institutions. Research in unchartered areas has no time limits since frontiers keep expanding continuously, which augurs well for biotechnology. The funding that goes to support academia and industries in light of the three levels of technology as above depends on the immediate needs of the society and the money available. References 1 Bull A.T., Biotechnology, the art of exploiting biology. In Microbial Diversity and Bioprospecting (ed. Bull,l A.T.). ASM Press, Washington. 2004. p. 3. 2 Brusca, R. and Brusca, G.. Invertebrates. Sunderland, Massachusetts: Sinauer Associates, Inc. 2003. 3 Rinkevich, B., Marine invertebrate cell cultures: New millennium trends. Mar. Biotechnol., 2005, 7, 429-439. 4 Wijffels, R.H., Potential of sponges and microalgae for marine biotechnology. Trends Biotechnol. 2007, 26, 26-31. 5 Sherr, E. and Sherr, B.,. Marine Microbes: An overview. In Microbial Ecology of the Oceans (ed Kirchman, D.L.). Wiley-Liss, Inc., New York. 2000. p. 13. 6 DeLong, E.F. and Karl, D.M., Genomic perspectives in microbial oceanography. Nature, 2005, 437, 336-342.


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