The ISCB initiative
The ISCB programme was initiated in 1974 by a bilateral agreement between the Indian government and the Swiss government represented by the Swiss Agency for Development and Cooperation (SDC) to explore ways of cooperating in various areas related to biotechnology. In the first phase, collaboration started between the Institute of Biotechnology at the Swiss Federal Institute of Technology (ETH) and the Biochemical Engineering Research Centre of the Indian Institute of Technology. Emphasis was put on the development of curriculum, infrastructure, and human resources in the area of biochemical engineering.
The main goal of this project was to attain academic and educational standards meeting international levels, thus providing highly-trained scientists.
However, from the beginning it was realized that a top quality biotechnological research centre must also develop techniques that are applicable for developing a biotechnology industries. Thus, capacity building was closely linked with applied aspects and resulted in the development of a pilot plant for technology transfer demonstration. After ten years, the Biochemical Engineering Research Centre was independent and became a prototype for the Indian government in establishing future biotechnology R&D centres. However, the basis for biotechnological development was still small at that time, and, equally important, it was very difficult to get the Indian industries interested in applying the products. Therefore, the Indian government decided to extend the programme.
After 1988, four Indian research institutions were selected for the second phase of the programme and after a project review in 1995, two more partners were added. This second programme phase did not differ in objectives and goals, but in the size and the number of different partners and activities, the competition in the selection of projects, and the increased size of its management unit. As before, the main objective was to strengthen the scientific and technological capabilities of Indian R&D institutions in biotechnology and to establish a network for product development and technology transfer. Within this network, different collaborations were projected: North-South R&D cooperations between public institutions; product development, for instance, biopesticides for agricultural pests, by private companies; product development, for instance, foot and mouth disease (fmd) diagnostic kits for the government-controlled Indian market. Projects were selected by a joint project committee, with representatives from the Indian Department of Biotechnology (DBT) and SDC, and an ISCB chair. The selection was based on relevance for the development of the respective institute, the region, the potential for technology transfer and future commercialization. These criteria explain the broad range of ISCB-supported biotechnology projects, including research on human health, animal husbandry, and microbial processes and products for agricultural purposes as well as for the pharmaceutical industry (see table). In principle, projects were approved for a period of three years by the joint project committee.
Over the last 10 years, the ISCB programme has received some US$ 8.04 million of funding, of which the DBT and SDC contributed 20 and 80 per cent respectively.

Strategy for capacity building
Biotechnology development requires a variety of different inputs such as biological resources, human, financial and technical capacities. Therefore, without the background of a multidisciplinary team and an adequate infrastructure, successful results can hardly be achieved. Moreover, technology routes cannot be exploited without proper linkages to producers and an established legal framework.
In order to enhance such multifaceted capacity building for R&D in the Indian partner institutes and to promote technology transfer, the ISCB supported not only the actual research activities, but also the steps alongside of the research. For instance, project proposals and annual action plans were assessed in collaboration with the scientific partners and, if required, with external experts. Moreover, specialized short- or long-term training events were organized at the Swiss partner institutes to strengthen knowledge and skills in newly emerging technologies. The ISCB also supported the purchase of essential laboratory equipment and other research tools, if this was necessary for training or research activities.
The programme facilitated joint research activities between the Indian and Swiss institutes. Workshops and seminars with guests invited from public, private, and government institutions enabled the researchers to discuss the potential routes for product development and to establish contacts with producers.
The ISCB also encouraged its partners to establish contacts with private institutions and offered the partners specific expertise, for instance validation of products such as biopesticides and FMD diagnostic tools. Projects were regularly monitored, which ensured coherence with national and international technology policies, for example on biosafety and risk management issues. For individual projects, guidance in biosafety issues was offered, such as consultancy in the establishment of a high-level safety laboratory for the work with FMD viruses. If required, policy questions were discussed at government level.

Biotechnology projects supported by the ISCB

Institute Project title Specific output Anna University,Centre for Biotechnology (Chennai) biopesticides from Bacillus thuringiensis and B. sphaericus Bacillus-based pesticides (2 applications for Indian patents to produce Bacillus-based pesticides); fully automated bioprocess lab up to 300 litre production capacity MS University, Biotechnology Centre (Baroda) bioprocess development and genetic manipulation in microbial systems (non-conventional yeasts, new bioactive molecules, bioconversion) systems for heterologous protein expression in nonconventional yeasts and their production; fully automated bioprocess lab up to 20 litre production capacity MK University, School of Biotechnology (Madurai) molecular analysis of Mycobacterium leprae and immunology of leprosy no products suitable for commercialization Indian Veterinary Research Institute (Bangalore) development of molecular and immunological tools for diagnosis of Foot and Mouth Disease (FMD) in India prototype diagnostic kits for detecting FMD BAIF Laboratories (Pune) diagnostics for Contagious Bovine Pleuro-Pneumonia (CBPP) no products suitable for commercialization National Environmental Engineering Research Institute (Nagpur) application of molecular genetics for the management of aromatics in waste  no products suitable for commercialization

General output infrastructure •  all laboratories at long-term partner institutes upgraded in terms of analytical instruments, bioprocess equipment, electronic communication, and availability of other essential research tools  technology transfer •  transfer of specific technologies (e.g., ELISA, PCR) •  laboratory manuals prepared for wider distribution •  8 international seminars held on product development research and training •  20 PhD theses •  56 Indian scientists trained at Swiss and other European institutes

Accomplishments and limitations of the cooperation
The external review of the programme in 1997 gave an overview on the achievements of the programme (see table), but also highlighted some of the restraints of the ISCB initiative.
At the outset of the programme, the socioeconomic status of biotechnology in Switzerland and India was different from today. R&D capacity building used to be the major focus of development collaboration, but today the DBT has developed considerable capacities for R&D in biotechnology. As a matter of fact, India and the ISCB programme face new problems in retaining well-trained human resources in technical sciences.
For instance, many PhD students leave their mother institutions for post-doctoral positions elsewhere, and university institutes generally have a high turnover rate of scientists. Therefore, to make Indian institutes profit from trained capacity, the programme made sure that PhD students following special courses abroad had to do this at least one or two years before they were supposed to finish their studies. On the other hand, the training of permanent faculty staff has its complications too. Although the programme ensured that all the trainees remained at their institutes, careful evaluation of the trainee’s real involvement in daily laboratory business must be made. Depending on the topic of the training, chances for technology transfer are low if techniques are taught to candidates that would not have to carry them out in their general work practice. Finally, the Indian industry can still not offer enough jobs that are sufficiently attractive scientifically, and therefore well-trained scientists often take the opportunity to leave the country.
Another important challenge for the programme is caused by the social and economic changes that have taken place in India: market liberalizations have facilitated the import of biotechnological products. Although Indian industry has shown interest in such products (see box), linkages between researchers and connections for technology transfer are still under-utilized. For instance, during the course of the programme, a heterologous protein expression system in non-conventional yeasts was developed. However, this has not fully been commercialized, because product development suffered from the missing link in validation between R&D and industry.
Today, therefore, the development of biotechnology products and processes is regarded as the core of the collaboration. This shift entails an approach that aims to integrate more partners, for example from the private sector, and to address transsectoral issues. Such an approach depends on institutions that do not only have a good track record in science but also a high management capacity, and where fast and flexible decisions are not hampered by hierarchic structures.
Although the ISCB tried to respond to the competitive environment in biotechnology, it proved to be difficult to foster the shift from scientific capacity building towards development of commercial products and processes within an ongoing programme. Several workshops were held under the heading ‘From an idea to a product’, to tackle the various phases of a product development process prior to the successful launch of a product on the market. This process requires knowledge on diverse subjects, ranging from R&D and technical development to registration and regulation.
However, these activities did not fully cover the programme premise that projects ought to move towards application and product development. There was still a need to involve new partners that were either capable of developing the research results and products up to the market level, or of giving advice regarding the management of Intellectual Property Rights (IPR), regulatory issues, technology transfer, and biosafety. A clear concept for creating these partnerships was never developed, which was partly due to a lack of regulations at the government level on both sides, as well as to the ISCB’s lack of guidelines on IPR.
Given the broad range of projects and partners within the ISCB, it is not surprising that it was sometimes difficult to reach agreement on a common goal. Applied research projects that had a limited time frame could reach the production stage within a set period. Other projects envisaged product development only on a long-term basis; for them, the building of scientific competitiveness and research capacity had first priority. However, the given organizational structure did not support the building of effective and strong research units between Indian and Swiss institutes. Project funds were allocated mainly for Indian activities and projects were defined by the Indian research partners. Therefore, the Swiss partners felt that they were not equally involved in planning and sharing of the results.

From research to commercial product In 1988, a scientific collaboration was initiated between the Centre for Biotechnology, Chennai, the Institute of Biotechnology at ETH in Zurich, and the Laboratory of Chemical and Biochemical Engineering at the Swiss Federal Institute of Technology (EPFL) in Lausanne. The main focus of this project lay on the production of biopesticides from Bacillus thuringiensis (Bt) and B. sphaericus. In the Indian partner institute, research had already reached a stage at which large scale production for field trials was required. The joint research enabled the development of quantitative analytical techniques and an understanding of the factors responsible for limiting growth in defined media, which is important for the industrial production of Bt pesticides. At the same time, isolation of new Bt strains using molecular biology based techniques and the study of the mode of action of the insecticidal crystal proteins were supported.  To foster technology transfer, knowledge exchange of new methodologies, and to make contacts, workshops were jointly organized on a regular basis. For instance, several practical courses in bioprocessing techniques, and automation and control were conducted. A seminar was held with international and national contributors from R&D institutions, policy and regulatory agencies, and private companies, to analyse the position of the project in the field of biopesticide development. To enter the stage of industrial production in India, the ISCB provided the necessary technical infrastructure, such as bioreactors and analytical instruments, while the Centre for Biotechnology managed to contract a local company, the Southern Petrochemicals Industries Corporation (SPIC), which agreed to finance the building of a new bioprocessing centre. In 1997, the products Spicturin (Bt) and Spicbiomass (B. sphaericus) were the first biopesticides entirely developed and registered in India. Furthermore, the Centre for Biotechnology filed two Indian patents on the processes. Its ability to upscale processes is now acknowledged by the industry and the centre has procured research assignments from several other Indian companies.

Towards a new ISCB programme
The external programme evaluation in 1997 led to the formulation of a new perspective for the ISCB. Based on these comments, it was decided that in the future more stakeholders should be involved. Negotiating and planning of the project should be done jointly with: research institutions; potential future users such as small-scale farmers; producers (industries); regulating state agencies or other official institutions; authorities dealing with safety matters; and organizations or individuals dealing with ethical questions. Moreover, project preparation should focus on the managerial capacities and flexibility of the research institutions concerned.
For the new ISCB programme a set of premises was defined:

•	Relevance of development issues. The new ISCB should address fundamental development concerns in India, including poverty alleviation for rural and urban populations and sustainable management of natural resources.
•	‘Integrated value chain’. The value chain concept is widely used for analysing trends in the biotechnology industry, but also applied as a planning and management instrument to move research activities to product development and diffusion. The concept is best understood as a chain of events that starts with the definition of a problem and ends with sustained market penetration of a new product, process, or service. A case-by-case evaluation is necessary to determine whether the needs of the resource-poor target group can be promoted by biotechnology and whether they will be able to afford products developed by the industries. The integrated value chain concept prevents unrealistic planning, strengthens synergy, supports innovation, integrates economic and social aspects from the outset, and gives valuable information on the amount of time needed to transfer a technology. Furthermore, it builds on already existing capacities and thus increases the chances for end-users to benefit from the new technology.
•	‘Transsectoral’ topics. A third important premise in the preparation process was that the new ISCB should focus on topics such as technology assessment and transfer, biosafety, ethics of biotechnology, and intellectual property management are to be given due importance in an area that is as innovative as it is controversial.
•	Funding for Swiss partners. To foster sustainable R&D partnerships, in the future the ISCB will also allow for funding of Swiss partners involved in the projects.

In September 1999, India and Switzerland signed a five-year bilateral agreement, which defines the framework for the future collaboration. A Joint Apex Committee consisting of eight representatives of SDC, DBT, universities, Non-Governmental Organizations (NGOs), and industry will assume overall responsibility for the programme.
It is expected that the ISCB programme will profit from the joint definition and management of individual projects by Indian and Swiss institutes or companies. This ownership and accountability at project level will be adequately reflected in the project implementation contracts.

New challenges ahead
The main task for the future ISCB programme will be to combine product development and commercialization with poverty alleviation. While the ISCB has already gained some experience in the former, achievements in the latter remain to be seen. This goal can be achieved only if ISCB will be able to develop capacities and strong partnerships along the entire biotechnology value chain.
In a first phase, the ISCB has now started to build up collaborative research partnerships following a systemic crop-based approach with specific focus on wheat and pulses. For full realization of the integrated value chain concept, however, a step-wise integration of more projects and partners who will accomplish the activities along the chain is planned. As such the ISCB must also ensure that appropriate technology transfer will take place at all phases and also takes into account newly emerging safety and regulatory issues. A permanent challenge will be not to lose track of the needs of resource-poor end-users. Towards this end, commercialization and distribution routes for delivery of the products have to be negotiated with the respective public and private stakeholders.
Katharina Jenny

ISCB, Institute of Biotechnology, ETH Hönggerberg, 8093 Zürich, Switzerland. Phone (+41) 1 633 21 95; Fax (+41) 1 633 10 76;
E-mail jenny@biotech.biol.ethz.ch
 

Sources
Jenny, K. and Schaltegger, E. (1999), "Ten Years of Indo-Swiss Collaboration in Biotechnology: Lessons learned and strategy for the future." In: Managing Agricultural Biotechnology-Addressing research program needs and policy implications. Wallingford, UK and The Hague, The Netherlands: CABI/ISNAR.

Nayak, A. (1999), "Point of View - Biotechnology in India." Genetic Engineering News, 19:(5)6, 1 March, pp. 6/30/48.

Rorke, M. (1993), Technology Transfer Manual for Research Institutes in Developing Countries. UNIDO, IPCT. 187. Austria, Vienna: UNIDO.