The Cuban case illustrates dramatically what can be achieved when a firm commitment is made to develop biotechnology capabilities and apply them to a wide range of areas in accordance with the country's economic priorities. In this section the Cuban case is examined in greater detail, paying particular attention to the way this country entered the field of new biotechnology, the areas in which new biotechnology has been applied, and the institutional changes brought about to facilitate the development of biotechnology. Finally, based on this case study, conclusions will be drawn regarding lessons for other developing countries.

2.4.4.1 General approach

The crucial watershed in Cuba's scientific and technological development occurred after the Cuban Revolution in 1959. Until then, Cuba depended primarily on agricultural activities, which lacked sophisticated processing and R&D capabilities, and on tourism. In this way foreign exchange was earned, which financed imports of manufactured products, largely from the United States. After the Revolution, a new set of priorities was established. Most important for development of the biological sciences in general, and biotechnology in particular, was the emphasis given to the role of science and to the development of the national health service. Frequent reference is made by Cuban scientists to the conviction prevailing at that time that the future development of Cuba was inextricably bound up with the future development of science in the country. It was this conviction that inspired rapid growth in the school and higher education system. At the same time, an important result of the Revolution was the expansion and extended delivery of medical services to all sections of the population. This meant that within a short time, Cuba was able to develop a relatively sophisticated medical system, which included training and research facilities in universities and other national institutions. It was this medical system that was later responsible for Cuba's rapid and successful entry into new biotechnology.

However, new areas of science and research do not emerge automatically; their emergence depends on new groups of scientists and researchers, committed to the new fields of study and devoted to the institutional changes required to realize new scientific research. From this point of view it is significant to observe that the new institutions which evolved in Cuba to develop the biological sciences and biotechnology emerged in a pluralistic rather than a linear way.

At the apex of Cuba's scientific planning establishment is the Cuban Academy of Sciences, which was originally established in 1861 but substantially restructured after the Revolution. The Academy contains the Superior Scientific Council, which consists of about 77 distinguished scientists elected from the Academy's various institutes, from the Ministry of Higher Education, and from industry. The Academy also contains a number of other smaller but influential advisory groups. However, it is significant that the Academy does not totally dominate or control the scientific establishment. For example, only about 10% of the total number of Cuban scientists and engineers work in Academy institutes.

The Ministry of Higher Education, with some degree of autonomy from the Academy, has also played an important role in the establishment of scientific institutions. From the point of view of the development of Cuban biotechnology, an important example is the establishment of the National Centre for Scientific Research (CENIC), which was the major biomedical and chemical research centre and was set up in 1965 to stimulate research in new areas. CENIC has a staff of approximately 1,000 and is divided into four main divisions: biomedicine, chemistry, bioengineering, and electronics. CENIC has played a significant role in research and in training scientists who subsequently have become involved in other spin-off institutes.

An important example is the Centre for Biological Research (CIB), which was established in January 1982. The establishment of CIB is of particular interest as a result of its innovative and unbureaucratic origins. In 1981 a 'Biological Front' was established essentially outside the existing bureaucratic framework. The Front consists of scientists and policy-makers with an interest in extending and developing biological research in various directions. It served to coordinate and articulate the interests of those in different Ministries and institutes who wished to strengthen Cuban involvement in biotechnology. While the leaders of the existing scientific establishment were closely involved with the activities of the Biological Front, the Front was set up as a high-level policy-making body, relatively autonomous from the Academy and the various Ministries involved in biological sciences and their areas of application.

From this position the Front supervised the establishment of CIB and later the Centre for Genetic Engineering and Biotechnology (CIGB). By helping to give birth to CIB and CIGB, the Biological Front served to increase pluralism in the Cuban scientific system. While biotechnology could be developed in existing institutions, such as those under the control of the Academy of Sciences and CENIC, this new set of technologies could also be advanced through new institutions such as CIB and CIGB.

CIB began with a staff of six researchers in a small laboratory. Its major initial mission was the production of interferon for use as an antiviral agent. The interest in interferon resulted in part from the outbreak in late 1980 of dengue haemorrhagic fever, which affected approximately 300,000 people and resulted in 158 deaths. In addition to this pragmatic goal, CIB also aimed to use interferon as a 'model' for development of the wider range of capabilities and assets analysed in Section 2.4.3. In other words, interferon would be used as a springboard for developing a Biotechnology-Creating System with expertise in the areas of genetic engineering and bioprocessing. CIB grew rapidly and by 1986 was divided into four laboratories: genetic engineering, immunology, chemistry, and fermentation. In addition to interferon, CIB also produces its own restriction enzymes. Its research also involves synthesis of oligonucleotides; cloning and expression of a number of other genes, and production of monoclonal antibodies for diagnostic purposes. Although recombinant DNA research was also done in a number of other institutes, notably CENIC and to a lesser extent the Cuban Institute for Research on Sugarcane Derivatives (ICIDCA), which was established in 1963, by the early 1980s CIB became the major location in Cuba for the development of capabilities in new biotechnology.

When CIB opened in January 1982, it began to produce human leukocyte alpha-interferon using a method (which did not involve genetic engineering) developed by Kari Cantell of the Central Public Health Laboratory in Helsinki. Cantell gave assistance by transferring his method to CIB and was surprised at the speed with which the Cubans mastered the method. Having mastered this conventional method for producing interferon, CIB embarked on rDNA-based techniques to produce various kinds of interferon.

In this latter task a central role was played by scientists such as Dr. Luis Herrera, who was Vice-Director of CIB. Herrera's background is particularly interesting because it illustrates personally the way Cuba was able to enter the field of new biotechnology. In 1969 Herrera studied molecular genetics (working on yeast) at Orsy University in Paris. The following year he took a post as researcher at CENIC, where he started a laboratory dealing with the genetics of yeast.

Yeast was of interest in Cuba because it was used to convert sugarcane derivatives into single-cell proteins. These were used as animal feed to substitute for imported soya feeds, since the Cuban climate is not suitable to grow soya. Research on yeast partly aimed to improve yeast strains to increase the nutritional value of the single-cell proteins by eliminating some of the undesirable nucleic acids. Under the auspices of ICIDCA there were in total 10 plants each producing 12,000 tons per annum of single-cell protein for animal consumption. In developing their work, researchers in this laboratory became interested in new biotechnology.

In 1979 Herrera returned to France to study molecular biology and genetic engineering. With the formation of the Biological Front and the establishment of CIB in 1982, he joined the Institute as its Vice-Director. In 1983 he once again went to France where he spent time at the Pasteur Institute. Representing a new breed of young, post-revolution scientists who were quickly able to master the latest international research techniques, he has since established an international reputation for his research in new biotechnology.

Although in the case of Dr. Herrera entry into new biotechnology involved access to European institutes, Cuban biotechnology and CIB in particular have also benefited from Soviet science. A notable example is the group of chemists working in CIB and mostly trained in the former USSR. With a strong background in organic chemistry some of these scientists moved on to synthesis of oligonucleotides and DNA. Other groups in CIB are involved in immunology, including immunochemistry and protein purification and fermentation.

There is widespread agreement that the Cuban mastery of new biotechnology has been impressive. One example is the conclusion by a team of UNIDO experts appointed to find a Third World location for the new International Centre for Genetic Engineering and Biotechnology. This team visited the major Third World countries involved in biotechnology and concluded that the Cuban biotechnology programme was one of the best they had seen. Another example is assessments made by distinguished foreign visitors to Cuba. While acknowledging that the Cubans are not attempting to do world frontier basic research, many of these visitors have been impressed with the level of achievement of Cuban biotechnologists.

2.4.4.2 Interferon as a 'model'

Some further comments are in order on CIB's use of interferon as a 'model' for the development of new biotechnology capabilities.

The first point is that the development of core scientific capabilities in new biotechnology at CIB drew on the already well-developed science base that existed in Cuba by the time the CIB was set up in 1982. Mention was made in the last section, for example, of the earlier research done at CENIC on the molecular genetics of yeast. In entering new biotechnology, therefore, Cuba was not starting ab initio. Thus, Cuban entry into new biotechnology was facilitated by a preexisting stock of substantial scientific capabilities. Clearly, many developing countries are not in as fortunate a position.

The second point is that interferon was an appropriate choice for Cuba largely as a result of the country's well-developed health sector. This meant that development of interferon using genetic engineering techniques was not simply a 'pure' research activity. Rather, it was an example of scientific work being linked closely to the production of useful output, namely the delivery of medical services, a high priority in post-revolutionary Cuba. This link established a unity between 'science push' and 'demand pull' determinants of technical change, which in turn ensured that this part of the science system was not 'alienated' from the needs of the rest of the socio-economy. Interestingly, interferon has also been used as a 'model' by many Japanese companies entering the field of new biotechnology. In their case, however, the need determined from the corporation's point of view was for a way to acquire new biotechnology capabilities while simultaneously producing a commercializable product. Interferon, it was believed, was one of the first new commercial products based on biotechnology. For other developing countries, however, a different product may represent a more appropriate 'road' to the development of new biotechnology, depending on the circumstances and priorities of the country. For Brazil, for example, the ethanol from sugar project may have provided an appropriate road. In other Latin American countries the development of mineral-leaching bacteria for mineral extraction may provide an appropriate way of entering new biotechnology.

Third, the possibility of using interferon as a 'model' for the development of other applications and products illustrates the pervasiveness of new biotechnology. This point is further supported in the Cuban case by the history of the Centre for Genetic Engineering and Biotechnology.

2.4.4.3 Realizing economies of scope: CIGB and the pervasive applicability of new biotechnology

Encouraged by the success of CIB in developing new biotechnology capabilities and impressed with the potential of this set of technologies, the Biological Front recommended the establishment of a new and larger institute which would carry on and extend the work of CIB. Accordingly, on I June, 1986, the Centre for Genetic Engineering and Biotechnology was established on a new site near CIB.

CIGB was structured in terms of the following five groups, each dealing with a specific problem area:

1. Proteins and hormones. The aim of this group is to use recombinant DNA techniques to produce proteins for applications in human medicine and veterinary science. This group continues the work done in CIB on the chemical synthesis of oligonucleotides and DNA.

2. Vaccines and medical diagnosis. The aim of this group is to develop vaccines against diseases prevalent in Cuba and other tropical and subtropical areas by cloning the surface proteins of viruses, parasites, or bacteria. The group is also working to develop monoclonal and polyclonal antibodies and DNA probes for detection and diagnosis of various illnesses.

3. Energy and biomass. The research of this group involves the transformation of various kinds of biomass via chemical methods and enzymes. For example, research is done on yeasts and fungi that transform the sugar by-products of molasses and bagasse into proteins for animal consumption. This group has produced a new strain of the yeast Candida, which increases the production of an amino acid important for both human and animal nutrition. CIGB will extend research in this area done at ICIDCA and CENIC.

4. Plant breeding and engineering. This group does research on improved plant varieties using genetic engineering and other biotechnologies, such as cell culture. Nitrogen fixation is one area singled out for study.

5. The genetics of mammalian eukaryotic cells. This group uses the cells of higher organisms to clone genes for protein production.

By using interferon as a 'model', first CIB and then CIGB have been able to develop core scientific capabilities in the area of new biotechnology and apply these capabilities to a wide range of areas consistent with Cuban development priorities. However, the research of CIGB has also been defined to include an emphasis on 'complementary capabilities 1', namely downstream bioprocessing. This has been done by making provision for a pilot bioprocessing plant at CIGB.

2.4.4.4 The importance of downstream bioprocessing

As noted earlier in this chapter, development of an effective biotechnology-creating system involves more than mastery of the core scientific capabilities. One necessary feature of such a system is downstream bioprocessing capabilities. To develop these capabilities, CIGB has established a pilot plant. Two groups work with this plant: one specializing in the fermentation process and doing research to optimize productivity, and the other working on questions of purification. Both of these groups face the difficulties inherent in scaling-up bioprocessing by using larger bioreactors. A major problem confronted by both groups is that there is little experience in Cuba in bioprocessing and scale-up. Furthermore, unlike many of the core scientific capabilities, where research is done in universities and the results are usually made public, a good deal of research on bioprocessing is done by private companies and the findings are kept commercially secret. Bioprocessing, requiring sophisticated engineering skills and specialized inputs, frequently constitutes more of a constraint in developing countries than mastery of the core scientific capabilities.

The same point was stressed by senior officials involved in biotechnology planning in the People's Republic of China during my visit there in 1987. In China, in strong contrast to the Cuban example, the core scientific capabilities were acquired rapidly, largely as a result of scientific interchange with the United States. However, major constraints exist in China in downstream bioprocessing, which depends on the capabilities of Chinese industrial and engineering enterprises.