WINE INTO VINEGAR-THE FALL OF CUBA'S BIOTECHNOLOGY Por José de la Fuente Ex Director de Investigaciones y Desarrollo (1991-1998) Centro de Ingeniería Genética y Biotecnología (CIGB) Cuba Nature Biotechnology October 2001 Volume 19 Number 10 pp 905 - 907 Octubre 11, 2001 For myself and many young Cuban scientists, the establishment of an advanced biotechnology center in Havana was the most challenging and rewarding endeavor we had ever undertaken. When our dreams were realized, the Cuban biotechnology program was a landmark in scientific accomplishment and a source of pride in the developing world. Less than 10 years later, that vision has been shattered, betrayed by a combination of intrigue, infighting, and bureaucracy. Cuba's once-vigorous biotechnology now is on the verge of expiration, strangled by increasing social and political tensions. Lacking capacity, creativity, and credibility, it is a paled and perhaps dangerous shadow of its former self. Beginnings Before the 1960s, scientific development in Cuba was marked by the work of a few outstanding biomedical researchers, such as Tomás Romay, Carlos J. Finlay, Felipe Poey, and Pedro Kourí, and lacked any sponsorship from the state. Shortly after the revolution, however, Fidel Castro proclaimed that "Cuba's future must, by necessity, be a future of scientists." This message was put into practice with the founding of the Cuban Institute for Research on Sugarcane Derivatives (ICIDCA) and the National Center for Scientific Research (CNIC). Over the years, these two centers served as the nuclei for the creation of numerous other scientific institutions, including the National Center for Animal and Plant Health (CENSA), the Center for Biological Research (CIB), the Center for Genetic Engineering and Biotechnology (CIGB), the Finlay Institute, the Center for Immunoassay (CIE), the Center for Molecular Immunology (CIM), the Center for Pharmaceutical Chemistry (CQF), the National Center for the Production of Laboratory Animals (CENPALAB), the International Center for Neurological Restoration (CIREN), the Center for Neurosciences (CNC), and the National Center for Bioproducts (CNB)1, 2. Education and health care were set as priorities3, and university centers grew from 6 in 1958 to more than 35 in 1980, with a matriculation of 240,000 alumni out of the 2.6 million students in 1990. Thousands of students were sent abroad, mainly to the Soviet Union, German Democratic Republic, and Czechoslovakia, for advanced scientific training. In 1997, more than 30,000 people were employed in 200 scientific institutions in the country. From them, according to the Ministry of Science, Technology and Environment (CITMA), 11,115 were professionals and 9,048 technicians4. The creation of this huge scientific pool of talent was a direct result of the revolution's policy in science and technology and followed Castro's ideas about the role of science in the development of socialist societies3, 5, 6. In some ways, therefore, Cuba experienced a scientific revolution within a process of political and socioeconomic transformation. Revolutionary science In 1980, Castro heard about experimental work with interferons (IFNs) for the treatment of cancer from a meeting with Lee Clark, then president of M.D. Anderson Hospital (Houston, TX)5, 6. Almost immediately thereafter, he made the decision to study IFNs and invest heavily in the "new" biotechnology, forming the Biological Front in 1981-a high-level policymaking body to speed the investment process. In January 1982, after a group of Cuban scientists led by Manuel Limonta trained at Lee's cancer hospital and at the Helsinki laboratory of Kari Cantell, the CIB was founded for the production and cloning of IFNs and for research in molecular biology and biotechnology5, 6 in general. Although IFNs turned out not to be the "magic bullets" predicted at the time, they served as a model for the development of molecular biology and biotechnology on the island7, 8. The inauguration of the CIGB in 1986 marked the beginning of the maturation of biotechnology in Cuba. An investment of approximately $US 100 million was used to fully equip modern research in areas covering pharmaceuticals, immunodiagnostics, vaccines, as well as animal, plant, and industrial biotechnology. Ten years later, the center had over 1,100 "employees" with more than 200 scientists in R&D working on a pipeline of 112 products. The impressive results of some projects (see Table 1), gave impulse to the creation of other research and production facilities, with a total investment of more than $US 1 billion6. As noted by Feinsilver5, the original impetus for the development of biotechnology was to meet domestic needs and to make Cuba a world medical power so as to accumulate symbolic capital (prestige, influence, credit, and goodwill) that ultimately could be converted into real capital (trade and aid). Furthermore, by creating this infrastructure, Cuba was in a position to take advantage of future developments in the rapidly advancing fields that compose biotechnology. The entire gigantic effort was oriented to the future, and the large expenditures were validated by potential. And in line with these expectations, the country's initial biotechnology effort resulted in several important scientific and economic contributions (Table 1), as well as earning enough in exports to sustain the biotechnology research and production program3, 5, 6, 9-11. In 1991, even though Castro had proclaimed a "special period in time of peace" a year earlier, the fourth Congress of the Communist Party of Cuba continued to stress the validity of the country's long-lasting strategy of using science and technology to promote socioeconomic development5. Apparently, the commitment to continue the development of biotechnology persisted despite the bleak economic situation faced by the country after the collapse of the USSR and European socialist block, and in the face of continued US political and economic hostility. In reality, the program would not continue along these relatively politically insulated lines for very long. Lengthening shadows Although we could not see it at the time, during the subsequent months, Cuba's biotechnology research gradually came under the influence of increasing institutional and political paralysis. Research centers lost the possibility of deciding internal policy; even for small things, decisions were now made by the Secretary of the State Council, José M. Miyar Barrueco ("Chomi") at Castro's personal insistence. For example, every proposal to attend a scientific meeting was personally reviewed and subject to Miyar's approval. But as Miyar was incapable of deciding scientific matters because of his background, he alternated between being overly cautious and extremely arrogant, and quickly became an unassailable wall between the centers and the government. As a consequence of the deteriorating economic situation of the country between 1990 and 1995, very limited resources were allocated for R&D. This both seriously impaired the possibilities for future scientific development and had negative repercussions for scientific enthusiasm and creativity. Research conducted during these years used the materials and resources stockpiled during the pre-1990 heavy-investment period. Despite repeated expressions of concern by the Cuban scientific community to policy-makers and Miyar, a desperate need for hard currency forced biotechnology medical products to the market without the due diligence that had previously characterized the country's biotechnology program. This is the case with a less than-successful recombinant erythropoietin produced in CHO cells and developed by the CIGB and CIM. Remaining resources were allocated only to short-term applied research or grandiose projects like the creation of a vaccine for AIDS. In the important area of agriculture, where biotechnology held great promise for Cuba, expectations have not been fulfilled because the fundamental problems lay in the inefficiency of the Cuban system of crop management, cultivation, and distribution, none of which is addressable by biotechnological intervention. This situation has led to a loss of confidence in the enterprise by the scientists whose enthusiasm and energy is needed to meet even modest goals, let alone the government's inflated claims for agbiotech progress on the island12. In the struggle to escape from the economic crisis, the government changed policy and decided that tourism, not biotechnology, was the way to rapidly attract capital. The commitment to biotechnology research decreased, and the technological gap between Cuba and industrialized countries continued to widen. In the past 10 years, for example, almost no capital improvements have been made to the CIGB, which at the time of its inauguration in 1986 was a state-of-the-art biotechnology facility. Scientific cooperation also suffered. While camaraderie between research centers continued to be an official slogan6, there was increasingly fierce competition between groups for resources and paternity rights over promising projects. Isolationism and regression The impact of these developments on international cooperation was sad and dramatic. In their relish to staunch a potential exodus of researchers, Cuban authorities mistakenly opted to obstruct participation in scientific meetings and joint projects-important components of the success during the early development of Cuba's biotechnology. Simultaneously, the number of productive visits by US scientists, who had played important roles in the rapid growth of the country's biotechnology, drastically reduced after 1996, mainly as a consequence of both the internal situation in the country, as well as the hardened US policy toward Cuba. The economic crisis and strategic myopia also adversely affected journal subscriptions, resulting in the discontinuation of many collections; much more significantly, however, access to the Internet has continued to be hindered by technical communication problems and especially by the government policy of restricting access to only "selected" centers and computers. As a result, ordinary scientists and graduate students throughout Latin America and the Caribbean now have more computing power and modern biotechnology tools at their fingertips than heads of some divisions at Cuba's most prestigious biotechnology institutions. To make matters worse, the approach for establishing strategic alliances in marketing and distribution with recognized biotechnology and pharmaceutical companies has been naive and unrealistic. In the past few years, the only international projects to have been realized are between the CIM and a Canadian venture capital company for producing "anticancer vaccines," an agreement between The Finlay Institute and the former SmithKline Beecham Pharmaceuticals (King of Prussia, PA) for the production of a meningitis B vaccine, and the sale to Iran12, 13 of the production technology for three of the CIGB's most significant accomplishments: a recombinant hepatitis B vaccine, IFN-IIb, and streptokinase. It is this last item that is profoundly disturbing to many of us who gave so much time and effort to the development of an economically viable but essentially altruistic biotechnology in our country. The strengthening of Cuban-Iranian cooperation began with Cuban aid shortly after the Iranian earthquake of 1990 (ref. 3). It has culminated in Iran buying outright the prized fruits of the CIGB, namely recombinant protein production technologies in yeast and Escherichia coli, as well as the large-scale purification protocols for both soluble and insoluble proteins synthesized in or excreted by them. There is no one who truly believes that Iran is interested in these technologies for the purpose of protecting all the children in the Middle East from hepatitis, or treating their people with cheap streptokinase when they suffer sudden cardiac arrest. Hopes extinguished The social and economic crisis in the country has of course become reflected in the values of the younger generations. The need for US dollars to acquire most goods in the market, and the deteriorating situation in the biotechnology sector, make work in the research centers less attractive than in sectors like tourism. Although the state previously favored scientists in biotechnology programs, paying "higher" wages and offering certain fringe benefits, these have become trivial under the present circumstances, and as there is no longer even the incentive of intellectual independence and the possibility of self-realization, many students no longer want to work in the biomedical centers. Worried about the socioeconomic crisis in the country, the Cuban Communist Party in coordination with the government in 1998 initiated a political crusade against scientists occupying prominent positions who defended ideas that diverged from the hard line dictated by the Party. The result was the firing or demotion of many senior scientists (myself included) and the imposition of political, rather than scientific, issues in the scientific centers. As a direct result of these policies, many scientists have been forced to abandon the centers or to leave Cuba and continue their careers in exile. 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