The Saga of Cuban Biosciences
The Cuban achievements in the life-sciences have been celebrated as the zenith of the Revolution and exemplary of its advanced educational system. A pivotal moment in the commitment to the State's investment in the national centers of excellence in the life sciences – to become known as the Polo Científico – is credited to the enthusiasm of the Cuban President Fidel Castro for the interferons in 1980 which, given the absence of patents in that jurisdiction, were appropriately and rapidly copied
In 1965 the Centro Nacional de Investigaciones Científicas (CNIC) was created to consolidate the most significant of the research groups on the island in a single and gigantic facility of a then-modern Soviet architectural design. The perestroikan movement for reformation in the USSR, leading to glasnost and the dissolution of the Union, resulted in the withdrawal of the Soviet presence in Cuba that was completed in 1992 so that the early Cuban recognition of the necessity for pharmaceutical independence – for livestock and crops, as well as for human health – was made even
and manufactured. Indeed commitment to science-based industry had previously been famously established in 1960 with his now widely-quoted remarks that “The future of our nation is necessarily the future of men of science.”
more critical by virtue of collapsing supplies and the continued US embargo that prohibited access to most of the world’s newest human and agricultural medicines and vaccines.
The goal of pharmaceutical independence was ambitious to a degree but realistic and achievable because Cuban scientists, of which there were many, were well advanced in chemical and biological sciences, resulting from years of collaboration with, and education in, leading institutions of the Socialist Block – principally Czechoslovakia, the German Democratic Republic and Russia – as well as a number other countries not intolerant of the Soviet and Cuban political systems, such as Canada, France, Sweden and the United Kingdom. In addition, the initiative was made possible by a massive investment by the State that resulted in a cluster (approximately 20 years prior to ”cluster” becoming fashionable in North America), the Polo Científico, principally located in Havana which together with a number of other centers of excellence throughout the country focused on human and agricultural health. All of this was supported by a rigorous regulatory body, the Centro Para el Control Estatal de Medicamentos (CECMED), and a national grid of clinical trial centers under the Centro Nacional Coordinador de Ensayos Clínicos (CENCEC) linking most of the hospitals across the entire island of a population of ~11 million. This novel approach to clinical trials was to have a huge beneficial impact effectively creating a CRO that was importantly differentiated by its access to some 200 clinical groups in over 100 facilities.
A 1989 report by the distinguished Dr. Manuel Limonta, the then director of Centro de Ingeniería Genética y Biotecnología (CIGB), provides a rich description of the explosion of early scientific successes. That scientific pursuit was seen as a cornerstone of the Revolution was expressly identified in “The Cuban “Exception”: The Development of an Advanced Scientific System in an Underdeveloped Country”; where Angelo Baracca and Rosella Franconi, the principal authors, introduce the extensive paper with, in part, “Even the collapse of the Soviet Union in the early 1990s, that could have put the achievements of the Revolution at risk, posing again the threat of subalternity, under an intentionally worsened American embargo, did not change this trend: once more Cuba addressed this challenge reconfirming the strategic choice of supporting its most advanced and profitable scientific sectors, especially the capital-intensive and typically-American field of health biotechnologies. This strategy proved to be once again a well-chosen course of action.”
A more comprehensive and meticulous review of the remarkable story, the reporting supported by extensive references and numerous insightful anecdotes, is Simon M. Reid-Henry’s 200-page “The Cuban Cure – Reason and Resistance in Global Science.” (University of Chicago Press, London – 2010)
In 1994, a Washington Post column reflected that Cuba once had the premier healthcare system in the Third World, one that rivaled those in many “developed countries” and, importantly, that “the US pharmaceutical industry would like to get a toehold in Cuba to avail itself of Cuba’s installed capacity in biotechnology in biomedical research and development.”
In May 1994, a Canadian company, specifically organized for the purpose, proposed a unique joint-venturing structure to the Consejo de Ministros of the Cuban Government for the development and international commercialization of a number of novel Cuban human and veterinary medicaments and devices that it estimated could achieve major-market regulatory approval and which it further assessed as being internationally competitive. The company’s submission in response to a request from the Consejo de Ministros was to propose a structure that would uniquely bridge the Cuban innovations to otherwise-inaccessible capital markets, to advance the products through the clinical and regulatory processes in major-market countries toward marketing approval, and to introduce Cuban science, largely unpublished in the “West” at that time, to multinational pharmaceutical companies for commercialization. The stated
intention of the company, that became known as YM BioSciences, was to be Cuba’s premier life sciences development partner and was structured with joint boards of directors and shared management in the operating subsidiaries. The proposed structure was embraced by the
To the knowledge of the authors of this paper no other joint-venture company has been established with any of the Cuban Scientific Centers for the major pharmaceutical market countries of the US, Europe or Japan as late as mid-2017. In 1999 SmithKline Beecham (now Glaxo SmithKline) licensed the world’s first meningococcal BC vaccine that had been developed at the Instituto Finlay for which SKB received an exemption from the US Office of Foreign Assets Control (OFAC) to license the vaccine – otherwise prohibited under various US provisions. To the knowledge of the authors the product was never entered into clinical trials by SKB or Glaxo. In 2004 the US company CancerVax, under a similar exemption from OFAC, licensed the Cuban-origin cancer vaccine – CIMAVax – as well as the TGFα and HER-1 vaccines originally licensed to YM's joint venture subsidiary, under an agreement with both the Centro de Inmunología Molecular, CIM, and YM BioSciences. YM's joint venture retained rights to CIMAVax, following its conclusion of an 84-patient Phase II clinical trial at six prestigious hospitals in Canada, and at Aberdeen (Royal Infirmary, Stobhill NHS Trust) and Leicester (Royal Infirmary) in the UK. However, the product never advanced into trials in the US as CancerVax ceased operations.
Consejo and YM initially established five joint venture companies incorporated in Canada and Barbados to hold licenses to products from five separate Scientific Centres, coincident with the approval of the licenses by the Consejo de Estado in May 1995.
A 1994 cornerstone presentation to the Asamblea Nacional del Poder Popular, the supreme body of State, described a portfolio of Cuban life-sciences' discoveries and innovations that, it was proposed, would bring to its economy the means to importantly diminish its reliance on tourism, tobacco, rum and sugar. Principal amongst the products listed were those that, a year later, constituted the joint venture portfolio with YM BioSciences – the EGFR monoclonal antibody, Nimotuzumab (CIM); Heberkinase, the world’s first recombinant streptokinase (CIGB); a novel computer-assisted diagnostic system, Diramic (CNIC); the antibiotic Dermofural (CBQ-U. Las Villas); and Udertan, a natural product for the treatment of mastitis (CENSA). Subsequently, a number of additional products that included the EGF vaccine – CIMAVax – radiolabeled and diagnostic versions of Nimotuzumab, a TGFα and a HER1 cancer vaccine were added to the joint ventures. Indeed, the majority of the products that
have since been referenced in international publications as Cuba's successes in the life-sciences, in addition to those joint ventured with YM, were listed in the 1994 presentation, extolled as prospectively-important contributions to the Cuban economy and notably included the first meningococcal B/C vaccine and the much-vaunted cholesterol-lowering medication, Ateromixol (policosanol-PPG). Medical devices for rapid immunodiagnosis, and hundreds of products that were originated in the numerous research facilities constituting the Polo Científico, were additionally referenced. Of the numerous facilities – currently reported as 38 - eight dominant centres account for the supermajority of the output with an additional half dozen more accounting for most of the balance.
SCIENCE AND MANUFACTURING CENTRES
POLO CIENTÍFICO
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Centro de Investigaciones Científicas (CNIC)
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Centro de Ingeniería Genética y Biotecnología (CIGB)
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Centro de Inmunología Molecular (CIM)
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Instituto Finlay de Sueros Vacunas
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Centro Nacional Animales de Laboratorio (CENPALAB)
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Centro de Biopreparados (BIOCEN)
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Centro de Bioactivos Químicos (CBQ -UCLV)
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Centro de Inmunoensayo (CIE)
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Centro de Neurociencias (CNEURO)
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Centro de Salud Animal (CENSA)
The extensive university network – particularly the Universidad de La Habana and the Universidad Central de Las Villas – makes an important contribution to innovative basic research.
Universidad de La Habana
Universidad Central de Las Villas