by Helen Yaffe
reprinted from London School of Economics
March 18, 2020
COVID-19 emerged in the Chinese city of Wuhan in late December 2019, and by January 2020 it had hit Hubei province like a tidal wave, swirling over China and rippling out overseas.
The Chinese state rolled into action to combat its spread and care for those infected. Amongst the 30 medicines chosen by the Chinese National Health Commission to fight the virus was a Cuban anti-viral drug called Interferon Alfa-2B, which has been produced in China by the Cuban-Chinese joint venture ChangHeber since 2003.
Interferon Alfa-2B and Cuban biotechnology
Cuban Interferon Alfa-2B has proven effective for viruses with characteristics similar to those of COVID-19. Cuban biotech specialist Dr Luis Herrera Martínez explains that “its use prevents aggravation and complications in patients, reaching that stage that can ultimately result in death.”
Cuba first developed and used interferons to arrest a deadly outbreak of the dengue virus in 1981, and that experience catalysed the development of the island’s now world-leading biotech industry.
The world’s first biotechnology enterprise, Genetech, was founded in San Francisco in 1976, followed by AMGen in Los Angeles in 1980. One year later, the Biological Front, a professional interdisciplinary forum, was set up to develop the industry in Cuba.
While most developing countries had little access to new technologies (recombinant DNA, human gene therapy, biosafety), Cuban biotechnology expanded and took on an increasingly strategic role in both the public-health sector and the national economic development plan. And this despite the US blockade, which obstructed access to technologies, equipment, materials, finance, and even knowledge exchange. Driven by public-health demand, it has been characterised by its fast track from research and innovation to trials and application, as the story of Cuban interferon shows.
The international history of Cuban interferons
Interferons are “signalling” proteins produced and released by cells in response to infections in order to prompt nearby cells to heighten their anti-viral defences. They were first identified in 1957 by Jean Lindenmann and Aleck Isaacs in London. In the 1960s, Ion Gresser, a US researcher in Paris, showed that interferons stimulate lymphocytes that attack tumours in mice. In the 1970s, US oncologist Randolph Clark Lee took up this research.
Catching the tail end of US President Carter’s improved relations with Cuba, Dr Clark Lee visited Cuba, met with Fidel Castro, and convinced him that interferons could become the wonder drug. Shortly afterwards, a Cuban doctor and a haematologist spent time in Dr Clark Lee’s laboratory, returning with the latest research about interferon and more contacts.
In March 1981, six Cubans spent 12 days in Finland with the Finnish doctor Kari Cantell, who in the 1970s had isolated interferon from human cells, and had shared the breakthrough by declining to patent the procedure. The Cubans learned to produce large quantities of interferons.
Within 45 days of returning to the island, they had produced the first Cuban batch of interferon, the quality of which was confirmed by Cantell’s laboratory in Finland. Just in time, it turned out.
Cuba’s 1981 dengue epidemic
Weeks later Cuba was struck by an epidemic of dengue, a disease transmitted by mosquitos. It was the first time this particularly virulent strand, which can trigger life-threatening dengue haemorrhagic fever, had appeared in the Americas.
The epidemic affected 340,000 Cubans, with 11,000 new cases diagnosed every day at its peak. 180 people died, including 101 children. The Cubans suspected the CIA of releasing the virus. The US State Department denied it, but a recent Cuban investigation claims to provide evidence that the epidemic was introduced from the US.
Cuba’s Ministry of Public Health authorised the use of Cuban interferon to halt the dengue outbreak. It was done at great speed, and mortality declined.
In their historical account, Cuban medical scientists Caballero Torres and López Matilla wrote:
It was the most extensive prevention and therapy event with interferon carried out in the world. Cuba began to hold regular symposia, which quickly drew international attention.
The first international event in 1983 was prestigious; Cantell gave the keynote speech and Clark attended with Albert Bruce Sabin, the Polish American scientist who developed the oral polio vaccine.
Convinced about the contribution and strategic importance of innovative medical science, the Cuban government set up the Biological Front in 1981 to develop the sector. Cuban scientists went abroad to study, many in western countries. Their research took on more innovative paths, as they experimented with cloning interferon.
By the time Cantell returned to Cuba in 1986, the Cubans had developed the recombinant human Interferon Alfa 2B, which has benefited thousands of Cubans since then. With significant state investment, Cuba also opened its showpiece Centre for Genetic Engineering and Biotechnology (CIGB) in 1986. But by then Cuba was submerged in another health crisis, a serious outbreak of meningitis B, though this too served to stimulate Cuba’s biotechnology sector.
Cuba’s meningitis miracle
In 1976, Cuba was struck by outbreaks of meningitis types B and C. Prior to that, only a few isolated cases had been seen on the island. Internationally, vaccines existed for meningitis types A and C, but not for type B.
Cuban health authorities secured a vaccine from a French pharmaceutical company to immunise the population against type C meningitis. However, in the following years, cases of type B began to rise. A team of specialists from different medical science centres was established, led by a woman biochemist, Concepción Campa, to work intensively on finding a vaccine.
By 1984, meningitis B had become the most serious health problem in Cuba. After six years of intense work, Campa’s team produced the world’s first successful meningitis B vaccine in 1988. A member of Campa’s team, Dr Gustavo Sierra recalled their joy:
This was the moment when we could say it works, and it works in the worst conditions, under the pressure of an epidemic and amongst people of the most vulnerable age.
Between 1989 and 1990, the three million Cubans most at risk were vaccinated. Subsequently, 250,000 young people were vaccinated with the VA-MENGOC-BC vaccine, a combined vaccine for meningitis types B and C. The vaccine recorded a 95 per cent efficacy rate overall, with 97 per cent in the high-risk age group of three months to six years. Cuba’s meningitis B vaccine was awarded a UN Gold Medal for global innovation. This was Cuba’s meningitis miracle.
Recalling a chart of the rise and sudden fall of meningitis B cases in Cuba, the Director of the Centre for Molecular Immunology (CIM) Agustín Lage told me, “one can work 30 years, 14 hours a day, just to enjoy that graph for 10 minutes … Biotechnology started for this. But then the possibilities of developing an export industry opened up, and today Cuban biotechnology exports go to 50 countries.”
Since its first application to combat dengue fever, Cuba’s interferon has shown its efficacy and safety in the therapy of viral diseases including hepatitis types B and C, shingles, HIV-AIDS, and dengue. Because it interferes with viral multiplication within cells, it has also been used in the treatment of different types of carcinomas. Only time will tell if Interferon Alfa 2B proves to be the wonder drug in tackling COVID-19.
• The views expressed here are of the authors rather than the Centre or LSE
• This article draws on the author’s new book We Are Cuba! How a Revolutionary People Have survived in a Post-Soviet World (Yale University Press, 2020) and particularly its fifth chapter, “The curious case of Cuba’s biotech revolution”
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