Monday, May. 13, 1996

MADE IN CUBA

By J. MADELEINE NASH/HAVANA

Gustavo De La Riva's lab boasts an imposing assortment of high-tech gear: automated machines for synthesizing DNA, centrifuges for swirling cell cultures, growth chambers for coddling delicate seedlings. There is even a particle gun that genetically transforms sugarcane embryos by peppering them with DNA-coated BBs. But what really impresses foreign visitors is the folding cot that occupies a corner of De la Riva's office. At the Centro de Ingenieria Genetica y Biotecnologia (CIGB) in Havana, Cuba, De la Riva explains, researchers strive to stay ahead of the competition by sleeping alongside their experiments.

Yes, Cuba--that impoverished island 90 miles and an ideological half-century away from Florida--has begun bootstrapping itself into a biotech minipower. This improbable endeavor ranks as one of the most idiosyncratic of President Fidel Castro's ventures, and despite the anticapitalist rhetoric that resurfaced during last week's May Day celebrations, it may well prove to be the most profitable. The flourishing technological barrio that has sprung up on the outskirts of Havana is not only supplying state-of-the-art health products to local hospitals and clinics but also selling more and more of its goods abroad, bringing in badly needed foreign currency in excess of $100 million a year.

Today Cuba is one of the world's largest producers of a recombinant vaccine against hepatitis B. It is the only producer of a vaccine against the bacterium that causes meningitis B, a particularly nasty form of the disease. It also makes a diverse line of pharmaceuticals: interferon for cancer treatment, epidermal growth factor for wound healing, streptokinase for heart attacks and monoclonal antibodies capable of diagnosing everything from pregnancy to infection with the AIDS virus.

Now Cuba's biotechnicians are expanding into agriculture and industry. Late last year CIGB was host to an international conference at which 250 scientists from the U.S., Europe and South America got a look at some of the products wending their way through the laboratory. Among the most promising: a recombinant vaccine that protects cattle against disease-bearing ticks, crops genetically engineered to repel insects, and industrial enzymes that cut energy consumption.

The Cuban romance with biotechnology began in 1980, when a visiting U.S. physician regaled Castro with tales of the latest wonder drug, interferon. Intrigued, Castro directed Dr. Manuel Limonta, a young Cuban hematologist and immunologist, to set up a facility to manufacture the protein. At first, Limonta and his small staff used human blood cells to produce interferon. But soon the advantages of recombinant DNA technology became apparent, and Limonta started making interferon in giant vats of genetically engineered yeast.

In 1986 Limonta became director of the brand-new CIGB, which quickly grew into a sprawling research dynamo, one of more than two dozen Cuban institutes dedicated to the biological sciences. The center--along with its marketing arm, a quasi-corporate entity called Heber Biotec--now employs more than 1,200 technicians and scientists. "We don't have an institute of this size devoted to biotechnology in all Australia," marvels Peter Willadsen, a molecular biologist who directs a center on animal diseases in Indooroopilly, Australia.

Cuba's research efforts have been highly pragmatic, aimed at solving real-life problems--of which Cuba has more than its share. Cuban agriculture nearly collapsed following the breakup of the Soviet Union, which for years subsidized Cuba with discount petroleum and petroleum-based fertilizers and pesticides. So scientists at CIGB concentrated on improving the food supply. Among other things, they equipped sugarcane and potatoes with bacterial genes that confer pest resistance and added an extra growth-hormone gene to tilapia, creating a faster-growing variant of that tasty freshwater fish.

CIGB scientists also tried to bolster sagging industrial productivity. Molecular biologist Manuel Raices helped develop a recombinant enzyme that dissolves dextran, a sticky substance that gums up the sugar-refining process. In tests conducted by local sugar mills, the enzyme reduced oil consumption up to 45%. Now Raices is working with Swedish researchers on an enzyme that digests lignin, a gluelike material that bedevils paper manufacturers.

Cuban researchers used to think of themselves as providers of biotechnology to their own country first, then to the Caribbean and finally to large developing nations like Brazil, China and Iran. Thus, Heber provides all Cuban newborns with the hepatitis-B vaccine for free and charges countries like India as little as $2 a shot. But the "special period"--as Cubans euphemistically refer to the economic crisis that followed the Soviet withdrawal--has redrawn these priorities, and Cuba's biotechnicians are entertaining larger ambitions. "We have the technology," declares Julio Delgado, who heads CIGB's industrial-enzyme program. "Now we're looking for partners with money."

Joint ventures with foreign firms could bolster Cuba's credibility in the global biotech marketplace. While Cuban institutions conduct clinical trials of vaccines and drugs and informally follow U.S. guidelines for field-testing recombinant organisms, the perception persists that Cuba sometimes releases its products prematurely. Recently, for example, scientists at the Citrus Institute developed a monoclonal antibody to detect tristeza, a lethal virus that threatens to devastate the Caribbean citrus industry. However, although the antibody works well in Cuba, it is being offered to countries whose crops may be infected with different strains.

Cuba clearly appeals to foreign pharmaceutical firms. It occupies a strategic location on the edge of major markets in North and South America and boasts more than 5,000 scientists and technicians--a skilled work force that is, by Western standards, grossly underpaid (average monthly salary: 400 pesos, or about $10). Peter Scott, chief executive of London-based Beta Funds Ltd., estimates that a European drugmaker could produce its drugs in Cuba for one-tenth the cost of local production.

Right now, however, the U.S. trade embargo prohibits American drug and chemical companies, Cuba's natural partners, from establishing joint ventures. The embargo likewise dissuades big European companies from striking deals with Cuba because products made in Havana cannot be sold in the U.S., which represents 50% of the global market for pharmaceuticals.

No one awaits the lifting of the U.S. embargo more eagerly than Cuban scientists, who struggle to obtain basic supplies--chemical reagents, for instance--that in the U.S. are but a phone call away, and whose incomes are starting to trail behind those of service workers buoyed by Cuba's rising tourist trade. CIGB has reportedly started paying its scientists partly in dollars to keep them from leaving the field. "I love my research," confides a hardworking scientist. "But if I have to drive a taxi to support my family, I will."

For scientists who are solving nature's intricate puzzles, the political obstacles that prevent them from working with U.S. colleagues seem relatively easy to solve. "All we require," says De la Riva, "is relaxation by the politicians, and then we can do great work together." Alas, for him and his friends, the crisis triggered by the downing of two U.S. planes in February has made that possibility seem more distant than ever.