Italian Company Seeks Foothold In U.S. Science

With a neuroscience institute in Washington and an emphasis on basic research, FIDIA aims to bolster respect worldwide WASHINGTON - Long after the vinyl and paper folders from a typical scientific conference have been tossed in the trash, a genuine imported leather portfolio with bright red decorative stitching and the inscription: "FIDIA-Georgetown Institute for the Neurosciences, November 3, 1985" is likely to remain on the shelves of many scientists. It's just too nice to throw away. That kind of staying power was precisely what FIDIA, an Italian drug company, hoped to achieve when it hired a top designer to help it celebrate its inaugural symposium here four years ago. The portfolio, designed to be a lasting souvenir, also illustrates the ingratiating style with which the expansionist firm has successfully courted an initially wary American neuroscience community. That style has featured an elegant banquet in the imposing grand hall of Washington's cavernous Pension Building, a private concert by an Italian orchestra at the majestic Kennedy Center for the Performing Arts, and a gathering of eminent scientists from around the world, all underwritten by FIDIA. "The attention to detail at FIDIA events is absolutely deliberate," confides Alberto Grignolo, an experimental psychologist trained in the United States and president of FIDIA Pharmaceutical Corp., the company's U.S. subsidiary. "People appreciate Italian design. They associate Italy with good taste, innovative products, good food, nice furnishings, art, history, poetry, and literature. Quite frankly, we try to capitalize on this." But that glamour is only a veneer for an ambitious effort to win over scientists who toil in decidedly more mundane settings. FIDIA wants to carve out a place for itself in a country that is the recognized leader in biomedical research. And its high-profile institute here is an important means to that end. As Grignolo notes, "In this country the name FIDIA does not elicit images of a drug company. It elicits images of science - and of style at scientific meetings." Indeed, FIDIA has endeared itself to many American neuroscientists through their minds as well as their pocketbooks. A nonprofit branch, the FIDIA Research Foundation, has endowed Georgetown University with a no-strings-attached, internationally recognized neuroscience institute. It's also bankrolling a sister institute in Moscow and a unique neuroscience educational center in a medieval Italian monastery (see accompanying story). The Washington-based foundation pays the travel expenses of young scientists at meetings; it finances publications, conferences, and other scientific exchanges worldwide; and it sponsors major awards in the neurosciences that are given out by the National Academy of Sciences and the Society for Neuroscience. Last spring it convened a week-long series of symposia at Georgetown University that featured presentations by six Nobel laureates. Meanwhile, the company's for-profit subsidiary tends to business. It is shepherding some of FIDIA's drugs through the Food and Drug Administration (FDA) approval process and is conducting trials through contracts with clinical investigators at major U.S. medical centers. The company's own research labs in Italy are supporting the basic research of selected U.S. investigators in areas of interest to the company. And the FIDIA Information Network is helping to launch two new scientific journals, filling niches in the emergent fields of neuroendocrinimmunology and veterinary neurology. FIDIA, an acronym for "Farmaceutici Italiani, Derivati Industriali e Affini" ("Italian Pharmaceuticals, Industrial Derivatives, and Related Products") is Italy's fourth largest drug company. It manufactures that country's best-selling prescription drug, Cronassial. A combination of four gangliosides (naturally occurring lipids), the drug is said to promote neural regeneration and is given for a wide range of "peripheral neuropathies." Launched in Bologna in the late 1940s, FIDIA sought to develop biologically derived compounds as potential therapeutic agents. The company began investing in neurobiology in the mid-1960s. Its "neuroscience ideology," according to Grignolo, is to create drugs based on an understanding of the workings of the brain and nervous system. The man behind that ideology is chemist Francesco della Valle, who now heads the parent company in Abano, Terme, Italy. Grignolo says that della Valle nurtured a "culture of neural plasticity and regeneration" in his country that made FIDIA's products popular among Italian physicians. Last spring, Georgetown University awarded della Valle an honorary doctorate for his commitment to supporting basic research in neurobiology. Erminio Costa presides over a fledgling empire in the neurosciences. At the core is his work at the joint institute at Georgetown. "We have in our hands compounds that are 10 to 20 times more active and that last three to four times longer than gangliosides," says Costa about FGIN's studies of neuromodulatory mechanisms that in his view could lead to a new generation of "magic bullet" drugs. "They can be taken by mouth and enter the brain." Compounds that target specific types of receptors - and only during pathological states - represent "the ideal condition for drug action," he says. He adds that he doesn't know if FIDIA is interested in developing them. But FIDIA isn't the only game in town for Costa and his team. Their success in obtaining federal grants, besides being a prerequisite to gaining tenure at Georgetown, gives FGIN's scientists "the right to be equal citizens in the academic world," said Costa. Institute scientists gain a leg up by receiving seed money from FIDIA for preliminary studies. So far they have been fairly successful: FGIN scientists currently hold about $900,000 annually in approved grants, notes Costa. The institute builds ties with NIH in other ways as well. Several visiting scientists have NIH Fogarty fellowships or other outside support. FIDIA is supporting doctoral and postdoctoral training programs for 11 students. And true to its internationalist tradition, the institute currently employs scientists from France, Spain, Italy, Yugoslavia, and Israel. Two Soviet molecular biologists training at FGIN will return to Moscow soon to establish a similar FIDIA Research Foundation-sponsored institute, which will be affiliated with one of the USSR's major psychiatric research hospitals. Costa also serves as chairman of the FIDIA Research Foundation's scientific advisory board and as director of its International School for Neuroscience. The school will be located at Praglia, an active abbey between Padua and Venice that was built in the 12th century. "It will be sort of like a `Woods Hole' for neuroscience," he explains. "The university has fulfilled so well the role set for it in the 1300s and 1400s - to spread culture among the people - that it can't any more be the think tank for developing new ideas. There is too much activity going on, too many people, too much pressure, too many students." Just as monasteries evolved into universities to spread culture, science must now return to the monastery conceptually - even literally - to develop "centers of higher thinking," says Costa. He hopes to create a network of small neuroscience centers throughout the world that would preserve the local "cultural flavor" that he sees as being "very important for development of new ideas." Contemplative environment at Praglia, mentors and younger investigators will engage in "tutorial interaction," planning and under- taking collaborative projects, he says. The school had 600 applicants for 30 slots in its first two-week session last spring, even though students had to bear half of the cost of their tuition. Enrollment will be expanded to 50 for the next class in September. The foundation sponsors a stream of noteworthy events. Each spring it puts on a major neuroscience conference at the National Academy of Sciences, which also serves as the conduit for a major award in the neurosciences underwritten by the foundation. Among other activities, the foundation holds a satellite symposium at the annual meeting of the Society for Neuroscience, through which it also channels a young investigator award. Future projects include a planned telefaxed weekly neuroscience newsletter, according to Darwin Cheney, a former government and CIBA-GEIGY Corp. neuropharmacologist who recently became president of the foundation. Publishing conference proceedings and other scholarly documents continues as one the foundation's stock-in-trade activities. Other FIDIA-backed publications emanate from the FIDIA Information Network, part of Grignolo's for-profit operation. It operates as something of a neuroscience intelligence agency, gathering and digesting the latest scientific developments in areas of corporate interest and funneling it back to Italy. It also disseminates a science news digest and has spawned the journals Progress in NeuroEndocrinImmunology and Progress in Veterinary Neurology. --J.A. However, although there is general agreement that the idea of neural plasticity is important in brain research, della Valle's emphasis on developing lipid-based drugs in treating various diseases is still not widely accepted among U.S. scientists. Mary Ann Markwell, a researcher at the National Institute of Mental Health, says she often encounters such "bias" against - and "ignorance" about - lipids among American scientists. "My work [the discovery that a glycolipid can serve as the receptor for a virus] has been confirmed in Russia, Japan, Sweden, and Switzerland, but no one in the U.S. has the expertise or the interest to do the experiments," she says. "Their attitude is: `If you can't clone it, we're not interested.' " She notes that it's easier for scientists to study the molecular basis of proteins than of lipids, which can only be assessed indirectly, via the enzymes that make them. That added difficulty doesn't bother Markwell. In fact, her NIMH lab has signed a collaborative agreement with FIDIA that helps her test the possible roles of glycolipids as autoantigens, receptors, "boundary" tissue, and markers in mental and neurological disorders. Whatever its scientific value, della Valle's focus on lipid-based drugs has been good for business. When della Valle joined FIDIA in 1968, it had 60 employees. Today it employs 1,200, 400 of whom are involved in research and development activities worldwide. A growth spurt over the past five years, during which the company doubled in size, coincided with a major effort to penetrate foreign markets. Last year FIDIA reinvested some $60 million, about a fourth of its total sales, on neuroscience research. Grignolo says that percentage is one of the highest among drug companies worldwide. "Our international strategy holds that by supporting innovative neuroscience research, both basic and clinical, we will be able to conquer foreign markets and develop drugs in ways that are most appropriate for those markets," he says. "That's the reason for our presence in the United States." FIDIA has used its contacts with experienced clinical investigators at major U.S. medical centers to conduct several double-blind, placebo-controlled clinical trials of gangliosides and other lipid-based drugs. The trials involved patients with various disorders, including stroke and age-associated memory impairment. FIDIA officials see the U.S. market as crucial to their long-term international success. Approval by the FDA, generally seen as the world's toughest drug regulatory agency, would give FIDIA leverage with its counterpart agencies in other countries. At the same time, most neuroscientists receiving FIDIA support in the U.S. aren't working on problems related to the company's products. "The most important aspect of FIDIA's style is that it promotes research without strings attached," asserts Erminio Costa, director of the FIDIA-Georgetown Institute for the Neurosciences (FGIN). "I don't have any duty to work for the drugs of FIDIA. I can work on whatever subject I want, provided it's neuroscience. That's the only limitation I have." FGIN has charted its own course since its highly celebrated debut in 1985. Scientists at the institute have studied the neurobiology of anxiety, signal transduction mechanisms, and the molecular biology of nerve growth factor. They have also published some 130 papers in a process that has been virtually free of any obligations to their corporate benefactor. Under its 1985 agreement with FIDIA, FGIN, and Georgetown University would share any royalties from patentable discoveries. FIDIA retains rights of first refusal for commercial exploitation of such discoveries and, in return, picks up the $3 million-plus annual tab for basic operation of the institute, plus the cost of designing and building a new facility. FGIN's 65 scientists and support personnel are free to compete for additional grant support, says Costa, who, like several of his FGIN colleagues, holds a faculty appointment at Georgetown as part of the deal. Costa says he proposed creating such an institute in 1984, shortly after he rejected an offer to head up the company's labs in Italy. An Italian-born physician with a flair for the romance of science, "Mimo," as his friends affectionately call him, apprenticed under National Institutes of Health neuropharmacology pioneer Bernard B. Brodie and is a member of the U.S. National Academy of Sciences. He is widely known for research on the fine-tuning of brain chemical messenger activity, particularly the workings of GABA, the inhibitory neurotransmitter system that mediates Valium and other minor tranquilizers (benzodiazepines). For more than a decade Costa directed a government preclinical pharmacology laboratory at Saint Elizabeths Hospital in Washington, D.C. Although housed in lackluster converted wards and geographically isolated from the rest of the NIH community, his lab became a mecca for neuropharmacologists. He helped to train 177 young neuroscientists in 17 years, nearly three fourths of them from abroad. Costa's scientific progeny now dominate neuropharmacology in Italy, where Costa is revered as a distinguished mentor and as a hometown boy who made good. His Italian ethnicity and language fluency notwithstanding, it was Costa's special talents as an educator and nurturer of "scientific culture" that attracted FIDIA to him, says Carl Pergler, who recently retired after five years as president of the research foundation. "There is no supervision by [FIDIA's] lawyers on the activities of the Institute," says Costa. "I am responsible for withholding from publication findings that I think are important for patents. We have already obtained two or three patents. I don't know whether FIDIA will use them, but if they do and earn money, they'll have to pay a royalty to the institute. This will apply also to collaborations we've initiated with Genentech and Hoffmann-La-Roche." Costa is building up the institute with an eye for its long-term health. "My dream is to keep this activity going through patent royalties," he says. "This is the way science and industry have to collaborate. Science has to furnish tools to industry, and it has to help industry's earnings to foster the growth of science." Jules Asher is a freelance science writer in Silver Spring, Md.

Italian Company Seeks Foothold In U.S. Science

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