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The Genomic Dream in Iceland (and elsewhere) v.s. Cystic Fibrosis
By Steindor J. Eerlingsson

The Iceland-based US genomics company deCODE Genetics has been the subject of much international discussion since 1998. In that year, the Icelandic Parliament passed a bill that gave the company exclusive rights to construct a commercial database, based on Iceland’s extensive medical records. The controversy surrounding the company has flared up again in Iceland. In January, 2002, deCODE announced that it had bought the US pharmaceutical company MediChem Lifesciences, enabling deCODE to conduct its own pharmacological researches. DeCODE plans to move MediChem’s operations to Iceland. In order to facilitate this $350 million move, the Icelandic Government is guaranteeing a $200 million loan to the company. This has met with great opposition in Iceland but the Government, with its secure parliamentary majority, is ignoring it. Critics in Iceland argue that deCODE’s pharmacological expansion is ill advised and, in light of the great financial risks involved this project, does not merit state sanction. deCODE plans to move from high-risk genomics research to an even more perilous project: using genetic information, that it has not yet produced, to develop drugs; a feat that no one has yet accomplished. In this context it is interesting to compare deCODE’s plans, and those of other genomics companies, with the story of cystic fibrosis.

Biotechnology, as we know it today, does not have a long history. It was not until the advent of the polymerase chain reaction (PCR) technology in the late 1980s that it could even be turned into an industry. Since then the technological advances in the life sciences have moved at a rapid pace, symbolized by the early completion of the Human Genome Project. The sequencing of the human genome is, indeed, one of the foundations underlying companies that are engaged in functional genomics. (Functional genomics can be defined as the development and application of genome-wide experimental approaches to assess gene function by making use of the information and reagents provided by structural genomics.) deCODE and other genomics companies are hence using relatively new technologies that have not yet produced any decisive results.

This is vividly shown in an article in the American Journal of Human Genetics (November 2001), entitled “Genomewide Scans of Complex Human Diseases: True Linkage is Hard to Find.” The article reviews 101 papers that report the findings of research based on genome-wide scans. These papers show that we are still a long way from finding the genes and their products that some scientists thought played a role in various human diseases, if there even is a correlation. deCODE now plans to venture into this still more uncertain business of developing drugs based on genetic information, which the company has not made public. Even if deCODE had all the necessary genetic information, gigantic difficulties would still await the company, as the cystic fibrosis (CF) story shows vividly.

The gene that plays a role in CF was found in 1989, and in a report in Science (September 1, 1989) it is hoped that this discovery would lead to “improved therapies for the now fatal disease.” In a paper in Science (May 8, 1992) entitled “Cystic Fibrosis: Molecular Biology and Therapeutic Implications,” Francis S. Collins states that “three new pharmacological approaches are currently in clinical trials and show considerable promise” and that the nature of cystic fibrosis has “increased the attractiveness of CF as one of the first major targets for human gene therapy.” Collins, it should be mentioned, owns a patent on the CF gene.

Nine years later neither of these approaches to treating CF have been successful, as was noted in the Lancet late in 2001. Even though “CFTR [the gene associated with CF] was among the first large human genes to be identified, cloned, and fully sequenced and an early candidate for use in gene therapy, technical challenges remain evident even after more than a decade of effort with this form of therapy. Meanwhile, pharmacological approaches directed at specific biochemical defects underlying the disorder have continued to be pursued.” Indeed, recent pharmacological “findings hold promise for the development of effective treatment protocols” (Lancet, December 15, 2001). In other words, it is obvious that 13 years of extensive efforts and huge financial investments to find a treatment for CF have still not borne fruit, either on the pharmacological or gene therapy fronts. An editorial in Science (October 13, 1989) stated that “the Cystic Fibrosis Foundation has spent $120 in the past 4 years on one illness, to say nothing of the other foundation and federal money spent on the same project.” But the article observes that, unlike CF, “illnesses such as manic depression, Alzheimer’s, schizophrenia, and heart disease are probably all multigenic and even more difficult to unravel.”

This story of the CF researches in the past decade throws a very interesting light on deCODE’s strategy and also on the genomics industry as a whole. deCODE plans to identify and describe the function of genes that contribute to the onset of 45 common diseases (http://www.decode.com/resources/diseases/), and to discover new and better drug targets. In addition, the company will use gene expression studies and protein-protein interaction systems to define molecular pathways that also may contain drug targets. All of these diseases are thought to be caused by an unknown number of genes and their interactions with the environment, while CF is associated with one gene whose expression is not known to be directly affected by the environment. deCODE and other genomics companies have still not made any significant progress in identifying the genes linked to the diseases they are studying, while the role of the CF-gene has been known for 13 years. deCODE is now planning to build a pharmaceutical company in Iceland that is supposed to produce drugs based on genetic information that still is not available (and may never come), while years of effort to find a cure for CF has so far been in vain.

Though these particulars also apply to other genomics companies, deCODE’s uniqueness lies in the fact that the company is part of one of the smallest economies in the world. Iceland only has a population of 285,000, and deCODE has now convinced the Icelandic government to guarantee a loan for $200 million ––roughly 15% of the annual state budget––to enable the company’s expansion. deCODE’s collapse would have a serious effect on Iceland’s small economy, as local investors, individuals, banks, and pension funds have already invested heavily in the company. And the fact is that deCODE’s collapse is now more likely than ever. As Rana Foroohar observed in a Newsweek article (February 18, 2002) entitled “The Gene Bubble,” deCODE, like the internet and telecom bubbles, “…had to burst. Stock prices of many bioinformatics firms have fallen sharply in recent years. LION Biosciences of Germany went public at $40 a share and now trades at about $13. deCODE is worth a fourth of its former high. Even Celera, the US firm that helped decode the human genome, is off its peak.” None of this bodes well for deCODE’s financial or scientific prospects.

Steindor J. Erlingsson holds BSc and MSc degrees in biology (emphasis on molecular and evolutionary biology) and history of science, respectively, from the University of Iceland. He is currently working on a PhD thesis in the history of science at the CHSTM, The University of Manchester, England. Between 1998 and 2000 he was the Director of the Information Resource Center, US Embassy, Reykjavik, Iceland. He is writing a book about the scientific and political implications of deCODE's operations in Iceland that will also be put into international context. It will be published in December 2002 by the Icelandic publisher Forlagid, an imprint of Edda Media & Publishing (http://edda.is/english/).

Email: steindor@akademia.is

Homepage http://www.raunvis.hi.is/~steindor/