The Uncertainty Gene: Cystic Fibrosis and Carrier Screening: The U.S. Experience
Prof. Susan Lindee - University of Pennsylvania
Organised byESRC Genomics Forum
ESRC Genomics Policy and Research Forum The University of Edinburgh College of Humanities and Social Science St John's Land Holyrood Road Edinburgh EH8 8AQ
40-minute work in progress presentation
In this paper, I will present some preliminary work that I am undertaking with Dr. Michael Mennuti at Penn. We are collaborating on a study of uncertainty and carrier screening in Cystic Fibrosis.
Cystic Fibrosis, by the simple quantitative metric of citations in PubMed, has been the focus of more scientific papers than any other genetic disease.[i] Yet the high scientific interest, high volume of research, and screening programs, rather than dispelling uncertainty, have increased it. In this paper, evoking popular, fanciful images of "couch-potato" genes and "divorce" genes, I characterize the CF gene as the "uncertainty" gene, considering how the case illuminates some fundamental issues in the development of science, health policy, and clinical care. I suggest that the CF case may shed light on the more general future of genomic medicine.
That future has long involved a complex set of promises, about potential treatments for those with genetic diseases, and about reproductive options that could enhance the control of prospective parents over their offspring, and possibly reduce the overall incidence of genetic disease in general. In the case of CF, treatment options have improved dramatically, though attributing those improvements to gene mapping would be problematic. CF is also the first genetic disease for which a relationship between adult carrier screening and reduced incidence in newborns has been tentatively tracked. In Massachusetts, where newborn screening began in 1999, and adult carrier screening in 2002, the number of live-born infants with CF dropped by about 50 percent in the four-year period after adult carrier screening began.[ii] While it is not clear exactly how and why this occurred, the case suggests that carrier screening has real consequences for reproduction and public health, and serious effects in both the intimate world of individual decision-making, and the public world of clinical care and accounting for health care costs. As carrier screening for many more genetic diseases—perhaps for dozens more—could conceivably become a routine part of the clinical management of prospective parenthood, it seems important to consider the CF case and its complex, multi-layered ambiguity.[iii]
Why has CF been studied with such intensity? Shaping scientific interest, certainly, is the high prevalence of the disease in the kinds of populations known to be interested in genetic disease testing, and able to afford genetic services. History, biology and industrial development intersect, then, to make the disease financially important, and the subject of biopharmaceutical interest. CF is also interesting and complicated in biological terms, a factor that shapes scientific interest. It has been associated with more than 1,300 different mutations in a single gene, CFTR, and its clinical manifestations range from almost undetectable to serious disability. It affects multiple organ systems and it varies from individual to individual. It therefore raises persistent clinical and scientific problems. CF also has powerful consumer advocates: the CF Foundation provides funding for CF research across a broad range (not just genetic research). Every genetic disease can potentially provide insight into the general processes of heredity and disease, but diseases with active and effective foundations may be more likely to become "model" diseases. And researchers interested in genetic disease generally might take advantage of CF Foundation funding. Like model organisms, which become important in research as much for historical as biological reasons,[iv] model diseases need advocates and supporters who promote their importance.
The ambiguities and uncertainties considered here operate at the biological level of the CFTR gene itself, at the level of legal responsibility, of the technologies of testing, the differences in different labs, the social interaction between physician and patient and between the patient and other family members, and the uncertainties in rational cost-benefit assessments and in policy statements from scientific groups charged with deciding these issues at an abstract level. Programs for CF carrier screening was the focus of sustained, serious, and thoughtful analysis and debate, with recommendations from ACMG and ACOG that evolved as the technologies did. The management of CF as a policy matter provides a case study of consensus and complexity.