Mechanisms Versus Causes in Biology and Medicine - Mechanism and Causality in Biology and Economics - page 26

The following subsections proceed as follows. First, I recount the history of the
discovery of the gene associated with cystic fibrosis. Then I describe the different
mechanisms associated with the disease of cystic fibrosis, based on different ways
of choosing the puzzling phenomenon of interest. The characterization of the
phenomenon is a crucial step in delineating the mechanism of interest. The choice
of the phenomenon (the effect?) and the goal of the research focus attention on
different aspects of a single mechanism (the cause?) or on different mechanisms
(different causes?) within the framework of a single disease. It is much too simple
to say that a single mutation in a single gene causes the disease of cystic fibrosis.
4.1 History of Cystic Fibrosis Prior to the Discovery of the Gene
Work in the early to mid-twentieth century connected symptoms in the lungs,
pancreas, and sweat glands. Medical researchers found that recurrent respiratory
infections, raised levels of chloride in sweat, and insufficient pancreatic enzymes
were all problems in the epithelial tissues in those organs and glands. The disease
was named “cystic fibrosis,” but the specific nature of the defect in epithelial tissues
was unknown until the 1980s (Knol 1995 ).
4.2 Discovery of the CFTR Gene
Mitchell Drumm ( 2001 ), a graduate student and then postdoc who worked in
Francis Collins's lab at the University of Michigan in the 1980s, wrote a lively
first person account of the discovery of the gene involved in cystic fibrosis (CF).
When these medical researchers started their investigation of CF, all the aspects of
the molecular genetic mechanism were a black box. Population genetic studies of
families with CF patients had shown that the disease is hereditary, not sex linked,
and requires two copies of the mutant gene to produce the disease symptoms;
carriers with one copy are not sick. In more technical genetic terms, it is an
autosomal recessive disease. It is more prevalent in those with Caucasian European
ancestry than among other groups in the USA. Before 1989, the gene was not
known and the protein it produces was unidentified. However, earlier work on the
symptom of salty sweat indicated that the protein was involved in the transport of
chloride in and out of the cell (Quinton 1983 ; discussed in Pearson 2009 ).
By the 1980s, molecular biological techniques for finding a gene could proceed
quickly if the protein and its accompanying messenger RNA could be identified.
A complementary DNA, called “cDNA,” could be constructed from the messenger
and then used as a probe for finding the nuclear DNA and the location on the
chromosome where the gene resided. But the search for the CF gene had to proceed
without such technological reversal of those later stages of the mechanism. It was