2.

3 Gene
The question of whether classical, Mendelian genetics could be (or already has been) reduced
to molecular biology (to be taken up in Section 3.1 below) motivated philosophers to
consider the connectability of the term they shared: the gene. Investigations of reduction and
scientific change raised the question of how the concept of the gene evolved over time,
figuring prominently in C. Kenneth Waters’ (1990, 1994, 2007, see entry on molecular
genetics), Philip Kitcher’s (1982, 1984) and Raphael Falk’s (1986) work. Over time,
however, philosophical discussions of the gene concept took on a life of their own, as
philosophers raised questions independent of the reduction debate: What is a gene? And, is
there anything causally distinct about DNA? (see the entry on the gene)
Falk (1986) explicitly asked philosophers and historians of biology, “What is a Gene?”
Discoveries such as overlapping genes, split genes, and alternative splicing (discussed
in Section 1.2) made it clear that simply equating a gene with an uninterrupted stretch of
DNA would no longer capture the complicated molecular-developmental details of
mechanisms such as gene expression (Downes 2004; Luc-Germain, Ratti and Boem 2015).
In an effort to answer Falk’s question, two general trends have emerged in the philosophical
literature: first, distinguish multiple gene concepts to capture the complex structural and
functional features separately, or second, rethink a unified gene concept to incorporate such
complexity. (For a survey of gene concepts defended by philosophers, see Griffiths and Stotz
2007, 2013.; Rheinberger and Muller-Wille 2018)
A paradigmatic example of the first line came from Lenny Moss’s distinction between Gene-
P and Gene-D (Moss 2001, 2002). Gene-P embraced an instrumental preformationism
(providing the “P”); it was defined by its relationship to a phenotype. In contrast, Gene-D
referred to a developmental resource (providing the “D”); it was defined by its molecular
sequence. An example will help to distinguish the two: When one talked about the gene for
cystic fibrosis, the most common genetic disease affecting populations of Western European
descent, the Gene-P concept was being utilized; the concept referred to the ability to track the
transmission of this gene from generation to generation as an instrumental predictor of cystic
fibrosis, without being contingent on knowing the causal pathway between the particular
sequence of DNA and the ultimate phenotypic disease. The Gene-D concept, in contrast,
referred instead to just one developmental resource (i.e., the molecular sequence) involved in
the complex development of the disease, which interacted with a host of other such resources
(proteins, RNA, a variety of enzymes, etc.); Gene-D was indeterminate with regards to the
ultimate phenotypic disease. Moreover, in cases of other diseases where there are different
disease alleles at the same locus, a Gene-D perspective would treat these alleles as individual
genes, while a Gene-P perspective treats them collectively as “the gene for” the disease. (For
other examples of gene-concept dividers, see Keller’s distinction between the gene as a
structural entity and the gene as a functional entity as well as Baetu’s distinction between the
gene as a syntax-based concept and the gene as a mapping concept (Baetu 2011; Keller
2000).)
A second philosophical approach for conceptualizing the gene involved rethinking a single,
unified gene concept that captured the molecular-developmental complexities. For example,
Eva Neumann-Held (Neumann-Held 1999, 2001; Griffiths and Neumann-Held 1999)
claimed that a “process molecular gene concept” (PMG) embraced the complicated
developmental intricacies. On her unified view, the term “gene” referred to “the recurring
process that leads to the temporally and spatially regulated expression of a particular
polypeptide product” (Neumann-Held 1999). Returning to the case of cystic fibrosis, a PMG
for an individual without the disease referred to one of a variety of transmembrane ion-
channel templates along with all the epigenetic factors, i.e., nongenetic influences on gene
expression, involved in the generation of the normal polypeptide product. And so cystic
fibrosis arose when a particular stretch of the DNA sequence was missing from this process.
(For another example of a gene-concept unifier, see Falk’s discussion of the gene as a DNA
sequence that corresponded to a single norm of reaction for various molecular products based
on varying epigenetic conditions (Falk 2001).)
Relatedly, philosophers have also debated the causal distinctiveness of DNA. Consider again
the case of cystic fibrosis. A stretch of DNA on chromosome 7 is involved in the process of
gene expression, which generates (or fails to generate) the functional product that transports
chloride ions. But obviously that final product results from that stretch of DNA as well as all
the other developmental resources involved in gene expression, be it in the expression of the
functional protein or the dysfunctional one. Thus, a number of authors have argued for a
causal parity thesis, wherein all developmental resources involved in the generation of a
phenotype such as cystic fibrosis are treated as being on par (Griffiths and Knight 1998;
Robert 2004; Stotz 2006).
Waters (2007, see also his entry on molecular genetics), in reply, has argued that there is
something causally distinctive about DNA. Causes are often conceived of as being difference
makers, in that a variable (i.e., an entity or activity in a mechanism) can be deemed causal
when a change in the value of that variable would counterfactually have led to a different
outcome (see the entry on scientific explanation). According to Waters, there are a number
of potential difference makers in the mechanisms involved in developing or not developing
cystic fibrosis; that is, an individual with two normal copies of the gene could still display
signs of cystic fibrosis if a manipulation was done to the individual’s RNA polymerase (the
protein responsible for transcribing DNA to RNA), thereby undermining the functional
reading of the stretch of DNA. So RNA polymerase is a difference maker in the development
or lack of development of cystic fibrosis, but only a potential difference maker, since
variation in RNA polymerase does not play a role in the development or lack of development
of cystic fibrosis in natural populations. The stretch of DNA on chromosome 7, however, is
an actual difference maker. That is, there are actual differences in natural human populations
on this stretch of DNA, which lead to actual differences in developing or not developing
cystic fibrosis; DNA is causally distinctive, according to Waters, because it is an actual
difference maker. Advocates of the parity thesis are thus challenged to identify the other
resources (in addition to DNA) that are actual difference makers.
Recently, Paul Griffiths and Karola Stotz (2013) have responded to this challenge by
offering examples in which, depending on context, regulatory mechanisms can either
contribute additional information to the gene products or create gene products for which
there is no underlying sequence. Thus, according to Griffiths and Stotz, to assign a causally
distinctive role to DNA, as Waters does, is to ignore key aspects of how the gene makes its
product.