## 1. Introduction




The term *molecular genetics* is now redundant because
contemporary genetics is thoroughly molecular. Genetics is not made up
of two sciences, one molecular and one non-molecular. Nevertheless,
practicing biologists still use the term. When they do, they are
typically referring to a set of laboratory techniques aimed at
identifying and/or manipulating DNA segments involved in the synthesis
of important biological molecules. Scientists often talk and write
about the application of these techniques across a broad swath of
biomedical sciences. For them, molecular genetics is an
*investigative approach* that involves the application of
laboratory methods and research strategies. This approach presupposes
basic knowledge about the expression and regulation of genes at the
molecular level.




Philosophical interest in molecular genetics, however, has centered, not on
investigative approaches or laboratory methods, but on theory. Early
philosophical research concerned the *basic theory* about the
make-up, expression, and regulation of genes. Most attention
centered on the issue of theoretical reductionism. The motivating
question concerned whether classical genetics, the science of T. H.
Morgan and his collaborators, was being reduced to molecular genetics.
With the rise of developmental genetics and developmental biology,
philosophical attention has subsequently shifted towards critiquing a
fundamental theory associated with contemporary genetics. The
*fundamental theory* concerns not just the make-up,
expression, and regulation of genes, but also the overall role of genes
within the organism. According to the fundamental theory, genes and
DNA direct all life processes by providing the information that
specifies the development and functioning of organisms.




This article begins by providing a quick review of the basic theory
associated with molecular genetics. Since this theory incorporates
ideas from the Morgan school of classical genetics, it is useful to
sketch its development from Morgan's
genetics. After reviewing the basic theory, I examine four questions
driving philosophical investigations of molecular genetics. The first
question asks whether classical genetics has been or will be reduced to
molecular genetics. The second question concerns the gene concept and
whether it has outlived its usefulness. The third question regards the
tenability of the fundamental theory. The fourth question, which
hasn't yet attracted much philosophical attention,
asks why so much biological research is centered on genes and
DNA. 


## 2. Basic Theory


### 2.1 The basic theory of classical genetics




The basic theory associated with classical genetics provided
explanations of the transmission of traits from parents to offspring.
Morgan and his collaborators drew upon a conceptual division between
the genetic makeup of an organism, termed its *genotype*, and
its observed manifestation called its *phenotype* (see the
entry on 
 the genotype/phenotype distinction).
The relation between the two was treated as causal: genotype in
conjunction with environment produces phenotype. The theory explained
the transmission of phenotypic differences from parents to offspring by
following the transmission of gene differences from generation to
generation and attributing the presence of alternative traits to the
presence of alternative forms of genes.




I will illustrate the classical mode of explanatory reasoning with a
simple historical example involving the fruit fly *Drosophila
melanogastor*. It is worth emphasizing that the mode of reasoning
illustrated by this historical example is still an important mode of
reasoning in genetics today, including what is sometimes called
molecular genetics.




Genes of *Drosophila* come in pairs, located in corresponding
positions on the four pairs of chromosomes contained within each cell
of the fly. The eye-color mutant known as purple is associated
with a gene located on chromosome II. Two copies of this gene,
existing either in mutated or normal wild-type form, are located at the
same locus (corresponding position) in the two
second-chromosomes. Alternative forms of a gene occurring at a
locus are called *alleles*. The transmission of genes from
parent to offspring is carried out in a special process of cellular
division called *meiosis*, which produces gamete cells
containing one chromosome from each paired set. The half set of
chromosomes from an egg and the half set from a sperm combine during
fertilization, which gives each offspring a copy of one gene from each
gene pair of its female parent and a copy of one gene from each gene
pair of its male parent. 




Explanations of the transmission of traits relate the presence of
alternative genes (genotype) to the presence of alternative observable
traits (phenotype). Sometimes this is done in terms of
dominant/recessive relations. Purple eye-color, for example, is
recessive to the wild-type character (red eye-color). This means
that flies with two copies of the purple allele (the mutant form of the
gene, which is designated *pr*) have purple eyes, but
*heterozygotes*, flies with one copy of the purple allele and
one copy of the wild-type allele (designated +), have normal wild-type
eyes (as do flies with two copies of the wild-type allele). See Table
1.



> 
> ![Table 1](table1SEP.jpg)
> 




To see how the classical theory explains trait transmission,
consider a cross of red-eyed females with purple-eyed males that was
carried out by Morgan's collaborators. The offspring
all had red eyes. So the trait of red eyes was passed from the females
to all their offspring even though the offspring's
male parents had purple eyes. The classical explanation of this
inheritance pattern proceeds, as do all classical explanations of
inheritance patterns, in two stages.




The first stage accounts for the transmission of genes and goes as
follows (Figure 1): each offspring received one copy of chromosome II
from each parent. The maternally derived chromosomes must have
contained the wild-type allele (since both second-chromosomes of every
female parent used in the experiment contained the wild-type allele --
this was known on the basis of previous experiments). The paternally
derived chromosomes must have contained the purple allele (since both
second-chromosomes of every male parent contained the purple allele --
this was inferred from the knowledge that purple is recessive to red
eye-color). Hence, all offspring were heterozygous (*pr* /
*+*). Having explained the genetic makeup of the progeny by
tracing the transmission of genes from parents to offspring, we can
proceed to the second stage of the explanation: drawing an inference
about phenotypic appearances. Since all offspring were heterozygous
(*pr* / *+*), and since purple is recessive to wild-type,
all offspring had red eye-color (the wild-type character). See Figure
1.



> 
> ![Figure 1](figure1SEP.jpg)
> 




Notice that the reasoning here does not depend on identifying the
material make-up, mode of action, or general function of the underlying
gene. It depends only on the ideas that copies of the gene are
distributed from generation to generation and that the difference in
the gene (i.e., the difference between *pr* and *+*),
whatever this difference is, causes the phenotypic difference. The idea
that the gene is the difference maker needs to be qualified:
differences in the gene cause phenotypic differences in particular
genetic and environmental contexts. This idea is so crucial and so
often overlooked that it merits articulation as a principle (Waters
1994):



> 
> 
> *Difference principle*: differences in a classical gene cause
> uniform phenotypic differences in particular genetic and environmental
> contexts.
> 
> 
> 




It is also worth noting that the difference principle provides a
means to explain the transmission of phenotypic characteristics from
one generation to the next without explaining how these characteristics
are produced in the process of an organism's
development. This effectively enabled classical geneticists to develop
a science of heredity without answering questions about
development. 



 The practice of classical genetics included the theoretical analysis of
complicated transmission patterns involving the recombination of
phenotypic traits. Analyzing these patterns yielded information about
the basic biological processes such as chromosomal mechanics as well as
information about the linear arrangement of genes in linkage groups.
These theoretical explanations did not depend on ideas about what genes
are, how genes are replicated, what genes do, or how differences in
genes bring about differences in phenotypic traits. 


### 2.2 Molecular-level answers to questions left behind by classical genetics




Research in molecular biology and genetics has yielded answers to
the basic questions left unanswered by classical genetics about the
make-up of genes, the mechanism of gene replication, what genes do, and
the way that gene differences bring about phenotypic differences. These
answers are couched in terms of molecular level phenomena and they
provide much of the *basic* theory associated with molecular
genetics.



**What is a gene?**  This question is dealt with
at further length in section 4 of this article, but a quick answer
suffices for present purposes: genes are linear sequences of
nucleotides in DNA molecules. Each DNA molecule consists of a double
chain of nucleotides. There are four kinds of nucleotides in DNA:
guanine, cytosine, thymine, and adenine. The pair of nucleotide chains
in a DNA molecule twist around one another in the form of a double
helix. The two chains in the helix are bound by hydrogen bonds between
nucleotides from adjacent chains. The hydrogen bonding is specific so
that a guanine in one chain is always located next to cytosine in the
adjacent chain (and vice-versa) and thymine in one chain is always
located next to adenine (and vice-versa). Hence, the linear sequence of
nucleotides in one chain of nucleotides in a DNA molecule is
complimentary to the linear sequence of nucleotides in the other chain
of the DNA molecule. A gene is a segment of nucleotides in one of
the chains of a DNA molecule. Of course, not every string of
nucleotides in DNA is a gene; segments of DNA are identified as genes
according to what they do (see below).



**How are genes replicated?** The idea that genes are
segments in a DNA double helix provides a straightforward answer to
this question. Genes are faithfully replicated when the paired chains
of a DNA molecule unwind and new chains are formed along side the
separating strands by the pairing of complementary nucleotides. When
the process is complete, two copies of the original double helix have
been formed and hence the genes in the original DNA molecule have been
effectively replicated.



**What do genes do?** Roughly speaking, genes serve as
templates in the synthesis of RNA molecules. The result is that the
linear sequence of nucleotides in a newly synthesized RNA molecule
corresponds to the linear sequence of nucleotides in the DNA segment
used as the template. Different RNA molecules play different functional
roles in the cell, and many RNA molecules play the role of template in
the synthesis of polypeptide molecules. Newly synthesized polypeptides
are linear sequences of amino acids that constitute proteins and
proteins play a wide variety of functional roles in the cell and
organism (and environment). The ability of a polypeptide to function in
specific ways depends on the linear sequence of amino acids of which it
is formed. And this linear sequence corresponds to the linear sequence
of triplets of nucleotides in RNA (codons), which in turn corresponds
to the linear sequence of nucleotides in segments of DNA, and this
latter segment is the gene for that polypeptide.



**How do differences in genes bring about differences in
phenotypic traits?** The modest answer given above to the
question 'What do genes do?'
provides the basis for explaining how differences in genes can bring
about differences in phenotypic traits. A difference in the nucleotide
sequence of a gene will result in the difference in the nucleotide
sequence of RNA molecules, which in turn can result in a difference in
the amino acid sequence of a polypeptide. Differences in the linear
sequences of amino acids in polypeptides (and in the linear sequences
of nucleotides in functional RNA molecules) can affect the roles they
play in the cell and organism, sometimes having an effect that is
observable as a phenotypic difference. The mutations (differences in
genes) identified by the Morgan group (e.g., the purple mutation) have
been routinely identified as differences in nucleotide sequences in
DNA.


### 2.3 Distinguishing between basic and fundamental theories of molecular genetics




The modest answer to the question 'What do genes do?' is
that they "code for" or "determine" the linear
sequences in RNA molecules and polypeptides synthesized in the
cell. (Even this modest answer needs to be qualified because RNA
molecules are often spliced and edited in ways that affect the linear
sequence of amino acids in the eventual polypeptide product.) But
biologists have offered a far less modest answer as well. The bolder
answer is part of a sweeping, fundamental theory. According to this
theory, genes are "fundamental" entities that
"direct" the development and functioning of organisms by
"producing" proteins that in turn regulate all the
important cellular processes. It is often claimed that genes provide
"the information", "the blueprint", or
"the program" for an organism. It is useful to distinguish
this sweeping, *fundamental* *theory* about the
allegedly fundamental role of genes from the modest, *basic
theory* about what genes do with respect to the synthesis of RNA
and polypeptides.


## 3. Was classical genetics reduced to molecular genetics?




Philosophers of science have been intrigued by ideals of
reductionism and the grand scheme that all science will one day be
"reduced" to a universal science of
fundamental physics (see the entry on
 inter-theory relations in physics)
 for philosophical and scientific concepts of reductionism in the
context of physical science). Philosophical reductionists believe that
scientific knowledge progresses when higher-level sciences
(e.g., chemistry) are reduced to lower-level sciences
(e.g., physics). The so-called *received view of scientific
knowledge*, codified in Nagel (1961) and Hempel (1966), promoted
reductionism as a central ideal for science, and confidently asserted
that much progress had been made in the reduction of chemistry to
physics. Nagel constructed a formal model of reduction and applied it
to illuminate how the science of thermodynamics, which was couched in
terms of higher-level concepts such as pressure and temperature, was
allegedly reduced to statistical mechanics, couched in terms of the
lower-level concepts of Newtonian dynamics such as force and mean
kinetic energy. In 1969, Schaffner claimed that the same kind of
advance was now taking place in genetics, and that the science of
classical genetics was being reduced to an emerging science of
"molecular genetics." Schaffner's claim, however, was
quickly challenged by Hull. Other philosophers of biology developed
Hull's anti-reductionist arguments and a near consensus developed that
classical genetics was not and would not be reduced to molecular
genetics. Although the philosophical case for anti-reductionism has
been challenged, many philosophers still assume that the
anti-reductionist account of genetics provides an exemplar for
anti-reductionist analyses of other sciences.


### 3.1 Schaffner's thesis that classical genetics is being theoretically reduced




Reductionism has many meanings. For example, the phrase *genetic
reductionism* concerns the idea that all biological phenomena are
caused by genes, and hence presupposes an ontological sense of
reductionism according to which one kind of micro-entity (in this case,
gene) exclusively causes a variety of higher-level phenomena (in this
case, biological features, cultural phenomena, and so forth). But
this is not the meaning of reductionism at issue in the philosophical
literature about the reduction of classical genetics. This literature
is more concerned with epistemology than metaphysics. The concept of
reductionism at issue is Nagel's concept of
*theoretical reduction*. (See Sarkar 1992 and Schaffner 1993 for
discussions of alternative conceptions of reduction.) According to
Nagel's concept, the reduction of one science to
another science entails the reduction of the central *theory* of
one science to the central *theory* of the other. Nagel believed
that this kind of theoretical reduction led to progressive changes in
scientific knowledge. He formulated two formal requirements for
theoretical reductions.




Nagel's first formal requirements was that the "laws" of
the reduced theory must be derivable from the laws and associated
coordinating definitions of the reducing theory. This deducibility
requirement was intended to capture the idea that the explanatory
principles (or laws) of the reducing theory ought to explain the
explanatory principles (or laws) of the reduced theory. Nagel's
second formal requirement, the connectability requirement, was that
all essential terms of the reduced theory must either be contained
within or be appropriately connected to the terms of the reducing
theory by way of additional assumptions. The connectability
requirement is presupposed by the derivability requirement,
but making it explicit helps emphasize an important task and potential
stumbling block for carrying out theoretical reduction.




Schaffner (1969) modified Nagel's model by
incorporating the idea that what the reducing theory actually derives
(and hence explains) is a corrected version of the reduced theory, not
the original theory. He argued that this revised model
better captured reductions in the physical sciences. He claimed his
revised model could also be used to show how a corrected version of
classical genetics was being reduced to a new theory of physicochemical
science called molecular genetics. Hull (1974) countered that classical
genetics was not being reduced, at least not according to the model of
reduction being applied by Schaffner. Hull argued that genetics did not
exemplify Nagelian reduction because the fundamental terms of classical
genetics could not be suitably connected to expressions couched in
terms of DNA.


### 3.2 The Anti-reductionist consensus about genetics




Most philosophers writing on genetics and reductionism have argued
that molecular genetics has not and will not reduce classical genetics
(e.g., see Wimsatt 1976a, Darden and Maull 1977, Kitcher 1984,
Rosenberg 1985 and 1994, Dupre 1993, and Burian 1996). Two
objections to Schaffner's reductionist thesis have been most
persuasive: the unconnectability objection and the gory details
objection. The *unconnectability objection* claims that the
terminology of classical genetics cannot be redefined at the molecular
level in terms of DNA. This objection effectively claims that
Nagel's second formal requirement, the connectability
requirement, cannot be satisfied. The *gory details*
*objection* alleges that molecular genetics cannot and will not
explain classical genetics or better explain the phenomena that are
already explained by the classical theory. This objection relates to
Nagel's first formal requirement, the derivability
requirement. But the gory details objection goes philosophically
deeper because it implies that even if the explanatory principles of
classical genetics could be derived from the explanatory principles of
molecular genetics, the derivations would not be explanatory. 




The most rigorous formulation of the unconnectability objection can be
found in the early writings of Rosenberg who once contended that there
is an unbridgeable conceptual gap between the classical and molecular
theories of genetics (1985, 1994). In support of this contention,
Rosenberg argued that relations between the gene concept of classical
genetics and the concepts of molecular genetics are hopelessly
complicated "many-many" relations that will forever
frustrate any attempt to systematically connect the two theories.
Rosenberg began his analysis by pointing out that in classical
genetics, genes are identified by way of their phenotypic effects.
Classical geneticists identified the gene for purple eye-color, for
example, by carrying out carefully orchestrated breeding experiments
and following the distribution of eye-color phenotypes in successive
generations of a laboratory population. The reason classical genetics
will never be reduced to a molecular-level science, according to
Rosenberg (1985), is that there is no manageable connection between
the concept of a Mendelian phenotype and that of a molecular gene:



> 
> 
> 
> The pathway to red eye pigment production begins at many distinct
> molecular genes and proceeds through several alternative branched
> pathways. ... The pathway from the [molecular] genes also
> contains redundant, ambiguous, and interdependent paths. If we give a
> biochemical characterization of the gene for red eye color either by
> appeal to the parts of its pathway of synthesis, or by appeal to the
> segments of DNA that it begins with, our molecular description of this
> gene will be too intricate to be of any practical explanatory
> upshot. (Rosenberg 1985, p. 101)
> 
> 
> 




Rosenberg concluded that since the relation between molecular genes
and Mendelian phenotypes is exceedingly complex, the connection
between any molecular concept and the Mendelian gene concept must also
be exceedingly complex, thereby blocking any systematic, reductive
explanation of classical genetics in terms of molecular-level
theory.




The gory details objection can be traced back to the writings of
Putnam (1965) and Fodor (1968) who argued against reductionism of the
mental on the basis that psychological functons are
multiply-realized. This objection against reductionism was further
developed in the context of genetics, most thoroughly by Kitcher
(e.g., see Kitcher 1984, 1999, 2001). Following Hull, Kitcher assumes
that classical genetics is transmission genetics. The classical
theory, according to Kitcher, explains the transmission of phenotypic
traits, not the development of phenotypic traits in individual
organisms. And transmission phenomena, on Kitcher's account, are best
explained at the level of cytology: "The distribution of genes
to gametes is to be explained, not by rehearsing the gory details of
the reshuffling of the molecules, but through the observation that
chromosomes are aligned in pairs just prior to the meiotic division,
and that one chromosome from each matched pair is transmitted to each
gamete." (Kitcher 1984, p. 370). Kitcher suggests that the
pairing and separation of chromosomes belong to a natural kind of pair
separation processes which are heterogeneous from the molecular
perspective because different kinds of forces are responsible for
bringing together and pulling apart different paired entities. The
separation of paired entities, he claims, "may occur because of
the action of electromagnetic forces or even nuclear forces; but it is
easy to think of examples in which the separation is effected by the
action of gravity." (Kitcher 1984, p. 350)




The image of genetics that emerges from the anti-reductionist
literature is of a two-tiered science composed of two discreet
theoretical discourses, one grounded in principles about entities at
the cytological level (such as chromosomes) and the other grounded in
principles about entities at the molecular level (such as nucleotide
sequences in DNA). Anti-reductionists believe some phenomena,
including transmission of genes, are best explained by a theory
grounded at the cytological level and other phenomena, including the
expression of genes, are best explained by a theory grounded at the
molecular level. Although Kitcher argues that classical genetics
provides the best explanation in an objective sense, some
anti-reductionists (e.g., Rosenberg 1985, 1994) believe that the
obstacles to reduction are merely practical*.* Rosenberg (1985,
1994) appealed to the concept of supervenience to argue that *in
principle*, molecular genetics would provide the best
explanations. But he argued that *in practice*, classical
genetics provides the "best" explanation of transmission
phenomena, in the sense that this is the best explanation available to
creatures with our cognitive limitations. Subsequently, however,
Rosenberg changed his position on this issue, largely on the grounds
that that technological advances in information storage and processing
"may substantially enhance our capacity to understand macromolecular
processes and their combinations" (Rosenberg 2006, p. 14).




Despite philosophically significant differences in their views about
the ultimate basis of the irreducibility of classical genetics, the
image of biological knowledge that emerges from the
antireductionists' writings is similar. The biological world
consists of different domains of phenomena and each domain is best
explained at a particular level of theoretical discourse. Hence, the
ideal structure for biology is akin to a layer-cake, with tiers of
theories, each of which provides the best possible account of its
domain of phenomena. Biological sciences such as classical genetics
that are couched in terms of higher levels of organization should
persist, secure from the reductive grasp of molecular science, because
their central theories (or patterns of reasoning) explain domains of
phenomena that are best explained at levels higher than the molecular
level. 


### 3.3 Challenges to the anti-reductionist consensus




The anti-reductionist consensus has not gone unchallenged (see Sarkar
1989, 1992 and 1998, Schaffner 1993, and Waters 1990 and 2000).
According to critics, the chief objections supporting the consensus
are mistaken. The unconnectability objection rests on the assumption
that classical genetics took the relationships between genes and
phenotypic traits to be simple one-to-one relationships. But classical
geneticists knew better. Consider what Sturtevant, one of Morgan's
star students and collaborators, had to say about genes and eye
color:



> 
> 
> 
> The difference between normal red eyes and colorless (white) ones in
> *Drosophila* is due to a difference in a single gene. Yet red
> is a very complex color, requiring the interaction of at least five
> (and probably of very many more) different genes for its
> production. And these genes are quite independent, each chromosome
> bearing some of them. Moreover, eye-color is indirectly dependent upon
> a large number of other genes such as those on which the life of the
> fly depends. We can then, in no sense identify a given gene with the
> red color of the eye, even though *there is a single gene
> differentiating it from the colorless eye*. So it is for all
> characters ... (my emphasis, quoted from Carlson 1988, p. 69)
> 
> 
> 




This quotation suggests that the relationship between gene and
eye-color in classical genetics exhibited the same complexity that
Rosenberg discussed at the molecular level (compare this quotation to
the passage from Rosenberg 1985 quoted in section 3.2). According to
this critique of the unconnectability objection, it is not the case
that genotype-phenotype relationships appear simple and uniform at
the level of classical genetics and complicated and dis-unified at the
molecular level. The situation appears similarly complex at both levels
of analysis (Waters 1990).




Classical genetics nevertheless finds a simple way to explain
transmission phenomena by appealing to the difference principle,
according to which particular *differences* in particular genes
cause particular *differences* in phenotypic traits in
particular contexts (see section 2.1). Sturtevant alludes to this
principle in the first sentence of the quotation above and again in
the emphasized clause. So the question arises, can this relationship
be captured at the molecular level? And the answer is yes. The
differences used by classical geneticists to explain inheritance
patterns have been routinely identified at the molecular level by
contemporary geneticists.




According to this critique, the gory details objection also fails.
This objection claims that biologists cannot improve upon
the classical explanations of transmission phenomena by citing
molecular details. The cytological level allegedly provides the best
level of explanation because explanations at this level uniformly
account for a wide range of cases that would look heterogeneous from a
molecular perspective. Consider Kitcher's formulation of this
objection. Kitcher believes that to explain is to unify (1989). It
follows that the best explanation of a class of phenomena is the
explanation that accounts for the class in a uniform way. Kitcher
claims meiosis exemplifies this kind of situation. The uniformity of
pair-separation processes is evident at the cytological level, but is
lost in the gory details at the molecular level where the process
"may occur because of the action of electromagnetic forces or
even of nuclear forces ..." (Kitcher 1984, p. 350). But
it is unclear what Kitcher could have in mind. The molecular
mechanisms underlying the pairing and separation of chromosomes are
remarkably uniform in creatures ranging from yeast to human beings; it
is not the case that some involve electromagnetic forces and others
involve nuclear forces. Kitcher's claim that "it is easy
to think of examples in which the separation is effected by the action
of gravity" has no basis in what molecular biologists have
learned about the pairing and separation of chromosomes.




Meiosis is an unpromising candidate to illustrate the idea that what
appears uniform at the level of classical genetics turns out to be
heterogeneous at the molecular level. But this idea is illustrated by
other genetic phenomena. Consider the phenomenon of genetic dominance.
In classical genetics, all examples of complete dominance are treated
alike for the purposes of explaining transmission phenomena. But
contemporary genetics reveals that there are several very different
mechanisms underlying different instances of dominance. According to
Kitcher's unificationist theory of scientific
explanation, the classical account of dominance provides an objectively
better basis for explaining transmission phenomena because it provides
a more unified organization of the phenomena. But this would imply that
the shallow explanations of classical genetics are objectively
preferable to the deeper explanations provided by the molecular theory
(Waters 1990). 


### 3.4 Moving beyond theoretical reduction and layer-cake antireductionism




Although Nagel's concept of theoretical reduction marks a common
starting point for discussions about the apparent reduction of
classical genetics, much of the literature on reduction is aimed at
seeking a better understanding of the nature of reduction by seeking
to replace Nagel's concept with a more illuminating one. This is true
of the anti-reductionists, who seek to clarify why molecular genetics
cannot reduce classical genetics, as well as those who have been more
sympathetic to reductionism. Hence, there are two levels of discourse
in the literature examining the question of whether molecular genetics
is reducing classical genetics. One level concerns what is happening
in the science of genetics. The other concerns more abstract issues
about the nature of (epistemological) reduction.




The abstract level of discourse began with Schaffner's idea that what
is reduced is not the original theory, but rather a corrected version
of the original theory. Wimsatt (1976a) offers a more ambitious
modification. He rejects the assumption that scientific theories are
sets of law-like statements and that explanations are arguments in
which the phenomena to-be-explained are derived from laws. Instead of
relying on these assumptions, Wimsatt uses Salmon's account of
explanation (Salmon 1971) to examine claims that molecular genetics
offered reductive explanations. Kitcher (1984) also rejects the
account of theorizing underlying Nagel's concept of reduction. He
constructs a new concept of reductive explanation based on his own
idea of what effectively constitutes a scientific theory and his
unificationist account of scientific explanation (1989). Likewise,
Sarkar (1998) rejects the account of theories and explanation
presupposed in Nagel's concept of reduction. In fact, he explicitly
avoids relying on any particular account of scientific theories or
theoretical explanation. Instead, he assumes that reductive
explanations are explanations without specifying what an explanation
is, and then seeks to identify the features that set reductive
explanations apart from other explanations.




Wimsatt, Kitcher, and Sarkar seek to replace Nagel's conception of
reduction with a conception that does not assume that scientic
explanation involves subsumption under universal laws. Weber (2005),
however, seeks to replace Nagel's conception with one that retains the
idea that reductive explanation involves subsumption under laws of the
reducing science. What Weber rejects is the idea that reductionism in
biology involves explaining higher-level biological laws. He argues
that, with some rare exceptions, biological sciences don't have
laws. He contends that reductionism in biology involves explaining
biological phenomena directly in terms of physical laws. Hence, he
rejects the "layer-cake" conception of reduction implicit in Nagel's
account.




The literature about reduction and molecular genetics has influenced
philosophers' thinking about reduction in other sciences. For example,
Kitcher's concept of reduction, which he uses to explain why molecular
genetics cannot reduce classical genetics, has subsequently been
employed by Hardcastle (1992) in her examination of the relationship
between psychology and neuroscience. On the other side, Sober develops
and extends the criticism of Kitcher's gory details objection (section 3.3) by re-examining the arguments of Putnam (1967, 1975) and Fodor
(1968, 1975) on multiple-realizability.




Sober (1999) argues that higher-level sciences can describe patterns
invisible at lower level, and hence might offer more general
explanations. But he insists that description should not be confused
with explanation. He maintains that although physics might not be able
to *describe* all the patterns, it can nevertheless
*explain* any singular occurrence that a higher-level science
can explain. Higher-level sciences might provide more "general"
explanations, but physics provides "deeper" ones. He suggests that
which explanation is better is in the eye of the beholder. He
concludes that



> 
> 
> ... reductionists might want to demure on this question of better
> and worse, and try to build on the bare proposition that physics in
> principle can explain wny singular occurrence that a higher-level
> science is able to explain. ... For reductionists, the
> interesting feature of physical explanations of social, psychological,
> and biological phenomena is that they use the same basic theoretical
> machinery that is used to explain phenomena that are nonsocial,
> nonpsychological, and nonbiological (Sober 1999, pp. 560-1).
> 
> 




The discussion has gone full circle. The multiple-realizability
argument being criticized by Sober was based on abstract
considerations in the context of philosophy of mind. Philosophers of
biology drew on this literature to construct the gory details
objection against the idea that molecular genetics is reducing
classical genetics. Other philosophers argued that this objection did
not stand up to a careful analysis of the concrete situation in
genetics. Sober has developed lessons from the discussion about
genetics to critique the original anti-realizability argument and draw
general conclusions about reductionism. 




Wimsatt's writings on reduction (1976a, 1976b, and 1979) emphasize the
fruitfulness of attempting to achieve a reduction, even when a
reduction is not achieved. He argues, for instance, that efforts to
discover the molecular make-ups of entities identified at higher
levels is often fruitful, even when identities between levels cannot
be found. In addition, Wimsatt points out that the "costs"
of working out reductive explanations of the many particulars already
explained at a higher level are relevant to the question of why there
is not a full-scale replacement of higher level explanations with
lower level ones. Perhaps the fact that molecular genetics has not
replaced classical genetics can be explained on the basis of high
costs rather than lack of epistemic merit. 




While Schaffner still maintains that molecular genetics can in
principle reduce classical genetics, he has conceded that attempts to
carry out the reduction would be "peripheral" to the
advance of molecular genetics. One might respond, along the lines of
Hull (1977), that the success of molecular genetics seems to be
reductive in some important sense. Hence, the failure to illuminate
this success in terms of reduction reveals a conceptual defiency. That
is, one might argue that Schaffner's peripherality thesis indicates
that his conception of reduction is not the epistemically relevant one
because it cannot illuminate the fruitfulness of reductive inquiry in
molecular genetics.




In fact, a general shortcoming in the debate about the reduction of
classical genetics is that it concerns only a fragment of scientific
reasoning. It is based almost exclusively on an analysis of
explanatory or theoretical reasoning and largely ignores investigative
reasoning. The philosophical literature on the alleged reduction of
classical genetics focuses on how geneticists *explain* or try
to explain phenomena, not how they *manipulate* or
*investigate* phenomena. This is even true of Wimsatt's (1976a)
account of heuristics, which stress heuristics for explanation.




Vance (1996) offers a more thorough shift in attention from theory to
investigative practice. He asserts that there is only one contemporary
science of genetics and describes how investigative methods of
classical genetics are an essential part of the methodology of what is
called *molecular genetics*. He concludes that reductionism
fails because contemporary genetics still depends on methods of
classical genetics involving breeding experiments. Vance's picture of
genetics is compelling. The laboratory methods of classical genetics
do indeed persist, even as they are greatly extended, augmented, and
often replaced by techniques involving direct intervention on DNA. But
Vance's picture does not match the anti-reductionist image of a
two-tiered science and the contention that classical genetics will
remain aloof from the reductive grasp of molecular biology.




A different image emerges from viewing genetics as an investigative
science involving an interplay of methodological and explanatory
reasoning (Waters 2004a). This image is not of a two-tiered science,
one (classical genetics) aimed at investigating and explaining
transmission phenomena and another (molecular genetics) aimed at
investigating and explaining developmental phenomena. Instead, there
is one science that retains much of the investigative and explanatory
reasoning of classical genetics by re-conceptualizing its theoretical
basis in molecular terms and by retooling its basic investigative
approach by integrating methodologies of classical genetics with
physically-based methods of biochemistry and new methods based on
recombinant DNA and RNA interference technologies.


## 4. What is a gene?




A common claim in the philosophical literature about molecular
genetics is that genes cannot be conceived at the molecular level. Of
course, philosophers do not deny that biologists use the term
*gene*, but many philosophers believe *gene* is a dummy
term, a placeholder for many different concepts. Different responses
to gene skepticism illustrate a variety of philosophical aims and
approaches. One kind of response is to analyze explanations closely
tied to experimental practice (rather than sweeping generalizations of
a fundamental theory) in order to determine whether there are uniform
patterns of reasoning about genes that could (a) be codified into
clear concepts, and/or (b) used to establish the reference of the
term. Another kind of response is to propose new gene concepts that
will better serve the expressed aims of practicing biologists. A third
kind of response is to implement survey analysis, rather than conduct
traditional methods of philosophical analysis. A fourth kind of
response is to embrace the (allegedly) necessary vagueness of the gene
concept(s) and to examine why use of the term *gene* is so
useful.


### 4.1 Gene skepticism




Gene skeptics claim that there is no coherence to the way
*gene* is used at the molecular level and that this term does
not designate a natural kind; rather, *gene* is allegedly used
to pick out many different kinds of units in DNA. DNA consists of
"coding" regions that are transcribed into RNA, different
kinds of regulatory regions, and in higher organisms, a number of
regions whose functions are less clear and perhaps in cases
non-existent. Skepticism about genes is based in part on the idea that
the term is sometimes applied to only parts of a coding region,
sometimes to an entire coding region, sometimes to parts of a coding
region and to regions that regulate that coding region, and sometimes
to an entire coding region and regulatory regions affecting or
potentially affecting the transcription of the coding region.
Skeptics (e.g., Burian 1986, Portin 1993, and Kitcher 1992) have
concluded, as Kitcher succinctly puts it: "a gene is whatever a
competent biologist chooses to call a gene" (Kitcher 1992,
p. 131).




Biological textbooks contain definitions of gene and it is
instructive to consider one in order to show that the conceptual
situation is indeed unsettling. The most prevalent contemporary
definition is that a gene is the fundamental unit that codes for a
polypeptide. One problem with this definition is that it
excludes many segments that are typically referred to as genes. Some
DNA segments code for functional RNA molecules that are never
translated into polypeptides. Such RNA molecules include transfer RNA,
ribosomal RNA, and RNA molecules that play regulatory and catalytic
roles. Hence, this definition is too narrow.




Another problem with this common definition is that it is based on
an overly simplistic account of DNA expression. According to this
simple account, a gene is a sequence of nucleotides in DNA that is
transcribed into a sequence of nucleotides making up a messenger RNA
molecule that is in turn translated into sequence of amino acids that
forms a polypeptide. (Biologists talk as if genes "produce the
polypeptide molecules" or "provide the information
for the polypeptide".) The real situation of DNA expression,
however, is often far more complex. For example, in plants and
animals, many mRNA molecules are processed before they are translated
into polypeptides. In these cases, portions of the RNA molecule,
called *introns*, are snipped out and the remaining segments,
called *exons*, are spliced together before the RNA molecule
leaves the cellular nucleus. Sometimes biologists call the entire DNA
region, that is the region that corresponds to both introns and exons,
the gene. Other times, they call only the portions of the DNA segment
corresponding to the exons the gene. (This means that some DNA
segments that geneticists call genes are not continuous segments of
DNA; they are collections of discontinuous exons. Geneticists call
these *split genes*.) Further complications arise because
the splicing of exons in some cases is executed differentially in
different tissue types and at different developmental stages. (This
means that there are *overlapping genes*.) The problem with the
common definition that genes are DNA segments that "code for
polypeptides" is that the notion of "coding for a
polypeptide" is ambiguous when it comes to actual complications
of DNA expression. Gene skeptics argue that it is hopelessly ambiguous
(Burian 1986, Fogle 1990 and 2000, Kitcher 1992, and Portin 1993).




Clearly, this definition, which is the most common and prominent
textbook definition, is too narrow to be applied to the range of
segments that geneticists commonly call genes and too ambiguous to
provide a single, precise partition of DNA into separate
genes. Textbooks include many definitions of the gene. In fact,
philosophers have often been frustrated by the tendency of biologists
to define and use the term *gene* in a number of contradictory
ways in one and the same textbook. After subjecting the alternative
definitions to philosophical scrutiny, gene skeptics have concluded
that the problem isn't simply a lack of analytical rigor. The
problem is that there simply is no such thing as a gene at the
molecular level. That is, there is no single, uniform, and unambiguous
way to divide a DNA molecule into different genes. Gene skeptics have
often argued that biologists should couch their science in terms of
DNA segments such exon, intron, promotor region, and so on, and
dispense with the term *gene* altogether (most forcefully
argued by Fogle 2000).


### 4.2 An analysis of concepts in practice, the *classical gene* and *molecular gene* concepts




It has been argued, against gene skepticism, that biologists have a
coherent, precise, and uniform way to conceive of genes at the
molecular level. The analysis underlying this
argument begins by distinguishing between two different ways
contemporary geneticists think about genes. Classical geneticists
often conceived of genes as the functional units in chromosomes,
differences in which cause differences in phenotypes. Today, in
contexts where genes are identified by way of observed phenotypic
differences, geneticists still conceive of genes in this classical
way, as the functional units in DNA whose differences are causing the
observed differences in phenotypes. This way of conceiving of genes is
called the *classical gene concept* (Waters 1994). But
contemporary geneticists also think about genes in a different way by
invoking a molecular-level concept. The *molecular gene
concept* stems from the idea that genes are units in DNA that
function to determine linear sequences in molecules synthesized via
DNA expression. According to this analysis, both concepts are at work
in contemporary geneticists. Moss 2003 also distinguishes between two
contemporary gene concepts, which he calls "genes-P
(preformationist)" and "genes-D (developmental)". He
argues that conflation of these concepts leads to erroneous thinking
in genetics.




Much confusion concerning the classical way to think about genes is
due to the fact that geneticists have sometimes talked as if
classically conceived genes are *for* gross phenotypic
characters (phenotypes) or as if individual genes produce phenotypes. This talk was very misleading on the part of
classical geneticists and continues to be misleading in the context of
contemporary genetics. The production of a gross phenotypic character,
such as purple eye-color, involves all sorts of genetic and
extra-genetic factors including various cellular enzymes and
structures, tissue arrangements, and environmental factors. In
addition, it is not clear what, if any, gross phenotypic level
functions can be attributed to individual genes. For example, it is no
clearer today than it was in Morgan's day that the function of the
purple gene discussed in section 2.1 is to contribute to the
production of eye color. Mutations in this gene affect a number of
gross phenotypic level traits. Legitimate explanatory reasoning
invoking the classical gene concept does not depend on any baggage
concerning what genes are for or what function a gene might have in
development. What the explanatory reasoning depends on is the
difference principle, that is, the principle that some difference in
the gene causes certain phenotypic differences in particular genetic
and environmental contexts (section 2.1). Many gene-based explanations
in contemporary biology are best understood in terms of the classical
gene concept and the difference principle.




Perhaps the reason gene skeptics overlooked the molecular gene concept
is that they were searching for the wrong kind of concept. The concept
is not a purely physicochemical concept, and it does not provide a
single partition of DNA into separate genes. Instead, it is a
functional concept that provides a uniform way to think about genes
that can be applied to pick out different DNA segments in different
investigative or explanatory contexts. The basic
molecular concept, according to this analysis, is the concept of a
gene for a linear sequence in a product of DNA expression:



> 
> 
>  A gene *g* for linear sequence *l* in product *p*
> synthesized in cellular context *c* is a potentially
> replicating nucleotide sequence, *n*, usually contained in DNA,
> that determines the linear sequence *l* in product *p*
> at some stage of DNA expression (Waters 2000)
> 
>  




The concept of the molecular gene can be presented as a 4-tuple:
<*n*,*l*,*p*,*c* >. This analysis
shows how geneticists can consistently include introns as part of a
gene in one epistemic context and not in another. If the context
involves identifying a gene for a primary, preprocessed RNA molecule,
then the gene includes the introns as well as the exons. If the
context involves identifying the gene for the resulting polypeptide,
then the gene includes only the exons. Hence, in the case of DNA
expression that eventually leads to the synthesis of a given
polypeptide, geneticists might talk as if "the" gene
included the intron (in which case they would be referring to the gene
*for the primary, preprocessed RNA*) and yet also talk as if
"the" gene excluded the introns (in which case they would
be referring to the gene *for the mature RNA or
polypeptide*). Application of the molecular gene concept is not
ambiguous; in fact, it is remarkably precise provided one specifies
the values for the variables in the expression "gene for linear
sequence *l* in product *p* synthesized in cellular
context *c*."




Gene skeptics have suggested that there is a lack of coherence in gene
talk because biologists often talk as if genes code for polypeptides,
but then turn around and talk about genes for RNA molecules that are
not translated into polypeptides (including genes for RNA [tRNA],
ribosomal RNA [rRNA], and interference RNA [iRNA]). This account shows
that conceiving of genes for rRNA involves the same idea as conceiving
of genes for polypeptides. In both cases, the gene is the segment of
DNA, split or not, that determines the linear sequence in the molecule
of interest.




An advantage of this analysis is that it emphasizes the limitations
of gene-centered explanations while clarifying the distinctive causal
role genes play in the syntheses of RNA and polypeptides: genes
determine the linear sequences of primary RNA transcripts and often
play a distinctive role, though not exclusive, in determining the
sequence of amino acids in polypeptides.


### 4.3 Analysis of reference in practice, how molecularization changed reference



 Weber (2005) examines the evolution of the gene concept by tracing
changes in the reference of the term *gene* through the history
of genetics. The *reference* or *extension* of a term is
the set of objects to which it reference. Weber adopts a mixed theory
of refence. According to mixed theories, the reference of a term is
determined how the relevant linguistic community causally interacts
with potential referents as well as how they describe potential
referents. This theory leads Weber to pay close attention, not just to
how geneticists theorized about genes or used the concept to explain
phenomena, but also how they conducted their laboratory
investigations. Following Kitcher (1978, 1982), he examines ways in
which modes of reference changed over time.




Weber identifies six different gene concepts, beginning with Darwin's
pangene concept (1868) and ending with the contemporary concept of
molecular genetics. He distinguishes the contemporary molecular
concept from the classical (or 'neoclassical') one on the
basis of how geneticists described their functional role (RNA/protein
coding versus general function unit), their material basis (RNA/DNA
versus chromosome), and their structure (discontinuous linear -- with
introns and exons versus continuous linear) as well as on the basis of
the criteria experimentalists used to identify genes (by gene product
versus complementation test). 




Weber examines how the investigation of several particular
*Drosophila* genes changed as the science of genetics
developed. His study shows that the methods of molecular genetics
provided new ways to identify genes that were first identified by
classical techniques. The reference of the term changed, not simply as
a result of theoretical developments, but also as a result of the
implementation of new methods to identify genes. He concludes that
unlike concepts of physical science that have been analyzed by
philosophers, the gene concept has a "nonessentialistic character that
allows biologists to lay down different natural classifications,
depending on the investigative methods available as well as on
theoretical interests" (Weber 2005, p. 228). Weber calls this feature
"floating references".


### 4.4 A proposal for a new concept, the *process molecular gene* concept




Neumann-Held (2001) proposes a new way to think about genes in the
context of developmental genetics. She says that in this context,
interest in genes is largely focused on the regulated expression of
polypeptides. She notes that textbook definitions of gene often
acknowledge this interest and quotes the following definition from a
scientific textbook:



> 
> 
>  A combination of DNA segments that together constitute an expressible
> unit, expression leading the formation of one or more specific
> functional gene products that may lead to either RNA molecules or
> polypeptides. The segments of a gene include (1) the transcribed unit
> ... and any regulatory segments included in the transcription
> unit, and (2) the regulatory sequences that flank the trancription
> unit and are required for specific expression. (Singer and Berg 1991,
> p. 41).
> 
>  




This definition emphasizes that regulatory sequences as well as
coding regions are required for "specific
expression." Only a small proportion of coding sequences
are transcribed in a given cell at a particular time, and whether a
particular sequence is transcribed depends in part on regulatory
regions external to the coding region.




Neumann-Held points out that if the aim is to specify what is
necessary for regulated synthesis of polypeptides, then one must
include even more than what is located in the DNA. This follows from
the fact that processes such as differential splicing (and RNA editing
processes such as methylation that I have not discussed in this
article) involve entities outside of DNA such as splicing agents. She
suggests that it is appropriate, at least in the context of
developmental genetics, to reconceive genes as processes. She proposes
the following *process molecular gene concept.*



> 
> 
> "Gene" is the process (i.e., the course of events) that
> binds together DNA and all other relevant non-DNA entities in the
> production of a particular polypeptide. The term *gene* in this
> sense stands for processes which are specified by (1) the specific
> interactions between specific DNA segments and specific non-DNA
> located entities, (2) specific processing mechanisms of resulting
> mRNA's in interactions with additional non-DNA located entities.
> (Neumann-Held 2001, p. 74).
> 
> 




Neumann-Held argues that this conception provides the clearest basis
for understanding how DNA sequences are "used in the processes
of *polypeptide* production." She points out that the
process molecular gene concept allows for the inclusion of coding
sequences in DNA, regulatory sequences in DNA and also entities not
located in DNA, all of which are causally involved in the production
of polypeptides. Neumann-Held's concept excludes transcription
processes and coding regions of DNA that lead to functional RNA
molecules that are not translated into polypeptides. Hence, according
to her account, there are not process molecular genes for tRNA
(transfer RNA), rRNA (ribosomal RNA) or snRNA (small nuclear
RNA). This feature of Neumann-Held's definition does not match the
textbook definition that she quotes to motivate her account (presented
above). Furthermore, the exclusion of these coding regions does not
track with recent discoveries about the important functions played by
non-coding RNA molecules such as snRNAs. Her definition could easily
be revised to accommodate these regions and processes. In any case,
Neumann-Held believes using this concept in developmental genetics,
rather than DNA-centered gene concepts, will help avoid the view that
"genes are the most important explanatory factors in biology
because of their unique causal powers" (Neumann-Held 2001,
p. 80).


### 4.5 Using a survey-based approach to identifying gene concepts




Stotz and Griffiths (2004) believe that the variety of gene concepts
used throughout the biological sciences calls for a more systematic
and explicitly empirical approach. They point out that individual
philosophers cannot grasp all the intricacies of the different
contexts across the broad range of biological sciences in which gene
concepts are employed. They have embarked upon an ambitious project to
survey practicing scientists in an attempt to help identify how
scientists *actually* conceive of genes. Their interest extends
far beyond understanding "molecular genetics." They hope
to learn about the concepts employed in many different areas and
contexts of biology by spotting differences in the way biologists from
different areas (and biologists in different age groups, sexes, etc.)
answer sophisticated questionnaires.




An initial motivation behind Stotz and Griffith's project was to test
philosophical accounts of the gene concept. As Griffiths asked, if
their survey-based study revealed that scientists don't actually
think of genes in the way set out by a philosophical account, then
what value could the account possibly have? There are, however, a
number of daunting, practical difficulties with using a questionnaire
to learn how a person is thinking, especially if the person's thinking
involves the use of multiple concepts and/or is sometimes or somewhat
muddled (Waters 2004b). It is also difficult to survey appropriate and
representative samples of scientists. Griffiths and Stotz are aware of
these difficulties and have refined their project through successive
surveys.




Even if Stotz and Griffith's survey succeeds in identifying how
scientists in different areas of biology actually think about genes in
different contexts, it does not follow that their findings would
provide an appropriate test of the classical, molecular, or process
molecular gene concepts. The aim of the proponents of these concepts
is to re-interpret the knowledge of contemporary genetics by replacing
sloppy thinking based on unclear concepts with more rigorous thinking
in terms of precise concepts. Showing that scientists' actual
thinking does not align with the precise application of these concepts
would not refute the analysis supporting the classical gene or
molecular gene concepts and it would not undermine the argument
motivating the proposal for the new process molecular gene
concept.




Although it appears that survey-based findings would not provide an
appropriate test of philosophical analyses of gene concepts, they
might provide, as Stotz and Griffiths claim, important information
relevant to those conducting philosophical research on gene concepts.
For example, if such surveys find significant differences in the way
evolutionary biologists and developmental geneticists answer questions
about what counts as gene, philosophers might examine whether the
contexts in which these biologists practice call for different gene
concepts. Survey results could provide a useful heuristic for
conducting concept analyses.


### 4.6 A pragmatic response to gene skepticism




Gene skeptics such as Burian, Portin, and Fogle claim that the term
*gene* has outlived its usefulness. They argue that the term is
both too vague and too restrictive. It is too vague, they believe,
because it does not provide a unique parsing of the genome. Borders
between genes are overlapping and allegedly ambiguous. It is not
clear, they argue, whether genes include or exclude introns,
regulatory regions, and so forth. The term is allegedly too
restrictive because it obscures the diversity of molecular elements
playing different roles in the expression and regulation of DNA. In
addition, any attempt to resolve the ambiguities, these skeptics
argue, will make the term even more restrictive.




Keller's account of the history of twentieth century genetics seems to
reinforce gene skepticism. For example, she argues that the question
about what genes are for has become increasingly difficult to answer
(Keller 2000). By the end of the twentieth century, she says,
biological findings have revealed a complexity of developmental
dynamics that make it impossible to conceive of genes as distinct
causal agents in development. Keller emphasizes that words have power
and devotes a good deal of attention to the way loose gene talk has
affected biological research by reinforcing the assumption that the
gene is "the core explanatory concept of biological structure
and function" (Keller 2000, p. 9), an assumption with which she
strongly disagrees. Yet Keller does not endorse the view of gene
skeptics who argue that biology would be improved if biologists
stopped talking about "genes" and restricted themselves to
terms designating molecular units such as nucleotide, codon, coding
region, promotor region, and so on. Keller maintains that the term
*gene* continues to have "obvious and undeniable
uses."




One use of the term *gene*, according to Keller, is that its
vagueness, the very feature that troubles philosophers, makes it
possible for biologists to be flexible, to communicate across
disciplinary boundaries, and to think in new ways:



> 
> 
> 
> The meaning of an experimental effect depends on its relation to
> other effects, and the use of language too closely tied to particular
> experimental practices would, by its very specificity, render
> communication across difference experimental contexts effectively
> impossible. (Keller 2000, p. 140).
> 
> 
> 




Keller identifies a second reason that *gene* talk is useful.
The term *gene* applies to entities that can be experimentally
manipulated to produce definite and reproducible effects (though given
Keller's criticism of gene concepts, it is unclear to what entities
she thinks the term refers). She suggests that genes are short-term
causes. She points out, however, that this does not mean genes are
long-term causes or that genes are the fundamental causal agents of
development. Rather, what it means (and Keller thinks this is an
important reason why gene talk will continue) is that genes can be
used as handles to manipulate biological processes (also see Waters
2000). And for these two reasons, Keller concludes,
gene talk will and should continue to play an important role in
biological discourse.


## 5. What do genes and DNA do?




The science called molecular genetics is associated with a fundamental
theory according to which genes and DNA direct all basic life
processes by providing the information specifying the development and
functioning of organisms. The genome is said to specify the
"developmental program," "master plan," or
"blue print" for development while other elements provide
the materials (e.g., Bonner 1965, Jacob and Monod 1961, Mayr 1961,
Maynard Smith 2000, Rosenberg 2006). Although the idea that the
chromosomes contain a "code-script" for the development
and functioning of an organism was famously expressed by Schrodinger
(1944) before the era of molecular genetics, today it is often
expressed in explicitly molecular terms. The information of
development and function, which is passed down from one generation to
the next, is allegedly encoded in the nucleotide sequences comprising
genes and DNA. This so-called "genetic information" is
first "transcribed" into RNA, then
"translated" into proteins, and finally
"expressed" in the development and functioning of
organisms.




The concept of genetic information has a prominent place in the
history of molecular genetics, beginning with Watson and Crick's
observation that since any sequence of nucleotide base pairs could fit
into the structure of any DNA molecule "that in a long molecule
many different permutations are possible, and it therefore seems
likely that the precise sequence of the bases is the code which
carries the genetic information." (Watson and Crick 1953). As
Downes (2005) recounts, the geneticists Jacob and Monod reinforced the
use of information language as did those who sought to crack the
"genetic code". By the early 1960s, the language of
information was well-entrenched in the field of molecular
genetics.




Philosophers have generally criticized the theory that genes and DNA
provide all the information and have challenged the use of sweeping
metaphors such as "master plan" and "progam"
which suggest that genes and DNA contain all developmental
information. Critics have taken a number of different positions. Most
seem to accept the notion that biological systems or processes contain
information, but they deny the idea that DNA has a exceptional role in
providing information. Some are content to argue that under various
existing theories of information, such as causal theories or standard
teleosemantic theories, information is not restricted to DNA. But
others contend that understanding what genes do requires a new
conception of biological information. One approach is to retreat to a
narrow conception of coding specifically aimed at clarifying the sense
in which DNA provides information for the synthesis of polypeptides,
but not for higher-level traits (e.g. Godfrey-Smith 2000). Another
approach is to construct a new, broad conception of biological
information and use this conception to show that the informational
role of genes is not exclusive (Jablonka 2002). A different approach
is to abandon information talk altogether and explain the
investigative and explanatory reasoning associated with genetics and
molecular biology in purely causal terms.


### 5.1 Criticism of idea that genes and DNA provide the information




The fundamental theory that says the role of DNA is to provide the
information for development has been criticized on many
grounds. Keller (2000) points out that the idea flounders on an
ambiguity. Does DNA provide the "program" or the
"data?" Others have argued that "information"
for development flows from a vast number of "resources,"
not just genetic resources. Oyama (1985) suggests that it is a mistake
to think information is contained within static entities such as
DNA. She believes that information exists in life-cycles. Other
criticisms challenge applications of particular conceptions or
theories of information, including applications of the causal and
teleosemantic conceptions. 




 Griffiths (2001) distinguishes between two ways to conceive of
information, causal and intentional, and then argues that under either
conception, information is not restricted to DNA. Causal theories of
information, based on Dretske's (1981), are related to the Shannon
mathematical theory of information (1948). Dretske distinguishes
between a source variable and background or channel conditions. On
Griffiths' (2001) reading of Dretske's theory, a source variable,
*X,* carries information about variable *Y* if the value
of *X* is correlated with the value of *Y.* Griffiths
describes the causal interpretation of this idea as follows:



> 
> 
> 
> There is a channel between two systems when the state of one is
> systematically causally related to the other, so that the state of the
> sender can be discovered by observing the state of the receiver. The
> causal information is simply the state of affairs with which it
> reliably correlates at the other end of the channel. Thus, smoke
> carries information about fire and disease phenotypes carry
> information about disease genes. (Griffiths 2001, p. 397)
> 
> 
> 




To capture the conventional ideas about genetic information under this
theory, genes are treated as source variables and environments are
treated as channel conditions. It follows that genes carry information
about phenotypes because phenotypic values reliably correlate with
genotypic values. But as Griffiths points out, nothing stops one from
treating environmental conditions as source variables and genes as
channel. Under this application of the causal theory, environmental
conditions carry information about phenotypes. Griffiths and others
have concluded that the idea that genes provide the information while
other causal factors merely provide material cannot be sustained under
causal theories of information.




Griffiths argues that the idea that genes and DNA provide all the
information fares no better under intentional theories of information.
Intentional theories are aimed at capturing the sense of
"semantic information" that human thoughts and utterances
allegedly contain (Godfrey-Smith 1999). The version of intentional
theory favored by philosophers of biology is teleosemantic. According
to teleosemantic theories, a signal represents whatever it was
selected to represent (in the process of evolution). Under this idea,
one might say that DNA contains information about development because
DNA's effects on development were selected for in the process of
evolution. But as Griffiths and Gray (1997) point out, this idea
applies to a wide range of entities involved in development, not just
DNA. 




Weber (2005) challenges Maynard Smith's (2000) teleosemantic
account. Maynard Smith draws an analogy between information in a
programmed computer and information in DNA. Computers execute
algorithms programmed by human beings and organisms express DNA that
has been programmed by natural selection. The information programmed
in a computer is intentional in that one could determine the
intentions of the human programmer by analyzing the algorithm. Maynard
Smith argues that the information programmed in DNA by natural
selection is intentional in the same sense. Weber offers two arguments
against this view. First, he points out that DNA might contain
nucleotide sequences that have arisen from chance mutations that
happen to be beneficial. If natural selection has not yet operated on
them, then Maynard Smith's teleosemantic theory implies they do not
contain information. Yet, causally, such a nucleotide sequence would
influence development in the same way as sequences that have been
selected for. Weber's second criticism of Maynard Smith's account
stems from a closer examination of the intentionality associated with
computer programs. Weber claims that intentional states associated
with computers are actually states of the human engineers who write
the programs, not states of the computers themselves: "A computer
program is a string of symbols that acquires a meaning only in the
context of a community of engineers who understand what the program
does and what it can be used for" (Weber 2005, p. 252). The analogue
to human programmers in Maynard Smith's account is natural
selection. But natural selection does not have intentional
states. Hence, Weber concludes, the teleosemantic approach fails to
save the idea that DNA contains information in the intentional
sense.




It is tempting to think that information talk is impotent in this
context and indeed, some philosophers have argued that such talk is
misleading and should be abandoned (e.g., Sarkar 1996,
Weber 2005, and possibly Rosenberg 2006). But others have taken the
view that more careful thinking about concepts of information could
lead to important insights (see next section).


### 5.2 Using a broadly biological concept of information to explain what genes do




Jablonka's aim is to construct a general definition of information
that recognizes different types of information associated with
different ways of acquiring, replicating, and transmitting information
through space and time (Jablonka 2002). One of her concerns is that
discussions about the meaning (or non-meaning) of information talk in
biology are biased by the assumption that the genetic system should
serve as the prototype for thinking about biological information. She
believes that a general definition of information, one designed to
capture the senses of information exemplified in environmental cues,
man-made instructions, and evolved biological signals, as well as the
sense of information in hereditary material, will lead to more useful
generalizations and perspectives.




Jablonka says that the sense of information in all these situations
involve a source, a receiver system (organism or organism-designed
system), and a special type of reaction of the receiver to the
source. She conceives the receiver's reaction as a complex, regulated
chain of events leading to a response. Variations in the form of the
source lead to variations in response. That is, the nature of the
reaction depends on the way the source is organized. In addition, she
points out, reactions in these situations are beneficial for the
receiver over an appropriate period of time (in the case of organisms,
over evolutionary time). Jablonka stresses that the benefit, or
function, in the case of organisms should be understood in terms of
evolution, with the focus on the evolution *of the reaction
system*, not on the evolution of the source or the evolution of
the final outcome of the reaction.




Jablonka's concept of information is intentional, and is related to
the teleosemantic conceptions discussed above. According to standard
teleosemantic conceptions, signals have information because the
production of the signal was selected for in evolutionary history.
According to Jablonka's view, however, an entity has information, not
because it was selected for, but because the receiver's response to it
was selected for. Whether something counts as information depends on
whether entities respond to it in a (proper) functional way.




Jablonka summarizes her general account in the following
definition:



> 
> 
> 
> A source -- an entity or process -- can be said to have
> information when a receiver system reacts to this source in a special
> way. The reaction of the receiver to the source has to be such that
> the reaction can actually or potentially change the state of the
> receiver in a (usually) functional manner. Moreover, there must be a
> consistent relation between variations in the form of the source and
> the corresponding changes in the receiver. (Jablonka 2002, p. 582)
> 
> 
> 




Jablonka points out that according to this definition, genes do not
have a theoretically privileged status; they are one among many sources
of information. In addition, she insists the focus should be on the
"interpretive system of the receiver of the
information", not on the source.




Jablonka argues that the information in DNA has little in common with
the information in an alarm call, a cloudy sky, or a chemical signal
in a bacterial colony. In the latter cases, the receivers'
reactions (or "responses") to the source are adaptive for
the receiver: "an alarm warns the bird there are predators
around; the cloudy sky alerts the ape to the coming storm; the
chemical alerts the bacteria to imminent starvation."
(p. 585). But in the case of DNA, the receiver does not seem to react
in a way that adapts the cell to anything in particular.
"Rather, DNA is simply 'read' by the cell, so it is
not information in the same sense ... DNA is information
'about' the cell or the organism, rather than
'for' the cell or the organism." (Jablonka 2002,
p. 585). Nevertheless, Jablonka claims that her concept applies to
genes even if it doesn't apply to DNA in general:



> 
> 
> 
> However, if instead of thinking about DNA in general we think about
> a particular locus with a particular allele, it is not difficult to
> think about the functional role of this particular allele in a
> particular set of environmental circumstances. Hence we can say for
> *all types of information*, including alarm calls and pieces of
> DNA, a source *S* (allele, alarm call, cloudy sky, etc.) carries
> information about a state *E* for a receiver *R* (an
> organism or an organism-designed product), if the receiver has an
> interpretation system that reacts to *S* in a way that usually
> ends up adapting *R* (or its designer, if *R* is humanly
> designed) to *E*. (Jablonka 2002, p. 585, my stress)
> 
> 
> 




Given that Jablonka says that DNA in general is not information in the
same sense as the alarm call and cloudy sky (and that this is the
sense specified in the statement above), it is puzzling why she claims
that the statement quoted above applies to "all types of
information." Furthermore, her claim that the statement above
applies to particular alleles (and apparently not to DNA in general)
is not straightforward. Jablonka's orignal account provides an
illuminating way to think about information in biological processes
such as cellular signaling processes. But her account does not
substantiate the idea that genes and DNA contain information or help
elucidate the role of genes and DNA. 


### 5.3 A causal interpretation of claims about what genes do



 Another approach to elucidating the role of genes and DNA is to
replace loose information talk with concrete causal descriptions
grounded in an explicit understanding of causation (Waters 2000, and forthcoming). This approach is
premised on the idea that the *basic* *theory* and
laboratory methods associated with molecular genetics can be
understood in purely causal terms. The basic
theory and methodology concerns the syntheses of DNA, RNA, and
polypeptide molecules, not the alleged role of DNA in "programming" or
"directing" development (section 2.3). The causal role of molecular
genes in the syntheses of these molecules can be understood in terms
of causally specific actual difference making. This involves two
causal concepts, actual difference making and causal
specificity. These concepts can be explicated in terms of the
 manipulability account of causation
 .



 The concept of actual difference making applies in the context of an
actual population containing entities that actually differ with
respect to some property. In such a population, there might be many
*potential* difference makers. That is, there may be many
factors that could be manipulated to alter the relevant property of
the entities in the population. But the *actual* difference
makers are (roughly speaking) the potential difference makers that
actual differ, and whose actual differences bring about the actual
differences in the property in the population.



 The concept of actual difference making can be illustrated with the
difference principle of classical genetics (section 2.1). According to
this principle, genes can be difference makers with respect to
phenotypic differences in particular genetic and environmental
contexts. So, it identifies potential difference makers. When this
principle is used to explain an actual hereditary pattern, it is
applied to genes that actually differed in the population exhibiting
the pattern (often an experimental population). In such cases, an
actual difference in the gene among the organisms in the population
caused the actual phenotypic differences in that population (see
Gifford 1990). That is, the gene was the actual
difference maker, not just a potential difference maker (in that
population). 



 The concept of actual difference making can be applied to molecular
genetics as follows. In an actual cell, where a population of
unprocessed RNA molecules differ with respect to linear sequence, the
question arises: what causes these differences? The answer is that
differences in genes in the cell cause the actual differences in the
linear sequences in the unprocessed RNA molecules, and also in
populations of RNA molecules and polypeptides. Genes are not the only
actual difference makers of the actual differences in the linear
sequences of these molecules. And this brings us to the second causal
concept, causal specificity. 



 Causal specificity has been analyzed by Lewis (2000). The basic idea
is that a causal relationship between two properties is specific when
many different values in a causal property bring about many different
and specifically different values of a resultant variable (the causal
relationships instantiate something like a mathematical function). An
on/off switch is not specific in this technical sense because the
causal property has only two values (on and off). A dimmer switch is
causally specific in this sense. Genes can be specific difference
makers because many specific differences in the sequences of
nucleotides in DNA result in specific differences in RNA
molecules. This is not the case with many other actual difference
makers, such as polymerases, which are more like on/off switches (with
respect to differences in linear sequences). Biologists have
discovered, however, the existence of other actual difference makers,
besides genes and DNA, that are causally specific with respect to the
linear sequences of processed RNA and polypeptides, to some degree at
least. For example, in some cells splicing complexes called
splicosomes actually differ in multiple ways that result in multiple,
specific differences in the linear sequences of processed RNA
molecules. 



 The fact that all kinds of entities are causally relevant to the
synthesis of RNA might lead one to think there is causal parity among
the causal elements. But this account shows that genes and DNA play a
distinctive causal role in that genes are the causally specific actual
difference makers of difference in the linear sequences of unprocessed
RNA molecules. This distinctive role extends (with important
qualifications) to the linear sequences of processed RNA molecules and
polypeptides. The basic theory associated with molecular genetics, as
distinguished from the fundamental theory, can be elucidated in causal
terms.


### 5.4 Causal accounts of how DNA programs development



 Weber (2005) and Rosenberg (2006) independently claim that DNA
contains a genetic program that is executed in development, but both
deny that this idea depends on the notion that DNA contains semantic
or intentional information. They illustrate this point by reviewing
the current explanation of the first stages of anterior-posterior
pattern formation in *Drosophila* embryos. This explanation
accounts for how a single-celled embryo with an intracellular gradient
of bicoid protein (the concentration of bicoid decreases from the
anterior to posterior end) develops into a multicellular embryo with
14 parasegments (the first three parasegments later form the head, the
next three will form the thorax, and the remaining segments will form
abdominal segments). Weber begins by explaining that the bicoid
gradient is "generated by the synthesis of protein from an mRNA
species that is derived from the mother (by transcription of maternal
genes) and is deposited in the egg cell at the anterior end by
maternal nurse cells." (Weber 2005, p. 244). He continues by
explaining how the biocoid protein differentially activates a set of
six *gap* genes, which in turn differentially activate and
deactive eight *pair-rule* genes, which differentially activate
and deactivate *segment polarity* genes and *homeotic
selector* genes.



 The details of the cascades of gene activations and deactivations
have been investigated experimentally. Weber's and Rosenberg's
summaries of the results indicate that biologists can explain initial
pattern formation in terms of successive concentration gradients that
regulate genes without essential appeal to information concepts. Weber
brings this point home by arguing in detail that the use of the term
'positional information' is metaphorical and that the
action of the bicoid gradient can be explained without the concept of
information. He concludes that this gradient and others do not carry
information in an intentional sense; rather, they play causal roles in
the formation of new gradients through the regulation of genes.



 Rosenberg discusses problems confronting the idea that DNA contains a
genetic program for development. He starts with the question of
whether the account of the early stages of pattern development, which
he and Weber summarize (separately), can be elaborated to give the
"whole story of development" (Rosenberg 2006, p.75). Will the whole
story be macromolecular? He also points out that the explanation of
pattern formation he describes is couched in terms of genes. He asks:
will this explanation survive if the gene concept does not? But in the
end, he expresses optimism in the grand idea that the explanation of
initial pattern development can be elaborated to account for the
entire process of development.



 Although both Rosenberg and Weber reject the idea that biologists'
explanation of the intitial stage of pattern formation makes essential
reference to the idea that genes or DNA have intentional information,
they assume that the explanation makes essential reference or implies
the existence of a genetic program. But it is unclear why the use of
the term *program* is any less metaphorical than the term
*positional information*. Rosenberg argues that we can infer
that DNA can execute programs from the fact that computers can be
built out of DNA and these DNA-based computers can execute programs in
the same sense that silicon-chip-based computers can execute
programs. Nevertheless, it is unclear what adding the phrase
"executing a genetic program" adds to the explanation of intial
pattern formation. Weber and Rosenberg present their summaries of the
explanation in causal terms such as 'generate',
'deposit', 'activate', and
'deactive'. One might ask whether the causal explanation
supersedes the metaphorical idea that DNA programs development.


### 5.5 Fundamental theorizing versus investigative pragmatics




Accounts such as the ones presented above, if successful, provide a
better basis for understanding the *basic theory* associated
with molecular genetics, but it is not clear that they can elucidate
the idea that genes are "fundamental" entities that "program" the
development and functioning of organisms by "directing" the syntheses
of proteins that in turn regulate all the important cellular
processes. In fact, there is considerable skepticism in the
philosophical community about this fundamental theory. A common
criticism (among philosophers) is that it is gene-centered.




Several philosophers have set out to replace the fundamental theory
associated with molecular genetics with a new fundamental theory that
does not "privilege" the gene. Among the proposals is Robert's
(2004). Drawing upon the writings of Burian, Griffiths, Keller, Oyama,
Moss, and others, Robert tries to construct a new "framework for
understanding and explaining organismal development" (p. 78)
that does not reduce "the problem of development" to the
problem of gene action and gene activation. He seeks a framework that
is free from the alleged assumption that development involves the
expression of "preformed genetic information" (p.
56). Robert says that his framework focuses on organisms rather than
genes and that it "takes seriously" the dynamical
complexities of development emphasized by Keller.




Philosophers engaged in fundamental theorizing have not, at least yet,
attracted much attention from practicing scientists. Perhaps the lack
of attention is due to a difference between the concerns of (many)
philosophers of biology and the needs of practicing
biologists. Wagner, a theoretical biologist who has conducted
mathematical/conceptual work in evolutionary theory as well as
empirical research on the evolution of morphological characters, makes
the following observation in a review of Robert's book,



> 
> 
> 
> Robert and his colleagues who argue for a similar interpretation are
> correct in that the genes alone cannot make an organism and instead are
> embedded in a large network of causal interactions. But scientists are
> usually not interested in general statements about what in principle is
> required to understand a phenomenon. 
> 
> 
> 
> 
> Yes, scientists make pragmatic decision about what to study, but I
> think that these decisions are anything but arbitrary. The power of
> molecular genetic approaches did not come easily, rather it is the
> result of a long history of strenuous research based on a vision that
> derived from the work of Richard Goldschmidt, Alfred
> Kuhn, and Thomas Hunt Morgan early in the 20th Century.
> It is thus not intellectual laziness that drives the genetic research
> program; instead we are raking in the spoils of a hard-won victory over
> biological complexity. (Wagner 2004, p. 1405)
> 
> 
> 




The discrepancy between (many) philosophers' interest in
fundamental theorizing and practicing biologists' need to make
pragmatic decisions about what to study raises an important question
about gene-centered sciences that has been largely overlooked by
philosophers: why is so much biological research centered on genes and
DNA?


## 6. Why is so much biological research centered on genes and DNA?




In official and public contexts, scientists appeal to the fundamental
theory associated with molecular genetics to justify centering
research on genes and DNA (e.g., see the websites of funding agencies
such as National Center for Biotechnology Information). Genes are
typically referred to as "the fundamental units" that are
responsible for guiding all basic life processes. Usually a
combination of causal and information metaphors are invoked to explain
the role of genes. Genes are said to produce RNA and polypeptides, to
provide instructions, or direct processes. But philosophical
investigation has shown that these kind of sweeping claims cannot
withstand careful scrutiny. Why, then, is so much research centered on
genes and DNA? One answer to this question is that biologists are
blinded by an ideology of genetic determinism. But Wagner's defense of
gene centrism suggests another answer, an answer that resonates with
Keller's explanation (2000) of why gene talk is useful.




It has been proposed that the real reason biologists center attention
on genes and DNA is that genes are difference makers that can be used
to trace and manipulate a broad range of biological processes (Waters
2004a and 2006). This scientific practice makes sense independently of
any fundamental theory associated with molecular genetics. In the case
of molecular genetics, it is investigative pragmatics, not fundamental
theorizing, that drives scientific research. The basic theory suffices
to explain the investigative utility and results of gene-centered
approaches. The fundamental theory is, in an important sense,
epiphenomenal with respect to the design and implementation of
gene-centered research. On this view, the role of the fundamental
theory should be understood in Latourian terms (1987, 1988), as a
platform for rallying the troops and bringing resources to research
endeavors. The design of the laboratory experiments and the reason
why the experiments work, can be explained in terms of broad
investigative strategies, the basic causal theory of molecular
genetics, and the details of the experimental contexts.


## 7. Conclusion




The philosophy of molecular genetics is a lively area of research that
reflects much of the excitement and diversity in contemporary
philosophy of science. Philosophers examining the related areas of
genetics have different philosophical interests and adopt contrasting
approaches. Some philosophical research is aimed at setting science
straight while other research is aimed at correcting our understanding
of science. Some philosophers employ traditional methods of philosophy
of science, for example the analyses of concepts and models, while
others are pioneering new philosophical approaches by drawing upon
methods from social science including survey studies. While some
philosophers focus their attention on fundamental theorizing, others
are investigating the dynamics of empirical investigation. Research in
the philosophy of molecular genetics is also generating new ideas
about basic concepts of general philosophical interest including
reductionism, information, and causation.