Molecular Biology

The field of molecular biology studies macromolecules and the macromolecular

mechanisms found in living things, such as the molecular nature of the gene and its
mechanisms of gene replication, mutation, and expression. Given the fundamental
importance of these macromolecular mechanisms throughout the history of
molecular biology, a philosophical focus on the concept of a mechanism generates
the clearest picture of molecular biology’s history, concepts, and case studies
utilized by philosophers of science.

1.1 Origins
The field of molecular biology arose from the convergence of work by geneticists, physicists,
and structural chemists on a common problem: the nature of inheritance. In the early
twentieth century, although the nascent field of genetics was guided by Mendel’s laws of
segregation and independent assortment, the actual mechanisms of gene reproduction,
mutation and expression remained unknown. Thomas Hunt Morgan and his colleagues
utilized the fruit fly, Drosophila melanogaster, as a model organism to study the relationship
between the gene and the chromosomes in the hereditary process (Morgan 1926; discussed in
Darden 1991; Darden and Maull 1977; Kohler 1994; Roll-Hanson 1978; Wimsatt 1992). A
former student of Morgan’s, Hermann J. Muller, recognized the “gene as a basis of life”, and
so set out to investigate its structure (Muller 1926). Muller discovered the mutagenic effect
of x-rays on Drosophila, and utilized this phenomenon as a tool to explore the size and
nature of the gene (Carlson 1966, 1971, 1981, 2011; Crow 1992; Muller 1927). But despite
the power of mutagenesis, Muller recognized that, as a geneticist, he was limited in the
extent to which he could explicate the more fundamental properties of genes and their
actions. He concluded a 1936 essay:
The geneticist himself is helpless to analyse these properties further. Here the physicist, as
well as the chemist, must step in. Who will volunteer to do so? (Muller 1936: 214)
Muller’s request did not go unanswered. The next decade saw several famous physicists turn
their attention to the nature of inheritance (Keller 1990; Kendrew 1967). In What is Life, the
physicist Erwin Schroedinger (1944) proposed ways in which the principles of quantum
physics might account for the stability, yet mutability, of the gene (see the entry on life)
(Elitzur 1995; Moore 1989; Olby 1994; Sarkar 1991; for a reinterpretation see Kay 2000).
Max Delbrueck also became interested in the physical basis of heredity after hearing a
lecture by his teacher, quantum physicist Niels Bohr (1933), which expounded a principle of
complementarity between physics and biology (McKaughan 2005; Roll-Hansen 2000). In
contrast to Schroedinger, Bohr (and subsequently Delbrueck) did not seek to reduce biology
to physics; instead, the goal was to understand how each discipline complemented the other
(Delbrueck 1949; Sloan and Fogel 2011). To investigate the self-reproductive characteristic
of life, Delbrueck used bacteriophage, viruses that infect bacteria and then multiply very
rapidly. The establishment of “The Phage Group” in the early 1940s by Delbrueck and
another physicist-turned-biologist Salvador Luria marked a critical point in the rise of
molecular biology (Brock 1990; Cairns et al. 1966; Fischer and Lipson 1988; Fleming 1968;
Lewontin 1968; Luria 1984; Morange 1998: Ch. 4; Stent 1968). Delbrueck’s colleague at Cal
Tech, Linus Pauling, utilized his knowledge of structural chemistry to study macromolecular
structure. Pauling contributed both theoretical work on the nature of chemical bonds and
experimental work using x-ray crystallography to discover the physical structure of
macromolecular compounds (Pauling 1939, 1970; Olby 1979; Hager 1995; Crick 1996;
Sarkar 1998).
As suggested in the brief history above, experimentation figured prominently in the rise of
molecular biology (see the entry on experiment in biology). X-ray crystallography allowed
molecular biologists to investigate the structure of macromolecules. Alfred Hershey and
Martha Chase (1952) used phage viruses to confirm that the genetic material transmitted
from generation to generation was DNA and not proteins (see Hershey-Chase Experiment
in Other Internet Resources). Muller (1927) used x-rays to intervene on and alter gene
function, thus revealing the application of methods from physics to a biological domain (see
Elof Carlson on Muller’s Research in Other Internet Resources).
Recognizing quite early the importance of these new physical and structural chemical
approaches to biology, Warren Weaver, then the director of the Natural Sciences section of
the Rockefeller Foundation, introduced the term “molecular biology” in a 1938 report to the
Foundation. Weaver wrote,
And gradually there is coming into being a new branch of science—molecular biology—
which is beginning to uncover many secrets concerning the ultimate units of the living
cell….in which delicate modern techniques are being used to investigate ever more minute
details of certain life processes (quoted in Olby 1994: 442).
But perhaps a more telling account of the term’s origin came from Francis Crick, who said
he started calling himself a molecular biologist because:
when inquiring clergymen asked me what I did, I got tired of explaining that I was a mixture
of crystallographer, biophysicist, biochemist, and geneticist, an explanation which in any
case they found too hard to grasp. (quoted in Stent 1969: 36)
This brief recapitulation of the origins of molecular biology reflects themes addressed by
philosophers, such as reduction (see Section 3.1), the concept of the gene (see Section 2.3),
and experimentation (see Section 3.4). For Schroedinger, biology was to be reduced to the
more fundamental principles of physics, while Delbrueck instead resisted such a reduction
and sought what made biology unique. Muller’s shift from Mendelian genetics to the study
of gene structure raises the question of the relation between the gene concepts found in those
separate fields of genetics. And the import of experimental methods from physics to biology
raised the question of the relation between those disciplines.