Moleculer Biology

Sunday, 3 July 2011

Molecular Biology

First published Sat june 19, 2007

; substantive revision Wed Sep 9, 2009

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, it will be argued that 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.
This encyclopedia entry is organized around these three themes. First, a historical overview of the developments in molecular biology from its origins to the present pays special attention to the features of this history referenced by philosophers. Philosophical analysis then turns to the key concepts in the field: mechanism, information, and the gene. Finally, philosophers have used molecular biology as a case study to address more general issues in the philosophy of science, such as theory reduction and scientific explanation, each of which are understood most clearly in molecular biology with a focus on the field's attention to mechanisms.

Mechanism

As the brief history of molecular biology showed, molecular biologists discover and explain by identifying and elucidating mechanisms, such as DNA replication, protein synthesis, and the myriad mechanisms of gene expression. The phrase “theory of molecular biology” was not used and for good reason; general knowledge in the field is represented by diagrams of mechanisms. Discovering the mechanism that produces a phenomenon is an important accomplishment for several reasons. First, knowledge of a mechanism shows how something works: elucidated mechanisms provide intelligibility. In some cases, one can literally see how the mechanism works from beginning to end. One can run a simulation in the mind's eye. Second, knowing how a mechanism works allows predictions to be made based upon the regularity in mechanisms. One may be able to say how a mechanism would work, if another instance is encountered, or if conditions or inputs are changed. Thirdly, knowledge of mechanisms potentially allows one to intervene to change what the mechanism produces, to manipulate its parts to construct experimental tools, or to repair a broken, diseased mechanism. In short, knowledge of elucidated mechanisms provides understanding, prediction, and control. Given the general importance of mechanisms and the fact that mechanisms play such a central role in the field of molecular biology, it is not surprising that philosophers of biology pioneered analyzing the concept of mechanism.
The new mechanistic perspective in philosophy of science developed, in part, in philosophy of molecular biology (as well as in studies of cell biology and neuroscience). As early as the 1970s, William Wimsatt (1972, 67) said, “At least in biology, most scientists see their work as explaining types of phenomena by discovering mechanisms...” In their seminal book, Discovering Complexity, William Bechtel and Robert Richardson (1993) investigated the roles of decomposition and localization as strategies for discovering mechanisms. Richard Burian (1993, 389) noted that molecular biology “mainly studies molecular mechanisms,” and expanded this perspective in Burian (2005).

Information

As revealed in the history of molecular biology, the language of information is used ubiquitously by molecular biologists. Genes as linear DNA sequences of bases are said to carry “information” for the production of proteins. During protein synthesis, the information is “transcribed” from DNA to messenger RNA and then “translated” from RNA to protein. During DNA replication, and subsequent inheritance, it is often said that what is passed from one generation to the next is the “information” in the genes, namely the linear ordering of bases along complementary DNA strands. Historians of biology have tracked the entrenchment of information-talk in molecular biology, and philosophers of biology have questioned whether a definition of “information” can be provided that adequately captures its usage in the field.
According to the historian Lily Kay, “Up until around 1950 molecular biologists…described genetic mechanisms without ever using the term information” (Kay 2000, 328). “Information” replaced earlier talk of biological “specificity.” Watson and Crick's second paper of 1953 (1953b), which discussed the genetical implications of their recently discovered double-helical structure of DNA (1953a), announced: “…it therefore seems likely that the precise sequence of the bases is the code which carries the genetical information…” (Watson and Crick 1953b, 244, emphasis added).
In 1958, Francis Crick used and characterized the concept of information in the context of stating what he called the central dogma of molecular biology. Crick characterized the central dogma as follows:

Gene

The question of whether classical genetics could be (or already has been) reduced to molecular biology (to be taken up below) motivated philosophers to consider the connectibility of the term they shared: the gene. Investigations of reduction and scientific change raised the question of how the concept of the gene evolved over time, figuring prominently in C. Kenneth Waters' (1990, 1994, 2007, see entry on molecular genetics), Philip Kitcher's (1982, 1984) and Raphael Falk's (1986) work. Over time, however, philosophical discussions of the gene concept took on a life of their own, as philosophers raised questions independent of the reduction debate: What is a gene? And, is there anything causally distinct about DNA?
Falk (1986) explicitly asked philosophers and historians of biology, “What is a Gene?” Falk drew on Kenneth MacCorquodale and Paul E. Meehl's distinction between quantities that can be obtained by manipulating values of empirical variables without hypothesizing the existence of unobserved entities or processes (dubbed “intervening variables”) and concepts which assert the existence of entities and the occurrence of events not reducible to the observable (dubbed “hypothetical constructs”) (MacCorquodale and Meehl 1948). Employing this distinction, Falk claimed that the gene began as an intervening variable but morphed into a hypothetical construct with Morgan's chromosomal theory of inheritance and then with molecular biology, when the gene became equated with a sequence of DNA.
Discoveries such as overlapping genes, split genes, and alternative splicing (discussed in Section 1.2) made it clear that simply equating a gene with an uninterrupted stretch of DNA would no longer capture the complicated molecular-developmental details of mechanisms such as gene expression (Downes 2004). In light of the enormous complexity found in the process of moving from a stretch of DNA to a protein product, Falk's (1986) question persists: What is a gene? Two general trends have emerged in the philosophical literature to answer this question and to accommodate the molecular-developmental phenomena: first, distinguish multiple gene concepts to capture the complex structural and functional features separately, or second, rethink a unified gene concept to incorporate such complexity.

Molecular Biology and General Philosophy of Science

. Molecular Biology and General Philosophy of Science

In addition to analyzing key concepts in the field, philosophers have employed case studies from molecular biology to address more general issues in the philosophy of science. The issue of reduction was addressed by considering whether classical genetics had been reduced to molecular biology. Cases from molecular biology have also been used to analyze the relationship between laws and explanation (see also the entry on philosophy of biology). For each of these philosophical issues, it will be argued, evidence from molecular biology directs philosophical attention toward understanding the concept of a mechanism for addressing the topic.

Theory Reduction and Integration of Fields

Reflecting on the historical origins of molecular biology discussed above, it should come as no surprise that the field appeared to many philosophers of science to offer an ideal case of reduction. Molecular biology emerged out of the search for the structure and function of the gene, so might the older field of classical genetics be (or have been) simply reduced to a successor—molecular biology?
Classical genetics had two laws, which, at first, seemed likely candidates for reduction to (derivation from) molecular laws. Based on patterns of inheritance of characters during breeding experiments, classical geneticists inferred regularities in the behavior of genes. These regularities were captured in Mendel's laws of segregation and independent assortment of genes in different linkage groups (as described in Section 1.1 above). The formal reduction of classical genetics to molecular biology required that these classical laws be logically deduced from laws of molecular biology. However, it was not possible to identify anything in molecular biology that was called a “law” or that played a role sufficient to allow logical derivation of Mendel's laws. Alternative analyses of the relation between classical genetics and molecular biology have included claims of replacement, informal reduction, explanatory extension, relations among practices, as well analysis of different mechanisms investigated in the two fields.

Bibliography

Abir-Am, Pnina (1985), “Themes, Genres and Orders of Legitimation in the Consolidation of New Scientific Disciplines: Deconstructing the Historiography of Molecular Biology”, History of Science, 23: 74–117.
––– (1987), “The Biotheoretical Gathering, Trans-Disciplinary Authority and the Incipient Legitimation of Molecular Biology in the 1930s: New Perspective on the Historical Sociology of Science”, History of Science, 25: 1–70.
––– (1994), “Converging Failure: Science Policy, Historiography and Social Theory of Early Molecular Biology”, in Tamara Horowitz and Allen I. Janis (eds.), Scientific Failure, New York: Roman and Littlefield Publishers, Inc., 141–166.
––– (2006), “Molecular Biology and Its Recent Historiography: A Transnational Quest for the ‘Big Picture’”, History of Science, 44: 95–118.
Alberts, Bruce, Dennis Bray, Julian Lewis, Martin Raff, Keith Roberts and James D. Watson (1983), Molecular Biology of the Cell, New York: Garland.
Alberts, Bruce, A. Johnson, J. Lewis, M. Raff, K. Roberts, and P. Walter (2002), Molecular Biology of the Cell, Fourth Edition. New York: Garland.
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––– (2003), “Sequencing the Genome from Nematode to Human: Changing Methods, Changing Science”, Endeavour, 27: 87–92.
Anonymous (1970), “Central Dogma Reversed,” News and Views, Nature, 226: 1198–1199.
Avery, Oswald T., C. M. MacLeod, and Maclyn McCarty (1944), “Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types”, Journal of Experimental Medicine, 79: 137–158.
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Barrell, B. G., Gillian M. Air, and Clyde A. Hutchison III (1976), “Overlapping Genes in Bacteriophage PhiX174”, Nature, 264: 34–41.
Beatty, John (1995), “The Evolutionary Contingency Thesis”, in James G. Lennox and Gereon Wolters (eds.), Concepts, Theories, and Rationality in the Biological Sciences, Pittsburgh, PA: University of Pittsburgh Press, 45–81.
Bechtel, William (2006), Discovering Cell Mechanisms: The Creation of Modern Cell Biology, New York: Cambridge University Press.

Explanation in Molecular Biology

Traditionally, philosophers of science took successful scientific explanations to result from derivation from laws of nature (see the entries on laws of nature and scientific explanation). On this deductive-nomological account (Hempel and Oppenheim 1948), an explanation of particular observation statements was analyzed as subsumption under universal (applying throughout the universe), general (exceptionless), necessary (not contingent) laws of nature plus the initial conditions of the particular case. Philosophers of biology have criticized this traditional analysis as inapplicable to biology, and especially molecular biology.
Since the 1960s, philosophers of biology have questioned the existence of biological laws of nature. J. J. C. Smart (1963) emphasized the earth-boundedness of the biological sciences (in conflict with the universality of natural laws). No purported “law” in biology has been found to be exceptionless, even for life on earth (in conflict with the generality of laws). And John Beatty (1995) argued that the purported “laws” of, for example, Mendelian genetics, were contingent on evolution (in conflict with the necessity of natural laws). (For further discussion, see Brandon 1997; Mitchell 1997; Sober 1997; Waters 1998.) Hence, philosophers' search for biological laws of nature, characterized as universal, necessary generalizations, has ceased.