vrijdag 14 maart 2008

Historische en filosofische beschouwing van de moleculaire biologie in Routledge: een vertrekpunt


Dietrich, Michael R., "Molecular biology", Routledge Encyclopedia of Philosophy, Edward Craig (eds.), London: Routledge, version 1.0, 1998.

Informatief extract:

[termen i.v.m. reductionisme en andere zaken die onderaan deze tekst behandeld worden heb ik in het vet gezet]

Molecular biology is the study of the structure, function and kinetics of biologically important molecules. Historically, molecular biology has often been identified with molecular genetics. Similarly, the chief philosophical concern with molecular biology has been the possibility of the reduction of classical genetics to molecular genetics. The nature and boundaries of molecular biology, however, are themselves disputed. To some, molecular biology seems to be a morass of molecular details without any overarching theory. To others molecular biology is an integrated interlevel theory. How philosophical issues, such as reduction, are addressed can depend importantly on how molecular biology is initially characterized.

1 Molecularizing biology

Although molecular biology can be broadly defined as the study of the structure, function and kinetics of biologically important molecules, the origins of molecular biology are usually traced back to two specific research traditions: the informational school and structural school. This historical approach has been strongly disputed. Nevertheless, it provides a starting place for historical analysis.

The informational school is identified with the study of bacterial viruses (bacteriophage or phage) begun in the late 1930s by Max Delbruck, Salvador Luria and Alfred Hershey. The phage group, as they would come to be known, took as its goal the elucidation of the physical basis of heredity through careful experimental study of virus self-replication within bacterial hosts. The problem of replication was itself a means of investigating how molecules could store and transmit genetic information. Chromosomes were the accepted material basis of heredity and were known to be mixtures of nucleic acids and proteins. Proteins, by virtue of their
known linear arrangement of specific units, were thought to be better candidates for information storage and transfer than were nucleic acids. This emphasis on proteins was overthrown by Alfred Hershey and Martha Chase’s experiments published in 1952 demonstrating that deoxyribonucleic acid (DNA) alone was injected into host bacteria. With the use of their Waring blender, Hershey and Chase had ingeniously shown that DNA, not protein, was responsible for virus replication.
At roughly the same time that the informational school was starting out in the 1930s, the structural school began extending traditions in structural chemistry to the study of biological molecules. In the USA, Linus Pauling used his expertise as a structural chemist to explain the helical structure of polypeptides essential to important biological proteins such as hemoglobin and myoglobin.
In England, W.T. Astbury and J.D. Bernal began using X-ray crystallography to study the internal structure of proteins. This programme was expanded as the Cavendish Laboratory at Cambridge and King’s College in London began X-ray diffraction studies of biological molecules.
These two schools of thought came together in the 1950s with the collaboration of James Watson and Francis Crick. Watson’s knowledge of phage genetics and Crick’s knowledge of X-ray crystallography both contributed to their now famous discovery of the double helical structure of DNA in 1953. The two-stranded model of DNA with its complementary base pairs explained the structural features of the DNA molecule and suggested how DNA could both store and transfer information.
The neat division of the origins of molecular biology into these two schools has been disputed on historical as well as historiographical grounds. The structural and informational schools were introduced as historical categories in the 1960s as biologists struggled to define molecular biology. Gunther Stent, a member of the phage group, strongly identified the phage group
with the origins of molecular biology. John Kendrew, who won the Nobel Prize in 1962 for determining the structure of myoglobin, had a completely different experience of the emergence of molecular biology. Kendrew introduced the idea that there were two schools. Gunter Stent agreed and extended Kendrew’s analysis in his reply. At the time Kendrew and Stent were writing, the emphasis in molecular biology was on integration of structure and function in biological molecules à la Watson and Crick. In effect Kendrew and Stent projected the reality of 1960s molecular biology into the past and in doing so created a history that legitimated present practice (Abir-Am 1985).
The structural and informational schools do not encompass the origins or the present state of molecular biology. It is not even clear to what extent the loose association of individuals doing structural work on biological molecules can be considered a school. The origins of molecular biology as well as its current practice represent a much more diverse array of traditions.
Molecular biology, as it was first defined by the National Science Foundation in 1954, covered a wide variety of biological phenomena, such as the: identification and structure of particulate matter such as mitochondria, chloroplasts, chromosomes, viruses, enzyme structure and kinetics - chemistry of coenzymes, electrochemical phenomena, membranes and fibers, solid and liquid state phenomena, reactions of proteins - long range forces, mathematical approaches to biological problems (quoted in Zallen 1993: 81).
Clearly, molecular biology could be seen as drawing on long-standing traditions in biochemistry, cell biology and bioenergetics, as well as those in phage research and structural chemistry. The history of molecular biology may be dominated by the history of molecular genetics, but the practice of molecular biology is and has been much more diverse.

2 Interlevel theories

As philosophers tried to come to grips with molecular biology and particularly the question of the reduction of classical genetics to molecular genetics, they were faced with the problem of how to characterize the structure of molecular biology (see Genetics §4).

While some thought of molecular biology as a scientific theory, characterized as a set of general laws or a set of axioms, others began to conceive of molecular biology in terms of interlevel theories and practices. These different approaches to theory structure can have important consequences for other philosophical issues, such as reduction.
Kenneth Schaffner has argued that most biomedical theories, including molecular biological theories, should be thought of as a series of overlapping interlevel temporal models (Schaffner 1993a, 1993b). This proposed analysis treats theories as families of models, as polytypic aggregates with some specified core characteristics. The entities represented by these models are usually undergoing some process and so are temporal. The theory is an interlevel theory because the entities represented by the theory can be grouped according to level of aggregation. Entities at one level of aggregation may share parts with entities at lower levels, but the defining properties of the entity at the higher level require organizing principles not found at the lower level.
It is often assumed that the successful reduction of a higher level theory to a lower level theory will result in the replacement of the higher level theory by the lower level theory. This strict reduction-replacement approach requires that the lower level theory use only lower level terms and entities. Schaffner’s interlevel theories require that this strict model of reduction-replacement be relaxed to allow partial or patchy reductions as a result of more complex connections between parts of different interlevel theories. With the complex interlevel processes considered in molecular biological theories, one should not expect complete unilevel reduction of a higher level theory to a lower level biochemical theory, which itself is often an interlevel theory. Molecular biological explanations, according to this view, are facilitated by partial reductions and causal generalizations regarding the temporal sequence of events represented by the relevant model (Schaffner 1993b).

3 Practices

Schaffner’s appreciation of the complexity of molecular biology is shared by Sylvia Culp and Philip Kitcher’s analysis of molecular biology in terms of practices. A practice consists of a language used by the scientific community of interest, the set of statements that community accepts, the set of questions they take to be important, the patterns of reasoning they use to answer those questions, the methodological directives or standards they use to evaluate solutions and experiments, and a set of experimental techniques (Culp and Kitcher 1989). Using this account of practices, Culp and Kitcher argue that the contemporary practice of molecular biology can be understood in terms of a hierarchy of questions concerning why some biologically important process occurs, and how accepted statements and experimental techniques contribute to the solution of that problem. The interlevel complexity described by Schaffner is captured in Culp and Kitcher’s practices by the hierarchy of questions. In the case of cell biology, for instance, Culp and Kitcher start out with the fundamental question of ‘how do organisms move?’. This question is then followed by the supposition that ‘motion requires contraction and extension of muscles’ and the related question of ‘how do muscles contract?’. This question is then followed by the supposition that ‘muscle cells contain actin and myosin’ and the related question of ‘how do actin and myosin contribute to the contraction of a cell?’ (Culp and Kitcher 1989). This nested set of questions leads to a nested set of explanations. Cellular theories of motion do not reduce to molecular biology within this hierarchy; instead the explanations of the action of myosin and actin extend the cellular explanatory scheme. An explanatory scheme is a schematic argument with specific filling instructions.

What makes explanatory extension different from strict reduction-replacement is that it allows different parts of an explanatory scheme to be extended in different directions by different theories. Molecular biology does not provide the only route for explanatory extension and it is not the case that all explanatory extensions will ultimately end with molecular biology (Kitcher 1984). Schaffner’s complex reduction-replacement model with its partially overlapping interlevel theories also allows theories and explanations to be elaborated in a number of ways, and agrees with much of Kitcher’s explanatory extension approach, although Schaffner and Kitcher and Culp continue to disagree on how to characterize theories in molecular biology (Schaffner 1993a).
One further aspect of Culp and Kitcher’s characterization of molecular biology deserves comment: namely, their emphasis on experiment. One of the most striking features of molecular biology is the prominence of experimental techniques (see Experiment).
A vital aspect of the structure of molecular biology is the presence and exportation of sets of techniques to address a vast array of different biological problems. While philosophers of science have been traditionally concerned with theories, the ongoing study of sciences like molecular biology is fuelling the growing concern with experimentation, so much so that it now seems difficult to characterize molecular biology without discussing the central role of experimental techniques, such as X-ray diffraction, electrophoresis, or polymerase chain reactions (Zallen 1993).

References and further reading

Abir-Am, P. (1985) ‘Themes, Genres, and Orders of Legitimation in the Consolidation of New Scientific Disciplines: Deconstructing the Historiography of Molecular Biology’, History of Science 23: 73-117.(Historiographical analysis of four major traditions in the history of molecular biology, including the history of the informational and structural schools.)
Cairns, J., Stent, G. and Watson, J. (eds) (1992) Phage and the Origins of Molecular Biology, Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.(Volume of papers in honour of Max Delbruck. The expanded edition includes Kendrew and Stent’s papers contesting the informational and structural schools.)
Culp, S. and Kitcher, P. (1989) ‘Theory Structure and Theory Change in Contemporary Molecular Biology’, British Journal of the Philosophy of Science 40: 459-83.(An analysis of structure and change in molecular biology based on a case study of the discovery on enzymatic RNA.)
Judson, H.F. (1979) The Eighth Day of Creation: Makers of the Revolution in Biology, New York: Simon & Schuster.(A detailed history of molecular biology notable for its attention to the individual contributions and accomplishments of a diverse array of scientists.)
Kitcher, P. (1984) ‘1953 and All That: A Tale of Two Sciences’, Philosophical Review 93: 335-73. (An antireductionist argument based on intertheoretic relationships and the concept of explanatory extension.)
Olby, R. (1974) The Path to the Double Helix, Seattle, WA: University of Washington Press.(A detailed reconstruction of the historical precursors to Watson and Crick’s discovery of the structure of DNA. It further develops the idea of the structural and informational schools.)
Schaffner, K. (1993a) Discovery and Explanation in Biology and Medicine, Chicago, IL: University of Chicago Press.(A broad survey and analysis of a number of important issues such as reduction, theory testing and explanation.)
Schaffner, K. (1993b) ‘Theory Structure, Reduction, and Disciplinary Integration in Biology’, Biology and Philosophy 8: 319-47.
(An analysis of theory structure in terms of integrated interlevel theories that allow for partial reduction and integration.)
Zallen, D. (1993) ‘Redrawing the Boundaries of Molecular Biology: The Case of Photosynthesis’, Journal of the History of Biology 26: 65-87.(A convincing argument for the reconception of molecular biology as a more diverse and complex field based on a case study of the history of bioenergetic research on the process of photosynthesis.)"

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Creatieve commentaar:

Uit dit artikel in Routledge etc., waarvan ik geen verwante heb gevonden in Encyclopedia of Philosophy of Stanford etc., extraheer ik mijn thema reductionisme en/in/door de moleculaire biologie. Het heeft geen subtitel in dit artikel maar neemt wel een belangrijke plaats in.

Een aantal zaken kunnen we hier uit leren, die nuttig kunnen zijn voor onze zoekopdracht.
1. Moleculaire genetica wordt in filosofische discussies regelmatig op gelijke hoogte geplaatst met moleculaire genetica, dat eigenlijk een onderdeel is van de moleculaire biologie. (Zoals aangehaald in de tekst is de moleculaire biologie veel ruimer. Men heeft immers ook nog de moleculaire celbiologie/fysiologie en biochemie die eerder handelen over de werking en functies van de moleculen in de cel en het lichaam.) We mogen onze zoektermen dus niet beperken tot 'molecular biology', maar zullen dus ook 'molecular genetics' moeten gebruiken.
2. Dat het reductievraagstuk gekoppeld is aan theorievorming. We mogen ons dus niet blind staren op het begrip 'reduction(ism)'
3. Dat Kenneth Schaffner, Sylvia Culp, Philip Kitcher’s belangrijke referentiepunten zijn.

4. De referenties die belangrijk zijn voor mijn verdere zoektocht heb ik in het vet aangeduid. Schaffner 1993a is niet voorradig in de Antwerpse bibliotheek, maar wel in Leuven dus zal ik het daar gaan halen. Schaffner 1993b is online of op papier niet beschikbaar via UA. Misschien heeft de KULeuven het wel op papier. Culp - Kitcher 1989 is beschikbaar via JSTOR.

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