In biochemical textbooks prior to , nucleic acids DNA and ribonucleic acid, RNA were relegated to a minor chapter.
The discoveries of the twenty-some amino acids, the building blocks of proteins, were major achievements of early twentieth century biochemistry. Items of interest to biochemists were covalent bonding a strong form of chemical bonding, that connects amino acids in proteins , the action of enzymes proteins that act as catalysts in biochemical reactions , and the energy requirements for reactions to occur. After Watson and Crick's a discovery of the structure of DNA, biochemistry showed increased emphasis on nucleic acids see, e.
This brief recapitulation of the origins of molecular biology reflects themes addressed by philosophers, such as reduction see Section 3. 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 classical genetics to the study of gene structure raises the question of the relation between the classical and molecular concept of the gene. These issues will be examined below. Molecular biology's classical period began in , with James Watson and Francis Crick's discovery of the double helical structure of DNA Watson and Crick a, b. Watson and Crick's scientific relationship unified various disciplinary approaches: Watson, a student of Luria and the phage group, recognized the need to utilize crystallography to elucidate the structure of DNA; Crick, a physicist enticed by Schroedinger's What is Life?
In the oft told story Watson , Watson and Crick collaborated to build a model of the double helical structure of DNA, with its two helical strands held together by hydrogen-bonded base pairs.
Taylor, Thomas N. Includes a wide selection of photographs of Watson in the centre pages. Columbia Biological Series. However, methods were available. Bernal, the sage of science , Oxford University Press, Oxford, pp.
They made extensive use of data from x-ray crystallography work on DNA by Maurice Wilkins and Rosalind Franklin at King's College, London Maddox , Crick's theoretical work on crystallography Crick , and the model building techniques pioneered by Pauling de Chadarevian ; Judson ; Olby , With the structure of DNA in hand, molecular biology shifted its focus to how the double helical structure aided elucidation of the mechanisms of genetic replication and function, the keys to understanding the role of genes in heredity.
This subsequent research was guided by the notion that the gene was an informational molecule. The linear sequence of nucleic acid bases along a strand of DNA provided coded information for directing the linear ordering of amino acids in proteins Crick Attempts to unravel the genetic code included failed theoretical efforts, as well as competition between geneticists Crick et al.
An important breakthrough came in when biochemists Marshall Nirenberg and J. Heinrich Matthaei, at the US National Institutes of Health NIH , discovered that a unique sequence of nucleic acid bases could be read to produce a unique amino acid product Nirenberg and Matthaei ; for discussion, see Judson ; Kay With the genetic code elucidated and the relationship between genes and their molecular products traced, it seemed in the late s that the concept of the gene was secure in its connection between gene structure and gene function.
The machinery of protein synthesis translated the coded information in the linear order of nucleic acid bases into the linear order of amino acids in a protein. In the late s, a series of discoveries by molecular biologists complicated the straightforward relationship between a single, continuous DNA sequence and its protein product.
Overlapping genes were discovered Barrell et al. And split genes were found Berget et al. In contrast to the colinearity hypothesis that a continuous nucleic acid sequence generated an amino acid chain, it became apparent that stretches of DNA were often split between coding regions exons and non-coding regions introns.
A series of exons could be spliced together in a variety of ways, thus generating a variety of molecular products. Discoveries such as overlapping genes, split genes, and alternative splicing forced molecular biologists to rethink their understanding of what actually made a gene…a gene Portin During this period of the s, molecular biologists developed a variety of techniques for manipulating the genetic material. The recombining of DNA from different species was made possible by the discovery of restriction enzymes that cut DNA at specific sites and ligases that then join these DNA segments.
Such transgenic forms aided both theoretical study and practical applications and also caused concern about possible hazards Krimsky ; Watson and Tooze These developments in molecular biology have received philosophical scrutiny. Molecular biologists sought to discover mechanisms see Section 2. Also, conceptualizing DNA as an informational see Section 2. Finally, the concept of the gene see Section 2. In a letter to Max Perutz, molecular biologist Sydney Brenner foreshadowed what would be molecular biology's next intellectual migration:.
Along with Brenner, in the late s and early s, many of the leading molecular biologists redirected their research agendas, utilizing the newly developed molecular techniques to investigate unsolved problems in other fields. The discovery of coordinated gene regulation in bacteria by molecular biologists at first appeared to provide a general, theoretical model for transforming descriptive embryology into molecular developmental biology.
Francois Jacob, Jacques Monod and their colleagues at the Institute Pasteur in Paris, discovered that three genes were coordinately controlled. Escherichia coli bacteria normally did not make enzymes for metabolizing the sugar in milk, but when placed in a medium with lactose as a food source, genes for metabolizing that sugar were induced. Work on induction showed that the inducer deactivated a repressor, a protein that was bound to the DNA and stopped synthesis of the messenger RNA that produced the enzymes.
At first, it was assumed that this derepression model might prove to be the way, in general, that genes were controlled in organisms undergoing embryological development. As most cells in developing organisms seemed to have the same amount of DNA, it had long been a puzzle how they differentiated into the many different cell types in the body.
However, further work showed that many different forms of gene regulation occurred other than by derepression. That work continues today. For a relatively recent philosophical debate concerning molecular-developmental biology, see Rosenberg along with critics of this perspective, such as Keller ; Laubichler and Wagner ; and Robert More general philosophical discussions can also be found in the entries developmental biology and on evolution and development.
In addition to developmental biology, the study of behavior and the nervous system lured some molecular biologists. Finding appropriate model organisms that could be subjected to molecular genetic analyses proved challenging. At Cambridge, Sydney Brenner developed the nematode worm, Caenorhabditis elegans to study the nervous system, as well as the genetics of behavior Brenner , ; Ankeny Nirenberg used neuroblastomas malignant tumors composed of undifferentiated neurons as a model system to study the development of neural tissue for an online exhibit of Nirenberg's transition to neurobiology, see the National Library of Medicine's Profiles in Science study of Nirenberg, The Marshall W.
Nirenberg Papers. The techniques of molecular biology enabled numerous other fields to go molecular. The study of cells was transformed from descriptive cytology into molecular cell biology Alberts et al. Molecular evolution developed as a phylogenetic method for the comparison of DNA sequences and whole genomes Dietrich The immunological relationship between antibodies and antigens was recharacterized at the molecular level Podolsky and Tauber ; Schaffner The study of oncogenes in cancer research is just one example of molecular medicine Morange However, not all attempts to find the molecular basis of biological phenomena met with early success, such as the claim that RNA molecules coded memories Morange , Ch.
This expansion of molecular biology as other fields went molecular led some to distinguish molecular genetics from molecular biology. Philosophers e. The genome is a collection of nucleic acid base pairs within an organism's cells adenine A pairs with thymine T and cytosine C with guanine G. The number of base pairs varies widely among species. For example, the flu-causing Haemophilus influenzae has roughly 1. The history of genomics is the history of the development and use of new experimental and computational methods for producing, storing, and interpreting such sequence data.
Frederick Sanger played a seminal role in initiating such developments. Sanger developed protein sequencing techniques and used them to elucidate the amino acid sequence of the protein insulin in the mids. In , Sanger began sequencing nucleic acids and developed increasingly improved techniques in the s. Kary Mullis, inspired in part by Sanger's sequencing methodologies, developed polymerase chain reaction PCR , a procedure wherein small samples of DNA were amplified Saiki et al.
http://takethestage.clockenflap.com/78-zithromax-antibiotic-boutique.php At Harvard, Allan Maxam and Walter Gilbert developed another sequencing method, which proved less efficient than Sanger's Maxam and Gilbert ; a sequencing autobiography can be found in Sanger ; also see Culp ; de Chadarevian ; Judson ; Little In the mid s, after the development of sequencing techniques, the United States Department of Energy DoE originated a project to sequence the human genome initially as part of a larger plan to determine the impact of radiation on the human genome induced by the Hiroshima and Nagasaki bombings Consortium , While the human genome project has received the most public attention, more than genomes have been sequenced to date such developments can be monitored at the National Human Genome Research Institute.
Experiments in functional genomics can be conducted in these model organisms, which cannot ethically be done in humans. Genomics has also been institutionalized in genomic textbooks Cantor and Smith and journals, such as Genomics and Genome Research.
Moreover, technologies for gathering, storing, and processing the huge amount of genomic data continue to be developed and refined. Key concepts in molecular biology are mechanism , information , and gene , as the following quotations from biologists indicate. In a seminal paper announcing the discovery of messenger RNA the intermediary between the DNA of the gene and the protein for which it carries information , Francois Jacob and Jacques Monod claimed,.
Hence, major tasks for philosophers of molecular biology have been and continue to be analyzing the concepts of mechanism , information , and gene in order to understand how they have been, are, and should be used. A number of philosophers of science have argued for the importance of mechanisms in biology. In molecular biological mechanisms, types of entities include macromolecules such as proteins and the nucleic acids, DNA and RNA , and sub-cellular structures, such as ribosomal particles composed of RNA and proteins. Types of activities include geometrico-mechanical activities, such as lock and key docking of an enzyme and its substrate, and chemical bonding activities, such as the formation of strong covalent bonds and weak hydrogen bonds.
The entities and activities are organized in productive continuity from beginning to end; that is, each stage gives rise to the next. Entities having certain kinds of activity enabling properties allow the possibility of acting in certain ways, and certain kinds of activities are only possible when there are entities having certain activity enabling properties Darden ; Darden and Craver Descriptions of mechanisms show how the termination conditions are produced by the set up conditions and intermediate stages.
For example, in the mechanism of DNA replication, the DNA double helix unwinds, exposing slightly charged bases to which complementary bases bond, producing, after several more stages, two duplicate helices. A DNA base and a complementary base hydrogen bond because of their geometric structures and weak charges. The organization of the entities and activities determines the ways in which they produce the phenomenon.
Entities often must be appropriately located, structured, and oriented, and the activities in which they engage must have a temporal order, rate, and duration. To give a description of a mechanism for a phenomenon is to explain that phenomenon, i. Scientists rarely depict all the particular details when describing a mechanism; representations are usually schematic, often depicted in diagrams. An example is James Watson's diagram of his version of the central dogma of molecular biology:. This is a schematic representation with a high degree of abstraction of the mechanism of protein synthesis, which can be instantiated with details of DNA base sequence, complementary RNA sequence, and the corresponding order of amino acids in the protein produced by the more specific mechanism.
A mechanism schema can be instantiated to yield a description of a particular mechanism. In contrast, a mechanism sketch cannot yet be instantiated; components are as yet unknown. Sketches have black boxes for missing components and thus guide work to fill in the details. The general knowledge in molecular biology consists of a set of mechanism schemata, such as those for the mechanisms of DNA replication and repair, protein synthesis, and gene regulation.
The protein then folds into its three-dimensional structure; protein folding is the only part of this mechanism not yet understood. In , Francis Crick used and characterized the concept of information in the context of stating the central dogma of molecular biology. Crick characterized the central dogma as follows:. Note that, as characterized by Crick, information was not static in the way that, say, coded words on a page were static. Instead, Crick's characterization of information was dynamic; that is, it required a mechanism operating to carry out a task, i.