What is molecular biology

William Wimsatt argued for a shift in the reduction debate from talk of relations between theories to talk of decompositional explanation via mechanisms. And Lindley Darden and Nancy Maull focused attention on the bridges between fields formed by part-whole relations, structure-function relations, and cause-effect relations.

This shift in attention was a precursor to understanding the philosophy of science through the lens of mechanisms. Darden, building on the work of Machamer, Darden, and Craver , has more recently returned to the question of how Mendelian and molecular genetics are related and viewed it through this lens Darden Rather than understanding the relationship as one of reduction, she suggests they can be understood as relating via a focus on different working entities often at different size levels that operate at different times.

Thus, the relation was one of integration of sequentially operating chromosomal and molecular hereditary mechanisms rather than reduction. For an alternative but still integrative reading of the relationship between classical genetics and molecular biology that focuses on their shared functional units, see Baetu Reduction can also be about explanation and methodology. That is, reduction can be about using reductive methodologies to dig down to lower levels because the thought is that this exercise leads to more reductive explanations and more reductive explanations are better than explanations at higher levels.

Rosenberg 4. Hence, the task of this explanatory reduction is to explain all functional biological phenomena via molecular biology. This particular debate can be understood as an instance of a more general debate occurring in biology and philosophy of biology about whether investigations of lower-level molecular biology are better than investigations of high-level systems biology Baetu a; Bechtel and Abrahamsen ; De Backer, De Waele, and Van Speybroeck ; Huettemann and Love ; Marco ; Morange ; Pigliucci ; Powell and Dupre ; see also the entries on feminist philosophy of biology , philosophy of systems and synthetic biology , and multiple realizability.

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 , 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 s, philosophers of biology have questioned the existence of biological laws of nature.

Smart emphasized the earth-boundedness of the biological sciences in conflict with the universality of natural laws. Without traditional laws of nature from which to derive explanations, philosophers of biology have been forced to rethink the nature of scientific explanation in biology and, in particular, molecular biology. Two accounts of explanation emerged: the unificationist and the causal-mechanical.

Philip Kitcher , developed a unificationist account of explanation, and he and Sylvia Culp explicitly applied it to molecular biology Culp and Kitcher An explanation of a particular pattern of distribution of progeny phenotypes in a genetic cross resulted from instantiating the appropriate deductive argument schema: the variables were filled with the details from the particular case and the conclusion derived from the premises.

Working in the causal-mechanical tradition pioneered by Wesley Salmon , , other philosophers turned to understanding mechanism elucidation as the avenue to scientific explanation in biology Bechtel and Abrahamsen ; Bechtel and Richardson ; Craver ; Darden a; Glennan ; Machamer, Darden, and Craver ; Sarkar ; Schaffner ; Woodward , There are differences between the various accounts of a mechanism, but they hold in common the basic idea that a scientist provides a successful explanation of a phenomenon by identifying and manipulating variables in the mechanisms thereby determining how those variables are situated in and make a difference in the mechanism; the ultimate explanation amounts to the elucidation of how those mechanism components act and interact to produce the phenomenon under investigation.

As mentioned above see Section 2. There are several virtues of the causal-mechanical approach to understanding scientific explanation in molecular biology. Molecular biologists rarely describe their practice and achievements as the development of new theories; rather, they describe their practice and achievements as the elucidation of molecular mechanisms Baetu ; Craver ; Machamer, Darden, Craver Another virtue of the causal-mechanical approach is that it captures biological explanations of both regularity and variation.

Unlike in physics, where a scientist assumes that an electron is an electron is an electron, a biologist is often interested in precisely what makes one individual different from another, one population different from another, or one species different from another.

Philosophers have extended the causal-mechanical account of explanation to cover biological explanations of variation, be it across evolutionary time Calcott or across individuals in a population Tabery , Difference mechanisms are regular causal mechanisms made up of difference-making variables, one or more of which are actual difference makers see Section 2.

There is regularity in difference mechanisms; interventions made on variables in the mechanisms that change the values of the variables lead to different outcomes in the phenomena under investigation. There is also variation in difference mechanisms; interventions need not be taken to find differences in outcomes because, with difference mechanisms, some variables are actual difference makers which already take different values in the natural world, resulting in natural variation in the outcomes.

But philosophers have also raised challenges to the causal-mechanical approach. While some argue that systems biology is best explained using mechanisms cf. Boogerd et al. Braillard ; Kuhlmann ; Silberstein and Chemero Processes are ontologically primary. Recent literature in molecular biology on molecular pathways cf. Boniolo and Campaner ; Brigandt ; Ioannides and Psillos ; Ross seems to be another instantiation of this shift from mechanistic to processual explanations.

As discussed earlier in the historical sections, molecular biologists have relied heavily on model organisms see the entry on models in science.

But making inferences from a single exemplary model to general biological patterns has been cause for worry. What grounds do biologists have for believing that what is true of a mere model is true of many different organisms? One answer, provided by Marcel Weber , is that the generality of biological knowledge obtained from studying exemplary models can be established on evolutionary grounds.

According to Weber, if a mechanism is found in a set of phylogenetically distant organisms, this provides evidence that it is also likely to be found in all organisms that share a common ancestor with the organisms being compared. Unlike the aim of exemplary models, the representative aim of a surrogate model is not necessarily to be broad. For example, biomedical researchers frequently expose surrogate models to harmful chemicals with the aim of modeling human disease.

However, if a chemical proves to be carcinogenic in rats, for example, there is no guarantee that it will also cause cancer in humans. Although this problem is not unique to surrogate models, it often arises when biomedical researchers use them to replicate human disease at the molecular level. Consequently, philosophers who write about the problem of extrapolation in the context of molecular biology often focus on such models see, for example, Ankeny ; Baetu ; Bechtel and Abrahamsen ; Bolker ; Burian b; Darden ; LaFollette and Shanks ; Love ; Piotrowska ; Schaffner ; Steel ; Weber ; Wimsatt Within the context of surrogate models, any successful solution to the problem of extrapolation must explain how inferences can be justified given causally relevant differences between models and their targets Lafollette and Shanks Cook and Campbell This method avoids the circle because it eliminates the need to know if two mechanisms are similar.

All that matters is that two outcomes are produced to a statistically significant degree, given the same intervention. For this reason, statistically significant outcomes in clinical trials are at the top of the evidence hierarchy in biomedical research Sackett et al. One problem with relying merely on statistics to solve the problem of extrapolation, however, is that it cannot show that an observed correlation between model and target is the result of intervention and not a confounder.

This approach avoids the circle because the suitability of a model can be established given only partial information about the target.

For example, Steel argues that only the stages downstream from the point where the mechanisms in the model and target are likely to differ need to be compared, since the point where differences are likely will serve as a bottleneck through which the eventual outcome must be produced. One worry, raised by Jeremy Howick et al.

For example, there may be an upstream difference that affects the outcome but does not pass through the downstream stages of the mechanism. This problem is taken up again below in Section 3.

The resulting big picture account of the experimental model is an aggregate of findings that do not describe a mechanism that actually exists in any cell or organism. Instead, as a number of authors have also pointed out Huber and Keuck ; Lemoine ; Nelson , the mechanism of interest is often stipulated first and then verified piecemeal in many different experimental organisms. These genetically engineered rodents are supposed to make extrapolation more reliable by simulating a variety of human diseases, e.

As Monika Piotrowska points out, however, this raises a new problem. The question is no longer how an inference from model to target can be justified given existing differences between the two, but rather, in what way should these mice be modified in order to justify extrapolation to humans? Piotrowska has proposed three conditions that should be met in the process of modification to ensure that extrapolation is justified. The first two requirements demand that we keep track of parts and their boundaries during transfer, which presupposes a mechanistic view of human disease, but the third requirement—that the constraints that might prevent the trait from being expressed be eliminated—highlights the limits of using a mechanistic approach when making inferences from humanized mice to humans.

As Piotrowska explains,. As our ability to manipulate biological models advances, philosophers will need to revisit the problem of extrapolation and seek out new solutions. The history of molecular biology is in part the history of experimental techniques designed to probe the macromolecular mechanisms found in living things. Philosophers in turn have looked to molecular biology as a case study for understanding how experimentation works in science—how it contributes to scientific discovery, distinguishes correlation from causal and constitutive relevance, and decides between competing hypotheses Barwich and Baschir In all three cases, the concept of a mechanism is central to understanding the function of experimentation in molecular biology also see the entry on experimentation in biology.

Take discovery. Darden has countered with a focus on the strategies that scientists employ to construct, evaluate, and revise mechanical explanations of phenomena; on her view, discovery is a piecemeal, incremental, and iterative process of mechanism elucidation.

In the s and s, for example, scientists from both molecular biology and biochemistry employed their own experimental strategies to elucidate the mechanisms of protein synthesis that linked DNA to the production of proteins. Molecular biologists moved forward from DNA using experimental techniques such as x-ray crystallography and model building to understand how the structure of DNA dictated what molecules it could interact with; biochemists simultaneously moved backward from the protein products using in vitro experimental systems to understand the chemical reactions and chemical bonding necessary to build a protein.

Tudor Baetu builds on the contemporary philosophy of mechanism literature as well to provide an account of how different experiments in molecular biology move from finding correlations, to establishing causal relevance, to establishing constitutive relevance Baetu b.

Much recent philosophical attention has been given to the transition from correlation to causal relevance. On a manipulationist account of causal relevance, some factor X is determined to be causally relevant to some outcome Y when interventions on X can be shown to produce the change in Y.

But these one-variable experiments, Baetu cautions, do not necessarily provide information about the causal mechanism that links X to Y. Is X causally relevant to Y by way of mechanism A , mechanism B , or some other unknown mechanism? In a two-variable experiment, two interventions are simultaneously made on the initial factor and some component postulated in the mechanical link, thereby establishing both causal and constitutive relevance.

An experiment is taken to be a crucial experiment if it is devised so as to result in the confirmation of one hypothesis by way of refuting other competing hypotheses. But the very idea of a crucial experiment, Pierre Duhem pointed out, assumes that the set of known competing hypotheses contains all possible explanations of a given phenomenon such that the refutation of all but one of the hypotheses deductively ensures the confirmation of the hypothesis left standing.

Duhem actually raised two problems for crucial experiments—the problem mentioned above, as well as the problem of auxiliary assumptions, which any hypothesis brings with it; for reasons of space, we will only discuss the former here.

Marcel Weber has utilized a famous experiment from molecular biology to offer a different vision of how crucial experiments work. After Watson and Crick discovered the double helical structure of DNA, molecular biologists turned their attention to how that macromolecule could be replicated see Section 1. The focus was in part on the fact that the DNA was twisted together in a helix, and so the challenge was figuring out what process could unwind and replicate that complexly wound molecule.

Three competing hypotheses emerged, each with their own prediction about the extent to which newly replicated DNA double helices contained old DNA strands versus newly synthesized material: semi-conservative replication, conservative replication, and dispersive replication. They grew E. By then taking regular samples of the replicating E. Moreover, any hypothesis of DNA replication had to satisfy mechanistic constraints imposed by what was already known about the physiological mechanism—that DNA was a double helix, and that the sequence of nucleotides in the DNA needed to be preserved in subsequent generations.

For a critique, see Baetu An overview of the history of molecular biology revealed the original convergence of geneticists, physicists, and structural chemists on a common problem: the nature of inheritance. Conceptual and methodological frameworks from each of these disciplinary strands united in the ultimate determination of the double helical structure of DNA conceived of as an informational molecule along with the mechanisms of gene replication, mutation, and expression.

With this recent history in mind, philosophers of molecular biology have examined the key concepts of the field: mechanism, information, and gene. Moreover, molecular biology has provided cases for addressing more general issues in the philosophy of science, such as reduction, explanation, extrapolation, and experimentation.

History of Molecular Biology 1. Concepts in Molecular Biology 2. Molecular Biology and General Philosophy of Science 3. History of Molecular Biology Despite its prominence in the contemporary life sciences, molecular biology is a relatively young discipline, originating in the s and s, and becoming institutionalized in the s and s.

He concluded a essay: The geneticist himself is helpless to analyse these properties further. 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….

According to Lily Kay, Up until around molecular biologists…described genetic mechanisms without ever using the term information. Crick —, emphasis in original It is important not to confuse the genetic code and genetic information. Brenner, letter to Perutz, Along with Brenner, in the late s and early s, many of the leading molecular biologists from the classical period redirected their research agendas, utilizing the newly developed molecular techniques to investigate unsolved problems in other fields.

Concepts in Molecular Biology The concepts of mechanism , information , and gene all figured quite prominently in the history of molecular biology. Phyllis McKay Illari and Jon Williamson have more recently offered a characterization that draws on the essential features of all the earlier contributions: A mechanism for a phenomenon consists of entities and activities organized in such a way that they are responsible for the phenomenon.

Stephen Downes helpfully distinguishes three positions on the relation between information and the natural world: Information is present in DNA and other nucleotide sequences. Other cellular mechanisms contain no information. DNA and other nucleotide sequences do not contain information, nor do any other cellular mechanisms. 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, such as reduction, explanation, extrapolation, and experimentation.

Rosenberg 4 Hence, the task of this explanatory reduction is to explain all functional biological phenomena via molecular biology. As Piotrowska explains, without the right context, even the complete lack of differences between two mechanisms cannot justify the inference that what is true of one mechanism will be true of another Piotrowska Conclusion An overview of the history of molecular biology revealed the original convergence of geneticists, physicists, and structural chemists on a common problem: the nature of inheritance.

Janis eds. Advanced search. Skip to main content Thank you for visiting nature. Meier Nature Chemical Biology 17 , Show more. Latest Research and Reviews Protocols 12 November Genome-wide quantification of transcription factor binding at single-DNA-molecule resolution using methyl-transferase footprinting This protocol describes experimental and computational procedures for genome-wide mapping of transcription factor binding at single-molecule resolution using methyl-transferase footprinting.

Nature Protocols , Nature Communications 12 , Research 12 November Open Access WRN helicase safeguards deprotected replication forks in BRCA2 -mutated cancer cells The tumor suppressor BRCA2 protects stalled DNA replication forks from unrestrained degradation; however the mechanism whereby unprotected stalled forks are preserved and restarted has remained elusive.

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Do you want to know more about intelligent packaging? In this article we tell you about it. Designing products that deliver the value the customer is looking for is essential in any research and development project. Design research allows the design team to focus on the right research methods for the product in question and ensure success.

In this article we explain what design research is, the different types that exist and […]. Enter your keyword. Molecular biology: definition and applications. Home News Molecular biology: definition and applications. Molecular biology: definition and applications Infinitia Research. What is molecular biology? Cusick, Kathleen Genes and pathways involved in copper tolerance, biofilm formation and nanoparticle synthesis in the marine bacterium Alteromonas; megaplasmids in bacterial niche adaptation.

Eisenmann, David We study the role of the Wnt signaling pathway in controlling cell fate decisions during C. We also study regulation and function of the Hox gene lin in C.

Erill, Ivan Cross-linking between experimental assays and in-silico data for regulatory elements. Farabaugh, Philip Molecular genetics of translational accuracy in the yeast Saccharomyces cerevisiae and bacterium Escherichia coli. Gardner, Jeffrey Studying bacterial physiology using systems and synthetic biology; Determining how microbes sense the environment and obtain energy examining the mechanisms of plant cell wall degradation in bacteria.

Green, Erin Understanding epigenetics and the regulation of the genome through investigation of histone post-translational modifications; dissecting the role of protein post-translational modifications in nuclear signaling pathways.