Advances in molecular biology have generally been taken to support the claim that biology is reducible to chemistry. I argue against that claim by looking in detail at a number of central results from molecular biology and showing that none of them supports reduction because (1) their basic predicates have multiple realizations, (2) their chemical realization is context-sensitive and (3) their explanations often presuppose biological facts rather than eliminate them. I then consider the heuristic and (...) confirmational implications of irreducibility and argue that purely biochemical approaches are likely to be unsound and to be unable to confirm an important range of statements. I conclude by sketching criteria for scientific unity that do not entail reducibility and yet leave an important place for identifying underlying mechanisms. Molecular biology, properly understood, provides an excellent paradigm of non-reductive unity between different explanatory levels. (shrink)

The first part of this paper has shown that the development of regulatory genetics and the lactose operon model stemmed from laboratory cultures rooted in local traditions. A "physiological" culture may be recognized in the Pasteurian context. The institutional continuity provided the basis for a tenuous link between Pasteur, Lwoff, and Monod. My claim is that the "national" value of regulatory and physiological genetics is an artifact produced in the course of the legitimization process accompanying the institutionalisation of the discipline. (...) In the 1960s, the lactose operon model was turned into a "flag-object," a symbol of the new culture. The work done by the Pasteurian group became therefore the most important, if not the only, exemplar of molecular biology in France.The second part o f the paper described the origins of general patterns that dominated the building of molecular biology in France. The study of the relationships between molecular biologists and biochemists or immunologists revealed the existence of alternatives to the development of operon research, or to the convergence with molecular biology. Both examples uncover specific paths leading to achievements that might be viewed as international trends: the expansion of RNA and translation studies, and the development of cellular immunology. They illustrate two possible patterns of linking local settings and disciplinary traditions: an oligopolistic situation where a few groups or one institution dominate an entire field, and the emergence of "collective" trends through collaboration networks or schools. (shrink)

The intellectual origins of molecular biology are usually traced back to the 1930s. By contrast, molecular biology acquired a social reality only around 1960. To understand how it came to designate a community of researchers and a professional identity, I examine the creation of the first institutes of molecular biology, which took place around 1960, in four European countries: Germany, the United Kingdom, France, and Switzerland. This paper shows how the creation of these institutes (...) was linked to the results of post-war economic reconstruction. Then, it compares how the promoters of these different institutional projects delimited the goals of their discipline, reflected on its history, and suggested how research should be organised. I show how they carefully positioned their new discipline within the emerging national science policy discourse of the 1950s, and aligned it with the current vision of scientific modernity. In particular, I discuss how they articulated the meaning of molecular biology with respect to five common themes: the role of physics in the atomic age, the relations between fundamental research and medical applications, the ‘Americanisation’ of scientific research, the value of science in the reconstruction of national identities, and the drive towards interdisciplinary research. This paper thus demonstrates that beyond the local and national accounts there is a European history of molecular biology. (shrink)

This article looks at Deleuze and Guattari's understanding of molecular biology, focusing particularly on their reading of two highly influential works by the eminent French molecular biologists François Jacob and Jacques Monod, La logique du vivant and Le hasard et la nécessité. In these two works, Jacob and Monod present the significance of molecular biology in broadly reductionist terms. What is more, the lac operon model of gene regulation that they propose serves to reinforce the (...) so-called Central Dogma of molecular biology, according to which information passes from DNA to RNA to proteins, with no reverse route. However, Deleuze and Guattari discover intensive potentials within the descriptions of molecular biology offered by both writers. It is argued that Jacob's work in particular, as it has developed in the years since the publication of La logique du vivant in 1970, has itself developed these intensive potentials. (shrink)

Molecular biology is a relatively new and very successful branch of science but currently it faces challenges posed by very complex issues that cannot be addressed by a traditional reductionist approach. However, despite its origins in the providential shift of some theoretical physicists to biology, currently molecular biology is immersed in a blind trend in which high-throughput technology, able to generate trillions of data, is becoming the leading edge of a discipline that has traded rational (...) and critical thinking for computer power, data crunching and statistics in hope of finding, once more, its way. However, the complex questions facing MB may only be solved by a paradigm shift in the causal way of thinking, so that complex, emergent, non-linear phenomena may be effectively understood in top-down and not in bottom-up terms. (shrink)

In the last few years, biologists and computer scientists have claimed that the introduction of data science techniques in molecular biology has changed the characteristics and the aims of typical outputs (i.e. models) of such a discipline. In this paper we will critically examine this claim. First, we identify the received view on models and their aims in molecular biology. Models in molecular biology are mechanistic and explanatory. Next, we identify the scope and aims (...) of data science (machine learning in particular). These lie mainly in the creation of predictive models which performances increase as data set increases. Next, we will identify a tradeoff between predictive and explanatory performances by comparing the features of mechanistic and predictive models. Finally, we show how this a priori analysis of machine learning and mechanistic research applies to actual biological practice. This will be done by analyzing the publications of a consortium—The Cancer Genome Atlas—which stands at the forefront in integrating data science and molecular biology. The result will be that biologists have to deal with the tradeoff between explaining and predicting that we have identified, and hence the explanatory force of the ‘new’ biology is substantially diminished if compared to the ‘old’ biology. However, this aspect also emphasizes the existence of other research goals which make predictive force independent from explanation. (shrink)

Current research into the molecular biology of blood‐clotting factors suggests that the basis of inherited bleeding disorders may soon be understood. In addition, the expression of cloned genes for the factors in mammalian cell lines provides the hope of pure factors being available for replacement therapy, uncontaminated with the causative agents for Hepatitis and Acquired Immune Deficiency Syndrome (AIDS), identified in the blood products at present available. The recent findings on the molecular biology of several of (...) the key blood clotting genes are described here. (shrink)

I offer a defense, albeit a qualified one, of machine analogies in biology, focusing on molecular contexts. The defense is rooted in my prior work (Levy in Philosopher’s Imprint 14(6), 2014), which construes the machine machine-likeness of a system as a matter of the extent to which it exhibits an internal division of labor. A concrete aim is to shore up the notion of molecular biological machines, paying special attention to processive molecular motors, such as Kinesin. (...) But I will also try to show how the division of labor account gives us guidance more broadly, both about where and why machine analogies can be expected to prove helpful and about their limitations. (shrink)

In the last few years, biologists and computer scientists have claimed that the introduction of data science techniques in molecular biology has changed the characteristics and the aims of typical outputs (i.e. models) of such a discipline. In this paper we will critically examine this claim. First, we identify the received view on models and their aims in molecular biology. Models in molecular biology are mechanistic and explanatory. Next, we identify the scope and aims (...) of data science (machine learning in particular). These lie mainly in the creation of predictive models which performances increase as data set increases. Next, we will identify a tradeoff between predictive and explanatory performances by comparing the features of mechanistic and predictive models. Finally, we show how this a priori analysis of machine learning and mechanistic research applies to actual biological practice. This will be done by analyzing the publications of a consortium—The Cancer Genome Atlas—which stands at the forefront in integrating data science and molecular biology. The result will be that biologists have to deal with the tradeoff between explaining and predicting that we have identified, and hence the explanatory force of the ‘new’ biology is substantially diminished if compared to the ‘old’ biology. However, this aspect also emphasizes the existence of other research goals which make predictive force independent from explanation. (shrink)

In recent years the number of scholarly publications devoted to Kant's theory of biology has rapidly growing, with particular attention being given to Kant's thoughts about the concepts of teleology, function, organism, and their respective roles in scientific practice. Moving from these recent studies, and distancing itself from their mostly evolutionary background, the main aim of the present paper is to suggest an original "cognitive turn" in the interpretation of Kant's theory of biology. More specifically, the Authors will (...) trace a connection between some Kantian theses about the “peculiar” or special nature of the human mind, advanced in the Critique of the Power of Judgement, and some specific epistemological issues pertaining to the research practice of contemporary molecular biology. (shrink)

Fanconi anaemia (FA) comprises a group of autosomal recessive disorders resulting from mutations in one of eight genes (FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF and FANCG). Although caused by relatively simple mutations, the disease shows a complex phenotype, with a variety of features including developmental abnormalities and ultimately severe anaemia and/or leukemia leading to death in the mid teens. Since 1992 all but two of the genes have been identified, and molecular analysis of their products has revealed a (...) complex mode of action. Many of the proteins form a nuclear multisubunit complex that appears to be involved in the repair of double‐strand DNA breaks. Additionally, at least one of the proteins, FANCC, influences apoptotic pathways in response to oxidative damage. Further analysis of the FANC proteins will provide vital information on normal cell responses to damage and allow therapeutic strategies to be developed that will hopefully supplant bone marrow transplantation. BioEssays 24:439–448, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Some real life processes, including molecular ones, are context-sensitive, in the sense that their outcome depends on side conditions that are most of the times difficult, or impossible, to express fully in advance. In this paper, we survey and discuss a logical account of context-sensitiveness in molecular processes, based on a kind of non-classical logic. This account also allows us to revisit the relationship between logic and philosophy of science (and philosophy of biology, in particular).

In this paper, I defend the agent/patient distinction against critics who argue that causal interactions are symmetrical. Specifically, I argue that there is a widespread type of causal interaction between distinct entities, resulting in a type of ontological asymmetry that provides principled grounds for distinguishing agents from patients. The type of interaction where the asymmetry is found is when one of the entities undergoes a change in kind, structure, powers, or intrinsic properties as a result of the interaction while the (...) other does not. Interactions of this type are widespread in molecular biology and chemistry. I focus specifically on (i) the actions of enzymes on substrates and (ii) water molecules breaking the bonds of polarized molecules. Finally, I respond to objections by laying out and to a limited extent defending three commitments of my account: emergent entities and powers, realism about chemical kinds or structures, and the assumption of the agent/patient distinction in functional attributions in biology. (shrink)

Desmosomes are junctions involved in intercellular adhesion of epithelial cells and hemidesmosomes are junctions involved in adhesion of epithelia to basement membranes. Both are characterised at the ultrastructural level by dense cytoplasmic plaques which are linked to the intermediate filament cytoskeleton of the cells. The plaques strongly resemble each other suggesting a relationship between the two kinds of junctions, as implied by their names. Recent characterisation of the molecular components of the junctions shows they are, in fact, quite unrelated (...) implying that structural similarity is fortuitous. The molecular biology raises many fascinating problems relating to their structure and function. (shrink)

Accession Number: ATLA0001712123; Hosting Book Page Citation: p 172-186.; Language(s): English; General Note: Bibliography: p 185-186.; Issued by ATLA: 20130825; Publication Type: Essay.

One of the most dynamic areas of plant molecular biology is the investigation of the actions of three classes of herbicides: s‐triazines (atrazine, simazine), glyphosate, and sulfonylureas (chlorsulfuron, sulfometuron methyl) (Figure 1). The results of this work are expected to provide the first significant applications of plant biotechnology: directly, in the genetic engineering of crop plants resistant to specific herbicides and, indirectly, in providing a molecular basis for the rational design of new herbicides for specific biological targets.s‐Triazines (...) affect photosynthesis by inhibiting the binding of quinones to the chloroplast membrane QB protein. An s‐triazine resistant QB protein isolated from weeds in fields consistently treated with the herbicide has a serine in place of a glycine in this highly conserved protein. Glyphosate inhibits 5‐enolpyruvyl‐shikimate‐3‐phosphate synthase (EPSP synthase), an enzyme in the aromatic amino acid biosynthetic pathway. Mutagenized bacteria produce a resistant EPSP synthase with a substitution of serine for proline. Sulfonylureas inhibit the acetolactate synthase (ALS) of bacteria, yeast, and higher plants; this enzyme catalyzes the first step in the synthesis of branched chain amino acids. Resistant ALS has been found in bacteria, yeast and tobacco with a proline substituted by serine in yeast ALS. These findings provide a strong basis for developing projected plant biotechnology applications. (shrink)

Taste cells respond to a wide variety of chemical stimuli: certain ions are perceived as salty (Na+) or sour (H+); other small molecules are perceived as sweet (sugars) and bitter (alkaloids). Taste has evolutionary value allowing animals to respond positively (to sweet carhohydrates and salty NaCl) or aversively (to bitter poisons and corrosive acids). Recently, some of the proteins involved in taste transduction have been cloned. Several different G proteins have been identified and cloned from taste tissue: gustducin is a (...) taste cell specific G protein closely related to the transducins. Work is under way to clone additional components of the taste transduction pathways. The combination of electrophysiology, biochemistry and molecular biology is being used to characterize taste receptor cells and their sensory transduction mechanisms. (shrink)

The intellectual origins of molecular biology are usually traced back to the 1930s. By contrast, molecular biology acquired a social reality only around 1960. To understand how it came to designate a community of researchers and a professional identity, I examine the creation of the first institutes of molecular biology, which took place around 1960, in four European countries: Germany, the United Kingdom, France, and Switzerland. This paper shows how the creation of these institutes (...) was linked to the results of post-war economic reconstruction. Then, it compares how the promoters of these different institutional projects delimited the goals of their discipline, reflected on its history, and suggested how research should be organised. I show how they carefully positioned their new discipline within the emerging national science policy discourse of the 1950s, and aligned it with the current vision of scientific modernity. In particular, I discuss how they articulated the meaning of molecular biology with respect to five common themes: the role of physics in the atomic age, the relations between fundamental research and medical applications, the 'Americanisation' of scientific research, the value of science in the reconstruction of national identities, and the drive towards interdisciplinary research. This paper thus demonstrates that beyond the local and national accounts there is a European history of molecular biology. (shrink)

Nerve cells - neurons - are arguably the most complex of all cells. From the action of these cells comes movement, thought and consciousness. It is a challenging task to understand what molecules direct the various diverse aspects of their function. This has produced an ever-increasing amount of molecular information about neurons, and only in Molecular Biology of the Neuron can a large part of this information be found in one source. In this book, a non-specialist can (...) learn about the molecules that control information flow in the brain or the progress of brain disease in an approachable format, while the expert has access to a wealth of detailed information from a wide range of topics impacting on his or her field of endeavour. The text is designed to achieve a balance of accessibility and broad coverage with up-to-date molecular detail. In the six years since the first edition of Molecular Biology of the Neuron there has been an explosion in the molecular information about neurons that has been discovered, and this information is incorporated into this second edition. Entirely new chapters have been introduced where recent advances have made a new aspect of neuronal function more comprehensible at the molecular level. Written by leading researchers in the field, the book provides an essential overview of the molecular structure and function of neurons, and will be an invaluable tool to students and researchers alike. (shrink)

Neurons are arguably the most complex of all cells. From the action of these cells comes movement, thought and consciousness. It is a challenging task to understand what molecules direct the various diverse aspects of their function. This has produced an ever-increasing amount of molecular information about neurons, and only in Molecular Biology of the Neuron can a large part of this information be found in one source. In this book, a non-specialist can learn about the molecules (...) that control information flow in the brain or the progress of brain disease in an approachable format, while the expert has access to a wealth of detailed information from a wide range of topics impacting on his or her field of endeavour. The text is designed to achieve a balance of accessibility and broad coverage with up-to-date molecular detail. In the six years since the first edition of Molecular Biology of the Neuron there has been an explosion in the molecular information about neurons that has been discovered, and this information is incorporated into this second edition. Entirely new chapters have been introduced where recent advances have made a new aspect of neuronal function more comprehensible at the molecular level. Written by leading researchers in the field, the book provides an essential overview of the molecular structure and function of neurons, and will be an invaluable tool to students and researchers alike. (shrink)

Complementary DNA clones corresponding to most of the proteins of a major amplification and effector of immune host defenses, the complement system, have been isolated and characterized. Availability of these molecular probes has substantially increased our information about and understanding of the structure of the complement proteins and regulation of complement gene expression. Information about the proteins has led to the generation of potential pharmacological agents for the selective control of inflammation. Understanding of the regulatory mechanism has provided insights (...) into the mechanisms accounting for the response to several cytokines including interferon‐gamma, interleukin‐1 and tumor necrosis factor. Finally, complement molecular genetics has been stimulated so that the basis for several complement deficiency disorders has been elucidated. (shrink)

The recent dramatic development of molecular neurobiology has focused almost entirely on biological events in individual brain cells, and it seems that many of the goals of such work will soon be attained. Yet, when we attain those goals, we will still have to ask how this information will enable us to understand the properties of brain cell collectivities and their presumptive roles in higher brain functions. Even general ideas about those functions are not yet well defined. Therefore, it (...) seems worthwhile to start studying correlations of the molecular events to these higher functions to help delineate the molecular aspects that need study.It is readily appreciated that we cannot tell what other animal species see, hear, taste, smell and feel when touching something, though we can foresee the time when we will be able to detail the biochemical and biophysical consequences of all inputs to those senses. Thus, however deep our understanding of the biology of those species, we are unable to establish relations between their biological responses to inputs and their presumptive mental perceptions. Even though humans can use language to talk about those perceptions, we cannot even verify whether someone else's perceptions are the same as our own, as with the old question of whether two individuals see the same thing when viewing something blue. Questions about still higher mental functions of human brains are even less accessible to analysis and can be approached at best, by using correlations. In this article are a number of such questions and their current correlation‐level answers. (shrink)

Many lymphokine genes have now been cloned from activated T cells and their products have been expressed in mammalian cells. Use of these recombinant lymphokines has provided the opportunity to evaluate both the spectrum of their biological activities and the mechanisms of their action in promoting proliferation and differentiation of hemopoietic and lymphoid cells. Characterization of the structure of lymphokine genes will provide information about their regulated expression in T‐cell activation.

The successes of molecular developmental biology over the last ten years have been particularly impressive in those directions favored by its major paradigms. New technologies have both guided and been guided by the progress of the field. I review briefly some of the major insights into embryonic development that have derived from research in four specific areas: early embryogenesis of various forms; “pattern formation”; evolutionary conservation of regulatory elements; and spatial mechanisms of gene regulation. There remain many major (...) problem areas, some of which may require new orientations to solve. (shrink)

Double‐minute chromosomes play a critical role in tumor cell genetics where they are frequently associated with the overexpression of oncogene products. They have been observed for many years in light microscopic examinations of metaphase chromosomes from tumor cells, but their origin remains unknown and is the subject of considerable speculation. However, molecular details of their structure and organization can now be described in conjunction with the microscopic examinations, to allow an evaluation of the various models that have been developed (...) to explain the genesis of double‐minutes. The evidence now favors simple models that invoke chromosome breakage and circularization of very large acentric chromosome fragments, permitting unequal segregation of the genes on the fragment during cell division. If there is selection for overexpression of one of the genes on the fragment, daughter cells with more fragments will grow faster than daughter cells with fewer fragments, and over time the population of cells will come to contain many double‐minutes per cell. (shrink)

Plasminogen activators are enzymes with multiple roles. They play vital parts in maintaining the functional integrity of the vascular system and they are also involved in processes of tissue reorganization. In this review, the molecular properties of these enzymes that make them ideal targets for genetic and biochemical engineering to satisfy a potential therapeutic role are described.

If the work carried out to gain a detailed understanding of the process of photosynthesis, and probably other types of bioenergetic conversions as well, fulfills the criteria of a molecular biology, and if the groups funding this research and those who worked in the laboratory regarded it as such, why has it been necessary for me to argue here that bioenergetics should always have been counted as part of - indeed, may have been in the forefront in establishing (...) — the molecular biology tradition? Why have the investigators themselves not insisted on correcting the historical record that has emerged thus far? I would like to offer two reasons: one institutional, the other scientific. (shrink)

The question that probably emerges when the title of this work is read is if it is possible to establish any relation between philosophy and a scientific discipline such as molecular biology. The common opinion, shared even by many renowned biologists and philosophers, is that each of these disciplines has got its own without taking into account the results of the other. However, the relation between science and philosophy is nowadays one of the most challenging topics, where philosophers (...) and biologists meet and each other to better understand what life is and how it works. Philosophical concepts such as information, causality, semiotics and function can be seen as instruments for a philosophical approach to biological topics. The aim of this work is to see if, studying a biological example in depth, there are elements that fit with the informational paradigm that is proposed as a philosophical framework. Biology has been considered as a discipline in which objects can be reduced to the laws of physics and chemistry. A different approach can be seen in this work. The philosophy of Charles Sanders Peirce can help us to see biological systems as informational systems, where molecules are more than their chemical structure, indeed, the cell can deal with them from a semiotic point of view; that is, treating them as signs that stand for other molecules or processes, allowing the system to canalize all this information to its own benefit. (shrink)

Plants growing in temperate regions are able to survive freezing temperatures from −5° to −30°C, depending on the species, through a process known as cold acclimation. In the last decade much work has been done on the molecular mechanisms of low temperature (LT) signal transduction and cold acclimation. Mutant studies and microarray analyses have revealed C-Repeat binding factor (CBF) -dependent and -independent signaling pathways in plants. Experimental evidence suggests the existence of ‘potential LT sensors’ but as yet there is (...) no direct proof. A number of signal transducers such as various kinases/phosphatases have been demonstrated but the signal transduction pathways have not been elucidated. An understanding of the molecular basis of the signaling process, however, is of potential practical application. Designing new strategies to improve cold tolerance in crop varieties could increase the plant productivity and also expand the area under cultivation. BioEssays 27:1048–1059, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

In 1937, a group of researchers in Nazi Germany began investigating tobacco mosaic virus with the hope of using the virus as a model system for understanding gene behavior in higher organisms. They soon developed a creative and interdisciplinary work style and were able to continue their research in the postwar era, when they made significant contributions to the history of molecular biology. This group is significant for two major reasons. First, it provides an example of how researchers (...) were able to produce excellent scientific research in the midst of dictatorship and war. Coupled with the group's ongoing success in postwar Germany, the German TMV investigators provide a dramatic example of how scientific communities deal with adversity as well as rapid political and social change. Second, since the researchers focused heavily on TMV, their story allows us to analyze how an experimental system other than phage contributed to the emergence of molecular biology. (shrink)

Most of our current knowledge of olfactory associative learning in Drosophila comes from the behavioral and molecular analysis of mutants that fail to learn. The identities of the genes affected in these mutants implicate new signaling pathways as mediators of associative learning. The expression patterns of these genes provide insight into the neuroanatomical areas that underlie learning. In recent years, there have been great strides in understanding the molecular and neuroanatomical basis for olfaction in insects. It is now (...) clear that much of the association between the conditioned stimuli and the unconditioned stimuli in olfactory learning occurs within mushroom bodies — third order olfactory neurons within the central brain. In this review, we discuss the nature of the behavioral tasks, the molecules, and the neuronal circuits involved in olfactory learning in Drosophila. BioEssays 23:571–581, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

The heme‐containing cytochromes P‐450 are a ubiquitous family of monooxygenase isozymes responsible for the oxidative metabolism of a wide variety of endogenous as well as exogenous compounds. Many of the compounds metabolized by this enzyme system are effectively detoxified and converted to derivatives more easily eliminated from the organism. However, some compounds can be activated to reactive species capable of eliciting a cascade of toxic lesions, including cancer. Since its discovery nearly 30 years ago, the cytochrome P‐450 enzyme system has (...) received a great deal of attention, particularly in the areas of their mechanisms of metabolism, range of substrate specificity, the purification and characterization of the multiple isozymes and, more recently, the regulation of expression of specific forms. This review will discuss current notions concerning the expression of at least one cytochrome P‐450 isozyme and future directions that should lead to a more complete understanding of cytochrome P‐450 gene expression in general, particularly as it impacts upon biochemical pharmacology. (shrink)

Our understanding of the sphingolipidoses has improved as a result of the investigation of molecular mechanisms causing clinical heterogeneity. This knowledge, derived from both the protein and gene structures, should bring therapy for these inherited disorders closer to a realistic possibility.

The transmission of electrical impulses in nerve and muscle cells depends fundamentally on the operation of specific ion channels in their membranes. Recent technical advances in electrical recording from cell membranes have permitted the analysis of the properties of single ion channels and the measurement of gating currents. The results have revealed considerable complexities, in particular in the operation of voltage‐gated sodium channels, and in the relationships between the several open and closed states of the channels. An important new development (...) is the cloning and analysis of the structural genes for the acetylcholine receptor and sodium channel protein, which promises to yield fresh insights into the functioning of these proteins. (shrink)

Cell lines and cell samples from patients provide opportunities for studying the mechanisms of leukemic cellular differentiation and proliferation. Phorbol esters and 1,25 dihydroxy vitamin D3 can induce differentiation of myeloid leukemic cells to macrophages. Differentiation to granulocytes can be induced by several different compounds. Myeloid differentiation is associated closely with the alteration in expression of several oncogenes. These regulatory events may be associated with the extent of methylation, unfolding or association of chromatin to the nuclear matrix. Oncogene amplification, mutation, (...) or deletion can occur with malignant transformation. Future studies point to the development of specific pharmacological agents which can modify the neoplastic transformation. (shrink)