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Didactics of Molecular Ecology
Theory Biosci. (2001) 120: 139±148 Ó Urban & Fischer Verlag http://www.urbanfischer.de/journals/theorybiosc
Didactics of Molecular Ecology Thomas Efferth Virtual Campus, Rhineland-Palatinate Mainz, Germany Address for correspondence: Privatdozent Dr. Thomas Efferth, Virtual Campus, Rhineland-Palatinate P.O. Box 43 80, 55033 Mainz, Germany, Phone: + 49-61 31-5 70 76 11 e-mail: [email protected] Received: November 16, 1999; accepted: March 2, 2000 Key words: Paradigm, Health, Environment
Summary: Molecular biology conferred enormous progresses in biosciences during the past few years. This paradigm permutation in biological research certainly challenges biological education. Nevertheless, this is no reason to fundamentally reorganise biological education at the universities. A most entire view of the matter should remain a central request which meets the capacity and imagination of students. Selected biological phenomena taken from the traditional treasury remain suitable in the future too to mediate basic biological ways ot thinking. Forthcoming syllabuses, however, will necessitate the expansion of this concept. The scope of the present contribution is to show, how the integration of molecular biology in the teaching of classical disciplines of biology may be reached. Choosing ecology and environmental biology as examples, molecular biology will not only strengthen explanation models of cause-effect relationships in these disciplines, but also will facilitate the interconnections to interdisciplinary fields such as health education, social, and political education. This may result in an entire structural concept of classical and molecular biology.
The challenge of molecular biology to biological teaching Didactics of molecular biology ± what for? Recent developments in molecular biology contribute not only to research activities, but will also influence teaching of biology at the universities in the future. The present article aims to draw the attention of biology teachers to some of the demands of biological education in the 21st century. Molecular biology may not only be understood as a simple necessity but also as a chance. Important proceedings frequently serve as headlines in the daily press and in TV causing sometimes emotional pros and cons in the public. Such ªbase-line levelsº of interest towards biological matters 1431-7613/01/120/02±139/$ 15.00/0
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being present among students afford lots of opportunities from lecturers to pick up molecular topics from the everyday reality of people and to hook up students to more sophisticated chapters of biology. ªGene soja beansº, ªsheep Dollyº or ªembryonal cloningº may be examples of useful catchwords in this context. Teaching success is not only measurable by examination of biological facts. It manifests as well in the long-termed creation of fundamental attitudes of mind-concerning biological questions in a socio-political context. The term ªsecret curriculumº describes such far-reaching consequences of pedagogic achievements. Biotechniques such as gene technology will not only contribute to a social and global alteration in the next few decades but may also influence the life of individual subjects (e. g. genetic diagnostics, somatic gene therapy). The maintenance of ethical rules is of relevance to meet the socio-potitical dimension of biotechnology. Estimations of consequences of techniques and legislative initiatives (i. e. protection by law of embryos) serve to protect basic human rights. Besides legal frameworks, the creation of a responsible climate towards new technologies represents another pedagogic obligation of extraordinary significance. Counterbalancing advantages and drawbacks in an objective way is a major aim. The strengthened consideration of molecular biology in traditional biological disciplines should students set in a position to raise the forthcoming demands of work force after finishing their study.
Permutation of paradigms in biology The progresses in biosciences challenges biological teaching. Considering the fact that knowledge in biosciences doubles every five years, former concepts of teaching as humorously shown in Figure 1 are largely inappropriate. Traditional descriptive concepts in biosciences were increasingly substituted by analytical and synthetic ones during the past decades. Molecular genetic techniques now add a new dimension. For the first time, a targeted manipulation of the map of life arises at the horizon. Molecular biology penetrates many other disciplines of biology and pushes established research concepts away. The power of this bioscientific development has been well recognized in science theory and has led to a number of competing theoretical considerations (Kuhn, 1981; Toulmin, 1983). Such paradigm permutations are scientific quantum transitions and not new in life sciences. Comparable developments of great scientific progresses were formerly observed with respect to the astronomy of Kopernikus, the optics of Newton, the relativity theory of Einstein etc. Eye-catching headlines like ªrising of the golden age of biologyº seem a little bit too euphoric. Nevertheless, molecular biology is a novel paradigm and will become a major player in the 21st century ± scientifically and economically.
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Fig. 1. The middle aged cartoon of the Nuremberg Funnel (copper engraving from David Manasser, around 1650) highlights a mechanical way of learning. This concept points to the view that there is a close relationship between mediation of facts (input) and knowledge (output). Learning is a passive reception process. As shown in the cartoon, the best way of funneling facts into as student's head will maximize the generation of knowledge. This is a behavioristic concept of learning (ªpushº model). It is inappropriate nowadays. As a paradigm permutation took place in biology, another paradigm change occurred in pedagogy. The recent ªpullª model focuses on self-directed learning assuming that self initiative and motivation causes more learning success. Central to this constructivistic learning theory is the arrangement of learning environments which enabke an effective autonomous learning (Knowles, 1975).
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Integration of results from molecular biological research into education Frameworks How far should biological teaching at universities follow this development? Of course, classical didactics and practical experiences in teaching of traditional biology remain further on valid as far as they do not follows behavioristic pedagogical models (see legend of Fig. 1). They are not to be refused for the sake of a new paradigm in research. The amalgamation of classical disciplines with molecular ones could be a pragmatic way to handle with pedagogic aims in an appropriate manner. Genetic, biochemical, bioinformatical and cell and structural lessons may enlarge molecular biological contents to create a basic knowledge in molecular biology. These basics may then be integrated into other lessons. Students may first be compromised with typical biological phenomena which are then causally explained ªat the level of the geneº. The didactic concept ªfrom phenotype to genotypeº (Figure 2) may be applicable for, i. e.: 1. Botany and zoology: Comparing the homologies of gene sequences is used to prove the relationships of species. This has impact on taxonomy and exploration of evolutionary diversification. 2. Physiology: Physiological processes in animals and plants represent the result of the interplay of gene products (proteins) and their functions.
Fig. 2. Integration of molecular biology traditional biology by explanation of phenotypes by underlying genotypes. This concept may be applicable for most classical disciplines. Basic knowledge from molecular biological oriented disciplines facilitate this connection.
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3. Evolution: A mal-adapted phenotype is bound to die or to re-adapt its genotype to new or altered environmental conditions. Evolutionary selection pressure causes ªgene driftsº. 4. Ethology: Although some hints for socio-biological behavious, i. e. schizophrenia or alcoholism, have been tried to ascribe to genetic factors (genetic polymorphisms, linkage analyses using marker genes), the current state of research seems to be rather inconsistent and is, therefore, less suited. 5. Human biology: It is easily feasible to teach human diseases on a molecular basis, i. e. AIDS, cancer, hereditary diseases etc. 6. Ecology and environmental biology: At first glance, the relations between ecological and environmental biology and molecular biology seem to be far less obvious as in other disciplines. Nevertheless, molecular biology is a driving force in these branches of biology as well. For this reason, I like to describe possibilities for the integration of molecular biology into ecological lessons in greater detail.
Human-centered ecology Human-centered ecology and environmental biology may be looked upon as parts of human biology. As proposed above, the major scopes of ecological oriented teaching are not to be redefined, but to be supplemented by molecular biology. Some scopes could be: 1) Understanding of ecological principles and of responses of the ecological balance towards anthropogenic influences. 2) Understanding of human health risks by anthropogenic environmental influences. 3) Understanding of cause-effect relationships between detrimental environmental influences and molecular processes of the human organism. 4) Development of responsibility and readiness to personal engagement and acting. Examples among the plethora of environmental stresses and detriments are suited to introduce molecular biological aspects in ecology/environmental biology. Toxic ingredients of industrial emissions (i. e. polycyclic hydrocarbons) and UV-rays may form adducts with DNA and proteins and generate aggressive oxygen radical molecules. Environmental noxes are recognised and processed by a battery of enzymes. Phase I enzymes (i. e. cytochrome P450 monoxigenase isoenzymes) activate and phase II enzymes (i. e. glutathione S-transferase isoenzymes) detoxify toxic compounds. As the cellular detoxification capacity is exceeded, radical molecules may damage proteins or nucleic acids. The individual susceptibility to environmental stress is at least in part be determined by single nucleotide polymorphisms in phase I or phase II enzymes, i. e. CYP2E1, N-acetyltransferase, GST-T1 etc. The analyses of genetic polymorphisms gain in-
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creasing importance in occupational medicine for the risk evaluation of employees exposed to industrial hazardous compounds. Genotoxic stress by such compounds may lead to the arrest of proliferating cells in cell cycle checkpoints. The blockage of cell cycle progression provides ample time to repair DNA damage before DNA lesions were passed on subsequent cell generations during cell divisions. Multifaceted mechanisms allow the repair of DNA (i. e. base mismatch repair, base excision repair, nucleotide excision repair) or of proteins (i. e. molecular chaperones). The complexity of repair pathways sheds light on their enormous significance for cellular and genetic integrity. Lethally damaged cells activate a genetically driven process called ªprogrammed cell deathº or ªapoptosisº. A central molecule in the regulation of cell cycle arrest, DNA repair, and apoptosis is the tumor suppressor protein p53 (Hainaut, 1995). This example illustrates a basic molecular principle of cell biology: molecular regulatory systems are frequently redundant. Several overlapping defence mechanisms try not to leave anything to chance: 1) Cytoplasmatic detoxification of environmental xenobiotics to prevent cellular damages. 2) Repair of damaged proteins and nucleic acids. 3) Apoptosis of cells affected with non-repairable DNA damage. These defence barriers all prevent malign cellular transformation and tumor development. The human organism is permanently exposed to a huge amount of environmental and endogenous DNA damaging agents. A multitude of molecular mechanisms repair DNA lesions by cutting out faulty segments and restoring the original nucleotide sequence. Even if the DNA repair machinery fails and a single DNA lesion persists, this must not be an initial event of tumorigenesis. Carcinogenesis is a multistage process (Fearon and Vogelstein, 1990). From the cell's point of view, carcinogenesis is an extremely rare event. Accumulation of DNA lesions over the entire span of life time may explain, why cancer is the second most cause of death in industrialized countries. Beside functions in malignant cell transformation mutations may contribute to genetic diseases and speed up ageing too. Interestingly, many of the above described cellular defence mechanisms are also involved in the development of resistance towards anti-tumor drugs (Volm et al., 1990) which severely hampers the treatment successes in oncology. Therefore, uncovering molecular mechanisms of drug resistance became a ªhunting fieldº in cancer research (Efferth and Volm, 1992; Efferth et al., 1997) to advice new treatment modalities. As adduct formation of environmental noxes with DNA may contribute to carcinogenesis, protein adducts may provoke responses of the immune system including allergic reactions and diseases. Allergens may be classified along their anthropogenic or non-anthropogenic origin. Air pollution, house dust, working place noxes, certain pharmaceuticals, certain kinds of food prepara-
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tion or food additives all harbour allergenic potentials. Non-anthropogenic allergens are plant seeds, insect stings, bacterial, viral, and fungal infections. Allergies relate to immunological reactions. The interaction of environment and immune system may, therefore, be a subject for biological education. Allergens induce a huge number of cell-cell interactions and humoral reactions, e. g. histamine release, activation of mast cells, T-lymphocytes, mononuclear phagocytes as well as of eosinophils or neutrophils (Stewart and Thompson, 1996; Umestu and DeKruyff, 1997).
The synecological concept Students should also become familiar with an enlarged definition of ecology. Synecology includes mankind as a part of the entire ecology, but not as the central one. Molecular biology gains increasing interest in synecology to describe structures of populations and biocenoses (Morgan, 1991). Synecology deals with three structural elements: organisms, populations, and biocenoses. The capability of adaptation to ecological niches determines the viability of these structures at constant or alterating environmental conditions. Such conditions can be biotic or abiotic in nature. Adaptation to ecological niches ensue from 1) alteration of organisms' behavior (which is a topic of ethology) and 2) genetic and molecular alterations in the organisms. At constant conditions, organisms and populations seek for biotopes which fit best to their requireÂments (ªenvironment preferenceº). Compromised with altering and suboptimal conditions, organisms and populations react differently: 1) Tolerance without genetic alterations. 2) Somatic, non-hereditary reactions, e. g. gene induction. Examples are: ± the induction of detoxification mechanisms upon contact with toxic agents; ± skin tanning after sun exposure as a consequence of increased melanin production. 3) Selection of pre-adapted genotypes which are germ line transmittable and irreversible. Examples of genotypic manifestations are: ± gene amplification, single nucleotide polymorphisms, point and chromosomal mutations, plasmids, transposons etc. involved in the development of resistance towards antibiotics, herbicides, or insecticides (Harms et al., 1992; Feyereisen, 1995). ± Multiplication of entire sets of chromosomes (polyploidy) e. g. in colored petales of plants for an effective attraction of insects or in the case of cultivation plants, i. e. Brassica (Song et al., 1995). 4) Destruction of ± individual organisms by acute toxic environmental influences, ± entire populations by reduced fertility and reproduction.
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The items 1) to 3) result in the successful adaptation and foster evolutionary processes. Molecular ecology represents a novel branch of general ecology. In cases where morphology fails, genetic analyses of tightly related species may dissect between distinct species, subspecies, races, or populations. Molecular taxonomy helps to identify rare species and to protect them from eradication. Characteristic modes of behavior in biocenoses are ± competition and rivalry, ± symbiosis and parasitism, ± hunter-plunder relations. Among a near endless list of symbioses, one important hypothesis concerns the endosymbiosis of one organism by another to explain the evolutionary origin of mitochondriae and plastides. The incorporation by eucaryotic cells of protocytes as precursors of mitochondriae or plastides represents an outstanding example for the significance of molecular biology in ecology. Mitochondriae consist of biosynthesis machineries for DNA, proteins, and fatty acids independent of the nuclear genome of cells. The incorporation of bacteria by the amoeba Pelomyxa palustris which lacks mitochondriae is an intriguing hint for an early precursor of mitochondrial evolution. Convincing evidence to support the endosymbiont hypothesis was provided from sequence comparisons. They revealed tight homologies between cellular plastides and cyanobacteria (i. e. Synechococcus) and between mitochondriae and phototrophic bacteria (i. e. Rhodopseudomonas) (Schwartz and Dayhoff, 1978; Schenk et al., 1987; Sitte and Eschenbach, 1991).
Aims of didactics of molecular biology The implementation of molecular biology in ecological teaching facilitates the combination of mediation of biological facts with ecological consciousness and acting. The following alterations of consciousness may be aspired to: 1) Students discern ecological balance as well-balanced structure which basically roots in molecular factors. The human being is integrated in this system but not as the central player. Nevertheless, humans can massively influence ecological balance (i. e. by destroying it). 2) As a consequence, ethical responsibilities towards nature and humans may be deduced. Nature represents a non-dispensable basis for human life. 3) As more and more is being exploited about molecular biological processes in nature, molecular ecology will open avenues for bio- and gene technological applications. Ethical and lawful rules are necessitated to prevent misuse.
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Example: Oil-producing plants (i. e. Croton) can biotechnically be used to saturate the economic energy demands in times of a scarcity of fossile mineral oil occurrence. The progressive destruction of tropical biotopes decreases the chances to explore and to use natural energy resources in the future. Thus, ecological destruction can cause economic detriment. 4) Biotechnology enables molecular ecologists to eliminate anthropogenic induced environmental detriments. Example 1: Genetically manipulated bacteria are able to eat spilled mineral oil after tanker damages by sea. After removal of oil carpets these oil-specialized bacteria die because of the deficiency of their nutriment basis. Example 2: The bacterium Thiobacillus ferrooxidans converts heavy metals (iron, chrome, arsenic) into non-toxic minerals, i. e. Schwertmannit. Example 3: The genetically manipulated bacterium Deinococcus radiodurans decomposes toxic organic solvents (i. e. toluole, indole, 3,4-dichlorobutene). The realization of gene technological approaches of molecular ecology to pave novel ways combatting ecological disasters will also depend on the political responsibility of countries. Alterations of the ecological consciousness should run into concrete reflections of students about their personal responsibility and acting. Three levels of acting may be distinguished: 1) Easy changeable situations: ± Restriction of the own behavior which is hazardous to the environment (car driving, household-refuse). ± Avoidance of the own behavior which is hazardous to health (i. e. extended sun baths, smoking habits). ± Prevention of health risks by means of nutrition (e. g. intake of vitamins as ªradical scavengersº). 2) Conditionally changeable situations: ± Realization of an environment-saving legislation. ± Promotion of environment-saving research and technology. 3) Unchangeable situations: Predispositions for rare hereditary diseases by environmental influences such as ± Xeroderma pigmentosum: The skin sensitivity towards UV-rays predisposes to skin cancer. - Li-Fraumeni syndrome: Germ line transmitted mutations in the p53 tumor suppressor gene inactivate the p53 protein and predisposes for several types of tumors. It is to be hoped that such ªvictims of their genesº will experience help from future gene therapy strategies. Molecular fundamentals ease the inclusion of social and political aspects into biological education. Inasmuch such pretentious aims will be transfer-
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able to the everyday reality, will depend both on the lecturer's personal engagement as well on the development of suitable syllabuses.
References: Efferth, T.; Volm, M. (1992) Immunohistochemical detection of P-glycoprotein, glutathione Stransferase pi and DNA topoisomerase II in human tumors. Oncology 49: 368±375. Efferth, T.; Fabry, U.; Osieka, R. (1997) Apoptosis and daunorubicin resistance to daunorubicin in human leukemic cells. Leukemia 11: 1180±1186. Fearon, E. R.; Vogelstein, B. (1990) A genetic model for colorectal tumorigenesis. Cell 61: 759±767. Feyereisen, R. (1995) Molecular biology of insecticide resistance. Toxicol. Lett. 82: 83±90. Guillemaud, T.; Rooker, S.; Pasteur, N.; Raymond, M. (1996) Testing the unique amplification event and the worldwide migration hypothesis of insecticide resistance genes with sequence data. Heredity 77: 535±543. Hainaut, P. (1995) The tumor suppressor protein p53: a receptor to genotoxic stress that controls cell growth and survival. Curr. Opin. Oncol. 7: 15±16. Harms, C. T.; Armour, S. L.; DiMaio, J. J.; Middlesteadt, L. A.; Murray, D.; Negretto, D. V.; Thompson-Taylor, H.; Weymann, K.; Montoya, A. L.; Shillito, R. D. et al. (1992) Herbicide resistance due to amplification of mutant acetohydroxyacid synthase gene. Mol. Gen. Genet. 233: 427±435. Knowles, M. (1975) Self-directed learning. Association Press. New York. Kuhn, T. S. (1981) Die Struktur wissenschaftlicher Revolutionen. Suhrkamp Taschenbuch Verlag. Frankfurt a. M. Morgan, J. A. (1991) Molecular biology: new tools for studying microbial ecology. Sci. Prog. 75: 265±277. Schenk, H. E. A.; Bayer, M. G.; Zook, D. (1987) Cyanelles ± from symbiont to organelle. Ann. N. Y. Acad. Sci. 503:151±167. Schwartz, R. M.; Dayhoff, M. O. (1978) Origin of prokaryotes, eukaryotes, mitochondria, and chloroplasts. Science 199: 395±403. Sitte, P.; Eschenbach, S. (1991) Cytosymbiosis and its significance in cell evolution. Prog. Bot. 53: 29±43. Song, K.; Lu, P.; Tang, K.; Osborn, T. C. (1995) Rapid genome change in synthetic polyploids of Brassica and its implications for polyploid evolution. Proc. Nat. Acad. Sci. U.S.A. 92: 7719±7723. Stewart, C. A.; Thompson, P. J. (1996) Review: The biochemistry of common aeroallergens. Clin. Exp. Allergy 26: 1020±1041. Toulmin, S. (1983) Kritik der kollektiven Vernunft. Suhrkamp Taschenbuch Verlag. Frankfurt a. M. Umestu, D. T.; DeKruyff, R. H. (1997) Th1 and Th2 CD4+ cells in the pathogenesis of allergic diseases. Proc. Soc. Exp. Biol. Med. 215: 11±20. Volm, M.; Zerban, H.; Mattern, J.; Efferth, T. (1990) Overexpression of P-glycoprotein in rat hepatocellular carcinomas induced with N-nitrosomorpholine. Carcinogenesis 11: 169± 172.
Didactics of Molecular Ecology Thomas Efferth Virtual Campus, Rhineland-Palatinate Mainz, Germany Address for correspondence: Privatdozent Dr. Thomas Efferth, Virtual Campus, Rhineland-Palatinate P.O. Box 43 80, 55033 Mainz, Germany, Phone: + 49-61 31-5 70 76 11 e-mail: [email protected] Received: November 16, 1999; accepted: March 2, 2000 Key words: Paradigm, Health, Environment
Summary: Molecular biology conferred enormous progresses in biosciences during the past few years. This paradigm permutation in biological research certainly challenges biological education. Nevertheless, this is no reason to fundamentally reorganise biological education at the universities. A most entire view of the matter should remain a central request which meets the capacity and imagination of students. Selected biological phenomena taken from the traditional treasury remain suitable in the future too to mediate basic biological ways ot thinking. Forthcoming syllabuses, however, will necessitate the expansion of this concept. The scope of the present contribution is to show, how the integration of molecular biology in the teaching of classical disciplines of biology may be reached. Choosing ecology and environmental biology as examples, molecular biology will not only strengthen explanation models of cause-effect relationships in these disciplines, but also will facilitate the interconnections to interdisciplinary fields such as health education, social, and political education. This may result in an entire structural concept of classical and molecular biology.
The challenge of molecular biology to biological teaching Didactics of molecular biology ± what for? Recent developments in molecular biology contribute not only to research activities, but will also influence teaching of biology at the universities in the future. The present article aims to draw the attention of biology teachers to some of the demands of biological education in the 21st century. Molecular biology may not only be understood as a simple necessity but also as a chance. Important proceedings frequently serve as headlines in the daily press and in TV causing sometimes emotional pros and cons in the public. Such ªbase-line levelsº of interest towards biological matters 1431-7613/01/120/02±139/$ 15.00/0
140
T. Efferth
being present among students afford lots of opportunities from lecturers to pick up molecular topics from the everyday reality of people and to hook up students to more sophisticated chapters of biology. ªGene soja beansº, ªsheep Dollyº or ªembryonal cloningº may be examples of useful catchwords in this context. Teaching success is not only measurable by examination of biological facts. It manifests as well in the long-termed creation of fundamental attitudes of mind-concerning biological questions in a socio-political context. The term ªsecret curriculumº describes such far-reaching consequences of pedagogic achievements. Biotechniques such as gene technology will not only contribute to a social and global alteration in the next few decades but may also influence the life of individual subjects (e. g. genetic diagnostics, somatic gene therapy). The maintenance of ethical rules is of relevance to meet the socio-potitical dimension of biotechnology. Estimations of consequences of techniques and legislative initiatives (i. e. protection by law of embryos) serve to protect basic human rights. Besides legal frameworks, the creation of a responsible climate towards new technologies represents another pedagogic obligation of extraordinary significance. Counterbalancing advantages and drawbacks in an objective way is a major aim. The strengthened consideration of molecular biology in traditional biological disciplines should students set in a position to raise the forthcoming demands of work force after finishing their study.
Permutation of paradigms in biology The progresses in biosciences challenges biological teaching. Considering the fact that knowledge in biosciences doubles every five years, former concepts of teaching as humorously shown in Figure 1 are largely inappropriate. Traditional descriptive concepts in biosciences were increasingly substituted by analytical and synthetic ones during the past decades. Molecular genetic techniques now add a new dimension. For the first time, a targeted manipulation of the map of life arises at the horizon. Molecular biology penetrates many other disciplines of biology and pushes established research concepts away. The power of this bioscientific development has been well recognized in science theory and has led to a number of competing theoretical considerations (Kuhn, 1981; Toulmin, 1983). Such paradigm permutations are scientific quantum transitions and not new in life sciences. Comparable developments of great scientific progresses were formerly observed with respect to the astronomy of Kopernikus, the optics of Newton, the relativity theory of Einstein etc. Eye-catching headlines like ªrising of the golden age of biologyº seem a little bit too euphoric. Nevertheless, molecular biology is a novel paradigm and will become a major player in the 21st century ± scientifically and economically.
Didactics of molecular ecology
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Fig. 1. The middle aged cartoon of the Nuremberg Funnel (copper engraving from David Manasser, around 1650) highlights a mechanical way of learning. This concept points to the view that there is a close relationship between mediation of facts (input) and knowledge (output). Learning is a passive reception process. As shown in the cartoon, the best way of funneling facts into as student's head will maximize the generation of knowledge. This is a behavioristic concept of learning (ªpushº model). It is inappropriate nowadays. As a paradigm permutation took place in biology, another paradigm change occurred in pedagogy. The recent ªpullª model focuses on self-directed learning assuming that self initiative and motivation causes more learning success. Central to this constructivistic learning theory is the arrangement of learning environments which enabke an effective autonomous learning (Knowles, 1975).
142
T. Efferth
Integration of results from molecular biological research into education Frameworks How far should biological teaching at universities follow this development? Of course, classical didactics and practical experiences in teaching of traditional biology remain further on valid as far as they do not follows behavioristic pedagogical models (see legend of Fig. 1). They are not to be refused for the sake of a new paradigm in research. The amalgamation of classical disciplines with molecular ones could be a pragmatic way to handle with pedagogic aims in an appropriate manner. Genetic, biochemical, bioinformatical and cell and structural lessons may enlarge molecular biological contents to create a basic knowledge in molecular biology. These basics may then be integrated into other lessons. Students may first be compromised with typical biological phenomena which are then causally explained ªat the level of the geneº. The didactic concept ªfrom phenotype to genotypeº (Figure 2) may be applicable for, i. e.: 1. Botany and zoology: Comparing the homologies of gene sequences is used to prove the relationships of species. This has impact on taxonomy and exploration of evolutionary diversification. 2. Physiology: Physiological processes in animals and plants represent the result of the interplay of gene products (proteins) and their functions.
Fig. 2. Integration of molecular biology traditional biology by explanation of phenotypes by underlying genotypes. This concept may be applicable for most classical disciplines. Basic knowledge from molecular biological oriented disciplines facilitate this connection.
Didactics of molecular ecology
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3. Evolution: A mal-adapted phenotype is bound to die or to re-adapt its genotype to new or altered environmental conditions. Evolutionary selection pressure causes ªgene driftsº. 4. Ethology: Although some hints for socio-biological behavious, i. e. schizophrenia or alcoholism, have been tried to ascribe to genetic factors (genetic polymorphisms, linkage analyses using marker genes), the current state of research seems to be rather inconsistent and is, therefore, less suited. 5. Human biology: It is easily feasible to teach human diseases on a molecular basis, i. e. AIDS, cancer, hereditary diseases etc. 6. Ecology and environmental biology: At first glance, the relations between ecological and environmental biology and molecular biology seem to be far less obvious as in other disciplines. Nevertheless, molecular biology is a driving force in these branches of biology as well. For this reason, I like to describe possibilities for the integration of molecular biology into ecological lessons in greater detail.
Human-centered ecology Human-centered ecology and environmental biology may be looked upon as parts of human biology. As proposed above, the major scopes of ecological oriented teaching are not to be redefined, but to be supplemented by molecular biology. Some scopes could be: 1) Understanding of ecological principles and of responses of the ecological balance towards anthropogenic influences. 2) Understanding of human health risks by anthropogenic environmental influences. 3) Understanding of cause-effect relationships between detrimental environmental influences and molecular processes of the human organism. 4) Development of responsibility and readiness to personal engagement and acting. Examples among the plethora of environmental stresses and detriments are suited to introduce molecular biological aspects in ecology/environmental biology. Toxic ingredients of industrial emissions (i. e. polycyclic hydrocarbons) and UV-rays may form adducts with DNA and proteins and generate aggressive oxygen radical molecules. Environmental noxes are recognised and processed by a battery of enzymes. Phase I enzymes (i. e. cytochrome P450 monoxigenase isoenzymes) activate and phase II enzymes (i. e. glutathione S-transferase isoenzymes) detoxify toxic compounds. As the cellular detoxification capacity is exceeded, radical molecules may damage proteins or nucleic acids. The individual susceptibility to environmental stress is at least in part be determined by single nucleotide polymorphisms in phase I or phase II enzymes, i. e. CYP2E1, N-acetyltransferase, GST-T1 etc. The analyses of genetic polymorphisms gain in-
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creasing importance in occupational medicine for the risk evaluation of employees exposed to industrial hazardous compounds. Genotoxic stress by such compounds may lead to the arrest of proliferating cells in cell cycle checkpoints. The blockage of cell cycle progression provides ample time to repair DNA damage before DNA lesions were passed on subsequent cell generations during cell divisions. Multifaceted mechanisms allow the repair of DNA (i. e. base mismatch repair, base excision repair, nucleotide excision repair) or of proteins (i. e. molecular chaperones). The complexity of repair pathways sheds light on their enormous significance for cellular and genetic integrity. Lethally damaged cells activate a genetically driven process called ªprogrammed cell deathº or ªapoptosisº. A central molecule in the regulation of cell cycle arrest, DNA repair, and apoptosis is the tumor suppressor protein p53 (Hainaut, 1995). This example illustrates a basic molecular principle of cell biology: molecular regulatory systems are frequently redundant. Several overlapping defence mechanisms try not to leave anything to chance: 1) Cytoplasmatic detoxification of environmental xenobiotics to prevent cellular damages. 2) Repair of damaged proteins and nucleic acids. 3) Apoptosis of cells affected with non-repairable DNA damage. These defence barriers all prevent malign cellular transformation and tumor development. The human organism is permanently exposed to a huge amount of environmental and endogenous DNA damaging agents. A multitude of molecular mechanisms repair DNA lesions by cutting out faulty segments and restoring the original nucleotide sequence. Even if the DNA repair machinery fails and a single DNA lesion persists, this must not be an initial event of tumorigenesis. Carcinogenesis is a multistage process (Fearon and Vogelstein, 1990). From the cell's point of view, carcinogenesis is an extremely rare event. Accumulation of DNA lesions over the entire span of life time may explain, why cancer is the second most cause of death in industrialized countries. Beside functions in malignant cell transformation mutations may contribute to genetic diseases and speed up ageing too. Interestingly, many of the above described cellular defence mechanisms are also involved in the development of resistance towards anti-tumor drugs (Volm et al., 1990) which severely hampers the treatment successes in oncology. Therefore, uncovering molecular mechanisms of drug resistance became a ªhunting fieldº in cancer research (Efferth and Volm, 1992; Efferth et al., 1997) to advice new treatment modalities. As adduct formation of environmental noxes with DNA may contribute to carcinogenesis, protein adducts may provoke responses of the immune system including allergic reactions and diseases. Allergens may be classified along their anthropogenic or non-anthropogenic origin. Air pollution, house dust, working place noxes, certain pharmaceuticals, certain kinds of food prepara-
Didactics of molecular ecology
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tion or food additives all harbour allergenic potentials. Non-anthropogenic allergens are plant seeds, insect stings, bacterial, viral, and fungal infections. Allergies relate to immunological reactions. The interaction of environment and immune system may, therefore, be a subject for biological education. Allergens induce a huge number of cell-cell interactions and humoral reactions, e. g. histamine release, activation of mast cells, T-lymphocytes, mononuclear phagocytes as well as of eosinophils or neutrophils (Stewart and Thompson, 1996; Umestu and DeKruyff, 1997).
The synecological concept Students should also become familiar with an enlarged definition of ecology. Synecology includes mankind as a part of the entire ecology, but not as the central one. Molecular biology gains increasing interest in synecology to describe structures of populations and biocenoses (Morgan, 1991). Synecology deals with three structural elements: organisms, populations, and biocenoses. The capability of adaptation to ecological niches determines the viability of these structures at constant or alterating environmental conditions. Such conditions can be biotic or abiotic in nature. Adaptation to ecological niches ensue from 1) alteration of organisms' behavior (which is a topic of ethology) and 2) genetic and molecular alterations in the organisms. At constant conditions, organisms and populations seek for biotopes which fit best to their requireÂments (ªenvironment preferenceº). Compromised with altering and suboptimal conditions, organisms and populations react differently: 1) Tolerance without genetic alterations. 2) Somatic, non-hereditary reactions, e. g. gene induction. Examples are: ± the induction of detoxification mechanisms upon contact with toxic agents; ± skin tanning after sun exposure as a consequence of increased melanin production. 3) Selection of pre-adapted genotypes which are germ line transmittable and irreversible. Examples of genotypic manifestations are: ± gene amplification, single nucleotide polymorphisms, point and chromosomal mutations, plasmids, transposons etc. involved in the development of resistance towards antibiotics, herbicides, or insecticides (Harms et al., 1992; Feyereisen, 1995). ± Multiplication of entire sets of chromosomes (polyploidy) e. g. in colored petales of plants for an effective attraction of insects or in the case of cultivation plants, i. e. Brassica (Song et al., 1995). 4) Destruction of ± individual organisms by acute toxic environmental influences, ± entire populations by reduced fertility and reproduction.
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The items 1) to 3) result in the successful adaptation and foster evolutionary processes. Molecular ecology represents a novel branch of general ecology. In cases where morphology fails, genetic analyses of tightly related species may dissect between distinct species, subspecies, races, or populations. Molecular taxonomy helps to identify rare species and to protect them from eradication. Characteristic modes of behavior in biocenoses are ± competition and rivalry, ± symbiosis and parasitism, ± hunter-plunder relations. Among a near endless list of symbioses, one important hypothesis concerns the endosymbiosis of one organism by another to explain the evolutionary origin of mitochondriae and plastides. The incorporation by eucaryotic cells of protocytes as precursors of mitochondriae or plastides represents an outstanding example for the significance of molecular biology in ecology. Mitochondriae consist of biosynthesis machineries for DNA, proteins, and fatty acids independent of the nuclear genome of cells. The incorporation of bacteria by the amoeba Pelomyxa palustris which lacks mitochondriae is an intriguing hint for an early precursor of mitochondrial evolution. Convincing evidence to support the endosymbiont hypothesis was provided from sequence comparisons. They revealed tight homologies between cellular plastides and cyanobacteria (i. e. Synechococcus) and between mitochondriae and phototrophic bacteria (i. e. Rhodopseudomonas) (Schwartz and Dayhoff, 1978; Schenk et al., 1987; Sitte and Eschenbach, 1991).
Aims of didactics of molecular biology The implementation of molecular biology in ecological teaching facilitates the combination of mediation of biological facts with ecological consciousness and acting. The following alterations of consciousness may be aspired to: 1) Students discern ecological balance as well-balanced structure which basically roots in molecular factors. The human being is integrated in this system but not as the central player. Nevertheless, humans can massively influence ecological balance (i. e. by destroying it). 2) As a consequence, ethical responsibilities towards nature and humans may be deduced. Nature represents a non-dispensable basis for human life. 3) As more and more is being exploited about molecular biological processes in nature, molecular ecology will open avenues for bio- and gene technological applications. Ethical and lawful rules are necessitated to prevent misuse.
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Example: Oil-producing plants (i. e. Croton) can biotechnically be used to saturate the economic energy demands in times of a scarcity of fossile mineral oil occurrence. The progressive destruction of tropical biotopes decreases the chances to explore and to use natural energy resources in the future. Thus, ecological destruction can cause economic detriment. 4) Biotechnology enables molecular ecologists to eliminate anthropogenic induced environmental detriments. Example 1: Genetically manipulated bacteria are able to eat spilled mineral oil after tanker damages by sea. After removal of oil carpets these oil-specialized bacteria die because of the deficiency of their nutriment basis. Example 2: The bacterium Thiobacillus ferrooxidans converts heavy metals (iron, chrome, arsenic) into non-toxic minerals, i. e. Schwertmannit. Example 3: The genetically manipulated bacterium Deinococcus radiodurans decomposes toxic organic solvents (i. e. toluole, indole, 3,4-dichlorobutene). The realization of gene technological approaches of molecular ecology to pave novel ways combatting ecological disasters will also depend on the political responsibility of countries. Alterations of the ecological consciousness should run into concrete reflections of students about their personal responsibility and acting. Three levels of acting may be distinguished: 1) Easy changeable situations: ± Restriction of the own behavior which is hazardous to the environment (car driving, household-refuse). ± Avoidance of the own behavior which is hazardous to health (i. e. extended sun baths, smoking habits). ± Prevention of health risks by means of nutrition (e. g. intake of vitamins as ªradical scavengersº). 2) Conditionally changeable situations: ± Realization of an environment-saving legislation. ± Promotion of environment-saving research and technology. 3) Unchangeable situations: Predispositions for rare hereditary diseases by environmental influences such as ± Xeroderma pigmentosum: The skin sensitivity towards UV-rays predisposes to skin cancer. - Li-Fraumeni syndrome: Germ line transmitted mutations in the p53 tumor suppressor gene inactivate the p53 protein and predisposes for several types of tumors. It is to be hoped that such ªvictims of their genesº will experience help from future gene therapy strategies. Molecular fundamentals ease the inclusion of social and political aspects into biological education. Inasmuch such pretentious aims will be transfer-
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able to the everyday reality, will depend both on the lecturer's personal engagement as well on the development of suitable syllabuses.
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