The ecological risks of transgenic plants.

Biotechnologies have been utilized "ante litteram" for thousands of years to produce food and drink and genetic engineering techniques have been widely applied to produce many compounds for human use, from insulin to other medicines. The debate on genetically modified (GM) organisms broke out all over the world only when GM crops were released into the field. Plant ecologists, microbiologists and population geneticists carried out experiments aimed at evaluating the environmental impact of GM crops. The most significant findings concern: the spread of transgenes through GM pollen diffusion and its environmental impact after hybridisation with closely related wild species or subspecies; horizontal gene transfer from transgenic plants to soil microbes; the impact of insecticide proteins released into the soil by transformed plants on non-target microbial soil communities. Recent developments in genetic engineering produced a technology, dubbed "Terminator", which protects patented genes introduced in transgenic plants by killing the seeds in the second generation. This genetic construct, which interferes so heavily with fundamental life processes, is considered dangerous and should be ex-ante evaluated taking into account the data on "unexpected events", as here discussed, instead of relying on the "safe until proven otherwise" claim. Awareness that scientists, biotechnologists and genetic engineers cannot answer the fundamental question "how likely is that transgenes will be transferred from cultivated plants into the natural environment?" should foster long-term studies on the ecological risks and benefits of transgenic crops.     

The emerging role of epigenetic mechanisms in the etiology of neural tube defects

The molecular requirements for neural tube closure are complex. This is illustrated by the occurrence of neural tube defects (NTDs) in many genetic mouse mutants, which implicate a variety of genes, pathways and cellular functions. NTDs are also prevalent birth defects in humans, affecting around 1 per 1,000 pregnancies worldwide. In humans the causation is thought to involve the interplay of fetal genes and the effect of environmental factors. Recent studies on the etiology of human NTDs, as well as analysis of mouse models, have raised the question of the possible involvement of epigenetic factors in determining susceptibility. A consideration of potential causative factors in human NTDs must now include both alterations in the regulation of gene expression, through mutation of promoter or regulatory elements and the additional analysis of epigenetic regulation. Alterations in the epigenetic status can be directly modified by various environmental insults or maternal dietary factors.Key words: neural tube defects, diet, folic acid, epigenome, epigenetic regulation, methylation, chromatin, histones, acetylation     

Human BRCA1 gene rescues the embryonic lethality of Brca1 mutant mice

Half of all familial breast cancers are due to mutation in the BRCA1 gene. However, despite its importance, attempts to model BRCA1-induced disease in the mouse have been disappointing. Heterozygous Brca1 knockout mice do not develop mammary tumors and homozygous knockout mice die during embryogenesis from ill-defined causes. Sequence analysis has shown that the coding region, genomic organization, and regulatory sequences of the human and mouse genes are not well conserved. This has raised the question of whether the mouse can serve as an effective model for functional analysis of the human BRCA1 gene. To address this question we have introduced a bacterial artificial chromosome containing the human BRCA1 gene into the germline of Brca1 knockout mice. Surprisingly, we have found that the embryonic lethality of Brca1 knockout mice is rescued by the human transgene. We also show that expression of human BRCA1 transgene mirrors the endogenous murine gene. Our "humanized" transgenic mice can serve as a model system for functional analyses of the human BRCA1 gene. Published 2001 Wiley-Liss, Inc.     

The emerging role of epigenetic mechanisms in the etiology of neural tube defects

The molecular requirements for neural tube closure are complex. This is illustrated by the occurrence of neural tube defects (NTDs) in many genetic mouse mutants, which implicate a variety of genes, pathways and cellular functions. NTDs are also prevalent birth defects in humans, affecting around 1 per 1000 pregnancies worldwide. In humans the causation is thought to involve the interplay of fetal genes and the effect of environmental factors. Recent studies on the aetiology of human NTDs, as well as analysis of mouse models, have raised the question of the possible involvement of epigenetic factors in determining susceptibility. A consideration of potential causative factors in human NTDs must now include both alterations in the regulation of gene expression, through mutation of promoter or regulatory elements, and the additional analysis of epigenetic regulation. Alterations in the epigenetic status can be directly modified by various environmental insults or maternal dietary factors.     

Evolutionary stability of coexistence due to the storage effect in a two-season model

The question of species coexistence has been central to ecology since its founding. Ever-present environmental variation may be one answer to that question. Previous models have demonstrated that species can exploit this variation to coexist with competitors by having different environmental responses (the storage effect). When traits governing species’ environmental response can evolve, however, coexistence is not assured. In this study, we use a continuous time, two-season model to determine the evolutionary outcome of competing species evolving in their seasonal performance trait. We extend the competitive exclusion principle to show that the storage effect can allow no more than N species to coexist on N discrete seasons with no relative nonlinearity. We find a broad region of parameter space where coexistence is evolutionarily stable. The size of this region depends on the period of fluctuations relative to the individual lifespan. Relatively long period fluctuations yield a large coexistence region, but as the period decreases, the region narrows and disappears asymptotically. Finally, we cast our adaptive dynamics technique in terms of Chesson’s concept of equalizing and stabilizing mechanisms to demonstrate that the breakdown in coexistence at short periods is due to loss of the stabilizing covariance between the environment and competition.     

Measuring preferences on environmental damages in LCIA. Part 2: choice and allocation questions in panel methods

Background, aim, and scope  Within life cycle impact assessment (LCIA), ‘panel methods’ has become a common term to denominate methods that elicit and measure stakeholders’ stated preferences on environmental impact categories. Such panel procedures use different question formats to elicit information on weighting across impact categories from the stakeholders. The two most frequently used question formats are score allocation and choice between alternatives. The differences between these two question formats were analyzed in order to give advice on how to frame future panel procedures. Materials and methods  A choice-based weighting procedure (choice experiment) for the three damage categories of human health, ecosystems quality, and resources was developed and executed. A logistic regression model was applied in order to estimate the weighting factors for the polled sample. Results from this choice-based procedure were compared to the results from an allocation-based procedure described in part 1 of this paper. Results  When weighting factors are elicited by score allocation questions, panelists tend to distribute the scores more equally. A factor of 1.5 between the least and the most weighted damage category was found. Weighting factors from a choice experiment were more spread, i.e., the most important category was weighted considerably higher, whereas the other two categories were weighted less. Thus, for the choice experiment, the range between the most and the least weighted categories was considerably bigger—by about a factor of 4. Discussion  A comparison of the two procedures revealed that the weighting of environmental damage categories is considerably influenced by the question of format. The reason for these variations may be different cognitive routines that are applied. In addition, several advantages and shortcomings of choice experiments are discussed. Conclusions  The developed, choice-based procedure provided meaningful results. Thus, choice experiments, often used for the monetary valuation of environmental goods, can also be applied in LCIA to elicit nonmonetary weighting factors. Recommendations and perspectives  Choice experiments form a new interesting approach for weighting procedures in the future as they have some advantages over the often used score allocation methods. They are simple and more realistic than other procedures, as panelists have practiced in choice tasks from everyday life. We, therefore, recommend such choice-based procedures for future panel studies.

Environment-sensitive epigenetics and the heritability of complex diseases

Genome-wide association studies have thus far failed to explain the observed heritability of complex human diseases. This is referred to as the "missing heritability" problem. However, these analyses have usually neglected to consider a role for epigenetic variation, which has been associated with many human diseases. We extend models of epigenetic inheritance to investigate whether environment-sensitive epigenetic modifications of DNA might explain observed patterns of familial aggregation. We find that variation in epigenetic state and environmental state can result in highly heritable phenotypes through a combination of epigenetic and environmental inheritance. These two inheritance processes together can produce familial covariances significantly higher than those predicted by models of purely epigenetic inheritance and similar to those expected from genetic effects. The results suggest that epigenetic variation, inherited both directly and through shared environmental effects, may make a key contribution to the missing heritability.     

The Fiftieth Anniversary of Soviet Psychophysiology

It must be generally recognized today that areas "contiguous" to a particular science have great theoretical and practical importance, which arises during contact of various sciences in some important objective. This is particularly true with respect to such a complex research objective as the thinking human brain. We find the ancients already beginning to speculate about the question of the relation of the "soul" to the body and about which body organ has the closest relation to psychological activity. Gradually this question became more concrete and was broken down into a group of more particular problems on which many scholars have been working. The early "classical" psychophysiology was primarily concerned with study of the relation of the senses and perception to the physical properties of stimuli and to the anatomical-physiological apparatuses of the peripheral sense organs. Currently, the main emphasis is shifting more and more to a study of the central mechanisms of psychological processes. This fundamental shift in approach to the traditional "psychophysical" problem (now frequently referred to as the psychophysiological problem) first took place in the area of studying the mechanisms of association, and was subsequently spread over studies of perception, emotion, voluntary movements, cognitive processes, and, finally, individual psychological differences.     

The quantal theory of immunity

Exactly how the immune system discriminates between all environmental antigens to which it reacts vs. all selfantigens to which it does not, is a principal unanswered question in immunology. As set forth in this review, because of the advances in our understanding of the immune system that have occurred in the last 50 years, for the first time it is possible to formulate a new theory, termed the ＂Quantal Theory of Immunity＂, which reduces the problem from the immune system as a whole, to the individual cells comprising the system, and finally to a molecular explanation as to how the system behaves as it does.     

Animals as Sentinels of Human Environmental Health Hazards: An Evidence-Based Analysis

Despite recognition that animals could be serving as sentinels for environmental risks to human health, there are no evidence-based guidelines for the use of animal sentinel data in human health decision making. We performed a systematic review of the animal sentinel literature to assess the evidence linking such events to human health. A search of MEDLINE identified peer-reviewed original studies of animals as sentinels for either chemical or biological environmental hazards. A limited search of the CAB and AGRICOLA databases was also performed. We classified a random sample of 100 studies from the MEDLINE search according to species, hazard, and health outcome examined; study methods; and linkages to human health. Animal sentinel studies were difficult to locate in MEDLINE because of a lack of adequate key words for this concept. We found significant limitations in the study methods used to investigate animal sentinel events. Clear linkages to human health were frequently absent. Studies of sentinel events in animal populations hold potential for the recognition and control of human environmental health hazards, yet a number of barriers exist to using such data for evidence-based human health decisions. There is a need for greater data sharing and cooperative research between human and animal health professionals regarding environmental hazards and health outcomes in animal and human populations.     

Beyond "the State" and Failed Schemes

In this article, I propose five ways to move beyond the analytical scheme of James Scott's Seeing Like a State (1998). I question the spatial optic that posits an "up there," all-seeing state operating as a preformed repository of power, spread progressively outward to "nonstate" spaces beyond its reach. I highlight the role of parties beyond "the state" that attempt to govern—social reformers, scientists, and the so-called nongovernmental agencies, among others. I look beyond authoritarian high modernism to the more general problematic of "improvement" emerging from a governmental rationality focused on the welfare of populations. I explore the recourse to mētis (contextualized, local knowledge and practice) situated beyond the purview of planning. Finally, I reframe the question posed by Scott—why have certain schemes designed to improve the human condition failed?—to examine the question posed so provocatively by James Ferguson: What do these schemes do? What are their messy, contradictory, conjunctural effects?     

Trends in the perception of ecological problems in the United Nations general debates

To what extent have recent warnings of deepening ecological problems become topics of discussion among international political elites? To address this question a content analysis was undertaken of the speeches comprising the general debates of the 1968, 1972, and 1976 sessions of the UN General Assembly to identify all instances in which ecological issues were mentioned. Despite other indications of an increase in environmental consciousness in the international community, it was found that ecological problems have not been discussed very extensively in the general debates and are far less salient than several other agenda items for which data were also collected. Moreover, the environment peaked as an issue in the 1972 session and declined in prominence in 1976. It was also found that the more developed a country is, the greater the tendency for its delegates to mention environmental problems in their speeches. The lack of prominence of ecological issues is interpreted on the basis of two alternative assumptions: first, that the degree of international awareness of environmental problems is not adequately represented in the general debates and, second, that the findings accurately reflect what is generally a low level of environmental concern in international circles.     

Is it possible to use the honey bee adult as a bioindicator for the detection of pesticide residues in plants?

Pesticide residues are usually determined by physical, chemical and biological methods. The simplicity and adaptability of bioassay methods have won their acceptance in the field of residue analysis. Theoretically, any organism that is susceptible to a pesticide may be used for its bioassay in any environmental sample. This means that such organism may serve as a bioindicator for the detection of certain pollutants. The susceptibility of honey bees (Apis melifera L.) to many insecticides commonly used in crop protection led to an attempt to use it as a bioindicator for the determination of residues of some insecticides in plant materials, as well as to detect toxicity hazards to honey bees of some commonly used insecticides. Results of this work which have been recently published may suggest "Yes" to answer the question posed in the title of this subject.     

Perceptions,paradigms and ethics: A perspective on the social context of environmental issues

The rapid evolution in public perceptions and understandings of environmental issues in Canada has evolved to the point where today such issues are beginning to be seen as cultural issues. The array of environmental and other societal problems is bringing into question the taken-for-granted assumptions or the worldview of cultural paradigm common to all industrialized countries. Many social analysts are suggesting that these problems are inherent in the industrial worldview and can therefore only be resolved by moving onward to another way of making sense of the world around us, and that elements of a new paradigm appear to be emerging. The major characteristics of the industrial worldview are described, and those of an emerging alternate worldview are sketched. Part of this societal questioning is evidenced in a resurgence of interest in environmental ethics but, except for deep ecology, this debate has yet to be linked to the broader discussion of shifting cultural paradigms. The changing social context suggests that there are opportunities to use different policy instruments than regulation that would prevent the occurence of environmental damage in the first place. It also suggests that the active involvement of thoughtful and responsible citizens is essential if the current period of questioning is to lead to a society that is sound and dynamic in ecological and human terms.     

Planet of the apes

What makes us humans so special? Our language, our genes, our culture, our cognitive skills? At the Max-Planck-Institute for Evolutionary Anthropology in Leipzig, psychologists, linguists and biologists tackle this old question in a truly multidisciplinary way. Their results have implications not just for our understanding of human evolution – they also touch directly on many social and environmental issues. Florian Maderspacher reports.     

Microbial rights?

Our ability to disrupt habitats and manipulate living organisms requires a discussion of the ethics of microbiology, even if we argue that microbes themselves have no rights.Synthetic biology and the increasing complexity of molecular biology have brought us to the stage at which we can synthesize new microorganisms. This has generated pressing questions about whether these new organisms have any place in our system of ethics and how we should treat them.The idea that microbes might have some moral claims on us beyond their practical uses or instrumental value is not a new question. Microbiologist Bernard Dixon (1976) presciently asked whether it was ethical to take the smallpox virus to extinction at the height of the attempts of the World Health Organization in the 1970s to eradicate it. There is no unambiguous answer. Today, we might still ask this question, but we might extend it to ask whether the destruction or extinction of a synthetic microbe that was made by humans is also ethically questionable or is such an entity—in that it is designed—more like a machine, which we have no compunction in terminating? Would two lethal pathogens, one of them synthetic and one of them natural, but otherwise identical, command the same moral claims?In a colloquial way, we might ask whether microbes have rights. In previous papers (Cockell, 2004) I have discussed the ‘rights'' of microbes and further explored some issues about the ethics we apply to them (Cockell, 2008). Julian Davies, in a recent opinion article in EMBO reports (Davies, 2010) described my assertion that they should have constitutional rights as ‘ridiculous''. Although I did suggest that environmental law could be changed to recognize the protection of microbial ecosystems—which would imply statutory rights or protection—nowhere have I claimed that microbes should have ‘constitutional'' rights. Nevertheless, this misattribution provides a useful demonstration of the confusion that exists about exactly how we should treat microbes.Few people are in any doubt that microbes should be conserved for their direct uses to humans, for example, in food and drug production, and their indirect uses such as the crucial role they have in the health of ecosystems. Indeed, these motivations can be used to prioritize microbial conservation and protection efforts (Cockell & Jones, 2009). The crucial question is whether microbes have ‘intrinsic value'' beyond their practical uses. If the answer is ‘no'', then we should have no guilt about deliberately driving microbes to extinction for our benefit. However, there are people who feel uneasy with this conclusion, a feeling that calls forth more complex ethical questions.The question is whether microbes have some sort of ‘interests'' that make demands on our treatment of them that go beyond a mere utilitarian calculation. These arguments themselves question what we define as ‘interests'' and whether interests make demands on us. A microbe has no future plans or thought processes; the sorts of interests that are accepted as being of sufficient scope to place demands on our treatment of other human beings, for instance. However, microbes do have biological interests. A halophilic microbe might eventually die if it is dropped into freshwater. Does our knowledge of what is in the biological interests of a microbe mean that we must show it any consideration beyond practical uses? The answer is not obviously negative (Taylor, 1981), but even if we decide that it is, this does not let us off the hook quite yet.There are other intrinsic value arguments that are more obscure, particularly those around the notion of ‘respect''; the idea that we should show empathy towards the trajectory, however deterministic, of other life forms. These unquantifiable and controversial arguments might, nevertheless, partly explain any unease that we have in watching a group of people smash up and destroy some exquisite microbial mats, just because they were bored.Clearly, human instrumental needs do trump microbes at some level. If they did not, we could not use bleach in our houses, an absurd end-point raised in a 1970s science fiction story that explored the futuristic ramifications of full microbial rights, in which household bleaches and deodorants are banned (Patrouch, 1977).However, we should not be so quick to ridicule ideas about microbial ethics and rights. Although it might be true that phages kill a large percentage of the bacterial population of the world every few days, as Julian Davies points out, human society has achieved an unprecedented capacity for destruction and creation. Our ability to poison and disrupt habitats has been unquantified, with respect to the loss of microbial species. Both synthetic biology and bioterrorism raise the spectre of creating new organisms, including pathogens, which we might need to control or deliberately pursue to extinction. Dixon''s dilemma about the smallpox virus, raised more than 30 years ago, has become an urgent point of discussion in the ethics of molecular biology and microbiology.     

Endocrine modulation and the fragile balance of homeostasis--an overview

Endocrine modulation by natural and synthetic chemicals and the eventually resulting beneficial or adverse effects for human and animal health are controversially debated not only among scientists but particularly in the public. Most information is available on so-called environmental estrogens, however the amount of information on substances interfering with other hormonal axes steadily increases, particularly on those exhibiting (anti)androgenic activities. The aim of this paper is to summarize existing data and to give an overview on the potential pathways leading to interferences of environmental hormones with homeostasis and eventually resulting health effects. Experimental evidence suggests the hypothesis that fetal and neonatal organisms may be at risk if exposed to environmental estrogens. In contrary, it appears as if phytoestrogens, particularly those with selective estrogen receptor modulator- (SERM-)like activities have the potential to be useful in medical application, both as dietary means and as pharmaceuticals. Lacking valid information about the detailed analysis of the molecular mode of action for environmental estrogens, the possibility for an ultimate classification of environmental estrogens in "dangerous endocrine disruptors" and phytoestrogens in "useful pharmaceuticals" cannot be supported conclusively. Nevertheless both activities are likely.     

Human enterobiasis in evolution: origin, specificity and transmission.

The co-evolutionary pathway seems to be the most plausible hypothesis for the explanation of the origin of human pinworms. Of the two modes of transmission of oxyurids among humans which have been documented, the direct oral/anal route is also observed in other Primates and seems to have been favoured by selection. As indirect air-borne transmission has also been shown for human enterobiasis, the question of "How this alternative to the standard transmission method could have arisen" is examined. The results of comparative studies of prevalence of Enterobius in human coprolites, in villages of Neolithic age of the arid west of North America, show that a higher prevalence of pinworms is correlated with the lower total amount of air-exchange in caves relative to other structures. The air-borne route of transmission of pinworms among humans is interpreted as an innovation in the human/Enterobius pair. This mode of transfer could have been favoured during the time when humans changed their behaviour from a hunting-gathering to a more sedentary existence, initially associated with cave habitats.     

Human obesity: toward functional genomics

Genetic and environmental aspects are recognized in the obesity field and attempts to elucidate multiple genes and gene/environment interactions are necessary. In rare cases of monogenic obesities, genetic tools have proved extremely powerful for identifying the genes responsible and for defining new syndromes. Abnormalities of genes involved in the leptin/melanocortin axis have been described. In common obesity, most studies include the search for genotype/phenotype associations without taking into account the influence of environment (diet, sedentary lifestyle) in the relationship. Many genes and candidate regions have been proposed to be involved in the determinism of human obesity. Among the limitations to this integrated approach, one can cite the difficulty of having large enough samples as well as biocomputing tools that are still in their infancy for accessing the question of multiple interactions with no "a priori hypotheses". This picture will probably change rapidly in the future. The purpose of this paper is to present some examples of the knowledge acquired in the field of obesity genetics and the new ongoing tools and developments that aim at studying the contribution of genes to obesity and their response to environmental changes. The capacity for studying multiple genes at once at the DNA or RNA levels is rapidly growing. Finally, tremendous progress in biocomputing will allow the integration of information from different sources (i.e. environment, phenotype, genotype, gene expression) and thus improve our ability to deal with complexity. Examples of these approaches exist in humans and in animal models.