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Show Summary Details. Subscriber Login Email Address. Password Please enter your Password. Library Card Please enter your library card number. Promiscuous individualism thus seems to imply that there are many, many different numbers of individuals present in this paradigm case.
But what of these and kindred concepts -- biological individual, organism, living thing, life -- themselves? Like pluralism about species, an interesting pluralism about these biological phenomena needs to be more than some kind of disjunctivism about the corresponding concept. For example, while they rightly point to problems in identifying the exact physical boundaries for individual biological entities as a reason to question whether that criterion is strictly necessary, they appear to take the ability to reproduce to be a necessary condition for being a living thing pp.
In addition, reproduction and metabolism, as central as they are to their view of living things, remain largely unexplained, despite the attention they have received in the work of others, such as James Griesemer and Peter Godfrey-Smith. Even in the space of this short sentence, a number of questions arise.
First, why should we think that there is such a single entity at all, especially if we are proponents of promiscuous individualism? Second, what is the concept of an organism that would support the view that this entity is an organism? For a pluralist, the same question could be asked of the various entities that make use of this communal resource.
Yet this does not obviate but instead highlights the need for some more sustained, positive discussion of what organisms are. When he says that "functioning biological individuals are typically symbiotic wholes involving many organisms of radically different kinds" p. But he is reluctant, perhaps consistently so given his promiscuous individualism, to embrace the idea that there is a single criterion, or set of criteria, that the concept of an organism answers to.
The tension that exists between this reluctance and the defence of particular claims about organisms e.
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The scientific community could collectively decide that such irreproducible inferences are part of progress — each one a potential impetus for a paradigm shift Kuhn, to be eventually realized by some discerning scientist s. Alternatively, we could explore ways to reduce the time and resources spent taking such missteps.
In either case, having an explicit overview of the basis for the overall inferences and conclusions drawn in a study could clarify the next experiments and stimulate exploration of alternative inferences. Currently, inferences are discussed in the introduction and discussion sections of papers: however, it would be much better if papers included explicit statements about the rationales for the inferences drawn by the authors as is currently done for experimental methods and statistical analyses.
This could be done in a relatively straightforward manner by adding two elements to the methods section of a paper: i an explicit statement of the prevailing paradigm or prior model as understood by the authors; ii a summary of the basis for any proposed modification of the model in plain language for example, 'Inferences for the proposed model were drawn based on a perturbation approach using two techniques with distinct caveats and a visualization approach using one technique'. Finally, a common taxonomy of approaches with acknowledged limitations, refined through periodic debates, could help outsiders develop their own critical overviews of progress in a field and help the next generation of scientists decide on their future research directions.
Authors and reviewers debate about methods, results, and inferences during peer review. In such debates, the approaches outlined in this article could provide a common context for articulating strengths and weaknesses. Such structured evaluation could benefit both peer review of a particular study and review articles that appraise a field to identify areas of future development. Since all doubt about the conclusions of any study cannot be eliminated, a commonly agreed upon level of support for claims is needed.
For example, it would be unreasonable to expect any study to include experiments from all six approaches. Moreover, since a study that uses a single experimental approach well could be better than a study that uses two or more approaches poorly, statements about quantity and quality need to be developed.
Such explicit statements about the acceptable level of doubt for publication in a particular journal, or for receiving a grant from a particular funding agency, could guide reviewers and authors through the process of peer review.
Peer review by journals or funding agencies also involves estimating the impact of the study. Since the ultimate value of any study is established through follow up work by the community at large, any estimate of potential impact made during peer review is at best an educated guess influenced by prevailing paradigms Park et al.
Furthermore, despite agreeing upon a common level of support for claims, there can be disagreements because of subjective interpretations for example, see Keeling et al. This subjectivity is underscored by studies on grant review that document low agreement when different panels judge the same proposal Pier et al. Given all this, being more specific about the paradigms involved in a paper or grant application — both in the paper or application itself, and during the review and assessment of the paper or application — should lead to better decisions being made.
Experiments are underway on the process of peer review Rennie, ; Rodgers, ; Polka et al. These exchanges are typically between experts and can be more abstruse than the paper being reviewed, making it difficult for the interested reader to decipher. One solution is to provide a summary of the discussion as is already done by some funding agencies. The editor of a manuscript could guide readers by summarizing the major points of debate during its review: ideally, this summary would be written in plain language e.
The exchanges that take place between authors and reviewers during peer review provide a genuine opportunity for readers to learn about the process of science. Biologists are engaged in understanding living systems through experimental and theoretical efforts in many subdisciplines. Placing new advances in the context of overall progress in biology can be challenging because of the dazzling variety and sophistication of techniques used. The six complementary approaches presented here provide a scaffold for classifying techniques and contextualizing discoveries.
Appreciating the scope and limitations of each approach could improve how inferences are drawn and how studies are reviewed. Together, better inference and better review could promote the realistic appraisal of discoveries and limit persistent illusions of knowledge. In the interests of transparency, eLife publishes the most substantive revision requests and the accompanying author responses.
Thank you for submitting your article "Knowledge and illusions when using the complementary approaches needed to understand living systems" to eLife for consideration as a Features Article. Your article has been reviewed by three peer reviewers, and I am writing to invite you to revise the article in response to the comments of these reviewers. The points that need to be addressed in the report of reviewer 1 are clear to see. In the report from reviewer 2, please address the points in the second and fourth paragraphs; please also take on board the comments in the third paragraph about making the article more readable but also note that if the article is accepted for publication, it will be edited for readability and clarity.
As regards the report from reviewer 3, it may be difficult to answer the questions in the second paragraph, but addressing the points raised by reviewer 1 will help to address some of these concerns. This Essay addresses methodological and philosophical aspects of Biology broadly conceived.
The author asks important questions, including "How is an outsider to evaluate [biologists'] progress? This and a number of other important meta-scientific questions, including reproducibility and fairness of review, are discussed.
Overall this is an important approach and I think will be valuable, but it seems a little thin on actionable suggestions except for the good and novel idea to be explicit in papers about inference and method with respect to a common taxonomy , or on deep insights that hadn't been made in longer pieces in the past admittedly, in journals that few biologists read. I suggest some points which will increase value for readers. The title might use a little work - I'm not sure everyone will understand the meaning of "illusions" without having read the paper first , but it may draw people in so perhaps it's fine.
Overall I find the arguments convincing. A few minor comments:. Overall I suggest that the Perturbation section not be exclusively focused on genetics, as this is just one of the perturbational tools in the biologists' toolbox. It's too narrowly conceived as written, to match the title of the piece which refers to "living systems" i.
I think if the author wants to stick to this level of analysis, the title might need to be made more specific - right now, it promises a more comprehensive view of biology. Lots of aspects of visualizing systems on the anatomical, metabolic, neurobiological, behavioral, and population levels are not even mentioned here.
The author is right to focus some spotlight on exploratory analyses, which are often hidden in favor of 'hard inference' storytelling, but not much is said here about what to do about this. Overall, the task of trying to systematize biology in these ways is valuable and I applaud the author for taking this on. However, as written, it's very narrowly construed and I'm not sure it provides the insights for all of Biology that the introductory text suggests, or that eLife readers will want.
One way to resolve this is to put "Molecular Biology" or similar in the title, and simply decide that this will be only about that level of investigation. On the other hand, if there is room, I would be happier to see a bigger piece that lived up to the much more fundamental and inclusive aim suggested in the Abstract: "acquire knowledge about living systems". As it is now, it's far too narrow for that as large a goal as that is.
I have found this a very difficult paper to review. Normally as a reviewer I try to assess the extent to which the methodology and results are rigorous and whether the underpinning literature is treated with appropriate scholarship, then whether the conclusions are justified or at least the speculations reasonable based on the information presented.
But this manuscript is not a scientific paper but an essay on epistemology, therefore an "opinion" piece. Therefore I cannot use my usual method to assess it. I can only answer with more "opinion" and I generally shy away from doing this as this is the realm of religion and politics, not Science.
Overall I do feel that this piece does raise some interesting points that are worthy of further discussion and consideration by many scientists. I am not sure I agree that this is a definitive classification of approaches for example simple "description" of the system at a chosen level or levels is not obviously included and many studies start this way, and there are various types of theoretical model building that are not easily included under "simulation" but the six chosen ones for functional analysis are common ones.
Whether this is the type of paper that eLife wants to publish, and under what heading, is a matter for the editors. I think it belongs more as an editorial in a journal like Nature or Science, or perhaps as an Essay in BioEssays or similar. In either case it needs to be written much more fluidly to make it more attractive and accessible to experimental scientists who are not otherwise inclined to think about these bigger philosophical and epistemological issues.
I find this quite difficult to read even as someone who has been thinking about these issues for some time. I don't like the proscriptive tone in relation to what reviewers should do - it gives an unnecessarily arrogant tone to the essay. While it is true that being aware of the strengths and limitations of particular types of approaches is essential to determine whether the conclusions of a set of experiments are justified, there are many different ways for reviewers to achieve this and this six-part classification is too rigid a framework to advocate for general use.
I think the paper would gain if the comments about peer review were removed. Where this classification or other ways of evaluating evidence and conclusions is probably particularly important is in the writing of reviews that synthesize the work of a number of papers in a field - many reviews are not sufficiently analytical or integrative and therefore often fail to undertake a critical evaluation that could allow readers to see the strengths and limitations of different studies more clearly.
This is an unusual paper for me to review and I offer my reactions to it — I am not sure whether what I have to say is in any objective way right or wrong. The author makes some interesting observations about how scientists use perturbation, visualization, substitution, characterization, reconstitution, and simulation of some aspect of a living system in an effort try to understand how it works. The author emphasizes how each of these approaches in isolation, coupled with sociological norms of scientists have contributed to erroneous or misleading conclusions, usually using one spectacular example to make the point for each approach in this essay.
Its not clear to what degree these examples are representative of the broader life science enterprise, though its clear they have played a role in sustaining some misconceptions for a long time. Is there some way in which the significance and frequency of examples used can be put into perspective?
The issues the author raises are certainly worth considering, and an essay that brings them to the reader's attention is important. However, it is not clear how effective the suggested solution of explicitly spelling out the assumed paradigm will be.
Other suggestions for the editor in capturing the discussions and making this a more transparent process are good — and already standard practice for eLife! Communicating more of the backstory behind a study including the blind alleys, alternate hypotheses and sometimes accidental discovery of the appropriate framework would also be helpful and interesting. Most scientists are quite aware of the contrived nature of the narrative that is often created to make a concise slick paper with few unresolved open questions.
Have space limitations and the perceived desires of some "premier" journals at least in the past played some role in encouraging the evolution of this contrived narrative? Perhaps digital publishing provides the opportunity to more easily respond to the issues emphasized in this essay, with opportunities to provide transparency and multiple opportunities to dig deeper through supplementary material into the back story, alternative hypotheses, statistical analysis etc.
I thank the reviewer for the positive words and for endorsing explicit inclusion of statements about inferences in the Methods section. Where possible, I have made suggestions for how one might address problems.
However, it is possible that some problems are not easily solvable at the present time potentially because of underdeveloped methods e. In such cases, I have merely drawn attention to the problem and highlighted the current difficulty. Editor's note: The title was later changed to: "The analysis of living systems can generate both knowledge and illusions". Collectively, the comments below suggest an expansion of the scope of the article to include the analysis of living systems on multiple scales.
Although the taxonomy can apply across multiple scales reason for representing living systems as an abstract network in Figure 1 , the previous version did not highlight this aspect and was focused on a single scale - molecular - for simplicity. I have now highlighted the multi-scale nature of the proposed taxonomy during the early part of the article and provided specific examples to address other scales throughout the article as suggested by the reviewer.
I thank the reviewer for pointing out this error. This statement was meant to draw attention to the prior conception of the living system that is necessary to infer what a perturbed outcome means or indeed that a perturbation has occurred. I have now expanded upon the statement to make the intended meaning clearer. I have also included some examples of the different kinds of perturbation suggested by the reviewer and illustrated the particular prior conceptions that impact the inference after a perturbation experiment.
For example, in the famous Spemann and Mangold experiments on the organizer in embryology, interpreting the results requires the idea that a piece of embryonic tissue could be the source of unknown factors that help pattern the entire embryo. Modern screening selects for particular perturbed outcomes based on the prior expectation of what a perturbed system of interest would look like or that a particular manipulation is a perturbation, which sometimes lead to unexpected outcomes.
A prominent recent case that highlights this problem is the disagreement between morpholino-based perturbations and Casmediated genome editing in Zebrafish Kok et al. Cell , , some of which is currently thought to be explained by transcriptional adaptation Ma et al. I have now used examples from multiple scales to illustrate the kinds of visualizations that are possible and the kinds of limitation that can confound inference.
For example, at the anatomical scale, limitations in the resolution of measurement combined with preconceptions promoted by prevailing theories can result in missed features of the system — e. At the population scale, difficulties in counting a particular species can distort the deduced composition and trophic relationships in an ecosystem.
At the behavioral level, inability to visualize aspects of behavior can result in profound misconceptions about an organism. For example, recent ability to see animal behavior at night in the wild without perturbation is changing our understanding of land animals. In the deep ocean, recent ability to image without perturbation has revealed light-based communication in benthic organisms.
I have now expanded this section to include reconstitution on additional scales. For example, human embryos can be formed from sperm and egg in vitro Edwards, et al. The complications introduced by the conflation of exploratory and confirmatory research when story telling is emphasized require a deeper analysis and debate by the scientific community that are beyond the scope of this article.
Unfortunately, a facile solution for this problem may not be available. Nevertheless, widespread awareness of the problem is the starting point for collectively working towards a solution. Therefore, the primary goals of this article remain to introduce a unified classification of approaches to understand living systems and invite the scientific community to debate the ways to implement such system-level and meta-scientific thinking to improve the practice of science.
I have now expanded the scope of the article to highlight the application of the taxonomy to additional scales and included illustrative examples across scales throughout the article. As noted by reviewer 1, this article addresses methodological and philosophical aspects of science, particularly as it applies to understanding living systems.
The spirit of the article is in keeping with the belief that philosophical considerations can have practical uses for science e. Methodologically, this article develops an overarching classification and invites future debates about such overall classifications. Philosophically, this article highlights the ever present unknown unknown when using any approach that can cast doubt over the most ardently held knowns.
As stated in the article, future periodic debates about the classification would help enrich and sharpen our understanding of the methods we have and will acquire. For example, when describing an ecosystem, we count the number of organisms, look at their shape, size and any other characteristics that we can see using the naked eye or using additional instruments.
I have strived to simplify sentences throughout the manuscript and appreciate the editorial help offered by the journal for improving clarity and readability. I hope that these efforts make the article more engaging. The intent of the suggestions is not to be proscriptive, but rather to add a specific suggestion that can either be taken on or ignored after debating its merits. I have now reworded the section to mitigate any perceived arrogance in tone.
As highlighted in the article, the process of peer review is currently undergoing a lot of experimentation and this suggestion adds to the debate on the best way to achieve peer review, which in my opinion is an invaluable part of science. I agree with the excellent opinion of the reviewer that this classification would help with the writing of more analytical and integrative reviews, and the revised manuscript now includes a sentence to highlight this use in the peer review section.
This is an unusual paper for me to review and I offer my reactions to it-I not sure whether what I have to say is in any objective way right or wrong. The reviewer raises an excellent and difficult question, answering which requires extensive study that is beyond the scope of this article. Specifically, the answer needs a comprehensive historical and predictive?
Evaluation of the frequency is being made all the more difficult by the growing volume of scientific literature. In the revised version of the article, application of the taxonomy to additional scales and subdisciplines are highlighted in an effort to underscore the broad use of such a taxonomy of methods across the life sciences and perhaps all sciences.
Other suggestions for the editor in capturing the discussions and making this a more transparent process are good -and already standard practice for eLife! Often these remain unstated and could result in quests for concepts and entities that may not exist — historical examples include the search for luminiferous ether as the medium transmitting light and phlogiston as the carrier of heat.
Nevertheless, the suggestions presented in the article are starting points for future debate. The primary goal of the article is to bring attention to these issues that impact how science is done, presented, and evaluated. Unlike eLife , many journals do not yet have active summaries of the review process by the editors. I hope the arguments presented in this article add to those presented elsewhere to aid wider adoption of this practice.
I agree with the reviewer that digital publishing can facilitate the clear declaration of the often tortuous route to discovery. However, our collective inability to evaluate the statistical rigor of the inferences in the study would remain. The article therefore highlights this difficulty to invite debate on the most productive courses of action for the scientific community. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
I thank Tom Kocher, Karen Carleton, Charles Delwiche, and members of the Jose lab for long discussions; and Tom Kocher, Karen Carleton, members of the Jose lab, the editor and the reviewers for their comments on the manuscript. This article is distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use and redistribution provided that the original author and source are credited.
Article citation count generated by polling the highest count across the following sources: Crossref , PubMed Central , Scopus. Immune challenges demand the gearing up of basal hematopoiesis to combat infection. Little is known about how during development, this switch is achieved to take care of the insult. During development, Relish is triggered by ecdysone signaling in the hematopoietic niche to maintain the blood progenitors.
Loss of Relish causes an alteration in the cytoskeletal architecture of the niche cells in a Jun Kinase dependent manner, resulting in the trapping of Hh implicated in progenitor maintenance. Notably, during infection, downregulation of Relish in the niche tilts the maintenance program towards precocious differentiation, thereby bolstering the cellular arm of the immune response.
The spatiotemporal distribution of mitochondria is crucial for precise ATP provision and calcium buffering required to support neuronal signaling. The importance for correct trafficking and precise mitochondrial positioning remains poorly elucidated in inhibitory neurons. Cited 1 Views 6, Annotations Open annotations. The current annotation count on this page is being calculated.
Cite this article as: eLife ;9:e doi: Article Figures and data Abstract Introduction Six approaches for analyzing living systems on multiple scales Potential applications Conclusion Data availability References Decision letter Author response Article and author information Metrics. It transcends in scope and depth any available publications on bioinformation known to me. It is an important scholarly contribution that will interest professional biologists, philosophers, and information theorists, and will be very useful in courses for advanced undergraduate and graduate students.
Since the s at least, it has become clear that we cannot content ourselves with describing living systems, and their life cycles, only in terms of matter and energy. An additional dimension—information—is the necessary complement. However, following an initial enthusiasm for an information-based approach to biology, conceptual developments and practical applications have been slow, to such an extent that doubts have eventually arisen, among biologists and philosophers alike, as to the real relevance, if not the legitimacy, of this approach.
How profoundly ill-advised were those concerns is dramatically demonstrated by this excellent collection. Information and Living Systems provides a convincing and healthily fresh overview of this subject area in many of its ramifications, throughout the whole of biology. Terzis and Arp have brought together an international array of experimental and theoretical scientists, philosophers, and cognitive scientists to explore the most consequential notion in modern biology—information.
The notion is indispensable to molecular biology, and yet we have no idea how seriously we need to take it in that domain. The role of information is equally central to the origin and maintenance of life in a Second Law-driven world that destroys order. And the naturalization of information is the only bridge that can be crossed from cognitive psychology to neuroscience. All of these issues are faced squarely and accessibly in this important volume.
This volume has the virtue of airing a number of refreshing voices that are not often heard on this side of the Atlantic, and that bring perspectives that should energize our conversations about information in living systems. Search Search. Search Advanced Search close Close. Information and Living Systems Philosophical and Scientific Perspectives Edited by George Terzis and Robert Arp The informational nature of biological organization, at levels from the genetic and epigenetic to the cognitive and linguistic.
Add to Cart Buying Options. Request Permissions Exam copy. Overview Author s Praise. Summary The informational nature of biological organization, at levels from the genetic and epigenetic to the cognitive and linguistic. April Share Share Share email. Robert Arp Robert Arp is a researcher and analyst for the U.
Army at Fort Leavenworth, Kansas, who has worked on ontologies for the U.