essay on experimental animals

Ethical care for research animals

WHY ANIMAL RESEARCH?

The use of animals in some forms of biomedical research remains essential to the discovery of the causes, diagnoses, and treatment of disease and suffering in humans and in animals., stanford shares the public's concern for laboratory research animals..

Many people have questions about animal testing ethics and the animal testing debate. We take our responsibility for the ethical treatment of animals in medical research very seriously. At Stanford, we emphasize that the humane care of laboratory animals is essential, both ethically and scientifically.  Poor animal care is not good science. If animals are not well-treated, the science and knowledge they produce is not trustworthy and cannot be replicated, an important hallmark of the scientific method .

There are several reasons why the use of animals is critical for biomedical research: 

••  Animals are biologically very similar to humans. In fact, mice share more than 98% DNA with us!

••  Animals are susceptible to many of the same health problems as humans – cancer, diabetes, heart disease, etc.

••  With a shorter life cycle than humans, animal models can be studied throughout their whole life span and across several generations, a critical element in understanding how a disease processes and how it interacts with a whole, living biological system.

The ethics of animal experimentation

Nothing so far has been discovered that can be a substitute for the complex functions of a living, breathing, whole-organ system with pulmonary and circulatory structures like those in humans. Until such a discovery, animals must continue to play a critical role in helping researchers test potential new drugs and medical treatments for effectiveness and safety, and in identifying any undesired or dangerous side effects, such as infertility, birth defects, liver damage, toxicity, or cancer-causing potential.

U.S. federal laws require that non-human animal research occur to show the safety and efficacy of new treatments before any human research will be allowed to be conducted.  Not only do we humans benefit from this research and testing, but hundreds of drugs and treatments developed for human use are now routinely used in veterinary clinics as well, helping animals live longer, healthier lives.

It is important to stress that 95% of all animals necessary for biomedical research in the United States are rodents – rats and mice especially bred for laboratory use – and that animals are only one part of the larger process of biomedical research.

Our researchers are strong supporters of animal welfare and view their work with animals in biomedical research as a privilege.

Stanford researchers are obligated to ensure the well-being of all animals in their care..

Stanford researchers are obligated to ensure the well-being of animals in their care, in strict adherence to the highest standards, and in accordance with federal and state laws, regulatory guidelines, and humane principles. They are also obligated to continuously update their animal-care practices based on the newest information and findings in the fields of laboratory animal care and husbandry.  

Researchers requesting use of animal models at Stanford must have their research proposals reviewed by a federally mandated committee that includes two independent community members.  It is only with this committee’s approval that research can begin. We at Stanford are dedicated to refining, reducing, and replacing animals in research whenever possible, and to using alternative methods (cell and tissue cultures, computer simulations, etc.) instead of or before animal studies are ever conducted.

Organizations and Resources

There are many outreach and advocacy organizations in the field of biomedical research.

• Learn more about outreach and advocacy organizations

Stanford Discoveries

What are the benefits of using animals in research? Stanford researchers have made many important human and animal life-saving discoveries through their work. 

• Learn more about research discoveries at Stanford

Animal experimentation: A look into ethics, welfare and alternative methods

• November 2017
• Revista da Associação Médica Brasileira 63(11):923-928
• 63(11):923-928

• Universidade Federal de Goiás

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A guide to open science practices for animal research

Contributed equally to this work with: Kai Diederich, Kathrin Schmitt

Affiliation German Federal Institute for Risk Assessment, German Centre for the Protection of Laboratory Animals (Bf3R), Berlin, Germany

* E-mail: [email protected]

• Kai Diederich, 
• Kathrin Schmitt, 
• Philipp Schwedhelm, 
• Bettina Bert, 
• Céline Heinl

Published: September 15, 2022

• https://doi.org/10.1371/journal.pbio.3001810
• Reader Comments

Translational biomedical research relies on animal experiments and provides the underlying proof of practice for clinical trials, which places an increased duty of care on translational researchers to derive the maximum possible output from every experiment performed. The implementation of open science practices has the potential to initiate a change in research culture that could improve the transparency and quality of translational research in general, as well as increasing the audience and scientific reach of published research. However, open science has become a buzzword in the scientific community that can often miss mark when it comes to practical implementation. In this Essay, we provide a guide to open science practices that can be applied throughout the research process, from study design, through data collection and analysis, to publication and dissemination, to help scientists improve the transparency and quality of their work. As open science practices continue to evolve, we also provide an online toolbox of resources that we will update continually.

Citation: Diederich K, Schmitt K, Schwedhelm P, Bert B, Heinl C (2022) A guide to open science practices for animal research. PLoS Biol 20(9): e3001810. https://doi.org/10.1371/journal.pbio.3001810

Copyright: © 2022 Diederich et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: The authors received no specific funding for this work.

Competing interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: All authors are employed at the German Federal Institute for Risk Assessment and part of the German Centre for the Protection of Laboratory Animals (Bf3R) which developed and hosts animalstudyregistry.org , a preregistration platform for animal studies and animaltestinfo.de, a database for non-technical project summaries (NTS) of approved animal study protocols within Germany.

Abbreviations: CC, Creative Commons; CIRS-LAS, critical incident reporting system in laboratory animal science; COVID-19, Coronavirus Disease 2019; DOAJ, Directory of Open Access Journals; DOI, digital object identifier; EDA, Experimental Design Assistant; ELN, electronic laboratory notebook; EU, European Union; IMSR, International Mouse Strain Resource; JISC, Joint Information Systems Committee; LIMS, laboratory information management system; MGI, Mouse Genome Informatics; NC3Rs, National Centre for the Replacement, Refinement and Reduction of Animals in Research; NTS, non-technical summary; RRID, Research Resource Identifier

Introduction

Over the past decade, the quality of published scientific literature has been repeatedly called into question by the failure of large replication studies or meta-analyses to demonstrate sufficient translation from experimental research into clinical successes [ 1 – 5 ]. At the same time, the open science movement has gained more and more advocates across various research areas. By sharing all of the information collected during the research process with colleagues and with the public, scientists can improve collaborations within their field and increase the reproducibility and trustworthiness of their work [ 6 ]. Thus, the International Reproducibility Networks have called for more open research [ 7 ].

However, open science practices have not been adopted to the same degree in all research areas. In psychology, which was strongly affected by the so-called reproducibility crisis, the open science movement initiated real practical changes leading to a broad implementation of practices such as preregistration or sharing of data and material [ 8 – 10 ]. By contrast, biomedical research is still lagging behind. Open science might be of high value for research in general, but in translational biomedical research, it is an ethical obligation. It is the responsibility of the scientist to transparently share all data collected to ensure that clinical research can adequately evaluate the risks and benefits of a potential treatment. When Russell and Burch published “The Principles of Humane Experimental Technique” in 1959, scientists started to implement their 3Rs principle to answer the ethical dilemma of animal welfare in the face of scientific progress [ 11 ]. By replacing animal experiments wherever possible, reducing the number of animals to a strict minimum, and refining the procedures where animals have still to be used, this ethical dilemma was addressed. However, in recent years, whether the 3Rs principle is sufficient to fully address ethical concerns about animal experiments has been questioned [ 12 ].

Most people tolerate the use of animals for scientific purposes only under the basic assumption that the knowledge gained will advance research in crucial areas. This implies that performed experiments are reported in a way that enables peers to benefit from the collected data. However, recent studies suggest that a large proportion of animal experiments are never actually published. For example, scientists working within the European Union (EU) have to write an animal study protocol for approval by the competent authorities of the respective country before performing an animal experiment [ 13 ]. In these protocols, scientists have to describe the planned study and justify every animal required for the project. By searching for publications resulting from approved animal study protocols from 2 German University Medical Centers, Wieschowski and colleagues found that only 53% of approved protocols led to a publication after 6 years [ 14 ]. Using a similar approach, Van der Naald and colleagues determined a publication rate of 60% at the Utrecht Medical Center [ 15 ]. In a follow-up survey, the respective researchers named so-called “negative” or null-hypothesis results as the main cause for not publishing outcomes [ 15 ]. The current scientific system is shaped by publishers, funders, and institutions and motivates scientists to publish novel, surprising, and positive results, revealing one of the many structural problems that the numerous efforts towards open science initiatives are targeting. Non-publication not only strongly contradicts ethical values, but also it compromises the quality of published literature by leading to overestimation of effect sizes [ 16 , 17 ]. Furthermore, publications of animal studies too often show poor reporting that strongly impairs the reproducibility, validity, and usefulness of the results [ 18 ]. Unfortunately, the idea that negative or equivocal findings can also contribute to the gain of scientific knowledge is frequently neglected.

So far, the scientific community using animals has shown limited resonance to the open science movement. Due to the strong controversy surrounding animal experiments, scientists have been reluctant to share information on the topic. Additionally, translational research is highly competitive and researchers tend to be secretive about their ideas until they are ready for publication or patent [ 19 , 20 ]. However, this missing openness could also point to a lack of knowledge and training on the many open science options that are available and suitable for animal research. Researchers have to be convinced of the benefits of open science practices, not only for science in general, but also for the individual researcher and each single animal. Yet, the key players in the research system are already starting to value open science practices. An increasing number of journals request open sharing of data, funders pay for open access publications and institutions consider open science practices in hiring decisions. Open science practices can improve the quality of work by enabling valuable scientific input from peers at the early stages of research projects. Furthermore, the extended communication that open science practices offer can draw attention to research and help to expand networks of collaborators and lead to new project opportunities or follow-up positions. Thus, open science practices can be a driver for careers in academia, particularly those of early career researchers.

Beyond these personal benefits, improving transparency in translational biomedical research can boost scientific progress in general. By bringing to light all the recorded research outputs that until now have remained hidden, the publication bias and the overestimation of effect sizes can be reduced [ 17 ]. Large-scale sharing of data can help to synthesize research outputs in preclinical research that will enable better decision-making for clinical research. Disclosing the whole research process will help to uncover systematic problems and support scientists in thoroughly planning their studies. In the long run, we predict that the implementation of open science practices will lead to the use of fewer animals in unintentionally repeated experiments that previously showed unreported negative results or in the establishment of methods by avoiding experimental dead ends that are often not published. More collaborations and sharing of materials and methods can further reduce the number of animal experiments used for the implementation of new techniques.

Open science can and should be implemented at each step of the research process ( Fig 1 ). A vast number of tools are already provided that were either directly conceptualized for animal research or can be adapted easily. In this Essay, we provide an overview of open science tools that improve transparency, reliability, and animal welfare in translational in vivo biomedical research by supporting scientists to clearly communicate their research and by supporting collaborative working. Table 1 lists the most prominent open science tools we discuss, together with their respective links. We have structured this Essay to guide you through which tools can be used at each stage of the research process, from planning and conducting experiments, through to analyzing data and communicating the results. However, many of these tools can be used at many different steps. Table 1 has been deposited on Zenodo and will be updated continuously [ 21 ].

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Application of open science practices at each step of the research process can maximize the impact of performed animal experiments. The implementation of these practices will lead to less time pressure at the end of a project. Due to the connection of most of these open science practices, spending more time in the planning phase and during the conduction of experiments will save time during the data analysis and publication of the study. Indeed, consulting reporting guidelines early on, preregistering a statistical plan, and writing down crucial experimental details in an electronic lab notebook, will strongly accelerate the writing of a manuscript. If protocols or even electronic lab notebooks were made public, just citing these would simplify the writing of publications. Similarly, if a data management plan is well designed before starting data collection, analyzing, and depositing data in a public repository, as is increasingly required, will be fast. NTS, non-technical summary.

https://doi.org/10.1371/journal.pbio.3001810.g001

https://doi.org/10.1371/journal.pbio.3001810.t001

Planning the study

Transparent practices can be adopted at every stage of the research process. However, to ensure full effectivity, it is highly recommended to engage in detailed planning before the start of the experiment. This can prevent valuable time from being lost at the end of the study due to careless decisions being made at the beginning. Clarifying data management at the start of a project can help avoiding filing chaos that can be very time consuming to untangle. Keeping clear track of a project and study design will also help if new colleagues are included later on in the project or if entire project parts are handed over. In addition, all texts written on the rationale and hypothesis of the study or method descriptions, or design schemes created during the planning phase can be used in the final publications ( Fig 1 ). Similarly, information required for preregistration of animal studies or for reporting according to the ARRIVE guidelines are an extension of the details required for ethical approval [ 22 , 23 ]. Thus, the time burden within the planning phase is often overestimated. Furthermore, the thorough planning of experiments can avoid the unnecessary use of animals by preventing wrong avenues from being pursued.

Implementing open scientific practices at the beginning of a project does not mean that the idea and study plan must be shared immediately, but rather is critical for making the entire workflow transparent at the end of the project. However, optional early sharing of information can enable peers to give feedback on the study plan. Studies potentially benefit more from this a priori input than they would from the classical a posteriori peer-review process.

Most people perceive guidelines as advice that instructs on how to do something. However, it is sometimes useful to consider the term in its original meaning; “the line that guides us”. In this sense, following guidelines is not simply fulfilling a duty, but is a process that can help to design a sound research study and, as such, guidelines should be consulted at the planning stage of a project. The PREPARE guidelines are a list of important points that should be thought-out before starting a study involving animal experiments in order to reduce the waste of animals, promote alternatives, and increase the reproducibility of research and testing [ 24 ]. The PREPARE checklist helps to thoroughly plan a study and focuses on improving the communication and collaboration between all involved participants of the study (i.e., animal caretakers and scientists). Indeed, open science begins with the communication within a research facility. It is currently available in 33 languages and the responsible team from Norecopa, Norway’s 3R-center, takes requests for translations into further languages.

The UK Reproducibility Network has also published several guiding documents (primers) on important topics for open and reproducible science. These address issues such as data sharing [ 25 ], open access [ 26 ], open code and software [ 27 ], and preprints [ 28 ], as well as preregistration and registered reports [ 27 ]. Consultation of these primers is not only helpful in the relevant phases of the experiment but is also encouraged in the planning phase.

Although the ARRIVE guidelines are primarily a reporting guideline specifically designed for preparing a publication containing animal data, they can also support researchers when planning their experiments [ 22 , 23 ]. Going through the ARRIVE website, researchers will find tools and explanations that can support them in planning their experiments [ 29 ]. Consulting the ARRIVE checklist at the beginning of a project can help in deciding what details need to be documented during conduction of the experiments. This is particularly advisable, given that compliance to ARRIVE is still poor [ 18 ].

Experimental design

To maximize the validity of performed experiments and the knowledge gained, designing the study well is crucial. It is important that the chosen animal species reflects the investigated disease well and that basic characteristics of the animal, such as sex or age, are considered carefully [ 30 ]. The Canadian Institutes of Health Research provides a collection of resources on the integration of sex and gender in biomedical research with animals, including tips and tools for researchers and reviewers [ 31 ]. Additionally, it is advisable to avoid unnecessary standardization of biological and environmental factors that can reduce the external validity of results [ 32 ]. Meticulous statistical planning can further optimize the use of animals. Free to use online tools for calculating sample sizes such as G*Power or the inVivo software package for R can further support animal researchers in designing their statistical plan [ 33 , 34 ]. Randomization for the allocation of groups can be supported with specific tools for scientists like Research Randomizer, but also by simple online random number generators [ 35 ]. Furthermore, it might be advisable when designing the study to incorporate pathological analyses into the experimental plan. Optimal planning of tissue collection, performance of pathological procedures according to accepted best practices, and use of optimal pathological analysis and reporting methods can add some extra knowledge that would otherwise be lost. This can improve the reproducibility and quality of translational biomedicine, especially, but not exclusively, in animal studies with morphological endpoints. In all animal studies, unexpected deaths in experimental animals can occur and be the cause of lost data or missed opportunities to identify health problems [ 36 , 37 ].

To support researchers in designing their animal research, the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) has also developed the Experimental Design Assistant (EDA) [ 38 , 39 ]. This online tool helps researchers to better structure in vivo research by creating detailed schemes of the study design. It provides feedback on the entered design, drawing researcher’s attention to crucial decisions in the project. The resulting schemes can be used to transparently share the study design by uploading it into a study preregistration, enclosing it in a grant application, or submitting it with a final manuscript. The EDA can be used for different study designs in diverse scenarios and helps to communicate researcher plans to others [ 40 ]. The EDA might be particularly of interest to clarify very complex study designs involving multiple experimental groups. Working with the EDA might appear rather complex in the beginning, but the NC3R provides regular webinars that can help to answer any questions that arise.

Preregistration

Preregistration is an effective tool to improve the quality and transparency of research. To preregister their work, scientists must determine crucial details of the study before starting any experiment. Changes occurring during a study can be outlined at the end. A preregistered study plan should include at least the hypothesis and determine all the parameters that are known in advance. A description of the planned study design and statistical analysis will enable reviewers and peers to better retrace the workflow. It can prevent the intentional use of the flexibility of analysis to reach p -values under a certain significance level (e.g., p-hacking or HARKing (Hypothesizing After Results are Known)). With preregistration, scientists can also claim their idea at an early stage of their research with a citable individual identifier that labels the idea as their own. Some open preregistration platforms also provide a digital object identifier (DOI), which makes the registered study citable. Three public registries actively encourage the preregistration of animal studies conducted around the world: OSF registry, preclinicaltrials.eu, and animalstudyregistry.org [ 41 – 45 ]. Scientists can choose the registry according to their needs. Preregistering a study in a public registry supports scientists in planning their study and later to critically reevaluate their own work and assess its limitations and potentials.

As an alternative to public registries, researchers can also submit their study plan to one of hundreds of journals already publishing registered reports, including many journals open to animal research [ 8 ]. A submitted registered report passes 2 steps of peer review. In the first step, reviewers comment on the idea and the study design. After an “in-principle-acceptance,” researchers can conduct their study as planned. If the authors conduct the experiments as described in the accepted study protocol, the journal will publish the final study regardless of the outcome. This might be an attractive option, especially for early career researchers, as a manuscript is published at the beginning of a project with the guarantee of a future final publication.

The benefits of preregistration can already be observed in clinical research, where registration has been mandatory for most trials for more than 20 years. Preregistration in clinical research has helped to make known what has been tested and not just what worked and was published, and the implementation of trial registration has strongly reduced the number of publications reporting significant treatment effects [ 46 ]. In animal research, with its unrealistically high percentage of positive results, preregistration seems to be particularly worthwhile.

Research data management

To get the most out of performed animal experiments, effective sharing of data at the end of the study is essential. Sharing research data optimally is complex and needs to be prepared in advance. Thus, data management can be seen as one part of planning a study thoroughly. Many funders have recognized the value of the original research data and request a data management plan from applicants in advance [ 25 , 47 ]. Various freely available tools such as DMPTool or DMPonline already exist to design a research data management plan that complies to the requirements of different funders [ 48 , 49 ]. The data management plan defines the types of data collected and describes the handling and names responsible persons throughout the data lifecycle. This includes collecting the data, analyzing, archiving, and sharing it. Finally, a data management plan enables long-term access and the possibility for reuse by peers. Developing such a plan, whether it is required by funders or not, will later simplify the application of the FAIR data principle (see section on the FAIR data principle). The Longwood Medical Area Research Data Management Working Group from the Harvard Medical School developed a checklist to assist researchers in optimally managing their data throughout the data lifecycle [ 50 ]. Similarly, the Joint Information Systems Committee (JISC) provides a great research data management toolkit including a checklist for researchers planning their project [ 51 ]. Consulting this checklist in the planning phase of a project can prevent common errors in research data management.

Non-technical project summary

One instrument specifically conceived to create transparency on animal research for the general public is the so-called non-technical project summary (NTS). All animal protocols approved within the EU must be accompanied by these comprehensible summaries. NTSs are intended to inform the public about ongoing animal experiments. They are anonymous and include information on the objectives and potential benefits of the project, the expected harm, the number of animals, the species, and a statement of compliance with the requirements of the 3Rs principle. However, beyond simply informing the public, NTSs can also be used for meta-research to help identify new research areas with an increased need for new 3R technologies [ 52 , 53 ]. NTSs become an excellent tool to appropriately communicate the scientific value of the approved protocol and for meta-scientists to generate added value by systematically analyzing theses summaries if they fulfill a minimum quality threshold [ 54 , 55 ]. In 2021, the EU launched the ALURES platform ( Table 1 ), where NTSs from all member states are published together, opening the opportunities for EU-wide meta-research. NTSs are, in contrast to other open science practices, mandatory in the EU. However, instead of thinking of them as an annoying duty, it might be worth thoroughly drafting the NTS to support the goals of more transparency towards the public, enabling an open dialogue and reducing extreme opinions.

Conducting the experiments

Once the experiments begin, documentation of all necessary details is essential to ensure the transparency of the workflow. This includes methodological details that are crucial for replicating experiments, but also failed attempts that could help peers to avoid experiments that do not work in the future. All information should be stored in such a way that it can be found easily and shared later. In this area, many new tools have emerged in recent years ( Table 1 ). These tools will not only make research transparent for colleagues, but also help to keep track of one’s own research and improve internal collaboration.

Electronic laboratory notebooks

Electronic laboratory notebooks (ELNs) are an important pillar of research data management and open science. ELNs facilitate the structured and harmonized documentation of the data generation workflow, ensure data integrity, and keep track of all modifications made to the original data based on an audit trail option. Moreover, ELNs simplify the sharing of data and support collaborations within and outside the research group. Methodological details and research data become searchable and traceable. There is an extensive amount of literature providing advice on the selection and the implementation process of an ELN depending on the specific needs and research area and its discussion would be beyond the scope of this Essay [ 56 – 58 ]. Some ELNs are connected to a laboratory information management system (LIMS) that provides an animal module supporting the tracking of animal details [ 59 ]. But as research involving animals is highly heterogeneous, this might not be the only decision point and we cannot recommend a specific ELN that is suitable for all animal research.

ELNs are already established in the pharmaceutical industry and their use is on the rise among academics as well. However, due to concerns around costs for licenses, data security, and loss of flexibility, many research institutions still fear the expenses that the introduction of such a system would incur [ 56 ]. Nevertheless, an increasing number of academic institutions are implementing ELNs and appreciating the associated benefits [ 60 ]. If your institution already has an ELN, it might be easiest to just use the option available in the research environment. If not, the Harvard Medical School provides an extensive and updated overview of various features of different ELNs that can support scientists in choosing the appropriate one for their research [ 61 ]. There are many commercial ELN products, which may be preferred when the administrative workload should be outsourced to a large extent. However, open-source products such as eLabFTW or open BIS provide a greater opportunity for customization to meet specific needs of individual research institutions [ 62 – 64 ]. A huge number of options are available depending on the resources and the features required. Some scientists might prefer generic note taking tools such as Evernote or just a simple Word document that offers infinite flexibility, but specific ELNs can further support good record keeping practice by providing immutability, automated backups, standardized methods, and protocols to follow. Clearly defining the specific requirements expected might help to choose an adequate system that would improve the quality of the record compared to classical paper laboratory notebooks.

Sharing protocols

Adequate sharing of methods in translational biomedical sciences is key to reproducibility. Several repositories exist that simplify the publication and exchange of protocols. Writing down methods at the end of the project bears the risk that crucial details might be missing [ 65 ]. On protocols.io, scientists can note all methodological details of a procedure, complete them with uploaded documents, and keep them for personal use or share them with collaborators [ 66 ]. Authors can also decide at any point in time to make their protocol public. Protocols published on protocols.io receive a DOI and become citable; they can be commented on by peers and adapted according to the needs of the individual researcher. Protocol.io files from established protocols can also be submitted together with some context and sample datasets to PLOS ONE , where it can be peer-reviewed and potentially published [ 67 , 68 ]. Depending on the affiliation of the researchers to academia or industry and on an internal or public sharing of files, protocols.io can be free of charge or come with costs. Other journals also encourage their authors to deposit their protocols in a freely accessible repository, such as protocol exchange from Nature portfolio [ 69 ]. Another option might be to separately submit a protocol that was validated by its use in an already published research article to an online and peer-reviewed journal specific for research protocols, such as Bio-Protocol. A multitude of journals, including eLife and Science already collaborate with Bio-Protocol and recommend authors to publish the method in Bio-Protocol [ 70 ]. Bio-Protocol has no submission fees and is freely available to all readers. Both protocols.io and Bio-Protocol allow the illustration of complex scientific methods by uploading videos to published protocols. In addition, protocols can be deposited in a general research repository such as the Open Science Framework (OSF repository) and referenced in appropriate publications.

Sharing critical incidents

Sharing critical or even adverse events that occur in the context of animal experimentation can help other scientists to avoid committing the same mistakes. The system of sharing critical incidents is already established in clinical practice and helps to improve medical care [ 71 , 72 ]. The online platform critical incident reporting system in laboratory animal science (CIRS-LAS) represents the first preclinical equivalent to these clinical systems [ 73 ]. With this web-based tool, critical incidents in animal research can be reported anonymously without registration. An expert panel helps to analyze the incident to encourage an open dialogue. Critical incident reporting is still very marginal in animal research and performed procedures are very variable. These factors make a systemic analysis and a targeted search of incidence difficult. However, it may be of special interest for methods that are broadly used in animal research such as anesthesia. Indeed, a broad feed of this system with data on errors occurring in standard procedures today could help avoid critical incidences in the future and refine animal experiments.

Sharing animals, organs, and tissue

When we think about open science, sharing results and data are often in focus. However, sharing material is also part of a collaborative and open research culture that could help to greatly reduce the number of experimental animals used. When an animal is killed to obtain specific tissue or organs, the remainder is mostly discarded. This may constitute a wasteful practice, as surplus tissue can be used by other researchers for different analyses. More animals are currently killed as surplus than are used in experiments, demonstrating the potential for sharing these animals [ 74 , 75 ].

Sharing information on generated surplus is therefore not only economical, but also an effective way to reduce the number of animals used for scientific purposes. The open-source software Anishare is a straightforward way for breeders of genetically modified lines to promote their surplus offspring or organs within an institution [ 76 ]. The database AniMatch ( Table 1 ) connects scientists within Europe who are offering tissue or organs with scientists seeking this material. Scientists already sharing animal organs can support this process by describing it in publications and making peers aware of this possibility [ 77 ]. Specialized research communities also allow sharing of animal tissue or animal-derived products worldwide that are typically used in these fields on a collaborative basis via the SEARCH-framework [ 78 , 79 ]. Depositing transgenic mice lines into one of several repositories for mouse strains can help to further minimize efforts in producing new transgenic lines and most importantly reduce the number of surplus animals by supporting the cryoconservation of mouse lines. The International Mouse Strain Resource (IMSR) can be used to help find an adequate repository or to help scientists seeking a specific transgenic line find a match [ 80 ].

Analyzing the data

Animal researchers have to handle increasingly complex data. Imaging, electrophysiological recording, or automated behavioral tracking, for example, produce huge datasets. Data can be shared as raw numerical output but also as images, videos, sounds, or other forms from which raw numerical data can be generated. As the heterogeneity and the complexity of research data increases, infinite possibilities for analysis emerge. Transparently reporting how the data were processed will enable peers to better interpret reported results. To get the most out of performed animal experiments, it is crucial to allow other scientists to replicate the analysis and adapt it to their research questions. It is therefore highly recommended to use formats and tools during the analysis that allow a straightforward exchange of code and data later on.

Transparent coding

The use of non-transparent analysis codes have led to a lack of reproducibility of results [ 81 ]. Sharing code is essential for complex analysis and enables other researchers to reproduce results and perform follow-up studies, and citable code gives credit for the development of new algorithms ( Table 1 ). Jupyter Notebooks are a convenient way to share data science pipelines that may use a variety of coding languages, including like Python, R or Matlab, and also share the results of analyses in the form of tables, diagrams, images, and videos. Notebooks contain source code and can be published or collaboratively shared on platforms like GitHub or GitLab, where version control of source code is implemented. The data-archiving tool Zenodo can be used to archive a repository on GitHub and create a DOI for the archive. Thereby contents become citable. Using free and open-source programming language like R or Python will increase the number of potential researchers that can work with the published code. Best practice for research software is to publish the source code with a license that allows modification and redistribution.

Choice of data visualization

Choosing the right format for the visualization of data can increase its accessibility to a broad scientific audience and enable peers to better judge the validity of the results. Studies based on animal research often work with very small sample sizes. Visualizing these data in histograms may lead to an overestimation of the outcomes. Choosing the right dot plots that makes all recorded points visible and at the same time focusses on the summary instead of the individual points can further improve the intuitive understanding of a result. If the sample size is too low, it might not be meaningful to visualize error bars. A variety of freely available tools already exists that can support scientists in creating the most appropriate graphs for their data [ 82 ]. In particular, when representing microscopy results or heat maps, it should be kept in mind that a large part of the population cannot perceive the classical red and green representation [ 83 ]. Opting for the color-blind safe color maps and checking images with free tools such as color oracle ( Table 1 ) can increase the accessibility of graphs. Multiple journals have already addressed flaws in data visualization and have introduced new policies that will accelerate the uptake of transparent representation of results.

Publication of all study outcomes

Open science practices have received much attention in the past few years when it comes to publication of the results. However, it is important to emphasize that although open science tools have their greatest impact at the end of the project, good study preparation and sharing of the study plan and data early on can greatly increase the transparency at the end.

The FAIR data principle

To maximize the impact and outcome of a study, and to make the best long-term use of data generated through animal experiments, researchers should publish all data collected during their research according to the FAIR data principle. That means the data should be findable, accessible, interoperable, and reusable. The FAIR principle is thus an extension of open access publishing. Data should not only be published without paywalls or other access restrictions, but also in such a manner that they can be reused and further processed by others. For this, legal as well as technical requirements must be met by the data. To achieve this, the GoFAIR initiative has developed a set of principles that should be taken into account as early as at the data collection stage [ 49 , 84 ]. In addition to extensively described and machine-readable metadata, these principles include, for example, the application of globally persistent identifiers, the use of open file formats, and standardized communication protocols to ensure that humans and machines can easily download the data. A well-chosen repository to upload the data is then just the final step to publish FAIR data.

FAIR data can strongly increase the knowledge gained from performed animal experiments. Thus, the same data can be analyzed by different researchers and could be combined to obtain larger sample sizes, as already occurs in the neuroimaging community, which works with comparable datasets [ 85 ]. Furthermore, the sharing of data enables other researchers to analyze published datasets and estimate measurement reliabilities to optimize their own data collection [ 86 , 87 ]. This will help to improve the translation from animal research into clinics and simultaneously reduce the number of animal experiment in future.

Reporting guidelines

In preclinical research, the ARRIVE guidelines are the current state of the art when it comes to reporting data based on animal experiments [ 22 , 23 ]. The ARRIVE guidelines have been endorsed by more than 1,000 journals who ask that scientists comply with them when reporting their outcomes. Since the ARRIVE guidelines have not had the expected impact on the transparency of reporting in animal research publications, a more rigorous update has been developed to facilitate their application in practice (ARRIVE 2.0 [ 23 ]). We believe that the ARRIVE guidelines can be more effective if they are implemented at a very early stage of the project (see section on guidelines). Some more specialized reporting guidelines have also emerged for individual research fields that rely on animal studies, such as endodontology [ 88 ]. The equator network collects all guidelines and makes them easily findable with their search tool on their website ( Table 1 ). MERIDIAN also offers a 1-stop shop for all reporting guidelines involving the use of animals across all research sectors [ 89 ]. It is thus worth checking for new reporting guidelines before preparing a manuscript to maximize the transparency of described experiments.

Identifiers

Persistent identifiers for published work, authors, or resources are key for making public data findable by search engines and are thus a prerequisite for compliance to FAIR data principles. The most common identifier for publications will be a DOI, which makes the work citable. A DOI is a globally unique string assigned by the International DOI Foundation to identify content permanently and provide a persistent link to its location on the Internet. An ORCID ID is used as a personal persistent identifier and is recommendable to unmistakably identify an author ( Table 1 ). This will avoid confusions between authors with the same name or in the case of name changes or changes of affiliation. Research Resource Identifiers (RRID) are unique ID numbers that help to transparently report research resources. RRID also apply to animals to clearly identify the species used. RRID help avoid confusion between different names or changing names of genetic lines and, importantly, make them machine findable. The RRID Portal helps scientists find a specific RRID or create one if necessary ( Table 1 ). In the context of genetically altered animal lines, correct naming is key. The Mouse Genome Informatics (MGI) Database is the authoritative source of official names for mouse genes, alleles, and strains ([ 90 ]).

Preprint publication

Preprints have undergone unprecedented success, particularly during the height of the Coronavirus Disease 2019 (COVID-19) pandemic when the need for rapid dissemination of scientific knowledge was critical. The publication process for scientific manuscripts in peer-reviewed journals usually requires a considerable amount of time, ranging from a few months to several years, mainly due to the lengthy review process and inefficient editorial procedures [ 91 , 92 ]. Preprints typically precede formal publication in scientific journals and, thus, do not go through a peer review process, thus, facilitating the prompt open dissemination of important scientific findings within the scientific community. However, submitted papers are usually screened and checked for plagiarism. Preprints are assigned a DOI so they can be cited. Once a preprint is published in a journal, its status is automatically updated on the preprint server. The preprint is linked to the publication via CrossRef and mentioned accordingly on the website of the respective preprint platform.

After initial skepticism, most publishers now allow papers to be posted on preprint servers prior to submission. An increasing number of journals even allow direct submission of a preprint to their peer review process. The US National Institutes of Health and the Wellcome Trust, among other funders, also encourage prepublication and permit researchers to cite preprints in their grant applications. There are now numerous preprint repositories for different scientific disciplines. BioASAP provides a searchable database for preprint servers that can help in identifying the one that best matches an individual’s needs [ 93 ]. The most popular repository for animal research is bioRxiv, which is hosted by the Cold Spring Harbor Laboratory ( Table 1 ).

The early exchange of scientific results is particularly important for animal research. This acceleration of the publication process can help other scientists to adapt their research or could even prevent animal experiments if other scientists become aware that an experiment has already been done before starting their own. In addition, preprints can help to increase the visibility of research. Journal articles that have a corresponding preprint publication have higher citation and Altmetric counts than articles without preprint [ 94 ]. In addition, the publication of preprints can help to combat publication bias, which represents a major problem in animal research [ 16 ]. Since journals and readers prioritize cutting-edge studies with positive results over inconclusive or negative results, researchers are reluctant to invest time and money in a manuscript that is unlikely to be accepted in a high-impact journal.

In addition to the option of publishing as preprint, other alternative publication formats have recently been introduced to facilitate the publication of research results that are hard to publish in traditional peer-reviewed journals. These include micro publications, data repositories, data journals, publication platforms, and journals that focus on negative or inconclusive results. The tool fiddle can support scientists in choosing the right publication format [ 95 , 96 ].

Open access publication

Publishing open access is one of the most established open science strategies. In contrast to the FAIR data principle, the term open access publication refers usually to the publication of a manuscript on a platform that is accessible free of charge—in translational biomedical research, this is mostly in the form of a scientific journal article. Originally, publications accessible free of charge were the answer to the paywalls established by renowned publishing houses, which led to social inequalities within and outside the research system. In translational biomedical research, the ethical aspect of urgently needed transparency is another argument in favor of open access publication, as these studies will not only be findable, but also internationally readable.

There are different ways of open access publishing; the 2 main routes are gold open access and green open access. Numerous journals offer now gold open access. It refers to the immediate and fully accessible publication of an article. The Directory of Open Access Journals (DOAJ) provides a complete and updated list for high-quality, open access, and peer-reviewed journals [ 97 ]. Charité–Universitätsmedizin Berlin offers a specific tool for biomedical open access journals that supports animal researchers to choose an appropriate journal [ 49 ]. In addition, the Sherpa Romeo platform is a straightforward way to identify publisher open access policies on a journal-by-journal basis, including information on preprints, but also on licensing of articles [ 51 ]. Hybrid open access refers to openly accessible articles in otherwise paywalled journals. By contrast, green open access refers to the publication of a manuscript or article in a repository that is mostly operated by institutions and/or universities. The publication can be exclusively on the repository or in combination with a publisher. In the quality-assured, global Directory of Open Access Repositories (openDOAR), scientists can find thousands of indexed open access repositories [ 49 ]. The publisher often sets an embargo during which the authors cannot make the publication available in the repository, which can restrict the combined model. It is worth mentioning that gold open access is usually more expensive for the authors, as they have to pay an article processing charge. However, the article’s outreach is usually much higher than the outreach of an article in a repository or available exclusively as subscription content [ 98 ]. Diamond open access refers to publications and publication platforms that can be read free of charge by anyone interested and for which no costs are incurred by the authors either. It is the simplest and fairest form of open access for all parties involved, as no one is prevented from participating in scientific discourse by payment barriers. For now, it is not as widespread as the other forms because publishers have to find alternative sources of revenue to cover their costs.

As social media and the researcher’s individual public outreach are becoming increasingly important, it should be remembered that the accessibility of a publication should not be confused with the licensing under which the publication is made available. In order to be able to share and reuse one’s own work in the future, we recommend looking for journals that allow publications under the Creative Commons licenses CC BY or CC BY-NC. This also allows the immediate combination of gold and green open access.

Creative commons licenses

Attributing Creative Commons (CC) licenses to scientific content can make research broadly available and clearly specifies the terms and conditions under which people can reuse and redistribute the intellectual property, namely publications and data, while giving the credit to whom it deserves [ 49 ]. As the laws on copyright vary from country to country and law texts are difficult to understand for outsiders, the CC licenses are designed to be easily understandable and are available in 41 languages. This way, users can easily avoid accidental misuse. The CC initiative developed a tool that enables researchers to find the license that best fits their interests [ 49 ]. Since the licenses are based on a modular concept ranging from relatively unrestricted licenses (CC BY, free to use, credit must be given) to more restricted licenses (CC BY-NC-ND, only free to share for non-commercial purposes, credit must be given), one can find an appropriate license even for the most sensitive content. Publishing under an open CC license will not only make the publication easy to access but can also help to increase its reach. It can stimulate other researchers and the interested public to share this article within their network and to make the best future use of it. Bear in mind that datasets published independently from an article may receive a different CC license. In terms of intellectual property, data are not protected in the same way as articles, which is why the CC initiative in the United Kingdom recommends publishing them under a CC0 (“no rights reserved”) license or the Public Domain Mark. This gives everybody the right to use the data freely. In an animal ethics sense, this is especially important in order to get the most out of data derived from animal experiments.

Data and code repositories

Sharing research data is essential to ensure reproducibility and to facilitate scientific progress. This is particularly true in animal research and the scientific community increasingly recognizes the value of sharing research data. However, even though there is increasing support for the sharing of data, researchers still perceive barriers when it comes to doing so in practice [ 99 – 101 ]. Many universities and research institutions have established research data repositories that provide continuous access to datasets in a trusted environment. Many of these data repositories are tied to specific research areas, geographic regions, or scientific institutions. Due to the growing number and overall heterogeneity of these repositories, it can be difficult for researchers, funding agencies, publishers, and academic institutions to identify appropriate repositories for storing and searching research data.

Recently, several web-based tools have been developed to help in the selection of a suitable repository. One example is Re3data, a global registry of research data repositories that includes repositories from various scientific disciplines. The extensive database can be searched by country, content (e.g., raw data, source code), and scientific discipline [ 49 ]. A similar tool to help find a data archive specific to the field is FAIRsharing, based at Oxford University [ 102 ]. If there is no appropriate subject-specific data repository or one seems unsuitable for the data, there are general data repositories, such as Open Science Framework, figshare, Dryad, or Zenodo. To ensure that data stored in a repository can be found, a DOI is assigned to the data. Choosing the right license for the deposited code and data ensures that authors get credit for their work.

Publication and connection of all outcomes

If scientists have used all available open science tools during the research process, then publishing and linking all outcomes represents the well-deserved harvest ( Fig 2 ). At the end of a research process, researchers will not just have 1 publication in a journal. Instead, they might have a preregistration, a preprint, a publication in a journal, a dataset, and a protocol. Connecting these outcomes in a way that enables other scientists to better assess the results that link these publications will be key. There are many examples of good open science practices in laboratory animal science, but we want to highlight one of them to show how this could be achieved. Blenkuš and colleagues investigated how mild stress-induced hyperthermia can be assessed non-invasively by thermography in mice [ 103 ]. The study was preregistered with animalstudyregistry.org , which is referred to in their publication [ 104 ]. A deviation from the originally preregistered hypothesis was explained in the manuscript and the supplementary material was uploaded to figshare [ 105 ].

Application of open science practices can increase the reproducibility and visibility of a research project at the same time. By publishing different research outputs with more detailed information than can be included in a journal article, researchers enable peers to replicate their work. Reporting according to guidelines and using transparent visualization will further improve this reproducibility. The more research products that are generated, the more credit can be attributed. By communicating on social media or additionally publishing slides from delivered talks or posters, more attention can be raised. Additionally, publishing open access and making the work machine-findable makes it accessible to an even broader number of peers.

https://doi.org/10.1371/journal.pbio.3001810.g002

It might also be helpful to provide all resources from a project in a single repository such as Open Science Framework, which also implements other, different tools that might have been used, like GitHub or protocols.io.

Communicating your research

Once all outcomes of the project are shared, it is time to address the targeted peers. Social media is an important instrument to connect research communities [ 106 ]. In particular, Twitter is an effective way to communicate research findings or related events to peers [ 107 ]. In addition, specialized platforms like ResearchGate can support the exchange of practical experiences ( Table 1 ). When all resources related to a project are kept in one place, sharing this link is a straightforward way to reach out to fellow scientists.

With the increasing number of publications, science communication has become more important in recent years. Transparent science that communicates openly with the public contributes to strengthening society’s trust in research.

Conclusions

Plenty of open science tools are already available and the number of tools is constantly growing. Translational biomedical researchers should seize this opportunity, as it could contribute to a significant improvement in the transparency of research and fulfil their ethical responsibility to maximize the impact of knowledge gained from animal experiments. Over and above this, open science practices also bear important direct benefits for the scientists themselves. Indeed, the implementation of these tools can increase the visibility of research and becomes increasingly important when applying for grants or in recruitment decisions. Already, more and more journals and funders require activities such as data sharing. Several institutions have established open science practices as evaluation criteria alongside publication lists, impact factor, and h-index for panels deciding on hiring or tenure [ 108 ]. For new adopters, it is not necessary to apply all available practices at once. Implementing single tools can be a safe approach to slowly improve the outreach and reproducibility of one’s own research. The more open science products that are generated, the more reproducible the work becomes, but also the more the visibility of a study increases ( Fig 2 ).

As other research fields, such as social sciences, are already a step ahead in the implementation of open science practices, translational biomedicine can profit from their experiences [ 109 ]. We should thus keep in mind that open science comes with some risks that should be minimized early on. Indeed, the more open science practices become incentivized, the more researchers could be tempted to get a transparency quality label that might not be justified. When a study is based on a bad hypothesis or poor statistical planning, this cannot be fixed by preregistration, as prediction alone is not sufficient to validate an interpretation [ 110 ]. Furthermore, a boom of data sharing could disconnect data collectors and analysts, bearing the risk that researchers performing the analysis lack understanding of the data. The publication of datasets could also promote a “parasitic” use of a researcher’s data and lead to scooping of outcomes [ 111 ]. Stakeholders could counteract such a risk by promoting collaboration instead of competition.

During the COVID-19 pandemic, we have seen an explosion of preprint publications. This unseen acceleration of science might be the adequate response to a pandemic; however, the speeding up science in combination with the “publish or perish” culture could come at the expense of the quality of the publication. Nevertheless, a meta-analysis comparing the quality of reporting between preprints and peer-reviewed articles showed that the quality of reporting in preprints in the life sciences is at most slightly lower on average compared to peer-reviewed articles [ 112 ]. Additionally, preprints and social media have shown during this pandemic that a premature and overconfident communication of research results can be overinterpreted by journalists and raise unfounded hopes or fears in patients and relatives [ 113 ]. By being honest and open about the scope and limitations of the study and choosing communication channels carefully, researchers can avoid misinterpretation. It should be noted, however, that by releasing all methodological details and data in research fields such as viral engineering, where a dual use cannot be excluded, open science could increase biosecurity risk. Implementing access-controlled repositories, application programming interfaces, and a biosecurity risk assessment in the planning phase (i.e., by preregistration) could mitigate this threat [ 114 ].

Publishing in open access journals often involves higher publication costs, which makes it more difficult for institutes and universities from low-income countries to publish there [ 115 ]. Equity has been identified as a key aim of open science [ 116 ]. It is vital, therefore, that existing structural inequities in the scientific system are not unintentionally reinforced by open science practices. Early career researchers have been the main drivers of the open science movement in other fields even though they are often in vulnerable positions due to short contracts and hierarchical and strongly networked research environments. Supporting these early career researchers in adopting open science tools could significantly advance this change in research culture [ 117 ]. However, early career researchers can already benefit by publishing registered reports or preprints that can provide a publication much faster than conventional journal publications. Communication in social media can help them establish a network enabling new collaborations or follow-up positions.

Even though open science comes with some risks, the benefits easily overweigh these caveats. If a change towards more transparency is accompanied by the implementation of open science in the teaching curricula of the universities, most of the risks can be minimized [ 118 ]. Interestingly, we have observed that open science tools and infrastructure that are specific to animal research seem to mostly come from Europe. This may be because of strict regulations within Europe for animal experiments or because of a strong research focus in laboratory animal science along with targeted research funding in this region. Whatever the reason might be, it demonstrates the important role of research policy in accelerating the development towards 3Rs and open science.

Overall, it seems inevitable that open science will eventually prevail in translational biomedical research. Scientists should not wait for the slow-moving incentive framework to change their research habits, but should take pioneering roles in adopting open science tools and working towards more collaboration, transparency, and reproducibility.

Acknowledgments

The authors gratefully acknowledge the valuable input and comments from Sebastian Dunst, Daniel Butzke, and Nils Körber that have improved the content of this work.

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Researchers and their experimental models: a pilot survey in the context of the european union health and life science research.

Simple Summary

1. introduction, 2. material and methods, 2.1. questionnaire design, 2.2. questionnaire distribution, 2.3. data analysis, 2.4. limits of the study, 3.1. participants information, 3.2. participants research fields and models, 3.3. experimental model establishment, 3.4. the model in use, 3.5. perspectives on model acceptance, 3.6. willingness in methods and model sharing, 3.7. research models drivers, 3.8. research funding opportunities perception, 3.9. experimental research teaching experience, 3.10. continuing education in life science and biomedical research, 3.11. perception of stakeholder participation in science, 3.12. researchers considerations on directive 2010/63/eu, 3.13. researchers’ conditions for animal-based research phased out, 4. discussion, 5. conclusions, supplementary materials, author contributions, institutional review board statement, informed consent statement, data availability statement, acknowledgments, conflicts of interest.

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Animal experimentation

Nonhuman animals are used in laboratories for a number of purposes. Examples of animal experimentation include product testing, use of animals as research models and as educational tools. Within each of these categories, there are also many different purposes for which they are used. For instance, some are used as tools for military or biomedical research; some to test cosmetics and household cleaning products, and some are used in class dissection to teach teenagers the anatomy of frogs or to have a subject for a Ph.D. dissertation.

The number of animals used in animal experimentation is certainly smaller than that of those used in others such as animal farming or the fishing industry. 1  Yet it has been estimated to be well above 100 million animals who are used every year. 2

The ways in which these animals can be harmed in experimental procedures, also known as vivisection, 3 vary. In almost all cases they are very significant and the majority of them end with the death of the animals.

There’s an important difference today between the consideration that is afforded to the potential and actual subjects used in experiments, depending on whether they are human or nonhuman animals. Few people today would condone experimenting on human beings in harmful ways, and in fact, indicative of this, such research is strongly restricted by law, when it isn’t just prohibited outright. When experimentation on humans is permitted it is always in a context of the individuals involved consenting to it, for whatever personal benefit that serves as an incentive for them. For nonhuman animals, this is not the case.

This is not because of any belief that experimentation on humans could not bring about important knowledge (in fact, it seems obvious that this practice would uncover far more useful and relevant knowledge than any experimentation on nonhuman animals ever can). Rather, the reason for this double standard is that nonhuman animals are not morally taken into account because the strong arguments against speciesism are not considered.

In the following sections the most important areas in which nonhuman animals are used in laboratories or classrooms, as well as the research methods that don’t use them, are addressed.

Animals used for experimentation

Environmental research.

Animals are made to suffer and are killed to test the impact that chemicals can have in the environment. Some of the most important environmentalist organizations have been lobbying for this practice and have often been successful despite the opposition of animal defenders.

Cosmetic and household products testing

While animal testing of new cosmetics and household products is now illegal in places such as the European Union and India, it’s still being carried out in the U.S. and other places, where many animals are blinded, caused extreme pain and killed.

Military experimentation

The use of animals to test new weaponry, bullets and warfare chemicals, as well as the effects of burns and poison for military purposes, remains mainly hidden today, but many animals die in terrible ways because of it.

Biomedical experimentation

Animals of a variety of species are harmed for numerous purposes in biomedical research because the non-animal methodologies aren’t implemented. Those animals are harmed in many ways that most people ignore.

Experimentation with new materials

When new materials are developed, they are often tested by using methods such as cell or tissue cultures, or computational models. However, materials are also commonly tested on animals who are killed afterwards.

Animals used in education

Animals used in primary and secondary education.

Dissecting animals and using them in other ways has been common practice in the U.S. and some other countries in primary and especially secondary education for many years. This means killing a huge number of animals and educating new generations in the idea that it’s acceptable to harm animals for our benefit.

Animals used in higher education

In the science departments of many different universities, research, teaching and training are successfully carried out without using animals as laboratory tools. However, animals are still subjected to all kind of procedures in many other places.

Towards a future without animals harmed in laboratories

Research methods that do not involve the use of nonhuman animals.

Defenders of animal experimentation often claim that there is no choice but to harm animals lest scientific progress be stopped, but this is not so. There are many non-harmful methods available today.

Companies that test on animals

Despite the fact that many other companies do not experiment on sentient animals, there are still companies that choose to continue carrying out animal tests out of a lack of will to implement new methods.

Companies that do not test on animals

Fortunately, although many companies today choose not to harm animals in product development, quality and safety isn’t affected in the least.

1 Every year tens of billions are killed in slaughterhouses and trillions are fished and killed in fish factories. For estimations regarding this see: Food and Agriculture Organization of the United Nations (2021) “ Livestock primary ”, FAO STAT , February 19 [accessed on 24 March 2013]. See also Mood, A. &  Brooke, P. (2010) “ Estimating the number of fish caught in global fishing each year ”, Fishcount.org.uk , July [accessed on 18 October 2020]; (2012) “ Estimating the number of farmed fish killed in global aquaculture each year ”, Fishcount.org.uk , July [accessed on 18 January 2021].

2  See Taylor, K.; Gordon, N.; Langley, G. & Higgins, W. (2008) “Estimates for worldwide laboratory animal use in 2005”,  Alternatives to Laboratory Animals , 36, pp. 327-342.

3 Although the term “vivisection” literally means “cutting a living animal,” this word has broadened its meaning in common language to denote any kind of laboratory invasive use of an animal. Defenders of animal experimentation prefer not to use it due to its negative connotations. Opponents of it claim that there shouldn’t be a problem with using this term given the meaning it already has in common language. They argue that its rejection is due to an intention to use language that is not explicit about how animals are used in this field.

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ANIMAL ETHICS IN OTHER LANGUAGES

Ethics Problems in Animal Experimentation Essay

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The issue of treating animals as equal to humans is one of the most controversial questions related to ethics and morality. Scientists use animals in experiments because this practice can contribute significantly to improving the quality of the people’s life and to developing lifesaving therapies. However, the people’s opinions on the ethical context of the issue are rather different. From this point, animal experimentation cannot be discussed only from one perspective, and the evaluation of different visions is necessary.

In spite of the fact that it is possible to find the arguments to support the idea of using animals in experiments, animal experimentation cannot be discussed as the ethical procedure because animals have the right to avoid sufferings as any other creatures without references to the idea that humans’ interests in the case are of the higher priority.

Those animals which are used in experiments have to feel pain and suffer for the benefit of humanity because this procedure is important for scientists to find the new ways of overcoming certain diseases and health problems. Nevertheless, people do not have ethical rights to cause animals’ sufferings in order to satisfy their needs.

Animals also have definite needs, and their rights should be taken into account. It is stated that animals can feel pain and pleasure as well as humans. Thus, using animals in experiments, people work to affect animals’ sufferings, and they become feeling pain. Although it is inappropriate to treat animals and people equally, it is important to pay attention to the fact that people are more persistent while discussing the problem of pain and sufferings in relation to humans.

As a result, the consequences of false morality are observed, and thousands of animals are used in experiments because they are discussed as belonging to the lower species. Furthermore, it is also immoral to distinguish between animals according to their species, size, and abilities because all of them belong to living creatures who can suffer as humans do.

A man has achieved significant results in developing technologies and science. Today, it is possible to find the relevant methods to assess medicines and procedures or to learn the necessary information on diseases without involving animals in experiments which can be harmful for them.

If this problem was more controversial decades ago because of the level of the scientific progress, nowadays this question is more associated with the aspects of morality and ethical treatment of animals. The reasons to discuss the experience of animal experimentation as immoral are connected with the idea that animals live not to satisfy the people’s needs, but to respond to their own needs which can seem insignificant for people.

In spite of the fact that people can see animals’ needs and interests as insignificant, humans cannot reject the fact that animals are born to live a pleasant and painless life as any other living creature. While using animals in experiments, people become torturers for those creatures who cannot protect themselves from the stronger humans.

Focusing on the idea that animals feel pleasure and pain as people do, it is important to discuss the ethical issue of using animals in experiments from the Utilitarian perspective. Utilitarianism is based on the idea that the action can be discussed as moral only after evaluating its consequences for the humanity because of the focus on the greatest happiness.

Two main concepts operated by the Utilitarian philosophers are pleasure and pain. Thus, people should concentrate on actions which result in pleasure and happiness for many people, and they should avoid those actions which can result in pain.

These actions are considered as immoral in their nature. Answering the discussed questions from the Utilitarian perspective, it is important to pay attention to the fact that the classical vision of Utilitarianism differs from modern interpretations of this theory. Thus, following the discussions by Jeremy Bentham and John Stuart Mill, it is possible to conclude that the usage of animals in experiments has the positive and moral consequences for the mankind as well as the use of animals for clothing and food.

The goal of greater happiness can be easily achieved, if these experiments contribute to relieving the people’s pain and sufferings. However, Peter Singer concentrates on the fact that in their interests and needs animals are close to people regarding their rights to be protected from pain. Causing pain and sufferings during the experiments, people act immorally because important purposes cannot justify the acts of discrimination directed toward animals because of their species.

Thus, having chosen the Utilitarian approach to discussion of the issue, it is necessary to pay attention to rather opposite opinions of the classical and modern Utilitarian philosophers on the problem. The variety of interpretations can be discussed as the weakness of the approach.

Nevertheless, people can agree that concentrating on the greater happiness as the positive consequence which can justify people’s actions, it is also significant to take into consideration the interests of animals as living creatures in relation to the process. In this case, the universal happiness proclaimed by the Utilitarian philosophers can be achieved completely.

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• Published: 29 May 2012

The '3Is' of animal experimentation

Nature Genetics volume  44 ,  page 611 ( 2012 ) Cite this article

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Animal experimentation in scientific research is a good thing: important, increasing and often irreplaceable. Careful experimental design and reporting are at least as important as attention to welfare in ensuring that the knowledge we gain justifies using live animals as experimental tools.

We have previously argued for the necessity of animal experimentation and the duty to explain the work to the public, despite the difficulty of doing so while treating animal experimentation as a problem in need of regulatory reduction ( Nat. Genet. 38 , 497–498, 2006). We now note that many experiments may be wasting human and animal lives because the focus on reduction in animal experiments can lead to unreliable results from underpowered experiments on too few animals.

In our opinion, the classic review by Sean Scott and colleagues ( Amyotroph. Lateral Scler. 9 , 4–15, 2008) should be required reading for anyone designing an animal experiment. It shows the danger of publishing positive results from underpowered studies on noisy experimental systems. By systematically investigating the standard model for familial motor neuron disease—the transgenic mouse bearing the human SOD1 G93A variant—this group showed that transgene copy number, non–amyotrophic lateral sclerosis (ALS) cause of death and litter clustering contributed to noise in mean survival time and that any two small groups of animals always had a very high probability of showing differential survival of the previously publishable magnitude without any drug treatment . Rather than the previous publication mode of 5–10 mice per group, they used their knowledge of the sources of experimental variation to redesign the standard assay with 24 mice per group (saving 6 animals per group by same-gender litter matching and including equal numbers of males and females in case of a gender-specific drug effect). They were then able to repeat over 50 published studies of drug trials, often with twice the number of mice used in the combined preceding studies and with 90% power to detect the published effects. None of the drugs showed the published effect. These authors systematically investigated welfare issues relevant to experimental outcome, finding that basic, clean and specific pathogen–free housing made no difference to mean survival time. They also developed a surrogate endpoint for complete paralysis (wherein a mouse on its side takes >30 s to right itself) to prevent distress in mice with advanced disease.

It has been difficult to arrive at international standards for animal research because of regional variations in attitudes and legislation, but there is broad agreement on principles and practices for humane and scientifically appropriate treatment of animals ( http://cioms.ch/publications/guidelines/1985_texts_of_guidelines.htm ). Still, it has been possible to export best practice from one region to another. The UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs; www.nc3rs.org.uk ) is an effective agency with broad support from scientists, funders, veterinarians and pharmaceutical companies, in spite of its quaint name (somewhat redolent of Orwellian doublespeak—in contrast, the US government has a plain Office of Laboratory Animal Welfare; http://grants.nih.gov/grants/olaw/olaw.htm ). The name reflects a 1959 UK Home Office policy (3Rs) that has consistently influenced that nation's approach to legal and ethical protection for animal research subjects, and the current NC3Rs and its collaborators have been able to develop reporting guidelines to encourage best practice. We have adopted these guidelines in our Guide to Authors ( http://www.nature.com/authors/policies/experimental.html ), in which the Nature journals insist upon authors applying the widely accepted Animals in Research: Reporting In Vivo Experiments (ARRIVE) guidelines for reporting animal research ( PLoS Biol. 8 , e1000412, 2010). In the form of a checklist, these guidelines are easy to follow and apply, and statistical issues, such as those discussed above, are front and foremost. However, one point, item 18c, may come as a surprise, as the recommendation is slanted in an entirely negative direction that may be unfamiliar to experimenters outside the UK:

“Describe any implications of your experimental methods or findings for the replacement, refinement, or reduction (the 3Rs) of the use of animals in research.”

In the interests of both good experimental design and continuing to explain to the public why animal research is useful and necessary, we emphasize that this duty to report scientific implications is also a duty to note any implications of your experiments for the importance, irreplaceability or, indeed, increase in animal experimentation. The privilege to know comes with a duty to explain.

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The '3Is' of animal experimentation. Nat Genet 44 , 611 (2012). https://doi.org/10.1038/ng.2322

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Published : 29 May 2012

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Right now, millions of mice, rats, rabbits, primates, cats, dogs, and other animals are locked inside cages in laboratories across the country. They languish in pain, ache with loneliness, and are deprived of everything that’s natural and important to them. All they can do is sit and wait in fear of the next terrifying and painful procedure that will be performed on them. A lack of environmental enrichment and the stress of their living situations cause some animals to develop neurotic behaviors, such as incessantly spinning in circles, rocking back and forth, pulling out their own fur, and even biting themselves. After enduring lives of pain, loneliness, and terror, almost all of them will be killed.

How PETA Helps Animals in Laboratories

Since PETA’s inception and the landmark  Silver Spring monkeys  case, we’ve been at the forefront of exposing and ending experiments on animals. Our scientists, campaigners, researchers, and other dedicated staff work hard to persuade universities, hospitals,  contract laboratories ,  other companies , and government agencies to abandon animal tests and embrace modern, non-animal methods.

Two teams lead PETA’s efforts to end tests on animals. Our Laboratory Investigations Department focuses on ending the use of animals in experiments not required by law, and our Regulatory Toxicology Department focuses on replacing the use of animals in tests required by law with human-relevant, animal-free toxicity testing approaches. With help from supporters like you, these teams and other hardworking staff at PETA win numerous  victories  for animals imprisoned in laboratories every year. Here’s how they do it:

• Promoting PETA’s Research Modernization Deal , the first comprehensive, science-backed plan to phase out tests on animals
• Conducting groundbreaking  eyewitness investigations and colorful advocacy campaigns to shut down laboratories and areas of animal experimentation
• Filing groundbreaking lawsuits to challenge public funding of wasteful, cruel animal experiments
• Working with members of Congress to enact laws to replace animals in laboratories
• Persuading government agencies to stop conducting and  requiring experiments on animals
• Encouraging  pharmaceutical, chemical , and  consumer product companies to replace tests on animals with more effective, non-animal methods
• Ending the use of animals in experiments at colleges and universities
• Helping  students and  teachers  end animal dissection in the classroom
• Developing and funding humane non-animal research methods
• Publishing scientific papers on reliable non-animal test methods and presenting them at scientific conferences
• Hosting free workshops and online seminars to share information about animal-free toxicity testing methods
• Urging  health charities not to invest in dead-end tests on animals

How Animals Are Exploited in Laboratories

More than 110 million animals suffer and die in the U.S. every year in cruel chemical, drug, food, and cosmetics tests. They also experience this fate in  medical training exercises , curiosity-driven  experiments at universities ,  classroom biology experiments , and  dissection even though modern, non-animal methods have repeatedly been shown to have more educational value, save teachers time, and save schools money. Exact numbers aren’t available, because mice, rats, birds, and cold-blooded animals—who make up more than 99% of animals used in experiments—aren’t covered by even the minimal protections of the federal Animal Welfare Act and therefore go uncounted.

Examples of chemical and toxicity tests on animals include forcing mice and rats to inhale toxic fumes, force-feeding dogs chemicals, and applying corrosive chemicals into rabbits’ sensitive eyes. Even if a product harms animals, it can still be marketed to consumers. Conversely, just because a product was shown to be safe in animals doesn’t guarantee that it will be safe to use in humans.

Much product testing conducted on animals today isn’t required by law. In fact, a number of countries have implemented bans on the testing of certain types of consumer goods on animals, such as the cosmetics testing bans in India, Israel, New Zealand, Norway, and elsewhere.

Meanwhile, at universities and other institutions, experimenters inflict suffering on and kill animals for little more than curiosity’s sake—even though the vast majority of their findings fail to advance human health . They tear baby monkeys away from their mothers , sew kittens’ eyes shut , mutilate owls’ brains , puncture the intestines of mice so that feces leak into their stomachs , and terrorize songbirds with the sounds of predators . At the end of experiments like these—which consume billions in taxpayer funds and charitable donations each year—almost all the animals are killed.

Animal Experiments Throughout History: A Century of Suffering

PETA created an interactive timeline, “ Without Consent ,” featuring almost 200 stories of animal experiments from the past century to open people’s eyes to the long history of suffering inflicted on nonconsenting animals in laboratories and to challenge them to rethink this exploitation. Visit “ Without Consent ” to learn more about harrowing animal experiments throughout history and how you can help create a better future for living, feeling beings.

Advancing Science Without Suffering: Animal-Free Testing

Testing on animals has been a spectacular failure that has resulted in the loss of trillions of dollars and has cost the lives of innumerable humans and other animals. Experiments on one species frequently fail to predict results in another. Even the National Institutes of Health, the world’s largest funder of biomedical research, acknowledges that 95% of all drugs that are shown to be safe and effective in animal tests fail in human trials.

Technologically advanced  non-animal research methods —such as those using human cells, computational models, or clinical studies—can be used in place of animal testing. These methods are more humane, have the potential to be faster, and are more relevant to humans.

Scientists in PETA’s Science Advancement & Outreach division , a part of the Laboratory Investigations Department, have developed a roadmap to phase out failing tests on animals with sophisticated, animal-free methods. Their Research Modernization Deal has gained the support of scientists, medical doctors, members of Congress, and thousands of others who care about ethical and effective science.

How You Can Help Animals Used in Experiments

Each of us can help prevent the suffering and deaths of animals in laboratories. Here are a few easy ways to get started:

• Sign up for PETA’s Action Team to be alerted when protests are taking place in your area.
• Urge your members of Congress to support PETA’s Research Modernization Deal .
• Search PETA’s Beauty Without Bunnies database to ensure that you’re buying only cruelty-free products.
• Donate only to charities that don’t experiment on animals .
• Request alternatives to animal dissection at your school.
• Call on your alma mater to stop experimenting on animals.
• Share information about animal experimentation issues with your friends and family—and invite them to join you in speaking up for animals.

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Free Argumentative Essay On Animal Testing Should Be Banned

Animals testing essay.

Arguably, animal testing has been an emotive subject with a lot of ethical, moral, and medical debate, and controversy for many decades. What we should all ask is, does the payback obtained by human beings from animal experimentation justify the inhumane, and harm caused to animals? Billions of animals in the world are killed in laboratories for experimental purposes (Monamy 17). Additionally, most of the animals die in the process of medical research, cosmetic experiments, as well as commercial research. Therefore, animal experimentation is harmful, inhumane, and cruel, and it should be banned.

Reasons why animal experimentation should be banned

Animal testing argumentative essay sample, introduction, argumentative essay on should we use animals for drug testing.

This paper examines the arguments for and against the sue of animals in experiments. It offers a brief examination of the historical development of the opposition to using animals; it considers the question form the practical and the ethical standpoint; it examines some of the evidence which shows the inefficiency and unreliability of animal use; and it also shows the way ethical standpoints have changed in the 21st century.

Key words: the three Rs; in vitro testing ; principle of equality; human volunteers; computer simulations.

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Do you believe that experimentation on animals for scientific purposes is justified. Are there any alternatives to animal experimentation?

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Include an introduction and conclusion

A conclusion is essential for IELTS writing task 2. It is more important than most people realise. You will be penalised for missing a conclusion in your IELTS essay.

The easiest paragraph to write in an essay is the conclusion paragraph. This is because the paragraph mostly contains information that has already been presented in the essay – it is just the repetition of some information written in the introduction paragraph and supporting paragraphs.

The conclusion paragraph only has 3 sentences:

• Restatement of thesis
• Prediction or recommendation

To summarize, a robotic teacher does not have the necessary disciple to properly give instructions to students and actually works to retard the ability of a student to comprehend new lessons. Therefore, it is clear that the idea of running a classroom completely by a machine cannot be supported. After thorough analysis on this subject, it is predicted that the adverse effects of the debate over technology-driven teaching will always be greater than the positive effects, and because of this, classroom teachers will never be substituted for technology.

Start your conclusion with a linking phrase. Here are some examples:

• In conclusion
• To conclude
• To summarize
• In a nutshell

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In some parts of the world traditional festivals and celebrations have dissapeared or are disappearing. What problem is this causing? What measures could be taken to counter this solution?

You recently went to a cinema where you tried watching a movie, however, you were bothered by a group of teenagers who were very loud in front of you. you complained to the manager but it was not paid attention to. write an email to a cinema manager in about 150-200 words. your email should include the following things: • describe your situation • explained what happened after you complained to the manager • suggest solutions to improve, some people think that studying history is a waste of time while others think that it is essential to learn. discuss both sides and give your opinion., in many nations , only a minority of young people are willing to do unpaid community service . there are many arguments that shows many negative outcomes because of this problem and the best solution are in demand ., some people argue job satisfaction is more important than job security. others believe a permanent job is more important. discuss both these views and give your own opinion..

vmTracking: Virtual Markers Overcome Occlusion and Crowding in Multi-Animal Pose Tracking

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In multi-animal tracking, addressing occlusion and crowding is crucial for accurate behavioral analysis. Consequently, we introduced Virtual Marker Tracking (vmTracking), which uses virtual markers for individual identification. Virtual markers, created from traditional markerless multi-animal pose tracking tools like multi-animal DeepLabCut (maDLC) and Social LEAP Estimate Animal Poses (SLEAP), attribute features to individuals, enabling consistent identification throughout the entire video without physical markers. Using these markers as cues, annotations were applied to multi-animal videos, and tracking was conducted with single-animal DeepLabCut (saDLC) and SLEAP's single-animal method. vmTracking minimized manual corrections and annotation frames needed for training, efficiently tackling occlusion and crowding. Experiments tracking multiple mice, fish, and human dancers confirmed vmTracking's variability and applicability. These findings could enhance the precision and reliability of tracking methods used in the analysis of complex naturalistic and social behaviors in animals, providing a simpler yet more effective solution.

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National Research Council (US) and Institute of Medicine (US) Committee on the Use of Laboratory Animals in Biomedical and Behavioral Research. Use of Laboratory Animals in Biomedical and Behavioral Research. Washington (DC): National Academies Press (US); 1988.

Use of Laboratory Animals in Biomedical and Behavioral Research.

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Executive Summary

The use of animals in scientific research has been a controversial issue for well over a hundred years. The basic problem can be stated quite simply: Research with animals has saved human lives, lessened human suffering, and advanced scientific understanding, yet that same research can cause pain and distress for the animals involved and usually results in their death. It is hardly surprising that animal experimentation raises complex questions and generates strong emotions.

Animal experimentation is an essential component of biomedical and behavioral research, a critical part of efforts to prevent, cure, and treat a vast range of ailments. As in the past, investigators are using animals to learn about the most widespread diseases of the age, including heart disease and cancer, as well as to gain basic knowledge in genetics, physiology, and other life sciences. Animals are also needed to combat new diseases, of which acquired immune deficiency syndrome (AIDS) is currently the most prominent example. At the same time, behavioral researchers are drawing on animal studies to learn more about such major causes of human suffering as mental illness, drug addiction, and senility.

The recognition that animals are essential in scientific research is critical in making decisions about their use, but these decisions are also made in the broad context of social and ethical values. In this report, the committee addresses these issues and examines how and why animals are used in research and how society oversees that research.

• Patterns of Animal Use

Data about the numbers and species of animals used for scientific experimentation in the United States come primarily from two sources: the National Research Council's Institute for Laboratory Animal Resources (ILAR) and the U.S. Department of Agriculture's Animal and Plant Health Inspection Service (APHIS). Though the information from both of these sources is incomplete, it provides a picture of the magnitude of animal experimentation in the United States. In 1983, an estimated 17 to 22 million animals were used for research, testing, and education in the United States. In this case, ''animal'' includes all vertebrates—namely, mammals, birds, reptiles, amphibians, and fish. The majority of animals used—between 12 million and 15 million—were rats and mice. These quantities are a small fraction of the total of over 5 billion animals used annually for food, clothing, and other purposes in the United States.

A significant portion of the laboratory animals used each year are involved not in research but in testing. Research and testing are not always separable, but testing generally entails the use of animals, primarily rats and mice, to assess the safety or effectiveness of consumer products such as drugs, chemicals, and cosmetics.

The data concerning the numbers of animals used in testing are not complete. Various sources estimate that anywhere from several million to more than half of the approximately 20 million animals used for research and testing in the United States are used for testing. In contrast, the use of animals in education is relatively small (i.e., only an estimated 53,000 animals are used per year in teaching in medical and veterinary schools) and has been declining in recent years.

In general, the data concerning animal use in the United States must be viewed as uncertain. The Office of Technology Assessment has concluded that it is not even possible to tell from the existing data whether the total number of animals used each year is increasing or decreasing. A survey now being planned by ILAR, the fourth in a series of ILAR surveys conducted since 1962, will provide some of this information.

Animal research encompasses a wide range of biomedical and behavioral experiments. One field of behavioral research entails observing animals in colonies that simulate their natural environments. Other animals undergo medical procedures such as surgery to gauge the effectiveness of new techniques. Some are exposed to toxic substances until death or disability results. Others are killed immediately to obtain an essential organ or tissue for further studies. Although long-term survival is sometimes the goal of animal experimentation, most research animals are humanely killed at some point during the course of the research.

• Benefits Derived from the Use of Animals

The use of animals in biomedical and behavioral research has greatly increased scientific knowledge and has had enormous benefits for human health. For example, in the United States, animal experimentation has contributed to an increase in average life expectancy of about 25 years since 1900. A few examples give an indication of the breadth and variety of these contributions.

• Animals have been used to study cardiovascular function and disease since the early 1600s. Heart-lung machines, which have made open-heart surgery possible, were developed with animals before being used with humans. More than 80 percent of all congenital heart diseases that were formerly fatal can now be cured by surgical treatment based on animal experiments. Similarly, a wide variety of surgical techniques and drug treatments, which have extended life for millions of Americans, were first perfected in animals.
• Studies of the biology of transplantation in animals have made it possible to transfer organs between people. Some 30,000 Americans now alive have transplanted kidneys, which free them from the laborious and uncomfortable dialysis treatments once needed to keep them alive. Other Americans are now alive because of transplanted hearts or livers, or have had their lives immeasurably improved because of skin or cornea transplants. Basic research on transplantation has also contributed greatly to the understanding of immunology, with wide ramifications for the treatment of many diseases.
• Animal research shed light on the nature of polio and has helped to nearly eliminate the disease from the United States. In the early 1900s, researchers succeeded in transmitting the polio virus to monkeys for the first time. In following years, investigators tested various altered or inactivated forms of the virus in monkeys until strains were found that could immunize the monkeys without giving them the disease. This work led to human vaccines that have reduced the number of cases of paralytic polio in the United States from 58,000 in 1952, at the height of one epidemic, to 4 in 1984.
• Many clinically useful methodologies were first tested on animals before being used with humans. Examples include computed axial tomographic (CAT) scans and magnetic resonance imaging (MRI).
• Animal studies have been essential in probing the functions of the brain in health and disease. Investigators have used animals to understand movement (and the movement dysfunctions caused by such diseases as epilepsy and multiple sclerosis), vision, memory (including the severe memory loss that occurs in 5 percent of persons over the age of 65), drug addiction, nerve cell regeneration, learning, and pain.

The use of animals is important if biomedical research is to continue to lead to the understanding and amelioration of diseases such as cancer, diabetes, and uncontrolled infectious diseases. It will also be essential in efforts to understand and control newly emergent human diseases. For example, researchers have identified viruses in monkeys and other animals that cause diseases in those species similar to AIDS. These animals can therefore act as model systems for the human disease, allowing investigation of possible treatments and vaccines.

Animal research does not only benefit humans. Much animal research also benefits animals, either directly because animal health is the subject of research or indirectly because the same procedures and treatments used in humans can be used in animals. Most of the animals that benefit from this research are domesticated and therefore assist humans in some way—as sources of food and fiber, for instance, or as pets and companions. Vaccines, antibiotics, anesthetics, and other products have improved the lives of countless animals.

• Alternative Methods in Biomedical and Behavioral Research

Scientists have been and are searching for alternative methods to the use of animals in biomedical and behavioral research for a variety of reasons, including an interest in the welfare of animals, a concern for the increasing costs of purchasing and caring for animals, and because in some areas alternative methods may be more efficient and effective research tools. In current usage, the term "alternative methods" includes replacements for mammals, reductions in the use of animals, and refinements in experimental protocols that lessen the pain of the animals involved.

One way to reduce the use of mammals is to modify experimental protocols so that fewer of them are needed. In the field of testing, for instance, methods have been found to assess toxicity using fewer mammals than were once thought necessary. In addition, in some experimental situations, features of mammals can be modeled by nonmammalian vertebrates (birds, reptiles, amphibians, and fish), invertebrates, plants, organs, tissues, cells, microorganisms, and nonbiological systems. For example, research conducted on the fruit fly Drosophila has led to understandings in genetics that apply to all living things, and mathematical models can increase the effectiveness of experiments by defining variables and checking theories, thus making experiments on biological systems more effective and economical. Finally, experimental protocols can be refined to reduce the pain and suffering experienced by laboratory animals. These approaches are all referred to as alternatives.

The search for alternatives to the use of animals in research and testing remains a valid goal of researchers, but the chance that alternatives will completely replace animals in the foreseeable future is nil. Nevertheless, successes have occurred in reducing the numbers of animals used, in developing nonmammalian models, and in refining experimental protocols to reduce the pain experienced by animals, and work continues in this area.

Recognizing the above, the committee recommends that:

• Research investigators should consider possible alternative methods before using animals in experimental procedures.

To enable researchers better to consider alternatives, it is important that they have access to relevant information. The committee therefore recommends that:

• Databases and knowledge bases should be further developed and made available for those seeking appropriate experimental models for use in the design of research protocols.

Furthermore, although the committee's work has focused mainly on research, it recommends that:

• Federal regulatory agencies should move rapidly to accept tests—as such tests become validated—that reduce the number of vertebrates used, insofar as this does not compromise the regulatory mission of an agency and protection of the public.
• Regulatory Issues

The laws and regulations governing animal research reflect the broad ethical considerations surrounding the use of animals by humans. The most important federal law affecting animal research in the United States is the Animal Welfare Act. Passed in 1966 and amended in 1970, 1976, and 1985, the act sets minimum standards for handling, housing, feeding, and watering laboratory animals and establishes basic levels of sanitation, ventilation, and shelter from temperature and weather extremes. The law covers those warm-blooded animals designated by the secretary of the U.S. Department of Agriculture, the overseer of the Animal Welfare Act. At present, this includes dogs, cats, nonhuman primates, rabbits, hamsters, guinea pigs, and marine mammals, but not rats, mice, birds, and farm animals used in biomedical research—although rats and mice account for about 85 percent of the animals used in research, education, and testing.

The most recent amendments to the Animal Welfare Act, which took the form of the Improved Standards for Laboratory Animals Act of 1985, added several important provisions to the law. The law requires investigators to consider alternative methods that do not involve animals and to consult with a veterinarian before beginning any experiment that could cause pain. It also requires that dogs receive proper exercise, that primates be provided with environments that promote their psychological well-being, and that all animals used receive adequate presurgical and postsurgical care and pain-relieving drugs. These amendments also require that each registered research facility appoint a committee to monitor animal research in that institution. These committees must include a veterinarian and a person unaffiliated with the research facility to represent the community's interests in animal welfare. Committee members must inspect the facility's animal laboratories twice a year and report deficiencies to the institution for correction. If the deficiencies are not corrected promptly, the U.S. Department of Agriculture must be notified for enforcement, and any funding agency must be informed so that it can decide whether to suspend or revoke grants or contracts to the violator.

A second long-standing, important document affecting animal research in the United States is a product not of the federal government but of the scientific community. In 1963, the Animal Care Panel released the Guide for Laboratory Animal Facilities and Care . The Guide has been revised five times since then by ILAR, most recently in 1985, and has been renamed the Guide for the Care and Use of Laboratory Animals to reflect its broadened scope. Its purpose is to assist investigators and institutions in caring for and using laboratory animals professionally and humanely. It is written in general terms so that it can be used by the wide variety of institutions that conduct experiments using animals.

A number of other government agencies and private organizations have drawn on the Guide in establishing standards for animal research. The 1985 Health Research Extension Act, which reauthorized funding for the National Institutes of Health (NIH), requires that researchers receiving funding from NIH adhere to the standards of the Guide . In 1986, the Public Health Service (PHS)—which includes NIH, the Food and Drug Administration, the Centers for Disease Control, and the Alcohol, Drug Abuse, and Mental Health Administration—released the most recent revision of its policy statement on the humane care and use of laboratory animals. This, too, requires compliance with the Guide . An Interagency Research Animal Committee incorporated the Guide by reference in its 1985 "U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training." On the nongovernmental side, the American Association for Accreditation of Laboratory Animal Care uses the Guide in evaluating the animal facilities of institutions seeking accreditation.

In addition to requiring compliance with the Guide , the PHS policy statement and 1985 Health Research Extension Act include several other important statutory and regulatory changes. They require that each institution receiving funds from PHS maintain an Institutional Animal Care and Use Committee (IACUC) to monitor animal research. As with the committees required by the Animal Welfare Act, each IACUC must include one veterinarian and one individual not affiliated with the institution. Investigators who plan to use animals must submit their research protocols to these committees, including a justification for the use of a particular kind of animal and a demonstration that they have considered methods that do not use animals.

The use of animals for research, testing, and education is also regulated in other ways in the United States. For example, the Food and Drug Administration and the Environmental Protection Agency have established Good Laboratory Practices (GLP) regulations that affect the use and care of animals.

Even with this abundance of regulatory activity, self-regulation is the most important determinant of humane treatment of animals. Professional societies have set up guidelines to be followed by their members. In addition, many individual institutions—governmental, academic, and private—have established policies governing animal experimentation and testing. Many institutions now provide information and instruction to animal users on the proper care and handling of research animals. Most important are individual investigators; under the review of their institutional animal committees, they ultimately have the greatest control over and responsibility for how an animal will be cared for and used. At the same time, most scientists acknowledge the need for regulations to set minimum standards and provide for public accountability.

Although humane care and use of laboratory animals characterize the scientific community, there have been from time to time some members of this community who have been found to care inadequately for their animals. The committee believes that the mistreatment or mishandling of animals is not acceptable. Maltreatment and improper care of animals used in research cannot be tolerated, and individuals responsible for such behavior must be subject to censure. Without such punishment, the continued use of animals by all scientists is threatened, as more regulations and restrictions are imposed by legislative and regulatory authorities in response to their perception that scientists who commit abuses are not punished.

Many scientists believe, however, that present regulatory procedures can in some instances be disruptive, in that they may decrease efficiency, increase costs, and slow progress. For instance, obtaining preliminary approval of all research protocols does delay some experiments. On the other hand, protocol review can help the researcher when it provides an opportunity for the scientist's peers to offer advice and assistance. This advice may result in a better-planned experiment that not only improves animal care and minimizes animal pain but also leads to more instructive results. In any case, more extensive regulations may have contributed to the increased expense of animal research, which constrains the research that can be done.

The requirement that investigators strictly comply with the Guide for the Care and Use of Laboratory Animals has also raised difficulties. The 1985 Health Research Extension Act essentially imparts the force of law to the Guide , but the Guide was not written to be a legal document. It was designed to provide for flexibility in interpretation, guided by professional judgment. As such, it has served the community of individuals using laboratory animals well in the more than 20 years since it was first published. Because it is now being used to set minimum standards for inspection, it may in some respects be too rigidly interpreted, as in the requirement for multiple separate areas and rooms for performing aseptic surgery. If the Guide is to act as law, it should be carefully examined and redrafted as needed to ensure that its language satisfies the intent, as distinct from the letter, of the law.

In the general area of regulation, the committee recommends the following:

• No additional laws or regulatory measures (except the regulations required by the Improved Standards for Laboratory Animals Act of 1985) affecting the use of animals in research should be promulgated until, based on experience, a careful accounting of the effects of the application of the present body of laws, regulations, and guidelines has been made and evidence of the need for more regulation is available.
• A mechanism should be established for ongoing review of the regulatory framework of federal agencies for animal experimentation. It is essential that research scientists who must abide by this regulatory framework be prominently involved in its assessment. Specifically, the Guide for the Care and Use of Laboratory Animals should be reviewed as soon as possible to determine whether revisions are necessary due to new information.
• Federal standards developed by different agencies for the care and use of laboratory animals should be congruent with each other.
• Sufficient federal funds should be appropriated for the inspections required for the enforcement of the Animal Welfare Act.
• Sufficient federal funds should be appropriated for maintenance and improvement of animal facilities to allow individuals and institutions to conduct animal research in compliance with government policies, regulations, and laws. It is important that such funds should be added to ongoing research support.
• Use of Pound Animals

One of the most controversial areas in the current debate involves the use of impounded dogs and cats. The emotions engendered have resulted in the passage of laws by a number of political jurisdictions that prohibit or restrict the release of impounded animals for use in research. These laws create a dilemma: the impounded animals are not released for use in research but are killed by the pound or shelter if not claimed. Each year more than 10 million such animals are destroyed at pounds or shelters, whereas fewer than 200,000 dogs and cats are released from pounds and shelters to scientific establishments for use in research—less than 2 percent of the number that are destroyed.

A prohibition against the use of pound animals also means that more animals are used each year. Instead of using one of the 10 million pound animals that will be destroyed, different animals are bred for use in research.

Whether a pound animal or a "purpose-bred" animal is the appropriate research model depends on the needs of the experiment. Pound animals are seen as having varied genetic backgrounds. In some experiments the genetic variability, because it is much like that found naturally in humans, is an advantage; in other cases it is necessary to know the genetic background of the animal, requiring an animal bred for research. For other experiments it may be necessary to use purpose-bred animals because the health history, physiological status, and age of pound animals are not well enough known to ensure that conditions present in the animals will not interfere with conduct of the experiment.

Twelve states have passed laws that prohibit the release of impounded animals for use in research. In 11 of these states, researchers can use animals impounded in other states, which are legally transported across state lines by dealers. In Massachusetts, a new law that went into effect in 1986 prohibits researchers from using any animals from pounds, no matter where those animals were impounded.

A prohibition against the use of pound animals inevitably increases the costs of animal research because the cost of an animal from a dealer is greater than the cost of a pound animal. If the impounded dogs used each year in research were not available, a substantial additional cost would be incurred from buying replacement dogs from dealers.

In addressing the use of pound animals:

• The committee unanimously recommends that pound animals be made available for research in which the experimental animals are used in acute experiments (i.e., in which the animals remain anesthetized until they are killed). While a majority of the committee supports the appropriate use of pound animals in all experiments, a minority opposes the use of pound animals for chronic, survival experiments.

American society is a pluralistic society in which public policy takes into account many different perspectives. No single ideology or theology governs people's ways of thinking. Similarly, decisions in the United States do not arise unilaterally from authorities. They reflect a consensus within society, as expressed through people's elected representatives.

Some people will continue to contend that animal research should be eliminated. The committee rejects such a view. Indeed, the committee concludes that:

• Humans are morally obliged to each other to improve the human condition. In cases in which research with animals is the best available method to reach that goal, animals should be used.

The committee also recognizes that:

• Scientists are ethically obliged to ensure the well-being of animals used in research and to minimize their pain and suffering.

The committee affirms the principle of humane care of all animals used in research and recommends that:

• All those responsible for the care and use of animals in research should adhere to the principle that these animals be treated humanely.
• Cite this Page National Research Council (US) and Institute of Medicine (US) Committee on the Use of Laboratory Animals in Biomedical and Behavioral Research. Use of Laboratory Animals in Biomedical and Behavioral Research. Washington (DC): National Academies Press (US); 1988. Executive Summary.
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The ASPCA: a Deep Dive into its Influence and Initiatives

“This essay about the ASPCA explores its profound impact and multifaceted initiatives in animal welfare. Founded in 1866 by Henry Bergh, the ASPCA has evolved into a pivotal force in advocating for legislative reforms and combating animal cruelty nationwide. From rescue operations and veterinary care to global partnerships in wildlife conservation, the organization remains dedicated to promoting responsible pet ownership and advancing humane treatment practices. Through extensive anti-cruelty efforts and research-driven advocacy, the ASPCA not only saves lives but also shapes policies that protect animals and educate the public. Supported by volunteers and donors, the ASPCA continues to lead efforts in creating a more compassionate world for all animals.”

How it works

Founded in 1866 by Henry Bergh in New York City, the ASPCA, or American Society for the Prevention of Cruelty to Animals, emerged as a pioneering force in animal welfare advocacy. Initially driven by a passion to protect horses from mistreatment, Bergh’s vision quickly expanded to encompass a broader mission of safeguarding all animals from cruelty and neglect.

Throughout its history, the ASPCA has evolved into a multifaceted organization dedicated to promoting the welfare of animals across the United States. Its initiatives span a wide spectrum of programs aimed at rescue, rehabilitation, advocacy, and education.

These efforts are not only aimed at immediate relief but also at fostering long-term systemic change in how society views and treats animals.

At the heart of the ASPCA’s impact lies its commitment to legislative reform. Over the decades, the organization has been instrumental in advocating for and enacting laws that protect animals from abuse. From lobbying against practices in puppy mills to advocating for humane treatment standards in agriculture, the ASPCA’s legislative efforts have reshaped animal welfare policies nationwide.

The ASPCA’s anti-cruelty efforts are a cornerstone of its mission. Each year, the organization responds to thousands of cases of animal abuse and neglect, working closely with law enforcement agencies to rescue animals from dire situations and ensure that perpetrators are held accountable. These interventions not only save lives but also serve as a deterrent against future acts of cruelty.

In addition to its domestic initiatives, the ASPCA extends its impact globally through collaborations with international organizations. By sharing expertise and resources, the ASPCA contributes to efforts in wildlife conservation, disaster response for animals, and the promotion of humane practices in agriculture worldwide. These global partnerships underscore the organization’s commitment to advancing animal welfare on a global scale.

Research and innovation play a vital role in the ASPCA’s approach to advocacy and education. The organization invests in scientific research to better understand animal behavior, welfare practices, and the effectiveness of legislative measures. By generating evidence-based insights, the ASPCA not only enhances its own programs but also informs broader discussions on animal welfare policy and practice.

Volunteers and donors are integral to the ASPCA’s ability to carry out its mission effectively. Their support enables the organization to fund critical programs such as emergency rescue operations, medical care for animals in need, and community outreach efforts to promote responsible pet ownership. Through their dedication and generosity, volunteers and donors play a crucial role in advancing the ASPCA’s impact and ensuring that animals receive the care and protection they deserve.

As the ASPCA continues to evolve, it remains committed to adapting its strategies to meet emerging challenges in animal welfare. By leveraging innovation and embracing new opportunities for collaboration and advocacy, the organization remains at the forefront of efforts to create a more compassionate world for animals.

In conclusion, the ASPCA’s journey from its founding in 1866 to its current role as a leading advocate for animal welfare reflects a legacy of compassion, dedication, and impact. Through its comprehensive programs, legislative advocacy, global outreach, and commitment to research and education, the ASPCA continues to make a profound difference in the lives of animals and inspire positive change in society’s treatment of all creatures.

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Why the Pandemic Probably Started in a Lab, in 5 Key Points

By Alina Chan

Dr. Chan is a molecular biologist at the Broad Institute of M.I.T. and Harvard, and a co-author of “Viral: The Search for the Origin of Covid-19.”

This article has been updated to reflect news developments.

On Monday, Dr. Anthony Fauci returned to the halls of Congress and testified before the House subcommittee investigating the Covid-19 pandemic. He was questioned about several topics related to the government’s handling of Covid-19, including how the National Institute of Allergy and Infectious Diseases, which he directed until retiring in 2022, supported risky virus work at a Chinese institute whose research may have caused the pandemic.

For more than four years, reflexive partisan politics have derailed the search for the truth about a catastrophe that has touched us all. It has been estimated that at least 25 million people around the world have died because of Covid-19, with over a million of those deaths in the United States.

Although how the pandemic started has been hotly debated, a growing volume of evidence — gleaned from public records released under the Freedom of Information Act, digital sleuthing through online databases, scientific papers analyzing the virus and its spread, and leaks from within the U.S. government — suggests that the pandemic most likely occurred because a virus escaped from a research lab in Wuhan, China. If so, it would be the most costly accident in the history of science.

Here’s what we now know:

1 The SARS-like virus that caused the pandemic emerged in Wuhan, the city where the world’s foremost research lab for SARS-like viruses is located.

• At the Wuhan Institute of Virology, a team of scientists had been hunting for SARS-like viruses for over a decade, led by Shi Zhengli.
• Their research showed that the viruses most similar to SARS‑CoV‑2, the virus that caused the pandemic, circulate in bats that live r oughly 1,000 miles away from Wuhan. Scientists from Dr. Shi’s team traveled repeatedly to Yunnan province to collect these viruses and had expanded their search to Southeast Asia. Bats in other parts of China have not been found to carry viruses that are as closely related to SARS-CoV-2.

The closest known relatives to SARS-CoV-2 were found in southwestern China and in Laos.

Large cities

Mine in Yunnan province

Cave in Laos

South China Sea

The closest known relatives to SARS-CoV-2

were found in southwestern China and in Laos.

philippines

The closest known relatives to SARS-CoV-2 were found

in southwestern China and Laos.

Sources: Sarah Temmam et al., Nature; SimpleMaps

Note: Cities shown have a population of at least 200,000.

There are hundreds of large cities in China and Southeast Asia.

There are hundreds of large cities in China

and Southeast Asia.

The pandemic started roughly 1,000 miles away, in Wuhan, home to the world’s foremost SARS-like virus research lab.

The pandemic started roughly 1,000 miles away,

in Wuhan, home to the world’s foremost SARS-like virus research lab.

The pandemic started roughly 1,000 miles away, in Wuhan,

home to the world’s foremost SARS-like virus research lab.

• Even at hot spots where these viruses exist naturally near the cave bats of southwestern China and Southeast Asia, the scientists argued, as recently as 2019 , that bat coronavirus spillover into humans is rare .
• When the Covid-19 outbreak was detected, Dr. Shi initially wondered if the novel coronavirus had come from her laboratory , saying she had never expected such an outbreak to occur in Wuhan.
• The SARS‑CoV‑2 virus is exceptionally contagious and can jump from species to species like wildfire . Yet it left no known trace of infection at its source or anywhere along what would have been a thousand-mile journey before emerging in Wuhan.

2 The year before the outbreak, the Wuhan institute, working with U.S. partners, had proposed creating viruses with SARS‑CoV‑2’s defining feature.

• Dr. Shi’s group was fascinated by how coronaviruses jump from species to species. To find viruses, they took samples from bats and other animals , as well as from sick people living near animals carrying these viruses or associated with the wildlife trade. Much of this work was conducted in partnership with the EcoHealth Alliance, a U.S.-based scientific organization that, since 2002, has been awarded over $80 million in federal funding to research the risks of emerging infectious diseases.
• The laboratory pursued risky research that resulted in viruses becoming more infectious : Coronaviruses were grown from samples from infected animals and genetically reconstructed and recombined to create new viruses unknown in nature. These new viruses were passed through cells from bats, pigs, primates and humans and were used to infect civets and humanized mice (mice modified with human genes). In essence, this process forced these viruses to adapt to new host species, and the viruses with mutations that allowed them to thrive emerged as victors.
• By 2019, Dr. Shi’s group had published a database describing more than 22,000 collected wildlife samples. But external access was shut off in the fall of 2019, and the database was not shared with American collaborators even after the pandemic started , when such a rich virus collection would have been most useful in tracking the origin of SARS‑CoV‑2. It remains unclear whether the Wuhan institute possessed a precursor of the pandemic virus.
• In 2021, The Intercept published a leaked 2018 grant proposal for a research project named Defuse , which had been written as a collaboration between EcoHealth, the Wuhan institute and Ralph Baric at the University of North Carolina, who had been on the cutting edge of coronavirus research for years. The proposal described plans to create viruses strikingly similar to SARS‑CoV‑2.
• Coronaviruses bear their name because their surface is studded with protein spikes, like a spiky crown, which they use to enter animal cells. T he Defuse project proposed to search for and create SARS-like viruses carrying spikes with a unique feature: a furin cleavage site — the same feature that enhances SARS‑CoV‑2’s infectiousness in humans, making it capable of causing a pandemic. Defuse was never funded by the United States . However, in his testimony on Monday, Dr. Fauci explained that the Wuhan institute would not need to rely on U.S. funding to pursue research independently.

The Wuhan lab ran risky experiments to learn about how SARS-like viruses might infect humans.

1. Collect SARS-like viruses from bats and other wild animals, as well as from people exposed to them.

2. Identify high-risk viruses by screening for spike proteins that facilitate infection of human cells.

2. Identify high-risk viruses by screening for spike proteins that facilitate infection of

human cells.

In Defuse, the scientists proposed to add a furin cleavage site to the spike protein.

3. Create new coronaviruses by inserting spike proteins or other features that could make the viruses more infectious in humans.

4. Infect human cells, civets and humanized mice with the new coronaviruses, to determine how dangerous they might be.

• While it’s possible that the furin cleavage site could have evolved naturally (as seen in some distantly related coronaviruses), out of the hundreds of SARS-like viruses cataloged by scientists, SARS‑CoV‑2 is the only one known to possess a furin cleavage site in its spike. And the genetic data suggest that the virus had only recently gained the furin cleavage site before it started the pandemic.
• Ultimately, a never-before-seen SARS-like virus with a newly introduced furin cleavage site, matching the description in the Wuhan institute’s Defuse proposal, caused an outbreak in Wuhan less than two years after the proposal was drafted.
• When the Wuhan scientists published their seminal paper about Covid-19 as the pandemic roared to life in 2020, they did not mention the virus’s furin cleavage site — a feature they should have been on the lookout for, according to their own grant proposal, and a feature quickly recognized by other scientists.
• Worse still, as the pandemic raged, their American collaborators failed to publicly reveal the existence of the Defuse proposal. The president of EcoHealth, Peter Daszak, recently admitted to Congress that he doesn’t know about virus samples collected by the Wuhan institute after 2015 and never asked the lab’s scientists if they had started the work described in Defuse. In May, citing failures in EcoHealth’s monitoring of risky experiments conducted at the Wuhan lab, the Biden administration suspended all federal funding for the organization and Dr. Daszak, and initiated proceedings to bar them from receiving future grants. In his testimony on Monday, Dr. Fauci said that he supported the decision to suspend and bar EcoHealth.
• Separately, Dr. Baric described the competitive dynamic between his research group and the institute when he told Congress that the Wuhan scientists would probably not have shared their most interesting newly discovered viruses with him . Documents and email correspondence between the institute and Dr. Baric are still being withheld from the public while their release is fiercely contested in litigation.
• In the end, American partners very likely knew of only a fraction of the research done in Wuhan. According to U.S. intelligence sources, some of the institute’s virus research was classified or conducted with or on behalf of the Chinese military . In the congressional hearing on Monday, Dr. Fauci repeatedly acknowledged the lack of visibility into experiments conducted at the Wuhan institute, saying, “None of us can know everything that’s going on in China, or in Wuhan, or what have you. And that’s the reason why — I say today, and I’ve said at the T.I.,” referring to his transcribed interview with the subcommittee, “I keep an open mind as to what the origin is.”

3 The Wuhan lab pursued this type of work under low biosafety conditions that could not have contained an airborne virus as infectious as SARS‑CoV‑2.

• Labs working with live viruses generally operate at one of four biosafety levels (known in ascending order of stringency as BSL-1, 2, 3 and 4) that describe the work practices that are considered sufficiently safe depending on the characteristics of each pathogen. The Wuhan institute’s scientists worked with SARS-like viruses under inappropriately low biosafety conditions .

In the United States, virologists generally use stricter Biosafety Level 3 protocols when working with SARS-like viruses.

Biosafety cabinets prevent

viral particles from escaping.

Viral particles

Personal respirators provide

a second layer of defense against breathing in the virus.

DIRECT CONTACT

Gloves prevent skin contact.

Disposable wraparound

gowns cover much of the rest of the body.

Personal respirators provide a second layer of defense against breathing in the virus.

Disposable wraparound gowns

cover much of the rest of the body.

Note: ​​Biosafety levels are not internationally standardized, and some countries use more permissive protocols than others.

The Wuhan lab had been regularly working with SARS-like viruses under Biosafety Level 2 conditions, which could not prevent a highly infectious virus like SARS-CoV-2 from escaping.

Some work is done in the open air, and masks are not required.

Less protective equipment provides more opportunities

for contamination.

Some work is done in the open air,

and masks are not required.

Less protective equipment provides more opportunities for contamination.

• In one experiment, Dr. Shi’s group genetically engineered an unexpectedly deadly SARS-like virus (not closely related to SARS‑CoV‑2) that exhibited a 10,000-fold increase in the quantity of virus in the lungs and brains of humanized mice . Wuhan institute scientists handled these live viruses at low biosafet y levels , including BSL-2.
• Even the much more stringent containment at BSL-3 cannot fully prevent SARS‑CoV‑2 from escaping . Two years into the pandemic, the virus infected a scientist in a BSL-3 laboratory in Taiwan, which was, at the time, a zero-Covid country. The scientist had been vaccinated and was tested only after losing the sense of smell. By then, more than 100 close contacts had been exposed. Human error is a source of exposure even at the highest biosafety levels , and the risks are much greater for scientists working with infectious pathogens at low biosafety.
• An early draft of the Defuse proposal stated that the Wuhan lab would do their virus work at BSL-2 to make it “highly cost-effective.” Dr. Baric added a note to the draft highlighting the importance of using BSL-3 to contain SARS-like viruses that could infect human cells, writing that “U.S. researchers will likely freak out.” Years later, after SARS‑CoV‑2 had killed millions, Dr. Baric wrote to Dr. Daszak : “I have no doubt that they followed state determined rules and did the work under BSL-2. Yes China has the right to set their own policy. You believe this was appropriate containment if you want but don’t expect me to believe it. Moreover, don’t insult my intelligence by trying to feed me this load of BS.”
• SARS‑CoV‑2 is a stealthy virus that transmits effectively through the air, causes a range of symptoms similar to those of other common respiratory diseases and can be spread by infected people before symptoms even appear. If the virus had escaped from a BSL-2 laboratory in 2019, the leak most likely would have gone undetected until too late.
• One alarming detail — leaked to The Wall Street Journal and confirmed by current and former U.S. government officials — is that scientists on Dr. Shi’s team fell ill with Covid-like symptoms in the fall of 2019 . One of the scientists had been named in the Defuse proposal as the person in charge of virus discovery work. The scientists denied having been sick .

4 The hypothesis that Covid-19 came from an animal at the Huanan Seafood Market in Wuhan is not supported by strong evidence.

• In December 2019, Chinese investigators assumed the outbreak had started at a centrally located market frequented by thousands of visitors daily. This bias in their search for early cases meant that cases unlinked to or located far away from the market would very likely have been missed. To make things worse, the Chinese authorities blocked the reporting of early cases not linked to the market and, claiming biosafety precautions, ordered the destruction of patient samples on January 3, 2020, making it nearly impossible to see the complete picture of the earliest Covid-19 cases. Information about dozens of early cases from November and December 2019 remains inaccessible.
• A pair of papers published in Science in 2022 made the best case for SARS‑CoV‑2 having emerged naturally from human-animal contact at the Wuhan market by focusing on a map of the early cases and asserting that the virus had jumped from animals into humans twice at the market in 2019. More recently, the two papers have been countered by other virologists and scientists who convincingly demonstrate that the available market evidence does not distinguish between a human superspreader event and a natural spillover at the market.
• Furthermore, the existing genetic and early case data show that all known Covid-19 cases probably stem from a single introduction of SARS‑CoV‑2 into people, and the outbreak at the Wuhan market probably happened after the virus had already been circulating in humans.

An analysis of SARS-CoV-2’s evolutionary tree shows how the virus evolved as it started to spread through humans.

SARS-COV-2 Viruses closest

to bat coronaviruses

more mutations

Source: Lv et al., Virus Evolution (2024) , as reproduced by Jesse Bloom

The viruses that infected people linked to the market were most likely not the earliest form of the virus that started the pandemic.

• Not a single infected animal has ever been confirmed at the market or in its supply chain. Without good evidence that the pandemic started at the Huanan Seafood Market, the fact that the virus emerged in Wuhan points squarely at its unique SARS-like virus laboratory.

5 Key evidence that would be expected if the virus had emerged from the wildlife trade is still missing.

In previous outbreaks of coronaviruses, scientists were able to demonstrate natural origin by collecting multiple pieces of evidence linking infected humans to infected animals.

Infected animals

Earliest known

cases exposed to

live animals

Antibody evidence

of animals and

animal traders having

been infected

Ancestral variants

of the virus found in

Documented trade

of host animals

between the area

where bats carry

closely related viruses

and the outbreak site

Infected animals found

Earliest known cases exposed to live animals

Antibody evidence of animals and animal

traders having been infected

Ancestral variants of the virus found in animals

Documented trade of host animals

between the area where bats carry closely

related viruses and the outbreak site

For SARS-CoV-2, these same key pieces of evidence are still missing , more than four years after the virus emerged.

For SARS-CoV-2, these same key pieces of evidence are still missing ,

more than four years after the virus emerged.

• Despite the intense search trained on the animal trade and people linked to the market, investigators have not reported finding any animals infected with SARS‑CoV‑2 that had not been infected by humans. Yet, infected animal sources and other connective pieces of evidence were found for the earlier SARS and MERS outbreaks as quickly as within a few days, despite the less advanced viral forensic technologies of two decades ago.
• Even though Wuhan is the home base of virus hunters with world-leading expertise in tracking novel SARS-like viruses, investigators have either failed to collect or report key evidence that would be expected if Covid-19 emerged from the wildlife trade . For example, investigators have not determined that the earliest known cases had exposure to intermediate host animals before falling ill. No antibody evidence shows that animal traders in Wuhan are regularly exposed to SARS-like viruses, as would be expected in such situations.
• With today’s technology, scientists can detect how respiratory viruses — including SARS, MERS and the flu — circulate in animals while making repeated attempts to jump across species . Thankfully, these variants usually fail to transmit well after crossing over to a new species and tend to die off after a small number of infections. In contrast, virologists and other scientists agree that SARS‑CoV‑2 required little to no adaptation to spread rapidly in humans and other animals . The virus appears to have succeeded in causing a pandemic upon its only detected jump into humans.

The pandemic could have been caused by any of hundreds of virus species, at any of tens of thousands of wildlife markets, in any of thousands of cities, and in any year. But it was a SARS-like coronavirus with a unique furin cleavage site that emerged in Wuhan, less than two years after scientists, sometimes working under inadequate biosafety conditions, proposed collecting and creating viruses of that same design.

While several natural spillover scenarios remain plausible, and we still don’t know enough about the full extent of virus research conducted at the Wuhan institute by Dr. Shi’s team and other researchers, a laboratory accident is the most parsimonious explanation of how the pandemic began.

Given what we now know, investigators should follow their strongest leads and subpoena all exchanges between the Wuhan scientists and their international partners, including unpublished research proposals, manuscripts, data and commercial orders. In particular, exchanges from 2018 and 2019 — the critical two years before the emergence of Covid-19 — are very likely to be illuminating (and require no cooperation from the Chinese government to acquire), yet they remain beyond the public’s view more than four years after the pandemic began.

Whether the pandemic started on a lab bench or in a market stall, it is undeniable that U.S. federal funding helped to build an unprecedented collection of SARS-like viruses at the Wuhan institute, as well as contributing to research that enhanced them . Advocates and funders of the institute’s research, including Dr. Fauci, should cooperate with the investigation to help identify and close the loopholes that allowed such dangerous work to occur. The world must not continue to bear the intolerable risks of research with the potential to cause pandemics .

A successful investigation of the pandemic’s root cause would have the power to break a decades-long scientific impasse on pathogen research safety, determining how governments will spend billions of dollars to prevent future pandemics. A credible investigation would also deter future acts of negligence and deceit by demonstrating that it is indeed possible to be held accountable for causing a viral pandemic. Last but not least, people of all nations need to see their leaders — and especially, their scientists — heading the charge to find out what caused this world-shaking event. Restoring public trust in science and government leadership requires it.

A thorough investigation by the U.S. government could unearth more evidence while spurring whistleblowers to find their courage and seek their moment of opportunity. It would also show the world that U.S. leaders and scientists are not afraid of what the truth behind the pandemic may be.

More on how the pandemic may have started

Where Did the Coronavirus Come From? What We Already Know Is Troubling.

Even if the coronavirus did not emerge from a lab, the groundwork for a potential disaster had been laid for years, and learning its lessons is essential to preventing others.

By Zeynep Tufekci

Why Does Bad Science on Covid’s Origin Get Hyped?

If the raccoon dog was a smoking gun, it fired blanks.

By David Wallace-Wells

A Plea for Making Virus Research Safer

A way forward for lab safety.

By Jesse Bloom

The Times is committed to publishing a diversity of letters to the editor. We’d like to hear what you think about this or any of our articles. Here are some tips . And here’s our email: [email protected] .

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Alina Chan ( @ayjchan ) is a molecular biologist at the Broad Institute of M.I.T. and Harvard, and a co-author of “ Viral : The Search for the Origin of Covid-19.” She was a member of the Pathogens Project , which the Bulletin of the Atomic Scientists organized to generate new thinking on responsible, high-risk pathogen research.

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Call for papers: Generating stronger evidence to inform policy and practice: natural experiments on built environments, health behaviours and chronic diseases

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https://doi.org/10.24095/hpcdp.44.6.11

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This call for papers in the HPCDP Journal licensed under a Creative Commons Attribution 4.0 International license

Guest editors: Dr. Stephanie Prince Ware (Public Health Agency of Canada), Dr. Gavin McCormack (University of Calgary)

HPCDP Journal Editors: Robert Geneau and Margaret de Groh (Public Health Agency of Canada)

Where we work, learn, play, eat and live has important implications for health. The built environment has been associated with the development of chronic disease, and with health behaviours often seen as critical pathways for this relationship. Footnote 1 Footnote 2 Built environments refer to components of the physical environment that are human-made or human-modified and include structures and buildings, recreation facilities, green spaces and parks, transportation systems and community design.

Natural experiments are interventions that occur without a researcher’s ability to manipulate the intervention or exposure to the intervention. Footnote 3 Footnote 4 Natural experiments offer the opportunity to evaluate the effects of “naturally occurring” interventions such as changes to the built environment (e.g. creation of a new bike path, park improvements, infrastructure changes to schools or workplaces, construction of a new recreation facility or grocery store) on health behaviours and chronic disease risk. Natural experiments are often more practical for investigating the health impacts of environmental interventions when compared to traditional experimental studies (e.g. randomized controlled trials). Compared to cross-sectional studies, natural experiments provide a means to generate rigorous evidence to better establish causality, as well as to understand the implementation of interventions in “real-world” scenarios.

This special issue answers the 2017 Canadian Public Health Officer annual report’s call to further evaluate the health impacts of community design features in Canada. Footnote 5 This special issue resonates with the expanding scholarly and policy-oriented interest in the utility of natural experiments as a critical tool in advancing the body of evidence and for informing interventions to improve public and population health. Footnote 6 Footnote 7 Specifically, the objective of this special issue on natural experiments is to provide timely evidence to further understand the effectiveness of built environment interventions on health behaviours and chronic disease prevention in a Canadian context.

Health Promotion and Chronic Disease Prevention in Canada: Research, Policy and Practice is seeking relevant topical research articles that present new findings or synthesize/review existing evidence on natural experiments of the built environment (or related policies) that influence health behaviours with implications for chronic disease prevention in Canada.

Relevant topic areas include, but are not limited to:

• Built environments, including community or neighbourhoods, workplaces, schools, transportation infrastructure, home environments, recreation environments, parks, playgrounds, green spaces, public open spaces, natural environments and seniors’ residences.
• All health-related behaviours, including physical activity, sedentary behaviour, sleep, food consumption, smoking and substance use.
• Chronic diseases and health-related outcomes, including body mass index, fitness, blood pressure, blood lipids, blood sugar, injuries, falls, mental health, stress, depression, anxiety, Alzheimer's disease, dementia, obesity, metabolic syndrome, cardiovascular disease, cancer, diabetes and lung disease.

International submissions will be considered if they include Canadian data, results (e.g. as part of multi-country studies or global comparisons) and/or evidence-based discussion of implications for community or population health in Canada.

Consult the Journal’s website for information on article types and detailed  submission guidelines for authors . Kindly refer to this call for papers in your cover letter.

All manuscripts should be submitted using the Journal’s  ScholarOne Manuscripts  online system. Pre-submission inquiries and questions about suitability or scope can be directed to  [email protected] .

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Title: vall-e 2: neural codec language models are human parity zero-shot text to speech synthesizers.

Abstract: This paper introduces VALL-E 2, the latest advancement in neural codec language models that marks a milestone in zero-shot text-to-speech synthesis (TTS), achieving human parity for the first time. Based on its predecessor, VALL-E, the new iteration introduces two significant enhancements: Repetition Aware Sampling refines the original nucleus sampling process by accounting for token repetition in the decoding history. It not only stabilizes the decoding but also circumvents the infinite loop issue. Grouped Code Modeling organizes codec codes into groups to effectively shorten the sequence length, which not only boosts inference speed but also addresses the challenges of long sequence modeling. Our experiments on the LibriSpeech and VCTK datasets show that VALL-E 2 surpasses previous systems in speech robustness, naturalness, and speaker similarity. It is the first of its kind to reach human parity on these benchmarks. Moreover, VALL-E 2 consistently synthesizes high-quality speech, even for sentences that are traditionally challenging due to their complexity or repetitive phrases. The advantages of this work could contribute to valuable endeavors, such as generating speech for individuals with aphasia or people with amyotrophic lateral sclerosis. See this https URL for demos of VALL-E 2.

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