Animal Models in Neuroscience: What Is the “Culture of Care”?

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

General comments: The title and abstract suggest that the paper is about a ‘culture of care’ as applied to animals used for neuroscience research but the content is quite different. The paper starts with a justification of why animal models are necessary in neuroscience research, moves on to discuss in a very general way why certain animal species are good models for studying neuroscience, and then moves to discuss a ‘culture of care’ broadly. The paper purports to establish a ‘staircase model’ for providing good animal welfare whereas the information on pgs 8 and 9 refer superficially to common and well developed principles of good animal care and ethical oversight of research animal use that are better summarized in other papers (see the PREPARE Guidelines). ’Climbing these steps’ does not ensure a good ‘culture of culture’ nor even excellence in animal welfare – it ensures at least a ‘culture of compliance’, since all of these elements are currently required under the EU Directive and by European regulatory oversight bodies. Missing is a discussion, with specific examples, of how to go above and beyond these commonly held precepts. The paper concludes that animal models must continue to be used. This reviewer felt that the paper just rehashes the status quo and neither enhances the reader’s understanding of what a ‘culture of care’ truly means for an institution in which animals are used for research nor explains why/how advancing a ‘culture of care’ as a concept will enhance the relevance and translatability of neuroscience research. A significant rewrite is needed to truly discuss how all aspects of a 'culture of care' should be addressed by institutions to meet public and research community expectations for ethical animal research.

 

Specific comments:

 

Abstract:

Pg 1, line 24 – is this a ‘chapter”? The abstract only seems to refer to the latter half of the paper. Please revise to ensure that it covers the contents of the entire paper.

 

In the abstract and throughout the paper new alternative methods are referred to as ‘AAs’ – suggest using the more commonly understand abbreviation of ‘NAMs’. Please revise to enhance reader comprehension.

 

Graphical abstract:

Pg 2, line 32 – pls replace ‘where’ with ‘in which’ (grammar; more precise in this context). Also, please consider replacing ‘Staff’ with ‘Personnel’ – in English, ‘staff’ does not usually refer to people in leadership positions whereas ‘personnel’ is inclusive of all levels of individuals working in an institution (which I am inferring from the text). Please consider replacing here and within the text of the paper.

 

Introduction:

 

General comment: based on the abstract, I thought I was reading a paper on the importance of the ‘culture of care’ to ethical and scientifically meaningful neuroscience work. Instead, the paper is largely trying to justify use of whole animal models while discounting the value of new alternative models (NAMS). Please ensure the Introduction clearly states the objectives of the paper and how the content will be organized/discussed in the following sections.

 

Pg 2, line 52; ‘thousands of years’ is an overstatement – ‘hundreds of years’ or ‘over two thousand years’ would be more appropriate given the references supplied – please revise.

 

Pg 2, line 56 – the dates given for Galen are unclear – listed as: (129 – 199/217 AD) – please check and correct. Also, AD is more commonly noted now as ‘CE’ (Common Era).

 

Pg 2, line 58 – ‘…meticulous experiments, meticulously…’ – please revise to remove redundancy of text

 

Pg 3, paragraphs 2-5 (lines 87-113) – there is significant redundancy in the text of these paragraphs – suggest revising and condensing to remove redundancy.

 

Pg 3, line 124 – zebrafish is not capitalized, please revise here and throughout (e.g., Figure 1 header, etc.).

 

Pg 7, line 232 – “In 2021, [54,56] effectively portrayed…” does not make sense grammatically – pls add names of the researchers, for example, ‘Smith et al and Jones et al both effectively portrayed …’.

 

 

Comments on the Quality of English Language

Please see above. Minor edits noted.

Author Response

RE: We sincerely thank all the reviewers for their valuable feedback, which has immensely contributed to enhancing our manuscript. We have carefully reviewed all the comments, incorporated the necessary revisions/corrections, and highlighted (blue) track changes in the resubmitted files. I've included the detailed responses below for you.

- A significant rewrite is needed to honestly discuss how all aspects of a 'culture of care' should be addressed by institutions to meet public and research community expectations for ethical animal research.

RE: We are grateful for the suggestions provided by the reviewer. In response to those suggestions, we have completely rewritten the work. We believe this opportunity has significantly improved the quality of the manuscript, and we would be happy to have the reviewer's approval again.

 Specific comments:

- Abstract:

Pg 1, line 24 – is this a ‘chapter”? The abstract only seems to refer to the latter half of the paper. Please revise to ensure that it covers the contents of the entire paper.

- In the abstract and throughout the paper new alternative methods are referred to as ‘AAs’ – suggest using the more commonly understand abbreviation of ‘NAMs’. Please revise to enhance reader comprehension.

 RE: The abstract has been completely reformulated in the light of comments received and  "alternative methods" are now referred to with the commonly understood abbreviation of ‘NAMs’.

Graphical abstract:

Pg 2, line 32 – pls replace ‘where’ with ‘in which’ (grammar; more precise in this context). Also, please consider replacing ‘Staff’ with ‘Personnel’ – in English, ‘staff’ does not usually refer to people in leadership positions whereas ‘personnel’ includes all levels of individuals working in an institution (which I am inferring from the text). Please consider replacing here and within the text of the paper.

 RE: The Graphical abstract has been replaced with a flowchart that accurately represents the updated manuscript. In addition, Staff has been replaced with “personnel”, and where with “in which”.

 

Introduction:

 General comment: based on the abstract, I thought I was reading a paper on the importance of the ‘culture of care’ to ethical and scientifically meaningful neuroscience work. Instead, the paper is largely trying to justify use of whole animal models while discounting the value of new alternative models (NAMS). Please ensure the Introduction clearly states the objectives of the paper and how the content will be organized/discussed in the following sections.

Pg 2, line 52; ‘thousands of years’ is an overstatement – ‘hundreds of years’ or ‘over two thousand years’ would be more appropriate given the references supplied – please revise.

 Pg 2, line 56 – the dates given for Galen are unclear – listed as: (129 – 199/217 AD) – please check and correct. Also, AD is more commonly noted now as ‘CE’ (Common Era).

 Pg 2, line 58 – ‘…meticulous experiments, meticulously…’ – please revise to remove redundancy of text

 Pg 3, paragraphs 2-5 (lines 87-113) – there is significant redundancy in the text of these paragraphs – suggest revising and condensing to remove redundancy.

 Pg 3, line 124 – zebrafish is not capitalized, please revise here and throughout (e.g., Figure 1 header, etc.).

 Pg 7, line 232 – “In 2021, [54,56] effectively portrayed…” does not make sense grammatically – pls add names of the researchers, for example, ‘Smith et al and Jones et al both effectively portrayed …’.

  RE: we thank the reviewer for his/her comment.  In the current version, all the points have been addressed, and the minor points have been incorporated into the overall structure of the new paper.

Reviewer 2 Report

Comments and Suggestions for Authors

Dear Authors,

thanks for the idea to write a publication about “Culture of Care” in the context of neuroscience.  

Unfortunately, I think, the manuscript has severe flaws.

First of all, the topic is very unbalanced: Culture of Care starts at page 7 out of 10… the beginning is more a summary of where animals are used in neuroscience.

Second, I have great ethical concerns: the point of view is based on anthropocentrism. That means in this context that the wellbeing of animals is only an issue because the non-wellbeing could harm the results of research. But there are other there are ethical idea like the pathocentrism, for which wellbeing of (every) animal is an intrinsic point. I do not want to judge your ethical ideas, but to emphasize the anthropocentrism several times without introducing the pathocentrism is in my eyes not correct.

Third I do not get the house graph. I was happy to see a graphical abstract, but for this topic, I do not think that it helps. I do not get the overall aim (is it the roof?) which would be good science only based on reliability and integrity of research? What about compassion fatigue, transparency and the interest of stakeholder?  You see, I miss some basics.

Because of these for me missing or misleading points, I recommend rejection.

Comments on the Quality of English Language

In the abstract, there are some phrases in which the commata impair the readability. 

Author Response

Unfortunately, I think the manuscript has severe flaws.

First of all, the topic is very unbalanced: Culture of Care starts at page 7 out of 10… the beginning is more a summary of where animals are used in neuroscience.

Second, I have great ethical concerns: the point of view is based on anthropocentrism. That means in this context that the well-being of animals is only an issue because well-being could harm the results of research. But there are other ethical ideas like the pathocentrism, for which wellbeing of (every) animal is an intrinsic point. I do not want to judge your ethical ideas, but to emphasize anthropocentrism several times without introducing ethnocentrism is, in my eyes, not correct.

 RE: we want to thank the reviewer for his/her productive comment.  In the current version of a paper, we have completely rewritten the whole manuscript in light of her/his comments. Since the abstract, the manuscript has been revised to introduce the idea of anthropocentrism and pathocentrism, which were discussed in the abstract. Each element has been reviewed to avoid suggesting the use of animals for experimentation. While animals have aided in significant advancements in neuroscience, we recognize the need to compare the use of animals to that of humans in clinical trials. We aim to promote the concept of equality between species rather than the dominance of one over the other (see paragraph 1.2 Ethical Paradigms: Anthropocentrism and Pathocentrism Examined).

Third, I need the house graph. I was happy to see a graphical abstract, but I do not think it helps for this topic. I do not get the overall aim (is it the roof?), which would be good science only based on the reliability and integrity of the research. What about compassion fatigue, transparency, and the interest of stakeholders?  You see, I miss some basics.

RE: The Graphical abstract has been replaced with a flowchart that accurately represents the newly updated manuscript. The house graph has been removed, and all concepts related to good science, integrity, compassion fatigue, etc., have been expressed in the new version of the paper.

Because of these missing or misleading points, I recommend rejection.

RE: We'd like to let you know that we have incorporated them into the new manuscript. We believe that the changes we have made address all the reviewers' comments. We respectfully request that reviewer #2 reconsider their decision to reject the entire writing process.

Reviewer 3 Report

Comments and Suggestions for Authors

In the manuscript titled “Animal models in neuroscience: what “Culture of Care”, the authors present a review highlighting the importance of the concept of Culture of Care in research that uses animal models and highlighting as well how keeping high welfare standards are fundamental not only for the animals, but to obtain reliable research outcomes.

My major comment is that animal welfare is constantly mentioned throughout the manuscript, however, it was not defined. Since this paper will play a role in educating people, I think this manuscript will benefit by explaining what animal welfare is. In addition, I suggest including a brief paragraph introducing the five freedoms, as these are the foundation to ensure good welfare.

Minor comments:

Line 269: Sentence seems repetitive.

Lines 273-275: I suggest moving this paragraph to line 284.

Lines 316-320: Repeated, please delete.

Graphical abstract and Figure 1: Please increase the font size of the text, as it is hard to read.

Author Response

Reviewer 3 response

In the manuscript titled “Animal Models in neuroscience: what “Culture of Care”, the authors present a review highlighting the importance of the concept of Culture of Care in research that uses animal models and highlighting as well how keeping high welfare standards are fundamental not only for the animals but to obtain reliable research outcomes.

My significant comment is that animal welfare is constantly mentioned throughout the manuscript, however, it was not defined. Since this paper will play a role in educating people, I think this manuscript will benefit by explaining what animal welfare is.

RE: We are grateful to the reviewer for his/her comment. In this version of the manuscript, we have introduced the definition of animal welfare by the European vision. Animal welfare, or well-being in extra-European states, is defined as a state in which humans recognize all animals as equals and sentient beings. This includes the inescapable right for animals to preserve their specific species' behaviors, have adequate food and habitats, not be exposed to suffering, and have opportunities for social aggregation and perpetuation of the species (see paragraph 1.1)

 

 In addition, I suggest including a brief paragraph introducing the five freedoms, as these are the foundation to ensure good welfare.

 

RE: We are pleased to have incorporated the reviewer's suggestion by adding a new paragraph titled 1.3 Synergizing Ethical Compasses: The Interplay between the Culture of Care and the Five Freedoms in Animal Welfare

 

Minor comments:

Line 269: Sentence seems repetitive.

Lines 273-275: I suggest moving this paragraph to line 284.

Lines 316-320: Repeated, please delete.

RE: The rewriting process absorbed the manuscript minor point’s revisions.

 

Graphical abstract and Figure 1: Please increase the font size of the text, as it is hard to read.

RE: In the present manuscript version, the Graphical abstract has been replaced with a flowchart that accurately represents the newly updated paper. The house graph has been removed.

Reviewer 4 Report

Comments and Suggestions for Authors

This is a well-written and well-structured manuscript. The manuscript is divided into two parts the first one is related to the necessity of using animals in neuroscience and the second one raises ethical concerns. Within this concept, the authors analyze in detail the importance of the "culture of care" and what this concept should include.

Both the graphical abstract and Figure 1 are very descriptive and the reference used is up-to-date.  My only recommendation is to strengthen the message for good collaboration, communication, and dissemination of good laboratory animal practice between those working with animals. This can be done in the chapters: (a) "Ethical Treatment in Research: Culture of Care" and  (b) "Conclusions".

Page 2, line 38: Please close the parenthesis  

Author Response

This is a well-written and well-structured manuscript. The manuscript is divided into two parts the first one is related to the necessity of using animals in neuroscience and the second one raises ethical concerns. Within this concept, the authors analyze in detail the importance of the "culture of care" and what this concept should include.

Both the graphical abstract and Figure 1 are very descriptive and the reference used is up-to-date. 

My only recommendation is to strengthen the message for good collaboration, communication, and dissemination of good laboratory animal practice between those working with animals. This can be done in the chapters: (a) "Ethical Treatment in Research: Culture of Care" and  (b) "Conclusions".

Page 2, line 38: Please close the parenthesis  

RE: We thank the reviewer for his/her encouragement and positive comments. Please note that in the current version of the manuscript, which has been improved by suggestions received from all, we have included the message for good collaboration, communication, and dissemination of good laboratory animal practice between those working with animals (see paragraph 2.1 Embracing Ethical Excellence: Cultivating a 'Culture of Care' in Animal Research) 

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

This reviewer appreciates the extensive editing of the original MS.

A few additional comments for consideration:

Line 47-48 - a culture of Care goes well beyond a 'culture of compliance', the latter being suggested by this sentence. Although minimally discussed, a Culture of Care includes: care of animals, care of those who work with animals [i.e., providing compassionate support for them], care for scientific integrity and quality, and care for transparency and openness. See: Robinson S, Sparrow S, Williams B, Decelle T, Bertelsen T, Reid K, Chlebus M. The European Federation of the Pharmaceutical Industry and Associations' Research and Animal Welfare Group: Assessing and benchmarking 'Culture of Care' in the context of using animals for scientific purpose. Lab Anim. 2019 Nov 19;54(5):23677219887998. This broader Culture of Care definition is being adopted by many organizations, including the international Culture of Care Consortium and will likely be adopted by AAALAC, Int'l. The broader definition places responsibility on individuals outside the vivarium, too, including institutional administration, re: transparency and openness of research processes within their facility. To enhance the relevance of this paper the authors may wish to apply a more contemporary definition of a 'culture of care'.

Line 70 - the Prepare Guidelines are not 'ethical guidelines' - Ethical guidelines refer to rules or principles for making moral judgements. The PREPARE Guidelines assist the researcher to better prepare for and conduct their studies. Please revise.

Section starting on Line 118 - the 5 Freedoms were developed in 1979 for farm animals and are considered a more antiquated model in that they focus on harm reduction. The 5 Domains are considered a more contemporary approach for assessing animal well-being because they focus more on the subjective experiences of the animal  (see URL for an explanation of the difference between 5 Freedoms vs 5 Domains - https://kb.rspca.org.au/knowledge-base/what-are-the-five-domains-and-how-do-they-differ-from-the-five-freedoms/). This section would be improved by reframing the discussion from the 5 Freedoms to the 5 Domains. These papers may be beneficial for this:

Mellor DJ (2017) Operational details of the Five Domains Models and its key applications to the assessment and management of animal welfare. Animals 7(8):60. doi:10.3390/ani7080060

Mellor DJ & Beausoleil NJ (2015) Extending the ‘Five Domains’ model for animal welfare assessment to incorporate positive welfare states. Animal Welfare 24:241–253. doi: 10.7120/09627286.24.3.241.

Mellor DJ, Beausoleil NJ, Littlewood KE et al (2020) The 2020 Five Domains Model: Including Human-Animal Interactions in Assessments of Animal Welfare. Animals 10(10):1870. doi: 10.3390/ani10101870.

In Sections 2.1 and 3, the authors fail to mention the most important impediment to establishing a robust Culture of Care which applies as much or more to neuroscience as to other scientific fields), which is resistance to change. Researchers are rewarded with publications and grants - doing things differently means down time for a lab and decreased productivity. It is far easier to embrace the status quo and keep churning things out in ways that have been successful in the past. Embracing a Culture of Care is disruptive, stormy, and requires extensive planning, consensus-building, and deft change management to implement. Recidivism is common and must be handled diplomatically. The difficulties are not mentioned anywhere in this paper. Embracing a 'culture of care' means doing things very differently than how they are done now in scientific institutions, with much more habituation of animals to handling, procedures, positive reinforcement training, etc. It means reflecting on the lived experiences of the animals and not just what will be most convenient for the lab. These elements are missing from these sections. 

This author fails to see the purpose of Table 1. What does the utility of mouse and rat models in neuroscience have to do with a Culture of Care? What would be more interesting is to provide a table listing examples of NAMs and areas of neuroscience in which they are augmenting or partially replacing the use of animal models (3 columns, 3rd column including references). A scientist embracing a CoC approach may choose to explore or test certain concepts with these NAMs first before jumping to an animal model. Animals will be needed in science for some time to come, but the point is to develop ways to use them more thoughtfully and only when needed.

Comments on the Quality of English Language

There are several examples of redundancy that remain e.g., Lines 52-61. Some sentences are worded awkwardly - copy editing is needed to improve flow and clarity of text.

Author Response

Comments on the Quality of English Language

Several examples of redundancy remain e.g., Lines 52-61. Some sentences are worded awkwardly - copy editing is needed to improve flow and clarity of text.

RE: Regarding the manuscript, we appreciate the reviewer's efforts to help us improve it and would like to thank he/she.

Line 47-48 - a culture of Care goes well beyond a 'culture of compliance', the latter being suggested by this sentence. Although minimally discussed, a Culture of Care includes: care of animals, care of those who work with animals [i.e., providing compassionate support for them], care for scientific integrity and quality, and care for transparency and openness. See: Robinson S, Sparrow S, Williams B, Decelle T, Bertelsen T, Reid K, Chlebus M. The European Federation of the Pharmaceutical Industry and Associations' Research and Animal Welfare Group: Assessing and benchmarking 'Culture of Care' in the context of using animals for scientific purpose. Lab Anim. 2019 Nov 19;54(5):23677219887998. This broader Culture of Care definition is being adopted by many organizations, including the international Culture of Care Consortium and will likely be adopted by AAALAC, Int'l. The broader definition places responsibility on individuals outside the vivarium, too, including institutional administration, re: transparency and openness of research processes within their facility. To enhance the relevance of this paper the authors may wish to apply a more contemporary definition of a 'culture of care'.

RE: We would like to thank the reviewer for his/her suggestion. In the present version of the manuscript, lines 47-48 correspond to a list of topics dealt with in the work.  We have considered the referee's valuable comments and made changes to the manuscript's introduction as suggested. You can see the revised version in red within the text.

Line 70 - the Prepare Guidelines are not 'ethical guidelines' - Ethical guidelines refer to rules or principles for making moral judgements. The PREPARE Guidelines assist the researcher to better prepare for and conduct their studies. Please revise.

RE: Thank you for the suggestion. We've actually revised it accordingly.

Section starting on Line 118 - the 5 Freedoms were developed in 1979 for farm animals and are considered a more antiquated model in that they focus on harm reduction. The 5 Domains are considered a more contemporary approach for assessing animal well-being because they focus more on the subjective experiences of the animal (see URL for an explanation of the difference between 5 Freedoms vs 5 Domains - https://kb.rspca.org.au/knowledge-base/what-are-the-five-domains-and-how-do-they-differ-from-the-five-freedoms/). This section would be improved by reframing the discussion from the 5 Freedoms to the 5 Domains. These papers may be beneficial for this:

• Mellor DJ (2017) Operational details of the Five Domains Models and its key applications to the assessment and management of animal welfare. Animals 7(8):60. doi:10.3390/ani7080060
• Mellor DJ & Beausoleil NJ (2015) Extending the ‘Five Domains’ model for animal welfare assessment to incorporate positive welfare states. Animal Welfare 24:241–253. doi: 10.7120/09627286.24.3.241.
• Mellor DJ, Beausoleil NJ, Littlewood KE et al (2020) The 2020 Five Domains Model: Including Human-Animal Interactions in Assessments of Animal Welfare. Animals 10(10):1870. doi: 10.3390/ani10101870.

 

RE: We would like to thank the reviewer for his/her suggestion. We could not mention the five freedoms for a specific referee's request. We restructured paragraph 1.3 to align with the broader discourse of the five domains. The new paragraph begins at line 148 and has a different title. We included the five domains' most innovative concepts, starting from staff 169. The changes have been highlighted in red.

In Sections 2.1 and 3, the authors need to mention the most important impediment to establishing a robust Culture of Care which applies as much or more to neuroscience as to other scientific fields), which is resistance to change. Researchers are rewarded with publications and grants - doing things differently means down time for a lab and decreased productivity. It is far easier to embrace the status quo and keep churning things out in ways that have been successful in the past. Embracing a Culture of Care is disruptive, stormy, and requires extensive planning, consensus-building, and deft change management to implement. Recidivism is common and must be handled diplomatically. The difficulties are not mentioned anywhere in this paper. Embracing a 'culture of care' means doing things very differently than how they are done now in scientific institutions, with much more habituation of animals to handling, procedures, positive reinforcement training, etc. It means reflecting on the lived experiences of the animals and not just what will be most convenient for the lab. These elements are missing from these sections

RE: we are grateful to review his/her suggestion. We have made changes to the text based on the reviewer's feedback. The revised version includes appropriate references, and any change is highlighted in red.

This author fails to see the purpose of Table 1. What does the utility of mouse and rat models in neuroscience have to do with a Culture of Care? What would be more interesting is to provide a table listing examples of NAMs and areas of neuroscience in which they are augmenting or partially replacing the use of animal models (3 columns, 3rd column including references). A scientist embracing a CoC approach may choose to explore or test certain concepts with these NAMs first before jumping to an animal model. Animals will be needed in science for some time to come, but the point is to develop ways to use them more thoughtfully and only when needed.

RE: Thank you for the suggestion. We have replaced the table of rats with a table of alternative methods in paragraph 3.2 from line 614. The text is underlined in red.

Comments on the Quality of English Language

There are several examples of redundancy that remain e.g., Lines 52-61. Some sentences are worded awkwardly - copy editing is needed to improve flow and clarity of text.

RE:  We are grateful to review his/her suggestion. the text was also revised in cooperation with an expert in the language.

Reviewer 2 Report

Comments and Suggestions for Authors

Dear Authors,

thanks for the revised version of your manuscript. I think it improved a lot! Just two small issues:

1) as it is a review with relatively long text, I would recommend a table of content at the beginning. That would give a bit more overview about what to expect.

2) in the chapter line 251-260 there seems to be some doubling of phrases (although with different references), please check.

 

Author Response

Dear Authors,

thanks for the revised version of your manuscript. I think it improved a lot! Just two small issues:

RE: We are glad that the reviewer thinks the manuscript has improved. We/we thank her for every valuable suggestion.

• as it is a review with relatively long text, I would recommend a table of content at the beginning. That would give a bit more overview about what to expect.

RE: Thank you. According to the referee’s suggestion, we added a table of content temporarily after the abstract for your reference. Please note that the publisher will create a table of content for the html file after its publication.

2) in the chapter line 251-260 there seems to be some doubling of phrases (although with different references), please check.

RE: we are grateful to review his/her suggestion. So that you know – we are changing the references accordingly.

Reviewer 3 Report

Comments and Suggestions for Authors

The authors incorporated the suggested changes and addressed all my comments. 

Author Response

The authors incorporated the suggested changes and addressed all my comments. 

RE: We want to thank the reviewer for his/her help in improving our manuscript.

 

 

Reviewer 4 Report

Comments and Suggestions for Authors

The manuscript was very much improved after the revision and we suggest to be accepted for publication in the present form  

Author Response

The manuscript was very much improved after the revision and we suggest to be accepted for publication in the present form  

RE: We are delighted that the auditor appreciated the changes we made. However, we want to thank him immensely for the suggestions that have made it possible to improve our manuscript.

 

 

Round 3

Reviewer 1 Report

Comments and Suggestions for Authors

Dear Authors, thank-you for your additional efforts and for transforming this paper into more forward-thinking work!

Reviewer 2 Report

Comments and Suggestions for Authors

Thanks for revising