Kathrin Herrmann - Academia.edu (original) (raw)

Papers by Kathrin Herrmann

BRILL eBooks, Apr 4, 2019

Animal Experimentation: Working Towards a Paradigm Change, 2019

Atla-alternatives To Laboratory Animals, Mar 1, 2023

The failure rate for the translation of drugs from animal testing to human treatments remains at ... more The failure rate for the translation of drugs from animal testing to human treatments remains at over 92%, where it has been for the past few decades. The majority of these failures are due to unexpected toxicity — that is, safety issues revealed in human trials that were not apparent in animal tests — or lack of efficacy. However, the use of more innovative tools, such as organs-on-chips, in the preclinical pipeline for drug testing, has revealed that these tools are more able to predict unexpected safety events prior to clinical trials and so can be used for this, as well as for efficacy testing. Here, we review several disease areas, and consider how the use of animal models has failed to offer effective new treatments. We also make some suggestions as to how the more human-relevant new approach methodologies might be applied to address this.

Alternatives to Laboratory Animals

The failure rate for the translation of drugs from animal testing to human treatments remains at ... more The failure rate for the translation of drugs from animal testing to human treatments remains at over 92%, where it has been for the past few decades. The majority of these failures are due to unexpected toxicity — that is, safety issues revealed in human trials that were not apparent in animal tests — or lack of efficacy. However, the use of more innovative tools, such as organs-on-chips, in the preclinical pipeline for drug testing, has revealed that these tools are more able to predict unexpected safety events prior to clinical trials and so can be used for this, as well as for efficacy testing. Here, we review several disease areas, and consider how the use of animal models has failed to offer effective new treatments. We also make some suggestions as to how the more human-relevant new approach methodologies might be applied to address this.

ALTEX

Parkinson's disease (PD) is a complex neurodegenerative condition with a multifactorial origin. T... more Parkinson's disease (PD) is a complex neurodegenerative condition with a multifactorial origin. To date, approaches to drug discovery for PD have resulted in symptomatic therapies for the motor manifestations and signs associated with neurodegeneration but have failed to identify preventive or curative therapies. This failure mainly originates from the persistence of major gaps in our understanding of the specific molecular basis of PD initiation and progression. New approach methodologies (NAMs) hold the potential to advance PD research while facilitating a move away from animalbased research. We report a workshop involving NAM experts in the field of PD and neurodegenerative diseases, who discussed and identified a scientific strategy for successful, human-specific PD research. We outline some of the most important human-specific NAMs, along with their main potentials and limitations, and suggest possible ways to overcome the latter. Key recommendations to advance PD research include integrating NAMs while accounting for multiple levels of complexity, from molecular to population level; learning from recent advances in Alzheimer's disease research; increasing the sharing of data; promoting innovative pilot studies on disease pathogenesis; and accessing philanthropic funding to enable studies using novel approaches. Collaborative efforts between different stakeholders including researchers, clinicians and funding agencies are urgently needed to create a scientific roadmap and support a paradigm change towards effective, human-specific research for neurodegenerative diseases without animals, as is already happening in the field of toxicology.

Animals, 2019

In November 2013, a group of international experts in animal research policy (n = 11) gathered in... more In November 2013, a group of international experts in animal research policy (n = 11) gathered in Vancouver, Canada, to discuss openness and accountability in animal research. The primary objective was to bring together participants from various jurisdictions (United States, Sweden, Australia, New Zealand, Germany, Canada and the United Kingdom) to share practices regarding the governance of animals used in research, testing and education, with emphasis on the governance process followed, the methods of community engagement, and the balance of openness versus confidentiality. During the forum, participants came to a broad consensus on the need for: (a) evidence-based metrics to allow a “virtuous feedback” system for evaluation and quality assurance of animal research, (b) the need for increased public access to information, together with opportunities for stakeholder dialogue about animal research, (c) a greater diversity of views to be represented on decision-making committees to a...

PloS one, 2016

Improving laboratory animal science and welfare requires both new scientific research and insight... more Improving laboratory animal science and welfare requires both new scientific research and insights from research in the humanities and social sciences. Whilst scientific research provides evidence to replace, reduce and refine procedures involving laboratory animals (the '3Rs'), work in the humanities and social sciences can help understand the social, economic and cultural processes that enhance or impede humane ways of knowing and working with laboratory animals. However, communication across these disciplinary perspectives is currently limited, and they design research programmes, generate results, engage users, and seek to influence policy in different ways. To facilitate dialogue and future research at this interface, we convened an interdisciplinary group of 45 life scientists, social scientists, humanities scholars, non-governmental organisations and policy-makers to generate a collaborative research agenda. This drew on methods employed by other agenda-setting exerci...

Drug Discovery Today, 2017

Towards a 21st-century roadmap for biomedical research and drug discovery: consensus report and r... more Towards a 21st-century roadmap for biomedical research and drug discovery: consensus report and recommendations. DRUG DISCOVERY TODAY.

This is an open access article distributed under the terms of the CC BY-NC 4.0 license.

ATLA (Alternatives to Laboratory Animals), 2018

Animal experimentation has been one of the most controversial areas of animal use, mainly due to ... more Animal experimentation has been one of the most controversial areas of animal use, mainly due to the intentional harms inflicted upon the animals used. In an effort to reduce these harms, research on refinement has increased significantly over the past 20 years. However, the extent to which these efforts have helped to reduce the severity of the research procedures, and thus animal suffering, is uncertain. To provide an indication of the awareness and implementation of refinement methods, we reviewed the experimental techniques for 684 surgical interventions described in 506 animal research applications that had been sent to the German competent authorities for approval in 2010. In this paper, we describe and discuss the severity categorisation of the proposed surgeries and the planned health monitoring strategies. We found that the researchers frequently underestimated the levels of pain, suffering, distress and lasting harm that were to be inflicted on the animals. Furthermore, th...

ALTEX, 2021

In response to a growing need to be conversant in innovative approaches in toxicology and biomedi... more In response to a growing need to be conversant in innovative approaches in toxicology and biomedical sciences, this Summer School will share knowledge and experience with a new generation of scientists on research and testing methods. The program will highlight modern alternatives to the use of animals—including in vitro and computational modeling—in toxicology and biomedical sciences. The state of scientific research will be explored through lectures and discussion.

Alternatives to Laboratory Animals

Animal experimentation has been one of the most controversial areas of animal use, mainly due to ... more Animal experimentation has been one of the most controversial areas of animal use, mainly due to the intentional harms inflicted upon the animals used. In an effort to reduce these harms, research on refinement has increased significantly over the past 20 years. However, the extent to which these efforts have helped to reduce the severity of the research procedures, and thus animal suffering, is uncertain. To provide an indication of the awareness and implementation of refinement methods, we reviewed the experimental techniques for 684 surgical interventions described in 506 animal research applications that had been sent to the German competent authorities for approval in 2010. In this paper, we describe and discuss the severity categorisation of the proposed surgeries and the planned health monitoring strategies. We found that the researchers frequently underestimated the levels of pain, suffering, distress and lasting harm that were to be inflicted on the animals. Furthermore, th...

ALTEX

of working somewhat in the dark, new statistics on animal use in Europe finally have been publish... more of working somewhat in the dark, new statistics on animal use in Europe finally have been published (EC, 2020). Each and every statistic is problematic, as it condenses data, often with the intention to "illustrate" something, i.e., with possible bias. Andrejs Dunkel's quote "It is easy to lie with statistics. It is hard to tell the truth without it" 3 makes this point very nicely 4. 1 Introduction These days, with a world in lockdown because of the COVID-19 crisis, show us impressively the importance of statistics for policy and public health decisions. Less acute, but a topic that is driving discussions in our part of the life sciences, after seven years

ALTEX - Alternatives to animal experimentation, 36(3), pp. 343-352, 2019

This year marks the 60th anniversary of Russell and Burch’s pioneering book, The Principles of Hu... more This year marks the 60th anniversary of Russell and Burch’s pioneering book, The Principles of Humane Experimental Technique. Their 3Rs framework has helped to inspire humane and scientific progress in experimental technique. However, it is time to update its strategic application. The 21st century has already seen the development of promising, high-tech non-animal models, such as organs-on-a-chip and computational approaches that, in our view, will replace animals as
the default option in biomedical experimentation. How fast this transition will take place will depend on the pace at which these new models are optimized to reflect the biology of humans, rather than that of non-human animals. While the new methods are likely to reshape all areas in which animals are currently used in science, we particularly encourage their
application in biomedical research, which accounts for the bulk of animals used. We call for the pursuit of a three-prong strategy that focuses on (1) advancing non-animal methods as replacements of animal experiments, (2) applying them to biomedical research, and (3) improving their relevance to human biology. As academics and scientists, we feel that educational efforts targeted at young scientists in training will be an effective and sustainable way to advance this vision. Our strategy may not promise an imminent end to the use of animals in science, but it will bring us closer to an era in which the 3Rs are increasingly perceived as a solution to a receding problem. Russell and Burch themselves surely would have
welcomed these positive changes.

Animal Experimentation: Working Towards a Paradigm Change, 2019

The 1st chapter 'Refinement on the way to replacement: Are we doing what we can?' of 'Animal Expe... more The 1st chapter 'Refinement on the way to replacement: Are we doing what we can?' of 'Animal Experimentation: Working Towards a Paradigm Change' starts by exploring the application of several refinement methods in practice, commencing with current housing and husbandry standards and a discussion about the benefits of a “culture of care”, followed by assessing important experimental refinements. To further assess the quality of animal-based research, it reviews necessary refinements in planning, conduct, and reporting practices of animal studies. The chapter then looks at feasible ways to reduce and replace animal use by first discussing tools to appraise animal studies that could lead to a significant reduction of animal experiments and thus numbers of animals used, and then reflecting on what the scientific community has been doing to move towards replacement of animals in research, testing, and education.

Anesthetic and Anlagesic Regimens Used in Animal Research Proposals, 2019

Pain has a profound effect on an animal’s wellbeing. In Germany, researchers using animals have b... more Pain has a profound effect on an animal’s wellbeing. In Germany, researchers using animals have been legally required to reduce any possible pain, suffering, distress or lasting harm to an absolute minimum since 1972. To evaluate how these provisions have been implemented in practice, an assessment of refinements to experimental techniques was conducted by retrospectively reviewing 684 surgical interventions described in 506 animal research applications that were sent to the German competent authorities for approval in 2010. This paper focuses on the efficacy of proposed anesthesia and peri- and postoperative analgesia. Postoperative analgesia was not proposed for 30% of surgeries. Following 10% of procedures, animals were to be given pain relieving medication if the investigators decided this was necessary; however, structured assessments to detect pain were absent. Consequences of unalleviated pain and omission of pain assessment techniques are discussed, and some recommendations to improve anesthesia and analgesia are given. The findings of this review highlight the need for improvement, both to fulfil legal requirements and to improve animal welfare. To monitor compliance with animal welfare regulations and ensure good veterinary and scientific practices, education and training need to be intensified. Adherence to the items listed in the PREPARE and ARRIVE guidelines and the Gold Standard Publication Checklist (GSPC) should become legally binding.

Decades of costly failures in translating drug candidates from preclinical disease models to huma... more Decades of costly failures in translating drug candidates from preclinical disease models to human therapeutic use warrant reconsideration of the priority placed on animal models in biomedical research. Following an international workshop attended by experts from academia, government institutions, research funding bodies, and the corporate and non-governmental organisation (NGO) sectors, in this consensus report, we analyse, as case studies, five disease areas with major unmet needs for new treatments. In view of the scientifically driven transition towards a human pathways-based paradigm in toxicology, a similar paradigm shift appears to be justified in biomedical research. There is a pressing need for an approach that strategically implements advanced, human biology-based models and tools to understand disease pathways at multiple biological scales. We present recommendations to help achieve this.

Books by Kathrin Herrmann

Animal Experimentation: Working Towards a Paradigm Change, 2019

Animal experimentation has been one of the most controversial areas of animal use, mainly due to ... more Animal experimentation has been one of the most controversial areas of animal use, mainly due to the intentional harms inflicted upon animals for the sake of hoped-for benefits in humans. Despite this rationale for continued animal experimentation, shortcomings of this practice have become increasingly more apparent and well-documented. However, these limitations are not yet widely known or appreciated, and there is a danger that they may simply be ignored. The 51 experts who have contributed to Animal Experimentation: Working Towards a Paradigm Change critically review current animal use in science, present new and innovative non-animal approaches to address urgent scientific questions, and offer a roadmap towards an animal-free world of science.

BRILL eBooks, Apr 4, 2019

Animal Experimentation: Working Towards a Paradigm Change, 2019

Atla-alternatives To Laboratory Animals, Mar 1, 2023

The failure rate for the translation of drugs from animal testing to human treatments remains at ... more The failure rate for the translation of drugs from animal testing to human treatments remains at over 92%, where it has been for the past few decades. The majority of these failures are due to unexpected toxicity — that is, safety issues revealed in human trials that were not apparent in animal tests — or lack of efficacy. However, the use of more innovative tools, such as organs-on-chips, in the preclinical pipeline for drug testing, has revealed that these tools are more able to predict unexpected safety events prior to clinical trials and so can be used for this, as well as for efficacy testing. Here, we review several disease areas, and consider how the use of animal models has failed to offer effective new treatments. We also make some suggestions as to how the more human-relevant new approach methodologies might be applied to address this.

Alternatives to Laboratory Animals

The failure rate for the translation of drugs from animal testing to human treatments remains at ... more The failure rate for the translation of drugs from animal testing to human treatments remains at over 92%, where it has been for the past few decades. The majority of these failures are due to unexpected toxicity — that is, safety issues revealed in human trials that were not apparent in animal tests — or lack of efficacy. However, the use of more innovative tools, such as organs-on-chips, in the preclinical pipeline for drug testing, has revealed that these tools are more able to predict unexpected safety events prior to clinical trials and so can be used for this, as well as for efficacy testing. Here, we review several disease areas, and consider how the use of animal models has failed to offer effective new treatments. We also make some suggestions as to how the more human-relevant new approach methodologies might be applied to address this.

ALTEX

Parkinson's disease (PD) is a complex neurodegenerative condition with a multifactorial origin. T... more Parkinson's disease (PD) is a complex neurodegenerative condition with a multifactorial origin. To date, approaches to drug discovery for PD have resulted in symptomatic therapies for the motor manifestations and signs associated with neurodegeneration but have failed to identify preventive or curative therapies. This failure mainly originates from the persistence of major gaps in our understanding of the specific molecular basis of PD initiation and progression. New approach methodologies (NAMs) hold the potential to advance PD research while facilitating a move away from animalbased research. We report a workshop involving NAM experts in the field of PD and neurodegenerative diseases, who discussed and identified a scientific strategy for successful, human-specific PD research. We outline some of the most important human-specific NAMs, along with their main potentials and limitations, and suggest possible ways to overcome the latter. Key recommendations to advance PD research include integrating NAMs while accounting for multiple levels of complexity, from molecular to population level; learning from recent advances in Alzheimer's disease research; increasing the sharing of data; promoting innovative pilot studies on disease pathogenesis; and accessing philanthropic funding to enable studies using novel approaches. Collaborative efforts between different stakeholders including researchers, clinicians and funding agencies are urgently needed to create a scientific roadmap and support a paradigm change towards effective, human-specific research for neurodegenerative diseases without animals, as is already happening in the field of toxicology.

Animals, 2019

In November 2013, a group of international experts in animal research policy (n = 11) gathered in... more In November 2013, a group of international experts in animal research policy (n = 11) gathered in Vancouver, Canada, to discuss openness and accountability in animal research. The primary objective was to bring together participants from various jurisdictions (United States, Sweden, Australia, New Zealand, Germany, Canada and the United Kingdom) to share practices regarding the governance of animals used in research, testing and education, with emphasis on the governance process followed, the methods of community engagement, and the balance of openness versus confidentiality. During the forum, participants came to a broad consensus on the need for: (a) evidence-based metrics to allow a “virtuous feedback” system for evaluation and quality assurance of animal research, (b) the need for increased public access to information, together with opportunities for stakeholder dialogue about animal research, (c) a greater diversity of views to be represented on decision-making committees to a...

PloS one, 2016

Improving laboratory animal science and welfare requires both new scientific research and insight... more Improving laboratory animal science and welfare requires both new scientific research and insights from research in the humanities and social sciences. Whilst scientific research provides evidence to replace, reduce and refine procedures involving laboratory animals (the '3Rs'), work in the humanities and social sciences can help understand the social, economic and cultural processes that enhance or impede humane ways of knowing and working with laboratory animals. However, communication across these disciplinary perspectives is currently limited, and they design research programmes, generate results, engage users, and seek to influence policy in different ways. To facilitate dialogue and future research at this interface, we convened an interdisciplinary group of 45 life scientists, social scientists, humanities scholars, non-governmental organisations and policy-makers to generate a collaborative research agenda. This drew on methods employed by other agenda-setting exerci...

Drug Discovery Today, 2017

Towards a 21st-century roadmap for biomedical research and drug discovery: consensus report and r... more Towards a 21st-century roadmap for biomedical research and drug discovery: consensus report and recommendations. DRUG DISCOVERY TODAY.

This is an open access article distributed under the terms of the CC BY-NC 4.0 license.

ATLA (Alternatives to Laboratory Animals), 2018

Animal experimentation has been one of the most controversial areas of animal use, mainly due to ... more Animal experimentation has been one of the most controversial areas of animal use, mainly due to the intentional harms inflicted upon the animals used. In an effort to reduce these harms, research on refinement has increased significantly over the past 20 years. However, the extent to which these efforts have helped to reduce the severity of the research procedures, and thus animal suffering, is uncertain. To provide an indication of the awareness and implementation of refinement methods, we reviewed the experimental techniques for 684 surgical interventions described in 506 animal research applications that had been sent to the German competent authorities for approval in 2010. In this paper, we describe and discuss the severity categorisation of the proposed surgeries and the planned health monitoring strategies. We found that the researchers frequently underestimated the levels of pain, suffering, distress and lasting harm that were to be inflicted on the animals. Furthermore, th...

ALTEX, 2021

In response to a growing need to be conversant in innovative approaches in toxicology and biomedi... more In response to a growing need to be conversant in innovative approaches in toxicology and biomedical sciences, this Summer School will share knowledge and experience with a new generation of scientists on research and testing methods. The program will highlight modern alternatives to the use of animals—including in vitro and computational modeling—in toxicology and biomedical sciences. The state of scientific research will be explored through lectures and discussion.

Alternatives to Laboratory Animals

Animal experimentation has been one of the most controversial areas of animal use, mainly due to ... more Animal experimentation has been one of the most controversial areas of animal use, mainly due to the intentional harms inflicted upon the animals used. In an effort to reduce these harms, research on refinement has increased significantly over the past 20 years. However, the extent to which these efforts have helped to reduce the severity of the research procedures, and thus animal suffering, is uncertain. To provide an indication of the awareness and implementation of refinement methods, we reviewed the experimental techniques for 684 surgical interventions described in 506 animal research applications that had been sent to the German competent authorities for approval in 2010. In this paper, we describe and discuss the severity categorisation of the proposed surgeries and the planned health monitoring strategies. We found that the researchers frequently underestimated the levels of pain, suffering, distress and lasting harm that were to be inflicted on the animals. Furthermore, th...

ALTEX

of working somewhat in the dark, new statistics on animal use in Europe finally have been publish... more of working somewhat in the dark, new statistics on animal use in Europe finally have been published (EC, 2020). Each and every statistic is problematic, as it condenses data, often with the intention to "illustrate" something, i.e., with possible bias. Andrejs Dunkel's quote "It is easy to lie with statistics. It is hard to tell the truth without it" 3 makes this point very nicely 4. 1 Introduction These days, with a world in lockdown because of the COVID-19 crisis, show us impressively the importance of statistics for policy and public health decisions. Less acute, but a topic that is driving discussions in our part of the life sciences, after seven years

ALTEX - Alternatives to animal experimentation, 36(3), pp. 343-352, 2019

This year marks the 60th anniversary of Russell and Burch’s pioneering book, The Principles of Hu... more This year marks the 60th anniversary of Russell and Burch’s pioneering book, The Principles of Humane Experimental Technique. Their 3Rs framework has helped to inspire humane and scientific progress in experimental technique. However, it is time to update its strategic application. The 21st century has already seen the development of promising, high-tech non-animal models, such as organs-on-a-chip and computational approaches that, in our view, will replace animals as
the default option in biomedical experimentation. How fast this transition will take place will depend on the pace at which these new models are optimized to reflect the biology of humans, rather than that of non-human animals. While the new methods are likely to reshape all areas in which animals are currently used in science, we particularly encourage their
application in biomedical research, which accounts for the bulk of animals used. We call for the pursuit of a three-prong strategy that focuses on (1) advancing non-animal methods as replacements of animal experiments, (2) applying them to biomedical research, and (3) improving their relevance to human biology. As academics and scientists, we feel that educational efforts targeted at young scientists in training will be an effective and sustainable way to advance this vision. Our strategy may not promise an imminent end to the use of animals in science, but it will bring us closer to an era in which the 3Rs are increasingly perceived as a solution to a receding problem. Russell and Burch themselves surely would have
welcomed these positive changes.

Animal Experimentation: Working Towards a Paradigm Change, 2019

The 1st chapter 'Refinement on the way to replacement: Are we doing what we can?' of 'Animal Expe... more The 1st chapter 'Refinement on the way to replacement: Are we doing what we can?' of 'Animal Experimentation: Working Towards a Paradigm Change' starts by exploring the application of several refinement methods in practice, commencing with current housing and husbandry standards and a discussion about the benefits of a “culture of care”, followed by assessing important experimental refinements. To further assess the quality of animal-based research, it reviews necessary refinements in planning, conduct, and reporting practices of animal studies. The chapter then looks at feasible ways to reduce and replace animal use by first discussing tools to appraise animal studies that could lead to a significant reduction of animal experiments and thus numbers of animals used, and then reflecting on what the scientific community has been doing to move towards replacement of animals in research, testing, and education.

Anesthetic and Anlagesic Regimens Used in Animal Research Proposals, 2019

Pain has a profound effect on an animal’s wellbeing. In Germany, researchers using animals have b... more Pain has a profound effect on an animal’s wellbeing. In Germany, researchers using animals have been legally required to reduce any possible pain, suffering, distress or lasting harm to an absolute minimum since 1972. To evaluate how these provisions have been implemented in practice, an assessment of refinements to experimental techniques was conducted by retrospectively reviewing 684 surgical interventions described in 506 animal research applications that were sent to the German competent authorities for approval in 2010. This paper focuses on the efficacy of proposed anesthesia and peri- and postoperative analgesia. Postoperative analgesia was not proposed for 30% of surgeries. Following 10% of procedures, animals were to be given pain relieving medication if the investigators decided this was necessary; however, structured assessments to detect pain were absent. Consequences of unalleviated pain and omission of pain assessment techniques are discussed, and some recommendations to improve anesthesia and analgesia are given. The findings of this review highlight the need for improvement, both to fulfil legal requirements and to improve animal welfare. To monitor compliance with animal welfare regulations and ensure good veterinary and scientific practices, education and training need to be intensified. Adherence to the items listed in the PREPARE and ARRIVE guidelines and the Gold Standard Publication Checklist (GSPC) should become legally binding.

Decades of costly failures in translating drug candidates from preclinical disease models to huma... more Decades of costly failures in translating drug candidates from preclinical disease models to human therapeutic use warrant reconsideration of the priority placed on animal models in biomedical research. Following an international workshop attended by experts from academia, government institutions, research funding bodies, and the corporate and non-governmental organisation (NGO) sectors, in this consensus report, we analyse, as case studies, five disease areas with major unmet needs for new treatments. In view of the scientifically driven transition towards a human pathways-based paradigm in toxicology, a similar paradigm shift appears to be justified in biomedical research. There is a pressing need for an approach that strategically implements advanced, human biology-based models and tools to understand disease pathways at multiple biological scales. We present recommendations to help achieve this.

Animal Experimentation: Working Towards a Paradigm Change, 2019

Animal experimentation has been one of the most controversial areas of animal use, mainly due to ... more Animal experimentation has been one of the most controversial areas of animal use, mainly due to the intentional harms inflicted upon animals for the sake of hoped-for benefits in humans. Despite this rationale for continued animal experimentation, shortcomings of this practice have become increasingly more apparent and well-documented. However, these limitations are not yet widely known or appreciated, and there is a danger that they may simply be ignored. The 51 experts who have contributed to Animal Experimentation: Working Towards a Paradigm Change critically review current animal use in science, present new and innovative non-animal approaches to address urgent scientific questions, and offer a roadmap towards an animal-free world of science.