WC11 webinars on 3Rs in COVID-19 research

WC11 webinars on 3Rs in COVID-19 research

Supported by the Netherlands National Committee for the protection of animals used for scientific purposes (website)


On 25 and 26 August 2020 at 3 PM CEST, the 11th World Congress on Alternatives and Animal Use in the Life Sciences organized two 1.5 h webinars on 3Rs in COVID-19 research. On both days, several excellent presentations highlighted innovative model systems to study COVID-19, and also discussed new strategies for the development of vaccines, therapeutics and diagnostics and much more!


Tuesday 25 August

Wednesday 26 August

Questions & Answers

During the webinars several questions were asked through the chat box. We have asked all the speakers to answer your questions. You can download an overview of the questions and answers below. These documents will be updated regularly.


Tuesday 25 August

Dr Penny Hawkins BSc PhD.
Head of Research Animals Department, RSPCA (United Kingdom)

Penny Hawkins 
Deputy Head RSPCA Research Animals Department
outside RSPCA HQ
Please read our licence terms supplied with this image. All digital images must be deleted after authorised use unless otherwise agreed in writing.
Photograph by
Andrew Forsyth/RSPCA
Tel: 0870 754 0150     Fax: 0870 753 0048    email: pictures@rspcaphotolibrary.com

Coronavirus research – anything goes?

There is a clear and urgent need to understand COVID-19, and develop vaccines and treatments. Thousands of animals are likely being used in SARS-CoV-2 related research worldwide, and some could unfortunately experience severe suffering. However, some recent approaches could, if maintained, help reduce the general impact of science on animals more widely. These include increased global communication and data sharing, increased use of non-animal technologies, and seeking to avoid some animal tests in vaccine trials. Could these approaches provide an ongoing basis for continued innovation and collaboration, changing scientific culture permanently for the better? This presentation will consider and invite discussion of the potential for positive change, and suggest some action points, particularly for Animal Welfare Bodies.

Koert Stittelaar, PhD.
General Manager, Viroclinics Xplore, Schaijk (The Netherlands)


Animal models and alternatives for COVID-19 research

Although repurposed licensed drugs may directly be tested in human clinical trials, pre-clinical assessment of the safety and efficacy of new vaccines and treatments requires the use of relevant animal models of SARS-CoV-2 infection and disease such as hamsters, ferrets, mice non-human primates while for discovery or otherwise early stage research alternatives like cell lines or organoids can be used. In vitroex vivo and in vivo models demonstrating susceptibility to SARS-CoV-2 infection and/or reproduction of COVID-19 disease have now been established and appear in the scientific literature allowing the field to choose the most suitable test platform. This presentation will address advantages and limitations of animal models as well as in vitro models. Also opportunities to reduce and refine animal studies will be discussed.


Christian Desaintes, PhD.
Policy Officer, European Commission (Belgium)


Research response of the European Commission to address the COVID-19 pandemic

The COVID-19 pandemic created an urgent demand for delivering rapid innovative solutions to contain and mitigate the outbreak, to better care for patients and survivors, to protect all individuals, including vulnerable groups and frontline health care staff. The European Commission has reacted quickly to fight the pandemic from different perspectives. Among these, the Commission has launched several special research actions related to COVID-19 and the Sars-CoV-2 virus that address epidemiology, preparedness and response to outbreaks, diagnostics, treatments and vaccines, as well as the infrastructures and resources that enable this research. This presentation will highlight the global effort from the Commission in supporting and coordinating research on the pandemic, and will provide a preliminary analysis of the laboratory animals and alternative methods involved.

Wednesday 26 August

Thomas Hartung
Director CAAT, Johns Hopkins University (United States of America)

Montreux Switzerland, 2019, may 11th, Studio photo-session at the 2019 Frontiers Forum.   ©Francesca Palazzi

COVID-19 – what is in the box of alternative methods?

The unprecedented challenge and medical success story of COVID-19 opens the door for the application of new approach methods. Advanced cell culture (microphysiological systems) and big data / A.I. have changed the repertoire of alternative methods and lend themselves now to help accelerating drug and vaccine development with faster and more human-relevant data. Examples from our own research on SARS-CoV-2 in BrainSpheres and A.I. to predict compound properties are given to illustrate this.

Shuibing Chen
Kilts Family Associate Professor, Director of Diabetes Program, Department of Surgery, Weill Cornell Medicine (United States of America)


Human Pluripotent Stem Cell Models for COVID-19 Disease Modeling and Drug Screening

SARS-CoV-2 has caused the COVID-19 pandemic. There is an urgent need for physiological models to study SARS-CoV-2 infection using human disease-relevant cells. COVID-19 pathophysiology includes respiratory failure but involves other organ systems including gut, liver, heart, and pancreas. We present an experimental platform comprised of cell and organoid derivatives from human pluripotent stem cells (hPSCs). A Spike-enabled pseudo-entry virus infects lung organoids, colon organoids, pancreatic endocrine cells, liver organoids, cardiomyocytes, and dopaminergic neurons. SARS-CoV-2 infection caused striking expression of chemokines, as also seen in primary human COVID-19 pulmonary autopsy samples. hPSC-derived cells/organoids provide valuable models for understanding the cellular responses of human tissues to SARS-CoV-2 infection, and for disease modeling of COVID-19.

This presentation is supported by STEMCELL Technologies (website)


Jan Willem van der Laan
Senior Assessor Pharmacology and Toxicology, Medicines Evaluation Board, Chair Safety Working Party CHMP, EMA (The Netherlands)


3Rs and COVID-19 Vaccine Development: Regulatory Aspects

Development of COVID-19 vaccines is ongoing under pressure. The International Coalition of Medicines Regulatory Authorities (ICMRA) has discussed the potential request of animal data and has confirmed that these data proving efficacy and safety (e.g. with respect to potential disease enhancement) might not be available at the time of clinical trial initiation.
Opportunities to use knowledge accumulated with platform technology might accelerate the development of a COVID-19 vaccine. This platform technology utilized to manufacture a vaccine already licensed, might enable the use of toxicology data from this licensed vaccine obviating the need for specific safety data for the new candidate COVID-19 vaccine.
The potential for vaccine-induced disease enhancement needs further attention, although it is acknowledged that no adequate animal models are available in this respect.

Moderator 25 + 26 August 2020

Brian Maguire
Journalist & Producer – Euractiv & EBX Media (Belgium)


Brussels-based journalist, producer and broadcaster, Brian Maguire, hosts live radio and television debates with European Commissioners, Ambassadors, Members of the European Parliament and independent experts. A EURONEWS Contributor and co-host, he also presents the EURACTIV series ‘The Presidency’ and ‘Over A Coffee’. He specialises in European politics and business; producing short documentary films and news reports exploring Europe’s competing policy dimensions. A graduate in Government and Law, he has worked across a broad range of publications, especially within the business-to-business sector. A specialist in corporate and political communications, his clients include start-ups, SMEs, blue chip companies, and NGOs with a human rights focus.
Follow on Twitter: @BrianMaguireE

Is there a role for the 3Rs in COVID-19 research?

In the past few weeks we have asked several people to answer the question: “Is there a role for the 3Rs in COVID-19 research?“.

Troy Seidle
Vice-President Research and Toxicology of the Humane Society International (Canada)


“Existing non-animal approaches can already help us understand the biology, behaviour and potential countermeasures to COVID-19, including human lung tissue cultures, organ-on-a-chip technologies, other cell-based models and computational tools. These methods don’t just spare animals. They are in general also more human-predictive and both time- and cost-efficient, maximizing the quality and relevance of the information we can gather. We are at a tipping point in bioscience research, where the “gold standard” is shifting from rodent to human biology, and non-animal technologies that can better simulate and predict human outcomes in the real world. Stakeholders need to work together to accelerate this shift, rallying scientific support for the necessary policy and financial instruments to establish animal-free research and safety assessment as a priority going forward. Especially now, in the context of a pandemic, we need to support the scientific community in developing and deploying new and better instruments suited to produce relevant results more quickly and reliably to save human lives.”

Thomas Hartung
Director Center for Alternatives to Animal testing, Johns Hopkins University Bloomberg School of Public Health (United States of America)


“COVID-19 urges us to have make drugs and vaccines available in months or few years, processes which typically take a decade. 3Rs methods are one accelerator and COVID-19 might be a door-opener for their broader use in the future.”

Benjamin Smith
Director, Innovations in Food and Chemical Safety Programme, Agency for Science, Technology and Research (Singapore)


“The short answer is yes. There is definitely a place for the 3Rs in COVID-19 research. The principle of the 3Rs needs to be carefully considered for all research areas. In fact, there is already a lot of work under way in the field of vaccines looking at non-animal alternatives, including for vaccine production. I also think that in vitro models, such as lung epithelial models and organoids that allow viral replication, can help us understand mechanisms of pathogenesis and allow us to more easily study interspecies differences and that such models will become more popular for virology research in the future. That being said, especially under pandemic conditions whereby we are rushing to develop vaccines, we have to acknowledge that animal models are still important, and although many of us support the eventual end goal of moving fully away from animal testing, for now we need to use every tool in our tool kit to battle COVID-19”.

Maurice Whelan
Head of the European Union Reference Laboratory for Alternatives to Animal Testing, European Commission, Joint Research Centre (Italy)


“One of the very worrying aspects of the pandemic is the specific vulnerabilities of certain subpopulations. No doubt many factors are at play but surely a better understanding of individual human biology and virology is central to combating the disease. We need human relevant approaches based on in vitro and in silico models to properly address knowledge gaps and ensure successful translation of research results into clinical practice to save lives. In taking on this virus, we simply can’t accept current failure rates of new therapies and trail-and-error approaches based on ineffective animal models. The reviews we’ve conducted recently at the JRC’s EURL ECVAM on the use of non-animal models and methods in biomedical disease-related research clearly show that alternatives are indeed fit to study COVID-19. During the pandemic we’ve also been hearing a great deal about antibodies, and how they are an essential scientific tool for research, diagnostics and treatment. Non-animal derived antibodies are without a doubt the better option for serious science, and proper use of research funds. Anyone considering using animals for developing and producing antibodies within the content of their COVID-19 research needs to seriously reconsider, starting by reading our latest EURL ECVAM Recommendation.”

Vijay Pal Singh
Joint Director of the Food Safety and Standards Authority of India (India)


“The 3Rs are always relevant in research and are getting undivided attention in the present scenario, since there is an urgent need for research to develop therapeutics and vaccines to defeat COVID-19. As we cannot afford to make mistakes because of time limitations, 3Rs application and guidelines are more relevant and applicable. In my opinion, the principle of 3Rs and robust experimental design is a very valuable tool for translational research in COVID-19 research.”

Volker Lauschke
Professor at the Department of Physiology and Pharmacology of the Karolinska Institutet and CEO of HepaPredict AB (Sweden)


“Model systems that accurately mimic the life cycle of SARS-CoV-2 are essential to understand the molecular events involved in viral entry, replication and secretion. While animal models allow to parse the interplay between virus and host at the system’s level, these can be subject to substantial species differences, result acquisition is overall slow and not compatible with the throughput required for drug screening. In vitro methods using human cell lines, organoids or organotypic primary tissue cultures offer an important alternative for COVID-19 research and aspire to overcome these limitations. Multiple studies have already provided important insights into the pathophysiology of the disease and have aided the identification and mechanistic characterization of promising new drug candidates in short time frames that would have been impossible to achieve using solely animals.”

Yasuyuki Sakai
Professor at the Department of Chemical System Engineering at the Graduate School of Engineering of the University of Tokyo-Japan and President of the Japanese Society for Alternatives to Animal Experiments (Japan)


“COVID-19 really reminded us of the importance of animal experiments to sustain our health and also of the importance of refinement and reduction. Simultaneously, new non-animal technologies for vaccine production and evaluation emerges, demonstrating the new potentials of “replacement”. In addition, deep involvement of human immune system suggest the importance of research/development of non-animal but human-cell derived new approach methods, where integration of physiological tissue/organ culture systems, multi-hierarchical comprehensive analyses and various numerical methods is really required to predict the situation of individual patients and optimize their treatment.”

Helena Kandárová
President of the European Society of Toxicology In Vitro (The Slovak Republic)


“COVID-19 is undoubtedly the most relevant viral disease in the scientific community these days. In recent months, tremendous activities have been being developed towards the understanding of the mechanisms of the disease, investigation of the possible treatments and vaccine development. In the battle with time and growing incidence of the disease, in vitro and in silico methods that contribute to the COVID-19 research are gaining momentum. In silico modelling is used to identify and predict transmission patterns and discover potential therapeutic candidates. Physiologically relevant organoids and in vitro 3D human cell-based models of healthy as well as diseased lungs are helping to test the mode-of-action hypotheses and select the most promising molecules for immunisation and disease treatments. Overall, these methods are not anymore “alternatives”, but highly relevant and reproducible tools in pre-clinical studies of new drug and vaccine candidates. They are saving time as well as lives of experimental animals necessary for the understanding of the disease, its treatment and prevention.”

Erin Hill
President of the Institute for In Vitro Sciences and President of the American Society for Cellular and Computational Toxicology (United States of America)


“There are very important roles for in vitro and in silico tools to investigate the biology of viruses, details of disease states and therapies. Human cell cultures, such as reconstructed tissues, organoids, and ex vivo models of the respiratory tract, such as human precision-cut lung slices, combined with controlled exposure systems, allow researchers to test the safety and efficacy of therapies to COVID-19 in a much faster timeline compared to animal models. The effect of the virus itself on lungs and other organs can also be investigated rapidly to better understand the mechanisms of disease development. When new therapies or vaccines are discovered, cell culture systems can be used to determine the quality (e.g. lot-to-lot reproducibility) of those medicines. As the sophistication of these tools increases with the use of micro-fluidic organ-on-a-chip systems and artificial intelligence, we will only see an increase in the utility of these methods to help protect public health.”

Amy J. Clippinger
President of the People for the Ethical Treatment of Animals International Science Consortium Ltd. (United Kingdom)


“In the race to develop lifesaving vaccines and treatments for COVID-19, many researchers have embraced the 3Rs. For instance, the US Food and Drug Administration has allowed companies to prioritize clinical trials instead of waiting for the results of animal tests that often fail to predict human responses to new drug candidates. Modern non-animal methods, such as 3D reconstructed human respiratory tissue models from MatTek and Epithelix, have taken center stage to study COVID-19 infection and screen for potential treatments. Researchers are also turning to the use of recombinant human antibodies in place of animal-derived antibodies because they are more scientifically robust, have defined sequences, and can be made faster than animal-derived antibodies. For example, in March, YUMAB GmBH announced that it had generated the first human antibodies against the new coronavirus strain, and the company has since confirmed likely therapeutic effects using the patient-derived coronavirus strain SARS-CoV-2. This is just the beginning of the world recognizing that non-animal methods give us our best chance at saving lives quickly and safely. Forward-thinking scientists are seeing this moment as an opportunity to reimagine our approach to science and establish non-animal methods as the gold standard for future research.”

Marcelo Asprea
Chief of Laboratory Animal Care and Experimental Surgery Childrens Hospital Prof. Dr. Juan P. Garrahan (Argentina)


“The COVID19 pandemic, which has surprised humanity, strikes us and makes us quickly consider new paradigms for science. The need to achieve results urgently means that traditional processes must be adapted to this new reality. Precisely this situation leaves us no choice but to take a shortcut on the way to our goal. The 3Rs are not only the future, but they have also been the past and are the present. Many of the trials, which are being carried out searching for new drugs through the use of nanoparticles and vaccines using biological synthetics, are developed under this vision. The need for minimal animal testing and parallel human testing means that technology in alternative methods must achieve perfection. In an unsustainable world, it is very likely that in the future we will have to face new diseases never seen before, so the development of more and better research on 3Rs becomes our present.”

Xiaoting Qu
Deputy Secretary General of the Society of Toxicity Testing and Alternative Methods, Chinese Environmental Mutagen Society (China)


“The COVID-19 pandemic posed great challenges to the speed of therapeutics identification and precision medicine. The 3Rs could help to fill the current knowledge and technology gaps, accelerate the discovery and development of drugs as well as the elucidation of the underlying mechanisms. Recent advances in in vitro models like organoid cultures offer a remarkable opportunity and promising tools for understanding of the pathogenesis of COVID-19, speedy identification of drug candidates, and optimization of the cocktail recipes for COVID-19. The 3Rs will also contribute to streamline vaccines production process via removing redundant tests. It is thus expected that the 3Rs will underpin the modern public health management system with profound understandings and effective measures for risk prevention and control.”

Katja Wolthers
Clinical virologist at the Department of Medical Microbiology of the University Medical Center Amsterdam and Director of Organovir (The Netherlands)


“The recent SARS-CoV-2 pandemic has led to an overwhelming amount of published papers on pathophysiology, treatment and vaccine development against COVID-19, and many of these studies include research with animals. Although animal models have historically contributed immensely, the limitations of these models for virology are also clear. Animal models do not adequately reproduce human viral disease pathophysiology and in some instances, pathogens have a unique human host range that cannot be replicated in an animal model. As a part of the preparedness against emerging infectious diseases, human models are needed that are better predictors of disease outcome, immune response, and potential therapeutics. The current pandemic provides ample opportunity to rapidly develop such human disease models, either in vitro with organoid technology or in silico with integrating data from different fields to build virtual disease models. A major future challenge lies in reduction and replacement of animal models for viral vaccine research. Now is the time to start.”

Félix Carvalho
President-Elect of EUROTOX, President of the Portuguese Society of Pharmacology, President of the Scientific Council of the Faculty of Pharmacy of the University of Porto and Vice-Director of the Applied Molecular Biosciences Unit (Portugal)


“The COVID-19 pandemic has severe health effects and serious implications for economic growth and social development. In this context, the scientific community has played an exemplary role in responding to this global emergency, prioritizing research into this disease. As the quest to find suitable vaccines and/or drugs follows an unprecedented swiftness, it is also time to emphasize the importance of the 3Rs implementation in COVID-19 research. A major difficulty in animal studies results from the lack of animal models that reflect the common pathology in the majority of COVID-19 patients, including infection dynamics and transmission, as well as similar immune response to vaccine candidates. Here, the application of new (animal-free) approach methodologies, such as human in vitro assays of different complexity ranging from high-throughput assays, 2D or 3D cellular models and human tissue slices to organ-on-a-chip approaches, can be proven to be extremely useful, allowing research based on specific features of human biology. Such approaches comply with the Directive 2010/63/EU, in which the principle of the 3Rs needs to be considered when selecting testing approaches to be used for regulatory testing of human and veterinary medicinal products, and may provide vital and swift data for a safe progression to clinical testing.”

Christine Mummery
President of the European Organ-on-Chip Society (The Netherlands)


“Emerging models proving very useful for COVID-19 research are human stem cells which can be differentiated to many cell types and incorporated in Organ-on-Chip formats. In this way they often capture human tissue physiology and its response to viral infection, since as importantly for COVID-19, SARS-COV-2 only infects human cells, not those of mice. By using existing human stem cell derived cardiac, lung, liver, gut and blood vessel models, researchers are able to rapidly evaluate the effects of anti-virals and drugs including their cardiotoxicity. Furthermore, these models are leading to better understanding of how infection affects the heart and other organs. By leveraging existing models and measurement methods, impact beyond conventional approaches will be accelerated by providing data immediately relevant to clinicians. In this way a reduction of preclinical cardiac safety assessment from months in animal models to just weeks in these systems can be expected. Another serious problem for COVID patients is thrombosis in small blood vessels which causes serious tissue damage. Blood vessels-on-chip through which blood from COVID-19 patients flows, are also promising tools to gain insight into how thrombosis occurs in COVID-19 patients and how to prevent it.”

Marize Campos Valadares
Director of the Laboratory of Education and Research in In Vitro Toxicology, Universidade Federal de Goiás (Brazil)


“The world is facing the biggest challenge of our generation with the spread of COVID-19, demanding speedy actions in discovering new therapeutic tools. Usually, innovation in pharmaceutical science is a very expensive and time-consuming process with no guarantees of success. Strategies in the context of 3Rs for drugs/vaccines discovery and development for COVID-19 treatment can accelerate the process as well as reduce the risk of failures. For instance in safety evaluations, new approach methods can predict mutagenicity/genotoxicity or even skin sensitization potential within days, instead of months using animal models. In terms of animal reductions, in the traditional full safety package, it is possible to combine animal studies, for example, carcinogenicity with chronic oral toxicity studies. Another example is vaccine batch control testing, one of most animal-consuming areas in regulatory testing, where in vitro potency assays can be performed. The drug/vaccine discovery research for COVID-19 treatments definitely can benefit from the advances in 3Rs. Artificial intelligence, in vitro, in chemico, and in silico models/high-throughput screening methods can play a crucial role to facilitate research and success in development of medicines/vaccines for COVID-19.”

Marina Goumenou
Research affiliate of Center of Toxicology Science & Research, Medical School, University of Crete, Senior Scientific Officer of General Chemical State Laboratory (Greece)


“The COVID-19 pandemic has severe health effects and serious implications for economic growth and social development. In this context, the scientific community has played an exemplary role in responding to this global emergency, prioritizing research into this disease. As the quest to find suitable vaccines and/or drugs follows an unprecedented swiftness, it is also time to emphasize the importance of the 3Rs implementation in COVID-19 research. A major difficulty in animal studies results from the lack of animal models that reflect the common pathology in the majority of COVID-19 patients, including infection dynamics and transmission, as well as similar immune response to vaccine candidates. Here, the application of new (animal-free) approach methodologies, such as human in vitro assays of different complexity ranging from high-throughput assays, 2D or 3D cellular models and human tissue slices to organ-on-a-chip approaches, can be proven to be extremely useful, allowing research based on specific features of human biology. Such approaches comply with the Directive 2010/63/EU, in which the principle of the 3Rs needs to be considered when selecting testing approaches to be used for regulatory testing of human and veterinary medicinal products, and may provide vital and swift data for a safe progression to clinical testing.”