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Animal protection groups support grant to fast-track non-animal approaches for COVID-19 vaccine research

24 June 2020

Humane Society International and the Humane Society of United States have supported a fast-track research grant for non-animal approaches to investigate mechanisms, medicines and vaccines for the novel coronavirus and COVID-19, sponsored by the Johns Hopkins Center for Alternatives to Animal Testing at the Johns Hopkins Bloomberg School of Public Health. The organizations believe that understanding the biological mechanisms that make humans especially susceptible to COVID-19 is urgently needed to inform the development and evaluation of effective countermeasures.

Laboratory investigations of human disease often attempt to artificially reproduce a condition in animals. Since the World Health Organization declared COVID-19 a pandemic, a flood of studies have described infecting mice, hamsters, ferrets, monkeys and other animals with COVID-19. Yet most report that the animals used were either immune to the new virus, or manifested symptoms that differ substantially from the human condition, including in the most severe clinical outcomes. In addition, the animal-based approach is limited in its ability to predict the impact of comorbidities— the presence of two chronic diseases—in COVID-19 patients, or how the various treatments could impact or worsen the infection.

“We have great faith in the Johns Hopkins Center for Alternatives to Animal Testing as a source of funding for research with the potential to spare humans, as well as animals in laboratories, from suffering caused by COVID-19,” says Kitty Block, president and CEO of HSUS and CEO of HSI. [Read more…]

Leveraging the future: in vitro methods also need a paradigm shift

12 June 2020

by Bianca Marigliani

In an era of drones, self-driving cars and 3D printing, biomedical research remains heavily rooted in methods of the past — namely, animal models and animal-derived tissues. This remains true even as the field of toxicology begins to shift from a near-total reliance on live animals toward human-based cell systems and other technologies.

In the context of the “3Rs” of replacement, reduction and refinement of animal use, in vitro methods are often assumed to be non-animal. But this is not necessarily so. In vitro cultures and associated modalities commonly use animals as a source of biological materials, even when relying primarily on human-derived cells and tissues. [Read more…]

Horizon Europe must focus on human-centric approaches to maximise impact

18 May 2020

by Lindsay Marshall

The European Union is on a mission to defeat cancer. This devastating disease disproportionately impacts Europeans, who represent one tenth of the global population, yet comprise one quarter of all cancer diagnoses worldwide. It is no surprise then, that cancer is one of the five mission areas of the EU’s most recent research and innovation framework programme, Horizon Europe. The goal of the mission area focused on cancer is to forestall the staggering number of cancer diagnoses, projected to increase to more than 4.3 million newly diagnosed cases by 2035.

The BioMed21 Collaboration’s team of experienced toxicologists and biomedical scientists, with varied backgrounds in computer modelling, read-across analysis, molecular biology and cellular physiology, has called on the Cancer Mission board to prioritise funding and build capacity for innovative, human-focused, animal-free research and testing strategies that enable the development of precise and reliable models for understanding cancer. We are keen to ensure that the mission adopts a modern research paradigm to enable effective research and development that advances public health through more judicious use of resources. [Read more…]

Funding Opportunity: Call for India-based Experts in Cancer Biology to Build Pathways to Better Science

30 March 2020

Cancer researchers based in India are invited to submit proposals for funding to support the integration of biological pathways related to cancer, building on the concept from the field of toxicology of Adverse Outcome Pathways (AOPs). More information on how to apply »

The need for this type of human-relevant research is evident. Cancer claims millions of lives worldwide each year. Yet, despite relentless efforts to find a cure, 97 percent of cancer drugs that reach clinical trials never make it to market. This points to a failure of our drug discovery pipeline, which relies heavily on animal testing. Back in 1997, Dr Richard Klausner, director of the U.S. National Cancer Institute, famously said, “The history of cancer research has been a history of curing cancer in the mouse. We have cured mice of cancer for decades – and it simply didn’t work in humans.” Sadly, little has changed since then. Further pursuit of cancer research in rodents — even ‘humanized’ rodents containing one or two human genes — will not get us where we need to go in our quest for a cure. [Read more…]

Research round-up: Organ-on-a-chip models for predicting drug-induced liver and cardiotoxicity and for studying the colon mucus layer

28 December 2019

‘Reproducing human and cross-species drug toxicities using a Liver-Chip’, delves into the research by Emulate Inc. with Janssen Pharmaceuticals, Astra Zeneca and the Wyss Institute at Harvard on the development of liver chips using species-specific cells to predict drug induced liver toxicity and reduce drug attrition rates. On the same lines of drug induced toxicity, Matsui et al. worked on developing 2D model systems with human iPSCs to predict cancer drug-induced cardiotoxicity, described in their paper ‘Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes’. Finally for this edition, ‘Human colon-on-a-chip enables continuous in vitro analysis of colon mucus layer accumulation and physiology’ by Sontheimer-Phelps et al. from the Wyss Institute, reports on their model which recapitulates the structure and composition of the native mucus layer of the human intestine – enabling in-depth study of this important defensive barrier. [Read more…]

South Korean Ministries invite proposals for funding of tissue chip-based drug development research

18 December 2019

The BioMed21 Collaboration welcomes a recent joint funding call by the South Korean Ministry of Science and ICT and Ministry of Trade, Industry and Energy to develop more human-predictive models for drug assessment. It is well known that there can be poor correlation between toxicity in humans and animals used in laboratory tests, with the latter being predictive of human toxicity only a percentage of the time. This can lead to failures of drugs in the clinic or withdrawal from the market.

This inter-ministerial collaborative project will support 16 RFPs aimed at development and use of human-mimetic methods from research to product development – to better predict the functions of human tissues or organs in vivo – with a view to overcoming the problem of interspecies variability.

This announcement follows a high-level forum in Korea’s National Assembly at which Ministries were invited to discuss proposed new federal legislation that would prioritize funding for human biology-based approaches in biomedical research, and formally establish the Korean Centre for the Validation of Alternative Methods (KoCVAM) under the law with a mandate to work closely with other authorities to advance non-animal method development, acceptance and use. [Read more…]

IABS Conference on Animal Testing for Vaccines – Implementing Replacement, Reduction and Refinement: Challenges and Priorities

5 December 2019

The 2019 IABS Conference, dedicated to the challenges and priorities in implementing alternative methods to animal testing for vaccines, gathered together key experts from companies, regulators and international organizations, with a meaningful participation of local representatives.

The objective of the conference was the presentation of the advancements of the last 5 years in the development and regulatory acceptance of alternative methods to animal testing for batch release testing, plus a discussion on what still needs to be accomplished by manufacturers and regulators to transition to non animal-based testing strategies, particularly in developing countries.

A full day has been devoted to dedicated workshops, one focused on the specific needs of developing countries with regards to the implementation of alternative methods, and another on the concepts of validation, implementation, acceptance and harmonization. The discussion prompted a general acknowledgement that in order to improve the chances of investment in, and acceptance of alternative methods, both regulators and manufacturers ought to raise the level of mutual trust and exchange, a result which could be achieved by increased sharing of data, and clearer communication of needs and expectations, already from the early stages of product development or product/testing strategy variation. [Read more…]

During COPD awareness month; time to stop smoking cigarettes, whether you’re a mouse, a dog or a human!

5 November 2019

Rats jammed face first into what look like small milk bottles, no room to move, no option to even turn their heads. The rats in glass cylinders are arranged rows deep, screwed into a huge central metal cylinder that will provide a constant stream of cigarette smoke, directed into their faces in what is known as the ‘nose-only’ exposure technique. Mice contained in small plastic boxes for hours on end, flooded with a constant stream of cigarette smoke at a rate of 10 cigarettes per hour, with no break. This is the ‘whole body’ exposure model. Dogs trapped, immobilised, their noses strapped into masks, their eyes just visible peeking above. Or how about mice, with patches shaved on their backs, cigarette tar painted onto the bare skin until tumours appear? Tobacco distillate rubbed into a rabbit’s skin? The toxic compounds we now associate with smoking-related disease fed to rats until they develop fatal oesophageal tumours? These approaches have all been used to examine the effects of cigarettes, and shockingly, many are still used today.

Experiments rubbing concentrated cigarette smoke extracts into animal skin were carried out for many years in attempts to discover whether cigarettes were harmful. Careers were made or destroyed here; the scientists using strains of mice that did not get cancer received further funding to continue down an essentially blind alley, whilst the researchers using animal models which showed that smoking could cause cancer were not funded again. I think that we are probably all aware of this back story; tobacco companies accused of not revealing all their data indicating that cigarettes were really harmful, and groups like the Guest Choice Network (now Center for Consumer Freedom), who were paid to try and stop smoking bans, but part of the issue here was that cigarettes were really not that harmful… if you were a rat or a mouse. This is still a huge problem with research using animals; animal models do not mimic the severity of (smoking-related lung) disease as we see it in people. [Read more…]

Stem cells cultured from human skin used to study fatty liver disease

1 October 2019

Non-alcoholic fatty liver disease comprises a range of conditions, ranging from the uncomplicated – hepatic steatosis – to the more severe hepatocellular carcinoma. Non-alcoholic steatohepatitis (NASH) is a form of non-alcoholic fatty liver disease in which there is hepatitis and liver cell damage, in addition to fat build-up. NASH may lead to cirrhosis or liver cancer and affects millions of people worldwide. To date, no drugs have been approved to cure NASH and the major obstacles in the development of high-potential anti-NASH drug candidates are the identification of possible drug targets and the lack of adequate NASH models.

Several animal models have been developed to study NASH, using genetic modifications, dietary-induced disease or a combination of these. However, due to the heterogeneous pathology of NASH, most animal models do not accurately represent the human condition and there is a need to develop new models that are more human-relevant and human-predictive than animals. Now, a team of innovative researchers at Vrije Universiteit in Brussels – led by Dr. Robim Rodriguez and Professor Tamara Vanhaecke – aims to find whether using stem cells grown from human skin will lead to better models for NASH that may indicate where to target more effective treatments. [Read more…]

Research round-up: Species-specific differences in the cerebral cortex revealed, a new retina-on-a-chip model and a functional microphysiological pancreas.

25 September 2019

Our October edition of Research Round-up has collected three very different advances in our understanding of human organ systems.

In the Nature article “Conserved cell types with divergent features in human versus mouse cortex,” Hodge et al. analyzed the cellular composition of the human cortex at the single nucleus RNA level.

In the eLIFE paper “Merging organoid and organ-on-a-chip technology to generate complex multi-layer tissue models in a human Retina-on-a-Chip platform,” Achberger et al. demonstrate the creation of a sophisticated retina-on-a-chip with vasculature-like perfusion, which can recreate drug-induced retinopathy.

Gleiberman et al. describe the development of a microfluidic pancreatic islet-on-a-chip to accelerate efforts to study and develop effective treatments for diabetes, in their latest paper “Synchronized stimulation and continuous insulin sensing in a microfluidic human Islet on a Chip designed for scalable manufacturing.”
[Read more…]

Standing with Vanda- supporting the stance against unnecessary animal testing

8 August 2019

Intermittent or chronic nausea. Bloating. Burning, shearing or gnawing abdominal pain. A feeling of fullness after eating just a few bites. Poor appetite and weight loss. These symptoms add up to the distressing condition known as gastroparesis – a chronic, life-limiting disorder that leads to weight loss and potentially life-threatening complications. Gastroparesis is characterised by delayed gastric emptying and, while it is often associated with type 1 diabetes, most cases are idiopathic. There are no cures, only treatments, and some of those are less than satisfactory – posing risks of serious side effects and losing potency over time.

Gastroparesis appears to associate with aberrant regulation of gastrointestinal function through neuropeptides binding to the neurokinin receptors, namely NK-1, -2 and -3. There are signs of a possible step forward with tradipitant, a second generation NK-1 receptor antagonist. There is evidence that this drug is well tolerated by humans, with only mild side-effects, and that it has benefited patients with gastroparesis. [Read more…]

Research round-up: Reliable 3D brain organoids, promising new FDA-approved drugs for treating lymphoma and an efficient cartilage-on-a-chip for screening disease-modifying osteoarthritic drugs.

19 July 2019

This edition of research round-up reports on very different aspects of applying human-focused technologies and strategies. The paper by Velasco et al. entitled ”Individual brain organoids reproducibly form cell diversity of the human cerebral cortex” and published in Nature shows that results obtained from brain organoids are reliable and can be replicated. In their paper ”Phosphorylation of SOCS1 inhibits the SOCS1-p53 tumor suppressor axis” published in Cancer Research, Ferbeyre et al. unveil the molecular mechanisms that turn a tumor suppression gene into an oncogene and suggest that an FDA-approved drug may stop this oncogene. Lastly, the study “Hyperphysiological compression of articular cartilage induces an osteoarthritic phenotype in a cartilage-on-a-chip” published in Nature Biomedical Engineering by Occhetta et al. reports on the development of a human cartilage-on-a-chip to be used for screening new drugs for Osteoarthritis.

Reliable 3D brain organoids

Embryonic brain development is essentially the same for every one of us- the same regions are formed, made up of the same cell types carrying out the same functions. Models of the human brain have been under development for many years, with increasing sophistication, such that we are now accustomed to reading about three dimensional, multi-cellular organoids and spheroids that exhibit increasing developmental maturity – but creating different models in different labs with different protocols has issues of its own. Besides the fact that animal data is not translatable to humans and that animals are poor models for human diseases, there is a reproducibility crisis in animal research – and research employing purely in vitro methods may not be far behind. For models that employ induced pluripotent stem cells (iPSC), it is crucial that researchers fully describe the differentiation protocol adopted – to ensure confidence in the cell type under test but also to permit the rigorous replicate studies that are necessary to advance the research. [Read more…]

Move over monkeys: combatting the world’s deadliest infections using groundbreaking human-mimetic tools

7 July 2019

A new article published in the journal Frontiers in Cellular and Infection Microbiology shows that research built around human-mimetic tools are more likely to succeed in the search for effective treatments for and prevention of flavivirus infection as compared to research using monkeys or other animals as laboratory models. The study, led by Dr. David Pamies at the University of Lausanne (formerly of the Johns Hopkins Center for Alternatives to Animal Testing), with researchers at Johns Hopkins University and the National Institute of Allergy and Infectious Diseases’ Vaccines Research Center in the U.S., carried out a comprehensive review of the models used to study deadly mosquito-borne flaviviruses (MBF) such as dengue fever and the Zika virus, known to cause neurological disease in humans.

The authors report that the host specificity of viral diseases presents a challenge for studying these human viruses in animals. Vaccines that had proved successful in primate tests have failed in human trials, leading to intense research using knockout and humanized transgenic mice. Thus, human genes relevant to the capacity of the virus to infect humans have been inserted into mice, but these modified animals are still mice, and the authors recognize drawbacks to this approach: “… several factors are recognized to influence the susceptibility of mice to MBF infection that limit applicability to humans.” For example, mice fail to display human disease symptoms if bitten by an infected mosquito (the human route of infection), and the mouse immune response varies depending on the animal’s age. Furthermore, the experiments are not reproducible in different laboratories – often an issue in animal experiments. [Read more…]

Korea’s first cross-ministerial forum to discuss new legislation supporting non-animal approaches

30 May 2019

Korea’s first-ever public forum to discuss replacing animal use in science will be hosted in Seoul at the National Assembly on May 30. Organized by Humane Society International (HSI) and Korean lawyers’ group People for Non-Human Rights (PNR), the forum is co-hosted by members of National Assembly – In-soon Nam, Kyungmi Park, Wanju Park, Seong-gon Wi, Sangmin Lee and the Assembly’s 4th Industrial Revolution Forum.

Newly proposed legislation prepared by HSI and PNR focuses on establishing an inter-ministerial entity to promote non-animal approaches in the toxicological and biomedical fields. Currently, the support of alternative research is limited to the Korea Center for Validation of Alternative Methods (KoCVAM), while the majority of animal research is funded by other ministries across multiple sectors. While these ministries support small-scale research projects on testing alternatives, there is no platform for exchanging research information or for providing major funding for programs that promote non-animal approaches. This forum will discuss collaborative support for adopting 21st-century approaches in scientific research and development without animal suffering. [Read more…]

New report sheds light on the UK’s growing medicines discovery industry

21 May 2019

The 2019 State of the Discovery Nation report offers a revealing insight into the current status of the drug discovery community in the UK, clearly indicating that companies are beginning to leverage technological advances to improve the drug discovery pipeline. The report is compiled from responses to survey questionnaires sent out to small and medium-sized enterprises (SMEs) in the UK by the BioIndustry Association in collaboration with the Medicines Discovery Catapult (MDC) to create a snapshot of the current situation. This is the second report of its kind and is focused on two key areas: artificial intelligence (AI) for drug discovery and complex preclinical cell models, or CCM.

SMEs are crucial in the drug discovery process, in terms of employment and the innovation that they bring to the process. In terms of clinical areas, cancer came out as the strongest, with almost half the SMEs analysed focusing on oncology and over 38 percent of drug assets in development aimed at this area. [Read more…]

Centre for Promoting Alternatives to Animal Experiments launched by Atal Incubation Centre at Centre for Cellular & Molecular Biology in Hyderabad, India

25 April 2019

Atal Incubation Centre (AIC) at the Centre for Cellular and Molecular Biology (CCMB), in collaboration with Humane Society International/ India (HSI/India), has launched the Centre for Predictive Human Model Systems, a centre dedicated to enable a paradigm shift in science by focusing on 21^st century new approach methodologies instead of animal models. The centre aims to prioritize investment in human-based, non-animal methodologies in life sciences research in India. This will be done by establishing a multi – stakeholder think-tank that represents the growing body of expertise on new approach methodologies on a scientific and policy level. Keeping in mind the 21^st century biomedical science and toxicology motive globally to break siloes and forge partnerships among the scientific community for better flow of knowledge, support for research and open-access publication of literature will be a focus of the centre.

“This centre is a natural alignment to AIC’s objective of supporting new innovation and technologies. This sector of predictive human biology is ripe for investment and I am certain that this partnership with HSI/India will kindle the much-needed investment in this field,” said Dr Madhusudan Rao, CEO of AIC – CCMB. [Read more…]

Research round-up: 3D oral mucosa models, diabetes in a dish, and tubuloids from human kidney

12 April 2019

Every day we come across innovative, intelligent studies that do not rely on animals to investigate human diseases and that instead find efficient and cost-effective solutions in biomedical research that are human-focused. In this edition of Research Round-up we highlight three papers from scientists who have developed novel human-focused models to mimic the oral mucosa as well as to study diabetes and renal disease.

A model of the oral mucosa

A new study shows that it is now possible to study human oral mucosa using a 3D model created in the lab. According to the authors, this new model is a promising alternative to animal testing and brings new possibilities to the field of regenerative medicine. [Read more…]

Putting people first – human-relevant research for Parkinson’s disease

3 April 2019

World Parkinson’s Day (April 11th) aims to raise awareness of Parkinson’s disease (PD) and the desperate need for effective new treatments. A recent review authored by members of the BioMed21 Collaboration identifies advances that could be implemented to better understand pathological processes, improve disease outcome, and reduce dependence on animal models. Many people may not be aware of how animals suffer in labs, used for research into Parkinson’s disease, when the answers we need may lie with patient-centred research and not animal testing.

For people, muscle tremors, or loss of fine control of movement, may be the first outward sign of Parkinson’s disease, but these motor symptoms are not the start. The death of dopamine-producing neurons in the brain ultimately cause the tremors, but the damage starts long before the tremors are apparent. Modelling this gradual loss of neurons is not possible in animals. Simulation of Parkinson’s disease in animals often uses injections of toxins directly into the brain. This destroys the dopamine-producing neurons, but the effects are instant and short-lived, compared to the slow progressive decline that occurs over decades in people. [Read more…]

For finding better treatments for TB, the computer is mightier than the mouse

13 March 2019

In March of 1882, Robert Koch used tissue from infected guinea pigs to show that the lung disease tuberculosis (TB) is caused by the organism Mycobacterium tuberculosis. At that time, TB was a constant presence in the population, infecting between 70 to 90 percent of people in urban areas of Europe and North America. Nowadays, although the mortality due to TB has reduced in developed countries, it remains a huge health issue and March is recognised globally as TB Awareness Month. In fact, the disease is still the leading cause of infection-related death worldwide, with up to one-third of the human population having latent TB.

Mice are resistant to TB, so in nature, you would never find a mouse with TB infection. Sadly, this does not save them from a life of laboratory experimentation. To get around their natural immunity, researchers manipulate mouse genetics, deleting mouse genes, and sometimes adding human genes, in order to create a TB-susceptible mouse. Whilst these manipulations are designed to make it easier for researchers to infect mice with different human diseases, this approach doesn’t necessarily create accurate and predictive models of the human condition. There is also huge wastage in this approach. For example, for one study requiring 50 genetically defined animals, 84 female “breeder mice” are used to produce a total of 400 animals, of which 350 are simply discarded and killed, being surplus to requirements. This over-breeding to generate animals with the requisite, manipulated genetics is not isolated to TB research – it is a strategy used throughout medical research. [Read more…]

Modelling the human heart: Predictive models for cardiotoxicity testing

22 February 2019

What do self-driving cars, solar airplanes and renewable energy have in common with the human heart? At first thought, not a great deal, yet a recent scientific endeavour called the Living Heart Project has brought together experts in engineering, aeronautics and energy to produce a sophisticated new model of the human heart for use in medical research. This 21^st century approach to understanding heart disease is vitally important and of particular relevance in February – American Heart Month. Heart failure is a serious problem affecting 26 million people worldwide; heart disease causes 1 in 4 deaths annually in America. It can occur at any age, but becomes more common as we get older. Plus, different forms of heart failure affect men and women differently and require different treatments.

Efforts like the Living Heart Project are long overdue, survival rates for heart failure patients have not improved since the 1990s. Despite a half-century of research funding and countless rodent experiments, translation of animal data to people has been poor to non-existent. Not surprising perhaps, considering the differences in size and development, heart rates, oxygen consumption, contractility, protein expression, and stem cell populations between humans and rodents. Calls for ‘improved animal models’ for human heart disease favored larger animals – such as dogs – due to closer resemblance of cardiac physiology between dogs and humans (compared to rats and humans). Experimental induction of heart failure in the young, healthy dogs employed as models is severe – often requiring complex, extensive surgery – and distressing. In addition to these ethical concerns, there are scientific reasons to move away from canine models of heart failure – the collateral coronary circulation in dogs creates inconsistency and heterogeneity in the response to myocardial lesions which make comparison of post-injury outcomes difficult. [Read more…]