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…]

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…]

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…]

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…]

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…]

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…]

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…]

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…]

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…]

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…]

18 January 2019

Organ-on-Chip in Development (ORCHID) is a European Horizon 2020 project that aims to capitalise on the innovative technology that is organ-on-chip, or OoC. The ORCHID consortium is made up of seven partners from six European countries and was launched in 2017 with the overall aim of building a network of OoC stakeholders, including academic, research, industrial and regulatory institutions, in order to move OoCs from laboratories to a more global awareness and utility.

We are in the midst of a ‘drugs drought‘, which means there could be no more new, approved compounds by around 2070 unless we radically alter the current drug discovery paradigm. Using animals as models of human disease for predicting safety and efficacy of novel drugs has proven to be time consuming, costly and about as effective as tossing a coin—with failure rates running as high as 99.6 % for some conditions.  While the reasons underpinning the failure of new chemical entities to reach the clinic, and successfully remain there, are complex and multi-factorial, there is no doubt that one of the greatest limitations for identifying new therapeutics for human diseases is the deficiencies in the animals employed/manipulated as models of the human condition.  [Read more…]