The harm-benefit analysis is a cornerstone of animal research regulation in the EU and elsewhere. When applications for research projects involving animals are submitted for licensing the regulators weigh up the harms that animals are expected to suffer against the anticipated benefits of that research to humans.
Researchers at the University of Bristol reviewed a sample of animal research studies from 1967 to 2005. All the studies were judged to be of poor quality and most involved severe harms to animals. When the harms to animals were weighed against the benefits to humans less than 7% of the studies were judged to be permissible in terms of minimising harms to animals whilst being associated with benefits for humans.
Dr Pandora Pound, who led the research, says, “The regulatory systems in place when these studies were conducted failed to safeguard animals from severe suffering or to ensure that only beneficial, scientifically rigorous research was conducted.” The research is published in PLOS ONE
Excerpt: Animals are used in biomedical research to study disease, develop new medicines, and test them for safety… A revolution in science and technology has produced a new generation of more relevant and predictive tools, which could be used to create safer medicines more quickly and at less cost: a win-win situation that should be supported by everyone. The obstacle preventing this from happening is governments’ continued insistence on animal testing. Yet the evidence is clear that reliance on animals as surrogate humans puts patients at risk, can delay medical progress, and can cause effective treatments to be wrongly discarded. There is a compelling case to be made that animal research is an ethical issue for humans as well as for animals.
A report was published in January by the Medicines Discovery Catapult and the BioIndustry Association, entitled: State of the Discovery Nation 2018. Based on surveys and in-depth interviews with more than 100 senior executives of drug discovery companies, the report offers a blueprint for successful pharmaceutical research, where patients and human data are placed at the heart of drug discovery. The current research process depends on animal models of disease and toxicology that are “poor approximations of humans”; consequently 40 per cent of new drugs fail when first tried in real patients. The rate at which new drugs are launched per $1bn spent on pharma R&D is one-30th of the level 40 years ago but “humanising” the early stages of research would ease the “productivity crisis” in pharmaceutical research.
“Discovery must start with biological targets derived from patient data and samples, which create candidate drugs that are highly selective for proven human disease targets in well-defined patient subgroups, not animal models,” said Chris Molloy, chief executive of the Medicines Discovery Catapult, quoted in the Financial Times.
Dr Azra Raza, Professor of Medicine at Columbia University in New York, and Science Adviser to Safer Medicines Trust, gives a fascinating one-hour interview on the human imperative in cancer research in this highly informative podcast. In 2014, Professor Raza gave a powerful and moving 13-minute TEDx Talk on the same theme, which you can view on YouTube.
Abbreviated abstract: Animal toxicity studies used to assess the safety of new candidate pharmaceuticals prior to their progression into human clinical trials are unable to assess the risk of non-pharmacologically mediated idiosyncratic adverse drug reactions (ADRs), the most frequent of which are drug-induced liver injury and cardiotoxicity… The chemical insults can be detected using in vitro assays. These enable useful discrimination between drugs that cause high versus low levels of idiosyncratic ADR concern… Widespread acceptance and use of such assays has been hampered by the lack of correlation between idiosyncratic human ADR risk and toxicities observed in vivo in animals.
Sir David Amess MP hosted the launch event, which was full to capacity with senior scientists and MPs whose enthusiasm and support were palpable.
Working together, the Alliance will help to speed the transition away from animal testing, towards more efficient and predictive models based on human biology. Many breakthroughs are lost in translation from animals to humans. There is now a tremendous opportunity to make drug development faster and safer, using human relevant technologies. Some exciting technologies were highlighted at the meeting, including cutting-edge models of the liver, linked together with other organs to realistically mimic the human body.
Sir David said: “Britain is a world leader in life science research. But we had better look to our laurels if we do not want to be left behind, while others take the lead in embracing more predictive tools based on human biology. I wish the new Alliance every success with this hugely important initiative.”
We are delighted to welcome Rebecca Ram, MSc as our new Scientific Consultant. Rebecca is also a Scientific Consultant to the Lush Prize team at the Ethical Consumer Research Association. She holds an MSc in Toxicology with Bioinformatics and has worked as a Clinical Data Manager at University College London Hospital, and in pharmaceutical clinical trials for GlaxoSmithKline. She was a Project Manager of cancer clinical trials and whole genome sequencing for Genomics England, as part of the 100,000 Genomes Project. In addition to her role with Safer Medicines Trust, she is also the Communications Officer for the Alliance for Human Relevant Science.
Dods conducted an online survey of 2,512 UK health and care professionals in March 2016.
They were asked one question about their perception of pharmaceutical testing regulations on behalf of Safer Medicines Trust.
The overwhelming majority of health professionals (79 per cent) agree that pharmaceutical companies should be legally obliged to test new medicines using methods demonstrated to be the most predictive of safety for humans.
Just three per cent of health professionals disagreed that pharmaceutical companies should be legally obliged to test new medicines using methods demonstrated to be the most predictive of safety for humans.
We are delighted to welcome Dr Gerry Kenna to Safer Medicines Trust, and look forward to him continuing to innovate and forge a route to improved safety of medicines, through human-relevant methods.
Dr Gerry Kenna is a Drug Safety Consultant and a leading figure in the field of human drug induced liver injury. Following his initial scientific training in biochemistry, at the Universities of Leeds (BSc Hons) and London (PhD), Dr Kenna established and led academic research teams which, for 19 years, studied the mechanisms by which medicines and other chemicals may damage cells of the liver. He then moved to industry (at Zeneca, Syngenta and AstraZeneca), where for 14 years he used his expertise to support human safety assessment of new medicines and agrochemicals. During this time, he also led research teams which developed improved human safety testing methods. These used human tissues and did not require use of animals. Dr Kenna is committed to ensuring that such human-relevant approaches are used routinely, by scientists in industry and in regulatory agencies, to aid the invention and development of safe new medicines.
Safer Medicines Trust is delighted to announce the appointment of Professor Barbara Pierscionek, PhD, MBA, LLM as our Scientific Director and Professor Chris Foster, MD, PhD, DSC, FRCPath as our Medical Director. They are both distinguished experts in human-focused biomedical research, who will lead the charity towards our goal of improving the safety of medicines and the future of biomedical research, by accelerating the paradigm shift from animal-based to human-relevant models.
Professor Pierscionek is Associate Dean of Research and Enterprise at Kingston University’s Faculty of Science, Engineering and Computing. She qualified with clinical and scientific degrees (PhD in protein chemistry and optics) from the University of Melbourne and obtained an MBA and legal qualifications in the UK including the theoretical degree required for practice as a solicitor in England and Wales as well as a Masters degree in Law (LLM). Her scientific expertise is in the area of eye and vision research. She is a pioneer of multidisciplinary approaches leading to new insights into the vision and the ageing eye that have potential to improve outcomes for cataract patients in the design of new intraocular implants. She also works on the ethico-legal aspects of medical and biomedical research.
Professor Foster is the Medical Director of HCA Healthcare Laboratories, London, and Emeritus Professor of Pathology at the University of Liverpool. He is a leading specialist in the pathology of human cancers, particularly of the prostate, bladder and breast. Professor Foster received his BSc in Biochemistry at University College London and qualified in Medicine at the Westminster Medical School. He received his PhD from the Institute of Cancer Research and his MD at the Children’s Hospital of Philadelphia and the National Institutes of Health, Washington DC. In 2002, Professor Foster was awarded a DSc for his contribution to understanding “The Cellular and Molecular Biology of the Metastatic Process”.
Both professors have been Scientific Advisers to Safer Medicines Trust for several years and we are delighted that they are now taking on these leading roles. We welcome them both very warmly and look forward to them helping to lead the transition from animal models to human-relevant models.
“…validation needs to become relative, rather than absolute. If a new test, or tests, can be shown to outperform what is currently required, that alone should suffice to ensure the continual and incremental replacement of underperforming tests with better ones, even if they are not yet perfect themselves. Unless this system of gradual improvement (which operates in almost every other sphere of endeavour) is adopted, the perfect will remain forever the enemy of the good.”
“Perhaps the greatest barrier to the replacement of animal tests is the legal protection that they afford to pharmaceutical companies in litigation regarding adverse drug reactions. It is therefore imperative to increase awareness of the fallacy of such protection: unpredictive tests do not protect patients, and should no longer protect companies who continue to use them, when more-predictive methods not reliant on interspecies extrapolation are available.”
Editor in Chief of the Turkish Journal of Gastroenterology, Professor Hakan Sentürk, challenges other scientific journals to follow his lead and avoid publishing animal research, saying:
“Given the limitations of animal models, publishing animal studies would mislead the scientific community into futile research and give the general public false hope. This is unethical.”
He says: “Human-relevant approaches should be more aggressively developed and utilized instead. Fortunately, non-animal research methods like established clinical, computational and in vitro models abound, and new technologies like guts and other organs-on-chips are constantly being developed and validated.”
Safer Medicines Trust, as part of a coalition led by US charity Center for Responsible Science, has filed a Citizen Petition asking the FDA to update preclinical testing requirements, so as to ensure safer and more effective medical products are available to patients.
”While recognizing that animal testing has long been a traditional component of biomedical research, it has become clearly apparent that the returns on investment in animal research are increasingly meager. To the extent that this type of research may continue, it is our recommendation that it be carried out after giving institutional committees, independent expert third party animal ethics committees, funding organizations and relevant regulatory authorities evaluating the proposed research (collectively ‘The Parties’) a more realistic and evidence-based estimate of the likely costs and benefits of the proposed protocols.” – view the declaration in full
Dr Bob Coleman, UK Science Director of Safer Medicines Trust, also spoke at the Conference on ‘Humanising Drug Safety Testing’ – view his presentation
A report by the Oxford Centre for Animal Ethics, supported by more than 150 leading academics and intellectuals, including Nobel Laureate J. M. Coetzee, concludes that animal experimentation is “one of the major moral issues of our time”. Safer Medicines would add that it is also a major moral issue for patients and all of us affected by biomedical research; i.e. all of us.
It is worth examining what the various political parties have pledged with respect to this issue in their 2015 election manifestos.
The Conservatives say they will: “work to accelerate the global development and take-up of alternatives to animal testing where appropriate.”
Labour does not mention the issue at all in their manifesto.
The Liberal Democrats say they will: “minimise the use of animals in scientific experimentation, including by funding research into alternatives. We remain committed to the three Rs of humane animal research: Replace, Reduce, Refine.”
The Green Party make clear commitments towards ending all animal experimentation, saying they would take immediate action to: “Introduce a comprehensive system for reviewing animal experiments and initiate a comparison of currently required animal tests with a set of human-biology based tests.”
UKIP say they will: “Challenge companies using animals for testing drugs or other medical treatments on the necessity for this form of testing, as opposed to the use of alternative technology.”
Of course, actually delivering on these pledges is another matter. The current coalition Government pledged in 2010 to “work to reduce the use of animals in scientific research”. Yet the number of animal experiments is now at its highest level since the current recording system began. The recently published Delivery Report shows that this Government made little attempt to honour its pledge, preferring instead to focus on efforts to communicate the importance of animal research to the public.
Let us hope that the next government will take the issue as seriously as it deserves.
“With growing evidence of the shortcomings of laboratory animal testing to reliably predict human responsiveness to chemicals, questions are now being asked as to whether it is appropriate to use animals as human surrogates at all.”
ATLA is FRAME’s peer-reviewed scientific journal, published six times a year
A landmark study published on 28 July reveals how animal tests create a false sense of security, putting patients at risk.
The Observer published our letter, signed by many expert scientists, commenting on the study and urging governments to replace animal-testing requirements with an obligation to use the most reliably proved methods available.
The Sunday Times also published our (different) letter, which began: “We hope the exciting technology mentioned in your article will become mainstream within three years as predicted. Meanwhile, other human-based technologies are already available that could be improving patient safety here and now. The impediment is not science but political will.”