Our article, written with Center for Responsible Science and published in ATLA, identifies some of the reasons for the glacial uptake of new, improved methods of safety assessment, and suggests ways forward, such as:
"...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."
Everyone understands that failing to update computer software leads to serious damage to computers. Yet we allow outdated protections for human health to go unfixed for decades. Is it any wonder that adverse drug reactions are now our fourth leading cause of death?
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.
At the International Conference of Alternatives to Animal Experimentation in Portugal, on 8th May 2015, Dr Philip Low presented - to unanimous support - the 'Declaration of Lisbon':
''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."
Dr Robert A. Coleman
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."
Our latest newsletter shows how close we are to reaching a tipping point, with science shifting inexorably towards human-focused research to deliver advances in medicine and more reliable safety tests.
Our mission is to accelerate this transition. Our comparative studies are designed to hasten this long-awaited shift. We have reached an exciting point, with partners ready to conduct our studies: the one thing we need now is funding, to get these studies underway.
Please help us if you can: the sooner we can demonstrate the superiority of human-based tests, the sooner they will be used routinely, in place of animal tests, to improve the safety of medicines.
Whatever you can afford to give will be extremely valuable and greatly appreciated - thank you!
AltTox.org is a project designed to provide timely information on scientific, technical, and regulatory aspects of non-animal toxicity testing methods. We were delighted to be invited to contribute a 'Way Forward' article, outlining the comparative studies that we are initiating, which is available here.
We are deeply honoured and proud that Tony Benn was our Patron for 9 years. He was a passionate advocate for Safer Medicines' belief that medicine should focus on humans rather than animals. His support for us included hosting the launch of our film in the House of Commons in 2007 and presenting our petition to 10 Downing Street in 2011 (pictured here with Caroline Lucas MP). He leaves an enduring legacy of inspiration and encouragement to change the world for the better, the aim to which he devoted his life.
FRAME has recently published an analysis of the value of studies in dogs for predicting the safety of human medicines. The salient feature of this study is the use of appropriate statistical metrics, which have not previously been applied to such data. The results shine a new light on our reliance on dogs for this purpose, suggesting that they contribute little or nothing to ensuring our safety. Read the paper or watch the presentation by lead author Dr Jarrod Bailey.
We look forward to working with FRAME and OpenTox on a new study to assess the value of human in vitro approaches to predict the safety of medicines. Data will kindly be provided by the US Government ToxCast programme, part of the Tox21 initiative, and by the US National Center for Toxicological Research. The study will measure the ability of human in vitro tests to predict drug-induced liver injury (DILI) against the ability of animal tests to do so.
We are thrilled to be working with the excellent EU-funded OpenTox project. OpenTox is working to support predictive toxicology, using a variety of human-relevant approaches, to meet the requirements of the REACH legislation and other global toxicological demands.
On 30 October, our US Science Director, Dr Katya Tsaioun, is speaking at the OpenTox USA InterAction meeting on Innovation in Predictive Toxicology. She will also present a poster outlining our groundbreaking proposal to compare the relative abilities of animal tests and human-based in vitro tests to predict the safety of medicines.
Dr Bob Coleman gave a presentation at the University of Linz, Austria on 17 September, entitled: "Humanising Toxicity Testing in the 21st Century".
In November, he spoke at the American College of Toxicology annual meeting in San Antonio, Texas, on the subject: "Ensuring Safety and Efficacy in New Medicines – Humanizing the Process" - view here
These are tremendous opportunities to communicate with many of the world's leading toxicologists, with the potential to initiate real changes to the mindset and practice of toxicology worldwide.
Our US Science Director, Dr Katya Tsaioun, has been selected to serve as a member of the Center for Scientific Review for the US National Institutes of Health. This immensely prestigious appointment is in recognition of Katya's expertise and achievements, and will make a valuable contribution to medical research in the field of drug discovery for the nervous system. Katya is a highly-regarded expert on in vitro methods in drug development and is the founder of Apredica and Pharma Launcher.
A further great honour for us is that Katya will be presenting a poster at the prestigious Gordon Research Conference on Cellular & Molecular Mechanisms of Toxicity from August 11-16. The poster will outline Safer Medicines Trust's groundbreaking proposal to compare the relative abilities of animal tests and human-based in vitro tests to predict the safety of medicines.
Dr Elias Zerhouni, Director of the National Institutes of Health (NIH: the world's largest supporter of medical research) from 2002-2008, laments that researchers have over-relied on animal data, saying:
“The problem is that it hasn’t worked, and it’s time we stopped dancing around the problem…We need to refocus and adapt new methodologies for use in humans to understand disease biology in humans.”
Dr Francis Collins, current NIH Director, has frequently criticised animal testing for being expensive, time consuming and unreliable. He says:
"With earlier and more rigorous target validation in human tissues, it may be justifiable to skip the animal model assessment of efficacy altogether."