Human-based Systems in Drug and Chemical Safety Testing - Toward Replacement, the 'Single R'
"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!
Our 'Way Forward' article posted on AltTox website
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.
Tony Benn 1925-2014
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.
Safer Medicines Trust collaborating with FRAME
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.
Safer Medicines Trust collaborating with OpenTox
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.
Honours for our US Science Director, Dr Katya Tsaioun
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.
Recognition at the highest levels in USA
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."
Human tissues vital for testing medicines
A new paper published by Expert Opinion on Drug Metabolism & Toxicology:
"Advances in the development and use of human tissue-based techniques for drug toxicity testing"
• Human tissues have a vital role to play in drug toxicity evaluation.
• For many toxicity issues, the reliability of animal models is so poor that the greater relevance of human tissues offers invaluable advantages.
Mice Fall Short as Test Subjects:
"For decades, mice have been the species of choice in the study of human diseases. But now, researchers report evidence that the mouse model has been totally misleading for at least three major killers - sepsis, burns and trauma. As a result, years and billions of dollars have been wasted following false leads, they say."
"They are so ingrained in trying to cure mice that they forget we are trying to cure humans."
"It argues strongly - go to the patients. Get their cells. Get their tissues whenever you can."
In an editorial entitled: "Of men, not mice", the journal Nature Medicine commented:
"Although the message that mice are an imperfect model for human disease is far from new, these recent results should prompt some soul-searching among disease researchers… Rather than overrelying on animal models to understand what happens in humans, isn't it time to embrace the human 'model' to move forward?"
New Scientist 15 December: “How human biology can prevent drug deaths”
“It is a tragedy that so many suffer or die through the use of inadequately tested drugs when tests based on human biology are readily available. Yet governments continue to mandate animal tests, despite the lack of a formal demonstration of fitness for purpose, and a growing global realisation among scientists that animal toxicity tests are inadequate and must be replaced.” See more...
The Government is in denial
The UK medicines regulator, the MHRA (Medicines and Healthcare products Regulatory Agency) appears to be out of step with global scientific opinion that better methods are needed to improve the safety of new medicines. Although current methods include computer models and in vitro tests, they rely mainly on tests in animals.
Despite global calls to modernise safety testing, the MHRA insists that animal tests are irreplaceable and is extraordinarily dismissive of two of the most exciting breakthroughs: microdosing and ‘body on chip’ devices, saying that they are “not superior technologies”.
Please write to them – see more...
MPs back our campaign above 99% of all parliamentary motions
With 160 MP signatures, our Early Day Motion (EDM 475) calling for safer medicines was among the most-signed 1% of over 3,000 EDMs in the 2010-12 session of parliament.
This was the 3rd time our EDM had been in the top 1% – previous motions in 2005-06 and 2008-09 attracted 250 and 243 signatures, respectively. Clearly, there is phenomenal parliamentary support for the modernisation of drug safety testing that we are calling for.
Thank you so much to all of you who contacted your MPs – you really made a difference.