As more and more researchers point to the inadequacy of using animal models to study human conditions, Australia’s National Health and Medical Research Council (NHMRC) – the major funder of biomedical research – still does not seem to make any moves towards encouraging more human-relevant research.
The NHMRC’s Corporate Plan 2018-2019 has just been published. From the NHMRC website:
The NHMRC Corporate Plan 2018–2019 covers the period 2018–19 to 2021–22. It identifies the major health issues for this period, how we will deal with these issues and a strategy for medical research and public health research, in line with the requirements of the NHMRC Act. It also describes NHMRC’s purposes, planned activities and performance measures for the period and addresses our capability, environment and risk oversight and management.
The Plan does not touch on the transition from outdated animal research to human-relevant research. While “advances in technology” and “engagement with industry and support of innovation” are mentioned in the section on “NHMRC’s environment”, the strategy to dealing with this “risk” is limited to “timely and effective leveraging of advanced technology to reduce the burden on applicants and assessors and enable reporting on the return on investment in health and medical research.”
Animal studies do not predict adequately what will happen in humans. Many research “breakthroughs” observed in animals do not translate to clinical trials with humans and into medical practice. However, this is not acknowledged in the Plan, which includes a section on research translation. (The NHMRC does fund several research and translation centres)
The value of animal experiments for predicting the effectiveness of treatment strategies in clinical trials has remained controversial, mainly because of a recurrent failure of interventions apparently promising in animal models to translate to the clinic. (van der Worp et al., 2010)
Following target discovery, as much as 90% of novel medications fail to make their way through the different phases of clinical trial to approval. The majority fail to pass at phase II – the transition through proof of concept to large scale trial at Phase III (Cook et al., 2014; Perrin, 2014; DiMasi et al., 2016). Many critics attribute this high rate of attrition to the models on which the targets are discovered – usually laboratory rodents; the argument being that the differences between animal models and human disease are too great to be able to draw valid conclusions between them. In other words, targets derived from animal models are not suitable for use in clinical populations, and hence fail at trial. (Perry & Lawrence 2017)
The lack of leadership is disappointing. Other countries’ government agencies are more proactive. For example:
- A review of the implementation of the European Union Directive 2010/63/EU on the protection of animals used for scientific purposes noted that “many Member States have increased their activities in promoting alternatives, e.g., increasing research funding, voluntary development of Three Rs centres, supporting educational events and other information dissemination efforts. Half of the Member States have submitted voluntary reports detailing the actions taken towards the development, validation and promotion of alternative methods”. (more here)
- The Brussels-Capital Region in Belgium recently announced a ban on experiments on dogs, cats and non-human primates. (more here)
- The Netherlands’ National Committee for the Protection of Animals Used for Scientific Purposes (NCad) has provided a schedule for the phasing out of animal procedures for research on the safety of chemicals by 2025. (more here)
- The National Institutes of Health in the U.S. have a “Roadmap to guide progress toward replacing animal use in toxicity testing” that encourages the use of new non-animal methods and technologies such as high-throughput screening, tissue chips and computational models. (more here)
- Last month, the United States Environmental Protection Agency announced funding of $4.25 million for “Advancing actionable alternatives to vertebrate animal testing for chemical safety assessment”.
- In 2012, the U.S. federal Defense Advanced Research Projects Agency (DARPA), the National Institutes of Health and the FDA provided a grant of $37 million towards creating 10 different human organs-on-chips.
- In 2016, the U.S. National Center for Advancing Translational Sciences announced $13.5 million in grants to create models of human disease using tissue chip technology for testing the effectiveness of new drugs.
- The European Commission is contributing to a range of projects that aim to replace the use of animals in research, for example Building a 3D innervated and irrigated muscle on a chip (EUR 1.26 million), 3D bioprinting of pancreatic tissue for biomedical research (EUR 788,865), Chromatin organization PROfiling with high-throughput super-resolution microscopy on a CHIP (EUR 601,250), Genetically engineered human pluripotent stem cells, functionalized silk-fibroin platforms and bio-inks: a novel solution for large-scale ex-vivo platelet production, transfusion and drug research (EUR 738,327).
Indeed, in the past few years, a substantial number of research grants have been invested in organ-on-a-chip projects from the National Institute of Health (NIH), the Food and Drug Administration (FDA), and the Defense Advanced Research Projects Agency (DARPA) in the USA, from Framework Program 7 (FP7) in the EU, and from Japan Agency for Medical Research and Development (AMED) in Japan. This investment also shows the magnitude of expectations for research related to organ-on-a-chip technology. (Kimura, 2018)
It’s disappointing that we are not pulling our weight in contributing to innovative biomedical research, that Australia is lagging behind comparable countries. It’s disappointing that a good proportion of public funds are wasted on ineffective research. It’s disappointing that, as a consequence, patients are not seeing the treatments and cures that are missed because our scientists study the wrong species. Actually, the latter is more than disappointing. It’s infuriating.