Posted: 19 November 2009. Updated: 8 December 2009
TH: I would characterize it as two sides of the same coin: both institutions have been promoting alternative methods for many years. ECVAM is giving scientific policy support especially to the European Commission and in addition is responsible for the formal validation of methods; CAAT has, for 28 years, provided a key information hub sponsored by private foundations and industry. CAAT does not work primarily on validation. As part of Johns Hopkins, one of the leading universities in the world, CAAT is primarily bound to sound science and more broadly to humane science approaches and the paradigm shift in toxicology. I would like to develop it further as a think tank of toxicology. Last but not least, education of students is one key role of any academic institution and we try to promote humane science in various curricula.
NAVS: What motivates you to be involved in the development of alternatives to animal testing?
TH: I want to progress the science of risk assessment and make it more humane, so that it is about the safety of patients and consumers AND animal welfare. I believe that alternative methods are forerunners for the revolution in risk assessment sciences ahead of us. They are the pilots for a new toxicology and for quality assurance in the life sciences in general. There is no other field, where the same effort is spent to ascertain the predictive value of models and to quality control them. That’s where science has to move – we are publishing far too much, which is not reproducible, not relevant or simply artefact.
NAVS: A growing number of alternatives are being validated and developed, and yet the number of animals used in experiments keeps rising, including in Europe. How do you explain this paradox, and how, according to you, can we significantly reduce the number of animals used?
TH: Regulatory testing makes up about 25% of all animal use in Europe (roughly 10% toxicology and 15% vaccine control). In these areas numbers continue to go down, but new programs such as REACH will reverse this soon, because even using less animals per substances, we are simply increasing the number of substances studied. Nanotechnologies, genetically modified organisms and cellular therapies, to name just a few, will add to this. However, the other 75% of animal use, which is mainly fundamental research and medical agent discovery also tend to use more animals . This is mainly because of the steadily increasing use of genetically modified mice.
NAVS: What barriers, do you think, prevent researchers in academia and working in pharmaceutical companies from using alternatives as opposed to animals?
TH: There are a few: Traditions, regulatory requirements, lack of information on opportunities. However, there is also pressure for change from quarters such as the biotech and informatics revolution, which provided new tools, the companies commercialising these, legislative pressures such as the European animal welfare legislation, REACH and the 7th amendment of the cosmetics directive. Furthermore, the need for higher testing throughput and increasing awareness of the shortcomings of current animal tests help a lot.
NAVS: Can you tell us about some of the current alternatives being developed with support from CAAT and which animal tests they replace?
TH: CAAT is really a catalyst for work rather than a developer on its own – in fact, only recently we created a laboratory, which is devoted to developmental neurotoxicity (DNT). This area is of special interest, as only recently an OECD test guideline for an animal test costing up to 1.4 million Euro per substance was completed. DNT is also critical as it is one of two modules for the extended one-generation reproductive toxicity study, a critical replacement for the two-generation study, which represents the bottleneck for REACH. However, over 28 years with many workshops and a funding program CAAT has initiated many activities towards new alternatives. Again DNT has been a focus of funding recently, but all areas have been covered to different degrees over the years.
NAVS:What are the advantages of using non-animal methods in toxicology?
TH: Simply, to overcome the limitations of animal testing, and these are not only ethical ones: Animal tests are costly, have a low throughput and often give the wrong results. Some of the tests were developed 40-80 years ago, especially in regulatory toxicology. In the meantime a whole new body of knowledge has been built on mechanisms, molecular targets and modes of action. This must be fully exploited before targeted, hypothesis-driven testing in animals starts, if this is even necessary.
NAVS: Do you think there will be a time when animal testing will not be a legal requirement in the regulatory testing of drugs?
TH: Yes – We have seen already that we are harming the drug development process with wrong decisions. “Killing” valuable substances under development also kills people. Furthermore, more than half of new drugs are human proteins, or antibodies to human proteins, making classical approaches useless. If we can show that we can handle these properly without animal testing, why shouldn’t we do the same for small molecules? We have now the forerunner of industrial chemicals – if we succeed in changing our approach here, this will have percussions to the drug safety area, where money and throughput are less of a concern.
NAVS: Do you believe that the use of primates in experiments can be replaced, and if yes, how?
TH: By moving to human testing this will bypass non-human primates, for example by microdosing. This certainly requires another level of certainty in the non-animal methods and non-primate models. The trend to use human proteins is certainly prompting a lot of primate use. However, the tragedy of the Tegenero antibody, (TGN1412) which had no effect in primates at doses 500times higher than in man and almost killed instantly the first six human volunteers treated, has shown that this testing has questionable results.
NAVS: Do you regard the new Directive on animal testing, as drafted by the European Commission, as a good text to regulate animal testing and promote alternatives?
TH: Europe has had the most progressive legislation for animal welfare in the world since 1986. The new draft is moving this even further, exactly how far, will be determined by the political decision process. It will certainly raise the standards further but also leave room for improvement for the next revision.
NAVS:Would you agree with the statement that the use of animals in experiments is a scientific dogma that must be challenged?
TH: I do not consider it a dogma – something believed to be true without question. Instead I consider it a tool with increasingly acknowledged limitations. The more we make these limitations obvious and develop other tools, the less useful and used the animal tools will become.
For information about the new Directive for the protection of animals used for scientific purposes, proposed to replace EC Directive 86/609/EC, click here.
To read about NAVS’s policy on scientific research and animal testing, click here.