When many people think about animal testing, they imagine rows of rodent cages in a pharmaceutical company lab. But according to data from European Union countries, the pharmaceutical sector uses almost half the number of animals that academic labs do, and animal use in drug development dropped significantly between 2005 and 2008 – the most recent statistics available. There are two reasons for this, says Thomas Hartung, Director of the Center for Alternatives to Animal Testing at Johns Hopkins University, in Baltimore, Maryland. First, drugs are increasingly designed to target specific molecular mechanisms, and these are best identified in culture dishes rather than live animals. Second, conducting experiments in 1,536-well cell culture dishes is vastly less expensive than in animals, so companies are motivated to use alternatives whenever they are available.
In the US and the EU, a drug’s efficacy and safety must be tested in animals before it enters human testing, though a 2010 directive from the EU calls for alternatives to be used when possible. Jan Ottesen, vice president of lab animal science at Danish company Novo Nordisk, which makes insulin and other drugs for diabetes and haemophilia, says his company actively seeks out tests that can replace animal use without compromising patient safety. Novo Nordisk decided 15 years ago to replace animal tests with cell cultures to verify the quality of each batch of drugs before it goes to market. The company had to provide the authorities with data proving that other tests worked just as well. It took until 2011 for the company to complete the switch.
However, for some types of experiments there are no equivalent non-animal options, says Ottesen. For example, in searching for new drugs that decrease joint pain due to arthritis, you need a model that mimics the human condition. The important thing, he stressed, is to set up the experiment so as to avoid unnecessary pain. For safety and toxicological testing of drugs, he adds, “I cannot see for the foreseeable future how we can completely avoid it. Having said that, all the replacements that can be implemented should be implemented."
Safety testing of substances other than human and veterinary drugs, such as cosmetics, toiletries, household cleaning products and industrial chemicals might be a different story. Currently, says Hartung, such tests are outdated and inaccurate, with toxicity in rodents predicting problems in humans just 43% of the time. Meanwhile, tens of thousands of these substances have undergone no toxicity testing at all.
Addressing this gap with animal studies alone would be expensive and impractical. An overhaul of chemical safety regulations in the EU called REACH and a toxicology modernisation initiative led by the US National Institutes of Health, are driving the search for alternatives.
Hartung believes that with enough investment and coordination, animal tests on products in this category can be replaced completely. He is leading the Human Toxome Project, an initiative that aims to map the ways substances disrupt hormones and endanger health, as well as to develop advanced, non-animal lab tests for toxicity testing. It’s slow going, Hartung concedes. “We don’t have human data to compare with, or really high-quality animal data,” he says, adding that this makes it tough to evaluate the quality of the tests.
Meanwhile, almost four in ten animals are used in basic, as opposed to applied, biological research – and this proportion is growing. Sarah Wolfensohn, a veterinary surgeon who heads Seventeen Eighty Nine, a consultancy advising researchers on animal welfare, based in Swindon, UK, says this is in part because a lot of this type of work is carried out in academia where the financial and performance pressures that motivate interest in non-animal-based techniques are weaker than in the commercial sector.