Prof. Jos Kleinjans Prof. Jos Kleinjans Harry Heuts

Alternatives to animal testing

Written by  Patrick Marx Wednesday, 20 January 2016 14:37

Jos Kleinjans is, much to his own frustration, regarded as someone who lands grants by the dozen. The professor of Environmental Health Science is working to develop better, animal-free methods to test the toxicity of chemical substances such as medicines and cosmetics. He’s pessimistic about the prospects for rapid legal approval of his animal-friendly, toxicogenomic alternatives: “I won’t be around to see it happen.”  

      

His office is big but bare: a low cupboard, two tables and a couple of chairs. On his desk is nothing but a lamp, a phone and a laptop. Kleinjans points at the laptop: “Everything’s in there.” That, apparently, is all it takes to lead a group of 35 toxicogenomics researchers.

DNA 

The relatively new field of toxicogenomics is shaking up traditional toxicology. Kleinjans and his colleagues are homing in on how chemicals influence the functioning of cells. “We’re studying the harmful effects of chemicals on the structure and functioning of DNA”, he explains. The genetic code in DNA controls not only the construction of cells, but also the everyday functioning of those cells. Chemicals can change that genetic code as well as the regulatory function of DNA. “For example, we can see if a chemical substance prompts DNA to produce unwanted proteins or to decrease the production of useful proteins. Toxicogenomics provides much more information than traditional testing methods, which simply count how many cultured cells are killed off by a chemical substance.”

Thanks to this wealth of information, the results of Kleinjans’s research surpass those of animal research. “Animal research is of limited value when it comes to predicting effects in humans. A substance that seems perfectly safe during animal research might not be safe for humans, or vice versa. This can cause problems in pharmaceutical research: a drug that passes animal testing could have severe side effects in humans, and then you’re back at square one.”

Kleinjans uses toxicogenomics to analyse the effects of chemicals on cultured human cells. One tangible outcome is a test for predicting contact allergies that is reliable in 85% to 90% of cases. Recently, Kleinjans and a number of colleagues founded the company ToxGenSolutions to market their testing methods. “Our main goal is to persuade the pharmaceutical industry that they’d be better off using our test in their toxicological research.”

Sluggish

Toxicogenomic tests may be on the rise, but that is not to say animal research will soon be a thing of the past. “The use of animals in toxicological research on chemicals, including medicines, is deeply embedded in the law”, Kleinjans explains. “And legislation changes so slowly that the word ‘sluggish’ is an understatement. I don’t think I’ll be around to see it happen. Look at TNO’s animal-friendly alternative to eye irritation tests on rabbits – it took 20 years to get approval from the international regulatory bodies.” The Kafkaesque maze of rules and regulations further fuel his pessimism. “Animal testing for cosmetics has been banned in the EU since 2013. Yet the legal requirement to test new cosmetic products on animals is still in place.”

The EU aims to speed up the pace of innovation by investing €30 million in EuToxRisk, a consortium led by Leiden University. “The technology and knowledge are developing so quickly that many researchers, us included, want to start using new techniques and insights before a validated end product becomes available”, Kleinjans says. Ideally, EuToxRisk will ensure that research on animal-friendly toxicogenomic tests that map the harmful effects of substances on the liver, heart, kidneys, nerves and foetuses can be put into practice as soon as possible. Of the total investment, €1.5 million will go to research in Maastricht.    

Funding

Between European and national funding, Kleinjans has received tens of millions of euros for the research he carries out in collaboration with international partners. De Volkskrant ranked him third on a list of researchers who have landed the most grant money in the Netherlands. “I wasn’t particularly happy with their reporting. It gives the impression that I can just rustle up funding left and right. That certainly isn’t the case. I have to write research proposals and take part in the competition just like the rest of my colleagues. Sometimes I hear people complain that funding always ends up in the same place, which makes me wonder if they’ve written as many project proposals as we have. Writing proposals is simply part of my job; it gives me the chance to immerse myself in the complexity of a topic. I have a warehouse full of ideas in my mind. Whenever I see an opportunity for a project proposal, I walk into my virtual warehouse and gather up ideas to work into a proposal with partners. Of course I don’t always hit the mark.”

What undoubtedly helps him land funding is his good reputation in the world of toxicology. Kleinjans is, after all, among the best in the world. “That’s a sensitive topic,” he says when prompted, scratching his head in contemplation. “But considering the scope of our activities and grants and the quality of our publications, I do think that might be the case.”

Jos Kleinjans (1954) studied biology in Nijmegen and has worked at Maastricht University since starting his PhD in 1979. He was appointed professor of Environmental Health Science and head of the Department of Health Risk Analysis and Toxicology in 1991. In 2011, he became head of the newly established Department of Toxicogenomics. He also served as director of the Netherlands Toxicogenomics Centre.

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