The Power of Positive Testing

Thomas Hartung has taken leadership of the Center for Alternatives to Animal Testing (CAAT) at an interesting time. Thirty years ago, finding alternatives to animal testing was still a fringe idea. Its foundational concept called the 3Rs—reduce the use of animals, refine experiments to minimize distress and pain, and replace animals with alternative techniques—was just beginning to find an audience. Today, alternatives are widely accepted. Fewer animals are now required for regulatory tests, which examine the safety of a product or chemical for human use and which account for the vast majority of animal tests. But CAAT still faces skepticism from industry experts and regulators, as well as animal rights activists. The Center is now working internationally to speed the shift from decades-old animal tests to the use of “modern science to evaluate modern products.” Hartung, MD, PhD, who replaced CAAT’s founding director, Alan Goldberg, in March, recently shared insights about his field and the challenges ahead with Johns Hopkins Public Health editor Brian W. Simpson.

What does animal testing actually mean?

There are three different types of animal-based research. You have basic research where you want to understand the organism and its reactions, as is typically done in universities. Then there is a very targeted type of animal experimentation where you use it to identify new agents, drugs…. And the last is regulatory testing, which means testing products to fulfill certain safety assessments before they can go to the market.

Give us an example of a regulatory test.

Let’s take the very famous rabbit eye test. In 1928, a cosmetic product for dyeing eyelashes called Lash-Lure led to five cases of blindness and one fatality. This “Lash-Lure scandal” led to regulation. And an FDA toxicologist, Mr. Draize, developed the rabbit eye test [which requires placing a substance into an albino rabbit’s eyes to measure the reaction]. So since the early ‘40s, we have a standardized rabbit eye test that is used for all chemicals, not only those used in cosmetic products. This is quite typical for toxicology. You have a scandal. And this scandal leads to a certain solution with the technology of its time. In all other areas of science, you would have an evolution and the methodologies would change over time. But the fact is that here we have a little bit of island outside of the normal stream of sciences.

Why?

There’s very many reasons for it. Among them, international agreements, which [establish] a certain methodology for a long period of time. They actually often inhibit the advancement of new methodologies.

Where do you find the greatest resistance to new methods?

There’s a certain alliance of the regulators and the regulatory community. For them, the drive to change appears to be mainly motivated by ethics, motivated by animal welfare activism. They have forgotten that it is also about the best possible type of assessment. And it is my strong belief that we need to apply modern science to evaluate modern products—nanoparticles, biological types of drugs, genetically modified organisms and their products—all these are things that we cannot address with methodologies that are simply outdated.

What are some alternative methods to animal testing?

For the cosmetic area, the most important developments have been the use of artificial human skin. Human artificial skin has originally been developed to treat patients with burns but has never made it to clinics.

Can the U.S. and Europe coordinate regulatory testing?

Actually we have a mechanism for this. The OECD, the Organization for Economic Collaboration and Development, has a program where agreements for individual tests to be applied are done and after this agreement, every member country has to accept the other’s test. The big advantage is that this has almost abolished duplicate testing…. And in the end, science is global. Science does not know borders. We’ve had a milestone in the U.S. with the vision document of the National Academy of Sciences’ National Research Council, which in 2007 published “Toxicity Testing for the 21st Century.” And this is having repercussions at the moment worldwide because this vision put forward the concept of moving away from animal testing to a human cell-based toxicology…. This was really a fire for dry wood. Toxicology was waiting for something like this … not changing small patches but really rethinking toxicology. I think this is also one of the attractions for me to be part of this process here.

How do you respond to scientists who say we need more animal testing and more animal facilities to attract top scientific talent?

I think the only thing to ask ourselves is what is the question we want to answer, and what do we want to sacrifice for this? Nobody likes to do animal experiments, and I think that every sane person would agree that doing harm to an animal without need is not acceptable…. Medical research is certainly the area where animal experimentation is best justified if there is no other approach. It’s extremely important to reflect regularly on its necessity. I know a lot of people who have a certain animal model running, and then after they publish, they look for the next problem they can solve with this animal. And this is not what should be driving research.

How reliable are mouse models?

That’s an extremely interesting point. For pharmaceuticals, we go to humans after the whole toxicology test toolbox has been passed. And still up to 30 percent of the substances have side effects that lead to stopping, not marketing the product. And we also have certain problems of repeat experiments. Typically reproducibility of 85 percent is reached when repeating a test in the same animal species—and it is much less when conducting the test in different animal species. So it is a very imprecise tool.

What are your priorities for CAAT?

We are, first of all, the most important center for alternatives in the U.S. CAAT is an extremely important information hub among science, industry, regulators and also, increasingly, animal welfare groups. It is a place of exchange, of understanding, of information. I aim at this moment to develop it further, to be an intellectual center for the paradigm shift in toxicology, a think tank. The vision of the National Academy of Sciences’ document requires quite a dramatic change of approaches in toxicology. And as I said this cannot be done by small changes. You need a quite substantial change, and this requires an out-of-the-box thinking.

That sounds very interesting and hugely ambitious, too.

Yeah. I mean I thought nothing less is expected at Johns Hopkins!