It is often claimed that animal testing could be abolished and replaced by alternative methods immediately. The most popular alternative methods mentioned in this context are computer simulations, microdosing, magnetic resonance imaging (MRI) and in vitro tests.
What is usually forgotten is that they are already routinely used to refine animal testing and to reduce the number of animals used in research. Computer simulations for example are very useful in developing new drugs. However the basis of these simulations is always data that was originally obtained in animal experiments. In the following we will discuss individual alternative methods in more detail but before that we should keep the following two points in mind:
- Animal testing is very expensive. Animals must be kept in suitably equipped buildings, they must be fed and cared for by qualified personnel and veterinarians. In comparison, non-animal test methods are much cheaper and less time consuming. Scientists whose research budget is limited, and pharmaceutical companies which operate profit oriented, therefore choose alternative testing methods whenever possible. The fact that animal experiments are still carried out shows that they cannot be fully replaced at this time.
- According to the Animal Protection Act alternative methods must be used whenever possible (Animal Welfare Act §7a paragraph 2, point 2). In addition, an experimental project can only be approved if “set forth a scientific justification that […] the desired result is not well known despite the information already available …” (Animal Welfare Act § 8, paragraph 1, point 1b). The competent national authorities shall examine each application for animal experiments to ensure that these conditions are met. An animal experiment is therefore only approved if no non-animal alternatives exist.
It should also be mentioned that animal testing for cosmetics and detergents is strictly prohibited in Germany (Animal Welfare Act §7a paragraph 4).
Computer Simulations
“Computers can do amazing things. But even the most powerful computers can’t replace animal experiments in medical research.”
Professor Stephen Hawking (Seriously Ill for Medical Research, 1996)
Computer simulations play an important role in research, however they are not a complete replacement for animal testing. In order to simulate a physiological process the process itself must be understood first. This understanding comes from experiments on animals. The basis of computer simulations are therefore animal experiments. Computers are also limited in their computing power. In 2007, the then-fastest supercomputer was needed to simulate a second of brain activity in one hemisphere of a mouse brain. Other brain structures and their connectivity that can be found in a real mouse brain were not even taken into account in this simulation. Computer simulations of organs other than the brain have a greater benefit. However, they need to focus on the main characteristics of the organ and cannot take into account finer processes. Thus for example a computer can simulate the movements of the heart muscle but not the reactions that take place in the individual heart cells. Professor Dennis Noble and his team programmed a virtual heart at Oxford University in England. With regard to the consequences for animal testing, he said: “Because hundreds of millions of differential equations are simultaneously being solved, it may take 30 hours just to do a few beats of the heart. […] I would say the real benefit of the model is that it can do a preliminary filter of your compounds, and that can replace some of the very early stages in animal experimentation“
Microdosing
Microdosing means the administration of very low doses of an experimental drug to humans. The doses here are so low that toxicity can be largely excluded. Therefore, it is reasonable to carry out microdosing without having first made a complete toxicity report in animals. In microdosing one follows the distribution of a substance through the body (pharmacokinetics) in order to exclude unsuitable substances at an early stage. Therefore microdosing reduces the number of animal experiments, since excluded substances do no longer need to be tested for toxicity in animals. Indeed microdosing provides information on the pharmacokinetics of particular substances; however it cannot fully replace toxicity testing as the toxicity of a full dose cannot be measured. Accordingly, substances that show potential in microdosing experiments (sometimes called clinical phase 0) must still be tested on animals for toxicity before they reach clinical phase 1 (test for side effects in a small group of healthy people) and possibly phases 2 and 3. Microdosing is already being used by pharmaceutical companies in medical research, but it is still a new method that needs to prove its effectiveness. Nevertheless, it is expected that microdosing will continue to replace a larger proportion of animal testing in drug development.
In Vitro Tests
In vitro assays include test tubes, cell cultures, petri dishes, or multi-well plates and a large number of cell and tissue techniques as well as cell-free methods. Dr Phil Stephens is one of the pioneers of in vitro tests based on genetic manipulations for the treatment of ulcers. He said the following: “There are a number of different animal models out there, but they are not really good models for these wounds. So, we began developing an in vitro system” This is a great example of replacement. Scientists always want a better model system for their work to obtain more accurate results. If an alternative method works better than an animal experiment, fine! In this case, the in vitro test not only provides better results, but is also much cheaper.
Nevertheless, Dr. Stephens also says: “The in vitro system is not going to replace the animal models, but it will enable a vast number of pre-screens to be undertaken, hopefully vastly reducing the number of animal experiments that go on.” Again, the goal is to refine animal testing and to reduce the number of animal experiments. Dr. Stephens says that in vitro tests do not replace animal testing altogether. The reason for this is clear. A new drug may work in a cell culture or a test tube but how it behaves in the body cannot be derived from in vitro tests. A test tube has no blood circulatory system, no liver, no brain, and no nervous system at all. A test tube cannot feel pain or get pregnant. Thus, there is no possibility for an in vitro test to predict whether a drug works or not. To answer this it has to be tested in an animal.
Magnetic Resonance Imaging (MRI)
British molecular biologist Professor Chris Higgins uses MRI to reduce the number of animals used in his experiments. He says: “One area we are looking at is what controls appetite and satiety. To do this in the traditional way, we would have to dissect the animal brain, but to avoid this we use in vivo imaging to look at the areas of the brain related to hunger and satiety.” Technological advances now allow scientists to scan the living brain of animals and humans to see which areas are active under certain conditions. From this data, conclusions can be drawn about which areas in the brain control different aspects of our bodies, thoughts and more. However, Professor Higgins also says: “The one thing that is difficult to do is to understand the genetic and the underlying molecular basis of obesity, and for this we need to use animals, mainly mice, if we are going to develop more effective therapies.” Again we find that this alternative method plays an important role in reducing the number of animal experiments, but it is not able to replace animal experiments entirely. MRI is helpful in the localisation of brain structures that are involved in certain processes but it cannot make any statement on genetic, molecular or cellular mechanisms. For this animal experiments are needed.
This text is based on the original version by Speaking of Research, but has since been revised and extended.