Primates non humains dans la recherche et l’expérimentation

3. Are there alternatives to the use of primates in research and safety testing?

• 3.1 Are there alternatives to the use of primates in safety testing of pharmaceuticals?
• 3.2 Are there alternatives to the use of primates in research on infectious diseases?
• 3.3 Are there alternatives to the use of primates in research on the human brain?
• 3.4 Are there alternatives to the use of primates in research on organ transplants?

Tests are first carried out on cells grown in the laboratory
Source: Jean Scheijen

To protect human health and the environment, it is essential to have accurate information on the effects of exposure to chemical, physical and biological agents. It is also important to do basic research to understand the human body and the diseases that can affect it, and to test any medicines or vaccines before they are given to humans. The Scientific Committee on Health and Environmental Risks (SCHER) agrees with the widely accepted guiding “three Rs” principle, which aims at reducing the number of animals being tested, refining the methodologies used and replacing the use of animals with alternative methods for research and testing. It considers that animals should only be used in medical research when it is unavoidable and when appropriate and validated alternative methods are not available.

SCHER also recognises that the results of tests on animals cannot predict accurately all the likely effects on humans. The use of non-human primates (NHPs) is therefore considered essential in certain cases because there are crucial differences between other species and humans, which make any results of studies on other animals of limited use.

Replacing animals in medical research is a long and difficult process and alternative testing methods are often not yet feasible. At present, non-animal testing methods are usually developed as complementary methods which answer questions at the level of single cells or limited numbers of cells, and cannot be applied to the highly complex problem of whole organs or interactions between different organs. Therefore, at this stage, these methods cannot completely replace methods involving animal testing. There are however, new, promising techniques that use laboratory tests and other animal species such as genetically modified mice, instead of primates.

Experiments are also carried out on human volunteers. There should be a constant feedback between human and animal research, as well as laboratory studies on cell cultures, to improve our knowledge and to make animal and human experiments more meaningful. More...

3.1 Are there alternatives to the use of primates in safety testing of pharmaceuticals?

At present it is impossible to totally replace animal experiments when testing pharmaceuticals for their safety and effectiveness, because laboratory studies cannot yet predict how a drug will affect real, living humans; and it is still necessary to establish below which dose no harmful effects are observed (NOAEL).

Because of scientific reasons, testing of new pharmaceuticals on non-human primates is a very small but almost compulsory part of the global testing procedure. The reason is that primates are usually the species that match humans more closely in terms of how drugs affect them and tests on other species are not adequate. Drugs involving the immune system can often only be tested on primates. In certain cases, genetically modified rodents may replace them but this is usually not yet accepted by regulators, who consider this alternative as a source of supportive data rather than as a means to replace the use of primates.

Microdosing, where people are given extremely low quantities of the pharmaceutical being tested to study how the substance behaves in the body, has been proposed as an alternative to animal testing. However, to make sure that the dose given is safe the toxicity of the drug must first be tested on animals. In any case, it is not obvious whether or not microdosing would lead to a reduction in the number of animals used.

Recently, the US National Academy of Sciences has proposed a combination of techniques that reduces the need for animal experimentation. These include testing cells in the laboratory, computer modelling and innovative tools in molecular biology. Animal testing should only be used when the results are unclear or where there are specific concerns. However, this method was developed for testing environmental chemicals where daily human doses are much lower than those used in medicines and is not suitable for testing the safety of pharmaceuticals. More...

3.2 Are there alternatives to the use of primates in research on infectious diseases?

There is no small mammal ideally suited for testing HIV vaccines and drugs. For instance, mice do not get infected with HIV. Despite this, some advances have been made to observe human immune reactions by introducing human immune cells into wild mice. Although this cell transplant does not last long, it has been used to investigate short-term immunity and to do quick screenings of candidate HIV vaccines.

It is very difficult to produce genetically modified mice susceptible to HIV infection. Recently, experiments have been carried out by combining the HIV-1 virus with another virus that infects mice. This method allows scientists to study how candidate vaccines and drugs work inside the body for longer periods of time. However, testing such vaccines still requires additional studies on non-human primates (NHPs).

Despite intensive research, no HIV vaccine developed so far has been successful in clinical trials on humans even though they had been tested on non-human primates beforehand. Some people claim that this shows that such testing on primates is ineffective. However, this research has increased our knowledge of how the immune system interacts with the virus both in humans and in primates. There have also been studies in cells grown in the laboratory which have improved our understanding of fundamental reactions in individual cells. However, these cannot explain how the whole body reacts to HIV infection. At present, laboratory studies on cells are complementary and cannot replace testing on primates in this area of research.

In the search for a malaria vaccine, scientists have used alternative methods that do not require the use of primates. However, it is impossible to replicate in the laboratory the extremely complex interactions between the different malaria parasites and the human immune system. Mice can be used for preliminary testing but cannot replace testing on primates, which will be needed to develop malaria vaccines in the future.

A new method has been developed to do research on hepatitis C using cells grown in the laboratory instead of primates. However, to see if a candidate vaccine is effective it needs to be tested in chimpanzees which are the only species, beside humans, susceptible to the infection. More...

3.3 Are there alternatives to the use of primates in research on the human brain?

In humans, the brain is routinely studied using non-invasive techniques that provide images of the brain’s structure and activity and detect abnormalities:

• Magnetic resonance imaging (MRI), which uses powerful magnets and radio waves to construct pictures of the internal structures of the brain, and
• Electroencephalography (EEG), which records the electrical impulses in the brain from electrodes placed on the scalp.

Recently, a new type of MRI has been developed that measures blood flow and levels of oxygen in the brain, and gives an indirect measure of brain activity. Although such techniques are very useful, they only measure how the brain works on a large scale and are not quick enough to respond to the way in which individual brain cells process information. Therefore, they cannot replace studies made by placing small electrodes in the brain. This latter technique is invasive but gives much more precise information on how different parts of the brain work because that can measure variations in the time range of milliseconds at which neurons process information.

New non-invasive techniques based on MRI have been developed and may greatly help to study how different nerve cells are connected both in healthy and in diseased brains. Although promising, these techniques still need to be developed further and have to be validated.

Computer modelling is rapidly improving but even the best attempts cannot simulate a functioning brain, partly because we still know little about the structure of the brain itself. The “Blue Brain project” has attempted to create a biologically accurate simulation of how the brain works. In the surface of the brain, nerve cells are organised in “columns” of thousands of interconnected nerve cells (neurons). The “Blue Brain project” managed to recreate a model of one of these columns of about 10 000 neurons of a rat brain but this took the full computational power of a supercomputer. A realistic model of a primate brain needs to have about 100 billion nerve cells so we do not know if and when such a model would be technically feasible. More...

3.4 Are there alternatives to the use of primates in research on organ transplants?

Studies on cells grown in the laboratory are useful in the initial stages of research to find out if an organ from an animal is likely to be rejected by the human immune system. Rodents are also used to see if drugs developed to prevent transplant rejection are effective. However, these cannot replace long-term studies on how transplanted organs will function in living animals, including non-human primates (NHPs). More...