‘The road ahead includes the use of human tissue’

What are your views on animal experiments and the transition to animal-free innovation?

When the Netherlands was forced to implement into Dutch law the EU Directive on the protection of animals used for scientific purposes, some people thought, no problem, those changes will be easy to make. There was a good thinktank in Brussels, and the new Directive on the protection of animals used for scientific purposes was innovative, both in terms of animal welfare and social accountability. However, at the time, a political debate had sparked in The Hague, and frustrations were already clear, because since 2010 member states had not been permitted any national ‘add-ons’ (in the form of additional regulations, ed.). The political ambition was: “would it be possible to phase out most animal experiments by 2025?” This sounded great, as animal experiments weigh heavily on people’s hearts and minds. But of course, it was impossible.

But surely solid innovations are on the horizon?

Technology is ’hip and happening’. There are interesting innovations, but these have their own dynamics and stimulating drivers. You do not need to pour additional funding into them due to alternatives to animal experiments. In my opinion, the TPI Transition Programme for Innovation is getting in the way of the modernisation and professionalisation of facilities that use laboratory animals, because it suggests that animal experiments can be replaced with other forms of testing in the short term. But if you look at what TPI focuses on, then you have to observe that the relevance of the humane models that are yet to be developed is limited to about 20% of the animal experiments conducted in the Netherlands. In other countries a lot of investments have been made to improve the infrastructure for animal experiments, which promotes refinement. The Netherlands is lagging behind in this area. As soon as you participate in consortiums in Europe, you can sense the vibe of technological improvements and the reduction of the numbers of laboratory animals used in projects. But in the Netherlands, hope of replacement is the holy grail.

With all this in mind, what is the way forward?

The road ahead includes the use of human tissue. But unfortunately, at present, we can do almost nothing with biomaterial obtained from patients. I do not think the legislation itself is the problem, but you need good organisation within those regulations. This is what we are working on now with Vital Tissue. UMC researchers can usually obtain human tissue, mostly directly connected to the disease their research focuses on. But labs that perform safety tests, for example, need healthy human tissue and this can be difficult to obtain.

The decision to use animals is not taken lightly. These experiments are done for good reason and this is assessed on a case-by-case basis. Researchers use all kinds of research methods. When COVID began, we very quickly turned our focus to lung organoids in combination with animal experiments. Those complementary methods are often performed by the same research group or individuals, so we need to move away from the one-sided focus on replacement, because that is the most uncertain.

What should be prioritised?

The investment agenda should focus on how to ensure the sustainable high quality of scientific work. Once you have obtained those organoids and you are keen to move on to application, making transplant tissue for example, then you should have the cells differentiated in a controlled manner. You need to prevent unchecked growth, because the result is cancer. So you must be reasonably convinced that no tumours will grow, and animals are needed for this research. Propagators are not suitable for modelling all normal mechanisms, such as the immune system, in a coherent manner. This means that what we need are combinations of methods and approaches.

Sometimes you can work with patients, but conducting biomedical innovation research in patients is not possible. Time for a change. Following large cohorts of people is enormously complicated and time consuming. This means that for the set up of small-scale and controlled studies, laboratory animals are still the go-to, in addition to cells, molecular research, and other methods. But that is a continuum, as the same researchers are often involved in developing and applying the various methods in coherence. It is important that a framework is developed for animal-free methods as well, both for the purpose of assessing claims and to check expectations (that can sometimes be high). At present, there is a lack of commitment.

In my opinion, the government is failing to meet its duty of care to science. The Experiments on Animals Act needs to be enforced, rather than only taking a leap forward with TPI, because in doing so you give society the impression that experiments on animals will become obsolete.

What do you believe requires further professionalisation?

Animal experiments are specified in law. It is necessary to ensure everything involved in animal experiments is clearly laid down in regulations, because we want to protect the animals involved. Animal lab employees are specifically trained to handle laboratory animals with great care. This professional practice is important and has unfortunately not yet been fully adopted by all professions that do work with animals.

Perhaps we were ahead of our time back in the 1980s. Back then, we were one of the first countries to have a legally-required course on Laboratory Animal Science. This professionalisation was useful. The course became an export product. Unfortunately, this head start has been a thing of the past for quite some time and it is very important right now to connect on an international level again.

TPI is long-term investment that will not automatically replace or reduce animal experiments. The animal-free methods also often show different effects in a living organism. This may mean that more drug candidates that were initially tested using animal-free methods move on to the next stage, which then still requires animal experimentation. TPI is profiled in a way that has a socially-polarising effect and absorbs all available government funding for this field.

What would you like to see happen in this area?

It would be my wish that scientific research and research policy are evidence based, and that political wishful thinking does not take over, resulting in a myriad of unintended side effects.