‘It is your duty to work hard to find alternatives to animal experiments’

How involved are you in the transition to animal-free innovation?

As MIMETAS, we frequently receive requests to participate in activities, for example from the Dutch Society for the Replacement of Animal Testing, Proefdiervrij. I was a judge for their Venture Challenge. I also participated in a discussion about organ transplants from animals to people. That subject was covered by the news at the time; a pig’s heart had been given to a heart patient who was already very ill, and he died.

We work with human cells ourselves, and our testing is almost entirely animal-free. In our disease models we try to apply human ingredients as much as possible, including in the tools we use for tissue growth. But sometimes there is no alternative to animal ingredients. For example we often need Matrigel, a component used in 3D cell cultures. Mice are used to create Matrigel. We are looking for alternatives, but that stuff is one of a kind. Without Matrigel we are unable to do a large part of our work. 

Or should we say, not able yet?

Absolutely! There are disadvantages to the use of Matrigel too. As it is made from animals, there are differences between the batches that are produced. That is unpleasant, but the results are still so good that we are unable to find an alternative. Because of the above-mentioned variation and the fact that we would like to move away from that, we will keep looking. We would prefer to work with a chemically-defined product because then we can know with absolute certainty what is in it. Then the quality would be better plus it would be animal-free.

So this is really how we look at all of our work: how can it be done better and without the use of laboratory animals at the same time? This means our focus is not so much on replacing laboratory animals, but rather on improving our models. Because laboratory animals are poor predictors of what will happen in patients. More than 90 percent of the new medicines developed in labs are never marketed, in part because it turns out they do not work in humans and in part because they are simply dangerous for patients.

We think that we can make an enormous step forward with our humane models by staying closer to the patient and improving our prediction of what ultimately happens when you give a patient a pill or injection. This is our primary objective: marketing better products.

Would the situation be different if laboratory animals were better predictors?

If I had to choose between the health of a human being and the health of an animal... well... I would have egg on my face, so to speak, if I were to choose animals. As a society, we make this decision frequently by eating meat. And on a personal note, I also say: I’m going to prioritise the health of people over the health of animals and there are choices involved in that. But our current situation has taught us that animals are often not good predictors, so it is important now to work even harder on finding alternatives.

How quickly do you think the transition to animal-free can be achieved?

I would like to be realistic. I think we are already very good at predicting toxicity and side effects of medicines in a number of areas, but what is lacking is the effect that a substance has on the total living system. You can isolate tissue, expose it to the substance, and measure its effects. But if I give this substance to an organism, this substance will be absorbed in the intestines and end up in the liver, potentially causing an issue there, or somewhere else. We cannot yet adequately mimic this sum of the processes. 

How does human-on-a-chip fit in?

At this point, it’s a distant dream. It is incredibly complex to make a good model of one organ. And link up two or three organs and everything becomes infinitely more complex. We do attempt this, but sparingly. Because your individual models need to be solid first, and only then can you carefully consider combinations. Otherwise, you will exponentially increase your uncertainties.

And yet it is not impossible. For example, a model on a chip has already been created of the menstrual cycle, with a piece of uterine lining and part of an ovary. This model can be used to imitate hormonal reactions between tissues. This works because we are already fairly familiar with those hormonal processes. In addition to that, we are working on combinations of immune-system organs and tumours and of important parts of the kidney. We will be making significant steps in the next 10 to 20 years. Not just because it’s cool but because we want to find answers to questions and develop better medicines.

What are your thoughts on the risks? Should we eliminate every risk at all cost?

Ultimately, the information from various tests will provide the best answer about the safety of medicines for people. A great example of another type of test is microdosing in humans. Microdosing is giving a small, innocent dose to a patient or test subject, using equipment to see how this small dose is absorbed by the body. This results in a lot of extra information about potential risks for human beings.

Ultimately, it will be very difficult to guarantee the safety of all medicines for the full 100%, no matter how good our new models and tests are. We always have to accept a certain risk. But we are doing everything in our power to maximise safety.

Do you have any experience with animal experiments yourself?

I am a developmental biologist and have done genetic testing on zebrafish. There came a point when I realised that I was walking around with buckets full of dead fish, and I realised that I was experimenting out of sheer curiosity, and not even really for the development of a new medicine. That hits home.

But then I ran into my current colleague Paul again, and we came up with the idea of developing organs-on-chips based on our own areas of expertise. MIMETAS now works for pharmaceutical companies, that obviously wish to market medicines. Unfortunately, this road still almost always involves laboratory animals. Pharmaceutical companies also agree that change is needed. This does not mean that everyone stops testing on laboratory animals effective tomorrow, but it does mean that we are heading in that direction, one step at a time.

What do you think is the right tone in having a dialogue about the transition?

I previously mentioned the Dutch Society for the Replacement of Animal Testing as an example. While they have an activist focus, the organisation has knowledge and understanding of the scientific reality. You need to work with caution and you are obligated to work hard and to try and find alternatives to animal experiments.

It is unreasonable to expect that, as a society, we will switch to animal-free research from one day to the next, but it is not impossible that we will achieve 90% progress in this field in one decade.

Some say animal-free research is very expensive, but animal experiments do not come cheap either. And during this transitional phase, there’s double the work. Two consecutive tests, one with and one without animals, are often needed, to make comparisons. And then contradictory results are also possible and you will need to figure out what is causing this contradiction. This makes the situation very complicated and expensive. But I do believe a major change is around the corner. And we are more than willing to take this step.