Interview with Professor Dr. Matthias P. Lütolf: Organoids

1. «Organoids are an exciting alternative to animal testing.»

Interview with Professor Matthias P. Lütolf on progress in organoid technology, how the technology is being used in pharmaceutical research and the Institute of Human Biology

Heike Scholten (HS): Professor Lütolf, could you start by explaining what exactly organoids are and why they are so revolutionary from a research perspective?

Prof. Matthias P. Lütolf (MPL): With pleasure. Organoids are essentially miniaturised organ mimetics grown from stem cells by cell culture. These stem cells can be taken either from a patient or “programmed” in the form of what are known as induced pluripotent stem cells. Organoids are particularly exciting because they provide a way of mimicking human tissues in three dimensions and with different cell types that fulfil various roles in the body. As a result, we can simulate complex physiological processes, something that is often not possible with conventional cell cultures.

«We can investigate whether certain medicines or combinations of medicines are more effective than others and in particular if a medicine attacks tumour cells without harming healthy cells.»

Prof. Dr. Matthias P. Lütolf

HS: That sounds fascinating. How are organoids used in real-world research and in medicines development in particular?

MPL: Organoids can be used in all phases of medicines development – from very early research, when the aim is to identify new targets or improve our understanding of disease mechanisms, right through to clinical research. At our institute, for example, we develop tumour organoids from cancer patients’ biopsy samples. We can use these miniature tumours to test the effect of medicines on a model of the patient. We can investigate whether certain medicines or combinations of medicines are more effective than others and in particular if a medicine attacks tumour cells without harming healthy cells. This is possible because in the same experiment, we can also test organoids grown from healthy cells from the same patient. The same principle can be applied to other diseases. This is a major advantage compared with conventional models, where you often have to wait until the clinical trial stage to find out whether a medicine has the desired effects and what its side effects are.

HS: So this technology is also helping to speed up medicines development?

MPL: Absolutely. The average development time for a medicine is about 13 years. Organoids provide a way of making better predictions in the early phases. As a result, Roche’s experts and decision makers can halt programmes sooner if they don’t hold out much hope of success, something that saves a huge amount of time and resources. About 95% of candidate medicines are known to fail before they even reach the clinical stage. We hope that organoids will significantly improve this success rate.

HS: And how about animal models in research? Are organoids capable of replacing them?

MPL: The use of animal models in research is a very important topic and Roche is firmly committed to the 3Rs. We are doing our utmost to advance alternatives such as organoids, but unfortunately we still cannot eliminate animals completely at this point. That being said, organoids are an exciting alternative to animal testing, particularly in areas where animal models are less effective. One example of this is immuno-oncology. Certain mechanisms that are important in human immune responses to cancer are virtually impossible to reproduce in mice. In cases like this, organoids provide a way of using human cell models to test the effect of new medicines, which reduces the need for animal testing considerably.

«If we manage to simulate human diseases in vitro and predict the efficacy and safety of medicines in these models, we could increase success rates in drug development considerably.»

Prof. Dr. Matthias P. Lütolf

HS: What is your vision for organoid research going forwards?

MPL: Our vision is to develop predictive models that depict with greater accuracy what is happening inside a patient or how a patient will respond to a medicine. The aim is to close the gap between basic research and clinical application. If we manage to simulate human diseases in vitro and predict the efficacy and safety of medicines in these models, we could increase success rates in drug development considerably. Another long-term goal is to develop organoids to the point where hospitals can use them for personalised healthcare. Imagine if an oncologist could test the best treatment options for a patient by growing miniature versions of the patient’s tumour in a laboratory and trying out various treatments on them.

HS: That sounds like a major step forward on the path towards personalised healthcare. What major challenges do you foresee along the way?

MPL: One of the biggest challenges is scalability and reproducibility. Organoids are very complex structures, and it isn’t always easy to produce large quantities of them to a consistent quality standard. This is where bioengineering comes in, because it helps us accurately control the cells’ development into organoids and to produce standardised organoids. Analysing the huge volumes of data these three-dimensional models generate is another challenge, particularly when we are studying live organoids in real time using sophisticated optical microscopes. This is where we rely on artificial intelligence and machine learning to process the data efficiently.

HS: The Institute of Human Biology was only founded in May 2023. How has it progressed so far?

MPL: We have already made a certain amount of significant progress. We have published important scientific articles in recent months, including in such prestigious journals as Nature. Within Roche, we’ve already successfully supported several projects by using our organoid models to contribute to decision-making.  That’s important because we want to have a genuine impact through our models on drug development and the strategic direction of projects.

HS: What role does cooperation with other research institutions play in your work?

MPL: This kind of cooperation is hugely important. We have close partnerships with major universities such as ETH Zurich and EPFL. Working with ETH, we have set up a doctoral programme under which students are supervised by us and the university. That way we can nurture the best talent and ensure that our research stays at the forefront of science. Although we also work with a large number of partners internationally, we regard it as our task to drive forward cutting-edge research in Switzerland in particular.

«In my view, the fact that we can now produce organoids that mimic human tissue with such accuracy is a genuine breakthrough in biology.»

Prof. Dr. Matthias P. Lütolf

HS: Finally, a personal question: what inspired you to devote your career to biology and stem cell research in particular?

MPL: I originally studied materials science, but discovered my interest in regenerative medicine and stem cell biology while I was working on my PhD. I was very much fascinated by the possibility of using stem cells to regenerate tissue and treat disease. In my view, the fact that we can now produce organoids that mimic human tissue with such accuracy is a genuine breakthrough in biology. There can hardly be any more exciting job than learning to understand how life works, how cells communicate with each other to create tissue and how we can use this knowledge to help patients.

HS: Thank you for this interesting discussion. I wish you continued success in your work!

* All IHB publications can be found here on the institute’s website.