Assessing the safety of chemicals and medicines without laboratory animals
One of the holy grails of drug research is to be able to assess the safety of chemicals and pharmaceuticals without using laboratory animals. Researchers from Leiden University, among others, now receive a grant from the National Science Agenda to pursue that goal.
The Leiden researchers are part of a large consortium with Utrecht University in the lead, and also involving private partners such as Galapagos, knowledge institutes such as RIVM, and Proefdiervrij. The consortium will receive 9.9 million euros from the Dutch National Research Agenda: Research on Routes by Consortia (NWA-ORC). Thanks to the contribution of foundations, the government and companies, the total funding of the project is 11.2 million euros.
A world in which we can accurately test the safety of chemicals and pharmaceuticals for our health without using laboratory animals. To be able to understand how we can safely use these substances at home, at school or at work during our lives, even for people who are extra vulnerable. That is the vision of the consortium for the Virtual Human Platform for safety assessment (VHP).
Limited predictive value
For lack of better alternatives, using laboratory animals currently is in some cases the least bad testing method Although all kinds of initiatives are underway that successfully reduce animal usage, we still cannot do without. 30 percent of the laboratory animals used are for legally required toxicological and safety tests. An additional problem with animal experiments is that animals have only limited predictive value for human health. The Horizon2020 project EU-ToxRisk integrates human in vitro test systems with in silico technology, to assess the safety of chemicals. In addition, the TransQST and eTRANSAFE projects have also been set up to look precisely at that translational predictive value of in vitro and in silico test methods. To date, however, despite the known shortcomings, there is no realistic alternative to study the biological effect of molecules on the entire complex organism that is man.
Consortium participant Gerard van Westen, Professor of Artificial Intelligence & Medicinal Chemistry: 'Using artificial intelligence, we can already replace various facets of the process of interaction between medicine and humans with computer models with reasonable reliability. This includes predicting the affinity of a drug for a relevant protein or predicting the concentration of a drug in specific tissues. But to date, it has not been possible to successfully combine these different facets into a large Virtual Human Platform. Solving the underlying problems is the core of this challenging NWA project.'
Professor of Drug Safety science Bob van de Water adds: 'Within the Virtual Human Platform, we integrate unique computational and bioinformatics methods to predict the effects of drugs and chemical substances. We make as much use as possible of knowledge of human physiology and pathology. The trick is to computationally qualify and quantify all the different steps that are important for the harmful effects of medicines. This includes molecular interactions, cell biological consequences and ultimately the (patho)physiological effects at the organ level. The LACDR's Drug Discovery and Safety division has unique expertise in this field. We are proud to be able to contribute to this national NWA project.'
A unique opportunity
Artificial intelligence researcher Joost Beltman: 'The development of this platform offers a unique opportunity to integrate the extensive knowledge of human physiology and the large amounts of data that have become available in recent years in the field of reactions of the human body to administered substances. We use a diverse set of computational methods for this. We will fully deploy the knowledge within our division of the underlying explanations for responses of human systems at the molecular, cell and tissue level, as well as computational methods, to make this ambitious NWA project a success. '
Accelerating the transition
The main goal of the project is to be able to determine, through a holistic, interdisciplinary Virtual Human Platform, whether chemicals and pharmaceuticals are safe for human health without the use of animal testing, based solely on human physiology and biology. By integrating innovations in computational methods and artificial intelligence, human tissue culture models and transition management, the researchers are accelerating the transition to animal-free safety assessment. Van Westen: 'Once we have a successfully working platform, the applications will be endless. Consider, for example, simulating the expected effects in small or vulnerable groups such as children, the elderly and the sick.'