Biotechnology and New Models of Disease and Development

Determining the extent to which changes in technology are transforming the pursuit of human-specific models of disease and development.

For biomedical researchers, there have historically been limited options to create models of human disease and development in laboratory settings. Animal models (especially mice) have been commonly used but are subject to both experimental and ethical problems. There is also the additional layer that many human diseases do not exist in non-human animals. On this front, the aim of developing therapies for human diseases by using animal models (what is usually called in vivo research) faces significant shortcomings. Similarly, the experimental use of human cells outside the human body (what is usually called in vitro research) has historically been based on cell lines that lack accuracy and robustness of human cellular physiology.

However, new kinds of research tools that are made of human cells have significantly increased the ability researchers have to study and model human disease. Our project explores how new cell-based technologies are opening up and transforming the pursuit of human-specific models of disease and development. This includes, for example, the making of human induced pluripotent stem cells (iPSCs) cells, a technology which allows researchers to generate almost every type of cell in the human body (they can be taken from both disease-specific patients and healthy individuals).

Our project explores this in two related but separate areas: first, we look at how researchers can now make organ-like structures in a dish, what are called ‘organoids’. These are three dimensional cellular structures resembling tiny versions of the organ they are meant to model. Organoids present new possibilities for human disease models that have not been possible in animal models while also addressing the increasing concern about the translatability of findings in animal models to humans. Second, while organoids recapitulate aspects of human cellular and tissue development, they may not fully allow for the study of complex physiology and diseases in a dish. We are also exploring the generation of in vivo models using human induced pluripotent stem cells to create interspecies mammalian chimera between humans and other animals such as pigs. Here techniques are used to transfer human cellular material to animals which has enabled the creation of animal models where a significant percentage of an animal’s tissues or organs are replaced with human tissues.

Our explorations will contribute to increasing public awareness and understanding of diverse forms of biomedical research, along with informing public debates about new biotechnology and the use of animals in research.