EMBL Forum Lectures
Monday, 7 May 2012, 11:00, CNR Seminar Room, EMBL Monterotondo
Robin Lovell-Badge, National Institute for Medical Research, United Kingdom
Animal-human chimeras - monsters or better models for research?
Animals such as mice and rats are frequently used in biomedical research to understand the causes of human disease and to develop treatments. But although much valuable information can be obtained by using such animals as 'models' of the human situation, it is recognised that they are often imperfect due to differences in genetics, physiology, behaviour, or even just size. It is also possible to use cells and some tissues from humans in culture, but these are frequently too simple to mimic complex tissues or organs and can never provide an adequate test where multiple organ or whole body interactions and physiology are relevant, particularly over extended periods of time. Such studies require whole animals.
One solution, therefore, is to study human genes or cells in the context of an animal. Such approaches are not new, but they are becoming increasingly sophisticated and dramatic. Mice have been made that carry an entire human chromosome 21 as a model of Down Syndrome, it is also possible to replace the immune system of a mouse with that of a human to study HIV etc, or to have a mouse whose liver is up to 95% human to study hepatitis C or look for drug toxicity. But what if we were to replace other organs in part or completely to give the animals human skin, gonads, or brain tissue, or otherwise genetically alter them to have characteristics that are recognisably human? And would both the result and our opinion of this type of research differ if larger animals were used, such as goats, pigs, or non-human primates?
The latter would be the closest to humans and therefore arguably the best model for understanding human disease and to discover treatments, and they may allow fundamental questions about the nature of being human to be answered. But what about ethical, societal and safety concerns? Should we worry about confusing species boundaries, is there an acceptable balance between the type of experiment and the severity of the disease, and how should experiments of this type be regulated? A working group of the Academy of Medical Sciences in the UK, of which I was a member, recently undertook a in-depth study of these issues. Their report and recommendations will be presented and discussed in the light of continuing developments in science.
Robin Lovell-Badge obtained his PhD in Embryology at University College London in 1978 under Martin Evans. After postdoctoral research in Cambridge and Paris, he established his independent laboratory in 1982 at the MRC Mammalian Development Unit, University College, London, directed by Anne McLaren. In 1988 he moved to the National Institute for Medical Research in Mill Hill, London, becoming Head of the Division of Stem Cell Biology and Developmental Genetics in 1993.
He has had long-standing interests in the biology and uses of embryonic stem cells, in how genes work in the context of development, and how decisions of cell fate are reached during embryogenesis. His lab, together with that of Peter Goodfellow, discovered the mammalian Y-linked sex determining gene, Sry, in 1990, and his subsequent work on this topic has led him to understanding of the genetic pathways leading to male-female differences. Major themes of his current work include sex determination, development of the nervous system, and the biology of stem cells within the early embryo, the CNS and the pituitary. He has published over 170 research papers, reviews and commentaries. He is keen to engage the public with science, being frequently called upon by the media to comment on issues relating to stem cells, embryology, genetics, and general issues such as animal research. He has also been involved in policy work, notably around the HFE Act and animal research, for the Academy of Medical Sciences, the Medical Research Council, the Human Fertilisation and Embryology Authority, the Royal Society, and other professional organisations..
He is an Honorary Professor in Biosciences at University College, London, a “Distinguished Visiting Professor” at the University of Hong Kong, and President of the Institute of Animal Technology. He was elected an EMBO Member in 1993, a Fellow of the Academy of Medical Sciences in 1999, and a Fellow of the Royal Society in 2001. He is the recipient of the 1995 Louis Jeantet Prize for Medicine, the Amory Prize for 1996 (Awarded by the American Academy of Arts and Sciences), the Feldberg Foundation Prize for 2008, and the Waddington Medal of the British Society for Developmental Biology for 2010.