Denis Noble


Denis Noble is Director of Computational Physiology at Oxford University. His research is focussed on using computer models of biological organs and systems to interpret function through from the molecular to the whole body levels. He was the first to develop computer models of the heart, published in Nature in 1960. With his international collaborators, he has used supercomputers to create the first virtual organ, the virtual heart. As Secretary-General of the International Union of Physiological Sciences, he played a major role in launching the Human Physiome Project, an international project to use computer simulations to create the quantitative physiological models necessary to interpret the genome. He is one of the founders of the new field of Systems Biology and is the author of the first popular science book on five other languages.

Denis Noble has received many national and international prizes and distinctions for his work, including election as a Fellow of the Royal Society, Honorary Fellow of the Royal College of Physicians. He is an Honorary Foreign Member of the Académie Royale de Médecine de Belgique and has received the Pavlov Medal of the Russian Academy of Sciences. He holds several honorary doctorates and was recently made Docteur Honoris Causa, Université de Bordeaux. In addition to English, he has lectured and published in French, Italian, Occitan, Japanese and Korean.


Systems biology: a new paradigm?

There are two approaches to systems biology. The first views it as a natural extension of molecular biology. Using the huge databases of genomics and proteomics we progressively build the organism from the bottom upwards. The second view is that higher levels of organisation, such as tissues, organs and systems, constrain and order the lower levels through what we may call downward causation. I will show that this necessarily changes the paradigm.

The metaphors that served well for reductionist biology (e.g. "selfish genes", DNA as the "book of life", the genome as a "genetic program") are misleading in the context of multilevel systems biology. Viewed from the perspective of the organism, or even from that of its environment, DNA is a database from which the organism extracts the information required to make the proteins it needs in the right quantities in the right places. This form of downward causation is effected through epigenetics: chemical marking of the genome to determine which genes are used or silenced at a given time. Genes therefore don't have much chance to be "selfish"; they are more like the "prisoners" of the organism.

"The book of life" is more like machine-coded data than a real book. Like the pipes of a huge organ (there are organs with as many pipes as there are genes in the human genome!), they are "played" in different ways by the different cells, tissues and organs of the body to produce the "music of life". And when we succeed in identifying "genetic programs" in the body, they turn out to be the functionality itself. Does this change in perspective matter? I believe it matters for two reasons. First, paradigms affect the way in which we do research because they determine which questions we ask.

Thus, it is easier to ask questions about inheritance of acquired characteristics (which exists, despite neo-Darwinist dogmas) from a systems perspective. Second, the social and ethical consequences of our choice of paradigm are important. Genes did not "create us, body and mind". They co-evolved with the systems that interpret them.