Approaches to Biology and Disease and the Emergence of Proactive P4 Medicine

Lee Hood Institute of Systems Biology, Seattle

The challenge for biology in the 21st century is the need to deal with the incredible complexity of biological systems. One powerful way to think of biology is to view it as an informational science. This view leads to the conclusion that biological information is captured, mined, integrated by biological networks and finally passed off to molecular machines for execution. Hence the challenge in understanding biological complexity is that of deciphering the operation of dynamic biological networks and molecular machines across the three time scales of life—evolution, development and physiological responses. One approach to deciphering this complexity is to generate lots of information about the systems of interest—across the multiple scales of biological information (DNA, RNA, protein, interactions, etc.). The challenge of high throughput data centers on signal to noise issues—noise that arises both from technical measurement issues and from the integration of multiple aspects of biology into any measure of phenotype. I will discuss the principles and infrastructure necessary for practicing systems biology that permit and deciphering of biological (disease) complexity.

I will then focus on our efforts at taking a systems approach to disease—looking at neurodegenerative (prion) disease and a brain tumor (glioblastoma) in mice. These studies have given us fundamental new “systems insights” into disease processes that include a deep understanding of pathophysiology, as well as new approaches to diagnostics and therapy. One interesting questions that I will discuss is how important animal models of disease are for understanding their dynamics and how closely the murine model diseases mimic their human counterparts.

Then I will discuss the emerging technologies that will transform biology and medicine over the next 10 years—e.g., next generation DNA sequencing and its applications to human genome and RNA sequencing, targeted mass spectrometry, microfluidic protein chips, new approaches to protein-capture agents, single-cell analyses and the use of induced pluripotential cells to understand development, disease mechanisms and stratify disease.

It appears that systems medicine, together with emerging technologies and the development of powerful new computational and mathematical tools will transform medicine over the next 5-20 years from its currently reactive state to a mode that is predictive, personalized, preventive and participatory (P4 medicine). I will describe the nature of P4 medicine and its societal implications for healthcare. I will also briefly mention our efforts to bring P4 medicine to patients. , M.D., Ph.D. [email protected]

Dr. Hood’s research has focused on the study of molecular immunology, biotechnology, and . His professional career began at Caltech where he and his colleagues pioneered four instruments—the DNA gene sequencer and synthesizer, and the protein synthesizer and sequencer—which comprise the technological foundation for contemporary molecular biology. In particular, the DNA sequencer has revolutionized genomics by allowing the rapid automated sequencing of DNA, which played a crucial role in contributing to the successful mapping of the human genome during the 1990s. In 1992, Dr. Hood moved to the University of Washington as founder and Chairman of the cross- disciplinary Department of Molecular Biotechnology. In 2000, he co-founded the Institute for Systems Biology in Seattle, Washington to pioneer systems approaches to biology and medicine. Most recently, Dr. Hood was elected to the Inventors Hall of Fame for the automated DNA sequencer. In addition, his lifelong contributions to biotechnology have earned him the 2006 Heinz Award in Technology, the Economy and Employment for his extraordinary breakthroughs in biomedical science at the genetic level; the prestigious 2004 Biotechnology Heritage Award; the esteemed 2003 Association for Molecular Pathology (AMP) Award for Excellence in Molecular Diagnostics; and the 2003 Lemelson–MIT Prize for Innovation and Invention. He was also awarded the 2002 Kyoto Prize in Advanced Technology and the 1987 Lasker Prize for his studies on the mechanism of immune diversity. More recently he received the NAE’s Russ Prize for developing the automated DNA sequencer that revolutionized genomics and medicine. He has published more than 650 peer-reviewed papers, received 14 patents, and has co- authored textbooks in biochemistry, immunology, molecular biology, and genetics. Dr. Hood is a member of the National Academy of Sciences, the American Philosophical Society, the American Association of Arts and Sciences, the Institute of Medicine and the National Academy of Engineering. He is one of seven (of more than 6,000 members) scientists elected to all three academies (NAS, NAE and IOM). Dr. Hood has also played a role in founding more than 14 biotechnology companies, including Amgen, Applied Biosystems, Systemix, Darwin, Rosetta, and the newly formed Hood diagnostic company, Integrated Diagnostics. He is currently pioneering systems medicine and the systems approach to disease.