A Personal Journey of Discovery: Developing Technology and Changing Biology

Abstract

This autobiographical article describes my experiences in developing chemically based, biological technologies for deciphering biological information: DNA, RNA, proteins, interactions, and networks. The instruments developed include protein and DNA sequencers and synthesizers, as well as ink-jet technology for synthesizing DNA chips. Diverse new strategies for doing biology also arose from novel applications of these instruments. The functioning of these instruments can be integrated to generate powerful new approaches to cloning and characterizing genes from a small amount of protein sequence or to using gene sequences to synthesize peptide fragments so as to characterize various properties of the proteins. I also discuss the five paradigm changes in which I have participated: the development and integration of biological instrumentation; the human genome project; cross-disciplinary biology; systems biology; and predictive, personalized, preventive, and participatory (P4) medicine. Finally, I discuss the origins, the philosophy, some accomplishments, and the future trajectories of the Institute for Systems Biology.

A personal view on systems medicine and the emergence of proactive P4 medicine: predictive, preventive, personalized and participatory

“…Descriptions of the emergence of the four paradigm changes that led to systems medicine and P4 medicine -high throughput biology, the human genome project, the creation of cross-disciplinary biology and systems biology -are discussed in Refs [8,9].…”

The human genome project: big science transforms biology and medicine

“…Understanding a complex biological system requires knowing the parts, how they are connected, their dynamics and how all of these relate to function [20]. The parts list has been essential for the emergence of ‘systems biology’, which has transformed our approaches to biology and medicine [21,22].…”

Diversity of genome research at the 2009 Plant and Animal Genome Conference

“…The protein matrix technology was discussed in the context of identifying specific blood proteins in particular, in order to provide biomarkers that can be utilized for disease diagnosis or for assessing the impact of drugs treatments in individuals. Hood indicated that advances in a range of technologies and resources such as next-generation DNA sequencing, targeted mass spectrometry, microfluidic chips, and DNA-encoded antibody libraries (Bailey et al 2007) would enable the implementation of a personalized medicine that was "predictive, preventive, personalized and participatory" (P4 medicine, Hood 2008). Engagement in personalized medicine programs was seen to be a new and challenging phase for biotechnology and matching progress in education was argued by Hood to be crucial as individuals needed to understand their own records and interventions aimed at reducing the risk factors affecting their health.…”

“…In his talk, L Hood argued that biology, as an informational science (systems biology), was now the driver for the integration of innovation in computational, chemical, and instrumentation disciplines. He used his group's analysis of the prion disease in mice to illustrate the combination of large-scale screening processes to identify all the prion-related genes (Hood 2008), building on earlier detailed genome-level analyses (Lee et al 1998) and an understanding of the biology (Moore et al 2001;Hood 2008). Monitoring the environment through characterizing oral, gut, and environmental bacteria was feasible using the new sequencing technologies and G Church reported that the high levels of antibiotic resistance that are now being found may eventually necessitate alternative approaches to combating unwanted life-forms in certain situations.…”