Abstract

Studying complex biological systems in a holistic rather than a “one gene or one protein” at a time approach requires the concerted effort of scientists from a wide variety of disciplines. The Institute for Systems Biology (ISB) has seamlessly integrated these disparate fields to create a cross-disciplinary platform and culture in which “biology drives technology drives computation.” To achieve this platform/culture, it has been necessary for cross-disciplinary ISB scientists to learn one another’s languages and work together effectively in teams. The focus of this “systems” approach on disease has led to a discipline denoted systems medicine. The advent of technological breakthroughs in the fields of genomics, proteomics, and, indeed, the other “omics” is catalyzing striking advances in systems medicine that have and are transforming diagnostic and therapeutic strategies. Systems medicine has united genomics and genetics through family genomics to more readily identify disease genes. It has made blood a window into health and disease. It is leading to the stratification of diseases (division into discrete subtypes) for proper impedance match against drugs and the stratification of patients into subgroups that respond to environmental challenges in a similar manner (e.g. response to drugs, response to toxins, etc.). The convergence of patient-activated social networks, big data and their analytics, and systems medicine has led to a P4 medicine that is predictive, preventive, personalized, and participatory. Medicine will focus on each individual. It will become proactive in nature. It will increasingly focus on wellness rather than disease. For example, in 10 years each patient will be surrounded by a virtual cloud of billions of data points, and we will have the tools to reduce this enormous data dimensionality into simple hypotheses about how to optimize wellness and avoid disease for each individual. P4 medicine will be able to detect and treat perturbations in healthy individuals long before disease symptoms appear, thus optimizing the wellness of individuals and avoiding disease. P4 medicine will 1) improve health care, 2) reduce the cost of health care, and 3) stimulate innovation and new company creation. Health care is not the only subject that can benefit from such integrative, cross-disciplinary, and systems-driven platforms and cultures. Many other challenges plaguing our planet, such as energy, environment, nutrition, and agriculture can be transformed by using such an integrated and systems-driven approach.

Highlights

  • An old Indian story talks about a group of blind men coming across an elephant

  • The Institute for Systems Biology (ISB) was established as a non-traditional institution, where scientific collaboration could take place across disciplines and where biologists and other scientists, along with technologists, could freely commingle, creating a milieu in which the cross-pollination of ideas was the rule and not the exception.[3]

  • Our cross-disciplinary culture is very much driven by the idea that leading-edge biology necessitates the need to invent new technologies and that these new technologies mandate the development of new mathematical and computational analytical tools

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Summary

INTRODUCTION

An old Indian story talks about a group of blind men coming across an elephant. Each of the blind men touched a different part of the elephant and gave a description of what he believed an elephant was. Based on the blind men’s confined level of interaction with the elephant, their observations made sense. If they had collaborated and holistically studied the elephant, its true structure would have become apparent. The hybridization of engineering and biology and the fertile cross-talk between engineers and biologists in the Hood laboratory in the period from 1970 to 1995 produced five different instruments for synthesizing, detecting, and sequencing DNA as well as synthesizing and sequencing proteins.[2,3,4] Several of these inventions, especially the automated DNA sequencer and the automated DNA synthesizer, made the sequencing of the complete human genome possible and transformed how molecular biology was executed. Each of the critics’ arguments turned out to be fundamentally flawed.[3,4,5,6]

THE ESTABLISHMENT OF THE INSTITUTE OF SYSTEMS BIOLOGY
SYSTEMS MEDICINE
Biology as an Information Science
Holistic Experimental Systems Approach to Disease
Proactive Diagnosis
FAMILY GENOME SEQUENCING
Single Cell Analysis
Induced Pluripotent Stem Cells
Wellness maintenance system
Findings
CONCLUSION

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