Review: Analysis Technology for the Complexity of Life: Challenges for the Postgenomic Era

Abstract

IN JUNE OF THIS YEAR, the 48th Annual Meeting of the American Society for Mass Spectrometry and Allied Topics attracted more than 4000 attendees, a large number of them no longer mass spectrometrists in the classical sense (1). Many came from the areas of pharmaceutical development and clinical or biomedical research. Although 10 years ago chemical applications from the field of small molecule detection dominated the applications sessions, today proteomics, functional genomics, and structural immunology are the topics to draw crowds. Mass spectrometry has evolved into one of the technologies that has the potential to become an important discovery tool for the postgenomic era (2). Traditionally the field belonged to physicists, engineers, and chemists. The creation of user-friendly instruments has helped biological and medical researchers into the arena. As the completion of genome sequencing efforts drew closer and the pharmaceutical industry began to realize the value and potential of genomics-derived biological therapeutics, enormous molecule-identification challenges arose. The growing need for adequate detection technology to aid medical and biological research has in the case of mass spectrometry led to the creation of a very diverse community of researchers who routinely operate at many interdisciplinary interfaces. This trend—the drive toward integration of technologies and knowledge from different areas of research in pursuit of a comprehensive understanding of complex systems—is an important development that will shape research in biology and medicine in the 21st century. Ultimately, the academic medical center of the future will be a study center that can address a variety of integrative issues: how vast numbers of cells can form stable, complex, functioning physiological systems as well as the dynamics of health, illness, healing, and dying (3). In a workshop on high-throughput automation for mass spectrometry at the ASMS conference, Brian Chait from Rockefeller University made an interesting point. He postulated that there is a hierarchy of difficulty associated with high-throughput applications in the field of proteomic discovery. The appropriate instrumentation is the easiest part of the problem and the true challenge lies in understanding the underlying complex biology. The challenge of understanding the origin and functionality of complex biology is not new. The problem influenced Darwin’s thoughts on evolution and the origin of species. Using the eye as an example, Darwin brilliantly convinced his audience that the variety of different light-sensing devices in nature, which have increasing degrees of complexity and sophistication, supports his theory of evolution. Yet he had to dismiss the question of the ultimate mechanism (4). He was able to do so because science had not progressed far enough in his time for the matter to be even remotely approachable. Today we appear to be on the other side of the problem. Scientific progress has evolved to a very high level of complexity. Modern instrumentation allows us to monitor biology at a molecular level in great detail: high-resolution mass spec-