Past-Present-Future

The dramatic discoveries, products, and solutions in bioscience in the last few decades cause many to characterize the 21st century as the “Century of Biology.” However, one must keep in mind that many of the discoveries and products of biological insights were possible because of new experimental techniques resulting from fundamental studies in physics and chemistry. Those studies have provided the basic discoveries that led to the major breakthrough in biology and emergence of new bio-related disciplines through better instrumentation, molecular separation processes, and automated experimentation. Bioinformatics developed out of mathematical principles and many other innovative biological products and processes were developed through engineering research and design. Therefore, it is more likely that the 21st century will be known as the era of integrated science, engineering, and innovative technology (Good 2002).

As noted by Pearse (2003), an integrated approach in biology has a long history. Before agriculture, our ancestors depended on a fully integrated knowledge of their world to successfully hunt and gather. The development of agriculture was a natural consequence of such knowledge. Democritus and Aristotle championed observation and synthesis to provide an integrated world view. The founding fathers of modern biology, Malpigi, Leeuwenhoek, Linnaeus, Lamarck, Cuvier, Wallace, Huxley, and Haeckel, all were integrative scientists. In the 19th century, an integrated approach carried great promise for science and rational thinking. The quintessential integrative scientist was Charles Darwin (Wake 2003). He carried out studies of systematics, morphology, development, behavior, physiology, and natural history, and out of it all emerged the grand synthesis that became the foundation of much of modern biology. However, a holistic understanding of biology became overwhelming as knowledge at all levels grew. By the beginning of the 20 th century it had become clear that few people could master all the developing disciplines in biology and adjacent fields, much less the diversity of organisms themselves. Instead, it was more productive to specialize in narrower areas or taxa. Reductionism replaced naturalism and became the predominant paradigm in biology in the 20 th century (Benson 1989).

recycle

As noted by Lander and Weinberg (2000), the 21st century disciplines will focus increasingly on the study of entire biological systems, by attempting to understand how component parts collaborate to create a whole. This new approach promises a stunning breadth of perspective. At the same time, it threatens to inundate scientists with a flood of data that will be overwhelming to interpret. Powerful new types of bioinformatics will clearly be required to assimilate and interpret the data that will issue from various types of genomics and proteomics research. For example, structural data from x-ray crystallography usually provide only a static frozen view of a complex system, which may not reflect the in situ conformational details ( Schlick 2002). Neither does it include the effect of protein dynamics on the functions of proteins. Because of these difficulties, mathematical modeling and computational simulations have become invaluable tools to provide insights into the microscopic aspects of reactions involving proteins (Warshel 1991; Mulholland and Karplus 1996; Mulholland and Richards 1998; Villa and Warshel 2001). Analysis of the huge amount of genomic and proteomic data requires interdisciplinary expertise and close collaboration between biological scientists and computational scientists. Similar examples can be found in the related fields of bioengineering, biochemistry, and biophysics.

The medical profession is also beginning to value a more integrated approach. Genetics and molecular biology have made significant inroads into the medical profession in the last decade. “I used to think of genetics as a sub-specialty of medicine. Now I think of medicine as a sub-specialty of genetics,” (Fred Bieber, Harvard). Furthermore, medicine is increasingly open to ideas derived from evolutionary biology, such as the co-evolution of viruses and humans. Evolutionary medicine is "possibly the most dynamically developing field of application" of the many ways that evolutionary biology is being used in applied science (Futumya 1995). In fact, Nesse and Williams (1997) state, "there is no branch of medicine that cannot benefit substantially from an evolutionary approach in its research and, sometimes, its current clinical practice." Examples include the evolution of disease virulence, somatic defense to disease, and aging.

Clearly, the study of complex biological systems is best approached by incorporating many perspectives, bringing together a diversity of complementary disciplines to unravel the complexity that is biology. In the past, this border-crossing approach was restrained in practice, owing to technological or knowledge limitations. Such limitations have become less severe in recent times, as a consequence of information technology improvements on one side and faster data accumulation on the other side. Hence, renewed emphasis on an integrated approach is becoming a prerequisite for advancing our understanding of biology at a higher level.

Sharp focus within a sub-discipline has made tremendous advances in the “parts catalog” of life. A narrow focus on selected aspects of larger issues is an efficient way to tease out the secrets of nature (Pearse 2003). At the same time, reductionist biology has failed to make significant progress in the study of complex systems (Savageau 1991). This is primarily because system dynamics often cannot be reduced to a linear causal model and many biological phenomena cannot be fully described without crossing the borders of biological hierarchies and associated sub-disciplines. As noted by the physiologist George Bartholomew (1964), each level of biological integration "offers unique problems and insights, and further, that each level finds its explanations of mechanisms in the levels below, and its significance in the levels above". Instead, most major advances in understanding complex systems have been made by interpreting results across levels of biological organization (molecular to ecosystem levels) and crossing the boundaries of disciplines. For example, Nobel-Prize winner Barbara McClintock did classical genetic research on corn in the 1940’s that led to the discovery of mobile genetic elements, or ‘jumping genes’. Application of her work has dramatically changed what we understand about molecular biology of cells, evolution of populations, and even introduction of genetically-modified organisms into the food chain.

The 1980’s and early 1990’s were times of extraordinary advances in our understanding of the molecular aspects of biology. It is now apparent that molecular approaches to exploring complex biological systems will drive the next phase of scientific progress. The past decade has seen the ascendance of high-throughput methods for measuring the global expression of different components of the biological landscape--genomics, proteomics, and metabolomics. These "omics", however, cannot stand in isolation. A strong motivation for the human genome project was to relate biological features to the structure and function of small sets of genes, and ideally to individual genes. However, it is now increasingly realized that many problems require a "systems" approach, emphasizing the interplay of large numbers of genes and the involvement of complex networks of gene regulation.

Xanthidium, an algal desmid, from a plankton sample collected at Garden Pond at The University of Akron’s Field Station on the Bath Nature Preserve. Images taken with a digital light microscope.

How do we define Integrated Bioscience? As defined by Wake (2003), integrative biology is both an approach to and an attitude about the practice of science. It seeks both diversity and incorporation. It deals with integration across all levels of biological organization, from molecules to the biosphere, and diversity across taxa, from viruses to plants and animals. It provides both a philosophy and a mechanism for facilitating science at the interfaces of "horizontally" arrayed disciplines, in both research and training. It finds appropriate techniques, often from unanticipated sources, and it makes appropriate, often novel, choices of taxa for observation and experimentation (so that it is not taxon-bound). It particularly stresses an approach to problems and questions from diverse perspectives, so that the explication of the research protocol has the potential to be innovative and integrative, as appropriate to the question(s) being addressed.
How does integrative biology relate to Integration Bioscience? We see this emerging field as an innovative combination of integrative biology, biochemistry, bioinformatics, and bioengineering. Integrated Bioscience incorporates but goes beyond inter-disciplinary science. In inter-disciplinary science, the research question is still focused within a sub-discipline or on a particular level of biological hierarchy. Because of its many facets, Integrated Bioscience requires diversity and a range of expertise, which depends on effective collaboration of scientists from a variety of disciplines. Bringing them together is often impeded by language barriers (Henry 2003). That expertise may be better provided by bio-scientists who are adaptable, flexible, and trained to address new questions that span levels of biological organization and extend to the “non-biological” realm (Wake 2003).