Scientific Program

Integrative & Comparative Systems Biomechanics

Integrative and comparative biomechanists and physiologists have been doing Systems Biology since the early 1600’s. Recently, Systems Biology has received renewed attention, but the definition has been narrowed [1]. “Systems Biology is a scientific discipline that endeavors to quantify all of the molecular elements of a biological system to assess their interactions and to integrate that information into graphical network models that serve as predictive hypotheses to explain emergent behaviors.” [2]

We contend that Systems Biology must integrate across:

1. Levels of organization (molecules to eco-systems)
2. Organisms (plants, invertebrates and vertebrates)
3. Time (evolution)

The creation of CiBER signals that we are in new age of integration. The broader view of Systems Biology DEMANDS integration not only within biology, but with physics, engineering, mathematics, chemistry and computer science to a degree not seen before. An INTERDISCINPLINARY Vision is a must.

We argue that comparative biomechanics is uniquely positioned to serve as an exemplar of this integration. The discipline focuses on the physics of how organisms function and interact with their environment. The goal is to discover basic physical principles that can be applied to a diversity of organisms and unique innovations. The fluid and solid mechanics of organisms are examined using direct experimentation, comparative and phylogenetic approaches and both mathematical and physical modeling.

Direct and Natural Experiments – A Comparative Approach

Integrative biomechanists conduct classical direct experiments. Imposed treatments and tight controls are most effective at establishing cause and effect. Comparative biomechanists add natural experiments to compare species that differ by the “treatment” parameter due to evolution. The advantage of natural experiments is substantial. Comparing systems that have evolved over millions of years can results in enormous differences in variables of interest. Organismal diversity can enable discovery. Comparing systems that differ naturally can avoid the disruption in function to a finely integrated system that can result from direct experimental perturbations pushed too far in search of a significant difference. For example, the metabolic cost of locomotion often varies by much less than ten-fold when speed, stride frequency, inclines or added loads are altered in individuals, whereas cost naturally differs by over five orders of magnitude when all legged animals are compared. Large variation in dependent variables found in natural systems permit isolation and investigation of processes of interest in nearly an ideal setting – one of exaggerated function in a normally operating system. Large differences in function are associated with differences in body mass, environmental extremes, and lifestyles. Fortunately, variation in dependent variables show remarkably general patterns and correlations which can be used to infer function and predict performance in animals not yet studied.
Equally important, however, are those systems that demonstrate spectacular performance and deviate from the general pattern. Characterization of these specialized systems can allow extrapolation to other systems in which the properties of interest are not present in the extreme, but which the principles of function are the same. For example, hopping red kangaroos can increase speed without an increase in metabolic energy cost. Further examination provided evidence of elastic strain energy storage in the tendons of kangaroo leg muscles. It is reasonable to conclude, at least in large vertebrates, such as humans, that tendons serve a similar role, albeit to a lesser extent than in specialized, bipedal hoppers. Although powerful, the comparative method is best used in conjunction with knowledge of evolutionary history or phylogeny [3-4]. The reason is simple. Natural experiments can be viewed as imperfect because they may lack an appropriate control. Seldom do the species being compared differ only by the variable of interest. The ideal comparison – very closely related species possessing a large difference in the process being studied – is rare. Fortunately, recently developed techniques in phylogenetic analysis [5-6] offer a tool to remove the effects of history or use them to hint at present function. If the process of interest has severe functional/structural constraints or complete adaptation has taken place, then the potentially confounding effects of historical differences may be of little consequence. If, however, functional constraint and adaptation have been less than completely dominant, then the most parsimonious assumption is that the process should operate as it did in the ancestor.

Finally, a comparative approach is invaluable for the discovery of new model organisms for direct and in depth experimentation. August Krogh said it best in 1929 at the 13th International Congress of Physiology in Boston: “For many problems there is an animal on which it can be most conveniently studied” [7].

References

1. Kitano, H. 2002. Systems Biology: A Brief Overview. Science 295, 1662-1644.
2. Hood. L., J. R. Heath, M. E. Phelps. Lin. 2004. Systems Biology and New Technologies Enable Predictive and Preventative Medicine. Science 306, 640-643.
3. Felsenstein, J. 1985. Phylogenies and the comparative method. Am. Nat. 125: 1-15.
4. Huey, R. B. 1987. Phylogeny, history and the comparative method. In New Directions in Ecological Physiology. Cambridge University Press, Cambridge. 76-97.
5. Garland, T. J. and S. C. Adolph. 1994. Why not to do two-species comparative studies: Limitations on inferring adaptation. Physiological Zoology 67(4): 797-828.
6. Garland, T., Jr., P. H. Harvey and A. R. Ives. 1992. Procedures for the analysis of comparative data using phylogenetically independent contrasts. Sys. Biol. 41: 8-32.
7. Krebs, H.A. (1975). The August Krogh Principle: “For many problems there is an animal on which it can be most conveniently studied.” J. Exp. Zool. 194, 221-226.