Implications of complex systems in biomedical research using animals as models of humans
Americans For Medical Advancement
Wichita State U
Last modified: April 26, 2006
The intact systems argument has historically been the animal modelers’ main argument: “We must test on animals because no experimental system be it in vitro, in silico, mathematical modeling, and so forth can predict what a drug will do to the intact living human system.” Ironically, it is the fact that each intact living system is a different complex system that invalidates the use of animal models.
Complex systems are more than the sum of their parts, and different complex systems respond differently to the same drug or disease. The implicit claim in the intact systems argument, that humans and other animal species are the same biochemical animals just dressed up differently, is not true. When we were ignorant of the function of a pancreas, this notion was used with some utility.
As our examination of living systems has become increasingly fine-grained, we have found that subtle differences between organisms tend to outweigh gross similarities, as explanations for biologic activity. Science could and did use animals to shed light on shared functions such as the basic function of the liver and pancreas, but today we are studying drug response and disease at the level that defines not only a species, but in many cases the individual.
Because of differences in gene regulation and gene networks vis-à-vis evolutionary and molecular biology we now understand why even two nearly identical complex systems (say a chimpanzee and a human, or even identical twins) may respond differently to the same stimuli, and hence why one complex system / species, cannot reliably predict response for a different complex system / species.
Current biomedical research is studying disease and drug response at the level where the differences between complex systems (be they 2 different species or even 2 different humans) manifest, hence using animal as causal analogical models for human disease and drug testing is a scientifically invalid paradigm.