A View of Comparative Biology in Medical Research

Comparative biology is a matter of studying differences between species that might provide insight into how particular cellular mechanisms of interest actually work - or might be altered so as to work better. The world has many species that regenerate more proficiently than we do, or live very much longer than would be expected for their size, or show other desirable characteristics as a result of their own particular evolved biology. How is this achieved at the level of cells and molecular mechanisms, and is it possible to recreate some of these changes in humans? These are questions that comparative biologists seek to answer, using the biology of other species as a shortcut to obtain environments that would otherwise be challenging or impossible at present to set up in the lab.

The authors of the paper quoted below argue that failing to take advantage of the panoply of varied evolved biochemistries in the natural world is holding back medical research. I'd suggest that disparities in regulation have a lot more to do with the differences they point out in progress in computing versus medicine. Regardless, there is certainly utility in the use of comparative biology to obtain new knowledge:

The pace at which science continues to advance is astonishing. From cosmology, microprocessors, structural engineering, and DNA sequencing our lives are continually affected by science-based technology. However, progress in treating human ailments, especially age-related conditions such as cancer and Alzheimer's disease, moves at a relative snail's pace. Given that the amount of investment is not disproportionately low, one has to question why our hopes for the development of efficacious drugs for such grievous illnesses have been frustratingly unrealized. Here we discuss one aspect of drug development - rodent models - and propose an alternative approach to discovery research rooted in evolutionary experimentation. Our goal is to accelerate the conversation around how we can move towards more translative preclinical work.

For more than a century, most biomedical research has relied primarily on mice and rats to study the basic biology, progression, and prevention of disease, with the overarching premise that "below the skin" all organisms are molecularly and biochemically alike. Indeed, several seminal discoveries and human therapies have been made using the premise of rodent models. However, advances in certain areas, especially age-related diseases, have been slow. In fact, one can argue that the numerous reported 'cures' for rodent obesity, cancer, and Alzheimer's disease have ultimately burdened the collective resources of the community to the point that a re-evaluation of the preclinical paradigm must be undertaken.

There is a growing call for additional discovery tools in biomedical research that provide more translative predictability for diseases that generally afflict humans in later life. Animal models that are considered long-lived on the basis of their body size are essential to fill the gap assessing the immutable role of time in aging and the manifestation of age-related diseases. Use of extremely long-lived models such as the naked mole-rat, or species that have adapted to extreme environments also enables one to evaluate whether nature has already evolved the appropriate mechanisms to overcome the environmental threats that contribute to sporadic and late onset diseases. An alternative approach towards target discovery employs natural, extreme biology where evolutionary experimentation has overcome many biological challenges. For instance, obesity is a natural and necessary state to survive months of fasting in hibernating animals. To this end we studied grizzly bears (Ursus arctos horribilis) before, during, and after hibernation to determine the effects of natural obesity on insulin sensitivity and cardiac function.

Link: http://www.impactaging.com/papers/v6/n11/full/100704.html


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