"Evolutionary Perspectives" 

      Theodosius Dobzhansky once said: “Nothing in biology (and by extension medicine) makes sense except in the light of evolution”. The application of evolutionary principles to an understanding of health and disease represents the foundation of a new discipline, termed Darwinian Medicine, which was largely popularized by R. Nesse and G. Williams in their trade book “Why we get Sick” and a follow-up feature article in Scientific America entitled: “The Evolutionary Origins of Disease” (see required reading list). In their book, Nesse and Williams make the following claim:

“When evolution is included in medical school curricula, it will give students not only a new perspective on disease but also an integrating framework on which to hang a million otherwise arbitrary facts. Darwinian Medicine could bring intellectual coherence to the chaotic enterprise of medical education”.

     An interesting way to look at the endothelium is through the lens of a landscape metaphor, as originally described by Richard Dawkins in his book, Climbing Mount Improbable. According to this metaphor, complex design rests at the peak of a mountain. Dawkins called the mountain Mount Improbable because the species or organ could not have reached the summit by chance alone. There are two sides to the mountain. For centuries, mankind recognized only the side with the cliff. Reaching the summit depended on giant leaps through divine intervention or single generation macromutations, a process referred to as saltation. In 1859, Charles Darwin exposed the other side of the mountain. He proposed that the gradual incline was surmountable by the cumulative selection of chance mutations, a mechanism that came to be known as natural selection. Once at the summit, the product carries the illusion of design. The endothelium metaphorically resting at the peak of a mountain, does indeed impress us with improbable perfection.
      As discussed by Dawkins, there are several rules to climbing this side of the mountain. First, each step represents an improvement. Every change must confer a survival or reproductive advantage. Second, the path is one way up. A species or organ system cannot get worse as a means towards eventual improvement. Third, there are no sudden leaps, or precipitous increases in ordered complexity. Finally, there is more than one peak or more than one way to solve a given problem.
     Evolutionary perspectives offer fresh insights into endothelial health and disease. In this lecture, we will consider the following questions: 1) how/why did the cardiovascular system and endothelium evolve, 2) how do we apply evolutionary considerations to an understanding of the vulnerability of the endothelium to disease? These questions will provide a crucial framework for the remainder of the course.