Our blood is as salty as the sea we used to live in! When we’re frightened, the hair on our skin stands up, just like it did when we had fur. We are history! Everything we’ve ever been on the way to becoming us, we still are.   —Terry Pratchett

Knowing of Nathan Clark’s work on the influence of evolution on the shared function of genes (see our Investigations story in this issue), and reading recently about the translucent sea walnut, Mnemiopsis leidyi, a comb jellyfish that has populated coastal waters for some 700 million years, my thoughts have turned to the immediate relevance of evolution to medicine. M. leidyi is known as “combed” because of its long rows of undulating cilia studded with luminescent neurons; when disturbed, it glows blue-green. In December, Science published the sequence of the 16,500 genes of this ancient life form; with these data in hand, the authors reconsidered both M. leidyi’s place on the tree of life and how neurons and muscle cells may have been gained and lost during early evolution. Such insights may well help us to understand human diseases of the nervous system and musculature. In fact, more than half of the known genes that, if mutated, lead to human diseases appear in the comb jelly’s genome!

In the quest for insight into the origins of disease, evolutionary biology promises a fresh perspective, and potentially even new approaches to prevention and treatment. Our genomes are remarkably stable, yet changeable enough that mutations occur—both for the good (otherwise we would still be M. leidyi) and the bad. We must weigh not just the dysfunction conveyed by a particular mutation, but also its benefits and historic origins within a complex system, asking, What has allowed this mutation to persist? Why has it not been selected against? Is it advantageous under certain environmental conditions? Imagine posing such questions to reframe our approach to cancer, allergies, autism, chronic inflammation, even depression.

Consider, for example, sickle cell anemia, a brutally painful condition owing to a mutation that reshapes the red blood cells. While a pair of such mutations may impose an early death, a single mutated gene seems to confer natural resistance to malaria, endemic in the same regions of the world in which the sickle cell mutation first emerged. What if insights into the sickle cell and malarial structures were employed to develop a malarial vaccine? Another case in point: Huntington’s disease is a devastating genetic condition. Why does this mutation persist across the generations? Why isn’t it selected against? The answer is simple: Symptoms don’t emerge until after the age of reproduction, so this dominant mutation is passed on from one generation to the next. Of an especially immediate relevance to common human ills, consider the rapid evolution of flu viruses (and thus the need for annual changes in the vaccine), HIV (which can evolve rapidly even in one patient), and antibiotic resistance in bacteria—all situations in which our ability to probe evolution, using powerful molecular, structural, computational, and cell biologic technologies, holds great promise. Even cancer may be understood in this way, i.e., realizing that a cancer cell exploits evolvable mechanisms that preexist in us, like cell division and migration. Given these thoughts, perhaps it would be welcome for medical schools to have a greater focus on evolutionary biology and even the fossil record.

Arthur S. Levine, MD
Senior Vice Chancellor for the Health Sciences
John and Gertrude Petersen Dean, School of Medicine