The Adolescent Genome
genetic imperfection Disease is a normal and inevitable part of life that arises from the way that organisms are put together.
unselfish genes The way that different flavors (alleles) of thousands of genes work together establishes how an organism looks or behaves, or how healthy it is.
how genes work and why they come in different flavors We all differ from one another at millions of places in the genome.
three reasons why genes might make us sick Rare alleles that have a large impact, common alleles that have a moderate one, or hundreds of alleles with very small effects can all contribute.
a unified theory of complex disease The combination of rapid human evolution and recent cultural change has pushed us out of a genetic comfort zone, predisposing many more people to disease.
the human genome project Public and private efforts have jointly produced a complete sequence of the human genome that lays the foundation for a century of medical research to come.
genomewide association The scalpel that will be used to isolate most of the major disease susceptibility alleles for complex disease of the next few decades.
Of all the paradoxes in the world, surely one of the most absurd is that the very same genome that gives us life inevitably also takes it away. Even when they aren’t killing us, our genes are generally making existence more difficult than seems absolutely necessary. Very few people escape this world having avoided a bout with cancer or diabetes or asthma or depression, and those who do often end up too senile to remember much of the journey anyway. What good reason could there possibly be for so much suffering and disease?
Maybe there is no good reason, other than that genetic disease is an unavoidable byproduct of the way organisms are assembled; disease arises because humans, like all other species on the planet, are an unfinished symphony. Perhaps we are even more unfinished than most, thoroughly out of equilibrium with the modern world, and even a little bit uncomfortable in our own skin. In short, we possess an adolescent genome.
This notion may seem counterintuitive, because we are so conditioned to think in terms of perfection. A simplistic way to think about biology is to imagine that every species is perfectly suited to whatever ecological niche it occupies. Its genome has evolved to ensure that each individual is made to be as close as possible to the optimum shape and set of functions that a perfect member of the species would have. Adaptation to a dragonfly is having exquisitely refined lace wings, to an orchid it is pitching the lips of its pouting petals at just the most attractive angle, and to a human it is whatever it takes to live a long and comfortable life. Maybe no one individual is ever truly cast as the ideal that defines the species, but all approximate the optimum.
If an individual doesn’t quite define perfection, it is either because optimality actually comes in a variety of shapes and sizes, or because forces are conspiring against the person. Debating whether humanity is more closely realized in the form of Colin Powell or Tiger Woods, Jennifer Lopez or Hillary Clinton, we would no doubt agree to disagree on what attributes are desirable in a person. We would, however, likely find common ground when it comes to health, concluding that some not-so-optimal types of genes floating around make us hypersensitive to pollen, push us to eat too much, or make us prone to mental illness. So the question is, why are such bad influences tolerated in the gene pool?
As the book unfolds, we will look closely at six different types of disease, each given its own chapter. It is first necessary to lay the foundation, so I have three goals in this opening chapter: first, to disavow you of any sense that there is such a thing as a “disease gene;” second, to lay out the general theory of complex disease that I enunciate as the book unfolds; and third, to explain how contemporary geneticists go about finding the genes that influence susceptibility to illness.