JOHN E. DOWNLING
The Biological Laboratories
Harvard University

Genes and the Brain

The Birth of the Mind: How a Tiny Number of Genes Creates the Complexities of Human Thought
By Gary Marcus. New York: Basic Books, 2004. 278 pp. Paper, $14.95.

I have been asked to review Gary Marcus's book, and he has been asked to review mine. Both books are concerned with brain development, brain plasticity, and the role of genes in development and behavior. We describe many of the same findings, but we have distinct differences in emphasis, perhaps reflecting our backgrounds—mine as a biologist, Marcus's as a psychologist. Marcus's emphasis is on the role of genes in brain function, as the subtitle of his book implies: "How a Tiny Number of Genes Creates the Complexities of Human Thought." My focus is on neurobiological mechanisms and what we can say about the biology of brain development, plasticity of the brain, and so forth. I say little about genes themselves because in my view they do not tell us that much about how the brain develops or functions. I have problems with statements such as "genes do shape our mental lives" and "genes do contribute to our personalities, our temperaments" (p. 3). Genes code for proteins (although clearly not exclusively), and it is the proteins that are critically important for understanding biological systems, including the brain. The subtitle of his book suggests, and Marcus makes this explicit in the book, that there is a large disconnect between the number of protein-coding genes we have (about 30,000) and the complexity of the brain. He is exactly right, but this fact has been understood for a long time and by itself is misleading. That is, one gene can produce many proteins through a process called alternative splicing, and he even mentions the most startling example of this, the DISCAM gene in fruit flies, which in theory could produce 38,000 different proteins. But even if every gene could produce 38,000 proteins, the total number of proteins would number about 1.1 billion, which is still not enough to specify the enormous number of neurons we have (100 billion) and the trillions of synaptic connections they make. So other factors are clearly in play, and an obvious one is that the brain uses combinations of proteins and protein gradients to specify pathways, neurons, and synapses. And how much of a particular protein is made or expressed at a particular time and place during brain development can be critically important. Another point to make here is that proteins can do quite different things in different places. The classic examples are the lens crystalline proteins, thought for many years to be unique proteins specialized for mediating light transmission through the lens. This has turned out not to be the case; some are common enzymes, such as lactic acid dehydrogenase, found in all cells (Wistow, Mulders, & de Jong, 1987). Another example is the RIBEYE protein, part of the synaptic ribbon complex in photoreceptor cell synaptic terminals (Schmitz, Königstorfer, & Südhof, 2000). In other tissues, part of this protein serves as a transcription factor, a protein that turns genes on and off. The bottom line is that not only can single genes code for many proteins, but one protein can do multiple things depending on where it is and when it is present.