Our Genes, Our Choices: How Genotype and Gene Interactions Affect Behavior

By David Goldman

Our Genes, Our Choices: How Genotype and Gene Interactions Affect Behavior — First Prize winner of the 2013 BMA Medical Book Award for Basic and Clinical Sciences — explains how the complexity of human behavior, including concepts of free will, derives from a relatively small number of genes, which direct neurodevelopmental sequence. Are people free to make choices, or do genes determine behavior? Paradoxically, the answer to both questions is "yes," because of neurogenetic individuality, a new theory with profound implications.

Author David Goldman uses judicial, political, medical, and ethical examples to illustrate that this lifelong process is guided by individual genotype, molecular and physiologic principles, as well as by randomness and environmental exposures, a combination of factors that we choose and do not choose.

Written in an authoritative yet accessible style, the book includes practical descriptions of the function of DNA, discusses the scientific and historical bases of genethics, and introduces topics of epigenetics and the predictive power of behavioral genetics.

• First Prize winner of the 2013 BMA Medical Book Award for Basic and Clinical Sciences
• Poses and resolves challenges to moral responsibility raised by modern genetics and neuroscience
• Analyzes the neurogenetic origins of human behavior and free will
• Written by one of the world's most influential neurogeneticists, founder of the Laboratory of Neurogenetics at the National Institutes of Health

• Language: English
• Publisher: Academic Press
• Release date: Dec 31, 2012
• ISBN: 9780123972019

David Goldman

David Goldman received his B.S. from Yale University in 1974, graduating in only three years, and his M.D. degree from the University of Texas Medical Branch in 1978. He joined the intramural program of the National Institutes of Health in 1979, and is currently Clinical Director and Chief of the Laboratory of Neurogenetics of the National Institute on Alcohol Abuse and Alcoholism. Throughout his career, he has identified genetic factors responsible for inherited differences in behavior, his laboratory pioneering in functional genomics – how differences in DNA sequence translate into behavioral differences from molecule to intermediate brain processes to behavior. He is recipient of many awards for his research and is one of the most highly cited scientists in biological psychiatry. His laboratory is currently exploring the genetics of substance use disorders and related health problems.

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Index

Chapter 1

The Neurogenetic Origins of Behavior

"

Transliterated as Timshel: Thou mayest choose

Genesis, Chapter 4, verse 16

Is the human will free? Do genes determine behavior? Paradoxically, the answer to both questions is yes. A new theory of behavior based on neurogenetic individuality has profound implications for conceptions of self, social expectations, ethics and justice.

This book begins with a challenge to free will from my research. The discovery: 2B or not 2B? involves a gene knockout of the human HTR2B gene, which encodes a receptor for the neurotransmitter serotonin. Serotonin is involved in many aspects of behavior including emotion and impulse control. The severely functional receptor variant causes some people to be impulsive, even to the extent of committing senseless murders. Remarkably, it is found in at least 100,000 people in the Finnish population, but as a founder mutation has so far only been observed in individuals who are of Finnish ancestry. Yet, while the inherited variant was a necessary factor in the impulsive murders that I and my partners in research studied, the gene alone was insufficient to explain the heinous behavior. In understanding why the carriers of the receptor gene variant became murderers, 2B or not 2B? was not the only question. The context of the gene, for example male sex and drunkenness, also mattered.

All human qualities, including those that are sublime, creative and adaptive, and those that are seemingly mundane, destructive and maladaptive, are ultimately emergent from the expression of a message in a molecule. That molecule is DNA. DNA is an information molecule – a polymer in which information is encoded. For example, our DNA contains some 25,000 genic protein-coding regions. However, DNA is ultimately only a chemical that is now fairly easy to synthesize in the laboratory. The total DNA of a bacterium was recently made in a laboratory, and it is probably only a matter of time and motivation before someone synthesizes the whole genome of a more complex creature – even a human. Also, because of the tools now available to study DNA and the ability to study its effects in powerful contexts, including in animal models in which genes are knocked out, the science of genetics has now achieved what seemed impossible only a few years ago. We have demonstrated the causal connection, and not just the correlation, between single genetic variants and complex human behaviors. As will be shown, this reductionistic explanation of human behavior is only in its infancy, and complicated by many difficulties and some false leads.

With some 25,000 protein building blocks and probably an equal number of regulatory RNA molecules, and even allowing for variations in structure, how is it possible that the DNA message can encode a human brain, with its 10¹⁵ (one billion×one million) connections? How, based on the DNA code, can a brain build itself? Is it possible that the complexity of human behavior, and even free will, can be derived from the chemistry of DNA? As will be proposed, the answer lies in the way that this relatively small complement of genes directs a developmental sequence that continues throughout life and that is guided by principles, stochastic in countless details and always completely individual.

Pathways from neurobiology to complex behavior, and the ability of things we cannot control to shape behavior, are illustrated by sex. Why do men and women behave as if from different planets and, beyond the effects of culture, how are we to understand the origins of variations in sexual behavior of sex-specific behaviors ranging from attachment, to aggression, to homosexuality? Is there a gay gene? Why is there a genetics of sexual behavior and how can we understand the diversity, or even perversity, of human sexual behavior? A clue is that in other animals there are sex genes and several have been identified, although in the human the identity of these genes is yet unknown. What are the implications for choice and conceptions of personal freedom that people are born male, female, or gay, or that a switch in the function of a single gene can cause a fish to stop acting like a female, and start acting like a