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, Second Edition explains how the complexity of human behavior, including concepts of free will, derives from a relatively small number of genes, which direct neurodevelopmental sequences. 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. Here, 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 the topics of epigenetics and the predictive power of behavioral genetics.

In the decade since the first edition published, knowledge of genetic influences on the neurogenetic underpinnings of behavior has been transformed by genomic technologies. Genome-Wide Association studies, for example, have revealed that hundreds of genes influence vulnerability to psychiatric disease and innate predisposition to risk-taking behaviors. This new edition has been thoroughly revised to focus on free will and its neurogenetic origins. In addition, the use of polygenic scores for behavioral prediction are discussed in-depth, reflecting the GWAS (Genome-Wide Association Study) revolution and combined use of genetic predictors in polygenic scores. Sections on epigenetics are also substantially expanded throughout, better defined, and tied to neuroplasticity and gene-environment interaction. Figures and illustrations have been added or improved throughout, and disease nosology and terminology has been updated.

• Updates on the previous edition which was the 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
• Features expanded sections on the neurogenetic basis of free will, polygenic risk scores, and epigenetic influence over behavior, as well as improved figures and updated terminology

• Language: English
• Publisher: Academic Press
• Release date: Sep 4, 2023
• ISBN: 9780443221620

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.

Book preview

Preface

This book is a story, and an analysis, of the neurogenetic origins of behavior and free will in the context of a modern appreciation of neurogenetic determinism. None of us chooses our parents, ancestors, or the past world that shaped our genomes and that in the present constrains our behaviors.

From early in life, we hear whatever will be will be or later the more elegant formulations of the inexorability of determinism such as that of Soren Kierkegaard, who said that we all come into this world with sealed orders. Conversely, we are taught that life and what we become is what we make it. From an early age, we learn to treat people as if they are free. We reward or punish them as if they choose, according to them the gift of respect as autonomous beings, rather than treating them as things.

In part, we treat others as free because we empathize with their thoughts and emotions and understand the conflicting motivations that led to the behavior that we may or may not like. The failure to make such an emotional connection turns other people into objects and, as they say, makes the world a little colder. However, what if a judge is confronted with a genetic finding that a murderer carries the 2B or not 2B variant, a human polymorphism found by my own laboratory that predisposes some individuals to impulsively murder? Should that information be used to mitigate a sentence or, paradoxically, should the carrier of this gene be viewed as even more dangerous and likely to repeat the act?

In writing this book, I was inspired in part by responses to lectures at national judges' courses on the validity and meaning of such evidence. DNA and brain scans are increasingly used in courtrooms. What should be allowed? How should it be weighed? Is there a neurogenetic basis for moral responsibility, or do we merely treat people as if they are free?

Since the publication of the first edition of Our Genes, Our Choices a decade ago, there have been dramatic advances in DNA technologies and in our understanding of human genetic variation and the influences of genes on behavior. This revised version updates and, in some instances, corrects the original. A revolution in personal genomics includes the new ability to sequence genomes, raising our consciousness about neurogenetic determinism and posing questions about how that information will be used, as illustrated in popular movies (e.g., GATTACA).

Millions of people have purchased genetic scans to better understand their ancestry and nature. However, whereas ancestry can be measured with remarkable precision, the reports they receive are sparse and subject to misinterpretation. People are intensely interested in what their genes say about their personalities and behaviors. Throughout this book, I try to minimize the jargon and the glossary (or even the internet) may assist people who get stuck on some piece of terminology. I strove to select stories to give a step-by-step account of how our DNA builds a brain capable of choosing whether to read all or any portion of a book like this.

Advances in genetics and genomics allowed the genetic code to be read, and although the meaning of the words is still incomplete, the story they are telling is already profound and often surprising. As illustrated by the story of the 2B or not 2B gene, the mystery of whether people are free has only been deepened by these new perspectives. As a neurogeneticist, it is a pleasure for me to chronicle some of the most interesting and profound ways in which genes influence human behavior, in the rich and strange new landscape unveiled by the genome revolution.

Reflecting the evolutionarily linked community of life on Earth, many human behaviors, for example, sexuality, are paralleled in other species, and some are even influenced by genetic variations that act in similar ways and with similar effects. As I like to say, it is my hope that something we learn about the elusive origins of human behavior of people will shed light on the elusive behavior of cats.

In people, neurogenetics gives us new insights into the origins of psychiatric diseases and everyday differences in behavior. I try to describe the ways by which genetic variation interacts with environmental stress and even endocrine differences to make some people warriors and others worriers. We are neurogenetically individual, but does that mean that from conception our DNA is destiny, or, as I will argue, is our DNA heritage paradoxically an essential ingredient in the freedom of the individual?

Life often comes full circle or echoes the events of our formative years, and in my case, the nature of the child was the blueprint for the adult. I became a neuroscientist because, as a child, I perceived that the brain contained the essence of self and humanity, and there is no better way to know oneself than to study the brain.

Simultaneously, and as became a lifelong interest, I perceived a problem. All life is based on causal relationships in the physical universe. The more I learned about myself and others, the more apparent became the connections within webs of causality. Could freedom exist in a world where things do not happen by magic? Why was it that as one of five children, I was like but also unlike my older sister, my younger brothers, and my parents? My dear brother Paul developed schizophrenia and later enriched the lives of all in our family with letters on diverse topics. What were the factors in his genetic predisposition, and what were the wages of his experience? Why do psychiatric diseases, and as I will describe, terrible and dissocial acts, strike close to home and blight the lives of so many of our fellow humans, whom we would also spare such travail?

The genomic era holds unprecedented promise for the discovery of clues to the origins of common, genetically influenced psychiatric diseases and, hopefully, will contribute to their prevention and treatment and perhaps even interrupt sequences of causality within those who would victimize others, the victimizers themselves being a type of victim. We are only at the beginning of the exhilarating process of discovering how genes encode the developmental program of the brain. The way the mystery is unfolding, and my own ability to make some contribution, is everything I could have hoped for when I first arrived at the National Institutes of Health in 1979 from Texas as a raw and overly optimistic young physician with a burning desire to understand the human brain and make a name for himself. The progress is also frustratingly slow and less than what is needed for families such as my own and for the millions of patients and families fighting their own everyday struggles against psychiatric diseases.

Severe psychiatric diseases, schizophrenia, depression, alcohol use disorder, other addictions, obsessive-compulsive disorder, attention deficit hyperactivity disorder, autism, bipolar disorder, phobias, panic disorder, eating disorder, borderline personality disorder and antisocial personality disorder, etc. are common and affect someone in nearly every family. Yet all are stigmatized to one degree or another, and many are frequently denied. A key to why they are stigmatized may be that they impair their capacity to choose. For each of these diseases, therapy is only partially effective. Several have been the particular focus of an antipsychiatry movement that would deny that these problems should be classified as diseases or that people with them can benefit from medical treatment. And, indeed, it is not uncommon that treatment is inappropriately applied.

However, even with our crude knowledge of psychiatric diseases, and a correspondingly pitiful number of diagnostic categories, we can be sure that genes play a strong role in causation. This is because of the inheritance of these diseases. Heritability = Genes. This book describes some of the first instances of gene discovery and false discovery and, in this revision, the rise of polygenic scores that are vastly increasing the power of genetic prediction. Those polygenic scores derive from the whole genome views of human behavior that were only achieved in the past decade via the application of high-throughput genotyping of a million or more genetic markers in populations of a million or more individuals, and as is even now being succeeded by whole exome and whole genome sequencing in such samples. The reason for the large samples is that the gene effects are small, but in their hundreds, they are beginning to add up. Although a genome-level understanding of behavior is still nascent and limited by both our molecular tools for linking sequence variation to behavior and limited knowledge of DNA function, the results are already startling, with hundreds of gene loci detected for even a single choice-related behavior such as risk-taking. As determinants of whatever type are identified, it is only logical that people turn to determinism. A decade ago, in the first edition of this book, I forecast that a new generation of scientists would soon be applying tools immeasurably more powerful, for example, using a new ability to measure the combined imprint of genotype and experience on the genome. In the last decade, not only has gene discovery accelerated, but epigenetic markers can now measure the impact of stress, drugs, and aging on the genome, unlocking part of the complexity of gene-by-environment interaction.

Others have also begun to speak of the implications of neurogenetics for behavioral determinism (e.g., Chris Wilmott in Biological Determinism, Free Will and Moral Responsibility: Insights from Genetics and Neuroscience, 2016). However, this territory remains relatively unknown in relation to its importance. Further, I weigh the evidence and make the case just a little bit differently, proposing that free will arises from the unique ability of humans to guide the paths they take toward choice, via top-down guided plasticity at the individual level and also from the larger choices we make about the nature of the environments in which we live. Other animals, brilliant or brilliantly adapted though may be, do not seem to be capable of that feat—within themselves, within their communities, and across generations, although if and when some such species are identified we should reconsider their status as moral agents.

Understanding the effects of genetic determinants on behavior is still nascent; however, the specter of neurogenetic determinism now looms much larger. We can already be certain of the role of environmental interaction, not only in terms of the general role of stress and endocrine factors but also via the specific gene-by-environment interaction stories that I tell. Genotype can itself become a determinant. With tens of millions of people having taken advantage of opportunities for personal, direct-to-consumer genomic analysis, it is commonplace to see genotypes being used to guide behavior—and, for example, a person who discovers they have genetic roots in Scotland may dutifully take on those cultural trappings, identifying with an ancestry and culture to which they otherwise have no connection.

This book describes how we know about the relationship of genes to behavior, which are foundations for theory of behavior or public policy. It describes a most exciting aspect of the story, which is that as we penetrate deeper into the brain's secret functions, we find that actions of genes tend to be progressively stronger. At the same time, many genetic variants altering human behavior are not disease genes but are literally genes for behavior, having been selected not to alter an obscure brain function but to influence the behavior itself, leading to differences in reaction range of personality and cognition. This fact, and the fact that we all carry thousands of genetic variants, some beneficial and some highly deleterious, represents a profound refutation of the eugenic impulse to identify some humans as fit and others as unfit. Fitness is all about context.

Behavioral genetics has a long and illustrious history but was also from its beginnings and throughout its course marred by eugenics, and polemics on gene vs environment and racial differences, as this book discusses. Putting the gen in genocide, the Nazis sought to exterminate anyone with a quantum of Jewish ancestry. Today, a drop of Ashkenazy ancestry is measured very easily and accurately, and again, people are placing great weight on ancestry and genetic predisposition, and genomics sees right through attempts to pass as having a different ancestry or genetic predisposition. The person in the top decile for body mass index polygenic score is always recognizable as being predisposed to obesity, even if throughout their life they have never been overweight.

Prior to the genome revolution, which happened only in the last decade of the 20th century, behavior geneticists quantified the inheritance of behavior by measuring the resemblance of people at different degrees of genetic relationship. However, with the completion of the draft sequence of the genome, neuropsychiatric genetics has leapt forward to the level of the specific genes and gene variants that alter behavior and how they work. This book tells the story of how this research is being conducted not on a gene-by-gene basis, but on a global, which is to say genomic basis. We have an exciting first glimpse at what we are, and why we are, and the results are startling and controversial in many ways. In modern scientific parlance, the old paradigm of understanding human behavior has been broken or disrupted and now our field is struggling to replace it with something new and based not on a quantitative appreciation of causality (people who experience stress tend to become depressed) but on a more exacting understanding of who that person was before and after the stress.

For me, it has been a privilege to be part of that first generation of behavioral genomicists who have been joined by new generations that have not known things any other way. They are a varied and fascinating lot and comprise part of the cast of characters in this book. I hope that I have not done any of them a disservice with how they are represented or by omitting them. I have mainly written about fellows, friends, colleagues, and scientific heroes who I personally know. Some were in my own lab, some at laboratories with which I collaborated or competed, and some are just old friends, with whom I have contended and created. It would not be in me or like me to write from a biographical perspective, for example, via systematic study of letters or interviews. Yet it is important to point out that in mentioning people in connection to one piece of science, shared events, or a memorable apercu, it was not my intention to minimize their lives or contributions. I only know what I know, and it is from that perspective, as a physician scientist that I wrote this book and more lately revised it. It also might go without saying that this book is not an autobiography. Much more remains unsaid than could be said, even if there was more space in the margins. Meanwhile, the stories I selected are directed toward one fascinating question: Are people free to make choices, or do genes determine behavior? Choosing the stories was the main enjoyment of writing this book. Neurogeneticists are spoiled for choice, and yet I have seen that most of these stories are scarcely known to the public. For example, in some fish, a single genetic switch changes female to male and female behavior to male behavior—both sex and gender are changed. Humans are more complicated—for example, sex and gender are not so tightly linked, but all human behaviors emerge from the expression of DNA.

Are people free to make choices, or do genes determine behavior, much as a genetic switch reprograms the behavior of the fish? My studies of human behavior convince me that paradoxically the answer to both questions is yes because of neurogenetic individuality and self-guided neural plasticity. In Our Genes, Our Choices, the complexity of human behavior and a person's ability to choose are explained as deriving from the ways in which a relatively small number of genes direct a neurodevelopmental sequence. This lifelong process is guided by individual genotype, molecular and physiological principles, by randomness, and by environmental exposures that we choose as well as ones that we do not choose. This theory affirms and provides a mechanism for the origins of free will and the ability to make moral choices, but I suspect that the debate will continue while humans exist.

Chapter 1: Introduction: Thou mayest choose

Abstract

Is the human will free? Do genes determine behavior? Paradoxically, the answer to both questions is yes. Inherited genetic variants cause behavioral differences, including variations in stress resiliency, arousal and impulsivity, sexual orientation, and vulnerability to psychiatric diseases. If people are not free to choose because their fates are controlled by genes and other determinants, then ethical systems built on the as if supposition are fragile. A new theory of behavior based on neurogenetic individuality, and the self-guided development of the brain, has profound implications for conceptions of self, social expectations, ethics, and justice.

Keywords

Free will; Neurogenetics; Gene-by-environment interaction; Neural development; Compatibilism

Timshel—Thou mayest–that gives a choice [between good and evil].

John Steinbeck—East of Eden

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 and top-down driven neural plasticity 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 HTR2B gene, which encodes a receptor for the neurotransmitter serotonin. Serotonin is involved in many aspects of behavior. The functionally disruptive receptor variant causes some people to be impulsive and hyperaroused and irritable, 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 it 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. 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 easy to synthesize in the laboratory. The total DNA of a species of bacteria was recently made in a laboratory, and it is only a matter of time and motivation before someone synthesizes the 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 edited, 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, and has now been vastly augmented, and folded into, polygenic prediction.

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 x one million = quadrillion) 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 the deep evolutionary, developmental, genetic, molecular and cellular levels of explanation to complex behavior, and the ability of things we cannot control to shape behavior, are illustrated by sex. Why do males and females 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 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 male?

Despite the complexity and using methods that can find the needles hidden in the genetic haystack, I and other neurogeneticists have identified the first genes that predict cognitive and emotional differences, and sometimes the same gene can have countervailing effects on both. The ability of genes to predict behavior is explained by example, as are the limitations and nuances that include gene-by-environment interaction. The genetic variants—even in large polygenic combinations—identified so far are not strongly predictive of behavior and their value should not be oversold, as has already been done. Yet they are of explanatory value and foreshadow the discovery of additional variants that must account for the heritability of human behavioral characteristics. Rapid advances in genetic behavioral prediction enhance the case for neurogenetic determinism. The new science of gene-by-environment interaction is explored via genes that can lead to depression, anxiety, impulsivity, and even suicide. For example, genes predispose some people to be resilient warriors and others to be less resilient and pain resistant but sometimes cognitively advantaged worriers. Furthermore, polygenic scores are accounting for increasingly larger fractions in the genetic variance (variation), and total variance in liability to a variety of psychiatric diseases, as well as everyday behaviors such as risk-taking.

The findings in this relatively young science of behavior genetics are not without controversy, as would be expected. Discovery of mechanisms of gene action lag behind gene identification. However, there are solid examples of genetic variations that affect behavior, and that also affect what the brain is doing during behavior, as is now observable with brain imaging, which is a window on the activity of the brain. By imaging the regional structure, activity, and chemistry of the brain, for the first time the basis of the effects of these behaviorally important genes has been understood. Also, their predictive effects on brain function itself are much stronger than on overtly manifested behaviors. Several genes with weak effects on anxiety and emotion have strong effects on brain responses to emotional challenges. Two genes that influence cognition have strong effects on brain activity while people are asked to perform cognitive tasks that challenge specific parts, and neuronal networks, of the brain. By studying the combined effects of many genes, overlaps in genetic causation that had been observed via cross-inheritance of different diseases in twins are now being observed at the gene level. Genes not only partly determine behavior, but the same genes influence multiple behaviors.

This book is concerned with the neurogenetic foundations of behavior and with the possibilities and limits of genetic behavioral prediction; however, it is unavoidable that these discoveries would be connected to conceptions of self and freedom. These questions are strongly embedded in popular culture, as I will touch upon in this book. In recent years the ages old debates about self and freedom have partly motivated many fine books, and here to cite a few (Churchland, 2011; Damasio, 2005; Dawkins, 1996; Dennett, 1984, 1996, 2004; Kane, 2005; Pereboom, 1997; Sternberg, 2010; Wilmott, 2016). Is it sufficient to treat people as if they have free will? I argue that it is not. The as if stance is inherently inconstant, setting the stage for the easy erosion of individual autonomy whenever situational ethics dictate that it is more expedient to treat people as slaves to causality. Compatibilism is the philosophical position that determinism and free will can be reconciled. However, I would also take issue with Daniel Dennett’s compatibilist formulation, which holds a dependency on culture, morality memes, and child upbringing, and even the idea that to have free will one it is necessary that one must believe in free will or be disabled as a chooser. All are metastable. As will be discussed, individual and group autonomy are the vital bases of moral ethics, for example as applied in the conduct of human research, where these are foundational principles. However, are these principles divined from a philosophical or practical calculus or are they inherent to human nature? Are they suppositions, in which case any system of moral ethics may define humans otherwise, or are they parameters based upon observation?

I will argue that individual free will, and by extension the autonomy of people, is neurogenetically encoded, to be revealed by ongoing self-guided neural plasticity throughout life, and that while it may be impaired in some, we have it whether we deny it. To begin with, and finally, each person, including an identical twin, is neurogenetically individual, and their brain development unfolds stochastically throughout life in a way that makes them unique and ultimately self-determined.

Consequently, people are predictably unpredictable, although it is not this unpredict–ability that itself represents free will, many events, and for example the weather a few months from now, being unpredictable. Freedom is bound to individuality, which is partly the product of neurogenetic determinism, which is itself bound to the ways the human genome, and brain, was shaped by evolution and that would include the random events that altered humankind’s evolutionary path.

Freedom does not consist of randomness: philosophers such as Robert Kane and Dennett were correct to emphasize that free will does not originate in quantum randomness—we cannot assign agency to randomness. However, our brains capitalize on randomness as raw material for the development of our individuality. Dennett warned that we should not look too closely at mental activities, or we may discover that we have no selves. Coming at the problems of self and free will from a neurogenetic perspective, I counter that the more closely we look the stronger the self emerges.

Our deepening understanding of genetic and environmental predictors inevitably improves behavioral prediction. With genotypes, epigenetic markers of environmental exposure and brain scans reading out the connectomics of the brain we can better anticipate responses of any person, be they neuroscientist or philosopher or someone intrigued by their musings. But whether someone may predict our choices, we may choose.

References

Churchland P. Braintrust: What Neuroscience Tells us about Morality. 2011.

Damasio A. Descartes’ Error: Emotion, Reason and the Human Brain. 2005.

Dawkins R. The Blind Watchmaker. 1996.

Dennett D. Elbow Room: The Varieties of Free Will Worth Wanting. 1984.

Dennett D. Darwin’s Dangerous Idea: Evolution and the Meaning of Life. 1996.

Dennett D. Freedom Evolves. 2004.

Kane R. A Contemporary Introduction to Free Will. 2005.

Pereboom D. Free Will. Hackett Readings in Philosophy; 1997.

Sternberg E.J. My Brain Made me Do it: The Rise of Neuroscience and the Threat to Moral Responsibility. 2010.

Wilmott C. Biological Determinism, Free Will and Moral Responsibility: Insights from Genetics and Neuroscience. 2016.

Chapter 2: The jinn in the genome

Abstract

Revolutions in genome knowledge and technology pose questions about the nature of humankind and application of this knowledge and technology. What is the nature of this knowledge? How well equipped by our evolution are humans to use it? A better understanding of our neurogenetic individuality, and underlying drives and weaknesses, can enable people to better use this knowledge, applying it with respect for individual autonomy.

Keywords

Human genome sequence; Neurogenetics; Determinism; Genetic evolution; Cultural evolution

I never saw no miracle of science

That didn’t go from a blessing to a curse

Sting—If I Ever Lose My Faith in You

Fifteen minutes of fame

In 2002 I helped conceive Our Genes/Our Choices, a Public Broadcasting series that explored ethical and legal choices created by the genome revolution. Topics of these Fred Friendly seminars included genetic reproductive decisions and genetic privacy. Our session, Genes, Choices and the Law, was adeptly moderated by Charles Ogletree, a well-known Harvard law professor. The scenario involved a person with Alcohol Use Disorder (then, wrongly called an alcoholic) accused of a crime committed while they were intoxicated, and a genetic test result that might be mitigating (Breyer et al., 2002). I was the geneticist with a predictive test. The scenario, more like science fiction in 2002, is close to reality today, with dozens of genes contributing to AUD identified, and polygenic scores accessible to nearly all following direct-to-consumer genetic testing. My molecular geneticist partner on hand was Dean Hamer, already celebrated for having discovered the gay gene (more on that later). Little did I know what I was getting into, and as they say, my 15 min went by so fast. Seated on my left was my boss Francis Collins. On my right was Justice Stephen Breyer.

Other celebrities included journalist Gwen Ifill, who in 2020 was recognized with her own US Forever stamp. Representing the defendant was Johnny Cochran. The case was a puzzle. Can genes predict behavior? Should predictive tests be used and if so, how? What about genetic tests that could stigmatize groups of people? If a judge rules that evidence can be introduced that a gene influences criminal behavior, would identification of this genetic link in a chain of causality influence our willingness to convict or modify the penalty? Several people including Dean Hamer suggested that I write a book about genes and behavior because of the new implications of neurogenetics for understanding the origins of human behavior. However, at that time (and while Dean was writing another) I was grappling with the puzzles of determinism and free will to which genetic prediction and inborn genetic determinants are bound. If I had not made up my own mind, what business did I have trying to change someone else’s? Eight years later, I attempted a new synthesis on human choice, based on a concept of neurogenetically determined behavioral individuality, and the result was the first edition of Our Genes, Our Choices.

Some famous geneticists and why they are famous

As has been well chronicled, the draft sequence of the human genome was published in 2001 by two rival groups, a corporation led by Craig Venter and a government consortium led by Francis Collins, who codiscovered the cystic fibrosis gene and at that time directed the Human Genome Institute (Lander et al., 2001; Venter and Adams, 2001). Later, Collins became NIH director, stepping down only recently. Because the race for the sequence ended in a virtual dead heat, it was appropriate that both were honored by President Clinton in a Rose Garden ceremony. However, as Collins observed, completion of the draft sequence was only the end of the beginning, bringing us to the starting line of a much longer race to understand how the genome works and to prevent and cure diseases. The advances keep coming. A decade later, Venter synthesized the complete genome of a bacterium (Gibson, 2010). This in-laboratory duplication of nature underlined the fact that all life on Earth, and its complex variations, is ultimately based on the expression of complex chemicals: DNA and RNA, and those chemicals are increasingly open to measurement and