Genetic Explanations

Sheldon Krimsky, Jeremy Gruber, Sheldon Krimsky, Jeremy Gruber

• Publisher: Harvard University Press
• Year: 2013
• ISBN:
  9780674071094
• Topic: Biological Sciences
• Subtopic: Genetics & Genomics
• Index: Biological Sciences

Can genes determine which fifty-year-old will succumb to Alzheimer's, which citizen will turn out on voting day, and which child will be marked for a life of crime? Yes, according to the Internet, a few scientific studies, and some in the biotechnology industry who should know better. Sheldon Krimsky and Jeremy Gruber gather a team of genetic experts to argue that treating genes as the holy grail of our physical being is a patently unscientific endeavor. Genetic Explanations urges us to replace our faith in genetic determinism with scientific knowledge about how DNA actually contributes to human development.The concept of the gene has been steadily revised since Watson and Crick discovered the structure of the DNA molecule in 1953. No longer viewed by scientists as the cell's fixed set of master molecules, genes and DNA are seen as a dynamic script that is ad-libbed at each stage of development. Rather than an autonomous predictor of disease, the DNA we inherit interacts continuously with the environment and functions differently as we age. What our parents hand down to us is just the beginning. Emphasizing relatively new understandings of genetic plasticity and epigenetic inheritance, the authors put into a broad developmental context the role genes are known to play in disease, behavior, evolution, and cognition.Rather than dismissing genetic reductionism out of hand, Krimsky and Gruber ask why it persists despite opposing scientific evidence, how it influences attitudes about human behavior, and how it figures in the politics of research funding.

PART ONE

New Understanding of Genetic Science

CHAPTER ONE

The Mismeasure of the Gene

RUTH HUBBARD

Conscious fraud is probably rare in science. It is also not very interesting, for it tells us little about the nature of scientific activity. Liars, if discovered, are excommunicated; scientists declare that their profession has properly policed itself, and they return to work, mythology unimpaired and objectively vindicated. The prevalence of unconscious finagling, on the other hand, suggests a general conclusion about the context of science. For if scientists can be honestly self-deluded … then prior prejudice may be found anywhere, even in the basics of measuring bones and toting sums.

—Stephen Jay Gould, The Mismeasure of Man

SCIENCE IS AN INTERPRETATION OF NATURE and, like other forms of interpretation, fits into the cultural framework of its time. I shall illustrate this fact by tracing some of the threads that, in the course of the twentieth century, have led to the notion that genes determine virtually all physical and social characteristics of humans and other animals. Currently, everything about us is “in the genes,” and this view offers the hope that once we learn to read our “genetic blueprint,” we will be able to change it and live happily ever after.

The most obvious place to begin this story is with the Austrian monk Gregor Mendel, who in the 1860s developed what have come to be known as Mendel’s laws of inheritance. Using pea plants as his experimental objects, Mendel examined the transmission of flower color and of the shape and texture of the seeds to successive generations. He deliberately selected these traits because they are transmitted in an all-or-nothing fashion, unlike traits that vary continuously, such as weight or size. After performing large numbers of crosses between plants that had been shown to breed true, he was able to describe the numerical regularities in the way the traits were passed from parents to successive generations of offspring that have come to be known as Mendel’s laws. However, he did not speculate about what mechanisms might account for the transmission of traits from one generation to the next and merely suggested that they probably involved “factors” within the plants.

That few scientists paid attention to Mendel’s paper when it was published in 1865 presumably had to do with the fact that there was no larger context into which to put his observations. This situation had changed dramatically by 1900, when his paper was independently “rediscovered” in three laboratories. By that time biologists had observed well-defined structures within the cell’s nucleus that took up chemical stains and were therefore called chromosomes. They had further noted that when cells divide, their chromosomes also divide, so that the two daughter cells end up with the same number of chromosomes as were present in the parent cell. The chromosomes, therefore, were generally accepted as the bearers of heredity, and the idea took hold that Mendel’s “factors” bore some relationship to them.

In 1905 the Danish botanist Wilhelm Johannsen coined the word “gene” to lend more concrete reality to Mendel’s “factors.” At a time when invisible atoms, electrons, and quanta were being accepted into the world of chemistry and physics, biologists had little problem accepting that heredity also was mediated by invisible material particles. Soon a series of groundbreaking experiments, done mainly with fruit flies and corn (maize), led them to decide that the genes must lie along the chromosomes, like beads on a string, and that when the chromosomes were replicated during cell division, the genes also got copied.

During the first half of the twentieth century, biologists became increasingly interested in exploring the molecular constitution of cells and the ways in which molecules participate in the metabolism and growth of organisms. They came up with molecular explanations of human diseases known to have hereditary components, such as sickle-cell disease and phenylketonuria, and identified the specific molecules associated with such conditions.

Chemists and biochemists described various biologically important substances, including vitamins and hormones, and characterized their biological functions in chemical terms. In the process they identified a series of hitherto-unknown carbohydrates and fats and also very large and complex proteins, which had previously been thought to be ill-defined aggregates and not discrete molecules at all. It was an exciting period in which chemically oriented biologists spoke of bringing biology to the molecular level. At the same time, they also tried to understand how different chemical components are integrated into the way whole organisms function, writing books with such titles as The Organism as a Whole, The Wisdom of the Body, and Dynamic Aspects of Biochemistry.1

These kinds of explorations led biochemists to identify protein molecules that function as enzymes, others that mediate muscular contraction and relaxation, and yet others that transport oxygen and CO2 around the body. As part of these kinds of explorations, biochemists came to realize that chromosomes contain both proteins and another type of very large molecule, called DNA, and this raised the question of the chemical nature of genes: are they made of proteins, DNA, or both?

Initially, many biologists favored the idea that DNA forms an inert chromosomal framework to which protein molecules attach themselves as genes. The reason was that although DNA is a very large molecule, it is made up of only six different components: a type of phosphate, a sugar, and the four so-called bases that are now familiar to us by the abbreviations A (adenine), G (guanine), C (cytosine), and T (thymine). The naturally occurring proteins, in contrast, contain twenty different subunits (called amino acids), strung together in many different combinations, and come in many different shapes and sizes. It therefore was easier to imagine that different proteins would be the ones to transmit the various traits for which genes are now assumed to be responsible.

In the late 1940s and early 1950s, however, experiments with bacteria and viruses showed that the hereditary material—the gene—consists of DNA. By then it had become clear that genes are involved in the synthesis of proteins, and biologists had concluded that DNA, in fact, specifies the composition of proteins, but the mechanism by which this happens was an open question. It is, however, crucial to realize that intriguing as this puzzle was, all this time, DNA was looked on as just one of the sorts of molecules that are important to the way cells and organisms function.

All this changed in April 1953 when James Watson and Francis Crick proposed their double-helix model of the structure of DNA.2 Since then DNA has come to be considered the most important molecule in biology, and “molecular biology” has come to refer exclusively to the biological functions of DNA.

To understand this shift in outlook, it is important to consider the social and political dimensions of how DNA and the double helix came to be propelled into the center of biological interest. Watson has described the discovery of the structure of DNA, from his point of view, in his best-selling memoir The Double Helix.3 Although it may be hazardous to do so, it is worth speculating how the story of DNA might have unfolded if one of the other two groups of scientists who were trying to elucidate its structure at that time had “won the race.” I am referring to the great chemist Linus Pauling and his group at the California Institute of Technology in Pasadena and to Rosalind Franklin and Maurice Wilkins, two experts in X-ray diffraction analysis at King’s College London.

For one thing, neither of these two groups was racing. They did not even know there was a race. Only Watson and Crick were racing. As for Pauling, he and his colleagues had recently elucidated the structure of the α-helix, a basic structural component of many of the proteins of biological importance. That was an enormous achievement for which Pauling was shortly awarded a Nobel Prize. Before turning to the structure of DNA, Pauling’s group had already determined the three-dimensional structure of the bases that compose DNA. It therefore seems reasonable to assume that had Pauling been the first to describe the full structure of DNA, it would have been exciting, but it would have been just another of his many major accomplishments.

By all accounts, at the time Watson and Crick unveiled their DNA model, Rosalind Franklin was close to solving the structure herself. She had been working on it for about two years, and although no one (including Franklin) knew it at the time, Watson and Crick drew heavily on her X-ray measurements and on the structural information she derived from them to come up with the double helix.4 Had Franklin been the one to solve the DNA structure, she would, of course, have published it, but she might not have announced it with great fanfare because that was not her style. The structure in itself was beautiful, and people would have been extremely interested, but it might well not have become the biology-shaking event of the century.

In contrast, from the moment Watson and Crick began to think about how to figure out the structure of DNA and long before they had bothered to find out what was known about its chemical composition, they thought of DNA as “the secret of life.” Indeed, Watson writes in The Double Helix that even before they had quite clinched their model, Crick rushed into the pub they frequented to announce in a booming voice that they had “found the secret of life.”5 That is also how they communicated the news of the structure to their colleagues and mentors, although their note in Nature struck the proper objective tone.

What the Watson-Crick model showed (and most people nowadays can find out by reading the newspapers) is that DNA can be pictured as two spiral ribbons wound in parallel to form a double helix. The four bases—the As, Gs, Cs, and Ts—are attached to the ribbons at regular intervals and point toward the center of the helix, hence toward one another much like the teeth on a zipper, except that in DNA the teeth meet rather than overlap one another. What makes the Watson-Crick model so exciting is the fact that in order to get the bases to fit into the double helix, an A on one ribbon, or strand, must abut on a T on the other, and a C on one must abut on a G on the other.

This geometric arrangement means that to copy DNA—the “gene”—the double helix must merely begin to unwind (or, in this metaphor, become unzipped). Each strand can then serve as a template for the synthesis of its partner. As this synthesis progresses, the old strands and their newly formed partners simply zip up to form two identical copies of the original. In other words, the double-helix structure itself explains how DNA—the gene—can get copied. The simplicity of this model has had several ideological consequences. One is that the way DNA is copied has been called “self-replication,” and DNA has come to be referred to as a “self-replicating” molecule. Of course, it is nothing of the sort. DNA does not replicate itself. Cells and, in real life, organisms copy their DNA using each strand of the double helix as the template for the synthesis of its partner. This process requires a whole series of physical and chemical conditions and reactions within the cell.

An important consequence of thinking of DNA as a “self-replicating” molecule, however, was that it sparked the imagination of a number of distinguished physicists and mathematicians who, until then, had shown little interest in biological and biochemical systems and, indeed, perhaps a temperamental aversion to their inherent messiness. At the end of World War II, after two atomic bombs had been dropped on two Japanese cities, many physicists had become disillusioned with physics (the harbinger of death) and were only too glad to turn their attention to biology (the harbinger of life). Following the lead of the German exile and Nobel Prize physicist Erwin Schrödinger, who in his short book What Is Life? had referred to the gene as a code and hailed it as the secret of life,6 they got excited about DNA. Familiar with wartime uses of cybernetics and code breaking, they decided to try to crack the “genetic code” by devising formal solutions for the way different sequences of A, G, C, and T could get translated into the sequences of amino acids that constitute different proteins.

It is important to pay attention to the differences in the conceptual and physical tools the scientists attacking these questions used. As the messy biochemical work of grinding up tissues and isolating their cells and molecules yielded first place to the skills of code breaking, centrifuges, spattered lab coats, and dirty glassware were replaced by paper and pencil and soon by computers. In the process different sequences of A, G, C, and T molecules became a “code,” and the biological and chemical complexities of living organisms were reduced to abstractions about how to translate the linear “code” of DNA into the linear array of the amino acids that make up proteins.

In the process what was conceptually pushed aside was the fact that this “translation” ordinarily happens inside dividing and metabolizing cells of organisms, which live in complicated relationships with their environments. The complexities of such biological and social realities got erased as scientific interest focused on computations and codes rather than on the interrelationships of gooey cells and A molecules and, indeed, of the organisms and social structures among which life gets played out. And although in the end the messy biochemists were the first to work out correspondences between the base sequences in DNA and the composition of proteins (for which they duly got their Nobel Prizes), much of the intellectual drama went with the more theoretical aspects of “breaking the code.”

Before moving on, it is important to remember that by itself, DNA is an inert, sticky glop. It takes organisms or, at least, the enzyme systems extracted from them, along with other essential molecules, to perform the synthetic processes within which DNA specifies either the composition of its own copies or the composition of proteins. As soon as we think of DNA as part of the living cells of living organisms, we realize that even a relatively simple trait, such as eye color, cannot possibly be “caused” by a single gene. Just the synthesis of the pigments that color the iris of our eyes involves the participation of several proteins, the composition of each of which is specified by a different DNA sequence (or “gene”). Further proteins are required to knit the base sequences of these genes together, these proteins require further genes for their synthesis, and so on. Up to this point, we have not even begun to consider how the pigment gets deposited in the proper location in the iris or how our eyes, including the iris, get formed during embryonic development.

We are dealing with a situation in which even the “simplest” inherited trait about which we speak as though it were transmitted by a single gene, such as sickle-cell disease or phenylketonuria, involves the participation of ma...

Table of contents

• Cover
• Half Title
• Title Page
• Copyright
• Dedication
• Contents
• Foreword by Richard Lewontin
• Introduction: Evolving Narratives of Genetic Explanation across Disciplines
• Part One: New Understanding of Genetic Science
• Part Two: Medical Genetics
• Part Three: Genetics in Human Behavior and Culture
• Conclusion: The Unfulfilled Promise of Genomics
• Notes
• Selected Readings
• Acknowledgments
• Contributors
• Index