DNA: The Secret of Life

DNA Tells the story of the amazing molecule since its discovery, following modern genetics from his own Nobel prize-winning work in the fifties to Dolly, the sheep, designer babies and GM foods. This guide to one of the most triumphant achievements of human science introduces the science of modern genetics, along with its history and its implications. Full description

Chapter One
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Beginnings of Genetics: From Mendel to Hitler

My mother, Bonnie Jean, believed in genes. She was proud of her father's Scottish origins, and saw in him the traditional Scottish virtues of honesty, hard work, and thriftiness. She, too, possessed these qualities and felt that they must have been passed down to her from him. His tragic early death meant that her only nongenetic legacy was a set of tiny little girl's kilts he had ordered for her from Glasgow. Perhaps therefore it is not surprising that she valued her father's biological legacy over his material one.

Growing up, I had endless arguments with Mother about the relative roles played by nature and nurture in shaping us. By choosing nurture over nature, I was effectively subscribing to the belief that I could make myself into whatever I wanted to be. I did not want to accept that my genes mattered that much, preferring to attribute my Watson grandmother's extreme fatness to her having overeaten. If her shape was the product of her genes, then I too might have a hefty future. However, even as a teenager, I would not have disputed the evident basics of inheritance, that like begets like. My arguments with my mother concerned complex characteristics like aspects of personality, not the simple attributes that, even as an obstinate adolescent, I could see were passed down over the generations, resulting in "family likeness." My nose is my mother's and now belongs to my three sons.

Sometimes characteristics come and go within a few generations, but sometimes they persist over many. One of the most famous examples of a long-lived trait is known as the "Hapsburg Lip." This distinctive elongation of the jaw and droopiness to the lower lip-which made the Hapsburg rulers of Europe such a nightmare assignment for generations of court portrait painters-was passed down intact over at least twenty-three generations.

The Hapsburgs added to their genetic woes by intermarrying. Arranging marriages between different branches of the Hapsburg clan and often among close relatives may have made political sense as a way of building alliances and ensuring dynastic succession, but it was anything but astute in genetic terms. Inbreeding of this kind can result in genetic disease, as the Hapsburgs found out to their cost. Charles II, the last of the Hapsburg monarchs in Spain, not only boasted a prize-worthy example of the family lip-he could not even chew his own food-but was also a complete invalid, and incapable, despite two marriages, of producing children.

Genetic disease has long stalked humanity. In some cases, such as Charles II's, it has had a direct impact on history. Retrospective diagnosis has suggested that George III, the English king whose principal claim to fame is to have lost the American colonies in the Revolutionary War, suffered from an inherited disease, porphyria, which causes periodic bouts of madness. Some historians-mainly British ones-have argued that it was the distraction caused by George's illness that permitted the Americans' against-the-odds military success. While most hereditary diseases have no such geopolitical impact, they nevertheless have brutal and often tragic consequences for the afflicted families, sometimes for many generations. Understanding genetics is not just about understanding why we look like our parents. It is also about coming to grips with some of humankind's oldest enemies: the flaws in our genes that cause genetic disease.

our ancestors must have wondered about the workings of heredity as soon as evolution endowed them with brains capable of formulating the right kind of question. And the readily observable principle that close relatives tend to be similar can carry you a long way if, like our ancestors, your concern with the application of genetics is limited to practical matters like improving domesticated animals (for, say, milk yield in cattle) and plants (for, say, the size of fruit). Generations of careful selection-breeding initially to domesticate appropriate species, and then breeding only from the most productive cows and from the trees with the largest fruit-resulted in animals and plants tailor-made for human purposes. Underlying this enormous unrecorded effort is that simple rule of thumb: that the most productive cows will produce highly productive offspring and from the seeds of trees with large fruit large-fruited trees will grow. Thus, despite the extraordinary advances of the past hundred years or so, the twentieth and twenty-first centuries by no means have a monopoly on genetic insight. Although it wasn't until 1909 that the British biologist William Bateson gave the science of inheritance a name, genetics, and although the DNA revolution has opened up new and extraordinary vistas of potential progress, in fact the single greatest application of genetics to human well-being was carried out eons ago by anonymous ancient farmers. Almost everything we eat-cereals, fruit, meat, dairy products-is the legacy of that earliest and most far-reaching application of genetic manipulations to human problems.

An understanding of the actual mechanics of genetics proved a tougher nut to crack. Gregor Mendel (1822-1884) published his famous paper on the subject in 1866 (and it was ignored by the scientific community for another thirty-four years). Why did it take so long? After all, heredity is a major aspect of the natural world, and, more important, it is readily, and universally, observable: a dog owner sees how a cross between a brown and black dog turns out, and all parents consciously or subconsciously track the appearance of their own characteristics in their children. One simple reason is that genetic mechanisms turn out to be complicated. Mendel's solution to the problem is not intuitively obvious: children are not, after all, simply a blend of their parents' characteristics. Perhaps most important was the failure by early biologists to distinguish between two fundamentally different processes, heredity and development. Today we understand that a fertilized egg contains the genetic information, contributed by both parents, that determines whether someone will be afflicted with, say, porphyria. That is heredity. The subsequent process, the development of a new individual from that humble starting point of a single cell, the fertilized egg, involves implementing that information. Broken down in terms of academic disciplines, genetics focuses on the information and developmental biology focuses on the use of that information. Lumping heredity and development together into a single phenomenon, early scientists never asked the questions that might have steered them toward the secret of heredity. Nevertheless, the effort had been under way in some form since the dawn of Western history.

The Greeks, including Hippocrates, pondered heredity. They devised a theory of "pangenesis," which claimed that sex involved the transfer of miniaturized body parts: "Hairs, nails, veins, arteries, tendons and their bones, albeit invisible as their particles are so small. While growing, they gradually separate from each other." This idea enjoyed a brief renaissance when Charles Darwin, desperate to support his theory of evolution by natural selection with a viable hypothesis of inheritance, put forward a modified version of pangenesis in the second half of the nineteenth century. In Darwin's scheme, each organ-eyes, kidneys, bones-contributed circulating "gemmules" that accumulated in the sex organs, and were ultimately exchanged in the course of sexual reproduction. Because these gemmules were produced throughout an organism's lifetime, Darwin argued any change that occurred in the individual after birth, like the stretch of a giraffe's neck imparted by craning for the highest foliage, could be passed on to the next generation. Ironically, then, to buttress his theory of natural selection Darwin came to champion aspects of Lamarck's theory of inheritance of acquired characteristics-the very theory that his evolutionary ideas did so much to discredit. Darwin was invoking only Lamarck's theory of inheritance; he continued to believe that natural selection was the driving force behind evolution, but supposed that natural selection operated on the variation produced by pangenesis. Had Darwin known about Mendel's work (although Mendel published his results shortly after The Origin of Species appeared, Darwin was never aware of them), he might have been spared the embarrassment of this late-career endorsement of some of Lamarck's ideas.

Whereas pangenesis supposed that embryos were assembled from a set of minuscule components, another approach, "preformationism," avoided the assembly step altogether: either the egg or the sperm (exactly which was a contentious issue) contained a complete preformed individual called a homunculus. Development was therefore merely a matter of enlarging this into a fully formed being. In the days of preformationism, what we now recognize as genetic disease was variously interpreted: sometimes as a manifestation of the wrath of God or the mischief of demons and devils; sometimes as evidence of either an excess of or a deficit of the father's "seed"; sometimes as the result of "wicked thoughts" on the part of the mother during pregnancy. On the premise that fetal malformation can result when a pregnant mother's desires are thwarted, leaving her feeling stressed and frustrated, Napoleon passed a law permitting expectant mothers to shoplift. None of these notions, needless to say, did much to advance our understanding of genetic disease.

By the early nineteenth century, better microscopes had defeated preformationism. Look as hard as you like, you will never see a tiny homunculus curled up inside a sperm or egg cell. Pangenesis, though an earlier misconception, lasted rather longer-the argument would persist that the gemmules were simply too small to visualize-but was eventually laid to rest by August Weismann, who argued that inheritance depended on the continuity of germ pl...