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Fifty years ago, James D. Watson, then just twentyfour, helped launch the greatest ongoing scientific quest of our time. Now, with unique authority and sweeping vision, he gives us the first full account of the genetic revolution--from Mendel's garden to the double helix to the sequencing of the human genome and beyond. Watson's lively, panoramic narrative begins with the fanciful speculations of the ancients as to why "like begets like" before skipping ahead to 1866, when an Austrian monk named Gregor Mendel first deduced the basic laws of inheritance. But genetics as we recognize it today--with its capacity, both thrilling and sobering, to manipulate the very essence of living things--came into being only with the rise of molecular investigations culminating in the breakthrough discovery of the structure of DNA, for which Watson shared a Nobel prize in 1962. In the DNA molecule's graceful curves was the key to a whole new science. Having shown that the secret of life is chemical, modern genetics has set mankind off on a journey unimaginable just a few decades ago. Watson provides the general reader with clear explanations of molecular processes and emerging technologies. He shows us how DNA continues to alter our understanding of human origins, and of our identities as groups and as individuals. And with the insight of one who has remained close to every advance in research since the double helix, he reveals how genetics has unleashed a wealth of possibilities to alter the human condition--from genetically modified foods to genetically modified babies--and transformed itself from a domain of pure research into one of big business as well. It is a sometimes topsy-turvy world full of great minds and great egos, driven by ambitions to improve the human condition as well as to improve investment portfolios, a world vividly captured in these pages. Facing a future of choices and social and ethical implications of which we dare not remain uninformed, we could have no better guide than James Watson, who leads us with the same bravura storytelling that made The Double Helix one of the most successful books on science ever published. Infused with a scientist's awe at nature's marvels and a humanist's profound sympathies,DNAis destined to become the classic telling of the defining scientific saga of our age. From the Hardcover edition.

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Chapter One . . . 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 plasm between generations and thus changes to the body over an individual's lifetime could not be transmitted to subsequent generations. His simple experiment involved cutting the tails off several generations of mice. According to Darwin's pangenesis, tailless mice would produce gemmules signifying "no tail" and so their offspring should develop a severely stunted hind appendage or none at all. When Weismann showed that the tail kept appearing after many generations of amputees, pangenesis bit the dust. gregor Mendel was the one who got it right. By any standards, however, he was an unlikely candidate for scientific superstardom. Born to a farming family in what is now the Czech Republic, he excelled at the village school and, at twenty-one, entered the Augustinian monastery at Brünn. After proving a disaster as a parish priest-his response to the ministry was a nervous breakdown-he tried his hand at teaching. By all accounts he was a good teacher, but in order to qualify to teach a full range of subjects, he had to take an exam. He failed it. Mendel's father superior, Abbot Napp, then dispatched him to the University of Vienna, where he was to bone up full-time for the retesting. Despite apparently doing well in physics at Vienna, Mendel again failed the exam, and so never rose above the rank of substitute teacher. Around 1856, at Abbot Napp's suggestion, Mendel undertook some scientific experiments on heredity. He chose to study a number of characteristics of the pea plants he grew in his own patch of the monastery garden. In 1865 he presented his results to the local natural history society in two lectures, and, a year later, published them in the society's journal. The work was a tour de force: the experiments were brilliantly designed and painstakingly executed, and his analysis of the results was insightful and deft. It seems that his training in physics contributed to his breakthrough because, unlike other biologists of that time, he approached the problem quantitatively. Rather than simply noting that crossbreeding of red and white flowers resulted in some red and some white offspring, Mendel actually counted them, realizing that the ratios of red to white progeny might be significant-as indeed they are. Despite sending copies of his article to various prominent scientists, Mendel found himself completely ignored by the scientific community. His attempt to draw attention to his results merely backfired. He wrote to his one contact among the ranking scientists of the day, botanist Karl Nägeli in Munich, asking him to replicate the experiments, and he duly sent off 140 carefully labeled packets of seeds. He should not have bothered. Nägeli believed that the obscure monk should be of service to him, rather than the other way around, so he sent Mendel seeds of his own favorite plant, hawkweed, challenging the monk to re-create his results with a different species. Sad to say, for various reasons, hawkweed is not well-suited to breeding experiments such as those Mendel had performed on the peas. The entire exercise was a waste of his time. Mendel's low-profile existence as monk-teacher-researcher ended abruptly in 1868 when, on Napp's death, he was elected abbot of the monastery. Although he continued his research-increasingly on bees and the weather-administrative duties were a burden, especially as the monastery became embroiled in a messy dispute over back taxes. Other factors, too, hampered him as a scientist. Portliness eventually curtailed his fieldwork: as he wrote, hill climbing had become "very difficult for me in a world where universal gravitation prevails." His doctors prescribed tobacco to keep his weight in check, and he obliged them by smoking twenty cigars a day, as many as Winston Churchill. It was not his lungs, however, that let him down: in 1884, at the age of sixty-one, Mendel succumbed to a combination of heart and kidney disease. Not only were Mendel's results buried in an obscure journal, but they would have been unintelligible to most scientists of the era. He was far ahead of his time with his combination of careful experiment and sophisticated quantitative analysis. Little wonder, perhaps, that it was not until 1900 that the scientific community caught up with him. The rediscovery of Mendel's work, by three plant geneticists interested in similar problems, provoked a scientific revolution. At last the scientific world was ready for the monk's peas. mendel realized that there are specific factors-later to be called "genes"-that are passed from parent to offspring. He worked out that these factors come in pairs and that the offspring receives one from each parent. Noticing that peas came in two distinct colors, green and yellow, he deduced that there were two versions of the pea-color gene. A pea has to have two copies of the G version if it is to become green, in which case we say that it is GG for the pea-color gene. It must therefore have received a G pea-color gene from both of its parents. However, yellow peas can result both from YY and YG combinations. Having only one copy of the Y version is sufficient to produce yellow peas. Y trumps G. Because in the YG case the Y signal dominates the G signal, we call Y "dominant." The subordinate G version of the pea-color gene is called "recessive." Each parent pea plant has two copies of the pea-color gene, yet it contributes only one copy to each offspring; the other copy is furnished by the other parent. In plants, pollen grains contain sperm cells-the male contribution to the next generation-and each sperm cell contains just one copy of the pea-color gene. A parent pea plant with a YG combination will produce sperm that contain either a Y version or a G one. Mendel discovered that the process is random: 50 percent of the sperm produced by that plant will have a Y and 50 percent will have a G. From the Hardcover edition. Excerpted from DNA: The Secret of Life by James D. Watson, Andrew Berry All rights reserved by the original copyright owners. Excerpts are provided for display purposes only and may not be reproduced, reprinted or distributed without the written permission of the publisher.

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Library Journal Review

Watson celebrates the 50th anniversary of the discovery of DNA. Catch him on the five-part PBS series in April or on the eight-city author tour. (c) Copyright 2010. Library Journals LLC, a wholly owned subsidiary of Media Source, Inc. No redistribution permitted.

Publishers Weekly Review

Who better than James Watson to lead a guided tour of DNA? When he and his English colleague, Francis Crick, discovered the double helix structure of the DNA molecule in 1953, little could they imagine that a mere 50 years later scientists would be putting the finishing touches on a map of the human genome. In this magisterial work, Watson, who won the Nobel Prize with Crick for their discovery, guides readers through the startling and rapid advances in genetic technology and what these advances will mean for our lives. Watson covers all aspects of the genome, from the layout of four simple bases on the DNA molecule through their complex construction into genes, then to the mechanisms whereby proteins produced by genes create our uniquely human characteristics-as well as the genetic mutations that can cause illnesses or inherited diseases like Duchenne muscular dystrophy and Huntington's disease. Watson may have mellowed a little over the years since he displayed his youthful brashness in The Double Helix, but he still isn't shy about taking on controversial subjects. He criticizes biotech corporations for patenting genes, making diagnostic medical procedures horribly expensive and damping further basic research. He notes that while China and other countries with large populations to feed have eagerly grasped the potential of genetically modified foodstuffs, America squandered $100 million on a recall of taco shells and the genetically modified corn used in them. He pleads passionately for the refinement and widespread use of prenatal genetic testing. Watson will probably provoke the most controversy with his criticism of scientists, corporations and government funding sources for their avoidance of important areas of research-notably the genetics of skin coloration-for political reasons. Every reader who wants to understand their own medical future will want to read this book. 100 color and b&w illus. 150,000 first printing; BOMC and History Book Club selection. (Apr. 7) FYI: A five-part PBS series on DNA featuring Watson will air later this year. (c) Copyright PWxyz, LLC. All rights reserved

CHOICE Review

This book is what one might expect from the author of perhaps the most popular and notorious book ever written about science. For the 50th anniversary of the discovery of the structure of DNA, Watson recaps The Double Helix (CH, May'68) and brings genetic research up-to-date. (Not disparaging his coauthor's contribution, the first-person voice throughout is clearly Watson's.) Whatever hesitation Watson may have felt about Crick proclaiming the DNA structure "the secret of life" in 1953, he has embraced the belief since. He offers an excellent, attractively produced insider account of both history and the state of the art, portraying the light-hearted and human sides of science along with the serious. The book is also a soapbox for Watson's advocacy of genetic engineering and condescension toward its critics. Invoking Frankenstein--and the film Gattaca (1999)--to illuminate public anxiety over genetic tinkering, he remains sanguine about the greater good to come of it. Physicists may have "known sin" after the atomic bomb, but Watson does not admit to any fall from grace for biologists. (Nor does he do much to right the wrong done to Rosalind Franklin in his earlier account.) A Web site supplements the book. ^BSumming Up: Recommended. General readers. L. W. Moore formerly, University of Kentucky

Booklist Review

Intended to enlighten those with "zero biological knowledge," this history of the genetics revolution coincides with the fiftieth anniversary of Watson and Francis Crick's coup in divining DNA's structure. A leader of the revolution as an administrator and public defender, Watson throughout the work addresses objections leveled at molecular manipulation. It's a fair-minded approach that fruitfully combines with Watson's clarity about the biochemistry underlying, for instance, the dread of genetically modified crops; if by his conclusion, a reader still adamantly opposes this or that technology, at least the stance won't be in the face of ignorance. Alongside this mission of enlightenment, Watson repeats a penchant for colorful characterization of rivals--perhaps the factor that made The Double Helix (1968) such a controversial classic. Previously caricatured, Rosalind Franklin now comes off more generously, Watson conceding that her work (vital to his and Crick's visualization of the double helix) justified a Nobel Prize had she not died tragically early. Nobel winners subsequently crowd Watson's narrative, accorded the laurels for their milestones in deducing pathways from DNA replication to protein production; in isolating individual genes; and in the invention of DNA amplification that makes fingerprinting and genome mapping possible. Whatever one's feelings about it, genetic engineering has rarely been as plainly explained as in this tremendously cogent tour d'horizon, a capstone worthy of Watson's career as a public scientist. --Gilbert Taylor

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James Dewey Watson James D. Watson was born on April 6, 1928. Watson was an extremely industrious student and entered the University of Chicago when he was only 15. He received his Bachelor of Science degree in Zoology four years later, and went on to earn a Ph.D. in the same subject at Indiana University. He was performing research at the University of Copenhagen in Denmark, when he first learned of the biomolecular research at the Cavendish Laboratory of Cambridge University in England. Watson joined Francis Crick in this work in 1951.

At the age of 25, he and colleague Crick discovered the structure of DNA, the double helix. Watson went on to become a Senior Research Fellow in Biology at the California Institute of Technology, before returning to Cambridge in 1955. The following year he moved to Harvard University, where he became Professor of Biology, a post he held until 1976. Watson and Crick won the 1962 Nobel Laureate in Medicine for their discoveries concerning the molecular structure of nuclear acids and its significance for information transfer in living material. In 1968, Watson published his account of the DNA discovery, "The Double Helix." The book became an international best-seller.

Watson became the Director and later President of the Cold Spring Harbor Laboratory. In 1988 he served as Director of the Human Genome Project at the National Institutes of Health, a massive project to decipher the entire genetic code of the human species. Watson has received many awards and medals for his work, along with the Nobel Prize, he has also received the Presidential Medal of Freedom.

(Bowker Author Biography)