Jacob's Ladder: The History of the Human Genome [Hardcover]

Henry Gee (Author)

Book Description

Publication Date: July 2004

What makes us as humans all alike and yet as individuals so different?

Jacob's Ladder delivers a remarkably lucid explanation of what the sequencing of the human genome really tells us. Decoding the sequence, evolutionary biologist Henry Gee shows, is just the beginning: seeing the letters and words. The next frontier is in understanding snatches of conversation between genes—how they interact to direct the growth of an organism. Gee takes us into the heart of that conversation, illuminating how genes govern a single egg cell's miraculous transformation into a human being, and how they continue to direct that person's day-by-day development throughout a lifetime.

Gee tells the story of what we know about the genome today and what we are likely to discover tomorrow. As our knowledge advances, we will be able to direct with increasing authority the conversations between genes: not only performing medical interventions but also creating whole scripts directing birth, ancestry, and diversity in a brave new world.

Editorial Reviews

Amazon.com Review

Although sequencing the human genome has brought speculation about all kinds of results--from curing to cloning--another sort of scientific payoff is in the works. In Jacob's Ladder, former UCLA professor Henry Gee shifts focus from the applied science of genomics to the basic research questions that can be addressed with this new information. "To describe the sequencing of the genome as a technical feat," he writes, "is to miss the point." Gee is most excited about the possibilities of understanding what makes us all human, rather than the individual genetic variances that make us individuals. He examines the genome as a motif representing the "pinnacle of human self-knowledge." Further, he claims that the philosophical shadow of Darwin has made us forget that one of the central questions of our being is how all of us are made from nothing, or rather from everything. To redirect thought, he closely describes how genes control the development of every human, both within and before each individual lifetime. While Gee's ideas are large enough to support a book on this by now well-covered subject, general readers will likely be put off by his somewhat dry and academic style. --Therese Littleton

From Publishers Weekly

So we've sequenced the human genome. Now what? Gee, a writer for Nature and former professor at UCLA, tackles this question in his examination of how nature generates "form from the formless." Gee takes his title seriously, describing not only the history of human understanding of biology, but also the history of the evolution of the genome itself. Stories of homunculi and Darwin's legendary journey to the Galápagos lead seamlessly into discussions of the first life to appear on earth. Gee uses comparative genomics to draw a vivid history of the evolution of life, tying together the usually distinct fields of embryology, genetics and evolution. The crowning gem of this work is the last section on the new network theory of genomics. Gee draws the reader into the new field of computational biology and shows that having the sequence of the human genome is just the beginning. By modeling how the thousands of genes act on and with each other, we can finally begin to answer questions like, where do new species come from? How does a single egg turn into a human baby? How does natural selection affect the genome? Why is there any variation at all? The author knows the details of molecular biology, and he's not afraid to use them. The text is littered with terms like "blastocyst," "T4 bacteriophage" and "Hox genes," though all are carefully defined. Because of this level of sophistication, this fine book is difficult enough to be more suitable for the amateur scientist than for the dabbler. 25 illus. not seen by PW.
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Product Details

• Hardcover: 352 pages
• Publisher: W. W. Norton & Company (July 2004)
• Language: English
• ISBN-10: 0393050831
• ISBN-13: 978-0393050837
• Product Dimensions: 9.1 x 6.1 x 1.1 inches
• Shipping Weight: 1.2 pounds
• Average Customer Review: 4.4 out of 5 stars  See all reviews (5 customer reviews)
• Amazon Best Sellers Rank: #509,548 in Books (See Top 100 in Books)

More About the Author

Henry Gee (b. 1962) is a Senior Editor at Nature, the international weekly journal of science. His writing has appeared in magazines and newspapers around the world. He lists his recreations as playing blues organ, supporting Norwich City FC and falling asleep. His blog 'The End Of The Pier Show' continues to delight its three regular readers. He lives in Cromer, Norfolk, England, with his family and numerous pets.

Customer Reviews

Most Helpful Customer Reviews

8 of 8 people found the following review helpful:

5.0 out of 5 stars The History and Potential of Genomics, November 29, 2004

By 

R. Hardy "Rob Hardy" (Columbus, Mississippi USA) - See all my reviews
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This review is from: Jacob's Ladder: The History of the Human Genome (Hardcover)

Once human DNA had been completely charted, some used to think, we'd have answers to just how fertilized eggs turn into humans, and even what it is to be human. Sequencing the human genome would be the foundation that would explain everything that cells do to work together and produce a human. It hasn't come close to doing this, of course. There is too much going on within even that simplest first fertilized egg cell for us to understand. Certainly, there has been much learned, including some humbling lessons; our DNA shows we are still very close in many ways to the mice that share our mammalian evolutionary heritage, and we are even close to fish and other vertebrates. But scientists didn't start asking questions about the issues in genomics only when genes or DNA were discovered. In _Jacob's Ladder: The History of the Human Genome_ (Norton), Henry Gee has looked at the ways people tried to understand what genes do even before they knew there were any such things. His book is valuable in showing that many of the questions that are still being asked today were being asked by the first men to record their thoughts about how reproduction was accomplished.

Aristotle knew about eggs, bird eggs, and he knew about menstruation. He formed the idea that when menstruation stopped, the unshed blood stayed in the woman and when it met with semen from the male, it was sparked into life. This dogma was first challenged in 1651 by William Harvey, who is more famous for having charted the activity of the circulatory system. He had the insight that life came from an egg, even in mammals. Of course he had no understanding of cells, or eggs and sperm being cells. He thought the egg was formless matter that somehow gave forth form. When microscopists eventually saw sperm, they thought that they were mere parasites, like so many worms that writhe within tissue. Some suspected they also played a role in fertilization, but as late as 1835 they were classed as a distinct order of worms. The nature-philosophers, with Goethe the most prominent exponent, regarded the problem of generation as intractable. It wasn't just that the technology of the time could not make it plain; rather, there was a mystical natural force that impressed form on the formless egg. The force shaped the organic being and pushed for ever-greater perfection. Darwin, who was always frank about any weakness in his ideas of "descent with modification," knew that a blending of father's and mother's characteristics to produce children would eventually produce only blandness, and not the variability that his theory required. He had to guess that there was some sort of particulate inheritance, but he was guessing, and there was no evidence for him to base such a guess on. It was a flaw in evolutionary theory, a flaw eventually made good by genetics, but objections were less often made against this flaw than against the challenge evolution posed to social and religious ideas.

The nature-philosophers stressed unity and complexity, and while Gee cannot accept their mysticism, his explanation in the second part of the book of what genes actually do owes much to their basic ideas. Despite the push to find the gene for schizophrenia or the gene for obesity, genes almost never act on their own, but in networks. There are tangles of genes responding to gene products in many interlocking biochemical pathways. The study of such pathways is "systems biology," with a mutation in one gene affecting a great many pathways. Computer analysis of such systems shows that they are very stable, producing a viable output when the many input variables are widely changed. It is this flexibility that in itself produces the variety that is the powerhouse for evolutionary change, as well as allowing minor changes without letting them completely derail embryonic development. Gee is an editor for the weekly journal _Nature_, and as such has watched the dizzying increase in the speed of biological research in the past decade. It is probably the most important science of our times, with prospects for the conquest of disease as well as the scary possibilities of our someday directing our own development. Gee's account is a useful look at the history of an important part of biological research, as well as a primer on systems biology, which holds promise of much explicatory power in the future.

8 of 9 people found the following review helpful:

5.0 out of 5 stars Makes a very long story short, November 26, 2004

By 

Stephen A. Haines (Ottawa, Ontario Canada) - See all my reviews
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This review is from: Jacob's Ladder: The History of the Human Genome (Hardcover)

Since the announcement of the coarse mapping of the human genome, the media have deluged us with promises of great advances. Medicine, agriculture, psychology, even biotechnology, all seem to be potential beneficiaries of the the unravelling of "what makes us human". Henry Gee, in presenting a sweeping background to these attractive promises, sounds a cautionary note. How is it, he asks, that from the moment of conception a process is unleashed that produces a living child in a mere 200 days? From the merging of two single cells, each carrying their share of the information that built you and i, what led to each of us being distinct individuals, yet bearing an inheritance reaching billions of years back in time?

Although the event is common, with 150 human births occuring every minute, Gee explains that understanding of the process was long in coming. From Aristotle, who thought babies came from menstrual blood to the Enlightenment, which accorded either eggs or sperm with possession of generations of nested individuals, there was a long, tortuous path to understanding conception. Behind that understanding lay much investigation, theorisation and speculation. Gee naturally positions Charles Darwin with a pivotal role in that understanding, but wants us to be aware of the host of other researchers and their contributions. A major hurdle was the distinction between "external" births such as chicken eggs and the delivery method of dogs, horses and humans.

Ironically, it was challenges to Darwin's great insight that led to major advances in genetics. William Bateson sharply criticised Darwin's notion of "gradualism" in forming new species. Bateson thought that gradual change should be visible in animal populations and went looking for them. At the same time, another Darwin critic, Thomas Hunt Morgan, was examining thousands of fruit flies to learn how to identify what Bateson was seeking. Morgan was probably the most reluctant Darwinian since Charles Lyell, but was finally won over by his labouring students who demonstrated how genes worked.

The buildup of the genome over the vast history of life on Earth becomes Gee's next topic. How did we get here and what's the present offer in the way of clues? He uses Graham Cairns Smith notion that the first step in creating a genome likely began in the dense environment of clay crystals. From this molecular origin, the author takes us to a menagerie of creatures, all of whom have something to contribute to the story. We are introduced to the mycoplasma - today's simplest creatures with less than 500 genes. Are they holdovers from an ancient form? We learn that parasites of bacteria have forced the trimming of genomes as a protective strategy. Why haven't we done the same, he asks, or are we in the process? The larger genome of humans, he reminds us, isn't sufficient to explain either our complexity or our uniqueness. Changes in our genome are traceable, with agriculture's introduction a major contributor.

When the history of the study of the genome, whether fruit fly, bacterium or human, has been delineated, Gee takes the investigation a step further. He notes the propensity of the media to tout "a gene for" any number of traits, physical or behavioural. We must use the Internet as a model, he urges. The networking of many computers serves as a template for the information management of the genome. Genes, selfish as they may be in trying to reproduce, must cooperate in complex organisms. Single steps to gain single goals is no longer feasible, if it ever was. The intricate network of genome activity demands further attention.

Like so many modern science writers, Gee chips away at Darwin iconology. He wants to demonstrate that all those "wrong" thinkers of the past made contributions. Unlike many iconoclasts, Gee keeps his critique muted, a welcome change. He also challenges us with questions about where the knowledge of the genome is leading. Knowledge of the human genome has the potential to elevate us from apes to angels. Are we prepared to face the issues that genome manipulation may generate? If you read this book, you will understand his concern. With the knowledge he provides, you will be more prepared. [stephen a. haines - Ottawa, Canada]

7 of 8 people found the following review helpful:

4.0 out of 5 stars Scholarly, serious, provocative, May 9, 2005

By 

Robert Adler "science writer & author" (Santa Rosa, CA USA) - See all my reviews
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This review is from: Jacob's Ladder: The History of the Human Genome (Hardcover)

In _Jacob's Ladder_, science writer Henry Gee sets out to survey the thinking and research on evolution and genetics that led to the sequencing of the human genome and today's focus on genetics and genomics. He also tries to look into the future to make out the outlines of where our newfound genetic knowledge and power may lead.

If you're interested in a serious survey of the story of genetics starting in antiquity, before getting into the human genome and current research, this is the book for you. You'll learn a lot about embryology, about early theories of development and evolution, and about researchers and thinkers whose contributions to this field, broadly construed, you may not have known about, from Aristotle to Caspar Wolff.

I thought the book really got interesting when it began to deal with the question of the evolution of form. How all the intricate forms that define an organism come about, in terms of evolution, genetics and embryology, remains one of the great unanswered questions of biology. Much of _Jacob's Ladder_ is shaped by Gee's fascination with this issue. His answer, that the answer will be found through understanding and modeling the structure and dynamic functioning of genetic networks, makes excellent sense.

I also felt that Gee's speculations about what we as a species may do with our newfound ability to modify our own genes and genetic networks well thought out and provocative.

If you would like to understand the rich soil from which the next year's or the next decade's genetic discoveries and interventions will spring, this would be an excellent place to start.

Robert Adler, author of _Science Firsts: From the Creation of Science to the Science of Creation_ (Wiley, 2002), and _Medical Firsts: From Hippocrates to the Human Genome_ (Wiley, 2004).