Über die Autorin bzw. den Autor

GLYN MOODY is the author of Rebel Code. His work following Linux and its creator Linus Torvalds has been highly acclaimed. Moody’s writings have appeared in numerous publications including Wired magazine, The Economist, New Scientist, Financial Times, The Guardian, and The Daily Telegraph.

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Praise for Digital Code of Life

"The man who wrote the best history yet of the open-source movement in Rebel Code gives us an equally lucid and penetrating look at bioinformatics. Well done!"
Eric S. Raymond
Author of The Cathedral and the Bazaar

"This book provides a riveting account of the history of bioinformatics and of the manner in which bioinformatics has contributed to advancing our knowledge of the human genome. Glyn Moody has chronicled through reviews of key scientific papers and through interviews with leading scientists, the major developments in the field of genomics in the past half century, from the discovery of the double helix to the emergence of proteomics, pointing to their relevance to science, medicine, and industry and to the critical contributions of bioinformatics."
Sam Hanash, University of Michigan
President of The Human Proteome Organisation

Aus dem Klappentext

In just a few decades, computers have become the single most important tool in genomics, thanks to their ability to unlock the meaning of the digital program that underlies all life. Driving this development is bioinformatics, the use of computers to store, search through, and analyze billions of DNA letters.

Bioinformatics turned the dream of sequencing the human genome into reality, allowing humanity to decode the deepest secrets contained in the digital core of life. The rise of bioinformatics has provided pharmaceutical companies with vital information that will aid the search for effective drugs and vaccines, helping to usher in the long-promised era of personalized medicine. It s no wonder that bioinformatics is rapidly becoming the core discipline within biotechnology today one that provides strategic inputs for pharmaceutical companies like Merck, GlaxoSmithKline, Pfizer, and Roche when they decide where to spend billions on the development of potentially lucrative products.

Digital Code of Life offers a behind-the-scenes look at the rapidly growing field of bioinformatics and what medical organizations and companies worldwide are doing to exploit its potential. Filled with in-depth insights and often surprising revelations, Digital Code of Life examines the personalities who have brought bioinformatics into being and explores the commercial applications and investment opportunities of this exciting and groundbreaking discipline, including those in emerging areas.

Glyn Moody, author of the widely praised Rebel Code, offers a fascinating account of the field of bioinformatics for both business technology enthusiasts and healthcare professionals. Here, for the first time, is the real drama of how the complete sequence of the human genome was put together, its resulting impact on the economy as well as the healthcare industry, and the fierce competition between the public and private sectors to reap its rewards.

Brimming with little-known insider facts and valuable insights on how to recognize growth companies in biotechnology and the pharmaceutical industries, Digital Code of Life will prove to be exciting reading for anyone interested in what is potentially the most important new high-technology sector and investment opportunity to emerge in recent years.

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Digital Code of Life

John Wiley & Sons

Chapter One

The digital era of life commenced with the most famous understatement in the history of science:

We wish to suggest a structure for the salt of deoxyribose nucleic acid (D.N.A.). This structure has novel features which are of considerable biological interest.

Thus began a paper that appeared in the journal Nature on April 25, 1953, in which its authors, James Watson and Francis Crick, suggested the now-famous double helix form of DNA. The paper was extraordinary in several ways: first, because Watson and Crick, both relatively young and unknown researchers, had succeeded in beating many more famous rivals in the race to explain the structure of DNA. Second, their proposal managed to meld supreme elegance with great explanatory power-a combination that scientists prize highly. Most of all, the paper was remarkable because it ended once and for all decades of debate and uncertainty about the mechanism of inheritance. In doing so, it marked the starting point for a new era in genetics, biology, and medicine-an era whose first phase would close exactly 50 years after Watson and Crick's paper with the announcement of the complete elucidation of human DNA. The contrast of that half-century's dizzying rate of progress with the preceding centuries' slow groping towards an understanding of inheritance could hardly be greater.

* * *

One hundred and fifty years ago, Gregor Mendel, an Augustinian monk working in what is now the city of Brno in Moravia, carried out the first scientific investigations of heredity. Prior to his meticulous work on crossbreeding sweet peas, knowledge about heredity had existed only as a kind of folk wisdom among those rearing animals or propagating plants.

Mendel crossed sweet peas with pairs of traits-two different seed shapes or flower colors-in an attempt to find laws that governed the inheritance of these characteristics in subsequent generations. After thousands of such experiments, painstakingly recorded and compared, he deduced that these traits were passed from parent to offspring in what he called factors. Mendel realized that these factors came in pairs, one from each parent, and that when the two factors clashed, they did not mix to produce an intermediate result. Rather, one factor would dominate the other in the offspring. The subjugated factor would still persist in a latent form, however, and might reappear in subsequent generations in a remarkably predictable way.

Although it offered key insights into the mechanism of inheritance, Mendel's work was ignored for nearly half a century. This may have been partly due to the fact that his work was not widely read. But even if it had been, his factors may have been too abstract to excite much attention, even though they turned out to be completely correct when recast as the modern idea of genes, the basic units of heredity. In any case, work on heredity shifted to an alternative approach, one based on studying something much more tangible: cells, the basic units of life.

Hermann Muller used just such an approach in 1927 when he showed that bombarding the fruit fly with X-rays could produce mutations-variant forms of the organism. This was important because it indicated that genes were something physical that could be damaged like any other molecule. A chance discovery by Fred Griffith in 1928 that an extract from disease-causing bacteria could pass on virulence to a strain that was normally harmless finally gave researchers the first opportunity to seek out something chemical: the molecule responsible for transmitting the virulence. It was not until 1944, however, that Oswald Avery and his coworkers demonstrated that this substance was deoxyribonucleic acid-DNA.

In many ways, this contrasted sharply with the accepted views on the biochemical basis for heredity. Although DNA had been known for three quarters of a century-Johann Friedrich Miescher discovered it in pus-filled bandages discarded by a hospital-it was regarded as a rather dull chemical consisting of a long, repetitive chain made up of four ingredients called nucleotides. These nucleotides consist of a base-adenine, cytosine, guanine or thymine-each linked to the sugar deoxyribose at one end and a phosphate group at the other. Chemical bonds between the sugar and phosphate group allow very long strings of nucleotides to be built up.

* * *

The conventional wisdom of the time was that genetics needed a suitably complex molecule to hold the amazing richness of heredity. The most complex molecules then known were proteins. They not only form the basic building blocks of all cells, but also take on all the other key roles there such as chemical signaling or the breakdown of food. It was this supposition about protein as the chosen carrier for heredity that made Watson and Crick's alternative proposal so daring. They not only provided a structure for DNA, they offered a framework for how "boring" DNA could store inherited traits.

This framework could not have been more different from the kind most researchers were using at the time. The key properties of a protein are its physical and chemical properties; to use a modern concept, its essence is analogue. Watson and Crick's proposal was that DNA stored heredity not physically (through its shape or chemical properties), but through the information encoded by the sequence of four nucleotides. In other words, the secret of DNA-and of life itself-was digital.

* * *

Because it is the information they represent rather than the chemical or physical properties they possess that matters, the four nucleotides can, for the purposes of inheritance and genetics, be collapsed from the four bases (adenine, cytosine, guanine, and thymine) to four letters. The bases are traditionally represented as A, C, G, and T. This makes explicit the fact that the digital code employed by Nature is not binary-0 and 1-as in today's computers, but quaternary, with four symbols. But the two codes are completely equivalent. To see this, simply replace the quaternary digit A with the binary digits 00, C with 01, G with 10 and T with 11. Then any DNA sequence-for example AGGTCTGAT-can be converted into an equivalent binary sequence-in this case, 00 10 10 11 01 11 10 00 11. Even though the representation is different, the information content is identical.

With the benefit of hindsight, it is easy to see why a digital mechanism for heredity was not just possible but almost necessary. As anyone knows who has made an analogue copy of an audio or video cassette from another copy, the quality of the signal degrades each time. By contrast, a digital copy of a digital music file is always perfect, which is why the music and film industries have switched from a semi-official tolerance of analogue copying to a rabid hatred of the digital kind. Had Nature adopted an analogue storage method for inheritance, it would have been impossible to make the huge number of copies required for the construction of a typical organism. For example, from the fertilized human egg roughly a hundred thousand billion cells are created, each one of which contains a copy of the original DNA. Digital copying ensures that errors are few and can be corrected; analogue copying, however, would have led to a kind of genetic "fuzziness" that would have ruled out all but the simplest organisms.

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