Sun, Dec 01, 2002 - Page 9 News List

Where will genetic knowledge lead us?

The language of DNA uses only the letters G, C, A and T, but the book written in this language will have an enormous impact on our future

By Leroy Hood

ILLUSTRATION: MOUNTAIN PEOPLE

Deciphering the human genome has provided insights into the nature of humanity, our relationship to the world and our future. We now have the set of instructions that specifies human development -- how each of us progressed from a single cell (a fertilized egg) to an adult human comprising a hundred trillion cells of thousands of different types. So what comes next?

The genome's language is DNA, whose alphabet has just four different letters: G, C, A and T. But the genome contains 3 billion of these letters. The Human Genome Project translated them into a Book of Life, that consists of 500 volumes, each with 1,000 pages averaging 1,000 six-letter words per page. Operationally, the human genome is composed of one long sentence of 3 billion letters cut into 24 pieces -- chromosomes -- that range in size from 45 million-280 million letters.

In a book, words are collected into sentences, sentences into paragraphs and paragraphs into chapters. Each level provides a higher, more coherent level of meaning. So, too, with the human genome. DNA's words are genes, which encode proteins -- the molecular building blocks of life. Genes and proteins are, in turn, gathered into the biological systems -- heart, brain, kidneys and so forth -- that execute the functions of life.

The first draft of the human genome, published in February last year, provided four new fundamental insights. First, humanity's Book of Life has only 30,000-35,000 different words, or genes. This is surprising, because the genome of a tiny worm that had been sequenced earlier contains about 20,000 genes. How we make do with only one-third more genes than this simple worm remains an unanswered puzzle.

Second, there are essentially no race-specific words in the Book of Life. Indeed, the Book of Life for two black people may differ more than that for a Caucasian person and a black person. The concept of race is cultural, not genetic.

Third, the books of life for humans, fish, flies, and yeast contain a large number of shared words (although the spellings are somewhat different). Many fundamental biological systems composed of these genes and proteins are remarkably similar. This underscores the descent of all life from a single common ancestor.

The fourth observation similarly highlights the interconnectedness of all life. For example, the Book of Life for humans contains around 200 genes derived from other organisms, contradicting the long-held view that all of our genes are transmitted vertically, from grandparents to parents to children. It seems that evolution also occurs in a horizontal context, in which any living creature can incorporate information from surrounding organisms.

The knowledge contained in the Book of Life has catalyzed paradigm changes in biology and medicine. We can now study a biological system in terms of how all of its components interact rather than one gene or one protein at a time. Indeed, the Institute for Systems Biology, which I cofounded two years ago, reflects my conviction that systems approaches will dominate biological study in the 21st century.

The paradigm change in medicine will be similarly radical. The next 10-15 years will see a shift away from our current reactive model -- you come in when you get sick and the physician attempts to make you well -- to a predictive, preventive and ultimately a personalized form of medicine.

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