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  / 

Sun, Dec 01, 2002 - Page 9

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.

For example, if you are a woman with a single bad copy of the breast cancer 1 gene, you have a 70 percent chance of getting breast cancer by the time you are 60 years old. Why only a 70 percent chance? In some cases, defective genes require certain environmental signals to be activated, while another, more likely, explanation is that single defective genes are not enough to cause disease; a number of defective genes must act in concert.

The important point is that within the next 10-15 years we will have identified hundreds of genes that predispose individuals to virtually all of the common, late-onset diseases, such as cancer and cardiovascular, neurological and metabolic diseases. We will be able to take a blood sample, determine the possibility of genetic defects, and create a probabilistic health history of what is likely to happen. Physicians will be able to study your genes in the context of the biological systems within which they operate and learn how to circumvent the limitations they impose.

The predictive, preventive and personalized medicine of the future could include changes in environment, specially designed drugs, gene engineering and embryonic stem cells. All of this will propel us into a very different world, one that may well extend humans' life span by 10-30 years, presenting enormous opportunities, but also confronting us with fascinating and perplexing ethical, social and legal issues.

How, for example, can we capture the enormous potential increase in creativity and productivity if the average human life span is extended into the 90s or even beyond? Who gets to know about predictive health histories? Will we permit doctrinaire religious views to block our ability to explore the enormous potential of embryonic stem cells and thereby lift the yoke of disease from tens of millions of people? These questions underscore our obligation to keep abreast of advances in science and technology, so that we may use the opportunities they provide to better humankind while dealing thoughtfully and rationally with the challenges they present.

Leroy Hood is resident and cofounder of the Institute for Systems Biology, a private nonprofit research institute in Seattle, Washington. One of the pioneers in the Human Genome Project and automated DNA sequencer developer, he won the 2002 Kyoto Prize in advanced technologies.

Copyright: Project Syndicate