Human genome sequences--a potential treasure trove, but how useful?

Abstract

Imagine trying to understand a country and its culture without knowing its language. Only a comprehensive knowledge of the language would give a newcomer the tools to begin to explore and understand the country. Publication of the human genome sequence in February this year (see box) was a little like equipping scientists with the language of the human body. Sequencing, genetics and medicine A genome comprises essentially four main types of molecules, or bases -- adenine, thiamine, guanine and cytosine -- arranged in pairs in a double helical structure. There are 3 billion base pairs and their order carries the instructions to make a human being. Of the entire human genome sequence, only 1.1-1.4% contains genes. Two sequences of the human genome were published simultaneously in February (see main text). They are roughly 92-94% complete. The published sequences suggest that there are 31 000 genes in the human body, far fewer than originally estimated -- vs about 26 000 genes for plants, 18 000 for worms, 13 000 for flies and 6000 for yeast. One sequence was the work of the publicly funded International Human Genome Sequencing Consortium and was published in Nature (15 February 2001). The consortium has made its data freely available to the public via the Internet on a daily basis. Its work was undertaken by about a thousand scientists in six countries, including one developing country, China. The other sequence and its analysis were published by the US commercial company Celera Genomics in Science (16 February 2001). Access to Celera's sequence data is more restricted and there has been much controversy and rivalry between the public and private ventures. The question is complex but what is clear is that Celera's entry into the mass sequencing game spurred the public effort to complete its task earlier than it would have done otherwise. "Making the data publicly available," says Dr Virander Chauhan, director of the International Centre for Genetic Engineering and Biotechnology in New Delhi, India, "has levelled the playing field, so that for the first time a university in New Delhi can compete directly with a university such as Harvard in the States." Though the Human Genome Project was conceived in 1985 and began in earnest in 1990, since the beginning of the century scientists have attempted to identify traits passed down through the generations. Then, with the advent of molecular biology tools, individual genes were isolated and sequenced. In the mid-1980s, biologists, mainly in the USA, began to consider sequencing the whole genome. Sequencing began in the late 1980s. About a decade later, the project got under way in earnest, moving away from earlier concerns about the function of genes and concentrating on the sequencing itself. To transform sequence data into diagnostic tests, vaccines, and therapies, scientists have important questions to answer. Although the location of most of the genes is now known, scientists need to know which gene makes which protein, in which cell and at what stage of life. Then they need to know a protein's specific tasks and how different proteins interact with one another. Equally importantly, researchers want to know how environmental factors influence gene expression. Now that the human genome sequence is known, the focus is firmly back on gene function, only this time researchers will be learning and exploring with an entire genetic language, not only the few words interpreted from isolated observations. The scientific community's reaction has been positive, but tempered by uncertainty over the time it will take for practical results to emerge. "Now," says Dr Virander Chauhan, director of the International Centre for Genetic Engineering and Biotechnology in New Delhi, India, "we can truly start to turn the genetic sequences into information important for medicine." But, cautions Dr Barry Bloom, dean of the Harvard School of Public Health in the USA, "there will be a long haul before the human genome is fully exploited -- even in the West. …