Scientists have for the first time decoded the complete DNA sequence of a single human being, a mammoth feat that shatters old beliefs about the "book of life" and marks a historic step toward the era when medical care can be tailored to an individual's genes.
With the boggling array of genetic quirks, burps and hiccups found in the full DNA sequence of one healthy middle-aged man, the human genome has now shrugged off its reputation for being perhaps the world's most boring and predictable molecule.
Coiled inside the body's cells, DNA is the chemical chain that encodes the instructions to build and operate a human in two sets of 23 chromosomes - one set passed down from each parent.
The first two maps of the human genome, published by an international government-funded consortium and a private company in 2001, were based on a patchwork of DNA from several donors. Both versions were also half maps, decoding only one set of the 23 chromosomes on the assumption the two sets would hardly differ.
Those maps suggested that humans were 99.9 per cent genetically identical, with only one one-thousandth of DNA information accounting for all the vibrant variety of humanity.
Now researchers from Canada, the United States and Spain have decoded all 46 of the chromosomes belonging to J. Craig Venter, the 60-year-old upstart American biologist whose company, Celera Genomics, compiled the private version of the human genome seven years ago. And the results indicate that those first celebrated DNA maps seriously underestimated the genetic diversity of humans - by a factor of at least five.
The new work suggests that the genetic code in the chromosomes we carry can vary widely, not only between any two strangers waiting at a bus stop, but between brothers and sisters.
"The biggest single surprise is how much we missed the boat with the human genome seven years ago, and how different we really are," Dr. Venter said in an interview. "The overwhelming message back then was that we are all like identical clones of each other. ... It's comforting to know we are more unique than that."
The findings, released today in PLoS Biology, a free, online scientific journal, give researchers a trove of new targets when hunting for genetic traits that contribute to disease. They also fuel hopes that people could one day learn from their codes which drugs best suit them, or what ills might befall them and take steps to prevent them.
At the same time, the study serves up a sobering dose of reality for genetic medicine. Diagnosing conditions through genetic tests may be trickier than expected, since the differences between maternal and paternal chromosomes means there could be two very different sides to every story. As well, the work shows that relying on DNA to predict anyone's medical future at the moment might be a lot like reading tea leaves: The picture could be fuzzy and fleeting for a long time to come.
"It is clear," Dr. Venter said, "that we are still at the earliest stages of discovery about ourselves and only with continued sequencing of more individual genomes will we be able to garner a full understanding of how our genes influence our lives."
The more genomes researchers can read, he said, the better they can understand how the genetic script relates to a person's actual performance and tease apart the effects of environmental forces.
Steve Scherer, the senior scientist in Genetics and Genome Biology at Toronto's Hospital for Sick Children who led the analysis of the Venter genome, noted for example that nearly half of Dr. Venter's 23,224 genes contained variants, or mutations - "a number geneticists have wondered about for 50 years." At this point, Dr. Scherer said, no one can interpret most of the new information. In fact, the researchers note that decoding Dr. Venter's DNA has so far revealed not much more about his potential health problems than knowing his family history.
