When scientists first embarked on the effort to decipher human DNA more than a decade ago, the plan seemed simple: Break the code, the thinking went, and cures for cancer, Alzheimer's and other diseases wouldn't be far behind.
Today scientists have broken the code -- publishing for the first time the sequence of the 3 billion chemical letters that make up the human DNA.
But the cures are yet to come. Amid all the hoopla surrounding the historic effort, scientists are buckling down for what could be an even more important -- and tougher -- challenge: finding all the genes buried inside DNA and figuring out what they do.
"We're not home yet," says Dr. Victor A. McKusick, a genetics pioneer at the Johns Hopkins University and co-author of a paper on the genome research appearing today in the journal Science.
Until this process--known as "annotation" -- is complete, the decoded genome is little more than a dictionary without the definitions, he says.
Some scientists estimate it could take another century before they fully understand the role genes play in human disease, longevity and behavior and are able to develop new wonder drugs or therapies that repair nature's mistakes.
Out of the estimated 26,000 to 40,000 human genes, the roles of only a fraction are understood. Scientists combing through the decrypted genetic code have so far discovered about 40 genes that appear to play a role in diseases such as deafness, color blindness and muscular dystrophy. Still, cures or interventions to prevent them are a long way off.
Genes are clusters of chemical letters scattered throughout DNA that manufacture proteins and other chemicals. Proteins control the biological machinery of the body's 60 trillion cells.
"Most of biology happens at the protein level, not the DNA level," said J. Craig Venter, head of Celera Genomics, one of the two groups to decode the human genome and announce their results today.
But finding out how proteins do what they do requires untangling the complex relationship between genes and proteins in the body.
Just a decade ago, scientists thought that there were approximately 100,000 different human genes and that each was responsible for making a single protein. But as the number of human genes has dropped, that notion is quickly flying out the lab window.
Although far fewer genes exist than expected, McKusick said, the body is thought to contain as many as 1 million proteins. Scientists now think that each gene must be responsible for producing several proteins.
Detective work
To make sense of our genetic machinery, scientists are resorting to old-fashioned detective work and an unusual collection of tools -- everything from the world's simplest life forms to its most powerful supercomputers. The field -- known as "proteomics" -- is drawing commercial and academic researchers in droves.
Some of the techniques they use are fairly primitive, says McKusick, such as breeding mice without a specific gene and then trying to figure out how these creatures differ from normal, healthy mice. Other scientists are using supercomputers to build virtual test tubes where they can model the behavior of proteins in the body.
Still more scientists are comparing the human genes we don't understand to genes in other animals whose function is better known -- a field known as comparative genomics.
Scientists are well on their way to creating a genetic Noah's ark -- computer databases containing the decoded DNA of a zoo's worth of creatures.
In the past few years, researchers have unscrambled the genetic blueprints for 600 viruses, 37 bacteria, one fungus, a weed, a worm, a fruit fly -- and now a human.
More are on the way. Celera has turned its DNA-reading robots to the mouse, a creature that shares about 90 percent of its DNA with humans. Other scientists hope to do the same with chimpanzees, which differ from humans by no more than two in every 100 genetic letters.
By pinpointing the genetic differences between humans and chimps, scientists may be able to learn how the animals' immune system shields them from the AIDS virus.
Mysteries will remain
But scientists warn that even knowing the function of all the genes will not explain all the mysteries of human life. Genes exert a powerful influence, but so do such factors as environment, upbringing, temperament and lifestyle.
"Our genes don't control everything," said Ari Patrinos of the U.S. Department of Energy, which helped to finance the research credited with decoding the human genome.
"Even if you have a cancer gene, it doesn't necessarily mean you're going to get cancer. It's a probability game," said Hamilton O. Smith, a Nobel Prize winner, Celera scientist and professor emeritus at Johns Hopkins.
Smith points out that identical twins, despite being genetic mirror images of one another, don't necessarily have the same health history. One might contract cancer; the other might not.
To put it another way, it means humans have one less excuse for their problems.
"Those who are looking for forgiveness of responsibility for their own lives in the genetic code will be very disappointed," said Venter.
Wire services contributed to this article.
