Now that rival teams of scientists have created first drafts of the human genetic text, they are about to take the next step toward creating tomorrow's wonder drugs. It's called annotation, and it consists of poring through the volumes of DNA to find all the genes and figure out what they do.
No one, perhaps, is more eager to start than Dr. Victor A. McKusick of Johns Hopkins University, 78, one of the founders of modern medical genetics. And few, perhaps, are better poised to influence what path the effort takes.
When President Clinton and British Prime Minister Tony Blair jointly announced the milestone Monday morning , McKusick was there in the East Room of the White House, sitting behind James Watson, co-discoverer of the structure of DNA.
To McKusick, who has spent more than three decades compiling one of the world's most comprehensive public catalogues of genes, it was a "spectacular" moment, the dawn of a new era. "It was of the same momentous nature as the moon landing in 1969," he says.
But, McKusick says, the real age of exploration is just beginning.
Recording the first human genetic text, the genome, is a little like discovering a copy of life's encyclopedia. "But there is no index, no table of contents, no headings, no nothing," says Dr. David Valle, one of McKusick's colleagues at Hopkins. In short, there is no efficient way to extract the ocean of information the genome contains. "Until it's annotated, it doesn't come close to providing the value that is there."
Annotation should pave the way for the discoveries that the genome promises - pinpoint diagnoses of illness; drugs that zero in on their metabolic targets like smart bombs; the identification of the families of genes that predispose people to common disorders such as cancer, Alzheimer's, major mental illness, allergies, asthma. "Almost any disease you can think of has at least some genetic predisposition involved," McKusick says.
Many of the genome's early explorers will likely be guided by McKusick's "Mendelian Inheritance in Man," a compendium of 2,281 genes that, when flawed, have been linked to at least one specific disorder. (Potentially, the malfunction of any of the genome's estimated 50,000 genes could cause disease.) The 34-year-old encyclopedia is now published online by the National Center for Biotechnology Information, and is read by thousands of researchers worldwide each day (www.ncbi.nlm.nih.gov/omim).
