In what many are hailing as a historic milestone in the annals of modern science, researchers have announced the successful completion of a project to sequence the human genome.
The 13-year, $2.7 billion undertaking drew to a close Monday, 50 years to the month after scientists Francis Crick and James Watson published their discovery of the structure of DNA, the biochemical instruction book for organic life archived in the centers of cells.
Now, biologists are unrolling a fresh research blueprint for genome-related research, drawn for what National Human Genome Research Institute Director Francis Collins and colleagues have termed "the true dawning of the genomic era."
They've assembled the parts list in the right order. Now they hope to accelerate efforts to understand how the genetic information they've uncovered yields the complexities and diversity of living organisms.
"We have opened the door into a vast and complex new biological landscape," says Aristides Patrinos, director of the US Department of Energy's Office of Biological and Environmental Research.
Even before the project ended, it was having a measurable impact on areas ranging from medicine to the war against bioterrorism. Researchers say information from the genome project has allowed them to develop genetic tests that can help identify broad classes of cancer. Gene therapies, in which defective genes are identified and replaced, remain in their infancy. But scientists claim some success in treating mice with sickle-cell disease.
Microcircuits that can quickly analyze DNA samples placed on them are being used in equipment designed to test for many of the microbes thought to be the most likely weapons in a bioterrorism attack.
Meanwhile, researchers using sequencing and computational techniques developed for the Human Genome Project are looking for microbes that could help clean up nuclear waste, refine gasoline more efficiently and with less energy, or act as a source of hydrogen for fuel.
The praise and predictions surrounding Monday's announcement of the Human Genome Project's end has a familiar ring. In February 2001, with fanfare that included capturing the covers of the world's two leading general-science journals, researchers with the Human Genome Project and a private human-genome effort published rough drafts of the sequence.
Yet the drafts were laced with errors and contained vast gaps in the sequence of pairings among the four chemical "bases" that combine to form the "runs" of the now-iconic twisted-ladder structure of DNA.
This time, it's complete
The version announced Monday is as complete as today's technology can make it, researchers say. The error rate has been cut from one mistake in every 1,000 base pairs to one in every 10,000 - an accuracy that applies to 99 percent of the genome's 3 billion base pairs.
Just as important, researchers add, are the finished product's vast stretches of uninterrupted genetic information which is expected to radically shorten the time it takes scientists to hunt for genes.
"It's a bit like moving on from a first-attempt demo music tape to a classic CD," says Jane Rogers, director of sequencing at Britain's Wellcome Trust Sanger Institute, a key player in the sequencing effort.
The information and technologies the project has generated already are profoundly affecting The information and technologies the project has generated already are profoundly affecting fields ranging from biomedicine and hazardous-waste clean-up to the study of the origins and evolution of organic life itself. The project also has laid at society's doorstep challenging ethical and legal questions about the use of human genetic information.
Now scientists are moving into a new generation of global research to build on the Human Genome Project's results. Writing in a forthcoming issue of the journal Nature, Dr. Collins and several colleagues outline what they see as the opportunities the completed genome offers for improving medical care, dealing with environmental issues, and assessing the effect genetic information can have on "concepts of race, ethnicity, kinship, individual and group identity, health, disease, and 'normality' for traits and behaviors."
Several projects already are under way. Last fall, the National Human Genome Research Institute and collaborators began the International HapMap Project, a three-year effort to pinpoint genetic variation within the human genome. Another project aims to build an encyclopedia covering all of the genes that code for proteins, and other important biochemicals, or that perform other functions. This would allow scientists to quickly distinguish useful genes from the junk genes the genome carries.
Meanwhile, the DOE is focusing efforts on one-celled organisms and the roles they may be able to play in meeting US energy needs and cleaning the environment. Over the next 10 to 20 years, researchers want to know how microbes, which make up an estimated 50 percent of Earth's biomass, function at such a level of detail that they can accurately simulate how organisms will respond to changes in their environment.
"We're just beginning to understand how to work with multiple influences" instead of single determining factors, notes Alta Charo, a professor of law and bioethics at the University of Madison at Wisconsin. Those multiple influences can be found in the interplay between genes and environment or the interplay of many genes within a genome required to trigger a particular set of biological processes.
The idea of multiple influences "does not work well within a medical system whose paradigm is to cure diseases that are presented to it. It requires thinking from a more preventative point of view," she says. "The Human Genome Project may push us toward a different organization of the healthcare system, if we use the information creatively."
As researchers probe the "sheer number of genetic variances and mutations, we're going to slowly realize that any individual has genetic variance", that variance is the norm, and consequently that, in biological terms at least, there is no idealized "normal."
The challenge for society as it continues to grapple with advances in genetics information "is not to say: we won't go there," Charo says. "The challenge is to say we will go there, and this is how."