The Human Genome Project, a worldwide quest to identify all the genes of the human species, could be completed in six years instead of 12 if a new breakthrough in DNA sequencing proves successful.
Scientists at Argonne National Laboratory, operated by the University of Chicago for the U.S. Department of Energy, on Wednesday announced a commercial agreement to use a biochemical “super chip” developed at Argonne. The technique reputedly can spell out the chemical subunits of genes 1,000 times faster and 10 times more economically than methods now in use.
Gene sequencing is the process of deciphering and ordering the chemical sequences of DNA base pairs that make up the 100,000 human genes, the master blueprint of life that resides in the nucleus of each cell.
The genetic terrain is immense-piecing together the genome puzzle has been likened to searching out and rebuilding from scratch every old Volkswagen Beetle in the Midwest.
Once a gene is found and sequenced, scientists can study its function, develop treatments for birth defects and other genetic diseases, and invent diagnostics for early detection of hereditary diseases, such as some cancers.
Discovery last week of BRCA1, the first gene known to cause hereditary breast cancer, was an early payback from the Genome Project, which began in earnest in 1991.
“This is a major milestone for commercial applications of the Human Genome Project that will have a far-reaching impact on human and veterinary medicine, as well as agriculture,” predicted Argonne Associate Director Harvey Drucker.
The agreement between ARCH Development Corp., a not-for-profit commercialization arm of the university, and Hyseq Inc., a privately held biotechnology firm in Sunnyvale, Calif., represents the type of technology transfer that the $3 billion Genome Project was designed to encourage, and upon which its fate depends.
Some 350 laboratories are racing each other to develop technologies to complete the massive project by the year 2006. The new technology could cut that timetable in half.
Martha Krebs, director of the Department of Energy’s Office of Energy Research, which funded the Argonne work, congratulated the scientists on behalf of the government. “They have developed a practical and economical system that simultaneously analyzes hundreds of thousands to millions of DNA clones,” Krebs said.
The core technology announced Tuesday was invented and patented by Hyseq’s vice presidents of research, Radoje T. Drmanac and Radomir B. Crkvenjakov, two Yugoslavian researchers formerly at Argonne.
“I’m motivated to be one of the first to read the book of life,” Crkvenjakov said. “That’s the big challenge: Who will be the first to get there?”
Each cell contains an aggregate of 3 billion DNA subunits, with functioning genes scattered among them like rocks along a highway. Costs of deciphering the entire code under current technology has been estimated at $1 a subunit-hence the $3 billion price tag-as well as being laborious and slow.
Current methods utilize gel electrophoresis, a 17-year-old technique that separates DNA fragments in an electrical field on the basis of length. The constituent subunits are then deduced.
The gel method relies on repetition for accuracy and must be interpreted by skilled personnel. New developments hinge on improving this essentially linear technique using robotics and computers that read sequences faster and more accurately.
In the past, a good graduate student could be expected to manually sequence about 12,000 DNA base pairs in a year. Modern genome labs can read a million base pairs in a year. The Argonne system, by comparison, claims to be able to do a million in a day.
Not only is the method, called Sequencing-by-Hybridization (SBH), faster than conventional gel sequencing, its developers claim it also is cheaper, more accurate and can be fully automated.
In fact, the entire human genome could be sequenced for about $300 million, according to Hyseq President and Chief Executive Officer Lewis Gruber.
Under the agreement, Hyseq was granted exclusive patent rights to a variation of SBH technology known as Format 3 that allows large-scale gene sequencing on a “super chip”-a 1-inch-square special plate capable of decoding the chemical sequence of hundreds of genes in one pass.
The company also gained non-exclusive worldwide rights to software used to analyze and interpret the genetic code deciphered by SBH.
Financial details were not revealed.
So far, over the past 20 years only between 2,000 and 3,000 human genes have been sequenced in their entirety. Drmanac and Crkvenjakov said they expected to sequence 15,000 commercially useful genes by 1997.
“It is quite likely that some of these genes will generate $1 billion a year in revenues,” predicted Gruber.
