Ten years ago, Francis Collins and J. Craig Venter held a joint press conference. At the time, Collins was head of the National Institutes of Health’s Human Genome Project; Venter was the president of Celera Corporation. For years, the two had been at the head of competing efforts to sequence the human genome. They came together to announce the completion of a draft sequence of the human genome.
The Human Genome Project was one of the largest and most ambitious projects the international scientific community has ever attempted. Its costs reached about $2.7 billion when it was officially finished in 2003. But the project’s expenses started to skyrocket when the academic venture turned into a fierce race with Venter’s Celera Genomics in 1998. Venter announced at the time that his private firm would sequence the human genome on their own for only $300 million dollars using a shotgun sequencing approach.
“The project was done at high cost because it was rushed in order to avoid a hypothetical threat of patenting human genes or gene variants,” says George Church, a geneticist who worked on the Human Genome Project and is currently a professor of genetics at Harvard Medical School. Celera indicated that they planned to patent up to 300 genes found during their sequencing efforts, which compelled the University of California at Santa Cruz to release their draft genome early, causing uproar in the scientific community. “Genes and variants were patented anyway and this has caused very few problems,” notes Church.
But Church believes that human health will benefit not from the first sequenced genome, rather the genomes that will be sequenced in the future. “As soon as the genome ‘race’ was over, the really interesting and fruitful work could begin, which is developing technology capable of sequencing not just one genome but everyone's.” Church is currently leading a new ambitious sequencing project called the Personal Genome Project (PGP), which seeks to develop effective and responsible personal genomics technologies and practices that are broadly available to the general public. The project hopes to involve over 100,000 informed participants.
Even though the complete genome was announced ten years ago, Church points out that the genome hasn’t truly been finished yet. Centromeres and telomeres—the central and end regions of the chromosome respectively—are notoriously difficult to sequence. So much so that they remain incomplete along with numerous gaps that researchers are still attempting to fill.
“There is still not a single convincing example of any human genome more than 93% sequenced,” said Church, “and this ignorance continues to cause troubles for disease gene discovery and diagnoses.”
When former U.S. President Clinton commented on the completed genome in 2000, his mind was set on discovering the basis of and diagnosing genetic diseases. In a statement, he said, “[This project] promises to lead to a new era of molecular medicine, an era that will bring new ways to prevent, diagnose, treat, and cure disease.”
Ten years later, the promise of cures for genetic diseases has seemingly been delayed as scientists continue to untangle the landscape of the human genome. “The genetic basis of human disease is turning out to be perhaps far more complex than had been anticipated when those promises were made,” said Jay Shendure, principle investigator in the Department of Genome Sciences at the University of Washington. Shendure, who previously worked in Church’s lab developing short-read DNA sequencing technology, now works on developing new methods and tools to look at biological systems.
“I think it has fallen short in terms of delivery,” says Shendure. “For example, [it has not] directly led to new drugs or been able to clearly predict disease risk from genetics in a way that, perhaps, we thought we would be able to. But I think those are still things that may potentially happen—it just may take another 10 years.”
Although it might not have lived up to expectations yet, Shendure believes the genome project was highly successful. “It was a very significant milestone, and will always be remembered as such, on par with the moon landing. It has had a tremendous impact in accelerating human genetics and biomedical research.” He believes that it’s only a matter of time before genome sequencing begins to fulfill the promises of the Human Genome Project.
The Human Genome Project also helped start a new phase not only in genomics research, but technology development as well. “There are many things that genomics doesn't do yet,” says Church, “but what it does is valuable, and its cost-effectiveness is improving faster than any other sector in biomedicine.”