The HGP's Place in History
Today, the human genome, genomics (a rarely used word 15 years ago), and sequencing inform virtually all of biology. GEN’s panelists agree the HGP was transformative, though perhaps differing on particulars. Much of what followed, they say, is derivative—intended to better exploit and explain how genetic code works.
The HGP was biology’s version of the U.S. moon shot, says Dr. Botstein: “You could argue there was no actual practical use for going to the moon; however, the technology that was built to take us to the moon changed society in many ways. I would say that the HGP paralleled this achievement, except that with the HGP, it was clear from the beginning that the sequence would be valuable.”
Insight into human biology flowed almost instantly from the genome; translation into medical practice has taken longer. Still, “ten years is a blink of the eye in terms of medical research. I think it’s been quite impressive,” offers the NHGRI’s Dr. Green. A trickle of genomics-based drugs, mostly in cancer, has reached the market—for example, the breast cancer drug trastuzumab (Herceptin), which only works for women whose tumors are HER2-positive, and gefitinib (Iressa) and erlotinib (Tarceva), which help patients whose tumors are positive for EGFR mutations.
Moreover, declining sequencing costs are accelerating the search for new drugs and pushing sequencing into the clinic. In 2010, St. Jude’s Research Hospital started the Pediatric Cancer Genome Project, a three-year project to sequence normal and cancer cell genomes of 600 pediatric cancer patients. It reached this goal ahead of schedule, having completed sequencing for 700 patients (accumulating 1,400 whole genomes) to date.
“We couldn’t have done this without the HGP,” says Dr. Evans. “We’re using next-generation sequencing, and our reads are 100–150 bp. If we didn’t have a nice framework to align these genomes on, this work would be close to impossible.”
“I see the sequence and sequencing tools as foundational. When we started, we were anticipating the average cost of each genome over a three-year period would be $35,000. That’s probably about what it turned out to be. Now we’re well under $5,000 per genome and rapidly heading toward $1,000 per genome,” adds Dr. Evans.
A follow-on project will allow St. Jude’s to sequence patients’ cancers in real-time and use the information to inform therapy decisions.
It’s also worth noting that until the HGP, biology was a classic “small science”—dominated by individual investigators or small multi-investigator group working in relative isolation. That’s changed dramatically. Given the cost and scope of the HGP, collaboration was necessary. Today there are many consortia-based efforts—the International HapMap Project and the 1000 Genomes Project, to name just two—pooling data and coordinating research.
The HGP has changed the discipline in yet another way: once primarily descriptive, biology has become a Big Data science. There’s no going back. New IT and bioinformatics tools are constantly in development, and they have forced researchers to retool skill sets. Moreover, the ongoing emergence of less-expensive, desktop-scale sequencers will give smaller labs a seat at the Big Science table. Ultimately, what it means to be a biologist and what tools one must be competent to use were forever changed by the HGP.