Despite widespread fear over the impact that the governmentsequester is having on already stretched-thin funding for U.S. biomedicalresearch, the world of genomic sequencing got a boost last month when the U.S.National Institutes of Health (NIH) awarded four grants to multidisciplinary researchteams to explore how genome sequencing can be used to advance medical care.
The new grants, funded as part of the National Human GenomeResearch Institute's (NHGRI) Clinical Sequencing Exploratory Research (CSER)program, total approximately $6.7 million in the first year, and if fundingremains available—and that could be a big "if" should the sequester continue toplunder federal research grants—could total approximately $27 million over fouryears.
The new grants expand on the initial CSER program awardsgiven to six research teams in December 2011, including approximately $5million from the National Cancer Institute. Since that time, the use ofclinical genome sequencing has seen tremendous growth, says Dr. BradleyOzenberger, CSER program director and deputy director of the Division ofGenomic Medicine at NHGRI.
"The cost of genome sequencing has dropped so precipitouslyin recent years that there is an explosion of genomic medicine—or precisionmedicine—to bring the option of applying this knowledge to the care ofindividual patients," Ozenberger says.
The areas of research being pursued by these new projectsinclude using genome sequencing to inform couples about reproductive risks,determining the genetic causes of childhood developmental delays andcommunicating findings to parents and detecting genomic alterations that canlead to cancer. But the focus of these projects will not be on developingtechnologies, Ozenberger notes.
"It's not so much that we need an effort like this to developtechnologies," he says. "We do still need to develop ways to put genomicinformation into a patient's medical record, but the exploratory need is thatthe psychosocial and ethical components of this. Technology is outpacing that.We can sequence a person's entire genome, but more importantly, their exome.There are all kinds of unintended or unanticipated results that come out ofthat. How do clinical labs communicate to physicians, how do physicianscommunicate with patients, what do patients want to hear?"
In the first project, which has been awarded $8.1 million,the Kaiser Foundation Research Institute in Portland, Ore., will examine theuse of whole-genome sequencing in informing couples, before they conceive achild, about their potential carrier status for genetic disease. They willcompare women and their partners who receive preconception genetic testing tothose who receive whole-genome sequencing in addition to the testing. Scientists will look for genetic mutationsfor about 100 rare conditions and expect to enroll 380 people in the trial.Couples with mutations that put children at risk for a condition will work witha genetic counselor and complete surveys to help researchers develop usefulapproaches to presenting information to patients.
In the second project, which will receive $7.66 million, theHudson-Alpha Institute for Biotechnology in Huntsville, Ala., will sequence thegenomes of nearly 500 children with developmental delays and otherdisabilities, along with their parents, in the hopes of discovering genomicalterations behind such disorders. The researchers hope to uncover genealterations that are common to more than one condition and gain insights towhether certain mutations cause milder or more severe cases of some conditions.
In the third project, awarded$7.97 million, principal investigator Arul Chinnaiyan and his team willsequence the genomes of tumors from 500 patients with advanced sarcoma or otherrare cancers to discover new information about genomic alterations, with thegoal of eventually customizing therapies. Few clinical trials have beenconducted in most rare cancers, and scientists would like to know more aboutthe genetic underpinnings of these diseases. Investigators also plan toevaluate the patient consent process, and the delivery and use of genomesequencing results.
Finally, in the fourth project, the recipient of $3 million,researchers at the University of Washington will lead the coordinating centerresponsible for pulling together all of the scientific teams, helping toorganize studies, interpreting study results and helping groups focus on commongoals. The coordinating center team members bring their own expertise inclinical genetics, genome sequencing, bioinformatics and ethics.
"These projects were planned out prior to thesequestration," Ozenberger points out. "These are four-year awards, so theprogram will wind down in three to four years—but the work will not be done,certainly not in such a complex field where we are striving for a societal impacton clinical care."
Ozenberger, who was an investigator for both the CancerGenome Atlas Project and at Wyeth Pharmaceuticals, says he expects theseefforts to have an eventual impact on drug discovery and the advent ofpersonalized medicine.
"There is a bit of a lag as pharma companies use data anddevelop therapeutics, but soon, drug discovery and technology will merge so wehave an armamentarium," he says. "When you think of projects like the CancerGenome Atlas, there is so much discovery that has been empowered by that data.Now, the big challenge is that if we sequence your breast cancer tumor anddiscover 120 mutations there, we can probably sort through the four that arereally important to the progression of that cancer, but now we need the drugs.We don't always have drugs specific to that aberration."
The major impact that genome sequencing is expected to haveon drug discovery or personalized medicine is in cancer, according toOzenberger.
"Cancer is a disease of the genome," he says. "We need tounderstand that we need to consider each individual person's individual tumoras a separate thing. That is where genome sequencing for patient care is beingapplied most broadly and quickly. We envision a time where we can use ourgenomic data for care throughout life. There will come a time when each personhas a genome sequence as part of his or her medical record. This will allow usto customize medications for them, and even adjust their lifestyle.
"We're really at the dawn of this new age of both geneticdiscovery as well as genomic medicine. Obviously, this is very exciting, butwhat will be most exciting is the ultimate benefit to public health," heconcludes.