Report from the Festival of Genomics

June 26, 2015

By Bio-IT World Staff

June 26, 2015 “This fall will be the 25th anniversary of the start of the Human Genome Project, which in many ways signified the start of this field of genomics,” said Eric Green, director of the National Human Genome Research Institute (NHGRI), as he rang in the Festival of Genomics this week in Boston. Between more precise cancer diagnostics and treatments, diagnoses for previously mysterious rare diseases, and science showing how patients’ DNA can affect their response to common medications, Green continued, the intervening 25 years have seen meaningful progress in medicine that could not have been delivered without a sustained commitment to understanding the genome.

The Festival of Genomics is a new event open to both professional scientists and members of the public who are simply curious about genomics, a field of research with enormous cultural salience. From the promise of medical revolutions, to consumer products and genetic engineering, genomics has a prominence in the public imagination that few other sciences can match. As Green said in his opening keynote address, “It’s the audacity and the excitement around the science that is driving this forward.”

2015 marks several notable anniversaries in this field besides the start of the Human Genome Project, which speakers at the festival made note of. Ting Wu, whose research at Harvard focuses on the cellular behavior of chromosomes, observed the 100th anniversary of Thomas Hunt Morgan’s publication revealing the basic mechanisms of genetic inheritance, including definitive proof that genes are carried on chromosomes. And J. Craig Venter, whose company Celera finished sequencing the human genome at the same time as the national public effort, added that this year is the 20th anniversary of the first sequenced genome of a free-living species (the bacterium Haemophilus influenzae), and the fifth anniversary of the first “synthetic organism” to survive with a human-designed chromosome. Venter himself directed both projects.

On the festival’s main stage, Venter was one of several scientific luminaries to share recent developments in genomics that he found personally significant. His company Synthetic Genomics has now created what he calls a “minimal viable cell,” an organism with the smallest possible number of genes needed to survive and reproduce itself. He noted that this cell still has roughly 50 genes whose purpose is unknown ― his team only knows that removing them kills the organism. Next steps include discovering the function of these essential genes, and an ambitious effort to “defragment” the genome, placing genes with related functions side by side in the genome rather than leaving them scattered around the chromosome. Venter also speculated about the ways synthetic genomics could one day change medical practice, revealing an ambitious, and ethically challenging, endpoint for the field. “The ultimate version of this,” he said, “would be a box fed to your home computer, for downloading peptide drugs, insulin, vaccines, or antibodies.”

Like other speakers at the festival, however, one of Venter’s major concerns was making genomic data more meaningful, by linking it reliably to information about people: their health, physical traits, lifestyles and environments. He described this as the biggest challenge facing his latest company, Human Longevity, Inc., which has the world’s largest sequencing facility capable of generating as many as 36,000 whole human genomes a year.

“The genome without phenotype is almost useless information to us,” Venter said. “The biggest effort we have at HLI is actually collecting phenotypes,” including health records, data on proteins and metabolites, and microbiomes. Human Longevity, he added, will open its first clinic this September to perform in-house testing to gather this information.

Heidi Rehm, who directs the molecular laboratory at Partners HealthCare and is a major contributor to the ClinGen project, advocated for scientists and the public alike to become more involved in data sharing. The ClinVar database, she said, has pioneered best practices for sharing data on specific genetic variants, but the community also needs to focus on sharing data at the level of individual patients, in a way that preserves meaningful links between genomics and health. “To realize the promise of precision medicine, we must embrace data sharing at scale and in fundamentally different ways,” she said.

Rehm also suggested that scientists and medical practitioners have not given the public enough reason to make their data available for research. “The focus should be, why should we share your data?” she said. “Patients have a right to share their data to advance medicine, and if we can start with that pitch, most patients, most participants, will actually be okay with the fact that we cannot guarantee the privacy and security of your data.” Rehm added that, in this respect, scientists could learn from private companies like 23andMe that have more fully embraced public enthusiasm for genetics.

Another speaker, Robert Green of Brigham and Women’s Hospital (no relation to Eric Green), offered a new way people can become involved in this kind of comprehensive data enterprise, unveiling the PeopleSeq project. This program will collect together people who have had their whole genomes sequenced, whether through academic or commercial ventures, and track their health outcomes over many years to see whether and how their genomic information affects their lives.

Diana Bianchi of Tufts University School of Medicine shared a dramatic example of how quickly genomic technologies can take root in medical practice when patients line up behind them. Bianchi works in the field of non-invasive prenatal testing, in which clinicians draw blood from pregnant women, then test their free-floating DNA to detect chromosomal disorders in their fetuses. As she noted, more than two million women have undergone this type of testing since it was introduced in 2011, contributing to a sharp decline in more invasive procedures. Bianchi attributes this extraordinary change to both the early commercialization of the technology, and to the engagement of pregnant women, who have both embraced and advocated for this testing.

“Women are truly leading the way,” she said. “This is probably the most mature aspect of genomic medicine. It’s transformed prenatal care in three and a half years.”

Perhaps the most enterprising move toward public engagement with genomics on display at the festival was Eric Green’s vision for the national Precision Medicine Initiative, which was announced earlier this year by President Obama. Like the Human Genome Project before it, Green said, the Precision Medicine Initiative is launching with only the broad contours of the project understood. At the beginning of the Human Genome Project, he recalled, “If you had asked me, how exactly are you going to map and sequence the human genome, I would have said I have no idea.” But the combination of an ambitious goal and a national effort allowed the technological hurdles to be vaulted along the way.

Similarly, the Precision Medicine Initiative has many goals that need to be worked out in much finer detail ― from clarifying and reforming the regulatory structures around genomic testing, to accelerating research on personalized cancer therapies. The centerpiece of the project, however, will be the creation of a “national cohort.”

“The idea is to sign up and properly consent at least a million individuals in the United States,” said Green, “who will agree to share, with all the appropriate protections put into place, health information, genomic information, lifestyle information, environmental exposure information, all linked to their electronic health records.” As with the Human Genome Project, the technological barriers are large: integrating, protecting, and standardizing data at this scale is a massive project that has never previously been accomplished in the United States. But if these problems can be solved, the positive effects could be felt across medicine and the life sciences.