By Kevin Davies
September 9, 2011 | The CEO of the Inova Translational Medicine Institute (ITMI), which recently signed a major deal to sequence the genomes of hundreds of pre-term babies, has shed light on the motivation and goals of the partnership with Bio-IT World.
Last month, Complete Genomics, the Bay Area sequencing service company, announced its first contract with a healthcare provider to conduct whole genome sequencing of its patients. The deal with ITMI calls for the sequencing of 1,500 genomes in all – including 250 pre-term babies, their parents and an equal number of controls.
Complete Genomics will begin delivering sequencing results to ITMI in the next 2-3 months and expects to finish most of the 1,500 genomes in the first quarter of 2012.
The ITMI CEO, John Niederhuber, believes that the research project will yield clues as to the genetic basis of premature births, and potentially even therapeutic targets for various obstetrical abnormalities.
ITMI is a not-for-profit research institute within the Inova Health System in Northern Virginia. Two years ago, Inova had provisionally agreed to be a major partner in the establishment of Dietrich Stephan’s Ignite Institute for Individualized Health in the Washington DC area, but after planned funding fell through, Stephan eventually set up a more modest version of his Ignite operation at the Fox Chase Cancer Institute in Philadelphia.
Niederhuber joined ITMI one year ago following his tenure as director of the National Cancer Institute (NCI). In that role, Niederhuber had already immersed himself in the potential medical benefits of next-generation sequencing (NGS). With growing confidence about the quality of assembled NGS data, Niederhuber and Francis Collins, his fellow director at the National Human Genome Research Institute at the time, decided to launch a pilot program of The Cancer Genome Atlas (TCGA), focusing on three tumors.
“When I left the government last July , I was wondering what could I do next?” Niederhuber says. He considered several leadership positions in academia, but his interests shifted to the clinical application of genomics technologies. “If we all believe the future of medicine is going to be transformed by this type of technology and others including proteomics, then I thought that maybe I could have some impact by working out how one is going to use this? Not just for research but making a difference at the point of care.”
As he settled into his new job at ITMI, Niederhuber’s initial focus was naturally on cancer and other adult diseases. “But after a while, thinking about the future of medicine, and knowing a lot of money is going into sequencing cancer, I thought that would be a ‘me too.’ Those databases are already being created.”
On the other hand, Niederhuber realized that Inova served a huge population of patients, with dozens of babies delivered every day, not to mention one of the largest regional neonatal intensive units (NICUs) at Inova Fairfax Hospital, with several admissions each day.
“Maybe the future of medicine is about being able to do this care characterization before birth or at birth and build from there, understanding the potential targets for managing risk and having a reference point if disease develops down the road. That’s really next-gen medicine! We know very little about the causes of obstetrical diseases. We have no clue at all about what causes preterm delivery,” says Niederhuber.
Much to his relief, Niederhuber received a positive reaction when he presented his ideas to his colleagues, including Inova CEO Knox Singleton. “They said, ‘No, you’re not crazy!’ If you think about the power of this technology, it makes a lot of sense. If I was being born today, I might want my DNA and white cells banked -- my ‘repair manual.’”
Although there were many potential problems – not least would physicians and patients be receptive? – the ITMI proposal sailed through IRB approval. “We couldn’t have predicted one year ago, we’d be where we are,” he says.
ITMI plans to sequence 250 pre-term babies with no known congenital abnormalities and 250 full-term newborns, along with their parents, for a total of 1,500 genomes. ITMI has been recruiting families since last June, with more than 150 entered to date. The first group of samples has already been sent to Complete Genomics for sequencing.
Niederhuber says he had a lot of confidence in Complete Genomics “because of our past work at NCI”. He considered BGI as a potential outsourcing partner, but didn’t talk to the Chinese institute about this specific project. “That was because of its pilot nature, and I suppose I wanted more control and accessibility,” he says.
The initial goal for Niederhuber and his colleagues and collaborators is “to mine that data and find markers for pre-term delivery.” But that will raise many more questions: “How are we going to integrate this information with the phenotypic information of patient care? How are we going to make that useful information at the point-of-care with the physician, who may not know much about genetics?”
Although Niederhuber praises Complete Genomics’ “robust analytics team,” which will deliver “tier 2” data to ITMI, a huge challenge will be how to perform the medical interpretation on 1,500 genome sequences – a challenge confronting many medical centers and healthcare systems of course. Niederhuber concedes it is a major issue, and that “conversations with variety of entities” are taking place, with the goal of developing new interpretation tools, either in-house or in conjunction with others.
“We will work with our own people, but we’ll also contract with others in partnership to apply the tools that exist. We’re very committed to trying not only to work on the data itself but also develop the tools to fill that space on the analytics side for patient care.”
The next phase of the program, which will include a longitudinal cohort of 2,000 offspring, is being finalized currently. Niederhuber outlined some of the likely areas of investigation: “What if we go to the obstetrics arena in the first trimester, and we consent the mothers, and look at proteins, genetics and so on, and follow through pregnancy? What if we followed after birth? What if we expand beyond parents into grandparents? That would be interesting.”