Expansion of Genome Research will Benefit Two Boston-area Research Centers

The four-year, $416 million plan of the National Human Genome Research Institute provides the largest grant to the Broad Institute, a genomics research center in Cambridge, and also includes money for Brigham and Women’s Hospital, for the first federally-funded clinical trial to study the use of technologies that map the full DNA sequences of patients in a routine medical setting.

“Lots of people have done sequencing. ... But the question no one has addressed in a systematic way is how in the world is sequencing going to be integrated into clinical medicine?” said Dr. Robert C. Green, a physician-scientist in the division of genetics at the Brigham, one of the leaders of the $9.6 million project.

“There are concerns about what [information] you give back to doctors and patients, concerns over whether doctors are anywhere near prepared to take such information in stride and use it sensibly in the practice of medicine. There’s this whole rich tapestry of issues,” Green said, describing some of the questions the project hopes to answer.

The announcement is evidence of the evolving and maturing field of genomics. A decade ago, decoding the 6 billion letters of a single human genome was a major feat that took more than a decade of work and $3 billion. Now, costs have dropped roughly a million-fold, and research has become large-scale science -- using hundreds or thousands of genomes -- to uncover the genetic roots of every tumor and the underpinnings of common ailments such as heart disease and diabetes.

This research is generally undertaken at large-scale sequencing centers such as the Broad Institute, which have the machinery and manpower to generate nearly unfathomable amounts of data that, in aggregate, begin to reveal the molecular causes of disease and aid the search for new therapeutics.

“I think in the course of the next five to 10 years, we’re just going to have the answer, have the catalogue, for all the mutations that drive cancers, the genes mutated in many if not most of the major diseases,” said Eric Lander, director of the Broad. The center will receive $36 million in the first year of the new federal initiative and then successively smaller amounts because of the continuing drop in the cost of producing such data.

As the price of decoding the human genome has plummeted, the major funder of such research has begun to branch into new areas.

“The long-term rationale of the human genome project was to improve human health,” said Eric Green, director of the National Human Genome Research Institute. Under its new plan, the institute will fund new programs, including three centers to investigate rare, inherited disorders, an effort focused on building software that could be used to analyze genetic data, and a program to explore the clinical use of the genome.

At the Brigham, the grant will support large teams of researchers and three interconnected projects, aimed at understanding how patients and doctors use such information in a clinical setting.

The Brigham will sequence the genomes of both people who are generally healthy and people suffering from a specific, genetic disease. That’s because in the future, many anticipate that genomes may become a standard part of people’s medical workup, leaving doctors with the challenge of figuring out how much information they should give to patients and how they should use it to guide their care. Researchers will study sequencing in a primary care setting, among 10 doctors and 100 patients. And they will look at its use in cardiology, including 10 cardiologists and 100 patients with hypertrophic cardiomyopathy, an inherited disease that causes thickening of the heart muscle.

Teams will create ways to analyze and interpret the data and provide patient reports for doctors. Others will study the use of the information in medical care and its impact on everything from cost to the emotional well-being of patients and their families. What kinds of information can and should be given to patients -- for example, would a young, healthy person want to know he or she carries a gene that increases the risk of developing cancer or Alzheimer’s disease later in life? Doctors will have to deal with the large gray area of genetic mutations that may increase a person’s risk for a disease, finding a way to explain findings that are not definitive.

“How do people use the information, how do people understand the information – does it increase medical spending, does it increase alarm, does it lead to advantages?” Green said. Will people be happier knowing about genetic risk factors that lurk in their genes, “or would you rather put the genie back in the bottle?”