We have a $1,000 genome. Now what?

by Tom Ulrich on October 2, 2013

Abstract model of the genome morphing into human shape representing clinical genomics.The Human Genome Project’s push to completely sequence the human genome ran a tab of roughly $2.7 billion and required the efforts of 20 research centers around the world using rooms full of equipment.

But that was using technology from the 1990s to early-2000s. As by a panel of genomics experts from industry and academia pointed out at last week’s National Pediatric Innovation Summit + Awards, a scientist in a single laboratory today can sequence a genome for as little as $1,000, making sequencing almost a medical commodity.

Now what? How do we go about making clinical genomics an everyday thing? The discussion left the answer to that question—and the other questions it raises—unclear. While the panelists expressed excitement about what’s possible, they cited great uncertainty among doctors, scientists, patients, payers, companies and regulators about how to make clinical genomics work.

First things first: Sequence the right patients

First you need to know whom to sequence. Christopher Walsh, MD, PhD, chief of the Division of Genetics at Boston Children’s, cited two sets of patients that might benefit from cheap sequencing:

  • Children highly likely to have a condition with a genetic basis. In such children, he said, exome sequencing returns a specific genetic diagnosis about 25 to 30 percent of the time.
  • Children with developmental or intellectual disabilities. “There, the rate of diagnosis is likely to be somewhat lower, maybe 5 to 15 percent, but the potential impact might affect a broader array of kids.”

He also noted that generally healthy adults don’t derive much value from sequencing; a whole genome scan might find a slightly increased risk of diabetes or heart disease, or occasionally a high-influence cancer mutation, “but for most people there’s not a lot there,” he said.

“But kids are different,” he continued. “Severely ill children are rare, and when they get severely ill, they almost always have a rare disease. Those are the kinds of patients where whole-genome and whole-exome sequencing are uniquely well suited to actually find the causative variants.

Questions needing answers

For much of the rest of the session, the panelists raised more questions than they answered. For instance, once you’ve identified the right person and obtained a sequence, how do you interpret and report it?

“You can go into the laboratory and, in the afternoon, run a chip, and five hours later have your whole exome sequenced,” said Claritas Genomics CEO Patrice Milos, PhD. “That poses a whole new challenge of the interpretation of variant information. What does the report that goes back to the patient and their physician look like? It’s something we really need to be thinking about collectively as a community.”

And who pays for test development and adoption? As Peter Barrett from the venture capital firm Atlas Venture noted, “The payers, especially in this political climate, aren’t going to step up to say ‘I’ll pay for things’ too easily. There’s a lot of optimism, but it’s going to take hundreds of millions of dollars to validate [genomic] technologies and get them reimbursed.”

Part of the issue with coverage, Walsh noted, is that historically clinical genomics has been hampered by the relatively high costs and low yields of single-gene tests, which themselves can cost $2,000 or more.

“Many of the insurance companies don’t pay for them, because they’re perceived as not necessarily altering clinical care,” he said. “There’s been this self-reinforcing cycle where the tests are expensive, so they don’t get used much. They’re not proven to be effective so there’s not much competition in the market, and the tests get more expensive and they’re used less.”

A lack of regulatory clarity compounds this situation. How the FDA will regulate genomic testing is a subject of a lot of discussion, Milos noted, calling for “new regulatory frameworks that totally challenge the existing framework.

“The political will to make sure we can do this is something that none of us are really talking about right now,” she added. “We really need to be engaged citizens in thinking about what we need from a regulatory environment and an insurance environment.”

Finally, what about the privacy of our genomic data? Stanley Lapidus, president of diagnostics developer SynapDx, thinks it’s an overblown issue. “The GINA legislation took a lot of the bad stuff off the table by not allowing at least health insurers to discriminate based on genetic information, certainly something that’s not true about our financial information.”

The demand is there

Citing personal experience, both Lapidus and Milos remarked on the enthusiasm for clinical genomics, especially among particular patient populations. Milos noted that in her days at Pfizer, clinical trial participants were asked whether they would be willing to contribute their genetic information for research, with the understanding that they likely wouldn’t benefit from it.

“They agreed more than 85 percent of the time,” she said. “If they contributed their DNA, they felt there might be help that would come to their children or another family member. They really understood that it was a new field emerging with potential promise.”

So when will the $1,000 genome (or cheaper genomes as time goes on) revolutionize pediatric care? Walsh counseled patience. “I was a resident in neurology when MRI was first introduced, and everyone said, ‘It makes pretty pictures, but what difference does it make to clinical care?’ Life is not going to be changed for the vast majority of children overnight by having their exome sequenced,but there are some kids who will have their lives impacted very quickly.”

Leave a comment

Previous post:

Next post: