Geneticist Elizabeth Worthey worked on the first-ever treatment of a patient based on DNA sequencing, helping doctors decide to give a bone marrow transplant to a 6-year-old boy who had suffered through more than a hundred operations. Now Worthey, an assistant professor at the Medical College of Wisconsin, is part of a team working to comb through the sequences of five more children.
Every Friday, she and her colleagues at Wisconsin Children’s Hospital meet to go over cases that other doctors have put forward for DNA sequencing. There have been about three dozen requests. An insurance company has even agreed to pay for one of the cases, although the money is not yet in the bank and the hospital will not disclose either the insurer or details about the patient. This is the first time that an insurer is known to have agreed to pay for the sequencing of an entire human genome!
“For some of these kids there is no alternative,” Worthey says, “You either guess, you do nothing, or you do something — in this case, sequence their genome.”
Wisconsin Children’s Hospital is the most prominent case of a hospital scaling up to help patients with DNA sequencing. The efforts of Worthey’s team have been chronicled in the Milwaukee Journal Sentinel, and on the Today show. Sequencing technology is decreasing in cost and increasing in power at a rate faster than anything since the microchip.
The first case of a diagnosis by DNA sequencing was published in 2009, when Yale researchers figured out why a Turkish infant was suddenly losing weight. Several more cases of using DNA sequencing, which reads out the 6 billion DNA letters that contain the protein recipes that make one person different from another, to understand the cause of disease have been published.
Illumina of San Diego, the leading maker of DNA sequencers, runs a service business that chief executive Jay Flatley has said has been seeing mainly infants and cancer patients. Knome, another company that does sequencing for researchers and individuals, has made similar comments.
When the Wisconsin team sequenced Nicholas Volker, the child whose intestinal troubles had necessitated all those surgeries, they found a genetic mutation that seemed to indicate a bone marrow transplant was necessary. Many of the current cases, Worthey says, are also ones in which such a transplant – a risky and expensive procedure – might help but doctors are not sure because they don’t know exactly what’s wrong.
That first case cost $75,000, and was done using a DNA sequencer made by Roche’s 454 Life Sciences division that decodes fewer bases than more modern models. The team also limited their DNA sequencing to stretches of DNA known to code for proteins – the known genes.
For the newer cases, they are sending samples out to Illumina, which processes them at a cost of about $12,000 and sends back a list of variants where they differ from known reference genomes. This also saves the hospital from having to save the primary data from the sequence – in this case, giant image files that would tax its computer systems. Worthey compares the variants to more than 200 genomes that are now in public databases, and uses software to try to figure out if any of those DNA changes could be the root cause of the child’s illness.
Unlike in the Volker case, she examines the entire 6 billion-letter DNA code. She says trying to look at only proteins, a process known as exome sequencing, misses some known genes. Once a variant looks like it might be a cause of disease, it is double-checked using Sanger sequencing, the older, more expensive process that was used to create the original draft of the human genome a decade ago.
Worthey is hoping that eventually the hospital will be able to do sequencing in house. She also hopes that newer technologies, such as Pacific Biosciences machine, might allow geneticists to look at longer stretches of DNA; MCW is getting a PacBio machine. Many researchers worry however, that this device has a high error rate, which might limit its usefulness. Illumina rival Life Technologies is betting heavily on a smaller, less expensive to buy machine that might be good for smaller projects.
The questions – how to regulate this new technology, how insurers will pay for it, and exactly what it can really do – are still huge, but so is the potential. “It’s really starting to be adopted,” Worthey says, “at least in children.”