Ushering in a new age in precision medicine, with patients at the forefront

Google Matt Might’s name and one of the first links to pop up will be Gizmodo and this intriguing headline: “Hunting Down My Son’s Killer.” It’s a riveting 5,000-word post he wrote in 2012 about the rare, genetic disorder known as N -glycanase 1 (NGLY-1) deficiency that afflicts his 7-year-old son, Bertrand.

At the time Bertrand was the only diagnosed case of NGLY-1— an autosomal recessive disorder triggered by mutations from both parents— but genetic databases suggested there could be around 500 individuals worldwide with NGLY-1 based on the frequency of the alleles. Finding even a handful of them would give researchers more to go on and potentially lead to therapies or even a cure for the disease, Might, a computer science researcher from Utah, reasoned.

So he engineered a post, embedded with search terms ranking high in Google, and took to the Internet to look for other patients. Might’s social media strategy was a huge success. Aside from Gizmodo, where the post immediately went viral, the detailed account of how Bertrand was diagnosed with NGLY-1 also generated a lot of traffic and attention on Reddit, Twitter, Might’s own website, and eventually the popular press. Importantly, Might’s call to action led to the discovery of 37 patients on nearly every continent. This small but growing community is now informing the science in ways that Bertrand, by himself, could not.

“There is nothing you can do in a traditional medical sense when you are the only patient in the world since obviously there is no drug waiting for you when this happens,” Might said during his keynote address at the Precision Medicine 2015 meeting at Harvard Medical School June 24 and 25. “So in the absence of any viable medicine it is science itself that becomes the medicine and science becomes actionable.”

Living laboratories

Precision medicine has been around in one form or another for centuries. Scientists have always been transfixed by the “exceptions” in the literature—orphan diseases that afflict a handful, like Bertrand, or subsets of patients with common diseases who defy the odds in intriguing ways. Why is it, for instance, that one in every 300 people with HIV can maintain undetectable viral loads without taking daily antiretroviral therapy or that only certain cancer patients respond favorably to a particular immunotherapy.

There was a time when it might have been all but impossible to dig into the weeds and find answers to these questions, but the ability to tease out trends and traits by rapidly analyzing extremely large data sets and the growing availabity of whole-genome sequencing, including whole-exome sequencing, to characterize disease variants is giving precision medicine a whole different feel. During his State of the Union address earlier this year, US President Barack Obama launched the US $215 million Precision Medicine Initiative in part because of discoveries and new treatments that are now tailored for people with certain genetic profiles. Here’s what the White House said: The future of precision medicine will enable health care providers to tailor treatment and prevention strategies to people’s unique characteristics, including their genome sequence, microbiome composition, health history, lifestyle, and diet.

How, when and if precision medicine strategies ever transform the way research and clinical care is carried out remains to be seen. For that matter, how one should even define precision medicine is an open question.

The Harvard conference offered a snapshot of the potential and challenges of precision medicine, and how critical patients will be to research success. Might’s story, a parent’s perspective told to an audience of mostly researchers from the academic, commercial and government sectors, showed what one can accomplish today with the help of social media. It’s also worth noting that the nearly three years it took to find the cause of his son’s symptoms—the frequent seizures, visual impairment, movement disorder, liver damage, developmental delays, lack of tears—was achieved with whole-exome Sequencing, a relatively new tool that can economically sequence the 2% or so of DNA responsible for the fast majority of most genetic disorders.

So what is behind the push in precision medicine? Disruptive business models, big data and the growth of electronic medical records are in play. So are patients and families that, increasingly, have become stewards and “experts” in their own health care, demanding state-of-the-art tests that even some medical practitioners are not always comfortable or confident in ordering.

More importantly is the culture shift occurring in how therapies are discovered and made available. “Patients feel empowered both morally and intellectually to lead in precision medicine research and delivery,” noted Isaac “Zak” Kohane, the chair of the newly created Department of Biomedical Informatics at Harvard Medical School. “That culture shift has already happened. I am quite sure [stories like Might’s] could not have happened 15 years ago both technologically and culturally.”

How to cite:

McEnery, R. A Bulls-Eye on Disease. Eureka blog. Jun 29, 2015. Available: http://eureka.criver.com/a-bulls-eye-on-disease/