LOS ANGELES -- Honors student Lilly Grossman sat propped up daintily in an armchair in her familys sunny living room, talking about what it was like being homecoming princess of her junior class.
The night of the game -- a come-from-behind victory for the La Jolla High School Vikings -- she rode around the schools field in a Jeep. At her side was the homecoming prince, a handsome football player in uniform.
Lilly held court the next night in a royal blue dress, her hair twisted into an up-do. When the moment came to dance, she offered her hands to the prince. He looked at her sheepishly, unsure what to do.
That was awkward, Lilly said with a smile and just the slightest bit of world-weary exasperation.
It isnt easy being 16, social, smart -- and sitting in a wheelchair.
Lilly has never been completely normal (quotation marks are her emphasis).
Afflicted with a mysterious form of muscle weakness since infancy, she has trouble walking, talking and eating. Its hard for her to hold her head up. At any moment, she might fall forward, slumped, until one of her parents lifts her back into position, wedging her into place with an ever-present pillow or two.
Because her speech can be difficult to understand, she depends on text messages and social media to gab with her friends. Sleep eludes her. Seizure-like fits rouse her at night, bringing her parents running to her bedside.
Perhaps worst of all, she spent most of her childhood not really knowing what was wrong with her.
Lilly and her parents wanted answers -- even if the journey of discovery would bring both hope and heartbreak.
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When scientists first assembled a draft of the human genome in 2000, they hoped sequencing technology could revolutionize medicine by revealing the genetic underpinnings of all sorts of ailments.
Since then, the cost of reading the 3 billion DNA letter pairs that make up a persons genetic blueprint has plummeted from hundreds of millions of dollars to about $1,000. It used to take months; now, technicians can get a read in about a day.
As more people had their DNA analyzed, scientists hoped, it might be possible to find rare mutations that caused poorly understood illnesses. If doctors knew what genes were making people sick, perhaps they could treat illnesses in a more precisely targeted way -- maximizing results and avoiding side effects.
Gay and Steve Grossman, sick of hearing doctors grasp at unconvincing explanations for their daughters woes, thought Lilly would be a perfect candidate for sequencing.
When they heard in 2011 about a study at the nearby Scripps Translational Science Institute that was using sequencing to find genetic causes for mysterious illnesses, they leaped at the chance to take part.
Lillys neurologist at San Diegos Rady Childrens Hospital, Dr. Jennifer Friedman, who has championed the girls efforts to understand and battle what ails her, signed on to help with the research.
The physician understood the desire to get some answers but also worried about how the process would affect the family.
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Once Lillys DNA was sequenced, the researchers found two suspicious mutations, in genes called ADCY5 and DOCK3. Scientists didnt know much about either one.
Reading up in the scientific literature, Friedman saw that a small group of people with mutations in one of the same genes seemed to respond well to a drug called acetazolamide. After talking it over with the Grossmans, Friedman decided to prescribe it for Lilly.
The first night was terrible, but within a week the drug had dramatically improved Lillys sleep. She no longer woke at night. With better rest, her strength and speech improved. She got more sassy, the Grossmans said.
I started my new shaking medication a week ago and ITS ACTUALLY WORKING!!!!! she wrote on her blog, Lilly Grossmans Life.
She penned a novel, The Girl They Thought They Never Knew, in which a fictional character named Lilly has her genome sequenced, takes a new pill and becomes normal overnight:
When I wake up on Friday morning, I feel ... different. I cant quite place what feels different. Until I stand up. Straight. Without feeling unstable. I tiptoe into my parents room. Wait, tiptoe? I usually sound like an elephant running through the house.
In the book, Lilly returns to school incognito, starts exacting revenge on kids whove been mean to her, and gets a boyfriend.
But within weeks, the real-life Lilly began having trouble operating her phone, computer and motorized wheelchair -- her lifelines to the world.
Friedman dialed back on the new drug, and Lillys sleeplessness returned.
By last August, on the eve of a long-anticipated trip to visit colleges, Lilly was suffering seizure-like tremors all night. The episodes came every 10 minutes. Things arent as simple as one might assume, Friedman said. Finding the gene is only the beginning.
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The Grossmans have come to terms with the fact that discovering a genetic cause for Lillys illnesses didnt reveal any obvious way to make her better.
Sometimes our friends ask, What did you get out of this? Things arent better for Lilly, Gay said.
But the Grossmans all say that sequencing Lillys DNA has been a good experience.
Just knowing her gene mutations -- and that she doesnt have a condition that could kill her at any time, once a major fear -- is huge for us, Gay said.
And now when they have a sleepless night, the family knows theres someone else out there thinking about Lilly and how to make her better, she added.
As the cost of sequencing was coming down, two more families had learned that their daughters shared the same ADCY5 mutation as Lilly. The mother of one of the girls contacted Gay on Facebook and met with Steve when he traveled to her town on a business trip.
Scripps researchers said they would like to study the three girls as a group, which should improve their understanding of ADCY5 and could point to a treatment.
It could take months for the work to begin. This doesnt bother the Grossmans.
This is a marathon -- its not a sprint, Steve said.