Within 24 hours, Quinlan was whisked away from their hospital to an intensive care unit at a nearby medical university. There he began a battery of tests in hopes of diagnosing his disorder, the start of a tortuous journey that has thrust the family into the center of a global economic race to push the limits of medicine.
The search for an answer has taken Quinlan to the cutting edge of the emerging field: the use of genomics, the study of our DNA, to tailor health care. The United States has long been the industry’s undisputed leader, performing much of the research that first decoded our DNA about 15 years ago.
But now China is emerging as America’s fiercest competitor, and it is sinking billions of dollars into research and funding promising new companies both at home and abroad — including a laboratory that handles some of the toughest cases at Boston Children’s Hospital, where Quinlan has become a favorite of the staff.
Finding an answer for Quinlan and children like him relies as much on Chinese expertise as it does American ingenuity. One of the founders of the lab was born and trained in China before immigrating to the United States. Chinese company WuXi NextCODE is one of its chief investors, and researchers there use WuXi’s programs to analyze the reams of data inside our DNA.
Under President-elect Donald Trump, America’s relationship with China has been defined by frustration over the loss of factory jobs in the nation’s industrial heartland to the assembly lines of the world’s second-largest economy. But experts say it is the battle for dominance in innovation and science that is more likely to determine the economy of the future.
“I’m very frustrated at how aggressively China is investing in this space while the U.S. is not moving with the same kind of purpose,” said Eric Schadt, director of the Icahn Institute for Genomics and Multiscale Biology at Mount Sinai. “China has established themselves as a really competitive force.”
For the Weekes family, the stakes couldn’t be higher.
“There’s some missing piece of the puzzle that we need to find right now,” Lindsay Weekes said.
‘Did you see that?’
Two years ago, on New Year’s Eve, Weekes and her husband were squirreled away in their tidy split-level home in the suburbs of Boston. Quinlan had spent four days in the hospital after his birth and then was sent home when doctors couldn’t pinpoint the problem.
Now he was about 4 months old. Weekes looked down at Quinlan cradled in her arms and realized his lips were blue, his eyes staring blankly back at her. He was having a seizure.
“Did you see that?” she called to her husband, Jaunel, who goes by the nickname “Bear.” By the time he walked over, Quinlan’s lips were once again a healthy pink.
But then it happened twice more, and Weekes and Bear were riding in an ambulance with Quinlan on their way to Boston Children’s Hospital when the clock struck midnight. He didn’t leave the hospital for another month.
The seizures weren’t the only problem. Quinlan had difficulty following objects with his eyes. He wasn’t rolling over. And his doctors still didn’t know why.
“We didn’t have the diagnosis, so it was just treat the symptoms,” Weekes said.
The family hoped genetic testing would provide an answer. The cost of sequencing DNA has dropped dramatically since researchers unraveled our biological building blocks for the first time in 2001. Estimates of the pricetag for that initial discovery range from several hundred to a few billion dollars. Decoding a genome now runs between a few hundred to a few thousand dollars, spawning a flurry of potential new applications.
Experts say the technology could prove as transformational as the Internet. Pharmaceutical companies want genetic information to concoct powerful new drugs. Hospitals hope to analyze genes to personalize medical care. And doctors believe genetic data could provide the keys to understanding rare and mysterious diseases like Quinlan’s — and maybe one day even develop a cure.
For China, the genomics revolution has been a chance to showcase its technical prowess as well as cultivate homegrown innovation. Over the past two decades, China transformed itself into an economic superpower through massive industrialization. But the country is now facing the limits of that model amid slowing growth, toxic pollution and the shift of manufacturing work to less-developed nations. To succeed over the next generation, China hopes to emulate Western-style entrepreneurship to transform its economy.
“When they looked out on the horizon, they saw that those who defined the cutting edge of the global economy are innovation leaders,” said Denis Simon, executive vice chancellor of Duke Kunshan University in China. “For China to play a central role in world affairs, as well as to have a very competitive economy, it would have to step up its innovation game.”
What China cannot create, it appears more than willing to buy. Chinese investors — both private and government-supported — are backing American start-ups in hopes of capturing the entrepreneurial spirit. China has sunk more than $3.6 billion into the U.S. health and biotechnology sector over the past 16 years, according to an analysis by Rhodium Group, a consulting firm.
Scientist and entrepreneur Ge Li is a poster child for China’s new model. Trained at Columbia University, Li was working as a laboratory scientist in Philadelphia in 2000 when he realized he could replicate his job in his home country for a fraction of the cost. His company, WuXi AppTec, which includes WuXi NextCODE, is now estimated to be worth more than $3.3 billion. Roughly 14,000 people carry out the company’s research and product development around the world.
In the United States, the company has helped finance an array of biotech start-ups, including the home DNA testing company 23andMe. It tests medical devices in St. Paul, Minn., and develops biologic drugs in Atlanta. In Philadelphia, it is one of the anchors of a technology hub in the city’s Navy Yard, opening its third biomanufacturing facility there this fall.
Until last year, WuXi’s largest division was listed on the New York Stock Exchange. The company is now privately owned, but speculation abounds that it will eventually go public again — on a Chinese exchange.
“We’re a U.S. company in the U.S., but we’re a Chinese company in China,” said Hannes Smarason, chief operating officer at WuXi NextCODE. “We’re local in every market.”
The Quinlan genome project
By about six months old, most babies are sitting up and smiling, laughing and clapping. Quinlan came down with a severe respiratory virus that sent him back to the hospital, then to a nearby rehabilitation center. His seizures became more severe, and he underwent a tracheotomy to help him breathe.
“You pull your hair out,” Weekes said. “I’m not a doctor by any means, and I’m sitting there trying to figure out, ‘Why is my baby doing these things?’ ”
Sequencing is only the first step in what doctors call the “diagnostic odyssey.” Making sense of the resulting mountain of data is its own challenge. Unspooling just one human genome takes up roughly 150 gigabytes, the equivalent of roughly 32 DVDs. The gene responsible for Quinlan’s disorder could be hidden in any one of them.
Geneticist Tim Yu is one of the founders of Claritas, the sequencing lab that handled Quinlan’s case, and he hunted through the entire library of the boy’s DNA for clues. A few years ago, a project this complex would have required getting bulky hard drives of genomic databases through the mail. WuXi NextCODE’s big breakthrough was to speed up the process by introducing the medical equivalent of an Internet search engine, able to scour roughly two dozen reference databases over the Internet to find similar mutations.
The creation of vast warehouses of genetic information has raised concerns about privacy, however. Critics have questioned drug companies’ access to the databases, and there have been several well-publicized cases of researchers connecting people to DNA samples that were submitted anonymously. Marcy Darnovsky, executive director of the advocacy group Center for Genetics and Society, said that China provides few safeguards for those who face discrimination based on what may be uncovered within their DNA.
“Technically it can’t be 100 percent assured that your data will remain anonymous,” she said.
Smarason called WuXi’s systems “ironclad,” arguing that the data is not identifiable and is encrypted to defend against hackers. Consent is required from every person who is part of the database.
“Many patients with diseases for which there is no treatment and many with rare disorders want their data shared, in order to contribute to a better understanding of their condition and to develop better drugs,” Smarason said.
Indeed, the larger the database, the better Yu’s chances of finding the gene responsible for Quinlan’s disorder. Yu looked for genes associated with Quinlan’s unique symptoms: a small head, seizures, involuntary movements and rigid muscles. WuXi NextCODE’s system found 120 that could have caused one of the symptoms.
Nearly half of those genes were strong matches on both of the systems the lab uses to sequence patients’ DNA. But WuXi’s program found only six could have been passed down from parents who showed no sign of the disorder.
One stood out to Yu, a clipped segment on chromosome 7, resulting in a mutation of the BRAT1 gene.
“They are almost invariably bad,” Yu said.
At the time, only a handful similar cases had been documented in medical literature. In all of them, the babies died within months.
Racing and waiting
Quinlan’s disorder now has a name: RMFSL, or rigidity and multifocal seizure syndrome, lethal neonate. But the description is no longer accurate: He has already survived much longer than the diagnosis would have predicted.
Quinlan celebrated his second birthday at his grandparents’ house. He wore a T-shirt with the Sesame Street character Grover on it, and his birthday cupcakes were decorated with blue icing and the Superman logo, a Q replacing the S.
“When we finally got the diagnosis, it was like a sigh of relief,” Weekes said. “We don’t know what the future is going to hold, but at least we know why.”
Gene mutations similar to Quinlan’s have recently been found in a handful of other children, suggesting a broader spectrum of symptoms and offering some hope for Quinlan’s progress. One is 10 years old with only mild mental disabilities. Others are more severely compromised than he is. Yu and Quinlan’s neurologist at Boston Children’s Hospital, Heather Olson, recently published a paper expanding the definition of the disorder.
Medically, the diagnosis has helped in small ways. Children with his mutation often have trouble breathing, so Quinlan is on an oxygen monitor to guard against sleep apnea. Common colds get immediate and aggressive treatment. His parents and nurses pound on his chest to help him clear his lungs several times a day.
There is no cure for Quinlan. But this past spring, Chinese officials launched a $9 billion investment in precision medicine, a wide-ranging initiative to not only sequence genes, but also develop customized new drugs using that data. The funding dwarfs a similar effort announced by President Obama a year ago that has an uncertain future in Trump’s new administration.
“The U.S. system has more dexterity and agility than the Chinese system,” said Simon, of Duke Kunshan University. “But the learning curve in China is very powerful, and the Chinese are moving fast. The question is not if. The question is when.”
Quinlan and his family are waiting for the answers.
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