China gains ground on US in genomics arms race, helping American doctors diagnose rare illnesses
How baby Quinlan’s extremely rare genetic mutation thrust his family into the centre of a global economic contest to push the limits of medicine
Lindsay Weekes knew something was wrong as soon as her son was born. The baby was a strapping 3.6kg, with thick, curly black hair. But from the first moment Quinlan drew air, Weekes could see he was tense, his muscles rigid.
Within 24 hours, Quinlan was whisked away to an intensive care unit. They began a battery of tests in hopes of diagnosing his disorder, the start of a tortuous journey that has thrust the family into the centre 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 US 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 at home and abroad – including a laboratory that handles some of the toughest cases at Boston Children’s Hospital in Massachusetts, where Quinlan has become a staff favourite.
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 emigrating to the US. Chinese company WuXi NextCODE is one of its chief investors, and researchers there use WuXi’s programs to analyse the reams of data inside our DNA.
Under US president-elect Donald Trump, America’s relationship with China has been defined by frustration over the loss of factory jobs to China. 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 US is not moving with the same kind of purpose,” says Eric Schadt, director of the Icahn Institute for Genomics and Multiscale Biology at Mount Sinai, New York. “China has established itself as a really competitive force.”
For the Weekes family, the stakes couldn’t be higher. Two years ago, on New Year’s Eve, Weekes and her husband were at home in the Boston suburbs. Quinlan had spent four days in the hospital after his birth and was sent home when doctors couldn’t pinpoint the problem.
Now he was about four months old. Weekes looked down at Quinlan cradled in her arms and realised his lips were blue, his eyes staring blankly back at her. He was having a seizure. She beckoned her husband, “Bear”, but by the time he walked over, Quinlan’s lips were once again a healthy pink.
But then it happened twice more, and they called an ambulance to take Quinlan to the Boston Children’s Hospital. He didn’t leave 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. The family hoped genetic testing would provide an answer.
The cost of sequencing DNA has dropped dramatically since researchers unravelled our biological building blocks in 2001. Estimates of the price tag for that initial discovery range from several hundred to a few billion US 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 analyse genes to personalise medical care. And doctors believe genetic data could provide the keys to understanding mysterious diseases like Quinlan’s – and maybe develop a cure.
For China, the genomics revolution has been a chance to showcase its technical prowess as well as cultivate home-grown innovation. Over the past two decades, China transformed itself into an economic superpower through massive industrialisation. To succeed over the next generation, it hopes to emulate Western-style entrepreneurship to transform its economy.
“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,” says Denis Simon, executive vice chancellor of Duke Kunshan University in Suzhou, Jiangsu province.
What China cannot create, it appears 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 US$3.6 billion into the US health and biotechnology sector over the past 16 years, according to 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 realised 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 US$3.3 billion. Roughly 14,000 people carry out the company’s research and product development around the world.
In the US, the company has helped finance an array of biotech start-ups, including the home DNA testing company 23andMe. 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 US company in the US, but we’re a Chinese company in China,” says Hannes Smarason, chief operating officer of WuXi NextCODE. “We’re local in every market.”
At about six months old, Quinlan came down with a severe respiratory virus that sent him back to the hospital, then to a nearby rehabilitation centre. His seizures became more severe, and he underwent a tracheotomy to help him breathe.
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 about 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 searched 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 post. 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.
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 says. At the time, only a handful of similar cases had been documented in medical literature. In all of them, the babies died within months.
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.
“When we finally got the diagnosis, it was like a sigh of relief,” Weekes says. “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.
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 apnoea. Common colds get immediate 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 in spring 2016, Chinese officials launched a US$9 billion investment in precision medicine, a wide-ranging initiative to not only sequence genes, but also develop customised new drugs using that data. The funding dwarfs a similar effort announced by US President Barack Obama a year ago that has an uncertain future in Trump’s administration.
“The US system has more dexterity and agility than the Chinese system,” says 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.