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China’s Genetics Giant Wants to Tailor Medicine to Your DNA

China’s Genetics Giant Wants Everyone to Live to at Least 99

(Bloomberg Businessweek) -- At the Shenzhen headquarters of the Chinese genetics company BGI Group, there’s no excuse for poor health. Employees are urged to punctuate their days with quick bursts of high-intensity exercise on the weight benches, pullup bars, and spin bikes placed in the open-plan offices’ breakout areas. Riding elevators is officially discouraged. For those who insist, the company has placed a simple injunction on the doors, in English and Chinese: “DO SQUATS if taking the lift.” For lunch, in-house coffee bars offer a selection of low-calorie “nutrition meals” as well as a curious “decreasing serum uric acid series.” During their off hours, employees set out on arduous group hikes up and down the verdant mountains surrounding the city, often led by senior executives for whom physical fitness is a component of annual performance reviews. “If I get fat, no bonus,” one jokes, a little anxiously.

BGI’s co-founder, chairman, and animating force, 65-year-old geneticist Wang Jian, insists on all this exertion not just because he believes healthy workers are more productive. He also wants the more than 6,000 employees of his company, one of the world’s largest producers of genetic research, to be walking advertisements for their products. To that end, employees and their families are encouraged to sample the wares, undergoing a regular battery of genetic and other tests to screen for such illnesses as cancer, heart disease, and dementia. Monitoring and prevention plans are put in place for those with worrisome results. With the right diagnostics and healthful lifestyles, Wang professes, everyone at BGI should live to 99 or older. It will take a while to test the claim: The average age of his employees is just over 30.

China’s Genetics Giant Wants to Tailor Medicine to Your DNA

Whole-genome sequencing, the technology that drives BGI’s business, is no longer particularly new. But Wang says genomics is about to become the core of modern medicine, for several reasons: Sequencing is becoming cheaper and more reliable; research is advancing to the point where genetic findings can underpin treatments; and governments—above all, China’s—are encouraging their deployment at large scale. And he says BGI, which manufactures sequencing equipment, sells diagnostic tests, and performs research for drug companies, can be the company to take it there, becoming China’s first global life-sciences giant in the process.

Someday soon, Wang predicts, getting your entire genome sequenced—a far more elaborate enterprise than commercial tests such as those from 23andMe Inc., which examine only small portions of a person’s DNA—will be as unremarkable as getting a vaccination. Such testing will be repeated throughout your life, informing health decisions, eating habits, and perhaps even your choice of mate. And it could guide your medical treatments, eventually provided in BGI hospitals that specialize in acting on genomic insights. “Nowadays, medicine mostly comes from the industrial revolution. It’s physical, it’s chemical: Kill the tumor, poison the tumor, burn the tumor,” Wang says. “We go back to real biology.”

The field of genomics has come a long way since the first draft sequence of the human genome—the complete list of the billions of chemical “letters” that make up our DNA—was unveiled in 2001. The world Wang describes may finally be possible. And if the challenges of realizing it were purely technological, then BGI might be better poised than anyone else to make it happen. But genomics is an ethically and politically fraught proposition, and for Wang to win the world over to his vision, he’ll have to answer a fundamental question: Why should anyone trust a Chinese company to do it?

Like many science-minded entrepreneurs of his generation in China, Wang got his start in publicly funded research. BGI began life in 1999 as the Beijing Genomics Institute, a state-backed lab dedicated to assisting the Human Genome Project (HGP)—the Clinton-era effort to assemble the first-ever comprehensive picture of human DNA. Compared with the participating Western institutions, BGI was tiny and its contribution modest. But the work gave Wang and his co-founders the confidence and international connections to strike out on their own. In 2007 they split from the Chinese Academy of Sciences, the state-controlled umbrella for high-level research, to create a private company focused on sequencing. They also decided to relocate to Shenzhen, China’s entrepreneurial hothouse.

At the time, sequencing was shifting from revolutionary to commonplace. The HGP, which wrapped up in 2003, required billions of dollars in funding; by mid-2008, according to the U.S. National Institutes of Health (NIH), a human-size genome could be mapped for less than $1 million. The cost has been dropping even faster since. With researchers around the world hungry for genetic data on everything from viruses to elephants, BGI established itself as a sort of Foxconn of sequencing. It commissioned some assignments itself, eager to demonstrate its scientific chops by placing articles in prestigious journals. In 2008 its researchers published, in Nature, the first genome sequence of an Asian person; later, a BGI team revealed the genetic details of an E. coli outbreak in Germany through the New England Journal of Medicine.

China’s Genetics Giant Wants to Tailor Medicine to Your DNA

At the same time, BGI gained a reputation for testing the field’s limits. In 2011 it created the Cognitive Genomics Lab, assembling a multinational group of scientists to investigate the genetic basis of intelligence—a taboo question for many Western researchers. The study, which would have examined the DNA of high-IQ subjects and compared them with a control group of average intellects, was never finished. Later, an executive revealed at a conference that BGI was working toward offering gene-edited “micropigs” in a rainbow of colors. This plan, too, was eventually dropped. Both projects were emblematic of a certain tendency toward corporate entropy—an eagerness to pursue anything as long as it vaguely involved DNA.

As it further diversified its business model, BGI was contemplating a deal that would make it an important provider of the field’s basic infrastructure. In 2012 it offered $118 million to acquire Complete Genomics, an unprofitable sequencing-machine manufacturer in Silicon Valley. At the time, BGI was believed to be the world’s largest buyer of sequencing equipment, primarily purchased from Illumina Inc. in San Diego. Control of Complete would give the Chinese company the ability to build its own sequencers and sell them to others, particularly emerging-market customers that might balk at Illumina’s prices.

The proposal attracted plenty of attention in the U.S., much of it negative. Illumina fought back vigorously with a counterbid and a Washington lobbying campaign. But U.S. authorities approved the proposal, despite fears that it might give China a leg up in genomics or put sensitive information in Beijing’s hands. “It’s hard to believe that any individual or any company that’s directed by the state to engage in certain activities wouldn’t do so,” says Michael Wessel, a member of the U.S.-China Economic and Security Review Commission who raised concerns about the deal.

Discussions about the security implications of genomics tend to be extremely speculative, and BGI has attracted nothing like the scrutiny that Huawei Technologies Co., China’s largest tech company, has faced over allegations that its equipment could be used for espionage. But the two companies are similar in at least one important respect: They have opaque structures that make it difficult for outsiders to understand the full extent of their operations, finances, and ownership.

China’s Genetics Giant Wants to Tailor Medicine to Your DNA

BGI’s official organization chart is depicted as a massive planet, BGI Group, orbited by eight moons of varying sizes. (It could also be read as a nucleus and its electrons.) Only one of these eight moons is publicly traded—BGI Genomics, which listed on the Shenzhen Stock Exchange in 2017 and has a market capitalization of about $3.5 billion. It derives most of its revenue from services such as prenatal tests. Another unit, MGI, incorporates the sequencing-machine business acquired from Complete. Much of the rest of BGI, which includes divisions dedicated to forensics and basic research as well as an open-access journal, is officially not for profit, subsidized by income from the commercial divisions and from grants.

The company has never disclosed how all this works or how its relatively modest earnings can sustain so much public-spirited research. Executives will say only that BGI is privately owned—Wang, with a net worth estimated by Forbes at $1.2 billion, is the largest shareholder—and has no special relationship with Beijing. It has received substantial loans from the government’s China Development Bank, however, and also operates a “biorepository” of frozen tissue samples and the China National GeneBank (CNGB), a Shenzhen facility that houses a vast trove of digitized genetic data, on behalf of the state.

BGI’s best insulation against suspicion is probably its roster of foreign partners. Over the years the company has collected a long list of scientific luminaries as advisers. One of its more enthusiastic collaborators has been George Church, a Harvard researcher who is arguably the most prominent geneticist in the U.S. He’s been involved with BGI since 2007, and one of its research institutes bears his name. Church describes BGI as “a bit more sophisticated” than Western competitors, particularly in applying genomic information to personal health. “It’s really unique in the whole world, what they’re trying to do and what they’ve done,” he says.

China’s Genetics Giant Wants to Tailor Medicine to Your DNA

Wang’s eagerness to be seen as a sexagenarian superhuman is rarely subtle. Near his desk, a pair of gymnastic rings is suspended from the ceiling—useful training tools for one of his primary hobbies, mountaineering. The halls of BGI’s main campus, which occupies a converted shoe factory near the Shenzhen port, are decorated with photos from his climbing expeditions, including one shot from the summit of Mount Everest. For an interview in August he wore a T-shirt and cargo pants made of a stretchy technical fabric, as though he might bolt off up a mountain at any moment.

BGI recently celebrated its 20th anniversary, and Wang, who has spiky salt-and-pepper hair and a kindly manner, insists it’s only getting started. “For the last 20 years we just built up the infrastructure,” he says in lightly accented English. “Now we really think we can do something for the country, for the world, and also for ourselves.”

He describes BGI as on its way to becoming the first full-stack genetics company: manufacturing sequencers, running them 24/7 with samples, and using research fueled by the resulting data to push the field forward, in turn creating even more demand for sequencing. Improving the basic technology is crucial to the strategy, and BGI is going after both ends of the market. Its entry-level sequencer, the printer-size DNBSEQ E, sells for about $12,000, making it ideal for small labs in developing countries. BGI says the machine can produce a full report on a sample in just eight hours, important when doctors need to rapidly identify a pathogen. The company’s top-of-the-line, $1 million T7—it looks a bit like an Imperial droid from Star Wars—is pitched to major research institutes and large drugmakers. It can churn through as many as 60 whole human genomes in a day.

The advances made by BGI and its competitors—above all Illumina, which still controls the majority of the sequencer market—have drastically lowered costs. As of August, according to the NIH, the cost of sequencing a human genome was $942, compared with about $4,000 in 2015, and BGI says its ultimate goal is to get to $100 or less.

“Everybody needs it, especially newborns, who need a baseline,” Wang says of whole-genome sequencing. That initial assessment can then be followed by “monitoring and testing for the lifetime.” The inherited infant genome doesn’t change, but as people age genetic programming can manifest in unpredictable ways. Subsequent tests could monitor the immune system by examining blood cells to determine which genes are active, or could track whether mutations are occurring more frequently than expected, which might indicate increased cancer risk. In China especially, “most tumor patients come to the hospital in the middle or late stages,” Wang says. With sufficiently early detection, “cancer is going to become a manageable, controllable disease.”

Making genetic tests ubiquitous, starting in China, is a central plank of the strategy. At BGI’s in-house coffee stands, employees can pick up test kits for human papillomavirus, which can cause cervical cancer, as well as for BRCA mutations, which are associated with an elevated risk of breast and ovarian cancer. The company sells tests to the public on Genebook, an online “BGI mall” that offers diagnostics as well as complementary products such as probiotic candies. (BGI doesn’t disclose its sales through such retail channels.)

So far the only people starting to experience Wang’s vision are BGI employees. One, Zhu Yanmei, describes having her genome sequenced after she joined the company as head of human resources in 2012. A generally healthy 47-year-old, Zhu was alarmed to learn she might be predisposed to develop Parkinson’s disease. It was the kind of genomic knowledge that’s at once significant and not especially useful: No drugs can head off Parkinson’s, and there’s only limited evidence that diet or exercise have a preventive effect. But Zhu figured she had to do something, so she began making small adjustments to her routines. In particular, she started using chopsticks with her left hand instead of her dominant right, a mental challenge that might in some small way help forestall dementia, which is common in Parkinson’s patients. If one day a preventive treatment comes along, she’ll know to take it and to monitor the scientific literature for relevant research.

China’s Genetics Giant Wants to Tailor Medicine to Your DNA

Not everyone wants this kind of foreknowledge, but Zhu says she’s confident that as sequencing becomes more accepted, most people will. “The next step,” she says, “is from million scale to billion scale”—led by China, where things are “top to bottom” with “not so many discussions.” She laughs. “One of our dreams is that everyone has an ID card with their genome,” informing both medical and nonmedical choices throughout a lifetime.

To that end, BGI has proposed a plan to sequence the genome of every baby born in Shenzhen, a city of more than 10 million. Doing this could provide valuable data, both for individual health management and large-scale study. But it would also raise serious privacy concerns. Asked whether the state would have access to individuals’ genomes, Wang demurs, arguing it’s not obvious what Chinese officials would gain from them—after all, they have plenty of tools to track citizens already. “Right now the Chinese government is not seriously thinking about these kinds of things,” he says. “It’s a little too early.” Current evidence suggests otherwise. Human Rights Watch and other groups have criticized China for systematically collecting genetic information from members of the Uighur minority without proper consent, and the national DNA database for law enforcement is the world’s largest. (BGI says it has strict procedures to protect patients’ privacy and adheres to international ethical standards.)

China’s Genetics Giant Wants to Tailor Medicine to Your DNA

Wang is accustomed to controversy. Last year he attracted a flurry of attention for saying it would be a “disgrace” for any of his employees to have a child with a birth defect, which would indicate a failure to use BGI’s prenatal tests to rule out problems—or to act accordingly.

In the interview, he argues for similar vigilance on a national scale. “China has 85 million disabled [people], and 70 to 80% of these disabilities are from birth defects,” he says. “We can really prevent this. We can do premarriage testing”—to flag relationships in which partners carry a worrisome combination of genes—“and prepregnant, prenatal.” He acknowledges that such ideas might sound alarming but predicts that, given the option, most potential parents will vote with their feet, so to speak: “People make their own choice.” Wang argues that perceptions Chinese scientists are too aggressive stem in large part from envy and echo criticisms directed at rising powers throughout history. “When people grow up and get big muscles, the older brother’s not happy with that,” he says. “After World War II, European people looked at the Americans and said the same thing—‘You cowboys.’ ”

There are limits to what Wang says he’s prepared to contemplate. The company, he points out, is no longer studying the genetic origins of intelligence. But he suggests that, if researchers are able to truly identify genes that produce smarts, a Gattaca-esque push for designer babies is probably inevitable, especially in ultracompetitive China, where there’s already a robust market for genetic tests that supposedly gauge innate talent for math or music. BGI has no plans to help parents customize their offspring, but “there’s lots of people who want to do it,” Wang says. “People never stop searching for interesting things.” Unless, that is, someone stops them.

Last November, as thousands of scientists arrived in Hong Kong for a conference on gene editing, a Chinese doctor named He Jiankui made a stunning announcement. Weeks before, He said, the world’s first genetically engineered babies had been born on the mainland. Working in secret, he’d used CRISPR, the powerful gene-editing tool, to alter the DNA of two twin girls, Lulu and Nana, to make them more resistant to HIV. Even more alarmingly, he’d done so via germline editing, a technique enabling the trait to be passed on to future generations, with unpredictable effects.

The reaction among Western scientists was predictably furious, and it soon became apparent that many Chinese scientists were just as angry. The country’s main genetics and cell biology bodies issued swift denunciations, and 122 researchers signed a joint statement that called He’s project “madness,” complaining it had “delivered a blow to the reputation and development of Chinese biological research.” BGI was among the organizations that condemned He’s work, which had no connection to the company.

The episode nevertheless illustrated how far China has to go before Western doctors and regulators will be comfortable giving even its most sophisticated corporations a central role in patient care. No country has a solid sense of how to regulate genomics, but in China, “it’s the wild, wild, wild West,” says Robert Green, a geneticist at Harvard Medical School who researches consumer genetic testing. Even the kind of straightforward diagnostics that underpin much of BGI’s current business present thorny questions. China has no equivalent to the 2008 Genetic Information Nondiscrimination Act, the U.S. law that bars insurers and employers from using DNA to make coverage or hiring decisions. And the scientific press is full of examples of eyebrow-raising research conducted at Chinese institutions, such as using CRISPR to breed ultramuscular beagles and giving macaques extra copies of a human gene that may promote intelligence. (No Planet of the Apes-style uprising has yet been reported, but it’s early days.)

China’s Genetics Giant Wants to Tailor Medicine to Your DNA

Green points out, too, that sequencing genomic data is one thing; drawing inferences about individuals from the results opens up another host of potential ethical issues. Companies might, for example, promote unproven claims about customers’ genetic makeup so they can sell them products or treatments. “We’re struggling with these issues in the U.S., and we haven’t claimed to have got it right, but you get the feeling that in China many of the companies are just blowing past,” Green says.

China’s leaders appear concerned that their country not be regarded as a genetic free-for-all. Although the government was initially slow to react to the Lulu and Nana revelation, it came down hard once the depth of international fury was clear, shutting down He’s lab and declaring that it wouldn’t tolerate similar experiments. (Ominously, he hasn’t been seen in public since.) Earlier this year the National Health Commission published draft regulations that would require researchers to receive central government approval to edit embryos or any cells that will be implanted in humans, with fines and criminal charges threatened for those who break the rules. Articles on gene editing in the heavily controlled media also frequently warn of its dangers, sometimes with reference to dystopian movies such as Resident Evil. With a vast architecture of surveillance and few checks on government power, Harvard’s Church says, “I don’t think the guardrails are less in China, I think they’re more.”

BGI’s public commitments on editing are fairly anodyne; in the wake of the He controversy, it issued a proposal calling for researchers to “strictly obey the laws, regulations and policies governing life science” and “strengthen ethical awareness.” Wang insists the company has no interest in experimentation that could bring it comparable opprobrium. “We can do pigs, we can do dogs, we can do monkeys,” he says of BGI’s gene-editing efforts. “There’s no reason for us to do humans.” He adds: “Do you want to use that technology to be the first one and make yourself the common enemy of society? We’re not that dumb.”

The genomics revolution Wang says is at hand will raise a series of difficult questions about ethics, privacy, regulation, and where the boundaries of science should fall. But in his telling, all that will really matter is outcomes—whatever the moral complexities, we’ll be healthier with genomics than without it. And Wang intends for his outcomes to be excellent. In the meeting room where he receives visitors, he keeps a little Lucite block, encasing a 3D image of himself as a young man. Etched into the surface, right above the Chinese characters for his name, is a pair of numbers that capture his aspirations: “1954–2074.”

To contact the editor responsible for this story: Daniel Ferrara at dferrara5@bloomberg.net, Jeremy Keehn

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