|State of the art sequencing in the proteomics labortory at genomics research company BGI in Shenzhen, China: The company is raising eyebrows, and hackles.
(Garrige Ho For the Globe and Mail)|
In the South China city of Shenzhen, a thriving manufacturing hub known for cheap goods and high-tech electronics, the genetic secrets of life roll off machines by the minute.Here at the global headquarters of BGI-Shenzhen, housed in a former shoe factory, the genomic revolution runs on an industrial scale. Powered by an army of young lab technicians and banks of high-end, U.S.-made sequencers that hum 24/7, the DNA of human kind is decoded with conveyor-belt speed and brute force.
But not just human DNA. Once known as the Beijing Genomics Institute, BGI is on a mission to sequence the genomes of a vast array of living things. It has already done rice, the cucumber, the Giant Panda, the Arabian camel, the chicken, the coronavirus behind severe acute respiratory syndrome (SARS), 40 strains of silkworm and the Tibetan antelope, to name just a few.
Its services are in high demand. It has unravelled the DNA of a 4,000-year-old Greenlander dubbed Inuk, teamed with Saudi Biosciences to sequence Arab genomes and with the University of Edinburgh to decode plants, animals and people in Scotland. Canadian and U.S. research groups are repeat customers.
As with many things made in China, the price is hard to beat. Drug companies, doctors and researchers around the world are in awe, and more than a bit envious of BGI’s resources.
As a Canadian government scientist tweeted: “China’s big push in genomics. 128 Illumina sequencers in an old shoe factory and I can’t get a single one for my lab.”
But along with the envy, there is discomfort and, in the United States, outright fear that an enterprise backed in part with bank loans supported by the Chinese government has unfettered access to the genetic building blocks of humanity. DNA, after all, contains the chemical hallmarks of what makes each of us unique – the raw material that may hold the keys to the next breakthroughs in science and medicine.
What might China – with its poor record of enforcing intellectual property laws and history of human-rights abuses – do with this information?
U.S. officials first raised eyebrows after BGI snapped up a record-breaking order for 128 cutting-edge sequencers made by San Diego-based Illumina. but the concerns are more urgent now that the authorities are deliberating whether to allow the Chinese company to buy Complete Genomics of California, a major U.S. sequencing company.
The acquisition would help to cement China’s supremacy as the world’s top genome sequencer, boost its technical prowess and give it a strong U.S. base, but the deal has officials there fretting over both the security of genetic data and national security.
Because the technologies involved “have national security implications related to bioweapons, this bears strict scrutiny,” says Michael Wessel, who sits on the U.S.-China Economic and Security Review Commission. “Are there capabilities here that can be adverse to American interests?” he told the Washington paper Politico last week.
But some feel that such fears have more to do with trade than security. Last week, The Associated Press reported that China has overtaken the United States as the world’s largest trading partner. This week, the United Nations found it also has surpassed the U.S. in patent applications, although the quality of its patents is often disputed.
Harvard University geneticist and entrepreneur George Church, an adviser to many biotech companies, dismisses concerns over China’s dominance in genomics as “misplaced nationalism.” Mark Poznansky, head of the Ontario Genomics Institute, agrees: “There’s recognition that we just can’t compete. I think that’s part of the paranoia.”
BGI argues that there’s “absolutely no basis for such a wild and speculative claim” of national-security threats and bioweapons risks. It says those fears are sour grapes seeded by Illumina, which also bid for Complete Genomics but lost to out to BGI.
Writing to Complete Genomics directors last month, Illumina said BGI is a “foreign state-owned entity,” and the deal raises “national security, industrial policy, personal identifier information protection and other concerns.”
BGI denies that it is state-owned, but, ironically, even as it makes a big play for the world’s DNA, China is cracking down to ensure that the genomes of its own citizens stay home. Its state council is now drafting regulations to protect the country’s “human genetic resources,” fearing that it will lose intellectual-property rights over its citizens’ genetic information.
Despite the international trade tangles over DNA, Canadian scientists familiar with BGI generally feel that the biotech giant should inspire, rather than intimidate, the rest of the world. Tom Hudson, president and scientific director of the Ontario Institute for Cancer Research, says many countries are more talk than action when it comes to research, but China makes things happen – “there’s extreme momentum.”
BGI’s list of goals tells the story: It aims to improve the human lifespan by five years, increase global food production by 10 per cent, decode half of all genetic diseases to seek treatments and cut birth defects by 50 per cent.
“We are a little bit ambitious,” says Wang Jun, BGI’s 36-year-old executive director, “but we are ambitious for good reason.”
Rise of a global player
It has grown up by the sea in Shenzhen since 2007, but the Beijing Genomics Institute was born in the Chinese capital on Sept. 9, 1999 (considered auspicious because the numbers are associated with longevity). It was the brainchild of three academics who had returned from the United States determined that China join the international effort to map the first human genome.
It was a daring move, as the researchers had yet to persuade the government – essentially China’s only source of research funding – that their cause was worthwhile. Even then, the Human Genome Project drew little attention in China; only when its completion was announced at the White House in June, 2000, did China’s president learn by watching CNN that his country had played a role.
Since then, BGI – which officially operates as a private non-profit company – has grown astronomically, luring back postdoctoral fellows trained in the West and hiring science grads by the hundreds straight out of school. The average age of its more than 4,000 employees is 26, and one-quarter of them are bused to and from company dorms, complete with cafeterias, a medical clinic and a gym.
The youthful labour force gives BGI an edge: Employees make a paltry sum by Western standards (but competitive for China) and they bring a youthful energy to the floor of what has been called “the sequence factory.”
Ontario’s Dr. Hudson considers such youth an asset: “What they lack in seasoned expertise they make up for in their boldness.” But he notes that there are two sides to BGI. One is the founding group of seasoned scientists, still big contributors to major collaborations, including the International Cancer Consortium, which he helped to launch (a 17-nation bid to decode the DNA of 25,000 cancer patients). BGI also has its flagship effort, called the 3M project, a bid to map, with international help, a million plant and animal genomes, a million human genomes and a million micro-ecosystems.
The other arm is the one fuelling BGI’s rapid growth – the global sequencing service – announced with a full-page ad in a leading science journal shortly after its 2010 sequencer shopping spree (each was worth about $500,000). The purchase was financed largely by the China Development Bank, and most of the machines now run non-stop in Shenzhen or in nearby Hong Kong, where regulations for importing samples are less restrictive than on the mainland.
As the ability to decode DNA becomes faster and cheaper, BGI expects to sequence 40,000 to 50,000 genomes this year – more than 10 a minute. And quantity isn’t the only improvement, says Dr. Poznansky of the Ontario Genomics Institute, He visited Shenzhen in 2010 and, “within a year, the quality of the data coming from BGI went from being horrible, to pretty darn good.”
Yet as BGI cements its role as the world’s sequencer, uneasiness persists about just how much genetic information it will collect and be the first to mine. Dr. Poznansky is familiar with the security concerns: “What if the Chinese keep the data … If they make the discoveries, they will own it. … Are we confident they won’t steal the data?”
This view, he says, stems largely from the ethos of the pharmaceutical industry: “We won’t go into China or India and build labs there because they won’t respect intellectual property laws.”
Dr. Wang, its executive director, says BGI is well aware of such concerns. He insists that it takes extra precautions to ensure that intellectual-property rights are respected: “We align with all international standards, because we are very international too.”
To that end, it has strived to demonstrate that it is independent of state control, in part by distancing itself from Beijing and the government-affiliated Chinese Academy of Science by moving to Shenzhen.
However, Dr. Wang does acknowledge the need for government support. And, along with government grants, the company’s major loan of $1.5-billion over 10 years from the state-backed development bank came amid a state infusion of investment designed to ward off economic recession. Not only does the bank lend on generous terms to projects deemed to be in the national interest, repayment is frequently extended significantly to let Chinese companies grow without fear of defaulting.
As well, several of BGI’s senior researchers are still with the science academy, dividing their time between government and company work, and its agriculture operation has been designated a “key state laboratory.” And the company is Beijing’s major partner in a new national gene bank to be housed nearby and to help China protect and make use of its “precious genetic resources,” according to state media.
Like most sizable enterprises in China, state-owned and private, BGI has a Communist Party committee. A banner in the sequencing lab reads: “Only with data can you find truth, and only with truth can you serve the country.”
Ethical debate just beginning
In the West, genetic research has long fuelled debates over ethics, privacy and the need to protect data – but less so in China, where the needs of the state have historically trumped individual rights. For instance, some wonder just how China, with its one-child policy, might use genetic technologies on its own people.
“We’ve seen other sorts of human-rights abuses in China,” says Marcy Darnovsky of the non-profit Center for Genetics and Society, based in Berkeley, Calif., noting the risk that prenatal tests could be used to phase out birth defects. “It starts to smack of … eugenics.”
In 2009, CNN reported on a unusual summer camp in Chongqing where children were given DNA tests to try to identify their natural talents so that they could be steered toward suitable careers. Most scientists, including those with BGI, dismiss the notion that such predictive tests have any credibility, but the program indicates how genetic technology could be deployed in the world’s most populous country.
At the same time, U.S. officials keep a constant vigil for examples of intellectual-property theft, and scandals of misappropriated medical data are rampant. This week, the dean of Nanjing University’s pharmacy school was accused of using blood samples from local hospitals without permission to create a private genetic data bank.
But even as the scandal plays out – and BGI staffers await word on the acquisition of Complete Genomics – the mood at the old shoe factory in Shenzhen is brimming with optimism. Researchers here see a new era dawning for China to make a major contribution to global health – one that includes sound ethics.
Qi Ming, the company’s deputy general manager, says BGI is diligent with patient consent forms, has an institutional review board for projects involving humans, and requires that its researchers adhere to standards required by international scientific journals.
“The bigger goal,” Dr. Wang adds, “is, ‘Can we do something good for society?’ ”
Dr. Qi, also director of Zhejiang University’s Centre for Genetic and Genomic Medicine, says BGI’s founders are well equipped to find their way through the ethical minefield. “We started from day one to pay attention to these issues. We all came from the U.S. or European schools so we all have that training.”
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