Chinese genome mappers

From most vantage points, this one-time shoe factory in southern China looks like a one-time shoe factory. SundayAGElogoSqueezed between other factories in this bleakly industrial zone of Shenzhen, just across the border from Hong Kong, it has a flavour of the ordinary.

The lobby is functional and unornamented. Thousands of young workers tramp and up down slightly shabby flights of stairs to get to from floor to floor. The pounding at a construction site out the back rattles the windows.

But despite the lack of ostentation, this is the world’s largest genetic research organisation. Here massive super-computers and arrays of ultra-sophisticated gene sequencers churn out the genetic data of anything from an echidna to a human tumour, from a microbe to a tapeworm to a strain of ultra-productive rice. This is the razor-edge frontier of gene science, where scientists produce and ponder the new genetic maps that may change the world.

BGI headquarters in Shenzhen

BGI headquarters in Shenzhen

Founded in 1999 and once known as the Beijing Genomics Institute, BGI leads the world in genomics; mapping literally thousands of genomes (a genome is the entirety of genetic information in any organism). Yet these BGI labs and workrooms in Shenzhen are remarkably casual and egalitarian. No-one wears a suit or tie. Workers live together and play together. And there’s a quasi-collegiate do-good feel. Massive sets of genetic data are posted on a website for free world-wide use. Human health is a BGI priority – both in the theoretical realms of advanced biological investigation, and at a practical level.

Here at the BGI headquarters, one lift only goes to the fifth and eighth floors, and one only to the eighth floor. The small on-site supermarket in this blocky eight-storey building sells fruit and yoghurt, but no cake, no ice-cream, no lollies. The wall menus in the canteen list the kilojoule value of the meals on offer; and they are all on the lean side. Sport is encouraged – basketball, soccer, badminton – and team photographs are prominently displayed.

This preoccupation with physical fitness is easily understood: some of BGI’s leaders have taken advantage of BGI’s enormous genome sequencing capabilities: they’ve had their own genomes sequenced and they know whether they carry the genes that render them susceptible to certain kinds of cancer, or diabetes, some auto-immune disorders, Huntington disease, heart disease or Alzheimer’s. Unlike most of us, they have peered into a crystal ball and seen the shadows.

Most common human diseases and disorders are caused by a complicated interplay between genes and life risks (smoking, a poor diet, excessive drinking, a lack of exercise): but reading the genes can provide an indication of future health concerns, and the BGI leaders have taken note. Their physical health, and the health of the BGI staff, has become a priority.

Zhang Gengyun, one of BGI’s vice presidents, says it’s not easy to decide to have your genome sequenced. Not everyone wants to know if they have a better-than-average chance of developing, say, cancer. It might mean decades of anxiety; fear of the apparently inexorable arrival of a tumour. On the other hand, sometimes the knowledge can give people the chance to fight back while there’s still a chance.

“It’s hard to say whether that’s worse or not,” Zhang says thoughtfully. “Even the BGI leaders, we don’t have agreement about whether that’s worse or not. Some people say, hey, why should I worry about something that could happen.”

He has yet to take the plunge. “I haven’t,” the 48-year-old adds with a grin. “I want to know, but I can wait. I’m not so worried about my health.”

Sitting in a sunny meeting room in BGI’s Shenzhen headquarters, Zhang looks tanned and healthy, casual in an open-necked olive-green shirt and beige trousers; but he says he knows he has at least one genetic weak point: “Like me, I cannot drink alcohol. That’s not a good allele (form of a gene)”.

Some high net worth individuals turn to sequencing after they have fallen ill. Battling cancer, Apple co-founder Steve Jobs reportedly paid US$100,000 for the sequencing and analysis of his entire genome and the tumour in his pancreas. He was upbeat about the science, but the tumour killed him in 2011. The essayist, polemicist and outspoken atheist Christopher Hitchens also turned to sequencing when he was diagnosed with cancer. He, too, died in 2011, but the sequencing helped doctors determine his body’s responsiveness to certain drugs, helping them find a way to modify his gruelling treatment regime.

With a doctorate from Rutgers University in the US, Zhang’s specialty is agriculture: using genomics to find higher-yielding and more drought- and pest-resistant plant crops; but he stays abreast of human health developments in sequencing. He’s confident the science will revolutionise cancer treatment.

“Within two or three years, the procedure for handling those patients with those diseases will be totally changed,” he says. “Steve Jobs: with the current technology we could sequence his samples perhaps every three months, even every month, to see what’s changed, what’s new that’s happening; whether the medicine is controlling some of those cancer cells. We can tell pretty clearly. I think that will be very good news for those patients.”

These genomics advances are proceeding at a rocketing pace. The first human genome sequence, the product of the international Human Genome Project, was completed in 2003. It took ten years and it cost about US$2.7 billion. BGI took part. Since then the price of full sequencing and analysis has plummeted. Jobs might have paid a six-figure sum for his sequencing, but these days the US$1,000 genome is in sight.

The price slide is so steep and so fast that soon this new “personalised medicine” could become routine. Scientists are even speculating on the potential of sequencing the genomes of newborn babies and predicting how the knowledge might change their lives.

Tasmanian devil

Tasmanian devil

The complete set of deoxyribonucleic acid, DNA, in any given organism (a human, a koala, a parasite, a mosquito, a virus), a genome is sometimes known as the blueprint for life. Genes are made of DNA, which consists of about 3 billion chemical bases, and 99 per cent of them are the same in every human. Each base, or nucleotide, is one of four chemicals, and the order, or sequence, of these four chemicals in each molecule of DNA determines the characteristics and development of all organisms.

Various methods can be used to map these strings of DNA sequences from tiny samples of matter. A speck of blood at a crime scene. A fragment of pollen. The root of a single human hair.

Genomics seems to have developed in an admirable way. Since the Human Genome Project, publicly funded research has to be made public, embracing the notion that important genetic data should be free, and freely available, to let others build on it. This sharing ethos has accelerated the pace of discovery and innovation and genomics rattles along much faster than, say, branches of chemistry research.

Still, (all too naturally), some firms are looking to cash in. In Australia, many scientists were startled and dismayed when the full bench of the Federal Court in early September ruled that a corporation could patent a breast cancer gene, running counter to a decision by the US Supreme Court, which in June last year decided the opposite. “A naturally occurring DNA segment is a product of nature,” the Supremes held, “and not patent eligible merely because it has been isolated.”

But even without patenting genes, there’s money to be made. The US-based firm 23andMe (the name refers to the pairs of human chromosomes – the packaged bundles of genes in cells) offers limited sequencing for US$99.

Consumers can buy a pack and send in a saliva sample. But, right now, 23andMe will provide only uninterpreted raw genetic data, or ancestry genetic reports. The US Food and Drug Administration blocked the firm’s health-targeted genetic reports late last year because it feared consumers would seize on the information and begin to self-medicate. Other companies though, provide the genetic information to doctors, and the FDA is fine with that.

Meanwhile, BGI forges on with more and more genetic discoveries, collaborating with universities, institutes and organisations around the world, including more than 200 in Australia. There are now BGI branches in the US and in Europe and a global staff of 5,000 people. The company’s aims are lofty: BGI wants to increase the average life span by five years, increase global food production by ten per cent, decode half of all genetic diseases, understand the origins of autism, and cut birth defects by half.

“We want to sequence more, and understand more about our genome,” Zhang says, with a gleam in his eye. “To provide more clues, more insight, about disease and treatments. That would give us a lot of new knowledge about our health and more insight about other species. The real idea to expand knowledge, that’s our top target.”

BGI in Shenzhen has a staff of nearly 2,700: scientists, lab workers and clerks. The average age is 27, and the atmosphere is university/YWCA/science club. Two-thirds of the employees live in sex-segregated dormitories near the BGI building, and many of them spend much of their leisure time following BGI team pursuits: sport and more sport, singing competitions, rock climbing.

Australian dragon

Australian dragon

Some geneticists have raised an eyebrow at BGI: noting this army of young and often not formally qualified workers, and the sheer output of this “gene factory”. Producing long streams of sequencing data is not the same as making the intuitive leaps needed to nose out unseen evolutionary paths or assemble the puzzles of disease control. Yet BGI is collaborating with respected scientists around the world and learning and developing all the time.

A giant in genomics sequencing, the company doesn’t seem to be in thrall to the Chinese government. It appears to be one of the world’s more admirable corporate citizens, rushing to help sequence the SARS virus when scores of Hong Kong citizens were dying of the disease a decade ago and to work on the E Coli strain that attacked Germans in 2011. With far more sequencing capacity than many countries, including Australia, BGI shares massive sets of sequencing data via the website of its Gigascience journal.

Some divisions of BGI also make money, from contracted sequencing and from revenue streams like the overseas sales of a pre-natal blood test. Older pregnant women have long been routinely advised to under an amniocentesis test, whereby amniotic fluid is drawn from the uterus via a fine, hollow needle and the fluid then tested to see whether the baby had Down Syndrome, spina bifida or cystic fibrosis. “Amnio” tests, though, carry risks, and can trigger miscarriages. The BGI test is a simple blood test, and BGI scientists say it has been proven almost 100 per cent accurate. It is likely to shake up the current standards of pre-natal testing.

Profits from this and other projects, Zhang says, will be used to pay costs and fund more research. “We want to sequence more, and understand more about our genome. To provide more clues, more insight, about disease and treatments,” he says. “That would give us a lot of new knowledge about our health and about other species.”

Genome sequencing has revolutionised the study of evolutionary biology. “Everybody is using genomic data,” says Australian geneticist Professor Jenny Graves, 71, now with La Trobe university’s Institute for Molecular Science. “Whether they’re looking at evolutionary relationships; how tusks develop in elephants; how things work in the microbial world; the relationships of different animals in the population, whether they’re endangered or inbred — everyone is using this kind of genome data.”

“We’re working on the Tasmanian devil, amongst many other things,” she adds. The devil is in trouble, with a devastating facial tumour disease, contracted via bites, which is ripping through the population. “The species doesn’t have a lot of genetic variation, particularly in one area. They’re almost clones of each other. You can transfer a cancer from one animal to another. That’s very rare. Tumours can pass from animal to animal. It’s not a virus or a bacterium, it’s an actual cell from a devil that gets passed.”

BGI is a prolific contributor within the Genome 10K community: scientists who are coordinating the sequencing of thousands of representative vertebrate species, Graves says. So far the Genome 10K project has managed to stack up 245 sequences for this genomic zoo, including the emu, black flying fox, short-beaked echidna, and the platypus. “It’s not just mammals, but a lot of birds, more and more fish, and reptiles: it’s sort of putting together the big jigsaw pieces so we can really understand vertebrate evolution”, Graves says.

Another Australian scientist, Professor Arthur Georges, director of the University of Canberra’s Institute of Applied Ecology, has twice visited BGI in Shenzhen to work on the whole genome sequencing of the Australian western bearded dragon lizard, with particular interest in how reptiles’ gender is determined. Again, it’s the forefront of understanding: “The genetic mechanisms aren’t well known for any of them,” says Georges, 60. “We know the sex determining gene for mammals, for birds, for amphibians, for fish, but no-one’s found the sex determining gene in a reptile.”

Impressed with the BGI work assisting with the dragon genome sequencing, he enjoyed the BGI scientists’ youth, enthusiasm and egalitarian spirit. “The guy at the top, in research, his desk is the same as everyone else’s (in a large open room); the only difference is that he has a running machine next to his desk.”

More generally, he was struck by BGI’s evident passion to improve the world. “They’re on a mission” he says. “They’ve got this incredible enthusiasm about the future; almost as if anything can be achieved.”

Genetic science is racing into the future, leaving the lawyers and ethicists panting a long way behind. One controversial BGI project to catalogue the genetic sequences of hundreds of ultra-intelligent people was written up around the world, prompting critical comments about eugenics, and headlines like “Get Ready for the Superbaby”. BGI now won’t grant interviews with the lead scientist on the project. Another scientist on staff feels the publicity was overblown, pointing out that the project was the work of only three people, from a pool of 5,000 BGI staff worldwide, and perhaps distrust of China and its population-control policies came into play.

Bicheng Yang, BGI’s communications director (who has a doctorate in life sciences), says a certain share of controversy is inevitable. Yes, personalised medicine can make people healthier, she says, but each new development is a double-edged sword. “There are a lot of benefits and advantages for people, but on the other side there will always be some controversial problems,” she says. “Some people accept this, some people don’t.”

Speaking very softly and deliberately, Yang, now 31, makes it clear it is up to the individual to decide which course to pursue for their health, and she is confident various governments around the world will carefully regulate the various types of genetic information.

Would-be parents, Yang believes, will probably not be able to simply choose to have a blonde, tall, intelligent baby with dimples and an artistic nature. “In the future, if it’s possible for you to select the characteristics of your baby, I think there will be certain kind of regulations about what kind of information you can get from the genome,” she says. “You need to have some kind of regulation or restriction.”

Anyway, she points out, geneticists are a long way from pinpointing the genes or the series of genes that code certain characteristics. Wearing an elaborately embroidered blouse and smiling, she shakes her head. “Currently we can only detect a few diseases,” she says. “Such characteristics like the IQ, the colour of the eye, colour of the hair, the height, are more complex reasons that you cannot predict.”

For his part, Gabor Vajta, a 63-year-old embryologist and pathologist at Central Queensland University, admires BGI’s energy. Working with BGI and spending a few months every year in Shenzhen, he has seen the work close up. “These people are cowboys, they are freelancers, they are going here, making contracts with these people, with those people, all around the world,” he says, adding that the formula is a success and a year ago BGI bought a large competitor in the US.

“I have collaborations all over the world. This is by far the most fruitful collaboration for me. BGI is the future.” He pauses and smiles broadly. “As you know, China is the synonym of low-level things, of cheap things, but this is absolutely the top.”