Beijing Genomics Institute (BGI), the world’s largest genome sequencing organization got its start a little more than a decade ago at a moment when idealism, patriotic fervor and more than a little chutzpah converged to create what one of its founders, Huanming Yang, Ph.D., recently acknowledged was “a Mission Impossible.”
Yang, then with the Chinese Academy of Sciences, promised to complete 1 percent of the Human Genome Project–at the time the biological equivalent of the moon shot of the 1960s. There was just one problem: He didn’t have a gene-sequencing machine!
What followed was one of the most thrilling rags-to-riches stories in modern science. Yang and his colleagues overcame immense technical, financial and political obstacles to deliver the DNA sequence of their portion of human chromosome 3. In doing so, they changed Chinese science forever and built a scientific-industrial juggernaut that now represents 20 percent of the world’s capacity for genome sequencing.
That same can-do spirit was clearly on display when I and Autism Speaks-funded Duke University researcher Yong-hui Jiang, M.D., Ph.D., visited BGI in Shenzhen after the Autism Research Collaboration Development Meeting, co-hosted by Children’s Hospital of Fudan University in Shanghai and Autism Speaks. Not coincidentally, Yang gave the keynote address to the meeting, which ended last weekend.
Today most of BGI is housed in a former shoe factory on a small campus that includes several high-rise dormitories for nearly 4,000 employees. In recent years, the institute has produced such high-impact scientific accomplishments as complete genome sequences of rice and potato plants and the human gut microbiome (our digestive microbes). Through genetic sequencing, it also identified the culprit behind this summer’s deadly E. coli outbreak in Germany. In the face of this public health crisis, BGI marshaled the staff and technology to sequence the entire genome of the toxic bacterial strain in less than three days.
In visiting BGI, I was impressed by more than the arrays of cutting-edge automated sequencers, which run 24/7. I was struck by BGI’s eclectic leadership.
BGI cofounder, Jian Wang, Ph.D., recently scaled Mount Everest, after three attempts over a two-month period. For inspiration he credits BGI’s landmark collaboration with U.S. and European scientists in documenting the rapid evolution of the Tibetan human genome to accommodate life at high altitudes.
BGI executive director Jun Wang, Ph.D., joined the institute when he was 23 and went on to amass 36 publications in Science and Nature over 12 years. For your average researcher, having 1 or 2 publications in Science or Nature is sufficient to secure a tenured position at a top U.S. or European university.
At age 25 years, Yirui Li is leading the bioinformatics efforts of BGI’s recently announced collaboration with Autism Speaks to sequence 10,000 autism genomes. With 16 Science and Nature publications to his name, Li dropped out of China’s elite Tsing Hua University at age 19.
Despite their intellectual firepower, drive and personal and professional accomplishments, they were a down-to-earth group. They thought nothing of coming in on a Sunday to meet with us. Sporting what appeared to be their regular uniform of T-shirts, jeans and flip-flops or running shoes, they looked more like grad students than high-profile executives of a leading international research institute.
Yang and his colleagues also have a refreshingly progressive view on science and its end game. Impatient with traditional distinctions among scientific disciplines–such as genetics versus environmental sciences–they advocate a “trans-omics” approach to scientific development. In their view, decoding the genome is part of a continuum of activities that includes epigenetics, proteomics, cell biology, systems biology and computer science.
Most importantly, perhaps, they see all these activities as integrated and dedicated to “advancing the science of medicine” and “improving the effectiveness of healthcare.” Clearly, they remain driven by the sense of urgency that allowed them to identify and decipher a deadly pathogen by sequencing its entire DNA sequence in three days.
I left BGI inspired by what I saw and heard. The BGI team seemed refreshingly unencumbered by the petty divisions and willful near-sightedness we too often encounter in science and society. They are pursuing a grander vision that I, too, have lost at times. More than ever, I am hopeful that with enough idealism, ambition and even a little chutzpah, Autism Speaks collaborations like this one will soon deliver a better future for all of our families.
After a few drinks and a dinner of simple and very spicy local fare in the BGI canteen, Yang leaned over to me and said matter-of-factly, “We’ll get it done.”
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The Autism Speaks science team traveled to Shanghai, China, last week with the goal of enhancing collaboration among Chinese and North American scientists. Despite the challenges of speaking different languages, we learned a lot from each other. Our Chinese colleagues were eager to hear about new research and treatments being developed in North America. The Americans were impressed with the technological prowess of the Chinese.
A prime example of this technological power is the Beijing Genome Institute, the largest genome sequencing institution in the world and a new Autism Speaks partner. In the coming year, the Beijing Genome Institute will be sequencing the DNA of families participating in our Autism Genome Resource Exchange (AGRE) program, allowing us to create the world’s largest whole genome sequence library for autism research. (See our related news item.)
Another example is a recently launched Chinese program that sends text messages to new mothers, alerting them to the early signs of autism. Chinese researchers are studying whether this innovative “eHealth” strategy results in better referral, assessment and intervention rates for children with early symptoms.
Although my conversations and learnings from my Chinese colleagues were enlightening and we planned many future collaborations, the most significant moment for me was talking to 200 Chinese parents of children with autism. I walked into a room filled with mothers and fathers eager to hear new information about autism. Through a translator, I described new research findings and treatments and fielded questions from the audience.
The questions were remarkably similar to those I hear from parents in the United States. One mother told me that her son had frequent tummy aches and constipation; she wondered if this could be related to his autism. Another parent asked what she should do about her daughter’s fear of fireworks, a common part of special events here. Should she keep her at home and miss the family outings? A father showed me a large bag filled with medicines he had purchased through the mail and asked if I thought they would help his child.
We talked about the association between autism and gastrointestinal problems and how treating these physical problems can relieve discomfort and, so, help children gain more from their educational programs. We talked about auditory sensitivities and discussed a range of strategies for helping children cope with loud noises. And we talked about how to evaluate whether a treatment is truly effective and safe for a child.
As our conversation continued, I was struck by the fact that, although China and the United States are very different cultures, autism is a common bond. Parents across the globe are looking for answers to help their children. My hope is that Autism Speaks Global Autism Public Health Initiative will be able to make a difference for these families. By partnering with scientists and clinicians in China, we can translate and adapt many of the tool kits and other resources we have developed here in North America—while also learning from our colleagues and families in China.
5|25: Celebrating Five Years of Autism Science Day 19: First Successful Autism Genome-Wide Association Study Results
In honor of the anniversary of Autism Speaks’ founding on Feb 25, for the next 25 days we will be sharing stories about the many significant scientific advances that have occurred during our first five years together. Our 19th item, First Successful Autism Genome-Wide Association Study Results, is from Autism Speaks’ Top 10 Autism Research Events of 2009.
Advances in technology and analytical methods over the past several years have enabled a better understanding of genetic risk factors for ASD. The human genome has over 6 billion DNA nucleotides. Until recently, it has been extremely difficult for scientists to compare two groups of individuals – one affected by a condition versus a comparison group – in terms of their detailed DNA because such comparisons require the analysis of at least half a million to a million individual locations in the genome of thousands of people. New methods, called Genome-Wide Association Studies (GWAS), have now made it possible to perform such comparisons and identify single changes in DNA nucleotides as specific genetic risk factors. Although this powerful technology has already produced exciting findings in other complex diseases, it wasn’t until 2009 that GWAS studies finally began to bear fruit for autism. In the Spring and again in the Fall, researchers reported successful application of GWAS technology to ASD.
GWAS is a powerful analysis technique that allows researchers to sift through hundreds of million of bits of genetic data to identify changes to the genetic code that are associated with a disease. Because the approach is not based on any specific biological hypothesis, scientists can cast the broadest experimental net possible, and use sophisticated statistical methods to establish the disease association. In recent years, GWAS has been successful in identifying susceptibility genes for such diverse conditions as macular degeneration, diabetes, rheumatoid arthritis, Crohn’s disease, and bipolar disorder. In April 2009, a large team of scientists led by investigators at Children’s Hospital of Philadelphia, reported results from the first successful GWAS study in autism. Tens of thousands of DNA samples are required for GWAS to produce meaningful results, so working with collaborators that included members of the Autism Genome Project, the researchers pooled samples from the Autism Speaks-funded Autism Genetic Resource Exchange (AGRE) combined with many other collections. The result was identification of a DNA variant associated with the genes cadherin 10 and 9, which are responsible for creating molecules that facilitate the formation of neural connectivity. This finding is consistent with accumulating evidence suggesting abnormal interactions between neurons may be at the core of the deficits seen in autism.
The idea that faulty connections between neurons plays a major role in ASD was further supported with the publication of the second autism GWAS study in October. Also working with AGRE and members of the Autism Speaks-funded Autism Genome Project, a collaboration led by investigators from Boston’s Autism Consortium and Johns Hopkins University used a very different statistical approach to discover an association between ASD and the gene semaphorin-5A. Similar to the cadherins identified in the first study, semaphorin 5A is thought to play an important role in neural development.
Taken together, these two groundbreaking studies confirm the potential for GWAS to make successful contributions to our understanding of autism genetics. Remarkably, out of the approximately 20,000 different human genes the experiments could have identified, the genetic variations that were uncovered are genes involved in brain development, serving to expand and reinforce our current thinking about biological mechanisms of autism. Like all new findings, they continue to focus the attention of the scientific community on the next directions for research and exploration.
Update since this story was published: DNA technology has once again advanced dramatically. New high-throughput techniques have finally made it possible to sequence entire stretches of genes, known as exons, in large numbers of patients. At the end of 2009, stimulus funds from the American Recovery and Reinvestment Act were awarded to investigators from the Autism Genome Project and the Autism Consortium who will use these new techniques to conduct a very detailed examination of 1,000 different genes linked to autism using several thousands of families who have kindly provided their DNA.