Breaching the Knowledge Monopoly
China Trumps the West in Sequencing Rice Genome
The Beijing Genomics Institute of China has taken the scientific world by surprise. It came up from behind to beat the West at its own game, finishing a draft of the rice genome in just 18 months, and has the potential to change the power politics of agriculture forever. Dr. Mae-Wan Ho reports on the remarkable scientist who heads the Institute, and his vision of equal and free access of genetic information for all.
Of the two papers in Science that announce the draft sequence of the rice genome, one is from Beijing Genomics Institute (BGI), the other from the biotech giant Syngenta.
Media attention has focussed on Syngenta, but the Chinese effort is the real landmark. If Yang Huanming, Director of the Beijing Genomics Institute, has any say in the matter, it could spell the beginning of the end for the knowledge monopoly held by the west and its transnational corporations.
China is the almost the only developing country in the genomics race, and the only one to make its mark. It has all the usual disadvantages, lack of finance, of supporting technologies and scientists. Whereas the United States and Japan have about 70 researchers and engineers per 10,000 population, China has only six. Despite that, she has come out well ahead of the west. And instead of hording the data on its own website like Syngenta, the BGI has deposited the rice genome data promptly into the public database GenBank that can be accessed by all. As the two versions of the rice genome are almost identical, there is no need for Syngenta’s data, except for the groups that are sequencing the rice genome itself. China has breached the knowledge monopoly in a big way. And it is surprising that none of this was even hinted at in the seven commentaries that accompany the scientific papers in Science.
How did China manage this mission impossible? It is definitely thanks to Yang and his team, featured in a special profile in Science. University of Washington geneticist Maynard Olson, who helped train many BGI scientists, recalled how Yang led a sceptical collection of scientists from around to world to see a completely empty, two-storey brick building in the northern reaches of Beijing, which was the then Beijing Genomics Institute. Yang said that the sequencing machines and employees were “on the way”, but neglected to mention that he had money for neither.
Today, the Beijing Genomics Institute, relocated to a much bigger building with a floor area of 10 000 square meters, has a staff of 500 that “grows by a dozen or so every month”. It also has more than 80 latest model automated sequencing machines, and four of the fastest computer in China. “It’s pretty startling”, Olson remarks, “When you think of being a support center for a scientific program in a developing country, you don’t expect them to become 10 times bigger than you are, in less than 4 years, and to start publishing in Science.” His colleague, Mary-Claire King remarks, “the Beijing Genomics Institute would be a miracle, except that the BGI guys make genomics miracles routine.”
Yang’s ability to translate his vision into reality is put down to his ability to tap “the increasingly diversified sources of support in a reform-minded China.”
But the most important factor for Yang’s success may be his ability to inspire young colleagues with his idealist vision of knowledge for the benefit of all, which provides a far stronger motivation than money could ever buy. This should be a lesson for policy-makers who place far too much emphasis on wealth-creation and the importance of the private sector for science.
Yang earned his Ph.D. in genetics at the University of Copenhagen, Denmark, then spent six years mapping genes on the X-chromosome in the CNRS Immunology Centre in Marseilles, France, in Harvard Medical School in Boston, and then University of California, Los Angeles. He returned to China in 1994 with the idea to start sequencing genes at high efficiency and low cost.
His first target was the international human genome sequencing effort, already well underway, and his intended vehicle, the Human Genome Centre, part of the Chinese Academy of Sciences (CAS) Institute of Genetics. But, like maverick Craig Venter in the United States, he broke from the Academy, because its “rules and traditions” would slow them down. And the original centre - the brick building shown to the visiting foreign scientists - never got off the ground.
Instead, Yang and three colleagues who had worked with Olson, took advantage of new laws, and in spring 1999, set up the BGI as a private, nonprofit research organisation. Seed money came from the CAS, the Institute of Genetics, Yang’s hometown municipal government, and even loans from employees, family, and friends. CAS also designated BGI as its Genomics and Bioinformatics Institute, although less than 10 members of BGI are employed by CAS.
BGI bought their first batch of sequencing machines on an installment plan and trained its staff on sequencing a heat-loving bacterium, Thermoanaerobacter tengcongensis, isolated from a hot spring in Tengcong, China. In September that year, Yang made his bid to sequence the human genome. There was only one hurdle. “Do you have the money?” “I lied” Yang admits, “We didn’t have the money, but I was sure we would get it.”
And he did get the money four months later. CAS agreed to fund three Chinese sequencing centres to do 1% of the human genome, and BGI received slightly more than half the total award. China completed its share of the draft on time, despite being the last to enter into the public consortium (see below), and has recently closed the gaps and corrected errors in the draft sequence.
This success helped Yang to convince the Hangzhou municipal official to provide a rent-free building and enough money to set up a sister centre, the Hanzhou Genomics Institute.
The youthful enthusiasm at the two institutes is impressive. The average age of the 100 authors on the Science paper is in the mid-20s. Wang Jun, who leads 150 programmers and computer scientists, entered Beijing University at 16, and is now 26. Heading the 100-person sample preparation and sequencing group is 29 year-old ‘police woman’ Deng Yajun, a former forensic investigator for the police department in her hometown of Xi’An.
BGI was able to save a lot of money by using home-grown technologies. For example, the 96-well plastic plate used in preparing DNA samples were imported at first at a cost of $2.54 each. But a local glassmaker provided it for just 36 cents. Similarly, the institute was barred from acquiring US supercomputers, so they relied on Dawning, a home-grown supercomputer company. Particularly crucial was the assembler, a piece of software to piece together the sequence of fragments. That, BGI developed in-house, starting from the assembly program used in the public Human Genome Project.
So, from start to finish, the BGI took an incredibly brief 18 months, using the latest, whole-genome shot-gun approach (see “Pubic/private partnership too close for comfort?”, this series). And watch this space for further developments.
I first met Yang at a conference organised by the World Health Organisation in Bangkok, Thailand in July 2001. That was when I became aware that China was a party to the international public consortium to sequence the human genome, and I had no doubt, even then, as to who was responsible for bringing China into the project. Yang has the youthful energy and infectious enthusiasm of a person much younger than his 50 years, and is immensely charming and likeable.
Yang gave by far the most challenging and entertaining talk in the conference, which was to explore Genomics and Health, especially for the Third World.
Yang was motivated by his concern that there should be “equal and free access to the basic information of the human genome” and that “ownership and benefit-sharing of genetic resources” should be secured for developing countries. The only way to achieve those objectives, he decided, was to establish genomics research capacity in a developing country - China.
He takes social responsibility of geneticists very seriously, and firmly believes that scientific advance should bring health care for all. China, he said, has strong desires to have innovative research and new technology, and is very sensitive to sharing the achievements from the Human Genome Project for improving health. Like Gro Harlem Brundtland, Director General of WHO, he finds it “ethically unacceptable” that “most biotechnology research is carried out in the industrialized world, and is primarily market-driven”.
“The human genome is in danger”, Yang said, of being “confiscated” by a few countries or companies”. That was why China became the latest contributor to the Human Genome Project. Despite being the latest to join, China was among the top 10 contributors when the working draft was announced in the journal Nature on 15 February, 2001. China finished the complete sequence map of the region of the human genome she has claimed in record time. That too, was a miracle.
“Immediately after joining the Human Genome Project Consortium in September 1999, China began to persistently call for the international effort to protect the human genome, as the unique member state from the developing world in the Consortium.” Yang recalled. He submitted five proposals to UNESCO, the first of which was to draft a statement “for the protection of the human genome sequences, to ensure the equal and free access to the genome sequence data by all”. This was the prelude to the statement released by Clinton and Blair in March 2000, followed by other statements that culminated in the United Nations Millennium Declaration (19 September 2000):
“To ensure free access to information on the human genome sequence.”
But that did not mean the human gene sequences could not be patented, as Clinton and Blair were quick to ‘clarify’ immediately after making their joint statement. Gene patents are overwhelmingly from the US, Western Europe and Japan. Yang roundly condemned the biopiracy of genetic resources up to and including the genes of people in developing countries.
To China’s horror, newspapers in the United States revealed that hundreds and thousands of human genetic samples have been taken and exported, without informed consent, and under the pretext of providing “free check-up” and “free treatment”. China has become the main provider of human tissues for several US companies, and several traditional medicinal herbs have also been patented in the north.
Craig Venter of Celera said, “With a significant portion of the world’s plant, animal and human genetic diversity located in China, access to this diversity will be fundamental in Celera expanding its genomic information.”
In Yang’s view, no nation can afford not to have biotechnology. “It would be more expensive”, he said, “you would be charged unreasonably high prices because you cannot do it yourself!” Indeed, two Chinese laboratories struck a deal with a foreign-owned company in the spring of 2000 in which the labs agreed to pay US $225 000 to sequence a prawn virus, and also ceded one-third of the intellectual property rights on the 300kb sequence. Yang is adamant that genetic material in China and in every other country must be shared, and the only way to assure that is “to develop our own research capacity!”
I remain very doubtful over the potential of human genomics research to contribute to health (see Inside human genomics and genetics series, Science in Society 13/14, February 2002 www.i-sis.org.uk ). But rice genomics is something else (see “Significance of the rice genome”, this series).
1. Normile D. From standing start to sequencing superpower. Science 2002, 296, 36-9.
2. Yang HM. Genomics & health - a regional or national perspective, WHO Multi-regional consultative Meeting, Bangkok, 23-25 July, 2001.