Medical researchers at odds with each other on H5N1
How academic flap hurt effort on Chinese bird flu
NICHOLAS ZAMISKA
February 24, 2006 7:03 AM
The Wall Street Journal
BEIJING -
China's efforts to maintain control over samples of avian flu taken on its soil, as well as the research done on them, have put it at odds with international health officials trying to defeat the disease.
The standoff pits a high-ranking veterinarian in China's Ministry of Agriculture named Jia Youling against international health authorities leading the fight against bird flu. Their conflict surfaced after wild birds began dying by the thousands last spring in a remote region of western China. At the ministry's headquarters in Beijing, officials from the World Health Organization and the United Nations' Food and Agriculture Organization asked Dr. Jia to share with them the samples of bird flu that scientists under his ministry had collected from the birds.
He didn't provide them. Instead, Dr. Jia - a professorial-looking 58-year-old who had risen steadily through the ministry's ranks since he joined it in 1979 - began to talk about a recent research paper he had noticed on avian flu. According to Julie Hall, the WHO's top communicable-disease expert in Beijing and a participant at the meeting, he had a complaint: Months earlier, a team led by American scientists published a paper in an academic journal using China's samples, but without crediting or consulting their Chinese counterparts. The occasion, Dr. Hall says, ''was used to express their deeper concern about ensuring that Chinese scientists were duly recognized.'' Dr. Jia declined to comment, saying, ''I don't want to mention those things because they are all in the past.''
Since that meeting, China hasn't provided a single sample from its infected flocks, despite repeated requests by WHO amid the roughly 30 outbreaks the country has reported in the past 12 months.
In another field, a dispute like this might seem like typical academic back-biting. But as the lethal form of bird flu known as H5N1 spreads beyond Asia into Africa and Europe, the stakes are rising fast. Since late 2003, at least 92 people in five Asian countries, as well as Turkey and Iraq, have died from avian flu, which has devastated flocks of birds across Asia. Disease experts fear human casualties could soar into the millions if the virus mutates to allow rapid transmission between people.
The genetic information contained in China's samples could help develop a more effective vaccine that could save countless lives. Currently, a human bird-flu vaccine produced by a unit of Sanofi-Aventis SA, Paris, is finishing clinical trials. Like many rival vaccines, it is based on an older strain of H5N1 taken from Vietnamese samples in 2004 and is endorsed by WHO. The Bush administration last fall asked Congress to spend $162.5 million on bird-flu vaccines, $100 million of which will be spent on Sanofi's vaccine.
But if the virus from China has changed significantly since then, scientists making the vaccine might never know, and Americans could be spending millions of dollars buying an antidote that is a year or more out of date.
''We think it's very important that (China) share viruses with the WHO as soon as they can, so we can test the vaccine efficacy,'' says Michael L. Perdue, an avian-flu expert with WHO at its headquarters in Geneva. ''When people start hoarding'' samples of bird flu, he says, ''it limits our capability to develop the optimal vaccine.''
Chinese officials have told WHO and FAO officials that they will begin sharing their samples again soon. A person familiar with China's position says it has taken time to negotiate a new agreement to ensure that Chinese researchers are involved in, and properly credited for, research on Chinese viruses. This person noted that other countries don't share their viruses with China.
''All the scientists should collaborate, but there's still a lot of competition,'' adds Shu Yuelong, the director of China's national influenza laboratory in Beijing. ''Scientists are human.''
Other countries from Indonesia to Turkey and Nigeria have provided international health authorities with samples of the virus from stricken birds.
China is widely considered to be a key laboratory for research. Scientists say the close proximity of poultry, people and pigs in southern China has spawned past influenza pandemics, including the Asian flu of 1957 and the Hong Kong flu of 1968.
For now, the more than 100 virus isolates Chinese veterinarians have collected from bird-flu outbreaks across China sit in refrigerators at China's National Influenza Research Center in Harbin, a city best known for its winter ice-carving festivals. The center employs around 500 scientists, at least 50 of whom are working on avian influenza and report to Dr. Jia's ministry.
One researcher worried that the Chinese lab would lose its competitive edge and would have less work to do if it was too generous in sharing their viruses.
''If we get the virus, and we send it out right away,'' a Chinese scientist says, we ''don't need those people.''
The Harbin scientists are proceeding with their own research. They have tested H5N1's virulence in mice, chickens, ducks and geese. The lab published six papers last year and three have been accepted this year, according to one scientist. The scientific journal Virology published a paper, written by a group of 10 researchers from China, in October. The paper used samples collected from China's outbreaks in 2004 to test an avian-flu vaccine made in China for use with birds.
When it comes to not sharing, China isn't alone. All over the world, competitive pressures can drive scientists to hoard data that might lead to ground-breaking research.
U.S. researchers have drawn flak. This past September, complaints over the failure of the Centers for Disease Control and Prevention in Atlanta to share the genetic sequences of flu viruses with outside researchers prompted the prominent scientific journal Nature to print an article titled, ''Flu researchers slam US agency for hoarding data.'' In the article, a CDC official said the need for openness ''must be balanced against the needs for maintaining high standards for data quality and for protecting sensitive information when the situation warrants.''
''There is a world-wide tendency to bash China for everything it does,'' says Juan Lubroth, a senior officer of the animal-health service for the FAO. ''I think it's important that countries hold a mirror up to themselves.''
China's handling of disease outbreaks has come under intense scrutiny from the international community before. In early 2003, Chinese government officials defied efforts by world health officials to investigate outbreaks of severe acute respiratory disease. SARS eventually killed at least 349 people in mainland China, more than in any other country.
By the next year, official attitudes in Beijing appeared to have changed somewhat. Bird flu began breaking out across the country early that year, killing flocks of chickens, ducks, geese and doves. Local officials shipped some of the dead birds to researchers in Harbin.
WHO officials asked China's Ministry of Agriculture if they could obtain specimens to share abroad. After months of talks over issues such as how to transport the samples, the ministry agreed to hand over around half a dozen isolates.
In other areas as well, international health officials say, China has been helpful and cooperative. The country's Ministry of Health recently shared two of the seven virus samples it has collected from its human cases, according to Dr. Hall. The Ministry of Agriculture also has shared genetic sequences of viruses it has collected.
By last summer, things had changed. On the shores of China's largest saltwater lake, in a remote corner of the Tibetan plateau, at least 5,000 geese, gulls and other wild birds had died from avian flu. It was the first report of the disease attacking birds other than domestic poultry in such large numbers. Chinese researchers traveled to obtain samples of the virus from the dead birds. At their meeting with the agriculture ministry in Beijing, officials from WHO and FAO asked for the samples.
Instead, Mr. Jia told them about the paper that appeared several months earlier in the Journal of Virology. His point: China's permission to use its samples was never sought, his scientists were excluded from the research and their names were noticeably missing from the list of 14 scientists who contributed to the study.
''That's when it surfaced in all of its entirety,'' says WHO's Dr. Hall.
The paper, whose lead author was Elena A. Govorkova, a Russian researcher at St. Jude Children's Research Hospital in Memphis, Tenn., seemed innocuous enough. The study concluded that some of the latest strains of the H5N1 virus killing birds in Asia were lethal to ferrets as well and still posed a serious threat to humans. It used two samples from China and 11 others from elsewhere in Asia.
Dr. Govorkova's use of the Chinese samples, however, was news to Chen Hualan, the director of the Harbin research center who isolated them.
Nobody had asked Dr. Chen's permission before using her samples, a violation of WHO guidelines. Dr. Chen, 36 years old, the daughter of rice farmers and a rising star in China's scientific ranks, first heard about the study when she received a call early last year from a young official with the Chinese Ministry of Agriculture, according to a person familiar with the situation. The official had been scanning the latest research articles on bird flu and came across Dr. Govorkova's study. He noticed the paper from Memphis seemed to reference samples that could have come only from Dr. Chen's lab. ''I've been burned,'' Dr. Chen told an international health official who spoke with her after she heard about the Memphis paper.
The Chinese researcher tried to clarify what happened with Dr. Govorkova's supervisor at St. Jude, an influenza specialist named Robert Webster. Dr. Webster quickly replied with an apology for what he described as a mix-up. WSJ(2/24) How Academic Flap Hurt Effort On -2-
Dr. Govorkova also sent Dr. Chen a note, apologizing for the oversight. ''I feel that this was an honest mistake,'' Dr. Govorkova says. ''We apologized almost immediately.'' For her part, Dr. Chen says: ''I really don't want to talk about that. It's something that happened a long time ago. Dr. Webster already apologized.'' She added that her laboratory will share the samples soon.
Both Drs. Webster and Govorkova say they believe China's Ministry of Agriculture is less concerned about this particular incident than in ensuring Chinese researchers have exclusive access to the country's viral samples.
''This has been used by the authorities as a crutch,'' Dr. Webster says. ''They want all the credit themselves, which is reasonable,'' he adds. ''They will eventually release them once they have a major publication.'' He points out that he has collaborated with Chinese scientists, including Dr. Chen, since the incident. Dr. Webster also points out that such oversights aren't unknown when so many researchers are involved, as is often the case, and at least one other similar incident happened in which the Chinese weren't properly credited for their work last year.
Dr. Govorkova says authorities ''are making an excuse'' and notes that even before the incident over her paper, ''it was very difficult to obtain samples'' from the Chinese. She says she has received an email from the Journal of Virology inquiring about the crediting of Dr. Chen's work and has replied suggesting a correction.
At another meeting in Beijing this fall, several WHO officials met with the Ministry of Agriculture again to try and coax China into sharing its samples. Dr. Jia again brought up the issue of the paper, according to two people who were in the room.
While the Ministry of Agriculture still hasn't shared any samples, it and WHO have been hammering out a new agreement for months that has been referred to as the ''Seven Steps'' plan, according to a person familiar with the talks. It is aimed at ensuring Chinese scientists are credited and involved in the work that comes from strains collected on Chinese soil.
''It's like a marriage,'' Dr. Hall says. ''You have to keep working at it.''
AP-WS-02-24-06 1002EST
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