Virologist Shi Zhengli at the National Biosafety Laboratory, the P4 level laboratory, in Wuhan, in February 2017. JOHANNES EISELE / AFP
Could the coronavirus have accidentally escaped from one of the research centers in this Chinese city, where the epidemic started? “Le Monde” immersed itself in this particular universe, where Franco-Chinese cooperation has shown its limits
When the epidemic started in Wuhan, Shi Zhengli experienced a moment of pure anguish. One of those fears that invades the mind, forcing you to redo every thought, to repeat each study. A specialist in coronaviruses at the Institute of Virology in the city, capital of the Chinese province of Hubei, she did not sleep for several days, constantly wondering: “What if the virus came from our laboratories? “
Who, in this month of December 2019, could have imagined the worry of this 55-year-old woman, frail but determined, that virologists around the world are used to meeting at international conferences? The disease still appeared to be confined to a few cases, reported by hospitals in Wuhan, an ugly and sprawling city where Shi Zhengli has lived since studying and working there. A kind of SARS, with fever, cough and infection of the lungs. One of those dirty infections that Shi Zhengli, alas, knows only too well.
In France, where she spent a few years for her thesis – at the University of Montpellier in 2000 – none of the researchers with whom she sometimes collaborates knew anything about her concerns. “Sheu”, as the French say in a rough imitation of the Chinese accent, is highly regarded. But apart from the fact that she speaks a little French and that a research minister once awarded her the academic awards, we only know about her research. “When the disease arrived in France, we received a support e-mail from our colleagues in Wuhan,” reports a researcher from Lyon, who knows her well. « But not an exchange, as long as the epidemic mainly raged in China. »
It’s not quiet the same in China. The newspapers have nicknamed her “Batwoman” since she studied these bats which, in the subtropical and southern regions of Guangdong, Guangxi and Yunnan, appear to be real virus factories. In 2005, the virologist had identified two coronaviruses close to SARS-CoV, the infectious agent behind the SARS epidemic in 2003, in a bat. Since then, coronaviruses have been her specialty. And this is also why, since the hospitalization of the first patients in Wuhan, she was immediately worried.
“What if the virus came from our laboratories?” Shi Zhengli started rereading the studies she had written during the last few years, anxious to find if this new killer, which appeared precisely in Wuhan, had the characteristic sequences which could have signaled a “leak” from her department, the Center for Infectious Diseases of the Institute of Virology. “It really made me lose my mind and deprived me of sleep, » she told Jane Qiu, journalist for the monthly Scientific American.
Hunting for bats
Shi Zhengli navigates between several universes. The dark and damp caves of remote provinces, where he has to enter in coveralls, masked and booted, fitted with a large net to catch bats without risking infection. And, on the other hand, the laboratories assigned to her department on the campus of the Wuhan Institute of Virology, near East Lake.
Her research on coronaviruses, developed, requires a laboratory of security level P3. But Shi Zhengli is also deputy director, also in Wuhan, of the new P4 laboratory, for class 4 pathogens, these viruses with the highest contamination and mortality rate, like Ebola, which kills almost 90% of those that it contaminates.
The “P4”, as researchers say to designate the National Biosafety Laboratory of Wuhan, is a funny place, a kind of square and gray blockhouse, flanked by a tower and an office building, backed by a forested area. Built under a Franco-Chinese cooperation agreement, modeled on the Jean-Mérieux P4 laboratory in Lyon, this highly strategic laboratory for China has taken nearly fifteen years to emerge. It became operational at the beginning of 2019, after two years of testing and adjustments.
The site that hosts it is located in the distant suburbs, some 30 km southwest of Wuhan, where industrial parks encroach on old villages and crops. The place had been isolated for a long time, but a new red brick campus, which emerged from the ground two years ago, is now attached to it: it welcomes researchers and students. The address and location of P4 are difficult to find: the official website of the Academy of Sciences and Google Maps both locate it, in an incorrect manner, on the historic campus of the Institute of Virology, near the Lake of the East.
Shi Zhengli, therefore, was horrid. And she’s not the only one. Long before the Washington Post published an article, on April 14, claiming that American diplomats had warned, as early as March 2018, of the lack of “technicians and investigators properly trained to operate this high security laboratory safely “, suspicions of a possible leak had first circulated in China itself.
The Chinese Web in turmoil
Since the end of January, the P4 laboratory and “Batwoman” had put the Chinese blogosphere in turmoil. It was also looking into the case of another laboratory, belonging to the Center for Control and Prevention of Infectious Diseases, located 280 meters from the seafood market in Huanan, in the heart of Wuhan, which became the first center of SARS-CoV-2 contamination.
It is not difficult to find, on YouTube, the report that a Shanghai television channel had devoted, on December 11, 2019, to a technician of this laboratory, Tian Junhua, in which we see him climbing the entrance to dark and terrifying caves of Hubei Province, dressed in a white jumpsuit and fitted with a bat net. “Nearly 2,000 types of virus have been discovered by Chinese researchers in the past twelve years, trumpets the report. The rest of the world had discovered only 284 in two hundred years. China is now at the forefront of basic virus research. “
A few weeks later, in the context of the epidemic spreading in Wuhan, this short film took on a whole new resonance on Chinese social networks. Suddenly, the researcher does not seem so well protected, with his thin jumpsuit and his latex gloves. “The simple contact of bat excrements on my bare skin could infect me,” he admits bluntly. He once had to put himself in a voluntary “fortnight”, he explains, after having received a few drops of urine from a bat. Could a similar incident have taken place in this laboratory?
Fears, rumors … The Chinese Web imagines a thousand more or less rational scenarios. Some ask questions, despite official denials, about the fate of a former student of the Institute of Virology, Huang Yanling, part of whose biography has been erased from the institute’s website. Even the fiercely patriotic Global Times daily deems “legitimate”, in a long investigation dated February 18, questions about possible synthetic coronaviruses possibly developed by the Wuhan Virology Institute, and asked if any experiments « were conducted on primates”. When famous commentator Cui Yongyuan launched a poll on Weibo, the Chinese Twitter, ten days later on the origin of the virus, 51% of the 10,000 people who answered were convinced that it was a “artificial virus which escaped by negligence ”, 24% believed that it was spread maliciously. Only 12% thought it was of natural origin …
The spacesuit and the freezer
“Batwoman” therefore reopened all of her files. Could she or her team have been negligent? They were only half a dozen members of the institute to have followed, years earlier, in Lyon, at the heart of the Jean-Mérieux Laboratory, managed by Inserm (French National Institute of Health and Medical Research), the difficult training in P4 security procedures. Because France has not only supplied China with the technology of the Wuhan laboratory, as well as very specialized French small and medium sized companies – even if the Chinese had imposed their own contracting authority at the last moment. France, also, had to teach the Chinese to use it and to follow the very strict security measures. In short, to work in an ultra-coded universe. “Three weeks of handling in a diving suit, details the Croatian-born immuno virologist Branka Horvat, to repeat gestures and procedures a thousand times, then several weeks of tests and follow-ups before being allowed access to the freezer where viruses are stored. Living in France for thirty years, where she works for Inserm in collaboration with Chinese researchers on the Nipah virus, Ms. Horvat followed the training with Shi Zhengli.
Such learning course is trying. You have to manage to breathe in a diving suit, calculate each gesture, know how to disconnect and reconnect your air supply to circulate in the laboratory. Prepare each experiment carefully before starting it to avoid forgetting a detail that would compromise handling. Claustrophobic and distracted persons better abstain. Even the gloves, which are thicker than those reserved for P2 and P3 labs, offer less sensitivity, so you have to get used to using them. The place is also protected by multiple airlocks which only open if one is duly badged. And you still have to take a decontaminating shower at the exit … Chinese researchers who came to Lyon to train have gone through all the stages. “Shi herself is an intelligent, lively and rigorous woman,” continues Branka Horvat. She has had a lot of contact with researchers around the world. Scientifically, she is of a very good standard. She is the target of several questions today, but I trust her.
The blogosphere is not the only agitated sphere in the new Chinese Lunar Year, which began two days after the confinement of Wuhan. At the highest level of the regime, a major decision was made: on January 31, Major General Chen Wei arrived from the Bacteriological Risk Unit of the Army. The national press devoted enthusiastic articles to her, all written on the same model. Described as “a goddess of war”, Major Chen Wei took over the P4 laboratory to, officially, develop a vaccine against Covid-19 there as soon as possible. The Party leadership would not have done it otherwise if it had wanted to send a plenipotentiary emissary to carry out an investigation … Did the country’s leaders also believe in a “leak” in one of the Wuhan laboratories?
It’s a fact that this kind of accident exists much more than we think. And not only in China. In 2014, the Institut Pasteur itself “lost” 2,349 SARS samples, previously stored in one of its P3-level laboratories. Fortunately, the case, first handled without any publicity or statement to the authorities, had had no serious consequences. The samples contained only part of the virus, and the virus was incomplete and harmless. In 2015, three samples of MERS, this respiratory system coronavirus from the Middle East, arrived at the Institut Pasteur, smuggled by a researcher, on a flight from Seoul to Paris. The virus, stored in a small box of cosmetic product, then remained on the shelf of the office of a researcher at the Institute without any health precautions for a whole week…
In 2014, an investigation in the United States found that non-inactivated anthrax samples had been sent across the country by error. The investigation also uncovered an accidental contamination of a sample of classic influenza with a much more deadly virus, H5N1, and the discovery of samples containing a living smallpox virus when it was believed to be inactivated.
High risk materials
In Wuhan, however, the leakage assumption takes on a more political turn as the epidemic spreads. Four days after the Washington Post article appeared on April 14, Yuan Zhiming, director of the P4 laboratory and “boss” of Shi Zhengli, stepped up to assure that “It is impossible that the virus comes from here. We have very specific and rigorous rules to prevent leaks and we are sure of that. A microbiologist trained in China, France and Denmark and a delegate to the Advisory Chamber of the Chinese Parliament, Mr. Yuan was defending the reputation of all Chinese research. He was aware of the rumors which run, abroad and in his country, concerning local laboratories, and also on the significant number of students who pass there – “sometimes twenty students for a researcher, when, in France, they are barely three, ”notes Branka Horvat. But Mr. Yuan dismissed without blinking the assumption of accidental contamination of one of them. “None of our students and none of our researchers have been infected,” he confirmed.
Research on coronaviruses is, however, plentiful in the institute’s laboratories. Shi Zhengli is thus conducting “gain of function” experiments with his teams, that is to say, reshaping viruses to make them contagious and then identifying weaknesses that would allow testing of treatments. In addition, when Shi Zhengli published the genome of the new virus on January 20, she demonstrated that it was the closest, at 96%, to a bat coronavirus, RaTG13, hitherto unknown. And for good reason: the institute recorded it at the same time- which raises questions about what is hidden in the institute’s freezer.
“Very tense meetings”
In February, in the Global Times, Yang Zhanqiu, the deputy director of the Pathogen Biology Department at Wuhan University, opened up another path. Chinese researchers in general – that is to say, apart from the few scientists trained in P4 procedures – are known to have little regard for the treatment of litter and dead animals. Normally, these require very strict packaging, transport and incineration processes.
However, recognized Yang Zhanqiu, “some researchers pour laboratory material down the drain after experiments, without a specific biological elimination mechanism”. The waste, he said, “may contain viruses, bacteria or microbes of human origin that can have a life-threatening impact on humans, animals or plants.” Are the new rules that the Chinese government has just issued to strengthen laboratory biosafety an indication that a leak of this nature could have been discovered within one of the Wuhan laboratories?
This risk of biological pollution has always worried observers of Chinese research. In particular, because it has increased with the race for discoveries in which laboratories in this country are engaged, in all fields. “In China, research is above all an instrument at the service of national power. It is conducted in an overly untransparent manner and with little or no respect for scientific and medical ethics. That makes possible all the deviations “, estimates the French neurobiologist Alexis Génin, who was interested in China as scientific advisor of Dafoh, an association against the trafficking of organs in the world. This highly productive environment implies a very high turnover of young researchers and, therefore, increased risks of mishandling and infection. As for whether a “reworked” virus could have escaped by mistake from one of the Wuhan research sites, only an inspection mission and the review of laboratory virology notebooks could clarify this point- adds Professor Génin. .
Epidemics often play the role of revealer. We would looking for the possible origin of this and, by chance, we discover other universes, vast and dark like chasms. Doubts about the P4 laboratory have thus revealed the difficulties of cooperation with China. Until now, in France, only a few disappointed companies, a small group of diplomats from the Quai d’Orsay and a few senior officials at the French Ministry of Defense had protested against this country’s ultranationalist and fundamentally opaque behavior. In light of the epidemic, we suddenly discover the « behind the scenes » of the Franco-Chinese cooperation agreement around the construction of the P4 laboratory led by Yang Zhiming and Shi Zhengli. And it seems increasingly clear that, despite the last visit, in March 2019, of a delegation of diplomats from the French consulate in Wuhan, whose photo appears on the website of the Institute of Virology, France had, in reality, been quickly removed from the real functioning of this “lab”.
In 2004, this P4 was jointly wanted by French President Jacques Chirac and his Chinese counterpart, Hu Jintao, in order, according to Chirac, to “give substance and amplify this alliance of our researchers and this confidence born at the heart of the terrible SARS epidemic. ” At the time, many French diplomats made no secret of their reluctance. “The Quai d’Orsay was convinced that the Chinese, like other countries, were seeking to develop a research program on biological weapons,” recalls Gérard Araud, director of strategic affairs at the Ministry of Foreign Affairs between 2000 and 2003. It was very difficult to ensure that P4 would not contribute, in one way or another, to such a program. “
Fearing isolation after France’s opposition to Western intervention in Iraq in 2003, Foreign Minister Dominique de Villepin was looking for rapprochement with both Moscow and Beijing. And then, argues today Hervé Raoul, director of P4 Lyonnais, “Virology always carries behind it the fear of bacteriological wars. That is why scientific collaboration is a proper way to rule out the use of a laboratory or research for other purposes. ” In short, in the enthusiasm of Sino-French cooperation, the prejudices had been swept away.
Had France been too optimistic about its ability to play equally with China? On February 23, 2017, the weather was nice and cool when the Prime Minister, Bernard Cazeneuve, chaired, alongside the secretary of the Communist Party in Wuhan and the mayor of the city, the official accreditation ceremony for the famous laboratory. At the time, there seemed to be no question of suspecting the Chinese. Better still, France seemed to be multiplying projects with them. On this beautiful winter day, Bernard Cazeneuve first came to Wuhan to celebrate, he remembers, “another cooperation program, this time on the sustainable city, on which Martine Aubry had worked a lot”. According to him, the director of Inserm at the time, Yves Lévy, husband of Agnès Buzyn, the future health minister, “insisted a lot” so that he would « kill two birds with one stone » and come also inaugurate the P4 in the name of France. Franco-Chinese cooperation on research into infectious diseases seemed promising. The French government had promised to allocate 1 million euros per year to this laboratory. China promised that the two countries will exchange resources, information and results.
It was not until the end of 2017 that Jean-Yves Le Drian, the former Minister of Defense under François Hollande who become Minister of Foreign Affairs under the new President Emmanuel Macron, entrusted the French Embassy in Beijing to write a note taking stock of the reality of this scientific cooperation. In conclusion, scientific cooperation was non-existent. “There were stormy meetings in Paris with Inserm and the research ministry,” recalls a source then involved. No advance has been registered ».
Indeed, if Shi Zhengli was well received in the P4 of Lyon, like other researchers coming from China, the opposite was far from being true. The industrialist Alain Mérieux, who was implicated “personally”, he said, in the construction of the building, withdrew “as soon as the laboratory was handed over to the Chinese authorities”. After the accreditation of these installations, an eighteen-month phase of ramp-up was planned, with “blank », that is « virus-free » operation. During this phase, a “Mr. Quality” was mandated by the Quai d’Orsay, René Courcol, an infectious disease doctor, to ensure the proper implementation of the necessary procedures. What facilities did he really have access to? What are his recommendations and possible concerns today? The latter refused to answer questions from Le Monde.
In truth, France completely ignores what is happening behind the walls of this laboratory which it has nevertheless helped to build. The director of P4 of Lyon, Hervé Raoul, who has accompanied a good part of the Franco-Chinese cooperation in Wuhan, underlines for his part that « the laboratory looked rather well designed, but, to be sure, it would have ben necessary to see it in operational mode. I have visited it several times, but I have not seen it in operation. » And Mr. Raoul recognizes that « There are no French researchers in the P4 of Wuhan, and I have no idea how it works. » In short, the bilateral relationship celebrated by Jacques Chirac in 2004 has become unilateral … « It is very typical of what all Franco-Chinese projects become », says an advisor to French companies wishing to launch in China. « There is always a huge gap between the expected exchanges and the result on arrival ».
It is this opacity that concerns us today. Not just because an incident could have happened in this Franco-Chinese lab. In fact, there is no factual evidence to support this hypothesis. «It is even much more improbable, assures a French source who followed the file, that an incident is more linked to P4 than to other laboratories », that is to say the laboratories of the Wuhan Institute of Virology or the Center for Disease Control and Prevention, where the bat hunter celebrated in the television report operated.
If this opacity worries, it is also because this cooperation should have made it possible to avoid the health and economic catastrophe which currently affects a large part of humanity.
In 2016, the French Ambassador to Beijing, Maurice Gourdault-Montagne, had decorated, in Wuhan, Yuan Zhiming and Shi Zhengli with the National Order of Merit and the Legion of Honor for their ardor in promoting cooperation in the area of prevention and emergence of infectious diseases. When the virus struck, neither Shi Zhengli’s research nor France’s position as a preferred partner for Chinese scientists seemed to have helped Paris understand or prepare for the epidemic.