P3 laboratory construction boom and mismatch

  Reporter of China News Weekly/Peng Danni

  Published in the 951th issue of China News Weekly on 2020.6.15

  On April 1, the Hubei Provincial Development and Reform Commission website intensively approved 10 construction projects of Huazhong University of Science and Technology. These projects are all related to improving the ability to respond to major public health emergencies. It is estimated that the total investment will exceed 10 billion yuan. Among them, the construction of the school's emergency prevention and control P3 laboratory and testing center will cost 1.7 billion yuan.

  In addition to the P4 laboratory of the Wuhan Institute of Virology, the Chinese Academy of Sciences, there are currently at least five P3 laboratories in Wuhan, and the planned P3 laboratory of Huazhong University of Science and Technology will be larger than the total area of ​​the existing P3 laboratories. In this regard, a virologist in Wuhan said that as a domestic virology research center and a place where nine provinces are connected, it is understandable to build a new P3 laboratory in Wuhan, but it is not possible to stand alone, but should build a platform-type P3 laboratory Radiation in Central China. More importantly, Huazhong University of Science and Technology does not have a foundation for virology research and lacks a team to support the operation and research of the P3 laboratory. "Rome was not built in a day."

  On the other hand, Wang Ruijun, former director of the Guangdong Provincial Department of Science and Technology and mayor of Shaoguan City, revealed at this year’s National Two Sessions that Guangdong Province is already promoting the development of the “Guangdong Province Biosafety Laboratory System Construction Plan (2020-2025)”, which is planned for construction 25~30 P3 laboratories, of which there must be at least seven or eight "P3+" laboratories capable of large animal model research, he said, "Hopefully we can solve the needs of basic P3 laboratories within three years, at least within five years Built a P4 laboratory."

  At present, although the reform plan for the disease control system has not yet been released, an upsurge in infrastructure construction related to the prevention and control of infectious diseases has already begun. Among them, the typical representative of the P3 laboratory is blooming all over the country.

Demand and threshold

  Biosafety laboratories are divided into P1, P2, P3, and P4 grades internationally. Among them, the negative pressure state of P3 laboratories can prevent the internal gas from leaking and causing pollution, so it is suitable for treatment. Pathogenic microorganisms or toxins that are severely infected or even fatal.

  Zhang Chenyu, professor and dean of the School of Life Sciences at Nanjing University, has been studying the antiviral effects of microRNAs. As early as 2017, when he was interviewed by the media, he once said, "We don't have P3, P4, we can't do experiments, we can only go to the laboratory outside to line up, two or three years in a row, very limited."

  During the new crown epidemic, Zhang Chenyu hoped that he could carry out experiments related to microRNA suppression of new crown virus, but lacked facilities. He told China News Weekly that he had tried to communicate with the relevant person in charge of the P3 laboratory of the Jiangsu Provincial Center for Disease Control-one of the only two P3 laboratories in Jiangsu Province, hoping to borrow it, but for various reasons. Did not agree. He finally found resources through various parties and queued up to conduct research at the P4 laboratory in Wuhan.

  Zhang Jingren, deputy dean of the School of Medicine of Tsinghua University, studied pathogens such as Mycobacterium tuberculosis. After returning to Tsinghua in 2010, he began to run for the construction of the P3 laboratory. In 2012, the school recruited an outstanding scholar from the Harvard University in the relevant field and promised to build a P3 laboratory for the other party to carry out research, but this has not been possible. The scholar later applied for a major project of the Gates Foundation, but because Tsinghua had no facilities, he could not leave the project at school and returned to Harvard last year.

  As the top bull school in China, the reason why Tsinghua could not build a P3 for so many years, Zhang Jingren explained that it was because of the great resistance to approval. In terms of procedures, it is necessary to report from the school to the Ministry of Education and then to the National Development and Reform Commission, as well as the Beijing Municipal Environmental Protection Bureau and the Ministry of Science and Technology. Among them, it is difficult to pass the EIA alone: ​​it is required to conduct a sample survey of residents within a two-kilometer radius, and everyone around you must agree. Therefore, the problem of location selection of P3 is already stuck. Conceptually, for a long time, the public and regulators believed that the danger of such facilities outweighed the benefits. In order to avoid danger, they tended not to build them. In contrast, the approval of P3 laboratories in the United States is much looser.

  Because there are no hardware facilities to study live viruses, the basic research on major infectious diseases of Tsinghua Medical College can only "study the "fur" and "bone" of the pathogen." Zhang Jingren said that after the new crown occurred, everyone was very anxious, despite the publication Many papers have been published, but they are all limited to protein, molecular level, or to find a cooperative institution to study together. "The state has invested a lot of money in schools like Tsinghua University, and there are many very creative people, but they can only make articles on the periphery of the problem and cannot do some substantive work."

  Regarding the number of domestic P3 laboratories, Zhang Jingren said that many years ago, the official figure was about 40, which has increased in recent years, but the total number should not exceed 60, most of which belong to the disease control system, mainly based on the application The goal is not to exceed 10 P3 laboratories for research in universities.

  Wuhan University was awarded the first domestic P3 laboratory in 2003, and a new animal P3 was created two years later. Lan Ke, director of the school's State Key Laboratory of Virology, told China News Weekly that the number of P3s in domestic universities is too small to match the research strength of universities. In turn, this lack will affect talent development. Because the number of scientific research workers in the field of pathogenic microbiology depends on the facility to some extent.

  Wang Ruijun, former director of the Guangdong Provincial Department of Science and Technology and mayor of Shaoguan, pointed out that there are nearly 1,500 P3 laboratories in the United States, and almost all medical institutions or medical schools have settings. In comparison, domestic P3 and P4 laboratories are short. The board is very prominent. According to statistics from the World Health Organization, as of the end of 2017, there were 7 P3+ laboratories in the United States and 10 P4 laboratories.

  As one of the scientific research infrastructure projects, the P3 laboratory of Nanjing University where Zhang Chenyu is located has also been completed. The construction cost is 12 million to 15 million yuan, and the annual operating fund is 3 million to 5 million yuan. After the new crown epidemic, Zhang Jingren believes that some colleges and universities, including Tsinghua’s P3 laboratory, will be built soon.

Idleness and cost

  After the end of SARS in 2003, the Jiangsu CDC built a new building. On the third floor of the building, a P3 laboratory of approximately 150 square meters landed here. At that time, in view of the fact that the old P3 laboratory built in 1989 had not really been used, Wang Hua, chairman of the Jiangsu Provincial Preventive Medicine Association and then director of the Jiangsu Center for Disease Control, firmly refused to build a new one, but at that time "this is a kind of "Fashion", built P3 is considered a sign of strength.

  Around May and June of the same year, the Jiangsu Provincial Center for Disease Control and Prevention just isolated the SARS virus in the new P3 laboratory and did a classified training. The relevant national authorities came to a document that does not allow the provinces to do SARS pathogen related work. Part of the specimens and cultured cells will be destroyed and part will be sent to Beijing. Since then, this laboratory has been vacant for a long time because it has not encountered any outbreaks caused by highly pathogenic pathogens. It is usually used for the study of pathogens such as HIV and drug-resistant tuberculosis. According to the director of the Jiangsu Provincial Center for Disease Control and Prevention Biosafety Laboratory, the average annual operating time of the laboratory is only about one month in these years.

  But now, more and more P3 laboratories will emerge. On May 9, the National Development and Reform Commission, the Health and Health Commission and the Chinese Medicine Bureau jointly formulated the "Public Health Prevention and Control Capacity Building Program" proposed to achieve the modernization of the disease control system, and the specific approach to achieve this goal, That is, each prefecture-level city has at least one P2 level laboratory, and each province has at least one P3 level laboratory to improve the ability to detect and detect pathogens.

  Some provinces have taken active action. At this year's National Two Sessions, Li Weimin, the dean of West China Hospital of Sichuan University, revealed that Sichuan will deploy two P3 laboratories in West China Hospital of Sichuan University and the Sichuan Center for Disease Control, and is expected to be completed within one year.

  In Fuzhou City, Fujian Province, a new disease control center covering an area of ​​50,000 square meters is about to rise, and the new site will include a public health emergency command center, a chronic disease prevention center, and a three-level laboratory for biological safety protection (ie P3 Lab) etc.

  In Jiangsu Province, Wang Hua told China News Weekly that there are about 15 to 20 institutions that recently filed an application report to build a P3, including universities and top three hospitals. But he pointed out, "Our overall domestic research level and pathogenic microorganism research level have not yet reached this demand. In the past, many P3 laboratories were placed there, and they are not used all year round. And there are so many P3 people to maintain it? Engaged in this People in this job have changed their careers because they have no corresponding majors."

  Many interviewed experts mentioned that there may be about 20 P3 laboratories in the National CDC, but most of them are not fully utilized, and P3 is not required for general pathogen detection and research. A public health expert directly questioned, "How many years have pathogens like SARS and the new crown been encountered only once over the years?"

  The P3 laboratory of Shanghai Municipal Public Health Department is a place with a relatively high utilization rate. Xu Jianqing, director of the Institute of New and Reproducible Infectious Diseases, Shanghai Public Health Clinical Center, said that on the one hand, there are many teams conducting pathogen research in Shanghai. On the other hand, the laboratory also supports these teams in using commissions or training methods to use this facility. One year, the laboratory's operating days reached 287 days, including maintenance, inspection, disinfection and other activities, has been in use for almost an entire year, but Xu Jianqing said that there are very few P3 laboratories with such a high domestic utilization rate.

  The construction and operation of the P3 laboratory is expensive. Some experts pointed out that if the construction cost of one square meter of civil houses is between 5,000 yuan and 10,000 yuan, then the construction cost of the P3 laboratory per square meter will reach 60,000 to 80,000. Once P3 is up and running, it cannot be easily turned off. The P3 laboratory of the Shanghai Public Health Clinical Center was put into operation in March 2008, with an area of ​​about 390 square meters and is of medium scale. Xu Jianqing has settled an account: the entire air filtration system of the laboratory, including the three systems of initial efficiency, intermediate efficiency and high efficiency, needs more than 1 million yuan to be updated once a year. Entering the laboratory once, if a better isolation suit is used, The cost of a set is about 95 yuan, not to mention the consumption of water and electricity. Its operating cost is dozens or even hundreds of times higher than that of ordinary laboratories.

  The P3 laboratory of CDC in Jiangsu Province has a relatively small area, with a core area of ​​only more than 20 square meters. With supporting preparation and buffer areas, the overall area is about 150 square meters. But even in such a projectile place, Wang Hua had a headache, "The negative pressure value should be adjusted every week, and it is very expensive to replace the filter membrane regularly. We have a set of people in it, and there are not hundreds of thousands of pieces every year. Money certainly won't work, this is not a general price."

How mismatches are bridged

  On the one hand, researchers cannot find the P3 laboratory for experiments, on the other hand, P3 in the disease control system has been idle for a long time. This mismatch points to the importance of resource sharing and coordination in P3 laboratories, but there is currently no mature cooperation mechanism.

  Zhang Jingren said that although there are many P3 laboratories for disease control, if borrowed, the other party is not necessarily willing to take the risk of management. Another way of cooperation is to apply for funding together with those scientific research teams that have the P3 laboratory conditions.

  A P3 laboratory manager in the eastern province of CDC told China News Weekly that they have no endogenous motivation to cooperate. He explained that as a national public welfare institution, half of the CDC's income is financed by the financial and the other half generates income by itself, but the upper limit of income generation is also limited to supplementing the other half. The income above this limit no longer belongs to the CDC. On the other hand, the delineation of risks and responsibilities under the high pressure of the P3 laboratory makes the CDC prefer not to cooperate or make mistakes.

  The laboratory accident in 2004 still has a fresh memory for those under the disease control system. At that time, researchers from the National CDC Viral Disease Prevention and Control Institute used unverified SARS virus inactivation methods to deal with the virus, and then manipulated the infected materials in non-P3 laboratories, resulting in SARS virus leakage incidents, which ultimately led to 1 death. 7 People infected. After the incident, Li Liming, the first director of the National CDC, voluntarily resigned.

  "Research facilities for highly pathogenic pathogens should be concentrated on construction." Xu Jianqing and others once suggested to the Shanghai Municipal Government not to build for construction. Some areas that do have major needs should be built, and they should be built for regional sharing and scale. Slightly larger, and equipped with a professional P3, P4 operation team and a truly shared mechanism. Otherwise, the investment is large, and the operation demand is high. The decentralized construction causes idleness and waste.

  Wang Hua, the former director of the Jiangsu Provincial Center for Disease Control, received a call halfway through the interview. The other party wanted him to participate in the discussion on the construction of the public health system in the province. He refused. "I went there several times and said that I haven't solved any practical problem for a long time. Now the whole country is doing infrastructure construction, and it is back to the situation of 2003 and 2004. The most critical operating mechanism has not been resolved. What is the use of these? They are lined up to build when they are hot. As for who will use it in the future?" Looking back at the scene after SARS in 2003, Wang Hua felt that history is so surprisingly similar.

  China News Weekly No. 22, 2020

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