Inside the Chinese lab poised to study world's most dangerous pathogens

Maximum-security biolab is part of plan to build network of BSL-4 facilities across China.

Editors’ note, January 2020: Many stories have promoted an unverified theory that the Wuhan lab discussed in this article played a role in the coronavirus outbreak that began in December 2019. Nature knows of no evidence that this is true; scientists believe the most likely source of the coronavirus to be an animal market.

22 February 2017 Updated:

Wuhan, China

Hazard suits hang at the National Bio-safety Laboratory, Wuhan, the first lab on the Chinese mainland equipped for the highest level of biocontainment.

A laboratory in Wuhan is on the cusp of being cleared to work with the world’s most dangerous pathogens. The move is part of a plan to build between five and seven biosafety level-4 (BSL-4) labs across the Chinese mainland by 2025, and has generated much excitement, as well as some concerns.

Some scientists outside China worry about pathogens escaping, and the addition of a biological dimension to geopolitical tensions between China and other nations. But Chinese microbiologists are celebrating their entrance to the elite cadre empowered to wrestle with the world’s greatest biological threats.

“It will offer more opportunities for Chinese researchers, and our contribution on the BSL‑4-level pathogens will benefit the world,” says George Gao, director of the Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology in Beijing. There are already two BSL-4 labs in Taiwan, but the National Bio-safety Laboratory, Wuhan, would be the first on the Chinese mainland.

The lab was certified as meeting the standards and criteria of BSL-4 by the China National Accreditation Service for Conformity Assessment (CNAS) in January. The CNAS examined the lab’s infrastructure, equipment and management, says a CNAS representative, paving the way for the Ministry of Health to give its approval. A representative from the ministry says it will move slowly and cautiously; if the assessment goes smoothly, it could approve the laboratory by the end of June.

BSL-4 is the highest level of biocontainment: its criteria include filtering air and treating water and waste before they leave the laboratory, and stipulating that researchers change clothes and shower before and after using lab facilities. Such labs are often controversial. The first BSL-4 lab in Japan was built in 1981, but operated with lower-risk pathogens until 2015, when safety concerns were finally overcome.

The expansion of BSL-4-lab networks in the United States and Europe over the past 15 years — with more than a dozen now in operation or under construction in each region — also met with resistance, including questions about the need for so many facilities.

“Viruses don’t know borders.”

The Wuhan lab cost 300 million yuan (US$44 million), and to allay safety concerns it was built far above the flood plain and with the capacity to withstand a magnitude-7 earthquake, although the area has no history of strong earthquakes. It will focus on the control of emerging diseases, store purified viruses and act as a World Health Organization ‘reference laboratory’ linked to similar labs around the world. “It will be a key node in the global biosafety-lab network,” says lab director Yuan Zhiming.

The Chinese Academy of Sciences approved the construction of a BSL-4 laboratory in 2003, and the epidemic of SARS (severe acute respiratory syndrome) around the same time lent the project momentum. The lab was designed and constructed with French assistance as part of a 2004 cooperative agreement on the prevention and control of emerging infectious diseases. But the complexity of the project, China’s lack of experience, difficulty in maintaining funding and long government approval procedures meant that construction wasn’t finished until the end of 2014.

The lab’s first project will be to study the BSL-3 pathogen that causes Crimean–Congo haemorrhagic fever: a deadly tick-borne virus that affects livestock across the world, including in northwest China, and that can jump to people.

Future plans include studying the pathogen that causes SARS, which also doesn’t require a BSL-4 lab, before moving on to Ebola and the West African Lassa virus, which do. Some one million Chinese people work in Africa; the country needs to be ready for any eventuality, says Yuan. “Viruses don’t know borders.”

Gao travelled to Sierra Leone during the recent Ebola outbreak, allowing his team to report the speed with which the virus mutated into new strains1. The Wuhan lab will give his group a chance to study how such viruses cause disease, and to develop treatments based on antibodies and small molecules, he says.

The central monitor room at China’s National Bio-safety Laboratory.

The opportunities for international collaboration, meanwhile, will aid the genetic analysis and epidemiology of emergent diseases. “The world is facing more new emerging viruses, and we need more contribution from China,” says Gao. In particular, the emergence of zoonotic viruses — those that jump to humans from animals, such as SARS or Ebola — is a concern, says Bruno Lina, director of the VirPath virology lab in Lyon, France.

Many staff from the Wuhan lab have been training at a BSL-4 lab in Lyon, which some scientists find reassuring. And the facility has already carried out a test-run using a low-risk virus.

But worries surround the Chinese lab, too. The SARS virus has escaped from high-level containment facilities in Beijing multiple times, notes Richard Ebright, a molecular biologist at Rutgers University in Piscataway, New Jersey. Tim Trevan, founder of CHROME Biosafety and Biosecurity Consulting in Damascus, Maryland, says that an open culture is important to keeping BSL-4 labs safe, and he questions how easy this will be in China, where society emphasizes hierarchy. “Diversity of viewpoint, flat structures where everyone feels free to speak up and openness of information are important,” he says.

Yuan says that he has worked to address this issue with staff. “We tell them the most important thing is that they report what they have or haven’t done,” he says. And the lab’s inter­national collaborations will increase openness. “Transparency is the basis of the lab,” he adds.

The plan to expand into a network heightens such concerns. One BSL-4 lab in Harbin is already awaiting accreditation; the next two are expected to be in Beijing and Kunming, the latter focused on using monkey models to study disease.

Lina says that China’s size justifies this scale, and that the opportunity to combine BSL-4 research with an abundance of research monkeys — Chinese researchers face less red tape than those in the West when it comes to research on primates — could be powerful. “If you want to test vaccines or antivirals, you need a non-human primate model,” says Lina.

But Ebright is not convinced of the need for more than one BSL-4 lab in mainland China. He suspects that the expansion there is a reaction to the networks in the United States and Europe, which he says are also unwarranted. He adds that governments will assume that such excess capacity is for the potential development of bioweapons.

“These facilities are inherently dual use,” he says. The prospect of ramping up opportunities to inject monkeys with pathogens also worries, rather than excites, him: “They can run, they can scratch, they can bite.”

Trevan says China’s investment in a BSL-4 lab may, above all, be a way to prove to the world that the nation is competitive. “It is a big status symbol in biology,” he says, “whether it’s a need or not.” Nature 542, 399–400 (23 February 2017) doi:10.1038/nature.2017.21487

https://www.nature.com/news/inside-the-chinese-lab-poised-to-study-world-s-most-dangerous-pathogens-1.21487

Virus-hit Wuhan has two laboratories linked to Chinese bio-warfare program

Virology institute there has China’s only secure lab for studying deadly viruse

The deadly animal virus epidemic spreading globally may have originated in a Wuhan laboratory linked to China’s covert biological weapons program, according to an Israeli biological warfare expert.

Radio Free Asia this week rebroadcast a local Wuhan television report from 2015 showing China’s most advanced virus research laboratory known the Wuhan Institute of Virology, Radio Free Asia reported.

The laboratory is the only declared site in China capable of working with deadly viruses.

Dany Shoham, a former Israeli military intelligence officer who has studied Chinese bio warfare, said the institute is linked to Beijing’s covert biological weapons program.

“Certain laboratories in the institute have probably been engaged, in terms of research and development, in Chinese [biological weapons], at least collaterally, yet not as a principal facility of the Chinese BW alignment,” Mr. Shoham told The Washington Times.

Work on biological weapons is conducted as part of a dual civilian-military research and is “definitely covert,” he said in an email.

Mr. Shoham holds a doctorate in medical microbiology. From 1970 to 1991 he was a senior analyst with Israeli military intelligence for biological and chemical warfare in the Middle East and worldwide, holding the rank of lieutenant colonel.

China in the past has denied having any offensive biological weapons. The State Department, in a report last year, said it suspects China has engaged in covert biological warfare work.

A Chinese Embassy spokesman did not return an email seeking comment.

Chinese authorities so far have said the origin of the coronavirus that has killed scores and infected hundreds in in central Hubei

Province is not known.

Gao Fu, director of the Chinese Center for Disease Control and Prevention, told state-controlled media initial signs as of Thursday indicated the virus originated from wild animals sold at a seafood market in Wuhan.

One ominous sign, said a U.S. official, is the that false rumors since the outbreak began several weeks ago have begun circulating on the Chinese Internet claiming the virus is part of a U.S. conspiracy to spread germ weapons.

That could indicate China is preparing propaganda

outlets to counter future charges the new virus escaped from one of Wuhan’s civilian or defense research laboratories.

The World Health Organization is calling the microbe novel coronavirus 2019-nCoV. At a meeting in Geneva Thursday, the organization stopped short of declaring a Public Health Emergency of International Concern.

The virus outbreak causes pneumonia-like symptoms and prompted China to deploy military forces to Wuhan this week in a bid to halt the spread. All travel out of the city of 11 million people was halted.

The Wuhan institute has studied coronaviruses in the past, including the including the strain that causes Severe Acute Respiratory Syndrome, or SARS, H5N1 influenza virus, Japanese encephalitis, and dengue.

Researchers at the institute also studied the germ that causes anthrax – a biological agent once developed in Russia.

“Coronaviruses (particularly SARS) have been studied in the institute and are probably held therein,” he said. “SARS is included within the Chinese BW program, at large, and is dealt with in several pertinent facilities.”

It is not known if the institute’s array of coronaviruses are specifically included in biological weapons program but it is possible, he said.

Asked if the new coronavirus may have leaked, Mr. Shoham said: “In principle, outward virus infiltration might take place either as leakage or as an indoor unnoticed infection of a person that normally went out of the concerned facility. This could have been the case with the Wuhan Institute of Virology, but so far there isn’t evidence or indication for such incident.”

After researchers sequence of the genome of the new coronavirus it might be possible to determine or suggest its origin or source.

Mr. Shoham, now with the Begin-Sadat Center for Strategic Studies at Bar Ilan University in Israel, said the virology institute is the only declared site in China known as P4 for Pathogen Level 4, a status indicating it uses the strictest safety standards to prevent the spread of the most dangerous and exotic microbes being studied.

The former Israeli military intelligence doctor also said suspicions were raised about the Wuhan Institute of Virology when a group of Chinese virologists working in Canada improperly sent samples to China of what he said were some of the deadliest viruses on earth, including the Ebola virus.

In a July article in the journal Institute for Defence Studies and Analyses, Mr. Shoham said the Wuhan institute was one of four Chinese laboratories engaged in some aspects of the biological weapons development.

He identified the secure Wuhan National Biosafety Laboratory at the institute as engaged in research on the Ebola, Nipah, and

Crimean-Congo hemorrhagic fever viruses.

The Wuhan virology institute is under the Chinese Academy of Sciences. But certain laboratories within it “have linkage with the PLA or BW-related elements within the Chinese defense establishment,” he said.

In 1993, China declared a second facility, the Wuhan Institute of Biological Products, as one of eight biological warfare research facilities covered by the Biological Weapons Convention (BWC) which China joined in 1985.

The Wuhan Institute of Biological Products is a civilian facility but is linked to the Chinese defense establishment, and has been regarded to be involved in the Chinese BW program, Mr. Shoham said.

China’s vaccine against SARS is probably produced there.

“This means the SARS virus is held and propagated there, but it is not a new coronavirus, unless the wild type has been modified, which is not known and cannot be speculated at the moment,” he said.

The annual State Department report on arms treaty compliance stated last year that China engaged in activities that could support biological warfare.

“Information indicates that the People’s Republic of China engaged during the reporting period in biological activities with potential dual-use applications, which raises concerns regarding its compliance with the BWC,” the report said, adding that the United States suspects China failed to eliminate its biological warfare program as required by the treaty.

“The United States has compliance concerns with respect to Chinese military medical institutions’ toxin

research and development because of the potential dual-use applications and their potential as a biological threat,” the report added.

The biosafety lab is located about 20 miles from the Hunan Seaford Market that reports from China say may have been origin point of the virus.

Rutgers University microbiologist Dr. Richard Ebright told London’s Daily Mail that “at this point there’s no reason to harbor suspicions” the lab may be linked to the virus outbreak.