Viral

The Search for the Origin of Covid-19

Alina Chan, Matt Ridley

• Publisher: Fourth Estate
• Year: 2021
• ISBN:
  9780008487515
• Topic: Scienze biologiche
• Subtopic: Microbiologia e biologia molecolare

Understanding how Covid-19 started is more important than we know for the future of humankind. Determining whether the virus came from nature or from a lab will help us to safeguard against the next pandemic.

This disease will forever punctuate modern history. It has led to the deaths of millions, sickened hundreds of millions and affected the lives of almost every person on the planet. We now know that Covid is here to stay.

Genetic engineering expert Dr Alina Chan and renowned science writer Matt Ridley examine the origins of SARS-CoV-2, the virus responsible for Covid-19, using their formidable skills to scrutinise arguments and rigorously analyse the sprawling data. Viral is a fascinating account that takes in pangolins, horseshoe bats, internet sleuths and misleading scientific papers. It details the evidence and investigates hypotheses for the virus origin, chief among them a potential laboratory leak or a natural spillover.

Science has made great strides over the last decades. Chan and Ridley give an insight into the proliferating pathogen research and virus hunting around the world. Whatever the source of the virus, the world needs to adopt new policies and strategies to prevent or mitigate future outbreaks.

Set in the caves and mineshafts, food markets and wildlife smugglers' stores, laboratories and databases of China and elsewhere, Viral is a page-turner that reads like a detective novel and goes deeper into the deepest mystery of the day than any other work.

1.

The copper mine

‘The very cave you are afraid to enter turns out to be the source of what you are looking for.’

Joseph Campbell

In the spring of 2012, six men were admitted to a hospital in Kunming, the capital of Yunnan province in south-west China. The chief symptoms were dry coughs, shortness of breath, high fevers, aching muscles, headaches and fatigue. All six had recently worked in the same mine in Mojiang County, clearing out bat guano, up to 150 metres deep in the bat-infested, man-made cave. The four oldest patients became critically ill and suffered respiratory failure; three eventually succumbed to the mysterious disease and died. There were signs that their immune systems had been severely damaged, allowing for opportunistic infections. This, in combination with other clinical diagnoses, suggested that an unknown viral infection was highly likely to be the cause of their affliction.

The first patient, 吕 (Lu; the full names of the patients were obscured in the thesis), aged forty-two, was admitted to the hospital on 25 April and died on 12 June. The oldest patient was admitted on 26 April and had the surname 周 (Zhou). Zhou was sixty-three years of age and died on 7 May. The two other patients also admitted on 26 April, 刘 (Liu, aged forty-six) and 李 (Li, aged thirty-two), both survived the ordeal, albeit Liu struggled in the hospital for months and was only discharged on 10 September. A fifth patient, 郭 (Guo, aged forty-five), was admitted on 27 April and died on 13 August. The last patient, 吴 (Wu, aged thirty), was admitted on 2 May. Both Li and Wu, only in their early thirties, were discharged on 28 May. The less time the patient had spent in the mine, and the younger they were, the better their prognosis and the shorter their hospital stay.

The outbreak caused alarm, and the attending physician noted afterwards that, if future cases of severe pneumonia were to be encountered in the hospital or clinic, it would be necessary to be alert to the possibility of infectious disease and take precautions against transmission in the hospital. In what sounds like an increasingly desperate attempt to diagnose and treat the cause of the sickness, which failed to respond to a barrage of antibiotics and antifungals, the doctors tested the patients for HIV, cytomegalovirus, Epstein-Barr Virus, Japanese encephalitis, haemorrhagic fever, dengue, Hepatitis B, SARS and influenza.

By the start of June, the oldest patient had died and the two youngest patients had been discharged. Senior medical experts were consulted for the remaining three critically ill cases. On 4 June, the hospital consulted Dr Xie Canmao of Sun Yat-sen University’s Department of Respiratory Medicine. He thought there was a ‘great possibility of fungus infection’; however, two more patients, Lu and Guo, died later in June and August respectively despite the administration of antifungal therapy. On 19 June, Dr Zhong Nanshan, also of Sun Yat-sen University, was consulted on Guo and Liu, by then the two remaining patients in the hospital, and came to a quite different conclusion: ‘great possibility of virus infection’. Dr Zhong is well known in China as one of the heroes of the Severe Acute Respiratory Syndrome (SARS) epidemic of 2002–3. Born in 1936 in Nanjing, Dr Zhong trained in Beijing and at Edinburgh University Medical School, where he obtained his medical degree in 1981. He was working at the Guangzhou Institute of Respiratory Diseases in 2002 when the SARS epidemic began. It was Dr Zhong who insisted, at some risk to his own reputation, that the disease threatened a major pandemic, and he subsequently devised a treatment, based on cortisone and oxygen, that saved many lives.

For both patients Dr Zhong recommended: one, identify the type of bats at the mine; two, test the patients for SARS virus and antibodies; three, treat them with a series of antifungals and antibiotics; and four, increase airway management and apply bronchoscopy for sputum suction. Sadly, Guo could not be saved and died on 13 August. Liu survived. In May, he had been treated with antithrombotic therapy (preventing blood clots) and showed significant improvement two days later. The doctors continued the anticoagulant treatment until he was discharged in September, more than four months after he had been admitted to the hospital.

The saga of the sick miners, potentially infected by a SARS-related coronavirus in a bat-infested mine, did not go unnoticed by prominent laboratories in China. This outbreak was of such import that as well as Dr Zhong Nanshan, it drew in the Wuhan Institute of Virology (WIV), the Chengdu Military Center for Disease Control, the Beijing Institute of Pathogen Biology and even the laboratory of Dr ‘George’ Fu Gao, the deputy director of China’s national Center for Disease Control and Prevention. (The CDC is a network of regional public health laboratories throughout China with headquarters in Beijing. Dr Gao was promoted to director in 2017.)

An abandoned copper mine

Six hours’ drive south of Kunming, not far from the border with Laos, lies Mojiang County. It is designated by the Beijing government as an autonomous county, in recognition that its indigenous inhabitants, the Hani people, are a distinct ethnic group. The area is hilly, heavily wooded and sparsely populated, but with terraced fields on some of the hillsides, accessed by switchback dirt roads. The terraces have been used for growing bananas, rubber, tobacco and tea, but dense, green vegetation cloaks many of the slopes. The biggest city in the area, Pu’er, has long been famous for its tea plantations and the dark, fermented tea made from them. East of Pu’er, about twenty kilometres south of the small town of Tongguan, in the partly wooded terrain on the left bank of the Babian river, a small creek called Bengpinghe leads up into the hills. On a ridge to the south of this creek, surrounded by groves of orange trees, stands a tiny hamlet called Danaoshan. A short distance from here are the remains of an abandoned copper mine.

Tongguan Township in Mojiang County, Yunnan, September 2018. (Zhou Lei/Xinhua/Alamy Live News Xinhua/Alamy Stock Photo)

The location of the mine where the six miners had worked has never been officially confirmed. However, relentless digging into Chinese databases by a group of diligent sleuths unearthed a 2016 doctoral thesis, this time from the laboratory of the deputy director of the Center for Disease Control and Prevention in Beijing, Dr George Gao, which identified the mine’s precise location: N 23°10’36’ E 101°21’28’. As revelations about the Mojiang miners and their potential connection to SARS-CoV-2 spread on Twitter in the second half of 2020 and early 2021, a growing number of journalists took it upon themselves to visit the mine, and each faced impromptu roadblocks, official excuses and local people deterring them from getting close to it.

In October 2020, using the GPS coordinates from the thesis, the BBC’s John Sudworth and colleagues attempted to drive to the mine from Kunming. According to Mr Sudworth, they were ‘followed constantly for hours by as many as half a dozen unmarked cars’. As they approached from the east, the road became impassable, so they got out of their car and tried to reach the site on foot. After a long hike on rough ground, they got to the village of Danaoshan, but they were being watched. A man they met on the path refused to speak. By the time they arrived at the area the coordinates pinpointed, it was pitch black and they had to return and try again the next day. Unfortunately, their first attempt had raised the alarm and ‘the authorities were more than ready’ for their second visit. Mr Sudworth and his team tried again by car from a different direction but encountered a red construction truck blocking the road. They outsmarted the plain-clothes police following them by squeezing past the truck ‘Houdini-like’, with millimetres to spare, only to find another roadblock ahead. They set out on foot again but were ‘intercepted by some very angry men, in a 4×4, clearly communicating with someone in higher authority’. Groups of men were hanging around the area, and Sudworth was warned that ‘they would soon turn violent’ if he did not leave. The BBC team backtracked and tried a different route but were blocked again and again. One man told them that his job was to keep them out and that they would not be able to enter Danaoshan village again. Sudworth gave up on the Mojiang mine but tried to visit a nearby bat cave, named Shitou cave, in Jinning County, where scientists had found viruses most closely matching the 2003 SARS virus. They were met by another lorry blocking the road and men in military uniforms. They were held in a field for more than an hour before being forced to leave. ‘By now you get the idea. It’s impossible to overstate just how large and coordinated the effort was – state-security, plain-clothes police, uniformed police, officials and local residents. When we tried to talk to anyone, they’d turn their backs,’ Mr Sudworth reported in May 2021, by which time he had relocated to Taiwan.

It was clear that efforts were being coordinated to stymie journalists trying to retrace the steps of the virologists who visited the mine, and John Sudworth was only one of many thwarted reporters. A team from NBC’s Today show were told that wild elephants were on the road so they could go no closer. In 2021, a team of undercover French journalists got close to the site and managed to speak to somebody in Danaoshan. Asked if there was a mine nearby, he replied, ‘Yes, the Bengping mine is hidden over there … It’s the government that closed it. They put surveillance cameras all around the place.’ In May 2021, the Wall Street Journal reported that its journalist did manage to get very close to the mine on a mountain bike and saw that the entrance had become overgrown with vegetation. He was detained by the Chinese police for five hours and forced to delete a photograph of the mine from his mobile phone.

The Chinese government has shown much diligence and energy in keeping people away from the mine. Yet according to its own pronouncements, it has shown less interest in conducting further investigations at the Mojiang mine. Either it has been doing such work but keeping the results secret or it has decided not to look further into what can be learned from the site. Both possibilities are concerning.

So it is to satellite images that we turn. Today the site is blanketed with greenery but images obtained from April 2012 – when the miners who fell ill were at work – show a well-used dirt road leading to a set of buildings near the top of the hill and a well-trodden path lower down the slope to what may be the entrance of a horizontal tunnel, known as an ‘adit’ or ‘drift’. Based on research into similar sites by Brian Reed, an American engineer who has travelled extensively in rural China, including Yunnan, the buildings appear to be a U-shaped, prefab structure alongside storage tanks, typical of a mineral exploration camp. Two books unearthed by Reed reveal that the Bengping copper mining and smelting operation was originally one of the local, home-grown industrialisation ventures that were encouraged by Mao Zedong during the Great Leap Forward of the 1950s: ‘In 1958, Sun Zhongxiu, deputy secretary of the county party committee, organized nearly 10,000 people to mine the Bengping copper mine.’ But by 1960, owing to poor results, the mine had been abandoned. It appears there were several sites, one of which was referred to as ‘Bat Cave’, from which sixty tons of 6 per cent ore were extracted but not sold ‘due to inconvenient transportation’. Other records show that in 1978 an attempt was made to restart the mine. Then, according to official permits, sometime around 2011, at a time of high copper prices and a boom in copper exploration, someone seems to have had the idea of reopening the mine.

In early April 2012, we know that a small group of men began to clear bat droppings from the mine, which was full of the animals, some perhaps waking from hibernation, although in this subtropical area many stay active all year. The bats were of several different kinds, but especially numerous were the small, gregarious, insect-eating species known as horseshoe bats. It was warm, dusty and dirty work, inhaling the dust and noxious smell from the huge numbers of bats and their faeces.

It is not clear why the men were shovelling bat guano. According to the 2016 doctoral thesis, before the cases of the sickened miners, ‘many people had repeatedly entered and exited the abandoned mine, but no outbreak occurred’, which implies a regular trade was being carried out. It is probable that the miners had been contracted either to clear the mine for copper mining or to collect the guano to sell as organic fertiliser, or both. The bat guano trade is a lucrative one in some parts of the world, with small amounts of nitrogen- and phosphorus-rich guano being used in traditional Chinese medicine, as well as large amounts being supplied to farmers as fertiliser. It is collected from caves mainly in Mexico, Cuba, Jamaica, Madagascar, Indonesia and Thailand. A study of bat guano in a Thai cave, performed in 2006 and 2007 (but not published till 2013), found genetic material from coronaviruses in a small percentage of the samples and warned that bat guano miners should take preventative measures against exposure to dangerous viruses.

We do not know how many men worked in the Mojiang mine that April and May, but six were admitted to a hospital – not to the one in Pu’er City, less than a two-hour drive away, nor the one in Yuxi, less than a four-hour drive away, but to the one in the provincial capital of Kunming, almost a six-hour drive to the north. These six men had been referred by their local hospitals and clinics for specialised treatment at the Kunming Medical University Hospital.

A medical thesis

We know the story of the Mojiang miners only because of the medical thesis written by 李旭 (Li Xu), a student at Kunming Medical University. Completed in May 2013 and entitled ‘The Analysis of Six Patients with Severe Pneumonia Caused by Unknown Viruses’, the thesis concluded that the six miners had been infected by a SARS-related coronavirus (SARSrCoV) from bats, and the author noted that it was essential to investigate the bats in the mine.

This thesis had only been discovered and shared on Twitter in May 2020 by the anonymous user called the Seeker. One of us (Alina) translated critical parts of the thesis within a day and read, with increasing distress, about each of the patients and the struggle against the unknown disease with seemingly Covid-like symptoms. We separately visited the Chinese database of academic theses and confirmed that such a medical thesis existed. Attempts by us and others to reach the supervisor and the author to further authenticate the thesis were unsuccessful.

Dr Li’s 2013 medical thesis states that, after consulting Dr Zhong Nanshan, a serum immunoglobulin-M (IgM) antibody test was performed on the four living patients by the Wuhan Institute of Virology, to which the samples were sent. IgM antibodies are the body’s first line of defence in response to exposure to a pathogen, so a positive IgM test means that there has been a recent exposure. The WIV test results were indeed positive, suggesting a virus infection. The thesis did not specify exactly which type of virus the WIV had found IgM antibodies for. However, the 2016 doctoral thesis from the Chinese CDC deputy director’s laboratory (that had revealed the precise location of the mine) stated that the WIV had found the samples positive for SARS virus antibodies: ‘The blood test results of four patients showed that: four people carried SARS virus IgG antibodies, among which two of the discharged patients with higher antibody levels, and two hospitalised patients had lower antibody levels (Wuhan Institute of Virology).’ The two discharged patients were likely the two youngest miners, Li and Wu, who had left hospital at the end of May 2012, while the two surviving patients still in the hospital were likely Guo and Liu. Curiously, the doctoral thesis described the tests as finding IgG instead of IgM antibodies. IgG antibodies are produced during the initial infection but persist for months and sometimes years as a form of long-term protection in case the body encounters a similar pathogen again. Therefore, a positive IgG test could mean that the patients had been exposed to a SARS-like virus recently or perhaps months earlier. The terms ‘SARS-like’ and ‘SARS-related’ can be used interchangeably: both refer to coronaviruses of the genus betacoronavirus in the subgenus sarbecovirus.

According to Google Maps, the WIV is 1,885 kilometres from Bengpinghe by road by the fastest route: further than New York is from Orlando or as far as London is from Rome. Yet being the leading laboratory studying SARS-like and bat-borne viruses made the WIV an obvious choice to test the patient samples. These were sent to the WIV on Dr Zhong Nanshan’s instruction – to test for SARS antibodies. An immunoglobulin test result is not necessarily definitive proof of a virus having caused the disease, as opposed to some other pathogen, but both the 2013 medical thesis and the 2016 doctoral thesis certainly suggested a strong likelihood of the miners having sickened from a SARS-like virus.

Fortunately none of the patients seemed to have passed the virus on to healthcare workers or family members. The virus or viruses responsible for their illness very likely had not evolved to be as transmissible among humans as SARS-CoV-2 is. It had only managed to infect the six miners, perhaps, because they had been exposed to massive doses of the virus via the disturbed dust of bat guano within the confines of a poorly ventilated mineshaft for extended periods of time.

Virologists in the mine

No fewer than three teams of virologists visited the mine seeking the cause of the mysterious disease. According to their subsequent publications or theses, they each suspected that a virus had sickened the miners. Aside from the Chinese CDC deputy director’s group, another team came from the Beijing Institute of Pathogen Biology at the Chinese Academy of Medical Sciences and was led by Dr Jin Qi. They took samples from twenty bats, nine rats and five musk shrews captured in the mine. They identified a new Henipavirus-like paramyxovirus in three rats and reported this discovery in a 2014 article in Science magazine, titled ‘A New Killer Virus in China?’ The article was to be the first indication received by the outside world that there had been a lethal outbreak two years earlier. The rodent paramyxovirus they discovered was similar to ones carried by fruit bats that have caused occasional lethal outbreaks in humans in Australia and Bangladesh. However, this virus was incapable of replication in monkey, human or hamster cells in the laboratory. They concluded in 2014 that it was ‘more likely a curiosity’. While at the site, Dr Jin took a photograph that was later reproduced in Science magazine. It shows three scientists in full protective gear, gloves and masks handling specimens on a slope just outside the entrance to the mine. By lightening the background of the photograph, we were able to get a clear image of the entry to the adit, temporarily blocked by timbers and with what looked like more timbers supporting the tunnel’s ceiling and walls.

The WIV team was the most persistent. It was led by Dr Shi Zhengli. Between August 2012 and July 2013, Dr Shi’s group mounted at least four different expeditions to the mine, and at least three more in the subsequent two years. After all, this might prove to be the first ever recorded case of people catching a SARS-like virus directly from a bat. ‘The mineshaft stunk like hell,’ Dr Shi told a reporter in 2020. ‘Bat guano, covered in fungus, littered the cave.’

By 2013, Dr Shi’s lab had been searching caves in southern China fo...