U.S. government gave $3.7 million grant to Wuhan lab at cent

Re: U.S. government gave $3.7 million grant to Wuhan lab at

Postby admin » Mon May 18, 2020 3:15 am

He Could Have Seen What Was Coming: Behind Trump’s Failure on the Virus: An examination reveals the president was warned about the potential for a pandemic but that internal divisions, lack of planning and his faith in his own instincts led to a halting response.
by Eric Lipton, David E. Sanger, Maggie Haberman, Michael D. Shear, Mark Mazzetti and Julian E. Barnes
New York Times
Published April 11, 2020
Updated May 4, 2020

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WASHINGTON — “Any way you cut it, this is going to be bad,” a senior medical adviser at the Department of Veterans Affairs, Dr. Carter Mecher, wrote on the night of Jan. 28, in an email to a group of public health experts scattered around the government and universities. “The projected size of the outbreak already seems hard to believe.”

A week after the first coronavirus case had been identified in the United States, and six long weeks before President Trump finally took aggressive action to confront the danger the nation was facing — a pandemic that is now forecast to take tens of thousands of American lives — Dr. Mecher was urging the upper ranks of the nation’s public health bureaucracy to wake up and prepare for the possibility of far more drastic action.

“You guys made fun of me screaming to close the schools,” he wrote to the group, which called itself “Red Dawn,” an inside joke based on the 1984 movie about a band of Americans trying to save the country after a foreign invasion. “Now I’m screaming, close the colleges and universities.”

His was hardly a lone voice. Throughout January, as Mr. Trump repeatedly played down the seriousness of the virus and focused on other issues, an array of figures inside his government — from top White House advisers to experts deep in the cabinet departments and intelligence agencies — identified the threat, sounded alarms and made clear the need for aggressive action.

The president, though, was slow to absorb the scale of the risk and to act accordingly, focusing instead on controlling the message, protecting gains in the economy and batting away warnings from senior officials.
It was a problem, he said, that had come out of nowhere and could not have been foreseen.

Even after Mr. Trump took his first concrete action at the end of January — limiting travel from China — public health often had to compete with economic and political considerations in internal debates, slowing the path toward belated decisions to seek more money from Congress, obtain necessary supplies, address shortfalls in testing and ultimately move to keep much of the nation at home.

Unfolding as it did in the wake of his impeachment by the House and in the midst of his Senate trial, Mr. Trump’s response was colored by his suspicion of and disdain for what he viewed as the “Deep State” — the very people in his government whose expertise and long experience might have guided him more quickly toward steps that would slow the virus, and likely save lives.

In sum, Democrats and their supporters had the exact prosecutor they all agreed was the embodiment of competence and integrity in Robert Mueller. He assembled a team of prosecutors and investigators that countless media accounts heralded as the most aggressive and adept in the nation. They had subpoena power, the vast surveillance apparatus of the U.S. government at their disposal, a demonstrated willingness to imprison anyone who lied to them, and unlimited time and resources to dig up everything they could.

The result of all of that was that not a single American – whether with the Trump campaign or otherwise – was charged or indicted on the core question of whether there was any conspiracy or coordination with Russia over the election. No Americans were charged or even accused of being controlled by or working at the behest of the Russian government. None of the key White House aides at the center of the controversy who testified for hours and hours – including Donald Trump, Jr. or Jared Kushner – were charged with any crimes of any kind, not even perjury, obstruction of justice or lying to Congress.

These facts are fatal to the conspiracy theorists who have drowned U.S. discourse for almost three years with a dangerous and distracting fixation on a fictitious espionage thriller involved unhinged claims of sexual and financial blackmail, nefarious infiltration of the U.S. Government by familiar foreign villains, and election cheating that empowered an illegitimate President. They got the exact prosecutor and investigation that they wanted, yet he could not establish that any of this happened and, in many cases, established that it did not.

THE ANTI-CLIMACTIC ENDING of the Mueller investigation is particularly stunning given how broad Mueller’s investigative scope ended up being, extending far beyond the 2016 election into years worth of Trump’s alleged financial dealings with Russia (and, obviously, Manafort’s with Ukraine and Russia). There can simply be no credible claim that Mueller was, in any meaningful way, impeded by scope, resources or topic limitation from finding anything for which he searched.

Despite efforts today by long-time conspiracist theorists to drastically move goalposts so as to claim vindication, the historical record could not be clearer that Mueller’s central mandate was to determine whether crimes were committed by Trump officials in connection with alleged Russian interference in the election. The first paragraph of the New York Times article from May, 2017, announcing Mueller’s appointment, leaves no doubt about that:

The Justice Department appointed Robert S. Mueller III, a former F.B.I. director, as special counsel on Wednesday to oversee the investigation into ties between President Trump’s campaign and Russian officials, dramatically raising the legal and political stakes in an affair that has threatened to engulf Mr. Trump’s four-month-old presidency.


As recently as one month ago, former CIA Director and current NBC News analyst John Brennan was confidently predicting that Mueller could not possibly close his investigation without first indicting a slew of Americans for criminally conspiring with Russia over the election, and specifically predicted that Trump’s family members would be included among those so charged:

Terry Moran

@TerryMoran
John Brennan has a lot to answer for—going before the American public for months, cloaked with CIA authority and openly suggesting he’s got secret info, and repeatedly turning in performances like this.

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Obviously, none of that happened. Nor were any of the original accusations that launched this three-year-long mania — from an accusatory August, 2016 online commercial from the Clinton campaign — corroborated by the Mueller Report:

Indeed, so many of the most touted media “bombshells” claiming to establish Trump/Russia crimes have been proven false by this report. Despite an extensive discussion of Paul Manafort’s activities, nothing in the Report even hints, let alone states, that he ever visited Julian Assange in the Ecuadorian Embassy, let alone visited him three times, including during the 2016 election. How the Guardian could justify still not retracting that false story is mystifying.

Faring even worse is the Buzzfeed bombshell from January claiming that “President Donald Trump directed his longtime attorney Michael Cohen to lie to Congress about negotiations to build a Trump Tower in Moscow” and that “Cohen also told the special counsel that after the election, the president personally instructed him to lie — by claiming that negotiations ended months earlier than they actually did — in order to obscure Trump’s involvement.” Mueller himself responded to the story by insisting it was false, and his Report directly contradicts it, as it makes clear that Cohen told Mueller the exact opposite:


But Cohen said that he and the President did not explicitly discuss whether Cohen's testimony about the Trump Tower Moscow project would be or was false, and the President did not direct him to provide false testimony. Cohen also said he did not tell the President about the specifics of his planned testimony. During the time when his statement to Congress was being drafted and circulated to members of the JDA, Cohen did not speak directly to the President about the statement, but rather communicated with the President's personal counsel -- as corroborated by phone records showing extensive communications between Cohen and the President's personal counsel before Cohen submitted his statement and when he testified before Congress.


Equally debunked is CNN’s major blockbuster by Jim Sciutto, Carl Bernstein, and Marshall Cohen from last July that “Michael Cohen, President Donald Trump’s former personal attorney, claims that then-candidate Trump knew in advance about the June 2016 meeting in Trump Tower.” The Mueller Report says the exact opposite: that Cohen had no knowledge of Trump’s advanced knowledge.

And the less said about the Steele Dossier, pee-pee tapes, secret meetings in Prague, and indescribably unhinged claims like this one, the better:




But beyond the gutting of these core conspiracy claims is that Mueller’s investigation probed areas far beyond the initial scope of Trump/Russia election-conspiring, and came up empty. Among other things, Mueller specifically examined Trump’s financial dealings with Russia to determine whether that constituted incriminating evidence of corrupt links:

Because Trump’s status as a public figure at the time was attributable in large part to his prior business and entertainment dealings, this Office investigated whether a business contact with Russia-linked individuals and entities during the campaign period—the Trump Tower Moscow project, see Volume I, Section IV.A.1, infra—led to or involved coordination.


Indeed, Mueller’s examination of Trump’s financial dealings with Russia long pre-dates the start of the Trump campaign, going back several years before the election:

Between at least 2013 and 2016, the Trump Organization explored a similar licensing deal in Russia involving the construction of a Trump-branded property in Moscow. The project, commonly referred to as a "Trump Tower Moscow" or "Trump Moscow" project, anticipated a combination of commercial, hotel, and residential properties all within the same building. Between 2013 and June 2016, several employees of the Trump Organization, including then-president of the organization Donald J. Trump, pursued a Moscow deal with several Russian counterparties. From the fall of 2015 until the middle of 2016, Michael Cohen spearheaded the Trump Organization's pursuit of a Trump Tower Moscow project, including by reporting on the project's status to candidate Trump and other executives in the Trump Organization.290


Mueller additionally made clear that he received authorization to investigate numerous Americans for ties to Russia despite their not being formally associated with the Trump campaign, including Michael Cohen and Roger Stone. And regarding Cohen, Mueller specifically was authorized to investigate any attempts by Cohen to “receive funds from Russia-backed entities.” None of this deep diving to other individuals or years of alleged financial dealings with Russian resulted in any finding that Trump or any of his associates were controlled by, or corruptly involved with, the Russian government.

Then there is the issue of Manafort’s relationship with the Ukrainians, and specifically his providing of polling data to Konstantin Kilimnik, an episode which Trump/Putin conspiracist Marcy Wheeler, along with many others, particularly hyped over and over. To begin with, Mueller said his office “did not identify evidence of a connection” between that act and “Russian interference in the election,” nor did he “establish that Manafort otherwise coordinated with the Russian government on its election-inteference efforts”:

Because of questions about Manafort's credibility and our limited ability to gather evidence on what happened to the polling data after it was sent to Kilimnik, the Office could not assess what Kilimnik (or others he may have given it to) did with it. The Office did not identify evidence of a connection between Manafort's sharing polling data and Russia's interference in the election, which had already been reported by U.S. media outlets at the time of the August 2 meeting. The investigation did not establish that Manafort otherwise coordinated with the Russian government on its election-interference efforts.


Also endlessly hyped by Wheeler and other conspiracists were the post-election contacts between Trump and Russia: as though it’s unusual that a major power would seek to build new, constructive relationships with a newly elected administration. Indeed, Wheeler went so far as to cite these post-election contacts to turn her own source into the FBI on the ground that it constituted smoking gun evidence, an act for which she was praised by the Washington Post (nothing Wheeler claimed about the evidence “related to the Mueller investigation” that she claimed to possess appears to be in the Mueller Report). Here again, the Mueller Report could not substantiate any of these claims:

B. Post-Election and Transition-Period Contacts

Trump was elected President on November 8, 2016. Beginning immediately after the election, individuals connected to the Russian government started contacting officials on the Trump Campaign and Transition Team through multiple channels -- sometimes through Russian Ambassador Kislyak and at other times through individuals who sought reliable contacts through U.S. persons not formally tied to the Campaign or Transition Team. The most senior levels of the Russian government encouraged these efforts. The investigation did not establish that these efforts reflected or constituted coordination between the Trump Campaign and Russia in its election-interference activities.


The centerpiece of the Trump/Russia conspiracy – the Trump Tower meeting – was such a dud that Jared Kushner, halfway through the meeting, texted Manafort to declare the meeting “a waste of time,” and then instructed his assistant to call him so that he could concoct a reason to leave. Not only could Mueller not find any criminality in this meeting relating to election conspiring, but he could not even use election law to claim it was an illegal gift of something of value from a foreigner, because, among other things, the information offered was of so little value that it could not even pass the $2,000 threshold required to charge someone for a misdemeanor, let alone the $25,000 required to make it a felony.

Neither the Trump Tower meeting itself nor its participants – for so long held up as proof of the Trump/Russia conspiracy – could serve as the basis for any finding of criminality. Indeed, the key Trumpworld participants who testified about what happened at that meeting and its aftermath (Trump Jr. and Kushner) were not even accused by Mueller of lying about any of it.

NONE OF THIS IS TO SAY that the Mueller Report exonerates Trump of wrongdoing. Mueller makes clear, for instance, that the Trump campaign not only knew that Russia was interested in helping it win the election but was happy to have that help. There’s clearly nothing criminal about that. One can debate whether it’s unethical for a presidential campaign to have dirt about its opponent released by a foreign government, though anyone who wants to argue that has to reconcile that with the fact that the DNC had a contractor working with the Ukrainian government to help Hillary Clinton win by feeding them dirt on Trump and Manafort, as well as a paid operative named Christopher Steele (remember him?) working with Russian officials to get dirt on Trump.

POLITICO
PRESIDENTIAL TRANSITION
Ukrainian efforts to sabotage Trump backfire
Kiev officials are scrambling to make amends with the president-elect after quietly working to boost Clinton.
By Kenneth P. Vogel and David Stern
01/11/2017 05:05 AM EST


As is true of all investigations, Mueller’s team could not access all relevant information. Some was rendered inaccessible through encryption. Other information was deleted, perhaps with corrupt motives. And some witnesses lied or otherwise tried to obstruct the investigation. As a result, it’s of course possible that incriminating evidence existed that Mueller – armed with subpoena power, unlimited resources, 22 months of investigative work, and a huge team of top-flight prosecutors, FBI agents, intelligence analysts and forensic accountants – did not find.

But anything is possible. It’s inherently possible that anyone is guilty of any crime but that the evidence just cannot be found to prove it. One cannot prove a negative. But the only way to rationally assess what happened is by looking at the evidence that is available, and that’s what Mueller did. And there’s simply no persuasive way – after heralding Mueller and his team as the top-notch investigators that they are and building up expectations about what this would produce – for any honest person to deny that the end of the Mueller investigation was a huge failure from the perspective of those who pushed these conspiracies.

Mueller certainly provides substantial evidence that Russians attempted to meddle in various ways in the U.S. election, including by hacking the DNC and Podesta and through Facebook posts and tweets. There is, however, no real evidence that Putin himself ordered this, as was claimed since mid-2016. But that Russia had done such things has been unsurprising from the start, given how common it is for the U.S. and Russia to meddle in everyone’s affairs, including one another’s, but the scope and size of it continues to be minute in the context of overall election spending:

To reach larger U.S. audiences, the IRA purchased advertisements from Facebook that promoted the IRA groups on the newsfeeds of U.S. audience members. According to Facebook, the IRA purchased over 3,500 advertisements, and the expenditures totaled approximately $100,000.


The section of Mueller’s report on whether Trump criminally attempted to obstruct the investigation is full of evidence and episodes that show Trump being dishonest, misleading, and willing to invoke potentially corrupt tactics to put an end to it. But ultimately, the most extreme of those tactics were not invoked (at times because Trump’s aides refused), and the actions in which Trump engaged were simply not enough for Mueller to conclude that he was guilty of criminal obstruction.

As Mueller himself concluded, a reasonable debate can be conducted on whether Trump tried to obstruct his investigation with corrupt intent. But even on the case of obstruction, the central point looms large over all of it: there was no underlying crime established for Trump to cover-up.

All criminal investigations require a determination of a person’s intent, what they are thinking and what their goal is. When the question is whether a President sought to kill an Executive Branch investigation – as Trump clearly wanted to do here – the determinative issue is whether he did so because he genuinely believed the investigation to be an unfair persecution and scam, or whether he did it to corruptly conceal evidence of criminality.

That Mueller could not and did not establish any underlying crimes strongly suggests that Trump acted with the former rather than the latter motive, making it virtually impossible to find that he criminally obstructed the investigation.

THE NATURE OF OUR POLITICAL DISCOURSE is that nobody ever needs to admit error because it is easy to confine oneself to strictly partisan precincts where people are far more interested in hearing what advances their agenda or affirms their beliefs than they are hearing the truth. For that reason, I doubt that anyone who spent the last three years pushing utterly concocted conspiracy theories will own up to it, let alone confront any accountability or consequences for it.

But certain facts will never go away no matter how much denial they embrace. The sweeping Mueller investigation ended with zero indictments of zero Americans for conspiring with Russia over the 2016 election. Both Donald Trump, Jr. and Jared Kushner – the key participants in the Trump Tower meeting – testified for hours and hours yet were never charged for perjury, lying or obstruction, even though Mueller proved how easily he would indict anyone who lied as part of the investigation. And this massive investigation simply did not establish any of the conspiracy theories that huge parts of the Democratic Party, the intelligence community and the U.S. media spent years encouraging the public to believe.


Those responsible for this can refuse to acknowledge wrongdoing. They can even claim vindication if they want and will likely be cheered for doing so.

But the contempt in which the media and political class is held by so much of the U.S. population – undoubtedly a leading factor that led to Trump’s election in the first place – will only continue to grow as a result, and deservedly so. People know they were scammed, that their politics was drowned for years by a hoax. And none of that will go away no matter how insulated media and political elites in Washington, northern Virginia, Brooklyn, and large West Coast cities keep themselves, and thus hear only in-group affirmation while blocking out all of that well-earned scorn.

-- Robert Mueller Did Not Merely Reject the Trump-Russia Conspiracy Theories. He Obliterated Them, by Glenn Greenwald


Decision-making was also complicated by a long-running dispute inside the administration over how to deal with China. The virus at first took a back seat to a desire not to upset Beijing during trade talks, but later the impulse to score points against Beijing left the world’s two leading powers further divided as they confronted one of the first truly global threats of the 21st century.

The shortcomings of Mr. Trump’s performance have played out with remarkable transparency as part of his daily effort to dominate television screens and the national conversation.

But dozens of interviews with current and former officials and a review of emails and other records revealed many previously unreported details and a fuller picture of the roots and extent of his halting response as the deadly virus spread:

The National Security Council office responsible for tracking pandemics received intelligence reports in early January predicting the spread of the virus to the United States, and within weeks was raising options like keeping Americans home from work and shutting down cities the size of Chicago. Mr. Trump would avoid such steps until March.

Despite Mr. Trump’s denial weeks later, he was told at the time about a Jan. 29 memo produced by his trade adviser, Peter Navarro, laying out in striking detail the potential risks of a coronavirus pandemic: as many as half a million deaths and trillions of dollars in economic losses.

The health and human services secretary, Alex M. Azar II, directly warned Mr. Trump of the possibility of a pandemic during a call on Jan. 30, the second warning he delivered to the president about the virus in two weeks. The president, who was on Air Force One while traveling for appearances in the Midwest, responded that Mr. Azar was being alarmist.

Mr. Azar publicly announced in February that the government was establishing a “surveillance” system in five American cities to measure the spread of the virus and enable experts to project the next hot spots. It was delayed for weeks. The slow start of that plan, on top of the well-documented failures to develop the nation’s testing capacity, left administration officials with almost no insight into how rapidly the virus was spreading. “We were flying the plane with no instruments,” one official said.

By the third week in February, the administration’s top public health experts concluded they should recommend to Mr. Trump a new approach that would include warning the American people of the risks and urging steps like social distancing and staying home from work. But the White House focused instead on messaging and crucial additional weeks went by before their views were reluctantly accepted by the president — time when the virus spread largely unimpeded.


When Mr. Trump finally agreed in mid-March to recommend social distancing across the country, effectively bringing much of the economy to a halt, he seemed shellshocked and deflated to some of his closest associates. One described him as “subdued” and “baffled” by how the crisis had played out. An economy that he had wagered his re-election on was suddenly in shambles.

He only regained his swagger, the associate said, from conducting his daily White House briefings, at which he often seeks to rewrite the history of the past several months. He declared at one point that he “felt it was a pandemic long before it was called a pandemic,” and insisted at another that he had to be a “cheerleader for the country,” as if that explained why he failed to prepare the public for what was coming.

Mr. Trump’s allies and some administration officials say the criticism has been unfair. The Chinese government misled other governments, they say. And they insist that the president was either not getting proper information, or the people around him weren’t conveying the urgency of the threat. In some cases, they argue, the specific officials he was hearing from had been discredited in his eyes, but once the right information got to him through other channels, he made the right calls.

“While the media and Democrats refused to seriously acknowledge this virus in January and February, President Trump took bold action to protect Americans and unleash the full power of the federal government to curb the spread of the virus, expand testing capacities and expedite vaccine development even when we had no true idea the level of transmission or asymptomatic spread,” said Judd Deere, a White House spokesman.

There were key turning points along the way, opportunities for Mr. Trump to get ahead of the virus rather than just chase it. There were internal debates that presented him with stark choices, and moments when he could have chosen to ask deeper questions and learn more. How he handled them may shape his re-election campaign. They will certainly shape his legacy.

The Containment Illusion

By the last week of February, it was clear to the administration’s public health team that schools and businesses in hot spots would have to close. But in the turbulence of the Trump White House, it took three more weeks to persuade the president that failure to act quickly to control the spread of the virus would have dire consequences.
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Re: U.S. government gave $3.7 million grant to Wuhan lab at

Postby admin » Wed Jun 03, 2020 8:15 am

COVID-19: Scientists Have High Hopes For Potential Breakthrough Virus Blocker
by Joe Lombardi
05/25/2020 7:03 p.m.

Image
Strains of cannabis Photo Credit: MOCA via Wikimedia Commons

A team of scientists has high hopes for a potential breakthrough blocker for the novel strain of coronavirus (COVID-19).

It has discovered that strains of medical cannabis may help prevent contracting COVID infections.

At least a dozen cannabis plants of the hundreds tested were high in CBD that appeared to affect the ACE2 pathways that the virus uses to access the body, the researchers from the University of Lethbridge in Alberta, Canada discovered.

The findings won't lead to a vaccine, but rather other delivery methods that could make people more resistant to COVID-19, says the Calgary Herald in this report.

Early indications are that the cannabis extracts could be used in mouthwash and throat gargle products as well as inhalers for both at-home treatment and clinical practice, according to CTV News.

The scientists say COVID's entry points could potentially be reduced by as much as 70 to 80 percent by cannabis.

“Our work could have a huge influence — there aren’t many drugs that have the potential of reducing infection by 70 to 80 percent,” one of the scientists told the Calgary Herald.

The next steps are for the study to be peer-reviewed and for clinical trials to be scheduled.

The scientists' results were published in Preprints, an online journal.
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Re: U.S. government gave $3.7 million grant to Wuhan lab at

Postby admin » Sat Jul 18, 2020 12:38 am

A Sinking Ship’: Arizona Docs Say Ducey Steered State Into COVID-19 Surge
SWITCH FLIPPED: The state has 130,000 coronavirus cases, and hospital workers say it didn’t have to happen.
by Emily Shugerman
Updated Jul. 17, 2020 12:16PM ET Published Jul. 17, 2020 3:59AM ET

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Matt Heinz, a hospital physician in Tucson, Arizona, remembers the day he knew a coronavirus surge was coming. Or really, it was two days: a night shift that stretched from the evening of June 3 into the early hours of June 4, when Heinz admitted four patients suspected of having COVID-19, instead of the usual one or zero. It was a little over two weeks after Gov. Doug Ducey allowed the state’s lockdown order to expire, Heinz said, and “it was like someone flipped a switch.”

“And someone did flip a switch,” said Heinz, a former Democratic state representative who also served in the Department of Health and Human Services. “It was the governor.”

As cases in Arizona skyrocket, physicians told The Daily Beast they feel increasingly abandoned by Ducey, who was one of the first leaders in the country to lift lockdown restrictions this spring. Despite the state’s record-setting spike in cases—and the urging of hundreds of health-care workers and multiple mayors—Ducey so far has refused to re-institute a lockdown order or issue a mask mandate, leaving doctors and nurses feeling helpless.

“You can’t bluff this virus,” said Quinn Snyder, an emergency physician in Mesa. “People keep trying to find shortcuts around the issues at hand, but the virus just doesn’t care about those kinds of shortcuts. It will win.”

“I have been trying to talk to people and speak up as much as possible,” he added. “And it feels like we are on a sinking ship.”

A spokesperson for the governor said Ducey had taken a number of steps to slow the spread of the virus, including prohibiting large gatherings and pausing the operations of gyms, bars, nightclubs, waterparks, and tubing establishments. He also noted that Ducey had allowed cities to pass their own mask ordinances and that nearly 90 percent of the state was now under a local mask mandate.

“We want everyone to wear a mask in public,” the spokesperson said. “Our approach has been focused on bringing about the maximum mask compliance possible.”

“It doesn’t seem like there’s any end in sight. But not necessarily because of the rhythm of the disease, but because of our government’s response to it.”

— Larry DeLuca


Arizona reported more than 3,200 new cases in a single day Thursday, putting it behind only Florida in the number of new cases per capita. The figures were actually a slight decrease from previous highs, but the situation in the hospitals still looked dire—the number of ICU beds and ventilators in use by suspected or confirmed coronavirus patients hit new records Sunday. On Thursday, 90 percent of the state’s ICU beds were taken and 53 percent of its ventilators were in use, according to state Health Department data.

Inside the hospitals, doctors told The Daily Beast they were working more than 100 hours a week, and “countless” nurses were out sick. At one Tucson-area hospital, a secondary ICU that closed when things leveled off over the spring recently reopened, and the post-anesthesia care unit was “cannibalized” to house coronavirus patients, according to emergency physician Larry DeLuca. Snyder said one of the hospitals where he works had started housing adult patients in its pediatric towers, and the emergency department was also shuffling beds to make room for COVID-positive patients.

Several of the half-dozen doctors who spoke to The Daily Beast characterized these next few weeks as a “tipping point” for Arizona, where things could go from under control to completely out of their hands.

“It doesn’t seem like there’s any end in sight,” DeLuca said. “But not necessarily because of the rhythm of the disease, but because of our government’s response to it.”

One ICU physician in Tucson, who asked not to be named for fear of employer retaliation, said the official numbers actually underplayed the severity of the crisis. When hospitals reported that 90 percent of their ICU beds and half of their ventilators were in use, the physician said, those numbers included the extra beds and machines they’d brought in for the pandemic. If those percentages ever reached 100, there would be no feasible way for the hospital to scale up.

“If you were going by our pre-COVID capacity, we would be actually operating at 120 percent of capacity,” the physician said, adding that the hospital where they work had run out of its own ventilator supply and was now using those supplied by FEMA.

Several hospitals have already launched part or all of their emergency plans, including calling in refrigerated trucks to use as morgues. The Maricopa County Medical Examiner’s Office also recently announced it is preparing for an increase in corpses, saying the office is “currently near capacity for body storage.” (It added that while this situation is common for this time of year, it is “further complicated by the current pandemic.”)

For many, the announcement called to mind the images of bodies being loaded into trucks by forklift during the height of the East Coast outbreak in March, or the weeks-long wait for funerals. But there is one key difference: While New York shut down all non-essential businesses and issued a mask mandate during the height of its surge, Arizona is still allowing haircuts, spa days, and indoor dining.

At a press conference earlier this month, on the same day the number of cases passed 112,000, Ducey acknowledged that his earlier shutdown order—one that mirrored many of New York’s restrictions—had worked. The number of new cases in the state stayed relatively stable from the time the order went out in March to the day it expired in mid-May. Cases began to skyrocket in June, shortly after the reopening.

But Ducey has refused to issue another lockdown order. Instead, at the press conference, he claimed that his June 29 order shuttering all gyms and bars—but allowing restaurants, barbershops, hair and nail salons to stay open—had achieved “some results.” And he decreased indoor dining allowances by only 50 percent, which public health officials said was totally inadequate. (A spokesperson for Ducey's office said the 50 percent reduction in restaurant capacity was part of recommendations made by the White House Coronavirus Task Force.)

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Heinz described watching the governor's press conference in shock. “We all think, ‘Finally, thank God, the deaths are all starting to go up … He’s going to take this seriously,’” he recalled. “And he announces some ridiculous non-measure.”

“We should have a stay-at-home order for at least 30 days, and that should have been re-initiated for all of June,” Heinz added. “We’re halfway through July.”

Ducey has also refused to issue a statewide mask mandate, despite the urging of more than 900 medical providers and five mayors, and only recently allowed cities to issue their own such ordinances. Earlier this month, photos of the governor going maskless to a June 6 graduation party sparked an uproar in the medical community. “That’s the guy in charge, so you know we’re in trouble,” Heinz said.

The Ducey spokesperson noted that the photo was originally claimed to have been taken a month later than it actually was, and called it a “smear-tactic meant to deceive and mislead.”

Meanwhile, hospitals in the state appear to be gearing up for a long fight. The Arizona Department of Health Services recently announced a partnership with Vizient, Inc. to bring in nearly 600 critical care nurses, in addition to those the National Disaster Medical System sent last month. Banner Health, the largest health-care system in the state, also posted an ad this month looking for out-of-state doctors, saying Arizona was “running low on ICU and hospitalist trained physicians.”

In a statement to The Daily Beast, a spokesperson said Banner Health had brought in nearly 750 travel nurses and other specialists over the course of the pandemic and were expecting 200 to 400 more to come soon. The spokesperson said they had also “upskilled” more than 700 team members, meaning they had trained providers from another area of the hospital to work in respiratory units.

Andrew Carroll, a family medicine doctor in Chandler, is one of those “upskilled” providers. Banner asked him months ago to get his emergency medicine privileges in case of a surge, he said, and officially called him in a few weeks ago. His first stint in the emergency room will consist of three straight shifts next weekend.

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Andrew Carroll, a family medicine doctor in Chandler, AZ
The American Academy of Family Physicians


Carroll said he was happy to help out, especially after hearing from so many emergency medicine colleagues who were already burned out. But he was also frustrated that it had come to this point.

“I'm angry that people still refuse to wear masks,” he said. “I'm angry that our government hasn’t made more mandatory public health policies.”

If the government had enacted those policies, he added, “I would not have to be dragged into the hospital to work three straight 12-hour shifts through the weekend, and come home and jump in the swimming pool before I see my family so they don’t get sick.”

“I'm willing, I’m ready, but I’m angry,” he said.
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Re: U.S. government gave $3.7 million grant to Wuhan lab at

Postby admin » Sat Jul 25, 2020 10:06 am

Prof. Francis Boyle Update: Covid-19 Bioweapon Is A Crime Against Humanity Interview
by Jason Liosatos, Outside The Box
Apr 29, 2020

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Re: U.S. government gave $3.7 million grant to Wuhan lab at

Postby admin » Sun Jul 26, 2020 8:43 pm

Part 1 of 3

A Proposed Origin for SARS-CoV-2 and the COVID-19 Pandemic [W/Comments]
by Jonathan Latham, PhD and Allison Wilson, PhD
Independent Science News for Food and Agriculture
July 15, 2020

Our supposition as to why there was a time lag between sample collection (in 2012/2013) and the COVID-19 outbreak is that the researchers were awaiting BSL-4 lab construction and certification, which was underway in 2013 but delayed until 2018.

We propose that, when frozen samples derived from the miners were eventually opened in the Wuhan lab they were already highly adapted to humans to an extent possibly not anticipated by the researchers. One small mistake or mechanical breakdown could have led directly to the first human infection in late 2019.

Thus, one of the miners, most likely patient 3, or patient 4 (whose thymus was removed), was effectively patient zero of the COVID-19 epidemic. In this scenario, COVID-19 is not an engineered virus; but, equally, if it had not been taken to Wuhan and no further molecular research had been performed or planned for it then the virus would have died out from natural causes, rather than escaped to initiate the COVID-19 pandemic.


-- A Proposed Origin for SARS-CoV-2 and the COVID-19 Pandemic, by Jonathan Latham, PhD and Allison Wilson, PhD


In all the discussions of the origin of the COVID-19 pandemic, enormous scientific attention has been paid to the molecular character of the SARS-CoV-2 virus, including its novel genome sequence in comparison with its near relatives. In stark contrast, virtually no attention has been paid to the physical provenance of those nearest genetic relatives, its presumptive ancestors, which are two viral sequences named BtCoV/4991 and RaTG13.

This neglect is surprising because their provenance is more than interesting. BtCoV/4991 and RaTG13 were collected from a mineshaft in Yunnan province, China, in 2012/2013 by researchers from the lab of Zheng-li Shi at the Wuhan Institute of Virology (WIV). Very shortly before, in the spring of 2012, six miners working in the mine had contracted a mysterious illness and three of them had died (Wu et al., 2014). The specifics of this mystery disease have been virtually forgotten; however, they are described in a Chinese Master’s thesis written in 2013 by a doctor who supervised their treatment.


We arranged to have this Master’s thesis translated into English. The evidence it contains has led us to reconsider everything we thought we knew about the origins of the COVID-19 pandemic. It has also led us to theorise a plausible route by which an apparently isolated disease outbreak in a mine in 2012 led to a global pandemic in 2019.

The origin of SARS-CoV-2 that we propose below is based on the case histories of these miners and their hospital treatment. This simple theory accounts for all the key features of the novel SARS-CoV-2 virus, including ones that have puzzled virologists since the outbreak began.

The theory can account for the origin of the polybasic furin cleavage site, which is a region of the viral spike protein that makes it susceptible to cleavage by the host enzyme furin and which greatly enhances viral spread in the body. This furin site is novel to SARS-CoV-2 compared to its near relatives (Coutard, et al., 2020). The theory also explains the exceptional affinity of the virus spike protein for human receptors, which has also surprised virologists (Letko et al., 2020; Piplani et al, 2020; Wrapp et al., 2020; Walls et al., 2020). The theory further explains why the virus has barely evolved since the pandemic began, which is also a deeply puzzling aspect of a virus supposedly new to humans (Zhan et al., 2020; van Dorp et al., 2020; Chaw et al., 2020). Lastly, the theory neatly explains why SARS-CoV-2 targets the lungs, which is unusual for a coronavirus (Huang et al., 2020).


We do not propose a specifically genetically engineered or biowarfare origin for the virus but the theory does propose an essential causative role in the pandemic for scientific research carried out by the laboratory of Zheng-li Shi at the WIV; thus also explaining Wuhan as the location of the epicentre.

Why has the provenance of RaTG13 and BtCoV/4991 been ignored?

The apparent origin of the COVID-19 pandemic is the city of Wuhan in Hubei province, China. Wuhan is also home to the world’s leading research centre for bat coronaviruses. There are two virology labs in the city, both have either collected bat coronaviruses or researched them in the recent past. The Shi lab, which collected BtCoV/4991 and RaTG13, recently received grants to evaluate by experiment the potential for pandemic pathogenicity of the novel bat coronaviruses they collected from the wild.

To add to these suggestive data points, there is a long history of accidents, disease outbreaks, and even pandemics resulting from lab accidents with viruses (Furmanski, 2014; Weiss et al., 2015).

This paper presents an historical review of outbreaks of PPPs [Potentially Pandemic Pathogens] or similarly transmissible pathogens that occurred from presumably well-funded and supervised nationally supported laboratories. It should be emphasized that these examples are only the “tip of the iceberg” because they represent laboratory accidents that have actually caused illness outside of the laboratory in the general public environment. The list of laboratory workers who have contracted potentially contagious infections in microbiology labs but did not start community outbreaks is much, much longer. The examples here are not “near misses;” these escapes caused real-world outbreaks.

-- Laboratory Escapes and “Self-fulfilling prophecy” Epidemics, by Martin Furmanski MD, Scientist’s Working Group on Chemical and Biologic Weapons, Center for Arms Control and Nonproliferation, February 17, 2014


For these and other reasons, summarised in our article The Case is Building that COVID-19 Had a Lab Origin, we (a virologist and a geneticist) and others have concluded that a lab outbreak is a credible thesis. Certainly, a lab origin has at least as much circumstantial evidence to support it as does any natural zoonotic origin theory (Piplani et al., 2020; Segreto and Deigin, 2020; Zhan et al., 2020).

Executive Summary

Biological threats—natural, intentional, or accidental—in any country can pose risks to global health, international security, and the worldwide economy. Because infectious diseases know no borders, all countries must prioritize and exercise the capabilities required to prevent, detect, and rapidly respond to public health emergencies. Every country also must be transparent about its capabilities to assure neighbors it can stop an outbreak from becoming an international catastrophe. In turn, global leaders and international organizations bear a collective responsibility for developing and maintaining robust global capability to counter infectious disease threats. This capability includes ensuring that financing is available to fill gaps in epidemic and pandemic preparedness. These steps will save lives and achieve a safer and more secure world.

The Global Health Security (GHS) Index is the first comprehensive assessment and benchmarking of health security and related capabilities across the 195 countries that make up the States Parties1 to the International Health Regulations (IHR [2005]).2 The GHS Index is a project of the Nuclear Threat Initiative (NTI) and the Johns Hopkins Center for Health Security (JHU) and was developed with The Economist Intelligence Unit (EIU). These organizations believe that, over time, the GHS Index will spur measurable changes in national health security and improve international capability to address one of the world’s most omnipresent risks: infectious disease outbreaks that can lead to international epidemics and pandemics.

The GHS Index is intended to be a key resource in the face of increasing risks of high-consequence3 and globally catastrophic4 biological events and in light of major gaps in international financing for preparedness. These risks are magnified by a rapidly changing and interconnected world; increasing political instability; urbanization; climate change; and rapid technology advances that make it easier, cheaper, and faster to create and engineer pathogens.


Developed with the guidance of an international expert advisory panel, the GHS Index data are drawn from publicly available data sources from individual countries and international organizations, as well as an array of additional sources including published governmental information, data from the World Health Organization (WHO), the World Organisation for Animal Health (OIE), the Food and Agriculture Organization of the United Nations (FAO), the World Bank, country legislation and regulations, and academic resources and publications. Unique in the field, the GHS Index provides a comprehensive assessment of countries’ health security and considers the broader context for biological risks within each country, including a country’s geopolitical considerations and health system and whether it has tested its capacities to contain outbreaks.

Knowing the risks, however, is not enough. Political will is needed to protect people from the consequences of epidemics, to take action to save lives, and to build a safer and more secure world.

WHY IS THE GHS INDEX NEEDED?

It is likely that the world will continue to face outbreaks that most countries are ill positioned to combat. In addition to climate change and urbanization, international mass displacement and migration—now happening in nearly every corner of the world—create ideal conditions for the emergence and spread of pathogens. Countries also face an increased potential threat of accidental or deliberate release of a deadly engineered pathogen, which could cause even greater harm than a naturally occurring pandemic. The same scientific advances that help fight epidemic disease also have allowed pathogens to be engineered or recreated in laboratories. Meanwhile, disparities in capacity and inattention to biological threats among some leaders have exacerbated preparedness gaps. The GHS Index seeks to illuminate those gaps to increase both political will and financing to fill them at the national and international levels. Unfortunately, political will for accelerating health security is caught in a perpetual cycle of panic and neglect. Over the past two decades, decision makers have only sporadically focused on health security, despite concerns stemming from the 2001 anthrax attacks, the emergence of the Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome coronaviruses, and the looming threat of a pandemic caused by a novel strain of influenza.

In September 2014, the United Nations (UN) Security Council met in crisis over the growing Ebola epidemic in West Africa. Massive global assistance was needed to stop the outbreak because of insufficient national capacities in Guinea, Liberia, and Sierra Leone to quickly detect and respond to the epidemic.

As a result, the West Africa Ebola epidemic killed at least 10,000 people and infected more than 28,000.5 The three affected countries lost $2.8 billion in combined GDP, and a massive global response totaled billions of dollars before the outbreak was contained. The crisis awakened the world to the reality that pathogens can emerge unexpectedly, and when outbreaks occur in countries that are unprepared, they can spill beyond borders, threatening the peace, health, and prosperity of all countries.
However, despite newly available vaccines and therapies, response to the Ebola outbreak that began in 2018 in eastern Democratic Republic of Congo has been hampered by violence and instability, community resistance to outbreak mitigation measures, hospital transmission, delays in detection and isolation, and lack of funding and resources.

Delays in the global response to Ebola in 2014 led to a restructuring of the WHO and prompted calls for measurement and transparent reporting of countries’ public health capacities, including the launch of the voluntary WHO IHR Joint External Evaluations (JEEs). Since then, health, policy, and security leaders have developed numerous high-level reviews and recommended ways to identify, finance, and fill major preparedness gaps. These recommendations are relevant for epidemic threats, such as Ebola, and high-consequence pandemic threats, such as a fast-spreading respiratory disease agent that could have a geographic scope, severity, or societal impact and could overwhelm national or international capacity to manage it.6 Some of those recommendations have been implemented, but many have been shelved owing in part to lack of financing. Nearly all recommendations pointed to a need to better understand and measure—on a transparent, global, and recurring basis—the state of international capability for preventing, detecting, and rapidly responding to epidemic and pandemic threats.

The GHS Index is designed to meet this need.

DEVELOPING THE GHS INDEX

The NTI, JHU, and EIU project team—with generous grants from the Open Philanthropy Project, the Bill & Melinda Gates Foundation, and the Robertson Foundation—worked with an international advisory panel of 21 experts from 13 countries to create a detailed and comprehensive framework of 140 questions, organized across 6 categories, 34 indicators, and 85 subindicators to assess a country’s capability to prevent and mitigate epidemics and pandemics.

The GHS Index relies entirely on open-source information: data that a country has published on its own or has reported to or been reported by an international entity. The GHS Index was created in this way with a firm belief that all countries are safer and more secure when their populations are able to access information about their country’s existing capacities and plans and when countries understand each other’s gaps in epidemic and pandemic preparedness so they can take concrete steps to finance and fill them. The indicators and questions that compose the GHS Index framework also prioritize analysis of health security capacity in the context of a country’s broader national health system and other national risk factors.

The 140 GHS Index questions are organized across six categories:

1. PREVENTION: Prevention of the emergence or release of pathogens

2. DETECTION AND REPORTING: Early detection and reporting for epidemics of potential international concern

3. RAPID RESPONSE: Rapid response to and mitigation of the spread of an epidemic

4. HEALTH SYSTEM: Sufficient and robust health system to treat the sick and protect health workers

5. COMPLIANCE WITH INTERNATIONAL NORMS: Commitments to improving national capacity, financing plans to address gaps, and adhering to global norms

6. RISK ENVIRONMENT: Overall risk environment and country vulnerability to biological threats

Among its 140 questions, the GHS Index prioritizes not only countries’ capacities, but also the existence of functional, tested, proven capabilities for stopping outbreaks at the source. Several questions in the GHS Index are designed to determine not only whether a capacity exists, but also whether that capacity is regularly—for example, annually—tested and shown to be functional in exercises or real-world events.

The GHS Index also includes indicators of nations’ capacities and capabilities to reduce Global Catastrophic Biological Risks (GCBRs), which are biological risks of unprecedented scale that could cause severe damage to human civilization at a global level, potentially undermining civilization’s long-term potential.7 These are events that could wipe out gains in sustainable development and global health because of their potential to cause national and regional instability, global economic consequences, and widespread morbidity and mortality.

FINDINGS AND RECOMMENDATIONS

This report summarizes the results of the first GHS Index, including overall findings about the state of national health security capacity across each of the six GHS Index categories, as well as additional findings specific to functional areas of epidemic and pandemic preparedness. The full report also offers 33 recommendations to address gaps identified by the GHS Index. All the findings and recommendations are summarized on pages 12–15 and described in detail throughout the full report, which begins on page 31.

Whereas every country has a responsibility to understand, track, improve, and sustain national health security, new and increased global biological risks may require approaches that are beyond the control of individual governments and will necessitate international action. Therefore, the recommendations contained in this report are made with the understanding that health security is a collective responsibility, and a robust international health security architecture is required to support countries at increased risk. As a result, in addition to the many recommendations intended for national leaders, the GHS Index also includes recommendations aimed at decision makers within the UN system, international organizations, donor governments, philanthropies, and the private sector. These are especially important in the case of fast-spreading, deliberately caused, or otherwise unusual outbreaks that could rapidly overwhelm the capability of national governments and international responders.

OVERALL FINDING: National health security is fundamentally weak around the world. No country is fully prepared for epidemics or pandemics, and every country has important gaps to address.

The GHS Index analysis finds no country is fully prepared for epidemics or pandemics. Collectively, international preparedness is weak. Many countries do not show evidence of the health security capacities and capabilities that are needed to prevent, detect, and respond to significant infectious disease outbreaks. The average overall GHS Index score among all 195 countries assessed is 40.2 of a possible score of 100. Among the 60 high-income countries, the average GHS Index score is 51.9. In addition, 116 high- and middle-income countries do not score above 50. Overall, the GHS Index finds severe weaknesses in country abilities to prevent, detect, and respond to health emergencies; severe gaps in health systems; vulnerabilities to political, socioeconomic, and environmental risks that can confound outbreak preparedness and response; and a lack of adherence to international norms.

Specific scores for the GHS Index categories are as follows:

PREVENTION: Fewer than 7% of countries score in the highest tier8 for the ability to prevent the emergence or release of pathogens.

DETECTION AND REPORTING: Only 19% of countries receive top marks for detection and reporting.

RAPID RESPONSE: Fewer than 5% of countries scored in the highest tier for their ability to rapidly respond to and mitigate the spread of an epidemic.

HEALTH SYSTEM: The average score for health system indicators is 26.4 of 100, making it the lowest-scoring category.

COMPLIANCE WITH INTERNATIONAL NORMS: Less than half of countries have submitted Confidence-Building Measures under the Biological Weapons Convention (BWC) in the past three years, an indication of their ability to adhere to important international norms and commitments related to biological threats.

RISK ENVIRONMENT: Only 23% of countries score in the top tier for indicators related to their political system and government effectiveness.

_______________

Notes:

1. As of April 16, 2013, there are 196 States Parties to the World Health Organization (WHO) 2005 International Health Regulations (IHR), including the Holy See. The Holy See is a sovereign juridical entity under international law, but it was not included in the country-specific research for this Index in light of the Holy See’s lack of an independent health system. This report will refer to the assessed “States Parties” as “195 countries.”

2. The WHO IHR (2005) is the foundational international standards for health. The IHR (2005) is a binding legal instrument to address cross-border public health risks. The goal of the IHR (2005) is to prevent, protect, control, and respond without disrupting international trade and traffic. The IHR (2005) provided the guiding regulations behind many of the indicators included in the GHS Index.

3. High-consequence biological events are defined here as infectious disease outbreaks that could overwhelm national or international capacity to manage them. For example, although international health security has improved following the 2014–2016 Ebola epidemic in West Africa, countries and international responders are not prepared to quell outbreaks that occur in violent or insecure settings; deliberate biological events that require close coordination and investigative links between security, health, and humanitarian actors; and fast-moving respiratory diseases with high mortality that could spread rapidly to become global pandemics.

4. Global Catastrophic Biological Risks are biological risks of unprecedented scale that could cause severe damage to human civilization at a global level, potentially undermining its long-term potential. See Nick Alexopoulos, “Center for Health Security Publishes First Working Definition of Global Catastrophic Biological Risks,” Johns Hopkins Center for Health Security, July 27, 2017, http://www.centerforhealthsecurity.org/ ... ition.html.

5. Centers for Disease Control and Prevention, “2014–2016 Ebola Outbreak in West Africa,” http://www.cdc.gov/vhf/ebola/history/20 ... index.html.

6 United Nations General Assembly, “Protecting humanity from future health crises: Report of the High-level Panel on the Global Response to Health Crises,” https://www.un.org/ga/search/view_doc.a ... l=A/70/723.

7. Monica Schoch-Spana et al.,“Global Catastrophic Biological Risks: Toward a Working Definition,” Health Security 15, no. 4 (2017): 323–28, http://www.liebertpub.com/doi/full/10.1089/hs.2017.0038.

8 The GHS Index scoring system includes three tiers. Countries that score between 0 and 33.3 are in the bottom tier (also called “low scores”), countries that score between 33.4 and 66.6 are in the middle tier (also called “moderate scores”), and countries that score between 66.7 and 100 are in the upper or “top” tier (also called “high scores”)

-- 2019 Global Health Security Index: Building Collective Action and Accountability, by Nuclear Threat Initiative, Center for Health Security, Johns Hopkins Bloomberg School of Public Health, and The Economist Intelligence Unit


The media, normally so enamoured of controversy, has largely declined even to debate the possibility of a laboratory escape. Many news sites have simply labelled it a conspiracy theory.

For decades, Dr. Daniel R. Lucey, an infectious disease specialist at Georgetown University, has crisscrossed the globe to study epidemics and their origins. His attention now is on the Covid-19 pandemic, which first came to public notice late last year in Wuhan, China. Its exact beginnings are sufficiently clouded that the World Health Organization has begun a wide inquiry into its roots. The advance team is to leave for China this weekend, and Dr. Lucey has publicly encouraged the health agency to address what he considers eight top questions....

The sixth and seventh questions go to whether the deadly pathogen leapt to humans from a laboratory. Although some intelligence analysts and scientists have entertained that scenario, no direct evidence has come to light suggesting that the coronavirus escaped from one of Wuhan’s labs.

Even so, given the wet market’s downgrading in the investigation, “It is important to address questions about any potential laboratory source of the virus, whether in Wuhan or elsewhere,” Dr. Lucey wrote in his blog post.

To that end, he urges the W.H.O. investigators to look for any signs of “gain of function” research — the deliberate enhancement of pathogens to make them more dangerous. The technique is highly contentious. Critics question its merits and warn that it could lead to catastrophic lab leaks. Proponents see it as a legitimate way to learn how viruses and other infectious organisms might evolve to infect and kill people, and thus help in devising new protections and precautions.

Debate over its wisdom erupted in 2011 after researchers announced success in making the highly lethal H5N1 strain of avian flu easily transmissible through the air between ferrets, at least in the laboratory.


Prompted by controversy over dangerous research and recent laboratory accidents, the White House announced Friday that it would temporarily halt all new funding for experiments that seek to study certain infectious agents by making them more dangerous.

It also encouraged scientists involved in such research on the influenza, SARS and MERS viruses to voluntarily pause their work while its risks were reassessed.

Opponents of this type of research, called gain of function — for example, attempts to create a more contagious version of the lethal H5N1 avian influenza to learn which mutations made it that way — were elated.

“Brilliant!” said Peter Hale, the executive director of the Foundation for Vaccine Research, which opposes such experiments. “The government has finally seen the light. This is what we have all been waiting for and campaigning for. I shall sleep better tonight.”

The announcement, which was made by the White House Office of Science and Technology Policy and the Department of Health and Human Services, did not say how long the moratorium would last. It said a “deliberative process to assess the potential risks and benefits” would begin this month and stretch at least into next year.

The move appeared to be a sudden change of heart by the Obama administration, which last month issued regulations calling for more stringent federal oversight of such research and requiring scientists and universities to disclose that their work might be risky, rather than expecting federal agencies to notice.

Critics at the time dismissed those rules as too weak.

The moratorium is only on research on influenza virus and the coronaviruses that cause SARS and MERS. It made no mention of Ebola or any related filovirus. Ebola is already extremely lethal, but it is not easily transmissible.

No scientist has publicly announced an attempt to make Ebola as easy to transmit with a sneeze as flu is. Given the current panic around Ebola, and congressional anger at federal health agencies, it is unlikely that federal funding for such a project would be given out.

The debate over the wisdom of “gain of function” research erupted in 2011 when the labs of Ron Fouchier of Erasmus University in the Netherlands, and Yoshihiro Kawaoka of the University of Wisconsin-Madison, separately announced that they had succeeded in making the lethal H5N1 avian flu easily transmissible between ferrets, which are a model for human susceptibility to flu.

The debate heated up further this year when the Centers for Disease Control and Prevention admitted it had suffered laboratory accidents that exposed dozens of workers to anthrax and shipped deadly avian flu virus to another federal lab that had asked for a more benign flu strain. Also this year, vials of smallpox that had been forgotten for 50 years were found in a lab at the National Institutes of Health.

The White House said the moratorium decision had been made “following recent biosafety incidents at federal research facilities.”


Dr. Kawaoka said he would not start any new gain-of-function experiments and would consult with the N.I.H. about which ones he had underway that met their criteria for the moratorium.

Many scientists were furious that such work had been permitted and even supported with American tax dollars. But others argued that it was necessary to learn which genetic mutations make viruses more dangerous. If those mutations began appearing naturally as the viruses circulated in animals and people, warnings could be issued and vaccines designed, they said.

Some scientists argued that the two scientists should not be permitted to publish all the details of their experiments, for fear that terrorists or unscrupulous scientists would duplicate them and start a fatal pandemic.

Others, like Richard H. Ebright, a molecular biologist and bioweapons expert at Rutgers University, argued that the long history of accidental releases of infectious agents from research labs made such work extremely risky and unwise to perform in the first place.


Dr. Ebright called Friday’s announcement “an important, albeit overdue, step.”

Michael T. Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, called the moratorium “a wise move — I congratulate the U.S. government on taking this step.”

The new policy had to be announced now, he explained, because the National Science Advisory Board for Biosecurity is to meet later this month. It will have 11 new members, and gain of function research is a principal agenda item.

Dr. Osterholm was one of 11 previous members who were removed from the board in the middle of the controversy.

All, like him, had been on it many years past their original five-year appointments and were due to be replaced, but had routinely been asked to stay, he said.

In April, he was the author of a letter to the National Institutes of Health complaining about government pressure on the advisory board. The institutes gave grants to support gain of function work.

The explanation given was that they had outlasted their tenures, but Dr. Osterholm said that “in the same week as the anthrax accident at the C.D.C., we all got an email on a Sunday night from a junior staffer telling us we were out.”

He called that a public relations failure: “P.R. zero point zero.”

-- White House to Cut Funding for Risky Biological Study, by Donald G. McNeil Jr., NYT, Oct. 17, 2014


In his blog, Dr. Lucey asks “what, if any,” gain-of-function studies were done on coronaviruses in Wuhan, elsewhere in China, or in collaboration with foreign laboratories.

“If done well scientifically, then this investigation should allay persistent concerns about the origin of this virus,” he wrote. “It could also help set an improved standard for investigating and stopping the awful viruses, and other pathogens, in the decades ahead.”

Finally, Dr. Lucey asks the W.H.O. team to learn more about China’s main influenza research lab, a high-security facility in Harbin, the capital of China’s northernmost province. In May, he notes, a Chinese paper in the journal Science reported that two virus samples from Wuhan were studied there in great detail early this year, including in a variety of animals. It reported that cats and ferrets were highly susceptible to the pathogen; dogs were only mildly susceptible; and pigs, chickens and ducks were not susceptible at all.


-- 8 Questions From a Disease Detective on the Pandemic’s Origins: Dr. Daniel R. Lucey wants answers to pointed questions that bear on how the coronavirus leapt from bats to humans, by William J. Broad, NYT, July 8, 2020


The principal reason for media dismissals of the lab origin possibility is a review paper in Nature Medicine (Andersen et al., 2020). Although by Jun 29, 2020 this review had almost 700 citations it also has major scientific shortcomings. These flaws are worth understanding in their own right but they are also useful background for understanding the implications of the Master’s thesis.

An influential paper was published in Nature Medicine on 17 March 2020. Andersen et al observed that several mutations have occurred in the receptor binding domain of SARS-CoV-2. These, they suggested, therefore sustain an hypothesis of natural evolution (Andersen et al., 2020). We do not agree. We do agree that it is indeed correct that several such mutations are to be seen and in a forthcoming companion article to this one, about three other viruses of interest, we will discuss further Andersen et al's evidence and argumentation in that context. But here we observe only that the contention that it is improbable that Covid-19 emerged through laboratory manipulation of a related SARS-CoV-like coronavirus because the ACE2 binding is not ideal is weakened because Andersen et al cite two authorities which actually say the reverse of what they say that they say.

Wan et al are cited by Andersen et al but offer them no support (Wan et al., 2020). Wan et al say, correctly in our view, that computational structural modelling of complex virus-receptor interactions can be used for structural predictions and that such models can potentially be used for Gain-Of-Function modelling. It is well known that models have been developed from data generated in animal model systems such as the palm civet. Wan et al say that the SARS-CoV-2 binding to the ACE2 receptor confirms the accuracy of the structural predictions. Therefore the data and conclusion in Wan et al contradicts Andersen et al's opinion that it is improbable that the virus could have emerged through laboratory manipulation.

There is a similar problem with (Sheahan et al., 2008). This deals with research on a civet strain SZ16 and the infective strain SARS-CoV Urbani. These strains were used to create a chimeric virus icSZ16-S. Sheahan et al go on to explain that by in vitro evolution of the chimeric virus icSZ16-S on human airway epithelial (HAE) cells in the lab, they have been able to produce two new viruses binding to such HAE cells. Therefore this reference supports the very opposite of the Andersen et al hypothesis. We are immediately wary of any paper containing such egregious errors.


-- The Evidence which Suggests that This Is No Naturally Evolved Virus: A Reconstructed Historical Aetiology of the SARS-CoV-2 Spike, by Birger Sørensen, Angus Dalgleish & Andres Susrud


The Nature Paper vs. the Lab-Made Hypothesis

But didn’t that Nature article refute the lab-made hypothesis? No, not really. There is no irrefutable evidence against it in the paper, just a loud “we don’t believe so” based on a shaky foundation. Judge for yourself — here are the authors’ key arguments in support of their conclusions:

While the analyses above suggest that SARS-CoV-2 may bind human ACE2 with high affinity, computational analyses predict that the interaction is not ideal and that the RBD sequence is different from those shown in SARS-CoV to be optimal for receptor binding. Thus, the high-affinity binding of the SARS-CoV-2 spike protein to human ACE2 is most likely the result of natural selection on a human or human-like ACE2 that permits another optimal binding solution to arise. This is strong evidence that SARS-CoV-2 is not the product of purposeful manipulation.


In the original paper, the quoted sentences are just below the diagram showing identical RBMs between CoV2 and pangolin-2019. So I am puzzled as to what “computational analysis” has to do with anything. Obviously, the most likely scenario for the lab-made hypothesis is the transfer of RBM from one strain to another — which virologists have done many times before. Therefore, the author’s chain of arguments does not make sense: “computer says binding is not ideal, thus CoV2 must be the result of natural selection. Ergo, this is strong evidence that CoV2 is not lab-made.” Wait, just because CoV2 differs from some “optimal” virus, doesn’t mean it could not have been created in a lab. Not the lab trying to create “optimal” bioweapons, but a lab creating chimeras of naturally found strains, say, in bats and pangolins.

The authors continue to surprise:


Furthermore, if genetic manipulation had been performed, one of the several reverse-genetic systems available for betacoronaviruses would probably have been used. However, the genetic data irrefutably show that SARS-CoV-2 is not derived from any previously used virus backbone.


Again, the same questionable logic dressed in categorical adjectives: “genetic analysis irrefutably proves that CoV2 was not created on the basis of previously known strains!” Well thanks, Captain Obvious. But why couldn’t potential creators of CoV2 make a cDNA backbone from unpublished strains related to or even derived from RaTG13? Then they could easily insert the pangolin RBM into it, as well as add a furin site (or maybe the cDNA backbone already had one). Virologists have been doing things like this for 20 years, and modern genetic engineering tools make such manipulations accessible even to a grad student.

As for the chances of the furin site arising in cell culture, the authors also express strange ideas:


The acquisition of both the polybasic cleavage site and predicted O-linked glycans also argues against culture-based scenarios. New polybasic cleavage sites have been observed only after prolonged passage of low-pathogenicity avian influenza virus in vitro or in vivo. Furthermore, a hypothetical generation of SARS-CoV-2 by cell culture or animal passage would have required prior isolation of a progenitor virus with very high genetic similarity, which has not been described. Subsequent generation of a polybasic cleavage site would have then required repeated passage in cell culture or animals with ACE2 receptors similar to those of humans, but such work has also not previously been described.


First off, the authors themselves cite previous works where the furin site arose in vitro as viruses were cultured in cells. And second, what do they mean, a strain with high genetic similarity has not been described — what about RaTG13? If it had its RBM replaced by one from the pangolin strain, and then the chimeric strain was cultured in vitro, then the furin site could well have arisen in this matter. Additionally, the new strain could thus acquire other mutations that distinguish CoV2 from RaTG13 and pangolin-2019.

But in terms of the potential lab-based origin of the furin site, I am more inclined to hypothesize a specific insertion — as in the Beijing paper from October 2019 with chicken coronavirus. After that, the synthetic strain could have acquired new mutations by subsequent culturing in vitro or in vivo — like the MA15 murine strain in 2007, for example. Or maybe even using the same mouse model with humanized lung tissues and immune system that was created at UNC by Baric’s and other groups in 2018, in which they reported testing several viruses including MERS:


The human innate and adaptive immune system of BLT-L mice

We generated an in vivo model with human lung implants and an autologous human immune system by constructing BLT mice with autologous human lung implants (BLT-L humanized mice).


Finally, even if CoV2 is the product of selection rather than intelligent design, that does not rule out a lab leak either — selection can happen in the lab just as well, both natural and artificial kinds. Different strains can recombine in research animals or in vitro by design or by chance.

-- Lab-Made? SARS-CoV-2 Genealogy Through the Lens of Gain-of-Function Research, by Yuri Deigin


Andersen et al., a critique

The question of the origin of the COVID-19 pandemic is, in outline, simple. There are two incontrovertible facts. One, the disease is caused by a human viral pathogen, SARS-CoV-2, first identified in Wuhan in December 2019 and whose RNA genome sequence is known. Second, all of its nearest known relatives come from bats. Beyond any reasonable doubt SARS-CoV-2 evolved from an ancestral bat virus. The task the Nature Medicine authors set for themselves was to establish the relative merits of each of the various possible routes (lab vs natural) by which a bat coronavirus might have jumped to humans and in the same process have acquired an unusual furin site and a spike protein having very high affinity for the human ACE2 receptor.

When Andersen et al. outline a natural zoonotic pathway they speculate extensively about how the leap might have occurred. In particular they elaborate on a proposed residence in intermediate animals, likely pangolins. For example, “The presence in pangolins of an RBD [Receptor Binding Domain] very similar to that of SARS-CoV-2 means that we can infer that this was probably in the virus that jumped to humans. This leaves the insertion of [a] polybasic cleavage site to occur during human-to-human transmission.” This viral evolution occurred in “Malayan pangolins illegally imported into Guangdong province”. Even with these speculations there are major gaps in this theory. For example, why is the virus so well adapted to humans? Why Wuhan, which is 1,000 Km from Guangdong? (See map).

Image
china province guide

The authors provide no such speculations in favour of the lab accident thesis, only speculation against it:

“Finally, the generation of the predicted O-linked glycans is also unlikely to have occurred due to cell-culture passage, as such features suggest the involvement of an immune system.” (italics added).

[Passaging is the deliberate placing of live viruses into cells or organisms to which they are NOT adapted for the purpose of making them adapted, i.e. speeding up their evolution.]

It is also noteworthy that the Andersen authors set a higher hurdle for the lab thesis than the zoonotic thesis. In their account, the lab thesis is required to explain all of the evolution of SARS-CoV-2 from its presumed bat viral ancestor, whereas under their telling of the zoonotic thesis the key step of the addition of the furin site is allowed to happen in humans and is thus effectively unexplained.

A further imbalance is that key information needed to judge the merits of a lab origin theory is missing from their account. As we detailed in our previous article, in their search for SARS-like viruses with zoonotic spillover potential, researchers at the WIV have passaged live bat viruses in monkey and human cells (Wang et al., 2019). They have also performed many recombinant experiments with diverse bat coronaviruses (Ge et al., 2013; Menachery et al., 2015; Hu et al., 2017). Such experiments have generated international concern over the possible creation of potential pandemic viruses (Lipsitch, 2018). As we showed too, the Shi lab had also won a grant to extend that work to whole live animals. They planned “virus infection experiments across a range of cell cultures from different species and humanized mice” with recombinant bat coronaviruses. Yet Andersen et al did not discuss this research at all, except to say:


“Basic research involving passage of bat SARS-CoV-like coronaviruses in cell culture and/or animal models has been ongoing for many years in biosafety level 2 laboratories across the world”

This statement is fundamentally misleading about the kind of research performed at the Shi lab.

A further important oversight by the Andersen authors concerns the history of lab outbreaks of viral pathogens. They write: “there are documented instances of laboratory escapes of SARS-CoV”. This is a rather matter-of-fact allusion to the fact that since 2003 there have been six documented outbreaks of SARS from labs, not all in China, with some leading to fatalities (Furmanski, 2014).

Andersen et al might have also have noted that two major human pandemics are widely accepted to have been caused by lab outbreaks of viral pathogens, H1N1 in 1977 and Venezuelan Equine Encephalitis (summarised in Furmanski, 2014). Andersen could even have noted that literally hundreds of lab accidents with viruses have resulted in near-misses or very localised outbreaks (summarised by Lynn Klotz and Sam Husseini and also Weiss et al., 2015).


Also unmentioned were instances where a lab outbreak of an experimental or engineered virus has been plausibly theorised but remains uninvestigated. For example, the most coherent explanation for the H1N1 variant ‘swine flu’ pandemic of 2009/10 that resulted in a death toll estimated by some as high as 200,000 (Duggal et al., 2016; Simonsen et al. 2013), is that a vaccine was improperly inactivated by its maker (Gibbs et al., 2009). If so, H1N1 emerged from a lab not once but twice.

Given that human and livestock viral outbreaks have frequently come from laboratories and that many scientists have warned of probable lab escapes (Lipsitch and Galvani, 2014), and that the WIV [Wuhan Institute of Virology] itself has a questionable biosafety record, the Andersen paper is not an even-handed treatment of the possible origins of the COVID-19 virus.

This chapter makes the case against performing exceptionally dangerous gain-of-function experiments that are designed to create potentially pandemic and novel strains of influenza, for example, by enhancing the airborne transmissibility in mammals of highly virulent avian influenza strains. This is a question of intense debate over the last 5 years, though the history of such experiments goes back at least to the synthesis of viable influenza A H1N1 (1918) based on material preserved from the 1918 pandemic. This chapter makes the case that experiments to create potential pandemic pathogens (PPPs) are nearly unique in that they present biosafety risks that extend well beyond the experimenter or laboratory performing them; an accidental release could, as the name suggests, lead to global spread of a virulent virus, a biosafety incident on a scale never before seen. In such cases, biosafety considerations should be uppermost in the consideration of alternative approaches to experimental objectives and design, rather than being settled after the fact, as is appropriately done for most research involving pathogens. The extensive recent discussion of the magnitude of risks from such experiments is briefly reviewed. The chapter argues that, while there are indisputably certain questions that can be answered only by gain-of-function experiments in highly pathogenic strains, these questions are narrow and unlikely to meaningfully advance public health goals such as vaccine production and pandemic prediction. Alternative approaches to experimental influenza virology and characterization of existing strains are in general completely safe, higher throughput, more generalizable, and less costly than creation of PPP in the laboratory and can thereby better inform public health. Indeed, virtually every finding of recent PPP experiments that has been cited for its public health value was predated by similar findings using safe methodologies. The chapter concludes that the unique scientific and public health value of PPP experiments is inadequate to justify the unique risks they entail and that researchers would be well-advised to turn their talents to other methodologies that will be safe and more rewarding scientifically.

-- Why Do Exceptionally Dangerous Gain-of-Function Experiments in Influenza?, by Marc Lipsitch


Yet its text expresses some strong opinions: “Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus….It is improbable that SARS-CoV-2 emerged through laboratory manipulation of a related SARS-CoV-like coronavirus…..the genetic data irrefutably show that SARS-CoV-2 is not derived from any previously used backbone….the evidence shows that SARS-CoV2 is not a purposefully manipulated virus….we do not believe that any type of laboratory-based scenario is possible.” (Andersen et al., 2020).

It is hard not to conclude that what their paper mostly shows is that Drs. Andersen, Rambaut, Lipkin, Holmes and Garry much prefer the natural zoonotic transfer thesis. Their rhetoric is forthright but the evidence does not support that confidence.

Indeed, since the publication of Andersen et al., important new evidence has emerged that undermines their zoonotic origin theory. On May 26th the Chinese CDC ruled out the Huanan “wet” market in Wuhan as the source of the outbreak. Additionally, new research on pangolins, the favoured intermediate mammal host, suggests they are not a natural reservoir of coronaviruses (Lee et al., 2020; Chan and Zhan, 2020). Furthermore, SARS-CoV-2 was found not to replicate in bat kidney or lung cells (Rhinolophus sinicus), implying that SARS-CoV-2 is not a recently-adapted spill over Chu et al., 2020).


The Mojiang mine and the Master’s thesis

In our own search to resolve the COVID-19 origin question we chose to focus on the provenance of the coronavirus genome sequences BtCoV/4991 and RaTG13, since these are the most closely related sequences to SARS-CoV-2 (98.7% and 96.2% identical respectively). See FIG 1. (reproduced from P. Zhou et al., 2020).

Image
Similarity of SARS-CoV-2 to RaTG13 (blue line) and other coronaviruses (red, green, pink) (Image from Zhou et al., 2020). The higher the line the more similar the virus.

For comparison, the next closest virus to SARS-CoV-2 is RmYN02 (not shown in Fig 1.) (H. Zhou et al., 2020). RmYN02 has an overall similarity to SARS-CoV-2 of 93.2%, making its evolutionary distance from SARS-CoV-2 almost twice as great.

BtCoV/4991 was first described in 2016. It is a 370 nucleotide virus fragment collected from the Mojiang mine in 2013 by the lab of Zeng-li Shi at the WIV [Wuhan Institute of Virology] (Ge et al., 2016). BtCoV/4991 is 100% identical in sequence to one segment of RaTG13. RaTG13 is a complete viral genome sequence (almost 30,000 nucleotides) that was only published in 2020, after the pandemic began (P. Zhou et al., 2020).

Despite the confusion created by their different names, in a letter obtained by us Zheng-li Shi confirmed to a virology database that BtCoV/4991 and RaTG13 are both from the same bat faecal sample and the same mine. They are thus sequences from the same virus.
In the discussion below we will refer primarily to RaTG13 and specify BtCoV/4991 only as necessary.

These specifics are important because it is these samples and their provenance that we believe are ultimately key to unravelling the mystery of the origins of COVID-19.

The story begins in April 2012 when six workers in that same Mojiang mine fell ill from a mystery illness while removing bat faeces. Three of the six subsequently died.

In a March 2020 interview with Scientific American Zeng-li Shi dismissed the significance of these deaths, claiming the miners died of fungal infections. Indeed, no miners or deaths are mentioned in the paper published by the Shi lab documenting the collection of RaTG13 (Ge et al., 2016).

But Shi’s assessment does not tally with any other contemporaneous accounts of the miners and their illness (Rahalkar and Bahulikar, 2020). As these authors have pointed out, Science magazine wrote up part of the incident in 2014 as A New Killer Virus in China?. Science was citing a different team of virologists who found a paramyxovirus in rats from the mine. These virologists told Science they found “no direct relationship between human infection” and their virus. This expedition was later published as the discovery of a new virus called MojV after Mojiang, the locality of the mine (Wu et al., 2014).

What this episode suggests though is that these researchers were looking for a potentially lethal virus and not a lethal fungus. Also searching the Mojiang mine for a [potentially lethal] virus at around the same time was Canping Huang, the author of a PhD thesis carried out under the supervision of George Gao, the head of the Chinese CDC.

All of this begs the question of why the Shi lab, which has no interest in fungi but a great interest in SARS-like bat coronaviruses, also searched the Mojiang mine for bat viruses on four separate occasions between August 2012 and July 2013, even though the mine is a 1,000 Km from Wuhan (Ge et al., 2016). These collecting trips began while some of the miners were still hospitalised.

Fortunately, a detailed account of the miner’s diagnoses and treatments exists. It is found in a Master’s thesis written in Chinese in May 2013. Its suggestive English title is “The Analysis of 6 Patients with Severe Pneumonia Caused by Unknown viruses“.

The original English version of the abstract implicates a SARS-like coronavirus as the probable causative agent and that the mine “had a lot of bats and bats’ feces”.


The findings of the Master’s thesis

To learn more, especially about the reasonableness of this diagnosis, we arranged to have the whole Master’s thesis translated into English and are here making the translation available. To read it in full see the embedded document below (or download it here).

[x]
Master's Thesis: "The Analysis of Six Patients With Severe Pneumonia Caused By Unknown Viruses"



The six ill miners were admitted to the No. 1. School of Clinical Medicine, Kunming Medical University, in short succession in late April and early May 2012. Kunming is the capital of Yunnan province and 250 Km from Mojiang.

Image
The Syndromes of the six Mojiang Mine patients

Of the descriptions of the miners and their treatments, which include radiographs and numerous CAT scans, several features stand out:

1) From their admission to the hospital their doctors informed the “medical office” of a potential “outburst of disease” i.e. a potential epidemic outbreak. Thus, the miners were treated for infections and not as if they had inhaled noxious gases or other toxins.

2) The symptoms (on admission) of the six miners were: a) dry cough, b) sputum, c) high fevers, especially shortly before death d) difficulty breathing, e) myalgia (sore limbs). Some patients had hiccoughs and headaches. (See Table 1).

3) Clinical work established that patients 1-4 had low blood oxygen “for sure it was ARDS” (Acute Respiratory Distress Syndrome) and immune damage considered indicative of viral infection.
Additionally, a tendency for thrombosis was noted in patients 2 and 4. Symptom severity and mortality were age-related (though from a sample of 6 this must be considered anecdotal).

4) Potential common and rare causes of their symptoms were tested for and mostly eliminated. For patients 3 and 4 these included tests for HIV, Cytomegalovirus, Epstein-Barr Virus (EBV), Japanese encephalitis, haemorrhagic fever, Dengue, Hepatitis B, SARS, and influenza. Of these, only patient 2 tested positive for Hepatitis and EBV.

5) Treatment of the six patients included ventilation (patients 2-4), steroids (all patients), antivirals (all except patient 5), and blood thinners (patients 2 and 4). Antibiotics and antifungal medications were administered to counter what were considered secondary (but significant) co-infections.

6) A small number of remote meetings were held with researchers at other universities. One was with Zhong Nanshan at Sun Yat-Sen University, Guangdong. Zhong is the Chinese hero of the SARS epidemic, a virologist, and arguably the most famous scientist in China.

7) Samples from the miners were later sent to the WIV in Wuhan and to Zhong Nanshan, further confirming that viral disease was strongly suspected. Some miners did test positive for coronavirus (the thesis is unclear on how many).

8) The source of infection was concluded to be Rhinolophus sinicus, a horseshoe bat and the ultimate conclusion of the thesis reads “the unknown virus lead to severe pneumonia could be: The SARS-like-CoV from the Chinese rufous horseshoe bat.” Thus the miners had a coronavirus but it apparently was not SARS itself.
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Part 2 of 3

The significance of the Master’s thesis

These findings of the thesis are significant in several ways.

First, in the light of the current coronavirus pandemic it is evident the miners’ symptoms very closely resemble those of COVID-19 (Huang et al, 2020; Tay et al., 2020; M. Zhou et al., 2020). Anyone presenting with them today would immediately be assumed to have COVID-19. Likewise, many of the treatments given to the miners have become standard for COVID-19 (Tay et al., 2020).

Second, the remote meeting with Zhong Nanshan is significant. It implies that the illnesses of the six miners were of high concern and, second, that a SARS-like coronavirus was considered a likely cause.

Third, the abstract, the conclusions, and the general inferences to be made from the Master’s thesis contradict Zheng-li Shi’s assertion that the miners died from a fungal infection. Fungal infection as a potential primary cause was raised but largely discarded.

Fourth, if a SARS-like coronavirus was the source of their illness the implication is that it could directly infect human cells. This would be unusual for a bat coronavirus (Ge et al., 2013). People do sometimes get ill from bat faeces but the standard explanation is histoplasmosis, a fungal infection and not a virus (McKinsey and McKinsey, 2011; Pan et al., 2013).

Fifth, the sampling by the Shi lab found that bat coronaviruses were unusually abundant in the mine (Ge at al., 2016). Among their findings were two betacoronaviruses, one of which was RaTG13 (then known as BtCoV/4991). In the coronavirus world betacoronaviruses are special in that both SARS and MERS, the most deadly of all coronaviruses, are both betacoronaviruses. Thus they are considered to have special pandemic potential, as the concluding sentence of the Shi lab publication which found RaTG13 implied: “special attention should particularly be paid to these lineages of coronaviruses” (Ge at al., 2016). In fact, the Shi and other labs have for years been predicting that bat betacoronaviruses like RaTG13 would go pandemic; so to find RaTG13 where the miners fell ill was a scenario in perfect alignment with their expectations.

The Mojiang miners passaging proposal

How does the Master’s thesis inform the search for a plausible origin of the pandemic?

In our previous article we briefly discussed how the pandemic might have been caused either by a virus collection accident, or through viral passaging, or through genetic engineering and a subsequent lab escape. The genetic engineering possibility deserves attention and is extensively assessed in an important preprint (Segreto and Deigin, 2020).

The origin of SARS-CoV-2 is still controversial. Comparative genomic analyses have shown that SARSCoV-2 is likely to be chimeric, most of its sequence being very close to the CoV detected from a bat, whereas its receptor binding domain is almost identical to that of CoV obtained from pangolins. The furin cleavage site in the spike protein of SARS-CoV-2 was previously not identified in other SARS-like CoVs and might have conferred the ability to cross species and tissue barriers. Chimeric viruses can be the product of natural recombination or genetic manipulation. The latter could have aimed to identify pangolins as possible intermediate hosts for bat-CoV potentially pathogenic for humans. Theories that consider a possible artificial origin for SARS-CoV-2 are censored as they seem to support conspiracy theories. Researchers have the responsibility to carry out a thorough analysis, beyond any personal research interests, of all possible causes for SARS-CoV-2 emergence for preventing this from happening in the future.

Several months have passed since the outbreak of SARS-CoV-2 in Wuhan, China, and its origin is still controversial. The theory that the Wuhan’s Huanan Seafood Wholesale Market was the first source for animal–human virus transmission has lost credibility. During the first phase of the epidemic in Wuhan, several hospitalized patients with confirmed SARS-CoV-2 infections had no link with the market.1 Unfortunately, the market was quickly closed and sanitized before enough animal samples could have been collected; the few market samples that did get collected exhibit only human-adapted SARS-CoV-2 and no traces of zoonotic predecessor strains.2


-- Is Considering a Genetic-Manipulation Origin for SARS-CoV-2 a Conspiracy Theory That Must Be Censored?, by Rossana Segreto, University of Innsbruck, and Yuri Deigrin, Youthereum Genetics Inc.


We do not definitively rule out these possibilities. Indeed it now seems that the Shi lab at the WIV did not forget about RaTG13 but were sequencing its genome in 2017 and 2018. However, we believe that the Master’s thesis indicates a much simpler explanation.

We suggest, first, that inside the miners RaTG13 (or a very similar virus) evolved into SARS-CoV-2, an unusually pathogenic coronavirus highly adapted to humans. Second, that the Shi lab used medical samples taken from the miners and sent to them by Kunming University Hospital for their research. It was this human-adapted virus, now known as SARS-CoV-2­, that escaped from the WIV in 2019.

We refer to this COVID-19 origin hypothesis as the Mojiang Miners Passage (MMP) hypothesis.

Passaging is a standard virological technique for adapting viruses to new species, tissues, or cell types. It is normally done by deliberately infecting a new host species or a new host cell type with a high dose of virus. This initial viral infection would ordinarily die out because the host’s immune system vanquishes the ill-adapted virus. But, in passaging, before it does die out a sample is extracted and transferred to a new identical tissue, where viral infection restarts. Done iteratively, this technique (called “serial passaging” or just “passaging”) intensively selects for viruses adapted to the new host or cell type (Herfst et al., 2012).

At first glance RaTG13 is unlikely to have evolved into SARS-CoV-2 since RaTG13 is approximately 1,200 nucleotides (3.8%) different from SARS-CoV-2. Although RaTG13 is the most closely related virus to SARS-CoV-2, this sequence difference still represents a considerable gap. In a media statement evolutionary virologist Edward Holmes has suggested this gap represents 20-50 years of evolution and others have suggested similar figures.

We agree that ordinary rates of evolution would not allow RaTG13 to evolve into SARS-CoV-2 but we also believe that conditions inside the lungs of the miners were far from ordinary. Five major factors specific to the hospitalised miners favoured a very high rate of evolution inside them.

i) When viruses infect new species they typically undergo a period of very rapid evolution because the selection pressure on the invading pathogen is high. The phenomenon of rapid evolution in new hosts is well attested among corona- and other viruses
(Makino et al., 1986; Baric et al., 1997; Dudas and Rambaut 2016; Forni et al., 2017).

ii) Judging by their clinical symptoms such as the CT scans, all the miner’s infections were primarily of the lungs. This localisation likely occurred initially because the miners were exerting themselves and therefore inhaling the disturbed bat guano deeply. As miners, they may already have had damaged lung tissues (patient 3 had suspected pneumoconiosis) and/or particulate matter was present that irritated the tissues and may have facilitated initial viral entry.

In contrast, standard coronavirus infections are confined to the throat and upper respiratory tract. They do not normally reach the lungs (Perlman and Netland, 2009). Lungs are far larger tissues by weight (kilos vs grammes) than the upper respiratory tract. There was therefore likely a much larger quantity of virus inside the miners than would be the case in an ordinary coronavirus infection.

Comparing a typical coronavirus respiratory tract infection with the extent of infected lungs in the miners from a purely mathematical point of view indicates the potential scale of this quantitative difference. The human aerodigestive tract is approximately 20cm in length and 5cm in circumference, i.e. approximately 100 cm2 in surface area. The surface area of a human lung ranges from 260,000-680,000 cm2(Hasleton, 1972). The amount of potentially infected tissue in an average lung is therefore approximately 4500-fold greater than that available to a normal coronavirus infection. The amount of virus present in the infected miners, sufficient to hospitalise all of them and kill half of them, was thus proportionately very large.

Evolutionary change is in large part a function of the population size. The lungs of the miners, we suggest, supported a very high viral load leading to proportionately rapid viral evolution.

Furthermore, according to the Master’s thesis, the immune systems of the miners were compromised and remained so even for those discharged. This weakness on the part of the miners may also have encouraged evolution of the virus.

iii) The length of infection experienced by the miners (especially patients 2, 3 and 4) far exceeded that of an ordinary coronavirus infection. From first becoming too sick to work in the mine, patient 2 survived 57 days until he died. Patient 3 survived 120 days after stopping work. Patient 4 survived 117 days and then was discharged as cured. Each had been exposed in the mine for 14 days prior to the onset of severe symptoms; thus each presumably had nascent infections for some time before calling in sick (See Table 2 of the thesis).

In contrast, in ordinary coronavirus infections the viral infection is cleared within about ten to fourteen days after being acquired (Tay et al., 2020). Thus, unlike most sufferers from coronavirus infection, the hospitalised miners had very long-term bouts of disease characterised by a continuous high load of virus. In the cases of patients 3 and 4 their illnesses lasted over 4 months.

iv) Coronaviruses are well known to recombine at very high rates: 10% of all progeny in a cell can be recombinants (Makino et al., 1986; Banner and Lai, 1991; Dudas and Rambaut, 2016). In normal virus evolution the mutation rate and the selection pressure are the main foci of attention. But in the case of a coronavirus adapting to a new host where many mutations distributed all over the genome are required to fully adapt to the new host, the recombination rate is likely to be highly influential in determining the overall speed of adaptation by the virus population (Baric et al., 1997).


Inside the miners a large tissue was simultaneously infected by a population of poorly-adapted viruses, with each therefore under pressure to adapt. Even if the starting population of virus lacked any diversity, many individual viruses would have acquired mutations independently but only recombination would have allowed these mutations to unite in the same genome. To recombine, viruses must be present in the same cell. In such a situation the particularities of lung tissues become potentially important because the existence of airways (bronchial tubes, etc.) allows partially-adapted viruses from independent viral populations to travel to distal parts of the lung (or even the other lung) and encounter other such partially-adapted viruses and populations. This movement around the lungs would likely have resulted in what amounted to a passaging effect without the need for a researcher to infect new tissues. Indeed, in the Master’s thesis the observation is several times made that areas of the lungs of a specific patient would appear to heal even while other parts of the lungs would become infected.

v) There were also a number of unusual things about the bat coronaviruses in the mine. They were abnormally abundant but also there were many different kinds, often causing co-infections of the bats (Ge et al., 2016). Viral co-infections are often more infectious or more pathogenic (Latham and Wilson, 2007).


As the WIV researchers remarked about the bats in the mine:

“we observed a high rate of co-infection with two coronavirus species and interspecies infection with the same coronavirus species within or across bat families. These phenomena may be owing to the diversity and high density of bat populations in the same cave, facilitating coronavirus intra- and interspecies transmissions, which may result in recombination and acceleration of coronavirus evolution.” (Ge et al., 2016).


The diversity of coronaviruses in the mine suggests that the miners were similarly exposed and that their illness may potentially have begun as co-infections.

Combining these observations, we propose that the miners’ lungs offered an unprecedented opportunity for accelerated evolution of a highly bat-adapted coronavirus into a highly human-adapted coronavirus and that decades of ordinary coronavirus evolution could easily have been condensed into months. However, we acknowledge that these conditions were unique.
They and their scale have no exact scientific precedent we can refer to and they would be hard to replicate in a lab; thus it is important to emphasize that our proposal is fully consistent with the underlying principles of viral evolution as understood today.

In support of the MMP theory we also know something about the samples taken from the miners. According to the Master’s thesis, samples were taken from patients for “scientific research” and blood samples (at least) were sent to the WIV.

“In the later stage we worked with Dr. Zhong Nan Shan and did some sampling. The patient* tested positive for serum IgM by the WuHan Institute of Virology. It suggested the existence of virus infection” (p62 in the section “Comprehensive Analysis”.)

(*The original does not specify the number of patients tested.)

The Master’s thesis also states its regret that no samples for research were taken from patients 1 and 2, implying that samples were taken from all the others.

We further know that, on June 27th, 2012, the doctors performed an unexplained thymectomy on patient 4. The thymus is an immune organ that can potentially be removed without greatly harming the patient and it could have contained large quantities of virus. Beyond this the Master’s thesis is unfortunately unclear on the specifics of what sampling was done, for what purpose, and where each particular sample went.

Given the interests of the Shi lab in zoonotic origins of human disease, once such a sample was sent to them, it would have been obvious and straightforward for them to investigate how a virus from bats had managed to infect these miners. Any viruses recoverable from the miners would likely have been viewed by them as a unique natural experiment in human passaging offering unprecedented and otherwise-impossible-to-obtain insights into how bat coronaviruses can adapt to humans.

The logical course of such research would be to sequence viral RNA extracted directly from unfrozen tissue or blood samples and/or to generate live infectious clones for which it would be useful (if not imperative) to amplify the virus by placing it in human cell culture. Either technique could have led to accidental infection of a lab researcher.


Our supposition as to why there was a time lag between sample collection (in 2012/2013) and the COVID-19 outbreak is that the researchers were awaiting BSL-4 lab construction and certification, which was underway in 2013 but delayed until 2018.

We propose that, when frozen samples derived from the miners were eventually opened in the Wuhan lab they were already highly adapted to humans to an extent possibly not anticipated by the researchers. One small mistake or mechanical breakdown could have led directly to the first human infection in late 2019.

Thus, one of the miners, most likely patient 3, or patient 4 (whose thymus was removed), was effectively patient zero of the COVID-19 epidemic.
In this scenario, COVID-19 is not an engineered virus; but, equally, if it had not been taken to Wuhan and no further molecular research had been performed or planned for it then the virus would have died out from natural causes, rather than escaped to initiate the COVID-19 pandemic.

Evidence in favour of the MMP proposal

Our proposal is consistent with all the principal undisputed facts concerning SARS-CoV-2 and its origin. The MMP proposal has the additional benefit of reconciling many observations concerning SARS-CoV-2 that have proven difficult to reconcile with any natural zoonotic hypothesis.

For instance, using different approaches, numerous researchers have concluded that the SARS-CoV-2 spike protein has a very high affinity for the human ACE2 receptor (Walls et al., 2020; Piplani et al., 2020; Shang and Ye et al., 2020; Wrapp et al., 2020). Such exceptional affinities, ten to twenty times as great as that of the original SARS virus, do not arise at random, making it very hard to explain in any other way than for the virus to have been strongly selected in the presence of a human ACE2 receptor (Piplani et al., 2020).

In addition to this, a recent report found that the spike of RaTG13 binds the human ACE2 receptor (Shang and Ye et al., 2020). We proposed above that the virus in the mine directly infected humans lung cells. The main determinant of cell infection and species specificity of coronaviruses is initial receptor binding (Perlman and Netland, 2009). Thus RaTG13, unlike most bat coronaviruses, probably can enter and infect human cells, providing biological plausibility to the idea that the miners became infected with a coronavirus resembling RaTG13.

Moreover, the receptor binding domain (RBD) of SARS-CoV-2, which is the region of the spike that physically contacts the human ACE2 receptor, has recently been crystallised to reveal its spatial structure (Shang and Ye et al., 2020). These authors found close structural similarities between the spikes of SARS-CoV-2 and RaTG13 in how they bound the human ACE2 receptor:


“Second, as with SARS-CoV-2, bat RaTG13 RBM [a region of the RBD] contains a similar four-residue motif in the ACE2 binding ridge, supporting the notion that SARS-CoV-2 may have evolved from RaTG13 or a RaTG13-related bat coronavirus (Extended Data Table 3 and Extended Data Fig. 7). Third, the L486F, Y493Q and D501N residue changes from RaTG13 to SARS CoV-2 enhance ACE2 recognition and may have facilitated the bat-to-human transmission of SARS-CoV-2 (Extended Data Table 3 and Extended Data Fig. 7). A lysine-to-asparagine mutation at the 479 position in the SARS-CoV-2 RBD (corresponding to the 493 position in the SARS-CoV-2 RBD) enabled SARS-CoV to infect humans. Fourth, Leu455 contributes favourably to ACE2 recognition, and it is conserved between RaTG13 and SARS CoV-2; its presence in the SARS CoV-2 RBM may be important for the bat-to-human transmission of SARS-CoV-2″ (Shang and Ye et al., 2020). (italics added)


The significance of this molecular similarity is very great. Coronaviruses have evolved a diverse set of molecular solutions to solve the problem of binding ACE2 (Perlman and Netland, 2009; Forni et al., 2017). The fact that RaTG13 and SARS CoV-2 share the same solution makes RaTG13 a highly likely direct ancestor of Sars-CoV-2.

A further widely noted feature of SARS-CoV-2 is its furin site (Coutard et al., 2020). This site is absent from RaTG13 and other closely related coronaviruses. The most closely related virus with such a site is the highly lethal MERS (which broke out in 2012). Possession of a furin site enables SARS-CoV-2 (like MERS) to infect lungs and many other body tissues (such as the gastrointestinal tract and neurons), explaining much of its lethality (Hoffman et al., 2020; Lamers et al., 2020). However, no convincing explanation for how SARS-CoV-2 acquired this site has yet been offered. Our suggestion is that it arose due to the high selection pressure which existed in the miner’s lungs and which in general worked to ensure that the virus became highly adapted to the lungs. This explanation, which encompasses how SARS-CoV-2 came to target lung tissues in general, is an important aspect of our proposal.

The implication is therefore that the furin site was not acquired by recombination with another coronavirus and simply represents convergent evolution (as suggested by Andersen et al., 2020).

An intriguing alternative possibility is that SARS-CoV-2 acquired its furin site directly from the miner’s lungs. Humans possess an epithelial sodium channel protein called ENaC-a whose furin cleavage site is identical over eight amino acids to SARS-CoV-2 (Anand et al., 2020). ENaC-a protein is present in the same airway epithelial and lung tissues infected by SARS-CoV-2.
It is known from plants that positive-stranded RNA viruses recombine readily with host mRNAs (Greene and Allison, 1994; Greene and Allison, 1996; Lommel and Xiong, 1991; Borja et al., 2007). The same evidence base is not available for positive-stranded animal RNA viruses, (though see Gorbalenya, 1992) but if plant viruses are a guide then acquisition of its furin site via recombination with the mRNA which encodes ENaC-a by SARS-CoV-2 is a strong possibility.

A further feature of SARS-CoV-2 has been the very limited adaptive evolution of its genome since the pandemic began (Zhan et al., 2020; van Dorp et al., 2020; Starr et al., 2020). It is a well-established principle that viruses that jump species undergo accelerated evolutionary change in their new host (e.g. Baric et al., 1997). Thus, SARS and MERS (both coronaviruses) underwent rapid and readily detectable adaptation to their new human hosts (Forni et al., 2017; Dudas and Rambaut, 2016). Such an adaptation period has not been observed for SARS-CoV-2 even though it has now infected many more individuals than SARS or MERS did. This has even led to suggestions that the SARS-CoV-2 virus had a period of cryptic circulation in humans infections that predated the pandemic (Chaw et al., 2020). The sole mutation consistently observed to accumulate across multiple studies is a D614G substitution in the spike protein (e.g. Korber et al., 2020). The numerically largest analysis of SARS-CoV-2 genomes, however, found no evidence at all for adaptive evolution, even for D614G (van Dorp et al., 2020).

The general observation is therefore that Sars-CoV-2 has remained functionally unchanged or virtually so (except for inconsequential genetic changes) since the pandemic began. This is a very important observation. It implies that SARS-CoV-2 is highly adapted across its whole set of component proteins and not just at the spike (Zhan et al., 2020). That is to say, its evolutionary leap to humans was completed before the 2019 pandemic began.

It is hard to imagine an explanation for this high adaptiveness other than some kind of passaging in a human body (Zhan et al., 2020). Not even passaging in human cells could have achieved such an outcome.


Two examples illustrate this point. In a follow up to Shang and Ye et al., (2020), a similar group of Minnesota researchers identified a distinct strategy by which the spike (S) protein (which contains the receptor bind domain; RBD) of SARS-CoV-2 evades the human immune system (Shang and Wan et al., 2020). This strategy involves more effective hiding of its RBD, but it implies again that the spike and the RBD evolved in tandem and in the presence of the human immune system (i.e. in a human body and not in tissue culture).

The Andersen authors, in their critique of a possible engineered origin for SARS-CoV-2, also stress the need for passaging in whole humans:

“Finally, the generation of the predicted O-linked glycans is also unlikely to have occurred during cell-culture passage, as such features suggest the involvement of an immune system” (Andersen et al., 2020).


The final point that we would like to make is that the principal zoonotic origin thesis is the one proposed by Andersen et al. Apart from being poorly supported this thesis is very complex. It requires two species jumps, at least two recombination events between quite distantly related coronaviruses and the physical transfer of a pangolin (having a coronavirus infection) from outside China (Andersen et al., 2020). Even then it provides no logical explanation of the adaptedness of SARS-CoV-2 across its whole genome or why the virus emerged in Wuhan.

By contrast, our MMP proposal requires only the one species jump, which is documented in the Master’s thesis.
Although we do not rule out a possible role for mixed infections in the lungs of the miners, nor the possibility of recombination between closely related variants in those lungs, nor the potential acquisition of the furin site from a host mRNA, only mutation was needed to derive SARS-CoV-2 from RaTG13. Hence our attention earlier to the figure from P. Zhou et al., 2020 showing that RaTG13 is the most closely related virus to SARS-CoV-2 over its entire length. This extended similarity is perfectly consistent with a mutational origin of SARS-CoV-2 from RaTG13.

In short, the MMP theory is a plausible and parsimonious explanation of all the key features of the COVID-19 pandemic and its origin. It accounts for the propensity of SARS-CoV-2 infections to target the lungs; the apparent preadapted nature of the virus; and its transmission from bats in Yunnan to humans in Wuhan.

Further questions

The hypothesis that SARS-CoV-2 evolved in the Mojiang miner’s lungs potentially resolves many scientific questions about the origin of the pandemic. But it raises others having to do with why this information has not come to light hitherto. The most obvious of these concern the actions of the Shi lab at the WIV.

Why did the Shi lab not acknowledge the miners’ deaths in any paper describing samples taken from the mine (Ge et al., 2016 and P. Zhou et al., 2020)? Why in the title of the Ge at al. 2016 paper did the Shi lab call it an “abandoned” mine? When they published the sequence of RaTG13 in Feb. 2020, why did the Shi lab provide a new name (RaTG13) for BtCoV/4991 when they had by then cited BtCoV/4991 twice in publications and once in a genome sequence database and when their sequences were from the same sample and 100% identical (P. Zhou et al., 2020)? If it was just a name change, why no acknowledgement of this in their 2020 paper describing RaTG13 (Bengston, 2020)? These strange and unscientific actions have obscured the origins of the closest viral relatives of SARS-CoV-2, viruses that are suspected to have caused a COVID-like illness in 2012 and which may be key to understanding not just the origin of the COVID-19 pandemic but the future behaviour of SARS-CoV-2.

These are not the only questionable actions associated with the provenance of samples from the mine. There were five scientific publications that very early in the pandemic reported whole genome sequences for SARS-CoV-2 (Chan et al., 2020; Chen et al., 2020; Wu et al., 2020; P. Zhou et al., 2020; Zhu et al., 2020). Despite three of them having experienced viral evolutionary biologists as authors (George Gao, Zheng-li Shi and Edward Holmes) only one of these (Chen et al., 2020) succeeded in identifying the most closely related viral sequence by far: BtCoV/4991 a viral sequence in the possession of the Shi lab at the WIV that differed from SARS-CoV-2 by just 5 nucleotides.

As we noted in our earlier article, the most important of the questions surrounding the origins of SARS-CoV-2 could potentially be resolved by a simple examination of the complete lab notebooks and biosafety records of relevant researchers at the WIV. Now that a credible and testable lab escape hypothesis exists this task becomes potentially much easier. This moment thus represents an opportune one to renew that call for an independent and transparent investigation of the WIV.

In requesting an investigation we are aware that no scientific institution anywhere has made a comparable request. We believe that this failure undermines public trust in a “scientific response” to the pandemic. Instead, the scientific establishment has labeled the lab escape theory a “rumor“, an “unverified theory” and a “conspiracy” when its proper name is a hypothesis. By taking this stance the scientific establishment has given the unambiguous message that scientists who take the possibility of a lab origin seriously are jeopardising their careers. Thus, while countless scientific publications on the pandemic assert in their introductions that a zoonotic origin for SARS-CoV-2 is a matter of fact or near-certainty (and Andersen et al has 860 citations as of July 14th), there is still not one published scientific paper asserting that a lab escape is even a credible hypothesis that deserves investigation.

Anyone who doubts this pressure should read the interview with Birger Sørensen in Norway’s Minerva magazine in which Sørensen discusses the “reluctance” of journals to publish his assessment that the existence of a virus that is “exceptionally well adjusted to infect humans” is “suspicious” and “cannot have evolved naturally”. The source of this reluctance, says Sørensen, is not rationality or scientific evidence. It results from conflicts of interest. This mirrors our experience. To find genuinely critical analysis of COVID-19 origin theories one has to go to Twitter, blog posts, and preprint servers. The malaise runs deep when even scientists start to complain that they don’t trust science.


Therefore we hypothesise the reconstructed historical aetiology of the Spike as follows:

In 2008, Dr Zheng-Li Si and WIV colleagues successfully demonstrated technical capabilities to interchange RBD’s between bat SARS-like and human SARS viruses. Building upon this, the 2010 work (Hou et al, 2010) perfected the ability to express receptors on human cells. On these foundations, the central Gain of Function work that underpins the functionalities of SARS-CoV-2 took place, carrying the WIV spike and plasmid materials to bond successfully to a UNC Chapel Hill human epithelial cell-line. This work (Menachery et al) produced a highly infectious chimeric virus optimised to the human upper respiratory tract.
In convergent support of this hypothesis, both Lu (Lu et al, 2020) and Jia (Jia et al, 2020) have now, in January and April 2020, shown that SARS-CoV-2 has a bat SARS-like backbone but is carrying an RBD from a human SARS and Zhan et al have, like us, noted unusual adaption to humans from the first isolate. In the 2015 Chapel Hill work it was only ACE2 receptors that were discussed. However, in 2018 Zhou P. et al demonstrated capabilities to clone other receptors like APN and DPP4 and to test and compare these against the (intestine) tissue specific SADS-CoV identified. Then, in the 2019-20 Covid-19 pandemic, profuse symptoms indicating compromise of the bitter/sweet receptors are reported. Taken all together, this implies that by employing insights gained after 2015, as just deduced, a further optimization of the 2015 chimeric virus for additional binding to receptors/co-receptors such as bitter/sweet specific upper airway epithelia receptors occurred. That would help to explain the otherwise puzzling high infectivity and pathology associated with SARS-CoV-2 and hence also help to explain the social epidemiology of its spread.

-- The Evidence which Suggests that This Is No Naturally Evolved Virus: A Reconstructed Historical Aetiology of the SARS-CoV-2 Spike, by Birger Sørensen, Angus Dalgleish & Andres Susrud


We nevertheless hope that journalists will investigate some of the conflicts of interest that are keeping scientists and institutions from properly investigating the lab escape hypothesis.

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Re: U.S. government gave $3.7 million grant to Wuhan lab at

Postby admin » Sun Jul 26, 2020 10:18 pm

Part 3 of 3

Comments37

Kurt Thomas
JULY 15, 2020 AT 9:50 PM REPLY
Very convincing arguments for the provenance, thank you for researching and sharing.

Lifeguard Larry
JULY 16, 2020 AT 11:01 AM REPLY
If lungs are such great places for the virus to better adapt to human hosts what chance do we have against it now that so many millions of lungs are infected?

M
JULY 16, 2020 AT 7:50 PM REPLY
What is the source of the translation? How did you become aware of the Master’s Thesis?

Jonathan Latham
JULY 17, 2020 AT 12:35 AM REPLY
We hired a Chinese speaker to translate the Chinese Master’s thesis for us quickly, but clearly enough so we could understand the diagnosis and treatment of the miners’ illnesses. The translator was not a doctor, so a doctor kindly checked the English translation to improve clarity/accuracy of the medical terms. We became aware of the Chinese Master’s thesis and later the Chinese PhD thesis (that both reported on the mine incident) after reading the two extremely informative preprints — Rahalkar and Bahulikar 2020 and Segreto and Deigin 2020 — both referenced in the our article. Both are well worth reading.

Charlie Knoll
JULY 16, 2020 AT 9:50 PM REPLY
Your assumption “…BtCoV/4991 and RaTG13 are both from the same bat faecal sample and the same mine. They are thus sequences from the same virus” is suspect at best. BtCoV/4991 only has 373 base pairs. How can you be sure that there were no significant mutations between the unpublished BtCov/4991 portion and RaTG13?

Jonathan Latham
JULY 16, 2020 AT 9:53 PM REPLY
The sequences of both are publicly available so it’s not an assumption. They are identical.

Timothy Jones
JULY 16, 2020 AT 10:38 PM REPLY
excerpt
“As we noted in our earlier article, the most important of the questions surrounding the origins of SARS-CoV-2 could potentially be resolved by a simple examination of the complete lab notebooks and biosafety records of relevant researchers at the WIV.”

Why haven’t these people reconciled the issue with the Bat Woman?
https://www.scientificamerican.com/arti ... onavirus1/
excerpt
“Back in Wuhan, where the lockdown was finally lifted on April 8, China’s bat woman is not in a celebratory mood. She is distressed because stories from the Internet and major media have repeated a tenuous suggestion that SARS-CoV-2 accidentally leaked from her lab—despite the fact that its genetic sequence does not match any her lab had previously studied. Other scientists are quick to dismiss the allegation. “Shi leads a world-class lab of the highest standards,” Daszak says.”

Either she’s lying or the virus is natural.

Charlie Knoll
JULY 16, 2020 AT 11:17 PM REPLY
Ah, sorry I didn’t realize they had published the entire BtCoV/4991 sequence.

Jonathan Latham
JULY 17, 2020 AT 12:39 AM REPLY
Your question is not silly though. Sequencing can have errors, for example. But even if it was a tiny bit different most people would still say it was the same virus on the grounds that its not different enough to be a new strain or species.

Allison Wilson
JULY 17, 2020 AT 12:21 AM REPLY
We hired a Chinese speaker to translate the Chinese Master’s thesis for us quickly, but clearly enough so we could understand the diagnosis and treatment of the miners’ illnesses. The translator was not a doctor, so a doctor kindly checked the English translation to improve clarity/accuracy of the medical terms. We became aware of the Chinese Master’s thesis and later the Chinese PhD thesis (that both reported on the mine incident) after reading the two extremely informative preprints — Rahalkar and Bahulikar 2020 and Segreto and Deigin 2020 — both referenced in the our article. Both are well worth reading.

Dave
JULY 17, 2020 AT 1:05 AM REPLY
Preprint by Xiaoxu Sean Lin and Shihong Chen “Major concerns on the identification of bat coronavirus strain RaTG13 and quality of related Nature paper” doi:10.20944/preprints202006.0044.v1

Jonathan Latham
JULY 17, 2020 AT 1:33 AM REPLY
Excellent question. We agree that questions can be asked about RaTG13. The main one for us is that it is not an infectious clone. I.e. it has not fulfilled Koch’s postulates of being able to infect a bat, cause disease, and fulfill its lifecycle. Therefore it may be a mutant or defective in some way.

M
JULY 17, 2020 AT 2:23 AM REPLY
” Rahalkar and Bahulikar 2020 and Segreto and Deigin 2020″

Have you contacted the authors?

Crocodilite
JULY 17, 2020 AT 6:26 AM REPLY
(Looks like the comments I left yesterday didn’t make it for some reason–perhaps you misunderstood my enthusiasm. I’ll rephrase, be less “colorful,” and try again.)

I think this is an amazingly well-researched and well-thought out coherent piece! Thank you!

(1) About this whole miner saga, this is the first time I’ve heard about the existence of the human tissue and blood samples! If proved true, I think this is incredibly significant!

Do you have witnesses and/or paper trails that could testify to the existence of these samples?

If true, the degree of deception involved in hiding this fact seems mind-boggling to me and this culpability should be highlighted.

In all their public utterance, Shi and company have only cryptically mentioned a tiny sample of bat poop. And have indirectly claimed that the sample is in fact used up, so all traces of anything are gone!

At no place was there ever mention of a big stash of human tissue samples that are, at least according to this piece, likely heavily laden with the virus(es) in question!

The whole legend surrounding the “batwoman” mystique would have been almost an entire fraud, since the most important information was in the abundant and readily available human samples that were shipped to her labs with industrial efficiency, not in the tiny, potentially heavily contaminated poop bits that needed to be painstakingly coaxed out of stinky dark caves!

Exactly what has happened to these samples, I hope, will at some point, become a focal point of inquiry!

Exactly which strain(s) of the virus are in these samples is an incredibly intriguing question. To what extent, if at all, are they different from today’s SARS-CoV-2 or its bat ancestors? Does it include the all-important furin site?

If the samples were destroyed, who did it? Why?

(2) Just WHY?!

The all-important question of why, why did Shi and company hide this entire saga and the existence of the samples, for all these years, the all-important question of *motive*.

I understand it’s kind of beyond the scope of this scientific piece so it was probably prudent for the authors not to go there. But it’s an obvious question at least a reader should ask!

BSL4 is a means; it’s not an end. Waiting for BSL4 is waiting for a means to do what?

The work required for publication, if indeed deemed to be too risky to be carried out in China at the time, could easily be done at any number of overseas facilities, with the aid of Shi’s many international collaborators. Even more dangerous viruses had been studied safely and surely the means existed.

Shi’s entire career is built on the premise that another bat virus after Sars could one day jump from bats to human. She’s been jumping up and down telling the whole world about it. The miner saga is the holy grail! To sit on this for half a decade and keeping quiet about it is not in her character. Sitting on such a dangerous time bomb and being quiet about it is not the best way to warn the world about its impending doom.

And after the miner incident in 2013, she continued splicing experiments, creating worse and worse hybrids. The justification for the splicing experiments was that, since they couldn’t find actual natural cases of bat viruses jumping into humans, they could benefit from artificially creating them so they could study them. The miner incident showed that such jumps did in fact occur in nature and it was indeed as bad as it could get and they had all the samples they needed. That should have removed the excuses for continued splicing experiments.

In summary, I fail to see what legimate work they could possibly have intended that justified waiting for so long and so patiently to perform!

(3) “RaTG13” is a term whose meaning is no longer clear.

It could have been from the bat poop, which, critically, could be very different from what’s in the miner samples, especially in light of the main thesis of this piece, that there had been significant adaptation inside the miner lungs.

It could have come from the miners’ samples.

It could be a hodge-podge of several things in the bat poop.

And, of course, it could even have been faked!

Considering a strong condemnation has been brought against the conduct of Shi and company, the sole source of the dubious information concerning RaTG13, we can no longer confidently invest any meaning or trust in even the existence of RaTG13, let alone the finer details of its essential characteristics.

Reading this piece on its first day of publication has been a privilege and an eye-opener! Thank you!

Philip Ward
JULY 17, 2020 AT 8:48 AM REPLY
One question that immediately comes to mind is that if these patients in 2012 had CoViD-19 then why did this not lead at least to wider local outbreaks – for example in the places where they were treated or amongst their families or the people who transported them to doctors and hospitals. Is there any information about that available?

Lance
JULY 17, 2020 AT 7:14 PM REPLY
Brilliant and very intriguing analysis. Came here through https://swprs.org/covid-19-virus-origin ... ypothesis/

They link to another worrying article: https://armswatch.com/project-g-2101-pe ... s-in-bats/

So “Eco Health Alliance” was working with both the WIV and the Pentagon.

Allison Wilson
JULY 17, 2020 AT 10:29 PM REPLY
To answer Philip Ward: Good question. Our best guess is that it took a while for virus to evolve to be highly transmissible from human to human — this most likely happened later, after the miner(s) were in hospital. Also, once the miners were in the hospital the thesis is clear they were treated as if they had infectious diseases — perhaps even SARS or other very deadly diseases. Thus we expect the hospital staff were taking every precaution. There are other possibilities — the others were infected but had no symptoms or that infections were not made public or that we just have not encountered the data yet.

Dob
JULY 18, 2020 AT 12:24 AM REPLY
Being a scientist but not a research scientist, it seems from the evidence so far that the miners were infected by an undeveloped strain of Covid-19. Even assuming that RaTG13 is natural and its postulated genome is correct and not a hypothesised extrapolation from the 370 nucleotide sample from BAT4991 (neither of which appears to have any surviving examples despite being listed as being used for research numerous times in 2017 and 2018 in the Chinese research database) there is ample scientific evidence in related research quoted in the above article that it would have taken between 20 -50 years for the RaTG13 genome to have mutated naturally to the C0vid-19 genome.

However, in 2013 previous coronoviruses had not had the human to human transmission of Covid-19 and you would not have expected doctors, nurses, ancilliary staff, let alone simple porters, stretcher bearers and good samaritans to have taken the infection precautions we now take automatically – and yet none appears to have been infected. This means at that time human to human transmission was not possible – because that part of the virus’s genome had not come to fruition.

From 2013 to 2019 various Gain of Function processes were actioned on Bat samples in the Wuhan lab to make the samples more infectious to humans in order, as the researchers are quick to explain, to enable vaccines or preventative infectious measures to become readily available. In seven years what sort of experiments could have been done to arrive at Covid-19 – look at what has been done just in the last 8 months to counter the infection. See Timothy Stout’s comments for the range of options.

What I would like to know is how the infections in Wuhan, mostly type B virus with some A and the infections in Guangdong, all type A tie up and the timeframes involved. Did researchers from Wuhan travel to Guangdong and infect locals and did the virus then mutate from A to B as A was less infectious in the Chinese hosts (possibly from previous coronavirus infections) and therefore the virus had to change. Much to be discussed.

Madeleine Love
JULY 18, 2020 AT 1:05 AM REPLY
Thank you so much for the effort to find and translate a very interesting thesis, and developing a new hypothesis.

I had questions on the time related epidemiology, and also on the question raised by Philip above. I have questions about the ability to extract full sequences some months after the infection event, based on government reporting from my home state.

The article read as though all miners passaged RaTG13 for the same outcome. One would think there’d be an infection precedent. On the hypothesis that the miners suffered from Sars-Cov-2, I would think that one would’ve passaged it first.
[The typcial reported course of the virus… There is average of 6 days from infection to mild symptoms (2-26?). Another week to symptoms becoming “serious” enough to require hospitalisation.]

Patients were admitted 26/4 (1), 25/4 (2), 27/4 (3), 26/4 (4), 2/5 (5), 26/4 (6). Patients (1)-(4) began at the mine on 2/4 and worked 2 weeks. Patients (5) and (6) began on 22/4, supposedly after (1)-(4) had left. I would ask questions about residence and contact. It’s possible the one of the first miners passaged the most successful virus, and working an enclosed space passed it to the others within a few days. Certainly patient (6) proceeded more rapidly to hospital (patient (5) quite quickly), so it would suggest they already had the virus. I’d be asking questions about where they lived – local or fly in/fly out? Do they live in a town with others? Is there any local report of doctors/hospital staff becoming infected? I suppose China had been through sars and were highly precautionary – this didn’t apply in Wuhan where there were many infections in medical staff, but perhaps this was a consequence of an avalanche of cases and low ppe availability. It’s said that 80% of cases pass the virus on to no-one and that 20% are the super-spreaders. Perhaps the 6 weren’t the spreading types?

If this was the Sars-Cov-2 virus, one would be looking for the greater prevalence of low symptom sufferers, understanding that the miners were a relatively unwell population.

Regarding the ability to extract full sequences some months after the infection event. Here in Victoria Australia there is a general view that people are non-infectious 10-14 days after first symptoms. They explain subsequent positive tests as being related to viral particles, not whole live viruses. They may not be right, or it may relate specifically to the tests they are using, but they lead me to ask questions about the extraction of full viral material from the thymus so long after the infection events.

Jonathan Latham
JULY 18, 2020 AT 12:18 PM REPLY
I hope I have understood your question correctly but our contention is that, while normal coronavirus passes through a person quickly, these miners had the disease continuously for months. They did not manage to clear it and there was a kind of stalemete between the virus and the immune system that took a long time to resolve, either in death or recovery. We don’t rule out that they may have passed it to each other. Jonathan

Madeleine Love
JULY 18, 2020 AT 4:46 AM REPLY
The fact that the miners were sick with Covid-19-like symptoms doesn’t preclude lab development to enhance human affinity. What they presented with may have been the symptoms of BtCoV/4991 and RaTG13. Although these coronaviruses may not have strong human affinity it may have been sufficient in damaged lungs. This could explain the lack of a public epidemic/health care worker report of illness. Are there any reports of anyone having been infected with BtCoV/4991 and RaTG13?

Aksel Fridstrøm
JULY 18, 2020 AT 1:41 PM REPLY
Thank you for a very interesting article, and for providing a link to my interview with Birger Sørensen in Minerva.

I have recently written two more articles on the works of Sørensen, you might find them interesting.

This one is about the struggle to publish his article:

https://www.minervanett.no/angus-dalgle ... cle/362519

The second one contains an upload of his full thesis:

https://www.minervanett.no/angus-dalgle ... rus/362529

Allison Wilson
JULY 18, 2020 AT 2:34 PM REPLY
Lance thank you for the link to Arms Watch and the excellent article connecting EcoHealth Alliance (which has links to the Gates Foundation) to the US Military. I hope many people will read this article and the Arms Watch website http://armswatch.com/. EcoHealth gets the vast majority of its money from the government but it also has corporate funding and foundation funding which it would be useful to know more about.

Brin
JULY 18, 2020 AT 4:28 PM REPLY
@Jonathan and Allison: Prof Balloux notes that “4 out of 7 known hCoVs have furin cleavage site”, including “common cold” viruses OC43 and HKU1. Is this correct or is there a difference to SARS2 and MERS that makes them special or requires “special explanation”?

https://twitter.com/BallouxFrancois/sta ... 5746233344

Allison Wilson
JULY 18, 2020 AT 4:31 PM REPLY
There may exist other reports on the Mojiang Mine Outbreak, or reports of people other than the miners being infected. However, the only reports we are aware of are 1. The Master’s thesis by Xu,Li (2013) 2. The Huang, Canping (2016) PhD thesis(chapter 3). 3. The Science news item “A New Killer Virus in China?” (this report only mentions the three miners who died) and 4. the short scientific report by Wu et al. 2014. The originals and/or translations of these documents are all linked to in the text and/or cited in the references of our article. We would like to hear about any other documented reports on this outbreak that people can find.

Brin
JULY 18, 2020 AT 4:35 PM REPLY
alright this seems to answers it: no other CoV has ACE2/FCS combination:

https://twitter.com/flavinkins/status/1 ... 3676516352
https://twitter.com/flavinkins/status/1 ... 7473904640

So FCS not unique in general but in hCov group 2B.

Crocodilite
JULY 18, 2020 AT 6:29 PM REPLY
This excellent piece has at least three key ideas or revelations. (1) The mine saga and human samples, a bombshell! (2) Significant and rapid adaptation by the virus in miner lungs. (3) ALL, not just some, features of the virus (including the all-important furin site) were acquired solely in miner lungs. Some may deem (2) and/or (3) controversial.

But one of the greatest contributions this piece could make is to alert people to a line of possible forensic inquiry that has a clear origin and narrative that should be pursued. We now have a solid lead, starting with the mine, to the hospital, to WIV. A lot of people were involved in this chain of events. There should be witnesses, paper trails, and medical samples. That these leads need to be pursued is entirely independent of whether one believes Idea (2) or Idea (3). The corrupt forces will likely want to confuse the matter. They would point to the potential controversies of Idea (2) or Idea (3) to discredit the entire piece and therefore obstruct an inquiry that starts with just Idea (1). People need to be aware of that and call that out if/when it happens.

And for people who believe an entirely man-made narrative, please be mindful that Idea (1) and Idea (2) are still compatible with later human manipulation. You wouldn’t want to go out of your way to discredit this piece just because you don’t believe in Idea (3). Unlike the disgraceful Andersen piece, this piece is your friend, not your enemy. The mine origin story could be one of the very few, if not the only, credible forensic leads that could be the starting point of an inquiry. If an investigation that starts with the mine ultimately leads to uncovering crimes that more closely resemble your pet theory than Idea (3), I believe the authors of this piece would have no problem, neither should you. We should be objective and critical about scientific details, but we should be united in our call for an inquiry that follows the trail leading from the mine, to the hospital, to WIV, and hopefully, to the ultimate truth!

Paul Jackson
JULY 18, 2020 AT 6:34 PM REPLY
How about the presence of a snippet of HIV in SARS-CoV-2? Does that exist? Does it point to some manipulation in the WIV lab?

Alan
JULY 19, 2020 AT 8:32 PM REPLY
The story is convincing in detail, but fails to support the conclusions. The story says that Covid19 evolved naturally in miners lungs in a hospital, then they concluded that it originated from a lab. According to the detail, the lab merely stored the virus and did no significant originating work on it before it escaped. this does NOT make the lab the origin of the virus, merely a multi-year storage point during which time it seems to have been eradicated elsewhere.

M
JULY 20, 2020 AT 7:06 AM REPLY
SARS-CoV-2, viruses that are suspected to have caused a COVID-like illness in 2012 and which may be key to understanding not just the origin of the COVID-19 pandemic but the future behaviour of SARS-CoV-2. Well said as Dr Yan limeng in the Fox News interview warn us we need find the truth.

Jonathan Latham
JULY 20, 2020 AT 7:47 PM REPLY
PS Apologies that the “REPLY” function seems not to be working. Attempting to fix this.

Jonathan Latham
JULY 22, 2020 AT 3:41 PM REPLY
A kind reader (John) has made this available as a Talking Paper to download and listen to. Hear his nice English accent at:
https://soundcloud.com/talkingpapers/pr ... r-sarscov2
Also available on youtube:
https://youtu.be/l3gQdkWn9u0
(link updated)

Paul Zhao
JULY 23, 2020 AT 9:38 AM REPLY
Would it be possible to publish the paper on mainstream science journals? If not, it’s unlikely to lead to an unbiased investigation, and the article will be ignored, as Dr. Sorensen’s.

Jonathan Latham
JULY 23, 2020 AT 12:40 PM REPLY
The conundrum of peer review is that it can take a long time and may not be fair. One of the things we have noticed in submitting ‘challenging’ papers is that editors (and/or reviewers) often take even longer than normal. It can take six months to get a “No” and that No is sometimes based on a trivial critique. We therefore don’t cite Sorensen just because he says it. We have personal experience. This paper of ours, for example ended up never being published even though no one (including peer-reviewers, editors, etc) has ever advanced a serious and substantive critique (https://2k4vbx44lajeo2rag2seu29o-wpengi ... Wilson.pdf).

But the other aspect is that, even if it becomes part of the published literature, it can still be ignored.

Lifeguard Larry
JULY 23, 2020 AT 11:01 PM REPLY
https://www.scientificamerican.com/arti ... onavirus1/

Notice
1) China says it has less infections and deaths now than it had in April
2) Shi says that the Mojiang miners suffered from a fungal infection when it was known almost immediately that they suffered from coronavirus.
3) Daszek is not willing to suspend his dangerous experiments despite the huge risks now evident to everyone.
4) Scientific American did not revise the numbers or comment on any of this when it republished the article. Nor has the scientific community subsequently.

Bob Clyatt
JULY 24, 2020 AT 4:51 PM REPLY
Following these papers and discussion with great interest. Thank you for your courageous and intellectually honest efforts. One question that I did not see addressed: what would explain the highly stable nature of Covid-19 in humans? Does that suggest some sort of passaging process might have been undertaken on the original miner’s samples at WIV during the past few years, and that one of those more evolved/stable versions, rather than the raw miner samples, was what leaked?

Will Lar
JULY 24, 2020 AT 7:45 PM REPLY
If it’s from the lab samples of WIV as suggested, it’s naturally to think that the workers especially the ones in the Shi lab in the institute were the first to be exposed and possibly infected. Do you have any information or data regarding the number of infected cases or deaths within WIV? Any information regarding the possible pathway of virus traveling from the lab to the outside world?
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Re: U.S. government gave $3.7 million grant to Wuhan lab at

Postby admin » Mon Jul 27, 2020 12:54 am

The most logical explanation is that it comes from a laboratory: The well-known Norwegian virologist Birger Sørensen and his colleagues have examined the corona virus. They believe it has certain properties which would not evolve naturally. These conclusions are politically controversial, but in this interview he shares the findings behind the headlines.
by Aksel Fridstrøm
Translated from Norwegian by Kathrine Jebsen Moore
July 2, 2020 - 19:10 SIST OPPDATERT Søndag 19. juli 2020 - 09:56

Image

“I understand that this is controversial, but the public has a legitimate need to know, and it is important that it is possible to freely discuss alternate hypotheses on how the virus originated” Birger Sørensen starts to explain when Minerva visits him in his office one morning in Oslo.

Despite the explosiveness of his statements and research, Sørensen remains calm and collected.

Sørensen has been a point of controversy ever since former MI6 director Richard Dearlove cited a yet to be published article by Sørensen and his colleagues in an interview with The Daily Telegraph. The article claims that the virus that causes Covid-19 most likely has not emerged naturally.

“It’s a shame that there has already been so much talk about this, because I have yet to publish the article where I put forward my analysis”, Sørensen says in the form of an exasperated sigh.


Together with his colleagues, Angus Dalgleish and Andres Susrud have authored an article that looks into the most plausible explanations regarding the origins of the novel coronavirus. The article builds upon an already published article in the Quarterly Review of Biophysics that describes newly discovered properties in the virus spike protein. The authors are still in dialogue with scientific journals regarding an upcoming publication of the article.

News outlets are thus confronted with a difficult question: Are the findings and arguments Sørensen and his colleagues put forward of a sufficiently high quality to be presented and discussed in the public sphere? Sørensen explains that they in their dialogue with scientific journals are encountering a certain reluctance to publishing the article – without, however, proper scientific objections. Minerva has read a draft of the article, and has after an overall assessment decided that the findings and arguments do deserve public debate, and that this discussion cannot depend entirely on the publication process of scientific journals.

In this interview with Minerva, Sørensen therefore puts forward his hypothesis on why it is highly unlikely that the coronavirus emerged naturally.

On May 18th, WHO decided to conduct an inquiry into the coronavirus epidemic in China. Sørensen believes that it is important that this inquiry looks into new and alternate explanations for how the virus originated, beyond the already well-known suggestion that the virus originated in the Wuhan Seafood Market.

“There are very few who still believe that the epidemic started there, so as of today we have no good answers on how the epidemic started. Then we must also dare to look at more controversial, alternative explanations for the origin,” Sørensen says.


Birger Sørensen and one of his co-authors, Angus Dalgleish, are already known as HIV researchers par excellence.

In 2008, Sørensen’s work came to international attention when he launched a new immunotherapy for HIV. Angus Dalgleish is the professor at St. George’s Medical School in London who became world famous in 1984 after having discovered a novel receptor that the HIV virus uses to enter human cells.

The purpose of the work Sørensen and his colleagues have done on the novel coronavirus, has been to produce a vaccine. And they have taken their experience in trialling HIV vaccines with them to analyse the coronavirus more thoroughly, in order to make a vaccine that can protect against Covid-19 without major side effects.

Exceptionally well adjusted

“The difference between our approach and other vaccine manufacturers is that we have a chemistry background, and we analyse the virus in detail as if we were making a drug,” Sørensen starts to explain.

“Biology is also chemistry, so by considering the virus from a chemistry perspective, we carry out more detailed analysis, zooming in on certain components.”


Sørensen takes us through the basic elements of their approach:

“The first thing you need to establish is which parts of the virus are changing, and which parts are stable. If you want to make a vaccine that lasts, you must stimulate the immune system to react against those parts of the virus that are constant, otherwise the effect will disappear and, in the worst-case scenario, lead to increased illness.

“Once we know this, we can try to make a vaccine. Where we differ is that we are trying to make a vaccine that uses elements that have as little in common with the body’s natural components as possible, so that the immune system is taught to recognise exactly what the vaccine should protect against”, Sørensen elaborates.

Sørensen believes this is an important insight which will prevent the immune system from being falsely stimulated in a way that could lead the vaccine to create too many dangerous side effects in the vaccinated person.

“When we have not succeeded in creating an HIV vaccine, despite the enormous efforts put into that endeavour for the past 30 years, it is because we haven’t understood this,” Sørensen continues.

He believes that there has not been enough interaction between the part of the pharmaceutical industry that makes HIV medicines and the part that runs the vaccine research. As a consequence, the knowledge you need to make a successful vaccine against HIV in the big pharmaceutical companies has not been adequately exploited by the big, international HIV preventing vaccine studies that have been carried out.”


Asked about what significance his approached has had when he has analyzed the coronavirus, Sørensen explains:

“We have examined which components of the virus are especially well suited to attach themselves to cells in humans. And we have done this by comparing the properties of the virus with human genetics. What we found was that this virus was exceptionally well adjusted to infect humans.”


He pauses for a second.

“So well that it was suspicious,” he adds.

Perfected to infect humans

It is already known that the novel coronavirus, like the virus that caused the SARS epidemic in Southeast Asia in 2002-2003, could attach itself to the ACE-2 receptors in the lower respiratory tract.

“But what we have discovered is that there are properties in this new virus which enables it to use an additional receptor, and create a binding to human cells in the upper respiratory tract and the intestines which is strong enough to produce an infection,” Sørensen elaborates.

Sørensen says that it is the use of this additional receptor that most likely results in a different illness in Covid-19 patients than the one resulting from SARS.

“This is what enables the virus to transmit to a greater degree between humans, without the virus having attached itself to the ACE-2 receptors in the lower respiratory tract, where it causes deep pneumonia.

“That is also why so many of the Covid-19 patients have mild symptoms at the start of the illness, and are contagious before they develop severe symptoms,” he adds.

It might also explain why some people are ‘super spreaders’ without being ill themselves, Sørensen says.


In the already published article Sørensen and his colleagues Angus Dalgleish and Andres Susrud describe what they claim is curious about the spike protein of the coronavirus, which makes it especially well suited to infect humans. These findings are the foundation for the hypothesis Sørensen and his colleagues develop in the new article, where they claim that the virus is not natural in origin.

“There are several factors that point towards this,” says Sørensen. “Firstly, this part of the virus is very stable; it mutates very little. That points to this virus as a fully developed, almost perfected virus for infecting humans.

“Secondly, this indicates that the structure of the virus cannot have evolved naturally. When we compare the novel coronavirus with the one that caused SARS, we see that there are altogether six inserts in this virus that stand out compared to other known SARS viruses,” he goes on explaining.

Sørensen says that several of these changes in the virus are unique, and that they do not exist in other known SARS coronaviruses.

“Four of these six changes have the property that they are suited to infect humans. This kind of aggregation of a type of property can be done simply in a laboratory, and helps to substantiate such an origin,” Sørensen points out.


FACT BOX – Spike Protein

A spike protein is a part of the virus attached to the surface of the virus. The spike protein is used by the virus when it enters cells, enabling it to stick in humans. The properties of the spike determines which receptors a virus can utilise and thus which cells the virus can enter to create illness.


An artificially created virus

Asked about whether this implies that the virus is not natural, Sørensen goes on to explain the laboratory process that leads to the creation of new viruses.

“In a sense it is natural. But the natural processes have most likely been accelerated in a laboratory,” he explains. “It’s also possible for a virus to attain these properties in nature, but it’s not likely. If the mutations had happened in nature, we would have most likely seen that the virus had attracted other properties through mutations, not just properties that help the virus to attach itself to human cells.”

Sørensen vividly explains this argument:

“Imagine that you have cultivated a billion coronaviruses you have gathered from nature, then you take this mass of viruses and inject them into a human cell culture from for example the upper respiratory tract. As a result, a few of these viruses will change in order to better attach themselves to this type of cell in the nose and throat region and therefore to infect humans more easily. You end up with a virus with a spike protein which is perfect for attaching to and penetrating human cells.” Sørensen explains.

Asked about the particular mutations in the virus that lead to this conclusion, Sørensens says:

“What we see is that an area that you could observe in the first SARS coronavirus has been moved, so that the parts of the virus that are particularly well suited to attach to humans, have become part of the spike protein that the virus uses to penetrate human cells. And it is this moving of the area of the virus which makes the virus, together with the injected areas explained above, able to utilise an additional receptor to infect humans.”


Image
Sørensen explains at the black board. Photo: Aksel Fridstrøm

On a board in the meeting room where Sørensen is hosting our meeting, he illustrates what he is trying to explain, and how a component of the virus which previously was situated on another part of the shell of the virus, now has become a part of the spike protein of the virus.

More than ninety percent confident

Sørensen is therefore quite confident that the virus has originated in a laboratory.

“I think it’s more than 90 percent certain. It’s at least a far more probable explanation than it having developed this way in nature”, Sørensen responds.


Sørensen also highlights other data than those related to the virus’ properties:

“The properties that we now see in the virus, we have yet to discover anywhere in nature. We know that these properties make the virus very infectious, so if it came from nature, there should also be many animals infected with this, but we have still not been able to trace the virus in nature.

“The only place we are aware of where an equivalent virus to that which causes Covid-19 exists, is in a laboratory. So the simplest and most logical explanation is that it comes from a laboratory. Those who claim otherwise, have the burden of proof,” Sørensen says.

Critical voices suppressed

There are indeed earlier known experiments where changes to the corona virus have been engineered. An interesting example of this kind of research is a collaborative effort between Wuhan Institute of Virology and University of North Carolina at Chapel Hill. In a 2015 article, Menachery et al. describe experiments with laboratory created corona viruses -– so called gain-of-function-studies. The purpose of this research is partly to be better prepared for new pathogenic variants of the virus. But the researchers also write: "the potential to prepare for and mitigate future outbreaks must be weighed against the risk of creating more dangerous pathogens". This risk must also be evaluated in light of previous known accidents where corona viruses have escaped from laboratories in China.



Fact box: Gain-of-function studies

According to US Department health & human services, gain-of-function studies refer to research which aims to increase the ability of a pathogen to cause disease. The method is controversial, because it entails risks, such as viruses escaping from labs. Between 2014 and 2018, this kind of research was prohibited in the United States, but in December 2017, American authorities announced that the ban would be lifted.


But several researchers have already pointed out that artificially created viruses would be easy to identify. We therefore ask Sørensen why this has not been identified earlier.

Sørensen believes there are several reasons for this.

“The first is that this is a very uncomfortable finding, and the production of new scientific articles that can be used to prove such findings has all but ground to a halt. Chinese scientists no longer publish articles that can be used to support such a hypothesis”, he says.

“And newer articles that are published about the virus must be thoroughly investigated, especially in relation to the basic material that is being used,” Sørensen expands, and points to a new x-ray article published in Nature by Shang et al., which Sørensen also earlier has criticised for being misleading.

“To do my analysis, I have therefore had to go back to the source material, and look at those articles that were published before the Covid-19 outbreak, where we have chosen to assume that the data that have been used is okay and reflects the actual conditions,” Sørensen says.


Asked about why there has not been more debate on this topic Sørensen has several explanations.

“This quickly becomes a discussion on politics, rather than science, Sørensen responds.

“Nobody wants to put forward the inconvenient truth, many scientists are also concerned about their own funding and position if they were to put forward such a controversial hypothesis. It is nevertheless a fact that many people on the web have engaged in such a debate. But so far, those who participate in such forums are characterized as conspiratorial. It is also the case that a debate about this type of viral research and the technologies used may damage reputation and lead to new restrictions on how to conduct molecular genetic research. With this in mind, it is not difficult to see that it must be difficult to get accepted papers in peer reviewed journals that focus on such research", Sørensen elaborates.

The fight for a controversial article

Birger Sørensen and Angus Dalgleish failed to get an article about the origins of the coronavirus published in a scientific journal. The authors suspect foul play and political considerations. Not everything gets published, is the answer from the journals. Minerva has obtained a draft of the paper, to let readers and researchers decide.


Hopes his arguments will be discussed properly

Sørensens himself is Chairman of the board at Immunor, a company which is working to develop their own vaccine candidate for Covid-19. Minerva has challenged him to address allegations that this hypothesis is launched publicly to attract funding for his own research.

“Of course, it’s in my interest that my research becomes known, but I am being completely open and have declared all my interests.

“At the same time, I argue that it must be possible for those of us who work for smaller biotechnology companies to present our findings and get them discussed properly. If anyone wishes to contest my findings, they are of course welcome to do so, but I hope they will engage thoroughly with the arguments rather than derail them by discussing my motives,” Sørensen responds.



*****************************

The fight for a controversial article: Birger Sørensen and Angus Dalgleish failed to get an article about the origins of the coronavirus published in a scientific journal. The authors suspect foul play and political considerations. Not everything gets published, is the answer from the journals. Minerva has obtained a draft of the paper, to let readers and researchers decide.
by Aksel Fridstrøm
July 13 2020 - 16:45 SIST OPPDATERT Mandag 13. juli 2020 - 20:10

In an interview with Minerva last week, the well-known Norwegian vaccine researcher and physical chemist Birger Sørensen argued that the novel coronavirus is not natural in origin.

Together with his colleagues Angus Dalgleish and Andres Susrud -– the latter in a data analytical role as statistician and data miner –- Sørensen has written a series of journal articles that put forward arguments for why the most likely explanation for the origin of the coronavirus is a laboratory.

If such findings were confirmed, there could be political ramifications. Naturally, therefore, Sørensen, Dalgleish and their unpublished paper have been mired in controversy ever since Sir Richard Dearlove, former head of the MI6, endorsed their conclusions. The authors themselves suspect that the controversial conclusions and the heated debate may have made journals reluctant to evaluate their paper objectively. However, tons of scientific articles are rejected for any number of reasons.

By tracing the writing of articles, the contact between the authors and the journals, and reviewing the findings, this article aims to shed light on a troubling question for the scientific community during the Corona crisis: One the one hand, there is an overabundance of papers and findings of highly variable quality -– some of which fuel conspiracy theories. On the other hand, the question of the origin of the Corona virus has become a fraught political question, with the Chinese government clamping down on independent research, and president Donald Trump claiming that the virus originated in a Chinese lab without producing any evidence to back up the assertion.

With the consent of Mr. Sørensen and his co-authors (henceforth: Sørensen and Dalgleish), Minerva has obtained a full print of the article, to be read freely by our readers – and by scientists, who may then discuss and dissect the paper.



Searching for a vaccine

It started out with something less controversial: Originally, the authors were engaged in analysis of the virus with the aim to create a vaccine. The discoveries that the authors claim to be relevant for determining the origin of the virus came as a by-product of this research.

In fact, Sørensen and Dalgleish have managed to get a paper on the corona virus peer reviewed and published, in Quarterly Reviews of Biophysics Discovery. This article, which is more closely linked to their vaccine development, deals with observations of the virus and the receptors that the virus can attach to in humans. Sørensen and Dalgleish do indeed believe that these properties indicate a lab origin for the virus. However, the article itself avoids any mention of this implication of the discovered properties.

Originally, the findings which are now published in Quarterly Reviews of Biophysics Discovery were part of a more condensed article, which included the lab origin hypothesis. To make this argument, the three have now instead written a second article, “The Evidence which Suggests that This Is No Naturally Evolved Virus”, that puts forward their arguments on why they believe the virus is likely to be a laboratory construct, by combining insights from the first paper with what is known from lab work on corona viruses.

However, this second article is yet to be accepted by a scientific journal -– having been rejected at different times and formats by three leading journals. Sørensen states that he is presently in dialogue with other journals regarding publication. A third paper on a related topic also taken from the original argument, is yet to be submitted.


Endorsed and criticized

Before we move on, let’s take a look on some of the reactions from within the scientific community. Sørensen has received both severe criticism and partial support.

Professor Kristian Andersen at the department of immunology and microbiology at Scripps Research, a medical research facility in California, was lead author on the article “The proximal origin of SARS-CoV-2” where he states that his “analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus”.

Andersen last week told Sky news that Sørensen’s and Dalgleish’s work was “complete nonsense, unintelligible, and not even remotely scientific – leading the authors to make unfounded and unsupported conclusions about the origin of SARS-CoV-2”. However, Andersen has not had an opportunity to read the second, unpublished article.

The principal reason for media dismissals of the lab origin possibility is a review paper in Nature Medicine (Andersen et al., 2020). Although by Jun 29, 2020 this review had almost 700 citations it also has major scientific shortcomings. These flaws are worth understanding in their own right but they are also useful background for understanding the implications of the Master’s thesis.

Andersen et al., a critique

The question of the origin of the COVID-19 pandemic is, in outline, simple. There are two incontrovertible facts. One, the disease is caused by a human viral pathogen, SARS-CoV-2, first identified in Wuhan in December 2019 and whose RNA genome sequence is known. Second, all of its nearest known relatives come from bats. Beyond any reasonable doubt SARS-CoV-2 evolved from an ancestral bat virus. The task the Nature Medicine authors set for themselves was to establish the relative merits of each of the various possible routes (lab vs natural) by which a bat coronavirus might have jumped to humans and in the same process have acquired an unusual furin site and a spike protein having very high affinity for the human ACE2 receptor.

When Andersen et al. outline a natural zoonotic pathway they speculate extensively about how the leap might have occurred. In particular they elaborate on a proposed residence in intermediate animals, likely pangolins. For example, “The presence in pangolins of an RBD [Receptor Binding Domain] very similar to that of SARS-CoV-2 means that we can infer that this was probably in the virus that jumped to humans. This leaves the insertion of [a] polybasic cleavage site to occur during human-to-human transmission.” This viral evolution occurred in “Malayan pangolins illegally imported into Guangdong province”. Even with these speculations there are major gaps in this theory. For example, why is the virus so well adapted to humans? Why Wuhan, which is 1,000 Km from Guangdong? (See map).

The authors provide no such speculations in favour of the lab accident thesis, only speculation against it:

“Finally, the generation of the predicted O-linked glycans is also unlikely to have occurred due to cell-culture passage, as such features suggest the involvement of an immune system.” (italics added).

[Passaging is the deliberate placing of live viruses into cells or organisms to which they are NOT adapted for the purpose of making them adapted, i.e. speeding up their evolution.]

It is also noteworthy that the Andersen authors set a higher hurdle for the lab thesis than the zoonotic thesis. In their account, the lab thesis is required to explain all of the evolution of SARS-CoV-2 from its presumed bat viral ancestor, whereas under their telling of the zoonotic thesis the key step of the addition of the furin site is allowed to happen in humans and is thus effectively unexplained.

A further imbalance is that key information needed to judge the merits of a lab origin theory is missing from their account. As we detailed in our previous article, in their search for SARS-like viruses with zoonotic spillover potential, researchers at the WIV have passaged live bat viruses in monkey and human cells (Wang et al., 2019). They have also performed many recombinant experiments with diverse bat coronaviruses (Ge et al., 2013; Menachery et al., 2015; Hu et al., 2017). Such experiments have generated international concern over the possible creation of potential pandemic viruses (Lipsitch, 2018). As we showed too, the Shi lab had also won a grant to extend that work to whole live animals. They planned “virus infection experiments across a range of cell cultures from different species and humanized mice” with recombinant bat coronaviruses. Yet Andersen et al did not discuss this research at all,
except to say:

“Basic research involving passage of bat SARS-CoV-like coronaviruses in cell culture and/or animal models has been ongoing for many years in biosafety level 2 laboratories across the world”

This statement is fundamentally misleading about the kind of research performed at the Shi lab.

A further important oversight by the Andersen authors concerns the history of lab outbreaks of viral pathogens. They write: “there are documented instances of laboratory escapes of SARS-CoV”. This is a rather matter-of-fact allusion to the fact that since 2003 there have been six documented outbreaks of SARS from labs, not all in China, with some leading to fatalities (Furmanski, 2014).

Andersen et al might have also have noted that two major human pandemics are widely accepted to have been caused by lab outbreaks of viral pathogens, H1N1 in 1977 and Venezuelan Equine Encephalitis (summarised in Furmanski, 2014). Andersen could even have noted that literally hundreds of lab accidents with viruses have resulted in near-misses or very localised outbreaks (summarised by Lynn Klotz and Sam Husseini and also Weiss et al., 2015).


Also unmentioned were instances where a lab outbreak of an experimental or engineered virus has been plausibly theorised but remains uninvestigated. For example, the most coherent explanation for the H1N1 variant ‘swine flu’ pandemic of 2009/10 that resulted in a death toll estimated by some as high as 200,000 (Duggal et al., 2016; Simonsen et al. 2013), is that a vaccine was improperly inactivated by its maker (Gibbs et al., 2009). If so, H1N1 emerged from a lab not once but twice.

Given that human and livestock viral outbreaks have frequently come from laboratories and that many scientists have warned of probable lab escapes (Lipsitch and Galvani, 2014), and that the WIV [Wuhan Institute of Virology] itself has a questionable biosafety record, the Andersen paper is not an even-handed treatment of the possible origins of the COVID-19 virus.

Yet its text expresses some strong opinions: “Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus….It is improbable that SARS-CoV-2 emerged through laboratory manipulation of a related SARS-CoV-like coronavirus…..the genetic data irrefutably show that SARS-CoV-2 is not derived from any previously used backbone….the evidence shows that SARS-CoV2 is not a purposefully manipulated virus….we do not believe that any type of laboratory-based scenario is possible.” (Andersen et al., 2020).

It is hard not to conclude that what their paper mostly shows is that Drs. Andersen, Rambaut, Lipkin, Holmes and Garry much prefer the natural zoonotic transfer thesis. Their rhetoric is forthright but the evidence does not support that confidence.

Indeed, since the publication of Andersen et al., important new evidence has emerged that undermines their zoonotic origin theory. On May 26th the Chinese CDC ruled out the Huanan “wet” market in Wuhan as the source of the outbreak. Additionally, new research on pangolins, the favoured intermediate mammal host, suggests they are not a natural reservoir of coronaviruses (Lee et al., 2020; Chan and Zhan, 2020). Furthermore, SARS-CoV-2 was found not to replicate in bat kidney or lung cells (Rhinolophus sinicus), implying that SARS-CoV-2 is not a recently-adapted spill over Chu et al., 2020)...

The final point that we would like to make is that the principal zoonotic origin thesis is the one proposed by Andersen et al. Apart from being poorly supported this thesis is very complex. It requires two species jumps, at least two recombination events between quite distantly related coronaviruses and the physical transfer of a pangolin (having a coronavirus infection) from outside China (Andersen et al., 2020). Even then it provides no logical explanation of the adaptedness of SARS-CoV-2 across its whole genome or why the virus emerged in Wuhan.

-- A Proposed Origin for SARS-CoV-2 and the COVID-19 Pandemic, by Jonathan Latham, PhD and Allison Wilson, PhD


Minerva has, however, shared that second article with Birgitta Åsjö, a professor emerita in virology at the university of Bergen. She is puzzled by Andersen’s comments, and rejects the notion that Sørensen’s and Dalgleish’ work is unscientific nonsense. “Andersen is harsh, I don’t know why he’s so harsh. I don’t want to dismiss it completely”, she told Minerva in an interview.

Åsjö does not consider the article to contain conclusive evidence that the novel coronavirus has a lab origin, but adds that she considers the article to contain “interesting findings”. She is herself critical of some of the arguments presented in Andersen’s own article on the origin of the virus.

In particular, Åsjö is interested in Sørensen’s and Dalgleish’ findings concerning properties of a swine corona virus detected in connection with an outbreak among piglets in Guandong in 2016–2017, and its possible significance for the present SARS-CoV-2 virus. So far, the controversy seems to resemble other controversies between academics who rarely hesitate to describe rivalling theories in the harshest possible terms. Indeed, Sørensen and Dalgleish originally intended to publish their arguments as a stark critique of the article by Andersen et al in Nature and what they describe “as puzzling errors in their use of evidence”.

Self-confident scientists and strict journals

With this aim, Angus Dalgleish wrote a letter to the editor in Nature on April 2, requesting that journal to publish an earlier version of these arguments.

This article was rejected by Nature five days later, on April 7. Announcing the rejection, João Monteiro, chief editor in Nature Medicine, wrote to Dalgleish:


First rejection from Nature Medicine

“While we appreciate that the points you have raised extend the discussion about the origin of SARS-CoV2 further our opinion is that the content complements other viewpoints that have been considered and published elsewhere, and therefore would be as appropriate for publication in the specialized literature. Please note that this is not a criticism regarding the importance of the matter or the quality of your analyses, but rather an editorial assessment of priority for publication, in a time when there are many pressing issues of public health and clinical interest that take precedence for publication in Nature Medicine, and limited space in the journal.”


Monteiro ended the email by encouraging Dalgleish to post his comments in one of “the accepted preprint repositories so that it remains visible and adds to the discussion about the origin of the virus.”

A clearly angered Dalgleish then wrote a response stating: “Thank you for your extraordinarily unhelpful replies. We can only conclude that the Nature editorial team does not understand that there is no scientific issue in the world at present more important than establishing with scientific precision the aetiology of the Covid-19 virus.”

After the first rejection by Nature, the authors approached another premier journal, Journal of Virology. However, by April 20, the first version of the paper had been rejected there as well. A few days later, this version of the paper was put to death by a rejection from bioRxiv, a non-peer-reviewed preprint repository. The stated reason for rejection was that the format of the paper did not conform to a normal, full research paper, with sections such as "Methods" and "Results".


The first iteration of rejections thus seem to fit into a typical pattern: Scientists with overconfidence not only in the quality of their own research, but also its relevance and significance, encountering journals with strict guidelines for format, each with its own mission and focus, and not very patient with professors that flaunt formal requirements.

Still, it seems that the actual arguments put forward might not have been properly evaluated, or could not be properly evaluated in this setting. And the findings, if correct, would seem to merit some sort of scientific attention. How to proceed?

A publication and new rejections

After the initial round of rejections, the authors made several revisions to their original article, with the arguments sectioned into separate articles. The first article –- an analysis of the novel coronavirus, for the purpose of vaccine design, without making the argument that the virus is engineered –- was published June 2 in the Quarterly Reviews of Biophysics Discovery which is one of the top peer-reviewed science journals in the world.

Having achieved this publication, and presumably regained confidence that the scientific quality of the work was all right, Sørensen and Dalgleish again reached out to several of the world’s most prestigious scientific journals. Now they wanted to publish the second article, which builds on the first, already accepted article, and presents their arguments for why the coronavirus is of a non-natural origin.

However this article was again rejected by Nature on June 24 – without being sent out to peer review. The rejection, written by Senior Editor Clare Thomas, states:

Second rejection from Nature Medicine

It is our policy to decline a substantial proportion of manuscripts without sending them to referees so that they may be sent elsewhere without further delay. In making this decision, we are not questioning the technical quality or validity of your findings, or their value to others working in this area, only assessing the suitability of the study based on the editorial criteria of the journal. In this case, we do not believe that the work represents a development of sufficient scientific impact such that it might merit publication in Nature. We therefore feel that the study would find a more suitable audience in another journal.


On July 1, Sørensen and his colleagues therefore challenged Science, another scientific journal to publish his article. Arguing for the publication of the article Sørensen wrote in an e-mail to editor Professor Holden Thorp:

“Now that Dr. Tedros Adhanom Ghebreyesus has indicated that WHO will pursue a long-overdue inquiry into the aetiology of the SARS-CoV-2 virus, which we welcome, we hope that you will support the very necessary debate that is now breaking in a second wave, following the publication of our vaccine. We are aware of significant responsible mainstream media interventions that are imminent. We are glad that this important question will now be addressed where it should be, in mainstream media and science journals, and not left to internet speculations, some of which have been both uninformed and therefore unhelpful, in our view.”

However, Sørensen was rebuffed also by Science the very next day. In an email to Sørensen, Professor Throp wrote that the article was unfit for publishing in Science, due to the fact that it criticizes work published in another journal.

Rejection from Science

Dr. Sorenson,

Thank you for your interest. We do not publish papers that are critiques of works in other journals, so we cannot consider something along these lines.

Holden

Holden Thorp

Editor-in-Chief


On the rejections from the scientific journals co-author Angus Dalgleish told Sky News: “I thought the whole point of a scientific journal was that you put forward some speculation and you opened it up to debate”, said Professor Dalgleish.

Agree or disagree with Dalgleish’s description of what a scientific journal does, the new round of rejections complicate the picture from the first round. A major part of the argument was accepted by a respectable journal -– the one that didn’t spell out the implications for the origin of the virus. The article that did spell it out, was now rejected twice, without peer review, and the second rejection on purely formal grounds that the authors vehemently contest, arguing that the paper in its current form is not first and foremost a critique of the Andersen et al. paper.

Minerva has asked both Nature and Science to elaborate on the reasons for why the articles by Sørensen and his co-authors have been rejected. Both Science and Nature have declined to comment on the specific rejection of the article as they view this information as confidential. However, Executive Director of the Science Press Package Meagan Phelan, replied that “Science receives upwards of 11,000 manuscripts per year, and the acceptance rate is 6%, so the vast majority of papers are rejected for one reason or another. Science’s acceptance rate for COVID-19-related submissions is even lower, at 4%. The journal continues to receive an exceptionally high volume of COVID-19-related submissions each week.”

At press time, the second article is still in search of a scientific journal willing to publish – or, at least, to subject it to peer review.

Correction: The name Quarterly Reviews of Biophysics has been changed to Quarterly Reviews of Biophysics Discovery
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The evidence which suggests that this is no naturally evolved virus
by Aksel Fridstrøm
July 13, 2020 - 16:47

In the article “The Evidence which Suggests that This Is No Naturally Evolved Virus” by Sørensen, Dalgleish and Susrud, uploaded by Minerva today, Sørensen and his co-authors present several arguments for why they consider a non-natural origin for the novel coronavirus to be the most logical explanation on how the virus evolved.

It is observations on the spike protein of the Sars-Cov-2 virus that leads Sørensen and his co-authors to believe that the virus has originated in a laboratory.

FACTBOX – Spike Protein

A spike protein is a part of the virus attached to the surface of the virus. The spike protein is used by the virus when it enters cells, enabling it to stick in humans. The properties of the spike determine which receptors a virus can utilise and thus which cells the virus can enter to create illness.


“There are several factors that point towards this”, Sørensen told Minerva in an interview last week. “Firstly, this part of the virus is very stable; it mutates very little. That points to this virus as a fully developed, almost perfected virus for infecting humans.

“Secondly, this indicates that the structure of the virus cannot have evolved naturally. When we compare the novel coronavirus with the one that caused SARS, we see that there are altogether six inserts in this virus that stand out compared to other known SARS viruses”, he goes on explaining.

Sørensen says that several of these changes in the virus are unique, and that they do not exist in other known SARS coronaviruses.

“Four of these six changes have the property that they are suited to infect humans. This kind of aggregation of a type of property can be done simply in a laboratory, and helps to substantiate such an origin”, Sørensen argues.

Sørensen was also quoted saying that he is quite confident that the virus originated in a laboratory. “I think it’s more than 90 percent certain. It’s at least a far more probable explanation than it having developed this way in nature”, Sørensen said.

Sørensen also highlights other data than those related to the virus’ properties:

“The properties that we now see in the virus, we have yet to discover anywhere in nature. We know that these properties make the virus very infectious, so if it came from nature, there should also be many animals infected with this, but we have still not been able to trace the virus in nature”, Sørensen also elaborated in last week's interview.


Chimera

In the article Sørensen and his co-authors add additional context to how they believe the virus evolved through experiments in laboratories.

The authors do this by pointing to earlier and open articles by Chinese and American researchers, where the researchers demonstrate and discuss how they have manipulated new chimeraviruses into existence, with SARS-coronavirus as a starting point.

FACTBOX – Chimeravirus

Chimeravirus is defined by U.S. Department of Agriculture's Animal and Plant Health Inspection Service as a hybrid micro-organism which is created by combining fragments from two or more micro-organisms where at least one of the two fragments contain the necessary genes for replication.


The word chimera derives from Greek mythology and refers to a fable being which was a third dragon, a third lion and a third goat.

Sørensen and his co-authors point to four different research projects where the chronology of the creation of a new chimeravirus is documented.

The first of these is the research project led by the world-famous Chinese scientist Dr. Zheng-Li Shi and her colleagues at Wuhan Virology Institute in 2008, which “successfully demonstrated technical capabilities to interchange RBD’s between bat SARS-like and human SARS viruses”.

These findings made the exchange of properties between SARS-coronavirus possible, Sørensen and his co-authors argue.


Furthermore, Sørensen’s article points to the fact that Wuhan’s Virology Institute again in 2010 took part in gain-of-function experiments with international collaborators, where SARS-coronavirus was provided with additional properties that increase the virus’s ability to infect humans: “In 2010 scientists from the ‘Special Viruses’ section of the Wuhan Institute of Virology were engaged in ‘gain of function’ experiments, jointly with international collaborators, to increase SARS-CoV infectiousness for humans. They used an HIV pseudovirus to express seven bat ACE2 receptors and compared their binding properties to human ACE2 receptors in order to pick the best for further optimizing a SARS-like coronavirus’s ability to bind to human cells”, they write.


FACTBOX – gain-of-function-research

Gain-of-function studies are according to the US Department Health and Human Services research which involves increasing the capacity of a pathogen to cause illness. The method is controversial because it can also risk new viruses leaking out of laboratories and into the population.

In the period 2014 to 2018 this type of research was prohibited in the US, but in December 2017 American authorities announced that these kinds of studies would again be allowed.


Chimerica

In order to build further on this research, Shi and her colleagues sought help from American researchers.

“The Chinese originally lacked the technology and competence to grow and measure the development of the virus”, Sørensen argues.

However, according to Sørensen, Shi and her colleagues received help from the University of North Carolina at Chapel Hill in the US, where a human cell culture was made available for further research on SARS-coronavirus.

In the article, Sørensen and his co-authors write: “In 2015 scientists from the ‘Special Viruses’ section of the Wuhan Institute of Virology were engaged in ‘gain of function’ experiments jointly with a majority team from the University of North Carolina Chapel Hill. Together, they manipulated bat viruses to create a mouse adapted chimeric virus SHC014-MA15 which binds to and can proliferate on human upper airway cells (2B4 Calu-3 – a cell line contributed by Chapel Hill).”

Sørensen and his co-authors write that this work created “a chimeric virus with very high infectivity potential targeted to the human upper respiratory tract” and that what is being described is “in fact, precisely SARS-CoV-2 properties”, which is the virus that causes Covid-19.

Sørensen and his co-authors writes that “the 2015 authors were well aware that the chimeric virus which they had created was very dangerous because they discussed this fact”
, but also explains that the creation of the chimeric virus of increased pathogenicity was not intentional. “In vivo experiments at Chapel Hill replicated the chimeric virus in mouse lung which showed significant pathogenesis which was the opposite of what the team had expected (“the creation of chimeric viruses like SHC014-MA15 was not expected to increase pathogenicity”).

The chimeric virus SHC014-MA15 that was created as a part of the collaboration between the Wuhan Institute of Virology and University of North Carolina at Chapel Hill is however according to an article published Shan-Lu Liu et al still different from the Sars-Cov-2 virus with a “divergence in the genetic sequence of this construct with the new SARS-CoV-2 (>5,000 nucleotides)”, Shan-Lu Liu writes.

Professor Kristian Andersen at the department of immunology and microbiology at Scripps Research again refers to the study conducted by Shan-Lu Liu when he writes that “the genetic data irrefutably show that SARS-CoV-2 is not derived from any previously used virus backbone”.

Sørensen and his co-authors is however not convinced that the divergence between the chimeric SHC014-MA15 virus created in 2015 and the novel coronavirus Sars-Cov-2 is enough to eliminate the possibility of Sars-Cov-2 being another chimeric virus that builds on this research.

To establish a connection between the chimeric viruses engineered by the Wuhan Institute of Virology and the Sars-CoV-2 virus Sørensen and his co-authors points to events back in 2016 when a new coronavirus started to infect pigs in China. This disease named SADS ended up killing approximately 25,000 piglets. The epidemic was investigated by the researcher at the Wuhan Institute of Virology, and tested against all known receptors used by coronaviruses, but none of these worked.

Sørensen and his co-authors therefore draws the conclusion that “SADS is a CoV infection utilising new tissue-specific binding domains”, and argues that the Sars-CoV-2 coronavirus has attained directly or indirectly properties from the SADS virus that makes it possible for the virus to use new receptors to attach to human cells in the upper airways.

Hence the evolution of the Sars-Cov-2 virus is summarized by Sørensen and his co-authors as follows: “In 2008, Dr Zheng-Li Si and WIV colleagues successfully demonstrated technical capabilities to interchange RBD’s between bat SARS-like and human SARS viruses. Building upon this, the 2010 work (Hou et al, 2010) perfected the ability to express receptors on human cells. On these foundations, the central Gain of Function work that underpins the functionalities of SARS-CoV-2 took place, carrying the WIV spike and plasmid materials to bond successfully to a UNC Chapel Hill human epithelial cell-line.

This work produced a highly infectious chimeric virus optimised to the human upper respiratory tract. In convergent support of this hypothesis, both Lu and Jia have now, in January and April 2020, shown that SARS-CoV-2 has a bat SARS-like backbone but is carrying an RBD from a human SARS and Zhan et al have, like us, noted unusual adaption to humans from the first isolate.

In the 2015 Chapel Hill work it was only ACE2 receptors that were discussed. However, in 2018 Zhou P. et al demonstrated capabilities to clone other receptors like APN and DPP4 and to test and compare these against the (intestine) tissue specific SADS-CoV identified. Then, in the 2019-20 Covid-19 pandemic, profuse symptoms indicating compromise of the bitter/sweet receptors are reported. Taken all together, this implies that by employing insights gained after 2015, as just deduced, a further optimization of the 2015 chimeric virus for additional binding to receptors/co-receptors such as bitter/sweet specific upper airway epithelia receptors occurred. That would help to explain the otherwise puzzling high infectivity and pathology associated with SARS-CoV-2 and hence also help to explain the social epidemiology of its spread”.


Thinking the unthinkable

The release of a potential pandemic pathogen from a laboratory is by many viewed as a too catastrophic event to even be considered.

However many scientists now argue that it has already happened.
In 1977 the H1N1 influenza virus caused an epidemic in the Soviet Union and China. This rapidly spreading epidemic was almost entirely restricted to persons younger than 26 years of age. A common explanation for this oddity is that the epidemic was caused by a frozen version of the virus that circulated in the 1950s, and in some way or another escaped laboratory containment.

It is also a known fact that the SARS-coronavirus that caused the SARS epidemic in 2003 has escaped laboratories in South-East Asia on at least four occasions. In 2003 WHO issued a statement calling for increased safety measures in laboratories that handle SARS-coronaviruses highlighting the risk of lab accidents: “The possibility that a SARS outbreak could occur following a laboratory accident is a risk of considerable importance, given the relatively large number of laboratories currently conducting research using the SARS-CoV or retaining specimens from SARS patients. These laboratories currently represent the greatest threat for renewed SARS-CoV transmission through accidental exposure associated with breaches in laboratory biosafety”, the WHO stated.

The laboratory operated by the Wuhan Institute of Virology was however built to adhere to far stricter security protocols than the ones criticized by the WHO back in 2003, and became the first Chinese laboratory that operated at the highest level of biosafety (level 4), when it was inaugurated in 2015.

At the Wuhan Institute of Virology lead scientist Dr. Shi Zhengli ferociously denies any possibility that the Sars-cov-2 virus is a lab escapee. In a rare interview with the Scientific American, Zhengli explains that “she frantically went through her own lab’s records from the past few years to check for any mishandling of experimental materials, especially during disposal. Shi breathed a sigh of relief when the results came back: none of the sequences matched those of the viruses her team had sampled from bat caves”.

“That really took a load off my mind”, she is quoted saying.

Dr. Zhengli has also published the genomic sequence of a new virus that her team had sampled in an abandoned mine shaft seven years ago that shares an overall genome sequence identity of 96.2% with the Sars-Cov-2 virus, the closest match so far according to her article.

The hypothesis that SARS-CoV-2 evolved in the Mojiang miner’s lungs potentially resolves many scientific questions about the origin of the pandemic. But it raises others having to do with why this information has not come to light hitherto. The most obvious of these concern the actions of the Shi lab at the WIV.

Why did the Shi lab not acknowledge the miners’ deaths in any paper describing samples taken from the mine (Ge et al., 2016 and P. Zhou et al., 2020)? Why in the title of the Ge at al. 2016 paper did the Shi lab call it an “abandoned” mine? When they published the sequence of RaTG13 in Feb. 2020, why did the Shi lab provide a new name (RaTG13) for BtCoV/4991 when they had by then cited BtCoV/4991 twice in publications and once in a genome sequence database and when their sequences were from the same sample and 100% identical (P. Zhou et al., 2020)? If it was just a name change, why no acknowledgement of this in their 2020 paper describing RaTG13 (Bengston, 2020)? These strange and unscientific actions have obscured the origins of the closest viral relatives of SARS-CoV-2, viruses that are suspected to have caused a COVID-like illness in 2012 and which may be key to understanding not just the origin of the COVID-19 pandemic but the future behaviour of SARS-CoV-2.

These are not the only questionable actions associated with the provenance of samples from the mine. There were five scientific publications that very early in the pandemic reported whole genome sequences for SARS-CoV-2 (Chan et al., 2020; Chen et al., 2020; Wu et al., 2020; P. Zhou et al., 2020; Zhu et al., 2020). Despite three of them having experienced viral evolutionary biologists as authors (George Gao, Zheng-li Shi and Edward Holmes) only one of these (Chen et al., 2020) succeeded in identifying the most closely related viral sequence by far: BtCoV/4991 a viral sequence in the possession of the Shi lab at the WIV that differed from SARS-CoV-2 by just 5 nucleotides.


-- A Proposed Origin for SARS-CoV-2 and the COVID-19 Pandemic, by Jonathan Latham, PhD and Allison Wilson, PhD


However, concerns about the operational safety at the Wuhan Institute of Virology persist. In an article written by Josh Rogin at The Washington Post, Rogin refers to a leak embassy cable sent from the American Embassy in Beijing that raised on concerns about the safety routines at the Wuhan laboratory

“During interactions with scientists at the WIV laboratory, they noted the new lab has a serious shortage of appropriately trained technicians and investigators needed to safely operate this high-containment laboratory”, states the Jan. 19, 2018, cable, which was drafted by two officials from the embassy’s environment, science and health sections who met with the scientists at the Wuhan Institute of Virology.

Two years before the novel coronavirus pandemic upended the world, U.S. Embassy officials visited a Chinese research facility in the city of Wuhan several times and sent two official warnings back to Washington about inadequate safety at the lab, which was conducting risky studies on coronaviruses from bats. The cables have fueled discussions inside the U.S. government about whether this or another Wuhan lab was the source of the virus — even though conclusive proof has yet to emerge.

In January 2018, the U.S. Embassy in Beijing took the unusual step of repeatedly sending U.S. science diplomats to the Wuhan Institute of Virology (WIV), which had in 2015 become China’s first laboratory to achieve the highest level of international bioresearch safety (known as BSL-4). WIV issued a news release in English about the last of these visits, which occurred on March 27, 2018. The U.S. delegation was led by Jamison Fouss, the consul general in Wuhan, and Rick Switzer, the embassy’s counselor of environment, science, technology and health. Last week, WIV erased that statement from its website, though it remains archived on the Internet.

What the U.S. officials learned during their visits concerned them so much that they dispatched two diplomatic cables categorized as Sensitive But Unclassified back to Washington. The cables warned about safety and management weaknesses at the WIV lab and proposed more attention and help. The first cable, which I obtained, also warns that the lab’s work on bat coronaviruses and their potential human transmission represented a risk of a new SARS-like pandemic.

“During interactions with scientists at the WIV laboratory, they noted the new lab has a serious shortage of appropriately trained technicians and investigators needed to safely operate this high-containment laboratory,” states the Jan. 19, 2018, cable, which was drafted by two officials from the embassy’s environment, science and health sections who met with the WIV scientists. (The State Department declined to comment on this and other details of the story.)

The Chinese researchers at WIV were receiving assistance from the Galveston National Laboratory at the University of Texas Medical Branch and other U.S. organizations, but the Chinese requested additional help. The cables argued that the United States should give the Wuhan lab further support, mainly because its research on bat coronaviruses was important but also dangerous.

As the cable noted, the U.S. visitors met with Shi Zhengli, the head of the research project, who had been publishing studies related to bat coronaviruses for many years. In November 2017, just before the U.S. officials’ visit, Shi’s team had published research showing that horseshoe bats they had collected from a cave in Yunnan province were very likely from the same bat population that spawned the SARS coronavirus in 2003.

“Most importantly,” the cable states, “the researchers also showed that various SARS-like coronaviruses can interact with ACE2, the human receptor identified for SARS-coronavirus. This finding strongly suggests that SARS-like coronaviruses from bats can be transmitted to humans to cause SARS-like diseases. From a public health perspective, this makes the continued surveillance of SARS-like coronaviruses in bats and study of the animal-human interface critical to future emerging coronavirus outbreak prediction and prevention.”

The research was designed to prevent the next SARS-like pandemic by anticipating how it might emerge. But even in 2015, other scientists questioned whether Shi’s team was taking unnecessary risks. In October 2014, the U.S. government had imposed a moratorium on funding of any research that makes a virus more deadly or contagious, known as “gain-of-function” experiments.


As many have pointed out, there is no evidence that the virus now plaguing the world was engineered; scientists largely agree it came from animals. But that is not the same as saying it didn’t come from the lab, which spent years testing bat coronaviruses in animals, said Xiao Qiang, a research scientist at the School of Information at the University of California at Berkeley.

“The cable tells us that there have long been concerns about the possibility of the threat to public health that came from this lab’s research, if it was not being adequately conducted and protected,” he said.

There are similar concerns about the nearby Wuhan Center for Disease Control and Prevention lab, which operates at biosecurity level 2, a level significantly less secure than the level-4 standard claimed by the Wuhan Insititute of Virology lab, Xiao said. That’s important because the Chinese government still refuses to answer basic questions about the origin of the novel coronavirus while suppressing any attempts to examine whether either lab was involved.

Sources familiar with the cables said they were meant to sound an alarm about the grave safety concerns at the WIV lab, especially regarding its work with bat coronaviruses. The embassy officials were calling for more U.S. attention to this lab and more support for it, to help it fix its problems.

“The cable was a warning shot,” one U.S. official said. “They were begging people to pay attention to what was going on.”

No extra assistance to the labs was provided by the U.S. government in response to these cables. The cables began to circulate again inside the administration over the past two months as officials debated whether the lab could be the origin of the pandemic and what the implications would be for the U.S. pandemic response and relations with China.

Inside the Trump administration, many national security officials have long suspected either the WIV or the Wuhan Center for Disease Control and Prevention lab was the source of the novel coronavirus outbreak. According to the New York Times, the intelligence community has provided no evidence to confirm this. But one senior administration official told me that the cables provide one more piece of evidence to support the possibility that the pandemic is the result of a lab accident in Wuhan.

“The idea that it was just a totally natural occurrence is circumstantial. The evidence it leaked from the lab is circumstantial. Right now, the ledger on the side of it leaking from the lab is packed with bullet points and there’s almost nothing on the other side,” the official said.


As my colleague David Ignatius noted, the Chinese government’s original story — that the virus emerged from a seafood market in Wuhan — is shaky. Research by Chinese experts published in the Lancet in January showed the first known patient, identified on Dec. 1, had no connection to the market, nor did more than one-third of the cases in the first large cluster. Also, the market didn’t sell bats.

Shi and other WIV researchers have categorically denied this lab was the origin for the novel coronavirus. On Feb. 3, her team was the first to publicly report the virus known as 2019-nCoV was a bat-derived coronavirus.

The Chinese government, meanwhile, has put a total lockdown on information related to the virus origins. Beijing has yet to provide U.S. experts with samples of the novel coronavirus collected from the earliest cases. The Shanghai lab that published the novel coronavirus genome on Jan. 11 was quickly shut down by authorities for “rectification.” Several of the doctors and journalists who reported on the spread early on have disappeared.

On Feb. 14, Chinese President Xi Jinping called for a new biosecurity law to be accelerated. On Wednesday, CNN reported the Chinese government has placed severe restrictions requiring approval before any research institution publishes anything on the origin of the novel coronavirus.

The origin story is not just about blame. It’s crucial to understanding how the novel coronavirus pandemic started because that informs how to prevent the next one. The Chinese government must be transparent and answer the questions about the Wuhan labs because they are vital to our scientific understanding of the virus, said Xiao.

We don’t know whether the novel coronavirus originated in the Wuhan lab, but the cable pointed to the danger there and increases the impetus to find out, he said.

“I don’t think it’s a conspiracy theory. I think it’s a legitimate question that needs to be investigated and answered,” he said. “To understand exactly how this originated is critical knowledge for preventing this from happening in the future.”


-- State Department cables warned of safety issues at Wuhan lab studying bat coronaviruses, by Josh Rogin, The Washington Post, April 14, 2020


WHO to investigate

On the 18-19th of May the WHO conducted its 73rd general assembly, and passed a resolution that “requests the Director-General, working with other organizations and countries, to identify the zoonotic source of the virus and the route of introduction to the human population”.

Sørensen and his co-authors argue that this investigation should not be limited to examining the origin of the Sars-Cov-2 virus solely based on the assumption of a zoonotic source.


The WHO investigation commenced on the 7th of July.
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Laboratory Escapes and “Self-fulfilling prophecy” Epidemics
by Martin Furmanski MD
Scientist’s Working Group on Chemical and Biologic Weapons
Center for Arms Control and Nonproliferation
February 17, 2014



Introduction

The danger to world or regional public health from the escape from microbiology laboratories of pathogens capable of causing pandemics, or Potentially Pandemic Pathogens (PPPs) has been the subject of considerable discussion1,2,3,4 including mathematical modeling of the probability and impact of such escapes5. The risk of such releases has generally been determined from estimates of laboratory infections that are often incomplete, except for the recent 2013 Centers for Disease Control (CDC) report6, which is a significant source of recent data on escapes from undetected and unreported laboratory-acquired infections (LAIs).

This paper presents an historical review of outbreaks of PPPs or similarly transmissible pathogens that occurred from presumably well-funded and supervised nationally supported laboratories. It should be emphasized that these examples are only the “tip of the iceberg” because they represent laboratory accidents that have actually caused illness outside of the laboratory in the general public environment. The list of laboratory workers who have contracted potentially contagious infections in microbiology labs but did not start community outbreaks is much, much longer. The examples here are not “near misses;” these escapes caused real-world outbreaks.

Methods of pathogen identification

Modern genetic analysis allows pathogens to be identified, and given a sufficient catalog of isolates of the same pathogen, it is possible to determine if two specimens are identical or very closely related. Because all pathogens that are circulating in the environment show genetic changes over time, one can date the time the pathogen circulated. For instance, for 20th century human and swine influenza viruses beginning in the 1930s, one can generally place a virus to a particular year. With modern rapid genomic analysis outbreaks can be traced with considerable accuracy: for instance the 2009 pandemic pH1N1 influenza outbreak has been analyzed with confidence limits of branchpoints in its first wave defined within days or weeks, and individual transmission chains can be identified7.

Example #1: British smallpox escapes, 1966, 1972, 1978

The WHO’s successful effort to eradicate natural transmission of smallpox in the 1970s highlighted the risk that virology laboratories posed as a source of epidemics. This was clearly demonstrated in the United Kingdom, where from 1963-1978 only 4 cases of smallpox (with no deaths) were reported from smallpox endemic areas, while during the same period at least 80 cases and 3 deaths were the result of three separate escapes of the smallpox virus from two different accredited smallpox laboratories.8 Much of the current policy and practice in biosafety and biocontainment of dangerous pathogens can be traced to the political and professional reaction to these outbreaks.

The UK became a sensitive test system for smallpox laboratory escapes because it ended compulsory smallpox vaccination in 1946. Public sentiment in the UK had always included significant resistance to and apathy towards vaccination, and so by the mid 1960s and through the 1970s a large proportion of children and young adults had never been vaccinated, and many older persons were never re-vaccinated after initial childhood or military vaccinations. Thus the protective herd immunity in the general public, which earlier rendered impotent any laboratory escapes, disappeared. At the same time, the considerable volume of travel and immigration from smallpox endemic areas of Africa and the Indian subcontinent meant that surveillance for imported smallpox cases was required. UK maintained several smallpox laboratories at medical schools for both research and to support clinical diagnosis.

The first laboratory outbreak to be recognized began in March 1972, in a 23 year old laboratory assistant at the London School of Hygiene and Tropical Medicine, who had observed harvesting of live smallpox virus from eggs. This had been done on an open bench, as was routine, the laboratory having no isolation cabinets at that time. Before she was placed in isolation, she infected two visitors to a patient in an adjacent bed, both of whom died. They in turn infected a nurse, who survived9.

The recognition of this laboratory escape resulted in several investigations, which led to the establishment of guidelines for laboratories handling smallpox and other dangerous pathogens. These recommendations included handling dangerous pathogens in biological safety cabinets only in certain dedicated rooms by specifically trained and designated personnel. Also guidelines were issued for isolation with dedicated gowns and gloves, and the establishment of proper ventilation facilities to maintain negative pressure in these rooms and cabinets. These recommendations are the direct precursors to the current Biosafety Laboratory (BSL) level protocols.


By 1977 the natural chain of smallpox transmission had been interrupted, and the WHO was in the process of reducing the number of laboratories holding smallpox virus. In August of 1978 a 40 year old medical photographer at Birmingham Medical School developed smallpox, and died. She infected her mother, who survived. She worked in a studio and darkroom that was immediately above the smallpox laboratory at Birmingham Medical School. Investigation revealed that although the long established laboratory had been inspected and approved to handle smallpox virus, it did not have sufficient facilities to meet the new biocontainment requirements, and was scheduled to be decommissioned at the end of 1978. Moreover, work on smallpox had accelerated substantially in order to complete existing projects before the closing, and work with smallpox was performed by laboratory personnel who did not receive appropriate training and supervision, and appropriate isolation practices were frequently violated. The most likely route of exposure of the Medical Photographer was by transport of infectious aerosols generated by a centrifuge through building ventilation ducts that were improperly sealed and allowed aerosols to be delivered to one of the Photographer’s working spaces. Laboratory notebooks and the photographer’s work logs indicated that the strain infecting the photographer was handled in the laboratory on the same days that the photographer worked in the potentially contaminated workspace, on dates consistent with the photographer’s calculated exposure date. Dr Henry Bedson, a world renowned smallpox investigator who was responsible for the Birmingham laboratory, committed suicide as a result of the outbreak (Shooter 1980).

The 1978 investigation re-examined a 1966 smallpox outbreak, which in retrospect was strikingly similar to the 1978 outbreak. The earliest case identified in 1966 was in a medical photographer who worked at Birmingham Medical School in the same facility as the 1978 case. This outbreak was caused by a low-virulence strain of smallpox (variola minor), and it caused at least 72 cases of smallpox from February to August 1966, spread through the midlands of Britain, and Wales. The vast majority of cases were in unvaccinated children or young adults. There were no deaths. Retrospective review again revealed variola minor had been manipulated in the smallpox laboratory at a time appropriate to cause the infection in the photographer working a floor above.


Example #2: The “re-emergence” of H1N1 human influenza in 1977.

Human influenza H1N1 viruses appeared with the 1918 pandemic, and persisted, slowing accumulating small changes in its genome (with a major change in 1947), until the H2N2 “Asian” flu appeared in 1957, causing a worldwide pandemic. H1N1 influenza virus then apparently became extinct, and was not isolated for 20 years. In 1969 the “Hong Kong” H3N2 virus replaced the H2N2 virus, and is still circulating.

In September 1977 an H1N1 influenza virus was isolated from human infections in the Far East region of the Soviet Union, and in early 1978 the Chinese reported they had isolated H1N1 virus in May of 1977 in northeast China adjacent to the Soviet outbreak1011. Using the early genetic tools available at the time, the 1977 H1N1 virus was found to be closely related to H1N1 human influenza viruses circulating in 1949-1950, but not to those circulating earlier or later12, 13.

The 1977 H1N1 flu virus rapidly spread worldwide, in a pandemic that was restricted largely to people under ~ 21 years of age. Older persons had been exposed to related H1N1 viruses prior to 1957, and carried substantial immunity. Mercifully, the “re-emergent” H1N1 virus was not very virulent. Although illness was widespread, affecting 20-70% of those under 20 years of age in school or military camp outbreaks in the first year14, deaths were few.
Many asymptomatic infections were detected by serology (Kung 1978).

The appearance of this “time-traveling throwback” puzzled virologists, because no similar examples had previously been identified in influenza or other similar viruses. Initially escape of a virus kept in storage from c1950 from a virology lab was discussed, but such a laboratory accident was denied by Chinese and Soviet virologists (Kung 1978, Beveridge 1978). Western virologists quietly let the matter of a laboratory escape origin for the 1977 H1N1 virus drop from discussion, out of an abundance of scientific caution, and also out of an eagerness not to offend the Russian and Chinese scientists, whose early gestures of cooperation in worldwide influenza surveillance system were very important to foster, because such cooperation would allow tracking influenza globally.

Discussions of the origins of the 1977 H1N1 gave rise to hypotheses of natural “biological stasis” or viral latency in an undefined animal. Experimental investigations of possible transmission of human H1N1 viruses in avians were pursued, but with minimal success and no demonstration of persistent avian transmission15, nor were human viruses identified in avians in very extensive subsequent surveys. The ambiguous term “frozen evolution” was coined, allowing for the freezing to be biologically functional, metaphorical, refrigerative, or natural.

A 2006 paper16 claimed to have isolated H1N1 influenza virus RNA from ice and meltwater from Siberian lakes that were frequented by migratory birds. Since migratory birds naturally carry and shed a wide variety of influenza viruses, and since year to year variations in the amount of thawing of lake ice might allow influenza viruses shed from the migratory birds to remain physically frozen for a number of years, the paper stated this might be the mechanism for the re-emergence of the 1977 H1N1 flu. It emphasized the 1977 H1N1 link because the RNA sequences it reported isolating from the lakes were closely related to sequences of three H1N1 reference viruses that it characterized as being of avian origin that circulated in the late 1960s.

Problems soon arose with this paper, however. The authors issued a correction17 in 2007 indicating the H1N1 reference strains originally characterized as avian and from the 1960s were in fact of human origin, and dated from the 1930s. A paper highly critical of the 2006 Siberian Lake paper was published in 2008 18, presenting strong evidence that the reported isolation of influenza RNA from nature was the result of contamination in the laboratory by the standard reference strain of human H1N1 virus (isolated in 1933) that was used as a positive control in that laboratory.

Presently, with detailed sophisticated genomic analysis available, and with 32 years of circulation of the 1977 H1N1 virus available for study, no evidence of natural genomic stasis has been identified. It has become clear that its appearance in 1977 was almost certainly due to escape from a virology lab of a virus sample that had been frozen since c1950. Only since 2008 have virologists actually begun to make the suggestion of a probable laboratory release in scientific papers: “The reemergence in 1977 is unexplained and probably represents reintroduction to humans from a laboratory source19,” and “…little A/H1N1 evolution is evident over the twenty-year period of the virus’s global disappearance, supporting earlier suggestions that this subtype was most likely accidentally reintroduced into human circulation from a laboratory environment20.” It should be noted that this paper calculates the 1977 H1N1 virus had been circulating for 1 year before it was reported, so that geographic origin cannot be stated with certainty.

Only since 2009-2010 did major papers begin to state directly the 1977 emergence of H1N1 influenza was a laboratory related release: “The most famous case of a released laboratory strain is the re-emergent H1N1 influenza A virus which was first observed in China in May of 1977 and in Russia shortly thereafter21.” The paper made this statement in part because the continued “agnostic” approach to the 1977 re-emergence introduced unacceptable errors in calculating the genomic divergence dates for influenza virus strains.

Public awareness of the 1977 H1N1 pandemic and its likely laboratory origins has been virtually absent. Virologists and public health officials with the appropriate sophistication were quickly aware that a laboratory release was the most likely origin, but they were content not to publicize this, aware that such embarrassing allegations would likely end the then nascent cooperation of Russian and Chinese virologists, which was vital to worldwide influenza surveillance. An abundance of caution in making such suggestions was also in their own self-interest. The 1976 “swine flu” alarm and subsequent immunization program that proved to be unneeded caused 532 cases of Guillain-Barre syndrome and 32 deaths. It was widely considered a misadventure, and had severely damaged the public and political credibility of the virology and public health communities. An acknowledgement of a pandemic originating from their laboratories would have only worsened it. The most plausible reason for a Chinese or Russian laboratory to thaw out and begin growing a c1950 H1N1 virus in 1976-77 was as a response to the US 1976 “swine flu” program, which resulted in a program to immunize the entire US population against H1N1 influenza virus. It was clearly a rational response for other countries with virology capabilities to explore making their own H1N1 vaccines. Thawing available frozen stocks of virus was necessary, because H1N1 was no longer circulating. Modern commentators have begun to articulate this connection between the 1976 Swine flu immunization program and the 1977 H1N1 re-emergence:


“Perhaps an even more serious consequence [of the 1976 swine flu episode] was the accidental release of human-adapted influenza A (H1N1) virus from a research study, with subsequent resurrection and global spread of this previously extinct virus, leading to what could be regarded as a ‘self-fulfilling prophecy’ epidemic.” (Zimmer 2009)


The speculation that the 1977 release may have been related to H1N1 vaccine research is supported by the observation that in the initial outbreaks in China, nine of the ten viral isolates expressed “temperature sensitivity” (Kung 1978). Temperature sensitivity normally an uncommon trait, but one that was in the 1970s (and still is) a fundamental trait for making live attenuated influenza vaccines. Temperature sensitivity generally occurs only after a series of substantial laboratory manipulations and selections. Interestingly, further investigation indicated the circulating strains in 1977-78 were often comprised of mixed temperature-sensitive and normal components, and that temperature sensitivity apparently disappeared from the post-1978 H1N1 lineage rapidly22. Escape of a mid-protocol population of H1N1 virus undergoing laboratory selection for temperature sensitive mutants would provide such a mixed population. In 1976-77 laboratory personnel in their late teens or early 20s would not have been exposed to pre-1957 H1N1 influenza viruses, and been susceptible to laboratory infections. The low severity of the 1977 pandemic might be in part due to the temperature sensitivity of the virus, a trait that limits virus replication in pulmonary tissues.

Example #3 Venezuelan Equine Encephalitis in 1995

Venezuelan Equine Encephalitis (VEE) is a viral disease transmitted by mosquitoes that intermittently erupts in regional or continental-scale outbreaks in the Western Hemisphere that involve equines (horses, donkeys and mules), termed epizootics, and often with concurrent epidemics among humans. The disease in equines creates high fever and severe neurological symptoms (colloquially termed “pesta loca” [crazy plague] in Spanish, or “blind staggers” in English) and a high, 19-83% fatality rate. In humans symptoms can vary from asymptomatic to a mild influenza-like febrile illness to a severe acute incapacitating febrile illness often with neurological symptoms (headache, depression, incoordination, mental clouding, epileptic seizures). Though its severity varies between outbreaks, VEE in humans may be fatal (up to ~5%) or, particularly in children, leave permanent neurological disability (epilepsy, paralysis, mental retardation) in 4 to 14% of clinical cases. In humans and equines miscarriages and stillbirths are increased.

Outbreaks typically occur in South America, though the 1969-71 continental-scale epizootic/epidemic reached from Central America through Mexico to Texas. VEE viruses are classified by their surface antigens, with the types causing large scale epizootics and epidemics being classed as type IAB and IC (termed epizootic strains), and types causing only sporadic human or equine disease in localized areas falling into types ID, IE, IF and II through VI (termed enzootic strains).

With modern genomic investigations available since the mid 1990s, programs of surveillance of mosquitoes and wildlife in regions at risk have discovered that in nature the enzootic VEE viruses are maintained by continuous transmission by mosquitoes in small mammals in the tropical and subtropical western hemisphere. The epizootic/epidemic type IAB and IC viruses appear suddenly without evidence of ongoing transmission during the long intervals between major outbreaks23. Moreover, genomic studies indicate that the epizootic types of VEE originate from the enzootic strains, specifically strain ID having given rise to the epizootic/epidemic types IAB and IC through a process of mutation24. VEE virus, like influenza virus shows rapid spontaneous changes in its genome, so that one can determine not only the genetic relatedness but also quantify the chronological distance separating different viral strains.

This is where the elegance of modern viral genomics becomes an embarrassment to virologists. It is clear from the genomics that while the enzootic type ID VEE virus can indeed mutate into the epizootic/epidemic types IAB and IC, it has, in fact, only done this on three occasions: ID to IAB some time in the 1930s and ID to IC in 1963 and 1992. There had been significant outbreaks of VEE every few years from the 1930s to the 1970s, however, and analysis showed that the numerous type IAB outbreaks were essentially matches to the original 1938 IAB VEE isolation that had been used in veterinary vaccines since the late 1930s. The veterinary vaccines had used inactivated (i.e. “killed”) whole virulent viruses. VEE is notoriously hard to inactivate in the lab, and laboratory infections were common. It was clear that many batches of the veterinary VEE vaccines had not been completely inactivated, in which residual infective virus remained.


From 1938 to 1972, the VEE vaccine was causing most of the very outbreaks that it was called upon to control, a vicious cycle indeed, and another example of “self-fulfilling prophecy” outbreaks.

The recognition that inadequately inactivated vaccines caused most VEE outbreaks caused a change in the veterinary vaccine seed virus to an attenuated strain, and VEE outbreaks apparently ceased for 20 years, from 1973 to 1992 25. Then, in 1992 a VEE outbreak in Venezuela occurred which proved to be a IC virus that was shown by genomic studies to have spontaneously arisen from enzootic type ID viruses circulating in the area where it arose, much like what had also occurred in the same area of Venezuela in 1962-64, when ID had mutated to a IC and caused an outbreak. The two IC VEE viruses, from 1962-64 and 1992, were distinct from each other, and arose from different genetic lines of ID viruses. The mystery of how epizootic VEE viruses arise naturally was apparently solved.

However, in 1995 a major VEE epizootic and epidemic hit Venezuela and Colombia, with a type IC virus also the cause. There were at least 10,000 human VEE cases with 11 deaths in Venezuela26 and an estimated 75,000 human cases in Colombia, with 3,000 neurological complications and 300 deaths27. Household attack rates ran 13-57% and VEE virus was isolated from 10 stillborn or miscarried human fetuses28.

Full genomic studies identified the 1995 virus as identical to an 1963 isolate with no sign that this virus had been circulating and the acquiring small genetic mutations indicative of replicating in hosts for 28 years. It was another case of “frozen evolution.”
But it could not be another case of an outbreak caused by a defective inactivated VEE vaccine, because the 1963 type IC VEE virus had never been used to make a vaccine. Possible trans-ovarian transmission in mosquito vectors had been explored previously with negative results29. Suspicion fell on an inadvertent release from a virology lab, either by an unrecognized infection of a lab worker or visitor, or escape of an infected laboratory animal or mosquito. VEE is easily transmitted by the aerosol route during laboratory manipulations, and laboratory infections with VEE are common in unvaccinated persons. In this outbreak there was considerable circumstantial evidence for such a laboratory escape. The 1963 type IC VEE virus was used in an “inactivated” form as a reagent for testing purposes, and this reagent preparation was tested and was found to contain live virus. This reagent was used in the virology laboratory in Venezuela located where the 1995 outbreak first appeared, which was in an area without ongoing circulation of type ID enzootic viruses related to the 1963/1995 IC virus, and an area removed from where de novo IC VEE outbreaks had previously originated. Moreover, a report from this lab of an IC virus isolated from a surveillance mosquito pool in 1983 proved to be identical to the IC antigen strain, indicating a previous laboratory contamination event. The major scientific group working on VEE published a paper in 2001 stating the outbreak most likely was a laboratory escape, though this could not be proven30.

The situation becomes less clear-cut, because in 2005 the same group reported small outbreaks from 2000 and 2003 with multiple isolations of IC virus from equids in Venezuela, this time one identical to the 1995 virus31. Yet another example of “frozen evolution” but during a period when the 1963/1995 IC virus was no longer used widely as a reagent preparation, and it originated in an area with ongoing enzootic transmission of VEE viruses. The VEE working group backed off its earlier conclusion that the 1995 outbreak was likely laboratory mediated, but was unable to propose a natural process for the genomic stasis they reported.

The VEE working group clearly has great expertise, and one must respect their judgment that the 2000 isolations are valid and laboratory circumstances are significantly different than in 1995, so that natural genomic stasis may indeed exist for VEE and is worthy of further investigation. Several proposed mechanisms for genomic stasis for VEE have been proposed and investigated. VEE circulates in a complex ecological pattern, with enzootic transmission involving a variety of mosquito and mammalian hosts, so various theories allowing genomic stasis have been proposed, such as latency in an arthropod line or mammalian host. These have been investigated with multi-year surveys in enzootic and post-epizootic areas, and no definite evidence of persistent epizootic strains have been found in arthropods or small mammals. In addition to the negative surveys, the short lifespans of small mammals and of the potential arthropod hosts preclude viral latency from explaining the 5 or 28 year hiatuses in the appearances of the “frozen” IC epizootic viruses, and no evidence has been found for latency in the longer-lived human and equine hosts. Transovarian “vertical” propagation of viruses in arthropods between mother and progeny has been described with some pathogens in arthropods, and this has been investigated experimentally with VEE in VEE vectors, without positive results32.

It is clear that laboratory strains of VEE virus have a decades-long established habit of re-appearing showing “frozen evolution,” and causing “self-fulfilling prophecy” epidemics. It is clear that escape of laboratory strains of this virus through faulty vaccines has occurred multiple times in the past. Strong circumstantial evidence exists for an inadvertent escape in 1995, and a re-emergence in 2000 is without explanation.

Example 4: SARS laboratory escapes outbreaks after the SARS epidemic

The SARS outbreak of 2002-2003 eventually spread to 29 countries, causing over 8,000 infections and at least 774 deaths. Because many cases were in hospital workers (1707, amounting to 21%), it had the potential to shut down health care services where it struck33. By imposing strict (sometimes draconian) quarantines on exposed persons and isolation of patients, and even more because of good fortune and dedicated (indeed, heroic) medical personnel, it was contained and extinguished by July 2003. Quarantines, closure of factories and travel restrictions caused economic losses estimated at $40 billion worldwide, with an estimated 2.6% GDP loss in China, 1.05% GDP loss in Hong Kong, and 0.15% GDP loss to Canada34.

SARS is particularly dangerous to handle in the laboratory because there is no vaccine, so all laboratory workers are susceptible. It can be transmitted through aerosol/droplet mechanisms: the very large (321 cases) Amoy Gardens outbreak in Hong Kong was traced to infectious aerosols created by turbulent flushing water flow in the sewer lines: this turbulent flow generated aerosols that were sucked back up into numerous adjacent apartments through dry floor drains by negative pressure generated by bathroom exhaust fans! (Abraham 2005).

Moreover, about 5% of SARS patients are “super-spreaders” who pass the infection to many (over 8) secondary cases35. One case (ZZ) spread SARS to directly to 28 persons during one 18-hour hospitalization, before transfer to another hospital, where he infected 93 additional hospital personnel. At a third hospital he infected 23 staff and 19 patients, and at a fourth 20 hospital staff (Abraham 2005). Another super-spreader in Beijing infected at least 59 secondary cases. A super-spreader originally infected by ZZ in China visited Hong Kong but fell ill and remained in his hotel room, but managed to spread SARS to 10 secondary cases whose only associations were using a common elevator or hallway. These Hong Kong hotel exposures were international tourists, however, and were responsible for spreading SARS to Canada, Ireland, the US, Singapore, and Vietnam36. A 72-year old was already ill when he boarded flight CA112 from Hong Kong to Beijing on March 15, after having visited a niece ill with SARS in a Hong Kong hospital. Besides introducing another transmission chain in Beijing, on the two-hour flight he infected 20 other passengers and 2 flight attendants, who spread the disease to Mongolia, Singapore, Taiwan, and re-introduced new infection chains back into Hong Kong37 (Abraham 2005).

The existence of SARS “super-spreaders” makes even a single laboratory infection into a potential pandemic.

SARS has not naturally recurred, but there have been six separate “escapes” from virology labs studying it: one each in Singapore and Taiwan, and in four distinct events at the same laboratory in Beijing.

The first escape was in Singapore in August 2003, in a 27-year-old virology graduate student at the National University of Singapore. He had not worked directly with SARS, but SARS was present in the virology laboratory where he worked with West Nile Virus (WNV). Investigation showed that his preparation of WNV was contaminated with SARS virus, and that this was the likely origin of his infection.
After falling ill on Aug 26, he sought outpatient medical care in several venues, and was admitted to the hospital only on September 3. Fortunately he recovered and there were no secondary cases. Investigation revealed multiple shortcomings in infrastructure, training and observed procedures at the laboratory, and remedial actions were ordered38.

The second escape was in Taiwan in December 2003, when a SARS research scientist fell ill on a return airflight after attending a medical meeting in Singapore Dec 7-10. Although he felt his illness was SARS, he remained at home for 5 days, unwilling to seek medical care because he dreaded bringing disgrace to himself and his institution. He was only persuaded to enter the hospital when his father threatened to commit suicide39. Preliminary investigation implicated a laboratory exposure due to an attempt to decontaminate a bag of leaking biological waste, perhaps without proper protection and against protocol the day before he left for Singapore40. His 74 contacts in Singapore were put under quarantine for ten days, but again, fortunately none developed SARS. An expert committee from WHO investigated the laboratory and its procedures, and recommended improvements41.

This second outbreak further shook the virology communities in Asia, where many labs held and worked on SARS samples. On December 18, 2003 WHO released a new protocol for handling SARS specimens in the post-outbreak period, with special emphasis on reducing risk of and performing surveillance to detect laboratory infections42. Although this protocol was clearly created after the first (Singapore) escape, WHO chose to parse its words to avoid offending members. Perhaps distinguishing between a primary laboratory infection and secondary spread into a community “outbreak,” it chose to treat the risk as hypothetical, stating in the introduction:

“The possibility that a SARS outbreak could occur following a laboratory accident is a risk of considerable importance, given the relatively large number of laboratories currently conducting research using the SARS-CoV or retaining specimens from SARS patients. These laboratories currently represent the greatest threat for renewed SARS-CoV transmission through accidental exposure associated with breaches in laboratory biosafety.”


The hypothetical outbreak was not long in coming.

On April 22, 2004 China reported a suspected case of SARS in a 20-year-old nurse who fell ill April 5 in Beijing. The next day it reported she had nursed a 26-year-old female laboratory researcher who had fallen ill on March 25. Still ill, the researcher had traveled by train to her home in Anhui province where she was nursed by her mother, a physician, who fell ill on April 8 and died April 19. The researcher had worked at the Chinese National Institute of Virology (NIV) in Beijing, which is part of China’s Center for Disease Control (CDC), and which was a major center of SARS research. The investigation at NIV also uncovered an unrelated laboratory infection in a 31-year old male laboratory researcher at the NIV who fell ill on 17 April [43]. The entire NIV institute was closed and all of its 200 employees placed in quarantine in a hotel. Subsequent investigation confirmed these first three cases as SARS, and eventually identified a total of nine cases, in three generations, including health care workers and their family contacts44. Neither of the two primary patients had worked with live SARS virus, and WHO investigators had “serious concerns” regarding biosafety procedures at the NIV45.

Several Chinese and international groups investigated the outbreak at the NIV, and identified in retrospect two additional SARS laboratory infections at the NIV that had previously gone unrecognized and had begun in February 2004 [46]. A joint China CDC and WHO investigation found many shortcomings in biosecurity at the NIV, and traced the specific cause of the outbreak to an inadequately inactivated preparation of SARS virus that was used in general (not biosecure) laboratory areas in the NIV, including the one in which the two primary cases worked. It had not been tested to confirm its safety after inactivation, as it should have been. The WHO also found more general shortcomings in the handling of live SARS virus and a lack of surveillance of laboratory personnel for laboratory infections.

Li Liming, director of the China CDC and his deputy directory, the director of the NIV and his deputy director, and the director of the division where the two index cases worked were removed from their positions and found guilty of negligence in overseeing safety at the institution47. The Chinese government also decided to move the China CDC campus from its position in a residential neighborhood to an area “more remote from downtown,” and to allocate funds for more advanced laboratory equipment and infrastructure48.

Interestingly, the virology community is still reticent to discuss laboratory escapes: despite the considerable alarm these escapes created in the public health community and the participation of US CDC personnel in their investigation, they go unmentioned in the “10 years after” historical review of SARS by the CDC.49

Example 5: Foot and Mouth Disease (FMD) from Pirbright 2007

Foot and Mouth Disease (FMD) is a veterinary disease that affects primarily cloven-hoofed domestic animals (pigs, sheep and cattle). It has been eradicated in North America and most of Europe. It is highly transmissible, capable of spreading through direct contact and even through some prepared meats (sausages, airline food), on boots of farm workers (or tourists’ shoes: that’s why there’s that question “have you visited a farm” on the re-entry customs checklist coming into the USA), and even by aerosol spread.

FMD only occasionally causes a mild disease in humans, though exposed humans can carry the virus for up to three days, potentially an important method of spread. FMD causes a more serious disease in animals. Often fatal in young animals, survivors are stunted and lose their economic value. Adult animals die less often, but fail to gain weight or drop in milk production, and can become carriers. Most importantly, strict international quarantine regulations mean that an outbreak will cause all livestock and meat from that country to be banned from international trade. Various methods of outbreak control exist, but all are draconian, requiring massive culling (killing) of “in contact” but otherwise healthy animals surrounding index cases. Restrictions on all animal movement and often all commerce through infected areas are imposed, resulting in secondary economic losses from loss of tourism and general economic activity.

For instance, in the UK in 2001 a FMD outbreak ran from February to October 2001, with travel and export restrictions lasting into 2002. To control the outbreak, all susceptible livestock within 3 kms of an active case were culled. At its peak, 80,000-93,000 animals a week were killed and burned on farms, a total about 10 million sheep and cattle. Its direct cost was about $6.9 billion with overall costs to the British economy estimated at $16 billion.

On August 3, 2007 an outbreak of FMD was reported on a farm in the UK, initially with at least 38 cases in cattle identified. Quarantine measures were introduced and an investigation begun, with culling of surrounding livestock. Most countries banned UK livestock and meat exports. The virus was quickly identified as a strain that had caused a 1967 outbreak in the UK, but was not currently circulating in animals anywhere. Another case of “frozen evolution.” However, this outbreak was 2.8 miles (4.6 kms) south of Pirbright, where the only two facilities in the UK that were authorized to hold FMD virus were located. One was the UK Institute for Animal Health (IAH), the other Merial, a commercial veterinary FMD vaccine manufacturer. They both used the 1967 FMD strain, the Merial facility in large amounts (10,000 l) for vaccine manufacture.
Operations were suspended at Merial on August 4 and its license to operate withdrawn. A second FMD outbreak quickly appeared near the first, and animal movement with the UK restricted and quarantine zones encompassing both the Pirbright campus and two affected farms were put in place on Aug 750. An initial investigation also published August 7 found no evidence for aerosol or surface water transmission of FMD virus from Pirbright, was investigating other wastewater issues, and suggested human carriage might have occurred51.

Investigation eventually showed that a waste-water line carrying partially treated waste water from the Merial vaccine plant to the final waste treatment plant run by IAH had gone without routine inspection or maintenance, was damaged, leaking, and had an unsealed manhole opening to the surface, so was capable of contaminating ground and surface water. It became clear that Merial and the IAH each considered the other responsible for such inspection and maintenance, and it had gone undone. The non-secure wastewater line ran through a construction area that recent heavy rains had turned into deep mud, and construction vehicles traversed it and exited the Pirbright campus without inspection or monitoring. These trucks sometimes used the road that passed by the first affected farm. It was concluded that contaminated mud from the defective wastewater line at Pirbright had been carried on tyres or underbody of construction vehicles and caused the first outbreak52.

For a brief time the outbreak was thought to have ended, and restrictions in the Pirbright area were lifted September 8, 2007. The UK applied to the EU to lift most restrictions on animal exports from the UK to EU on September 11, 2007.

However, on September 12, 2007 FMD was again reported, this time 30 miles north of Pirbright, again with the same 1967 strain of FMD. From September 18-30 multiple additional outbreaks of FMD appeared in the same area. A national embargo on all animal shipment was imposed, and new surveillance zones expanded rapidly until, overlapping they encompassed a portion of Heathrow Airport and were cut across by the major M4, M3 and M25 motorways. Rapid (real-time) genomic analysis had been ongoing during this outbreak, and indicated a single escape of FMD from Pirbright, which first spread between the two farms of the August outbreak, then went unnoticed at third farm before it blossomed again in mid September. Follow-up investigations identified the intermediate farm53.

The 2007 UK FMD outbreak identified 278 infected animals, and required 1578 animals to be culled54. It disrupted UK agricultural production and exports, and cost an estimated 200 million pounds. The ban of meat exports was particularly damaging as UK beef had only just exited a 10-year embargo by the EU because of BSE (Mad Cow Disease) in May of 2006.

FMD is such an easily transmitted virus with such potential to cause massive economic damage it would appear that manipulating it in a virology laboratory in a FMD free area is manifestly fraught with hazard. Particularly when it might escape by an “invisible” breach in biosafety as it did at Pirbright, and where it might lurk undetected despite heavy surveillance as it did between the two outbreaks.


In the US, previous law had banned it on the continental US, so FMD virus is currently only held in the USDA Plum Island facility off of Long Island (in a facility originally built in the 1950s for anti-animal BW [biological weapons] work). Currently a replacement facility under the Department of Homeland Security (DHS), the National Bio-and Agro-Defense Facility (NBAF) is under construction in Manhattan, KS. The move of FMD research to the agricultural heartland of the US was opposed by many groups, including the GAO, but DHS decided on the KS location and construction is ongoing. So much for learning from other’s experience.

Conclusions

There are some common themes in these narratives of escaped pathogens. Undetected flaws in the functioning of what was considered at the time to be an adequate standard of technical biocontainment is one theme, as demonstrated in the UK smallpox and FMD cases. Transfer to and handling of inadequately inactivated preparations of dangerous pathogens in areas of the laboratory with reduced biosecurity levels (allowable if the preparation is actually inactivated) is another theme, demonstrated in the SARS and VEE escapes. Poor training of personnel and slack oversight of laboratory procedures negated policy efforts by national and international bodies to achieve biosecurity in the SARS and UK smallpox escapes. The recent appearance of a cohort of immunologically naïve people in the general population, which previously had been uniformly immune was a factor in the UK smallpox and the 1977 H1N1 escapes; in this regard it should be remembered that there is no immunity at all in the general population to most potentially pandemic pathogens currently under discussion, such as Avian influenza and SARS.

It is hardly reassuring that despite stepwise technical improvements in containment facilities and increased policy demands for biosecurity procedures in the handling of dangerous pathogens, that escapes of these pathogens regularly occur and cause outbreaks in the general environment. Looking at the problem pragmatically, question is not if such escapes will happen in the future, but rather what the pathogen may be and how such an escape will be contained, if indeed it can be contained at all.

Advances in genetic manipulation now allow the augmentation of virulence and transmissibility in dangerous pathogens, and such experiments have been funded and performed, notably in the H5N1 avian influenza virus. The advisability of performing such experiments at all, and particularly in laboratories placed at universities in heavily populated urban areas, where laboratory personnel who are potentially exposed are in daily contact with a multitude of susceptible and unaware citizens is clearly in question.

If such manipulations should be allowed at all, it would seem prudent to conduct them in isolated laboratories where personnel are sequestered from the general public and must undergo a period of “exit quarantine” before re-entering civilian life55.
Such isolated “detached duty”, while inconvenient for the lifestyle of virologists, is hardly foreign to them, since many experience prolonged periods of inconvenient and dangerous field work in the collection of viruses in the field, and certainly many other natural scientists do prolonged and isolated field work as well. The “inconvenience” barrier that requiring such isolation may present to principal investigators and other personnel may act as a natural screening factor to insure that dangerous manipulations to dangerous pathogens are only undertaken when genuinely indicated.

_______________

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