Monday the 9th November 2015 was an unremarkable day in world events. It was sunny and warm in Britain – 13C in London; the Russians were banned from athletics for doping offences; Seaworld was under pressure for its treatment of killer whales; a painting by the Italian artist, Modigliani became the second most expensive piece of art – reaching $170m at auction – and Justin Bieber released the single “Love Yourself” – which would earn him a Grammy Award the following year.
But on that same day, a respected scientific journal published a paper by a group of researchers from the Department of Epidemiology at the University of North Carolina about a recent discovery they had made whilst experimenting with a group of viruses, derived from samples of bat excrement.
Their paper examined the potential for a particular strain of coronavirus – similar to that which had created the SARS and MERS outbreaks – that one of the researchers had isolated in horseshoe bats in Shitou Cave near Yunnan, China – where they conducted intense sampling during different seasons over five consecutive years.
Dr Shi Zhengli—a virologist – who is often called China’s “bat woman” by her colleagues because of her virus-hunting expeditions in bat caves, was one of the authors. She was on secondment to the UNC during the research, which was co-funded by the US military bio-warfare division at Fort Detrick.
In essence, the paper established the potential for a reverse engineering a coronavirus called SHC014-CoV and increasing its lethality through a series of modifications to its structure. This process is called “gain of function”.
In 2012, a Dutch virologist, Ron Fouchier, published details of an experiment on the recent H5N1 strain of bird flu. This strain was extremely deadly, killing an estimated 60% of humans it infected – far beyond even the Spanish flu. Yet its inability to pass from human to human had so far prevented a pandemic. Fouchier wanted to find out whether (and how) H5N1 could naturally develop this ability. He passed the disease through a series of 10 ferrets, which are commonly used as a model for how influenza affects humans. By the time it passed to the final ferret, his strain of H5N1 had become directly transmissible between mammals.
The work caused fierce controversy. Much of this was focused on the information contained in his work. The US National Science Advisory Board for Biosecurity ruled that his paper had to be stripped of some of its technical details before publication, to limit the ability of bad actors to cause a pandemic. And the Dutch government claimed that the research broke EU law on exporting information useful for bioweapons. But it is not the possibility of misuse that concerns me here. Fouchier’s research provides a clear example of well-intentioned scientists enhancing the destructive capabilities of pathogens known to threaten global catastrophe.
But the USNSABB were silent when the researchers from UNC published their paper in 2015 and it remains online today. Just like Fouchier’s paper three years earlier – it provided a blueprint for ‘bad actors’ to initiate a pandemic – as noted by scientists a week after publication.
The abstract for the paper is instructive:
“The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS)-CoV underscores the threat of cross-species transmission events leading to outbreaks in humans. Here we examine the disease potential of a SARS-like virus, SHC014-CoV, which is currently circulating in Chinese horseshoe bat populations. Using the SARS-CoV reverse genetics system, we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone. The results indicate that group 2b viruses encoding the SHC014 spike in a wild-type backbone can efficiently use multiple orthologs of the SARS receptor human angiotensin converting enzyme II (ACE2), replicate efficiently in primary human airway cells and achieve in vitro titers equivalent to epidemic strains of SARS-CoV. Additionally, in vivo experiments demonstrate replication of the chimeric virus in mouse lung with notable pathogenesis. Evaluation of available SARS-based immune-therapeutic and prophylactic modalities revealed poor efficacy; both monoclonal antibody and vaccine approaches failed to neutralize and protect from infection with CoVs using the novel spike protein. On the basis of these findings, we synthetically re-derived an infectious full-length SHC014 recombinant virus and demonstrate robust viral replication both in vitro and in vivo. “
The paper describes how they achieved the dramatic gain of function by manipulating the genome sequence of a SHC014-CoV virus obtained from Fort Detrick, then combining various intermediary host pathways that enable cross-species transmission with enhanced adaptations, to increase its lethality.
These experiments – even in military laboratories – are extremely controversial. President Obama called a moratorium on gain of function experiments in 2014 – and the authors’ make comment to the risks in their summary.
“In addition to offering preparation against future emerging viruses, this approach must be considered in the context of the US government–mandated pause on gain-of-function (GOF) studies. On the basis of previous models of emergence, the creation of chimeric viruses such as SHC014-MA15 was not expected to increase pathogenicity, (however) relative to the Urbani spike–MA15 CoV, SHC014-MA15 shows a gain in pathogenesis.
On the basis of these findings, scientific review panels may deem similar studies building chimeric viruses based on circulating strains too risky to pursue, as increased pathogenicity in mammalian models cannot be excluded.“
But the information or blueprint was there for any ‘bad actors’ to exploit, should they so wish. However, there is also another, more reasonable and innocent explanation, if the virus eventually is determined to be of chimeric origin.
Dr Shi left UNC in September last year and returned to the Key Laboratory of Special Pathogens and Biosafety at the Wuhan Institute of Virology, which is located about 200m from the animal market, reported to be the source of the current outbreak. She now specialises in horseshoe bat coronavirus pathology and is a leading authority on gain potentiation in engineered methodology.
It is certainly a coincidence that the first victims of a mysterious fatal pneumonia were recorded in Wuhan in workers from a food market – a short distance away from a BSL-4 laboratory just a few weeks after Dr Shi returned from the USA. But this would have likely gone unnoticed, had it not been for the Department of Justice – who arrested another scientist – a Harvard University Professor in Chemical Biology, specialising in nanotechnology – and issued a press release in February this year.
Last week, the authors of the paper issued an update.
30 March 2020
Editors’ note, March 2020: We are aware that this article is being used as the basis for unverified theories that the novel coronavirus causing COVID-19 was engineered. There is no evidence that this is true; scientists believe that an animal is the most likely source of the coronavirus.
When scientists use the words “believe” and “most likely” in defending a hypothesis – particularly when they are themselves the focus of understandable speculation, it is surely time for a very transparent independent investigation – and full public disclosure.
Most countries operate clandestine biowarfare research facilities – the UK has Porton Down, USA has Fort Detrick- Mossad run several as do Russia and China. It really doesn’t matter if it were accidentally released by Chinese scientists working at Wuhan – or a deliberate release by China – or any of the other actors, who wanted to exploit the circumstances to punish China. What matters is that all these secret facilities – & all of the intelligence & security agencies with their nefarious agendas, are dismantled immediately and never resurrected.
Whatever the excuse or justification, we must never again allow the irresponsible and dangerous experimentation with any element – biological, chemical or nuclear – that can has such catastrophic consequences if misused or when mistakes are made.
Now is not the time, but after, when we start to rebuild, there will be a thorough examination of all the activities and experiments, conducted in secret, but in our name, by governments and their agencies – and we will learn from this and never, ever permit these circumstances to arise again.
UPDATE: – Newsweek 8 May 2020
“Dr. Anthony Fauci is an adviser to President Donald Trump and something of an American folk hero for his steady, calm leadership during the pandemic crisis. At least one poll shows that Americans trust Fauci more than Trump on the coronavirus pandemic—and few scientists are portrayed on TV by Brad Pitt.
But just last year, the National Institute for Allergy and Infectious Diseases, the organization led by Dr. Fauci, funded scientists at the Wuhan Institute of Virology and other institutions for work on gain-of-function research on bat coronaviruses.
In 2019, with the backing of NIAID, the National Institutes of Health committed $3.7 million over six years for research that included some gain-of-function work. The program followed another $3.7 million, 5-year project for collecting and studying bat coronaviruses, which ended in 2019, bringing the total to $7.4 million.
Many scientists have criticized gain of function research, which involves manipulating viruses in the lab to explore their potential for infecting humans, because it creates a risk of starting a pandemic from accidental release.
SARS-CoV-2 , the virus now causing a global pandemic, is believed to have originated in bats. U.S. intelligence, after originally asserting that the coronavirus had occurred naturally, conceded last month that the pandemic may have originated in a leak from the Wuhan lab. (At this point most scientists say it’s possible—but not likely—that the pandemic virus was engineered or manipulated.)
Dr. Fauci did not respond to Newsweek’s requests for comment. NIH responded with a statement that said in part: “Most emerging human viruses come from wildlife, and these represent a significant threat to public health and biosecurity in the US and globally, as demonstrated by the SARS epidemic of 2002-03, and the current COVID-19 pandemic…. scientific research indicates that there is no evidence that suggests the virus was created in a laboratory.”
The NIH research consisted of two parts. The first part began in 2014 and involved surveillance of bat coronaviruses, and had a budget of $3.7 million. The program funded Shi Zheng-Li, a virologist at the Wuhan lab, and other researchers to investigate and catalogue bat coronaviruses in the wild. This part of the project was completed in 2019.
A second phase of the project, beginning that year, included additional surveillance work but also gain-of-function research for the purpose of understanding how bat coronaviruses could mutate to attack humans. The project was run by EcoHealth Alliance, a non-profit research group, under the direction of President Peter Daszak, an expert on disease ecology. NIH canceled the project just this past Friday, April 24th, Politico reported. Daszak did not immediately respond to Newsweek requests for comment.
The project proposal states: “We will use S protein sequence data, infectious clone technology, in vitro and in vivo infection experiments and analysis of receptor binding to test the hypothesis that % divergence thresholds in S protein sequences predict spillover potential.”
In layman’s terms, “spillover potential” refers to the ability of a virus to jump from animals to humans, which requires that the virus be able to attach to receptors in the cells of humans. SARS-CoV-2, for instance, is adept at binding to the ACE2 receptor in human lungs and other organs.
According to Richard Ebright, an infectious disease expert at Rutgers University, the project description refers to experiments that would enhance the ability of bat coronavirus to infect human cells and laboratory animals using techniques of genetic engineering. In the wake of the pandemic, that is a noteworthy detail.
Ebright, along with many other scientists, has been a vocal opponent of gain-of-function research because of the risk it presents of creating a pandemic through accidental release from a lab.
Dr. Fauci is renowned for his work on the HIV/AIDS crisis in the 1990s. Born in Brooklyn, he graduated first in his class from Cornell University Medical College in 1966. As head of NIAID since 1984, he has served as an adviser to every U.S. president since Ronald Reagan.
A decade ago, during a controversy over gain-of-function research on bird-flu viruses, Dr. Fauci played an important role in promoting the work. He argued that the research was worth the risk it entailed because it enables scientists to make preparations, such as investigating possible anti-viral medications, that could be useful if and when a pandemic occurred.
The work in question was a type of gain-of-function research that involved taking wild viruses and passing them through live animals until they mutate into a form that could pose a pandemic threat. Scientists used it to take a virus that was poorly transmitted among humans and make it into one that was highly transmissible—a hallmark of a pandemic virus. This work was done by infecting a series of ferrets, allowing the virus to mutate until a ferret that hadn’t been deliberately infected contracted the disease.
The work entailed risks that worried even seasoned researchers. More than 200 scientists called for the work to be halted. The problem, they said, is that it increased the likelihood that a pandemic would occur through a laboratory accident.
Dr. Fauci defended the work. “[D]etermining the molecular Achilles’ heel of these viruses can allow scientists to identify novel antiviral drug targets that could be used to prevent infection in those at risk or to better treat those who become infected,” wrote Fauci and two co-authors in the Washington Post on December 30, 2011. “Decades of experience tells us that disseminating information gained through biomedical research to legitimate scientists and health officials provides a critical foundation for generating appropriate countermeasures and, ultimately, protecting the public health.”
Nevertheless, in 2014, under pressure from the Obama administration, the National of Institutes of Health instituted a moratorium on the work, suspending 21 studies.
Three years later, though—in December 2017—the NIH ended the moratorium and the second phase of the NIAID project, which included the gain-of-function research, began. The NIH established a framework for determining how the research would go forward: scientists have to get approval from a panel of experts, who would decide whether the risks were justified.
The reviews were indeed conducted—but in secret, for which the NIH has drawn criticism. In early 2019, after a reporter for Science magazine discovered that the NIH had approved two influenza research projects that used gain of function methods, scientists who oppose this kind of research excoriated the NIH in an editorial in the Washington Post.
“We have serious doubts about whether these experiments should be conducted at all,” wrote Tom Inglesby of Johns Hopkins University and Marc Lipsitch of Harvard. “[W]ith deliberations kept behind closed doors, none of us will have the opportunity to understand how the government arrived at these decisions or to judge the rigor and integrity of that process.”