Wednesday, April 29, 2020

Another expert challenges assertions that SARS-CoV-2 was not genetically engineered/ GM Watch

Biochemist in hazmat suit sitting near microscope
Another expert on biotechnology has attacked the evidence being used to quash suggestions that SARS-CoV-2, the virus strain that causes COVID-19, might have been genetically engineered. Professor Stuart Newman, professor of cell biology and anatomy at New York Medical College, says that a key argument used to deny that it could be a genetically engineered strain that escaped from a laboratory actually points to the exact opposite. In other words, it indicates that SARS-CoV-2 could well be genetically engineered and that it could have escaped from a lab.
The evidence that is being cited as proving that SARS-CoV-2 is “not a laboratory construct or a purposefully manipulated virus” is a paper published by the immunologist Kristian Andersen and colleagues in Nature Medicine. As Adam Lauring, an associate professor of microbiology, immunology and infectious diseases at the University of Michigan Medical School, has noted, Andersen’s paper argues that, "the SARS-CoV-2 virus has some key differences in specific genes relative to previously identified coronaviruses – the ones a laboratory would be working with. This constellation of changes makes it unlikely that it is the result of a laboratory 'escape’.”
Prof Stuart Newman
But Professor Newman says that this is totally unconvincing because “The ‘key differences’ were in regions of the coronavirus spike protein that were the subject of genetic engineering experiments in labs around the world (mainly in the US and China) for two decades.”
So not only does Newman think that the virus could have escaped from a lab, he also thinks that it could have originated in a virus stock that had undergone genetic engineering at some point.

In an email interview with GMWatch, Newman, who is editor-in-chief of the journal Biological Theory and co-author (with Tina Stevens) of the book Biotech Juggernaut, amplified this speculation by noting, “The Nature Medicine paper points to variations in two sites of the spike protein of the new coronavirus that the authors claim must have arisen by natural selection in the wild. However, genetic engineering of one of these sites, the ACE2 receptor binding domain, has been proposed since 2005 in order to help generate vaccines against these viruses (see this paper). It is puzzling that the authors of the Nature Medicine commentary did not cite this paper, which appeared in the prominent journal Science.”
Moreover, Newman added, “The second site that Andersen et al. assert arose by natural means, a target of enzyme cleavage not usually found in this class of viruses, was in fact introduced by genetic engineering in a similar coronavirus in a paper they do cite. This was done to explore mechanisms of pathogenicity.”
Newman said that he does not believe that these changes were deliberately introduced to increase the pathogenicity of any single strain, but that SARS-CoV-2 may have had genetically engineered components in its history before being inadvertently introduced into the human population.

Newman is not the only scientist that has spoken out about the possibility of a genetically engineered element to the virus. We recently published an article in which the molecular geneticist Dr Michael Antoniou also cast doubt on these assertions. Dr Antoniou set out a method by which the virus could have been genetically manipulated and selected for increased infectivity in the laboratory.

Neither Dr Antoniou, nor Prof Newman, nor we ourselves make any suggestion that, in the event that genetic engineering was involved, the intention was to create a bioweapon. Such “enhanced infectivity” research is carried out on viruses all over the world (and not just in China) to investigate their behaviour and to develop vaccines and other therapies, as well as for “biodefence” purposes.

But the question of whether genetic engineering did play a part in the emergence of SARS-CoV-2 must continue to be investigated so that humanity can place appropriate limits and safeguards on such research.

NIH funded coronavirus research in Wuhan to make more virulent viruses/Newsweek

Great detailed pieces from Newsweek, which has been delving into the US government's financial support for "gain of function" (which means increasing the virulence of a pathogen) research in Wuhan, China, which might have contributed to the formation of SARS-CoV-2. They were posted April 27, and 29.  From the latest story:
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.
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 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...
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.
Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, testifies on Capitol Hill on Wednesday, Sept. 23, 2020, in Washington.

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.
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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..."
In other words, until you can find the evidence proving we funded this virus, NIH (and Fauci in particular) is admitting nothing.  How likely do you think it is that the evidence still exists?

Theory of how SARS-CoV-2 was created in a lab/ Prof Nikolai Petrovsky

Dr. Petrovsky, of Flinders University, Australia, was asked his opinion on the origin of SAR-2 and wrote the following
"An extremely important but still unanswered question is what was the source of COVID-19 virus. While COVID-19 has close similarities to SARS and other bat viruses no natural virus matching to COVID-19 has been found in nature despite an intensive search to find its origins. This raises the very legitimate question of whether the COVID-19 virus might be the result of human intervention.

Certainly, our and other analyses of the genomic sequence of the virus do not reveal any artificial gene inserts that would be the hallmark of a gene jockey, genetic engineers who manipulate or even create viruses by splicing in artificial inserts into their genome. These are generally easily recognisable and hence clear signatures of human intervention in the creation of a virus. The fact that these artificial inserts are not present has been interpreted by some to mean this virus is not the result of human manipulation.

However, this logic is incorrect as there are other ways in which humans can manipulate viruses and that is caused by natural selection. What do I mean? All viruses and bacteria mutate and adapt to their environment over time, with selection of the fittest individuals for survival in that particular environment.

Take a bat coronavirus that is not infectious to humans, and force its selection by culturing it with cells that express human ACE2 receptor, such cells having been created many years ago to culture SARS coronaviruses and you can force the bat virus to adapt to infect human cells via mutations in its spike protein, which would have the effect of increasing the strength of its binding to human ACE2, and inevitably reducing the strength of its binding to bat ACE2.

Viruses in prolonged culture will also develop other random mutations that do not affect its function. The result of these experiments is a virus that is highly virulent in humans but is sufficiently different that it no longer resembles the original bat virus. Because the mutations are acquired randomly by selection there is no signature of a human gene jockey, but this is clearly a virus still created by human intervention.

My group in collaboration with other Australian researchers have been using a modelling approach to study the possible evolutionary origins of COVID-19 by modelling interactions between its spike protein and a broad variety of ACE2 receptors from many animals and humans.

This work which we will publish on a prepress server next week shows that the strength of binding of COVID-19 to human ACE2 far exceeds the predicted strength of its binding to the ACE2 of any of the other species. This points to the virus having been selected for its high binding to human ACE2.  In the absence of evidence of historic human infections with this virus, which could result in such selection, this either is a remarkable coincidence or a sign of human intervention.

This, plus the fact that no corresponding virus has been found to exist in nature, leads to the possibility that COVID-19 is a  human-created virus. It is therefore entirely plausible that the virus was created in the biosecurity facility in Wuhan by selection on cells expressing human ACE2, a laboratory that was known to be cultivating exotic bat coronaviruses at the time. Is so the cultured virus could have escaped the facility either through accidental infection of a staff member who then visited the fish market several blocks away and there infected others, or by inappropriate disposal of waste from the facility that either infected humans outside the facility directly or via a susceptible vector such as a stray cat that then frequented the market and resulted in transmission there to humans.

Whilst the facts cannot be known at this time, the nature of this event and its proximity to a high-risk biosecurity facility at the epicentre of the outbreak demands a full and independent international enquiry to ascertain whether a virus of this kind of COVID-19 was being cultured in the facility and might have been accidentally released."

Viral Shedding Continues Up to 6 Weeks After Coronavirus Symptom Onset

(Reuters Health) - Patients may continue to shed the SARS-CoV-2 virus for up to six weeks after symptoms emerge, a small study of recovered COVID-19 patients suggests.  One third tested positive 4 weeks after start of symptoms... so when can you go back to work after getting COVID?

Dr. Zhang and colleagues summarized their experience with 56 COVID-19 patients (median age 55; 61% men) admitted to Tongi Hospital in Wuhan in January and February. Throat or deep nasal cavity swab samples were collected on different dates after symptom onset. SARS-CoV-2 was diagnosed by real-time reverse transcription polymerase chain reaction (RT-PCR) assays All patients had mild-moderate infection.

As reported in Clinical Infectious Diseases, 299 RT-PCR assays were performed (about five tests per patient). The longest duration between symptom onset and an RT-PCR test was 42 days, whereas the median duration was 24 days.

In the first three weeks after symptom onset, the majority of RT-PCR results were positive for SARS-CoV-2. From week three onward, negative results increased. All tests were negative at week six after symptom onset. 

The rate of positive results was highest at week one (100%), followed by 89.3%, 66.1%, 32.1%, 5.4% and 0% at weeks two, three, four, five and six, respectively.

Tuesday, April 28, 2020

Monday, April 27, 2020

Gilead's COVID-19 hopeful remdesivir may get swift Japanese approval

From FierceBiotech:

"Japanese Prime Minister Shinzo Abe is set to grant Gilead Sciences' experimental COVID-19 drug remdesivir a special, speedy approval, despite it failing to show any definitive clinical signs that it works.
The report, from Japanese news site Kyodo, could make Japan the first country in the world to approve the med, which was once being tested for Ebola. A green light for the med could come as early as May, Kyodo reports.
“The pharmaceutical approval (of remdesivir) will be possible shortly,” Abe told a parliamentary session, as quoted by the news agency. Gilead will have to make an application for an approval, at which time the Japanese government is set to fast-track its way to market..."
Approved for human use before applying for a license? Wonder how much that cost.  Once the first domino is down, approval in other countries gets a lot easier.

From STAT:

"New data on Gilead’s remdesivir, released by accident, show no benefit for coronavirus patients. Company still sees reason for hope"

Sunday, April 26, 2020

Who is immune to the coronavirus?/ NY Times

Excellent discussion of what we know, don't know, and may be assuming incorrectly--by Marc Lipsitch, PhD, professor at Harvard School of Public Health.

Friday, April 24, 2020

Did this Virus Come from a Lab? Maybe Not — But it Exposes the Threat of a Biowarfare Arms Race/ Sam Husseini @ Salon

Dangerous pathogens are captured in the wild and made deadlier in government biowarfare labs. Did that happen here?

There has been no scientific finding that the novel coronavirus was bioengineered, but its origins are not entirely clear. Deadly pathogens discovered in the wild are sometimes studied in labs — and sometimes made more dangerous. That possibility, and other plausible scenarios, have been incorrectly dismissed in remarks by some scientists and government officials, and in the coverage of most major media outlets.
Regardless of the source of this pandemic, there is considerable documentation that a global biological arms race going on outside of public view could produce even more deadly pandemics in the future.
While much of the media and political establishment have minimized the threat from such lab work, some hawks on the American right like Sen. Tom Cotton, R-Ark., have singled out Chinese biodefense researchers as uniquely dangerous. But there is every indication that U.S. lab work is every bit as threatening as that in Chinese labs. American labs also operate in secret, and are also known to be accident-prone.
The current dynamics of the biological arms race have been driven by U.S. government decisions that extend back decades. In December 2009, Reuters reported that the Obama administration was refusing even to negotiate the possible monitoring of biological weapons.Much of the left in the U.S. now appears unwilling to scrutinize the origin of the pandemic — or the wider issue of biowarfare — perhaps because portions of the anti-Chinese right have been so vocal in making unfounded allegations. 
Governments that participate in such biological weapon research generally distinguish between "biowarfare" and "biodefense," as if to paint such "defense" programs as necessary. But this is rhetorical sleight-of-hand; the two concepts are largely indistinguishable. 
"Biodefense" implies tacit biowarfare, breeding more dangerous pathogens for the alleged purpose of finding a way to fight them. While this work appears to have succeeded in creating deadly and infectious agents, including deadlier flu strains, such "defense" research is impotent in its ability to defend us from this pandemic. 
The legal scholar who drafted the main U.S. law on the subject, Francis Boyle, warned in his 2005 book "Biowarfare and Terrorism" that an "illegal biological arms race with potentially catastrophic consequences" was underway, largely driven by the U.S. government.
For years, many scientists have raised concerns regarding bioweapons/biodefense lab work, and specifically about the fact that huge increases in funding have taken place since 9/11. This was especially true after the anthrax-by-mail attacks that killed five people in the weeks after 9/11, which the FBI ultimately blamed on a U.S. government biodefense scientist. A 2013 study found that biodefense funding since 2001 had totaled at least $78 billion, and more has surely been spent since then. This has led to a proliferation of laboratories, scientists and new organisms, effectively setting off a biological arms race. 
Ebola outbreak in west Africa in 2014, the U.S. government paused funding for what are known as "gain-of-function" research on certain organisms. This work actually seeks to make deadly pathogens deadlier, in some cases making pathogens airborne that previously were not. With little notice outside the field, the pause on such research was lifted in late 2017.
During this pause, exceptions for funding were made for dangerous gain-of-function lab work. This included work jointly done by U.S. scientists from the University of North Carolina, Harvard and the Wuhan Institute of Virology. This work — which had funding from USAID and EcoHealth Alliance not originally acknowledged — was published in 2015 in Nature Medicine
A different Nature Medicine article about the origin of the current pandemic, authored by five scientists and published on March 17, has been touted by major media outlet and some officials — including current National Institutes of Health director Francis Collins — as definitively disproving a lab origin for the novel coronavirus. That journal article, titled "The proximal origin of SARS-CoV-2," stated unequivocally: "Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus." This is a subtly misleading sentence. While the scientists state that there is no known laboratory "signature" in the SARS-Cov-2 RNA, their argument fails to take account of other lab methods that could have created coronavirus mutations without leaving such a signature.

Indeed, there is also the question of conflict of interest in the Nature Medicine article. Some of the authors of that article, as well as a February 2020 Lancet letter condemning "conspiracy theories suggesting that COVID-19 does not have a natural origin" — which seemed calculated to minimize outside scrutiny of biodefense lab work — have troubling ties to the biodefense complex, as well as to the U.S. government. Notably, neither of these articles makes clear that a virus can have a natural origin and then be captured and studied in a controlled laboratory setting before being let loose, either intentionally or accidentally — which is clearly a possibility in the case of the coronavirus. 
Facts as "rumors"
This reporter raised questions about the subject at a news conference with a Center for Disease Control (CDC) representative at the now-shuttered National Press Club on Feb. 11. I asked if it was a "complete coincidence" that the pandemic had started in Wuhan, the only place in China with a declared biosafety level 4 (BSL4) laboratory. BSL4 laboratories have the most stringent safety mechanisms, but handle the most deadly pathogens. As I mentioned, it was odd that the ostensible origin of the novel coronavirus was bat caves in Yunnan province — more than 1,000 miles from Wuhan. I noted that "gain-of-function" lab work can results in more deadly pathogens, and that major labs, including some in the U.S., have had accidental releases
CDC Principal Deputy Director Anne Schuchat said that based on the information she had seen, the virus was of "zoonotic origin." She also stated, regarding gain-of-function lab work, that it is important to "protect researchers and their laboratory workers as well as the community around them and that we use science for the benefit of people." 
I followed up by asking whether an alleged natural origin did not preclude the possibility that this virus came through a lab, since a lab could have acquired a bat virus and been working on it. Schuchat replied to the assembled journalists that "it is very common for rumors to emerge that can take on life of their own," but did not directly answer the question. She noted that in the 2014 Ebola outbreak some observers had pointed to nearby labs as the possible cause, claiming this "was a key rumor that had to be overcome in order to help control the outbreak." She reiterated: "So based on everything that I know right now, I can tell you the circumstances of the origin really look like animals-to-human. But your question, I heard." 
This is no rumor. It's a fact: Labs work with dangerous pathogens. The U.S. and China each have dual-use biowarfare/biodefense programs. China has major facilities at Wuhan — a biosafety level 4 lab and a biosafety level 2 lab. There are leaks from labs. (See "Preventing a Biological Arms Race," MIT Press, 1990, edited by Susan Wright; also, a partial review in Journal of International Law from October 1992.)
Much of the discussion of this deadly serious subject is marred with snark that avoids or dodges the "gain-of-function" question. ABC ran a story on March 27 titled "Sorry, Conspiracy Theorists. Study Concludes COVID-19 'Is Not a Laboratory Construct.'" That story did not address the possibility that the virus could have been found in the wild, studied in a lab and then released.
On March 21, USA Today published a piece headlined "Fact Check: Did the Coronavirus Originate In a Chinese Laboratory?" — and rated it "FALSE."  That USA Today story relied on the Washington Post, which published a widely cited article on Feb. 17 headlined, "Tom Cotton keeps repeating a coronavirus conspiracy theory that was already debunked." That article quoted public comments from Rutgers University professor of chemical biology Richard Ebright, but out of context and only in part. Specifically, the story quoted from Ebright's tweet that the coronavirus was not an "engineered bioweapon." In fact, his full quote included the clarification that the virus could have "entered human population through lab accident." (An email requesting clarification sent to Post reporter Paulina Firozi was met with silence.) 
Bioengineered ≠ From a lab
Other pieces in the Post since then (some heavily sourced to U.S. government officials) have conveyed Ebright's thinking, but it gets worse. In a private exchange, Ebright — who, again, has said clearly that the novel coronavirus was not technically bioengineered using known coronavirus sequences — stated that other forms of lab manipulation could have been responsible for the current pandemic. This runs counter to much reporting, which is perhaps too scientifically illiterate to perceive the difference. 
In response to the suggestion that the novel coronavirus could have come about through various methods besides bioengineering — made by Dr. Meryl Nass, who has done groundbreaking work on biowarfare — Ebright responded in an email:
The genome sequence of SARS-CoV-2 has no signatures of human manipulation.
This rules out the kinds of gain-of-function (GoF) research that leave signatures of human manipulation in genome sequences (e.g., use of recombinant DNA methods to construct chimeric viruses), but does not rule out kinds of GoF research that do not leave signatures (e.g., serial passage in animals). [emphasis added] 
Very easy to imagine the equivalent of the Fouchier's "10 passages in ferrets" with H5N1 influenza virus, but, in this case, with 10 passages in non-human primates with bat coronavirus RaTG13 or bat coronavirus KP876546.
That last paragraph is very important. It refers to virologist Ron Fouchier of the Erasmus Medical Center in Rotterdam, who performed research on intentionally increasing rates of viral mutation rate by spreading a virus from one animal to another in a sequence. The New York Times wrote about this in an editorial in January 2012, warning of "An Engineered Doomsday."
"Now scientists financed by the National Institutes of Health" have created a "virus that could kill tens or hundreds of millions of people" if it escaped confinement, the Times wrote. The story continued: 
Working with ferrets, the animal that is most like humans in responding to influenza, the researchers found that a mere five genetic mutations allowed the virus to spread through the air from one ferret to another while maintaining its lethality. A separate study at the University of Wisconsin, about which little is known publicly, produced a virus that is thought to be less virulent.
The word "engineering" in the New York Times headline is technically incorrect, since passing a virus through animals is not "genetic engineering." This same distinction has hindered some from understanding the possible origins of the current pandemic. 
Fouchier's flu work, in which an H5N1 virus was made more virulent by transmitting it repeatedly between individual ferrets, briefly sent shockwaves through the media. "Locked up in the bowels of the medical faculty building here and accessible to only a handful of scientists lies a man-made flu virus that could change world history if it were ever set free," wrote Science magazine in 2011 in a story titled "Scientists Brace for Media Storm Around Controversial Flu Studies."  It continues: 
The virus is an H5N1 avian influenza strain that has been genetically altered and is now easily transmissible between ferrets, the animals that most closely mimic the human response to flu. Scientists believe it's likely that the pathogen, if it emerged in nature or were released, would trigger an influenza pandemic, quite possibly with many millions of deaths.
In a 17th floor office in the same building, virologist Ron Fouchier of Erasmus Medical Center calmly explains why his team created what he says is "probably one of the most dangerous viruses you can make" — and why he wants to publish a paper describing how they did it. Fouchier is also bracing for a media storm. After he talked to ScienceInsider yesterday, he had an appointment with an institutional press officer to chart a communication strategy.
Fouchier's paper is one of two studies that have triggered an intense debate about the limits of scientific freedom and that could portend changes in the way U.S. researchers handle so-called dual-use research: studies that have a potential public health benefit but could also be useful for nefarious purposes like biowarfare or bioterrorism.
Despite objections, Fouchier's article was published by Science in June 2012. Titled "Airborne Transmission of Influenza A/H5N1 Virus Between Ferrets," it summarized how Fouchier's research team made the pathogen more virulent:
Highly pathogenic avian influenza A/H5N1 virus can cause morbidity and mortality in humans but thus far has not acquired the ability to be transmitted by aerosol or respiratory droplet ("airborne transmission") between humans. To address the concern that the virus could acquire this ability under natural conditions, we genetically modified A/H5N1 virus by site-directed mutagenesis and subsequent serial passage in ferrets. The genetically modified A/H5N1 virus acquired mutations during passage in ferrets, ultimately becoming airborne transmissible in ferrets.
In other words, Fouchier's research took a flu virus that did not exhibit airborne transmission, then infected a number of ferrets until it mutated to the point that it was transmissible by air. 
In that same year, 2012, a similar study by Yoshihiro Kawaoka of the University of Wisconsin was published in Nature:
Highly pathogenic avian H5N1 influenza A viruses occasionally infect humans, but currently do not transmit efficiently among humans. ... Here we assess the molecular changes ... that would allow a virus ... to be transmissible among mammals. We identified a ... virus ... with four mutations and the remaining seven gene segments from a 2009 pandemic H1N1 virus — that was capable of droplet transmission in a ferret model. 
In 2014, Marc Lipsitch of Harvard and Alison P. Galvani of Yale wrote regarding Fouchier and Kawaoka's work
Recent experiments that create novel, highly virulent and transmissible pathogens against which there is no human immunity are unethical ... they impose a risk of accidental and deliberate release that, if it led to extensive spread of the new agent, could cost many lives. While such a release is unlikely in a specific laboratory conducting research under strict biosafety procedures, even a low likelihood should be taken seriously, given the scale of destruction if such an unlikely event were to occur. Furthermore, the likelihood of risk is multiplied as the number of laboratories conducting such research increases around the globe.
Given this risk, ethical principles, such as those embodied in the Nuremberg Code, dictate that such experiments would be permissible only if they provide humanitarian benefits commensurate with the risk, and if these benefits cannot be achieved by less risky means.
We argue that the two main benefits claimed for these experiments — improved vaccine design and improved interpretation of surveillance — are unlikely to be achieved by the creation of potential pandemic pathogens (PPP), often termed "gain-of-function" (GOF) experiments. 
There may be a widespread notion that there is scientific consensus that the pandemic did not come out of a lab. But in fact, many of the most knowledgeable scientists in the field are notably silent. This includes Lipsitch at Harvard, Jonathan A. King at MIT and many others. 
Just last year, Lynn Klotz of the Center for Arms Control and Non-Proliferation wrote a paper in the Bulletin of the Atomic Scientists entitled "Human Error in High-biocontainment Labs: A Likely Pandemic Threat." Wrote Klotz: 
Incidents causing potential exposures to pathogens occur frequently in the high security laboratories often known by their acronyms, BSL3 (Biosafety Level 3) and BSL4. Lab incidents that lead to undetected or unreported laboratory-acquired infections can lead to the release of a disease into the community outside the lab; lab workers with such infections will leave work carrying the pathogen with them. If the agent involved were a potential pandemic pathogen, such a community release could lead to a worldwide pandemic with many fatalities. Of greatest concern is a release of a lab-created, mammalian-airborne-transmissible, highly pathogenic avian influenza virus, such as the airborne-transmissible H5N1 viruses created in the laboratories of Ron Fouchier in the Netherlands and Yoshihiro Kawaoka in Madison, Wisconsin.
"Crazy, dangerous"
Boyle, a professor of international law at the University of Illinois, has condemned Fouchier, Kawaoka and others — including at least one of the authors of the recent Nature Medicine article in the strongest terms, calling such work a "criminal enterprise." While Boyle has been embroiled in numerous controversies, he's been especially dismissed by many on this issue. The "fact-checking" website Snopes has described him as "a lawyer with no formal training in virology" — without noting that he wrote the relevant U.S. law.
As Boyle said in 2015
Since September 11, 2001, we have spent around $100 billion on biological warfare. Effectively we now have an Offensive Biological Warfare Industry in this country that violates the Biological Weapons Convention and my Biological Weapons Anti-Terrorism Act of 1989.
The law Boyle drafted states: "Whoever knowingly develops, produces, stockpiles, transfers, acquires, retains, or possesses any biological agent, toxin, or delivery system for use as a weapon, or knowingly assists a foreign state or any organization to do so, shall be fined under this title or imprisoned for life or any term of years, or both. There is extraterritorial Federal jurisdiction over an offense under this section committed by or against a national of the United States."
Boyle also warned: 
Russia and China have undoubtedly reached the same conclusions I have derived from the same open and public sources, and have responded in kind. So what the world now witnesses is an all-out offensive biological warfare arms race among the major military powers of the world: United States, Russia, Britain, France, China, Israel, inter alia.
We have reconstructed the Offensive Biological Warfare Industry that we had deployed in this county before its prohibition by the Biological Weapons Convention of 1972,  described by Seymour Hersh in his groundbreaking expose "Chemical and Biological Warfare: America's Hidden Arsenal." (1968) 
Boyle now states that he has been "blackballed" in the media on this issue, despite his having written the relevant statute. The group he worked with on the law, the Council for Responsible Genetics, went under several years ago, making Boyle's views against "biodefense" even more marginal as government money for dual use work poured into the field and critics within the scientific community have fallen silent. In turn, his denunciations have grown more sweeping. 
In the 1990 book "Preventing a Biological Arms Race," scholar Susan Wright argued that current laws regarding bioweapons were insufficient, as there were "projects in which offensive and defensive aspects can be distinguished only by claimed motive." Boyle notes, correctly, that current law he drafted does not make an exception for "defensive" work, but only for "prophylactic, protective or other peaceful purposes."
While Boyle is particularly vociferous in his condemnations, he is not alone. There has been irregular, but occasional media attention to this threat. The Guardian ran a piece in 2014, "Scientists condemn 'crazy, dangerous' creation of deadly airborne flu virus," after Kawaoka created a life-threatening virus that "closely resembles the 1918 Spanish flu strain that killed an estimated 50m people":
"The work they are doing is absolutely crazy. The whole thing is exceedingly dangerous," said Lord May, the former president of the Royal Society and one time chief science adviser to the UK government. "Yes, there is a danger, but it's not arising from the viruses out there in the animals, it's arising from the labs of grossly ambitious people."
Boyle's charges beginning early this year that the coronavirus was bioengineered — allegations recently mirrored by French virologist and Nobel laureate Luc Montagnier — have not been corroborated by any publicly produced findings of any U.S. scientist. Boyle even charges that scientists like Ebright, who is at Rutgers, are compromised because the university got a biosafety level 3 lab in 2017 — though Ebright is perhaps the most vocal eminent critic of this research, among U.S. scientists. These and other controversies aside, Boyle's concerns about the dangers of biowarfare are legitimate; indeed, Ebright shares them. 
Some of the most vocal voices to discuss the origins of the novel coronavirus have been eager to minimize the dangers of lab work, or have focused almost exclusively on "wet markets" or "exotic" animals as the likely cause. 
The media celebrated Laurie Garrett, the Pulitzer Prize–winning author and former senior fellow at the Council on Foreign Relations, when she declared on Twitter on March 3 (in a since-deleted tweet) that the origin of the pandemic was discovered: "It's pangolins. #COVID19 Researchers studied lung tissue from 12 of the scaled mammals that were illegally trafficked in Asia and found #SARSCoV2 in 3. The animals were found in Guangxi, China. Another virus+ smuggled sample found in Guangzhou."
She was swiftly corrected by Ebright: "Arrant nonsense. Did you even read the paper? Reported pangolin coronavirus is not SARS-CoV-2 and is not even particularly close to SARS-CoV-2. Bat coronavirus RaTG13 is much closer to SARS-CoV-2 (96.2% identical) than reported pangolin coronavirus (92.4% identical)." He added: "No reason to invoke pangolin as intermediate. When A is much closer than B to C, in the absence of additional data, there is no rational basis to favor pathway A>B>C over pathway A>C." When someone asked what Garrett was saying, Ebright responded: "She is saying she is scientifically illiterate." 
The following day, Garrett corrected herself (without acknowledging Ebright): "I blew it on the #Pangolins paper, & then took a few hours break from Twitter. It did NOT prove the species = source of #SARSCoV2. There's a torrent of critique now, deservedly denouncing me & my posting. A lot of the critique is super-informative so leaving it all up 4 while." 
At least one Chinese government official has responded to the allegation that the labs in Wuhan could be the source for the pandemic by alleging that perhaps the U.S. is responsible instead. In American mainstream media, that has been reflexively treated as even more ridiculous than the original allegation that the virus could have come from a lab. 
Obviously the Chinese government's allegations should not be taken at face value, but neither should U.S. government claims — especially considering that U.S. government labs were the apparent source for the anthrax attacks in 2001. Those attacks sent panic through the U.S. and shut down Congress, allowing the Bush administration to enact the PATRIOT Act and ramp up the invasions of Afghanistan and Iraq. Indeed, in October 2001, media darlings like Richard Butler and Andrew Sullivan propagandized for war with Iraq because of the anthrax attacks. (Neither Iraq nor al-Qaida was involved.)
The 2001 anthrax attacks also provided much of the pretext for the surge in biolab spending since then, even though they apparently originated in a U.S. or U.S.-allied lab. Indeed, those attacks remain shrouded in mystery
The U.S. government has also come up with elaborate cover stories to distract from its bioweapons work. For instance, the U.S. government infamously claimed the 1953 death of Frank Olson, a scientist at Fort Detrick, Maryland, was an LSD experiment gone wrong; it now appears to have been an execution to cover up for U.S. biological warfare. 
Regardless of the cause of the current pandemic, these biowarfare/biodefense labs need far more scrutiny. The call to shut them down by Boyle and others needs to be clearly heard — and light must be shone on precisely what research is being conducted.
The secrecy of these labs may prevent us ever knowing with certainty the origins of the current pandemic. What we do know is this kind of lab work comes with real dangers. One might make a comparison to climate change: We cannot attribute an individual hurricane to man-made climate disruption, yet science tells us that human activity makes stronger hurricanes more likely. That brings us back to the imperative to cease the kinds of activities that produce such dangers in the first place.
If that doesn't happen, the people of the planet will be at the mercy of the machinations and mistakes of state actors who are playing with fire for their geopolitical interests.

Thursday, April 23, 2020

Coronavirus: mortality rates, questionable data, treatment. Part 3

Mortality rates and spread

We have had 5 weeks of quarantine.  I earlier pointed out that there is an average 4 week lag between exposure to SARS-CoV-2 and death (or recovery) for those with a significant Covid-19 illness.  So, if the quarantine was going to work as planned, we should now be able to see whether the number of cases and deaths have dropped significantly as a result.  Have they?

Let's look at some (mostly) official figures. For the US, daily mortality rose to about a peak of 2,000 per day on April 6.  Since then, mortality has held steady.  While it stopped rising, it has not fallen.  Based on mortality alone, the number of people to whom each infected person passes the infection, has dropped considerably (from estimates that varied between 2.3 and 5.7).  It may even be as low as 1.  But that is still not good enough to allow normal life to restart.  To get back to normal, we need new infections to get down enough so that we have the resources to do case finding and tracking for every single one.

Grossly, looking at total deaths divided by total diagnosed infections, US mortality is 6%.  The same rough calculation yields mortality in France of 14%, in Italy 13%, in Spain 10% , in Germany 4%, in Sweden 12%. 

There were over 32,000 new infections in the US diagnosed in the past 24 hours, the highest number yet.  While expanded testing accounts for some of the rise, we are nowhere near putting a lid on covid's spread.


NY state was hit hardest, so let's focus there. NY has had a total of 15,740 deaths. The number of people currently hospitalized is 15,021, down from a peak over 18,000, of whom 5,016 are in ICUs.  Recorded deaths have dropped from about 800 to about 500 per day in NY.  

But there are questions about the numbers.  CDC has instructed doctors who complete death certificates to stop using Covid-19 as the immediate cause of death, and to instead list it as the underlying cause of death.  According to Bob Hennelly at Salon,

...on April 15 New Jersey's Office of Vital Statistics and Registry, in accordance with the CDC's National Vital Statistics System, had ordered that deaths of confirmed or suspected COVID-19 patients should no longer be reported with that disease as the immediate cause of death... "Last week, because of changes on the national level, the primary cause of death can no longer be COVID-19. It can be a secondary cause or a consequence of the primary cause of death. But the primary cause of death must be something other than the virus itself."

Furthermore, Hennelly noted in an article written 2 weeks earlier, that NYC's Emergency Medical Services were being called for up to ten times more cardiac arrests per shift than in the same period a year ago.  These were likely not being counted as Covid deaths. His reporting suggested these deaths were disproportionately occurring in racial and ethnic minorities.

Gov. Cuomo reported a preliminary study of 3,000 New Yorkers, of whom 13.9% had antibodies to coronavirus.  But NY is the hardest-hit state, and even if this accurately extrapolates to NY's population of 19.4 million, that still leaves 86% of New Yorkers without antibodies and presumably vulnerable.

Vo, Italy 

preprint study from a small town in northern Italy was just released. In February, over 70% of its eligible population, over 2,000 people, received nasal swab tests 2 weeks apart.  About 43% of those who had a positive swab had no symptoms. Seventeen percent of those positive (but about 30% with symptoms) required hospitalization.

These data support earlier studies, which showed that most of those who become infected do develop disease. Less than half were asymptomatic.  

What is our Plan B?

While a general hope was that SARS-CoV-2 might slowly spread through the population and confer immunity without significant cost, that seems unlikely, based on these and other data. 
The vast majority of Americans remain unchallenged by Covid-19 and without immunity.  

Furthermore, the WHO warns that the presence of antibodies has not been shown to correlate with immunity.  While I suspect this reflects the questionable accuracy of the dozens of antibody tests currently on the market, or the fact that the specific antibodies being measured are not the best to show immunity, it could also mean that people do not develop strong immunity following SARS-CoV-2 infection. Sometimes this happens. For example, having one bout of Lyme disease does not prevent you from having another. 

The bottom line is that simply maintaining the current level of quarantine will not solve the Covid problem. It did end the exponential rise in the number of infections, and prevented (or at least postponed) a collapse of the medical system.  But it does not appear that the elapse of time will yield immunity without predictably high morbidity and mortality.

On the other hand, it is possible that neither our antibody nor our nasal swab PCR tests are adequately capturing infections and immunity, and things are actually way better than the numbers I cited above, show.  My friends tell me Sweden has claimed 1/3 of the population will be immune by May 1. Yet the numbers I see suggest only 0.2% of Swedes have tested positive, similar to the percentage in the USSweden's deaths are dropping, while ours are flat.  If Sweden has found a way out of this mess, I will be the first to follow their lead.

To me, the only workable Plan B involves finding preventive measures and effective treatments. Patients need cures.  The 88% mortality rate of those who were placed on ventilators in NY's largest hospital system is unacceptable.

In China, patients received a multitude of different treatments, simultaneously.  While that may create datasets that are hard for researchers to parse, since they are accustomed to determining the efficacy of one treatment at a time, more aggressive use of treatments might improve otherwise dismal mortality rates.  

The duty of a treating physician is exclusively to the patient, not to the fidelity of a pharma or grant-supported dataset or clinical trial.  It is time to throw the kitchen sink at our patients, and especially try vitamin and nutraceutical combinations that are unlikely to cause harm.  These are being used in some hospitals and recommended by some physicians already, for example, Vitamin D and glutathione, substances that the body requires and therefore are perfectly safe in therapeutic doses.  Or famotidine (pepcid) an OTC drug for heartburn. Here is another drug that may be useful.

Furthermore, treatment needs to be started early. When this virus hits hard, it happens fast and overwhelms us.  We need to lower the viral load before that happens. The common medications used for viral diseases: influenza, herpes simplex and varicella zoster infections (acyclovir, famciclovir, valacyclovir, oseltamvir) are all recommended to be started within 48 hours of the onset of symptoms.  Guidelines that recommend withholding safe medications, or waiting until patients are severely ill and hospitalized before using them, lack valid scientific and ethical justification for doing so. They should be consigned to the scrap heap.

Changes made by CDC to reporting guidelines for Covid-19 death certificates may corrupt mortality data. Out-of-hospital deaths may also do so.  Cities and states need their epidemiologists to scrutinize all deaths to make sure Covid deaths are correctly assigned. (Fox points out that Pennsylvania keeps changing the number of those who have died.) The data used by the federal government to make critical decisions about managing this pandemic must be accurate. It is not clear they are.