Category Archives: Human Genetic Engineering

A recently published scientific article states:

Due to the broad-spectrum of research conducted over almost 20 years on bat SARS-CoV [severe acute respiratory syndrome coronaviruses] justified by their potential to spill over from animal to human, a possible synthetic origin by laboratory engineering of SARS-CoV-2 [COVID-19] is a reasonable hypothesis.

China would like that hypothesis erased from the public consciousness.

The Chinese government, the media and some scientists are desperately trying to convince the public that COVID-19 is a naturally-occurring disease, which was transmitted from animals to humans in the Wuhan Seafood Market.

If COVID-19 leaked from a laboratory, the political and economic consequences for China are enormous.

If it was man-made and leaked from a laboratory, the implications are too grim for many to imagine.

The argument that COVID-19 is naturally-occurring is based nearly entirely on a single, but widely-cited Nature Medicine article entitled The Proximal Origin of SAR-CoV-2.

That conclusion stems primarily from a structural analysis comparing COVID-19 with bat and pangolin (scaly anteater) coronaviruses suggesting a natural evolutionary process in which COVID-19 mutated in an animal population and acquired the ability to infect humans.

Such a scenario does occur and it appears to be the origin of a number of animal-borne coronavirus infections in humans.

Based on the evidence provided in the much-cited Nature Medicine article, however, that conclusion is not obvious.

Although COVID-19 bears a striking structural similarity to the bat coronavirus RaTG13, the critical receptor binding domain, which initiates attachment to human cells, is closer to pangolins.

It is highly unlikely that the bat RaTG13 coronavirus and the pangolin coronavirus combined naturally through a process called reassortment because it would require simultaneous infection of the two viruses in the same animal cell.

It could, however, have been accomplished in a laboratory.

As the recently-published scientific article notes, a new chimeric or combined RaTG13-pangolin coronavirus strain could have been created through an artificial recombinant event, using well-established bioengineering methods.

Another possible indication of genetic manipulation is the presence of a furin polybasic cleavage site in COVID-19 as represented by the PRRA amino acid insertion, which does not exist in any of the bat or pangolin close relatives and is completely out of frame compared to the bat RaTG13 and pangolin sequences.

Perhaps not coincidentally, the furin polybasic cleavage site in COVID-19 occurs in the precise location known to enhance pathogenicity and transmissibility in viruses.

Methods for the insertion of a polybasic cleavage site in infectious bronchitis coronavirus have been described by Chinese scientists and that artificial genetic alteration resulted in increased pathogenicity.

In parallel, animal models for the addition of structures important to the function of coronaviruses, called O-linked glycans, have been used by Chinese scientists at the Chongqing Military Medical University, as well as animal models to specifically select for the human angiotensin-converting enzyme-2 receptor, the entry step for COVID-19 infection.

There is no doubt that China has the knowledge and technology to have created COVID-19. Whether that actually was done is yet to be determined and should be undergoing vigorous scientific investigation.

(Disclaimer: The opinions expressed above are the personal views of the author and do not reflect the views of ZMCL)

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Facts that China is trying to suppress about origin of COVID-19 - WION

Apr 29th 2020

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AURIC GOLDFINGER, villain of the novel which bears his name, quotes a vivid Chicago aphorism to James Bond: Once is happenstance, twice is coincidence, the third time its enemy action.

Until 2002 medical science knew of a handful of coronaviruses that infected human beings, none of which caused serious illness. Then, in 2002, a virus now called SARS-CoV surfaced in the Chinese province of Guangdong. The subsequent outbreak of severe acute respiratory syndrome (SARS) killed 774 people around the world before it was brought under control. In 2012 another new illness, Middle Eastern respiratory syndrome (MERS), heralded the arrival of MERS-CoV, which while not spreading as far and as wide as SARS (bar an excursion to South Korea) has not yet been eliminated. It has killed 858 people to date, the most recent of them on February 4th.

The third time, it was SARS-CoV-2, now responsible for 225,000 covid-19 deaths. Both SARS-CoV and MERS-CoV are closely related to coronaviruses found in wild bats. In the case of SARS-CoV, the accepted story is that the virus spread from bats in a cave in Yunnan province into civets, which were sold at markets in Guangdong. In the case of MERS-CoV, the virus spread from bats into camels. It now passes regularly from camels to humans, which makes it hard to eliminate, but only spreads between people in conditions of close proximity, which makes it manageable.

Third time unluckyAn origin among bats seems overwhelmingly likely for SARS-CoV-2, too. The route it took from bat to human, though, has yet to be identified. If, like MERS-CoV, the virus is still circulating in an animal reservoir, it could break out again in the future. If not, some other virus will surely try something similar. Peter Ben Embarek, an expert on zoonoses (diseases passed from animals to people) at the World Health Organisation, says that such spillovers are becoming more common as humans and their farmed animals push into new areas where they have closer contact with wildlife. Understanding the detail of how such spillovers occur should provide insights into stopping them.

In some minds, though, the possibility looms of enemy action on the part of something larger than a virus. Since the advent of genetic engineering in the 1970s, conspiracy theorists have pointed to pretty much every new infectious disease, from AIDS to Ebola to MERS to Lyme disease to SARS to Zika, as being a result of human tinkering or malevolence.

The politics of the covid-19 pandemic mean that this time such theories have an even greater appeal than normal. The pandemic started in China, where the governments ingrained urge to cover problems up led it to delay measures that might have curtailed its spread. It has claimed its greatest toll in America, where the recorded number of covid-19 deaths already outstrips the number of names on the Vietnam War Memorial in Washington, DC.

These facts would have led to accusations ringing out across the Pacific come what may. What makes things worse is a suspicion in some quarters that SARS-CoV-2 might in some way be connected to Chinese virological research, and that saying so may reapportion any blame.

There is no evidence for the claim. Western experts say categorically that the sequence of the new viruss genomewhich Chinese scientists published early on, openly and accuratelyreveals none of the telltales genetic engineering would leave in its wake. But it remains a fact that in Wuhan, where the outbreak was first spotted, there is a laboratory where scientists have in the past deliberately made coronaviruses more pathogenic.

Such research is carried out in laboratories around the world. Its proponents see it as a vital way of studying the question that covid-19 has brought so cruelly into the spotlight: how does a virus become the sort of thing that starts a pandemic? That some of this research has been done at the Wuhan Institute of Virology (WIV) seems all but certainly a coincidence. Without a compelling alternative account of the diseases origin, however, there is room for doubt to remain.

The 4% differenceThe origin of the virus behind the 2003 SARS outbreakclassic SARS, as some virologists now wryly call itwas established in large part by Shi Zhengli, a researcher at WIV sometimes referred to in Chinese media as the bat lady. Over a period of years she and her team visited remote locations all across the country in search of a close relative of SARS-CoV in bats or their guano. They found one in a cave full of horseshoe bats in Yunnan.

It is in the collection of viral genomes assembled during those studies that scientists have now found the bat virus closest to SARS-CoV-2. A strain called RaTG13 gathered in the same cave in Yunnan shares 96% of its genetic sequence with the new virus. RaTG13 is not that viruss ancestor. It is something more like its cousin. Edward Holmes, a virologist at the University of Sydney, estimates that the 4% difference between the two represents at least 20 years of evolutionary divergence from some common antecedent, and probably something more like 50.

Although bats could, in theory, have passed a virus descended from that antecedent directly to humans, experts find the idea unlikely. The bat viruses look different from SARS-CoV-2 in a specific way. In SARS-CoV-2 the spike protein on the viral particles surface has a receptor-binding domain (RBD) that is adept at sticking to a particular molecule on the surface of the human cells the virus infects. The RBD in bat coronaviruses is not the same.

One recent study suggests that SARS-CoV-2 is the product of natural genomic recombination. Different coronaviruses infecting the same host are more than happy to swap bits of genome. If a bat virus similar to RaTG13 got into an animal already infected with a coronavirus which boasted an RBD better suited to infecting humans, a basically batty virus with a more human-attuned RBD might well arise. That is what SARS-CoV-2 looks like.

Early on, it was widely imagined that the intermediate host was likely to be a species sold in Wuhans Huanan Seafood and Wildlife Market, a place where all sorts of creatures, from raccoon dogs to ferret badgers, and from near and far, are crammed together in unsanitary conditions. Many early human cases of covid-19 were associated with this market. Jonathan Epstein, vice-president of science with EcoHealth Alliance, an NGO, says of 585 swabs of different surfaces around the market, about 33 were positive for SARS-CoV-2. They all came from the area known to sell wild animals. That is pretty much as strong as circumstantial evidence gets.

The first animal to come under serious suspicion was the pangolin. A coronavirus found in pangolins has an RBD essentially identical to that of SARS-CoV-2, suggesting that it might have been the virus with which the bat virus recombined on its way to becoming SARS-CoV-2. Pangolins are used in traditional medicine, and though they are endangered, they can nonetheless be found on menus. There are apparently no records of them being traded at the Huanan market. But given that such trading is illegal, and that such records would now look rather incriminating, this is hardly proof that they were not.

The fact that pangolins are known to harbour viruses from which SARS-CoV-2 could have picked up its human-compatible RBD is certainly suggestive. But a range of other animals might harbour such viruses, too; its just that scientists have not yet looked all that thoroughly. The RBD in SARS-CoV-2 is useful not only for attacking the cells of human beings and, presumably, pangolins. It provides access to similar cells in other species, too. In recent weeks SARS-CoV-2 has been shown to have found its way from humans into domestic cats, farmed mink and a tiger. There is some evidence that it can actually pass between cats, which makes it conceivable that they were the intermediatethough there is as yet no evidence of a cat infecting a human.

The markets appeal as a site for the human infections behind the Wuhan outbreak remains strong; a market in Guangdong is blamed for the spread of SARS. Without a known intermediate, though, the evidence against it remains circumstantial. Though many early human cases were associated with the market, plenty were not. They may have been linked to people with ties to the market in ways not yet known. But one cannot be sure.

Where to begin?The viral genomes found in early patients are so similar as to suggest strongly that the virus jumped from its intermediate host to people only once. Estimates based on the rate at which genomes diverge give the earliest time for this transfer as early October 2019. If that is right there were almost certainly infections which were not serious, or which did not reach hospitals, or which were not recognised as odd, before the first official cases were seen in Wuhan at the beginning of December. Those early cases may have taken place elsewhere.

Ian Lipkin, the boss of the Centre for Infection and Immunity at Columbia University, in New York, is working with Chinese researchers to test blood samples taken late last year from patients with pneumonia all around China, to see if there is any evidence for the virus having spread to Wuhan from somewhere else. If there is, then it may have entered Huanan market not in a cage, but on two legs. The market is popular with visitors as well as locals, and is close to Hankou railway station, a hub in Chinas high-speed rail network.

Further research may make when, where and how the virus got into people clearer. There is scope for a lot more virus hunting in a wider range of possible intermediate species. If it were possible to conduct detailed interviews with those who came down with the earliest cases of covid-19, that genetic sampling could be better aimed, says Dr Embarek, and with a bit of luck one might get to the source. But the time needed to do this, he adds, might be quick, or it might be extremely long.

If it turns out to have originated elsewhere, the new viruss identification during the early stages of the Wuhan epidemic may turn out to be thanks to the citys concentration of virological know-howknow-how that is now surely being thrown into sequencing more viruses from more sources. But until a satisfactory account of a natural spillover is achieved, that same concentration of know-how, at WIV and another local research centre, the Wuhan Centre for Disease Control and Prevention, will continue to attract suspicion.

In 2017 WIV opened the first biosecurity-level 4 (BSL-4) laboratory in Chinathe sort of high-containment facility in which work is done on the most dangerous pathogens. A large part of Dr Shis post-SARS research there has been aimed at understanding the potential which viruses still circulating among bats have to spill over into the human population. In one experiment she and Ge Xingyi, also of the WIV, in collaboration with American and Italian scientists, explored the disease-like potential of a bat coronavirus, SHC014-CoV, by recombining its genome with that of a mouse-infecting coronavirus. The WIV newsletter of November 2015 reported that the resulting virus could replicate efficiently in primary human airway cells and achieve in vitro titres equivalent to epidemic strains of SARS-CoV. In early April this newsletter and all others were removed from the institutes website.

This work, results from which were also published in Nature Medicine, demonstrated that SARS-CoVs jump from bats to humans had not been a fluke; other bat coronaviruses were capable of something similar. Useful to know. But giving pathogens and potential pathogens extra powers in order to understand what they may be capable of is a controversial undertaking. These gain of function experiments, their proponents insist, have important uses such as understanding drug resistance and the tricks viruses employ to evade the immune system. They also carry obvious risks: the techniques on which they depend could be abused; their products could leak. The creation of an enhanced strain of bird flu in 2011 in an attempt to understand the peculiar virulence of the flu strain responsible for the pandemic of 1918-19 caused widespread alarm. America stopped funding gain-of-function work for several years.

Filippa Lentzos, who studies biomedicine and security at Kings College, London, says the possibility of SARS-CoV-2 having an origin connected with legitimate research is being discussed widely in the world of biosecurity. The possibilities speculated about include a leak of material from a laboratory and also the accidental infection of a human being in the course of work either in a lab or in the field.

Leaks from laboratories, including BSL-4 labs, are not unheard of. The worlds last known case of smallpox was caused by a leak from a British laboratory in 1978. An outbreak of foot and mouth disease in 2007 had a similar origin. In America there have been accidental releases and mishandlings involving Ebola, and, from a lower-containment-level laboratory, a deadly strain of bird flu. In China laboratory workers seem to have been infected with SARS and transmitted it to contacts outside on at least two occasions.

Heres one I made earlierThings doubtless leak out of labs working at lower biosafety levels, too. But how much they do so is unknown, in part because people worry about them less. And as in other parts of this story the unknown is a Petri dish in which speculation can grow. This may be part of the reason for interest in a lab at the Wuhan Centre for Disease Control and Prevention. A preprint published on ResearchGate, a website, by two Chinese scientists and subsequently removed suggested that work done there may have been cause for concern. This lab is reported to have housed animalsincluding, for one study, hundreds of bats from Hubei and Zhejiang provincesand to have specialised in pathogen collection.

Richard Pilch, who works on chemical and biological weapons non-proliferation at the Middlebury Institute of International Studies, in California, says that there is one feature of the new virus which might conceivably have arisen during passaging experiments in which pathogens are passed between hosts so as to study the evolution of their ability to spread. This is the polybasic cleavage site, which might enhance infectivity. SARS-CoV-2 has such a site on its spike protein. Its closest relatives among bat coronaviruses do not. But though such a cleavage site could have arisen through passaging there is no evidence that, in this case, it did. It could also have evolved in the normal way as the virus passed from host to host. Dr Holmes, meanwhile, has said that there is no evidence that SARS-CoV-2...originated in a laboratory in Wuhan, China. Though others have speculated about coincidences and possibilities, no one has been able, as yet, to undermine that statement.

Many scientists think that with so many biologists actively hunting for bat viruses, and gain-of-function work becoming more common, the world is at increasing risk of a laboratory-derived pandemic at some point. One of my biggest hopes out of this pandemic is that we address this issueit really worries me, says Dr Pilch. Today there are around 70 BSL-4 sites in 30 countries. More such facilities are planned.

Again, though, it is necessary to consider the unknown. Every year there are tens of thousands of fatal cases of respiratory disease around the world of which the cause is mysterious. Some of them may be the result of unrecognised zoonoses. The question of whether they really are, and how those threats may stack up, needs attention. That attention needs laboratories. It also needs a degree of open co-operation that America is now degrading with accusations and reductions in funding, and that China has taken steps to suppress at source. That suppression has done nothing to help the country; indeed, by supporting speculation, it may yet harm it.

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The pieces of the puzzle of covid-19s origin are coming to light - The Economist

In the fall of 2011, Dr. Ron Fouchier developed one of the most dangerous viruses you can make. Fouchier, a Dutch virologist at the Erasmus Medical Center in Rotterdam, claimed that his team had done something really, really stupid and mutated the hell out of H5N1.At nearly the same time, Dr. Yoshihiro Kawaoka at the University of Wisconsin-Madison worked on grafting the H5N1 spike gene onto 2009 H1N1 swine flu, creating another transmissible, virulent strain.

Despite only 600 human cases of the H5N1 (bird flu) virus in the previous two decades, the exceptionally high mortality rate greater than 50 percent pushed the National Science Advisory Board for Biosecurity to block the publication of both teams research. After a heated debate in the scientific community, the World Health Organization deemed it safe to publish the findings. While Kawaokas paper appeared in the journal Nature, Fouchiers original study appeared in Science. Although both teams generated viruses that were not as lethal as their wild forms, critics worried that the papers would enable rogue scientists to replicate the manipulations and weaponize a more contagious virus.

While some arms control experts like Graham Allison believe that terrorists are more likely to be able to obtain and use a biological weapon than a nuclear weapon, others have dismissed bioweapons due to dissemination issues, exemplified in failed biological attacks with botulinum toxin and anthrax by the terrorist group Aum Shinrikyo. Furthermore, studies from the U.S. Office of Technology Assessment indicated that bioweapons could cause tens of thousands of deaths under ideal environmental conditions but would not severely undermine critical infrastructure. In 2012, Dr. Anthony Fauci, the longtime director of the National Institute of Allergy and Infectious Diseases, argued that the benefits in vaccine advancement from Fouchiers research outweighed the risks of nefarious use.

Today, however, Fauci is at the helm of Americas response to a global pandemic. Although the world has never experienced a mass-casualty bioweapons incident, COVID-19 has caused sustained, strategic-level harm. In the absence of a vaccine, it has killed more than 60,000 Americans and forced over 30 million Americans into unemployment. The isolation of large segments of society has crippled the economy and traditional sources of American power: domestically, cascading, second- and third-order effects plague critical national infrastructure; and internationally, power projection wanes, epitomized by the U.S. Navys sidelining of the USS Theodore Roosevelt.

While the SARS-CoV-2 virus that causes COVID-19 is not a bioweapon, technological advances increase the possibility of a future bioweapon wreaking similar strategic havoc. Specifically, advancements in genetic engineering and delivery mechanisms may lead to the more lethal microorganisms and toxins and, consequently, the most dangerous pandemic yet. Therefore, the United States should develop a new strategy to deter and disrupt biological threats to the nation.

Engineering the Next Pandemic

Although a bioweapon-induced pandemic seems unlikely in the short term, preparedness for future attacks begins with understanding the possible threat. According to the Centers for Disease Control, bioweapons are intentionally released microorganisms bacteria, viruses, fungi or toxins, coupled with a delivery system, that cause disease or death in people, animals, or plants. In contrast to other chemical, biological, radiological, or nuclear weapons, they have distinctive dangerous characteristics: miniscule quantities even 10-8 milligrams per person can be lethal; the symptoms can have a delayed onset; and ensuing waves of infection can manifest beyond the original attack site. The Centers for Disease Control grouped over 30 weaponizable microorganisms and toxins into three threat categories based on lethality, transmissibility, and necessity for special public heath interventions. While Categories A and B cover existing high and moderate threats, respectively, Category C focuses on emerging pathogens, like the Nipah virus and hantavirus, that could be engineered for mass dissemination. Historically, though, bioweapons were relatively unsophisticated and inexpensive when compared to chemical and nuclear production chains, which explains their protracted use.

One of the earliest examples of biological warfare occurred over 2,000 years ago, when Assyrians infected enemy wells with rye ergot fungus. In 1763, the British army presented smallpox-infested blankets to Native American during the Siege of Fort Pitt. During World War II, the Japanese army poisoned over 1,000 water wells in Chinese villages to study typhus and cholera outbreaks. In 1984, the Rajneeshee cult contaminated salad bars in Oregon restaurants with Salmonella typhimurium, causing 751 cases of enteritis. Most recently, Bacillus anthracis spores sent in the U.S. postal system induced 22 cases of anthrax and five deaths in 2001, and three U.S. Senate office buildings shut down in February 2004 after the discovery of ricin in a mailroom.

Despite this history of usage, the challenge of disseminating the biological agent has, thus far, meant that bioweapons attacks have not produced high casualties. Bioweapons can be delivered in numerous ways: direct absorption or injection into the skin, inhalation of aerosol sprays, or via consumption of food and water. The most vulnerable and often most lethal point of entry is the lungs, but particles must fall within a restrictive size range of 1 micrometer to 5 micrometers to penetrate them. Fortunately, most biological agents break down quickly in the environment through exposure to heat, oxidation, and pollution, coupled with the roughly 50 percent loss of the microorganism during aerosol dissemination or 90 percent loss during explosive dissemination.

The revolution in genetic engineering provides a path for overcoming delivery issues and escalating a biological attack into a pandemic. First, tools for analyzing and altering a microorganisms DNA or RNA are available and affordable worldwide. The introduction of clustered regularly interspersed short palindromic repeats (CRISPR) a technique that acts like scissors or a pencil to alter DNA sequences and gene functions in 2013 made biodefense more challenging. Even as experienced researchers struggle to control clustered regularly interspersed short palindromic repeats and prevent unintended effects, malevolent actors with newfound access can attempt to manipulate existing agents to increase contagiousness; improve resistance to antibiotics, vaccines, and anti-virals; enhance survivability in the environment; and develop means of mass production. Infamously, Australian researchers in 2001 endeavored to induce infertility in mice by inserting the interleukin-4 gene into the mousepox virus. Instead, they inadvertently altered the virus to become more virulent and kill previously vaccinated mice, insinuating that the same could be done with smallpox for humans.

Moving one step further, genetic engineering raises the possibility of creating completely new biological weapons from scratch via methods similar to the test-tube synthesis of poliovirus in 2002. It is, thankfully, hard to use this process to create agents that can kill humans. However, genetic engineering can be used to create non-lethal weapons that, when coupled with longer-range delivery devices, could kill crops and animals, and destroy materials fuel, plastic, rubber, stealth paints, and constructional supplies that are critical to the economy.

Skeptics might question why a rational adversary would risk creating and employing bioweapons that are unpredictable and relatively hard to deliver to a target. First, some potential terrorists are irrational in the sense that death does not deter their service to a higher purpose; or, they may simply show a willingness to carry out orders from a state sponsor or a lack of concern for public opinion. Second, future state aggressors might genetically engineer a vaccine to immunize their populations prior to unleashing a bioweapon so that the attack would only be indiscriminate within targeted nations. Third, the unprecedented harm done by COVID-19 demands a transformation of 9/11-era priorities to recognize that preparing for domestic threats like pandemics will be far greater concerns for most Americans than threats from foreign adversaries. Bioweapons combine the worst of these national and international threats.

Ultimately, for a bioweapon attack to turn into a pandemic like the SARS-CoV-2 virus, three initial conditions must be met: first, the microorganism or toxin must not have an effective remedy available; second, it must be easily transmittable; and third, it must be fatal for some victims. Whereas a number of natural-born microbes satisfied these conditions in the past, it is possible for a genetically engineered bioweapon to have the same strategic impact in the future.

Prepare for the Worst

John Barrys The Great Influenza: The Story of the Deadliest Pandemic in History provides insight into what the world might look like in the approaching age of biological attacks. It portrays how researchers failed to counter the 1918 flu strain while it spread to one-third of the global population. With a mortality rate of approximately 20 percent, the Spanish flus viral mutations proved especially fatal for military members with strong immune systems. Young people with previous exposure to milder flu strains likely suffered from immunological memory, which prompted a dysregulated immune response to the 1918 strain. At the time of the books publication in 2004, President George W. Bush took notice.

In a November 2005 speech at the National Institutes of Health, with Fauci notably in attendance, Bush warned, If we wait for a pandemic to appear, it will be too late to prepare. And one day many lives could be needlessly lost because we failed to act today. Similarly, the government should prepare now to respond to a future bioweapon attack whether from terrorism or interstate warfare. This preparation ought to proceed along three categories of action: deterrence, disruption, and defense.

Deterrence

In the realm of biological warfare, the most effective way to save lives is to persuade an adversary that an attack will not succeed. Specifically, deterrence by denial makes the act of aggression unprofitable by rendering the target harder to take, harder to keep, or both. To this end, the United States can harden its biowarfare response by increasing interagency cooperation, wargaming the resulting plans, and compiling the materials required for their execution.

The Department of Defense the largest agency in the U.S. government is the logical choice to organize a whole-of-government approach to countering bioweapons. Last November, the Pentagon released the Joint Countering Weapons of Mass Destruction doctrine, which outlined how the military will synchronize its response with governmental stakeholders like the Director of National Intelligence, the United States Agency for International Development, the Department of Energy, and the Department of Health and Human Services. Partnerships, however, should expand beyond governmental agencies via a military joint task force with leadership from the medical community and information technology professionals. The Department of Homeland Security and Centers for Disease Control should coordinate with medical schools to incorporate more curriculum and periodic exercises on pandemic control and emergency response. Likewise, the Pentagon should develop best practices for establishing communications, sustaining services, and combatting disinformation during a pandemic.

While increased interagency cooperation will encourage more robust pandemic plans, wargaming is key to testing how such plans fare in a biowarfare crisis. Last September, the Naval War College in Newport, Rhode Island, ran a two-day wargame called Urban Outbreak 2019, in which 50 experts combatted a notional pandemic. Even though this scenario had a vaccine available from the start, the findings offer prescient insight into actions surrounding COVID-19 particularly that experienced leaders may display significant resistance when encountering first-time situations or prevent troops from interfacing with infected populations. Military and agency leaders should use wargames with worst-case, extraordinary bioweapons to recognize and overcome inherent biases while simultaneously brainstorming how to lower infection rates, implement quarantines, and communicate best practices to the public.

Wargaming should also help planners identify which materials require stockpiling ahead of the next pandemic. COVID-19, for example, exposed shortages of durable protective masks, hand sanitizer, antiseptic wipes, and surface cleaners. The 300,000 businesses that make up the defense industrial base should prepare for the research, production, and delivery of personal protective equipment whenever shortages arise. They should also expect to be tapped for antibiotic, vaccine, or anti-viral production, depending on the nature of the bioweapon.

Disruption

A pandemic is a lot like a forest fire, Bush said in his 2005 speech. If caught early it might be extinguished with limited damage. If deterrence fails, American policy should focus on the early detection and disruption of bioweapons. To achieve this goal, the United States can advocate for increased verification measures and high-performing information operations.

Although the Biological Weapons Convention went into force in 1975 and has 182 state parties, the treaty lacks verification procedures and merely prohibits the production, stockpiling, and transfer of biological agents for warfare purposes. Since the treaty permits defensive research, a major challenge is the dual-use nature of production chains, wherein the technology for allowable projects also supports harmful weapons. Given the complex and sensitive nature of vital biological research, the United States has chosen not to support the establishment of a verification agency for routine facility inspections. This choice stands in contrast to the American approach toward the Organization for the Prohibition of Chemical Weapons and the International Atomic Energy Agency, both of which have robust verification mechanisms. Without this accountability, however, the Soviet Union established the Biopreparat after signing the Biological Weapons Convention treaty, employing over 50,000 people to produce tons of anthrax bacilli, smallpox virus, and multidrug-resistant plague bacteria.

To assist with the early warning of bioweapon threats, the United States should improve its understanding of international biological facilities. For instance, International Gene Synthesis Consortium members use automated software and a common protocol to screen their customers, as well as synthetic gene orders with dangerous sequences from the Regulated Pathogen Database. Particular attention should be paid to biosafety level-4 and biosafety level-3 labs around the world, where human error has led to the unintentional escape of pathogens. The U.K. foot and mouth outbreak of 2007 was traced to a faulty waste disposal system at Pirbright Laboratory in Surrey. Additionally, SARS laboratory accidents occurred in China in 2004. Increasing the priority given to intelligence gathering and analysis related to bioweapons would be an important step in the right direction.

Defense

If the United States is unable to deter or disrupt a bioweapons attack, it should be prepared to execute a strong defense against it. First and foremost, the military ought to maintain the health of its servicemembers through a COVID-19-inspired operational plan for screening and quarantine. This plan would facilitate prompt and sustained emergency responses and combat operations, including key missions like strategic nuclear deterrent patrols. Domestically, the military will need to assist in civil support, law enforcement, border patrol, and the defense of critical infrastructure. Internationally, the Defense Department will serve as a logistics powerhouse.

At home, the armed forces have the manpower and experience to aid in a variety of national security sectors. In addition to the deployment of U.S. Navy hospital ships to New York City and Los Angeles during COVID-19, the National Guard has conducted drive-through testing, delivered water to vulnerable populations, and carried out state governors law enforcement orders for curfews and quarantines. For critical national infrastructure, the military will serve as first responders to newfound issues with electrical generation, water purification, sanitation, and information technology.

Abroad, the military could benefit from military-to-military planning and exercises with what former Supreme Allied Commander Europe Adm. (ret.) James Stavridis calls the equivalent of a North Atlantic Treaty Organization against pandemics. In the absence of this organization, the Air Force can coordinate logistics efforts to move overseas medical supplies to the United States and bring Americans home.

The United States should draw lessons learned from past international pandemic responses. The cholera outbreak among half a million Haitians following a 2010 earthquake demonstrated that the American military could work with international military counterparts to regenerate critical infrastructure in other countries. The Ebola outbreak in West Africa in 2014 extended that cooperation to nongovernmental organizations like the Red Cross, Doctors Without Borders, and Project Hope.

Successful military cooperation abroad will fulfill basic international needs and build trust for peaceful scientific cooperation, shifting the focus to future questions like whether the bioweapon is mutating, how environmental factors affect its spread, if infected people develop short- or long-term immunity, and which mitigation efforts are effective. Successful in-situ defense will fill interdisciplinary gaps in deterrence and disruption while a layered 3D approach will determine how well the world fares during the most dangerous pandemic yet.

Conclusion

The COVID-19 pandemic foreshadows how a future bioweapons attack would unfold without proper preparation. Planning for a bioweapons attack is incredibly difficult bioweapons can be delivered by states or terrorist groups, originate from existing agents or from scratch, and can be delivered in a number of different ways. While establishing a permanent military joint task force with appropriate funding is an achievable first step, combined efforts in deterrence, disruption, and defense are key in anticipating these variables of an attack and surviving it once unleashed.

Lt. Andrea Howard is a nuclear submarine officer aboard the USS Ohio. Following her graduation from the U.S. Naval Academy in 2015, she was a Marshall Scholar at the University of Oxford and Kings College London, where she focused on the intersection of technology, security, and diplomacy in weapons of mass destruction policy. Lt. Howard won the U.S. Naval Institutes 2019 Emerging and Disruptive Technologies Essay Contest and is a member of the Seattle Chapter of the Truman National Security Project.

Image: North Carolina Air National Guard (Photo by Tech. Sgt. Julianne Showalter)

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The Pandemic and America's Response to Future Bioweapons - War on the Rocks

Why are the origins of the pandemic so controversial?

How Covid-19 began has become increasingly contentious, with the US and other allies suggesting China has not been transparent about the origins of the outbreak.

Donald Trump, the US president, has given credence to the idea that intelligence exists suggesting the virus may have escaped from a lab in Wuhan, although the US intelligence community has pointedly declined to back this up. The scientific community says there is no current evidence for this claim.

This follows reports that the White House had been pressuring US intelligence community on the claim, recalling the Bush administrations pressure to stove pipe the intelligence before the war in Iraq.

A specific issue is that the official origin story doesnt add up in terms of the initial epidemiology of the outbreak, not least the incidence of early cases with no apparent connection to the Wuhan seafood market, where Beijing says the outbreak began. If these people were not infected at the market, or via contacts who were infected at the market, critics ask, how do you explain these cases?

Two laboratories in Wuhan studying bat coronaviruses have come under the spotlight. The Wuhan Institute of Virology (WIV) is a biosecurity level 4 facility the highest for biocontainment and the level 2 Wuhan Centre for Disease Control, which is located not far from the fish market, had collected bat coronavirus specimens.

Several theories have been promoted. The first, and wildest, is that scientists at WIV were engaged in experiments with bat coronavirus, involving so-called gene splicing, and the virus then escaped and infected humans. A second version is that sloppy biosecurity among lab staff and in procedures, perhaps in the collection or disposal of animal specimens, released a wild virus.

The scientific consensus rejecting the virus being engineered is almost unanimous. In a letter to Nature in March, a team in California led by microbiology professor Kristian Andersen said the genetic data irrefutably shows that [Covid-19] is not derived from any previously used virus backbone in other words spliced sections of another known virus.

Far more likely, they suggested, was that the virus emerged naturally and became stronger through natural selection. We propose two scenarios that can plausibly explain the origin of Sars-CoV-2: natural selection in an animal host before zoonotic [animal to human] transfer; and natural selection in humans following zoonotic transfer.

Peter Ben Embarek, an expert at the World Health Organization in animal to human transmission of diseases, and other specialists also explained to the Guardian that if there had been any manipulation of the virus you would expect to see evidence in both the gene sequences and also distortion in the data of the family tree of mutations a so-called reticulation effect.

In a statement to the Guardian, James Le Duc, the head of the Galveston National Laboratory in the US, the biggest active biocontainment facility on a US academic campus, also poured cold water on the suggestion.

There is convincing evidence that the new virus was not the result of intentional genetic engineering and that it almost certainly originated from nature, given its high similarity to other known bat-associated coronaviruses, he said.

The accidental release of a wild sample has been the focus of most attention, although the evidence offered is at best highly circumstantial.

The Washington Post has reported concerns in 2018 over security and management weakness from US embassy officials who visited the WIV several times, although the paper also conceded there was no conclusive proof the lab was the source of the outbreak.

Le Duc, however, paints a different picture of the WIV. I have visited and toured the new BSL4 laboratory in Wuhan, prior to it starting operations in 2017- It is of comparable quality and safety measures as any currently in operation in the US or Europe.

He also described encounters with Shi Zhengli, the Chinese virologist at the WIV who has led research into bat coronaviruses, and discovered the link between bats and the Sars virus that caused disease worldwide in 2003, describing her as fully engaged, very open and transparent about her work, and eager to collaborate.

Maureen Miller, an epidemiologist who worked with Shi as part of a US-funded viral research programme, echoed Le Ducs assessment. She said she believed the lab escape theory was an absolute conspiracy theory and referred to Shi as brilliant.

While the experts who spoke to the Guardian made clear that understanding of the origins of the virus remained provisional, they added that the current state of knowledge of the initial spread also created problems for the lab escape theory.

When Peter Forster, a geneticist at Cambridge, compared sequences of the virus genome collected early in the Chines outbreak and later globally he identified three dominant strains.

Early in the outbreak, two strains appear to have been in circulation at roughly at the same time strain A and strain B with a C variant later developing from strain B.

But in a surprise finding, the version with the closest genetic similarity to bat coronavirus was not the one most prevalent early on in the central Chinese city of Wuhan but instead associated with a scattering of early cases in the southern Guangdong province.

Between 24 December 2019 and 17 January 2020, Forster explains, just three out of 23 cases in Wuhan were type A, while the rest were type B. In patients in Guangdong province, however, five out of nine were found to have type A of the virus.

The very small numbers notwithstanding, said Forster, the early genome frequencies until 17 January do not favour Wuhan as an origin over other parts of China, for example five of nine Guangdong/Shenzhen patients who had A types.

In other words, it still remains far from certain that Wuhan was even necessarily where the virus first emerged.

The pandemic has exacerbated existing geopolitical struggles, prompting a disinformation war that has drawn in the US, China, Russia and others.

Journalists and scientists have been targeted by people with an apparent interest in pushing circumstantial evidence related to the viruss origins, perhaps as part of this campaign and to distract from the fact that few governments have had a fault-free response.

The current state of knowledge about coronavirus and its origin suggest the most likely explanation remains the most prosaic. Like other coronaviruses before, it simply spread to humans via a natural event, the starting point for many in the scientific community including the World Health Organization.

Further testing in China in the months ahead may eventually establish the source of the outbreak. But for now it is too early.

Read more from the original source:
Where did Covid-19 come from? What we know about its origins - The Guardian

The team's results, posted as a preprint in BioRxiv earlier this month, proposed a handful of ACE2 variants suspected of boosting SARS-CoV-2 binding and, potentially, host susceptibility, along with several variants predicted to dial down ACE2 interactions with the viral spike protein that may be protective.

"What we can conclude is that this new virus has evolved new modality to interact with the ACE2 receptor," Jura noted. "Unfortunately, it seems like there are polymorphisms in the human population that will make some individuals more susceptible to binding this virus because these mutations are enhancing this unique part of the interface."

Seshagiri noted that such insights might make it possible to design potential therapeutic versions of ACE2 that are particularly adept at binding coronavirus spike proteins, thereby preventing the viruses from interacting with an individual's own ACE2 receptors, for example.

In a recent Cell paper, a team from Sweden, Spain, Austria, and Canada proposed its own strategy for engineering soluble, clinical-grade forms of the human ACE2 protein that appeared to dial down early-stage infections by SARS-CoV-2 in otherwise susceptible cell types.

"We are not the first to come up with the idea of saying ACE2 could be a therapeutic," he said, though he suggested that engineering soluble forms of the receptors protein that bind well to SARS-CoV-2 may serve as a strategy for "future proofing" against the emergence of these and other related viruses down the road.

The researchers plan to profile ACE2 polymorphisms in still more human samples for the final version of the study, which will likely be submitted for peer review in the coming weeks, Seshagiri said.

He and MedGenome CEO Rayman Mathoda noted that the diagnostic company, which is active in India and other emerging markets, is also a founding member of a GenomeAsia 100K project.

"We've made a very intentional effort to build on a data-focused set of efforts, where we take our proprietary data as we grow, but build in other data source," Mathoda said.

The investigators are not alone in attempting to establish a baseline understanding of ACE2 variation across and within populations.

At the University of Siena in northern Italy, Alessandra Renieri and her colleagues have been delving into ACE2 genetic variation using available exome sequences for some 7,000 healthy participants in the Network of Italian Genomes project. As they reported in a preprint posted to MedRxiv in early April, the investigators saw significant variation in ACE2 in that retrospective dataset, including both common and rare, missense variants predicted to influence the protein's stability and its interactions with the coronavirus viral spike.

"There is pretty wide genetic variability," Renieri said. "There are both polymorphisms, so variants found in a percentage of the population, and there are also rare variants a lot of rare variants."

It may be possible for the individual centers participating in the Network of Italian Genomes to recontact individuals in the future to try to find out who became infected with SARS-CoV-2 and to assess ACE2 variation alongside clinical outcomes, Renieri noted, though she cautioned that "ACE2 is just one of the many genes that could be involved."

For the reCOVID project, members of the team are seeking funding through the European Commission's Innovative Medicines Initiative IMI2 call for proposals to do functional analyses on ACE2 and other genes, for example, in the hopes of developing candidate therapeutics.

Renieri is also part of a team that been working since mid-March to prospectively collect samples from 2,000 COVID-19 patients at least 21 different hospitals in Italy as part of the GEN-COVID study, part of the COVID-19 Host Genetics Initiative.

For that project, researchers in Italy will use whole-exome sequencing to assess patient samples collected in conjunction with very detailed clinical information, she explained, while collaborators in Finland will genotype the samples for a related genome-wide association study.

Continued here:
A gene that could unlock the mysteries of COVID-19 - ModernHealthcare.com

TORONTO, April 21, 2020 (GLOBE NEWSWIRE) -- Along-standing regulatory requirementto bringvaccinesto marketinvolvestesting them onanimal models prior to clinical trials with humans.Although thisseems like a very good safety measure for humans,most people donot know that90% of whatworked on animal models didn't workforhumans andinsomecaseseven caused harm.

This acceptance of a 10% predictive rate using animal models is in stark contrast with the85-90% predictive rate using modern vitro technologies. According to veterinarian Dr. Andre Menache, "the requirement for testing on animal models dates back to theNuremberg Codes of 1947 and is still the norm in national and international legislation today."

Liz White, Director of Animal Alliance of Canada, a national animal advocacyorganization, states, "What most people do not know is that mice are resistant to the COVID-19 virus. Mice are forced through genetic engineering to have the human version of the enzyme that causes COVID-19. Researchers then use the mice to test a vaccine in order tomeet regulatory requirements before starting clinical trials on humans. This process seems scientifically flawed."

We need a vaccine to combat COVID-19 (SARS-CoV2), a virus globally ravaging populations and economies today. Consequently, we need to discuss and challenge testing on animal models when we should be using human relevant models. According to Dr. Menache, "there are some high-performance technologies of the 21st century we can use for example 'MIMIC' (Modular IMune In vitro Construct). It's an in vitro model of the human immune system." According to Michael Rivard, vice president of corporate development at VaxDesign, "the information you get from this type of test is far beyond what you'd get out of a mouse study both because it's humans and because you can see the effect across a spectrum of genotypes".

Because we're in an emergency situation, researchers decided to test new treatments directly on volunteer patients. Importantly, these are drugs that have already been tested on animals for their intended uses.

In the recent past, there have been other COVID related viruses, like SARS, for which we still don't have a vaccine. Dr. Menache states, "Perhaps the COVID-19 pandemic will help us to question some of our outdated scientific practices as well as the obsolete regulations that still impose them."

We urge the Trudeau government and theresearch community to establish a research institution whose mandate is the exploration and development of human-relevant research not using animal models to create a better future for all of us,said White. We need to move our research objectives out of the 19th century and into the 21st century.

Liz White, Director, Animal Alliance of CanadaCell (Canada): 416-809-4371Email: liz@animalalliance.ca

Dr. Andre Menache, CEO of Antidote Europe, is a European Veterinary Specialist in Animal Welfare Science, Ethics and Law and a member of theEuropean College of Animal Welfare and Behavioural Medicine. He is a zoologist and a veterinary surgeon with a particularinterest in medical law and was instrumental in amending the Declaration of Helsinki (DH) see DH here:https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/

Dr. Menache,BSc (zoology), BSc(Hons), BVSc, MRCVSCell (France):+33 6 23 42 62 95 Email:andre.menache@gmail.com

Excerpt from:
What Animal Alliance of Canada would like everyone to know about COVID-19 Vaccine Testing - GlobeNewswire