Category Archives: Genetic Engineering

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

WITH food security trending across social media sites, its important to take note of the blue-sky research being carried out in Australia to future-proof our food.

While panic buying and poor logistics have caused the majority of food shortages on Australian supermarket shelves, long-term climate trends and the commercial realities of needing to 'grow more with less' have been driving researchers toward altering the way plants grow at a fundamental level.

Despite the long-winded name, the Australian National University's (ANU) Australian Research Council Centre of Excellence for Transitional Photosynthesis has a rather straightforward mission - research the ways photosynthesis can be altered to increase yield in food crops.

Centre director and ANU professor Robert Furbank said photosynthesis, the process green plants use to convert sunlight into chemical energy, could give farmers the tools to increase crop production while battling with changes to the climate.

"Australian plant scientists are punching above their weight by participating in global, interdisciplinary efforts to find ways to increase crop production," professor Furbank said.

"We essentially need to double the production of major cereals before 2050 to secure food availability for the rapidly growing world population."

Initial outcomes from the research were recently published in the Journal of Experimental Botany.

Co-editor and ANU researcher professor John Evans said the publications showed how improving photosynthesis could benefit food production.

"We are working on improving photosynthesis on different fronts, from finding crop varieties that need less water, to tweaking parts of the process in order to capture more carbon dioxide and sunlight," professor Evans said.

"We know that there is a delay of at least a decade to get these solutions to the breeders and farmers, so we need to start developing new opportunities now before we run out of options."

Professor Evans said the research covers everything from genetic engineering to synthetic biology, working across crops such as wheat, rice and sorghum.

While the pay-off from this sort of 'blue-sky' research can be decades away, professor Furbank said it was important the research was conducted now.

"It is similar to finding a virus vaccine to solve a pandemic, it doesn't happen overnight.

"We know that Australia's agriculture is going to be one area of the world that is most affected by climate extremes, so we are preparing to have a toolbox of plant innovations ready to ensure global food security in a decade or so."

Professor Furbank said this was why long-term proactive funding for blue-sky research was needed.

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Blue-sky thinking for food production - Farm Weekly

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

Merck & Co. said today it will partner with the Institute for Systems Biology (ISB) to identify targets for medicines and vaccines against COVID-19 by investigating and defining the molecular mechanisms of the disease and specifically SARS-CoV-2 infection.

While the value of the collaboration was not disclosed in the announcement, Merck and ISB did say they will use a contract awarded to the pharma giant in 2016 by the Biomedical Advanced Research and Development Authority (BARDA). That contract (HHSO100201600031C) has a potential value of $78.5 million ($78,531,649), and was originally awarded August 29, 2016, to advance development of the vaccine candidate V920 against Ebola virus using a recombinant vesicular stomatitis virus vector, according to a contract summary published by GovTribe.

The contract has been extended from its scheduled end of May 31, 2020, through September 30, 2024.

In December, Merck announced FDA approval of the vaccine under the name ERVEBO (Ebola Zaire Vaccine, Live), indicated for the prevention of disease caused byZaire ebolavirusin individuals 18 years of age and older.

Merck said it had agreed to provide research funding and work with researchers at ISB to characterize targets for potential therapeutic intervention and vaccine development.

Through the collaboration with Merck, scientists from ISB, health workers from the Swedish Medical Center, and a consortium of research organizations and biomedical companies plan to analyze blood samples and nasal swabs from Swedish Medical Center patients with SARS-CoV-2 using samples from several time points that include initial presentation, acute illness and convalescence.

Merck and ISB said proteomic, metabolomic, transcriptomics and genetic techniques will be applied toward examining blood samples, with the aim of evaluating the impact of infection on different organs, and identifying potential biomarkers to predict the risk of severe disease.

In addition, samples will be analyzed to create a profile of the immune response, including quantitative changes in immune cells in patients following SARS CoV-2 infection and characterization of neutralizing antibodies in samples from convalescent patients. These insights can be used to inform vaccine design and antibody therapy, Merck and ISB reason.

The study will initially analyze samples from 200 patients with the potential to expand to 300, Merck and ISB said.

The announcement is Mercks first regarding development of a potential COVID-19 therapeutic. Last month, Merck announced donations of 500,000 personal protective masks to New York City Emergency Management and 300,000 masks to New Jerseys Office of Homeland Security and Preparedness, both toward urgent efforts to address COVID-19 emergency response.

This collaboration with Merck provides critical support for the recently launched scientific trial being co-led by ISB and Swedish Medical Center, both part of the Providence St. Joseph Health network. We launched this trial with the urgent need to improve our understanding of COVID-19, James R. Heath, PhD, president and professor at ISB, said in a statement. By applying the full power of our systems biology capabilities, we hope to gain important insights into the molecular basis for the dramatically contrasting outcomes observed for patients infected with SARS-CoV-2.

Heath and Jason D. Goldman, MD, at Swedish Medical Center, will be the studys principal investigators.

Initial funding support for the study came from the Wilke Family Foundation, M.J. Murdock Charitable Trust, Swedish Foundation, Parker Institute for Cancer Immunotherapy, and Washington State Andy Hill CARE Fund. Other research collaborators on the study include Stanford University, Adaptive Biotechnologies, Bloodworks Northwest, Isoplexis, Metabolon, Nanostring, Olink, Providence Molecular Genomics Laboratory, Scisco Genetics and 10x Genomics.

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Merck & Co. Partnering with ISB to Study Targets for COVID-19 Therapeutics - Genetic Engineering & Biotechnology News

The statement by the pro-GMO expert in an article published in the Ethiopia Observer: [GMOs] in principle, [] could allow increased yield and lower production costs, which translates to increased farm income, lacks moral correctness and it is built more on theory than reality.

The author has every right to promote Genetically Modified Organisms (GMOs) but his article is one-sided, selective in its use of studies, and full of factual errors. The author who has a manifestly unbridled enthusiasm for GMOs makes some overconfident claims, starting from his opening line which says, genetically modified (GM) traits can be valuable and the discussion around them should be based on facts and in a case-by-case approach. However, he did not provide enough case-by-case examples of these traits that could be relevant to solve the problems of smallholder farmers in Ethiopia. After all, any technological intervention must be based on the needs and realities of those smallholder farmers who are the main producers of food and raw material for industrial production in Ethiopia. For instance, we have yet to see GM traits that could be effective to mitigate the devastating wheat rust, withstand extreme drought and frost, and provide a higher yield than existing crop varieties. There are numerous writings that wax lyrical about the virtues of GMOs, many of them written by paid advocates. But independent assessments on the nature and performance of GM crops in comparison with conventionally improved varieties are rare. Even if we must advocate for GMOs, it must be in consideration of the countrys interest than that of the multinationals, whose sole motive is nothing more than profit. We must also communicate facts that are relevant for smallholder farming in Ethiopia instead of stories from commercial farming in the U.S. or other industrialized countries. If the GM traits must be there, it must be with the aim to solve farmers problems.

Indeed, GMOs should not be confused with the use of biotechnology as a science. There are biotechnology tools such as marker-assisted selection that are cheaper and can be helpful in countries like Ethiopia to develop new varieties in a short period of time for use. These kinds of technologies are less risky and easy to integrate with conventional breeding in pro-poor public research institutions.

In the first paragraph, the author wrote, the genome of organisms can be altered to contain [a] genetic variants so that the GMO can express a desired trait, which could, for instance, be drought-tolerance. He adds, in principle, this could allow increased yield and lower production costs, which translates to increased farm income. The truth of the matter is, we have not yet seen super varieties or GM cultivars that have led to a huge surge in yields and tolerate moisture stress. High yield already exists in conventionally breed improved varieties. Most GMOs are created by inserting genes (e.g. from bacteria) into these high yielding varieties to produce toxins that kill insects or to become herbicide tolerant. Thus, two types of GM crops dominate todays market.

Insect-resistant GM crops these types of GM crops are developed by introducing a gene fromBacillus thuringiensis(Bt), a soil bacterium. Such GM plants or Bt-plants were created to produce toxins that kill insect pests. The advantage is that we avoid spraying synthetic chemicals to control insect-pest by growing Bt-crops. This is useful for the environment and the economy of the producer. But things get murkier when the insect evolves through time and develop resistance to Bt toxin produced by the plants. Insect resistance by GM crops breaks as much as those varieties developed through conventional breeding. Studies have already shown this problem. This would force farmers to go back to using chemicals to control the pest, making the cost of production higher as farmers would be obliged to buy expensive GM seeds as well as associated insecticidal chemicals. It also means farmers would be required to spray more chemicals, which is bad for the environment. Another problem with GM crops is that they do not have certain features compared to their counterpart conventional varieties while they maintain insect resistance. For instance, the Bt-cotton failed in Burkina Faso because the fiber quality of cotton was below standard, and farmers were forced to sell at a low price. Generally, GM crops have not demonstrated superior performance compared to conventional varieties in this regard but one thing that we could speak with certitude is they increase production costs. This is because all GMOs are patented, which makes the seeds and associated agrochemical inputs more expensive. Thus, the patent on such GM crops is an incentive for the multinationals to accumulate wealth at the expense of poor farmers.

Herbicide-tolerant GM crops these types of GM crops are modified to tolerate huge doses of chemical herbicide e.g. Roundup Ready GM soybeans. Roundup kills non-modified normal soya plants and weeds. In other words, normal soya plants and all other unwanted plants in the field (weeds) die except those GM soya plants when we spray them with Roundup. Indeed, this makes weed control easier or manageable when we have a huge soya field which otherwise is difficult to control weeds by manual weeding. This can be beneficial for large scale farmers in developed countries where labor is expensive. The problem with this type of GM crop is the emergence of superweeds as observed in recent years. These are tolerant weeds that are no longer killed by Roundup and growers must spray more of it to control weed infestation. This means it exacerbates the environmental hazard. It increases water, soil, and air pollution, which can have a devastating effect on human and ecosystem health. Still, the winners are companies who earn from the sale of a patented chemical (roundup) and GM soya seeds.

Companies are now grabbing plant genetic resources by incorporating genes from traditional plant varieties and wild relatives into GM crops through patenting.

The author correctly points out that altering the genomes of plants and animals did not begin with the emergence of genetic engineering (GE) and genetic modification in recent decades. In fact, people have been altering the genomes of plants and animals for thousands of years starting from domestication through to traditional selection and modern-day breeding, he wrote. This is why many observers find patenting plants and animals outrageous because the diversity of crops that we have today is the result of thousands of years of selection and management by farmers. Companies are now grabbing plant genetic resources by incorporating genes from traditional plant varieties and crop wild relatives into GM crops through patenting It must be underlined that companies are not inventing genes, but they are simply isolating them from farmers varieties or genetic resources in the public domain. They would go on introducing these genes to a new one to claim a patent, which gives them complete monopoly of the genes. The example of introducing a gene that confers resistance to Xanthomonas from sweet pepper to banana shows this technological practice. The same thing is being tried on Enset. This becomes unfair when the technology is monopolized by a handful of multinational companies through patents.

In my view, it is insincere to promote GMOs in a country that has weak or insufficient biosafety regulatory frameworks such as biotechnology and/or biosafety policy, laws, regulations and guidelines, administrative systems, decision-making systems and mechanisms for public engagement.

In addition to hiding these socio-economic harms from use of GMOs, the author intentionally avoids distinguishing genetic engineering from conventional breeding including the selection of better plant varieties by farmers. Genetic engineering (that involves the transfer of genes from unrelated organism to another such as between bacteria and plants to create transgenic organisms), and Genetic modification (that involves modifying the DNA of an organism by removing, replacing some genes or inserting genes from other plants of the same species) is different from farmers selection practices (conscious or unconscious). The later resulted in an enormous diversity of crops and animals we have today. This is a common communication practice by pro-GMO experts to ignore the socio-economic and ecological risks of GMOs. In my view, it is insincere to promote GMOs in a country that has weak or insufficient biosafety regulatory frameworks such as biotechnology and/or biosafety policy, laws, regulations and guidelines, administrative systems, decision-making systems and mechanisms for public engagement. While the authors doubt about Ethiopias eco-leadership is forgivable, the fact he stressed regarding earlier cultivation of GMOs in other African countries is undeniable.

I leave it to the author to learn about Ethiopias Pan-African environmental initiative by reading Dr. Melaku Woreds work and that of Dr. Tewolde Berhan Gebre Egziabher. Earlier cultivation of GMOs in other African countries is true, as the author points out. But he avoids mentioning that the use of GMOs has been restricted to few crops and countries on the continent. The U.S. and its agri-conglomerates pushed for commercial cultivation of GM crops in South Africa in the late 1990s following the countrys transition to democracy from apartheid. It is no accident, that they are trying to push for the same market opportunity in Ethiopia today. They see a similar moment in the countrys history a transition from authoritarian rule to democracy. In the last 20 years, big commercial farmers in South Africa have been growing GMOs. Egypt and Sudan have allowed GM crop cultivation, especially Bt-Cotton. Burkina Faso tried to do the same, but it largely failed. Overall, GMOs have not expanded to many African countries as hoped by the U.S and its companies in the 1990s and later years. Ethiopia, Rwanda, and Uganda seem to be the new target countries now. Uganda has allowed trials for the genetically modified banana in the last few years. Rwanda is considering opening up to genetically modified potato. GMOs have also made their way to the African Union in the form of policy through the development of the African Seed and Biotechnology Programme in 2008. But the program focuses on overall seed system development and states that GMOs can be one alternative, but it should be managed safely. I would also like to remind the author that this program was developed based on the African Model law that Ethiopia drafted in 2000, before its relaxation due to pressure from western donors and new philanthropists such as Bill and Melinda Gates Foundation. It is understandable for the author to say that GM can be a valuable tool but is no cure-all when he argues using a study done by people from Agri-food group and a study that uses data from the internet (a literature review of studies mostly done/financed by Monsanto and other companies) instead of filed level environmental and socio-economic impacts of GMOs to make conclusions. What we have been lacking is an independent study of GMOs that has no affiliation to pro- and ant-GMO movements. So, all these praises dont support the authors claims.

The author also tells that for countries with foreign currency bottlenecks like Ethiopia, reduced use of inputs such as pesticide, insecticide, and herbicide could translate to substantial foreign currency savings. Unfortunately, this is premised on flawed reasoning. Ethiopia could earn more foreign currency from exporting its organic products. Buying a technology that others benefit from will not solve its currency problem. Rather Ethiopias export will be questioned after the adoption of GMOs especially in Europe where GMOs are not welcomed both by consumers and their strict regulatory framework.

Another argument by the author is the labor-saving benefits of insect-resistant and herbicide-tolerant maize varieties. This is beside the point. It is strange to argue in this manner in a country where millions of young people are not in employment. The country might have many other problems but not labor. The author also said, GM also offers an adaptive capacity against an increasingly unpredictable future. What is proof of this? Of course, there is not. The author has simply overstretched himself. In my view, there is no risk that vulnerable smallholder farmers can bear, and Pro-GMO experts need to be honest and build public trust in Ethiopia

Image: Cotton farmers near Arba Minch, southern Ethiopia, photo Ecotextile.

This article is published under aCreative Commons Attribution-NonCommercial 4.0 International licence. Please cite Ethiopia Observer prominently and link clearly to the original article if you republish. If you have any queries, please contact us at ethiopiaobserver@protonmail.com. Check individual images for licensing details.

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The Covid-19 pandemic that has swept the globe has led to a massive search for a drug with which to combat this deadly virus, yet despite many pharmaceutical companies continuing to pour their resources into a cure for this virus, the development of prophylactic vaccines for Covid-19 appears to be lagging.

According to GlobalDatas Pharma Intelligence Center Pipeline Database and the Coronavirus Disease 2019 (Covid-19) dashboard, there are, as of 23 April, 80 therapeutic drugs in Phases I, II, and III that may be able to treat Covid-19, but only nine prophylactic vaccine drugs in Phases I and II, indicating that while a possible cure for Covid-19 may be imminent, a prophylactic vaccine to combat the pandemic may need more time to come to fruition.

The response from pharma and biotech companies globally to finding a Covid-19 vaccine has contributed to 438 unique drugs to treat Covid-19: 298 therapeutic drugs and 140 prophylactic vaccines, spread across all stages of development (Discovery, Preclinical, Phase I, Phase II, and Phase III), which is especially remarkable considering that the virus was only identified at the beginning of this year. In these unprecedented times, this massive pipeline in such a short time is demonstrative of the pharmaceutical industry compiling resources and talent, to finding a drug to combat this pandemic of the Covid-19 virus.

Therapeutic drugs account for two thirds of the entire pipeline, with prophylactic vaccines accounting for the remaining third of the current Covid-19 pipeline. Therapeutic drugs have 73% of their pipeline in early-stage development (Preclinical and Discovery) and 27% in late-stage development (Phases I, II, and III); despite the majority of drugs being in early stages, there is a viable pipeline of late-stage drugs that may in the coming months offer a solution to the ongoing crisis. The key drugs to watch are two small moleculebased drugs, remdesivir by Gilead Sciences Inc. and favipiravir by Fujifilm Toyama Chemical Co Ltd, and sarilumab, a monoclonal antibody by Regeneron Pharmaceutical, all three of which are currently in Phase III. At the same time as they are being developed for the Covid-19 virus, these drugs are also being developed for multiple other indications.

In direct contrast, the prophylactic vaccine pipeline largely comprises drugs in early-stage development, with 94% of the pipeline. There are currently only three drugs in Phase II, the current highest stage of development for prophylactic vaccine pipeline. These three Covid-19 vaccines are being developed by Sinovac Biotech Ltd, the University of Oxford, and the third vaccine, named CIGB-2020, is being developed by the Center for Genetic Engineering and Biotechnology. This huge disparity in late-stage and early-stage development is indicative of a lack of focus within the industry for vaccines in comparison to the therapeutic drugs pipeline. The massive global response towards the coronavirus and the massive increase in the therapeutic pipeline, however, does mean that this state of affairs is liable to change in the coming weeks. As this pandemic continues and governments and pharmaceutical companies continue to look for ways to combat Covid-19, the therapeutic landscape is sure to change, but as of now any hopes for a fast vaccine may not materialize.

You can view more information on the Covid-19 therapeutic landscape on GlobalDatas Pharma Intelligence Center Pipeline Database and the Coronavirus Disease 2019 (Covid-19) dashboard where the most up-to-date and latest information on drugs, trials, and news on Covid-19 can be found.

GlobalData is this websites parent business intelligence company.

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Covid-19 treatment on the horizon but vaccine remains elusive - Pharmaceutical Technology

BOSTON & WALTHAM, Mass.--(BUSINESS WIRE)--Vertex Pharmaceuticals Incorporated (Nasdaq:VRTX) and Affinia Therapeutics announced today that the two companies have entered into a strategic research collaboration to engineer novel adeno-associated virus (AAV) capsids to deliver transformative genetic therapies to people with serious diseases. Affinia Therapeutics proprietary AAVSmartLibrary and associated technology provides capsids for improved tissue tropism, manufacturability and pre-existing immunity. The collaboration will leverage Affinia Therapeutics capsid engineering expertise and Vertexs scientific, clinical and regulatory capabilities to accelerate the development of genetic therapies for people affected by Duchenne muscular dystrophy (DMD), myotonic dystrophy type 1 (DM1) and cystic fibrosis (CF).

This collaboration with Affinia Therapeutics will enhance our existing capabilities in discovering and developing transformative therapies for people with serious diseases, said Bastiano Sanna, Executive Vice President and Chief of Cell and Genetic Therapies at Vertex. Affinia Therapeutics innovative approach to the discovery and design of AAV capsids brings yet another tool to our Vertex Cell and Genetic Therapies toolkit, and were excited to partner with them to bring together their technology platform with our research and development expertise.

At Affinia Therapeutics, were setting a new standard in genetic therapy by leveraging our platform to methodically engineer novel AAV vectors that have unique therapeutic properties, said Rick Modi, Chief Executive Officer. Vertex is an established leader in developing transformative medicines for genetic diseases and renowned for its scientific rigor. We are thankful for the scientific validation this partnership brings and look forward to working closely with them to advance life-changing, differentiated genetic therapies and make a meaningful difference to those affected by these diseases.

About the Collaboration

Under the terms of the agreement, Affinia Therapeutics will apply its vector design and engineering technologies to develop novel capsids with improved properties. The agreement provides Vertex an exclusive license under Affinia Therapeutics proprietary technology and intellectual property (IP) in DMD and DM1 with an exclusive option to license rights for CF and an additional undisclosed disease. The scope of the agreement covers all genetic therapy modalities in these diseases. Affinia Therapeutics will be eligible to receive over $1.6 billion in upfront and development, regulatory and commercial milestones, including $80 million in upfront payments and research milestones that will be paid during the research term, plus tiered royalties on future net global sales on any products that result from the collaboration. Affinia Therapeutics will be responsible for the discovery of capsids that meet certain pre-determined criteria. Vertex will be responsible for and will fund the design and manufacturing of genetic therapies incorporating the selected capsids, preclinical and clinical development efforts, and commercialization of any approved products in the licensed diseases.

About Affinia Therapeutics

At Affinia Therapeutics, our purpose is to develop gene therapies that can have a transformative impact on people affected by devastating genetic diseases. Our proprietary platform enables us to methodically engineer novel AAV vectors and gene therapies that have remarkable tissue targeting and other properties. We are building world-class capabilities to discover, develop, manufacture and commercialize gene therapy products with an initial focus on muscle and central nervous system (CNS) diseases with significant unmet need. http://www.affiniatx.com.

About Vertex Pharmaceuticals

Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has multiple approved medicines that treat the underlying cause of cystic fibrosis (CF) a rare, life-threatening genetic disease and has several ongoing clinical and research programs in CF. Beyond CF, Vertex has a robust pipeline of investigational small molecule medicines in other serious diseases where it has deep insight into causal human biology, including pain, alpha-1 antitrypsin deficiency and APOL1-mediated kidney diseases. In addition, Vertex has a rapidly expanding pipeline of genetic and cell therapies for diseases such as sickle cell disease, beta thalassemia, Duchenne muscular dystrophy and type 1 diabetes mellitus.

Founded in 1989 in Cambridge, Mass., Vertex's global headquarters is now located in Boston's Innovation District and its international headquarters is in London, UK. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia and Latin America. Vertex is consistently recognized as one of the industry's top places to work, including 10 consecutive years on Science magazine's Top Employers list and top five on the 2019 Best Employers for Diversity list by Forbes. For company updates and to learn more about Vertex's history of innovation, visit http://www.vrtx.com or follow us on Facebook, Twitter, LinkedIn, YouTube and Instagram.

Special Note Regarding Forward-Looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including, without limitation, Dr. Sannas statements in the second paragraph of the press release, Mr. Modis statements in the third paragraph of the press release, and statements regarding future activities of the parties pursuant to the collaboration. While Vertex believes the forward-looking statements contained in this press release are accurate, these forward-looking statements represent Vertex's beliefs only as of the date of this press release and there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, Vertex may not realize the anticipated benefits of the collaboration, and the other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through the company's website at http://www.vrtx.com. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

(VRTX-GEN)

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Vertex Pharmaceuticals and Affinia Therapeutics Establish Multi-Year Collaboration to Discover and Develop Novel AAV Capsids for Genetic Therapies -...

Researchers are interested in genetically modifying trees for a variety of applications, from biofuels to paper production. They also want to steer clear of modifications with unintended consequences. These consequences can arise when intended modifications to one gene results in unexpected changes to other genes. A new model aims to predict these changes, helping to avoid unintended consequences, and hopefully paving the way for more efficient research in the fields of genetic modification and forestry.

The research at issue focuses on lignin, a complex material found in trees that helps to give trees their structure. It is, in effect, what makes wood feel like wood.

Whether you want to use wood as a biofuel source or to create pulp and paper products, there is a desire to modify the chemical structure of lignin by manipulating lignin-specific genes, resulting in lignin that is easier to break down, says Cranos Williams, corresponding author of a paper on the work and an associate professor of electrical and computer engineering at NCState. However, you dont want to make changes to a trees genome that compromise its ability to grow or thrive.

The researchers focused on a tree called Populus trichocarpa, which is a widely used model organism meaning that scientists who study genetics and tree biology spend a lot of time studying P. trichocarpa.

Previous research generated models that predict how independent changes to the expression of lignin genes impacted lignin characteristics, says Megan Matthews, first author of the paper, a former Ph.D. student at NCState and a current postdoc at the University of Illinois. These models, however, do not account for cross-regulatory influences between the genes. So, when we modify a targeted gene, the existing models do not accurately predict the changes we see in how non-targeted genes are being expressed. Not capturing these changes in expression of non-targeted genes hinders our ability to develop accurate gene-modification strategies, increasing the possibility of unintended outcomes in lignin and wood traits.

To address this challenge, we developed a model that was able to predict the direct and indirect changes across all of the lignin genes, capturing the effects of multiple types of regulation. This allows us to predict how the expression of the non-targeted genes is impacted, as well as the expression of the targeted genes, Matthews says.

Another of the key merits of this work, versus other models of gene regulation, is that previous models only looked at how the RNA is impacted when genes are modified, Matthews says. Those models assume the proteins will be impacted in the same way, but thats not always the case. Our model is able to capture some of the changes to proteins that arent seen in the RNA, or vice versa.

This model could be incorporated into larger, multi-scale models, providing a computational tool for exploring new approaches to genetically modifying tree species to improve lignin traits for use in a variety of industry sectors.

In other words, by changing one gene, researchers can accidentally mess things up with other genes, creating trees that arent what they want. The new model can help researchers figure out how to avoid that.

The paper, Modeling cross-regulatory influences on monolignol transcripts and proteins under single and combinatorial gene knockdowns in Populus trichocarpa, is published in the journal PLOS Computational Biology. The paper was co-authored by Ronald Sederoff, a professor emeritus of forestry and environmental resources at NCState; Jack Wang, an assistant professor of forestry and environmental resources at NCState; and Vincent Chiang, a Jordan Family Distinguished Professor Emeritus and Alumni Outstanding Research Professor with the Forest Biotechnology Group at NCState.

This work was supported by the National Science Foundation Grant DBI-0922391 to Chiang and by a National Physical Science Consortium Graduate Fellowship to Matthews.

-shipman-

Note to Editors: The study abstract follows.

Modeling cross-regulatory influences on monolignol transcripts and proteins under single and combinatorial gene knockdowns in Populus trichocarpa

Authors: Megan L. Matthews, Ronald Sederoff and Cranos M. Williams, North Carolina State University; Jack P. Wang and Vincent L. Chiang, Northeast Forestry University, Harbin, China, and North Carolina State University

Published: April 10, PLOS Computational Biology

Abstract: Accurate manipulation of metabolites in monolignol biosynthesis is a key step for controlling lignin content, structure, and other wood properties important to the bioenergy and biomaterial industries. A crucial component of this strategy is predicting how single and combinatorial knockdowns of monolignol specific gene transcripts influence the abundance of monolignol proteins, which are the driving mechanisms of monolignol biosynthesis. Computational models have been developed to estimate protein abundances from transcript perturbations of monolignol specific genes. The accuracy of these models, however, is hindered by their inability to capture indirect regulatory influences on other pathway genes. Here, we examine the manifestation of these indirect influences on transgenic transcript and protein abundances, identifying putative indirect regulatory influences that occur when one or more specific monolignol pathway genes are perturbed. We created a computational model using sparse maximum likelihood to estimate the resulting monolignol transcript and protein abundances in transgenicPopulus trichocarpabased on targeted knockdowns of specific monolignol genes. Using in-silicosimulations of this model and root mean square error, we showed that our model more accurately estimated transcript and protein abundances, in comparison to previous models, when individual and families of monolignol genes were perturbed. We leveraged insight from the inferred network structure obtained from our model to identify potential genes, including PtrHCT, PtrCAD, and Ptr4CL, involved in post-transcriptional and/or post-translational regulation. Our model provides a useful computational tool for exploring the cascaded impact of single and combinatorial modifications of monolignol specific genes on lignin and other wood properties.

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Better Predicting the Unpredictable Byproducts of Genetic Modification - NC State News

Sales of fiction about epidemics have increased considerably in recent months, suggesting that readers are leaning to themes of the moment. The list below offers you a look at a few books prominent for their theme of a pandemic:

Blindness by Jos Saramago

Blindness tells the story of an epidemic that spreads in a European city where the inhabitants start losing their sight. Like any mysterious contagious outbreak, this plague sets off panic, chaos and confusion, and violence. Government quarantines the early-infected people in an abandoned mental asylum and the army guarding it shoots anyone trying to escape. The quarantine camp soon becomes a living hell. The meager supply of food and civil amenities with no one to guide the inmates through their dark world reduce them to bare animals. But the real hell breaks loose when there is a fire in the asylum and the inmates burst forth.

The Painted Veil by Somerset Maugham

This novel is set in the rural China, the heart of a cholera epidemic in the 1920s. Unfaithful Kitty Fane, betrayed by her lover is compelled to go to China with her forgiving husband Walter Fane, who is a bacteriologist and physician. Walter dedicates himself to the service of the cholera affected people risking his life. He falls ill while experimenting on himself to find a cure for cholera and eventually sacrifices his life.

The Painted Veil explores human beings capacity to love, forgive, sacrifice and transform.

The Plague by Albert Camus

Set in the plague-infested French-Algerian city of Oran in the 1940s, The Plague keeps faith in humanity and reaffirms that there is more to admire than to despise in humans. When two doctors approach the town authorities to warn that the town may be in the brink of an epidemic, the authorities fail to understand the gravity of the situation and take it as a false alarm. Eventually, situation worsens and the plague-decimated city is sealed off and the inhabitants are quarantined. Many people come forward to combat the plague, though their motivations differ. While some join the voluntary service being driven by religious principles, the others are motivated by code of morals. The main character of this novel, Dr Bernard Rieux does not serve the victims out of any altruistic or religious obligation. He relieves peoples suffering simply because thats what his job is.

The Stand by Stephen King

Its a post-apocalyptic 1978 novel that narrates the story of a pandemic that wipes out most of the human race. It shows that a computer error in a defense department laboratory leads to the spread of a deadly super-flu. A patient escapes from a biological testing facility, unknowingly carrying an extremely contagious and lethal biological weapon that causes death of 99 percent of the world population. The rest are left to struggle to cope with this new world.

Oryx and Crake by Margaret Atwood

Margaret Atwoods Oryx and Crake is a 2003 post-apocalyptic dystopian fiction, the first volume of her MaddAdam trilogy. It tells the story of a world ravaged by genetic engineering. BlyssPluss, a wonder drug promising health and happiness, causes a pandemic that wipes out the human race. Snowman, presumably, the last surviving human being on earth, lives near a group of bioengineered primitive human like creatures called Crakers, named after their creator, Crake.

Love in the Time of Cholera by Gabriel Garcia Marquez

Plagues are like imponderable dangers that surprise people,, the author of Love in the Time of Cholera, Gabriel Garcia Marquez, told the New York Times in a 1988 interview.Set in the backdrop of cholera outbreak in Cartagena, this novel parallels between the symptoms of love and cholera. Dr Juvenal Urbino, one of the three major characters of this triangular love story, is committed to the eradication of cholera from the town. But there is another type of cholera that no medicine can cure. His wife Fermina Dazas lover Floretino Ariza suffers from the sickness of unrequited love for 50 long years. Here, lovesickness has been compared to an illness, as debilitating and deadly as cholera.

The Eyes of Darkness by Dean Koontz

Published in 1981, The New York Times Best Seller author Dean Koontz thriller novel The Eyes of Darkness tells the story of a mother grieving her sons death. When she finds a strange message claiming that her son is alive, she sets off on a terrifying journey to find the truth. This novel mentions a biological weapon called Wuhan-400 created in China aimed to wipe out an entire city or a country. This virus has a mortality rate of 100% and kills the affected in less than 24 hours.

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Fiction about pandemics and dystopian future - Dhaka Tribune

David Lynch has been the name on everybodys lips of late. The Twin Peaks director has been under the spotlight for his damn fine creation, as it enjoyed its the 30th birthday this week.

It has seen the auteur be interview by Vice in relation to the big day but also to get his feelings and thoughts on the ongoing coronavirus pandemic. The response was one of hope that following the lifting of lockdown restrictions, when we can all share our time with one another again that the world will be a more spiritual, much kinder place to be.

Lynch has been, like many of us, holed up in his Los Angeles home over the past few weeks. While some have struggled to adjust, for Lynch, it has been very similar to his normal day. My routine is pretty much the same now as it was before, Lynch said. I get up, and I get a coffee. After that, I meditate and then I go to work.

All those getting excited about a new film or television project will probably be disappointed. The director has instead been working on two wall sconcestwo little lamps. It involves lightbulbs, electricity, polyester resin plastic, and those kinds of things.

In the current climate, working with electricity and the connection it can bring to those more lonely than others, has been an awakening for Lynch. For some reason, we were going down the wrong path and Mother Nature just said, Enough already, weve got to stop everything, reflected Lynch about the ongoing pandemic.

This is going to last long enough to lead to some kind of new way of thinking.

Lynch believes that the world will emerge from quarantine as more spiritual and much kinder humans. He continued, Its going to be a different world on the other side and its going to be a much more intelligent world. Solutions to these problems are going to come and lifes going to be very good. The movies will come back. Everything will spring back and in a much better way probably.

We can all hope.

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David Lynch believes the world will be a more spiritual, much kinder place after lockdown ends - Far Out Magazine