Monthly Archives: March 2021

Before the pandemic, Anne Leonards friends and family had only a cursory interest in her two decades of work manufacturing pharmaceuticals.

But recently, when her grandmother learned that her work as the director of quality assurance at the Catalent facility in Indiana meant that her granddaughter was helping keep the Johnson & Johnson and Moderna vaccines safe, she was so proud, she told all her friends about her granddaughters efforts to help end the pandemic.

She didnt actually realize how close to the manufacturer of the Covid vaccine I was, said Leonard. She was so tickled by it.

Leonard said even her 9- and 11-year-old kids know that, while she has to work really long days, what she is doing is important work.

I tell them Im doing this for you guys, and for grandma, and for your teachers, Leonard said.

With the US Food and Drug Administrations authorization last week, Johnson & Johnson said about 4 million doses of its coronavirus vaccine would immediately head to states to help meet enormous demand. The company has said it expects to make enough doses to vaccinate 20 million people by the end of March, and has a goal to produce 1 billion doses globally by the end of the year.

But as President Joe Biden said Tuesday, it simply wasnt coming fast enough.

Biden announced that drugmaker Merck will help manufacture the Johnson & Johnson vaccine a decision made after it became clear that J&J would fall short of its manufacturing goals. The planned partnership was first reported by The Washington Post.

The White House said it was utilizing the Defense Production Act to help equip two Merck facilities to manufacture the Johnson & Johnson product, including by bolstering fill-finish capacity, when the doses are placed in vials, and by increasing availability of the components of the vaccines.

There may still be delays, but Biden said Tuesday the United States would have enough Covid-19 vaccine doses for every adult American by the end of May.

Before the J&J vaccine can ever get into someones arm, it must go through a sophisticated and complicated process that involves several companies. It cant happen overnight, but companies say vaccine manufacturing has moved at a speed that has never been seen before in the history of pharmaceutical manufacturing.

J&J said it has been working with urgency to increase production of the vaccine candidate, but it isnt easy.

The production of our vaccine is a highly complex process that requires very particular capabilities and experiences, Dr. Richard Nettles, J&Js vice president of US medical affairs told the subcommittee on Oversight and Investigations for the House Committee on Energy & Commerce last week.

It takes about five or six weeks to genetically engineer and then grow, purify, and finish the vaccine before it can be bottled and sealed and sent on its way to be distributed to vaccine centers.

Put another way, Dr. Paul Stoffels, chief scientific officer for Johnson & Johnson, told CNN, you cant accelerate it by yelling at it.

J&J has looked at 100 potential production sites and found eight that meet its needs so far, Nettles said. Three have produced test batches of the vaccine. It expects to have additional capacity by the second quarter of the year and will be made in the US, Europe, Asia and Africa.

Leonard works at the bustling Catalent facility in Bloomington, Indiana, that sits in a nondescript building tucked away by the indoor pickleball court and the Budweiser distributor. Five shifts of 2,000 employees keep the buzzing production lines going 24 hours a day, seven days a week.

It started production of the J&J vaccine at the end of January and should get the regulatory authority to ship from the plant soon. The doses going out this week come from elsewhere.

Catalent hopes to meet the increasing demands for vaccines to help end the pandemic.

We are going as fast as we can, Leonard said. In such a regulated industry, there are certain steps that you just cant speed up any faster, but I think we are doing amazing things to get the vaccine out as quickly as we have. Everyone at the site feels a great responsibility to do that and were working day and night to get it done.

The plant that, decades ago, made TVs is now helping make the substance that the country is counting on to end its isolation.

The company that actually starts the manufacturing process for J&J is not Catalent, but Baltimore-based Emergent Biosolutions.

Emergent does the work genetically engineering a virus known as adenovirus 26 that causes the common cold in humans. Genes are removed from the virus so it wont replicate and spread in the body. Genetic material is also removed to make room for the genetic instructions for making a piece of the coronavirus spike protein that it uses to attach to cells.

This adenovirus vector is grown in vats of human cells in large reactors. The resulting virus is purified to remove debris. Its a biologic process that takes several weeks before the resulting product can be frozen and shipped hundreds of miles to companies such as Catalent.

For both the J&J and Moderna vaccine, Catalent is one of the companies doing whats known in the industry as the fill/finish part of the manufacturing process.

Catalent will be a part of the effort to scale up J&Js manufacturing. They are a last manufacturing step before it heads out to a distributor and a vaccination site that can get it into someones arm.

What that involves is taking the bulk drug substance, formulating that into its final form, sterile filling it into vials doing 100% visual inspection, packaging, and then the final quality control testing, said Mike Riley, region president, biologics, North America for Catalent. These products need to be completely sterile so that whole process is highly controlled and highly validated.

Manufacturing a vaccine needs to be clean and carefully managed. Workers put on sterile garments before they enter a clean room, where they then reach through gloves that go through glass to get into isolator equipment where the sterile vaccine product goes into the glass containers.

The vaccines are inspected and then fly through high speed manufacturing lines conveyors that pass-through label machines that then get packed up into safe cases that get shipped out from there.

Every step is carefully regulated and every step must be kept under a close watchful eye so nothing else can be introduced into the glass vials beyond the vaccine itself.

Its a complex process, Leonard said.

During the pandemic, Catalent, with manufacturing facilities around the world, has worked with more than 80 Covid-19 related compounds from 60 different companies to make antivirals, other treatments and vaccines. It has done this all while continuing to make hundreds of other critical medications to treat everything from cancer to heart disease.

Knowing the demand, it is continually increasing the rate of its production. The company accelerated the expansion of the Indiana facility by about 10 months so that it could have the capacity to produce the vaccines at the scale that is needed.

Activities that sometimes will take place over the course of two or three years, weve been doing over months, Riley said. Construction partners, subcontractors, you know all of them, weve had a really singular focus on how we can accomplish this and get ourselves out of the pandemic.

Catalent also hired a significant amount of staff in the past year, Riley said, to keep up with it. Leonard, was one of those new hires in August. She had never even set foot into the factory before she took the job. She was hired over Zoom.

I jumped in right at the busiest time here ever, Leonard said. Its been a big challenge but it is also very exciting.

Riley said Catalent has been working and planning with vaccine companies about how they would make these vaccines for almost a year now, long before scientists had figured out what a successful vaccine would look like and got authorization from the US Food and Drug Administration.

When we started work with Johnson and Johnson, with Moderna, with others, we anticipated having to ramp up very substantially our production, said Riley. As such, weve been adding significant staff over the past year just to make sure that we can run 24 hours, seven day production once the vaccine was approved.

Riley said that Catalents employees have been doing extraordinary things during a global pandemic.

Im going to quote our chief operating officer. The impossible is not impossible, it just hasnt been done yet, Riley said. Theres no other choice. As an industry, as a country, weve got to find a way out of this pandemic.

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'The impossible is not impossible': The push to make Covid-19 vaccines at record speed - ABC17NEWS - ABC17News.com

To remind herself that hurried work can have consequences, the anonymous virologist I interviewedkeeps a quote on her office wall from Richard Feynman, the Nobel Prizewinning physicist. As a lesson in drug development, she often tells the story of Feynmans devastating conclusions about the 1986 explosion of the space shuttle Challenger. Its set during an inquiry about the disaster. During a famous line of questioning about the dangerous disconnect between the caution of NASAs engineers and the ambition of the agencys management, Feynman took out an O-ring that engineers had identified prelaunch as a part that could fail catastrophically, especially in freezing temperatures. He dropped it in ice water and the part failed. For a successful technology, reality must take place over public relations, Feynman said. For Mother Nature cant be fooled.

Data is king, the virologist says, echoing Feynman. In my field, a drug is either going to work or its not.

Basically, she thinks that Glanville, who has yet to publish any results from his coronavirus research in a major scientific publication, has oversold the importance of discovering antibodies that can neutralize CoV-2 in a dish or a hamster, even though hes succeeded in doing both. In experiments with hamsters, Glanvilles antibodies reduced viral load by 97 percent in rodents that received the drug as a treatment, andeven more than thatwhen they were given prophylactically. The virologist says this is a good start, but it still doesnt demonstrate the ability to neutralize the virus in people;it doesnt show whether the treatment can cause dangerous side effects;and it doesnt reveal how much to give in a dose, where and how the dose should be administered, whether the antibody actually disperses to the parts of the body that harbor the virus, and whether the drug can even be manufactured.

Thats the problem with biology, says the virologist. It gets more and more complicated the deeper you get into drug development. Between the discovery of an antibody, even a potent one, and the development of an actual drug, there isa gauntlet of manufacturing and safety hurdles that, because of the expertise and moneyneeded to navigate them, giant pharmaceutical companies are better equipped to clear. Although Glanvilles team includes researchers with experience shepherding antibodies from discovery to the marketplace, he is having to learn the bureaucracy of drug approval on the fly. His public optimism, the virologist argues, may be dangerously and even cruelly misleading to those outside the industry.

Glanville is now one in a crowded field of researcherstrying to improve antibodies efficacy against COVID-19.By late 2020, there were at least 21 other monoclonal antibodies in some form of clinical trials, including five knocking on the door of FDA approval in phase three. And after watching the mixed success of the leading antibody drug manufacturer, Glanville decidedto stop trying to emulate the front-runners.Regeneron, the multibillion-dollar company whose antibody-based drug was approved for emergency use by the FDA in late November, took all the right steps, but itsdrug is far from the effective cure ithoped it would be. Before the FDA grantedits final approval, early results suggested it could be hugely successful. Because of this, doctors gave an experimental version of it to President Trump, who claimed that it cured him, despite there being no scientific way to know this, since he received several treatments at once.

What has become clear is that Regenerons cocktail, like Eli Lillys drug bamlanivimab, only works well against milder cases of COVID-19. These drugs arent being widely used by hospitals, because when people fall critically ill, even massive doses of the antibodies delivered intravenously do little to revive them.Antibodies only target the virus, and once an infection is established, there is simply too much virus for the administered antibodies to control, and they can do nothing to tamp down the symptoms that ultimately cause death. This fact, plus issues related to storage and cost, explains why many in the industry no longer pin their hopes of taming COVID-19 on antibodies.

That Glanvilles competitors havent been huge successes might seem like a good reason for him to abandon his project. So, too, that by midwinter no agencies or private investors had come forward to fund his efforts, despite almost a full year of persistent, exhausting, and ultimately deflating lobbying efforts. By early March, Glanville estimated hed met withalmost a dozen government agencies funding COVID research, from the Army and Navy to Operation Warp Speed. The Gates Foundation turned him down. So did a handful of other big-dollar foundations. He raised only $9 million, barely enough to get his antibodies through animal trials. The challenge seems to have only hardened his resolve. Reality, he says, is driving him forward. Very rarely in the history of pathogens have we vaccinated enough people worldwide to eliminate them, he says (smallpox being the lone example). COVID is here to stay.

When CoV-2 first infected a person somewhere in rural China, the new bug was far stickier to the ACE-2 receptor. For the virus, its hard to imagine a better evolutionary move. For a human, its hard to imagine one that could be worse.

Glanville maintains that his antibody is one answer. His sales pitch is as convincing as ever: an antibody potent enough that doses can be smaller;capable of beingdelivered in a shot rather than an IV;engineered to cause fewer side effects in the immune-system response than his competitors;and, because it targets a part of the virus that hasnt changed even as the human pandemic has spawned new viral mutations in Brazil, South Africa, and England, effective against new variants. True to his Robin Hood style, Glanville also wants his drug to be widely available and relatively cheap. He has mapped out a sort of Walmart distribution method for his drug, a model in which bulk production will keep the price down. Instead of $2,000 a dose, it will be $800, maybe $900, but certainly less than the cost of an iPhone, he says. (Glanville isnt alone in his pharmaceutical goodwill. AstraZeneca is trying to sell itsvaccine for $4 a dose.) Driving the cost savings for Glanville is smaller overhead30 employees versus 30,000 at a company like Eli Lillyand a novel manufacturing approach. Glanville had a team of interns identify more than 500 companies around the world with bioreactors that are capable of brewing his antibodies. Instead of cooking drugs through in-house bioreactors or subcontractors with restrictive terms, as the big companies have done, his plan is for many hands to make light work. By increasing supply, Glanville will fill the need and lower the costs.

The virologist who asked to remainanonymousis unwaveringly skeptical that this will play out as Glanville is willing it to, especially with so many researchers on pace or way out ahead of him. Skeptical is the safe bet, Glanville said of her take. Odds are we fail.

And that looked to be his antibodys fate. But then, in early February, Glanville got a few pieces of good news. He refused to call them unexpected. The first was that Nature Biotechnology, an esteemed journal in his field, agreed to publish his work on the coronavirus. Andin late February, Merck bought Pandion for $1.9 billion. The significance to Glanville was that Pandion used his patented technologies for some of itsdrug-discovery work. The announcement demonstrates thatantibodies he has designed have clinical value.Most exciting for himis that he is finalizing an agreement with a federal entitywhich he wont nameuntil the deal is finalthat will fund his phase-oneresearch.

Whether his antibody becomes a drug or not, entering the race to find a COVID-19 treatment clarified for Glanville why he got into this businessto help people. To that end, in the first week of January, heand his partners sold Distributed Bioto a much larger pharmaceutical company called Charles River Labs for more than $100 million. Hes since founded a new firm called Centivax that will focus solely onmakingtherapeutic drugs and vaccines and getting the ones hes already developed to market. The time is nigh, he says. This work needs the best version of me possible. As such, at 40, he quit drinking and started swimming in the ocean each day. To get just enough of the altered reality he needs to maintain sanity, he smokes three cigars daily on his rooftop office, looking out over the oceanand thinking about wherethe next bad bug might emerge.

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The Antibody Avenger and the Quest for a COVID-19 Cure - Outside

SOUTH SAN FRANCISCO, Calif. & BOULDER, Colo.--(BUSINESS WIRE)--Twist Bioscience Corporation (NASDAQ: TWST), a company enabling customers to succeed through its offering of high-quality synthetic DNA using its silicon platform, and Watchmaker Genomics today announced a broad partnership to enable innovative research across a wide range of high throughput sequencing applications including oncology and tumor profiling, inherited disease detection, liquid biopsy assays, and minimal residual disease monitoring.

In their first product offering together, Twist will leverage Watchmakers expertise in enzyme engineering by incorporating the companys high-fidelity library amplification master mix into Twists enzymatic library preparation kit, providing a superior solution that can be accessed from Twist as a single source.

With our eye squarely on working in service of our customers, this partnership brings together two teams relentlessly focused on innovation and execution to provide superior products, said Emily M. Leproust, Ph.D., CEO and co-founder of Twist Bioscience. By pairing superior enzymes with best-in-class DNA, we expect to offer differentiated products that simplify and streamline workflows before putting samples on the sequencer.

This is the first in what we believe will be a series of joint product development opportunities between Twist and Watchmaker aimed at driving continued improvement in performance and data quality for high-resolution genomic applications including NGS-based cfDNA and ctDNA studies, single-cell work, low allele somatic variant detection and tumor mutation burden, said Trey Foskett, co-founder of Watchmaker. In addition, we look forward to bringing our protein engineering technologies into the product mix to fuel new avenues of research across many disease areas.

About Watchmaker Genomics

Watchmaker Genomics applies advanced enzymology to enable breakthrough applications for the reading, writing, and editing of DNA and RNA. The company combines deep domain expertise in protein engineering with large-scale enzyme manufacturing to address the demanding quality, performance, and scale requirements of high-growth genomics applications.

Watchmakers product portfolio includes enzymes and kits for next-generation sequencing library preparation, synthetic biology, and molecular diagnostics. Based in Boulder, Colorado, Watchmaker Genomics is co-founded by Trey Foskett, Brian Kudlow, and Stephen Picone. The team brings decades of collective experience building successful life science companies, commercializing novel technologies, and advancing clinical genomics applications. Watchmaker partners directly with innovative life science companies, commercial sequencing providers, and pioneering research labs. For more information, visit http://www.watchmakergenomics.com

About Twist Bioscience Corporation

Twist Bioscience is a leading and rapidly growing synthetic biology and genomics company that has developed a disruptive DNA synthesis platform to industrialize the engineering of biology. The core of the platform is a proprietary technology that pioneers a new method of manufacturing synthetic DNA by writing DNA on a silicon chip. Twist is leveraging its unique technology to manufacture a broad range of synthetic DNA-based products, including synthetic genes, tools for next-generation sequencing (NGS) preparation, and antibody libraries for drug discovery and development. Twist is also pursuing longer-term opportunities in digital data storage in DNA and biologics drug discovery. Twist makes products for use across many industries including healthcare, industrial chemicals, agriculture and academic research.

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Legal Notice Regarding Forward-Looking StatementsThis press release contains forward-looking statements. All statements other than statements of historical facts contained herein, including Twist and Watchmaker entering into a definitive agreement with respect to the partnership and the ability of the partnership to offer differentiated products that simplify and streamline workflows, to improve performance and data quality for genomic applications and to fuel new avenues of research across many disease areas, are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements involve known and unknown risks, uncertainties, and other important factors that may cause Twist Biosciences actual results, performance, or achievements to be materially different from any future results, performance, or achievements expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the risks and uncertainties of the ability to attract new customers and retain and grow sales from existing customers; risks and uncertainties of rapidly changing technologies and extensive competition in synthetic biology could make the products Twist Bioscience is developing obsolete or non-competitive; uncertainties of the retention of a significant customer; risks of third party claims alleging infringement of patents and proprietary rights or seeking to invalidate Twist Biosciences patents or proprietary rights; and the risk that Twist Biosciences proprietary rights may be insufficient to protect its technologies. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to Twist Biosciences business in general, see Twist Biosciences risk factors set forth in Twist Biosciences Quarterly Report Form 10-Q filed with the Securities and Exchange Commission on February 9, 2021 and subsequent filings with the SEC. Any forward-looking statements contained in this press release speak only as of the date hereof, and Twist Bioscience specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise.

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Twist Bioscience and Watchmaker Genomics Announce Partnership to Drive New Applications of High-throughput Genetic Sequencing - Business Wire

If a two-year-old child living in poverty in India or Bangladesh gets sick with a common bacterial infection, there is more than a 50%chance an antibiotic treatment will fail. Somehow the child has acquired an antibiotic resistant infection even to drugs to which they may never have been exposed. How?

Unfortunately, this child also lives in a place with limited clean water and less waste management, bringing them into frequent contact with faecal matter. This means they are regularly exposed to millions of resistant genes and bacteria, including potentiallyuntreatable superbugs. This sad story is shockingly common, especially in places where pollution is rampant and clean water is limited.

For many years, people believed antibiotic resistance in bacteria was primarily driven by imprudent use of antibiotics in clinical and veterinary settings. Butgrowing evidencesuggests that environmental factors may be of equal or greater importance to the spread ofantibiotic resistance, especially in the developing world.

Here we focus on antibiotic resistant bacteria, but drug resistance also occurs in types of other microorganisms such as resistance in pathogenic viruses, fungi, and protozoa (called antimicrobial resistance or AMR). This means that our ability to treat all sorts of infectious disease is increasingly hampered by resistance, potentially including coronaviruses like SARS-CoV-2, which causes COVID-19.

Overall, use of antibiotics, antivirals, and antifungals clearly must be reduced, but in most of the world, improving water, sanitation, and hygiene practice a practice known as WASH is also critically important. If we can ensure cleaner water and safer food everywhere, the spread of antibiotic resistant bacteria will be reduced across the environment, including within and between people and animals.

Asrecent recommendations on AMRfrom the Food and Agriculture Organization of the United Nations (FAO), the World Organisation for Animal Health (OIE), and World Health Organization (WHO) suggest, to which David contributed, the superbug problem will not be solved by more prudent antibiotic use alone. It also requires global improvements in water quality, sanitation, and hygiene. Otherwise, the next pandemic might be worse than COVID-19.

To understand the problem of resistance, we must go back to basics. What is antibiotic resistance, and why does it develop?

Exposure to antibiotics puts stress on bacteria and, like other living organisms, they defend themselves. Bacteria do this by sharing and acquiring defence genes, often from other bacteria in their environment. This allows them to change quickly, readily obtaining the ability to make proteins and other molecules that block the antibiotics effect.

Thisgene sharing processis natural and is a large part of what drives evolution. However, as we use ever stronger and more diverse antibiotics, new and more powerful bacterial defence options have evolved, rendering some bacteria resistant to almost everything the ultimate outcome being untreatable superbugs.

Antibiotic resistance has existedsince life began, but has recently accelerated due to human use. When you take an antibiotic, it kills a large majority of the target bacteria at the site of infection and so you get better. But antibiotics do not kill all the bacteria some are naturally resistant; others acquire resistance genes from their microbial neighbours, especially in our digestive systems, throat, and on our skin. This means that some resistant bacteria always survive, and can pass to the environment via inadequately treated faecal matter, spreading resistant bacteria and genes wider.

The pharmaceutical industry initially responded to increasing resistance by developing new and stronger antibiotics, but bacteria evolve rapidly, making even new antibiotics lose their effectiveness quickly. As a result, new antibiotic development has almost stopped because it garnerslimited profit. Meanwhile, resistance to existing antibiotics continues to increase, which especially impacts places withpoor water quality and sanitation.

This is because in the developed world you defecate and your poo goes down the toilet, eventually flowing down a sewer to a community wastewater treatment plant. Although treatment plants are not perfect, they typically reduce resistance levels by well over 99%, substantially reducing resistance released to the environment.

In contrast, over70% of the worldhas no community wastewater treatment or even sewers; and most faecal matter, containing resistant genes and bacteria, goes directly into surface and groundwater, often via open drains.

This means that people who live in places without faecal waste management are regularly exposed to antibiotic resistance in many ways. Exposure is even possible of people who may not have taken antibiotics, like our child in South Asia.

Antibiotic resistance is everywhere, but it is not surprising that resistanceis greatestin places with poor sanitation because factors other than use are important. For example, a fragmented civil infrastructure, political corruption, and a lack of centralised healthcare also play key roles.

One might cynically argue that foreign resistance is a local issue, but antibiotic resistance spread knows no boundaries superbugs might develop in one place due to pollution, but then become global due to international travel. Researchers from Denmark compared antibiotic resistance genes in long-haul airplane toilets and foundmajor differences in resistance carriageamong flight paths, suggesting resistance can jump-spread by travel.

The worlds current experience with the spread of SARS-CoV-2 shows just how fast infectious agents can move with human travel. The impact of increasing antibiotic resistance is no different. There are no reliable antiviral agents for SARS-CoV-2 treatment, which is the way things may become for currently treatable diseases if we allow resistance to continue unchecked.

As an example of antibiotic resistance, the superbug gene, blaNDM-1, was first detected inIndiain 2007 (although it was probably present in other regional countries). But soon thereafter, it was found in ahospital patient in Swedenand thenin Germany. It was ultimately detected in 2013 in Svalbard inthe High Arctic. In parallel,variantsof this gene appeared locally, but have evolved as they move. Similar evolution has occurred asthe COVID-19 virushas spread.

Relative to antibiotic resistance, humans are not the only travellers that can carry resistance. Wildlife, such as migratory birds, can also acquire resistant bacteria and genes from contaminated water or soils and then fly great distances carrying resistance in their gut from places with poor water quality to places with good water quality. During travel, they defecate along their path, potentially planting resistance almost anywhere. The global trade of foods also facilitates spread of resistance from country to country and across the globe.

What is tricky is that the spread by resistance by travel is often invisible. In fact, the dominant pathways of international resistance spreadare largely unknownbecause many pathways overlap, and the types and drivers of resistance are diverse.

Resistant bacteria are not the only infectious agents that might be spread by environmental contamination. SARS-CoV-2 has been found in faeces and inactive virus debris found in sewage, but all evidence suggests water isnot a major routeof COVID-19 spread although there are limited data from places with poor sanitation.

So, each case differs. But there are common roots to disease spread pollution, poor water quality, and inadequate hygiene. Using fewer antibiotics is critical to reducing resistance. However, without also providing safer sanitation and improved water quality at global scales, resistance will continue to increase, potentially creating the next pandemic. Such a combined approach is central to the new WHO/FAO/OIE recommendations on AMR.

Industrial wastes, hospitals, farms, and agriculture are also possible sources or drivers of antibiotic resistance.

For example, about ten years ago, one of us (David) studied metal pollution in a Cuban river andfoundthe highest levels of resistant genes were near a leaky solid waste landfill and below where pharmaceutical factory wastes entered the river. The factory releases clearly impacted resistance levels downstream, but it was metals from the landfill that most strongly correlated with resistance gene levels in the river.

There is a logic to this because toxic metals can stress bacteria, which makes the bacteria stronger, incidentally making them more resistant to anything, including antibiotics. We saw the same thing with metals inChinese landfillswhere resistance gene levels in the landfill drains strongly correlated with metals, not antibiotics.

In fact, pollution of almost any sort can promote antibiotic resistance, including metals, biocides, pesticides, and other chemicals entering the environment. Many pollutants can promote resistance in bacteria, so reducing pollution in general will help reduce antibiotic resistance an example of which is reducing metal pollution.

Hospitals are also important, being both reservoirs and incubators for many varieties of antibiotic resistance, including well known resistant bacteria such as Vancomycin-resistant Enterococcus (VRE) and Methicillin-resistant Staphylococcus aureus (MRSA). While resistant bacteria are not necessarily acquired in hospitals (most are brought in from the community), resistant bacteria can be enriched in hospitals because they are where people are very sick, cared for in close proximity, and often provided last resort antibiotics. Such conditions allow the spread of resistant bacteria easier, especially superbug strains because of the types of antibiotics that are used.

Wastewater releases from hospitals also may be a concern.Recent datashowed that typical bacteria in hospital sewage carry five to ten times more resistant genes per cell than community sources, especially genes more readily shared between bacteria. This is problematic because such bacteria are sometimes superbug strains, such as those resistant tocarbapenem antibiotics. Hospital wastes are a particular concern in places without effective community wastewater treatment.

Another critical source of antibiotic resistance is agriculture and aquaculture. Drugs used in veterinary care can be very similar (sometimes identical) to the antibiotics used in human medicine. And so resistant bacteria and genesare foundin animal manure, soils, and drainage water. This is potentially significant given that animals producefour times morefaeces than humans at a global scale.

Wastes from agricultural activity also can be especially problematic because waste management is usually less sophisticated. Additionally, agricultural operations are often at very large scales and less containable due to greater exposure to wildlife. Finally, antibiotic resistance can spread from farm animals to farmers to food workers, which has been seen inrecent European studies, meaning this can be important at local scales.

These examples show that pollution in general increases the spread of resistance. But the examples also show that dominant drivers will differ based on where you are. In one place, resistance spread might be fuelled by human faecal contaminated water; whereas, in another, it might be industrial pollution or agricultural activity. So local conditions are key to reducing the spread of antibiotic resistance, and optimal solutions will differ from place to place single solutions do not fit all.

Locally driven national action plans are therefore essential which the newWHO/FAO/OIE guidancestrongly recommends. In some places, actions might focus on healthcare systems; whereas, in many places, promoting cleaner water and safer food also is critical.

It is clear we must use a holistic approach (what is now called One Health) to reduce the spread of resistance across people, animals, and the environment. But how do we do this in a world that is so unequal? It is now accepted that clean water is a human right embedded in the UNs 2030Agenda for Sustainable Development. But how can we achieve affordable clean water for all in a world where geopolitics often outweigh local needs and realities?

Global improvements in sanitation and hygiene should bring the worldcloser to solving the problem of antibiotic resistance. But such improvements should only be the start. Once improved sanitation and hygiene exist at global scales, our reliance on antibiotics will decline due to more equitable access to clean water. In theory, clean water coupled with decreased use of antibiotics will drive a downward spiral in resistance.

This is not impossible. We know of a village in Kenya where they simply moved their water supply up a small hill above rather than near their latrines. Hand washing with soap and water was also mandated. A year later, antibiotic use in the village was negligible because so few villagers were unwell. This success is partly due to the remote location of the village and very proactive villagers. But it shows that clean water and improved hygiene can directly translate into reduced antibiotic use and resistance.

This story from Kenya further shows how simple actions can be a critical first step in reducing global resistance. But such actions must be done everywhere and at multiple levels to solve the global problem. This is not cost-free and requires international cooperation including focused apolitical policy, planning, and infrastructure and management practices.

Some well intended groups have attempted to come up with novel solutions, but those solutions are often too technological. And western off-the-shelf water and wastewater technologies are rarely optimal for use in developing countries. They are often too complex and costly, but also require maintenance, spare parts, operating skill, and cultural buy-in to be sustainable. For example, building an advanced activated sludge wastewater treatment plant in a place where 90% of the population does not have sewer connections makes no sense.

Simple is more sustainable. As an obvious example, we need to reduce open defecation in a cheap and socially acceptable manner. This is the best immediate solution in places with limited or unused sanitation infrastructure, such asrural India. Innovation is without doubt important, but it needs to be tailored to local realities to stand a chance of being sustained into the future.

Strong leadership and governance is also critical. Antibiotic resistance ismuch lowerin places with less corruption and strong governance. Resistance also is lower in places with greater public health expenditure, which implies social policy, community action, and local leadership can be as important as technical infrastructure.

While solutions to antibiotic resistance exist, integrated cooperation between science and engineering, medicine, social action, and governance is lacking. While many international organisations acknowledge the scale of the problem, unified global action is not happening fast enough.

There are various reasons for this. Researchers in healthcare, the sciences, and engineering are rarely on the same page, and expertsoften disagreeover what should be prioritised to prevent antibiotic resistance this muddles guidance. Unfortunately, many antibiotic resistance researchers also sometimes sensationalise their results, only reporting bad news or exaggerating results.

Science continues to reveal probable causes of antibiotic resistance, which shows no single factor drives resistance evolution and spread. As such, a strategy incorporating medicine, environment, sanitation, and public health is needed to provide the best solutions. Governments throughout the world must act in unison to meet targets for sanitation and hygiene in accordance with the UN Sustainable Development Goals.

Richer countries must work with poorer ones. But, actions against resistance should focus on local needs and plans because each country is different. We need to remember that resistance is everyones problem and all countries have a role in solving the problem. This is evident from the COVID-19 pandemic, where some countries have displayedcommendable cooperation. Richer countries should invest in helping to provide locally suitable waste management options for poorer ones ones that can be maintained and sustained. This would have a more immediate impact than any toilet of the future technology.

And its key to remember that the global antibiotic resistance crisis does not exist in isolation. Other global crises overlap resistance; such as climate change. If the climate becomes warmer and dryer in parts of the world with limited sanitation infrastructure, greater antibiotic resistance might ensue due to higher exposure concentrations. In contrast, if greater flooding occurs in other places, an increased risk of untreated faecal and other wastes spreading across whole landscapes will occur, increasing antibiotic resistance exposures in an unbounded manner.

Antibiotic resistance will also impact on the fight against COVID-19. As an example, secondary bacterial infections are common in seriously ill patients with COVID-19, especially when admitted to an ICU. So if such pathogens are resistant to critical antibiotic therapies, they will not work and resultin higher death rates.

Regardless of context, improved water, sanitation, and hygiene must be the backbone ofstemming the spread of AMR, including antibiotic resistance, to avoid the next pandemic. Some progress is being made in terms of global cooperation, but efforts are still too fragmented. Some countries are making progress, whereas others are not.

Resistance needs to be seen in a similar light to other global challenges something that threatens human existence and the planet. As with addressing climate change, protecting biodiversity, or COVID-19, global cooperation is needed to reduce the evolution and spread of resistance. Cleaner water and improved hygiene are the key. If we do not work together now, we all will pay an even greater price in the future.

David W. Graham is a Professor of Ecosystems Engineering at Newcastle University. Davids work combines methods from engineering, theoretical ecology, mathematics, biochemistry, and molecular biology to solve problems in environmental engineering at a fundamental level.

Peter Collignon is a Professor of Infectious Diseases and Microbiology at the Australian National University. Particular interests are antibiotic resistance (especially in Staph), hospital acquired infections (especially blood stream and intravascular catheter infections) and resistance that develops through the use of antibiotics in animals. Peter can be found on Twitter @CollignonPeter

A version of this article was originally published at the Conversation and has been republished here with permission. The Conversation can be found on Twitter @ConversationUS

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Fighting the next pandemic: Antibiotic resistance - Genetic Literacy Project

This article is by Featured BloggerJos Morey from hisblogpage.Republished with the authors permission.

December 31, 2019 is a day that will live in infamy. On this day, a pneumonia of unknown origin in the Hubei province of China was reported to the World Health Organization (WHO). We did not know it then, but this would be the day that the world would change. At the time of writing this article, there have beenmore than 4 million confirmed casesand nearly 300,000 confirmed deaths worldwide.

This global enemy, which we have learned to call COVID-19, has ravaged lives, regardless of age, creed or socioeconomic status. It has causedeconomic turmoiland hasdisrupted the livesof almost every human across the globe.

The impact that an entity approximately120 nanometers in diameter-- approximately 1/100th the diameter of a human hair -- can have on the world is remarkable. But as indelible a mark as the virus has had, so too has been the call to arms by the scientific community. Every generation tends to be called to rise to a great challenge, and the response of this generation of scientists, technologists, engineers and mathematicians will shape the future of humanity and health more than SARS-CoV-2 itself.

As mentioned in a recentarticleon Forbes, the mobilization of biotechnology is similar to the allies storming the beaches on D-Day. Just like that fateful day, the attack on coronavirus is multipronged. There are new-generation vaccine methods, such as synthetic peptide-based vaccines and nucleic acid-based vaccines, that are genetically engineered.Retrovirals, diabetic medications, immunologic drugs, antibiotics and even anticoagulants have all been proposed to combat the pandemic. By the last count,over 250 medicationsare being evaluated at various stages.

Before the Defense Research Advanced Projects Agency's (DARPA) support of this work in 2011, the concept of engineering vaccines into DNA strands was at the edge of science. This allows the immune system to generate proteins directly. Prior to this, conventional vaccines were created by inducing an immune response by introducing antigens into the body. Now, many of the vaccines that are being evaluated are using the more novel approach, includingModernasvaccine, the first to enter phase one human trials, andInoviosvaccine, scheduled to enter trials this summer.

But newer, even more audacious biotechnological solutions are currently underway by DARPA in a project they're callingCOVID-19 Shield,as part of the Pandemic Protection Platform. The cutting-edge concept is to harvest B cells from survivors of the disease and replicate and mass produce them via genetic engineering. This concept, if successful, could potentially mitigate any future potential pandemic in a matter of weeks and allow time for a vaccine to be developed while maintaining a flat infection curve.

However, DARPA is not the only group actively seeking solutions. There are myriad others, including the Biomedical Advanced Research and Development Authority (BARDA), which is seeking both low and high technology readiness level (TRL) solutions through a broad agency announcement (BAA). This includes a large vaccinecontract with J&Jworth over $1 billion andfast-tracking an IL-6 inhibitor by Actemra that could mitigate the lung manifestations of COVID-19.

This joins several other immune-mediated drug therapies to attempt to ameliorate the suspect cytokine storm cascade that occurs in more severe cases. BARDA is also reviewing advances from the pinnacle of bioengineering by exploring the use ofextremophiles for drug therapies.

Then there is theCOVID-19 Open Research Dataset (CORD-19),a multi-institutional initiative that includes The White House Office of Science and Technology Policy, Allen Institute for AI, Chan Zuckerberg Initiative (CZI), Georgetown Universitys Center for Security and Emerging Technology (CSET), Microsoft, and the National Library of Medicine (NLM) at the National Institutes of Health (NIH).

The goal of this initiative is to create new natural language processing and machine learning algorithms to scour scientific and medical literature to help researchers prioritize potential therapies to evaluate for further study. AI is also being used toautomate screeningat checkpoints byevaluating temperaturevia thermal cameras, as well as modulations in sweat and skin discoloration. What's more, AI-powered robots have even been used to monitor and treat patients. In Wuhan, the original epicenter of the pandemic, an entire field hospital was transitioned into a smart hospital fully staffed by AI robotics.

Any time of great challenge is a time of great change. The waves of technological innovation that are occurring now will echo throughout eternity. Science, technology, engineering and mathematics are experiencing a call to mobilization that will forever alter the fabric of discovery in the fields of bioengineering, biomimicry and artificial intelligence. The promise of tomorrow will be perpetuated by the pangs of today. It is the symbiosis of all these fields that will power future innovations.

December 31, 2019 is a day that will always be remembered. Currently, the day is known as the beginning of a disruption to our lives that few -- if any -- have ever experienced, but none shall ever forget. However, as time passes and life begins anew, I believe it will be remembered for a different reason. It will be remembered as the day science and technology went to war. A day in which humanity united to unleash the full capacity of scientific innovation on anenemy that was indiscriminate to race, religion or creed. And on that fateful day, in our darkest hour, science shined brightest. And in science we trust.

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Technology In A Time Of Crisis: How DARPA And AI Are Shaping The Future - Straight Talk

Transitional shelters have proven to be cost-effective over time if implemented correctly

Strengthening resilience to climate-related hazards is an urgent target of Goal 13 of the United Nations-mandated Sustainable Development Goals (SDG).

Stocking emergency supplies or preparing a family evacuation plan can substantially minimise loss and damages from natural hazards. However, the level of preparedness among households is often low even in disaster-prone areas.

Studies have shown that human suffering and other damage do not end with the event itself. Therefore, there is a need to focus on the complicated process of recovery and reconstruction in the months and years following a disaster.

Amid the pandemic

Cyclone Amphan, which caused massive destruction in West Bengal and adjacent areas, intensified rapidly on May 17, 2020 to become a super cyclonic storm of category 5. It, however, weakened to category 3 before making a landfall on May 20.

The devastating cyclone came at a time when people were struggling with surging cases of the novel coronavirus disease (COVID-19). Lockdowns and travel restrictions during the COVID-19 pandemic complicated the response and evacuation process during the disaster.

The challenge was to protect the vulnerable people within the emergency shelters from Cyclone Amphan as well as COVID-19. Most of them were craving for their basic rights of food, shelter and clothing.

Implementation of shelter and toilet rebuilding programme is an immediate need to let them survive.

The process of building resilience requires systematic methods which can be implemented through community interactions to understand the context of their living conditions. Awareness campaigns to understand the purpose of each individual and sensible living facility like eco-friendly shelters and toilets can facilitate the return to normalcy.

Long-term solutions from temporary shelters

Transitional shelters, built for survivors of natural disasters, are unable to hold up against intensifying calamities and the advanced construction technologies are yet to penetrate the population living in acute poverty in West Bengal.

Over the years, use of concrete materials and better technologies in transitional shelters, has made these dwellings stronger against cyclones. The concept, however, is taking time to get widely accepted.

The adaptation of transitional shelters can provide an important insight into cyclone preparedness and resilience and can help develop a community-based approach for disaster management.

Transitional shelter, being an incremental process rather than a multi-phased approach, needs acceptance. Such rapid, post-disaster shelters are made from materials that can be upgraded or re-used in more permanent structures, or can be relocated from temporary sites to permanent locations.

Transitional shelters have proven to be cost-effective over time if implemented correctlyand provide good opportunities for scaling-up by using common, local and regional materials. With building transitional shelters comes in meaningful engagement with affected communities /individuals. This ensures design and implementation is context-appropriate and the needs of marginalised and vulnerable groups are considered.

However, knowledge of good, safe building practices is inculcatedso thathouses incorporate disaster risk reduction measures. Pressure should not be taken off permanent housing reconstruction effort. The integration of other sectors or issues such as livelihoods, Water, Sanitation and Hygiene (WASH) and transport, is important for the success of the transition.

There are several ways to boost infrastructure resilience. Hazards can be addressed partially through the widespread deployment of green infrastructure, while preventing the development of grey infrastructure.

Energy resilience can be enhanced through the development of distributed renewable power such as rooftop solar installations. The primary need is avoiding water pollution.

The practice of setting up toilets right beside ponds can be replaced with ecological sanitation toilets. Manure collected from these units can also help the local community in irrigation.

Community engagement for effective recovery

Delivering shelter-recovery programmes is complex and often subject to significant competing interests and obstacles. The needs of women, girls, men and boys and that of different households can vary significantly.

A one-size-fits-all shelter design has limited flexibility to meet these needs. Governments and non-governmental organisations should greatly strengthen their approaches to community engagement in shelter projects, with the aim to improve community ownership of projects and individual ownership of shelters.

Future programmes should aim to empower people to take charge of their own shelter recovery, including giving them meaningful control and choices over shelter design and construction, hence leading to improved outcomes overall.

To do so, developing a communal understanding of the different risks disaster-affected people face and ensuring they have the knowledge to make choices about these risks is required. This will require strong community engagement and technical support capacity.

Any future climate adaptation strategy needs to account for material needs of the most vulnerable communities, prioritising the building of a social safety net that will enable them to resume their livelihoods and continue to live with dignity.

Moreover, among the various stakeholders that build and carry community resilience are government, grassroots organisations and volunteer networks. These stakeholders are those who understand the local community and show up in solidarity at the hour of need, as disasters around the world have shown time and again.

Yezdani Rahman is the chief of programmes,Sustainable Environment and Ecological Development Society(SEEDS).

Views expressed are the authors own and dont necessarily reflect those of Down To Earth.

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Cyclone Amphan: Building back with resilient infrastructure and community engagement - Down To Earth Magazine