Mars from above: NASA shares photos of the Red Planet captured by its Reconnaissance Orbiter to mark the spacecraft's 15th anniversary since launch - including a spectacular shot of an avalanche

The NASA Mars Reconnaissance Orbiter launched for the Red Planet to study its geology on August 12, 2005

Over the 15 years the orbiter has been studying the Red Planet it has made some major scientific discoveries

This includes signs of briny water, avalanches and active seasonal changes such as dust storms and dunes 

To mark 15 years of operation a team from NASA JPL shared a selection of photos taken by the spaceship

By RYAN MORRISON FOR MAILONLINE  PUBLISHED: 14 August 2020

A spectacular shot of a Martian avalanche, an image of a dust devil and a long-distance portrait of planet Earth are among a selection of photos shared by NASA to mark 15 years of the agencies Mars Reconnaissance Orbiter.

The images were all taken of the Red Planet and its surroundings from space using equipment onboard the orbiter - which is the oldest spacecraft currently active around Mars.

Since leaving Earth 15 years ago, NASA's Mars Reconnaissance Orbiter has reshaped our understanding of the Red Planet including discovering information on dust storms, temperatures and subsurface minerals.

However, while the scientific discoveries have been remarkable, the orbiter has become best know for its stunning images showing remarkable features on the surface of the alien world.

HiRISE captured avalanches in action. As seasonal ice vaporised in the spring, these 1,640-foot-tall (500-meter-tall) cliffs at Mars' north pole began to crumble


As HiRISE pans over large swaths of Mars' surface, it occasionally discovers surprises like this towering dust devil, which was captured from 185 miles (297 kilometers) above the ground

Among its instruments, MRO carries three cameras: A fisheye lens, one for 19-mile-wide black and white terrain shots and the High-Resolution Imaging Science Experiment (HiRISE) which provides the most striking photos.

Able to zoom in on surface features at the highest resolution, the detailed, colour images from HiRISE have captured dramatic scenes of nature on the Red Planet that have captivated audiences back on Earth.

These scenes include tumbling avalanches, sky scraping dust devils, and other features of a changing landscape that show Mars is more than just a red rock.

The camera has also provided images of other NASA spacecraft at Mars, like the Curiosity and Opportunity rovers, the Martian moon Phobos and even a picture of Earth.

As of early August 2020, the HiRISE camera alone had taken 6,882,204 images, generating 194 terabytes of data sent from Mars since 2006.


This 'false colour' image shows sand ripples from February 2009. The 'false colour' has been added to this image to accentuate certain details, like the tops of dunes and ripples. Many of these landforms are migrating, as they do on Earth


A dramatic, fresh impact crater dominates this image taken by HiRISE. The crater spans approximately 100 feet (30 meters) in diameter and is surrounded by a large, rayed blast zone

The Mars Reconnaissance Orbiter is managed by NASA's Jet Propulsion Laboratory (JPL) in Southern California and the team that run the spacecraft selected a number of images they deem 'among the most striking' of the planet.

One of those images shared by the JPL team shows a red dusty avalanche plunging down a 1,640 foot tall cliff in May 2019 - caused by seasonal ice vaporising in the Spring.

Every Spring the Sun shines on the sides of the stack of layers at the North Pole of the Red Planet and the warmth destabilised the ice - with blocks of it and dust breaking loose.

As this happened the cliffs at Mars' north pole began to crumble and this exposed the many layers of ice and dust that have settled along its face during the different Martian eras.

Like the rings of a tree, each layer has a story to tell scientists about how the environment was changing.

When the rocks reach the bottom of the cliff face, the blocks kick up a cloud of dust that appears as an avalanche in the photos shared by the NASA JPL team.

Dust was a major factor in a few of the images shared by the team as dust storms are routine on Mars.

Most are limited to small regions and are not as dramatic as what's portrayed in movies but once or twice a decade a series of regional storms create 'domino effect' that result in the dust covering the whole planet.

The MRO captured one of these events in 2018 and it darkened the region above the Opportunity rover, depriving its solar panels of sunlight and ultimately leading to the end of the mission.

NASA rovers are featured in some of the other images shared from the MRO by the JPL team - they show the final traverse map of Opportunity and the tracks made by Curiosity in the Martian soil.

The pictures shared in the NASA photo essay show a changing and active landscape including seasonal dark marks on the Martian equatorial slope and ripples in sand dunes on the surface of the Red Planet.

Land changes over time, so having a spacecraft at Mars for more than 15 years offers a unique perspective, according to Leslie Tamppari, deputy project scientist at JPL, who said 'the more we look, the more we discover'.

'Before MRO, it wasn't clear what on Mars really changed, if anything. We thought the atmosphere was so thin that there was almost no sand motion and most dune movement happened in the ancient past.'


This composite image shows how the appearance of dark markings on Martian slope changes with the seasons. These dark streaks appear in the same places at around the same times of year



This is the final traverse map for Opportunity, showing where the rover was on June 10, 2018, the last date it made contact with its team before it was lost in a dust storm

Other images include a dramatic impact crater spanning 100ft across from a large meteorite than wouldn't have been able to penetrate Earth's atmosphere.

Mars has a thin atmosphere – just 1 per cent as dense as Earth's. As a result, there's less of a protective barrier to burn up space debris. That means larger meteors make it through the Red Planet's atmosphere than Earth's.

NASA also shared an image showing dark marks on an equatorial Martian slope that appear in the same place and at around the same times every year.

It takes sharp eyes to find unique features on Mars, like recurring slope lineae. It was initially proposed they were caused by brine, since salt could allow water to remain liquid in the thin Martian atmosphere.

The consensus now, however, is that they're actually caused by dark sand sliding down inclines.

The streaks were discovered by Lujendra Ojha, who was an undergraduate at the University of Arizona, which operates the HiRISE camera, and now is a professor at Rutgers University.

'Sometimes you're just looking at the right place at the right time,' Ojha said. 'I was completely baffled when I first spotted this, because I was just a student at the time – I wasn't even in a planetary program.'


On the left is a picture of Mars taken by MRO showing the planet before the 2018 dust storm enveloped the whole planet - as seen by the nearly featureless world shown in the right hand image

It wasn't just the planet itself that MRO focused on, during its mission it turned its sights back to Earth to get a view of our world and captured a detailed image of the Martian moon Phobos.

Named for the Greek god of fear, Phobos is one of Mars' two moons - the other is called Deimos, named for the god of terror.

Phobos is only about 13 miles (21 kilometers) across but despite its small size, Phobos is of great interest to scientists as nobody is sure how it came to be within the orbit of Mars.

A Japanese mission is scheduled to launch to Phobos in the near future, and the moon has been proposed as a staging ground for astronauts before they go to Mars.

The Mars Reconnaissance Orbiter left Earth for the Red Planet on August 12, 2005 and cost $720 million - its purpose is the study the geology and climate of the planet and provide reconnaissance for future landing sites.

In 2021 the Mars 2020 Perseverance rover and the NASA Ingenuity helicopter will land in the Jezero Crater to search for signs of ancient Martian life.

The rover is equipped with a number of cameras and will be able to send back new pictures of the surface of the Red Planet to show one of our nearest stellar neighbours in greater detail than has been seen so far.

HiRISE took two images of the larger of Mars' two moons, on March 23, 2008. Called Phobos, the moon is only 13 miles across


A composite image of Earth and the Moon. During its mission HiRISE has been turned towards the Earth to capture images of our home world and our natural satellite

The helicopter is a technology demonstration to test the first powered flight on Mars and is currently on board the Mars 2020 spacecraft attached to the belly of the Perseverance rover.

NASA recently marked a milestone in the development of Ingenuity - which will operate a number of test flights over 30 Martian days in the spring of next year.

The space agency recharged the batteries of the helicopter up to 35 per cent to make sure it was able to 'speak' to the device and test its instruments.

'This was a big milestone, as it was our first opportunity to turn on Ingenuity and give its electronics a 'test drive' since we launched on July 30,' said Tim Canham, the operations lead.

'Since everything went by the book, we'll perform the same activity about every two weeks to maintain an acceptable state of charge.'

Even after Perseverance has landed and Ingenuity has made its tests flights, the Mars Reconnaissance Orbiter will continue its mission to study the Martian atmosphere and share more sensational images of its surface.
NASA plans for helicopter 'Ingenuity' to land on Mars in 2021

NASA MARS 2020: THE MISSION WILL SEE THE PERSEVERANCE ROVER AND INGENUITY HELICOPTER SEARCH FOR LIFE

NASA's Mars 2020 mission will search for signs of ancient life on on the Red Planet in a bid to help scientists better understand how life evolved on Earth.

Named Perseverance, the main car-sized rover will explore an ancient river delta within the Jezero Crater, which was once filled with a 1,600ft deep lake.

It is believed that the region hosted microbial life some 3.5 to 3.9 billion years ago and the rover will examine soil samples to hunt for evidence of the life.


Nasa's Mars 2020 rover (artist's impression) will search for signs of ancient life on Mars in a bid to help scientists better understand how life evolved on our own planet

The $2.5 billion (£1.95 billion) Mars 2020 spaceship launched on July 30 with the rover and helicopter inside - and will land on February 18, 2021.

Perseverance is designed to land inside the crater and collect samples that will eventually be returned to Earth for further analysis.

A second mission will fly to the planet and return the samples, perhaps by the later 2020s in partnership with the European Space Agency.


This concept art shows the Mars 2020 rover landing on the red planet via NASA's 'sky-crane' system

It’s lyfe, Jym

BY PHILIP BALL 14 AUGUST 2020

Do we need a broader definition of life, and a new word to go with it?

‘Is there lyfe on Mars?’ That might sound like a Chaucerian remix of David Bowie’s song, but astrobiologists Stuart Bartlett and Michael Wong have suggested it might be the proper way to pose the question.1 They propose that we broaden the notion of ‘life’ into a more all-encompassing category called ‘lyfe’, to include anything that satisfies ‘all four processes of the living state, namely: dissipation, autocatalysis, homeostasis, and learning.’

But are these really the necessary and sufficient properties of living systems – and if so, do we really need a new word to describe them?
Source: © CBS/Getty Images
Commander Spock never actually said ’It’s life, Jim. But not as we know it’. Though if he had, perhaps he would have opted for ‘lyfe’ instead. 

The meaning of lyfe

Some of the initial responses to Bartlett and Wong’s article have grumbled that the answer to the second question is ‘no’. But you can see the logic of their position. The search for life (including intelligent kinds) on other worlds has long struggled to escape parochialism. For example, Nasa’s watchword in looking for habitable worlds was for many years ‘follow the water’. Yet while we know of no terrestrial life that can do without liquid water, and there are subtle reasons why it would be a hard solvent to equal for making life possible, there’s no reason to make it a sine qua non for life.2 And as far as Seti (the search for extraterrestrial intelligence) is concerned, astrobiologist Nathalie Cabrol has accused it of ‘searching for other versions of ourselves’. 3 By coining ‘lyfe’, Bartlett and Wang hope to free our minds from terracentric preconceptions.

Nasa defines life as ‘a self-sustaining chemical system capable of Darwinian evolution’. Even though that makes no reference to any specific chemical basis, evidently it insists that the mechanism by which life elsewhere evolves will be the same as that on Earth. Assuming natural selection will apply to aliens too is not as presumptuous as it might seem – as biologist Arik Kershenbaum has pointed out, we know of ‘no serious alternative contenders’ for how complex life might arise from scratch.4

On Titan, for example, the partitioning made possible by extreme cold might permit “lyving” systems without membranes

All the same, Bartlett and Wong refuse to be tied to even that assumption. They say that ‘life as we know it’ can be considered a subset of a more general category of chemical systems that warrants astrobiological attention. One vital shared attribute is autocatalysis: an ability to assist in making more of itself, which presumably becomes replication when the systems are discretely compartmentalised. Equally essential is the maintenance of an ordered, low-entropy configuration, which typically involves tapping some energy source and using it to maintain a non-equilibrium steady state: what is called a dissipative system. (Some such systems can clearly be non-living in themselves: for example the patterns seen in convecting fluids.) Origin-of-life theories that invoke disequilibria at hydrothermal vents, for example, suggest that this dissipation might tap redox or chemiosmotic gradients. Lyfe too has to be a non-equilibrium phenomenon, but could be more diverse in the disequilibria it exploits.

Two other features are needed. Homeostatic regulation preserves the system in the face of external perturbations, while information about the environment is harnessed and processed via memory and learning. Filtering and remembering environmental information that is predictively useful seems to be a universal requirement for complex physical systems that function with high thermodynamic efficiency.5 Natural selection can be considered a special kind of learning in which a memory of salient environmental information is passed in encoded form between generations.

Choose lyfe

Bartlett and Wong say that their view of lyfe doesn’t reside at any particular scale – it isn’t some intrinsic property of, say, a group of molecules, or a cell-like structure, or a discrete organism. Harking back to James Lovelock’s Gaia theory, they say that ‘the living state may best be assessed at an ecosystem or planetary scale’ – echoing Lovelock’s view that life cannot persist precariously on a planet.

One attraction of this list of criteria is that it allows for a clear distinction between systems that share some lifelike features – chemical reaction–diffusion patterns or viruses, say – and those that truly constitute lyfe. The two researchers also hope that their scheme might resolve some of the disputes and ambiguities in origin-of-life studies, which they feel are sometimes talking at cross-purposes. Between a top-down approach that seeks to identify the features of ‘Luca’ (the last universal common ancestor) from phylogenetic analysis, and bottom-up approaches that try to plot a route from abiotic geochemistry to protocells, there remains a potentially unbridgeable gulf because neither direction imposes constraints that can converge on a unique trajectory.

The duo suggest that this view of what we might call ‘lyfe’s grandeur’ could help others be clearer about the questions they are addressing. And they sketch out a few scenarios that their scheme suggests for the existence of lyfe-like entities in decidedly non-terrestrial settings. On Saturn’s organic-rich moon Titan, for example, the partitioning made possible by the extreme cold might permit “lyving” systems that are not compartmentalised by membranes.

So whether or not the notion of lyfe is needed, it raises interesting questions. Perhaps one obstacle to adopting the term is that, to distinguish it verbally, the researchers propose the pronunciation ‘loif’. Much as it would be fun to hear astrobiologists talk like Hollywood movie pirates, I can’t see it catching on.

References

1 S Bartlett and M L Wong, Life, 2020, 10, 42 (DOI: 10.3390/life10040042)

2 S A Benner, A Ricardo and M A Carrigan, Curr. Opin. Chem. Biol., 2004, 8, 672 (DOI: 10.106/j.cbpa.2004.10.003)

3 N Cabrol, Astrobiology, 2016, 16, 661 (DOI: 10.1089/ast.2016.1536)

4 A Kershenbaum, The Zoologist’s Guide to the Galaxy, Viking, 2020

5 S Still et al., Phys. Rev. Lett., 2019, 109, 120604 (DOI: 10.1103/physrevlett.109.120604)

EPA settles Gold King mine disaster five years later

The US Environmental Protection Agency (EPA) has reached a $220 million (£169 million) settlement with Utah over the agency’s botched investigation of the abandoned Gold King mine in Colorado. The settlement comes exactly five years to the day since a dam was accidentally breached at the mine, releasing 11 million litres of contaminated water into major US waterways in Colorado, Utah and New Mexico. The leaked wastewater contained lead, cadmium, manganese, iron, zinc, copper and arsenic, as well as mercury, and it turned downstream waters orange.

BY REBECCA TRAGER 12 AUGUST 2020 CHEMISTRYWORLD.COM

Source: © Theo Stroomer/Getty Images
The spill started in Cement Creek in Colorado’s San Juan mountains and flowed downstream into the Animus River and the San Juan River, turning their waters orange.

Under the agreement, the EPA will fund efforts to address contamination at the Bonita Peak Mining District Superfund Site, which includes the Gold King mine and other abandoned mines in Utah. This could involve monitoring and cleaning mining areas located in other states. In addition, the EPA will initiate assessments at multiple sites across Utah to determine if further remediation is necessary, and the agency will bear the cost, which may exceed $200,000 per site.

‘After years of intense litigation and negotiations, we are very pleased that millions of dollars can now be spent towards mitigation, remediation and assuring water quality in Utah rather than years of more litigation, trial and appeals,’ said Utah’s attorney general, Sean Reyes. ‘We are highly encouraged the EPA has stepped up and committed hundreds of millions of dollars toward cleaning up several dangerous mining districts containing billions of gallons of potentially harmful substances that threaten Utah if they are released.’

Reyes, who referred to the agreement as a ‘landmark settlement’, said Utah’s Department of Environmental Quality has been monitoring the San Juan River and Lake Powell since the 2015 incident, and there is no evidence that the metals from the release are impacting public health or the environment.

Native American tribes and the state of New Mexico have also taken legal actions against the agency to recover damages sustained as a result of the incident. The San Juan River is a key water source for the Navajo and Southern Ute Indian Nations, and the wastewater spill began in the Animas River that flows into New Mexico where it joins the San Juan River. New Mexico’s case is expected to go to trial in 2021. Colorado state has decided not to sue the EPA over the spill.

PODCAST
Book club – Three books on pandemics 

BY KATRINA KRÄMER, JAMIE DURRANI, MONSERRAT GARDUÑO-CASTRO

8 JULY 2020

In this episode we’re tackling the coronavirus information overload by comparing three books on pandemics past and present: Outbreaks and Epidemics by Meera Senthilingam, Adam Kucharski’s The Rules of Contagion, and The Pandemic Century by Mark Honigsbaum (the only one written well before the current pandemic hit).

Find out what we thought about each of these titles, what readers might get out of them, and hear from Outbreaks and Epidemics author Meera Senthilingam about what it was like to write about pandemics while being in the middle of one.

You can also read Monserrat’s full review of The Rules of Contagion here.

What are the risks of fast-tracking a Covid-19 vaccine?

The global rush is on to find a safe and effective vaccine against Covid-19. Experts and companies claim one could be on the market in 12–18 months. The US president wants one by the end of the year. According to the World Health Organization (WHO), 17 candidates are in clinical trials, with one already in Phase 3 and two others likely to enter in July.

BY KATRINA MEGGET 13 JULY 2020 CHEMISTRYWORLD.COM


Source: © John Holcroft/Ikon Images

The multitude of vaccines in development give us many shots at a potentially useful vaccine. But rushed development could mean missing information about long-term safety and protection

The accelerated speed of development has public health experts concerned that vaccines might be approved with incomplete data and analysis. At least one candidate has skipped animal testing, for example. Meanwhile, in China, CanSino Biologic’s experimental Covid-19 vaccine has been approved for the country’s military before Phase 3 trials have finished.

The concern intensifies when no vaccine against a coronavirus has ever been approved before, while many of the vaccine platforms in development against Covid-19 are unproven new technologies. ‘Developing a vaccine in about a year is unprecedented,’ says Byram Bridle, a viral immunologist at the University of Guelph in Canada, who has received Covid-focused funding to develop a new vaccine platform. ‘As a scientist with expertise in the field I am personally concerned that conducting science too fast could risk compromising the rigour needed to properly assess vaccines. A vaccine that is ineffective and/or unsafe will not be useful.’

Among the top concerns is the potential that a fast-tracked vaccine will have unintended side-effects. No vaccine is 100% safe, but if a billion people are vaccinated, a one in 10,000 serious adverse event will affect 100,000 of those people. In May, it was revealed that four out of 45 people in Moderna’s Phase 1 vaccine trial experienced ‘medically significant’ adverse events.


The most important thing is that fast tracking does not mean a compromise on safety or efficacy

KATHERINE O’BRIEN, WHO

In the upcoming Phase 3 trials, there will be up to 30,000 participants. But reliably identifying a one in 10,000 adverse event requires testing 38,500 people. Rarer events need even larger trials, explains Gregory Poland, director of vaccines research at the Mayo Clinic in Minnesota, US. ‘We won’t know about rare events until after the vaccine is licensed.’

One potential adverse event is antibody-dependent enhancement (ADE), a type of immune reaction where vaccination makes subsequent exposure to the virus more dangerous. The condition – which has been observed with vaccines for measles, respiratory syncytial virus and dengue virus, as well as in animal models for the original Severe Acute Respiratory Syndrome (Sars) virus – occurs when the body, primed by a vaccine, generates antibodies that don’t sufficiently neutralise the virus when later exposed to it and instead encourage the virus into cells to replicate, exacerbating the disease.

According to Bridle: ‘There is definitely a risk of ADE; how much of a risk cannot be stated with any certainty though.’ Yet the US National Institute of Allergy and Infectious Diseases’ (NIAID) Vaccine Research Centre, which is collaborating on Moderna’s vaccine, has downplayed the possibility of ADE in a Covid-19 vaccine. Barney Graham, deputy director of the unit, told Proceedings of the National Academy of Sciences that because the Sars-CoV-2 coronavirus is structurally different to the cases where ADE has been seen, he doubts similar activity would apply.


How long would it take to determine if a vaccine can confer immunological memory for one year? Of course, it would take at least one year

BYRAM BRIDLE, UNIVERSITY OF GUELPH, CANADA

Regardless, Bridle says developers need to carefully assess the type of immune response their vaccines induce and test the response in vaccinated animal models exposed to the virus to ensure ADE does not occur. Poland has expressed concern that animal studies may not be completed before moving to human testing, which transfers extra risk to humans. However, he says that vaccine developers can’t really mitigate for side effects, apart from making sure the vaccine doesn’t contain amino acid sequences similar to human proteins and that the vaccine induces a balanced immune response.

To allay safety fears, the US Food and Drug Administration (FDA) released guidance at the end of June stating that nonclinical safety studies are necessary for novel vaccines and drug companies will be required to monitor their vaccines after approval. The WHO’s director of immunisation and vaccines, Katherine O’Brien, says fears of cutting corners are unfounded: ‘The most important thing is that fast tracking does not mean a compromise on safety or efficacy.’
Making memory

However, there is still a lot we don’t know about coronaviruses, which is another concern with speedy vaccine development. For example, the question mark over immunity – are antibodies protective and how long does immunity last?

Bridle says fast tracking vaccines risks compromising assessments of immunological memory. ‘Arguably, a vaccine against Covid-19 should confer immunity for more than one year to reduce the risk of future recurrences. But how long would it take to determine if a vaccine can confer immunological memory for one year? Of course, it would take at least one year. So how does that fit into the goal of getting a vaccine into broad public use in under a year? A prophylactic vaccine is useless if it does not confer long-term immunological memory’ to respond when exposed to the virus.

In addition, a fast-tracked vaccine may not be particularly effective. Bridle notes that the goalposts for success have already shifted from the search for a vaccine that protects against disease to one that merely reduces disease severity. The risk, says Bridle, is that poor-quality vaccines could potentially turn people into asymptomatic carriers that spread the virus.

At the end of June, Anthony Fauci, the White House health advisor and NIAID director, said the US was unlikely to develop herd immunity as a vaccine would potentially be only partially effective, adding he would be happy if a first vaccine was only 70%­–75% effective. A day later the FDA released its vaccine guidance saying a vaccine would only need to be 50% effective in a placebo-controlled trial: an efficacy similar to the annual flu jab. Response has been mixed, with some experts saying the 50% figure is too low and others saying it is too high.

O’Brien says the WHO hasn’t specified the minimum effectiveness of a Covid vaccine, calling the determination complex ‘but there are certainly arguments for an efficacy lower than 50%’. She says as long as trials can enrol participants quickly and take place in areas where the disease is circulating then efficacy can be established in less than 12 months.
Maintaining confidence

Ensuring a vaccine is safe and effective will be essential in keeping the public’s trust in vaccines. There is a risk a fast-tracked vaccine could dent this and compromise vaccination programmes. Already in the US, around 30% of the public say they would reject a covid vaccine, according to various surveys. Poland says policies have to be driven by the science and effectively communicated to the public.

But with economies flagging from the health crisis, will society accept more risk in a vaccine? Bridle acknowledges this could be the case with Covid-19. Poland says the risk­–benefit ratio of all vaccines will be carefully reviewed by authorities but notes risk boundaries are subjective.

O’Brien notes that trials will be halted either when a safety event is flagged or when the vaccine is found to be effective but ‘we can’t hold back an effective vaccine and forgo the benefit of it in the short-term in a pandemic situation just to wait for long-term safety evaluations’. Safety monitoring will continue after approval anyway, she adds.

But safety and efficacy concerns aside, there is more at stake here. Covid-19 won’t be the only coronavirus pandemic in the future, Bridle explains. The risk is we don’t build on the scientific gains once this pandemic recedes and we fail to use the data and technology to be ready to develop a safe and effective vaccine for the next coronavirus. Without funding, he says, this could be a real possibility.

Favipiravir
Originally developed to treat flu and marketed in Japan as Avigan, promising Covid-19 trial results have seen countries stockpiling this medication by the millions
BY BEN VALSLER 31 JULY 2020 CHEMISTRYWORLD.COM 

PODCAST TRANSCRIPT
Ben Valsler

Most of the potential Covid-19 treatments we’ve looked at on the Chemistry in its element podcast have been evaluated on their ability to treat severe disease – drugs that can prevent deaths, reduce time in intensive care or get people discharged from hospital sooner. And in the peak of a pandemic that certainly makes sense. But we’ve said little about drugs that treat milder cases – those that don’t necessitate a trip to hospital. New clinical trial data suggests that favipiravir, a drug licenced in Japan to treat influenza and also known as Avigan, may significantly reduce Covid symptoms and viral load in just a few days.



Source: © kitzcorner / Shutterstock.com
The night shopping area of Dotonbori, draws crowds of tourists visiting Osaka

Favipiravir seems to be effective against a wide range of viruses – including well known ones like influenza and norovirus, but also alphavirus, filovirus, arenavirus and the flaviviruses responsible for West Nile fever, Dengue, Zika and yellow fever. It works by preventing viruses from replicating through inhibiting RNA-dependent RNA polymerase – a similar mechanism to remdesivir. Taken orally, it’s what’s known as a prodrug – it’s metabolised into its active form once inside the body. It seems to have relatively few side effects with one major exception – it can cause significant defects to a developing embryo, so should be avoided by people who are pregnant or trying to become pregnant.

In the aftermath of the fatal H5N1 epidemic in Hong Kong in 1997, demand grew for medications that could treat new strains of influenza. A joint effort between Fujifilm’s Toyama Chemical Co, Hokuriku University and the University of Toyama screened 30,000 candidate molecules for biological activity, looking for antibacterial, anti-inflammatory, immunomodulatory and antiviral properties. One, a derivative of the tuberculosis medication pyrazinamide, known as T-705 compared favourably with established flu drug oseltamivir, which you might know as Tamiflu.




One big advantage of favipiravir is that it seems to be relatively difficult for viruses to become resistant. In lab studies that actively tried to develop resistant influenza, researchers struggled to evolve a virus that was both resistant to the drug and capable of enough reproduction to become the dominant virus type. There’s also no evidence of resistance developing during clinical trials – something that has been seen in trials of oseltamivir and other antivirals. That’s not to say it can’t happen, of course – mutations have been identified that offer protection against the drug, but at a cost. If another mutation can compensate for the loss in viral fitness, resistance could evolve. Life (or in this case an ‘organism on the edge of life’) finds a way.

It may come as a surprise, then, that favipirivir is not widely licenced for use against influenza. The risks in pregnancy may have been enough to cause most countries to stick to their existing flu provisions. Even in its home country of Japan, it’s licenced only as a treatment for novel or re-emerging strains of influenza, and not for the seasonal infection. That’s not to say it failed as a medication; In 2017, Japan created a stockpile of the drug – enough to treat 2 million people in the event of an influenza epidemic.



Source: © kitzcorner / Shutterstock.com
Face masks were common in populated areas of Japan prior to the Covid-19 pandemic…

In a pattern that is probably becoming familiar to covid-treatment-trackers and podcast listeners, favipiravir has also shown promise in treating Ebola. In 2014, a French volunteer nurse who contracted the disease in Liberia recovered after receiving favipirivir alongside other experimental treatments, but initial trials showing positive results in mild cases were criticised for poor experimental design.

Ebola, then, as was the case with remdesivir, leads us to Sars-CoV-2, the coronavirus responsible for Covid-19. Chinese clinical trials showed favipiravir to be ‘clearly effective’ – patients tested negative for the virus in an average of just four days, compared to 11 days for controls. Symptoms improved alongside reduced viral load, with lung function improving in 91% of patients on the drug, vs 62% of those without. In a Russian trial, body temperature in 68% of patients on favipiravir returned to normal in half the time of those in the control group. A trial in Japan, however, showed limited effect in people with higher viral load, suggesting it’s most likely to be of use in mild to moderate cases. Trials are also underway worldwide exploring the efficacy of favipiravir alone and in tandem with other drugs.



Source: © Ned Snowman / Shutterstock.com
…now even the shop mascots are wearing them.

The promising results so far have led to a spike in demand. Thailand has ordered 400,000 tablets from China and Japan, Germany is said to be purchasing millions. While companies in China, Russia, Bangladesh and India are amongst those producing their own supply of generic favipiravir, following fast-tracked approval.

It’s now been more than eight months since Covid-19 was first identified, over 17 million cases have been reported and nearly 2000 clinical trials undertaken worldwide. In that time we’ve seen the rise and fall of a number of promising treatments. Favipirivir is on the rise – will it be the next promising candidate to fall?

Next week, Mike Freemantle on gypsum, and a fantastic discovery in Mexico.

Mike Freemantle

One of the geologists who subsequently visited to research the cave described it as ‘the Sistine Chapel of crystals’. The crystals were up to a dozen metres long, four metres wide, and 55 tons in weight. They are thought to be the largest natural crystals in the world.

Ben Valsler

Join Mike next time, and many thanks to Jeff Silver for suggesting we take a look at favipirivir – Jeff certainly seems to have demonstrated some foresight when he got in touch back in April. If you would like to suggest any compounds for us to cover – email chemistryworld@rsc.org or tweet @chemistryworld. And you can find all of our previous pods at chemistryworld.com/podcasts. I’m Ben Valsler, thanks for joining me.

Additional information

Theme: Opifex by Isaac Joel, via Soundstripe

Additional music: Serene Waters by Aeroplanes and Cherry Blossom by Simple Thieves, via Soundstripe

UPDATES TOO
Encouraging signs from initial Covid-19 vaccine trials
BY ANTHONY KING11 AUGUST 2020

There’s been a surge of data emerging from Covid-19 vaccine trials. The studies are mostly Phase 1 safety trials, but can give some hints of immune response to the vaccines. At the same time, trials in which animals are immunised and then deliberately exposed to the virus give positive indications of potential protection. However, we still don’t know what level of immune response will be protective for humans, nor how long that protection will last.



Source: © Felix Dlangamandla/Beeld/Gallo Images/Getty Images

As initial data shows the vaccines are safe and elicit positive immune responses, companies are racing to start larger trials in areas where the virus is most prevalent to determine its efficacy

The acknowledged leader is the candidate from the University of Oxford, UK, which is a chimp adenovirus vector (ChAdOx1) expressing the entire spike protein of Sars-CoV-2. A randomised controlled trial of over 1000 healthy adults showed an encouraging antibody and T cell response.1 The vaccine is to be manufactured by AstraZeneca.

‘Both arms of the immune system were very well stimulated, including a very good T cell response,’ says Adrian Hill, director of Oxford’s Jenner Institute. The immune response, especially in terms of neutralising antibodies, was significantly increased by a second dose. That will be influential in planning future trials and any eventual rollout, Hill confirms.


The big question is how strong an immune response you need to induce protection

ADRIAN HILL, UNIVERSITY OF OXFORD

The levels of antibodies or T cells needed for protection are as yet undetermined, points out Dennis Burton, an immunologist at the Scripps Research Institute in La Jolla, US. ‘That is the acid test for any vaccine,’ he says. It’s likely that T cells in particular will be important for long-term protection.

China’s CanSino Biologics reported results on the same day as Oxford from a study that administered two different doses of its adenovirus-type 5 (Ad5) vectored vaccine in a trial of 600 volunteers in Wuhan.2 Ad5 is relatively common in humans, and 52% of the trial participants already showed antibodies against it, but levels of Ad5 immunity will vary in different populations. People with high existing antibody levels to Ad5 produced around half as many antibodies to Sars-CoV-2. The T cell response was similar in those with and without pre-existing antibodies to Ad5.

The only other adenoviral vaccine on the market in Europe is for Ebola, approved on 1 July 2020. Scientists in Europe and the US have given Ad5 a wide berth, since an experimental HIV vaccine, developed by Merck & Co, appeared to increase rates of HIV infection. ‘The Chinese and Russians clearly did not believe [the data]. For the 2014 Ebola outbreak, they made Ad5 vaccines and both got licensed in their respective countries,’ says Hill.

Moderna, Pfizer, Sinovac

Also in July, Moderna finally reported full data from the Phase 1 trial of its mRNA vaccine.3 Researchers have expressed annoyance at the company’s tendency to press release headline results, rather than publish full datasets. Moderna has ‘dribbled out small amounts of data over time, which is frustrating and unhelpful,’ says Gregory Poland, director of vaccines research at the Mayo Clinic in Minnesota, US.

Its trial of 45 healthy adults tested two vaccinations of mRNA encoding the spike protein, 28 days apart. Binding antibodies to the spike protein increased rapidly after the first vaccination, and again with the second dose. Moderna is to begin a Phase 3 trial with the US National Institutes of Health, involving approximately 30,000 volunteers.

More than half of Moderna’s volunteers experienced minor side effects such as fever, chills, fatigue, headache and pain at the injection site. This is relatively common with vaccination. For the Oxford group, there were enough fevers and systemic side effects that the trial protocol was modified to include paracetamol before vaccination.

Earlier in July, Pfizer and BioNTech reported on their mRNA vaccine candidate, which encodes the receptor binding domain of the spike protein, encapsulated in a lipid nanoparticle. The preprint described a robust T cell and a strong antibody response4 in 60 participants in Germany who received either one or two doses. Since then, the companies have announced that a different vaccine candidate, which encodes the entire spike protein, is to start a Phase 2/3 study.

‘The caution here is that these vaccine platforms have never been licensed before in humans,’ notes Poland. In a larger trial with 20,000 people receiving active vaccine, a serious side effect that occurs in one in ten thousand people might be missed, he warns. Regulators will have to decide what compromises and level of risk is acceptable.


The fact a vaccine induces an immune response is not proof that it will prevent infection

GREGORY POLAND, MAYO CLINIC

Sinopharm and Sinovac’s inactivated virus candidate is also advancing to Phase 3 trials. It will be given to over 8000 healthcare workers in China, as well as trials in the United Arab Emirates and Brazil. ‘This is super old technology, and it is often hard to grow the virus, which is why rabies vaccine is so expensive,’ says Hill. For some, this brings advantages. ‘We know how to deal with the inactivated approaches,’ says Florian Krammer, immunologist at the Icahn School of Medicine in New York City, US. ‘We don’t have a single RNA vaccine on the market.’

This strategy tends to require two or three vaccine doses, and often an adjuvant such as alum to bolster the response. ‘[The World Health Organization is] not so keen on those vaccines,’ says Hill. This is mainly because when vaccines for Sars were tested in animals, there was some evidence of antibody-dependent enhancement – in which exposure after vaccination can lead to more severe disease. ‘I don’t think this is a major concern at this point,’ says Burton of the Covid-19 candidates.
Up to the challenge?

Early vaccine trial reports prompted a rash of optimistic headlines. ‘The big question is how strong an immune response you need to induce protection,’ says Oxford’s Hill. ‘Most people [are focusing on] neutralising antibodies, because they don’t induce high levels of T cells, but we do.’ Nonetheless, the responses from different aspects of the immune system necessary for protection remain unclear.

‘The major concern remains efficacy, and the durability of efficacy, which is why these Phase 3 trials will be so critical,’ says Poland. ‘The fact a vaccine induces an immune response is not proof that it will prevent infection. Many companies have got to this point and failed in Phase 3 trials.’ In the case of Ebola, inducing small amounts of antibodies with vaccine was enough to provide protection. Whereas even the highest antibody levels to malaria do not offer a strong defence on their own.

I was quietly pleased. The vaccines did what they said on the tin. So far, so good

DANNY ALTMANN, IMPERIAL COLLEGE LONDON

To try and get a handle on how these immune responses might translate into protection, researchers are conducting challenge studies. These involve animals – in this case mostly primates – being either infected or vaccinated and then deliberately exposed to the virus. One such trial, led by Dan Barouch at Harvard University, US, in May showed that macaques challenged with Sars-CoV-2 five weeks after an initial infection displayed strong resistance to the virus.5 A second paper revealed that macaques given a series of DNA vaccine candidates also appeared to have good protection when challenged with the virus.6 ‘We are trying to race into vaccines [for Covid-19], but we haven’t got a clue what the correlates of protection are,’ says Danny Altmann, an immunologist at Imperial College London, UK. Animal studies can provide some insights into where that bar lies.

Challenge trials in macaques conducted by Janssen,7 Oxford,8 Moderna,9 Sinopharm–Sinovac10 and Inovio11 have all produced some level of protection, although the precise details vary. ‘There are half a dozen groups trying to zoom into Phase 3 trials where the stakes and costs are high,’ notes Altmann. He says the animal data support all the vaccines as plausible candidates. ‘I was quietly pleased. The vaccines did what they said on the tin. So far, so good,’ says Altmann. ‘The Oxford one stands out in the rip-roaring levels of T cell immunity that they showed,’ he adds.
Lasting protection

With the coronaviruses that cause the common cold, immunity starts to wane around 80 days after infection. Burton, however, argues this is irrelevant. ‘They are two separate things,’ he says. ‘A vaccine can do a lot better than a natural infection.’ Burton describes the early results from the mRNA vaccines as promising. We can make guesses as to how long the response will last, he says, ‘but you have to put the vaccine into people to understand what happens in a larger population’. The spectrum of possible outcomes include preventing transmission entirely, preventing infection or just preventing an infection from developing into the disease. ‘If we had a vaccine that could prevent the disease in large numbers of people, that would be very welcome,’ says Burton.

Results from the Oxford­–AstraZeneca Phase 3 trials in the US, Brazil and South Africa could be available by September–October if all goes well. With five other candidates also already in Phase 3 trials, Burton believes that efficacy data for several vaccines will become available before the end of 2020, but warns against predictions. ‘In this whole pandemic, a lot of things have been done faster than one would have imagined even six months ago,’ he says. ‘But this is a new pathogen and nature may have lots of surprises along the way.’

References

1. P M Folegatti et al, Lancet, 2020, DOI: 10.1016/S0140-6736(20)31604-4

2. F-C Zhu et al, Lancet, 2020, DOI: 10.1016/S0140-6736(20)31605-6

3. L A Jackson et al, N. Engl. J. Med., 2020, DOI: 10.1056/NEJMoa2022483

4. U Sahin et al, medRxiv, 2020, DOI: 10.1101/2020.07.17.20140533

5. A Chandrashekar et al, Science, 2020, DOI: 10.1126/science.abc4776

6. J Yu et al, Science, 2020, DOI: 10.1126/science.abc6284

7. N B Mercado et al, Nature, 2020, DOI: 10.1038/s41586-020-2607-z

8. N van Doremalen et al, Nature, 2020, DOI: 10.1038/s41586-020-2608-y

9. K S Corbett et al, N. Engl. J. Med., 2020, DOI: 10.1056/NEJMoa2024671

10. Q Gao, Science, 2020, DOI: 10.1126/science.abc1932

11. A Patel et al, bioRxiv, 2020, DOI: 10.1101/2020.07.28.225649

A coronavirus vaccine is on the horizon, thanks to a key discovery by these researchers

by Lara Korte

Credit: Pixabay/CC0 Public Domain

When the latest coronavirus emerged, Jason McLellan and his team were ready to take action.

McLellan, an associate professor of molecular biosciences at the University of Texas, has been studying respiratory diseases for years. In 2017, McLellan's postdoctoral researcher Nianshuang Wang identified genetic mutations necessary to stabilize a key component of diseases like MERS, also a coronavirus.

So when Chinese researchers shared the genetic sequence of the new coronavirus on Jan. 10, UT researchers were able to quickly map the virus and inject it with previously-discovered mutations, allowing the researchers to freeze a key protein in a way that would become essential for creating a vaccine.

"Now every pretty much everybody's using them," McLellan said. "I think four of the five leading coronavirus vaccines all contain the stabilizing proteins my lab designed."

Several major companies, bankrolled by billions of dollars from the federal government, are in a race to complete clinical trials for their version of a coronavirus vaccine. It can normally take years for a vaccine to pass through clinical tests before it becomes available to the public, but the process has been expedited over the past several months for coronavirus vaccine candidates from companies including Pfizer, Johnson & Johnson, Novavax and Moderna.

The vaccine candidates are either in or close to the final stages of clinical trials before final authorization by federal drug authorities, and all four are using the UT team's discovery in their vaccine formulas.

"It's really exciting," McLellan said. "It's like everything I hoped for when I wanted to start doing research."

The success of the UT team's discovery hinges on the ability to map and identify what McLellan called the "Achilles' heel" of the coronavirus—the protein spike. This protein is the part of the virus that fuses onto healthy cells and transmits the infection. Researchers used mutations from earlier research to freeze the protein in its pre-fusion form. By putting a pre-fusion version of the protein into a vaccine, a person's immune system is trained to identify the virus before it latches onto cells, and create antibodies to fight it off.

"Antibodies need to recognize elements that are on the outside of the virus because they can't get inside of the virus," McLellan said. "So the spike is this massive entity on the outside of the virus, and it needs the spike in order to attach and fuse to cells, and if you stop either of those, you stop viral entry."

The researchers designed the necessary mutations within about a day of receiving the coronavirus genome. The McLellan lab completed the atomic-level structure, and graduate student Daniel Wrapp harvested and purified the spike protein.

Researchers at the National Institute of Allergy and Infectious Diseases, who are working on the Moderna vaccine, published the results of their Phase 1 trials with mice on Wednesday. The paper reported that the use of McLellan's stabilized spike protein elicited a positive immune response and prevented coronavirus infections in the lungs and noses of mice.

Moderna began its crucial Phase 3 testing late last month and plans to include 30,000 subjects from 89 centers around the U.S. It could be several months before the results of the study are clear.

A spokesman for the university said researchers so far have not received any payment for the use of their research in vaccine candidates. However, UT and the scientists may eventually see monies from licensing and royalties. The details are still being worked out between the university, the National Institute of Health and the drug companies, the spokesman said.

Meanwhile, the federal government is investing in mass production capabilities, with the hopes that one of the vaccine candidates will be viable by the end of the year. Last month, President Donald Trump announced a $265 million deal to secure manufacturing resources at a plant in College Station for the Novavax vaccine candidate. If Novavax makes it through clinical trials, the majority of its doses will be produced in Texas.

©2020 Austin American-Statesman, Texas
Distributed by Tribune Content Agency, LLC.

UPDATES

Russian vaccine launch shocks scientists
Sputnik V to be approved without large human trial data

 BY ANTHONY KING 14 AUGUST 2020 CHEMISTRYWORLD.COM

Russia’s unexpected authorisation of a largely untested Covid-19 vaccine has shocked researchers. Full scale production of the vaccine is to begin in September, with initial doses going to healthcare workers and vulnerable populations, followed by national rollout in January 2021.

The vaccine, developed at the Gamaleya Research Institute in Moscow, has apparently been tested on just 76 people. No data from animal or clinical studies have been published on potential efficacy or safety.



Russia coronavirus vaccine vials
Source: © Russian Health Ministry/Handout/Anadolu Agency/Getty Images

Rolling out the Sputnik V vaccine without the normal trials is a spectacular gamble when it comes to both its effectiveness at preventing the disease, and its potential for side effects

This is in stark contrast to even the most accelerated clinical programmes for other vaccines, in which phase 3 trials will recruit tens of thousands of volunteers to try and establish safety and effectiveness. Such large trials are also needed to spot uncommon side effects, which can quickly become a serious issue when a vaccine is given to millions of people. ‘Vaccine trials are harder to do in terms of safety and effectiveness because you must wait for people to get exposed,’ says epidemiologist Daniel Salmon, director of the Institute for Vaccine Safety at Johns Hopkins University, US. ‘It is really in phase 3 trials where you get a much better understanding of safety.’


Vaccines shouldn’t be the domain of Cold War political dispute

President Vladimir Putin’s televised announcement of the approval, dubbed Sputnik V, has an air of political point-scoring to it. ‘Putin says he will give it to other countries in October or November, which is just as we have our elections [in the US],’ says Hildegund Ertl, vaccine researcher at the Wistar Institute in Philadelphia,US, who is suspicious of this timing. ‘[Donald Trump] keeps saying we will have a vaccine by November.’ She hopes that the US and other countries will not tolerate political pressure on scientists to rush approval of vaccines. ‘Vaccines shouldn’t be the domain of Cold War political dispute,’ agrees Danny Altmann, immunologist at Imperial College London, UK. ‘This is incredibly unhealthy. The [potential] downsides are spectacular at every level.’

The Gamaleya vaccine trial used human adenoviruses to deliver RNA encoding the viral spike protein. The official website for Sputnik V describes its adenoviral vector technology as having been in development since the 1980s, with numerous studies showing effectiveness and safety. However, while Russia licensed vaccines using adenoviral vectors for Middle East Respiratory Syndrome (Mers) and Ebola, there were no large phase 3 studies for them. ‘Neither the adenovirus vectors nor the RNA vaccine have been licensed for any disease [in Western countries],’ notes Ertl. ‘Some have undergone large scale clinical trials, but we have zero experience in mass vaccinations.’

The Russian vaccine uses two different viral vectors, human adenovirus type 26 (Ad26) in an initial dose, and human adenovirus type 5 (Ad5) in a booster three weeks later. Both normally cause common colds, so a proportion of people will already have antibodies to them. That may lessen the vaccine’s effectiveness at stimulating an immune response against the Sars-CoV-2 virus. Ad26 is the same vector being employed by Johnson & Johnson (J&J), while China’s CanSino Biologics is using Ad5.

In principle, Ertl in principle likes the Russian approach of using two vectors. ‘It has a chance of being efficacious, and a reasonable chance of being safe. I just wish they would do a phase 3 trial like everyone else,’ she says. ‘It would take them another two or three months and then I would say great, wonderful job. But this way, I am just shaking my head, like every other scientist in this country.’

If the Russian gamble fails, it could damage public acceptance of other Covid-19 vaccines. ‘If there is a surprise, an adverse reaction which shows up once you inject 20,000 people, then people who wanted the vaccine will change their minds and we will never get a handle on this pandemic, until we have herd immunity in about 20 years,’ says Ertl. Such a failure could also impact acceptance of the vaccines that share the same vectors.

Salmon says he is not worried about European or US regulators pushing the limits in terms of vaccine safety, but has concerns about politicians who ‘don’t always appreciate the value of science’.

Anthony King

I am a freelance science journalist based in Dublin, Ireland. I cover a variety of topics in chemical and biological sciences, as well as science policy, health and innovation.

EU agrees first Oxford Covid-19 vaccine deal with AstraZeneca in WHO blow

A volunteer participates in the vaccine trial in Oxford, England (AP)

 Updated: 14 Aug 2020 Reuters

The deal included an option to purchase 100 million additional doses from the British drugmaker should its vaccine prove safe and effective
The EU said over the past two weeks it was in advanced talks with Johnson & Johnson and Sanofi for their vaccines under development

Brussels: The European Union has agreed to buy at least 300 million doses of AstraZeneca's potential COVID-19 vaccine in its first such advance purchase deal, which could weaken plans led by the World Health Organisation for a global approach.

The European Commission, which is negotiating on behalf of all 27 EU member states, said the deal included an option to purchase 100 million additional doses from the British drugmaker should its vaccine prove safe and effective.

The EU's bilateral deal mirrors moves by the United States and other wealthy states, some of which are critical of the WHO's initiative, and further reduces the potentially available stock in the race to secure effective COVID-19 vaccines.

The EU agreement follows an initial deal with AstraZeneca reached in June by Europe's Inclusive Vaccines Alliance (IVA), a group formed by France, Germany, Italy and the Netherlands to secure vaccine doses for all member states.

The Commission did not disclose the terms of the new deal and declined to say whether it had replaced the IVA's.

"This new agreement will give all EU member states the option to access the vaccine in an equitable manner at no profit during the pandemic," AstraZeneca said in a statement.

The EU executive said its deals are aimed at financing part of the upfront costs to develop vaccines. The funding would be partial down-payments to secure the shots, but actual purchases would be decided at a later stage by each EU state.

The EU said over the past two weeks it was in advanced talks with Johnson & Johnson and Sanofi for their vaccines under development.

It is also in talks with Pfizer , Moderna and CureVac to buy upfront their potential COVID-19 vaccines, EU officials told Reuters in July.

BLOW TO WHO?

The EU move could make more difficult efforts led by the WHO and GAVI, a global alliance for vaccines, to buy shots on behalf of rich and developing countries with a separate scheme.

The Commission has urged EU states to shun the WHO-led initiative because it sees it as too expensive and slow, EU officials told Reuters in July.

Now the Commission is openly saying that vaccines bought from AstraZeneca, and from other vaccine makers, could be donated to poorer states, effectively taking on the very task that the WHO is pursuing with the so-called ACT-Accelerator Hub.

Brussels has publicly said that its purchasing scheme is complementary to the WHO's, but in private told EU states that there may be legal issues if they joined the WHO programme.

Sex workers in India find new ways to earn amid coronavirus pandemic

Sex workers in India have had to adapt to new norms during the pandemic. While some have been doing temperature checks on clients and sanitizing their rooms after every visit, a few have turned to phone and internet sex.


When India entered its first lockdown on March 25 to contain the spread of the novel coronavirus, hundreds of thousands of sex workers across the country were cut off from their major source of income.

Even as help slowly trickled in, it was difficult for many of them to find a way to make ends meet.

"Until the end of June, there was no dhanda [a colloquial term meaning 'business'] for the sex workers. In Mumbai, the police vigilance was so strong that there was no activity in the brothels of Kamathipura," Priti Patkar, co-founder and director of the NGO Prerana Anti-Trafficking, Mumbai, told DW.

"While there was relief in the form of food grains and utilities, this did not help the women with their rent and debt payments," she said.

Read more: Street crime and cyberfraud are on the rise in India during the pandemic

Since the start of the pandemic, authorities have been providing aid in the form of essential food commodities to economically underprivileged citizens, including sex workers.

"However, the government only provides for those who are able to produce ration cards. More than 50% of sex workers across India do not have ration cards, or any such documentation," Smarajit Jana, chief adviser to the Durbar Mahila Samanwaya Committee, told DW.

The DMSC, which represents more than 65,000 sex workers, has been working to provide essential food items, sanitary napkins and other necessities to sex workers. The collective operates in Sonagachi, Kolkata, Asia's largest red-light district.

Adapting to the pandemic

With the lockdowns in place, sex workers found it almost impossible to work. As India began to loosen restrictions in May, activity returned to the red-light districts as well.

"We have been doing temperature checks and screening customers for symptoms when they enter the district. We also sanitize the room before and after the customers leave," Kajol Bose, a sex worker and the DMSC's secretary, told DW.

"Some of the higher-class-category sex workers have been able to earn with the use of phone and internet sex. But this is not an option for all of us," Bose said.

Read more: Is the Kerala model in India really working during the pandemic?

Prerana's Patkar said phone sex, though a better option in terms of physical distancing, may not be viable for the most vulnerable. "It is an option for those who cater to the middle- and high-income clientele," she said. "But lower-income sex workers do not have the necessary skills, space, and connections for this."

Alternate income sources

Patkar said a few sex workers had been able to find alternatives to their profession to earn a living. The NGO was able to organize grants for a few women to set up microbusinesses, such as stores for selling dry fish, onions and potatoes, or tea stalls.

The women of DMSC have been employed in making masks and sanitizers, which have been used by the community themselves. "In the coming days, we're also going to start producing PPE kits. As we increase our production, we are planning to sell all these items in the future," the DMSC adviser Jana said.

Sex workers are among the people most severely affected by the pandemic.

Food supplies and donations have not been able to supplement their needs. Many of them have been struggling to meet their financial needs, such as paying rent and school fees for their children.

"Some of them also had to face harassment and violence from their brothel keepers," Patkar said.

Read more: India's HIV and TB patients suffer consequences of coronavirus pandemic

Though many migrant workers and daily-wage laborers chose to go back to their hometowns, a lot of sex workers didn't have that option.

Sex workers face massive discrimination in the South Asian country, and there's a lot of social stigma attached to the profession. Sex workers are also often trafficked to big cities.

Cities such as Mumbai and Kolkata have the highest number of cases of women and child trafficking, according to the National Crime Records Bureau. "Going back to the village? That's not an option for me. I am not wanted there. I have to find another option for a livelihood. Give me any other job and ask me to learn anything," said Mira, from Mumbai's Kamathipura district.

The German company that enabled the Holocaust

Topf & Sons helped make the Holocaust possible by building incinerators for Nazi concentration camps. After the war, the owners saw themselves as victims, with only one family member standing up to take responsibility.


Auschwitz-Birkenau, Buchenwald, Dachau, Mauthausen: When Allied liberating forces arrived in Nazi concentration camps at the end of the Second World War they discovered piles of dead bodies and crematoria bearing the logo of J.A. Topf & Sons.

The infamous German company, based in the eastern city of Erfurt, had collaborated with the Nazis, designing, building and delivering equipment for the mass incineration of prisoners — a ghastly invention that made the Holocaust possible.

Read more: A German town and Josef Mengele, Auschwitz 'angel of death'

Success under the Nazis

The company, founded by Johannes Andreas Topf in 1878, initially specialized in constructing brewery equipment and exported its wares around the globe. Then, after the First World War, the owners discovered another business opportunity – building ovens for city crematoria. During the Weimar Republic Topf & Sons became a market leader in oven manufacturing known for its "optimal implementation of the commandments of piety."

The company's business continued to flourish after Adolf Hitler came to power. From July 1937 onward, both the company's bosses, Ludwig Topf and his brother Ernst Wolfgang – who had since joined the Nazi party – could see the Buchenwald concentration camp from their office windows.

Read more: 'I think it can happen again' — Holocaust survivor meets Merkel ahead of Auschwitz liberation anniversary

The SS orders its first ovens

Buchenwald would soon become the first camp to use the company's ovens, as the growing number of dead in the camp — through torture or starvation — posed a serious logistical problem for the SS troops operating it. This problem was compounded after Germany invaded Poland on September 1, 1939. At that point, the camp was faced with an enormous influx of prisoners, and masses of those prisoners were dying.

Company bosses Ludwig and Ernst Wolfgang Topf

Before the war had even begun, SS officers had already looked into the idea of erecting large crematoria on site. In May 1939, Kurt Prüfer, Topf & Sons' chief engineer, presented his first design for a "mobile, oil-fired Topf & Sons cremation oven."

"The incinerator marked a radical departure from the culture and the rules of cremation. Human beings were burnt in them like refuse," writes Annegret Schüle, curator of the memorial site on the grounds of the former factory.

Read more: World Holocaust Forum: Israelis want action on anti-Semitism, not words

Collaboration reaches new heights

Prüfer was encouraged by the initial success of his design, and soon presented the Nazis with a new oven featuring two incineration chambers. That model was eventually installed in the Dachau concentration camp in November 1939. Thereafter, the ambitious engineer designed his first stationary crematorium. The company was so proud of its work that it applied for a patent on the design.

"Prüfer's attitude, exemplified by personal initiative with no moral qualms, was emblematic of the stance of those in the technical department," says Rüdiger Bender, chairman of the Society for the Promotion of the Topf & Sons Place of Remembrance. Bender emphasizes, however, that leading engineers at the company were not staunch Nazis.

"The company was never forced to build the ovens, quite the opposite in fact. Rather, it did its best to beat out competition from other companies, like Heinrich Kori in Berlin, which was also vying for the contract," says Annegret Schüle. She says engineers at Topf & Sons took the initiative and designed increasingly powerful ovens. The company was happy to oblige the regime, and a correspondence with the SS written on company letterhead documents as much, it reads: "Always a pleasure to do business with you."

The Topf & Sons headquarters in Erfurt, pictured in 1935

When Nazi leaders decided to make Auschwitz-Birkenau a central hub in the Holocaust, the oven manufacturer's complicity reached new heights. "When SS administrators at Auschwitz discovered they could kill thousands of people in minutes using Cyclone B (hydrogen cyanide), they were faced with the problem of disappearing the bodies," says Schüle. The answer was provided by Top & Sons' ovens.

On August 19, 1942, Prüfer met with SS construction managers. During the meeting it was decided that three massive crematoria would be needed on the site. Two more would later be added. By the summer of 1942, the Nazis were incinerating up to 9,000 bodies a day.

But Prüfer's success was a thorn in the side of his colleagues, and in September 1942, his boss, Fritz Sander, presented a new invention of his own: The multi-muffle oven. This new oven was designed to allow the uninterrupted cremation of bodies in a "production-line" system.

Read more: The Nazi archives: Where Germany's dark past is stored on paper

'Textbook example' of Holocaust complicity

Technicians from Erfurt, including fitter Heinrich Messing, were soon dispatched to Auschwitz to begin construction of the new design. They spent long periods of time at the camp and were well aware of the genocide taking place there.

Interestingly, Messing was a communist and a member of the Communist Party of Germany, or KPD. Still, his own beliefs did not keep him from conscientiously completing the job at Auschwitz ahead of schedule. "Theoretically, he could have sabotaged the project, or at least delayed completion. But he didn't," says Rüdiger Bender.

Today, the site of the former Topf & Sons headquarters has been turned into a memorial

Annegret Schüle writes, "In the early 1940s, technology designed for the incineration of human beings and the disposal of bodies only accounted for about 2% of J.A. Topf & Sons' annual profits." Still, she says, the company is a "textbook example of how companies were complicit in the Holocaust."

Read more: Retracing Germany's tragic Kindertransport, 80 years later

One boss commits suicide, the other flees

When Nazi Germany was defeated in May 1945, Ludwig Topf committed suicide by swallowing a cyanide capsule after he was informed of his pending arrest by US military officers. In a suicide note, he defiantly declared his innocence, writing: "… if the people want blood, I'll do it myself. I was always forthright — the opposite of a Nazi — everyone knows it."

His brother Ernst Wolfgang fled to the Western occupation zone, where he rebuilt the company, and investigations into his wartime activities were eventually closed. It wasn't until the publication of the book "Macht ohne Moral" (Power without Morals), written by concentration camp survivor Reimund Schnabel, that the West German public was reminded of the company's earlier activities. After that, Topf was no longer extended credit and the company soon went bankrupt.

Engineer Kurt Prüfer, meanwhile, died in a Soviet prison camp in 1952.

Topf & Sons' Nazi past was all but forgotten in East Germany after it was nationalized and its name changed to VEB Erfurt Malting and Storage Company, eventually going bankrupt in 1994. It was not until the fall of the Berlin Wall and an attempt by a Topf heir to gain restitution that the public became aware of the company's dark past.

Read more: Heiress downplays factory's forced labor use during Holocaust

Fighting to keep memory of Topf & Sons' history alive

That was when Hartmut Topf, a great-grandson of company founder J.A. Topf, got involved. The journalist decided to make it his life's work to research the company's history and preserve it for coming generations. "After the Wall fell, I saw a newspaper article about a West German woman seeking restitution from the city of Erfurt," says the 85-year-old.

Hartmut Topf has kept the memory of the company's history alive

"That set off alarm bells for me. I thought – wait a minute – if there is any money at all, it should be given to civic education programs or to victim compensation funds," he says.

Initially, politicians in Erfurt were less than enthusiastic about his plan to open a memorial site on the grounds of the former factory. But in the end, Topf and his associates won out, and a place of remembrance was opened on the site of the company's former administrative offices in 2011. There, a permanent exhibition illustrates the company's history.

Topf also faced prejudice when in Poland. Two years ago, when he mentioned his name at the Memorial and Museum Auschwitz-Birkenau, the elderly greeter at the entrance became irritated. "Your name does not have a very good reputation here," said the man. To which Topf replied, "I know, that's why I am here."

From the "Guilt without atonement" series, a project of DW's Polish department, the Interia portal and the Wirtualna Polska media group.