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Last month, at the start of a fourth Covid-19 wave in the US, a nurse in a Seattle-area intensive-care unit announced her resignation on Twitter. “No amount of money could convince me to stay on as a bedside ICU nurse right now,” she wrote. “I can’t continue to live with the toll on my body and mind. Even weekly therapy has not been enough to dilute the horrors I carry with me from this past year and a half.”

The nurse, Sara, who asked to be identified by her first name so she could speak freely about her experiences at work, told Vox that she’s been offered incredible bonuses in exchange for extra hours. She said she could make an entire month’s mortgage payment just by working one extra shift, but has declined. “We’re not soldiers,” Sara said. “We’re not the saviors of humanity. We’re humans who have families and the need to take care of ourselves.”

In June, Julia Belluz wrote for Vox about the many structural barriers that prevent physicians from getting mental health treatment. It led to an outpouring of support, and a question: What about the nurses?

The roughly 3 million registered nurses (RNs) currently employed in the United States are, in Sara’s words, “the eyes and the ears and hands and feet of providing health care.” But nurses are leaving the profession at a staggering rate. According to a 2021 report from Nursing Solutions, the turnover rate for registered nurses last year was close to 20 percent. This leaves hospitals understaffed: About 10 percent of hospital RN positions were vacant last year, the same report found, perpetuating a cycle of burnout and likely worsening the quality of care for patients.

As an ICU nurse, Sara said the pressure and strain have felt unbearable. When Covid-19 arrived, she was often the only health care provider in the room with a critically ill patient, “feeling like this person’s life was completely in my hands, and it was up to me,” she told Vox. She said her own symptoms now mirror some of those of post-traumatic stress disorder: traumatic flashbacks, nightmares, uncontrolled moods, and crying.

Sara was able to carve out time to find a therapist and join a virtual support group, but she worries that many nurses don’t have the capacity to seek support on their own. “It feels like everybody’s running on fumes,” she said. “We need to make the barriers to accessing [mental health support] quite a bit lower because people are just so exhausted.”

The mental health of nurses was taxed even before the Covid-19 pandemic. Female nurses in particular were at twice the risk of dying by suicide as women in the general population, according to research published earlier this year. And that’s only “the tip of the iceberg,” said Christopher Friese, a professor of nursing at the University of Michigan and a co-author of the study. “What I worry about is the large number of nurses that we can’t even quantify, that are suffering in silence.”

Friese, who has practiced as a registered nurse for 27 years, spoke with Vox about the toll nursing can take on mental health, and what has to change for nurses to get the support they need. Our conversation has been edited for length and clarity.

“There’s real consequences for our nation’s health”

What have been some of the biggest strains on nurses, before the pandemic, that might put them at these greater risks for mental health challenges?

I think there are a couple of buckets to think about. The first bucket is their personal experience. Nurses are not only delivering care to the patients and their communities, but they’re also caring for their children, their family members, and loved ones. They take on an added caregiving role beyond their job. So I think we need to understand that better.

The second bucket is the workplace. The health care workplace has not been healthy for nurses for some time. We’ve known for over a decade that nurses have been concerned about their workloads. They’ve been concerned about the resources that they have to take care of patients or communities. And they are often the group that we add new tasks on to. So adding the electronic health record has placed that very heavy burden on nurses because nurses are sort of a catchall for all of that work. And we haven’t taken anything away from nurses. The only thing we’ve done is continued to pile on to their work.

And I think the final point that we need to be aware of, and I’ve certainly seen, is increased hostility in the workplace. Nurses more frequently are bearing the brunt of verbal and physical abuse from patients, patients’ family members, and some staff. And we have not created a safe environment to work.

Have you experienced some of these strains firsthand in your time as a clinical nurse?

Nursing is a very rewarding profession, but there are times when it can be very draining. I’m deeply worried by what I’m seeing. Despite all my experience, it is definitely harder work than it was when I started. It was getting harder before the pandemic, and the pandemic only exposed those fault lines where the system has not served nurses well.

Could you talk more about how Covid-19 might have impacted nurses’ mental health?

In our data, we had over 700 nurses die from suicide in the 2017-2018 period. That was an all-time high. So we were trending up, and then Covid-19 hits. They were dealing with these really risky clinical scenarios where we don’t have good information, early on in the pandemic. How do we protect people? Do people have the right protective gear?

There is also a unique combination of their personal health at risk, their loved ones’ safety, and then the societal split in our approach to this public health crisis, which you’re seeing right now. We have really good tools to protect our population — we have really effective and very safe vaccines. We’ve learned in this pandemic that masking and staying out of crowds is effective. And yet we have a swath of the population who is not doing that. And they’re in our ICU and they’re in our hospital beds, and nurses have to live with that duality.

The other thing we’re observing is staff shortage — either people have left the workforce, or they’re ill themselves, or their loved ones are ill and they’re caring for family members. Everybody’s picking up more work. That just perpetuates the cycle. We’re on a hamster wheel here, where nurses just can’t get off.

Are you worried about attrition from the nursing profession, especially from the added strain of the pandemic?

I’m deeply worried. I’m already aware of particularly experienced nurses who have left their clinical position, and you can’t really replace them, their decades of experience. Those are the folks who train our next generation and help support physicians and others. So it’s a real brain drain.

Then it creates this cyclical problem where you’re always running short. We have very clear evidence: when you don’t have enough nurses, patients have more complications, they’re more at risk of dying, etc. So there’s a direct connection to a healthy, fully staffed nursing workforce and public health. There’s real consequences for our nation’s health if we do not curb this crisis.

Access to mental health care isn’t just about health insurance

Do you find nurses tend to have good access to mental health care?

Most employed nurses have relatively good health insurance, so they probably have access on paper. But it’s very difficult for health care professionals — and especially nurses — to seek out mental health services because of the stigma we have in place. Nurses might be concerned that if they seek out mental health services and undergo treatment, that might jeopardize their employment.

There are numerous examples. As nurses are applying for positions and interviewing and going under intake questioning, they might disclose that they have a mental health condition or they’re taking medication. And leadership is questioning whether they’re suitable for those positions: Can they handle the pressure of that work? So that only makes it more likely that you’re not going to disclose and you’re not going to access services.

We need a really different kind of model for nurses. We all need mental health services that are safe, accessible, and confidential.

The final piece of that is the disciplinary process for nurses. Right now, if a nurse makes what is assessed to be a clinical error, we quickly go down the disciplinary route, and we don’t realize that there might be someone in trouble, a human being in front of us who needs care. Is this person well? Do they need help? And what kind of help? These should be the first questions we ask, and then we can get to the other things.

As my colleague Julia Belluz reported earlier this year, physicians often seem reluctant to get mental health treatment because in some states, and in some cases, they are worried it could jeopardize their medical license. Do nurses have similar disclosure requirements or licensing concerns?

I don’t know of boards of nursing that formally ask if you have a mental health diagnosis or you’re taking medication. But in a lot of the boards, you have these statements about “moral character.” Assessing one’s character can get wrapped into mental health very quickly in our country. So I think we really want to separate that out. We want people to feel comfortable knowing you can be an excellent nurse and also have a mental health condition. And we want to make sure that you’re getting the recommended treatment you need. It’s just like having diabetes or some other condition. We need to get that stigma out of mental health.

I appreciate there are many nurses who are very public about their struggles, but they’re the exception. And there’s nothing magical that would exempt nurses from having the same underlying health conditions — mental or otherwise — [as] the rest of the population.

Are you comfortable disclosing whether you’ve ever struggled with mental health issues as a registered nurse?

I wouldn’t say that I’ve had a crisis situation. I’ve certainly had stressful moments. I can vividly remember days on the unit even decades later. The work nurses do is physically demanding, and it can be emotionally taxing. It can also be very rewarding. But the kind of work we’re doing, with people’s lives in our hands in very fragile emotional states, you can’t just walk away from that. It sticks with you. I’m thankful that I’ve been able to navigate that, but there are certain events in my career that I will never forget and come back to haunt me.

Do you see your findings about suicide as a potential indicator for the risk of mental health challenges overall?

Below the surface of this is a much larger group of nurses who are, day-to-day, struggling with these issues. We may not even know they are in trouble or they are struggling, and we have no way to know whether they’re getting the help they need. The challenge is to make sure that we can keep them safe before they’re even contemplating suicide.

We have the tools to take better care of nurses

It seems like physicians and their struggles may get more attention than nurses, even though there are so many more nurses in the country. Why do you think that is?

First, we have better data collected on physicians, so it’s a bit easier to track them over time. Their professional organizations have a fairly robust data set. It’s been a little harder to track nurses over time. We only do surveys of nurses. I think, too, the medical profession has done a better job of understanding this risk and developing unique programs for physicians.

One of the areas to think about is the power differential. Physicians tend to enjoy a relatively privileged place, particularly in the US, relative to other health care workers. So their concerns and issues more often reach prominence. We don’t have a lot of information about other demographic factors, such as gender or sexual identity, etc., but you could imagine that groups that are historically disadvantaged are going to be less likely to be heard on this issue.

There’s a ton of other health care professionals — respiratory therapists, pharmacists — who have been strained, too. And the challenge is to get good data on them. This is only the surface of what the problem may be. We don’t have the fundamental research to help us understand why these things are occurring.

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Are there other barriers you see standing in the way of nurses getting mental health care?

We need a different model that is specific to nurses. I think that’s the missing piece. We have specific programs for veterans. We have specific programs for rural residents and adolescents. We don’t really have that for nurses, despite the really alarming data we presented.

We also don’t know the sequence of events. Is it the workplace that’s triggering this? The family environment? Unless we do some really basic registry work, we’ll never know the answer to that. So it limits our ability to help, without research, and that adds to the stigma. If we don’t know what we’re dealing with, then we can’t even let nurses know that there are greater risks and maybe they need to reach out.

How can we take better care of nurses?

We all have a family member or a loved one who’s a nurse. And I think oftentimes we don’t necessarily check in with them and ask them how they’re doing, how their day was. We know their work is difficult. Sometimes they’re not able to tell us a lot for privacy reasons. But checking in with loved ones who are nurses, making sure they know they’re valued. If a family member is struggling, making sure they know that is a normal thing and that seeking help is perfectly okay.

I think we also need to have a conversation as a nation about how we value nurses — and how we structure health care so that they can actually be the best nurse they can be for our patients and for our loved ones. Right now, it’s very transactional. We really need to think carefully, particularly after this pandemic: Can we redesign their work so that we take full advantage of their clinical skill? I think right now we’re not doing that.

The last thing would be to advocate for research on nurses. That has not been valued. Just like we want better understanding of diabetes and cancer, we want to have a better understanding of: Are nurses at risk, and what can we do to help them? We have the tools to do this.

Do we as a society want to put value on this? Do we want to try to better understand how we can have a healthy, safe nursing workforce? I think, for our loved ones, that’s the question. Because if we don’t, we’re going to be in big trouble.

Every several years — sometimes just once a decade — when the rains come in just the right amounts and at just the right times, rare flowers speckle the Mojave Desert in California. Some, like the Barstow woolly sunflower, emerge from plants no larger than a thumbnail. They spring forth from seeds that have persisted in the dry soil for years, waiting for just such a sporadic event.

In these brief “super-blooms,” the desert floor looks “like a carpet of wildflowers unfurled across the landscape,” said Karen Tanner, a researcher at University of California, Santa Cruz. The quick flash of flora helps replenish the seeds for future generations.

At other times, large sections of this deceptively fragile ecosystem look “like the moon,” Tanner said. Which, under the punishing sun, makes it seem like an ideal place to build large solar installations. Swaths of the desert, which spans four states, have already been converted to solar facilities, and more are on the way — in the Mojave and across the US. More than 4,600 square miles of land is projected to be covered by solar installations by 2030.

A massive expansion of solar electricity is a crucial part of US plans to reach 80 percent renewable energy by the beginning of the next decade. This is essential to cutting carbon emissions and slowing catastrophic climate change — which poses a dire threat to plants and animals the world over, humans included.

But the race to erect large-scale, maximally efficient solar operations could hurt local ecosystems if operators aren’t careful. Based on her research, Tanner suspects many of these solar projects as they are traditionally executed are causing more local harm than some realize. She has spent nearly a decade closely studying — often on hands and knees with a magnifying glass — experimental solar plots in the Mojave, all located within six miles of four large solar installations. Her most recent findings, published earlier this year, have noted that solar panels changed the immediate microhabitat and had a detrimental impact on rarer plants, such as the Barstow woolly sunflower.

One thing is clear to her: “It’s just not enough to do one survey in one year and be like, ‘Oh yeah, there’s nothing here. Go ahead and install the infrastructure,’” she said.

Solar doesn’t have to be a zero-sum game that prioritizes either clean energy or biodiversity, scientists told Vox. Many projects and studies are currently looking for ways that solar installations can better protect — and potentially even improve — local ecosystems, along with the bottom lines of operators and even nearby landholders like farmers. These solutions can be as simple as prioritizing native plants or picking a location that’s already been disturbed by humans.

The darker side of solar

Solar installations, on the scale needed to supply power grids, are massive by necessity, transforming the lands where they’re located into a new kind of built environment. They can alter everything from sun exposure to moisture to surface temperatures. This can have unintended and unexpected impacts on local plants, animals, and even the area’s microbiome.

Photovoltaic panels shade the land while blocking some areas from rainfall and dousing others with heavy runoff. This changes the growing conditions for plants, with implications for other connected species. The other prominent form of solar, concentrating solar — in which mirrors focus the sun’s rays — generates so much heat that it “can incinerate insects and burn the feathers of birds that fly through,” Jeffrey Lovich, a research ecologist with the US Geological Survey who studies the environmental impacts of these installations, wrote to Vox.

In areas like the US Southwest, solar installations appear to contribute to bird mortality. Scientists aren’t entirely sure why this is, but one prevailing idea, known as the “lake-effect” hypothesis, is that migrating waterfowl making their way through the arid landscape mistake the installations for bodies of water and crash into them.

Large solar facilities in particular can also fragment important wildlife habitat or migration corridors via fences and landscape alteration, and can restrict gene flow for animal as well as plant populations.

Operators of these installations are generally keen to cut the costs of construction and maintenance, so most solar facilities replace the existing land cover with graded packed dirt, gravel, or mowed grass, further harming local biodiversity. “‘Blade-and-grade’ site prep that removes all vegetation clearly has a negative effect on biodiversity,” Lovich said. He expects mowed grass would “stress plant communities and the animals that use them.”

Many of the impacts remain unknown. It’s often difficult for researchers to gain access to solar facilities and the environmental data they collect — “even though the majority of facilities are situated on publicly owned lands,” Lovich and colleagues noted in a 2017 paper.

But it’s possible to dial down the potential harms of big solar farms. The type of solar infrastructure — whether concentrated solar or photovoltaic, and whether panels are fixed or rotating, high, or low — affects the potential downsides of large-scale installations. So does the nature of the landscape itself.

How solar can help native plants and crucial pollinators

Some solar operators are reimagining their facilities as prime protected habitats for native plants, bringing back key local species and potentially improving lands that humans have already disturbed. “Solar can be a net benefit in terms of restoring a native habitat and improving ecosystem services, like storm water control and carbon storage and sequestration,” said Leroy Walston, a landscape ecologist with Argonne National Laboratory who studies the relationship between renewable energy and the environment.

One in-vogue mitigation measure is pollinator-friendly foliage. At one experimental solar installation in Minnesota, pollinator-friendly plants helped boost energy yields a tad (by making the microclimate a touch cooler) and slightly reduced long-term maintenance costs (due to less-frequent mowing), according to a 2019 analysis from the Center for Business and the Environment at Yale University. The report also noted bigger wins: The plants helped reduce erosion, increasing groundwater stores and bolstering crop yields.

Experts have brought up concerns that solar operators will use a few flowers to green the image, but not the substance, of their operations. To help prevent this, some 15 states now have pollinator-friendly solar scorecards that aim to measure the actual impact of solar projects on the crucial creatures that carry pollen from plant to plant.

“They are voluntary, but they do help solar facilities to attain an objective certification that they’re pollinator-friendly, that’s been helpful to encourage some use of pollinator habitat at solar facilities,” said Heidi Hartmann, a colleague of Walston who works as a program manager for land resources and energy policy at Argonne. For example, the California renewable electricity provider MCE is now asking its facilities on arable land to use “reasonable efforts” to hit a certain score on these pollinator tallies.

Walston calls for an even broader approach to solar — one that focuses not only on bees and butterflies, but on native habitat restoration overall. Native plants are keenly tuned to the local environment, thriving in specific climate conditions, improving soil retention, and often benefiting the widest range of other area species, in ways non-native, flashy pollinator species might not.

Hartmann and Walston have modeled the impact of switching from maintained grass to native plantings. They found that in the US Midwest, native plants would bring in three times the number of pollinators. They’d also boost the carbon storage potential of the soil by 65 percent and would be more effective, once established, at keeping weeds at bay, which could reduce the need for harmful herbicide use.

“The equation is complex,” said Alyssa Edwards, vice president of environmental affairs at solar producer Lightsource BP, about the company’s impact on local habitats. Lightsource advertises itself as protecting ecosystems and boosting biodiversity. “Pollinator habitat, considerations of seed availability, vegetation height, insurance requirements, fire risk, and cost all come into play. Not to mention that pollinator habitat may not be the right choice for all sites, as other initiatives may be more valuable contributions to sustainability.” The company, a joint venture with the oil and gas giant BP, says it’s working on various solar projects that incorporate pollinator habitat, conservation of short-grass prairie land, and even animal grazing.

Wildlife corridors are another way solar installations could help support biodiversity. But for large sites to become a part of corridors, they may require substantial adjustments to fencing and other built infrastructure (and even then, they’d probably pose barriers to some larger species).

As more sites incorporate biodiversity as a benchmark, the devil is in the details. Tanner and others have found that solar panels can actually increase the number of plant species that grow beneath them, especially in harsh environments like the desert. However, some of these additional species are invasive or threaten to outcompete the smaller, rarer native ones that could tolerate such extreme desert conditions.

These kinds of wrinkles make it all the more important that scientists and operators actually measure their impact on ecosystems — that they’re “pausing for a moment and considering what sort of species we are considering that are making up the diversity,” Tanner said.

Build solar on lands that humans have already messed with, one expert says

Solar operators tend to look for new sites based on sun and climate conditions, but also proximity to the existing power grid — and a utility company in the market for their energy. Scientists told Vox that firms should also look for places that humans have disturbed, because the local ecosystem may have less to lose.

Lovich suggests siting more solar farms on “brown fields, roof tops, abandoned agricultural fields, dry lakes, and even airports — where wildlife are unwanted.” They’re also well-suited for canals and human-made reservoirs, where they’re sometimes called “floatovoltaics,” not least because they can slow water loss by evaporation. These less-conventional arrangements may have higher up-front costs, but the eventual environmental costs will be lower.

Building on an ecologically sensitive site can also be costly. Take for example BrightSource Energy, which spent at least $56 million relocating threatened desert tortoises from its Ivanpah solar development site in the Mojave Desert. Although these efforts allowed the project to go through, scientists are still learning about the consequences. An early study found that the relocated tortoises needed more time and effort to settle into normal movement patterns, potentially exposing them to additional threats. But as Lovich pointed out, “since tortoises are long-lived, results for the long term are not yet available.”

Such experiences have not deterred other desert sun-seeking operations. “Solar farms are operating or planned in excellent tortoise habitat affecting hundreds to thousands of tortoises,” Lovich said. Simply moving the tortoises — pricey as it may be — is not a sure cure. “Translocation has a checkered history of success,” he said.

Lovich is currently studying the impact of the Gemini Solar Project in Nevada, which would cover 11 square miles of publicly owned tortoise habitat and is home to hundreds of these long-lived, vanishing animals. For this project, the plan is to capture the animals, place them in a holding center for up to two years during construction, and then release them into the facility grounds “to see how they fare,” Lovich said.

“All energy sources will come with a cost to some wildlife,” Lovich and his colleagues noted in a 2020 paper. “The best mitigation strategy is to avoid developing sensitive and pristine areas.”

Other landscapes would not only tolerate solar farms, but could benefit from them. For example, a pollinator-friendly solar installation could add yield for farmers whose soy, citrus, almonds, cotton, or alfalfa needs some pollination help. More than 500 solar facilities already exist within easy buzzing-distance — less than a mile — from these crops in California, Massachusetts, and North Carolina, respectively, according to a 2018 study by Walston, Hartmann, and their colleagues. Nationally, more than 1,350 square miles of cropland would benefit if existing solar installations added pollinator-friendly plants, they concluded.

As solar has moved into lands that could otherwise be farmed, it has caused some tension with local residents. But solar farms and actual farms don’t necessarily need to be in opposition. It’s possible to co-locate solar and crops into “agrivoltaic systems,” which can feature grazing grass, corn grown for biogas, and even lettuce and tomatoes that may flourish under solar panels. Other crops could even be grown under semi-transparent solar panels.

Solar can protect plants and animals while it helps the planet

Redesigning solar developments — and steering them to the places where they won’t cause harm — isn’t easy. Maximizing energy output means finding locations with the right combinations of sun, temperature, wind, and humidity (one study pegged the best spots as croplands, grasslands, and wetlands) and packing solar-harvesting devices as densely as possible. All of these often work at cross-purposes with supporting a diverse range of plant and animal species.

Additionally, permits for these facilities are typically done at a very local level. (President Barack Obama had instructed these sorts of projects on federal lands to have a mitigation strategy — an order that President Donald Trump struck down his second month in office.) So it’s a patchwork of different levels of regulations and approval processes, some of which are more in tune with thoughtful evaluation of sites and long-term impacts. There is “more education that can be done at local government levels,” Hartmann said.

Without more thorough before-and-after research, we may remain in the dark about how these large facilities are changing the landscapes they cover. If site evaluations are performed over a relatively brief period of time — such as a single season in the run-up to the construction of a solar farm — operators could easily miss key aspects of biodiversity, like the Barstow woolly sunflower, which waits for just the right pattern of rare desert rain to emerge.

“We’re just starting to scratch the surface and determine how different organisms are likely to respond” to solar, said Tanner, the UC Santa Cruz researcher. For now, it behooves us to mess with their environment as little as possible, she noted, and to preserve as much as we can. “Especially in a context of climate change, we don’t know what species are going to be able to pass through that aperture in the future.”

As the world barrels toward climate catastrophe, scaling up carbon-neutral energy production as quickly as possible couldn’t be more urgent. “We need all the help we can get, and we need to move quickly,” Tanner said. On a planetary scale, clean electricity can help safeguard all species, and could arguably be worth the trade-off if it harms a few local species in the process.

But maybe there doesn’t need to be a trade-off, Tanner suggested. “I’m not sure it’s an either-or question,” she said.

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Since Covid-19 patients started showing up at clinics and hospitals a year and a half ago, doctors and researchers have been hard at work trying to figure out how to treat them. Most drugs and treatments haven’t panned out, producing either no results or small ones in large-scale clinical trials. Many of the few that work are expensive and difficult to administer.

Hydroxychloroquine, enthusiastically endorsed by President Trump last year, has been shown to have no measurable benefits. New drugs like monoclonal antibodies — proteins meant to imitate the immune system’s response to the disease — have been approved by regulators but must be administered by a doctor through an IV or series of injections.

But scientists haven’t stopped searching, and the results of a new massive clinical trial suggest they’re getting somewhere. In a large, randomized clinical trial conducted with thousands of patients over the past six months, researchers at McMaster University tested eight different Covid-19 treatments against a control group to figure out what works.

One drug stood out: fluvoxamine, an antidepressant that the Food and Drug Administration has already found to be safe and that’s cheap to produce as a generic drug.

These new results follow some promising findings in small-scale trials last year. In those smaller studies, researchers found that fluvoxamine was strikingly good at reducing hospitalization for Covid-19 patients — but small-scale trials can sometimes turn up spurious good results, so those findings were obviously tempered by a lot of caveats.

This study, called the TOGETHER study, is a lot bigger — more than 3,000 patients across the whole study, with 800 in the fluvoxamine group — and supports the promising results from those previous studies. The authors released it this week as a preprint, meaning that it is still under peer review.

Patients given fluvoxamine within a few days after testing positive for Covid-19 were 31 percent less likely to end up hospitalized and similarly less likely to end up on a ventilator. (Death from Covid-19 is rare enough that the study has wide error bars when it comes to how much fluvoxamine reduces death, meaning it’s much harder to draw conclusions.) It’s a much larger effect than any that has been found for an outpatient Covid-19 treatment so far.

“This is a huge finding,” study co-author Ed Mills, a professor of health sciences at McMaster University, told me. “The game changers are things we already had in the cupboards.”

What makes this result potentially such a big deal is that fluvoxamine is inexpensive and has already been FDA approved for obsessive-compulsive disorder (OCD), so any doctor can prescribe it for Covid-19 using their clinical judgment (what’s called “off-label” prescribing). It’s a pill, which means it doesn’t need to be administered in a hospital or by a medical professional.

To be clear, these results have just been released, and clinicians around the world will want to take a close look at them as they decide whether or not to prescribe fluvoxamine. Future research could also moderate this exciting result.

Here’s what we know: This is a large and well-designed study that affirms previous studies that pointed in the same direction. More research is needed, but the results from this trial might already start changing how we treat Covid-19. And the way researchers stumbled upon the drug as a potential treatment is a worthwhile story in itself about the scientific process and the unseen and often unheralded work that’s helping humanity fight the pandemic.

The shifting landscape of Covid-19 treatment

Covid-19 treatments fall into two categories: treatment for severe illness, generally administered in the hospital to reduce the risk of death; and treatment for the onset of illness, which hopefully reduces the odds that a patient will need to be hospitalized at all.

The FDA has granted emergency authorization to a variety of Covid-19 treatments, but the evidence base for many is limited and the effect sizes have tended to be small. Hopes were high for repurposed antiviral drugs, for instance. Many of them are routinely administered and at least one was shown to reduce the length of hospital stays, but some studies have found no effect on mortality.

The same is true of convalescent plasma, transfusions of blood proteins from people who recovered from Covid-19. After more than a year of research, it mostly looks like these treatments aren’t effective, though there’s still lots we don’t know.

The FDA has issued emergency use authorization for monoclonal antibody treatments — proteins that mimic the ones the immune system would produce to fight off the virus — for those at severe risk from Covid-19. Monoclonal antibodies are also infused intravenously or as a series of four injections. They cost $2,100 a dose, which in the US is paid by the federal government so they are free to patients. They seem to work best when given early, pre-hospitalization, and while under those conditions they appear to be highly effective. However, getting people who recently tested positive for Covid-19 and still have mild symptoms to a medical setting for an intravenous infusion or four injections is a logistical challenge — and the cost and the difficulty of delivery mean monoclonal antibodies will never be an option in much of the world.

Corticosteroids, which are powerful anti-inflammatory medicines, have a solid track record. Studies have found that administering the cheap steroid dexamethasone, which can be given as a pill or an infusion, to patients hospitalized with Covid-19 reduces their risk of death. But because it can constrain the immune system, it isn’t recommended early in the course of the disease, when the main concern is the direct damage from the virus.

That leaves a glaring hole: Where are cheap, outpatient treatments that can reduce the risk of hospitalization in the first place and don’t require a medical professional to administer in a medical setting? Fluvoxamine could hopefully fill that gap.

Fluvoxamine’s journey, explained

Fluvoxamine is an antidepressant, and in the US, it’s mostly prescribed for treating OCD. It is what is known as an SSRI, short for selective serotonin reuptake inhibitor — the same class of drugs as popular antidepressants like Zoloft, Prozac, and Lexapro.

Through an unusual journey, it ended up on scientists’ radars as a potential Covid-19 treatment — and subsequent research seems to bear that out.

Years ago, before the novel coronavirus had infected its first patient, Angela Reiersen, a psychiatrist at Washington University in St. Louis, was studying patients with a rare genetic disorder called Wolfram syndrome, which affects cellular stress responses. She noticed that they seemed to tolerate some SSRIs well and others poorly and dove into the differences in SSRI chemistry to figure out why.

It turned out that one of the SSRIs that worked well, fluvoxamine, binds to a receptor in cells that regulates cellular stress response and the production of cytokines, proteins that tell the body something is wrong and cause inflammation. Researchers at the University of Virginia found that fluvoxamine reduced inflammation in animals. Reiersen wondered if that was why it worked well for her patients.

Then the pandemic hit. One leading theory of what happens when patients suffer through Covid-19 is that cells damaged by the disease release tons of cytokines, which then causes inflammation in the lungs that can make it hard to breathe and cause lasting tissue damage. Early in the pandemic, Reiersen went to her colleagues at the Washington University School of Medicine in St. Louis with a wild idea: Fluvoxamine might help Covid-19 patients.

Eric Lenze, a leading clinical researcher, agreed they should test it with a randomized controlled trial. “I emailed him on March 25, 2020. We got the trial started by April 10,” Reiersen told me.

They spent the spring and summer recruiting and treating Covid-19 patients. By the fall, they had results: Of the 152 participants, half in the placebo group (receiving a sugar pill rather than active medication) and half in the fluvoxamine group, six patients in the placebo group had met their study’s threshold for respiratory difficulties. None in the fluvoxamine group had.

The results were published in the Journal of the American Medical Association. “What I think is the most supported mechanism is an anti-inflammatory effect,” Reiersen told me. “Fluvoxamine can reduce the level of these chemicals called cytokines, which are involved in inflammation, so you’d get less damage in the lungs.”

The results were promising, but 152 patients isn’t that many. Reiersen and Lenze started recruiting for a larger-scale trial, looking for more evidence that fluvoxamine could be a first-line Covid-19 treatment.

In the meantime, evidence was coming in from other angles, too. After a mass outbreak in California, researchers gave affected people the option to take fluvoxamine; 65 people opted to take it and 48 declined. None of those who took it required hospitalization, while six did among those who declined it.

In France, Nicolas Hoertel, a psychiatry researcher at the University of Paris who is not affiliated with the TOGETHER study, had conducted and published an observational study finding that patients on certain antidepressants were less likely to have severe Covid-19. “This effect is not just fluvoxamine, but it’s not all antidepressants,” he told me.

Observational studies don’t assign patients a specific treatment but just record what treatment they receive and how well they do. They don’t involve randomization, so they can be misleading if, say, people on antidepressants are systemically different from people not on antidepressants or if people who agree to try an experimental medication are healthier than people who refuse. So the results from these studies couldn’t be taken as definitive — but it was additional data.

The limited, promising literature around fluvoxamine prompted its inclusion in the large-scale study of treatments for Covid-19 run by Ed Mills at McMaster University and primarily conducted in Brazil. Dubbed the TOGETHER study after other prominent mega-clinical trials like RECOVERY and SOLIDARITY by other organizations, it randomized patients across eight prospective treatments, including metformin (a diabetes medication), hydroxychloroquine (an antimalarial), and ivermectin (an antiparasite).

The team announced their results at an August 6 symposium that was sponsored by the National Institutes of Health. Most of the treatments failed: Their study couldn’t detect an effect. “A lot of drugs against Covid just don’t work very well,” Mills told me. Two other treatments were still in progress, and it was too early to rule out the chance that they’ll work.

But fluvoxamine was a different story. In the trial, it improved patient outcomes substantially — and while it’s not the first drug to do that, ease of delivery and price give it the potential to have an outsized impact on patient care, especially outside the rich world.

Do we know enough to recommend fluvoxamine to Covid-19 patients?

In the research conducted so far, fluvoxamine was prescribed to patients who started experiencing Covid-19 symptoms.

In the TOGETHER study, they typically visited a doctor to enroll in the trial — and start taking medication or a placebo — three days after their symptoms began.

The results of the study are strong enough that researchers are suggesting changing clinical practice to recommend fluvoxamine to people with symptomatic Covid-19.

“We have now growing evidence from different kinds of research — technical, clinical — indicating that [treatment with certain antidepressants] is very likely to be effective in Covid,” Hoertel said. “The likelihood of benefits is very high.”

Critical to changing clinical recommendations is having enough information about the risks and benefits of a treatment. Since fluvoxamine is decades old, its risks are already well understood.

“We know a great deal about the safety and tolerability of fluvoxamine,” Lenze told me. “It can cause in about one-quarter of people some nausea, which is usually mild. It’s not fatal even in overdose, it’s been around for over a quarter of a century so there’s not going to be any unpleasant surprises about safety issues, and it’s really easy to use — it’s just a pill. I don’t see anything that should stop people from taking it.”

There are still things scientists want to know about fluvoxamine, including exactly how it works within the body. And pinning down precisely how much the drug reduces hospitalization and death will definitely take more evidence — though from the 31 percent reduction in hospitalizations in the McMaster study, the researchers who spoke to Vox think it’s likely that the effect is real and sizable.

The TOGETHER trial hasn’t yet been peer-reviewed, though I spoke with numerous unaffiliated researchers who’d seen the results and found them convincing.

“Bottom line, in my opinion at least, Ed [Mills]’s finding proves that the drug works,” Lenze told me.

“We’ve all been burned by promising studies of these repurposed drugs, and it’s quite reasonable to reserve final judgment until we see the complete data, and even other studies. … But this already feels different from hydroxychloroquine and company given the high quality of the research,” Paul Sax argued in NEJM Journal Watch Infectious Diseases. “We might finally be onto something.”

Another possibility to account for when looking at clinical trial data is publication bias — studies that find results get published, while those that find null results often don’t. Lenze is attempting a large-scale replication of his small-scale fluvoxamine study from last year, and so far hasn’t been able to validate the huge reduction in hospitalizations he found the first time around — mainly because recruiting for Covid-19 clinical trials in the US has gotten increasingly difficult as most high-risk people are vaccinated and not at risk of hospitalization, and unvaccinated people are less likely to enroll in clinical trials or adhere to a recommended course of medication. (The TOGETHER study got around this problem by recruiting in Brazil.)

Another worry is that variants will make our understanding of Covid-19 treatments obsolete as soon as we develop one. The TOGETHER study was mostly conducted before the delta variant predominated in Brazil. There’s no strong reason to think fluvoxamine wouldn’t work against delta, but we’ll need additional research to see if the effect size remains the same.

But crucially, we don’t have to answer every unanswered question for doctors to prescribe fluvoxamine to patients. Researchers do have answers to the questions of “Is the drug safe?” and “Does the balance of evidence suggest significant improvement in patient outcomes?” The evidence on those two points looks convincing, so even though there’s lots more to learn, the researchers and clinicians studying fluvoxamine feel ready to say that the drug is a good idea.

One question lots of doctors and patients have about a Covid-19 treatment, of course, is: “Is it FDA-approved?” Fluvoxamine is FDA-approved — but for OCD, not for Covid-19. In fact, Lenze told me, ”I don’t think the FDA ever will approve it for Covid. The reason the FDA will never approve it for Covid is exactly the reason it’s so useful for Covid, namely it’s cheap and it’s widely available. No one can make any money off it, so no one is going to spend the money to appeal to the FDA to approve it.”

Doctors can prescribe drugs the FDA has approved as a treatment for one condition to treat another condition off-label, using their clinical judgment. Doctors may vary in how comfortable they feel with it, but it is common and fully permitted by US regulations.

How Covid-19 is changing the process of clinical trials

One other thing about the emergence of fluvoxamine worth discussing is the process by which it happened: a new approach to clinical trials that is changing how we find new treatments.

Conducting clinical trials takes a long time. Most people will not be eligible to join a given trial. Finding the eligible ones and recruiting and enrolling them is time- and labor-intensive.

In order to find moderate-effect sizes and be confident in the results, a clinical trial needs to enlist thousands of patients, but that also means it will take much longer to recruit for and conduct — and with Covid-19, delays have costs in human lives. Clinical trials on this scale are expensive, too. TOGETHER is funded by private philanthropists, including Fast Grants, an initiative by Silicon Valley billionaire Patrick Collison and economist Tyler Cowen to speed pandemic response by getting grant money out rapidly.

For the past year, Mills has been using a new approach to clinical trials in order to test potential Covid-19 treatments faster. The key thing was to conduct them in parallel using what’s called an adaptive platform trial. “They’re multi-armed, so you’re testing lots of substances at a time, which allows you to only have one control group,” Mills told me. “What all of the useful trials in Covid have in common is that they’re an adaptive platform trial.”

Running, say, eight clinical trials, with eight control groups, requires many thousands of patients to get an informative sample, which can take a long time. Having eight experimental groups sharing a single control group cuts the number of patients required nearly in half.

This study model reallocates patients among treatment groups once a given treatment has been demonstrated not to work. That leads them to have larger, more convincing sample sizes for the most promising treatments. “You make decisions based on the data that emerges early,” Mills said. “After you have randomized 200 patients to the drug, if you can’t tell that it’s working, it’s probably not a very good drug. Every drug that’s not showing effects is a waste of patients.”

Fluvoxamine was one of eight treatments Mills and colleagues tested. Over time, as other treatments showed no effect, more patients got randomized to the fluvoxamine arm of the trial — letting the researchers learn more about the drug that seemed the most promising.

Mills says that played a huge role in their ability to quickly figure out what worked and what didn’t. “Prior to Covid, it was really just MD Anderson [the cancer hospital in Houston] doing this design. I think it’s going to be how almost all clinical trials happen going forward.”

Vaccines are great — but treatments are as badly needed as ever

Now that there are Covid-19 vaccines, the race for a treatment might seem less urgent than it was last year. But researchers say that mindset would be a mistake.

Vaccine uptake has stalled in most rich countries around 60 to 70 percent, and the delta variant means that the virus is still spreading. Effective treatments could mean dramatically fewer people hospitalized in places where hospitals are overwhelmed.

In poor countries, the situation is starker. Vaccines are not yet widely available, and the prospects for mass vaccinations are grim. And many existing treatments for Covid-19 are unaffordable for the global poor. That’s where fluvoxamine’s promise really comes in.

“It’s $2,000 for a dose for a monoclonal antibody,” Mills told me. “Our drug costs $4.” The supply chain, too, is simpler. Fluvoxamine doesn’t need to be kept in a freezer, doesn’t expire quickly, and can be mass-manufactured cheaply. If it continues to show health benefits for Covid-19 patients, making it widely available in poor countries could help them weather delta.

The fight to discover new treatments isn’t over, either. When I talked with Mills, he was excited about research in the UK finding that steroid inhalers — another cheap, widely available medication — reduced Covid-19 hospitalizations. Mills is also in the process of enrolling patients for a study of both steroids and fluvoxamine, to see whether the benefits are greater when patients take both drugs. “We go from having no drugs for early treatment that are cheap and widely available to having two,” he told me. “What does it look like if we use them together?”

The world is still months of research away from an answer to that question. But even the partial answers available today might make all the difference for some patients.

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Nearly nine months after the first Americans received their shots, the Covid-19 vaccine from Pfizer/BioNTech received full approval from the Food and Drug Administration for people 16 and older on Monday. This could help increase the number of people willing to get vaccines and make it easier to compel those who are less willing — if health officials can cut through the mounting confusion around their efficacy, booster shots, and the threat of the delta variant.

Covid-19 vaccines from Johnson & Johnson, Pfizer/BioNTech, and Moderna have thus far been distributed across the US under emergency use authorizations. This form of limited approval allows the FDA to fast-track the distribution of drugs, vaccines, and medical devices during a public health emergency, like a pandemic.

Getting an emergency use authorization requires data from clinical trials showing that an intervention is safe and effective, but the bar for full approval is higher. Now, with 200 million people at least partially vaccinated, the FDA has effectively removed the asterisks from Pfizer/BioNTech’s mRNA vaccine.

“While millions of people have already safely received Covid-19 vaccines, we recognize that for some, the FDA approval of a vaccine may now instill additional confidence to get vaccinated,” said Janet Woodcock, acting commissioner of the FDA, in a statement on Monday.

Full approval grants the vaccine manufacturers permission to advertise their products and allow them to continue selling them after the public health emergency around Covid-19 ends. For doctors, full approval also allows them to use vaccines off-label, potentially as booster shots.

But perhaps the most significant change would be a potential boost in public confidence in the vaccines, amid a rising tide of confounding information. Full approval could serve as a valuable messaging tool and help close some of the lingering gaps in immunization across the country.

A significant share of unvaccinated people — millions of people, according to polling — say that full approval will increase the likelihood that they’ll get a Covid-19 vaccine. These individuals may be hesitating “because they know there will be much more data available at the time of an approval … three times as much data on safety and three times as much data on effectiveness,” said Sidney Wolfe, founder and senior adviser at the health research group at Public Citizen.

More employers may also be willing to require vaccines among their workers (some have already begun to do so). And full approval from the FDA could bolster support for these vaccines in other countries that look to the US agency for its rigor. However, to get the maximum public health value out of a full approval, messengers from the president on down to local doctors have to be ready to explain what it all means.

Full approval requires long-term evidence that Covid-19 vaccines are safe and effective

For vaccines, the FDA grants emergency use authorizations after it reviews at least two months of follow-up results for clinical trial participants who received the actual injection. For full approval, known in FDA-speak as a “biologics license application,” the agency wants to see six months of data to ensure there are no widespread problems or to detect adverse reactions. Both reviews examine safety and efficacy while also studying what the optimal distribution strategy might be.

In May, Pfizer and BioNTech submitted their license application. Moderna began its application in June, and Johnson & Johnson said it will begin the process later this year.

With vaccines in general, almost all complications that occur tend to happen shortly after the vaccine is administered, often within a day or two. Most side effects of the Covid-19 vaccines in the US tend to be mild or moderate, ranging from pain at the injection site to fatigue to fever. A very small number of recipients reported severe allergic reactions shortly after their shots, which is why most vaccine clinics have a waiting period where they can monitor patients for 15 to 30 minutes.

But in clinical trials, some extremely rare complications can be hard to detect even among tens of thousands of people after following them for two months. In April, the CDC and FDA paused the distribution of the Johnson & Johnson Covid-19 vaccine after 15 people reported a rare blood-clotting disorder out of the 8 million people who had received a dose at that point. After investigating, regulators concluded the benefits of the vaccine far outweigh the risks and allowed distribution to resume.

Monitoring clinical trial participants over six months also yields more information about how long protection from the vaccine lasts and whether any subsets of the population are more vulnerable. And it presents an opportunity to see how well the vaccines hold up against variants that were not widely circulating earlier in the pandemic.

This additional information — not just from clinical trials but from wide-scale distribution — helps the FDA identify any risks and better tailor its recommendations for use of the vaccine. Full approval also requires inspections of vaccine production facilities, looking at how the shots are made and how they’re packaged to ensure that production is consistent.

“That’s a much larger package of data, and that in itself means it takes much longer” to review, Wolfe said.

The licensing process for vaccines usually takes about a year. By granting full approval to the Pfizer/BioNTech vaccine just four months after the companies applied, Covid-19 vaccines have broken yet another speed record.

One caveat is that the full vaccine license only applies to the specific age groups included in a given clinical trial. The original trials mainly included adults, and Covid-19 vaccine testing in younger children has only recently begun, so the FDA has fully approved the Pfizer/BioNTech vaccine for use in adults 16 and older. Children 12 to 15 can continue to receive the shot under the emergency use authorization that was already in place.

Full FDA approval for a Covid-19 vaccine may help convince the hesitant

At this point, the majority of adults in the US have received at least one dose of a Covid-19 vaccine under an emergency use authorization. The spread of the delta variant has increased the rate of new vaccinations, which reached more than a million doses in a day on August 19, but the rate is still far below the April peak of more than 4.4 million doses per day. There remain pockets of the country where fewer than half of all eligible people have been vaccinated, and these regions are driving the rise in new Covid-19 cases, hospitalizations, and deaths.

There are several factors that divide the vaccinated from the unvaccinated, including political affiliation, race, income, and age. The reasons these people cite vary, such as a lack of access, a belief that Covid-19 isn’t that serious, and concerns that the vaccines have not been fully vetted.

According to polling from the Kaiser Family Foundation, almost one-third of unvaccinated people said they would be more inclined to get a shot if it graduates from an emergency use authorization to a full license. Full FDA approval could mean a lot for this last group of people.

But convincing people to get shots is not the job of the FDA; that falls to other public health messengers, and they have to be prepared to seize the opportunity. “It can have a modest effect or be a game changer, depending on how it’s handled,” said Drew Altman, president and CEO of the Kaiser Family Foundation. “It’s a question then of what the president does, what state and local public health leaders do, what the experts on television do.”

It’s not clear that people who cite the lack of FDA approval as a reason for not getting vaccinated are genuinely concerned with regulatory procedure or whether that’s just a proxy for general hesitancy. There’s also widespread confusion about the approval process: Kaiser’s polling also showed that at least two-thirds of US adults believed that Covid-19 vaccines already had full approval or weren’t sure about their regulatory status.

As for vaccine mandates, it’s already legal for private and public institutions to require their employees and customers to get shots. Companies like Google, Disney, and Walmart have begun to require many workers to get Covid-19 vaccines. But full approval could tip more employers, airlines, event venues, and other institutions that are on the fence to impose vaccinate mandates.

“I would look for significant movement on the part of more employers after full approval comes down from the FDA,” Altman said.

Now that the Pfizer/BioNTech vaccine is fully approved for people 16 and older, that doesn’t mean Moderna and Johnson & Johnson will stop distributing their vaccines under emergency use authorizations. While one of the conditions for granting an emergency use authorization is that there is no FDA-approved alternative available, emergencies like Covid-19 affect the calculus, the agency told Vox.

“For example, if the approved vaccine is only available in limited quantities, that vaccine may not be considered adequate to address the public health emergency,” said an FDA spokesperson in an email. “Another example would be if the vaccine is approved for use only in a limited population, then that vaccine may not be considered adequate to address the public health emergency for other populations.”

All the while, the dynamics of the pandemic are still changing, particularly with the surging delta variant of the coronavirus. While vaccines remain highly protective against severe Covid-19, delta seems to have increased the likelihood of breakthrough infections. Recent CDC data suggests that the shots aren’t as protective for vulnerable people like older adults who were vaccinated many months ago.

To counter this, the FDA is now on the verge of approving booster doses for many Covid-19 vaccine recipients. Meanwhile, the Centers for Disease Control and Prevention has gone back to recommending face masks in some circumstances for vaccinated people.

For health officials, it’s a fine line to walk: reassuring people vaccines are safe and effective while also noting that precautions are still needed. Regulators like the FDA also have to balance the needs of an urgent public health crisis with taking the time to go through the proper procedures.

And there are tough challenges that will remain even after a vaccine gets the bright green light from the FDA. There are still parts of the US where vaccination rates remain stubbornly low, and many unvaccinated people are not just hesitant but outright refusing to get immunized. Convincing these holdouts is difficult, but necessary, because as long as they remain unprotected, the virus will have ample opportunity to wreak havoc.

Update, August 23, 10 am ET: This article has been updated with the FDA’s full approval of the Pfizer/BioNTech vaccine.

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The origins of the novel coronavirus that caused the Covid-19 pandemic remain a mystery. US intelligence agencies have now completed a 90-day probe into the origins of SARS-CoV-2, but their classified findings, according to the New York Times, were inconclusive as to whether the virus escaped from a laboratory in Wuhan, China, or made a natural jump from an animal into a human.

Yet to prevent the next pandemic, scientists don’t need a definitive answer about the genesis of Covid-19. Regardless of how the coronavirus outbreak started, researchers say the world urgently needs to do more to prevent both lab leaks and so-called “spillover” infections from animals. Tracing the route of the virus is an important scientific question, but countries can and should take steps to reduce these risks now, even without a final answer.

“We don’t have to wait for all these results to start acting,” said Andrew Weber, senior fellow at the Council on Strategic Risks and a former assistant secretary of defense for nuclear, chemical, and biological defense programs under President Barack Obama. “There’s some big policy decisions that we can make now.”

Right now, the Covid-19 pandemic is continuing to rage around the world; dozens of countries are fighting the spread of the highly contagious delta variant, and many are struggling to get enough vaccines to protect themselves. Figuring out just where the virus came from would do little to mitigate the current crisis.

It may be years before the world gets a satisfying answer, and one may never emerge. But in the meantime, from regulating wildlife markets to transparency around biological research, there are many measures that can reduce the risk of future outbreaks.

Both spillovers and laboratory leaks of pathogens have happened before

There were warnings that humanity was at risk of a pandemic even before Covid-19, and at several points the world has come scarily close.

Several dangerous pathogens have escaped laboratories in the past and gone on to infect people. In 1977, an outbreak of H1N1 influenza erupted on the border between China and the Soviet Union. Based on a genetic analysis of the strain, many researchers concluded the virus escaped from a lab. Smallpox, meanwhile, was eradicated from the wild in 1977; the following year, Janet Parker, a photographer at Birmingham Medical School in the UK, became infected and later died. The building she worked in housed a research laboratory where scientists were studying smallpox.

In 2004, at least two unnamed researchers contracted the SARS virus at the Chinese National Institute of Virology in Beijing. One of the researchers went on to infect her mother, who later died, as well as a nurse at the hospital where her mother was treated. The outbreak led to 1,000 people being quarantined or placed under medical supervision. At the time, the World Health Organization (WHO) reported there may have been similar outbreaks of SARS in Taiwan and Singapore that also may have originated in labs.

There have been even more alarming close calls where scientists were exposed to dangerous pathogens due to equipment failure or lax adherence to containment protocols.

However, every known lab leak to date has involved a pathogen that was previously identified. There has never been a confirmed case of a never-before-seen virus escaping a research facility.

At the other end of the spectrum of possibilities, virologists point out that the vast majority of pathogens that infect humans originate in nature, and almost all come from interactions with animals. Over the past century, about two new viruses per year have been discovered in humans, most of which spilled over from animals, according to a 2012 paper in Philosophical Transactions of the Royal Society B.

“All these spillovers, wherever they are, it’s because human activity is encroaching upon animal activity,” Vincent Racaniello, a virologist at Columbia University, told Vox in June.

Influenza, for example, is found in birds, poultry, pigs, and seals. HIV likely originated in chimpanzees. Measles has an ancestor in cattle.

In fact, another coronavirus, the 2003 SARS virus, was found to have jumped from bats to civet cats before making the leap to humans. And scientists have warned for years that another bat coronavirus could trigger an outbreak in people.

The debate over Covid-19’s origins may never be resolved to everyone’s satisfaction

Many researchers in the early days of the Covid-19 pandemic were quick to attribute the emergence of the SARS-CoV-2 virus to a natural occurrence, likely a human contact with a bat coronavirus via an intermediary. Two recent papers, one in the journal Science and one in the journal Cell, emphasized this conclusion, citing genetic evidence tracing both the lineage of the virus and the circumstances in China in late 2019 that increased the likelihood of humans coming into contact with wild animals that could harbor the pathogen.

Still, some scientists have argued for closer scrutiny of the possibility that the novel coronavirus escaped from a lab. The most basic hypothesis is that a worker at the Wuhan Institute of Virology was infected by a naturally occurring virus under study there. There is no direct evidence for this, nor any indication that SARS-CoV-2 or a progenitor was being studied at the lab, let alone that someone who worked there was infected. Wuhan is about 1,000 miles away from where the bats that harbor a similar virus are found, raising the question of how SARS-CoV-2 crossed that distance. The laboratory was also known to handle its viral samples at a lower safety level than most scientists recommend for such a pathogen. In addition, no one has found an animal that clearly hosted the virus or a precursor just before it leaped into humans.

More fringe ideas are also circulating, like the notion that the virus was deliberately engineered to be more dangerous or deliberately released as a bioweapon. There’s no evidence for these claims.

With the passage of time, however, it’s becoming more difficult for scientists to study the origins of Covid-19. In a recent article in the journal Nature, WHO researchers warned that time is running out: “The window of opportunity for conducting this crucial inquiry is closing fast: any delay will render some of the studies biologically impossible.”

Another complication is that the question of where the virus came from has become a political issue domestically and internationally. Within the US, some politicians have been eager to blame a lab for the pandemic and shift the blame to China.

That, in turn, has become a major source of friction between the United States and China. Chinese officials stopped cooperating with a WHO investigation into the origins of the coronavirus earlier this year and responded with their own allegations that the virus originated in a US lab (for which there is no evidence).

And without cooperation from Chinese authorities, it’s unlikely that a definitive answer — one way or the other — will emerge anytime soon.

Scientists already know how to stop lab leaks

There are many ways to improve safety in laboratories and install safeguards to prevent dangerous diseases from escaping and wreaking havoc. Even scientists who think the emergence of SARS-CoV-2 was a natural event say that preventing lab leaks should be a high priority.

Gigi Gronvall, senior scholar at the Johns Hopkins Center for Health Security, said it’s important to think about two key concepts: “Biosafety” is about protecting people who work with pathogens from the things they are studying, usually through accidents. “Biosecurity” is preventing misuse of pathogens via deliberate actions.

Both are essential to prevent leaks of biological agents, but they’re often afterthoughts when it comes to conducting research on pathogens. “It’s hard to make this exciting,” Gronvall said. “That is why very often the money goes to research, and biosafety is less emphasized.”

One way to enhance biosafety is to deploy several different methods of containment in a laboratory. For instance, biosafety level 3 precautions for handling pathogens that can spread through the air include only handling samples in “biological safety cabinets” that filter air, controlling lab access with two sets of self-locking doors, and wearing respirators, eye protection, and lab coats. It also includes routine medical screening of lab workers.

“Ideally, if there is any kind of accident, there are still multiple layers before it becomes an issue for anyone outside a laboratory,” Gronvall said.

Biosafety also hinges on the type of studies being conducted. Of particular concern is gain-of-function research, in which pathogens are deliberately modified to become more dangerous to humans. The goal is to map out potential changes that could emerge in the wild and develop ways to counter them before they become major threats. It’s a controversial form of research, and some have alleged that the Wuhan Institute of Virology was conducting such experiments — though, again, there is no evidence this occurred. US officials have also been adamant that they have not funded any gain-of-function research, either in the US or abroad.

Some scientists say this kind of research should not be conducted at all because the risk of an escape is too great, but others say gain-of-function studies can be conducted safely with appropriate precautions.

“Lab incidents will still occur. A robust biosafety and biosecurity system, along with appropriate institutional response, helps to ensure that these incidents are inconsequential,” biosafety experts David Gillum (Arizona State University) and Rebecca Moritz (Colorado State University) wrote for the Conversation. “The challenge is to make sure that any research conducted — gain-of-function or otherwise — doesn’t pose unreasonable risks to researchers, the public and the environment.”

Building a robust biosecurity system requires cooperation from institutions ranging from laboratories to regulators to governments. It demands rigorous oversight to enforce safety standards. Transparency among institutions about the kinds of biological research they’re conducting, as well as potential mishaps and accidents, is also critical. But there’s a pervasive fear among laboratories and the individuals who work there that disclosing problems will hurt their reputations.

“If there is a biosafety incident, it is very hard to get that addressed in a way that doesn’t cause problems for an institution,” Gronvall said. “They have a lot of incentives to keep it under wraps.”

That’s also why it’s been hard to know whether China is stonewalling investigators because of a potential lapse in laboratory protocol or out of general distrust of other countries and institutions like the WHO. “A bat could’ve walked out of a cave wearing a name tag and China would behave the same way,” Gronvall said.

Fixing this requires a change in the culture surrounding biological research to create an environment where mistakes and problems are discussed openly and addressed immediately. Inspections, monitoring, and documentation would also make it harder to sweep any problems under the rug.

What’s tougher is enforcing these principles around the world. There is an international agreement restricting research on biological weapons, the Biological Weapons Convention, but there’s no similar agreement for general biological research. Many countries have their own research programs for pathogens, and it’s the Wild West when it comes to what standards are used and what studies are done.

“There’s really no international body that has the authority to oversee biological security or biological safety,” said Weber, from the Council on Strategic Risks. “We should work with [the] international community to adopt real standards for biosecurity and for high-risk research.”

Some pathogen laboratories, like the US Army’s Fort Detrick in Maryland, already have exchange programs with researchers around the world. More exchanges and international inspections of biological research labs could help ensure that every facility adopts best practices and upholds the highest safety and security standards. But setting up such a regime requires trust and cooperation, and that’s in short supply.

“Natural” spillovers, which often have human causes, can be prevented, too

Pathogens found in the wild have infected people for millennia, but there are ways to tame this force of nature. “What we can do is reduce the rate of exposure of humans,” said Andrew Dobson, professor of ecology and evolutionary biology at Princeton University.

For example, a key route for new human diseases is contact with wildlife. Such interactions increase as cities sprawl into the wilderness and people venture further into remote areas in search of food, fuel, and raw materials. When humans destroy habitats, especially through deforestation, they force animals to flee to new areas and interact with people in cities and suburbs. In one paper published in the journal Science in 2020, Dobson reported that when more than 25 percent of original forest cover is lost, it’s much more likely for humans and their livestock to come into contact with wildlife that may carry diseases.

“That’s what’s exposing people to the hosts and the carriers of these viruses,” said Dobson. Drastically reducing deforestation and placing strict limits on how much people can encroach into forests, grasslands, and deserts can slow the emergence of dangerous new parasites, viruses, bacteria, and fungi.

Domesticated animals, particularly livestock, can also be a source of new diseases. The combination of changes in land use and factory farming of cattle, chicken, and hogs can increase the risk of a pathogen hopping between species.

Another way to reduce the chances of a spillover is to close unregulated markets that sell wildlife as food, ingredients for medicines, or materials for clothing. Phasing out legal wildlife markets and screening the health of animals that humans do come into contact with would also reduce the risks of new diseases jumping into people. “There needs to be [many] more international treaties around that to protect people,” said Dobson.

The hurdle is that the wildlife trade is quite lucrative. The legal wildlife market is worth about $300 billion, while estimates of the value of illegal wildlife trading can be as high as $23 billion. So reducing some of the highest-risk forms of wildlife trade also demands an economic solution for people whose livelihoods would be affected, such as helping them find new jobs.

Surveillance — actively looking for dangerous pathogens in the wild to stay ahead of outbreaks — is another important tactic, but there are some risks. Sending researchers into remote areas to collect samples and study them could expose them to dangerous diseases.

“We need to think more about the precautions people take and the security level in those labs,” Dobson said. “[But] the amount we’ll learn will significantly reduce the risk of future outbreaks.”

The history of narrowly averted pandemics is full of crucial lessons

Beyond probing the roots of the Covid-19 pandemic, it’s also worth investigating close calls of the past. Viruses like the original SARS virus in 2003, for example, had the potential to go global but didn’t. The virus itself had some traits that prevented it from spreading further, and while many of the countries most acutely affected by the outbreak, like China and Vietnam, learned critical public health lessons, much of the rest of the world remained complacent.

In a 2013 paper in the Journal of Management, researchers looking at problems with uncrewed NASA missions highlighted the important lessons that can be found in near-miss scenarios like this. “Disasters are rarely generated by large causes,” the authors noted. “Instead disasters are produced by combinations of small failures and errors across the entire organizational system.” So whether SARS-CoV-2 came from a lab or a natural event, a lot of other things also had to go wrong for it to become an international crisis.

When all these factors don’t align in a particular instance and fail to produce a disaster, it’s easy to take the wrong lesson — that humans were adequately prepared or that the status quo of science and public health is good enough already. But it’s dangerous to ignore close calls, whether it’s a near collision between satellites or a new pathogen that was narrowly contained.

“If near-misses masquerade as successes, then organizations and their members will only learn to continue taking the risks that produced the near-miss outcome until a tragedy occurs,” the researchers wrote.

That’s why it’s important to study the factors behind not just the Covid-19 pandemic but also other outbreaks like those of Ebola, SARS, and MERS, which raised alarms and revealed weaknesses in national and global public health systems.

We may not unravel the origins of SARS-CoV-2 anytime soon — if ever. But by treating both spillovers and lab leaks as urgent risks right now, scientists, health officials, and governments can protect us all from outbreaks of the future.

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Another explosive wildfire season is underway in California, with more than a million acres already burned in 2021. While still short of the unprecedented 2020 fire season, the blazes this year are well above average and are still gaining ground.

The Caldor Fire burning near Lake Tahoe has forced thousands of people to evacuate as it has spread to more than 207,000 acres, an area larger than New York City. The blaze ignited August 14 and was 23 percent contained as of Thursday.

The Dixie Fire near Chico, California, that ignited on July 14 has scorched more than 847,000 acres. It was 52 percent contained as of Thursday.

Spread by winds reaching 40 mph and fueled by abundant dry vegetation, wildfires across the Golden State have whipped up enormous clouds of smoke and ash. Some have even spawned fire tornadoes.

Across the United States as a whole, more than 2.7 million acres have been charred in wildfires this year, according to the National Interagency Fire Center.

Researchers said that the current fires align with what they forecast earlier this year, noting that the region was parched by a massive drought, was facing severe heat, and had plenty of trees, brush, and grass ready to burn.

Even so, the blazes have proved surprising in other ways. The Caldor and Dixie fires are the first wildfires on record to cross the Sierra Nevada mountain range, posing new challenges for firefighters working to contain them. “These two big fires started in very steep canyons [that are] difficult to access, with very dry, overloaded forests that are burning intensely and so it’s very hard to get a handle on this,” said Craig Clements, director of the Wildfire Interdisciplinary Research Center at San Jose State University.

And as humans continue to drive up wildfire risks — from building in fire-prone regions to suppressing natural fires to changing the climate — scientists are having to rethink what’s possible.

Even by California standards, the current wildfires are surprising

There are several key ingredients needed for wildfires. They need favorable weather, namely dry and windy conditions. They need fuel. And they need an ignition source.

The California Department of Forestry and Fire Protection said that they are still investigating the origins of most of the blazes underway. But other factors this year stacked the deck in favor of massive conflagrations.

California and much of the western US are in the midst of a years-long drought. With limited moisture, plants dry out and turn into kindling. Ordinarily, vegetation at higher altitudes would still hang onto some moisture and act as a barrier to wildfires in places like the Sierra Nevada. However, the severity of the drought has caused even this greenery to turn yellow and gray.

“That’s the unique thing, that these fires have burned over the Sierra Nevada crest,” said Clements. “The fuel moistures are still at record lows across the state of California. That’s allowing these fires to burn at higher altitudes.”

Moisture in the soil and in vegetation can also act as a cooling mechanism as it evaporates. With the drought, this effect is diminished, allowing even more heat to accumulate and pushing temperatures up to the new record highs achieved this summer. The hot weather in turn drove even more drying across the landscape, reaching aridity levels not typically seen until October.

It’s likely that even more fires are in store for the rest of the year across the West. As the autumn Santa Ana and Diablo winds pick up, the risks remain high.

People make wildfires worse, but can take steps to mitigate them

Wildfires are a natural part of ecosystems across much of the western United States. They serve vital functions like clearing decaying vegetation, regulating forest density, restoring nutrients to soils, and helping plants germinate.

But human activity has made wildfires worse at every step. Climate change caused by burning fossil fuels is increasing the aridity of western forests and increasing the frequency and severity of extreme heat events.

People are also building closer to wildland areas. That means that when fires do occur, they cause more damage to homes and businesses. That proximity also means that humans are more likely to spark new infernos. The vast majority of wildfires are ignited by people, up to 84 percent, whether through errant sparks, downed power lines, or arson.

And for hundreds of years, people have suppressed naturally occurring fires. European settlers also halted cultural burning practices from the Indigenous people of the region. Stopping these smaller fires has allowed forests, grasslands, and chaparral to grow much denser than they would otherwise. Paradoxically, that means more fuel is available to burn when fires do occur, causing blazes to spread farther and faster.

The combination of these factors leads wildfires to keep breaking records, forcing scientists to reevaluate what kinds of fires are possible. Decades ago, a 20,000-acre blaze would have been considered massive. Now, wildfires can gain that much ground overnight. “What we’re finding is that even forecasting the fires is so difficult for us because the domain size is huge,” Clements said. “These fires are massive and we keep having to expand the domain of our weather models.”

There are well established ways to reduce the risks of destructive wildfires. Directly attacking a fire once it’s ignited can only go so far, so much of the focus has to be on prevention. One key way is to reduce fuel load. That can take the form of forest thinning and prescribed burns. Towns and cities in fire-prone regions can build defensible perimeters, cutting fire breaks and clearings to reduce the chances of a fire encroaching.

Building codes that demand fire-resistant materials and avoiding construction in the highest-risk areas can reduce the impact of fires as well. Ignitions can be reduced by hardening or burying power lines.

Restoring Indigenous burning practices can also help mitigate wildfire risk — but that will require governments to address historical wrongs, restoring tribes’ access to and sovereignty over ancestral lands.

Over the long term, slowing climate change by drastically reducing greenhouse gas emissions can also stop fires from becoming even more destructive.

The factors that laid the foundation for massive wildfires took centuries to build and won’t be reversed overnight. But the process of reducing these risks can begin now.

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During the pandemic, I’ve spent a lot of time alone. I live by myself. I work from home. At times, I experienced fits of fidgetiness and restlessness, contributing to feelings of burnout.

Here’s what helped: reappraising the situation.

What I was feeling was isolation, and the loneliness that comes with it. Instead of letting it gnaw at me, I tried to remember: Loneliness is normal, sometimes even useful. I remembered that sadness existed in part to remind me of something I really value, the company of other people. I knew, when the opportunity arose, I’d reorient myself to immersion with others. And when that time came, I’d embrace it; it was a reminder that I was still capable of feeling the joy I had been lacking. And as a consolation, that felt good.

Cognitive reappraisal — sometimes called cognitive reframing — is most commonly encountered in therapy, where it’s used to regulate emotions. It’s a component of cognitive behavioral therapy, a whole suite of strategies that can encourage positive patterns of thinking and behavior.

Reappraisals are useful. But they’re not something people learn exclusively in the context of clinical care. It’s arguably a skill we all can benefit from. And by “we all,” I mean just about everyone, all across the globe.

Recently, hundreds of researchers in 87 countries published the results of the largest cognitive reappraisal study to date in Nature Human Behavior. They were asking a simple question: Could they make people feel better about the pandemic, if only for one moment in time, by teaching reappraisals? The study, which amassed data on more than 20,000 participants, came back with a resounding answer: yes.

The new study validates the concept of reappraisal. But it also suggests that it could potentially be feasible to deploy as a large-scale global health intervention.

It’s a simple skill, but it could help many people foster resilience in a chaotic world.

Cognitive reappraisal, explained

The peer-reviewed paper in Nature Human Behavior is the most recent project from the Psychological Science Accelerator, a group of hundreds of researchers who combine their resources to pull off psychological studies with massive participant pools and an unusually rigorous methodology.

Near the start of the pandemic, the group put out a call for project proposals to test psychological interventions that could, simply, help people feel better.

“The reason why we choose cognitive reappraisal is because it has been the most widely studied and well-understood strategy,” Ke Wang, the Harvard Kennedy School doctoral student who first proposed this massive project, explains. It’s also a strategy that people don’t always use spontaneously on their own: It helps to be taught.

(The group has two other papers testing different psychological interventions, on how public health messaging in the pandemic can influence behavior. Of note: They’re testing whether “loss aversion,” an influential idea that suggests people respond more strongly when they think they have something to lose, encourages people to protect their health during a pandemic.)

Cognitive reappraisal works because “there’s a link between our thoughts and our feelings,” Kateri McRae, a University of Denver psychologist who studies emotion and who was not involved in this study, says. “A lot of times, our feelings are preceded by certain thoughts.” So when we shift our thoughts, that can precipitate a change in our emotions.

It can be a strategy to cope with a bout of anxiety or depression, or it can just be used to foster mental health resilience. “Individuals who report greater amounts of well-being and daily positive emotion report using reappraisal more frequently than people who report daily negative emotion,” McRae says — though she adds that “there is a little bit of a chicken-and-egg thing here.” What comes first: Do positive people reappraise, or do reappraisers become positive people? “But I certainly think that most people consider it to be something that might serve as a buffer.”

Once you get the hang of the technique, it’s easy to apply reappraisal thinking to many different situations. For instance, sometimes when I felt the excruciating boredom of the pandemic winter lockdown, I tried to reappraise the feeling of boredom as peacefulness, the absence of a bad thing. “I’m lucky to be bored,” I’d think. It would make the bitter pill go down more easily.

Emotion regulation passes a massive worldwide test

Wang and the hundreds of other authors wanted to see if they could teach thousands of people around the world similar coping strategies, to help deal with the stress of the pandemic.

They conducted a preregistered study — meaning a study where the methods and analysis plans are locked into place before data collection begins, to help ensure rigor — and tested two subtly different reappraisal methods, targeting negative emotions associated with living through the pandemic.

The first method is called “refocusing.” It might be better described as “looking on the bright side.”

Let’s say you’re feeling sad, staying home during a lockdown. You can refocus your thoughts to some of the more positive aspects of staying at home. Like: “Staying at home is not that bad,” as Wang explains. “You may find more time to spend with your family, or do things you may not have had time to do, such as cooking.”

Another is called “reconstruing.” This goes a little beyond just looking at the bright side of any particular burden, trying to find an overall less-negative narrative to tell ourselves about the pandemic. It’s less about finding the positive in our individual circumstances and more about looking at the big picture in a new light.

In reconstruing the burdens of the pandemic, for example, you could think: “In the past, people have overcome many challenges that seemed overwhelming at the time, and we will overcome Covid-19 related challenges too,” as the study text suggested to participants.

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This isn’t about becoming a blinkered robot that’s only allowed to think positive thoughts. “In our intervention, we’re not forcing them to feel positive all the time,” Wang explains. “We’re teaching them to use it to regulate emotions.” It’s about intervening when thoughts become distressing.

It’s not about never acknowledging negative thoughts, either. “I think there’s a really delicate balance between acknowledging the reality, allowing people to sometimes sit with negativity, but also realizing that positive interpretations of things are possible,” McRae says.

In the study, participants were assigned to read about refocusing, reconstruing, or two control conditions. Participants took a survey before they learned the technique to assess their baseline emotional state. Afterward, they were measured again and asked to assess their feelings overall about the pandemic, and how they are responding to it.

Notably, both techniques fared equally well in decreasing people’s negative emotions, and the effects, the authors report, aren’t just statistically significant — they seemed to make a big practical difference for people.

The difference in feelings between those who learned reappraisals, compared to those who did not, was as big as the difference between people who had faced extreme hardships due to the pandemic, compared to those who had not. That’s a notable improvement. (Of course, the interventions are not “guaranteed” to work for any particular individual. The study reported changes on average.)

Also, the interventions didn’t seem to decrease willingness to engage in Covid-safe behaviors like masking. “Some people may worry that if you improve emotions, people may be less cautionary,” Wang says. “But we don’t find that in our study.”

Notably, too, the interventions — which were translated by a team of hundreds of people into 44 languages — broadly worked in every country tested, though there was some variability. The interventions were most effective in Brazil, Germany, and Hungary, and they were least effective in Russia, Romania, and Egypt. “So far, we haven’t found anything that can systematically explain what country can benefit more or less,” Wang says. (The researchers didn’t have representative samples in all the countries studied, so there could be a lot of reasons why they found the variation.)

A psychological finding you can trust

The narrower conclusion of this study, that cognitive reappraisal works, is not super surprising. “The finding that reappraisal decreases negative emotion and increases positive emotion is something that has been replicated over and over and over ad nauseam,” McRae says. “I couldn’t just get that finding published if I really wanted to, because it’s been so well-established.”

But there were aspects of the study that are new and significant. “I think this scale, scope, and timeliness to speak to the crisis we’re in right now were the most impressive parts about it,” she says.

There’s a burgeoning research movement in psychology dedicated to testing out single-session interventions, delivered either online or remotely. Mental health care is often inaccessible and expensive, so the more psychological interventions that can be unbundled from a whole suite of intensive therapy, the more good they can potentially do around the world. Many people whose distress doesn’t rise to the level of a mental health diagnosis could still benefit, the study suggests.

That said, there’s still more work to do here. Other researchers not involved in the project wish it had studied these participants over time, to see if the intervention had a lasting effect.

“A study this large would have provided a particularly informative test of whether a single-session universal intervention could exert lasting, more generalized effects,” says Jessica Schleider, a Stony Brook University psychologist who specializes in studying single-session psychological interventions. “I do think it’s scientifically valuable to know that reappraisal can provide in-the-moment support this broadly, and it can be recommended as one coping option to try for folks in distress.”

The authors of the paper acknowledge this limitation, and some others. The study had people view photos reminding them of Covid-19 stresses, which “might not represent local situations for different groups of participants,” the authors report. It also doesn’t represent all the myriad emotional triggers we encounter living during a pandemic. But most of all, they see this work as foundational for other questions.

The Psychological Science Accelerator, the group behind the massive undertaking of the paper, was launched in response to psychology’s “replication crisis.” Over the past decade, many famous psychological theories have collapsed under rigorous re-testing. As many as 50 percent of all psychology papers might not be replicable, though no one knows the true extent of the rot in the foundations of psychology. There have also been some high-profile cases of outright data fraud related to some of psychology’s most popular findings. The Accelerator, which operates on a shoestring budget (it reports that this study of tens of thousands of people cost only $17,000, much of which came from individual lab members), is seeking to rebuild the field on a firmer foundation.

It’s a “credibility crisis,” Patrick Forscher, a psychologist and member of the Accelerator who worked on the reappraisal paper, says. “Because there are more issues rather than just replicability. So my personal view is that you can look at a lot of psychological findings and just put a question mark on them — not that they’re definitely false. We know that some of the practices that were used to produce a lot of those findings are, themselves, not all that credible.”

The latest test of cognitive reappraisals puts the science of mental health interventions on a firmer foundation. Psychology encompasses a lot of flimsy ideas that claim to make your life better. Here’s one that seems to actually work.

On Monday, the United Nations announced an environmental and public health milestone: the end of the use of leaded gasoline in automobiles and road vehicles worldwide.

The last holdout was Algeria, which had large stockpiles of leaded gasoline; in July, those stockpiles ran out, and Algeria has now made the transition to unleaded gasoline.

Lead poisoning causes immense societal harm: brain damage, chronic illness, lowered IQ, elevated mortality. Lead exposure in childhood has been linked with violent crime rates decades later. Extremely high lead levels can lead to seizures, coma, and death. Lower levels tend to cause less detectable harm, but there’s no safe level of lead exposure: Scientists’ current best guess is that any lead exposure at all causes harm.

Many of lead’s dangers have been known for decades. Leaded gasoline was invented by a General Motors research lab in the 1920s, and already at that time, there were people noticing that children exposed to high levels of lead suffered devastating health consequences. But Thomas Midgley Jr., leaded gasoline’s inventor, campaigned to convince the world that it was safe. (Midgley also invented ozone-depleting refrigerants called CFCs, which would end up being banned by the 1987 Montreal Protocol; he’s been called a “one-man environmental disaster.”)

For more than 50 years after the invention of leaded gas, virtually all cars around the world pumped aerosolized lead into the air.

In the 1970s, though, following more research firmly establishing lead’s harms, rich countries started addressing the problem. In the US, the Clean Air Act imposed restrictions on lead pollution, and a few years later, the Environmental Protection Agency mandated that gas pumps offer unleaded gas, as the first step toward a transition away from leaded fuels.

The EPA estimates that the amount of lead used in automotive gasoline in the US fell by 99 percent between 1976 and 1989. Measured blood lead levels followed. Crime rates dropped, too. Those benefits were realized even though the lead used in gasoline (and in paint and other consumer products) before bans on its use is still widespread in our soil and dust and still posing a major public health challenge.

In 1996, the EPA completely banned leaded gasoline for on-road vehicles. Japan and Europe issued their own bans over the same time period. In 2000, China and India followed.

How the United Nations phased out leaded gasoline worldwide

In 117 countries around the world, though — largely low-income ones — leaded gasoline was still in use.

In 2002, the UN’s Environment Program (UNEP) launched a sustained effort to phase out leaded gasoline, called the Partnership for Clean Fuels and Vehicles.

UNEP Director Inger Andersen describes it as a “UN-backed alliance of governments, businesses and civil society,” and its tactics were quite flexible: convincing governments of policy bans, teaching businesses how to make cleaner vehicles, finding investment for better refineries, and in one case navigating a massive bribery scandal, when it turned out that a leaded gasoline producer, the chemical company Innospec Ltd., was fighting to keep its product legal in Indonesia by bribing government officials.

The UN’s initiative saw fast adoption in sub-Saharan Africa, where 25 countries signed on to a plan to de-lead their gasoline in 2005. It made slower progress elsewhere, especially in the Middle East, where many countries had enormous stockpiles of leaded gasoline.

In 2011, a study by Peter L. Tsai and Thomas H. Hatfield estimated the phaseout of leaded gas was increasing global GDP by 4 percent, or $2.4 trillion (counting health savings as well as social benefits from higher IQ and lower crime).

They also estimated the direct benefits in lives saved at 1.2 million a year. The phaseout of leaded gasoline has been the “single most important strategy” for combating lead poisoning, they conclude, “with the economic benefits exceeding costs by more than 10 times.”

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And while there’s a lot of academic debate about the exact magnitude of lead’s effect on crime, there’s no debate that transitioning away from lead fuels passes almost any cost-benefit analysis: Poisoning your entire population is just really bad, and transitioning away from leaded fuels is one of the cheapest ways to dramatically reduce lead poisoning.

By 2014, automotive leaded gasoline was legal only in parts of Algeria, Iraq, Yemen, Myanmar, North Korea, and Afghanistan.

By 2016, it was just Algeria, Yemen, and Iraq. And now, two decades after the campaign kicked off, cars everywhere in the world will use unleaded gas.

The road ahead

The end of leaded gasoline in automobiles is a big step forward, and one worth celebrating. But the fight to end lead poisoning’s effects on our world and on the next generation has a lot further to go.

In the US, leaded gasoline in cars has been illegal for more than 25 years. But the lead from that gasoline has settled in the soil and dust, and still contributes to poisoning children today.

The Centers for Disease Control and Prevention tracks lead exposure across the country. In 2018, the most recent year for which data is available, it found that in most states, between 1 and 5 percent of children had more than 5 micrograms per deciliter of lead in their blood — enough to potentially cause them serious health problems and lifelong harm. (Children exposed to lead in the US today are mostly exposed through soil and dust ingestion. Often, dust has lead in it because paint in old houses contains lead.)

Worldwide, UNICEF estimates that around one in three children have lead levels in excess of the 5 µg/dL line. While leaded gasoline for automotives has historically been the single biggest contributor to lead levels in population centers, there are others: heavy industry, inadequate battery recycling and disposal, decaying pipes, and lead-based pottery glazes, for example.

In the US, lead-based fuels, though illegal on the road, are still allowed in aviation and a few other specialized contexts — and there’s no real progress toward phasing them out. While they cause a lot less lead exposure than automotive leaded gasoline did, the fact that there’s no known safe level of lead exposure should still give us pause — even the smaller exposures from these rarer sources can cause problems.

The end of leaded gasoline throughout the world will do a lot to fight lead poisoning by itself, but ideally it would be accompanied by measures to attack the other ways lead enters children’s bodies. The bipartisan infrastructure bill making its way through the US Congress includes money for lead remediation measures and lead pipe replacement — but it’s probably not enough to replace all aging lead pipes in the US.

UNICEF calls for “completely removing the potential for exposure to lead in areas where children live, play and learn,” and while it would be a tremendous expense, it would have a tremendous return. Poisoning the next generation is about as shortsighted as it gets, and investment in lead protection is an investment in our future.

Celebrating — and learning from — humanity’s achievements

The UN is frequently criticized as “bloated, undemocratic”, not focused on the world’s biggest problems, and not capable of moving us toward meaningful solutions.

But the worldwide elimination of leaded gasoline in cars is a genuine achievement worth celebrating — and worth examining, to see how the world can use the tactics that triumphed against leaded gasoline to combat the other huge problems requiring international coordination that face us in the 21st century.

The team at work on it has already expanded their focus to the next crucial transition for road vehicles: a move from gasoline-based ones to lower-emissions and zero-emissions alternatives. The leaded-gas initiative “is testament to the power of multilateralism to move the world towards sustainability and a cleaner, greener future,” Andersen, the director of UNEP, argued in a press release accompanying the announcement. “We are invigorated to change humanity’s trajectory for the better through an accelerated transition to clean vehicles and electric mobility.”

They’re also at work phasing out lead paint, another major source of household lead exposure.

The road map that the UN used for the fight against leaded gasoline — a combination of technological solutions that made it easier to switch away from lead in engines, political coalition-building, partnerships with businesses, and a few prosecutions of bad actors who used bribery to keep lead in business — is a road map that can be applied to challenges like climate change as well.

And separate from all of that, it’s worth taking a moment to rejoice in humanity’s achievements over death, disease, and our own self-inflicted horrors. Leaded gasoline and its mass use was one of the biggest mistakes of the 20th century. Ending it is one of the first big global triumphs of the 21st.

Medicare, the federal health insurance program that covers Americans over 65, is facing an impossible dilemma: Should it cover a new and expensive medication for Alzheimer’s disease, which afflicts 6 million Americans and for which there is no existing treatment, even though the drug might not actually work?

It is an enormous question. Alzheimer’s patients and other families with members who endure mild cognitive impairment that may progress to Alzheimer’s have been waiting decades for an effective treatment. For them, even a few more months of life with improved cognition, one more birthday party or a grandchild’s graduation, is the priority.

But the evidence on whether Biogen’s treatment, called aducanumab, is effective is, at best, mixed; the FDA approved it this week over the objections of its own advisory committee. And with a preliminary announced price of nearly $60,000 annually per patient, covering the treatment could cost upward of $100 billion a year, mostly to Medicare, which would almost double the program’s drug spending. Patients themselves could be on the hook for thousands of dollars in out-of-pocket costs.

What Medicare does about aducanumab will have major ramifications not only for the millions of patients who could potentially be eligible for the drug, but for the future of US health care writ large.

The dilemma results from a feature of the American health care system: Unlike in other countries, the federal government has little room to negotiate what Medicare will pay for treatments.

Independent analysts think the drug is worth more like $8,000, but Medicare has no authority to charge a lower price. Instead, the federal program is likely in effect obligated to cover the new drug now that it has FDA approval. The tools it has to make a determination about whether or not to cover aducanumab and for whom are fraught with legal and ethical risk.

The government now finds itself trying to figure out how to satisfy patients who desperately need help, even though scientists think this particular treatment lacks strong evidence for its effectiveness and policy experts warn it is setting up a budgetary nightmare for Medicare in the future.

“Every conversation we’re going to have for the next few years about health care access is going to be about this drug, whether implicitly or explicitly,” Rachel Sachs, a law professor at Washington University in St. Louis who studies drug pricing, told me this week.

The troubled path to aducanumab’s approval

Alzheimer’s is a terrible disease that robs people of their agency during the final years of their lives and robs families of the loved ones they once knew. The emotional and financial costs are severe. And as the number of Americans over 65 grows, those costs are only expected to increase.

In recent history, the decades-long search for an effective treatment or cure has been driven by what’s known as the amyloid hypothesis, which holds that plaque in the brain found in Alzheimer’s patients is at least in part responsible for the disease and removing that plaque could help relieve the symptoms.

Aducanumab, accordingly, targets the amyloid plaque. Clinical trials of the drug started in 2015 but were halted in March 2019 because it did not appear it would meet the threshold for clinical effectiveness established at the start of the trials. It appeared, in other words, as though the drug didn’t work.

Normally, that would be the end of the story. But an unexpected twist came a few months later when Biogen revealed that, after additional data analysis with the FDA, some patients in one trial had actually seen “better but ultimately mixed results,” as the authors of a Health Affairs post on the controversy put it. Biogen announced it would push ahead with seeking FDA approval in October 2019, with the FDA’s apparent support.

Then, in November 2020, Biogen and aducanumab faced what looked like the ultimate setback: The FDA’s advisory committee on neurological therapies voted the data did not demonstrate the drug was clinically effective. The vote was all but unanimous, with zero in favor, 10 nays, and one uncertain. They raised concerns about potential side effects, such as brain swelling in patients who were given high doses.

But, in defiance of its own advisory committee’s recommendation, the FDA granted aducanumab its approval on Monday. The news was welcomed by Alzheimer’s patient groups but roundly criticized by experts in drug development.

“The FDA … has failed in its responsibility to protect patients and families from unproven treatments with known harms,” the Institute for Clinical and Economic Review (ICER), an independent non-government group that gauges the value of new drugs, said in a blistering statement.

And the agency not only approved the drug over the advice of its scientific advisers, but it put effectively no restrictions on which patients with cognitive impairment should be given the drug, a decision that further stunned experts, as STAT reported.

“For the FDA to approve it and with a very broad indication, I was shocked,” Stacie Dusetzina, who studies drug costs at Vanderbilt University, told me. “I really expected them to say no, based on the body of evidence.”

Medicare almost always covers FDA-approved drugs

Now that aducanumab is approved by the FDA, the issue of coverage falls largely to Medicare; because of the age of the patient population most affected by Alzheimer’s, the federal program is likely to bear the brunt of the drug’s costs.

In practice, if the FDA approves a drug, Medicare will pay for it. Aducanumab would be covered through Medicare Part B, which covers outpatient care, because it is an infusion treatment administered directly by doctors. To be covered by Part B, medical care must be “reasonable and necessary” — a vague standard that has, for medications, historically been mostly synonymous with FDA approval.

Because the drug is covered by Part B, doctors will even have a financial incentive to prescribe it. For prescription drugs, the program pays physicians the average price plus 6 percent, a policy that both Presidents Obama and Trump proposed changing but nevertheless remains in place. Determining which patients would benefit from the drug requires expensive scans, and practices will be able to bill Medicare for those, too.

At the individual level, patients could face out-of-pocket costs anywhere from $0 for patients eligible for both Medicare and Medicaid, to $10,000 annually, since Medicare Part B can hold patients responsible for up to 20 percent of costs, advocates told me.

When I asked Russ Paulsen, chief operating officer of UsAgainstAlzheimer’s, about Biogen’s list price, he responded with an audible sigh, saying: “It’s a big number.”

He continued: “We care a lot about making sure the people who are disproportionately affected by this disease, which includes poor people, have the ability to access this drug.”

Medicare’s inability to determine the price it pays for aducanumab is a uniquely American problem compared to health systems in the rest of the developed world. Countries like Australia and the United Kingdom have independent boards that evaluate a new drug’s effectiveness and set a price based on that estimated value. The US pharma industry says the US system is important for encouraging innovation, and companies have made amazing breakthroughs, such as the hepatitis-C drugs that effectively cure that disease.

But, as the standards for approving have sometimes seemed to slip in recent years, the chances of the FDA approving very expensive drugs with only marginal benefits have risen.

“We don’t require prices to reflect the value of treatment, period,” Dusetzina said. “Companies can price their drugs as high as they want. Companies can also get drugs approved with little evidence.”

So Biogen is planning to charge $56,000 annually for aducanumab. ICER, which evaluates the estimated value of new drugs, estimates, based on the clinical evidence, that it’s worth more like $8,000; perhaps as little as $2,500 or as much as $23,100. Regardless, the price announced after Biogen secured FDA approval “far exceeds even this optimistic scenario,” ICER concluded.

“If we were talking about a cure for Alzheimer’s disease, we would figure it out,” Dusetzina told me. “It would be so important to address that burden on our society, we would need to figure it out.”

But aducanumab is not that drug, according to the available data. So what is Medicare to do?

Despite the tradition of honoring FDA approval, experts do not expect Medicare to simply announce it is going to cover the drug with no limitations. One option would be for the program to conduct “national coverage determination,” a lengthy review process to figure out whether to cover the drug and for which patients. (The price would not be on the table.)

The decision that would lead to is unclear. Many experts are urging Medicare to pursue what is called “coverage with evidence development”: essentially setting up its own clinical trial by authorizing aducanumab for use by some patients and collecting real-world data on their outcomes.

“I think it’d be a really smart move,” Dusetzina, who recently joined Medicare’s payment advisory board, said. “This is the perfect time to reevaluate why we need to consider value when we consider what is a fair price for a treatment.”

Along those lines, the private health insurer Cigna announced it would pursue a value-based contract with Biogen to cover the drug, though it did not provide any more details.

But for Medicare, none of these options are ideal. A previous attempt to set up coverage with evidence development for a new cancer drug in 2017 ended up being scuttled after pushback from the drug industry and doctors. Patients with Alzheimer’s and their families are desperate for treatment and will likely object if Medicare tries to restrict access to the drug while undertaking that data collection.

Alzheimer’s advocates are mindful of aducanumab’s cost to the US health care system as well as individual patients, and its potential limitations. They are not necessarily opposed to more evaluation of its effectiveness.

But their ultimate goal is to buy patients more time. As Paulsen told me: “This drug doesn’t do it perfectly, doesn’t do it amazingly well for every single person. But it’s the first one that does that.”

They say they worry about restricting access to patients who are living with this disease right now, for whom time is running out. They point out that cancer drugs with marginal benefits have also been approved by the FDA, with exponentially higher costs per patient than aducanumab.

“We do not want to see delays in the ability of patients and doctors to begin to discuss whether this treatment is right for them,” Robert Egge, chief public policy officer of the Alzheimer’s Association, said. “And if it is, if that’s their decision together, we want them to have access to it. What we do not want to see is a long protracted process that effectively delays the ability for people to begin this treatment now that approval has been given.”

The stakes are enormous — for everyone. The cost of expensive drugs ultimately trickles down in the form of higher premiums or taxes. As the investment advisory firm Capital Alpha DC pointed out this week in a note that warned the drug “could break the Medicare program,” the Medicare trustees are expected to issue a report any time now with an updated estimate of when the program’s hospital benefit might start to become insolvent — which could be as soon as 2024.

As Sachs told me: “It’s very difficult to see how our health system moves through this without significant negative consequences.”

Medicare’s inability to negotiate pharmaceutical prices has meant that a budget crisis is always just one drug approval away. With aducanumab, that crisis has arrived — even when evidence so far suggests there may be minimal benefit for patients in return.

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The world’s leading health organization, the WHO, repeatedly broke its own rules and spent millions of dollars on high-priced management consultants, according to a new independent audit — even as the United Nations agency has struggled to pay for lifesaving equipment and vaccines in its global Covid-19 response.

An unnamed consulting company, which Vox has identified as BCG, charged the World Health Organization $11.72 million since the start of the pandemic for contracts that were dubiously awarded, according to the audit.

These revelations, which one expert called “disturbing” in an interview with Vox, came after a Vox investigation showed how management consulting firms such as BCG and McKinsey have become ubiquitous in global public health organizations, despite the concerns of many health practitioners about multimillion-dollar price tags, potential conflicts of interest, and the opaque nature of consulting work.

WHO researchers told Vox that the auditor report raised questions about the agency’s ability to responsibly and transparently spend public money from the 194 member countries that fund it. In recent months, the WHO has requested donations from its members and the general public, citing a funding gap of more than a billion dollars for its pandemic response.

Given that the WHO’s 2020-21 budget is $5.84 billion, $12 million may not sound like a massive amount — “but $12 million for a health care system in a low-income country would comprise a significant portion of their funding,” says Adam Kamradt-Scott, the incoming global health chair at the School of Transnational Governance in Florence, who studies the WHO. That amount could pay for about 600,000 Covid-19 vaccine doses from Pfizer/BioNTech or Moderna. (The WHO is part of Covax, whose aim is to ensure all countries have equitable access to vaccines.) “If it’s money being wasted, that’s a lot of vaccines that could have been purchased,” Kamradt-Scott added.

The audit, which examines a sampling of the WHO’s biggest contracts, analyzed the agency’s work with BCG, known as “Consulting Firm A” in the report, and uncovered multiple violations of WHO policies. The auditors claim WHO staff sought to circumvent the organization’s public procurement rules in order to help BCG win a contract. Staff at the agency also broke WHO rules by repeatedly starting work with the firm before seeking formal approval to do so, according to the report.

Before the pandemic, Vox revealed the WHO committed at least $12 million on consultants to support the agency’s reform, approximately a quarter of which has been paid for directly by the Bill and Melinda Gates Foundation. At the time, a WHO spokesperson said the agency welcomed consultants’ work. “The [consulting] companies have supported WHO in areas where we lack in-house expertise or want to tap the current best-in-class standards.”

But controversy has surrounded high-priced consultants in a field dedicated to improving the health of the world’s poorest people. The consulting firm McKinsey advised the Trump administration on how to cut spending on food and medical care for migrants and played a role in increasing sales of prescription opioids, which have been linked to the deaths of hundreds of thousands of people around the world. Vox also documented how BCG helped boost sales of sugary drinks in India, although the WHO has called for reducing sugary drinks consumption and supports taxing the products.

The findings in the audit were recently accepted by the WHO’s member states at the annual World Health Assembly. In a statement, the WHO said it “takes seriously the recommendations of our oversight bodies and uses the constructive comments to address any identified weaknesses in our control environment — we are a learning organization, and these reports help us to continuously improve in all identified areas.”

The international agency said the contracts were awarded in the context of an unprecedented health emergency, but added that the agency is taking the recommendations in the report seriously, and has “already begun implementing many of those related to procurement.”

In a statement, BCG said, “As the global pandemic unfolded last year, BCG rapidly mobilized teams to support worldwide efforts to fight the spread of the virus. We are extremely proud of our work that contributed to saving lives in this unprecedented time and remain committed to providing our best minds and efforts to support the progress of public health.”

It’s possible “the high stress and the insufficient human resources at the onset of the pandemic made things worse and made WHO even more in need of consultants’ support and more vulnerable to their conditions,” said Gian Luca Burci, the WHO’s former legal counsel.

But “this seems to have been a misuse of funds,” Kamradt-Scott said. “This is disturbing. At least on the surface, it would appear that due diligence checks in how external agencies are engaged don’t appear to have been followed.”

“The auditor’s report raises a red flag, and the issue of WHO’s contracts with management consulting firms deserves more scrutiny,” said Suerie Moon, co-director of the Global Health Centre at the Graduate Institute of Geneva. At the end of the day, Kamradt-Scott said, the WHO has a “moral obligation to ensure every cent is spent appropriately.”

How the WHO broke its rules to work with BCG

Publicly funded agencies, including those that are part of the UN system like the WHO, are supposed to follow stringent rules when hiring external contractors such as management consultants. According to WHO policy, staff should “obtain the best value for money” when hiring external contractors, allow for “transparent competition among prospective providers,” and treat contractors equally.

According to the audit, BCG won eight contracts with the WHO in 2020 for a total value of $11.72 million, and the auditors closely scrutinized the two highest-value contracts, for which the WHO paid $5.4 million.

1) The auditors found WHO staff changed criteria to help BCG win work at the agency. For a contract that lasted from December 2020 to May 2021, the organization asked consultants for competitive proposals to “support the long-term vision for WHO supply chain and to build capabilities to execute the long-term supply chain vision.” Of the four consultants that submitted bids, BCG was one of two that were deemed technically qualified. But another firm won the highest score and should have been awarded the contract, the audit found. “WHO changed the evaluation criteria and re-evaluated the bids as per which Consultant A [BCG] scored higher and was awarded the consultancy,” the report said.

“The findings of the independent auditor suggest this doesn’t seem to be a case of negligence where protocols haven’t been followed because someone didn’t know what to do,” Kamradt-Scott told Vox. “It would appear WHO staff knowingly sought to circumvent the rules in order to engage a preferred provider.”

2) BCG started working for the WHO ahead of formal approval, according to the report. For the second contract, which ran from March to October 2020, BCG was hired to help the WHO purchase personal protective equipment and other essential supplies during the pandemic. Here, too, the auditors uncovered multiple irregularities.

The WHO started the work with BCG “without due approval of the competent authority, despite the fact that it entailed payment of $2.53 million by WHO,” the auditors wrote. WHO staff only sought formal approval four months after BCG started work for the agency and three of the four phases of their contract were complete, the audit found.

In the report, the WHO says it didn’t have the human resources to go through the proper procurement processes, but the auditors rejected this reasoning. “We are of the view that the formal process of approval should have been adopted before accepting the offer of [BCG] and engaging the firm. The delay in getting the approval of the competent authority was not justified.”

3) The auditors questioned whether BCG provided value for money. In one of the nine purchase orders that BCG negotiated on behalf of the WHO, the consultants got a 20 percent price reduction on protective gowns. The WHO and the consultants placed the order and approved the quality of the gowns. But an external PPE supplier, which was supporting the WHO, deemed the gowns low-quality and canceled the order. In another case, auditors flagged a missed opportunity for savings. Consultants negotiated a discount of 0.08 percent off N95 masks, for a savings of $9,750. In the same month, the same supplier fulfilled another mask order with a discount that amounted to $303,200. “We noted that [BCG] did not negotiate this price, which had better potential for saving,” the auditors wrote.

4) WHO paid millions of dollars for “pro bono” work. Another revealing finding from the audit was that BCG characterized its PPE procurement work as “pro bono,” even though one seven-month contract cost $7.3 million, of which $2.53 million was paid for by the WHO. Only the cost of the first of three phases and a transition period was covered by the consulting firm. “We are of the view that calling this engagement pro bono is not correct,” the report says.

The report comes at a time when the WHO is trying to strengthen its finances and wrangle more flexibility over how it spends money. The agency is asking for more support from countries that fund it — known as “assessed contributions” — which can be spent on a variety of expenses. The WHO is also funded by donors, such as the Gates Foundation, but that money tends to be earmarked for specific purposes.

As troubled as Moon was by the audit report’s findings, she suggested that scrutiny from the auditors is a step toward a stronger World Health Organization. “You can only have less earmarking if it’s followed by more accountability and transparency,” she said. “Heightened scrutiny of contracts with management consulting firms is one place to start.”

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