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Winter has long reigned in the globe’s northern latitudes, where vast expanses of frozen soils called permafrost nurture a rich, if still mysterious, mix of microbes that can tolerate year-round subzero temperatures. But as climate change warms the permafrost, that microbe community is changing in ways scientists are still trying to understand. Most worrisome is what will happen to the permafrost’s huge store of long-frozen carbon that newly awakened microbes can now feast on, and how that may propel further changes in climate.

Janet K. Jansson, a microbial ecologist at the Pacific Northwest National Laboratory in Richland, Washington, was one of the first scientists to study how the bacterial community in permafrost has shifted as the soils have thawed. Understanding the complexity of life in soils — permafrost or other — has long been made difficult by the fact that scientists are unable to culture a majority of the species that grow there in the lab. But Jansson and her collaborators have found a way to take a molecular census of these exotic organisms to better track changes in soil communities affected by climate change, including the icy north as well as grasslands in the south.


Microbial ecologist Janet K. Jansson

Pacific Northwest National Laboratory

Metagenomics — a technique in which scientists isolate, sequence and analyze DNA of microbial communities directly from the environment — and other molecular technologies, termed “omics,” are offering new insights about underground life and the transformations wreaked by warming temperatures, Jansson described earlier this year at a meeting of the American Association for the Advancement of Science held in Washington, DC, and in a paper she coauthored in the 2016 Annual Review of Earth and Planetary Sciences.

She recently spoke with Knowable about soil critters and how they are adjusting to a warming planet.

This conversation has been edited for length and clarity.

Why is so much still unknown about the soil’s microbes?

For a very long time, the microbes that have lived in the soil, especially in extreme environments, have been difficult to study because they don’t grow well under laboratory conditions. Now we’re starting to be able to look into this “black box” — the soil microbiome — and start to understand what the microbes are doing, and how they’re influenced by the environment. And that’s exciting because once we have that knowledge, we can start to use soil microorganisms to potentially help mitigate the negative impacts of environmental change.

You’ve spent many years studying one example of an extreme soil environment — the permafrost. What makes the microorganisms there distinct?

Permafrost is a special environment. A large fraction of the terrestrial carbon is trapped in the world’s permafrost — about as much carbon as is currently in the atmosphere and in plants combined. The permafrost is like a huge carbon freezer.

What’s really important is that as the permafrost starts to thaw, the microbes that are there start to become more active and metabolize the carbon compounds stored in the soil. And as they degrade them, the microbes produce greenhouse gases like carbon dioxide and methane, which get released into the atmosphere and can drive further warming.

Permafrost is covered by a layer of soil active with microbial life and is characterized by high amounts of carbon (brown) and liquid water (blue), but low levels of oxygen (green). When permafrost thaws in lowlands, more water and less oxygen are available, creating the perfect conditions for anaerobic bacteria to thrive. As a result, the soil community fixes less nitrogen and releases more carbon dioxide and methane into the atmosphere. At higher elevations, however, permafrost thawing can increase soil porosity, which allows oxygen to penetrate farther down. In this condition, aerobic bacteria thrive and release carbon dioxide to the atmosphere. In both scenarios, greenhouse gas output increases as the frozen soils warm.

Bacteria, in the permafrost or elsewhere, all need carbon to grow and produce cellular biomass. But they have other ways to get energy. One of our more unexpected findings were a lot of proteins for the reduction of iron within the frozen permafrost. Microbes can reduce iron for energy — it’s a process that can occur under conditions with no oxygen, but usually requires liquid water.

We were able to replicate this in the laboratory and show that iron reduction is carried out by organisms living in frozen soil. This was key to understand how they survive and — slowly — grow in such low temperatures with little oxygen. It turns out that at subzero conditions it is still possible to have liquid water because salts become concentrated and lower the freezing point of water. So the proteins we found were probably produced by the active iron-reducing bacteria living in salt brines.

How is the polar microbial community responding to warming temperatures?

We’re doing incubations in the laboratory and monitoring in field areas where the permafrost has already started to thaw. I have collaborations with scientists from several different areas in the Arctic: Svalbard, Greenland and Alaska.

What we and others have found is that, as permafrost thaws, the microorganisms that are there start to change — it’s a real turnover. You get a different composition of microorganisms, more of the ones that are better adapted to degrading carbon versus other types of metabolisms. We see a shift in function toward fermentation processes or methane generation. Methanogens — bacteria that produce methane — often increase in numbers. And that makes sense because they now have access to it, if you compare them to the microorganisms in frozen permafrost.

Using our molecular tools, we see not only which organisms are there, but also what pathways they’re expressing to be able to produce these gases. This is important because methane is a potent greenhouse gas and its production can amplify global warming.

One way to see into the black box that is the soil microbiome is by using “meta-omics” — a range of different biological censuses. How can each “omic” help us understand the microbes’ functions?

Each “omic” technology gives you a slightly different view. You start, on one end, by looking at the DNA in the genomes. For these types of organisms, their identity is all about the total number of genes and the type of genes they have — that’s how we know who’s there. But you don’t know if those genes are all expressed or not. The genomic view just shows you what they are potentially capable of doing.

Scientists use a repertoire of molecular techniques to paint a more complete picture of the make-up and dynamics of the soil microbiome. The concept of the metaphenome of the community arises from combining these separate analyses with information about the local environment and other factors.

If you go to the next step, you can look at which organisms are actively transcribing which genes into RNA, what’s called the transcriptome. This gives us a clue about metabolic processes that are active at a given time, and which ones are favored under different conditions.

The next step is the proteome, because not all expressed genes actually are translated into proteins. So, if you look at the proteins that’s an even better confirmation that the expressed genes are dictating the functions that were carried out in that environment, at that particular point in time.

And then, the last step in this “omic” pipeline would be the metabolome. Metabolites — the intermediate molecules of microbial metabolism — are very valuable, because detecting specific metabolites gives us clues about all the biochemical reactions that are occurring in the environment. They are the ultimate signature of the metabolic processes carried out by the microbial community.

To understand how microbes living in one particular environment change as a whole, you’re looking at something called the metaphenome. Can you describe what that is?

The metaphenome is a new concept. It’s a term that represents the combined biological functions, such as using iron for energy or carbon for growth, carried out by all the microorganisms living in a community. You can think of a single organism that has a genome and depending on the resources available or the environment, certain genes are expressed into RNA, but not all — it depends on the situation and can change over time.

If you look at the whole community, that would be a metaphenome: the product of all of those functions carried out by all the microorganisms. Studying that will allow us to predict the impact of environmental change on the microbiome, as well as think of new ways to manage our soil.

What do we know about the role of viruses and fungi in the soil?

We have a big research push right now on the soil virome — the collection of DNA and RNA from all the viruses in a given spot — and that is very exciting. We screened for hundreds and hundreds of soil metagenomes and we were able to find what types of viruses are there. Some of these viruses contain metabolic genes that could potentially help with nutrient cycling in soil.

The viruses are probably really important, and we just don’t know much about them. It is definitely a new frontier because these viruses outnumber all of the other organisms that you have in soil.

We’re also looking at fungi in grasslands, and one of the things we’re really interested in is that when the soil starts to dry, the water no longer connects different locations in the soil. The microorganisms need water to be able to exchange metabolites and interact with each other. So, in dry soils, you have these disconnected “islands” of microorganisms. But fungi can grow these long filaments, called hyphae, that can bridge these disconnected islands and serve as the train for carrying nutrients back and forth between bacteria and to other organisms in the system.

Droughts change the soil microbiome in subtle and not so subtle ways. In grasslands, for example, groups of soil bacteria normally communicate with one another by sending chemical messages through water and through fungal threads called hyphae. In a drought, however, hyphae may be the only option for communicating across long distances. Metabolic interactions within the soil community release carbon dioxide.

The soils of grasslands are another ecosystem you study. How are the microbes there faring with climate change?

I’m concerned about how climate change will affect these highly productive regions of the world, especially with increasing droughts.

Looking at the metaphenome, and the influence of the soil drying on the metagenome, we have found that the microbial community starts to shift its metabolism toward the production of metabolites that help them survive dryness, like sugars and different kinds of osmolites, molecules that help keep the cells from bursting when the soil gets dry.

The thing that really impresses me is that we can now look at a whole community and dissect what the community is doing in response to drought.

What other big questions are you trying to answer?

One of them is: How do these microorganisms across different kingdoms — the bacteria, viruses and fungi — live together in the same system and interact? We don’t know how, because most studies have looked at a single or a couple of organisms in isolation. So how are they functioning as a community? That’s one of our big questions. And then, of course, the second one is: How are these community interactions impacted by climate change or by access to different kinds of resources, like water?

Have these findings changed your view of the Earth’s soil?

I do not consider soil to be dirt, let’s put it that way. It is one of our most precious resources on the planet. Improper land management, such as over-tillage and leaving the soil barren and free of plants, is a problem because it causes erosion. And that happens at a faster rate than new soil is being formed.

We have to conserve our soils. They are alive — they carry billions and billions of microorganisms in a single gram. So, this is a living resource that we have to protect from being eroded and degraded.

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A sunny disposition isn’t just good for your mental health. It’s good for your body, too. It can even add years to your life. Sarah Pressman, a health psychologist at the University of California, Irvine, has spent her career investigating the link between positive emotions and physical health.

In the 2019 Annual Review of Psychology, she and her colleagues explore why a positive outlook generates physical health benefits. Knowable asked her about some of the high points, and how doctors and their patients can make use of the knowledge. This conversation has been edited for length and clarity.


Psychologist Sarah Pressman

University of California, Irvine

How did you get interested in studying this?

For decades, researchers have been studying all the detrimental ways that stress can make us sick and lead to pain, and minor and major illness. As a graduate student, I got interested in the opposite: What can protect our bodies against the harmful effects of stress? At that time, in the early 2000s, the field of positive psychology was really just starting. I saw a natural synergy there — there are these positive factors, and maybe they could be protective against stress and have health benefits, or at least protect us against health harm.

And does a positive outlook make a measurable difference?

The negative effect on your health of being socially isolated is stronger than the effect of being overweight, a regular smoker or a heavy drinker. That kind of comparison hasn’t been done yet in positive emotion research. But there’s a host of studies — probably in the dozens now — that show that people who are more positive tend to live usually five to 10 years longer than those individuals who are less positive. That’s a pretty large effect.

What causes this effect?

We have a lot of hypotheses. Positive emotion changes our stress perception so stressors don’t seem as bad. It changes how we react to stressors, and it helps us recover. Both our stress reaction and our stress recovery have been shown to predict important outcomes. Pick a disease — heart disease, for example. If you feel calmer, your blood pressure is lower, your heart rate is lower. And we know one of the things that predicts heart disease is arteries blocked up with plaques. And where do those plaques come from? Partially, from damage from high-speed, high-pressure blood. If your blood pressure is lower, and your heart rate is lower, you have less of that turbulent blood flow, and therefore over time you might have less damage to arteries and less plaque.

Positive emotions also change how our immune system works. We don’t know exactly how, but we do know that if I make you feel positive, if I make you feel calm, we change the numbers of your immune cells, and we tend to drop your inflammation level. For example, there’s a marker of inflammation called interleukin 6, or IL-6. People who are generally more positive, or who are induced to feel more positive, have lower levels of IL-6.

But even aside from that, when we are feeling positive, we’re much more likely to engage in healthier behavior. We take better care of ourselves, we’re more likely to sleep better and exercise, we have a better diet. People who are more positive tend to have more relationships, better-quality relationships. They’re more likely to be married and stay married for longer. If you have good relationships, those people will encourage you to take care of yourself.

That gives us some really compelling pathways for how this can happen, both on the behavioral end and by directly altering cardiovascular function, hormonal function, immune function. If I’m happy today, that doesn’t mean I’m going to live longer. But if I’m happy for a few years, that might make a difference.

How do we know that positive emotion causes better health, rather than the other way around?

To do the perfect study would require that we experimentally assign people to an intervention that makes them happier, or less happy, and see if that affects longevity. That has not been done. But we have a lot of studies of groups of people where we know the health and the emotional state of each person at the start. We control for sociodemographic factors, we control for medications and immune function. So we know that those people who were less happy at the beginning weren’t less happy because they were already more sick.

Then we can look over time. If you control for smoking and health at the start and you still see the effect of positive emotion five or 10 years later, it’s more suggestive than a study looking at people at just one point in time and just saying, “Oh, happy people feel healthier.”

In a classic study, people with a more positive outlook were less likely to get sick after experimenters introduced cold viruses into their noses. The researchers measured the volunteers’ sickness both objectively (by weighing a day’s worth of used tissues) and subjectively (by asking the volunteers if they had a cold).

Have you also done experiments?

We measured people’s naturally occurring positive emotions. Then they were experimentally wounded. It was kind of a nasty study, actually. We damaged their skin by putting tape on it over and over and ripping the tape off. We monitored to see how quickly water was being lost from the skin surface. As that water loss decreases, we know the skin cells are healing. This is really an immune-system function test, because the more quickly your immune system is able to traffic white blood cells to the injury, the faster you will heal. We saw about a 20 percent shorter healing time for those individuals who were more positive versus those who were less positive.

There is another study, not yet published, where we manipulated positive emotion. There’s something called the facial feedback hypothesis, where if you fake an emotion, it sends a message to your brain that you’re feeling that emotion. If we trick people into smiling by holding things in their mouth, it can trigger a positive emotion.

So we had people smile while getting a fake flu shot. Some people were smiling and others were not. Those who were smiling had about 40 percent less pain from that needle, and their heart rate recovered faster from the stress of it.

Do we know that positive emotions — and not just the absence of negative ones — are causing the benefit?

That we actually know really, really well. Through the last 20 years of research, almost every study does a good job of accounting for that by controlling for negative emotions.

Time and time again, you see that it really does seem to be the presence of positivity, independent of negativity, that’s driving health effects. It’s the presence of positive emotions, not the absence of negative ones, that can help undo stress. If I have to give a talk and I’m feeling neutral, that isn’t helping me — but if I can say, “Actually, I’m really excited about giving this talk,” that can change my stress trajectory. That’s very different than the absence of a negative emotion.

Are there health conditions where a positive attitude doesn’t help?

For individuals who have a serious chronic illness that’s far gone — stage 4 cancer, end-stage kidney disease — the data are inconsistent. Some studies show benefit, some show harm, some show no effect. If we’re talking about a minute immunological change from laughing, that’s not going to kill millions of cancer cells.

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On the other hand, if you are feeling hopeful and positive, and able to adhere to your doctor’s recommendations, and take the medications that you’re supposed to, and exercise when you’re supposed to, and quit smoking, those things are helped by positive emotions, and can have an important role in helping at earlier stages.

This is something we have to work on, because if people want to design positive interventions for these severe illnesses, we have to really understand when it will be helpful. That’s a really important next step for the field.

Isn’t there a risk that people with serious diseases will be stigmatized into thinking it’s their own fault for not being more positive?

We certainly don’t want to say that. There’s absolutely no evidence in health psychology that being unhappy causes cancer, or causes disease to happen. If someone gets diagnosed with cancer, you don’t want to tell them to be happy all the time. There’s good evidence that keeping negative feelings locked up inside is harmful to our health. They have to go somewhere. You have to let it out — express your negativity and process it. Once you’ve accomplished that, we can try to teach you how to find benefit.

It is very important for people to deeply understand the power of mind over body, because if you are depressed and you are stressed it can be hurting you, and we want to help you cope with that. There is value in pursuing happiness. It’s not a selfish, silly, soft thing that you don’t have to do. This is actually an important piece of being a healthy human. And at a time when your health is compromised it can be especially important.

Are there ways to change people’s happiness level? Aren’t some people innately Eeyores and others Poohs?

Some work suggests that as much as 40 percent to 50 percent of happiness is based on genetics — you just luck into being born a more positive person. But that leaves a lot of room to manipulate.

Although some people naturally tend toward a more positive or negative outlook — like Winnie the Pooh and Eeyore — studies suggest that happiness is based on much more than genetics or innate setpoints. Exercise, relationships and personally meaningful activities can help an Eeyore see the bright side, which may also impact health.


A good amount of our day-to-day wellbeing — maybe 30 percent to 40 percent — is due to how we choose to spend our time. We can choose to spend our time on things we know improve positive emotion, like spending time with the people we love, having good relationships, getting enough sleep, exercising.

But on top of that, there are some specific, well-researched interventions — little tweaks that can help you focus on positive things. We can train our brains to hang onto positive emotions, which should help promote that positive emotion in our daily lives. Some of the more popular activities are gratitude exercises, where before you go to bed you write down three things you’re grateful for, and meditation.

The nice thing about happiness is you don’t have to buy some expensive medicine. Much of this is free. Happiness is not just a luxury that rich people should be pursuing — it’s something that absolutely everyone should be investing time in every day.

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Alfalfa, oats and red clover are soaking up the sunlight in long narrow plots, breaking up the sea of maize and soybeans that dominates this landscape in the heart of the US farm belt. The 18-by-85-meter sections are part of an experimental farm in Boone County, Iowa, where agronomists are testing an alternative approach to agriculture that just may be part of a greener, more bountiful farming revolution.

Organic agriculture is often thought of as green and good for nature. Conventional agriculture, in contrast, is cast as big and bad. And, yes, conventional agriculture may appear more environmentally harmful at first glance, with its appetite for synthetic pesticides and fertilizers, its systems devoted to one or two massive crops and not a tree or hedge in sight to nurture wildlife. As typically defined, organic agriculture is free of synthetic inputs, using only organic material such as manure to feed the soil. The organic creed calls for caring for that soil and protecting the organisms within it through methods like planting cover crops such as red clover that add nitrogen and fight erosion.

But scientists bent on finding ways to produce more food globally with as little environmental impact as possible are finding that organic farming is not as green as it seems. In a simple contest of local environmental benefits, organic wins hands down. That doesn’t hold true on a global scale, though, because organic farming can’t match the high-yield muscle of big agriculture. A widespread shift to organic would leave billions hungry, researchers predict, unless farmers put more land to work by turning now-unfarmed habitats into food-producing fields — doing more harm than good to natural ecosystems.

Red clover (foreground) grows alongside corn (background) in a crop rotation experiment at Iowa State University’s experimental farm in Boone County.


“Organic farming is often seen as synonymous with sustainable farming, but it is not the Holy Grail of sustainable agriculture,” says Verena Seufert, an environmental geographer at VU Amsterdam who studies sustainable food systems. But the strategies being tested in those fields in Iowa, and similar methods finding their way onto hundreds of millions of acres of farmland globally, might just be. In experiments in Europe and across North America, agronomists are testing hybrid approaches that weave together the green touch of organic farming with a dash of chemical fertilizer and pesticide applied only when needed — an approach known as low-input agriculture. They hope that this cocktail of farming techniques will steer future farming to a truly sustainable footing.

This shift toward fusion farming comes at a time of increasing political interest in greener, more productive agriculture. Heads of state and governments will meet in September at the United Nations in New York for a summit to discuss progress toward 17 global sustainability targets to be met by 2030. Producing more food with fewer impacts is key to reaching many of these goals, which include ending hunger and slashing water pollution. That’s also in line with meeting a separate set of targets that countries party to the Convention on Biological Diversity are working toward.

Many experts worry that little progress has been made, particularly on saving biodiversity. But others are confident that a greener agricultural revolution is not far off. “It’s optimistic, but it’s not a pipe dream,” says Jules Pretty, an agroecologist at the University of Essex in the UK, who studies sustainable agriculture. “Agriculture could be at a turning point.”

And turn it must, says Andrew Balmford, a conservation scientist who studies farming’s impacts on biodiversity at the University of Cambridge in the UK. “Agriculture is by far the biggest threat to biodiversity, and that will only get worse as we try to feed 10 billion people in the future.”

Many studies show that organic farming is beneficial to biodiversity, especially for creatures like birds, spiders and some soil-dwelling insects. The effect is less pronounced for animals like butterflies. Outcomes for other critters, such as beetles, are more uncertain, with individual studies showing a breadth of effects.

Organic aims

Over the next 30 years, agricultural economists estimate, food production will need to at least double to feed billions of extra bellies as the global population grows. But the current farming system cannot carry on as it is without wreaking great damage, experts conclude. The International Union for Conservation of Nature, a science-based conservation organization, says that of the 8,500 threatened species it has studied, agriculture alone imperils 62 percent, ranging from the elegant African cheetah to California’s lovable Fresno kangaroo rat. Fertilizers running off farmland and into rivers and lakes are fueling toxic algal blooms across the world, suffocating fish and damaging ecosystems. And agriculture has its hand in around 80 percent of global deforestation.

The organic movement was sparked, in part, from similar environmental concerns in the early twentieth century. With its roots in Europe and the US, organic farming grew from the idea that soils nurtured with compost rather than synthetic fertilizers could safeguard the soil and biodiversity while producing more nutritious food. Today, organic produce is a must-have stock on the shelves of many major Western supermarkets, and organic farming is practiced in more than 180 countries, on more than 172 million acres of farmland. Although this is still just 1.4 percent of global agricultural land, land farmed organically has increased more than sixfold since 1999 and is rising.

Organic farming could easily spread further and help put more food on the global dinner table, says John Reganold, an agroecologist at Washington State University. “In many ways, organic farming is leading the way towards food security and sustainability because it is a well-recognized farming system that is economically successful — and so more farmers want to try it. I think we owe credit to organic for that,” he says. But he and many others who have studied the issue say that without a massive change in diet, organic could never grow enough food globally on existing farmland despite its demonstrated pluses.

Many studies have shown that organic farming has benefits for biodiversity on farms. For example, in an assessment comparing organic and conventional farming published in Science Advances in 2017, Seufert reported that organic farms host up to 50 percent more organisms such as bees and birds than conventional farms. They nurture greater biodiversity largely because they don’t use synthetic herbicides and pesticides, allowing plants, insects and other animals to thrive. Farm workers also benefit from lower pesticide exposure, Seufert says.

The benefits of organic farming depend a lot on what is being measured. For a variable like low pesticide residues, organic farming has clear benefits over conventional farming, as indicated by the petal extending beyond the red circle, which demarks where organic performance equals that of conventional farming. But for a variable like low nitrogen loss, organic farming’s benefit diminishes when output is assessed (right) rather than area (left).

Organic farms also take better care of soil than average conventional farms, studies show. Enriched with compost from rotted animal manure or plant matter, organic soils can contain up to 7 percent more organic matter than their chemically enhanced counterparts, according to Matin Qaim, an agricultural economist at the University of Goettingen in Germany, and colleague Eva-Marie Meemken, writing in the 2018 Annual Review of Resource Economics. Organic matter, rich in diverse microbes, is key to the health and structure of soil, helping it hold on to water and reducing erosion.

Qaim and Meemken report that, acre for acre, organic farming consumes less energy largely because it doesn’t use synthetic fertilizers. It also releases lower levels of some greenhouse gases such as carbon dioxide and methane, and leaches fewer polluting nutrients such as nitrates from fertilizers into rivers and groundwater. Organic fields are also an experimental ground for greener farming techniques, such as planting cover crops including the leguminous hay crop red clover (Trifolium pratense). Cover crops help suppress weeds and guard against erosion.

Yield is the one crucial feature where organic farming falls short, Qaim concludes. Organic yields are on average up to 25 percent lower than conventional farming yields. Some crops grow better than others under organic conditions: Legumes, which fix nitrogen from the air and thus can meet some of their own nitrogen needs, tend to produce deficits of just 10 to 15 percent. But yields of nitrogen-thirsty cereals are 21 percent to 26 percent lower on organic soils, due to limited nutrient supply as well as greater susceptibility to pest outbreaks and encroachment by weeds, Qaim says.

“The facts are not in favor of organic — the observation that organic yields are lower than in conventional practices cannot be denied,” he says.

Different crops grown in the same field at the same time can boost yields and help control weeds and pests. Here, strips of corn grow alongside alfalfa and soybeans in test plots at the US Department of Agriculture’s Agricultural Research Service Farming System project, in Beltsville, Maryland.


Small yields add up to a big problem. Switching all the world to organic would mean turning 24 percent more natural habitats into agricultural land to meet future demands, researchers calculate. Small yields also drive up greenhouse gas emissions produced by organic farming because land must stay working rather than being allowed to regularly go fallow. Organic’s land-use costs would undo much of the ecological good that organic brings locally, Qaim says.

Organic advocates, however, question the size of yield gaps reported in much of the scientific work. The Rodale Institute, an organic advocacy and research center in Kutztown, Pennsylvania, says its own work shows that under certain conditions organic farming can match or exceed conventional yields. Andrew Smith, the institute’s chief scientist, acknowledges that organic yields are overall lower. But he says they have plenty of scope to grow if greater investment is made in developing crop and animal breeds better suited to organic’s challenges, and in doing more research on best practices. Global funding for research on organic farming is less than 1 percent of that spent on conventional farming and food, according to a 2017 report from the International Federation of Organic Agriculture Movements.

Conventional farming’s failures

The researchers who conclude that organic could not feed the globe’s growing population also recognize that conventional agriculture can’t carry on as it is, either. So agronomists are doubling down on the middle road, testing a fusion of techniques where farmers use green practices topped with synthetic inputs when necessary. Many of these green techniques, such as planting cover crops and growing different crops in the same field one year to the next, were once routinely used in agriculture to manage weeds and soil health but fell out of favor after World War II when the cost of synthetic fertilizers and herbicides dropped. These methods are now making a supercharged comeback in the low-input agriculture movement.

Studies are starting to show that low-input fusion farming comes up trumps for both yields and the environment. After an eight-year experiment ending in 2016, agronomists at the universities of Minnesota and Iowa State reported promising results from three-crop rotation systems on a 22-acre experimental farm at Iowa State. The crops were switched over periods of two, three or four years and assessed for yield, profit and environmental effects such as soil erosion and nitrogen leaching into rivers and groundwater.

Average yields in the Marsden Farm crop rotation experiments are higher than that of conventional commercial farms in Boone county.

In the two-year crop rotation, researchers planted maize and soybeans in alternating years, but added a mixed crop in the three-year rotation, planting oats and red clover together for year three. They planted oats along with a different legume, alfalfa, in year three of the four-year rotation field, then let the alfalfa keep growing into the fourth year, after the oats were harvested.

The team was able to slash the input of synthetic chemicals. Researchers added fertilizers in the two-year rotation plots at rates typical of conventional farms, but used substantially less in the three- and four-year rotation plots: on average 85 percent and 91 percent less synthetic nitrogen (13 and 8 kilograms per hectare per year, respectively). The researchers added manure to boost nitrogen but it contained about half the amount of nitrogen that a full application of synthetic fertilizer supplies. They also added substantially less herbicide active ingredient to the low-input maize and soybean crops: 94.8 percent (0.06 kg/ha) and 92.5 percent (0.12 kg/ha), respectively. Herbicide application did not differ across the longer and shorter rotations.

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Yields rose as the number of rotations increased and were unaffected by the lower herbicide use in the longer rotations. On average, maize yields were 4.5 percent higher and soybean yields 25 percent higher in the three- and four-year rotations compared with the two-year rotations. The alfalfa and clover steps are key for this effect, says Matt Liebman, an agronomist at Iowa State and one of the study’s authors. “You begin to see big changes in nutrient dynamics because the hay crops like alfalfa and clover take atmospheric nitrogen and put it into the soil” for the crops that follow, he says. “So you don’t have to have anywhere near as much fertilizer.”

Problems with weeds and disease also looked somewhat better. Despite a lower use of herbicide in the three- and four-year rotations, weeds intruded equally in the two- and four-year rotation plots. And soybeans grown in the longer rotations succumbed less often to soybean sudden death syndrome, a fungal infection common to the Midwestern farm belt. “The crop rotations typically result in much more effective management of insect disease and weed pests with much lower investment in chemical pesticides because you disrupt the life cycles of many of the pests that are specialized for particular crops,” Liebman says.

Finally, the low-input, longer rotation strategies also had environmental benefits. The potential harm to freshwater ecosystems caused by the herbicide (known as toxicity load) was 99.9 percent lower in the low-input maize plots than in the conventional maize plots. And though the longer rotations required more labor, profits for all three rotation systems were similar overall.

Narrow plots of corn (m), soybeans (sb/s), oats (g), and alfalfa (a) grow at Iowa State University’s Marsden Farm where agronomists tested how crop rotations and low levels of synthetic inputs, like herbicides and fertilizers, affect yields. All three crop rotations (2-year, 3-year and 4-year) were tested in four replicate blocks (1, 2, 3, 4). The more diverse crop rotations had yields that were equal to or better than the conventional system, despite receiving fewer synthetic inputs.


Balancing yields and pollution

Other studies in Europe and across the US are reporting similar results. A meta-analysis of 15 studies done in the US, Canada, France, Sweden, Switzerland and Norway concluded that yields of maize grown under low-input conditions were equal to those produced under conventional conditions, and 24 percent higher than organic crops. Wheat yields were 12 percent lower than conventional, but 43 percent higher than organic, according to the analysis, published in 2016 in Agronomy Journal. On average, crops grown under low-input conditions received less than half the synthetic pesticide applied to conventionally grown crops and were often cultivated as part of a crop rotation that included more plant species than in conventional systems.

Agronomist Laure Hossard of the Montpellier campus of the French National Institute for Agricultural Research, a coauthor of the meta-analysis, says it’s unclear why wheat yields dropped but maize yields didn’t under low-input conditions. Perhaps wheat succumbed more to uncontrolled disease or needed more fertilizer. Still, the low-input wheat yield losses were small, and the study’s overall conclusion is that low-input farming can dramatically cut back on pesticide use without drastically harming yields.

There are some potential downsides to low-input farming, Hossard says. Money spent on pesticides and fertilizers may not always compensate for lost income from slightly lower yields. Although studies have shown that it is possible to cut pesticide use by around 30 percent without reducing farmers’ income, these calculations may vary from year to year as prices for crops and synthetic inputs fluctuate. Also, low-input crops don’t command higher prices like organic products do, so they may be less profitable than conventional products, she says.

Even as researchers fine-tune low-input strategies in experimental plots, farmers are beginning to apply these tactics in their own fields. It’s unclear how many farmers are taking on a fusion farming approach, but a survey of 2,012 farmers across the US found they are increasingly using green techniques, such as planting cover crops, and that acreage planted in cover crops nearly doubled between 2012 and 2016.

Organic crops such as corn (pictured) typically produce lower yields than their conventionally grown counterparts. That casts doubt on the ability of organic farming to feed the world’s growing population. But fusion farming techniques, which combine organic and conventional approaches, have higher yields, providing a path to feed more people while reducing environmental impacts.


And in an analysis of 400 global sustainable farming programs published last year, Pretty and colleagues  found that 47 of the initiatives are running on a large scale, meaning they are practiced on more than 10,000 farms or the same number of hectares (almost 24,700 acres) of farmland globally...

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Plant biologist Pamela Ronald is concerned with the pressing problem of feeding the world without destroying it. The question of how to grow enough food for an expanding global population has grown more urgent in the face of climate change. And it’s only made harder, she says, by the push-back against the use of the genetic tools now at scientists’ disposal.

Ronald’s views have emerged from nearly 30 years of research on how plants resist disease and tolerate stress, work that is ongoing in her lab at the University of California, Davis. Much of that work has focused on rice, a staple crop that feeds nearly half the globe. While she’s an outspoken advocate for using genetic engineering to modify crops — her TED Talk The Case for Engineering Our Food has been translated into 26 languages and watched more than 1.7 million times — she’s also married to an organic farmer, Raoul Adamchak. Together, they wrote the book Tomorrow’s Table: Organic Farming, Genetics, and the Future of Food , exploring how the best of both approaches might be needed for long-term sustainability.


Plant biologist Pamela Ronald

University of California, Davis

We spoke with Ronald about her research and her views on genetic modification and its place in the sustainable agriculture toolbox. This conversation has been edited for length and clarity.

How do genetically modified crops fit into the sustainable agriculture landscape?

Sustainable agriculture has three pillars: social, economic and environmental. It creates food that’s nutritious, it allows farmers to reduce the amount of land and water they use, to foster soil fertility and genetic diversity, and to reduce toxic inputs. And it enhances food security for the very poorest farmers and families in the world. So, for example, if you can breed resistance into a plant, whether through conventional or genetic engineering, and that means you can reduce the amount of sprayed chemicals you use, that’s part of sustainable agriculture.

Any type of agriculture is pretty challenging. Most farmers are trying to move their farm toward more sustainable approaches. Unfortunately, there’s no magic bullet because farmers in different regions of the world face different challenges, grow different crops and have different markets.

The book you and your husband cowrote is titled Tomorrow’s Table. What does tomorrow’s table look like to you?

In the book, we describe what’s on our table and explain how the foods were developed — the kinds of genetic techniques and organic farming techniques used to produce that food. We try to give the reader an idea of what geneticists do and what organic farmers do. We have a number of recipes.

But the book isn’t about nutrition, it’s about: How do we produce and provide that nutritious food with minimal environmental impacts? How do we ensure that farmers and rural communities can afford the food? How do we address this critical challenge of our time: to produce sufficient, nourishing food without further devastating the environment? There are a lot of issues, a lot of people on the globe right now, and even more in the future. They all need to eat.

Sticky “mutant” rice, included in this recipe from the book Pamela Ronald and her husband wrote, came into being more than a thousand years ago. The stickiness arose thanks to a spontaneous genetic mutation that disrupted the gene for making the starch amylose, which helps make non-sticky rice fluffy. The recipe juxtaposes that ancient genetic modification with a more modern one: genetically engineered papaya, which farmers began planting in the late 1990s after papaya ringspot virus decimated orchards.

Does your husband have a different view of the future of food?

It’s a shared view. We both think people should focus on the challenges and not get distracted by the concept of genes in our food. We really want to use all the tools that are available and use scientific-based farming practices, such as those that minimize pests and disease. There are many organic farming practices that are very useful, such as crop rotation.

It’s the combination of farming strategies and genetic strategies that are going to continue to be quite important for producing our food and moving forward to a sustainable farming future. Farming is destructive. But, as my husband says, we farm because we have to eat. Some people say, well, let’s change our diets, or reduce waste. Those are both important, but we still need technological change. All these aspects are even more critical as the population continues to grow.

A lot of your research has focused on rice, a hugely important staple crop. Did you always want to work on rice?

I was working on peppers and tomatoes as a graduate student at UC Berkeley and as I was making the transition to a postdoc, I thought, what do I want to do, because this may last my whole career. And I decided to work on rice because it feeds half the world’s people. It’s also a very good genetic system; it’s easy to do genetic analysis of rice. So I thought if we can make any kind of incremental advance we could potentially help millions of people.

One of those advances has been the development of flood-resistant rice. I’ve seen so many photos of rice paddies flooded with water, doesn’t rice tolerate flooding?

The rice plants that many of us are familiar with grow well in standing water. But most rice plants will die if they are completely submerged for more than three days. When the leaves are submerged, they can’t carry out photosynthesis. My UC Davis colleague David Mackill was working with this ancient variety of rice, discovered at the International Rice Research Institute, that could be completely submerged in water for two weeks, and then can start to grow again when the water is removed. So this was very, very exciting.

Breeders then tried to use conventional breeding to introduce this trait from the ancient variety into varieties grown by farmers. But when you cross-pollinate with another variety, even though it has a nice trait, you can bring a lot of other traits you don’t want. So, the result from conventional breeding were rice varieties that were rejected by farmers because they had traits that the farmers did not want such as reduced yield, or a change in the texture of the rice grain.

How did you tackle the problem?

First, we carried out the initial work of isolating the flood-tolerance gene, called Sub1a, from the ancient variety. Then we introduced the gene into a model rice plant using genetic engineering. We then grew up those plants and submerged them, in large tanks in our greenhouses for two weeks.

The plants that carried the Sub1a gene were very robust; you could see the difference right away. Plants without Sub1a turned yellow, had very long leaves and soon died. This is because when the leaves try to grow out of the water, they deplete their chlorophyll content and energy reserves. But the plants that carry the Sub1a gene just stay kind of metabolically inert — they don’t grow very fast, they just kind of wait out the flood. And when the flood’s gone, they start to regrow. The Sub1 plants remained green and healthy, indicating we had indeed isolated the correct gene.

Is Sub1 rice now being grown by farmers?

Yes. As I described we used genetic engineering tools to isolate and validate the submergence-tolerance gene in the greenhouse. That genetic knowledge was then used to develop a flood-tolerant variety through a different approach called marker-assisted breeding. That work was done by the International Rice Research Institute. The ancient, flood-tolerant variety was cross-pollinated with a modern variety that farmers like because of its flavor and high yields. Seeds derived from those hybrids were planted, and tested for the preferred genetic fingerprint that included Sub1a but did not carry genes from the ancient variety that affected traits important to the farmers.

Rice bred to contain the Sub1a gene can survive even when completely submerged for 17 days. This flood-tolerant rice yielded 3.8 tons per hectare (pile on left), compared with 1.4 tons per hectare for the same variety lacking the flood-tolerant gene (pile on right).


Marker-assisted breeding is very focused, you don’t drag in genes that you don’t want, you can just drag in a very small region of a chromosome. And because the genetic fingerprint can be determined at the seedling stage, it saves a lot of time and labor that would normally be spent on submerging hundreds of plants.

Farmers have now been growing Sub1 varieties for several years. In 2017, more than 5 million farmers grew it. Sub1 rice is disproportionately benefiting the poorest farmers in the world, who often have the most flood-prone land. Compared with conventional rice varieties, farmers growing Sub1 rice are able to harvest three- to fivefold more grain after floods. The Intergovernmental Panel on Climate Change predicts that flooding will become more frequent and last longer as the climate changes.

These various breeding approaches underscore the difficulty in defining “genetically modified” crops. How do you define them?

The term “genetically modified” is scientifically meaningless, and so it’s not useful. The FDA does not use the term.

With Sub1 rice, for example, scientists can introduce the Sub1a gene with either genetic engineering or marker-assisted breeding. In each of these cases, the genetic region that’s introduced is smaller than the huge number of genes that you bring in with conventional breeding, in which you are mixing two genomes together.

Grafting is another kind of conventional breeding that mixes two genomes. There are a lot of grafted varieties on farms in California. The walnuts harvested in California are actually a graft of two different species where the rootstock is a different species than the top part of the plant. Then there are foods that we eat that have been developed through radiation and chemical mutagenesis, like grapefruit. Those approaches create many random uncharacterized changes in the genome and are not regulated. They can also be sold as “certified organic.”

What do you think most consumers mean when they say genetically modified organism or GMO?

I think some consumers are concerned only about plants engineered to contain genes from another species, like the bacterial Bt gene. It sounds a little strange to put bacterial genes into a plant, but it is important to consider the risks versus the benefits. Organic farmers spray Bt to prevent insect damage to their crops. It is safe to use. But spraying Bt is not always effective. In Bangladesh, for example, there is an insect that can destroy an entire eggplant crop and spraying doesn’t keep the insect from getting into the plant. And the Bt sprays are expensive and difficult to get. So Bangladeshi and Cornell scientists engineered eggplants with the bacterial gene so that the plants produce the Bt organic insecticide in the crop. And it’s been tremendously successful over the last five years, allowing farmers to reduce their insecticide sprays dramatically.

Among the challenges to feeding the world’s growing population is crops lost to disease. Developing rice strains that can resist infection by the extremely destructive rice blast fungus (spores shown) is an active area of research.


One reason that the FDA and many scientists don’t find the term “GMO” useful is because it means different things to different people. You can’t really compare an eggplant engineered for farmers in Bangladesh that has allowed them to reduce insecticide use to, say, the “Golden Rice” plants engineered to have higher amounts of provitamin A to help save the lives of children in developing countries, or herbicide-tolerant canola grown in developed countries. These are different traits, different crops, and different people benefit.

Why do you think there is so much distrust of modern genetic approaches?

I think part of the issue is that less than 2 percent of people in the US are farmers and are somewhat removed from food production. Many people aren’t familiar with the challenges faced by farmers and may not understand that Bt crops have massively reduced the use of insecticides in the US and globally. The World Health Organization estimates that 200,000 people die every year from misuse or overuse of insecticides, primarily in less developed countries.

The use of genetic technologies has become very politicized like several other issues in science — vaccines, climate change. The major scientific organizations have concluded that the climate is changing, that vaccines can save lives, and that genetically engineered crops are safe to eat and safe for the environment.

I think most of us know someone who has been very sick and we would do anything to help them. Often that means using a genetically engineered drug. Or maybe we know someone with diabetes who uses genetically engineered insulin. We accept that use of the technology, most consumers accept it, because they have some understanding of it in their own world. But I think very few Americans have seen a malnourished Bangladeshi kid, so it’s not in their world. It’s not that they aren’t compassionate, it’s that at some level they don’t understand or see it. They don’t really understand why farmers need genetically improved crops.

I think people understand with computer technology that there are different applications of that single technology. People wouldn’t say “computers are bad.” But somehow it gets confusing to people when it comes to agriculture, maybe because so many of us are so removed from actual farming. 

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A frog the size of a fingernail. A poncho-clad farmer leading his mule. A tree, some intertwining leaves, a silhouetted figure holding a pot. Such logos are stamped on labels of coffee, cocoa, mangoes, jeans and myriad other products, certifying that the object for sale is in some way “sustainable” — made, in other words, in a way that meets humanity’s needs without jeopardizing the ability of future generations to meet their own.

The idea of sustainable economic development was first proposed in the 1980s, when a commission established by the United Nations concluded that human activities were exhausting natural resources and launched efforts to tackle the problem. The concept spans three dimensions: social (for example, ensuring workers are treated fairly), economic (increasing profits, improving quality of life) and environmental (managing land, water and biodiversity so they aren’t lost to future generations). And over the years, a slew of standards that focus on these dimensions in different ways have been implemented by nonprofits and multinational companies.


Environmental scientist Eric Lambin

Stanford University

Consider coffee farms. The Rainforest Alliance standard (that little green frog) requires coffee farmers to increase tree cover on their plantations and ensure fair treatment of workers, among other things. Fair-trade certificationsthere are a variety, with logos of leafy yin-yangs, dancing figures and more — require farmers to use water efficiently, prohibit bonded labor and offer safe working conditions. The Smithsonian Migratory Bird Center’s Bird Friendly certification checklist requires a coffee farm to have at least 10 different tree species and at least 40 percent of the plantation covered in shade. Farmers who comply can then sell their certified products at a higher price.

These efforts have led to a deluge of more than 400 ways to certify various goods and services — and much confusion for those consumers who want to choose responsibly. (At my local grocery store, I couldn’t find a single package of coffee without one of these many symbols, or at least the word “sustainable,” printed on it.) What’s more, the data are still unclear on which certifications truly make a product better for the planet or for farmers, says environmental scientist Eric Lambin of Stanford University and the Catholic University of Louvain, who co-authored an article on the topic in the 2018 Annual Review of Environment and Resources.

Lambin says that one thing is clear: Certifications are most likely to work when, in addition to consumers following through on their green intentions by buying certified products, nonprofits put significant muscle into the effort and governments offer their support. This conversation has been edited for length and clarity.

Why are there so many different ways for a product to get certified as sustainable?

In the 1980s, it was largely thought that sustainability objectives would be achieved via government policies that would mandate certain basic sustainability practices. Over the years it became clear that most states — especially developing countries — were not able to do this effectively because they had other priorities and limited capacity. This whole realm of voluntary sustainability standards emerged when private actors, such as non-governmental organizations, various societies and private companies, stepped in. The goal at that stage — was to achieve “governance without government,” a slogan at the time.

This history explains why each certification emerged independently, rather than in an organized fashion. The traders or a local non-governmental organization might start an initiative to make timber or coffee production more sustainable. Someone else might look at golf courses, or water consumption. A lot of these certifications are specific to one commodity, or to a place, such as the tropical rainforest. It’s an uncoordinated, sort of free-market approach.

Sustainability standards can emerge from a number of different routes and players. Variables include who sets the standards, such as an NGO or private company, and who verifies compliance: the firm who set the standard (first party), a party associated with the firm (second party), or an independent group (third party).

Is it useful to have so many standards?

Yes and no. Some level of competition forces standards to demonstrate effectiveness. But too much duplication leads to wasted resources in terms of transaction costs, manpower, verification work, fundraising and advertising.

The other problem is that when you have many organizations that do exactly the same thing, one of them might create a very easy sustainability certification that anyone can get because it doesn’t require much change. And that leads to a race to the bottom. But some do try to be more effective and demonstrate real impact.

Are some standards emerging as clear winners?

We are only starting to have reliable evidence on this. Until four or five years ago, most studies trying to evaluate the impact of the standards were not sufficiently rigorous. Even now, the evidence is still very mixed.

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For example, we found that in one province of Colombia, coffee farmers who were Rainforest Alliance–certified planted more trees on their farms compared to neighbors who were not certified. We also noticed that these farmers’ children had studied more years at school than the kids of their neighbors who were not certified. There was a significant difference between the two groups.

It turned out that because a farm must meet 90 criteria to receive the certification, many of these farmers, who were not literate, were quite happy to keep the kids at school for a few more years so they could help with the administrative work of reading forms and filing reports to get certified. In this way, the certification provided more than just environmental benefits — it provided social and potentially economic benefits, too. When kids get a few additional years of schooling, it has a positive impact — not just on farming, but also on job opportunities and innovation.

But when another research group studied coffee certification in Honduras, they came up with slightly different results: While few Rainforest Alliance–certified farmers were expanding their fields into forests, farmers certified by Fairtrade, UTZ and 4C were still causing deforestation.

Growing coffee under a tree canopy, as shown here in Nicaragua, benefits farmers and is more environmentally friendly than coffee grown in open fields.


Why the difference?

Mostly because the social and policy context in Honduras is different. Also, these studies are done by different teams, and we use slightly different methods and definitions, making it tough to compare results. In Honduras, they surveyed farmers to ask about forest clearing but not about tree planting, whereas in Colombia, we used satellite data to find out. The field is only starting to adopt a systematic approach to compare and evaluate the effectiveness of eco-certification.

But these nuanced findings led me to look beyond evaluating the effectiveness of a single standard. In more recent work, we have found that these sustainability certification standards become clearly successful and transformative when they are supported by, or get integrated into, public policy.

How does a voluntary certification become public policy?

Here’s an example: Bolivia was reforming its forestry code a few years ago. A few forest concessions [public lands that timber companies lease from the state for wood extraction] were eco-certified under the label of the Forest Stewardship Council (FSC), and they were more productive and profitable. So the government decided that rather than write a forestry code from scratch, they would reuse entire segments of the FSC guidelines as the new code.

Suddenly this certification system that was purely voluntary was now public policy.

Large multinational companies also contribute to such upscaling. For example, a company such as Unilever might say that by 2020 or 2030, they commit to completely eliminating tropical deforestation from their supply chain. That means the property of every producer from whom they buy palm oil has to be deforestation-free. With a large company, that’s a significant proportion of the global palm oil production.

But then how does the multinational meet that goal? They might try to implement a change by mandating a certification by the nonprofit Roundtable on Sustainable Palm Oil (RSPO) for all their palm oil suppliers. So now suddenly every producer who wants to sell to Unilever has to be RSPO-certified. Again, you have this powerful upscaling mechanism of a voluntary certification system. And that’s when you start to have a big impact.

It’s almost as if the idea of governance without government doesn’t really work.

Exactly — and for another reason that’s even more fundamental. One of the reasons the Rainforest Alliance coffee certification was successful in Colombia, or RSPO for palm oil is more likely to work in the Sabah state in Malaysia, is because these governments made sustainability a goal with a range of supportive policies.

At a palm oil plantation in Malaysia, workers transport fruit by hand to trucks at the ends of rows of trees. This plantation is certified by the Roundtable on Sustainable Palm Oil, a nonprofit organization that develops and implements global standards for sustainable palm oil.


In Colombia, for example, the Colombian Coffee Growers Federation supported cooperatives of producers to help smallholders meet sustainability standards. These cooperatives then promoted new varieties of plants, introduced technology and explained the benefits of certification to farmers. The government also worked to develop an export market, boosting the reputation of — and demand for — Colombian coffee as this high-quality, eco-certified coffee.

These supportive policies are necessary for a certification system to succeed. It’s not just that you need the government to upscale a voluntary certification, it’s that government intervention is necessary to make efforts successful in the first place, beyond the most progressive producers.

Do consumers also contribute to the success of sustainability efforts?

Commodities that have a consumer-facing aspect tend to be certified more often than ones that are processed and integrated into other products.

For example, you or I make an individual decision to buy this pack of coffee or chocolate over another one, perhaps based on packaging marked with a “certified sustainable” label. For these products, there’s a very short supply chain linking the producer to you, the consumer. So the pressure from the consumers on retailers — and therefore on the whole supply chain — is much more direct, and there’s a greater incentive for producers to make this claim of sustainability.

The products that sport these seals have been manufactured in ways that are considered sustainable from an economic, environmental or social standpoint, but measuring the success of these certification programs is difficult and the labels can be confusing for consumers.

But that’s not the case for other types of products. Take palm oil, for example — about half the goods that you find in a supermarket have some palm oil in them. It’s in your shampoo, your biscuits, your soap, etc. But you never go and buy a bottle of palm oil. Because it’s just one of many ingredients in a product, it’s difficult to check whether the palm oil has been certified. So there’s also less direct consumer pressure on companies to improve their standards.

Can consumers play a part in improving the standards?

Yes, it’s a combination of consumers and non-governmental organizations. Consumers often have a very poor understanding of the nitty gritty of a certification. But large companies conduct marketing campaigns, and the companies clearly sense that, at least in Europe and North America, there is a new wave of consumer demand for sustainably produced items.

In the past, companies would decide that external certification standards were too stringent, and come up with a much weaker, internal standard to call themselves sustainable. But now a number of studies have shown that this kind of “greenwashing” is penalized by consumers. [Editor’s note: See, for example, this study on greenwashing, another one on greenwashing and hotels, and a third on how consumers perceive corporate attempts at greenwashing.] If a company makes a big sustainability claim, and then a non-governmental organization, scientist or investigative journalist demonstrates the claim was bogus, the company’s reputation is damaged much more severely than if it made no claim whatsoever. [Editor’s note: See this article on the Volkswagen emissions scandal.]

Pressure is especially effective when the supply chain is very concentrated, meaning a few companies hold a large market share. For example, five large companies control about 90 percent of the global trade in palm oil. When it’s that concentrated, consumers and nonprofits can campaign hard, name and shame the companies into taking action on sustainability, like Greenpeace has been doing with Nestlé, Unilever and more. Companies tend to quickly adopt sustainability standards just to protect their reputation among consumers.

What are some choices or actions consumers can take to support sustainability efforts?

Just buying certified products and pushing for more stringent standards helps. Consider coffee: Only 25 percent of the coffee that’s produced under some certification label is sold with a certified label. The rest is just sold as conventional coffee with no price premium, which suggests that consumer demand still doesn’t match production. In surveys, consumers say sustainability is very important to them, but studies of actual market behavior show that their purchasing of certified products is still very low. They don’t translate the preferences they express into actual buying decisions.

It’s really a paradox. Think about it, these smallholder coffee farmers in remote areas are quite poor. They make all the effort to comply with 90 different criteria and get audited every year. It’s a lot of work. And if there’s little consumer demand for certified coffee, the price premium for producers decreases over time. In our Colombia study, for example, the price premium decreased from 20 percent to 2 percent above the price of conventional coffee, and some farmers were abandoning the certification because it was too much work for 2 percent more income.

And most coffee or chocolate consumers are wealthy people in rich countries. All that’s needed is for them to take a second, check on the package whether the product is certified, and pay a few extra cents for it. And too few of them do it.

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Rod Serling knew all about dimensions.

His Twilight Zone was a dimension of imagination, a dimension of sight and sound and mind, a dimension as vast as space and timeless as infinity. It was all very clear except for the space and time part, the dimensions of real life. Serling never explained them.

Of course, ever since Einstein, scientists have also been scratching their heads about how to make sense of space and time. Before then, almost everybody thought Isaac Newton had figured it all out. Time “flows equably without relation to anything external,” he declared. Absolute space is also its own thing, “always similar and immovable.” Nothing to see there. Events of physical reality performed independently on a neutral stage where actors strutted and fretted without influencing the rest of the theater.

But Einstein’s theories turned Newton’s absolute space and time into a relativistic mash-up — his equations suggested a merged spacetime, a new sort of arena in which the players altered the space of the playing field. It was a physics game changer. No longer did space and time provide a featureless backdrop for matter and energy. Formerly independent and uniform, space and time became inseparable and variable. And as Einstein showed in his general theory of relativity, matter and energy warped the spacetime surrounding it. That simple (hah!) truth explained gravity. Newton’s apparent force of attraction became an illusion perpetrated by spacetime geometry. It was the shape of spacetime that dictated the motion of massive bodies, a symmetric justice since massive bodies determined spacetime’s shape.

“The emergence of spacetime and gravity is a mysterious phenomenon of quantum many-body physics that we would like to understand.”

Brian Swingle

Verification of Einstein’s spacetime revolution came a century ago, when an eclipse expedition confirmed his general theory’s prime prediction (a precise amount of bending of light passing near the edge of a massive body, in this case the sun). But spacetime remained mysterious. Since it was something rather than nothing, it was natural to wonder where it came from.

Now a new revolution is on the verge of answering that question, based on insights from the other great physics surprise of the last century: quantum mechanics. Today’s revolution offers the potential for yet another rewrite of spacetime’s résumé, with the bonus of perhaps explaining why quantum mechanics seems so weird.

“Spacetime and gravity must ultimately emerge from something else,” writes physicist Brian Swingle in the 2018 Annual Review of Condensed Matter Physics. Otherwise it’s hard to see how Einstein’s gravity and the math of quantum mechanics can reconcile their longstanding incompatibility. Einstein’s view of gravity as the manifestation of spacetime geometry has been enormously successful. But so also has been quantum mechanics, which describes the machinations of matter and energy on the atomic scale with unerring accuracy. Attempts to find coherent math that accommodates quantum weirdness with geometric gravity, though, have met formidable technical and conceptual roadblocks.

At least that has long been so for attempts to understand ordinary spacetime. But clues to a possible path to progress have emerged from the theoretical study of alternate spacetime geometries, thinkable in principle but with unusual properties. One such alternate, known as anti de Sitter space, is weirdly curved and tends to collapse on itself, rather than expanding as the universe we live in does. It wouldn’t be a nice place to live. But as a laboratory for studying theories of quantum gravity, it has a lot to offer. “Quantum gravity is sufficiently rich and confusing that even toy universes can shed enormous light on the physics,” writes Swingle, of the University of Maryland.

A strange type of spacetime with unusual curvature known as anti de Sitter space, illustrated here, is nothing like the universe we live in, but could nevertheless provide clues to the quantum processes that may be responsible for producing ordinary spacetime.


Studies of anti de Sitter space suggest, for instance, that the math describing gravity (that is, spacetime geometry) can be equivalent to the math of quantum physics in a space of one less dimension. Think of a hologram — a flat, two-dimensional surface that incorporates a three-dimensional image. In a similar way, perhaps the four-dimensional geometry of spacetime could be encoded in the math of quantum physics operating in three-dimensions. Or maybe you need more dimensions — how many dimensions are required is part of the problem to be solved.

In any case, investigations along these lines have revealed a surprising possibility: Spacetime itself may be generated by quantum physics, specifically by the baffling phenomenon known as quantum entanglement.

As popularly explained, entanglement is a spooky connection linking particles separated even by great distances. If emitted from a common source, such particles remain entangled no matter how far they fly away from each other. If you measure a property (such as spin or polarization) for one of them, you then know what the result of the same measurement would be for the other. But before the measurement, those properties are not already determined, a counterintuitive fact verified by many experiments. It seems like the measurement at one place determines what the measurement will be at another distant location.

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That sounds like entangled particles must be able to communicate faster than light. Otherwise it’s impossible to imagine how one of them could know what was happening to the other across a vast spacetime expanse. But they actually don’t send any message at all. So how do entangled particles transcend the spacetime gulf separating them? Perhaps the answer is they don’t have to — because entanglement doesn’t happen in spacetime. Entanglement creates spacetime.

At least that’s the proposal that current research in toy universes has inspired. “The emergence of spacetime and gravity is a mysterious phenomenon of quantum many-body physics that we would like to understand,” Swingle suggests in his Annual Review paper. Vigorous effort by several top-flight physicists has produced theoretical evidence that networks of entangled quantum states weave the spacetime fabric. These quantum states are often described as “qubits” — bits of quantum information (like ordinary computer bits, but existing in a mix of 1 and 0, not simply either 1 or 0). Entangled qubits create networks with geometry in space with an extra dimension beyond the number of dimensions that the qubits live in. So the quantum physics of qubits can then be equated to the geometry of a space with an extra dimension. Best of all, the geometry created by the entangled qubits may very well obey the equations from Einstein’s general relativity that describe motion due to gravity — at least the latest research points in that direction. “Apparently, a geometry with the right properties built from entanglement has to obey the gravitational equations of motion,” Swingle writes. “This result further justifies the claim that spacetime arises from entanglement.”

Still, it remains to be shown that the clues found in toy universes with extra dimensions will lead to the true story for the ordinary spacetime in which real physicists strut and fret. Nobody really knows exactly what quantum processes in the real world would be responsible for weaving spacetime’s fabric. Maybe some of the assumptions made in calculations so far will turn out to be faulty. But it could be that physics is on the brink of peering more deeply into nature’s foundations than ever before, into an existence containing previously unknown dimensions of space and time (or sight and sound) that might end up making The Twilight Zone into Reality TV.

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Call it the body’s postal system. Cells package goodies into little envelopes made of membranes. Then these packages cruise the bloodstream — billions of them in every milliliter of blood — to recipient cells far and near, delivering freight such as genetic material and proteins.

These little bubbles, known as extracellular vesicles, or EVs, tell the receiving cell to change its biology, with far-reaching consequences, potentially influencing how we learn, the timing of childbirth, where diseases like cancer spread to, and more.

Scientists first caught a glimpse of EVs in the 1940s, and when researchers studied them in more detail in the 1980s, they thought they were looking at mundane cellular trash bags. Then, a couple of decades later, a team of interdisciplinary researchers discovered that tumors send EVs to distant tissues, laying the groundwork for cancer to take hold in new places. Today, scientists are finding that the messages EVs deliver are important in multiple sites around the human body, both in health and sickness. Cells of animals and plants, protozoans and fungi, and even bacteria release EVs, mailing their messages to other organs or other creatures they’re interacting with.

The cellular packages called exosomes have membranes studded with various sets of proteins, fats and other particles (center). Ranging from 30 to 100 nanometers across, exosomes travel to distant cells in a variety of body fluids.

EVs are a mixed bag; scientists are still finding new varieties and figuring out how to categorize them. Different types originate in different cellular packaging plants. They vary in size from 20 to 1,000 nanometers, or up to about one-thousandth of a millimeter. On the smaller side, types called exosomes are created inside specialized cellular factories and then exported. Others that pinch off from a cell’s own membrane are called microvesicles or ectosomes, and tend to be larger.

The contents vary too, but one frequent cargo is small molecules of RNA — snippets of genetic material that can turn genes on or off in the cells they are dispatched to.

In many cases, scientists are just starting to figure out how the cells that send out EVs package their specific cargoes, what those cargoes are and how the EVs influence the cells where they end up. Medical applications are under investigation too, by companies like Codiak BioSciences, ReNeuron, Exosomics and Exosome Sciences. Specific EVs found in body fluids might help doctors diagnose diseases, for example, and lab-created EVs might package and deliver drugs to therapeutic targets.

Here’s a taste of some of the things that EVs do — and how scientists could harness them for novel purposes.

EVs known as exosomes are generated in a special cellular depot called the multivesicular body and sent out for delivery to recipient cells, which can take up the contents or the entire vesicle and use the proteins or genetic material inside.

EVs in cancer: A tool for tracking

David Lyden, a cancer biologist at Weill Cornell Medicine in New York, studies how cancer spreads from one tumor to other parts of the body — say, when a melanoma in the skin sends out cells to set up shop in the lungs and form a secondary malignancy.

Working with mice that had melanoma, Lyden and colleagues first used a technical trick to tag blood cells and tumor cells so they glowed green and red, respectively. Observing the mice over time, they noticed that the green blood cells got to the lungs before the red tumor cells arrived there, findings reported in Nature in 2005. Moreover, as described in 2012 in Nature Medicine, the team saw tiny red specks joining those blood cells early on, indicating that the tumors were sending in EVs to prepare the area. EVs seem to build up blood flow, change immune responses and remodel the environment outside cells to better support the incoming cancer cells.

Cells from mouse connective tissue take up human-derived EVs (green) and concentrate them around the nucleus (blue); part of the cellular skeleton (red) is also visible. Many cells in the body make EVs, including tumor cells, so tracking the spread of EVs could help with the targeting of cancer therapies.


The team also analyzed EVs extracted from the blood of people with advanced melanoma. They discovered that EVs from tumors carried a complement of proteins, fats and genetic material entirely distinct from vesicles coming from healthy tissues.

EVs could help doctors diagnose and track cancer, as well as predict if it will spread. One of Lyden’s collaborators, Johan Skog, cofounded Exosome Diagnostics, a company that has developed urine and blood tests for cancer-derived vesicles. For example, if patients have tumors removed but still have cancer EVs in their blood, it would suggest there’s still some cancer around, sending out seeds for its next move. The patients could then receive more aggressive treatment.

EVs from parasites: Preparing a niche?

Trypanosomes are slug-shaped protozoans that cause African sleeping sickness. Transmitted by the bite of the tsetse fly, they cause fevers, rashes and anemia, followed by seizures, personality changes and daytime sleepiness as the illness worsens.

Trypanosomes have tail-like structures, but scientists didn’t think much about those tails until recent work by the lab of Stephen Hajduk, a biochemist at the University of Georgia in Athens. “They actually look like beads on a string,” Hajduk says. When the beads reach the end of the string, they pinch off and float away as EVs called ectosomes, Hajduk’s group reported in the journal Cell in 2016.

A super-resolution microscope image of three trypanosomes, the cause of African sleeping sickness. The parasites may use EVs to prepare their favorite body niches for invasion.


Hajduk isn’t sure what the EVs do for the trypanosomes in infected people, but he thinks they act much like tumor EVs, preparing far-off regions of the body for future colonization, in this case by the parasite. To nail down that theory, he’s working in mice to see if the ectosomes reach sites where trypanosomes like to settle: the reproductive organs, fat tissue and the brain. He’s also collaborating with the US Centers for Disease Control and Prevention to use trypanosome EVs as a potential means to diagnose sleeping sickness.

EVs may also explain why trypanosomes cause anemia. The researchers found that the ectosomes fuse with red blood cells, making their membranes less flexible. Immune cells, scouting for broken-down old blood cells, recognize this membrane rigidity as a sign of aging and clear the cells away.

EVs on your mind: Sharing memories

The brain has its own EVs. At the University of Utah in Salt Lake City, neuroscientist Jason Shepherd studies a gene called Arc, which carries instructions for a protein that’s key for long-term memory. His team reported in Cell in 2018 that this Arc protein assembles to form containers similar to the shells of viruses. Once assembled, these structures pop out of nerve cells, picking up a membrane coat along the way.

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“This was a real surprise,” recalls Shepherd. He wasn’t expecting a gene in nerve cells to make something that looked like a virus. “It’s kind of a crazy biology.”

The team also found that these Arc EVs carry RNAs inside them — ones bearing instructions to make the Arc protein itself, and perhaps others — that seem to be used by the cells that take them up. Given Arc’s known function in memory and the ability of EVs to transfer materials from cell to cell, he suspects that the Arc-based EVs help nerve cells communicate with each other so that memories can form.

Shepherd is also investigating other, unshelled, EVs in the brain. These can cause problems, too, in diseases such as Alzheimer’s and Parkinson’s, where cells fill up with toxic, malformed proteins. “The garbage disposal is sort of blocked, or it can’t work anymore,” Shepherd says. EVs may then carry the dangerous proteins from cell to cell, across the nervous system, bringing the disease along with them.

EVs in a glass of milk: They do a body good

The average American drinks 17 gallons of milk every year, and it’s packed with cow exosomes that have the potential to make their mark on human biology. Janos Zempleni, director of the Nebraska Center for the Prevention of Obesity Diseases at the University of Nebraska-Lincoln, and colleagues described the exosome component of milk in 2019 in the Annual Review of Animal Biosciences. In one study, Zempleni tested the blood of people after they drank milk and found cow RNAs there. The group reported in 2014 in the Journal of Nutrition that some of these RNAs control a human gene involved in making bone cells. So it’s possible they could influence skeletal growth.

Zempleni went on to genetically engineer mother mice so they couldn’t make milk exosomes. Their nursing pups weighed 25 to 30 percent less than pups getting exosome-loaded milk, he says.

Many milk exosomes end up in the brain, where they appear to influence thinking. Mice on a low-exosome diet can take up to twice as long to find the exit to a maze, compared to ones fed exosomes, Zempleni’s team reported in the FASEB Journal in 2017. “They really have a very, very poor performance in any test related to spatial learning and memory,” he says — though the mice do catch up in mental skills as they grow.

Incorporating a fluorescent tag into genetic material allowed researchers to follow the fate of glowing exosomes delivered via breast milk from mother mice to their pups’ organs, such as the brain and liver (left). Organs from a control mouse pup, without such genetic tagging, are also shown (right).


So what does this mean for the human infant diet? Zempleni and other researchers have tested formulas made from either soybean or cow milk proteins, and neither contained many exosomes, he says. Still, he suspects that children in developed nations get such rich nutrition that any exosome deficiency doesn’t make much of a difference to long-term brain development. But a lack of exosomes might be a problem for children in developing nations.

EVs in pregnancy: Bringing babies to term

Speaking of babies, exosomes have key roles in childbirth as well.

At the University of Texas Medical Branch in Galveston, reproductive biologist Ramkumar Menon is trying to understand how the fetus signals to the mother that it’s time to come out.

The membranes surrounding a fetus begin to age as the end of term approaches. They release exosomes, filled with cellular garbage, that incite inflammation in the mother.

Those junk-filled exosomes are enough to cause labor, Menon’s team reported this year in Scientific Reports. In mice, pregnancy lasts for 19 to 20 days. The researchers collected exosomes from the blood of mice that had been pregnant for 18 days — close to term — and injected them into mice that were 15 days pregnant. “And boom, they went into preterm labor,” typically delivering a day or two earlier than normal, Menon says.

Menon hopes that this work could lead to exosome-based tests for women at risk for preterm labor, or treatments to prevent preterm birth.

EVs in your heart: Delivering the goods

Cardiologist and researcher Eduardo Marbán also has treatments in mind: He wants to repair people’s tickers after heart attacks. He hoped that stem cells — blank-slate cells that can develop into a broad variety of tissues — would be able to rebuild heart muscle. And indeed, cardiac stem cells did help build up heart tissue after scientists in Marbán’s lab, at Cedars-Sinai Medical Center in Los Angeles, induced heart attacks in mice.

But when the researchers looked more closely, in a 2011 study in the journal Circulation, they saw that most of the stem cells disappeared within weeks, though the benefits lasted months. The timing wasn’t adding up. The team eventually figured out, and noted in Stem Cell Reports in 2014, that the stem cells released EVs containing RNAs that helped heart muscle and blood vessels grow. Based on these and other results, Marbán cofounded a company, Capricor Therapeutics, to develop exosomes as delivery vehicles for medicines. He and his Capricor colleague Ahmed Ibrahim summarized the state of exosome research in the cardiovascular system in the Annual Review of Physiology in 2016.

Scientists envision using EVs derived from stem cells as medicine-delivery vehicles. Large quantities of ready-to-use vesicles could be used to treat any patient (top), or EVs could be harvested from specific patients, their contents customized and then delivered back to that patient (bottom).

In another recent study in Stem Cell Reports, Marbán’s group used EVs to treat heart failure in mice engineered to mimic the muscle-wasting disease Duchenne muscular dystrophy. Not only did the EVs help the heart work better, they also helped skeletal muscles.

EVs loaded with therapeutic cargos would be much easier to use as a treatment than stem cells, Marbán says. They could deliver RNAs, genes, proteins —whatever scientists load them with. Unlike most stem cells, the EVs can be freeze-dried for convenient storage. And they can cross into the brain, making them potential delivery trucks to treat neurological conditions such as Alzheimer’s.

EVs in plants: Killing invaders

Plants make EVs, too. They appear to use them for defense, fighting off fungi and bacteria.

Roger Innes, a plant biologist at Indiana University in Bloomington, has collected EVs from the leaves of Arabidopsis, a relative of mustard and broccoli that scientists often use in the lab. The EVs were full of proteins that plants manufacture to respond to infections and other stressful situations, Innes and his student Brian Rutter reported in the journal Plant Physiology in 2017.

These EVs stick to fungi, and the fungal cells take them up. That can be a fatal mistake, because some of the cargoes seem to comprise a two-part anti-fungus poison. Innes has evidence that some EVs contain chemicals called glucosinolates, which are harmless on their own. Other EVs hold enzymes that act like molecular scissors, slicing those glucosinolates in half. That slicing produces a killer molecule that prevents fungal cells from making energy, so they die. (Glucosinolates are also responsible for the characteristic odor of plants like mustard and broccoli.)

To take advantage of plant EVs, scientists might engineer them to carry small RNAs that would improve crops’ resistance to pests and disease, Innes says. He also sees applications for plant EVs in medicine, because animals can take up EVs from the plants they eat. He thinks it would be easier and cheaper to engineer plants to make therapeutic EVs, and to grow entire fields full of medicinal crops, than to make drug-toting EVs in a lab.

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But before we get to enjoy salads laden with beneficial EVs, scientists have a long way to go. Researchers don’t fully understand how cells shunt specific cargoes into EVs as they’re made. In many cases, they still don’t know what those cargoes are, and how they influence the cells that receive and open the packages.

Another major mystery is how these vesicles are addressed so they’re delivered to the right cell recipients. Researchers do know that some exosomes are studded with proteins that hook up with ones on the membranes of target tissues. To create therapeutic EVs, Marbán and others are working on ways to put artificial addresses on the vesicles, modifying their membranes so they find the right place in the body.

Though EV research is just getting started, it has already built a picture of a bloodstream packed with letters and packages of diverse sizes bobbing along in the flow, somehow finding their addressees amid the chaos. It’s like the most hectic post office on the day before Christmas — all day and all night, all over our bodies.

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In the murky darkness, blue and green blobs are dancing. Sometimes they keep decorous distances from each other, but other times they go cheek to cheek — and when that happens, other colors flare.

The video, reported last year, is fuzzy and a few seconds long, but it wowed the scientists who saw it. For the first time, they were witnessing details of an early step — long unseen, just cleverly inferred — in a central event in biology: the act of turning on a gene. Those blue and green blobs were two key bits of DNA called an enhancer and a promoter (labeled to fluoresce). When they touched, a gene powered up, as revealed by bursts of red.

Enhancers, promoters and mRNA - YouTube

Activation of a gene — transcription — is kicked off when proteins called transcription factors bind to two key bits of DNA, an enhancer and a promoter. These are far from each other, and no one knew how close they had to come for transcription to happen. Here, working with fly cells, researchers labeled enhancers blue and promoters green and watched in real time. Also tweaked was the gene itself, such that mRNA copies, hot off the press, would glow red. The red flare is so bright it's almost white, because several mRNAs at a time are being made. The study found that the enhancer and the promoter have to practically touch in order to kick off transcription.


The event is all-important. All the cells in our body contain by and large the same set of around 20,000 distinct genes, encoded in several billion building blocks (nucleotides) that string together in long strands of DNA. By awakening subsets of genes in different combinations and at different times, cells take on specialized identities and build startlingly different tissues: heart, kidney, bone, brain. Yet until recently, researchers had no way of directly seeing just what happens during gene activation.

They’ve long known the broad outlines of the process, called transcription. Proteins aptly called transcription factors bind to a place in the gene — a promoter — as well as to a more distant DNA spot, an enhancer. Those two bindings allow an enzyme called RNA polymerase to glom onto the gene and make a copy of it.

That copy is processed a bit and then makes its way to the cytoplasm as messenger RNA (mRNA). There, the cellular machinery uses the mRNA instructions to create proteins with specific jobs: catalyzing metabolic reactions, say, or sensing chemical signals from outside the cell.

This textbook take is true as far as it goes, but it raises many questions: What tells a given gene to turn on or off? How do transcription factors find the right sites to bind to? How does a gene know how much mRNA to make? How do enhancers influence gene activity when they can be a million DNA building blocks away from the gene itself?


For decades, scientists had only blunt and indirect tools to probe these questions. Ideas about DNA, RNA and proteins came from grinding up cells and separating components. Then, in the 1980s, scientists began using a game-changing technique called FISH (short for fluorescence in situ hybridization) to see DNA and RNA directly, right in the cell. Other methods followed — microscopes with better resolution, new ways to tag (and thus track) players in this molecular symphony as it played out. Researchers could parse transcription as it happened, in detail.

Before, it was like trying to hear the symphony by looking at a static picture of the orchestra, says Zhe Liu, a molecular biologist at the Howard Hughes Medical Institute's Janelia Research Campus in Virginia. “You would never figure out what they are playing,” he says. “You could never appreciate how beautiful the symphony is.”

Here’s a taste of what molecular biologists are learning by spying on this key, nanoscopic process — increasingly in real time, in living cells.

The life and times of transcription factors

Though scientists have long known that transcription factors dictate whether or not a gene powers up, it’s been mysterious how these proteins navigate the ridiculously crowded space in the nucleus to find their binding sites.

Consider that, uncoiled, the DNA in a human cell would run a meter or two long. The nucleus is about 5 to 10 micrometers in diameter, so the packaging of our genome is akin to stuffing a string that could wrap 10 times around the Earth inside a chicken egg, Liu says.

Researchers are just starting to tackle how this coiling and looping affects gene transcription. For one thing, they suspect it could help explain how enhancers can influence a gene’s activity from a great distance — because something far away when DNA is stretched out may be a lot closer when the genetic material is bundled up.

And if it seems miraculous that transcription factors know where they are going — well, most of them don't. By tracking these proteins in a single cell over time, researchers find that they spend fully 97 percent of their life jiggling hither and thither, bouncing off of whatever bits of DNA they encounter until they luck out. (A few types may act as leaders, scanning the genome, latching on to their target and setting up the right conditions for a larger pack to follow.)

Transcription factors in action - YouTube

To see how transcription factors move around inside the nucleus, researchers watched one specific transcription factor, Sox2, in living cells taken from mouse embryos. Shown are Sox2 molecules labeled with fluorescence, in a 3-D grid. Researchers recorded the movements of several Sox2 molecules within a single cell nucleus using a special microscopy approach that stacks 2-D images to make a 3D one. Each of the traces represents the movement of a separate transcription factor.


One would imagine, at least, that when a transcription factor finally found its binding site, it could stay stuck and do its job for hours. Scientists used to believe so from experiments with dead, preserved cells.

But studies on live cells show that’s far from true. Liu’s lab and others have shown over the past five years that transcription factors bind only for seconds, and that high concentrations of them congregate near the binding site, helping each other glom on. “It’s mind-boggling how transcription factors actually work,” Liu says.

And there are a lot of them: Up to 10 percent of the genes in a mammal carry instructions for making ones of different flavors. Recent evidence suggests that this affords huge precision to the cell. For any given gene, varied combinations of transcription factors can ramp up or tamp down the process, potentially making the system exquisitely tunable.

Hooking up at the polymerase party

If transcription factors are the gas pedal and brakes, the engine is RNA polymerase. In the basic model, RNA polymerase pulls apart a gene’s two strands, then slithers down one of them to make an mRNA copy of it. Turns out things are a hair more complicated.

Studies in mashed-up and preserved cells had hinted that many polymerase molecules cluster together to make this mRNA magic happen. But no one had ever seen such a clump in living cells, so no one knew how or when — or even if — the clumps formed. By attaching a fluorescing chemical tag to RNA polymerase in live cells, researchers saw multiple polymerases repeatedly group together for about five seconds — then scatter.

Last year, the same team of scientists spotted gatherings of other proteins as they congregated to help RNA polymerase do its job. These beasts — known as mediator proteins — form giant clusters numbering in the hundreds that join the RNA polymerases on the DNA.

Mediator proteins and RNA polymerases - YouTube

Specialized groups of proteins called the mediator complex (green) gather around a gene to help RNA polymerase do its job of copying DNA into mRNA (magenta). The box outline marks a 3-dimensional region surrounding the gene. The study showed that the two clusters fuse together and interact directly with the gene during transcription.


The two gaggles seem to concentrate into distinct droplets, like blobs of oil in water. Then they fuse, perhaps creating a kind of self-assembling, cordoned-off transcription mill. A lesson from this? “Beyond the biochemistry, there are all these physical phenomena that may have a role in telling us how genes get turned on,” says biophysicist Ibrahim Cissé of MIT, who led the work.

Messenger RNA is made in fits and starts

For decades, researchers assumed that when a gene is active, transcription simply goes into “on” mode and cranks out mRNA at a steady clip. But a breakthrough technique called MS2 tagging, first developed in 1998 and still widely used, has radically changed that view.

Invented by cell biologist and microscopist Robert Singer and colleagues at the Albert Einstein College of Medicine in New York, MS2 tagging allowed scientists to see mRNAs in living cells for the very first time. (Key ingredients of the method come from a virus called MS2 — hence the technology’s name.)

In a nutshell, scientists use engineering tricks so that mRNA made from a specific gene bears distinctive structures called stem-loops. Through a second trick, those stem-loop locations are made to glow fluorescently so researchers can “see” mRNA from the gene of their choice whenever it is made and wherever it travels to, under a microscope and in real time.

Singer, who coauthored a 2018 article about mRNA imaging in the Annual Review of Biophysics, used MS2 tagging to show, with his colleagues, that the production rate of mRNAs from a gene fluctuates wildly over 25 minutes or so. It turned out that the size of these bursts doesn’t vary much, but their frequency does, and that’s what dictates how energetically a gene pumps out its mRNA product. Increasing or decreasing the rate of this transcriptional “bursting” may allow the system to ramp up or slow down a gene’s activity to meet the cell’s needs.

Researchers think that the on-off kinetics of transcription factors, meaning the rate at which they pop on and off of their binding sites, somehow regulates transcriptional bursting. But they don’t yet know how.

Trekking towards translation

Making mRNA is just the first step in a gene’s strutting its stuff. Next comes translating instructions in that mRNA to make proteins. For that to happen, the mRNA must journey out of the nucleus and into the cytoplasm where the protein-making factories reside.

Scientists had assumed that the cell’s molecular machinery carefully transported mRNA to the nucleus’s membrane and then pumped it out into the cytoplasm. Using the same MS2 method, Singer’s lab found that wasn’t so. Instead, mRNAs bounce around — “buzzing around in the nucleus like a swarm of angry bees,” as Singer terms it — until they happen to hit a pore in the nuclear membrane. Only then does the cell’s machinery lift a finger and actively shuttle mRNA through this gate.

mRNAs departing the nucleus - YouTube

In this video, proteins in the pores of the nuclear membrane are labeled red, and mRNA is labeled green. Using a special microscope designed to record at a very fast frame rate, researchers could watch individual mRNAs as they zipped around the nucleus until they hit a pore and passed through the pore into the cytoplasm, where protein synthesis takes place.


More recently, Singer and colleagues created mutant mice that enabled them to watch as mRNA shuttled up and down a nerve cell’s delicate dendrites, the structures that receive signals from other nerves. The team even got to spy on memory-making in action. The mRNAs they were tracking carried instructions for making a protein — β-actin — that is abundant in nerve cells and is thought to help bolster connections when memories are made in the brain. In a video that looks like a network of roads at nighttime, within 10 minutes after a nerve cell was activated, mRNAs cruised to points of contact with other nerves, ready for actin production to shore up those nerve-nerve connections.

The Molecular Basis of Memory: Tracking mRNA in Brain Cells in Real Time - YouTube

Researchers devised a way to track mRNAs of a gene crucial for making memories as they traveled through living brain cells. The team engineered a mouse so that all the mRNA copied from this gene, which codes for a protein called β-actin, was labeled. β-actin helps neurons reshape tiny protrusions called spines that other neurons connect to, a process thought to be important in learning and memory. When neurons grown in a dish were stimulated, β-actin mRNAs were produced in the nucleus within 10 to 15 minutes. In this video, you can see about 6 seconds of β-actin mRNAs cruising through the neuron's branches, or dendrites, after stimulation. The researchers believe that these mRNAs are searching the dendrites for spines that have just made connections, so that they can synthesize β-actin protein right there on the spot.


Scads of details about gene activity remain mysterious still, but it’s already clear that the process is far more dynamic than once assumed. “The change has been phenomenal, and it’s accelerating rapidly,” Singer says. “There’s a lot of information to be gleaned just by watching.”

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Whether a business model is built on gigabytes, interest rates or the latest innovations in aluminum siding, every company ultimately depends on its people — some more than others. Businesses of any size have stars that drive productivity and get results, but look beyond those high achievers — the break room might be one place to check — and you’ll find others who drag the company down with shoddy performance.

The ultimate success or failure of a company often comes down to the quality of employees. As Jack Welch, former chairman of General Electric, once said, “the team with the best players wins.” But as CEOs and managers try to set up winning companies, they face a surprisingly difficult task: sorting the good employees from the bad ones. Baseball pitchers have earned run averages and quarterbacks have touchdowns, but the value of a given coder or salesperson can be much harder to define. Companies spend millions of dollars and burn countless hours conducting performance reviews and devising checklists to assess their employees, and business scholars have studied the issue with great urgency and intensity.

The results so far? By all available evidence, formal attempts to rate employees don’t seem to meaningfully improve employee performance or give companies any sort of competitive advantage, says Elaine Pulakos, a management expert and CEO of PDRI, a management consulting company based in Arlington, Virginia. “They end up being extremely costly and have no impact on productivity,” she says. Pulakos discussed the science of employee evaluation in a 2018 issue of the Annual Review of Organizational Psychology and Organizational Behavior.


Despite many efforts, no one has been able to come up with a rating system that can reliably discern which companies are blessed with a deep bench of high performers and which brim with mediocrity. You certainly can’t tell simply by looking at the bottom line. Pulakos cites a 2012 report that gathered more than 23,000 employee ratings from 40 companies and found no sign that ratings had any effect on profits or losses. “Performance ratings have no relation to organizational performance whatsoever,” she says.

Out of all of the methods used to rate and grade employees, the dreaded annual or semiannual performance reviews are especially unhelpful and potentially harmful, Pulakos says. “They’re really toxic and people hate them,” she says. “You’re creating artificial steps just to check a box.” Pulakos points to brain imaging research positing that even high-performing employees automatically go into a defense mode during performance reviews, turning a supposedly productive meeting into a fight-or-flight scenario.

Formal annual performance reviews can be extremely damaging to a company’s culture, says Herman Aguinis, the Avram Tucker Distinguished Scholar and professor of management at George Washington University in Washington, DC. “It’s a soul-crushing enterprise,” he says. “The employee doesn’t know what they’re supposed to do, and the manager doesn’t see any value in it. They’re only doing it because human resources told them to.”

All too often, Aguinis says, formal performance reviews become a self-serving exercise in politics, not a realistic examination of an employee’s strengths and weaknesses. “Some managers will give biased ratings on purpose,” he says. “I have personally seen a supervisor giving a bad employee a good rating just so that employee could get promoted out of his unit.”


Still, some HR experts continue to see some value in annual performance reviews. In a February post on her popular Evil HR Lady blog, Suzanne Lucas says “annual performance reviews aren’t all bad. Formal ratings provide a macro-view of performance and engagement levels across the company. If the results of any group (department, experience level, etc.) stick out — it can indicate a bright spot or potential problem worth looking into.”

The growing body of research questioning the value of performance reviews has encouraged many companies to rethink their approach. Dell, Microsoft, IBM and other big business names such as the Gap, Accenture and General Electric have ditched the process, a move at times fanfared in press releases and headlines. But a 2018 survey by the research firm WorldatWork found that 80 percent of companies still used formal performance reviews. “Behavior change in organizations is really hard,” Pulakos says.

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Businesses that abandon formal performance reviews still have to keep tabs on employees, Aguinis says: “Companies that say they are getting rid of ratings are still using ratings. They just have different labels.” For one thing, managers must have some rationale for assigning promotions and raises. If there’s no data on performance, the process of handing out promotions and raises can turn chaotic. In some cases, companies could be vulnerable to lawsuits if they don’t have a way to justify decisions.

To really understand the value of their employees, Aguinis says, managers should double down on the practice of everyday management. That means checking in on employees every day and giving them real-time feedback on things they’re doing well and areas where they can improve. “When performance is a conversation, when it’s not something that happens just once a year, the measurement becomes very easy and straightforward with no surprises,” he says. He adds that it’s important to gather input from many different people within the system — peers as well as supervisors. “The best source of data is often not the manager,” he says.

When rating employees, it’s best to keep things simple, says Seymour Adler, a talent and rewards partner at Aon, a management and HR consulting firm headquartered in London. He ruefully remembers a mistake early in his career, when he was part of a team that came up with a 40-point scale to rate employees. “That’s an over-engineered solution in my view,” he says.


Rating employees solely on objective measures such as sales numbers, absentee days, or customer calls may seem like a winning strategy, but those data points can be wildly misleading, Adler says. A salesperson with the most sales may have a better territory or better luck than others, not more talent or drive. “Objective measures may seem straightforward, but you have to think about all the factors that are beyond an employee’s control,” he says.

Daily evaluation and feedback may sound like an onerous task, but Adler says there’s an important loophole: Most employees do just fine without constant scrutiny. “When I work with companies, I encourage them to get away from ratings and start managing by exception,” he says, meaning that the exceptional employees need the most attention. Out of 100 employees, there might be three or four who are struggling so mightily that they need an intervention or a career change. At the other end, there might be five or so excellent employees who should get special treatment because they drive the company’s success. A 2012 study by Aguinis and coauthor Ernest O’Boyle Jr. found that the top 1 percent of workers account for 10 percent of a company’s productivity. The hardworking, competent but unexceptional workers in between the extremes — Adler calls them “the Mighty Middle” — are going to make about the same contribution to a company’s bottom line regardless of how much time they spend in performance reviews.

Some companies have taken appreciation of superstar employees to extremes. In his 2015 book Work Rules!, former Google executive Laszlo Bock reveals that the company routinely pays high-performing employees five or six times as much as other employees at the same level, maybe even more. He also cites such instances as one worker’s receiving a $1 million stock bonus while another received just $10,000.

Of course, Google is an industry outlier in many ways. Pulakos notes that the company lives on data, and it has methods for rating and ranking employees that just wouldn’t work anywhere else. That’s one of the big lessons of modern business scholarship: Every company has to figure out its own approach to getting the most out of its employees. “You have to evaluate your own strategic goals,” she says. “What works for Google is not going to work the same way for anyone that is not Google.”

In the world of business, there aren’t many universal truths. Just one, really: Annual performance reviews are the worst.

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The suicide rate in the United States continues to spiral upward, with seemingly no end in sight. More than 45,000 Americans take their own lives each year, 33 percent more than did so in 1999, according to the most recent federal data.

It’s a national public health crisis — one that researchers and clinicians have struggled to thwart because the triggers of suicide are so poorly understood. People may wrestle with suicidal thoughts for years, but not follow through. Depression and other mental health conditions are clearly risk factors, but such diagnoses aren’t linked to roughly half of all US suicides. Some prevention efforts, such as asking a patient to sign a “contract” to not commit suicide, have proved to be largely useless.

But there’s been some encouraging progress in recent years, both in understanding the suicidal thought process and in developing individual and societal interventions to better assist those caught in the crucible of such a crisis. Instead of encouraging people to sign no-suicide contracts, clinicians now are more likely to work with a patient to design a personalized prevention plan to use when suicidal thoughts flare. Clinicians and suicide prevention experts are tackling how suicide is portrayed in the media, working to debunk misunderstandings and trying to slow access to pills, guns and other means, particularly for individuals who have expressed suicidal thoughts.

“From a clinical perspective, we can do a lot better than just leaving people on their own to figure out how to deal with not killing themselves,” says Barbara Stanley, a clinical psychologist at New York City’s Columbia University. “We can give them strategies and skills.”

Across the United States, suicide rates are rising. Here are the percentage increases for different states from 1999 through 2016. Read more about the statistics at the CDC’s website.

What turns thought to action?

Some 15 years ago, researchers began to view suicide as two distinct processes —suicidal thoughts, also called ideation, and the progression that can lead to an attempt. That shift in thinking has spawned research on when and how ideation leads to action, and the risk factors involved.

David Klonsky, a psychologist at the University of British Columbia, and Alexis May, then a graduate student and now at Connecticut’s Wesleyan University, posited that three steps tip the balance from ideation to action. They explore their Three-Step Theory, and several others with overlapping elements, as part of a look at suicidal ideation and attempts in the 2016 Annual Review of Clinical Psychology.

The first step — the psychological groundwork — is laid when someone is living with unremitting emotional or physical pain, which is further amplified if it’s overlaid by a sense of hopelessness: a feeling that there’s no way out. “Another way to think about step one,” Klonsky says, “is that it’s creating that desire to not want to be alive.”

The second step in the theory rests on the degree to which that pain and hopelessness is ameliorated by connectedness to others or to a broader community. Those ties might be rooted not just in personal relationships — a challenge in today’s America where loneliness appears to be on the upswing — but also connections to a job, a personal cause or even the outcome of the current football season.


The National Suicide Prevention Lifeline (1-800-273-8255) is open 24 hours a day. Prefer to chat online? Go to the Lifeline’s homepage and click on the “chat” button in the top right corner.

The Means Matter Campaign of Harvard’s School of Public Health has an array of information and resources about suicide.

Gun shops, gun owner groups and mental health advocates are joining up to try to prevent firearm suicides. Read about the project at the Means Matter website and in an editorial at JAMA Internal Medicine.

A downloadable document tackling frequently asked questions about suicide and suicide prevention is available from the National Institute of Mental Health.

If bleakness and disconnectedness align, a person becomes vulnerable to taking the critical third step: the leap from thoughts to action. Basic personality plays a role here: Someone less squeamish about blood and violence will have lowered sensitivity to inflicting pain and harm on themselves. But in large part, the leap to step three is a matter of practical capability — access to lethal means and the knowledge to use them. In America, that often means guns. “If someone is living with a firearm and they … know how to use it, their practical capability is very, very high,” Klonsky says.

Heightened practical capability can also figure in the emergence of apparently related suicides, such as the unsettling deaths this March involving survivors of the Parkland school shootings. Knowing that someone you know, or who appears similar to you, has committed suicide can make taking one’s own life seem more feasible, suicide prevention experts say.

A troubling influence

For this reason, experts were highly critical of the popular Netflix dramatic series “13 Reasons Why,” which first aired in 2017 and featured a teenage girl who, after her suicide, released 13 score-settling tapes describing the ways people in her life had failed her. Not only could other teens identify with the girl, but the program also showed the method in graphic detail, presenting suicidally inclined viewers with a means.

“That was a lot of the backlash with the show,” says Catherine Glenn, who studies self-injury risk factors in adolescents at the University of Rochester in New York. “That played out [the method] in almost a step-by-step fashion.” And hospitalizations for suicide attempts and suicidal thoughts did indeed increase after the show aired, according to a recent study in the Journal of Adolescent Health.

Of the people who think about suicide, relatively few go the next step and translate their thoughts into action. This image depicts the path by which suicidal thoughts (also known as suicidal ideation) lead to follow-through. Pain and hopelessness without a counterbalancing connectedness to people and other valued things intensify the ideation. Then comes “capacity” to act, which is somewhat influenced by personality but even more by easy access to, and knowhow about, the means to carry out an attempt.

But there is a surprising safety net for all potential suicide victims: time. It’s on their side if they can be kept away from guns or other immediately lethal means. Research shows again and again that the window of peak suicide risk is narrow, frequently just an hour or so, and sometimes less than 20 minutes. “The choice to take one’s life is rarely a long-term stable choice,” Klonsky says. “It’s usually made in the moment of crisis that’s not as bad even five or six hours later.”

Keeping the window to life open

Still, clinicians are frequently faced with a longer-term dilemma: what to do if patients are considered suicidal — either because they’ve attempted suicide or admit to suicidal thoughts — but not ill enough to be hospitalized. How best to keep them safe in the weeks and months to come?

“By and large, if someone is in your office or in an emergency room, they at least have mixed feelings about killing themselves,” says Stanley. “As a clinician, you align with the part of them that wants to stay alive.”

Previously, and sometimes even today, patients who have expressed suicidal thoughts or attempted suicide have been asked to sign a contract promising not to try again. Research into this contractual approach has been limited, but what data exist don’t show benefit. There also are some practical reasons why this approach has proved to be a non-starter, Stanley says. Patients have described the paperwork as little more than a way to shield clinicians and clinicians’ employers against future liability. Plus, a contract by definition requires that both parties “have skin in the game,” Stanley points out. “For a no-suicide contract, the only person giving is the patient.”

Instead, clinicians have begun working with at-risk patients to create individual prevention plans. Working together, they design a concrete series of steps for recognizing a burgeoning suicidal crisis and heading it off.

The crisis moment triggering a suicide attempt can be very brief, and measures to deter action can make the difference between a life fully lived and one cut short. The safety net shown in this artist's rendering is under construction at San Francisco’s Golden Gate Bridge, where almost 1,700 people have died by suicide since it was built in 1937. The nets will be installed 20 feet below the sidewalk and extend out 20 feet, retaining views from the bridge and the structure’s iconic appearance, while making it harder to jump into the water.


Patients identify warning signs, such as drinking more, or spending a lot of time alone. With clinicians, they brainstorm coping strategies and ways to distract from or soothe their mood, such as doing chores or listening to music. For times when they need outside help, they list names of close friends, family members and mental health clinicians.

The plans are not a substitute for treating underlying risk factors such as depression or post-traumatic stress disorder, but they do provide something tangible to rely on during a person’s darkest moments, says Stanley, co-developer of one such approach called the Safety Planning Intervention. “When you’re in a suicide crisis, you’re not thinking straight — you don’t want to have to think.”

Stanley says she has many examples in which the plan made a difference — such as, one time, “somebody going to the George Washington Bridge, realizing that the safety plan was in his pocket, feeling it, and saying, ‘OK, let me try this first instead of jumping.’”

A recent study in JAMA Psychiatry of the Safety Planning Intervention reported that it cut short-term suicidal behaviors nearly in half. It looked at 1,640 patients getting care at Veterans Affairs emergency departments, finding that among 1,186 who completed a plan and got at least two follow-up phone calls shortly after hospital discharge, the rate of attempts or near attempts in the subsequent six months was 3 percent, versus 5.3 percent for 454 patients getting usual care, which was typically referral to a mental health clinician.

How guns make a difference

These prevention plans often also involve restricting access to suicidal means. Researchers affiliated with Means Matter, a Harvard School of Public Health campaign, have promoted this approach with strategies that include reducing access to dangerous or lethal doses of medications and storing guns away from at-risk individuals or, at a minimum, locking them up. The campaign is working with an array of gun owner groups and gun shops across the country to promote suicide prevention as a basic tenet of firearm safety.

One frequently cited study in the 2007 Journal of Trauma found that access to guns does make a difference. It compared a group of states with high rates of gun ownership to a second group with low ownership, and found suicides in the first group were nearly twice as high. Virtually all of that disparity was attributable to firearm suicides; there was scant difference in non-firearm suicides between the two groups. The pattern remained in a study published in 2013.

A 2013 study found sharply higher rates of suicide in a group of US states with high levels of gun ownership compared to another group of states with low gun ownership levels. Total suicide rates, not just suicides by firearms, were lower in the states with fewer guns, while rates of non-firearm suicides were about the same. Ready access to a means for suicide make it more likely that someone in crisis will follow through, say mental health experts. (Data are for total numbers of suicides in 2008 and 2009; population sizes of the high-gun and low-gun groups were close to equivalent.)

“When you try with a gun, you usually don’t get a second chance,” says Matthew Miller, one of the studies’ authors and a suicide researcher at Boston’s Northeastern University who has studied access to firearms.

While any discussion about gun restrictions can become a hot-button subject in the US, researchers can quickly check off numerous examples where blocking access to means has saved lives. When the United Kingdom discovered a less toxic form of gas to fuel ovens and heaters, the rate of suicides by domestic gas fell to nearly zero by the late 1970s. Similarly, banning the most highly toxic pesticides commonly used in Sri Lanka reduced that country’s overall suicide rate. And suicide barriers on bridges — such as the steel net now under construction beneath the Golden Gate Bridge — have reduced the incidence of suicide by jumping.

A graph shows dips in suicide rates in Sri Lanka after it outlawed various poisonous pesticides. Read more about it in a 2017 paper in the Lancet.


There’s good reason to be hopeful about interventions like these, particularly because the popular perception that someone contemplating suicide is nearly unstoppable is wrong, Miller says. A 2006 study he was involved with, based on a survey of 2,770 members of the public, found that 34 percent didn’t believe installing a barrier at the Golden Gate Bridge would avert even a single death. In other words, they believed that 100 percent of potential jumpers would have found another way. “That just shows you in some sense how fatalistic people are,” Miller says.

In reality, most people’s unsuccessful suicide attempts do not ultimately lead to a later death by suicide — a fact that offers hope. One analysis of 90 studies, which followed people who had been treated for self-harm, found that while some had gone on to attempt again, more than nine years later just 7 percent had taken their own lives.  

“If people have a suicidal crisis and don’t die,” Klonsky says, “they’re overwhelmingly likely to live a life that does not end in suicide.”

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