Johnson & Johnson is facing its second trial in New Jersey over claims that their talc powder products caused one man to develop mesothelioma.
Stephen Lanzo of Verona, New Jersey, says his use of Johnson & Johnson baby powder exposed him to asbestos and caused him to develop mesothelioma. He and his wife are seeking monetary damages.
Lanzo is the second person to sue Johnson & Johnson (J&J) for claims that their talc powder products cause mesothelioma. This is the first case to be tried at the Middlesex County Courthouse.
Last year, a court in Los Angeles favored J&J in a similar lawsuit. In that case, a 61-year-old woman said her use of the company’s baby powder caused her to develop cancer.
“Johnson’s Baby Powder has been around since 1894 and it does not contain asbestos or cause mesothelioma or ovarian cancer,” said J&J after the case in California.
Several other cases across the country allege that the company’s baby powder products caused ovarian cancer.
“It’s true, we don’t know how many Johnson & Johnson users have mesothelioma,” said Moshe Maimon, Lanzo’s lawyer, in the case’s opening statements. “And the fact is that the defendants have never studied that.”
Lanzo’s lawsuit alleges that J&J knew its products contained asbestos, but failed to properly warn consumers. J&J’s legal team asserts that its products do not contain asbestos, and claim that the plaintiffs used faulty test methods to prove otherwise.
Other defendants in the case include Cyprus Amax Minerals Co. and Imerys Talc America.
J&J is facing more than 5,000 cases asserting talc-related claims. Most of the cases are largely based on claims that the company failed to warn women about the risks of developing ovarian cancer from their products.
Out of five trials in Missouri involving ovarian cancer, juries found the company liable four times and awarded $307 million to the plaintiffs. In California, a judge tossed a $417 million verdict awarded to one woman.
We get old and then we die. At least, that’s the best-case scenario for humans: Each encroaching year means you’re one step closer to the grave. This fact of life is academically laid out by the Gompertz-Makeham law of mortality, which states that our chances of death increase exponentially as time wears on.
At least one animal, however, defies Gompertz’s law: the naked mole rat. In a study released Wednesday, scientists explain that a naked mole rat’s risk of dying does not appear to increase with age. While mice in captivity only live an average of four years, naked mole rats can live to be 30, with some breeding females remaining fertile until they die.
“This absence of hazard increase with age, in defiance of Gompertz’s law, uniquely identifies the naked mole rat as a non-aging mammal, confirming its status as an exceptional model for biogerontology,” the researchers write in the journal eLife.
While some scientists not associated with the study warn that more data are necessary before the subterranean rodents are ruled out as non-aging, the study’s lead author Rochelle Buffenstein, Ph.D., says her team’s 3,000 data points show a clear picture of an animal defying Gompertz aging.
“To me, this is the most exciting data I’ve ever gotten,” the comparative biologist told Science magazine. “It goes against everything we know in terms of mammalian biology.”
In this study, Buffenstein, who works at Calico, a Google-backed longevity research institute, worked with her team to analyze 30 years of naked mole rat data collected in her lab, including each rat’s date of birth and date of death as well as data on whether each rat was killed in an experiment or given away to another researcher. Altogether, they looked at data on 3,299 naked mole rats.
On average, the animals didn’t show the same weakening homeostasis and increased vulnerability that affects other organisms as they age. After the naked role rats reached their sexual maturity at six months old, their daily chance of dying was about one in 10,000 — and it stayed that way for the rest of their life.
It’s not clear what’s going on here. We know that mole rats are definitely sturdy creatures and have unusual biology: the notably coldblooded mammals (yes, you read that right) can survive for 18 minutes without oxygen and are highly resistant to cancer, but whether that has anything to do with their unusually long lives remains to be seen. It’s possible their 30-year maximum lifespan could be the result of their high rates of DNA repair and high levels of molecular chaperones, which help DNA fold and unfold properly, but more data is needed to confirm any link.
Regardless, naked mole rats, already the longest-lived rodents known to scientists, are a fascinating model to study longevity. Scientists are hopeful that they may teach us to improve our own longevity as we better understand what exactly makes these ugly and defiant critters tick.
Some people’s careers take off, while others’ take longer — or even stall out.
Common wisdom says that the former attend elite MBA programs, land high-powered jobs right out of school at prestigious firms, and climb the ladder straight to the top, carefully avoiding risky moves. But our data shows a completely different picture.
We conducted a 10-year study, which we call the CEO Genome Project, in which we assembled a data set of more than 17,000 C-suite executive assessments and studied 2,600 in-depth to analyze who gets to the top and how. We then took a closer look at “CEO sprinters” — those who reached the CEO role faster than the average of 24 years from their first job.
We discovered a striking finding: Sprinters don’t accelerate to the top by acquiring the perfect pedigree. They do it by making bold career moves over the course of their career that catapult them to the top. We found that three types of career catapults were most common among the sprinters. Ninety-seven percent of them undertook at least one of these catapult experiences and close to 50% had at least two. (In contrast, only 24% had elite MBAs.)
Through these career catapults, executives build the specific behaviors that set successful CEOs apart — including decisiveness, reliability, adaptability, and the ability to engage for impact — and they get noticed for their accomplishments. The catapults are so powerful that even people in our study who never aspired to become CEO ultimately landed the position by pursuing one or more of these strategies.
Go Small to Go Big
The path to CEO rarely runs in a straight line; sometimes you have to move backward or sideways in order to get ahead. More than 60% of sprinters took a smaller role at some point in their career. They may have started something new within their company (by launching a new product or division, for example), moved to a smaller company to take on a greater set of responsibilities, or started their own business. In each case, they used the opportunity to build something from the ground up and make an outsize impact.
In his late twenties, “James” was hired in a strategy and business development role inside a multibillion-dollar marketing and communications business. Early in his career, he was offered the chance to build out one of the new businesses. It felt like a demotion, or at best a lateral move, to be handed a blank org chart and a highly uncertain future. “It was zero revenue when I stepped in, and we built that business to $250 million,” he says. By building a new business from scratch, he picked up essential management skills, such as running a P&L, managing a budget, and setting a strategic vision — all critical prerequisites to becoming a CEO (over 90% of the CEOs we studied had general management experience). Thirteen years later, he found himself the CEO of a $1.5 billion education and training business.
Make a Big Leap
More than one-third of sprinters catapulted to the top by making “the big leap,” often in the first decade of their careers. These executives threw caution to the wind and said yes to opportunities even when the role was well beyond anything they’ve done previously and they didn’t feel fully prepared for the challenges ahead.
Take, for example, “Jerry,” who at age 24 joined a $200 million business as a senior accountant. Eight months after being hired, he was offered the CFO position, leapfrogging the controller who hired him. Though he was young and still learning the ropes, he embraced the challenge with gusto. “I was very young for my level, and I was given responsibility ahead of my readiness,” he says. As CFO, he gained insight into a broad set of functions and proved his ability to thrive in a new, uncertain environment. Within nine years, after a stint as COO, he landed his first CEO role.
If you don’t expect this kind of opportunity to fall into your lap, you are not alone. However, what we heard from these sprinters is an attitude of “You make your own luck.” Seek out cross-functional projects that touch numerous aspects of the business. Get involved in a merger integration. Ask your boss for additional responsibilities. Tackle tough, complex problems. Above all, make a habit of saying “yes” to greater opportunities — ready or not.
Inherit a Big Mess
It may feel counterintuitive, and a bit daunting, but one way to prove your CEO mettle is by inheriting a big mess. It could be an underperforming business unit, a failed product, or a bankruptcy — any major problem for the business that needs to be fixed fast. More than 30% of our sprinters led their teams through a big mess.
Messy situations cry out for strong leadership. When faced with a crisis, emerging leaders have an opportunity to showcase their ability to assess a situation calmly, make decisions under pressure, take calculated risks, rally others around them, and persevere in the face of adversity. In other words, it’s great preparation for the CEO job.
“Jackie,” the CEO of a transport company, didn’t wait for the big mess to find her. She sought it out. “I liked working on something that was a mess and needed to be figured out: IT, cost, tax. It didn’t matter,” she says. “I got the ugliest assignments. I could unscramble them and figure out an answer.” By stepping up and risking her career on the jobs nobody else dared to tackle, Jackie proved she could deliver results for the good of the company. She landed her first CEO role 20 years after day one in her first job.
While there is no single path to the CEO seat, these career catapults can be replicated by anyone who aspires to a leadership position, and could be especially powerful for those who may find it harder to get to the top. Women, for example, take 30% longer to get to the CEO role, according to Korn Ferry.
Accelerating your career through these catapults doesn’t require an elite MBA or a select mix of inborn traits, but it does require a willingness to make lateral, unconventional, and even risky career moves. It’s not for the faint of heart. But if you aspire to top leadership, you might as well get used to it.
Brandon Hendrickson had already been submerged face down in the pool for more than four minutes, motionless under the dappled Grand Cayman sky, when the struggle phase began. That’s the term of art among free divers and competitive breath-holders for the point at which the human body, sensing an alarming rise in internal carbon-dioxide levels, tries to forcibly override the will. For most people, the respiratory muscles begin contracting within a minute or two, and these involuntary breathing movements, or I.B.M.s, trigger an immediate intake of air. But for élite free divers such as Hendrickson, who grew up spearfishing in Florida but now runs a tree-care service in landlocked Olathe, Kansas, the struggle phase is just the beginning. Some pros endure more than a hundred I.B.M.s before, finally, they yield.
Humans test their limits in an endless variety of ways, but none is simpler or more elemental than breath-holding. There’s no pacing, no tactics, no bonus points; you simply deprive your body of its most urgent need until you can’t anymore. As a result, it offers a convenient laboratory for exploring the nature of human limits, for parsing the gradations of meaning between “won’t” and “can’t.” Scientists have long speculated that what feel like physical limits are often merely warning signals generated by the brain’s protective circuitry. In the case of breath-holding, a spate of recent studies offers a glimpse of what it takes to tap into the hidden reserves beyond these boundaries—and what price you might pay for access.
For Hendrickson, who competed last May in the “static apnea” (that is, motionless breath-hold) category of a weeklong free-diving competition called Deja Blue, the challenge became increasingly psychological as the seconds ticked on and the spasms escalated. He cycled through head-to-toe body scans, making sure that every muscle in his body was relaxed, and studiously avoided thinking about time. A tap on the shoulder from his spotter after five minutes gave him his first benchmark; a few minutes later, he reached fumblingly for the pool deck, his head still submerged; shortly after that, he pulled himself up, looking a little stunned. Hendrickson yanked off his nose clip, gave a hand signal, and said “I’m O.K.” within fifteen seconds, as required by the competition rules. “That was the most hypoxic I’ve ever been,” he said later. “I actually had a bit of tunnel vision. It’s the first time I’ve ever experienced that.” Hendrickson had set a new American and continental record of eight minutes and thirty-five seconds—almost twice as long as the “limit” demarcated by his struggle phase.
In the eighteen-nineties, the French physiologist Charles Richet conducted a series of gruesome experiments in which he tied off the windpipes of ducks and timed how long it took them to die. In open air, they lived for an average of seven minutes, but if they were dunked underwater they survived for an average of twenty-three minutes. This was one of the first demonstrations of a phenomenon known as the diving reflex: in many creatures, including humans, immersing the face in water triggers a series of automatic responses that conserve oxygen, including a decrease in heart rate. Some scientists speculate that this is why splashing cold water on your face can calm you down; it’s also why breath-holding competitions such as Deja Blue are held in swimming pools.
In the absence of tied-off windpipes, most of us reach our voluntary breath-hold limits owing to an excess of carbon dioxide rather than a lack of oxygen. A small cluster of chemical sensors called the carotid bodies, located near the throat, senses oxygen and carbon-dioxide levels in the blood and eventually helps trigger I.B.M.s. If you dull the signal from these sensors by taking a low dose of dopamine, according to Anthony Bain, who completed a Ph.D. on the physiology of extreme breath-holding at the University of British Columbia, Okanagan, in 2016, you’ll be able to hold your breath for longer—if you’re a normal civilian, that is. In a series of experiments with the Croatian national apnea team (yes, that’s a thing), Bain showed that dopamine had almost no effect on the breath-holding performance of élite free divers. They had already learned to ignore their internal carbon-dioxide warning system.
Hendrickson’s time, though impressive, sits well below the official world record of eleven minutes and thirty-five seconds, set by the French diver Stéphane Mifsud, in 2009. (Unofficially, the Serbian apneist Branko Petrović managed to eke out an additional nineteen seconds, in 2014.) Feats like that, Bain said, bump up against a much firmer physiological limit. In the Croatian divers, the end of a breath-hold coincided with oxygen pressures in their blood of about thirty millimetres of mercury—verging on the minimum required to sustain consciousness. “Unlike in the untrained breath-holder, it is surprisingly easy for trained divers to perform a breath-hold until they lose consciousness,” Bain, who is now a postdoctoral researcher at the University of Colorado Boulder, told me. That’s one of the reasons that free diving is so dangerous: competitors sometimes black out far below the surface.
Even that seemingly ironclad limit can be circumvented, as the magician David Blaine showed, in 2008, when he held his breath for seventeen minutes and four seconds on “The Oprah Winfrey Show.” Blaine’s trick was to breathe pure oxygen prior to his demonstration, delaying the point at which his blood chemistry went critical. The record for oxygen-assisted breath-holding, set by the Spanish free diver Aleix Segura Vendrell, in 2016, stands at twenty-four minutes and three seconds. If you watch a video of Vendrell’s attempt, you’ll note this curious detail: when he finally surfaces, instead of exhaling, he inhales. This is because, during a breath-hold, oxygen is steadily absorbed from the lungs into the bloodstream; since Vendrell’s lungs contained nothing but oxygen to begin with, they were literally empty by the end, on the verge of collapse. The ultimate limit in this case, in other words, was mechanical rather than metabolic. Indeed, when Bain put the Croatians through oxygen-assisted breath-holds, the best predictor of performance was the maximum volume of their lungs.
But is circumventing the body’s internal warning systems really a good idea? Last October, François Billaut, a French researcher at the Université Laval, in Quebec City, published a paper examining the effects of apnea on cognitive function. Billaut spent part of his childhood in Tahiti, and he is still a scuba instructor and recreational free diver (best breath-hold: four minutes). Working with several French universities and the French National Apnea Commission, he and his colleagues recruited twelve élite free divers, twelve novice free divers, and twelve control subjects with no free-diving experience. All of them completed a series of five written tests and three computerized tests. Billaut’s team found that the élite divers scored poorly on a task called the modified Stroop test, which measures executive function. Damningly, the subjects’ scores got progressively worse as their experience increased. The most accomplished diver, a nineteen-year veteran with a best breath-hold of seven minutes and sixteen seconds, fell within the pathological range of impairment.
When I asked Billaut how his subjects had reacted to the results, he smiled and shrugged. “Apnea is not different from many other sports, in the sense that practice at a high level often leads to deleterious impacts on human physiology,” he said. “Think about alpinists going to Mount Everest, climbers, gymnastics, marathon runners—every sport has its drawbacks when performed at the élite level.” Some of Billaut’s subjects didn’t really believe the data and hoped that the study was flawed. But, for the most part, he said, they simply accepted it as the price of admission. Bain wasn’t surprised. “The Croatian divers have the exact same sentiment as the French,” he said. “This is their life style. They’re not stopping.”
When I asked Hendrickson about Billaut’s results, he emphasized the importance of understanding the hair’s-breadth difference between enough and too much. He has seen competitors at free-diving competitions black out thirty metres underwater, nearly drown, and then return to try the same dive a few days later. In contrast, he said, “I’ve dived ninety-two, ninety-three metres a couple times, but I probably won’t attempt to go one metre deeper until I’ve done it ten times.” What about his breath-hold record, I asked? Was eight minutes and thirty-five seconds his ultimate limit? Hendrickson sighed. “I’m in the process of mentally trying to decide on that right now,” he finally said.
Networks regulate everything from ant colonies and middle schools to epidemics and the internet. Here’s how they work
We live enmeshed in networks. The internet, a society, a body, an ant colony, a tumour: they are all networks of interactions, among people, ants or cells – aggregates of nodes or locations linked by some relation. The power of networks is in their local connections. All networks grow, shrink, merge or split, link by link. How they function and change depends on what forms, or disrupts, the connections between nodes. The internet dominates our lives, not because it is huge, but because each of us can make so many local links. Its size is the result, not the cause, of its impact on our communication.
Nowhere is the decisive influence of local interactions easier to see than in ants, which I study. The local is all an ant knows. A colony operates without central control, based on a network of simple interactions among ants. These are local by necessity, because an ant cannot detect anything very far away. Most ant species can’t see, and all of them rely on smell, which they do with their antennae. The important interactions are when ants touch antennae, smelling each other, or the ground, smelling chemicals deposited by other ants.
The shifting network of brief interactions transforms a group of ants, each unable to assess any global purpose, into the orderly chaos that is ant-colony behaviour. In the tangled canopy of branches and vines in the tropical dry forest of the Estación Biológica de Chamela in western Mexico, turtle ants create and repair a circuit of trails that links their nests and food sources. The turtle ants never descend to the ground, so the trails can proceed only along a plant branch or stem. As each ant moves along, it puts down little drops of trail pheromone that quickly evaporate. Whenever an ant comes to a junction, where one stem crosses another, it chooses the path that smells most strongly of pheromone, which is the path that most ants took most recently. In this way, the trails of ants create a network within the network of tropical vegetation.
In the jungle, the network of vegetation can be broken. A passing chameleon can wipe out many nodes’ worth of ant trail by breaking a cluster of delicate intertwined vines and branches. The ants’ nests are made in the tunnels of larval beetles, who prefer to burrow in soft, rotting wood, and the result is that the branches with nests break easily. The nest lands on the ground and the ants pour out, many carrying larvae and pupae, and head up the nearest tree in search of the trail.
In response to any break in the trail, the ants repair it by slight alterations in their local, node-to-node choices of path. A group of students and I marked ants with nail polish, and found that day after day the same ants tend to use the same part of the network. But ants can’t always go in the same place or they’d never find new food sources. By putting out baits a few junctions away from the trail, I learned that ants sometimes veer off the path and follow the branch that does not have the most pheromone.
These local mistakes, taking a path that is not reinforced, are what make the whole network resilient. When the path is ruptured, some ants must abandon what has suddenly become a dead end. A few ants go to the node nearest the broken one and try from there to reach the original trail. (This is called ‘greedy search’ in the language of computer search algorithms.) Eventually the new part of the repaired path, linking the two ends of the original one, is reinforced by the ants coming from the other direction. Occasionally wandering off at junctions also allows the ants to find food, or shorter or less complicated paths, and prune unnecessary nodes or loops from the trail.
Local interactions among ants are the key to effective search. Collective search always involves a trade-off between thoroughness, ensuring that nothing is overlooked, and covering ground, ensuring that the entire area is searched. Consider what would happen if you lost a diamond ring on a football field. If you have just a few friends to help you search, they all have to move around a lot to cover the whole field, but if there are many searchers, then each can search very thoroughly nearby.
Argentine ants solve this problem by using local interactions to regulate their searching. They adjust their search paths to density. When there are many ants searching, each ant turns around a lot, almost at random. If there are only a few ants, they walk in straighter lines. The cue to density seems to be brief antennal contacts with other ants. The apparent rule is: ‘If I meet another ant often, I can turn around more. If I don’t, I have to walk in a straighter line.’ These simple interactions between pairs of ants function in the aggregate to adjust the scale of the network to the optimal size for the number of ants available.
We recently asked another species of ant to solve this problem in microgravity, in the International Space Station (ISS). We sent pavement ants up to the ISS in small arenas with a barrier inside. To learn how the ants adjust their paths when density decreased, the astronauts opened the barrier, so that the exploring ants suddenly found themselves in a larger space where they met less often. The arenas were very shallow so there was not much room for the ants to float around, but every now and then an ant lost hold of the surface and went skittering around in a Michael-Jackson-like dance, until it was able to get back down. It seemed that the ants were working so hard to stay attached to the surface that they were not able to adjust their paths to search as effectively as the ants in control arenas did on Earth. You can try the experiment yourself in gravity with your favourite ant species (Ant Colony Search); a simple arena, without the beautiful machining that NASA did, works just fine.
Engineers designing robots to search a burning building, or another planet, are using systems like those of the ants, based on networks of local communication. These swarm methods can be simpler, cheaper and more robust to failure than a system using central control. If each searcher has to relay information back to a central station that in turn makes a map and tells each player what to do, sophisticated central control is required, and if it breaks down, all function is lost. By contrast, local interactions have redundancy; if one doesn’t work, another might.
Local interactions regulate many natural systems. Ecological networks show an enormous variety of types of links: one organism can live inside another, stick to it, climb along it, eat it, feed it by gathering or digesting its nutrients, help it reproduce by carrying its pollen or dispersing its seeds. All organisms operate in some kind of ecological network; no living entity operates independently. Even each of our cells contains organelles joined together in an ancient collaboration among bacteria.
For example, cancer, like everything else that cells do, progresses in response to local interactions. Cancer cells are the descendants of healthy ones, and they can thrive and proliferate because they still speak the local language of their ancestors. These conversations allow them to find comfortable neighbourhoods in which to metastasise, summon a blood supply, disarm their immune-system cousins, and turn off the instructions from other cells that would stop them from reproducing. Interrupting these conversations would obstruct the growth of the cancer.
Relations among cancer cells account for many of the failures of chemotherapy. Tumours contain many different forms of cancer cells, each derived from a different evolutionary lineage. Even when chemotherapy wipes out detectable signs of a tumour, cancer cells can still remain. Continued application of the poisonous treatment favours the evolution of ever more resistant cells. These resistant cells, no longer competing for resources with their late, more sensitive neighbours, can reproduce rapidly, and there might be no drugs available to kill them.
In the same way, human intervention in ecological networks has produced insect scourges of agricultural crops and bacterial infections that drugs cannot stop. Individuals in a population differ from each other in susceptibility. Using the same resources links them to each other by competition – what one individual eats is a loss for another. A pesticide or antibiotic assault kills all but the most resistant individuals, selecting for resistance over susceptibility. The resistant ones suddenly have the resources to grow rapidly in number. New methods are being devised to maintain both susceptible and resistant individuals in the networks of cancercells, pathogens or agricultural pests, so that they continue to compete with each other. Integrated pest-management and ‘adaptive chemotherapy’, for example, both work to kill only some, not all, of the sensitive pests or cancer cells. They leave the rest to help suppress the resistant ones. These new forms of control take into account the local interactions that regulate networks of pests or cells.
The most popular girl is the most linked-in – all bonds of friendship pass through her
Networks come in different shapes, depending on the arrangement of links. The familiar tree-shaped network, for example, is a hierarchy. The factory owner gives orders to the manager, who gives orders to the foremen, who give orders to the workers. Evolution produced phylogenetic tree-shaped networks of ancestors and descendants. The original unicellular organisms gave rise to a huge tree of bacteria, while another split in the trunk led to our small branch of vertebrates, nestled in the batch of twigs called mammals.
The tree and the fully connected network sit at extreme ends of a spectrum of possible network shapes. Human social life can produce complex network shapes, as any girl who has ever been to middle school knows. Two girls are linked in the network by being publicly recognised as friends. The popular girls are the hubs of the network, with many friends, some of whom are also linked to many others, while the loners or outsiders have no friends at all. In between the hubs and the outsiders, we find the girls linked to someone in the golden inner circle, but also some that have no hope of ever being noticed by the anointed.
Wherever a girl’s position in the network is, it can be described by how completely it is linked to the rest of the network. This is called its ‘betweenness centrality’: it denotes the number of links between all other pairs of nodes that pass through that node. The most popular girl is the one that is the most linked-in – all bonds of friendship eventually pass through her. In my middle school, understanding ‘betweenness centrality’ was so complex, and important, that one girl kept a notebook tracking day-to-day changes in the links. By diagramming who was friends with whom, it was easy to see how close each one was to the Most Popular one, the ‘betweenness centrality’ of each aspirant to the inner circle. At lunch, girls crowded round the owner of the notebook to see where their name came up that day on the list.
Facebook has made many of us into middle-school girls, as its features perform all these functions, and not just at lunch, but 24/7. The software that suggests products for you on Amazon does much the same thing. For every product X that you buy, it counts up the links, the number of times that someone else who bought X also bought Y, Z and so on, and gives the products that are most often linked to X. The H index on Google Scholar, anxiously monitored by academics and reported to deans and tenure committees, is another version. Counting up these local links between scholars, when one cites the work of another, has begun to rule hiring and promotion at universities.
The greater the betweenness centrality of any node, the more power over the network it exerts. In political terms, if you want to rule, set things up so that others cannot act without your permission, ie so that your betweenness centrality is very high and well-enforced. But such power can be undermined by the local; for example, climate change cannot be dismissed when everyone realises it is what they see outside the window (Land Talk), and disparate realities begin to blend when their adherents engage in face-to-face conversation.
A tacit recognition of the power of a well-connected network underlies a widespread fear of ants. What is scary about ants on the kitchen counter? A moment’s reflection should reassure anyone that they are indeed much bigger and stronger than even hundreds of ants. What is alarming is the sense that the ants are all connected and working together. But ants function using networks of interactions, not as they do in horror movies, urged on to attack by malevolent leaders. Their effectiveness is not due to powerful individuals who are situated to influence the behaviour of others.
Ants do very well without any identity; nothing distinguishes the hubs from the outsiders. Betweenness centrality is not important for them: an ant’s interaction rate depends only on whether it happens to run into others, and ants don’t seem to care which other ant they meet. In his novel War and Peace (1869), Leo Tolstoy argues that local relations among people, rather than the military strategy of the generals, allowed and then repelled Napoleon’s invasion of Russia. As Tolstoy pointed out, rather than following orders, people acted like ants.
Highly connected networks trade resiliency for security. More connections mean easier repair, but also more vulnerability. The Internet of Things will soon let your phone direct your thermostat and coffee machine but not, it is to be hoped, your neighbour’s shower. To prevent this will require a system that allows local connections between some nearby devices, but prevents others. Ants have this problem, too. A few ant species have been observed to read the chemical signals of another species. This links the networks of both species: one finds food and lays a chemical trail; the other species hops onto the same trail, and can take the food instead.
The first infected person flew to another continent, and a worldwide epidemic was launched
How a network changes depends not just on its shape, but on how quickly and how often the local connections shift. Neural networks, for example, form links slowly, a fact that profoundly influences human society. Neurons must grow to find others, and the growth of neurons produces the synapses that carry signals. If synapses in neural networks are not used, they get pruned, disappearing from the axon. Pruning happens much more rapidly in young mammals than in old ones; networks in the brains of babies are in rapid flux. In this way, the time course of change in neural networks shapes another network, that of the family, which is based on the obligation to protect babies while their brains are forming, until they can protect themselves.
An epidemic is another form of network whose time course depends on how links are formed, as one sick person infects another. The epidemic spreads most steadily, in a widening wave of disease, when everyone is easily linked to everyone else. If a virus can live on door handles, faucets and elevator buttons, a quick touch can infect passing strangers. The movie Contagion (2011) presented a terrifyingly realistic example, based on the actual spread of SARS in 2002 from a hotel in Hong Kong, of a network of infection that spread quickly around the world. In the film, a virus proceeded from a handshake between a chef and client, to the waiter who touched the client’s glass, and on from there to everyone who touched any object any of them had touched. The first infected person went to an airport and flew to another continent, and a worldwide epidemic was launched.
By contrast, when an infection requires special circumstances to be transmitted, the time course of an epidemic will be slower and more erratic. At first, there is a rapid burst in the numbers of sick people, as all the hubs, the people who are in a position to transmit to many people, infect everyone they can. After that, the disease will ooze out more slowly from those with fewer links. For example, for one person to infect another with a sexually transmitted disease, a lot more has to happen than a quick touch of a door handle, and so people vary greatly in the numbers they infect. Initially, HIV travelled quickly among people who had many sexual contacts, but then, in places where people had access to information and to condoms to prevent transmission, the virus no longer reached all the sexual partners of all infected people, and its rate of spread slowed. Vaccines slow down epidemics not just because the vaccine prevents infection, but because every person not infected does not then spread it herself.
Networks in nature show how, for the networks that we engineer and those that tie us to each other, the pattern of links at the local scale sets the options for stability and transformation. Almost everything that happens in life is the result of a network. Making, or breaking, local links is the way to change.
Volatile element delivery and retention played a fundamental part in Earth’s formation and subsequent chemical differentiation. The heavy halogens-chlorine (Cl), bromine (Br) and iodine (I)-are key tracers of accretionary processes owing to their high volatility and incompatibility, but have low abundances in most geological and planetary materials. However, noble gas proxy isotopes produced during neutron irradiation provide a high-sensitivity tool for the determination of heavy halogen abundances. Using such isotopes, here we show that Cl, Br and I abundances in carbonaceous, enstatite, Rumuruti and primitive ordinary chondrites are about 6 times, 9 times and 15-37 times lower, respectively, than previously reported and usually accepted estimates. This is independent of the oxidation state or petrological type of the chondrites. The ratios Br/Cl and I/Cl in all studied chondrites show a limited range, indistinguishable from bulk silicate Earth estimates. Our results demonstrate that the halogen depletion of bulk silicate Earth relative to primitive meteorites is consistent with the depletion of lithophile elements of similar volatility. These results for carbonaceous chondrites reveal that late accretion, constrained to a maximum of 0.5 ± 0.2 per cent of Earth’s silicate mass, cannot solely account for present-day terrestrial halogen inventories. It is estimated that 80-90 per cent of heavy halogens are concentrated in Earth’s surface reservoirs and have not undergone the extreme early loss observed in atmosphere-forming elements. Therefore, in addition to late-stage terrestrial accretion of halogens and mantle degassing, which has removed less than half of Earth’s dissolved mantle gases, the efficient extraction of halogen-rich fluids from the solid Earth during the earliest stages of terrestrial differentiation is also required to explain the presence of these heavy halogens at the surface. The hydropilic nature of halogens, whereby they track with water, supports this requirement, and is consistent with volatile-rich or water-rich late-stage terrestrial accretion.
A routine invasive strategy is recommended for patients with non-ST-elevation acute coronary syndromes (NSTE-ACS). However, optimal timing of invasive strategy is less clearly defined. Individual clinical trials were underpowered to detect a mortality benefit; we therefore did a meta-analysis to assess the effect of timing on mortality.
We identified randomised controlled trials comparing an early versus a delayed invasive strategy in patients presenting with NSTE-ACS by searching MEDLINE, Cochrane Central Register of Controlled Trials, and Embase. We included trials that reported all-cause mortality at least 30 days after in-hospital randomisation and for which the trial investigators agreed to collaborate (ie, providing individual patient data or standardised tabulated data). We pooled hazard ratios (HRs) using random-effects models. This meta-analysis is registered at PROSPERO (CRD42015018988).
We included eight trials (n=5324 patients) with a median follow-up of 180 days (IQR 180-360). Overall, there was no significant mortality reduction in the early invasive group compared with the delayed invasive group HR 0·81, 95% CI 0·64-1·03; p=0·0879). In pre-specified analyses of high-risk patients, we found lower mortality with an early invasive strategy in patients with elevated cardiac biomarkers at baseline (HR 0·761, 95% CI 0·581-0·996), diabetes (0·67, 0·45-0·99), a GRACE risk score more than 140 (0·70, 0·52-0·95), and aged 75 years older (0·65, 0·46-0·93), although tests for interaction were inconclusive.
An early invasive strategy does not reduce mortality compared with a delayed invasive strategy in all patients with NSTE-ACS. However, an early invasive strategy might reduce mortality in high-risk patients.
EGFR antibodies have shown promise in patients with advanced non-small-cell lung cancer (NSCLC), particularly with squamous cell histology. We hypothesised that EGFR copy number by fluorescence in-situ hybridisation (FISH) can identify patients most likely to benefit from these drugs combined with chemotherapy and we aimed to explore the activity of cetuximab with chemotherapy in patients with advanced NSCLC who are EGFR FISH-positive.
We did this open-label, phase 3 study (SWOG S0819) at 277 sites in the USA and Mexico. We randomly assigned (1:1) eligible patients with treatment-naive stage IV NSCLC to receive paclitaxel (200 mg/m2; every 21 days) plus carboplatin (area under the curve of 6 by modified Calvert formula; every 21 days) or carboplatin plus paclitaxel and bevacizumab (15 mg/kg; every 21 days), either with cetuximab (250 mg/m2 weekly after loading dose; cetuximab group) or without (control group), stratified by bevacizumab treatment, smoking status, and M-substage using a dynamic-balancing algorithm. Co-primary endpoints were progression-free survival in patients with EGFR FISH-positive cancer and overall survival in the entire study population. We analysed clinical outcomes with the intention-to-treat principle and analysis of safety outcomes included patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov (number NCT00946712).
Between Aug 13, 2009, and May 30, 2014, we randomly assigned 1313 patients to the control group (n=657; 277 with bevacizumab and 380 without bevacizumab in the intention-to-treat population) or the cetuximab group (n=656; 283 with bevacizumab and 373 without bevacizumab in the intention-to-treat population). EGFR FISH was assessable in 976 patients and 400 patients (41%) were EGFR FISH-positive. The median follow-up for patients last known to be alive was 35·2 months (IQR 22·9-39·9). After 194 progression-free survival events in the cetuximab group and 198 in the control group in the EGFR FISH-positive subpopulation, progression-free survival did not differ between treatment groups (hazard ratio [HR] 0·92, 95% CI 0·75-1·12; p=0·40; median 5·4 months [95% CI 4·5-5·7] vs 4·8 months [3·9-5·5]). After 570 deaths in the cetuximab group and 593 in the control group, overall survival did not differ between the treatment groups in the entire study population (HR 0·93, 95% CI 0·83-1·04; p=0·22; median 10·9 months [95% CI 9·5-12·0] vs 9·2 months [8·7-10·3]). In the prespecified analysis of EGFR FISH-positive subpopulation with squamous cell histology, overall survival was significantly longer in the cetuximab group than in the control group (HR 0·58, 95% CI 0·36-0·86; p=0·0071), although progression-free survival did not differ between treatment groups in this subgroup (0·68, 0·46-1·01; p=0·055). Overall survival and progression-free survival did not differ among patients who were EGFR FISH non-positive with squamous cell histology (HR 1·04, 95% CI 0·78-1·40; p=0·77; and 1·02, 0·77-1·36; p=0·88 respectively) or patients with non-squamous histology regardless of EGFR FISH status (for EGFR FISH-positive 0·88, 0·68-1·14; p=0·34; and 0·99, 0·78-1·27; p=0·96; respectively; and for EGFR FISH non-positive 1·00, 0·85-1·17; p=0·97; and 1·03, 0·88-1·20; p=0·69; respectively). The most common grade 3-4 adverse events were decreased neutrophil count (210 [37%] in the cetuximab group vs 158 [25%] in the control group), decreased leucocyte count (103 [16%] vs 74 [20%]), fatigue (81 [13%] vs 74 [20%]), and acne or rash (52 [8%] vs one [<1%]). 59 (9%) patients in the cetuximab group and 31 (5%) patients in the control group had severe adverse events. Deaths related to treatment occurred in 32 (6%) patients in the cetuximab group and 13 (2%) patients in the control group.
Although this study did not meet its primary endpoints, prespecified subgroup analyses of patients with EGFR FISH-positive squamous-cell carcinoma cancers are encouraging and support continued evaluation of anti-EGFR antibodies in this subpopulation.
National Cancer Institute and Eli Lilly and Company.
Purpose We evaluated the relationship between prostate-specific antigen (PSA) and overall survival in the context of a prospectively randomized clinical trial comparing androgen-deprivation therapy (ADT) plus docetaxel with ADT alone for initial metastatic hormone-sensitive prostate cancer. Methods We performed a landmark survival analysis at 7 months using the E3805 Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) database ( ClinicalTrials.gov identifier: NCT00309985). Inclusion required at least 7 months of follow-up and PSA levels at 7 months from ADT initiation. We used the prognostic classifiers identified in a previously reported trial (Southwest Oncology Group 9346) of PSA ≤ 0.2, > 0.2 to 4, and > 4 ng/dL. Results Seven hundred nineteen of 790 patients were eligible for this subanalysis; 358 were treated with ADT plus docetaxel, and 361 were treated with ADT alone. Median follow-up time was 23.1 months. On multivariable analysis, achieving a 7-month PSA ≤ 0.2 ng/dL was more likely with docetaxel, low-volume disease, prior local therapy, and lower baseline PSAs (all P ≤ .01). Across all patients, median overall survival was significantly longer if 7-month PSA reached ≤ 0.2 ng/dL compared with > 4 ng/dL (median survival, 60.4 v 22.2 months, respectively; P < .001). On multivariable analysis, 7-month PSA ≤ 0.2 and low volume disease were prognostic of longer overall survival (all P < 0.01). The addition of docetaxel increased the likelihood of achieving a PSA ≤ 0.2 ng/dL at 7 months (45.3% v 28.8% of patients on ADT alone). Patients on ADT alone who achieved a 7-month PSA ≤ 0.2 ng/dL had the best survival and were more likely to have low-volume disease (56.7%). Conclusion PSA ≤ 0.2 ng/dL at 7 months is prognostic for longer overall survival with ADT for metastatic hormone-sensitive prostate cancer irrespective of docetaxel administration. Adding docetaxel increased the likelihood of a lower PSA and improved survival.
Darwin thought evolution was too slow to change the environment on observable timescales. Ecologists are discovering that he was wrong.
It took Timothy Farkas less than a week to catch and relocate 1,500 stick insects in the Santa Ynez mountains in southern California. His main tool was an actual stick.
“It feels kind of brutish,” says Farkas. “You just pick a stick up off the ground and beat the crap out of a bush.” That low-tech approach dislodged hordes of stick insects that the team easily plucked off the dirt.
On this hillside outside Santa Barbara, there are two kinds of bush that the stick insect (Timema cristinae) inhabits. The creature comes in two corresponding colorations: green and striped. Farkas and his fellow ecologists knew that the stick insects had evolved to blend in with their surroundings. But the researchers wanted to see whether they could turn this relationship around, so that an evolved trait — camouflage — would affect the organism’s ecology.
To find out, the team relocated mixtures of green and striped insects to different plants, so that some insects’ coloration clashed with their new home. Suddenly maladapted, these insects became targets for hungry birds, and that caused a domino effect1. Birds drawn to bushes with mismatched stick insects stuck around to eat other residents, such as caterpillars and beetles, stripping some plants clean. “That this evolutionary force can cause local extinction is striking,” says Farkas, an ecologist at the University of New Mexico in Albuquerque. “It affects the entire community.” All this happened because of an out-of-place evolutionary trait.
Ecologists have generally ignored evolution when studying their systems; they thought it was impossible to test whether such a slow process could change ecosystems on observable timescales. But they have come to realize that evolution can happen more quickly than they assumed, and a wave of studies has capitalized on this idea to observe evolution and ecology in unison.
Such eco-evolutionary dynamics could be important for understanding how new populations emerge, or for predicting when one might go extinct. Experiments suggest that evolutionary changes alter some ecosystems just as much as shifts in more-conventional ecological elements, such as the amount of light reaching a habitat. “Eco-evolutionary dynamics is the dragon lots of people are chasing right now,” says Troy Simon, an ecologist at the University of Georgia in Athens.
Rapid evolution can sometimes offset some of the detrimental effects of a warming climate and other known drivers of change; in other cases, it can worsen those effects. Even for the most common processes, such as changes in population size or food chains, ecologists must take evolution into consideration, researchers say. “Everybody realized rapid evolution was occurring everywhere,” says evolutionary ecologist Andrew Hendry of McGill University in Montreal, Canada.
Darwin in reverse
It all goes back to Charles Darwin’s finches. When the naturalist visited Ecuador’s Galapagos Islands in 1835, he documented some variation in the beaks of finches living on different islands and eating different foods. Years after the voyage, he hinted in his Journal of Researches that this variation suggested a tight relationship between the birds’ ecology and their evolution.
Darwin never imagined seeing this in action, because he thought that evolution occurs only at the “long lapse of ages”. But by the late 1990s, ecologists had started to realize that evolution could be observed within a few generations of a given species — a timescale that they could work with.
Organisms that live and die quickly provided some of the early data demonstrating how evolution influences ecology. A key study2 published in 2003 focused on algae and rotifers, microscopic predators that feed on algae; both species can tick through up to 20 generations in the course of a couple of weeks. The study mixed the organisms together in tanks and showed that when algae evolve rapidly, they throw off normal predator–prey population dynamics.
Usually, the two species play out a cycle between ‘boom’ and ‘bust’. The algal population grows; the rotifers then gobble them up and their own population explodes. When the predators have depleted the algae, their numbers crash. The algae then rebound and the pattern starts again. But when the researchers introduced different algal varieties — seeding some genetic diversity — the algae began to evolve rapidly and the cycle changed completely. The algal population remained elevated for longer, and the rotifers’ own boom was abnormally delayed because the new algae were more resistant to predation.
Similar studies in aphids3 and water fleas4 have confirmed that rapid evolution can affect characteristics of populations, such as how fast they grow. These ecological changes can alter future rounds of evolution and selection. Seeing such rapid evolution in action has changed ecologists’ picture of what they thought was a predictable and fundamental ecological process, and showed how important it is to consider evolution when studying how populations interact. “Everything about ecology has to be re-examined in light of the fact that evolution is more important than we thought,” says Stephen Ellner, an ecologist at Cornell University in Ithaca, New York. “This changes everything.”
After these initial lab studies, ecologists started to think bigger. Experiments conducted indoors at small scales can’t reproduce the intricacies of natural ecosystems, so researchers have been testing their ideas in grander, less artificial set-ups.
Working out whether eco-evolutionary dynamics affect the real world is one of the field’s biggest challenges, says Rebecca Best, an evolutionary ecologist at Northern Arizona University in Flagstaff, because so many uncontrollable factors can affect wild ecosystems.
She has found a middle ground by incorporating natural elements into a tightly controlled experiment. At a site overlooking Lake Lucerne in Switzerland, she and her team set up 50 miniature lakes: large plastic tanks each holding 1,000 litres of water, plus a slurry of sediment, plant life, algae, invertebrates and water collected from three lakes — Geneva, Constance and Lucerne. Once these ‘mesocosms’ were settled, with plankton reproducing and plants taking root, the team introduced into each tank one of two genetically distinct lineages of adult threespine sticklebacks (Gasterosteus aculeatus): one lineage from Lake Constance and the other from Lake Geneva. A few weeks later, the researchers removed the fish and replaced them with a mixture of lab-raised juveniles from both locations, plus some hybrids of the two lineages.
They found5 that how the adults had manipulated their environments affected the survival of the next generation of fish (see ‘Fishy feedback’). If the adult fish removed prey of a certain size, for example, younger fish that shared characteristics with the adults — in this case, mouth size — went hungry. Juveniles that were different from the former occupants fared better. The study showed that the traits of the adult fish shaped the environment for the next generation — enough to dictate the evolutionary trajectory of those that followed.
Best says that her mesocosm experiments are more sophisticated and realistic than lab studies, but less easy to control. Ideally, she says, the team would run the experiment in the field, but that would come with its own obstacles, such as having to factor in the evolution of other species in the ecosystem, or the risk of events such as extreme storms.
Experiments such as Best’s are “vastly easier and more controlled than anything you can do in nature”, Hendry says. But they might not reflect what happens in real ecosystems. “That’s the watershed moment we’re at right now. Does this actually play out in the real world?”
In the messy real world, it can be difficult to pinpoint the impact of a single feature, either an ecological attribute (such as rainfall) or an evolutionary one (such as a change in camouflage).
A few intrepid ecologists are trying anyway. Last year, a study6 on guppies in Trinidad demonstrated that the fish’s evolution can drive an ecological change as strongly as an environmental factor: the amount of light available.
The study focused on two populations of guppies (Poecilia reticulata) in the northern part of the island. Their habitats differ in several ecological characteristics, including how much shade they receive from the forest canopy, which affects how many algae grow in the streams.
The team moved populations of guppies — which differed in evolved traits such as body proportions and colour — between eight rivers in the watershed, and measured the canopy above the water. In some of the study sites, introducing a new kind of guppy altered algal populations as much as allowing 20% more light to stream onto the water did. Even a natural ecosystem, say the researchers, is a product of evolution as well as ecology.
This experiment did use a more natural setting than many others, but Trinidadian guppies are ecological celebrities that have appeared in hundreds of studies, and the rivers they inhabit have been highly manipulated already. Researchers want to know whether the forces at work in the guppy populations also play out in species that are not necessarily famous for evolutionary dynamics, says McGill ecologist Gregor Fussmann. “We need systems that are generic,” he says.
That’s exactly what Thomas Schoener, an evolutionary ecologist at the University of California, Davis, and his team have set out to do with two populations of lizard in the Bahamas. Their project is part of an ongoing multigenerational study, begun in 1977. They have been attempting to simulate accelerated evolution by catching curly-tailed lizards (Leiocephalus carinatus) and moving them to a string of tiny islands inhabited by brown anoles (Anolis sagrei), to see how the ecosystems change as a result.
Curly-tails are natural predators of the smaller brown anole, so when the team first moved the curly-tails onto islands with the anoles, populations of the latter dropped7. Spider populations increased when anoles — their main predator — took a hit, and the excess spiders then ate more springtail insects (Collembola). Researchers spotted surviving anoles fleeing to the trees to escape their new predator, and that triggered damage to plants. The team knew from previous work8 that anoles adapt fairly quickly to tree climbing by favouring shorter-limbed offspring.
But then something unexpected happened. Hurricane Irene hit the islands in 2011, followed by Hurricane Sandy in 2012. Populations of both anoles and curly-tailed lizards crashed. On some islands, anoles were completely wiped out after the storm.
“The hurricanes are a mixed blessing because on the one hand, they give us all kinds of interesting data about disturbance,” Schoener says. “But on the other hand, it can slow down what might be a normal progression of evolution.”
The team has managed to keep its project on track, and is observing evolutionary changes in leg length and the lizards’ re-colonization of the islands after the hurricane.
Surprisingly, the anoles that survived the storm have longer limbs than the pre-hurricane population7 — the opposite of the team’s prediction, but perhaps better for holding on to branches tightly during a storm. The team has just received funding to study how this evolutionary change will affect the ecosystem.
The hurricanes certainly complicated Schoener’s study, but other researchers appreciate the unplanned intervention because it provides a chance to study the consequences of real events and watch the lizards recolonize the islands. Even in the absence of a natural disaster, any number of dynamics could also change the course of an organism’s evolution, says Best. “Those potential interactions are going on for everything in the ecosystem.”
She and others say there is plenty more to do, both in the lab and in more-elaborate field studies. Some researchers want to add genetic data to their work, to understand what is driving evolution in the first place. This would tell them whether a particular trait — growth rate, for example — is truly heritable and evolving, rather than a characteristic that can be directly affected by an animal’s environment. Genomic data could also help to find hidden characteristics — those harder to observe than body size or growth rate — that might affect ecology.
In a study9 of algae and rotifers, Lutz Becks, an evolutionary ecologist at the Max Planck Institute for Evolutionary Biology in Plön, Germany, and his colleagues watched several cycles in which populations waxed and waned as the algae clumped together and dispersed. But when the team looked at individual genes underlying clumping behaviour, they found that their expression varied wildly from one cycle to the next, even though the clumping looked the same. They have since observed co-evolution of three species at once — algae, rotifers and a virus — and found10 that the rotifers slowed the rate at which the algae and virus co-evolved. The team plans to repeat this type of experiment, analysing genome data to see how specific details of the algal and viral genes change over time. “We’d like to get to a point where we can actually predict what genomic architecture might be needed for rapid evolution,” says Becks.
Rapid evolution can offset — at least partially — the damaging effects of climate change and other ecological disturbances. In 2011, for instance, a group led by Ellner reanalysed11 35 years of data from dormant eggs of Daphnia water fleas, exhumed from a sediment core in Lake Constance. The data represented periods before, during and after a time when the lake was affected by blooms of cyanobacteria, a microbe with low nutritional value for Daphnia. The team found that as the Daphnia’s food became less nutritious, juvenile fleas grew poorly and ended up as smaller adults. But after several generations, evolutionary changes caused the growth rate of juveniles to return to normal. And the adults regained some of their lost stature, although they didn’t reach the same size as they had before the blooms. The researchers suggest that rapid evolution is likely to occur most often when the environment is changing, but the effects are hidden because they pull in opposite directions. “Evolution is going to be part of how the biosphere responds to climate change,” Ellner says.
Farkas has these questions about evolution and ecology at the front of his mind as he beats the bushes around Santa Barbara and sorts his stick insects. He and his team are planning even more elaborate schemes. They want to catch a full feedback cycle unfolding — ecology affecting evolution affecting ecology once more — all while collecting genetic data. “Comparing how large these effects of evolution will be and understanding when and where evolution is happening is going to be important,” says Farkas. “To me, it’s the final frontier. But it’s going to take a really long time.”