Posts Tagged ‘science’

A 3D rendering of Homo erectus from an exhibit at the Museum of Natural History in Vienna, Austria.


Homo sapiens have existed in the form we do today for only about 50,000 years. Go back 2 million years ago though, and there were several kinds of archaic humans. It was near the end of the Australopithecus era (you may have heard of Lucy), and the beginning of the time of Paranthropus and Homo erectus, one of Homo sapiens’ direct ancestors. It’s easy to assume that one group died off before the next came on the scene, but they overlapped, according to new research.

“We know that the old idea, that when one species occurs another goes extinct and you don’t have much overlap, that’s just not the case,” study coauthor Andy Herries, a paleoanthropologist at La Trobe University in Australia, told Smithsonian magazine.

The recent find, published in the journal Science, comes out of the Drimolen Paleocave System in South Africa. This area is a gold mine of ancient ancestry; over 160 remains have been found there already, and now, the oldest Homo erectus discovery, a cranium, has been found there, dating to about 2 million years ago. Also found were skull fragments and teeth of Paranthropus robustus, and our earlier human ancestor, Australopithecus, who was also known to live in the same area at the same time.

Lucy belonged to the extinct species Australopithecus afarensis, portrayed here in a sculptor’s rendering. (Photo: Dave Einsel/Getty Images)

These recently discovered fossils are the oldest examples of their respective species ever discovered.

“Here we have evidence of all three genera, Homo, Paranthropus and Australopithecus, sharing the landscape at just about the same time,” David Strait, a paleoanthropologist at Washington University in St. Louis and co-author of the paper, told The New York Times. “It is our first really good look at the time that this replacement is taking place and that’s pretty exciting.”

It’s well-known that the later human variants (hominins is the term scientists use for modern and related humans) diverged, evolved and then intermixed: Groups of hominins left East Africa and explored North Africa, Europe and Asia. As those early humans moved through various environments, some stayed and adapted to local conditions while others moved on. They might bump into each other again, sometimes using the same places to fish, or shelter. And sometimes they would die there, leaving the fossil record for modern Homo sapiens to find.

“The truth is that from about 2 million years ago until around 10,000 years ago, the world was home, at one and the same time, to several human species. And why not? Today, there are many species of foxes, bears, and pigs. The earth of a hundred millennia ago was walked by at least six different species of man,” writes Yuval Harari in his book, “Sapiens: A Brief History of Humankind.”

A reconstruction of a Neanderthal who lived some 50,000 years ago in what’s now Spain, by Italian scientist Fabio Fogliazza. (Photo: Cesar Manso/AFP/Getty Images)

Muscular, bulky Neanderthals were well-suited to the Ice Age climate of western Eurasia, and Homo erectus populated east Asia (and did so successfully for 2 million years). Homo soloensis was found on the Indonesian island of Java, and another tiny island was home to Homo floresiensis; the people there were petite, reaching a maximum height of just 3 1/2 feet due to limited local food resources. The remains of Homo denisova were found in a Siberian cave, but they traveled far and wide; their DNA has been found in modern Australian aborigines, Polynesians, Fijiians and others.

Other humans continued to evolve within Africa, including Homo rudolphenisis and Homo ergaster. And like the others, Homo sapiens (that’s us) also came out of Africa, and then met up with many of these species as we moved around the world. And by “met up with,” I mean a few things, including sex that resulted in offspring. Just last year, a half-Denisovan, half-Neanderthal child, was found, proving that successful procreation occurred.

And of course, the proof is also in our DNA. As mentioned above, Denisovan DNA is present in some populations and most non-Africans have some Neanderthal DNA. (For example, according to my 23andMe report, I have 249 variants, which is lower than average.)

We Homo sapiens live in a lonely time: Throughout most of human history, there were many other kinds of humans on the planet with us — we are still discovering new ones all the time. So what happened to them all?

There are plenty of theories: “The Interbreeding Theory tells a story of attraction, sex, and mingling,” writes Harare. “As the African immigrants spread around the world, they bred with other human populations, and people today are the outcome of this inbreeding.”

This idea is at least partially backed up by Denisovan and Neanderthal DNA found in modern humans. But another possibility is that Homo sapiens outcompeted Neanderthals and others, over time starving them of resources. Or we may have killed these other people for being so different from us. As Harare writes, “Tolerance is not a sapiens trademark.”

Professor David Stern examines test corn plants at Boyce Thompson Institute with Coralie Salesse-Smith. They are looking for varieties that will be better able to cope with cold weather. | Boyce Thompson Institute photo

Corn is the third largest grain crop in Canada and the number one crop in Ontario in terms of production. Nationally, yields vary depending on weather, and 2019 was a particularly challenging year.

Heavy rain and colder than normal temperatures made planting conditions difficult in Eastern Canada. Very dry conditions persisted into the growing season in parts of Western Canada, while unseasonal rain and early snow on the Prairies slowed harvest for many farmers.

Corn is one of the world’s most important crops, not only for food but for animal feed and biofuel. However, as a grass of tropical origin, it is particularly sensitive to cold weather. That trait can be problematic, especially when the growing season is only four or five months.

At Cornell University’s Boyce Thompson Institute in New York, scientists have developed a chill-tolerant corn variety that recovers much more quickly after a cold snap. It could broaden the latitudes in which corn can be grown and help farmers increase yields, especially in the face of wildly fluctuating weather patterns due to climate change.

“While the research is too early-stage to know for sure, the chilling-tolerant corn has promise to help crops cope with early cold snaps, as well as recover more quickly from drought,” said David Stern, president of the Boyce Thompson Institute and adjunct professor of plant biology in Cornell University’s College of Agriculture and Life Sciences.

“In terms of cold snaps, the combination of cold weather and strong spring sunlight can cause corn leaves to bleach, weakening or even killing the plants. The chilling-tolerant corn is less prone to bleaching, allowing it to recover more quickly. As a result, farmers could potentially plant earlier and harvest earlier, avoiding the frequent drought-prone conditions of late summer that occur just when ears are filling with grain. The potential benefits are a more flexible spring planting schedule, and an earlier harvest.”

Research in 2018 showed that increasing levels of an enzyme called rubisco led to bigger and faster-maturing plants. Rubisco is needed by plants to turn atmospheric carbon dioxide into sugar but, in cold weather, its levels in corn leaves decrease dramatically.

“Plants are very good at sensing temperature and seem to deliberately reduce the amount of rubisco when it’s cold,” said Stern.

“In doing so, plants can save the energy it takes to make rubisco and other proteins, as well as generally slow down metabolism, just like many living organisms do in the cold (think of hibernation).”

Rubisco is made up of proteins — eight large subunits and eight small ones with help from a third protein called RAF1. Because rubisco is a protein, it is made up of amino acids, which are rich in nitrogen, making rubisco a nitrogen reservoir. However, Rubisco is actually an inefficient enzyme so boosting its function will boost plant growth.

“We introduced transgenes that increase the abundance of (the) three proteins: the large subunit of rubisco, the small subunit and RAF1,” said Stern.

“In the modified corn, all three proteins are more abundant, thus increasing the level of Rubisco.”

The scientists grew plants for three weeks at 25 C, lowered the temperature to 14 C for two weeks and then returned it to 25 C, which is a considerable temperature swing. The intent was to test resistance and monitor the factors that can help plants withstand stress.

“The corn with more rubisco performed better than regular corn before, during and after chilling,” said Coralie Salesse-Smith, a PhD candidate in Stern’s lab during the study and the research paper’s first author.

“We were able to reduce the severity of chilling stress and allow for a more rapid recovery.”

Compared to traditional corn, the genetically modified corn had higher photosynthesis rates throughout the experiment and recovered more quickly from the chilling stress with less damage to the molecules responsible for photosynthesis. As a result, the plant grew taller and developed mature ears more quickly following a cold spell.

“What scientists are trying to build into plants is resilience — the ability to withstand a variety of shocks whose frequency and magnitude cannot be reliably predicted,” said Stern.

“In the laboratory, we can only test a small number of simulated climactic conditions. What happens when cold is combined with drought? Flooding with a heat wave? The real world of agriculture is far more complicated than a lab study. So, putting this kind of corn in the field is the best way to test its resilience.”

He said that the technology to bolster corn into a chill-resistant variety is being tested for the first time this growing season by a large seed company. They will know later this year or early next year if the plant is responding the way they expect and if it works as well in their elite field varieties as it does in the laboratory.

“If it does, the traits would move into their standard breeding pipeline and farmers would see the seed in six to 10 years. That is the reality of breeding for new corn traits,” said Stern.

Meanwhile, several research projects continue.

“One is to improve the activity, or speed, of the rubisco enzyme,” he said.

“In corn, only about 70 percent of the enzyme is working at any given time. We would like to increase that to 80 percent or 90 percent. Another path is to combine the rubisco trait with other genes that can increase photosynthesis. Rubisco is only one player in a complicated metabolic network, and we need to target other steps in the pathway as well. A third direction is to combine this higher photosynthesis-chilling tolerance trait with genes that improve tolerance to insects, drought or heat. This moves towards the ‘optimal’ resilient and climate-ready plant that would be a long-term goal.”

It is possible this approach could be used on other crops such as sugar cane and sorghum. The research paper was published online in the Plant Biotechnology Journal.

New corn variety copes better with cold

Thin, transparent and flexible, organic solar cells look perfect for harnessing the sun’s energy from pretty much any surface, including windows, vehicles and smartphones. But they’ve been dogged by the perception that they’re not stable enough to survive in the real world. Now researchers in the US have demonstrated it’s possible to create organic solar cells that reliably work for 27,000 years outdoors, quashing the idea that long-lived devices are impossible.

The reliability of organic photovoltaic (OPV) cells has been one of the biggest hurdles to practical applications. Even the most stable ones typically don’t last longer than seven years, degrading due to the effects of light and heat. It led many to believe that solar cells made from weakly bonded organic materials simply couldn’t be made to rival the longevity of traditional silicon devices.

But Stephen Forrest’s group at the University of Michigan has put this idea to rest by showing that C70 fullerene-based single junction OPVs can survive the glare of the sun for far longer than any commercial device would require – around 27,000 years. The team extrapolated this number by artificially ageing the cells using heat and intense light.

‘We have shown that organic solar cells aren’t particularly difficult to stabilise – it depends on choice of materials, fabrication processes and device architectures,’ says Forrest. ‘It is now clear that the intrinsic lifetime of OPVs can be sufficient to achieve the practical lifetimes met by conventional, inorganic cells.’

The researchers made thin-film organic solar cells in a series of layers, like a nano-scale multi-layered sandwich, using vapour deposition to precisely control the thickness and purity of each layer. The experimental devices had efficiencies of 6–7% – by comparison commercial silicon solar cells have efficiencies of around 20%. Initial experiments, which simulated the light and heat intensity of the sun using a xenon arc lamp revealed that the cells degraded too slowly to be measured over the course of a year. So the team rigged up a system of white LEDs which could artificially age a fresh set of OPV cells by subjecting them to light intensities that delivered the equivalent of up to 37 suns.

After exposure for more than 68 days, the cells maintained more than 87% of their starting efficiency. The team were able to extrapolate from the results that it would take the equivalent of 27,000 years outdoors for the cells to lose 20% of their original efficiency – the point at which the team deemed the device no longer useful. What’s more, no efficiency loss was observed in cells subjected to nine years’ worth of UV radiation.

‘The extrapolated lifetimes were exceptionally long, particularly compared to all previous reports of device lifetimes. Yet, “short lifetime” as a feature of all organic devices is a myth, as has been proven for [organic LEDs],’ explains Forrest. ‘So while the very long intrinsic lifetime is surprising, it is within reasonably expected values for the best organic devices reported in other application spaces.’

‘The excitement of this paper is that it debunks the common belief that organic materials are unstable and that long-lived organic solar cells are simply not possible,’ says Paul Dastoor, who develops organic solar cells, including a solar paint, at the University of Newcastle, Australia. ‘Indeed, our own work is showing that it is the packaging and encapsulation that is far more critical to obtaining long device lifetimes rather than organic material stability.’

Q Burlingame et al, Nature, 2019, DOI: 10.1038/s41586-019-1544-1

By Laura Sanders

Although it’s tricky for us humans to see, mouse feelings are written all over their furry little faces.

With machine learning tools, researchers reliably spotted mice’s expressions of joy, fear, pain and other basic emotions. The results, published in the April 3 Science, provide a field guide for scientists seeking to understand how emotions such as joy, regret and empathy work in animals other than humans (SN: 11/10/16; SN: 6/9/14; SN: 12/8/11).

Using machine learning to reveal mice’s expressions is “an extraordinarily exciting direction,” says Kay Tye, a neuroscientist at the Salk Institute for Biological Studies in La Jolla, Calif. The findings “lay the foundation for what I expect will be a game changer for neuroscience research on emotional states.”

Neuroscientist Nadine Gogolla of the Max Planck Institute of Neurobiology in Martinsried, Germany, and colleagues gave mice experiences designed to elicit distinct emotions. Sugar water evoked pleasure, a shock to the tail triggered pain, bitter quinine water created disgust, an injection of lithium chloride evoked a nauseated malaise, and a place where shocks previously had been delivered sparked fear. For each setup, high-speed video cameras captured subtle movements in the mice’s ears, noses, whiskers and other parts of the face.

Observers can generally see that something is happening on the mouse’s face, Gogolla says. But translating those subtle clues into emotions is really hard, “especially for an untrained human being,” she says.

Machine learning techniques handle the job beautifully, the researchers found. The methods were able to spot subtle face movements that came with good or bad experiences. For instance, on the face of a mouse drinking sweet water — and presumably happy about it — the ears move forward and fold at the back toward the body, and the nose moves down toward the mouth. A mouse tasting bitter quinine sends its ears straight back, and the nose curls slightly backward, too.

Activity of nerve cells in the mice’s brains also changed with distinct emotions, other analyses showed. These cells reside in the insular cortex, a deeply buried spot known to be involved in human emotions, too.

By prodding these cells to fire signals, the researchers could prompt the mice to display certain facial expressions. These connections among brain activity and facial expressions may lead to insights about the neural basis of emotions, and what goes awry in disorders such as anxiety, the researchers suggest.

Mice’s facial expressions can reveal a wide range of emotions

Goldenrods that evolved in the presence of herbivores release volatile chemicals that trigger defenses in neighboring plants of their species, even those that are genetically unrelated.

by Ashley Yeager

When a beetle larva bites into the leaf of a goldenrod plant, a perennial herb known for its bright yellow flowers, it gets a mouthful of food to fuel its growth. But the plant’s perspective is rather different. The bite damages the goldenrod (genus: Solidago), causing it to launch molecular defenses against the insect and to emit a concoction of chemicals that change the physiology of goldenrod plants nearby. It’s as if the plants are communicating about the invader.

For researchers studying plants’ responses to herbivory, the reasons for this communication are something of a mystery. “We don’t have a good understanding of why these plants are emitting these cues,” Rick Karban, an entomologist who studies plant communication at the University of California, Davis, tells The Scientist. “We don’t even know if the cues that plants are emitting—that other plants can perceive and respond to—are somewhat intentional,” or just a byproduct of leaf damage.

The notion that plants communicate was controversial until the end of the 20th century. Biologists first argued that trees and plants could “talk” to one another in the 1980s, but data supporting the idea were dismissed by many researchers as statistically sketchy. Over the past few decades, however, the scientific community has revised its opinion. A series of papers have shown that when a plant such as goldenrod is damaged, it releases volatile organic compounds (VOCs) that prompt neighboring plants to mount their own chemical defenses against an impending herbivore attack. Karban says researchers are now focused on why the emitting plant puts out this signal, and whether it derives a benefit from telling those around it that it’s being eaten.

It’s possible that surrounding plants are merely eavesdropping on the signal emitter, which derives no benefit from the situation. Researchers have also proposed two alternative hypotheses that involve a benefit to the emitter. The first—the kin selection hypothesis—states that the plant emitting the signal indirectly benefits thanks to the increased survival of genetically related individuals in its vicinity, even if the plant itself is damaged by herbivory. The second—the mutual benefit hypothesis—posits that the plant emitting the signal directly benefits from communication because the preemptive chemical defenses launched by all its neighbors result in a hostile environment that encourages the herbivorous insect to move away from the area.

Finding evidence to distinguish between these scenarios hasn’t been easy, especially because plant communication is a small field. But a long-running project offers new clues. In 1996, a team at Cornell University started an elaborate experiment on one goldenrod species, S. altissima, regularly spraying rows and rows of the plant with the insecticide fenvalerate, while leaving other rows untreated. After 12 years, the researchers collected plants from each of the rows, brought them to the lab, snipped the stems, and grew clones. Then, the team set up collections of the clones in pots at a nearby farm, let goldenrod beetle larvae munch on some of the plants, and measured the emission of VOCs.

“This research was really mostly curiosity driven,” says Aino Kalske, a postdoctoral researcher in ecology and evolution biology at the University of Turku in Finland and a former graduate student at Cornell who helped with the experiment. She and her colleagues were particularly interested to see if the goldenrod’s chemical messages would evolve differently depending on whether the plants had been treated with insecticide and were protected from insect attacks or had been left untreated and experienced higher levels of herbivory. Differences in signaling between the treated and untreated plants’ descendants might be a small step toward determining which hypothesis about plant communication was correct.

The team found that VOCs emitted by goldenrod plants whose predecessors had been sprayed with the insecticide only induced genetically identical plants to mount preemptive chemical defenses to insect invasion—consistent with the kin selection hypothesis. But VOCs emitted by goldenrod whose predecessors hadn’t been sprayed with the insecticide induced the preemptive defense from all the other goldenrod plants around them, even plants that weren’t their kin—consistent with the mutual benefit hypothesis.

Additionally, the plants exposed to herbivory converged on a shared VOC signal over the course of the study—with all of the goldenrod plants eventually emitting the same chemical signals whether they were genetically identical to the emitter plant or not. Plants treated with insecticide showed no such signal convergence, the researchers reported in Current Biology last September. This sort of convergence on a single chemical signal is thought to benefit plants exposed to herbivory by providing a stronger deterrent against invading insects or a stronger attraction for the herbivores’ natural enemies. Kalske says the study provides the first concrete evidence that plants aren’t merely eavesdropping on one another, and that the emitter derives a benefit from releasing its chemical messages.

“The main value of the paper is the extremely long-lasting experiment needed to assess an evolutionary change in an organism,” Emilio Guerrieri, a researcher at the National Research Council of Italy’s Institute for Sustainable Plant Protection who was not involved in the study, writes in an email to The Scientist. The experiment, he says, “represents a sound demonstration that herbivores shape the VOC emission of a plant.”

Researchers still don’t know much about how the plants actually receive and respond to the VOC cues, Kalske notes, or whether the presence of other types of herbivores, such as mammals, influences similar signal changes. These are questions that the team would still like to answer, she says, not least because of the potential agricultural applications. “Understanding the intricacies of the plant world and plant-plant communication in more detail can potentially help us in plant protection in the agricultural context, if we can learn how to use these volatiles to turn on defenses in crop plants effectively.”


The way oral bacteria sets up shop in our mouths is not unlike how we humans settle into our cities, a new study has found.

There’s a reason bacteria are said to live in ‘colonies’, and the more we learn about how these tiny architects build their communities, the more familiar their behavior seems to us.

A new study following how multiple individual settlers develop into microcolonies has found growth patterns and dynamics that mirror our own urban inclinations.

“We take this ‘satellite-level’ view, following hundreds of bacteria distributed on a surface from their initial colonisation to biofilm formation,” says Hyun Koo from the University of Pennsylvania.

“And what we see is that, remarkably, the spatial and structural features of their growth are analogous to what we see in urbanisation.”

Just as in nature, bacteria in your mouth live in complex structures known as biofilms. In fact, 99.9 percent of prokaryotes live crammed together with millions of other neighbours in one of these settlements.

Biofilms are everywhere, but if they’re on your teeth, we refer to them as plaque. This dense and sticky deposit is hard to remove, thereby protecting resident microbes from environmental assaults, like toothpaste, floss or even antibiotics.

It builds up when several individual settlers develop into microcolonies, but exactly how this happens remains underexplored.

Using the oral bacterium Streptococcus mutans, researchers have shown that microbial cells settle at random and regardless of the surface type. Nevertheless, only a subset of colonisers actually begin clustering, expanding their scope “by amalgamating neighboring bacteria into densely populated microcolonies.”

“We thought that the majority of the individual bacteria would end up growing,” says Koo. “But the actual number was less than 40 percent, with the rest either dying off or being engulfed by the growth of other microcolonies.”

Once the clusters arise, something really curious happens: they begin to interact with one another, growing and organising into densely populated “micron-scale microcolonies that further expand and merge” to form a biofilm superstructure.

This sort of cooperation is interesting, as previous studies have reported bacterial competition in other species, especially when there was a scarcity of nutrients.

In this case, the nutrients only impacted the actual forming of the colonies. After that, “the individual microcolonies (distant or in close proximity) continued to grow without disruption until merging with each other, and the merged structures behaved and grew like a single new harmonised community,” the researchers write.

Only when more antagonistic foreign species were introduced did it affect that seemingly peaceful unit, and the growth of the microcolonies was lowered.

“These communities (microcolonies) can expand and merge with each other in a collaborative fashion, without competition between adjacent communities,” the authors conclude.

It’s the type of growth that indicates “communal behavior between microorganisms”, and it looks similar to human urbanisation, where some settlers stay static, while others grow into villages that further expand into densely-populated microcolonies or cities, which then merge into microbial megacities.

Of course, there are limits to this idea of bacterial urbanisation. The authors aren’t saying microbes build traffic signs, roads and supply lines, but the general idea is the same and it can not only help us tackle infections better, it might also help us build more sustainably.

“It’s a useful analogy, but it should be taken with a grain of salt,” Koo says. “We’re not saying these bacteria are anthropomorphic. But taking this perspective of biofilm growth gives us a multiscale, multidimensional picture of how they grow that we’ve not seen before.”

The study was published in Nature Communications.

Evidence of a worm-like creature about the size of a grain of rice has been uncovered in South Australia, and researchers believe it is the oldest ancestor on the family tree that includes humans and most animals.

The creature lived 555 million years ago.

It’s considered to be the earliest bilaterian. Bilaterians are organisms with a front, back, two openings on either end and a gut that connects them. They were an evolutionary step forward for early life on Earth.

Some of the oldest life on Earth, including those sponges and algal mats, is referred to as the Ediacaran Biota. This group is based on the earliest fossils ever discovered, providing evidence of complex, multicellular organisms.

But those aren’t directly related to animals living today. And researchers have been trying to find fossilized evidence of the common ancestor of most animals.

Developing bilaterian body structure and organization successfully allowed life to move in specific, purposeful directions. This includes everything from worms and dinosaurs to amphibians and humans.

But for our common ancestor, they knew that fossils of the tiny, simple creatures they imagined would be nearly impossible to find because of its size and soft body.

Burrows were found in stone that belonged to a tiny creature who lived billions of years ago.

Then, they turned to fossilized burrows, dated to the Ediacaran Period some 555 million years ago, found in Nilpena, South Australia. For 15 years, scientists knew they were created by bilaterians. But there was no evidence of what made the burrows and lived in them.

That is, until researchers decided to take a closer look at the burrows. Geology professor Mary Droser and doctoral graduate Scott Evans, both from the University of California, Riverside, spotted impressions shaped like ovals near the burrows.

A 3-D laser scan revealed the impressions contained evidence of a body shaped and sized like a rice grain, with a noticeable head, tail and even V-shaped grooves suggesting muscles.

Contractions of the muscles would have enabled the creature to move and create the burrows, like the way a worm moves. Patterns of displaced sediment and signs of feeding led the researchers to determine that it had a mouth, gut and posterior opening.

And the size of the creature matched with the size of the burrows they found.

The study published Monday in the journal Proceedings of the National Academy of Sciences.
“We thought these animals should have existed during this interval, but always understood they would be difficult to recognize,” Evans said. “Once we had the 3D scans, we knew that we had made an important discovery.”

A 3D scan revealed the shape and characteristics of the creature that made the burrows.

The researchers involved in the study named the creature Ikaria wariootia. The first name translates to “meeting place” in the Adnyamathanha language. Adnyamathanha is the name of contemporary Indigenous Australian people that live in the area where the fossil was found. And the name of the species is a variation on a waterway in the area, called Warioota Creek.

The fossilized burrows were found beneath the impressions of other fossils in the lowest layer of Nilpena’s Ediacaran Period deposits. During its lifetime, Ikaria searched for the organic matter it fed on by burrowing through layers of sand on the ocean floor. Given that the burrows track through sand that was oxygenated, rather than toxic spots, suggest the creature had basic senses.

“Burrows of Ikaria occur lower than anything else. It’s the oldest fossil we get with this type of complexity,” Droser said. “We knew that we also had lots of little things and thought these might have been the early bilaterians that we were looking for.”

Droser also explained that other, larger fossils belonging to other creatures they found in the past were likely evolutionary dead-ends.

“This is what evolutionary biologists predicted,” Droser said. “It’s really exciting that what we have found lines up so neatly with their prediction.”

By Anette Breindl

The first attempt at using existing drugs to treat patients infected with SARS-CoV-2 has yielded disappointing results.

In 200 hospitalized patients with severe COVID-19, a 14-day regimen of twice-daily treatment with Kaletra/Aluvia (lopinavir/ritonavir, Abbvie Inc.) did not hasten recovery when added to the standard of care. Chinese clinicians led by Bin Cao of the National Clinical Research Center for Respiratory Diseases reported their findings in the March 19, 2020, issue of The New England Journal of Medicine.

Lopinavir is a protease inhibitor, while ritonavir increases the half-life of lopinavir by inhibiting its metabolism. The drug was tested because screening studies had flagged it as having activity against MERS-CoV, which has led to a clinical trial of a combination of Kaletra/Aluvia and interferon-beta for the treatment of MERS-CoV in the Kingdom of Saudi Arabia.

In the COVID-19 trial, 199 patients were treated, split evenly between drug and standard-of-care groups. The study’s primary endpoint, time to improvement, was the same between the two groups, both of which took 16 days to improve. Mortality and viral load at various time points were also not different.

In an editorial published alongside the paper, Lindsey Baden, of Harvard Medical School, and Eric Rubin, of the Harvard TH Chan School of Public Health, wrote that “the results for certain secondary endpoints are intriguing,” but also acknowledged that those results were hard to interpret, due to a mix of trial size, possible differences in illness severity at baseline, and the fact that the trial was randomized but not blinded.

And if certain endpoints were intriguing, others were discouraging. In particular, viral loads did not differ between the groups, tellingly so, according to Baden and Rubin. “Since the drug is supposed to act as a direct inhibitor of viral replication, the inability to suppress the viral load and the persistent detection of viral nucleic acid strongly suggest that it did not have the activity desired,” they wrote. “Thus, although some effect of the drug is possible, it was not easily observed.”

It is possible that larger trials will yet uncover an effect of Kaletra/Aluvia. But for now, perhaps the best hope is that other drugs will work better – in particular, remdesivir (Gilead Sciences Inc.), which was originally developed for Ebola virus disease, but proved less effective there than several other options.

A paper in the Jan. 10, 2020, issue of Nature Communications investigated the effects of Aluvia on MERS-CoV in mouse experiments, where it showed ho-hum effects. The authors of the Nature Communications paper reported that “prophylactic [Kaletra/Aluvia plus interferon-beta] slightly reduces viral loads without impacting other disease parameters.”

But remdesivir was more effective. “Both prophylactic and therapeutic [remdesivir] improve pulmonary function and reduce lung viral loads and severe lung pathology” in a mouse model of MERS, the authors reported.

Remdesivir is in both an NIH-sponsored clinical trial and a Japanese-Chinese trial as potential COVID-19 treatment, after a January case report of a patient who showed rapid improvement after he was treated with the drug for COVID-19.

Though the Kaletra/Aluvia trial’s results were not as hoped, Baden and Rubin noted that the trial itself was an encouraging bit of news, as well as a “heroic effort…. As we saw during the 2014 Ebola outbreak in West Africa, obtaining high-quality clinical trial data to guide the care of patients is extremely difficult in the face of an epidemic, and the feasibility of a randomized design has been called into question. Yet Cao’s group of determined investigators not only succeeded but ended up enrolling a larger number of patients (199) than originally targeted.”

Dive Brief:

Rheumatoid arthritis drug Kevzara will be used in an international study of patients infected with the new coronavirus and suffering from acute respiratory distress syndrome, Regeneron Pharmaceuticals and Sanofi announced Monday.

The trial will kick off in disease hotspot New York City, expanding to a total of 16 U.S. sites and enrolling 400 patients. The companies aim to study whether Kevzara can reduce fever and the need for supplemental oxygen in patients severely affected by COVID-19, the illness caused by the virus.

Roche’s Actemra, which has a similar mechanism of action, has been tested in Chinese patients and led to a decrease in fever and oxygen use, prompting the country to include it in treatment guidelines. The drug’s use shows the speed with which global public health officials are willing to consider using drugs off-label in order to address the coronavirus pandemic.

Dive Insight:

A vaccine to prevent infections of the novel coronavirus SARS-CoV-2 is likely a year or more away — at best — and treatments specifically designed to fight this virus or its complications are similarly far off.

Possible treatments, however, could already be available in the form of marketed or existing experimental drugs. Global public health officials, eager for a weapon to use in the midst of a global pandemic, are showing a willingness to be flexible in terms of the clinical trials and the evidence needed to prove treatments’ effectiveness.

Earlier this month, China OK’d the use of Actemra in patients with lung complications and high levels of interleukin-6, or IL-6, a protein that mediates inflammatory and immune response. High levels of IL-6 have been associated with a greater risk of death in patients with community-acquired pneumonia.

Actemra and Kevzara both block IL-6 and are prescribed for rheumatoid arthritis, a disorder in which an overactive immune system creates joint-damaging inflammation and pain. Actemra is similarly approved in conjunction with cancer cell therapy, which can sometimes trigger an immune reaction known as cytokine release syndrome.

The U.S.-based Kevzara trial is a two-part design that will initially evaluate fever and oxygen use in patients with acute respiratory distress syndrome, or ARDS. Two different dose levels will be used and compared to a placebo.

Longer-term, the trial hopes to measure prevention of death, use of ventilation, supplemental oxygen or hospitalization, but the design will be “adaptive” to determine the number of patients that will be followed and the endpoints to be used. ARDS often causes permanent lung damage and can lead to early death.

The trial aims to enroll 400 patients in the U.S. Regeneron’s partner Sanofi will handle international trial sites, naming Italy as one likely location for testing in coronavirus patients.

To get the trial underway quickly, Regeneron and Sanofi worked closely with the Food and Drug Administration and the Biomedical Advanced Research and Development Authority, the division of HHS involved in preparing for natural and man-made biological threats.

by Emily Makowski

Some ants produce natural antibiotic chemicals to defend themselves against fungi and bacteria. Ecologist Joachim Offenberg of Aarhus University in Denmark wondered what effect these compounds had on the health of the plants the ants called home. “We had this thought that if ants produce antibiotics, maybe these antibiotics could have an effect . . . on the diseases of the plants they walk on,” he tells The Scientist.

In a review of studies investigating the effect of ants on plant pathogens, he and fellow Aarhus ecologist Christian Damgaard found that, out of 30 plant species that were commonly inhabited by some kind of ant, 18 showed a decrease in the effects of pathogens. These included reduced bacterial load and increased germination rates enjoyed by plants inhabited by ants compared with plants of the same species that did not host ants.

Data have long confirmed that ants provide protection to their botanical hosts by eating pests, says Andreas Schramm, a microbiologist at Aarhus University who was not involved with the study. “The chemical defense of plants is really another direction that the authors quite convincingly put out here,” he says. Overall, Offenberg and Damgaard estimated that the effects of ants’ antibiotics were comparable to the benefits plants receive from the insects’ consumption of herbivorous pests.

Six of the plant species had increased pathogen incidence with ants, however, and six either had no significant difference between groups or insufficient data. Offenberg notes that a plant that hosts ants may already have a major infection that can’t be controlled with ant-produced antimicrobial compounds. Moreover, the insects can inadvertently disperse pathogens: fungal spores, for example, can cling to their legs.