Cognitive tasks showed that these patients have difficulty with the ability to plan ahead, display self-control, sustain focus despite distractions and suppress inappropriate behavior; imaging showed decreased activity in two brain regions responsible for those tasks.

Because depression has traditionally been defined as a mood disorder, doctors commonly prescribe antidepressants that target serotonin (known as selective serotonin reuptake inhibitors or SSRIs), but these are less effective for patients with cognitive dysfunction. Researchers said that targeting these cognitive dysfunctions with less commonly used antidepressants or other treatments may alleviate symptoms and help restore social and occupational abilities.

The study, published June 15 in JAMA Network Open, is part of a broader effort by neuroscientists to find treatments that target depression biotypes, according to the study’s senior author, Leanne Williams, PhD, the Vincent V.C. Woo Professor and professor of psychiatry and behavioral sciences.

“One of the big challenges is to find a new way to address what is currently a trial-and-error process so that more people can get better sooner,” Williams said. “Bringing in these objective cognitive measures like imaging will make sure we’re not using the same treatment on every patient.”

Finding the biotype

In the study, 1,008 adults with previously unmedicated major depressive disorder were randomly given one of three widely prescribed typical antidepressants: escitalopram (brand name Lexapro) or sertraline (Zoloft), which act on serotonin, or venlafaxine-XR (Effexor), which acts on both serotonin and norepinephrine. Seven hundred and twelve of the participants completed the eight-week regimen.

Before and after treatment with the antidepressants, the participants’ depressive symptoms were measured using two surveys — one, clinician-administered, and the other, a self-assessment, which included questions related to changes in sleep and eating. Measures on social and occupational functioning, as well as quality of life, were tracked as well.

The participants also completed a series of cognitive tests, before and after treatment, measuring verbal memory, working memory, decision speed and sustained attention, among other tasks.

Before treatment, scientists scanned 96 of the participants using functional magnetic resonance imaging as they engaged in a task called the “GoNoGo” that requires participants to press a button as quickly as possible when they see “Go” in green and to not press when they see “NoGo” in red. The fMRI tracked neuronal activity by measuring changes in blood oxygen levels, which showed levels of activity in different brain regions corresponding to Go or NoGo responses. Researchers then compared the participants’ images with those of individuals without depression.

The researchers found that 27% of the participants had more prominent symptoms of cognitive slowing and insomnia, impaired cognitive function on behavioral tests, as well as reduced activity in certain frontal brain regions — a profile they labeled the cognitive biotype.

“This study is crucial because psychiatrists have few measurement tools for depression to help make treatment decisions,” said Laura Hack, MD, PhD, the lead author of the study and an assistant professor of psychiatry and behavioral sciences. “It’s mostly making observations and self-report measures. Imaging while performing cognitive tasks is rather novel in depression treatment studies.”

Pre-treatment fMRI showed those with the cognitive biotype had significantly reduced activity in the dorsolateral prefrontal cortex and dorsal anterior cingulate regions during the GoNoGo task compared with the activity levels in participants who did not have the cognitive biotype. Together, the two regions form the cognitive control circuit, which is responsible for limiting unwanted or irrelevant thoughts and responses and improving goal selection, among other tasks.

After treatment, the researchers found that for the three antidepressants administered, the overall remission rates — the absence of overall depression symptoms — were 38.8% for participants with the newly discovered biotype and 47.7% for those without it. This difference was most prominent for sertraline, for which the remission rates were 35.9% and 50% for those with the biotype and those without, respectively.

“Depression presents in different ways in different people, but finding commonalities — like similar profiles of brain function — helps medical professionals effectively treat participants by individualizing care,” Williams said.

Depression isn’t one size fits all

Williams and Hack propose that behavior measurement and imaging could help diagnose depression biotypes and lead to better treatment. A patient could complete a survey on their own computer or in the doctor’s office, and if they are found to display a certain biotype, they might be referred to imaging for confirmation before undergoing treatment.

Researchers at the Stanford Center for Precision Mental Health and Wellness, which Williams directs, in partnership with the Stanford Translational Precision Mental Health Clinic, which Hack directs, are studying another medication — guanfacine — that specifically targets the dorsolateral prefrontal cortex region with support from Stanford University Innovative Medicines Accelerator. They believe this treatment could be more effective for patients with the cognitive subtype.

Williams and Hack hope to conduct studies with participants who have the cognitive biotype, comparing different types of medication with treatments such as transcranial magnetic stimulation and cognitive behavioral therapy. In transcranial magnetic stimulation, commonly referred to as TMS, magnetic fields stimulate nerve cells; in cognitive behavioral therapy, patients are taught to use problem-solving strategies to counter negative thoughts that contribute to both emotional dysregulation and loss of social and occupational abilities.

“I regularly witness the suffering, the loss of hope and the increase in suicidality that occurs when people are going through our trial-and-error process,” Hack said. “And it’s because we start with medications that have the same mechanism of action for everyone with depression, even though depression is quite heterogeneous. I think this study could help change that.”

Researchers from the Sierra-Pacific Mental Illness Research, Education and Clinical Center; the Veterans Affairs Palo Alto Health Care System; Brain Dynamic Centre, Westmead Institute for Medical Research; and the University of Sydney, Westmead, contributed to the work.

The study was funded through Brain Resource Company Operations Pty Ltd. and Stanford University’s Clinical and Translation Science Award Program overseen by the National Center for Advancing Translational Sciences at the National Institutes of Health (grant UL1TR003142-01).

A new study projecting the economic futures of four income groups of countries over the next century finds growth will be slower than predicted, with developing countries taking longer to close the wealth gap and approach the income of wealthier nations. What economists have thought of as a worst-case scenario for global economic growth may, in fact, be a best-case scenario, according to the new study published today in Communications Earth & Environment.

The findings suggest governments need to start planning for slower growth and wealthier countries may need to help lower-income nations finance climate change adaptations in the coming decades, according to the study authors.

“We’re at a point where we maybe need to significantly increase financing for [climate] adaptation in developing countries, and we’re also at a point where we might be overestimating our future ability to provide that financing under the current fiscal paradigm,” said Matt Burgess, a CIRES fellow, director of the Center for Social and Environmental Futures, and assistant professor of environmental studies at CU Boulder who led the new study.

“We can now start to winnow down the range of possibilities and move forward in more tangible ways,” said Ryan Langendorf, a postdoctoral scholar at CU Boulder and co-author of the new study.

In the new study, Burgess and his colleagues used two economic models to project how much the global economy will grow over the next century and how quickly developing countries will approach the income levels of wealthier nations.

Both models found the global economy will continue to grow, but that growth will be slower than most economists expected and there will be a larger income gap between wealthier and poorer nations. This means richer countries may need to help finance climate adaptations for poorer countries, and debt-ceiling crises, like what the United States experienced this spring, may become more common.

“Slower growth than we think means higher deficits than we expect, all else equal,” Burgess said. “That means debt would likely become more contentious and important over time, and could mean more frequent debt-ceiling fights.”

Similar to a flight emergency, where individuals should put their own oxygen masks on first, wealthier nations should focus on getting their own financial houses in order so they can be in a position to support lower-income nations in financing climate adaptations, according to the researchers.

“We’re talking about relatively less growth, relatively more inequality, but we’re still talking about a world that is richer than today and more equal across countries than today’s world,” Burgess said.

Still, many wealthy nations are accustomed to growing their way out of debt, but that may not be possible under the new scenario, according to Ashley Dancer, a graduate student at CU Boulder and co-author of the study.

“The next question is: what are some ways that we should be or could be helping [lower-income countries] adapt, if the expectation is that they’re not going to meet the level of wealth that would allow them to do that quickly and aggressively?” Dancer said.

Now, Salk scientists have found that pairing specific diets with disease-causing bacteria can create lasting immunity in mice without the costs of developing sickness, revealing a new potential vaccination strategy. Their findings, published in Science Advances on June 23, 2023, pave the way for the development of new vaccines that could promote immunity for those with diarrheal diseases and possibly other infections.

“We discovered that immunization against diarrheal infections is possible if we allow the bacteria to retain some of its disease-causing behavior,” says senior author Professor Janelle Ayres, Salk Institute Legacy Chair and head of the Molecular and Systems Physiology Laboratory. “This insight could lead to the development of vaccines that could reduce symptoms and mortality, as well as protect against future infections.”

In 2018, Ayres’ lab looked at how dietary interventions can create an asymptomatic infection, which Ayres calls a cooperative relationship between bacteria and host (the person or animal that the bacteria have infected) where the host does not experience any symptoms. They discovered that an iron-rich diet enabled mice to survive a normally lethal bacterial infection without ever developing signs of sickness or disease. The high-iron diet increased unabsorbed sugar (glucose) in the mice’s intestines, which the bacteriacould feast on. The excess sugar served as a “bribe” for the bacteria, keeping them full and incentivized to not attack the host.

This process produced long-term asymptomatic infection with the bacteria, leading the researchers to believe that the adaptive immune system (cells and proteins that “remember” infections) may be involved.

“Being able to generate lasting immunity against bacteria like C. rodentium or E. coli has not been possible using established vaccination strategies. We wanted to figure out what mechanism was sustaining this lasting immunity, so we could use that mechanism to create an impactful solution to these diarrheal diseases,” says first author Grischa Chen, a former postdoctoral researcher in Ayres’ lab.

The researchers moved to figure out how the body suppresses infection symptoms, whether infection without symptoms can create long-term immunity, and whether that immunity is reproducible as a vaccination strategy.

The team compared mice with iron-rich and normal diets after C. rodentium infection to find whether the diet impacted symptomless infection. Immediately after infection, mice fed an iron-rich diet had no symptoms whereas mice fed a normal diet did have symptoms. All mice were then put on a normal diet to see whether the asymptomatic infection would last.

Mice with nonfunctional adaptive immune systems (the immune system that “remembers” previous infections), regardless of whether they had ever been on an iron-rich diet, could not continue to maintain a cooperative relationship with the bacteria. Although the iron-rich diet suppressed symptoms immediately after infection, the adaptive immune system was required for lasting cooperation. Importantly, the mice with functional adaptive immune systems had the disease without any symptoms, with lastingimmunity, as demonstrated by survival upon reinfection after a month.

Ayres and team concluded that an iron-rich diet alone can prevent bacteria from creating deadly symptoms in mice during active infection. But a functional adaptive immune system is required for immunity against future infection in the absence of dietary supplementation.

Some bacterial strains, if mutated enough, don’t cause symptoms. To test whether such bacteria could produce lasting immunity, the team repeated their iron-diet versus normal-diet experiment in mice, but this time using bacteria that could cause disease and bacteria that could not cause disease. They found that only mice that received disease-causing, unmutated bacteria were able to support immunity upon reinfection.

The scientists note that people shouldn’t consume large amounts of iron after reading this study. Their findings are preliminary and will need to be confirmed in human subjects.

The researchers hope their insights will provide a basis for future research in humans and the creation of a vaccination regiment that protects and prevents against diarrheal illness.

Other authors include Natalia R. Thorup, Abigail J. Miller, and Yao-Cheng Li of Salk.

The work was supported by the National Institutes of Health (DPI AI144249, R01AI4929), the NOMIS Foundation, a DARPA Yong Faculty Award (YFA15 D15AP00097), a Hillblom Foundation Fellowship Grant, the Chapman Foundation, the Helmsley Charitable Trust,

The team reports in the journal Science Advances a drug that, in laboratory cultures and animal models, significantly reduces the ability of bacteria to develop antibiotic resistance, which might prolong antibiotic effectiveness. The drug, called dequalinium chloride (DEQ), is a proof-of-concept for evolution-slowing drugs.

“Most people with bacterial infections get better after completing antibiotic treatment, but there are also many cases in which people decline because the bacteria develop resistance to the antibiotic, which then can no longer kill the bacteria,” said corresponding author Dr. Susan M. Rosenberg, Ben F. Love Chair in Cancer Research and professor of molecular and human genetics, biochemistry and molecular biology and molecular virology and microbiology at Baylor. She also is a program leader in Baylor’s Dan L Duncan Comprehensive Cancer Center (DLDCCC).

In this study, Rosenberg and her colleagues looked for drugs that could prevent or slow down E. coli bacteria from developing resistance to two antibiotics when exposed to a third antibiotic, ciprofloxacin (cipro), the second most prescribed antibiotic in the U.S. and one associated with high bacterial resistance rates.

The resistance is caused by new gene mutations that occur in the bacteria during infection. The drug DEQ reduces the speed at which new mutations are formed in bacteria, the team finds.

Previous work from the Rosenberg lab had shown that bacterial cultures in the lab exposed to cipro turn up mutation rate. They found a mutational “program” that is switched on by bacterial stress responses. Stress responses are genetic programs that instruct cells to increase production of protective molecules during stress, including stress from low concentrations of cipro. Low concentrations occur at the beginning and end of antibiotic therapies and if doses are missed.

The same stress responses also increase the ability to make genetic mutations, the Rosenberg group, then many other labs, have shown. Some of the mutations can confer resistance to cipro, while other mutations can allow resistance to antibiotics not yet encountered. Mutation-generating processes that are turned on by stress responses are called stress-induced mutation mechanisms.

Bacteria with antibiotic resistance mutations can then sustain an infection in the presence of cipro. This study is the first to show that in animal infections treated with cipro, the bacteria activate a known stress-induced genetic mutational process. Cipro resistance occurs mostly by the bacteria developing new mutations, both clinically and in the laboratory, rather than by acquiring genes that confer antibiotic resistance from other bacteria.

Looking to prevent the development of antibiotic resistance, the researchers screened 1,120 drugs approved for human use for their ability to dial down the master bacterial stress response, which they showed counters the emergence of resistance mutations. In addition, and counterintuitively, they wanted “stealth” drugs that would not slow bacterial proliferation, which would confer a growth advantage to any bacterial mutants that resist the mutation-slowing drug itself. That is, drugs that are not antibiotics themselves.

“We found that DEQ fulfilled both requirements. Given together with cipro, DEQ reduced the development of mutations that confer antibiotic resistance, both in laboratory cultures and in animal models of infection, and bacteria did not develop resistance to DEQ,” said first author Yin Zhai, a postdoctoral associate in the Rosenberg lab. “In addition, we achieved this mutation-slowing effect at low DEQ concentrations, which is promising for patients. Future clinical trials are needed to evaluate the ability of DEQ to decelerate bacterial antibiotic resistance in patients.”

Other contributors to this work include John P. Pribis, Sean W. Dooling, Libertad Garcia-Villada, P.J. Minnick, Jun Xia, Jingjing Liu, Qian Mei, Devon M. Fitzgerald, Christophe Herman, P.J. Hastings and Mauro Costa-Mattioli. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, the Dan L Duncan Comprehensive Cancer Center and Rice University.

This work was supported by NIH Directors Pioneer Awards DP1-AI52073 and DP1-AG072751, and NIH grants R35-GM122598 and R01-CA250905, P30-AI036211, P30-CA125123 and S10-RR024574, the Dan L Duncan Comprehensive Cancer Center and the John S. Dunn Gulf Coast Consortium for Chemical Genomics. Further support was provided by the State of Nebraska LB595 and LB692 and NIH/NIEHS R00ES033259 awards.

Working with a type of polymer known as polyacrylate elastomers, the researchers found that they could increase the materials’ resistance to tearing up to tenfold, simply by using a weaker type of crosslinker to join some of the polymer building blocks.

These rubber-like polymers are commonly used in car parts, and they are also often used as the “ink” for 3D-printed objects. The researchers are now exploring the possible expansion of this approach to other types of materials, such as rubber tires.

“If you could make a rubber tire 10 times more resistant to tearing, that could have a dramatic impact on the lifetime of the tire and on the amount of microplastic waste that breaks off,” says Jeremiah Johnson, a professor of chemistry at MIT and one of the senior authors of the study, which appears today in Science.

A significant advantage of this approach is that it doesn’t appear to alter any of the other physical properties of the polymers.

“Polymer engineers know how to make materials tougher, but it invariably involves changing some other property of the material that you don’t want to change. Here, the toughness enhancement comes without any other significant change in physical properties — at least that we can measure — and it is brought about through the replacement of only a small fraction of the overall material,” says Stephen Craig, a professor of chemistry at Duke University who is also a senior author of the paper.

This project grew out of a longstanding collaboration between Johnson, Craig, and Duke University Professor Michael Rubinstein, who is also a senior author of the paper. The paper’s lead author is Shu Wang, an MIT postdoc who earned his PhD at Duke.

The weakest link

Polyacrylate elastomers are polymer networks made from strands of acrylate held together by linking molecules. These building blocks can be joined together in different ways to create materials with different properties.

One architecture often used for these polymers is a star polymer network. These polymers are made from two types of building blocks: one, a star with four identical arms, and the other a chain that acts as a linker. These linkers bind to the end of each arm of the stars, creating a network that resembles a volleyball net.

In a 2021 study, Craig, Rubinstein, and MIT Professor Bradley Olsen teamed up to measure the strength of these polymers. As they expected, they found that when weaker end-linkers were used to hold the polymer strands together, the material became weaker. Those weaker linkers, which contain cyclic molecules known as cyclobutane, can be broken with much less force than the linkers that are usually used to join these building blocks.

As a follow-up to that study, the researchers decided to investigate a different type of polymer network in which polymer strands are cross-linked to other strands in random locations, instead of being joined at the ends.

This time, when the researchers used weaker linkers to join the acrylate building blocks together, they found that the material became much more resistant to tearing.

This occurs, the researchers believe, because the weaker bonds are randomly distributed as junctions between otherwise strong strands throughout the material, instead of being part of the ultimate strands themselves. When this material is stretched to the breaking point, any cracks propagating through the material try to avoid the stronger bonds and go through the weaker bonds instead. This means the crack has to break more bonds than it would if all of the bonds were the same strength.

“Even though those bonds are weaker, more of them end up needing to be broken, because the crack takes a path through the weakest bonds, which ends up being a longer path,” Johnson says.

Tough materials

Using this approach, the researchers showed that polyacrylates that incorporated some weaker linkers were nine to 10 times harder to tear than polyacrylates made with stronger crosslinking molecules. This effect was achieved even when the weak crosslinkers made up only about 2 percent of the overall composition of the material.

The researchers also showed that this altered composition did not alter any of the other properties of the material, such as resistance to breaking down when heated.

“For two materials to have the same structure and same properties at the network level, but have an almost order of magnitude difference in tearing, is quite rare,” Johnson says.

The researchers are now investigating whether this approach could be used to improve the toughness of other materials, including rubber.

“There’s a lot to explore here about what level of enhancement can be gained in other types of materials and how best to take advantage of it,” Craig says.

The finding by researchers Dr Robert Kelly-Bellow and Karen Lee in the group of Professor Enrico Coen at the John Innes Centre, started with a curious observation in a dwarf mutant of the carnivorous plant Utricularia gibba.

The stems of this floating plant are filled with airspaces and this hollowness means that the vascular column inside the stem can buckle when under stress. This effect would not be apparent in most plants, which have solid stems.

The researchers saw that in a dwarf mutant the central column was wavy instead of straight. They hypothesised that this wobbly spine was caused by an internal conflict, a disparity between what was happening inside the plant stem and the epidermis or skin. Computational modelling by coauthor Dr Richard Kennaway showed this idea could account for what was observed.

“We realized that in these types of dwarf, only the epidermis, the skin of the stem, wants to be short, the internal tissue still wants to be long hence the buckling effect,” explains Professor Enrico Coen of the John Innes Centre, an author of the study which appears in Science.

“This was a surprise — previously people had thought that dwarf varieties, which are very important in agriculture, would be dwarf because everything in the stem is affected to grow less but in fact it’s just the skin in this case, creating a sort of straitjacket.”

Further investigations revealed that the Utricularia gibba dwarf mutant lacked a growth hormone called brassinosteroid.

They theorized that this hormone normally allows the skin to stretch, giving a more forgiving straitjacket and allowing the plant stem to elongate.

To test this idea, they used a mutant in the model plant Arabidopsis that weakens the glue between cells, to see if reducing brassinosteroid would cause major cracks to form in the skin of the stem as a result of the stresses.

“That is exactly what we saw,” explains Professor Coen. “Normally an Arabidopsis stem with weakened glue will crack slightly because the hormone is there to loosen the straitjacket. But when the hormone was missing, the skin was completely ripped off and the plant was almost skinless.”

Computational modelling by coauthor Professor Richard Smith showed brassinosteroid hormone was likely easing the straitjacket by loosening fibres in the epidermal cell walls.

“Plant cells are stuck together and are forced to behave in a coordinated way just by their pectin, their glue, that binds them. What we show in this study is that this is an incredibly powerful force; the glue is so strong you only need to change growth in one layer and the other cells will follow,” explains Professor Coen.

“Previous studies have emphasised that plants send molecular signals to grow in a coordinated way, and this is still a part of the explanation. But what our study shows is that the glueyness of plant cells is also a vital component in coordinating growth. Sticking together is very important.”

Coauthor Dr Christopher Whitewoods at the Sainsbury Laboratory, Cambridge University, emphasizes the potential importance of these findings for future research. “The fact that mechanical interactions between cell layers control growth in the stems of two wildly different species raises the question of whether they control other aspects of plant development, such as the complex internal patterning of leaves. We are excited to test whether this is the case.”

The findings shed light on dwarfing varieties of crops, like wheat and rice, which underpin agriculture’s Green Revolution, explaining how genes control their growth and how we might improve their efficiency in future.

Their findings also relate to developmental processes in animals, such as formation of crocodile skin cracks and shaping of the intestine, where mechanical interactions between layers are also thought to play a part.

Many hypotheses look promising to begin with but then fail to last the full experimental course. Not so in this case, reflects Professor Coen.

“The first glimpse of the wobbly tissue in our dwarf aquatic plant was exciting because as soon as we saw that, we had an idea of what might be going on. But the biggest excitement came from testing the idea in a completely different system.

“Nature is elusive. Ninety-nine percent of nice ideas fall flat on their face when put to a critical test. But occasionally an idea survives and you then know that nature has revealed one of its secrets to you,” he says.

Brassinosteroid co-ordinates cell layer interactions in plants via cell wall and tissue mechanics, appears in Science.

The same is true of nectar-filled flowers, which are an ideal gathering place for yeast — a type of fungus — and for bacteria that metabolize sugar and produce ethanol.

To University of California, Berkeley biologist Robert Dudley, this raises a host of questions. How much alcohol do hummingbirds consume in their daily quest for sustenance? Are they attracted to alcohol or repelled by it? Since alcohol is a natural byproduct of the sugary fruit and floral nectar that plants produce, is ethanol an inevitable part of the diet of hummingbirds and many other animals?

“Hummingbirds are eating 80% of their body mass a day in nectar,” said Dudley, UC Berkeley professor of integrative biology. “Most of it is water and the remainder sugar. But even if there are very low concentrations of ethanol, that volumetric consumption would yield a high dosage of ethanol, if it were out there. Maybe, with feeders, we’re not only farming hummingbirds, we’re providing a seat at the bar every time they come in.”

During the worst of the COVID-19 pandemic, when it became difficult to test these questions in the wilds of Central America and Africa, where there are nectar-feeding sunbirds, he tasked several undergraduate students with experimenting on the hummers visiting the feeder outside his office window to find out whether alcohol in sugar water was a turn-off or a turn-on. All three of the test subjects were male Anna’s hummingbirds (Calypte anna), year-round residents of the Bay Area.

The results of that study, published this week in the journal Royal Society Open Science, demonstrate that hummingbirds happily sip from sugar water with up to 1% alcohol by volume, finding it just as attractive as plain sugar water.

They appear to be only moderate tipplers, however, because they sip only half as much as normal when the sugar water contains 2% alcohol.

“They’re consuming the same total amount of ethanol, they’re just reducing the volume of the ingested 2% solution. So that was really interesting,” Dudley said. “That was a kind of a threshold effect and suggested to us that whatever’s out there in the real world, it’s probably not exceeding 1.5%.”

When he and his colleagues tested the alcohol level in sugar water that had sat in the feeder for two weeks, they found a much lower concentration: about 0.05% by volume.

“Now, 0.05% just doesn’t sound like much, and it’s not. But again, if you’re eating 80% of your body weight a day, at .05% of ethanol you’re getting a substantial load of ethanol relative to your body mass,” he said. “So it’s all consistent with the idea that there’s a natural, chronic exposure to physiologically significant levels of ethanol derived from this nutritional source.”

“They burn the alcohol and metabolize it so quickly. Likewise with the sugars. So they’re probably not seeing any real effect. They’re not getting drunk,” he added.

The research is part of a long-term project by Dudley and his UC Berkeley colleagues — herpetologist Jim McGuire and bird expert Rauri Bowie, both professors of integrative biology and curators at UC Berkeley’s Museum of Vertebrate Zoology. They seek to understand the role that alcohol plays in animal diets, particularly in the tropics, where fruits and sugary nectar easily ferment, and alcohol cannot help but be consumed by fruit-eating or nectar-sipping animals.

“Does alcohol have any behavioral effect? Does it stimulate feeding at low levels? Does it motivate more frequent attendance of a flower if they get not just sugar, but also ethanol? I don’t have the answers to these questions. But that’s experimentally tractable,” he said.

Part of this project, funded by the National Science Foundation, involves testing the alcohol content of fruits in Africa and nectar in flowers in the UC Botanical Garden. No systematic studies of the alcohol content of fruits and nectars, or of alcohol consumption by nectar-sipping birds, insects or mammals, or by fruit-eating animals — including primates — have been done.

But several isolated studies are suggestive. A 2008 study found that the nectar in palm flowers consumed by pen-tailed tree shrews, which are small, ratlike animals in West Malaysia, had levels of alcohol as high as 3.8% by volume. Another study, published in 2015, found a relatively high alcohol concentration — up to 3.8% — in the nectar eaten by the slow loris, a type of primate, and that both slow lorises and aye-ayes, another primate, preferred nectar with higher alcohol content.

The new study shows that birds are also likely consuming alcohol produced by natural fermentation.

“This is the first demonstration of ethanol consumption by birds, quote, in the wild. I’ll use that phrase cautiously because it’s a lab experiment and feeder measurement,” Dudley said. “But the linkage with the natural flowers is obvious. This just demonstrates that nectar-feeding birds, not just nectar-feeding mammals, not just fruit-eating animals, are all potentially exposed to ethanol as a natural part of their diet.”

The next step, he said, is to measure how much ethanol is naturally found in flowers and determine how frequently it’s being consumed by birds. He plans to extend his study to include Old World sunbirds and honey eaters in Australia, both of which occupy the nectar-sipping niche that hummingbirds have in America.

Dudley has been obsessed with alcohol use and misuse for years, and in a 2014 book, The Drunken Monkey, Why we drink and abuse alcohol, presented evidence that humans’ attraction to alcohol is an evolutionary adaptation to improve survival among primates. Only with the coming of industrial alcohol production has our attraction turned, in many cases, into alcohol abuse.

“Why do humans drink alcohol at all, as opposed to vinegar or any of the other 10 million organic compounds out there? And why do most humans actually metabolize it, burn it, and use it pretty effectively, often in conjunction with food, but then some humans also consume to excess?” he asked.

“I think, to get a better understanding of human attraction to alcohol, we really have to have better animal model systems, but also a realization that the natural availability of ethanol is actually substantial, not just for primates that are feeding on fruit and nectar, but also for a whole bunch of other birds and mammals and insects that are also feeding on flowers and fruits,” he said. “The comparative biology of ethanol consumption may yield insight into modern day patterns of consumption and abuse by humans.”

In addition to McGuire and Bowie, other co-authors of the paper are former undergraduates Julia Choi and Lilianne Lee, graduate student Aleksey Maro and postdoctoral researcher Ammon Corl, all of UC Berkeley. The work was supported by the National Science Foundation (DEB-1831833) and UC Berkeley’s Undergraduate Research Apprentice Program.