Study reveals how pollinators cope with plant toxins

Peer-Reviewed Publication

UNIVERSITY OF EXETER

Pollinators such as honeybees produce special enzymes that detoxify defence chemicals produced by plants, new research shows.

Many plants produce alkaloids as protection against herbivores, and these toxins are also found in their nectar and pollen.

The new study, by the University of Exeter and Bayer AG, examined the genes of several species in a group called Hymenoptera – insects including bees, wasps, ants and sawflies that share a common ancestor about 280 million years ago.

Remarkably, all the species tested produce the same group of enzymes (the CYP336 family of cytochrome P450 enzymes) to tackle alkaloid toxins.

“These species differ greatly, but one thing they share is this ability to detoxify alkaloids,” said Dr Angie Hayward, from Exeter’s Penryn Campus in Cornwall.

“We were fascinated to discover this family of genes has been preserved across almost 300 million years of evolution by a whole order of insects with very diverse lifestyles.

“Although some of these species have very little contact with certain key alkaloids, such as nicotine, they appear to have retained the ability to metabolise them, almost as an aspect of their genetic heritage, rather like the case of the human tailbone or appendix.”

The researchers examined the genomes of key hymenopteran species, creating an “evolutionary tree” for the family.

They also extracted the enzymes produced by these species and placed them in a cell-line to see how they would react with alkaloids – and found they do indeed detoxify them.

“Understanding how insects react to specific toxins is vital – it should inform how we produce any new chemicals such as pesticides and insecticides,” said Dr Bartek Troczka, also from the University of Exeter.

“To avoid environmental damage, we need very specific compounds that do very specific things.

“Our paper feeds into the wider attempt to understand how chemicals are broken down by insects and to what extent the genes responsible persist across insect groups.”

Dr Julian Haas, insect toxicologist at Bayer AG, said: “This study highlights the promise of multidisciplinary teamwork to better understand the molecular and evolutionary basis of detoxification mechanisms in insects which will ultimately aid with the understanding of their interaction with other toxins including insecticides.”

The study was funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and Bayer AG.

The paper, published in the journal Science Advances, is entitled: “A conserved hymenopteran-specific family of cytochrome P450s protect bee pollinators from toxic nectar alkaloids.”

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JOURNAL

Science Advances

DOI

10.1126/sciadv.adg0885 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

A conserved hymenopteran-specific family of cytochrome P450s protect bee pollinators from toxic nectar alkaloids.

ARTICLE PUBLICATION DATE

12-Apr-2023

Coral-eating fish poo may act as ‘probiotics’ for reefs

Although coral-eating fish can cause damage to coral, their poo contains potentially beneficial bacteria

Peer-Reviewed Publication

FRONTIERS

Until recently, fish that eat coral — corallivores — were thought to weaken reef structures, while fish that consume algae and detritus — grazers — were thought to keep reefs healthy. But scientists have discovered that feces from grazers leave large lesions on coral, possibly because they contain coral pathogens. By contrast, feces from corallivores may provide a source of beneficial microbes that help coral thrive.

“Corallivorous fish are generally regarded as harmful because they bite the corals,” said Dr Carsten Grupstra of Rice University, lead author of the study published in Frontiers in Marine Science. “But it turns out that this doesn’t tell the whole story. Corallivore feces contain many of the bacterial taxa that associate with healthy corals under normal conditions, potentially resulting in the natural dispersal of ‘coral probiotics’, analogous to fecal microbiota transplantation therapy in humans.”

Good bacteria for healthy reefs?

Tropical coral reefs harbor lots of fish, which defecate all the time. Although fish feces disperse nutrients which may help support a healthy coral reef, they also contain pathogens and sediments which can smother parts of living coral: these dying patches of coral are called lesions. To protect delicate coral reef ecosystems, we need to understand how this cycle of waste and nutrients works.

Grupstra and colleagues studied the effects of feces from both corallivores and grazers on live coral. They placed pieces of coral in jars with sterile seawater and applied feces from corallivore and grazer fish to different jars. Some samples were sterilized, to determine whether the physical characteristics of the feces alone caused the lesions. After the experiment, each piece of coral was examined and categorized as apparently healthy, containing lesions, or dead.

Finally, the scientists sampled the feces of several corallivore and grazer species to find out what bacteria they contained. This helped them understand what kinds of bacteria might be contributing to the effects seen on the coral, whether the feces contained specific coral pathogens, and whether their results from the feces addition experiment could be generalized to other fish that also ate coral or algae and detritus.

Keeping coral healthy

Adding feces to the jars sometimes caused lesions on coral pieces, and potentially even the death of the fragment; fragments without any feces remained healthy. Feces from grazers caused lesions or death in all coral pieces, while feces from corallivores caused fewer and smaller lesions and rarely caused death. Sterilized feces from either type of fish caused little harm, comparable to the low levels of damage caused by corallivore feces. The scientists suspected that this was because of the greater abundance of coral pathogens found in the fresh feces of grazers, and the higher abundance of beneficial microbes found in the fresh feces of corallivores. The fish we assumed were harmful may thus be contributing to important processes that promote coral reef health.

“More research needs to be done to test how fish feces affect corals to see how we might use these feces in management efforts to support coral reef health,” said Grupstra.

The scientists pointed out that the lesion effects of feces may not be so severe under real-world conditions and may not be evenly distributed. The territories and behaviors of fish affect where and when they defecate; feces could disintegrate in the water, limiting lesion formation. Some feces are eaten by other fish, and organisms that live on coral may also move remaining feces that fall on corals, potentially diminishing feces effects.

“Together, these findings result in a more nuanced understanding of the roles of fish on coral reefs and may help us better understand the interactions that are happening on reefs around the world,” said Grupstra. “Both corallivores and grazers have important ecological roles and understanding these roles can help us better manage and conserve these important ecosystems.”

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JOURNAL

Frontiers in Marine Science

DOI

10.3389/fmars.2023.1110346 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Consumer feces impact coral health in guild-specific ways

ARTICLE PUBLICATION DATE

13-Apr-2023

$9.9 million Bezos grant for virtual fencing combats climate change

Grant and Award Announcement

CORNELL UNIVERSITY

ITHACA, N.Y. - The Bezos Earth Fund has awarded $9.9 million to the College of Agriculture and Life Sciences (CALS) at Cornell University to support a project developing low-cost virtual livestock fencing that would benefit farmers and animals, improve public health in developing countries and combat climate change.

The multidisciplinary project, housed within CALS’ new Food Systems and Global Change program, aims to improve existing virtual fencing technology, combine it with animal-monitoring technology and make it affordable and accessible to the low-income farmers who need it most.

The Earth Fund, founded in 2020 by Amazon CEO Jeff Bezos, has committed to donating $10 billion this decade to address climate change and protect natural resources. The award to CALS, announced March 15, is the second grant awarded to an educational institution, and the first to an agricultural college.

“Virtual fencing presents an exciting opportunity for grazing systems where traditional fencing may be costly and labor-intensive,” said Mario Herrero, the Nancy and Peter Meinig Family Investigator in the Life Sciences and professor of global development, who is heading the project and directs the Food Systems and Global Change program in collaboration with Julio Giordano, associate professor of animal science, and David Erickson, the S.C. Thomas Sze Director of the Sibley School of Mechanical and Aerospace Engineering in Cornell Engineering.

“This technology could enhance grazing management while increasing productivity, mitigating greenhouse gas emissions and improving livelihoods. The key is to develop a low-cost system that is accessible to the majority of producers, especially those in impoverished areas. We are thrilled to be partnering with the Bezos Earth Fund to develop and deploy these systems at scale,” said Herrero, also a Cornell Atkinson Scholar.

Livestock production is an enormous and growing component of the global economy and food supply: 40% of Earth’s ice-free land area is used for grazing, and livestock contribute 40%-50% of total agricultural GDP. While people in many parts of the developed world overconsume animal products, for subsistence farmers in developing countries, livestock are a critical resource. They provide additional sources of income, their manure is used to fertilize plant crops without chemical fertilizers and they offer a safety net food source in times of war or crop failure.

Some of the most promising strategies to reduce the environmental impact of livestock farming rely on fencing to prevent animals from overgrazing, protect water sources and reduce human-wildlife conflict. However, in much of the Global South, livestock producers often use hundreds to thousands of acres to support their herds, and fencing is prohibitively expensive.

Fencing prevents animals from overgrazing, which reduces soil erosion and allows plants to recover, thereby increasing their capacity to sequester carbon and combat climate change. It also keeps animals away from sensitive areas such as water sources used by humans, reducing contamination and disease transmission. And it keeps livestock away from areas with known predator populations, decreasing livestock loss and the human-wildlife conflict that often follows.

Virtual fencing involves equipping animals with wearable, GPS-enabled devices that discourage them from leaving grazing areas designated by animal managers. Existing technologies, however, are too expensive for most farmers in low- and middle-income countries.

“Our primary objective is to develop lower-cost virtual fencing systems that are more accessible in areas of the world where farmers will never be able to buy them on their own,” Giordano said. “And once you have these devices on animals, you can also monitor their behavior and physiology, which leads to opportunities for improved animal health and productivity. This ultimately benefits farmers, animals and the environment.”

Benjamin Houlton, the Ronald P. Lynch Dean of CALS, highlighted the variety of long-term efforts across campus that will both support this project and benefit from the insights it uncovers.

“This foundational support by the Bezos Earth Fund will catalyze our impactful work in the 2030 Project and AI Initiative, from local to global scales, leveraging Cornell’s unique model of collaboration,” he said. “By combining CALS’ approach to moonshot thinking with the Cornell Atkinson Center and the Cornell Institute for Digital Agriculture, these projects will enlist the power of transdisciplinary scholarship, pushing beyond the idea of discipline or domain for real-world impact.”

“The partnership with Cornell CALS, our first grant to an agricultural college, is all about knowledge generation,” said Andy Jarvis, the director of Future of Food for the Bezos Earth Fund. “We need to create knowledge in a space where others can access it. By working with CALS, we’re making this technology open access so that researchers and farmers in developing countries across the globe can access it and adapt it to their needs. These innovative solutions can significantly increase the productivity of land, reduce emissions and make livestock production more sustainable.”

Finding the dream team to beat the heat

Large, superheated objects can be difficult to cool. In Jonathan Boreyko’s lab, the team has found that ice, water, and vapor could be the ideal combination.

Peer-Reviewed Publication

VIRGINIA TECH

 

IMAGE: CAMRYN COLÓN SETS UP AN EXPERIMENT IN ASSOCIATE PROFESSOR JONATHAN BOREYKO'S LAB. PHOTO BY ALEX PARRISH FOR VIRGINIA TECH. view more 

CREDIT: VIRGINIA TECH

Associate Professor Jonathan Boreyko leads a team at Virginia Tech that has built a strong portfolio of work with ice and water, exploring the possibilities for de-icing planes, building novel water harvesting devices, and creating snow globes out of bubbles. This familiarity with water has given the team a strong sense of its behavior in different states, leading to a new project that shows how ice quenches heat in comparison to water. The findings were published in Chem on April 14.

Mojtaba Edalatpour and master’s student Camryn Colón carried out this project. They investigated methods of quenching heat from metal, a critical step in applications such as metallurgy and firefighting. Both instances require speed. Metallurgists need to rapidly drop the temperature of a forged piece to achieve specific material properties, while firefighters work to stop destruction of property as quickly as possible.  Quenching with water is only effective beneath a critical temperature — any higher and the water levitates on its own vapor and can no longer boil the heat away. 

WATCH VIDEO: https://video.vt.edu/id/1_yk54e4pp

Boreyko’s team wanted to see if using ice, rather than water, could bypass the levitation issue to enable the quenching of ultra-hot surfaces.

Measuring, heating, and measuring again

To conduct this research, Edalatpour and Colón heated an aluminum stage and measured the cooling rate of water versus ice. To ensure a direct comparison, they released the same amount of water and ice onto the surface after it was heated to a desired temperature.

When the initial surface temperature of the stage was between 100 and 300 degrees Celsius, both the water and the ice successfully quenched the surface below 100 C. The ice, however, achieved that result in half the time. At higher initial temperatures — 300 to 500 C — only quenching with ice was successful. Heat transfer with ice was more than 100 times more effective than with liquid water at these high temperatures.

What was the difference? The properties of water prevent it from hitting the sweet spot for removing heat.

That sweet spot is boiling, because the steam escaping in bubbles most efficiently carries the heat away. Because water easily levitates on its vapor at high temperatures, it becomes insulated from the surface and the boiling never occurs. Ice behaves differently. When dropped onto a hot surface, ice absorbs much of the heat as it melts. This reduces the amount of heat available for producing vapor bubbles, preventing the levitation problem. In other words, the meltwater boils at a slower pace compared to pure water, thus helping to maintain boiling at high temperatures. 

Boreyko compared the unusual liquid behavior with worker productivity.

“Think about a workaholic who is always focusing on their job,” he said. “They start off hyper-productive but quickly burn out and become ineffective. It turns out that water is the same way when exposed to ultra-high temperature surfaces: It is so focused and productive at boiling water into vapor that it experiences ‘burnout,’ which is the scientific term for levitation and the catastrophic failure in cooling that results. So ice is like the slow and steady tortoise that wins in the long run. It doesn’t make vapor bubbles very well, but this allows it to keep boiling and avoid levitation when things get heated.”

The frozen path continues

The group’s hypothesis of using ice for quenching followed its recent discovery that ice does not levitate and lose its boiling capability until 550 C, compared to  150 C for water. Based on those findings, Boreyko’s team began several new projects applying its principles. This heat transfer is the first outgrowth to be published.

Colón’s follow-up work includes measuring the cooling performance of ice when the surface is fixed at a constant temperature rather than being allowed to cool down. 

“When you have a constant temperature, you can measure the steady-state heat flux, which would allow us to directly compare the heat transfer of ice versus state-of-the-art boilers,” said Colón. 

The team is also brainstorming how to implement a practical ice quenching system.

“It remains to be seen exactly how to implement three-phase heat transfer for real life applications, but we’re excited to figure it out over the next several years,” said Boreyko. “It might involve making spray nozzles that are able to eject ice particles instead of water, or perhaps it will look more like releasing a pre-formed block of ice onto an overheated surface.  There’s a lot more to figure out before this becomes an on-the-shelf technology.”

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JOURNAL

Chem

Ambrosia beetles can recognise their food fungi by their scents

Peer-Reviewed Publication

UNIVERSITY OF FREIBURG

 

IMAGE: NEST OF A BLACK STEM BORER (XYLOSANDRUS GERMANUS) IN A HAZELNUT BRANCH WITH ADULT FEMALES (LARGE), A MALE (SMALL) AND INDIVIDUAL LARVAE. THE GREYISH FUNGAL COATING OF THE FOOD FUNGUS IS VISIBLE ON THE WALLS OF THE TUNNEL SYSTEM. view more 

CREDIT: ANTONIO GUGLIUZZO

Certain ambrosia beetles species engage in active agriculture. As social communities, they breed and care for food fungi in the wood of trees and ensure that so-called weed fungi spread less. Researchers led by Prof. Dr. Peter Biedermann, professor of Forest Entomology and Forest Protection at the University of Freiburg, now demonstrate for the first time that ambrosia beetles can distinguish between different species of fungi by their scents. "The results can contribute to a better understanding of why beetles selectively colonise trees with conspecifics and how exactly their fungiculture works," says Biedermann. "In addition, the scents of the fungi could be used to develop attractants to control non-native ambrosia beetles."

Beetles orientate themselves by fungal scents

A research team led by Biedermann and the environmental scientist Dr. Antonio Gugliuzzo from the University of Catania/Italy was able to show for the first time that the black stem borer (Xylosandrus germanus) perceives scents of its food fungi and that these act as so-called aggregation pheromones. This means that the beetle uses the scent of the food fungus to find trees that are already colonised by conspecifics. The beetle is an invasive species that is now widespread in Germany and is mainly found in fruit trees. The results have just been published in the journal Frontiers in Microbiology.

"Until now, we could not explain how these beetles attack trees in groups," says Biedermann - because no corresponding scent of the insects' own had been found so far. The experiment now showed that the beetles react to the scents of the specific food fungi that their conspecifics have already cultivated in the branches of a tree. "This enables the beetles to colonise weakened trees in greater numbers and to overcome the tree's defences more easily, thus causing the tree to die," says Biedermann. Further chemical analyses can now be done to determine a component of the fungus scent, which could then be used as an attractant for traps in fruit growing.

Even larvae can distinguish fungi

In another study, environmental scientist Denicia Kassie and biologist Janina Diehl were able to experimentally demonstrate for the first time that another ambrosia beetle species, the fruit-tree pinhole borer (Xyleborinus saxesenii), can recognise and distinguish between its food fungi and so-called weed or harmful fungi based on their scents. Diehl is a doctoral student with Biedermann at the University of Freiburg. "Depending on the condition of the fungi, the beetles in the experiments either specifically sought out the fungal cultures or avoided them," says Diehl. The ability to recognise a potential threat to food fungi or their own health gives the beetles the opportunity to react - and either avoid or specifically combat the harmful fungi. The results of the study have been published in the journal Symbiosis.

The scientists were able to demonstrate the ability to distinguish between different food and harmful fungi in both larvae and adult individuals of the fruit-tree pinhole borer - which each take on their own tasks in the social network in the social maintenance of the food fungus cultures. "These findings are another building block to better understand how the control of fungal breeding by ambrosia beetles works functionally," says Biedermann. "This could also result in ideas for our agriculture to control harmful organisms in a sustainable and environmentally friendly way."

Nest of a fruit-tree pinhole borer (Xyleborinus saxesenii) with adult beetles and larvae. The yellow fungal mycelium of the food fungus is visible in the vicinity of the nest.

CREDIT

Davide Vallotto

Cultures of the food fungus Ambrosiella grosmanniae of the black stem borer in the laboratory of the University of Freiburg

CREDIT

Antonio Gugliuzzo

Factual overview:

• Original publications: Gugliuzzo, A., Kreuzwieser, J., Ranger, Ch. M., Tropea Garzia, G., Biondi, A., Biedermann, P. H. W.: Volatiles of fungal cultivars act as cues for host-selection in the fungus-farming ambrosia beetle Xylosandrus germanus. In: Front. Microbiol. 14:1151078 (2023).https://www.frontiersin.org/articles/10.3389/fmicb.2023.1151078/full
  Diehl, J.M.C., Kassie, D., Biedermann, P.H.W.: Friend or foe: Ambrosia beetle response to volatiles of common threats in their fungus gardensSymbiosis (2023). https://link.springer.com/article/10.1007/s13199-023-00914-y
• Peter Biedermann is Professor of Forest Entomology and Forest Conservation at the University of Freiburg. His research interests include bark beetles, symbioses between insects and microorganisms, especially fungi, and the social behaviour of insects. Janina Diehl is a doctoral student at the University of Freiburg, Denicia Kassie wrote her bachelor's thesis on the topic at the University of Freiburg. Antonio Gugliuzzo is a research assistant at the University of Catania/Italy.
• The research was supported by a DAAD scholarship for Antonio Gigliuzzo, by an Emmy Noether Grant from the DFG for Peter Biedermann and by funding from the University of Freiburg for open access publications.

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DOI

10.3389/fmicb.2023.11510 

Farmer’ beetle finds suitable host trees by tracing scent of its fungus crop

First known chemical cue for aggregation of ambrosia beetles that isn’t synthesized by the species itself

Peer-Reviewed Publication

FRONTIERS

 

IMAGE: ALNUS AMBROSIA BEETLES (XYLOSANDRUS GERMANUS) IN THEIR GALLERIES, TENDING THE BROOD AND FUNGUS view more 

CREDIT: ANTONIO GUGLIUZZO

The alnus ambrosia beetle Xylosandrus germanus, also known as the black stem borer, was accidentally introduced by humans from its native east Asia to North America and Europe around the beginning of the 20th century. X. germanus is a so-called ambrosia beetle, which means that it farms its own food: a specialized fungal symbiont which it ‘sows’ and tends inside the galleries that it digs inside wood. It is a destructive invasive pest, known to attack more than 200 species from 51 families of broadleaf and conifer trees. While it prefers to colonize dead wood, it can also infest and ultimately kill weakened or stressed trees.

A proven way to monitor or even control insect pests is by hijacking their communication system and manipulating it to trap them to their doom. Females of the alnus ambrosia beetle are known to aggregate on individual trees, suggesting that they use chemical signals to find each other and identify suitable trees. And now, scientists have cracked this chemical code. The results are published in Frontiers in Microbiology.

“Here we show that the alnus ambrosia beetle doesn’t produce its own pheromones during tree-host colonization, but rather uses the volatile compounds of their own fungal symbionts to aggregate en masse and potentially kill trees,” said the study’s senior author Dr Peter Biedermann, a professor at the Forestry Institute of the University of Freiburg in Germany.

First evidence of aggregation pheromones in ambrosia beetles

First author Antonio Gugliuzzo, a PhD student at the Department of Agriculture, Food and Environment of the University of Catania in Italy, added: “This is the first evidence for the existence of aggregation pheromones in ambrosia beetles of the tribe Xyleborini.”

Like all ambrosia beetles, X. germanus females carry their fungal symbionts in special pockets inside their head. The authors here used molecular methods to culture and identify the two most common symbionts as Ambrosiella grosmanniae, most likely the beetles’ primary food source, and an unknown species of Acremonium that the beetles may or may not eat. In 2020, the researchers caught mated dispersing X. germanus females near Freiburg, and allowed these dig galleries in an artificial medium based on beech sawdust, grow these two fungi, and rear their offspring.

They then used these fungi as bait in two-choice experiments in an apparatus called a still-air olfactometer. Here, X. germanus females were placed in an arena with two dead ends to enter and hide in: for example, one containing an isolate of the two symbionts A. grosmanniae and Acremonium sp., and another with an isolate of an unrelated fungus expected to be unattractive to the beetles – here, an uncharacterized Cladosporium species. The beetles’ preference will depend on their relative attraction to microbial volatile organic compounds (MVOCs) released by the fungi.

In a variant of this experiment, previously healthy beech branches infected with different fungi were presented to the beetles as options for choice.

Beetles prefer odor of symbionts and colonized branches

The results showed that the beetles were most attracted to A. grosmanniae MVOCs and least to Cladosporium MVOCs, and more to branches already colonized by A. grosmanniae than to uncolonized branches. The authors conclude that X. germanus uses MVOCs released by its two symbiont strains as a ‘synomone’ – a chemical signal that benefits both the emitter like and the receiver.

“Occupied tree branches may signal the beetles suitable substrate for the food fungi they depend on. This suitability is probably a delicate balance: trees need specific requirements to allow the beetles to farm the fungus successfully,” said Biedermann.

“But this isn’t an absolute requirement: if a female can’t find any conspecifics, or detect any MVOCs, she could still independently colonize a new tree branch.”

Promising avenue for biological control

These results immediately suggest a new method for biological control.

“Now that we know that the fungi produce attractive volatiles, we may be able to develop new trapping lures for the beetles on the basis of these compounds,” said Biedermann.  

“Moreover, the use of specific volatile compounds for trapping purposes could contribute to the development of innovative and selective trapping methods targeting specific ambrosia beetle species, thereby minimizing catches of non-target arthropods living in the same environment.”

Alnus ambrosia beetles (Xylosandrus germanus) in their galleries, tending the brood and fungus

CREDIT

Antonio Gugliuzzo

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JOURNAL

Frontiers in Microbiology

DOI

10.3389/fmicb.2023.1151078 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Volatiles of fungal cultivars act as cues for host-selection in the fungus-farming ambrosia beetle Xylosandrus germanus

ARTICLE PUBLICATION DATE

14-Apr-2023

Single-use surgical items contribute two-thirds of carbon footprint of products used in common operations

Peer-Reviewed Publication

SAGE

A new analysis of the carbon footprint of products used in the five most common surgical operations carried out in the NHS in England shows that 68% of carbon contributions come from single-use items, such as single-use gowns, patient drapes and instrument table drapes. Published by the Journal of the Royal Society of Medicine, the analysis highlights significant carbon contributors were the production of single use items and their waste disposal, together with processes for decontaminating reusable products.

Researchers from Brighton and Sussex Medical School and the University of Warwick carried out the study, which is the first to systematically evaluate the carbon footprint of products used in common operations. The analysis was based on direct observation of operating rooms across three sites of University Hospitals Sussex NHS Foundation Trust.

Applying the carbon dioxide equivalent (CO2e), the standard unit for measuring carbon footprints, to each of the operations, the researchers showed that the operation with the highest product carbon footprint was knee replacement (85.5kg CO2e). This was followed by gall bladder removal (20.3kg CO2e), carpal tunnel decompression surgery (12.0kg CO2e), hernia repair (11.7kg CO2e) and tonsillectomy (7.5kg CO2e).

Across the five operations, the researchers found that relatively few products (23%) were responsible for more than 80% of the product carbon footprint. This indicates that strategies for reducing greenhouse gas emissions associated with surgical operations should focus on the few products with highest emissions, typically large single-use (often plastic) items.

Lead researcher Dr Chantelle Rizan, Clinical Lecturer in Sustainable Healthcare at Brighton and Sussex Medical School, said: “Mitigating the carbon footprint of products used in resource-intensive areas such as surgical operating rooms will be important in achieving net zero carbon healthcare. Strategies should include eliminating or finding low carbon alternatives for products with the biggest contribution.”

Strategies to eliminate products, write the researchers, include avoiding non-sterile gloves, where they could be replaced with hand-washing, not opening gauze swab packs unless required and asking suppliers to remove rarely used items from single-use pre-prepared packs. The researchers also suggest that a number of single-use high carbon products have reusable alternatives. For example, single-use gowns, patient drapes and instrument table drapes were high carbon contributors in the study, yet the researchers note there is no evidence that reusable surgical textiles, which hold significant reductions in carbon footprint, are clinically inferior.

Dr Rizan concludes: “Eliminating single-use items or switching to reusables where feasible, alongside optimising associated decontamination processes and waste segregation and recycling, could reduce product carbon footprint by one third. This model was based on reusable alternatives already on the market, and this figure may be surpassed where industry rises to the challenge of sustainable surgical product innovation.”

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JOURNAL

Journal of the Royal Society of Medicine

DOI

10.1177/01410768231166135 

SUBJECT OF RESEARCH

People

ARTICLE TITLE

The carbon footprint of products used in five common surgical operations: identifying contributing products and processes

ARTICLE PUBLICATION DATE

14-Apr-2023

Disclaimer: AAAS 

BIG PHARMA PRICE GOUGING

Study: Anti-obesity medications could be sold for lower prices

Change in cost may improve affordability, access to treatment

Peer-Reviewed Publication

THE OBESITY SOCIETY

ROCKVILLE, Md.—New research shows that several anti-obesity medications could be manufactured and profitability sold worldwide at far lower estimated lower prices compared to their high costs, according to a new study in Obesity, The Obesity Society’s (TOS) flagship journal.

“Access to medicine is a fundamental element of the human right to health. While the obesity pandemic grows, especially amongst low-income communities, effective medical treatments remain inaccessible for millions in need. Our study highlights the inequality in pricing that exists for effective anti-obesity medications, which are largely unaffordable in most countries. However, we show that these drugs can actually be produced and sold profitably for low prices. A public health approach that prioritizes improving access to medications should be adopted, instead of allowing companies to maximize profits,” said Jacob Levi, Intensive Care Medicine, Royal Free Hospital NHS Trust, London, United Kingdom. Levi is the corresponding author of the study.

Experts explain that the increasing recognition that diet and exercise alone is unlikely to result in sustained weight loss had led to renewed interest in medication to supplement lifestyle changes. Randomized controlled trials have demonstrated positive results with oral and injectable medications. However, these medications remain prohibitively expensive in most countries. Such high prices make it challenging for millions of people to afford the medications and obtain access to treatment.

“It would be great if everyone had affordable access to all medicines that might improve their health. Yet that is simply not possible, nor will it ever be. What is truly needed is a better way to ration the health care dollars currently available in efforts to maximize population health. That is the challenge ahead not just for anti-obesity medications but for all treatments,” said Eric A. Finkelstein, professor, Duke-NUS Medical School, Singapore, in a commentary about the study.

On the other hand, the authors have called for a public health based approach to obesity management similar to that used with other diseases. Andrew Hill, Department of Pharmacology and Therapeutics, University of Liverpool, United Kingdom, supervising author of the study, commented, "Worldwide, more people are dying from diabetes and clinical obesity than HIV, tuberculosis and malaria combined now. Millions of lives have been saved by treating infectious diseases at low cost in poor countries. Now we need to repeat this medical success story, with mass treatment of diabetes and clinical obesity at low prices. Pharmaceutical companies have an ethical responsibility to make their new treatments for diabetes and obesity available for anyone in need, in any country."

The study’s authors searched national drug price databases and collected information on six medications: orlistat, naltrexone/bupropion, topiramate/phentermine, liraglutide, semaglutide and tirzepatide across a range of 16 low-, middle- and high-income countries. In each country, researchers assessed multiple online national price databases and selected the lowest available price from each of the sources. Medications selected were chosen because they are proven effective and because they illustrate a range of different monotherapies, combination tablets and injectable treatments.

Estimated minimum prices (EMPs) for anti-obesity medications were calculated using established methodology using active pharmaceutical ingredients from the Panjiva database. EMPs were calculated per 30-day course and include costs of active pharmaceutical ingredients, excipients, formulation, taxation and 10% profit margin.

Results revealed that national prices of oral and injectable anti-obesity medications were significantly higher than calculated EMPs.

Oral Medications:

• Orlistat: Prices for a 30-day course of treatment were greater than $100 in the United States and less than $1 in Vietnam. The calculated EMP from export API data was approximately $7 per 30-day course.
• Naltrexone/bupropion: Costs for naltrexone/bupropion combination tablets range from $326 in the United States to $56 in South Africa compared with an EMP of $55 per 30-day course.
• Topiramate/phentermine: Price data was only available in the United States since the medication is not licensed for use for weight loss in several countries because of safety concerns. Prices in the United States ranged from $120 to $199 per course compared with the EMP of the combination tablets at $5. Prices were also searched separately of topiramate and phentermine and combined with available data together from the United States, South Africa and Kenya. EMP’s for each drug individually were $0.86 for topiramate and $0.53 for phentermine (total of $1.39 per course) based on API export data.

Injectable Medications:

• Liraglutide: Injectable anti-diabetic and weight loss agent liraglutide costs $1,418 in the United States and $252 in Norway. The EMP per 30-day course was $50. Researchers note that this price was calculated assuming the most efficient concentration and dosage of available pens for injection.
• Semaglutide: National price data for subcutaneous semaglutide were all higher than EMPs ranging from $804 in the United States to $95 in Turkey. The EMP of subcutaneous semaglutide was calculated to be approximately $40 per 30-day course.
• Tirzepatide: National price data was only available in the United States, where the medication was recently licensed for use in type 2 diabetes by the Food and Drug Administration. The medication is not licensed for obesity alone. Prices for 30-day course ranged from about $715.56 to $1,100.70. Insufficient data existed in the database to calculate an EMP.

The study’s authors note that EMPs are meant as realistic targets for competitive generic production rather than patented versions.

Caroline M. Apovian, MD, FTOS, co-director, Center for Weight Management and Wellness and professor of medicine at Harvard Medical School in Boston, Mass., commented, “Once we have shown that anti-obesity agents notably GLP-1 and combinations thereof lower cardiovascular risk, we can then demand universal insurance coverage of these agents. These agents used for obesity prior to the advent of type 2 diabetes, cardiovascular disease and other complications, have the power to reduce the cardiovascular burden and lower mortality worldwide.” Apovian was not associated with the research.

Other authors of the study include Junzheng Wang, Medical Sciences Office, Oxford University, Clinical Academic Graduate School, University of Oxford, Oxford, United Kingdom and Francois Venter, Ezintsha, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

Venter has received support from the Bill and Melinda Gates Foundation, U.S. Agency for International Development, Uni-taid, SA Medical Research Council, Foundation for Innovative New Diagnostics, the Children’s Investment Fund Foundation, Gilead, ViiV, Mylan, Merck, Adcock-Ingram, Aspen, Abbott, Roche, Johnson & Johnson, Sanofi, Virology Education, SA HIV Clinicians Society and Dira Sengwe. The other authors declared no conflict of interest.

Funding for this study was provided by the Make Medicines Affordable/International Treatment Preparedness Coalition,  grant number  ITPC-MV_2020,https://makemedicinesaffordable.org/about/, and National Heart, Lung, and Blood Institute of the National Institutes of Health under award number UG3HL156388.

The study, titled “Estimated Minimum Prices and Lowest Available National Prices for Anti-obesity Medications: Improving Affordability and Access to Treatment,” is online and will be published in the print issue of Obesity in May 2023.

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The Obesity Society (TOS) is the leading organization of scientists and health professionals devoted to understanding and reversing the epidemic of obesity and its adverse health, economic and societal effects. Combining the perspective of researchers, clinicians, policymakers and patients, TOS promotes innovative research, education and evidence-based clinical care to improve the health and well-being of all people with obesity. For more information, visit www.obesity.org.

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COI STATEMENT

Francois Venter has received support from the Bill and Melinda Gates Foundation, U.S. Agency for International Development, Uni-taid, SA Medical Research Council, Foundation for Innovative New Diagnostics, the Children’s Investment Fund Foundation, Gilead, ViiV, Mylan, Merck, Adcock-Ingram, Aspen, Abbott, Roche, Johnson & Johnson, Sanofi, Virology Education, SA HIV Clinicians Society and Dira Sengwe. The other authors declared no conflict of interest.