Tag Archives: University of Florida

Fishes ‘talk’ and ‘sing’

This posting started out with two items and then, it became more. If you’re interested in marine bioacoustics especially the work that’s been announced in the last four months, read on.

Fish songs

This item is about how fish sounds (songs) signify successful coral reef restoration got coverage on BBC (British Broadcasting Corporation), CBC (Canadian Broadcasting Corporation) and elsewhere. This video is courtesy of the Guardian Newspaper,

Whoops and grunts: ‘bizarre’ fish songs raise hopes for coral reef recovery https://www.theguardian.com/environme…

A December 8, 2021 University of Exeter press release (also on EurekAlert) explains why the sounds give hope (Note: Links have been removed),

Newly discovered fish songs demonstrate reef restoration success
Whoops, croaks, growls, raspberries and foghorns are among the sounds that demonstrate the success of a coral reef restoration project.
Thousands of square metres of coral are being grown on previously destroyed reefs in Indonesia, but previously it was unclear whether these new corals would revive the entire reef ecosystem.
Now a new study, led by researchers from the University of Exeter and the University of Bristol, finds a heathy, diverse soundscape on the restored reefs.
These sounds – many of which have never been recorded before – can be used alongside visual observations to monitor these vital ecosystems.
“Restoration projects can be successful at growing coral, but that’s only part of the ecosystem,” said lead author Dr Tim Lamont, of the University of Exeter and the Mars Coral Reef Restoration Project, which is restoring the reefs in central Indonesia.
“This study provides exciting evidence that restoration really works for the other reef creatures too – by listening to the reefs, we’ve documented the return of a diverse range of animals.”
Professor Steve Simpson, from the University of Bristol, added: “Some of the sounds we recorded are really bizarre, and new to us as scientists.
“We have a lot still to learn about what they all mean and the animals that are making them. But for now, it’s amazing to be able to hear the ecosystem come back to life.”
The soundscapes of the restored reefs are not identical to those of existing healthy reefs – but the diversity of sounds is similar, suggesting a healthy and functioning ecosystem.
There were significantly more fish sounds recorded on both healthy and restored reefs than on degraded reefs.
This study used acoustic recordings taken in 2018 and 2019 as part of the monitoring programme for the Mars Coral Reef Restoration Project.
The results are positive for the project’s approach, in which hexagonal metal frames called ‘Reef Stars’ are seeded with coral and laid over a large area. The Reef Stars stabilise loose rubble and kickstart rapid coral growth, leading to the revival of the wider ecosystem.
Mochyudho Prasetya, of the Mars Coral Reef Restoration Project, said: “We have been restoring and monitoring these reefs here in Indonesia for many years. Now it is amazing to see more and more evidence that our work is helping the reefs come back to life.”
Professor David Smith, Chief Marine Scientist for Mars Incorporated, added: “When the soundscape comes back like this, the reef has a better chance of becoming self-sustaining because those sounds attract more animals that maintain and diversify reef populations.”
Asked about the multiple threats facing coral reefs, including climate change and water pollution, Dr Lamont said: “If we don’t address these wider problems, conditions for reefs will get more and more hostile, and eventually restoration will become impossible.
“Our study shows that reef restoration can really work, but it’s only part of a solution that must also include rapid action on climate change and other threats to reefs worldwide.”
The study was partly funded by the Natural Environment Research Council and the Swiss National Science Foundation.

Here’s a link to and a citation for the paper,

The sound of recovery: Coral reef restoration success is detectable in the soundscape by Timothy A. C. Lamont, Ben Williams, Lucille Chapuis, Mochyudho E. Prasetya, Marie J. Seraphim, Harry R. Harding, Eleanor B. May, Noel Janetski, Jamaluddin Jompa, David J. Smith, Andrew N. Radford, Stephen D. Simpson. Journal of Applied Ecology DOI: https://doi.org/10.1111/1365-2664.14089 First published: 07 December 2021

This paper is open access.

You can find the MARS Coral Reef Restoration Project here.

Fish talk

There is one item here. This research from Cornell University also features the sounds fish make. It’s no surprise given the attention being given to sound that the Cornell Lab of Ornithology is involved. In addition to the lab’s main focus, birds, many other animal sounds are gathered too.

A January 27, 2022 Cornell University news release (also on EurekAlert) describes ‘fish talk’,

There’s a whole lot of talking going on beneath the waves. A new study from Cornell University finds that fish are far more likely to communicate with sound than generally thought—and some fish have been doing this for at least 155 million years. These findings were just published in the journal Ichthyology & Herpetology.

“We’ve known for a long time that some fish make sounds,” said lead author Aaron Rice, a researcher at the K. Lisa Yang Center for Conservation Bioacoustics at the Cornell Lab of Ornithology [emphasis mine]. “But fish sounds were always perceived as rare oddities. We wanted to know if these were one-offs or if there was a broader pattern for acoustic communication in fishes.”
The authors looked at a branch of fishes called the ray-finned fishes. These are vertebrates (having a backbone) that comprise 99% of the world’s known species of fishes. They found 175 families that contain two-thirds of fish species that do, or are likely to, communicate with sound. By examining the fish family tree, study authors found that sound was so important, it evolved at least 33 separate times over millions of years.

“Thanks to decades of basic research on the evolutionary relationships of fishes, we can now explore many questions about how different functions and behaviors evolved in the approximately 35,000 known species of fishes,” said co-author William E. Bemis ’76, Cornell professor of ecology and evolutionary biology in the College of Agriculture and Life Sciences. “We’re getting away from a strictly human-centric way of thinking. What we learn could give us some insight on the drivers of sound communication and how it continues to evolve.”
The scientists used three sources of information: existing recordings and scientific papers describing fish sounds; the known anatomy of a fish—whether they have the right tools for making sounds, such as certain bones, an air bladder, and sound-specific muscles; and references in 19^th century literature before underwater microphones were invented.

“Sound communication is often overlooked within fishes, yet they make up more than half of all living vertebrate species,” said Andrew Bass, co-lead author and the Horace White Professor of Neurobiology and Behavior in the College of Arts and Sciences. “They’ve probably been overlooked because fishes are not easily heard or seen, and the science of underwater acoustic communication has primarily focused on whales and dolphins. But fishes have voices, too!”

Listen:
Oyster Toadfish, William Tavolga, Macaulay Library
Longspine squirrelfish, Howard Winn, Macaulay Library
Banded drum, Donald Batz, Macaulay Library
Midshipman, Andrew Bass, Macaulay Library
What are the fish talking about? Pretty much the same things we all talk about—sex and food. Rice says the fish are either trying to attract a mate, defend a food source or territory, or let others know where they are. Even some of the common names for fish are based on the sounds they make, such as grunts, croakers, hog fish, squeaking catfish, trumpeters, and many more.

Rice intends to keep tracking the discovery of sound in fish species and add them to his growing database (see supplemental material, Table S1)—a project he began 20 years ago with study co-authors Ingrid Kaatz ’85, MS ’92, and Philip Lobel, a professor of biology at Boston University. Their collaboration has continued and expanded since Rice came to Cornell.

“This introduces sound communication to so many more groups than we ever thought,” said Rice. “Fish do everything. They breathe air, they fly, they eat anything and everything—at this point, nothing would surprise me about fishes and the sounds that they can make.”

The research was partly funded by the National Science Foundation, the U.S. Bureau of Ocean Energy Management, the Tontogany Creek Fund, and the Cornell Lab of Ornithology.

I’ve embedded one of the audio files, Oyster Toadfish (William Tavolga) here,

Here’s a link to and a citation for the paper,

Evolutionary Patterns in Sound Production across Fishes by Aaron N. Rice, Stacy C. Farina, Andrea J. Makowski, Ingrid M. Kaatz, Phillip S. Lobel, William E. Bemis, Andrew H. Bass. Ichthyology & Herpetology, 110(1):1-12 (2022) DOI: https://doi.org/10.1643/i2020172 20 January 2022

This paper is open access.

Marine sound libraries

Thanks to Aly Laube’s March 2, 2022 article on the DailyHive.com, I learned of Kieran Cox’s work at the University of Victoria and FishSounds (Note: Links have been removed),

Fish have conversations and a group of researchers made a website to document them.
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It’s so much fun to peruse and probably the good news you need. Listen to a Bocon toadfish “boop” or this sablefish tick, which is slightly creepier, but still pretty cool. This streaked gurnard can growl, and this grumpy Atlantic cod can grunt.
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The technical term for “fishy conversations” is “marine bioacoustics,” which is what Kieran Cox specializes in. They can be used to track, monitor, and learn more about aquatic wildlife.
The doctor of marine biology at the University of Victoria co-authored an article about fish sounds in Reviews in Fish Biology and Fisheries called “A Quantitative Inventory of Global Soniferous Fish Diversity.”
It presents findings from his process, helping create FishSounds.net. He and his team looked over over 3,000 documents from 834 studies to put together the library of 989 fish species.
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A March 2, 2022 University of Victoria news release provides more information about the work and the research team (Note: Links have been removed),

Fascinating soundscapes exist beneath rivers, lakes and oceans. An unexpected sound source are fish making their own unique and entertaining noise from guttural grunts to high-pitched squeals. Underwater noise is a vital part of marine ecosystems, and thanks to almost 150 years of researchers documenting those sounds we know hundreds of fish species contribute their distinctive sounds. Although fish are the largest and most diverse group of sound-producing vertebrates in water, there was no record of which fish species make sound and the sounds they produce. For the very first time, there is now a digital place where that data can be freely accessed or contributed to, an online repository, a global inventory of fish sounds.
Kieran Cox co-authored the published article about fish sounds and their value in Reviews in Fish Biology and Fisheries while completing his Ph.D in marine biology at the University of Victoria. Cox recently began a Liber Ero post-doctoral collaboration with Francis Juanes that aims to integrate marine bioacoustics into the conservation of Canada’s oceans. Liber Ero program is devoted to promoting applied and evidence-based conservation in Canada.
The international group of researchers includes UVic, the University of Florida, Universidade de São Paulo, and Marine Environmental Research Infrastructure for Data Integration and Application Network (MERIDIAN) [emphasis mine] have launched the first ever, dedicated website focused on fish and their sounds: FishSounds.net. …
According to Cox, “This data is absolutely critical to our efforts. Without it, we were having a one-sided conversation about how noise impacts marine life. Now we can better understand the contributions fish make to soundscapes and examine which species may be most impacted by noise pollution.” Cox, an avid scuba diver, remembers his first dive when the distinct sound of parrotfish eating coral resonated over the reef, “It’s thrilling to know we are now archiving vital ecological information and making it freely available to the public, I feel like my younger self would be very proud of this effort.” …

There’s also a March 2, 2022 University of Florida news release on EurekAlert about FishSounds which adds more details about the work (Note: Links have been removed),

Cows moo. Wolves howl. Birds tweet. And fish, it turns out, make all sorts of ruckus.
“People are often surprised to learn that fish make sounds,” said Audrey Looby, a doctoral candidate at the University of Florida. “But you could make the case that they are as important for understanding fish as bird sounds are for studying birds.”
The sounds of many animals are well documented. Go online, and you’ll find plenty of resources for bird calls and whale songs. However, a global library for fish sounds used to be unheard of.
That’s why Looby, University of Victoria collaborator Kieran Cox and an international team of researchers created FishSounds.net, the first online, interactive fish sounds repository of its kind.
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“There’s no standard system yet for naming fish sounds, so our project uses the sound names researchers have come up with,” Looby said. “And who doesn’t love a fish that boops?”
The library’s creators hope to add a feature that will allow people to submit their own fish sound recordings. Other interactive features, such as a world map with clickable fish sound data points, are also in the works.
Fish make sound in many ways. Some, like the toadfish, have evolved organs or other structures in their bodies that produce what scientists call active sounds. Other fish produce incidental or passive sounds, like chewing or splashing, but even passive sounds can still convey information.
Scientists think fish evolved to make sound because sound is an effective way to communicate underwater. Sound travels faster under water than it does through air, and in low visibility settings, it ensures the message still reaches an audience.
“Fish sounds contain a lot of important information,” said Looby, who is pursuing a doctorate in fisheries and aquatic sciences at the UF/IFAS College of Agricultural and Life Sciences. “Fish may communicate about territory, predators, food and reproduction. And when we can match fish sounds to fish species, their sounds are a kind of calling card that can tell us what kinds of fish are in an area and what they are doing.”
Knowing the location and movements of fish species is critical for environmental monitoring, fisheries management and conservation efforts. In the future, marine, estuarine or freshwater ecologists could use hydrophones — special underwater microphones — to gather data on fish species’ whereabouts. But first, they will need to be able to identify which fish they are hearing, and that’s where the fish sounds database can assist.
FishSounds.net emerged from the research team’s efforts to gather and review the existing scientific literature on fish sounds. An article synthesizing that literature has just been published in Reviews in Fish Biology and Fisheries.
In the article, the researchers reviewed scientific reports of fish sounds going back almost 150 years. They found that a little under a thousand fish species are known to make active sounds, and several hundred species were studied for their passive sounds. However, these are probably both underestimates, Cox explained.
…

Here’s a link to and a citation for the paper,

A quantitative inventory of global soniferous fish diversity by Audrey Looby, Kieran Cox, Santiago Bravo, Rodney Rountree, Francis Juanes, Laura K. Reynolds & Charles W. Martin. Reviews in Fish Biology and Fisheries (2022) DOI: https://doi.org/10.1007/s11160-022-09702-1 Published 18 February 2022

This paper is behind a paywall.

Finally, there’s GLUBS. A comprehensive February 27, 2022 Rockefeller University news release on EurekAlert announces a proposal for the Global Library of Underwater Biological Sounds (GLUBS), Note 1: Links have been removed; Note 2: If you’re interested in the topic, I recommend reading either the original February 27, 2022 Rockefeller University news release with its numerous embedded images, audio files, and links to marine audio libraries,

Of the roughly 250,000 known marine species, scientists think all ~126 marine mammals emit sounds – the ‘thwop’, ‘muah’, and ‘boop’s of a humpback whale, for example, or the boing of a minke whale. Audible too are at least 100 invertebrates, 1,000 of the world’s 34,000 known fish species, and likely many thousands more.
Now a team of 17 experts from nine countries has set a goal [emphasis mine] of gathering on a single platform huge collections of aquatic life’s tell-tale sounds, and expanding it using new enabling technologies – from highly sophisticated ocean hydrophones and artificial intelligence learning systems to phone apps and underwater GoPros used by citizen scientists.
The Global Library of Underwater Biological Sounds, “GLUBS,” will underpin a novel non-invasive, affordable way for scientists to listen in on life in marine, brackish and freshwaters, monitor its changing diversity, distribution and abundance, and identify new species. Using the acoustic properties of underwater soundscapes can also characterize an ecosystem’s type and condition.
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“A database of unidentified sounds is, in some ways, as important as one for known sources,” the scientists say. “As the field progresses, new unidentified sounds will be collected, and more unidentified sounds can be matched to species.”
This can be “particularly important for high-biodiversity systems such as coral reefs, where even a short recording can pick up multiple animal sounds.”
Existing libraries of undersea sounds (several of which are listed with hyperlinks below) “often focus on species of interest that are targeted by the host institute’s researchers,” the paper says, and several are nationally-focussed. Few libraries identify what is missing from their catalogs, which the proposed global library would.
“A global reference library of underwater biological sounds would increase the ability for more researchers in more locations to broaden the number of species assessed within their datasets and to identify sounds they personally do not recognize,” the paper says.
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The scientists note that listening to the sea has revealed great whales swimming in unexpected places, new species and new sounds.
With sound, “biologically important areas can be mapped; spawning grounds, essential fish habitat, and migration pathways can be delineated…These and other questions can be queried on broader scales if we have a global catalog of sounds.”
Meanwhile, comparing sounds from a single species across broad areas and times helps understand their diversity and evolution.
Numerous marine animals are cosmopolitan, the paper says, “either as wide-roaming individuals, such as the great whales, or as broadly distributed species, such as many fishes.”
Fin whale calls, for example, can differ among populations in the Northern and Southern hemispheres, and over seasons, whereas the call of pilot whales are similar worldwide, even though their home ranges do not (or no longer) cross the equator.
Some fishes even seem to develop geographic ‘dialects’ or completely different signal structures among regions, several of which evolve over time.
Madagascar’s skunk anemonefish … , for example, produces different agonistic (fight-related) sounds than those in Indonesia, while differences in the song of humpback whales have been observed across ocean basins.
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Phone apps, underwater GoPros and citizen science
Much like BirdNet and FrogID, a library of underwater biological sounds and automated detection algorithms would be useful not only for the scientific, industry and marine management communities but also for users with a general interest.
“Acoustic technology has reached the stage where a hydrophone can be connected to a mobile phone so people can listen to fishes and whales in the rivers and seas around them. Therefore, sound libraries are becoming invaluable to citizen scientists and the general public,” the paper adds.
And citizen scientists could be of great help to the library by uploading the results of, for example, the River Listening app (www.riverlistening.com), which encourages the public to listen to and record fish sounds in rivers and coastal waters.
Low-cost hydrophones and recording systems (such as the Hydromoth) are increasingly available and waterproof recreational recording systems (such as GoPros) can also collect underwater biological sounds.
…

Here’s a link to and a citation for the paper,

Sounding the Call for a Global Library of Underwater Biological Sounds by Miles J. G. Parsons, Tzu-Hao Lin, T. Aran Mooney, Christine Erbe, Francis Juanes, Marc Lammers, Songhai Li, Simon Linke, Audrey Looby, Sophie L. Nedelec, Ilse Van Opzeeland, Craig Radford, Aaron N. Rice, Laela Sayigh, Jenni Stanley, Edward Urban and Lucia Di Iorio. Front. Ecol. Evol., 08 February 2022 DOI: https://doi.org/10.3389/fevo.2022.810156 Published: 08 February 2022.

This paper appears to be open access.

If you want ‘shredded pecs’, train like a burrowing frog

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Caption: Forward burrowers use pointed snouts and powerful forelimbs bolstered by strong pectoral muscles to scrabble into the earth. They’re often orb-shaped to improve their ability to hold water. Credit: Rachel Keeffe

It’s always enjoyable to see the scientific community indulge in a little fun and I’m using that as an excuse for including a frog story here.

From an August 31, 2020 Florida Museum of Natural History news release (also on EurekAlert but published on Sept. 1, 2020) by Halle Marchese announces some research into a little known frog,

You might think the buffest frogs would be high jumpers, but if you want shredded pecs, you should train like a burrowing frog. Though famously round, these diggers are the unsung bodybuilders of the frog world. We bring you tips from frog expert Rachel Keeffe, a doctoral student at the University of Florida, and physical therapist Penny Goldberg to help you get the burrowing body of your dreams.
But first, a caveat: According to Keeffe, no workout regimen can help you train your way into a highly specialized frog physique honed by 200 million years of evolution. To better understand burrowing frog anatomy, Keeffe and her adviser David Blackburn, Florida Museum of Natural History curator of herpetology, analyzed CT scans from all 54 frog families to show these frogs boast a robust and quirky skeleton that is more variable than previously thought.
“People think about frogs as being clean and smooth and slimy, or the classic ‘green frog on a lily pad,’ but a lot of them are dirty – they like to scoot around and be in the dirt,” Keeffe said. “Burrowing frogs are really diverse and can do a lot of cool things. And when you look at the skeletons of known burrowers, they’re very different from what you would call a ‘normal frog.'”
Burrowing frogs are found all over the world from deserts to swamps, but their underground lifestyle makes them difficult to study, Keeffe said. Most tunnel hind end-first with their back legs. But a few species are forward burrowers, using pointed snouts and powerful forelimbs bolstered by strong pectoral muscles to scrabble into the earth.
Keeffe’s sample of 89 frog species revealed radical differences in burrowing bone structure, from clavicles the size of eyelashes to other bones that are unusually thick.
“They’re so diverse that it’s challenging to think about even comparing them. It’s almost a black hole of work that we can do with forward burrowers because we tend to focus on the legs,” she said.
Some burrow to seek refuge, whether from arid temperatures or predators, and underground habitats can be hunting grounds or secluded hiding places. Other burrowing frogs can spend months at a time as deep as 3 feet belowground, surviving on a high-protein diet of termites and ants. The takeaway: If you want to compete for resources with the pros, don’t be afraid to put in the work.
Get the burly burrowing body
To train like a burrowing frog, Goldberg, assistant director of ReQuest Physical Therapy in Gainesville, recommended dedicating time to strengthening your upper back.
“In humans, the most important muscle group to focus on if you were to train like one of these frogs would be the scapular stabilizers,” she said. “These include 17 muscles, such as the lats and rotator cuff, with attachments all the way down to the pelvis that allow the upper back to generate power. To burrow like a forward burrower, you need to strengthen this entire region.”
One strengthening move Goldberg recommended is the “Prone W.” Lie facedown with elbows bent and palms on the floor. Squeeze your shoulder blades down and toward your spine as you lift your arms to the ceiling for a couple seconds at a time.
Like any elite athlete, burrowing frogs also maintain an optimal form. They’re often orb-shaped to improve their ability to hold water.
“Personally, if I were a sphere, I think it would be hard for me to dig, but it doesn’t seem to affect these frogs at all,” Keeffe said. “However, frogs with stumpy legs are definitely worse at jumping, and they tend to stagger when they walk.”
For these frogs, time away from the tunnels might be spent swimming instead, Keeffe said. To compete here, Goldberg recommends the breaststroke, adding that her top training tips for getting the upper back and pecs of a forward burrower would include pullups and pushups to develop the shoulder blade area.
“In my world, we would use resistance bands and pushing or pulling motions to train this area,” Goldberg said. “Anything focusing predominantly on building strength in the upper back region.”
If resistance bands are part of your workout routine, try grasping one with both hands and extending your arms while keeping your elbows straight. For best results, Goldberg recommended starting with three sets of 10.
Burrowing frogs might also hold key answers to gaps in scientists’ understanding of amphibian evolution at large. Keeffe’s analysis also found that forward-burrowing behavior evolved independently at least eight times in about one-fifth of frog families, and the trait’s persistence in the frog family tree suggests it’s a beneficial adaptation. Keeffe also found that forward burrowers tended to have a highly contoured humerus, the bone that connects the shoulder to the elbow in humans.
Understanding how bone shape relates to musculature can help scientists identify which frogs, both modern and extinct, are forward burrowers, a helpful tool given their covert behavior.
“Even though it can be frustrating, I like them because they’re secretive,” Keeffe said. “But the whole thing underlying this study is that frogs can do a lot of cool things – they don’t just jump and they’re not just green.”
CT scans were generated from the National Science Foundation-funded oVert project.

Do take a look at the August 31, 2020 Florida Museum of Natural History news release as the researchers have provided pictures of real ‘forward burrowing frogs’ along with more cartoons and other other images that have been embedded in Marchese’s release.

Here’s a link to and a citation for the paper,

Comparative morphology of the humerus in forward-burrowing frogs by Rachel Keeffe, David C Blackburn. Biological Journal of the Linnean Society, blaa092, DOI: https://doi.org/10.1093/biolinnean/blaa092 Published: 28 August 2020

This paper is behind a paywall.

Xenotransplantation—organs for transplantation in human patients—it’s a business and a science

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The last time (June 18, 2018 post) I mentioned xenotransplantation (transplanting organs from one species into another species; see more here), it was in the context of an art/sci (or sciart) event coming to Vancouver (Canada).,

Patricia Piccinini’s Curious Imaginings Courtesy: Vancouver Biennale [downloaded from http://dailyhive.com/vancouver/vancouver-biennale-unsual-public-art-2018/]

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The latest edition of the Vancouver Biennale was featured in a June 6, 2018 news item on the Daily Hive (Vancouver),

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Melbourne artist Patricia Piccinini’s Curious Imaginings is expected to be one of the most talked about installations of the exhibit. Her style of “oddly captivating, somewhat grotesque, human-animal hybrid creature” is meant to be shocking and thought-provoking.

Piccinini’s interactive [emphasis mine] experience will “challenge us to explore the social impacts of emerging biotechnology and our ethical limits in an age where genetic engineering and digital technologies are already pushing the boundaries of humanity.”

Piccinini’s work will be displayed in the 105-year-old Patricia Hotel in Vancouver’s Strathcona neighbourhood. The 90-day ticketed exhibition [emphasis mine] is scheduled to open this September [2018].

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(The show opens on Sept. 14, 2018.)

At the time, I had yet to stumble across Ingfei Chen’s thoughtful dive into the topic in her May 9, 2018 article for Slate.com,

In the United States, the clock is ticking for more than 114,700 adults and children waiting for a donated kidney or other lifesaving organ, and each day, nearly 20 of them die. Researchers are devising a new way to grow human organs inside other animals, but the method raises potentially thorny ethical issues. Other conceivable futuristic techniques sound like dystopian science fiction. As we envision an era of regenerative medicine decades from now, how far is society willing to go to solve the organ shortage crisis?

I found myself pondering this question after a discussion about the promises of stem cell technologies veered from the intriguing into the bizarre. I was interviewing bioengineer Zev Gartner, co-director and research coordinator of the Center for Cellular Construction at the University of California, San Francisco, about so-called organoids, tiny clumps of organlike tissue that can self-assemble from human stem cells in a Petri dish. These tissue bits are lending new insights into how our organs form and diseases take root. Some researchers even hope they can nurture organoids into full-size human kidneys, pancreases, and other organs for transplantation.

Certain organoid experiments have recently set off alarm bells, but when I asked Gartner about it, his radar for moral concerns was focused elsewhere. For him, the “really, really thought-provoking” scenarios involve other emerging stem cell–based techniques for engineering replacement organs for people, he told me. “Like blastocyst complementation,” he said.

Never heard of it? Neither had I. Turns out it’s a powerful new genetic engineering trick that researchers hope to use for growing human organs inside pigs or sheep—organs that could be genetically personalized for transplant patients, in theory avoiding immune-system rejection problems. The science still has many years to go, but if it pans out, it could be one solution to the organ shortage crisis. However, the prospect of creating hybrid animals with human parts and killing them to harvest organs has already raised a slew of ethical questions. In 2015, the National Institutes of Health placed a moratorium on federal funding of this nascent research area while it evaluated and discussed the issues.

As Gartner sees it, the debate over blastocyst complementation research—work that he finds promising—is just one of many conversations that society needs to have about the ethical and social costs and benefits of future technologies for making lifesaving transplant organs. “There’s all these weird ways that we could go about doing this,” he said, with a spectrum of imaginable approaches that includes organoids, interspecies organ farming, and building organs from scratch using 3D bioprinters. But even if it turns out we can produce human organs in these novel ways, the bigger issue, in each technological instance, may be whether we should.

Gartner crystallized things with a downright creepy example: “We know that the best bioreactor for tissues and organs for humans are human beings,” he said. Hypothetically, “the best way to get you a new heart would be to clone you, grow up a copy of yourself, and take the heart out.” [emphasis mine] Scientists could probably produce a cloned person with the technologies we already have, if money and ethics were of no concern. “But we don’t want to go there, right?” he added in the next breath. “The ethics involved in doing it are not compatible with who we want to be as a society.”

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This sounds like Gartner may have been reading some science fiction, specifically, Lois McMaster Bujold and her Barrayar series where she often explored the ethics and possibilities of bioengineering. At this point, some of her work seems eerily prescient.

As for Chen’s article, I strongly encourage you to read it in its entirety if you have the time.

Medicine, healing, and big money

At about the same time, there was a May 31, 2018 news item on phys.org offering a perspective from some of the leaders in the science and the business (Note: Links have been removed),

Over the past few years, researchers led by George Church have made important strides toward engineering the genomes of pigs to make their cells compatible with the human body. So many think that it’s possible that, with the help of CRISPR technology, a healthy heart for a patient in desperate need might one day come from a pig.

“It’s relatively feasible to change one gene in a pig, but to change many dozens—which is quite clear is the minimum here—benefits from CRISPR,” an acronym for clustered regularly interspaced short palindromic repeats, said Church, the Robert Winthrop Professor of Genetics at Harvard Medical School (HMS) and a core faculty member of Harvard’s Wyss Institute for Biologically Inspired Engineering. Xenotransplantation is “one of few” big challenges (along with gene drives and de-extinction, he said) “that really requires the ‘oomph’ of CRISPR.”

To facilitate the development of safe and effective cells, tissues, and organs for future medical transplantation into human patients, Harvard’s Office of Technology Development has granted a technology license to the Cambridge biotech startup eGenesis.

Co-founded by Church and former HMS doctoral student Luhan Yang in 2015, eGenesis announced last year that it had raised $38 million to advance its research and development work. At least eight former members of the Church lab—interns, doctoral students, postdocs, and visiting researchers—have continued their scientific careers as employees there.

“The Church Lab is well known for its relentless pursuit of scientific achievements so ambitious they seem improbable—and, indeed, [for] its track record of success,” said Isaac Kohlberg, Harvard’s chief technology development officer and senior associate provost. “George deserves recognition too for his ability to inspire passion and cultivate a strong entrepreneurial drive among his talented research team.”

The license from Harvard OTD covers a powerful set of genome-engineering technologies developed at HMS and the Wyss Institute, including access to foundational intellectual property relating to the Church Lab’s 2012 breakthrough use of CRISPR, led by Yang and Prashant Mali, to edit the genome of human cells. Subsequent innovations that enabled efficient and accurate editing of numerous genes simultaneously are also included. The license is exclusive to eGenesis but limited to the field of xenotransplantation.

A May 30, 2018 Harvard University news release by Caroline Petty, which originated the news item, explores some of the issues associated with incubating humans organs in other species,

The prospect of using living, nonhuman organs, and concerns over the infectiousness of pathogens either present in the tissues or possibly formed in combination with human genetic material, have prompted the Food and Drug Administration to issue detailed guidance on xenotransplantation research and development since the mid-1990s. In pigs, a primary concern has been that porcine endogenous retroviruses (PERVs), strands of potentially pathogenic DNA in the animals’ genomes, might infect human patients and eventually cause disease. [emphases mine]

That’s where the Church lab’s CRISPR expertise has enabled significant advances. In 2015, the lab published important results in the journal Science, successfully demonstrating the use of genome engineering to eliminate all 62 PERVs in porcine cells. Science later called it “the most widespread CRISPR editing feat to date.”

In 2017, with collaborators at Harvard, other universities, and eGenesis, Church and Yang went further. Publishing again in Science, they first confirmed earlier researchers’ fears: Porcine cells can, in fact, transmit PERVs into human cells, and those human cells can pass them on to other, unexposed human cells. (It is still unknown under what circumstances those PERVs might cause disease.) In the same paper, they corrected the problem, announcing the embryogenesis and birth of 37 PERV-free pigs. [Note: My July 17, 2018 post features research which suggests CRISPR-Cas9 gene editing may cause greater genetic damage than had been thought.]

“Taken together, those innovations were stunning,” said Vivian Berlin, director of business development in OTD, who manages the commercialization strategy for much of Harvard’s intellectual property in the life sciences. “That was the foundation they needed, to convince both the scientific community and the investment community that xenotransplantation might become a reality.”

“After hundreds of tests, this was a critical milestone for eGenesis — and the entire field — and represented a key step toward safe organ transplantation from pigs,” said Julie Sunderland, interim CEO of eGenesis. “Building on this study, we hope to continue to advance the science and potential of making xenotransplantation a safe and routine medical procedure.”

Genetic engineering may undercut human diseases, but also could help restore extinct species, researcher says. [Shades of the Jurassic Park movies!]

It’s not, however, the end of the story: An immunological challenge remains, which eGenesis will need to address. The potential for a patient’s body to outright reject transplanted tissue has stymied many previous attempts at xenotransplantation. Church said numerous genetic changes must be achieved to make porcine organs fully compatible with human patients. Among these are edits to several immune functions, coagulation functions, complements, and sugars, as well as the PERVs.

“Trying the straight transplant failed almost immediately, within hours, because there’s a huge mismatch in the carbohydrates on the surface of the cells, in particular alpha-1-3-galactose, and so that was a showstopper,” Church explained. “When you delete that gene, which you can do with conventional methods, you still get pretty fast rejection, because there are a lot of other aspects that are incompatible. You have to take care of each of them, and not all of them are just about removing things — some of them you have to humanize. There’s a great deal of subtlety involved so that you get normal pig embryogenesis but not rejection.

“Putting it all together into one package is challenging,” he concluded.

In short, it’s the next big challenge for CRISPR.

Not unexpectedly, there is no mention of the CRISPR patent fight between Harvard/MIT’s (Massachusetts Institute of Technology) Broad Institute and the University of California at Berkeley (UC Berkeley). My March 15, 2017 posting featured an outcome where the Broad Institute won the first round of the fight. As I recall, it was a decision based on the principles associated with King Solomon, i.e., the US Patent Office, divided the baby and UCBerkeley got the less important part of the baby. As you might expect the decision has been appealed. In an April 30, 2018 piece, Scientific American reprinted an article about the latest round in the fight written by Sharon Begley for STAT (Note: Links have been removed),

All You Need to Know for Round 2 of the CRISPR Patent Fight

It’s baaaaack, that reputation-shredding, stock-moving fight to the death over key CRISPR patents. On Monday morning in Washington, D.C., the U.S. Court of Appeals for the Federal Circuit will hear oral arguments in University of California v. Broad Institute. Questions?

How did we get here? The patent office ruled in February 2017 that the Broad’s 2014 CRISPR patent on using CRISPR-Cas9 to edit genomes, based on discoveries by Feng Zhang, did not “interfere” with a patent application by UC based on the work of UC Berkeley’s Jennifer Doudna. In plain English, that meant the Broad’s patent, on using CRISPR-Cas9 to edit genomes in eukaryotic cells (all animals and plants, but not bacteria), was different from UC’s, which described Doudna’s experiments using CRISPR-Cas9 to edit DNA in a test tube—and it was therefore valid. The Patent Trial and Appeal Board concluded that when Zhang got CRISPR-Cas9 to work in human and mouse cells in 2012, it was not an obvious extension of Doudna’s earlier research, and that he had no “reasonable expectation of success.” UC appealed, and here we are.

…

For anyone who may not realize what the stakes are for these institutions, Linda Williams in a March 16, 1999 article for the LA Times had this to say about universities, patents, and money,

The University of Florida made about $2 million last year in royalties on a patent for Gatorade Thirst Quencher, a sports drink that generates some $500 million to $600 million a year in revenue for Quaker Oats Co.

The payments place the university among the top five in the nation in income from patent royalties.

Oh, but if some people on the Gainesville, Fla., campus could just turn back the clock. “If we had done Gatorade right, we would be getting $5 or $6 million (a year),” laments Donald Price, director of the university’s office of corporate programs. “It is a classic example of how not to handle a patent idea,” he added.

Gatorade was developed in 1965 when many universities were ill equipped to judge the commercial potential of ideas emerging from their research labs. Officials blew the university’s chance to control the Gatorade royalties when they declined to develop a professor’s idea.

…

The Gatorade story does not stop there and, even though it’s almost 20 years old, this article stands the test of time. I strongly encourage you to read it if the business end of patents and academia interest you or if you would like to develop more insight into the Broad Institute/UC Berkeley situation.

Getting back to the science, there is that pesky matter of diseases crossing over from one species to another. While, Harvard and eGenesis claim a victory in this area, it seems more work needs to be done.

Infections from pigs

An August 29, 2018 University of Alabama at Birmingham news release (also on EurekAlert) by Jeff Hansen, describes the latest chapter in the quest to provide more organs for transplantion,

A shortage of organs for transplantation — including kidneys and hearts — means that many patients die while still on waiting lists. So, research at the University of Alabama at Birmingham and other sites has turned to pig organs as an alternative. [emphasis mine]

Using gene-editing, researchers have modified such organs to prevent rejection, and research with primates shows the modified pig organs are well-tolerated.

An added step is needed to ensure the safety of these inter-species transplants — sensitive, quantitative assays for viruses and other infectious microorganisms in donor pigs that potentially could gain access to humans during transplantation.

The U.S. Food and Drug Administration requires such testing, prior to implantation, of tissues used for xenotransplantation from animals to humans. It is possible — though very unlikely — that an infectious agent in transplanted tissues could become an emerging infectious disease in humans.

In a paper published in Xenotransplantation, Mark Prichard, Ph.D., and colleagues at UAB have described the development and testing of 30 quantitative assays for pig infectious agents. These assays had sensitivities similar to clinical lab assays for viral loads in human patients. After validation, the UAB team also used the assays on nine sows and 22 piglets delivered from the sows through caesarian section.

“Going forward, ensuring the safety of these organs is of paramount importance,” Prichard said. “The use of highly sensitive techniques to detect potential pathogens will help to minimize adverse events in xenotransplantation.”

“The assays hold promise as part of the screening program to identify suitable donor animals, validate and release transplantable organs for research purposes, and monitor transplant recipients,” said Prichard, a professor in the UAB Department of Pediatrics and director of the Department of Pediatrics Molecular Diagnostics Laboratory.

The UAB researchers developed quantitative polymerase chain reaction, or qPCR, assays for 28 viruses sometimes found in pigs and two groups of mycoplasmas. They established reproducibility, sensitivity, specificity and lower limit of detection for each assay. All but three showed features of good quantitative assays, and the lower limit of detection values ranged between one and 16 copies of the viral or bacterial genetic material.

Also, the pig virus assays did not give false positives for some closely related human viruses.

As a start to understanding the infectious disease load in normal healthy animals and ensuring the safety of pig tissues used in xenotransplantation research, the researchers then screened blood, nasal swab and stool specimens from nine adult sows and 22 of their piglets delivered by caesarian section.

Mycoplasma species and two distinct herpesviruses were the most commonly detected microorganisms. Yet 14 piglets that were delivered from three sows infected with either or both herpesviruses were not infected with the herpesviruses, showing that transmission of these viruses from sow to the caesarian-delivery piglet was inefficient.

Prichard says the assays promise to enhance the safety of pig tissues for xenotransplantation, and they will also aid evaluation of human specimens after xenotransplantation.

The UAB researchers say they subsequently have evaluated more than 300 additional specimens, and that resulted in the detection of most of the targets. “The detection of these targets in pig specimens provides reassurance that the analytical methods are functioning as designed,” said Prichard, “and there is no a priori reason some targets might be more difficult to detect than others with the methods described here.”

As is my custom, here’s a link to and a citation for the paper,

Xenotransplantation panel for the detection of infectious agents in pigs by Caroll B. Hartline, Ra’Shun L. Conner, Scott H. James, Jennifer Potter, Edward Gray, Jose Estrada, Mathew Tector, A. Joseph Tector, Mark N. Prichard. Xenotransplantaion Volume 25, Issue 4 July/August 2018 e12427 DOI: https://doi.org/10.1111/xen.12427 First published: 18 August 2018

This paper is open access.

All this leads to questions about chimeras. If a pig is incubating organs with human cells it’s a chimera but then means the human receiving the organ becomes a chimera too. (For an example, see my Dec. 22, 2013 posting where there’s mention of a woman who received a trachea from a pig. Scroll down about 30% of the way.)

What is it to be human?

A question much beloved of philosophers and others, the question seems particularly timely with xenotransplantion and other developments such neuroprosthetics (cyborgs) and neuromorphic computing (brainlike computing).

As I’ve noted before, although not recently, popular culture offers a discourse on these issues. Take a look at the superhero movies and the way in which enhanced humans and aliens are presented. For example, X-Men comics and movies present mutants (humans with enhanced abilities) as despised and rejected. Video games (not really my thing but there is the Deus Ex series which has as its hero, a cyborg also offer insight into these issues.

Other than popular culture and in the ‘bleeding edge’ arts community, I can’t recall any public discussion on these matters arising from the extraordinary set of technologies which are being deployed or prepared for deployment in the foreseeable future.

(If you’re in Vancouver (Canada) from September 14 – December 15, 2018, you may want to check out Piccinini’s work. Also, there’s ” NCSU [North Carolina State University] Libraries, NC State’s Genetic Engineering and Society (GES) Center, and the Gregg Museum of Art & Design have issued a public call for art for the upcoming exhibition Art’s Work in the Age of Biotechnology: Shaping our Genetic Futures.” from my Sept. 6, 2018 posting. Deadline: Oct. 1, 2018.)

At a guess, there will be pushback from people who have no interest in debating what it is to be human as they already know, and will find these developments, when they learn about them, to be horrifying and unnatural.

Montreal Neuro creates a new paradigm for technology transfer?

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It’s one heck of a Christmas present. Canadian businessmen Larry Tannenbaum and his wife Judy have given the Montreal Neurological Institute (Montreal Neuro), which is affiliated with McGill University, a $20M donation. From a Dec. 16, 2016 McGill University news release,

The Prime Minister of Canada, Justin Trudeau, was present today at the Montreal Neurological Institute and Hospital (MNI) for the announcement of an important donation of $20 million by the Larry and Judy Tanenbaum family. This transformative gift will help to establish the Tanenbaum Open Science Institute, a bold initiative that will facilitate the sharing of neuroscience findings worldwide to accelerate the discovery of leading edge therapeutics to treat patients suffering from neurological diseases.

‟Today, we take an important step forward in opening up new horizons in neuroscience research and discovery,” said Mr. Larry Tanenbaum. ‟Our digital world provides for unprecedented opportunities to leverage advances in technology to the benefit of science. That is what we are celebrating here today: the transformation of research, the removal of barriers, the breaking of silos and, most of all, the courage of researchers to put patients and progress ahead of all other considerations.”

Neuroscience has reached a new frontier, and advances in technology now allow scientists to better understand the brain and all its complexities in ways that were previously deemed impossible. The sharing of research findings amongst scientists is critical, not only due to the sheer scale of data involved, but also because diseases of the brain and the nervous system are amongst the most compelling unmet medical needs of our time.

Neurological diseases, mental illnesses, addictions, and brain and spinal cord injuries directly impact 1 in 3 Canadians, representing approximately 11 million people across the country.

“As internationally-recognized leaders in the field of brain research, we are uniquely placed to deliver on this ambitious initiative and reinforce our reputation as an institution that drives innovation, discovery and advanced patient care,” said Dr. Guy Rouleau, Director of the Montreal Neurological Institute and Hospital and Chair of McGill University’s Department of Neurology and Neurosurgery. “Part of the Tanenbaum family’s donation will be used to incentivize other Canadian researchers and institutions to adopt an Open Science model, thus strengthening the network of like-minded institutes working in this field.”

What they don’t mention in the news release is that they will not be pursuing any patents (for five years according to one of the people in the video but I can’t find text to substantiate that time limit*; there are no time limits noted elsewhere) on their work. For this detail and others, you have to listen to the video they’ve created,

The CBC (Canadian Broadcasting Corporation) news online Dec. 16, 2016 posting (with files from Sarah Leavitt and Justin Hayward) adds a few personal details about Tannenbaum,

“Our goal is simple: to accelerate brain research and discovery to relieve suffering,” said Tanenbaum.

Tanenbaum, a Canadian businessman and chairman of Maple Leaf Sports and Entertainment, said many of his loved ones suffered from neurological disorders.

“I lost my mother to Alzheimer’s, my father to a stroke, three dear friends to brain cancer, and a brilliant friend and scientist to clinical depression,” said Tanenbaum.

He hopes the institute will serve as the template for science research across the world, a thought that Trudeau echoed.

“This vision around open science, recognizing the role that Canada can and should play, the leadership that Canadians can have in this initiative is truly, truly exciting,” said Trudeau.

The Neurological Institute says the pharmaceutical industry is supportive of the open science concept because it will provide crucial base research that can later be used to develop drugs to fight an array of neurological conditions.

Jack Stilgoe in a Dec. 16, 2016 posting on the Guardian blogs explains what this donation could mean (Note: Links have been removed),

With the help of Tanenbaum’s gift of 20 million Canadian dollars (£12million) the ‘Neuro’, the Montreal Neurological Institute and Hospital, is setting up an experiment in experimentation, an Open Science Initiative with the express purpose of finding out the best way to realise the potential of scientific research.

…

Governments in science-rich countries are increasingly concerned that they do not appear to reaping the economic returns they feel they deserve from investments in scientific research. Their favoured response has been to try to bridge what they see as a ‘valley of death’ between basic scientific research and industrial applications. This has meant more funding for ‘translational research’ and the flowering of technology transfer offices within universities.

… There are some success stories, particularly in the life sciences. Patents from the work of Richard Axel at Columbia University at one point brought the university almost $100 million per year. The University of Florida received more than $150 million for inventing Gatorade in the 1960s. The stakes are high in the current battle between Berkely and MIT/Harvard over who owns the rights to the CRISPR/Cas9 system that has revolutionised genetic engineering and could be worth billions.

Policymakers imagine a world in which universities pay for themselves just as a pharmaceutical research lab does. However, for critics of technology transfer, such stories blind us to the reality of university’s entrepreneurial abilities.

For most universities, evidence of their money-making prowess is, to put it charitably, mixed. A recent Bloomberg report shows how quickly university patent incomes plunge once we look beyond the megastars. In 2014, just 15 US universities earned 70% of all patent royalties. British science policy researchers Paul Nightingale and Alex Coad conclude that ‘Roughly 9/10 US universities lose money on their technology transfer offices… MIT makes more money from selling T-shirts than it does from licensing’. A report from the Brookings institute concluded that the model of technology transfer ‘is unprofitable for most universities and sometimes even risks alienating the private sector’. In the UK, the situation is even worse. Businesses who have dealings with universities report that their technology transfer offices are often unrealistic in negotiations. In many cases, academics are, like a small child who refuses to let others play with a brand new football, unable to make the most of their gifts. And areas of science outside the life sciences are harder to patent than medicines, sports drinks and genetic engineering techniques. Trying too hard to force science towards the market may be, to use the phrase of science policy professor Keith Pavitt, like pushing a piece of string.

Science policy is slowly waking up to the realisation that the value of science may lie in people and places rather than papers and patents. It’s an idea that the Neuro, with the help of Tanenbaum’s gift, is going to test. By sharing data and giving away intellectual property, the initiative aims to attract new private partners to the institute and build Montreal as a hub for knowledge and innovation. The hypothesis is that this will be more lucrative than hoarding patents.

This experiment is not wishful thinking. It will be scientifically measured. It is the job of Richard Gold, a McGill University law professor, to see whether it works. He told me that his first task is ‘to figure out what to counts… There’s going to be a gap between what we would like to measure and what we can measure’. However, he sees an open-mindedness among his colleagues that is unusual. Some are evangelists for open science; some are sceptics. But they share a curiosity about new approaches and a recognition of a problem in neuroscience: ‘We haven’t come up with a new drug for Parkinson’s in 30 years. We don’t even understand the biological basis for many of these diseases. So whatever we’re doing at the moment doesn’t work’. …

Montreal Neuro made news on the ‘open science’ front in January 2016 when it formally announced its research would be freely available and that researchers would not be pursuing patents (see my January 22, 2016 posting).

I recommend reading Stilgoe’s posting in its entirety and for those who don’t know or have forgotten, Prime Minister’s Trudeau’s family has some experience with mental illness. His mother has been very open about her travails. This makes his presence at the announcement perhaps a bit more meaningful than the usual political presence at a major funding announcement.

*The five-year time limit is confirmed in a Feb. 17, 2017 McGill University news release about their presentations at the AAAS (American Association for the Advancement of Science) 2017 annual meeting) on EurekAlert,

umpstarting Neurological Research through Open Science – MNI & McGill University

Friday, February 17, 2017, 1:30-2:30 PM/ Room 208

Neurological research is advancing too slowly according to Dr. Guy Rouleau, director of the Montreal Neurological Institute (MNI) of McGill University. To speed up discovery, MNI has become the first ever Open Science academic institution in the world. In a five-year experiment, MNI is opening its books and making itself transparent to an international group of social scientists, policymakers, industrial partners, and members of civil society. They hope, by doing so, to accelerate research and the discovery of new treatments for patients with neurological diseases, and to encourage other leading institutions around the world to consider a similar model. A team led by McGill Faculty of Law’s Professor Richard Gold will monitor and evaluate how well the MNI Open Science experiment works and provide the scientific and policy worlds with insight into 21st century university-industry partnerships. At this workshop, Rouleau and Gold will discuss the benefits and challenges of this open-science initiative.

Harvard University announced new Center on Nano-safety Research

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The nano safety center at Harvard University (Massachusetts, US) is a joint center with the US National Institute of Environmental Health Sciences according to an Aug. 29, 2016 news item on Nanowerk,

Engineered nanomaterials (ENMs)—which are less than 100 nanometers (one millionth of a millimeter) in diameter—can make the colors in digital printer inks pop and help sunscreens better protect against radiation, among many other applications in industry and science. They may even help prevent infectious diseases. But as the technology becomes more widespread, questions remain about the potential risks that ENMs may pose to health and the environment.

Researchers at the new Harvard-NIEHS [US National Institute of Environmental Health Sciences] Nanosafety Research Center at Harvard T.H. Chan School of Public Health are working to understand the unique properties of ENMs—both beneficial and harmful—and to ultimately establish safety standards for the field.

An Aug. 16, 2016 Harvard University press release, which originated the news item, provides more detail (Note: Links have been removed),

“We want to help nanotechnology develop as a scientific and economic force while maintaining safeguards for public health,” said Center Director Philip Demokritou, associate professor of aerosol physics at Harvard Chan School. “If you understand the rules of nanobiology, you can design safer nanomaterials.”

ENMs can enter the body through inhalation, ingestion, and skin contact, and toxicological studies have shown that some can penetrate cells and tissues and potentially cause biochemical damage. Because the field of nanoparticle science is relatively new, no standards currently exist for assessing the health risks of exposure to ENMs—or even for how studies of nano-biological interactions should be conducted.

Much of the work of the new Center will focus on building a fundamental understanding of why some ENMs are potentially more harmful than others. The team will also establish a “reference library” of ENMs, each with slightly varied properties, which will be utilized in nanotoxicology research across the country to assess safety. This will allow researchers to pinpoint exactly what aspect of an ENM’s properties may impact health. The researchers will also work to develop standardized methods for nanotoxicology studies evaluating the safety of nanomaterials.

The Center was established with a $4 million dollar grant from the National Institute of Environmental Health Science (NIEHS) last month, and is the only nanosafety research center to receive NIEHS funding for the next five years. It will also play a coordinating role with existing and future NIEHS nanotoxicology research projects nantionwide. Scientists from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS), MIT, University of Maine, and University of Florida will collaborate on the new effort.

The Center builds on the existing Center for Nanotechnology and Nanotoxicology at Harvard Chan School, established by Demokritou and Joseph Brain, Cecil K. and Philip Drinker Professor of Environmental Physiology, in the School’s Department of Environmental Health in 2010.

A July 5, 2016 Harvard University press release announcing the $4M grant provides more information about which ENMs are to be studied,

The main focus of the new HSPH-NIEHS Center is to bring together scientists from across disciplines- material science, chemistry, exposure assessment, risk assessment, nanotoxicology and nanobiology- to assess the potential environmental Health and safety (EHS) implications of engineered nanomaterials (ENMs).

The $4 million dollar HSPH based Center which is the only Nanosafety Research Center to be funded by NIEHS this funding cycle, … The new HSPH-NIEHS Nanosafety Center builds upon the nano-related infrastructure in [the] collaborating Universities, developed over the past 10 years, which includes an inter-disciplinary research group of faculty, research staff and students, as well as state-of-the-art platforms for high throughput synthesis of ENMs, including metal and metal oxides, cutting edge 2D/3D ENMs such as CNTs [carbon nanotubes] and graphene, nanocellulose, and advanced nanocomposites, [emphasis mine] coupled with innovative tools to assess the fate and transport of ENMs in biological systems, statistical and exposure assessment tools, and novel in vitro and in vivo platforms for nanotoxicology research.

“Our mission is to integrate material/exposure/chemical sciences and nanotoxicology-nanobiology to facilitate assessment of potential risks from emerging nanomaterials. In doing so, we are bringing together the material synthesis/applications and nanotoxicology communities and other stakeholders including industry, policy makers and the general public to maximize innovation and growth and minimize environmental and public health risks from nanotechnology”, quoted by Dr Philip Demokritou, …

This effort certainly falls in line with the current emphasis on interdisciplinary research and creating standards and protocols for researching the toxicology of engineered nanomaterials.

Using light to make gold crystal nanoparticles

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Gold crystal nanoparticles? Courtesy: University of Florida

A team from the University of Florida has used gold instead of silver in a process known as plasmon-driven synthesis. From a July 8, 2016 news item on phys.org,

A team of University of Florida researchers has figured out how gold can be used in crystals grown by light to create nanoparticles, a discovery that has major implications for industry and cancer treatment and could improve the function of pharmaceuticals, medical equipment and solar panels.

A July 6, 2016 University of Florida news release, which originated the news item, provides more detail,

Nanoparticles can be “grown” in crystal formations with special use of light, in a process called plasmon-driven synthesis. However, scientists have had limited control unless they used silver, but silver limits the uses for medical technology. The team is the first to successfully use gold, which works well within the human body, with this process.

“How does light actually play a role in the synthesis? [This knowledge] was not well developed,” said David Wei, an associate professor of chemistry who led the research team. “Gold was the model system to demonstrate this.”

Gold is highly desired for nanotechnology because it is malleable, does not react with oxygen and conducts heat well. Those properties make gold an ideal material for nanoparticles, especially those that will be placed in the body.

When polyvinylpyrrolidone, or PVP, a substance commonly found in pharmaceutical tablets, is used in the plasmon-driven synthesis, it enables scientists to better control the growth of crystals. In Wei’s research, PVP surprised the team by showing its potential to relay light-generated “hot” electrons to a gold surface to grow the crystals.

The research describes the first plasmonic synthesis strategy that can make high-yield gold nanoprisms. Even more exciting, the team has demonstrated that visible-range and low-power light can be used in the synthesis. Combined with nanoparticles being used in solar photovoltaic devices, this method can even harness solar energy for chemical synthesis, to make nanomaterials or for general applications in chemistry.

Wei has spent the last decade working in nanotechnology. He is intrigued by its applications in photochemistry and biomedicine, especially in targeted drug delivery and photothermal therapeutics, which is crucial to cancer treatment. His team includes collaborators from Pacific Northwest National Laboratory, where he has worked as a visiting scholar, and Brookhaven National Laboratory. In addition, the project has provided an educational opportunity for chemistry students: one high school student (through UF’s Student Science Training Program), two University scholars who also [sic] funded by the Howard Hughes Medical Institute, five graduate students and two postdocs.

Here’s a link to and a citation for the paper,

Polyvinylpyrrolidone-induced anisotropic growth of gold nanoprisms in plasmon-driven synthesis by Yueming Zhai, Joseph S. DuChene, Yi-Chung Wang, Jingjing Qiu, Aaron C. Johnston-Peck, Bo You, Wenxiao Guo, Benedetto DiCiaccio, Kun Qian, Evan W. Zhao, Frances Ooi, Dehong Hu, Dong Su, Eric A. Stach, Zihua Zhu, & Wei David Wei. Nature Materials (2016) doi:10.1038/nmat4683 Published online 04 July 2016

This paper is behind a paywall.

Silver nanoparticles and wormwood tackle plant-killing fungus

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I’m back in Florida (US), so to speak. Last mentioned here in an April 7, 2015 post about citrus canker and zinkicide, a story about a disease which endangers citrus production in the US, this latest story concerns a possible solution to the problem of a fungus, which attacks ornamental horticultural plants in Florida. From a May 5, 2015 news item on Azonano,

Deep in the soil, underneath more than 400 plant and tree species, lurks a lethal fungus threatening Florida’s $15 billion a year ornamental horticulture industry.

But University of Florida plant pathologist G. Shad Ali has found an economical and eco-friendly way to combat the plant destroyer known as phytophthora before it attacks the leaves and roots of everything from tomato plants to oak trees.

Ali and a team of researchers with UF’s Institute of Food and Agricultural Sciences, along with the University of Central Florida and the New Jersey Institute of Technology, have found that silver nanoparticles produced with an extract of wormwood, an herb with strong antioxidant properties, can stop several strains of the deadly fungus.

A May 4, 2015 University of Florida news release, which originated the news item, describes the work in more detail,

“The silver nanoparticles are extremely effective in eliminating the fungus in all stages of its life cycle,” Ali said. “In addition, it has no adverse effects on plant growth.” [emphasis mine]

The silver nanoparticles measure 5 to 100 nanometers in diameter – about one one-thousandth the width of a human hair. Once the nanoparticles are sprayed onto a plant, they shield it from fungus. Since the nanoparticles display multiple ways of inhibiting fungus growth, the chances of pathogens developing resistance to them are minimized, Ali said. Because of that, they may be used for controlling fungicide-resistant plant pathogens more effectively.

That’s good news for the horticulture industry. Worldwide crop losses due to phytophthora fungus diseases are estimated to be in the multibillion dollar range, with $6.7 billion in losses in potato crops due to late blight – the cause of the Irish Potato Famine in the mid-1800s when more than 1 million people died – and $1 billion to $2 billion in soybean loss.

Silver nanoparticles are being investigated for applications in various industries, including medicine, diagnostics, cosmetics and food processing. They already are used in wound dressings, food packaging and in consumer products such as textiles and footwear for fighting odor-causing microorganisms.

Other members of the UF research team were Mohammad Ali, a visiting doctoral student from the Quaid-i-Azam University, Islamabad, Pakistan; David Norman and Mary Brennan with the University of Florida’s Plant Pathology-Mid Florida Research and Education Center; Bosung Kim with the University of Central Florida’s chemistry department; Kevin Belfield with the College of Science and Liberal Arts at the New Jersey Institute of Technology and the University of Central Florida’s chemistry department.

Ali’s comment about silver nanoparticles not having any adverse effects on plant growth is in contrast to findings by Mark Wiesner and other researchers at Duke University (North Carolina, US). From my Feb. 28, 2013 posting (which also features a Finnish-Estonia study showing no adverse effects from silver nanoparticles in crustaceans),

… there’s a study from Duke University suggests that silver nanoparticles in wastewater which is later put to agricultural use may cause problems. From the Feb. 27, 2013 news release on EurekAlert,

In experiments mimicking a natural environment, Duke University researchers have demonstrated that the silver nanoparticles used in many consumer products can have an adverse effect on plants and microorganisms.

…

The main route by which these particles enter the environment is as a by-product of water and sewage treatment plants. [emphasis] The nanoparticles are too small to be filtered out, so they and other materials end up in the resulting “sludge,” which is then spread on the land surface as a fertilizer.

…

The researchers found that one of the plants studied, a common annual grass known as Microstegium vimeneum, had 32 percent less biomass in the mesocosms treated with the nanoparticles. Microbes were also affected by the nanoparticles, Colman [Benjamin Colman, a post-doctoral fellow in Duke’s biology department and a member of the Center for the Environmental Implications of Nanotechnology (CEINT)] said. One enzyme associated with helping microbes deal with external stresses was 52 percent less active, while another enzyme that helps regulate processes within the cell was 27 percent less active. The overall biomass of the microbes was also 35 percent lower, he said.

“Our field studies show adverse responses of plants and microorganisms following a single low dose of silver nanoparticles applied by a sewage biosolid,” Colman said. “An estimated 60 percent of the average 5.6 million tons of biosolids produced each year is applied to the land for various reasons, and this practice represents an important and understudied route of exposure of natural ecosystems to engineered nanoparticles.”

“Our results show that silver nanoparticles in the biosolids, added at concentrations that would be expected, caused ecosystem-level impacts,” Colman said. “Specifically, the nanoparticles led to an increase in nitrous oxide fluxes, changes in microbial community composition, biomass, and extracellular enzyme activity, as well as species-specific effects on the above-ground vegetation.”

Getting back to Florida, you can find Ali’s abstract here,

Inhibition of Phytophthora parasitica and P. capsici by silver nanoparticles synthesized using aqueous extract of Artemisia absinthium by Mohammad Ali, Bosung Kim, Kevin Belfield, David J. Norman, Mary Brennan, & Gul Shad Ali. Phytopathology http://dx.doi.org/10.1094/PHYTO-01-15-0006-R Published online April 14, 2015

This paper is behind a paywall.

For anyone who recognized that wormwood is a constituent of Absinthe, a liquor that is banned in many parts of the world due to possible side effects associated with the wormwood, here’s more about it from the Wormwood overview page on WebMD (Note: Links have been removed),

Wormwood is an herb. The above-ground plant parts and oil are used for medicine.

…

Wormwood is used in some alcoholic beverages. Vermouth, for example, is a wine beverage flavored with extracts of wormwood. Absinthe is another well-known alcoholic beverage made with wormwood. It is an emerald-green alcoholic drink that is prepared from wormwood oil, often along with other dried herbs such as anise and fennel. Absinthe was popularized by famous artists and writers such as Toulouse-Lautrec, Degas, Manet, van Gogh, Picasso, Hemingway, and Oscar Wilde. It is now banned in many countries, including the U.S. But it is still allowed in European Union countries as long as the thujone content is less than 35 mg/kg. Thujone is a potentially poisonous chemical found in wormwood. Distilling wormwood in alcohol increases the thujone concentration.

Returning to the matter at hand, as I’ve noted previously elsewhere, research into the toxic effects associated with nanomaterials (e.g. silver nanoparticles) is a complex process.

US Dept. of Agriculture awards $3.8M for nanotechnology research grants

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I wonder just how much funding the US Dept. of Agriculture (USDA) is devoting to nanotechnology this year (2015). I first came across an announcement of $23M in the body of a news item about Zinkicide (my April 7, 2015 posting),

Found in Florida orchards in 2005, a citrus canker, citrus greening, poses a serious threat to the US state’s fruit industry. An April 2, 2105 news item on phys.org describes a possible solution to the problem,

Since it was discovered in South Florida in 2005, the plague of citrus greening has spread to nearly every grove in the state, stoking fears among growers that the $10.7 billion-a-year industry may someday disappear.

Now the U.S. Department of Agriculture has awarded the University of Florida a $4.6 million grant aimed at testing a potential new weapon in the fight against citrus greening: Zinkicide, a bactericide invented by a nanoparticle researcher at the University of Central Florida.

An April 29, 2015 article by Diego Flammini for Farm.com describes the latest USDA nanotechnology funding announcement,

In an effort to increase America’s food security, nutrition, food safety and environmental protection, the United States Department of Agriculture’s (USDA) National Institute of Food and Agriculture (NIFA) announced $3.8 million in nanotechnology research grants.

Flammini lists three of the eight recipients,

University of Georgia
With $496,192, the research team will develop different sensors that are able to detect fungal pathogens in crops. The project will also develop a smartphone app for farmers to have so they can access their information whenever necessary.

Rutgers University
The school will use its $450,000 to conduct a nationwide survey about nanotechnology and gauge consumer beliefs about it and its relationship to health. Among the specifics it will touch on is the use of visuals to communicate nanotechnology.

University of Massachusetts
The researchers will concentrate their $444,200 on developing a platform to detect pathogens in food that is better than the current methods.

A full list of the recipients can be found in the April 27, 2015 USDA news release featuring the $3.8M in awards,

The University of Georgia, Athens, Ga., $496,192

University of Iowa, Iowa City, Iowa., $496,180

University of Kentucky Research Foundation, Lexington, Ky., $450,000

University of Massachusetts, Amherst, Mass., $444,200

North Dakota State University, Fargo, N.D., $149,714

Rutgers University, New Brunswick. N.J., $450,000

Pennsylvania State University, University Park, University Park, Pa., $447,788

West Virginia University, Morgantown, W. Va., $496,168

University of Wisconsin-Madison, Madison, Wis., $450,100

You can find more details about the awards in this leaflet featuring the USDA project descriptions for the eight recipients.

Citrus canker, Florida, and Zinkicide

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Found in Florida orchards in 2005, a citrus canker, citrus greening, poses a serious threat to the US state’s fruit industry. An April 2, 2105 news item on phys.org describes a possible solution to the problem,

Since it was discovered in South Florida in 2005, the plague of citrus greening has spread to nearly every grove in the state, stoking fears among growers that the $10.7 billion-a-year industry may someday disappear.

Now the U.S. Department of Agriculture has awarded the University of Florida a $4.6 million grant aimed at testing a potential new weapon in the fight against citrus greening: Zinkicide, a bactericide invented by a nanoparticle researcher at the University of Central Florida.

An April 2, 2015 University of Central Florida news release by Mark Schlueb (also on EurekAlert), which originated the news item, describes the problem and the solution (Zinkicide),

Citrus greening – also known by its Chinese name, Huanglongbing, or HLB – causes orange, grapefruit and other citrus trees to produce small, bitter fruit that drop prematurely and is unsuitable for sale or juice. Eventually, infected trees die. Florida has lost tens of thousands of acres to the disease.

“It’s a hundred-year-old disease, but to date there is no cure. It’s a killer, a true killer for the citrus industry,” said Swadeshmukul Santra, associate professor in the NanoScience Technology Center at UCF.

The bacteria that causes HLB is carried by the Asian citrus psyllid, a tiny insect that feeds on leaves and stems of infected citrus trees, then carries the bacteria to healthy trees.

Zinkicide, developed by Santra, is designed to kill the bacteria.

The $4.6 million grant is the largest of five totaling $23 million that were recently announced by the USDA’s National Institute of Food and Agriculture.

The evaluation of Zinkicide is a multi-institute project involving 13 investigators from six institutions. Evan Johnson of UF’s [University of Florida] Citrus Research and Education Center at Lake Alfred is the project director, and there are a dozen co-principal investigators from UF, UCF, Oak Ridge National Laboratory (ORNL), Auburn University, New Mexico State University and The Ohio State University.

”Managing systemic diseases like HLB is a difficult challenge that has faced plant pathologists for many years,” said Johnson “It is a privilege to work with an excellent team of researchers from many different disciplines with the goal of developing new tools that are both effective and safe.”

A portion of the grant money, $1.4 million, flows to UCF, where Santra leads a team that also includes Andre Gesquiere, Laurene Tetard and the Oak Ridge National Laboratory collaborator, Loukas Petridis.

HLB control is difficult because current bactericidal sprays, such as copper, simply leave a protective film on the outside of a plant. The insect-transmitted bacteria bypasses that barrier and lives inside a tree’s fruit, stems and roots, in the vascular tissue known as the phloem. There, it deprives the tree of carbohydrate and nutrients, causing root loss and ultimately death. For a bactericide to be effective against HLB, it must be able to move within the plant, too.

Zinkicide is a nanoparticle smaller than a single microscopic cell, and researchers are cautiously optimistic it will be able to move systemically from cell to cell to kill the bacteria that cause HLB.

“The bacteria hide inside the plant in the phloem region,” Santra said. “If you spray and your compound doesn’t travel to the phloem region, then you cannot treat HLB.”

Zinkicide is derived from ingredients which are found in plants, and is designed to break down and be metabolized after its job is done. [emphasis mine]

It’s the first step in a years-long process to bring a treatment to market. UF will lead five years of greenhouse and field trials on grapefruit and sweet orange to determine the effectiveness of Zinkicide and the best method and timing of application.

The project also includes research to study where the nanoparticles travel within the plant, understand how they interact with plant tissue and how long they remain before breaking down. [emphasis mine]

If effective, the bactericide could have a substantial role in combatting HLB in Florida, and in other citrus-producing states and countries. It would also likely be useful for control of other bacterial pathogens infecting other crops.

The Zinkicide project builds as a spinoff from previous collaborations between Santra and UF’s Jim Graham, at the Citrus Research and Education Center to develop alternatives to copper for citrus canker control.

The previous Citrus Research and Education Foundation (CRDF)-funded Zinkicide project has issued three reports, for June 30, 2014, Sept. 30, 2014, and Dec. 31, 2014. This project’s completion date is May 2015. The reports which are remarkably succinct, consisting of two paragraphs, can be found here.

Oddly, the UCF news release doesn’t mention that Zinkicide (although it can be inferred) is a zinc particulate (I’m guessing they mean zinc nanoparticle) as noted on the CRDF project webpage. Happily, they are researching what happens after the bactericide has done its work on the infection. It’s good to see a life cycle approach to this research.

Metaphors in a brief overview of the nanomedicine scene circa August 2014

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An Aug. 1, 2014 article by Guizhi Zhu (University of Florida), Lei Mei ((Hunan University; China), and Weihong Tan (University of Florida) for The Scientist provides an overview of the latest and greatest regarding nanomedicine while underscoring the persistence of certain medical metaphors. This overview features a prediction and a relatively benign (pun intended) metaphor,

Both the academic community and the pharmaceutical industry are making increasing investments of time and money in nanotherapeutics. Nearly 50 biomedical products incorporating nanoparticles are already on the market, and many more are moving through the pipeline, with dozens in Phase 2 or Phase 3 clinical trials. Drugmakers are well on their way to realizing the prediction of Christopher Guiffre, chief business officer at the Cambridge, Massachusetts–based nanotherapeutics company Cerulean Pharma, who last November forecast, “Five years from now every pharma will have a nano program.”

…

Technologies that enable improved cancer detection are constantly racing against the diseases they aim to diagnose, and when survival depends on early intervention, losing this race can be fatal. [emphasis mine] While detecting cancer biomarkers is the key to early diagnosis, the number of bona fide biomarkers that reliably reveal the presence of cancerous cells is low. To overcome this challenge, researchers are developing functional nanomaterials for more sensitive detection of intracellular metabolites, tumor cell–membrane proteins, and even cancer cells that are circulating in the bloodstream. (See “Fighting Cancer with Nanomedicine,” The Scientist, April 2014.)

So, the first metaphor ‘racing’ gives the reader a sense of urgency, the next ones, including “fighting cancer’, provoke a somewhat different state of mind,

Eye on the target

The prototype of targeted drug delivery can be traced back to the concept of a “magic bullet,” proposed by chemotherapy pioneer and 1908 Nobel laureate Paul Ehrlich. [emphasis mine] E[hrlich envisioned a drug that could selectively target a disease-causing organism or diseased cells, leaving healthy tissue unharmed. A century later, researchers are developing many types of nanoscale “magic bullets” that can specifically deliver drugs into target cells or tissues.

It would seem we might be in a state of war as you ‘fight cancer’ with your ‘eyes on the target’ as you ‘shoot magic bullets’ in time to celebrate the 100th anniversary of the start to World War I.

Kostas Kostarelos wrote a Nov. 29, 2013 posting for the Guardian Science Blogs where he (professor of nanomedicine at the University of Manchester and director of the university’s Nanomedicine Lab) discussed war metaphors in medicine and possible unintended consequences (Note: A link has been removed). Here’s his discussion about the metaphors,

Almost every night I have watched the news these past few months my senses have been assaulted by unpleasant, at times distressing, images of war: missiles, killings and chemical bombs in Syria, Kenya, the USA. I wake up the next morning, trying to forget what I watched the night before, and going to work with our researchers to develop the next potential high-tech cure for cancer, thinking: “does what we do matter at all … ?”

So I was intrigued by an article that will be published in one of the scientific journals in our field entitled: “Nanomedicine metaphors: from war to care”. The next lab meeting we had was very awkward, because I was constantly thinking that indeed a lot of the words we were using to communicate our science were directly imported from the language of war. Targeting, stealth nanoparticle, smart bomb, elimination, triggered release, cell death. I struggled to find alternative language.

…

… Hollywood analogies and simplistic interpretations about “good” and “bad” may be inaccurate, but they do seem appropriate and convincing.

I must say, however, that even in pathology, modern medicine increasingly considers the disease to be part of our body, often leading to successful treatment not by “eradication” and “elimination” but by holistic management of a chronic condition. The case of HIV therapeutics is perhaps the brightest example of such revisionist thinking, which has transformed the disease from a “death sentence” in the early years after its discovery to a nonlethal chronic infection today.

Kostarelos then contrasts the less warlike ‘modern medicine’ metaphors with nanomedicine,

In nanomedicine, which is the application of nanotechnologies and nanomaterials to design medical treatments, the war imagery is even more prevalent. Two of the most clinically successful and intensively studied technologies that operate at the nanoscale are “stealth” and “targeted” medicines. “Stealth” refers to a hydrophilic (water-loving) shield built around a molecule or nanoparticle, made from polymers, that minimises its recognition by the body’s defence mechanisms. “Targeting” refers to the specific binding of certain molecules (such as antibodies, peptides and others) to receptors (or other proteins) present only at the surface of diseased cells. The literature in nanomedicine is abundant with both “stealthing”, “targeting” and combinations thereof.

Kostarelos then asks this question,

The question I keep asking myself since I read the article about war metaphors in nanomedicine has been whether we are using terminology in a simplistic, single-minded manner that could stifle creative and out-of-the-box thinking.

Intriguing unintended consequences, yes?

Getting back to The Scientist article, which I found quite informative and interesting, its ‘war metaphors’ seem to extend even to some of the artwork accompanying the article,

[downloaded from http://www.the-scientist.com/?articles.view/articleNo/40598/title/Nanomedicine/]

Is that a capsule or a bullet? Regardless, this * article provides a good overview of the research.

* The word ‘a’ was removed on Aug. 8, 2014.

FrogHeart

Commentary about nanotech, science policy and communication, society, and the arts

Tag Archives: University of Florida

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Silver nanoparticles and wormwood tackle plant-killing fungus

US Dept. of Agriculture awards $3.8M for nanotechnology research grants

Citrus canker, Florida, and Zinkicide

Metaphors in a brief overview of the nanomedicine scene circa August 2014