Tag Archives: US National Institutes of Health

Yes! Art, genetic modifications, gene editing, and xenotransplantation at the Vancouver Biennale (Canada)

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

Up to this point, I’ve been a little jealous of the Art/Sci Salon’s (Toronto, Canada) January 2018 workshops for artists and discussions about CRISPR ((clustered regularly interspaced short palindromic repeats))/Cas9 and its social implications. (See my January 10, 2018 posting for more about the events.) Now, it seems Vancouver may be in line for its ‘own’ discussion about CRISPR and the implications of gene editing. The image you saw (above) represents one of the installations being hosted by the 2018 – 2020 edition of the Vancouver Biennale.

While this posting is mostly about the Biennale and Piccinini’s work, there is a ‘science’ subsection featuring the science of CRISPR and xenotransplantation. Getting back to the Biennale and Piccinini: A major public art event since 1988, the Vancouver Biennale has hosted over 91 outdoor sculptures and new media works by more than 78 participating artists from over 25 countries and from 4 continents.

Quickie description of the 2018 – 2020 Vancouver Biennale

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

The Vancouver Biennale will be bringing new —and unusual— works of public art to the city beginning this June.

The theme for this season’s Vancouver Biennale exhibition is “re-IMAGE-n” and it kicks off on June 20 [2018] in Vanier Park with Saudi artist Ajlan Gharem’s Paradise Has Many Gates.

Gharem’s architectural chain-link sculpture resembles a traditional mosque, the piece is meant to challenge the notions of religious orthodoxy and encourages individuals to image a space free of Islamophobia.

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].

Given that this blog is focused on nanotechnology and other emerging technologies such as CRISPR, I’m focusing on Piccinini’s work and its art/science or sci-art status. This image from the GOMA Gallery where Piccinini’s ‘Curious Affection‘ installation is being shown from March 24 – Aug. 5, 2018 in Brisbane, Queensland, Australia may give you some sense of what one of her installations is like,

Courtesy: Queensland Art Gallery | Gallery of Modern Art (QAGOMA)

I spoke with Serena at the Vancouver Biennale office and asked about the ‘interactive’ aspect of Piccinini’s installation. She suggested the term ‘immersive’ as an alternative. In other words, you won’t be playing with the sculptures or pressing buttons and interacting with computer screens or robots. She also noted that the ticket prices have not been set yet and they are currently developing events focused on the issues raised by the installation. She knew that 2018 is the 200th anniversary of the publication of Mary Shelley’s Frankenstein but I’m not sure how the Biennale folks plan (or don’t plan)  to integrate any recognition of the novle’s impact on the discussions about ‘new’ technologies .They expect Piccinini will visit Vancouver. (Note 1: Piccinini’s work can  also be seen in a group exhibition titled: Frankenstein’s Birthday Party at the Hosfselt Gallery in San Francisco (California, US) from June 23 – August 11, 2018.  Note 2: I featured a number of international events commemorating the 200th anniversary of the publication of Mary Shelley’s novel, Frankenstein, in my Feb. 26, 2018 posting. Note 3: The term ‘Frankenfoods’ helped to shape the discussion of genetically modified organisms and food supply on this planet. It was a wildly successful campaign for activists affecting legislation in some areas of research. Scientists have not been as enthusiastic about the effects. My January 15, 2009 posting briefly traces a history of the term.)

The 2018 – 2020 Vancouver Biennale and science

A June 7, 2018 Vancouver Biennale news release provides more detail about the current series of exhibitions,

The Biennale is also committed to presenting artwork at the cutting edge of discussion and in keeping with the STEAM (science, technology, engineering, arts, math[ematics]) approach to integrating the arts and sciences. In August [2018], Colombian/American visual artist Jessica Angel will present her monumental installation Dogethereum Bridge at Hinge Park in Olympic Village. Inspired by blockchain technology, the artwork’s design was created through the integration of scientific algorithms, new developments in technology, and the arts. This installation, which will serve as an immersive space and collaborative hub for artists and technologists, will host a series of activations with blockchain as the inspirational jumping-off point.

In what is expected to become one of North America’s most talked-about exhibitions of the year, Melbourne artist Patricia Piccinini’s Curious Imaginings will see the intersection of art, science, and ethics. For the first time in the Biennale’s fifteen years of creating transformative experiences, and in keeping with the 2018-2020 theme of “re-IMAGE-n,” the Biennale will explore art in unexpected places by exhibiting in unconventional interior spaces.  The hyperrealist “world of oddly captivating, somewhat grotesque, human-animal hybrid creatures” will be the artist’s first exhibit in a non-museum setting, transforming a wing of the 105-year-old Patricia Hotel. Situated in Vancouver’s oldest neighbourbood of Strathcona, Piccinini’s interactive experience will “challenge us to explore the social impacts of emerging bio-technology and our ethical limits in an age where genetic engineering and digital technologies are already pushing the boundaries of humanity.” In this intimate hotel setting located in a neighborhood continually undergoing its own change, Curious Imaginings will empower visitors to personally consider questions posed by the exhibition, including the promises and consequences of genetic research and human interference. …

There are other pieces being presented at the Biennale but my special interest is in the art/sci pieces and, at this point, CRISPR.

Piccinini in more depth

You can find out more about Patricia Piccinini in her biography on the Vancouver Biennale website but I found this Char Larsson April 7, 2018 article for the Independent (UK) more informative (Note: A link has been removed),

Patricia Piccinini’s sculptures are deeply disquieting. Walking through Curious Affection, her new solo exhibition at Brisbane’s Gallery of Modern Art, is akin to entering a science laboratory full of DNA experiments. Made from silicone, fibreglass and even human hair, her sculptures are breathtakingly lifelike, however, we can’t be sure what life they are like. The artist creates an exuberant parallel universe where transgenic experiments flourish and human evolution has given way to genetic engineering and DNA splicing.

Curious Affection is a timely and welcome recognition of Piccinini’s enormous contribution to reaching back to the mid-1990s. Working across a variety of mediums including photography, video and drawing, she is perhaps best known for her hyperreal creations.

As a genre, hyperrealism depends on the skill of the artist to create the illusion of reality. To be truly successful, it must convince the spectator of its realness. Piccinini acknowledges this demand, but with a delightful twist. The excruciating attention to detail deliberately solicits our desire to look, only to generate unease, as her sculptures are imbued with a fascinating otherness. Part human, part animal, the works are uncannily familiar, but also alarmingly “other”.

Inspired by advances in genetically modified pigs to generate replacement organs for humans [also known as xenotransplantation], we are reminded that Piccinini has always been at the forefront of debates concerning the possibilities of science, technology and DNA cloning. She does so, however, with a warm affection and sense of humour, eschewing the hysterical anxiety frequently accompanying these scientific developments.

Beyond the astonishing level of detail achieved by working with silicon and fibreglass, there is an ethics at work here. Piccinini is asking us not to avert our gaze from the other, and in doing so, to develop empathy and understanding through the encounter.

I encourage anyone who’s interested to read Larsson’s entire piece (April 7, 2018 article).

According to her Wikipedia entry, Piccinini works in a variety of media including video, sound, sculpture, and more. She also has her own website.

Gene editing and xenotransplantation

Sarah Zhang’s June 8, 2018 article for The Atlantic provides a peek at the extraordinary degree of interest and competition in the field of gene editing and CRISPR ((clustered regularly interspaced short palindromic repeats))/Cas9 research (Note: A link has been removed),

China Is Genetically Engineering Monkeys With Brain Disorders

Guoping Feng applied to college the first year that Chinese universities reopened after the Cultural Revolution. It was 1977, and more than a decade’s worth of students—5.7 million—sat for the entrance exams. Feng was the only one in his high school to get in. He was assigned—by chance, essentially—to medical school. Like most of his contemporaries with scientific ambitions, he soon set his sights on graduate studies in the United States. “China was really like 30 to 50 years behind,” he says. “There was no way to do cutting-edge research.” So in 1989, he left for Buffalo, New York, where for the first time he saw snow piled several feet high. He completed his Ph.D. in genetics at the State University of New York at Buffalo.

Feng is short and slim, with a monk-like placidity and a quick smile, and he now holds an endowed chair in neuroscience at MIT, where he focuses on the genetics of brain disorders. His 45-person lab is part of the McGovern Institute for Brain Research, which was established in 2000 with the promise of a $350 million donation, the largest ever received by the university. In short, his lab does not lack for much.

Yet Feng now travels to China several times a year, because there, he can pursue research he has not yet been able to carry out in the United States. [emphasis mine] …

Feng had organized a symposium at SIAT [Shenzhen Institutes of Advanced Technology], and he was not the only scientist who traveled all the way from the United States to attend: He invited several colleagues as symposium speakers, including a fellow MIT neuroscientist interested in tree shrews, a tiny mammal related to primates and native to southern China, and Chinese-born neuroscientists who study addiction at the University of Pittsburgh and SUNY Upstate Medical University. Like Feng, they had left China in the ’80s and ’90s, part of a wave of young scientists in search of better opportunities abroad. Also like Feng, they were back in China to pursue a type of cutting-edge research too expensive and too impractical—and maybe too ethically sensitive—in the United States.

Here’s what precipitated Feng’s work in China, (from Zhang’s article; Note: Links have been removed)

At MIT, Feng’s lab worked on genetically engineering a monkey species called marmosets, which are very small and genuinely bizarre-looking. They are cheaper to keep due to their size, but they are a relatively new lab animal, and they can be difficult to train on lab tasks. For this reason, Feng also wanted to study Shank3 on macaques in China. Scientists have been cataloging the social behavior of macaques for decades, making it an obvious model for studies of disorders like autism that have a strong social component. Macaques are also more closely related to humans than marmosets, making their brains a better stand-in for those of humans.

The process of genetically engineering a macaque is not trivial, even with the advanced tools of CRISPR. Researchers begin by dosing female monkeys with the same hormones used in human in vitro fertilization. They then collect and fertilize the eggs, and inject the resulting embryos with CRISPR proteins using a long, thin glass needle. Monkey embryos are far more sensitive than mice embryos, and can be affected by small changes in the pH of the injection or the concentration of CRISPR proteins. Only some of the embryos will have the desired mutation, and only some will survive once implanted in surrogate mothers. It takes dozens of eggs to get to just one live monkey, so making even a few knockout monkeys required the support of a large breeding colony.

The first Shank3 macaque was born in 2015. Four more soon followed, bringing the total to five.

To visit his research animals, Feng now has to fly 8,000 miles across 12 time zones. It would be a lot more convenient to carry out his macaque research in the United States, of course, but so far, he has not been able to.

He originally inquired about making Shank3 macaques at the New England Primate Research Center, one of eight national primate research centers then funded by the National Institutes of Health in partnership with a local institution (Harvard Medical School, in this case). The center was conveniently located in Southborough, Massachusetts, just 20 miles west of the MIT campus. But in 2013, Harvard decided to shutter the center.

The decision came as a shock to the research community, and it was widely interpreted as a sign of waning interest in primate research in the United States. While the national primate centers have been important hubs of research on HIV, Zika, Ebola, and other diseases, they have also come under intense public scrutiny. Animal-rights groups like the Humane Society of the United States have sent investigators to work undercover in the labs, and the media has reported on monkey deaths in grisly detail. Harvard officially made its decision to close for “financial” reasons. But the announcement also came after the high-profile deaths of four monkeys from improper handling between 2010 and 2012. The deaths sparked a backlash; demonstrators showed up at the gates. The university gave itself two years to wind down their primate work, officially closing the center in 2015.

“They screwed themselves,” Michael Halassa, the MIT neuroscientist who spoke at Feng’s symposium, told me in Shenzhen. Wei-Dong Yao, another one of the speakers, chimed in, noting that just two years later CRISPR has created a new wave of interest in primate research. Yao was one of the researchers at Harvard’s primate center before it closed; he now runs a lab at SUNY Upstate Medical University that uses genetically engineered mouse and human stem cells, and he had come to Shenzhen to talk about restarting his addiction research on primates.

Here’s comes the competition (from Zhang’s article; Note: Links have been removed),

While the U.S. government’s biomedical research budget has been largely flat, both national and local governments in China are eager to raise their international scientific profiles, and they are shoveling money into research. A long-rumored, government-sponsored China Brain Project is supposed to give neuroscience research, and primate models in particular, a big funding boost. Chinese scientists may command larger salaries, too: Thanks to funding from the Shenzhen local government, a new principal investigator returning from overseas can get 3 million yuan—almost half a million U.S. dollars—over his or her first five years. China is even finding success in attracting foreign researchers from top U.S. institutions like Yale.

In the past few years, China has seen a miniature explosion of genetic engineering in monkeys. In Kunming, Shanghai, and Guangzhou, scientists have created monkeys engineered to show signs of Parkinson’s, Duchenne muscular dystrophy, autism, and more. And Feng’s group is not even the only one in China to have created Shank3 monkeys. Another group—a collaboration primarily between researchers at Emory University and scientists in China—has done the same.

Chinese scientists’ enthusiasm for CRISPR also extends to studies of humans, which are moving much more quickly, and in some cases under less oversight, than in the West. The first studies to edit human embryos and first clinical trials for cancer therapies using CRISPR have all happened in China. [emphases mine]

Some ethical issues are also covered (from Zhang’s article),

Parents with severely epileptic children had asked him if it would be possible to study the condition in a monkey. Feng told them what he thought would be technically possible. “But I also said, ‘I’m not sure I want to generate a model like this,’” he recalled. Maybe if there were a drug to control the monkeys’ seizures, he said: “I cannot see them seizure all the time.”

But is it ethical, he continued, to let these babies die without doing anything? Is it ethical to generate thousands or millions of mutant mice for studies of brain disorders, even when you know they will not elucidate much about human conditions?

Primates should only be used if other models do not work, says Feng, and only if a clear path forward is identified. The first step in his work, he says, is to use the Shank3 monkeys to identify the changes the mutations cause in the brain. Then, researchers might use that information to find targets for drugs, which could be tested in the same monkeys. He’s talking with the Oregon National Primate Research Center about carrying out similar work in the United States. ….[Note: I have a three-part series about CRISPR and germline editing* in the US, precipitated by research coming out of Oregon, Part 1, which links to the other parts, is here.]

Zhang’s June 8, 2018 article is excellent and I highly recommend reading it.

I touched on the topic of xenotransplanttaion in a commentary on a book about the science  of the television series, Orphan Black in a January 31,2018 posting (Note: A chimera is what you use to incubate a ‘human’ organ for transplantation or, more accurately, xenotransplantation),

On the subject of chimeras, the Canadian Broadcasting Corporation (CBC) featured a January 26, 2017 article about the pig-human chimeras on its website along with a video,

The end

I am very excited to see Piccinini’s work come to Vancouver. There have been a number of wonderful art and art/science installations and discussions here but this is the first one (I believe) to tackle the emerging gene editing technologies and the issues they raise. (It also fits in rather nicely with the 200th anniversary of the publication of Mary Shelley’s Frankenstein which continues to raise issues and stimulate discussion.)

In addition to the ethical issues raised in Zhang’s article, there are some other philosophical questions:

  • what does it mean to be human
  • if we are going to edit genes to create hybrid human/animals, what are they and how do they fit into our current animal/human schema
  • are you still human if you’ve had an organ transplant where the organ was incubated in a pig

There are also going to be legal issues. In addition to any questions about legal status, there are also fights about intellectual property such as the one involving Harvard & MIT’s [Massachusetts Institute of Technology] Broad Institute vs the University of California at Berkeley (March 15, 2017 posting)..

While I’m thrilled about the Piccinini installation, it should be noted the issues raised by other artworks hosted in this version of the Biennale are important. Happily, they have been broached here in Vancouver before and I suspect this will result in more nuanced  ‘conversations’ than are possible when a ‘new’ issue is introduced.

Bravo 2018 – 2020 Vancouver Biennale!

* Germline editing is when your gene editing will affect subsequent generations as opposed to editing out a mutated gene for the lifetime of a single individual.

Art/sci and CRISPR links

This art/science posting may prove of some interest:

The connectedness of living things: an art/sci project in Saskatchewan: evolutionary biology (February 16, 2018)

A selection of my CRISPR posts:

CRISPR and editing the germline in the US (part 1 of 3): In the beginning (August 15, 2017)

NOTE: An introductory CRISPR video describing how CRISPR/Cas9 works was embedded in part1.

Why don’t you CRISPR yourself? (January 25, 2018)

Editing the genome with CRISPR ((clustered regularly interspaced short palindromic repeats)-carrying nanoparticles (January 26, 2018)

Immune to CRISPR? (April 10, 2018)

Santiago Ramón y Cajal and the butterflies of the soul

The Cajal exhibit of drawings was here in Vancouver (Canada) this last fall (2017) and I still carry the memory of that glorious experience (see my Sept. 11, 2017 posting for more about the show and associated events). It seems Cajal’s drawings had a similar response in New York city, from a January 18, 2018 article by Roberta Smith for the New York Times,

It’s not often that you look at an exhibition with the help of the very apparatus that is its subject. But so it is with “The Beautiful Brain: The Drawings of Santiago Ramón y Cajal” at the Grey Art Gallery at New York University, one of the most unusual, ravishing exhibitions of the season.

The show finished its run on March 31, 2018 and is now on its way to the Massachusetts Institute of Technology (MIT) in Boston, Massachusetts for its opening on May 3, 2018. It looks like they have an exciting lineup of events to go along with the exhibit (from MIT’s The Beautiful Brain: The Drawings of Santiago Ramón y Cajal exhibit and event page),

SUMMER PROGRAMS

ONGOING

Spotlight Tours
Explorations led by local and Spanish scientists, artists, and entrepreneurs who will share their unique perspectives on particular aspects of the exhibition. (2:00 pm on select Tuesdays and Saturdays)

Tue, May 8 – Mark Harnett, Fred and Carole Middleton Career Development Professor at MIT and McGovern Institute Investigator Sat, May 26 – Marion Boulicault, MIT Graduate Student and Neuroethics Fellow in the Center for Sensorimotor Neural Engineering Tue, June 5 – Kelsey Allen, Graduate researcher, MIT Center for Brains, Minds, and Machines Sat, Jun 23 – Francisco Martin-Martinez, Research Scientist in MIT’s Laboratory for Atomistic & Molecular Mechanics and President of the Spanish Foundation for Science and Technology Jul 21 – Alex Gomez-Marin, Principal Investigator of the Behavior of Organisms Laboratory in the Instituto de Neurociencias, Spain Tue, Jul 31– Julie Pryor, Director of Communications at the McGovern Institute for Brain Research at MIT Tue, Aug 28 – Satrajit Ghosh, Principal Research Scientist at the McGovern Institute for Brain Research at MIT, Assistant Professor in the Department of Otolaryngology at Harvard Medical School, and faculty member in the Speech and Hearing Biosciences and Technology program in the Harvard Division of Medical Sciences

Idea Hub
Drop in and explore expansion microscopy in our maker-space.

Visualizing Science Workshop
Experiential learning with micro-scale biological images. (pre-registration required)

Gallery Demonstrations
Researchers share the latest on neural anatomy, signal transmission, and modern imaging techniques.

EVENTS

Teen Science Café: Mindful Matters
MIT researchers studying the brain share their mind-blowing findings.

Neuron Paint Night
Create a painting of cerebral cortex neurons and learn about the EyeWire citizen science game.

Cerebral Cinema Series
Hear from researchers and then compare real science to depictions on the big screen.

Brainy Trivia
Test your brain power in a night of science trivia and short, snappy research talks.

Come back to see our exciting lineup for the fall!

If you don’t have a chance to see the show or if you’d like a preview, I encourage you to read Smith’s article as it has embedded several Cajal drawings and rendered them exceptionally well.

For those who like a little contemporary (and related) science with their art, there’s a March 30, 2018 Harvard Medical Schoo (HMS)l news release by Kevin Jang (also on EurekAlert), Note: All links save one have been removed,

Drawing of the cells of the chick cerebellum by Santiago Ramón y Cajal, from “Estructura de los centros nerviosos de las aves,” Madrid, circa 1905

 

Modern neuroscience, for all its complexity, can trace its roots directly to a series of pen-and-paper sketches rendered by Nobel laureate Santiago Ramón y Cajal in the late 19th and early 20th centuries.

His observations and drawings exposed the previously hidden composition of the brain, revealing neuronal cell bodies and delicate projections that connect individual neurons together into intricate networks.

As he explored the nervous systems of various organisms under his microscope, a natural question arose: What makes a human brain different from the brain of any other species?

At least part of the answer, Ramón y Cajal hypothesized, lay in a specific class of neuron—one found in a dazzling variety of shapes and patterns of connectivity, and present in higher proportions in the human brain than in the brains of other species. He dubbed them the “butterflies of the soul.”

Known as interneurons, these cells play critical roles in transmitting information between sensory and motor neurons, and, when defective, have been linked to diseases such as schizophrenia, autism and intellectual disability.

Despite more than a century of study, however, it remains unclear why interneurons are so diverse and what specific functions the different subtypes carry out.

Now, in a study published in the March 22 [2018] issue of Nature, researchers from Harvard Medical School, New York Genome Center, New York University and the Broad Institute of MIT and Harvard have detailed for the first time how interneurons emerge and diversify in the brain.

Using single-cell analysis—a technology that allows scientists to track cellular behavior one cell at a time—the team traced the lineage of interneurons from their earliest precursor states to their mature forms in mice. The researchers identified key genetic programs that determine the fate of developing interneurons, as well as when these programs are switched on or off.

The findings serve as a guide for efforts to shed light on interneuron function and may help inform new treatment strategies for disorders involving their dysfunction, the authors said.

“We knew more than 100 years ago that this huge diversity of morphologically interesting cells existed in the brain, but their specific individual roles in brain function are still largely unclear,” said co-senior author Gordon Fishell, HMS professor of neurobiology and a faculty member at the Stanley Center for Psychiatric Research at the Broad.

“Our study provides a road map for understanding how and when distinct interneuron subtypes develop, giving us unprecedented insight into the biology of these cells,” he said. “We can now investigate interneuron properties as they emerge, unlock how these important cells function and perhaps even intervene when they fail to develop correctly in neuropsychiatric disease.”

A hippocampal interneuron. Image: Biosciences Imaging Gp, Soton, Wellcome Trust via Creative CommonsA hippocampal interneuron. Image: Biosciences Imaging Gp, Soton, Wellcome Trust via Creative Commons

Origins and Fates

In collaboration with co-senior author Rahul Satija, core faculty member of the New York Genome Center, Fishell and colleagues analyzed brain regions in developing mice known to contain precursor cells that give rise to interneurons.

Using Drop-seq, a single-cell sequencing technique created by researchers at HMS and the Broad, the team profiled gene expression in thousands of individual cells at multiple time points.

This approach overcomes a major limitation in past research, which could analyze only the average activity of mixtures of many different cells.

In the current study, the team found that the precursor state of all interneurons had similar gene expression patterns despite originating in three separate brain regions and giving rise to 14 or more interneuron subtypes alone—a number still under debate as researchers learn more about these cells.

“Mature interneuron subtypes exhibit incredible diversity. Their morphology and patterns of connectivity and activity are so different from each other, but our results show that the first steps in their maturation are remarkably similar,” said Satija, who is also an assistant professor of biology at New York University.

“They share a common developmental trajectory at the earliest stages, but the seeds of what will cause them to diverge later—a handful of genes—are present from the beginning,” Satija said.

As they profiled cells at later stages in development, the team observed the initial emergence of four interneuron “cardinal” classes, which give rise to distinct fates. Cells were committed to these fates even in the early embryo. By developing a novel computational strategy to link precursors with adult subtypes, the researchers identified individual genes that were switched on and off when cells began to diversify.

For example, they found that the gene Mef2c—mutations of which are linked to Alzheimer’s disease, schizophrenia and neurodevelopmental disorders in humans—is an early embryonic marker for a specific interneuron subtype known as Pvalb neurons. When they deleted Mef2c in animal models, Pvalb neurons failed to develop.

These early genes likely orchestrate the execution of subsequent genetic subroutines, such as ones that guide interneuron subtypes as they migrate to different locations in the brain and ones that help form unique connection patterns with other neural cell types, the authors said.

The identification of these genes and their temporal activity now provide researchers with specific targets to investigate the precise functions of interneurons, as well as how neurons diversify in general, according to the authors.

“One of the goals of this project was to address an incredibly fascinating developmental biology question, which is how individual progenitor cells decide between different neuronal fates,” Satija said. “In addition to these early markers of interneuron divergence, we found numerous additional genes that increase in expression, many dramatically, at later time points.”

The association of some of these genes with neuropsychiatric diseases promises to provide a better understanding of these disorders and the development of therapeutic strategies to treat them, a particularly important notion given the paucity of new treatments, the authors said.

Over the past 50 years, there have been no fundamentally new classes of neuropsychiatric drugs, only newer versions of old drugs, the researchers pointed out.

“Our repertoire is no better than it was in the 1970s,” Fishell said.

“Neuropsychiatric diseases likely reflect the dysfunction of very specific cell types. Our study puts forward a clear picture of what cells to look at as we work to shed light on the mechanisms that underlie these disorders,” Fishell said. “What we will find remains to be seen, but we have new, strong hypotheses that we can now test.”

As a resource for the research community, the study data and software are open-source and freely accessible online.

A gallery of the drawings of Santiago Ramón y Cajal is currently on display in New York City, and will open at the MIT Museum in Boston in May 2018.

Christian Mayer, Christoph Hafemeister and Rachel Bandler served as co-lead authors on the study.

This work was supported by the National Institutes of Health (R01 NS074972, R01 NS081297, MH071679-12, DP2-HG-009623, F30MH114462, T32GM007308, F31NS103398), the European Molecular Biology Organization, the National Science Foundation and the Simons Foundation.

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

Developmental diversification of cortical inhibitory interneurons by Christian Mayer, Christoph Hafemeister, Rachel C. Bandler, Robert Machold, Renata Batista Brito, Xavier Jaglin, Kathryn Allaway, Andrew Butler, Gord Fishell, & Rahul Satija. Nature volume 555, pages 457–462 (22 March 2018) doi:10.1038/nature25999 Published: 05 March 2018

This paper is behind a paywall.

Colliding organic nanoparticles caught on camera for the first time

There is high excitement about this development in a November 17, 2017 news item on Nanowerk,

A Northwestern University research team is the first to capture on video organic nanoparticles colliding and fusing together. This unprecedented view of “chemistry in motion” will aid Northwestern nanoscientists developing new drug delivery methods as well as demonstrate to researchers around the globe how an emerging imaging technique opens a new window on a very tiny world.

A November 17, 2017 Northwestern University news release (also on EurekAlert) by Megan Fellman, which originated the news item, further illuminates the matter,

This is a rare example of particles in motion. The dynamics are reminiscent of two bubbles coming together and merging into one: first they join and have a membrane between them, but then they fuse and become one larger bubble.

“I had an image in my mind, but the first time I saw these fusing nanoparticles in black and white was amazing,” said professor Nathan C. Gianneschi, who led the interdisciplinary study and works at the intersection of nanotechnology and biomedicine.

“To me, it’s literally a window opening up to this world you have always known was there, but now you’ve finally got an image of it. I liken it to the first time I saw Jupiter’s moons through a telescope. Nothing compares to actually seeing,” he said.

Gianneschi is the Jacob and Rosaline Cohn Professor in the department of chemistry in the Weinberg College of Arts and Sciences and in the departments of materials science and engineering and of biomedical engineering in the McCormick School of Engineering.

The study, which includes videos of different nanoparticle fusion events, was published today (Nov. 1 [2017]7) by the Journal of the American Chemical Society.

The research team used liquid-cell transmission electron microscopy to directly image how polymer-based nanoparticles, or micelles, that Gianneschi’s lab is developing for treating cancer and heart attacks change over time. The powerful new technique enabled the scientists to directly observe the particles’ transformation and characterize their dynamics.

“We can see on the molecular level how the polymeric matter rearranges when the particles fuse into one object,” said Lucas R. Parent, first author of the paper and a National Institutes of Health Postdoctoral Fellow in Gianneschi’s research group. “This is the first study of many to come in which researchers will use this method to look at all kinds of dynamic phenomena in organic materials systems on the nanoscale.”

In the Northwestern study, organic particles in water bounce off each other, and some collide and merge, undergoing a physical transformation. The researchers capture the action by shining an electron beam through the sample. The tiny particles — the largest are only approximately 200 nanometers in diameter — cast shadows that are captured directly by a camera below.

“We’ve observed classical fusion behavior on the nanoscale,” said Gianneschi, a member of Northwestern’s International Institute for Nanotechnology. “Capturing the fundamental growth and evolution processes of these particles in motion will help us immensely in our work with synthetic materials and their interactions with biological systems.”

The National Institutes of Health, the National Science Foundation, the Air Force Office of Scientific Research and the Army Research Office supported the research.

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

Directly Observing Micelle Fusion and Growth in Solution by Liquid-Cell Transmission Electron Microscopy by Lucas R. Parent, Evangelos Bakalis, Abelardo Ramírez-Hernández, Jacquelin K. Kammeyer, Chiwoo Park, Juan de Pablo, Francesco Zerbetto, Joseph P. Patterson, and Nathan C. Gianneschi. J. Am. Chem. Soc., Article ASAP DOI: 10.1021/jacs.7b09060 Publication Date (Web): November 17, 2017

Copyright © 2017 American Chemical Society

This paper is behind a paywall.

A bioengineered robot hand with its own nervous system: machine/flesh and a job opening

A November 14, 2017 news item on phys.org announces a grant for a research project which will see engineered robot hands combined with regenerative medicine to imbue neuroprosthetic hands with the sense of touch,

The sense of touch is often taken for granted. For someone without a limb or hand, losing that sense of touch can be devastating. While highly sophisticated prostheses with complex moving fingers and joints are available to mimic almost every hand motion, they remain frustratingly difficult and unnatural for the user. This is largely because they lack the tactile experience that guides every movement. This void in sensation results in limited use or abandonment of these very expensive artificial devices. So why not make a prosthesis that can actually “feel” its environment?

That is exactly what an interdisciplinary team of scientists from Florida Atlantic University and the University of Utah School of Medicine aims to do. They are developing a first-of-its-kind bioengineered robotic hand that will grow and adapt to its environment. This “living” robot will have its own peripheral nervous system directly linking robotic sensors and actuators. FAU’s College of Engineering and Computer Science is leading the multidisciplinary team that has received a four-year, $1.3 million grant from the National Institute of Biomedical Imaging and Bioengineering of the [US] National Institutes of Health for a project titled “Virtual Neuroprosthesis: Restoring Autonomy to People Suffering from Neurotrauma.”

A November14, 2017 Florida Atlantic University (FAU) news release by Gisele Galoustian, which originated the news item, goes into more detail,

With expertise in robotics, bioengineering, behavioral science, nerve regeneration, electrophysiology, microfluidic devices, and orthopedic surgery, the research team is creating a living pathway from the robot’s touch sensation to the user’s brain to help amputees control the robotic hand. A neuroprosthesis platform will enable them to explore how neurons and behavior can work together to regenerate the sensation of touch in an artificial limb.

At the core of this project is a cutting-edge robotic hand and arm developed in the BioRobotics Laboratory in FAU’s College of Engineering and Computer Science. Just like human fingertips, the robotic hand is equipped with numerous sensory receptors that respond to changes in the environment. Controlled by a human, it can sense pressure changes, interpret the information it is receiving and interact with various objects. It adjusts its grip based on an object’s weight or fragility. But the real challenge is figuring out how to send that information back to the brain using living residual neural pathways to replace those that have been damaged or destroyed by trauma.

“When the peripheral nerve is cut or damaged, it uses the rich electrical activity that tactile receptors create to restore itself. We want to examine how the fingertip sensors can help damaged or severed nerves regenerate,” said Erik Engeberg, Ph.D., principal investigator, an associate professor in FAU’s Department of Ocean and Mechanical Engineering, and director of FAU’s BioRobotics Laboratory. “To accomplish this, we are going to directly connect these living nerves in vitro and then electrically stimulate them on a daily basis with sensors from the robotic hand to see how the nerves grow and regenerate while the hand is operated by limb-absent people.”

For the study, the neurons will not be kept in conventional petri dishes. Instead, they will be placed in  biocompatible microfluidic chambers that provide a nurturing environment mimicking the basic function of living cells. Sarah E. Du, Ph.D., co-principal investigator, an assistant professor in FAU’s Department of Ocean and Mechanical Engineering, and an expert in the emerging field of microfluidics, has developed these tiny customized artificial chambers with embedded micro-electrodes. The research team will be able to stimulate the neurons with electrical impulses from the robot’s hand to help regrowth after injury. They will morphologically and electrically measure in real-time how much neural tissue has been restored.

Jianning Wei, Ph.D., co-principal investigator, an associate professor of biomedical science in FAU’s Charles E. Schmidt College of Medicine, and an expert in neural damage and regeneration, will prepare the neurons in vitro, observe them grow and see how they fare and regenerate in the aftermath of injury. This “virtual” method will give the research team multiple opportunities to test and retest the nerves without any harm to subjects.

Using an electroencephalogram (EEG) to detect electrical activity in the brain, Emmanuelle Tognoli, Ph.D., co-principal investigator, associate research professor in FAU’s Center for Complex Systems and Brain Sciences in the Charles E. Schmidt College of Science, and an expert in electrophysiology and neural, behavioral, and cognitive sciences, will examine how the tactile information from the robotic sensors is passed onto the brain to distinguish scenarios with successful or unsuccessful functional restoration of the sense of touch. Her objective: to understand how behavior helps nerve regeneration and how this nerve regeneration helps the behavior.

Once the nerve impulses from the robot’s tactile sensors have gone through the microfluidic chamber, they are sent back to the human user manipulating the robotic hand. This is done with a special device that converts the signals coming from the microfluidic chambers into a controllable pressure at a cuff placed on the remaining portion of the amputated person’s arm. Users will know if they are squeezing the object too hard or if they are losing their grip.

Engeberg also is working with Douglas T. Hutchinson, M.D., co-principal investigator and a professor in the Department of Orthopedics at the University of Utah School of Medicine, who specializes in hand and orthopedic surgery. They are developing a set of tasks and behavioral neural indicators of performance that will ultimately reveal how to promote a healthy sensation of touch in amputees and limb-absent people using robotic devices. The research team also is seeking a post-doctoral researcher with multi-disciplinary experience to work on this breakthrough project.

Here’s more about the job opportunity from the FAU BioRobotics Laboratory job posting, (I checked on January 30, 2018 and it seems applications are still being accepted.)

Post-doctoral Opportunity

Dated Posted: Oct. 13, 2017

The BioRobotics Lab at Florida Atlantic University (FAU) invites applications for a NIH NIBIB-funded Postdoctoral position to develop a Virtual Neuroprosthesis aimed at providing a sense of touch in amputees and limb-absent people.

Candidates should have a Ph.D. in one of the following degrees: mechanical engineering, electrical engineering, biomedical engineering, bioengineering or related, with interest and/or experience in transdisciplinary work at the intersection of robotic hands, biology, and biomedical systems. Prior experience in the neural field will be considered an advantage, though not a necessity. Underrepresented minorities and women are warmly encouraged to apply.

The postdoctoral researcher will be co-advised across the department of Mechanical Engineering and the Center for Complex Systems & Brain Sciences through an interdisciplinary team whose expertise spans Robotics, Microfluidics, Behavioral and Clinical Neuroscience and Orthopedic Surgery.

The position will be for one year with a possibility of extension based on performance. Salary will be commensurate with experience and qualifications. Review of applications will begin immediately and continue until the position is filled.

The application should include:

  1. a cover letter with research interests and experiences,
  2. a CV, and
  3. names and contact information for three professional references.

Qualified candidates can contact Erik Engeberg, Ph.D., Associate Professor, in the FAU Department of Ocean and Mechanical Engineering at eengeberg@fau.edu. Please reference AcademicKeys.com in your cover letter when applying for or inquiring about this job announcement.

You can find the apply button on this page. Good luck!

CRISPR-CAS9 and gold

As so often happens in the sciences, now that the initial euphoria has expended itself problems (and solutions) with CRISPR ((clustered regularly interspaced short palindromic repeats))-CAAS9 are being disclosed to those of us who are not experts. From an Oct. 3, 2017 article by Bob Yirka for phys.org,

A team of researchers from the University of California and the University of Tokyo has found a way to use the CRISPR gene editing technique that does not rely on a virus for delivery. In their paper published in the journal Nature Biomedical Engineering, the group describes the new technique, how well it works and improvements that need to be made to make it a viable gene editing tool.

CRISPR-Cas9 has been in the news a lot lately because it allows researchers to directly edit genes—either disabling unwanted parts or replacing them altogether. But despite many success stories, the technique still suffers from a major deficit that prevents it from being used as a true medical tool—it sometimes makes mistakes. Those mistakes can cause small or big problems for a host depending on what goes wrong. Prior research has suggested that the majority of mistakes are due to delivery problems, which means that a replacement for the virus part of the technique is required. In this new effort, the researchers report that they have discovered just a such a replacement, and it worked so well that it was able to repair a gene mutation in a Duchenne muscular dystrophy mouse model. The team has named the new technique CRISPR-Gold, because a gold nanoparticle was used to deliver the gene editing molecules instead of a virus.

An Oct. 2, 2017 article by Abby Olena for The Scientist lays out the CRISPR-CAS9 problems the scientists are trying to solve (Note: Links have been removed),

While promising, applications of CRISPR-Cas9 gene editing have so far been limited by the challenges of delivery—namely, how to get all the CRISPR parts to every cell that needs them. In a study published today (October 2) in Nature Biomedical Engineering, researchers have successfully repaired a mutation in the gene for dystrophin in a mouse model of Duchenne muscular dystrophy by injecting a vehicle they call CRISPR-Gold, which contains the Cas9 protein, guide RNA, and donor DNA, all wrapped around a tiny gold ball.

The authors have made “great progress in the gene editing area,” says Tufts University biomedical engineer Qiaobing Xu, who did not participate in the work but penned an accompanying commentary. Because their approach is nonviral, Xu explains, it will minimize the potential off-target effects that result from constant Cas9 activity, which occurs when users deliver the Cas9 template with a viral vector.

Duchenne muscular dystrophy is a degenerative disease of the muscles caused by a lack of the protein dystrophin. In about a third of patients, the gene for dystrophin has small deletions or single base mutations that render it nonfunctional, which makes this gene an excellent candidate for gene editing. Researchers have previously used viral delivery of CRISPR-Cas9 components to delete the mutated exon and achieve clinical improvements in mouse models of the disease.

“In this paper, we were actually able to correct [the gene for] dystrophin back to the wild-type sequence” via homology-directed repair (HDR), coauthor Niren Murthy, a drug delivery researcher at the University of California, Berkeley, tells The Scientist. “The other way of treating this is to do something called exon skipping, which is where you delete some of the exons and you can get dystrophin to be produced, but it’s not [as functional as] the wild-type protein.”

The research team created CRISPR-Gold by covering a central gold nanoparticle with DNA that they modified so it would stick to the particle. This gold-conjugated DNA bound the donor DNA needed for HDR, which the Cas9 protein and guide RNA bound to in turn. They coated the entire complex with a polymer that seems to trigger endocytosis and then facilitate escape of the Cas9 protein, guide RNA, and template DNA from endosomes within cells.

In order to do HDR, “you have to provide the cell [with] the Cas9 enzyme, guide RNA by which you target Cas9 to a particular part of the genome, and a big chunk of DNA, which will be used as a template to edit the mutant sequence to wild-type,” explains coauthor Irina Conboy, who studies tissue repair at the University of California, Berkeley. “They all have to be present at the same time and at the same place, so in our system you have a nanoparticle which simultaneously delivers all of those three key components in their active state.”

Olena’s article carries on to describe how the team created CRISPR-Gold and more.

Additional technical details are available in an Oct. 3, 2017 University of California at Berkeley news release by Brett Israel (also on EurekAlert), which originated the news item (Note: A link has been removed) ,

Scientists at the University of California, Berkeley, have engineered a new way to deliver CRISPR-Cas9 gene-editing technology inside cells and have demonstrated in mice that the technology can repair the mutation that causes Duchenne muscular dystrophy, a severe muscle-wasting disease. A new study shows that a single injection of CRISPR-Gold, as the new delivery system is called, into mice with Duchenne muscular dystrophy led to an 18-times-higher correction rate and a two-fold increase in a strength and agility test compared to control groups.

Diagram of CRISPR-Gold

CRISPR–Gold is composed of 15 nanometer gold nanoparticles that are conjugated to thiol-modified oligonucleotides (DNA-Thiol), which are hybridized with single-stranded donor DNA and subsequently complexed with Cas9 and encapsulated by a polymer that disrupts the endosome of the cell.

Since 2012, when study co-author Jennifer Doudna, a professor of molecular and cell biology and of chemistry at UC Berkeley, and colleague Emmanuelle Charpentier, of the Max Planck Institute for Infection Biology, repurposed the Cas9 protein to create a cheap, precise and easy-to-use gene editor, researchers have hoped that therapies based on CRISPR-Cas9 would one day revolutionize the treatment of genetic diseases. Yet developing treatments for genetic diseases remains a big challenge in medicine. This is because most genetic diseases can be cured only if the disease-causing gene mutation is corrected back to the normal sequence, and this is impossible to do with conventional therapeutics.

CRISPR/Cas9, however, can correct gene mutations by cutting the mutated DNA and triggering homology-directed DNA repair. However, strategies for safely delivering the necessary components (Cas9, guide RNA that directs Cas9 to a specific gene, and donor DNA) into cells need to be developed before the potential of CRISPR-Cas9-based therapeutics can be realized. A common technique to deliver CRISPR-Cas9 into cells employs viruses, but that technique has a number of complications. CRISPR-Gold does not need viruses.

In the new study, research lead by the laboratories of Berkeley bioengineering professors Niren Murthy and Irina Conboy demonstrated that their novel approach, called CRISPR-Gold because gold nanoparticles are a key component, can deliver Cas9 – the protein that binds and cuts DNA – along with guide RNA and donor DNA into the cells of a living organism to fix a gene mutation.

“CRISPR-Gold is the first example of a delivery vehicle that can deliver all of the CRISPR components needed to correct gene mutations, without the use of viruses,” Murthy said.

The study was published October 2 [2017] in the journal Nature Biomedical Engineering.

CRISPR-Gold repairs DNA mutations through a process called homology-directed repair. Scientists have struggled to develop homology-directed repair-based therapeutics because they require activity at the same place and time as Cas9 protein, an RNA guide that recognizes the mutation and donor DNA to correct the mutation.

To overcome these challenges, the Berkeley scientists invented a delivery vessel that binds all of these components together, and then releases them when the vessel is inside a wide variety of cell types, triggering homology directed repair. CRISPR-Gold’s gold nanoparticles coat the donor DNA and also bind Cas9. When injected into mice, their cells recognize a marker in CRISPR-Gold and then import the delivery vessel. Then, through a series of cellular mechanisms, CRISPR-Gold is released into the cells’ cytoplasm and breaks apart, rapidly releasing Cas9 and donor DNA.

Schematic of CRISPR-Gold's method of action

CRISPR-Gold’s method of action (Click to enlarge).

A single injection of CRISPR-Gold into muscle tissue of mice that model Duchenne muscular dystrophy restored 5.4 percent of the dystrophin gene, which causes the disease, to the wild- type, or normal, sequence. This correction rate was approximately 18 times higher than in mice treated with Cas9 and donor DNA by themselves, which experienced only a 0.3 percent correction rate.

Importantly, the study authors note, CRISPR-Gold faithfully restored the normal sequence of dystrophin, which is a significant improvement over previously published approaches that only removed the faulty part of the gene, making it shorter and converting one disease into another, milder disease.

CRISPR-Gold was also able to reduce tissue fibrosis – the hallmark of diseases where muscles do not function properly – and enhanced strength and agility in mice with Duchenne muscular dystrophy. CRISPR-Gold-treated mice showed a two-fold increase in hanging time in a common test for mouse strength and agility, compared to mice injected with a control.

“These experiments suggest that it will be possible to develop non-viral CRISPR therapeutics that can safely correct gene mutations, via the process of homology-directed repair, by simply developing nanoparticles that can simultaneously encapsulate all of the CRISPR components,” Murthy said.

CRISPR-Cas9

CRISPR in action: A model of the Cas9 protein cutting a double-stranded piece of DNA

The study found that CRISPR-Gold’s approach to Cas9 protein delivery is safer than viral delivery of CRISPR, which, in addition to toxicity, amplifies the side effects of Cas9 through continuous expression of this DNA-cutting enzyme. When the research team tested CRISPR-Gold’s gene-editing capability in mice, they found that CRISPR-Gold efficiently corrected the DNA mutation that causes Duchenne muscular dystrophy, with minimal collateral DNA damage.

The researchers quantified CRISPR-Gold’s off-target DNA damage and found damage levels similar to the that of a typical DNA sequencing error in a typical cell that was not exposed to CRISPR (0.005 – 0.2 percent). To test for possible immunogenicity, the blood stream cytokine profiles of mice were analyzed at 24 hours and two weeks after the CRISPR-Gold injection. CRISPR-Gold did not cause an acute up-regulation of inflammatory cytokines in plasma, after multiple injections, or weight loss, suggesting that CRISPR-Gold can be used multiple times safely, and that it has a high therapeutic window for gene editing in muscle tissue.

“CRISPR-Gold and, more broadly, CRISPR-nanoparticles open a new way for safer, accurately controlled delivery of gene-editing tools,” Conboy said. “Ultimately, these techniques could be developed into a new medicine for Duchenne muscular dystrophy and a number of other genetic diseases.”

A clinical trial will be needed to discern whether CRISPR-Gold is an effective treatment for genetic diseases in humans. Study co-authors Kunwoo Lee and Hyo Min Park have formed a start-up company, GenEdit (Murthy has an ownership stake in GenEdit), which is focused on translating the CRISPR-Gold technology into humans. The labs of Murthy and Conboy are also working on the next generation of particles that can deliver CRISPR into tissues from the blood stream and would preferentially target adult stem cells, which are considered the best targets for gene correction because stem and progenitor cells are capable of gene editing, self-renewal and differentiation.

“Genetic diseases cause devastating levels of mortality and morbidity, and new strategies for treating them are greatly needed,” Murthy said. “CRISPR-Gold was able to correct disease-causing gene mutations in vivo, via the non-viral delivery of Cas9 protein, guide RNA and donor DNA, and therefore has the potential to develop into a therapeutic for treating genetic diseases.”

The study was funded by the National Institutes of Health, the W.M. Keck Foundation, the Moore Foundation, the Li Ka Shing Foundation, Calico, Packer, Roger’s and SENS, and the Center of Innovation (COI) Program of the Japan Science and Technology Agency.

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

Nanoparticle delivery of Cas9 ribonucleoprotein and donor DNA in vivo induces homology-directed DNA repair by Kunwoo Lee, Michael Conboy, Hyo Min Park, Fuguo Jiang, Hyun Jin Kim, Mark A. Dewitt, Vanessa A. Mackley, Kevin Chang, Anirudh Rao, Colin Skinner, Tamanna Shobha, Melod Mehdipour, Hui Liu, Wen-chin Huang, Freeman Lan, Nicolas L. Bray, Song Li, Jacob E. Corn, Kazunori Kataoka, Jennifer A. Doudna, Irina Conboy, & Niren Murthy. Nature Biomedical Engineering (2017) doi:10.1038/s41551-017-0137-2 Published online: 02 October 2017

This paper is behind a paywall.

Melting body fat with a microneedle patch

For many people this may seem like a dream come true but there is a proviso. So far researchers have gotten to the in vivo testing (mice)  with no word about human clinical trials, which means it could be quite a while, assuming human clinical trials go well, before any product comes to market. With that in mind, here’s more from a Sept.15, 2017 news item on Nanowerk,

Researchers have devised a medicated skin patch that can turn energy-storing white fat into energy-burning brown fat locally while raising the body’s overall metabolism. The patch could be used to burn off pockets of unwanted fat such as “love handles” and treat metabolic disorders like obesity and diabetes, according to researchers at Columbia University Medical Center (CUMC) and the University of North Carolina.

A Sept. 15, 2017 Columbia University Medical Center news release on EurekAlert, which originated the news item, describes the research further,

Humans have two types of fat. White fat stores excess energy in large triglyceride droplets. Brown fat has smaller droplets and a high number of mitochondria that burn fat to produce heat. Newborns have a relative abundance of brown fat, which protects against exposure to cold temperatures. But by adulthood, most brown fat is lost.

For years, researchers have been searching for therapies that can transform an adult’s white fat into brown fat–a process named browning–which can happen naturally when the body is exposed to cold temperatures–as a treatment for obesity and diabetes.

“There are several clinically available drugs that promote browning, but all must be given as pills or injections,” said study co-leader Li Qiang, PhD, assistant professor of pathology and cell biology at CUMC. “This exposes the whole body to the drugs, which can lead to side effects such as stomach upset, weight gain, and bone fractures. Our skin patch appears to alleviate these complications by delivering most drugs directly to fat tissue.”

To apply the treatment, the drugs are first encased in nanoparticles, each roughly 250 nanometers (nm) in diameter–too small to be seen by the naked eye. (In comparison, a human hair is about 100,000 nm wide.) The nanoparticles are then loaded into a centimeter-square skin patch containing dozens of microscopic needles. When applied to skin, the needles painlessly pierce the skin and gradually release the drug from nanoparticles into underlying tissue.

“The nanoparticles were designed to effectively hold the drug and then gradually collapse, releasing it into nearby tissue in a sustained way instead of spreading the drug throughout the body quickly,” said patch designer and study co-leader Zhen Gu, PhD, associate professor of joint biomedical engineering at the University of North Carolina at Chapel Hill and North Carolina State University.

The new treatment approach was tested in obese mice by loading the nanoparticles with one of two compounds known to promote browning: rosiglitazone (Avandia) or beta-adrenergic receptor agonist (CL 316243) that works well in mice but not in humans. Each mouse was given two patches–one loaded with drug-containing nanoparticles and another without drug–that were placed on either side of the lower abdomen. New patches were applied every three days for a total of four weeks. Control mice were also given two empty patches.

Mice treated with either of the two drugs had a 20 percent reduction in fat on the treated side compared to the untreated side. They also had significantly lower fasting blood glucose levels than untreated mice.

Tests in normal, lean mice revealed that treatment with either of the two drugs increased the animals’ oxygen consumption (a measure of overall metabolic activity) by about 20 percent compared to untreated controls.

Genetic analyses revealed that the treated side contained more genes associated with brown fat than on the untreated side, suggesting that the observed metabolic changes and fat reduction were due to an increase in browning in the treated mice.

“Many people will no doubt be excited to learn that we may be able to offer a noninvasive alternative to liposuction for reducing love handles,” says Dr. Qiang. “What’s much more important is that our patch may provide a safe and effective means of treating obesity and related metabolic disorders such as diabetes.” [emphasis mine]

The patch has not been tested in humans. The researchers are currently studying which drugs, or combination of drugs, work best to promote localized browning and increase overall metabolism.

The study was supported by grants from the North Carolina Translational and Clinical Sciences Institute and the National Institutes of Health (1UL1TR001111, R00DK97455, and P30DK063608).

Notice the emphasis on health and that the funding does not seem to be from industry (the National Institutes of Health is definitely a federal US agency but I’m not familiar with the North Carolina Translational and Clinical Sciences Institute).

Getting back to the research, here’s an animation featuring the work,

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

Locally Induced Adipose Tissue Browning by Microneedle Patch for Obesity Treatment by Yuqi Zhang†, Qiongming Liu, Jicheng Yu†, Shuangjiang Yu, Jinqiang Wang, Li Qiang, and Zhen Gu. ACS Nano, Article ASAP DOI: 10.1021/acsnano.7b04348 Publication Date (Web): September 15, 2017

Copyright © 2017 American Chemical Society

This paper is behind a paywall.

I would imagine that Qiang and his colleagues will find a number of business entities will be lining up to fund their work. While the researchers may be focused primarily on health issues, I imagine business types will be seeing dollar signs (very big ones with many zeroes).

The US White House and its Office of Science and Technology Policy (OSTP)

It’s been a while since I first wrote this but I believe this situation has not changed.

There’s some consternation regarding the US Office of Science and Technology Policy’s (OSTP) diminishing size and lack of leadership. From a July 3, 2017 article by Bob Grant for The Scientist (Note: Links have been removed),

Three OSTP staffers did leave last week, but it was because their prearranged tenures at the office had expired, according to an administration official familiar with the situation. “I saw that there were some tweets and what-not saying that it’s zero,” the official tells The Scientist. “That is not true. We have plenty of PhDs that are still on staff that are working on science. All of the work that was being done by the three who left on Friday had been transitioned to other staffers.”

At least one of the tweets that the official is referring to came from Eleanor Celeste, who announced leaving OSTP, where she was the assistant director for biomedical and forensic sciences. “science division out. mic drop,” she tweeted on Friday afternoon.

The administration official concedes that the OSTP is currently in a state of “constant flux” and at a “weird transition period” at the moment, and expects change to continue. “I’m sure that the office will look even more different in three months than it does today, than it did six months ago,” the official says.

Jeffrey Mervis in two articles for Science Magazine is able to provide more detail. From his July 11, 2017 article,

OSTP now has 35 staffers, says an administration official who declined to be named because they weren’t authorized to speak to the media. Holdren [John Holdren], who in January [2017] returned to Harvard University, says the plunge in staff levels is normal during a presidential transition. “But what’s shocking is that, this far into the new administration, the numbers haven’t gone back up.”

The office’s only political appointee is Michael Kratsios, a former aide to Trump confidant and Silicon Valley billionaire Peter Thiel. Kratsios is serving as OSTP’s deputy chief technology officer and de facto OSTP head. Eight new detailees have arrived from other agencies since the inauguration.

Although there has been no formal reorganization of OSTP, a “smaller, more collaborative staff” is now grouped around three areas—science, technology, and national security—according to the Trump aide. Three holdovers from Obama’s OSTP are leading teams focused on specific themes—Lloyd Whitman in technology, Chris Fall in national security, and Deerin Babb-Brott in environment and energy. They report to Kratsios and Ted Wackler, a career civil servant who was Holdren’s deputy chief of staff and who joined OSTP under former President George W. Bush.

“It’s a very flat structure,” says the Trump official, consistent with the administration’s view that “government should be looking for ways to do more with less.” Ultimately, the official adds, “the goal is [for OSTP] to have “probably closer to 50 [people].”

A briefing book prepared by Obama’s outgoing OSTP staff may be a small but telling indication of the office’s current status. The thick, three-ring binder, covering 100 issues, was modeled on one that Holdren received from John “Jack” Marburger, Bush’s OSTP director. “Jack did a fabulous job of laying out what OSTP does, including what reports it owes Congress, so we decided to do likewise,” Holdren says. “But nobody came [from Trump’s transition team] to collect it until a week before the inauguration.”

That person was Reed Cordish, the 43-year-old scion of billionaire real estate developer David Cordish. An English major in college, Reed Cordish was briefly a professional tennis player before joining the family business. He “spent an hour with us and took the book away,” Holdren says. “He told us, ‘This is an important operation and I’ll do my best to see that it flourishes.’ But we don’t know … whether he has the clout to make that happen.”

Cordish is now assistant to the president for intragovernmental and technology initiatives. He works in the new Office of American Innovation led by presidential son-in-law Jared Kushner. That office arranged a recent meeting with high-tech executives, and is also leading yet another White House attempt to “reinvent” government.

Trump has renewed the charter of the National Science and Technology Council, a multiagency group that carries out much of the day-to-day work of advancing the president’s science initiatives. … Still pending is the status of the President’s Council of Advisors on Science and Technology [emphasis mine], a body of eminent scientists and high-tech industry leaders that went out of business at the end of the Obama administration.

Mervis’ July 12, 2017 article is in the form of a Q&A (question and answer) session with the previously mentioned John Holdren, director of the OSTP in Barack Obama’s administration,

Q: Why did you have such a large staff?

A: One reason was to cover the bases. We knew from the start that the Obama administration thought cybersecurity would be an important issue and we needed to be capable in that space. We also knew we needed people who were capable in climate change, in science and technology for economic recovery and job creation and sustained economic growth, and people who knew about advanced manufacturing and nanotechnology and biotechnology.

We also recruited to carry out specific initiatives, like in precision medicine, or combating antibiotic resistance, or the BRAIN [Brain Research through Advancing Innovative Neurotechnologies] initiative. Most of the work will go on in the departments and agencies, but you need someone to oversee it.

The reason we ended up with 135 people at our peak, which was twice the number during its previous peak in the Clinton administration’s second term, was that this president was so interested in knowing what science could do to advance his agenda, on economic recovery, or energy and climate change, or national intelligence. He got it. He didn’t need to be tutored on why science and technology matters.

I feel I’ve been given undue credit for [Obama] being a science geek. It wasn’t me. He came that way. He was constantly asking what we could do to move the needle. When the first flu epidemic, H1N1, came along, the president immediately turned to me and said, “OK, I want [the President’s Council of Advisors on Science and Technology] to look in depth on this, and OSTP, and NIH [National Institutes of Health], and [the Centers for Disease Control and Prevention].” And he told us to coordinate my effort on this stuff—inform me on what can be done and assemble the relevant experts. It was the same with Ebola, with the Macondo oil spill in the Gulf, with Fukushima, where the United States stepped up to work with the Japanese.

It’s not that we had all the expertise. But our job was to reach out to those who did have the relevant expertise.

Q: OSTP now has 35 people. What does that level of staffing say to you?

A: I have to laugh.

Q: Why?

A: When I left, on 19 January [2017], we were down to 30 people. And a substantial fraction of the 30 were people who, in a sense, keep the lights on. They were the OSTP general counsel and deputy counsel, the security officer and deputy, the budget folks, the accounting folks, the executive director of NSTC [National Science and Technology Council].

There are some scientists left, and there are some scientists there still. But on 30 June the last scientist in the science division left.

Somebody said OSTP has shut down. But that’s not quite it. There was no formal decision to shut anything down. But they did not renew the contract of the last remaining science folks in the science division.

I saw somebody say, “Well, we still have some Ph.D.s left.” And that’s undoubtedly true. There are still some science Ph.D.s left in the national security and international affairs division. But because [OSTP] is headless, they have no direct connection to the president and his top advisers.

I don’t want to disparage the top people there. The top people there now are Michael Kratsios, who they named the deputy chief technology officer, and Ted Wackler, who was my deputy chief of staff and who was [former OSTP Director] Jack Marberger’s deputy, and who I kept because he’s a fabulously effective manager. And I believe that they are doing everything they can to make sure that OSTP, at the very least, does the things it has to do. … But right now I think OSTP is just hanging on.

Q: Why did some people choose to stay on?

A: A large portion of OSTP staff are borrowed from other agencies, and because the White House is the White House, we get the people we need. These are dedicated folks who want to get the job done. They want to see science and technology applied to advance the public interest. And they were willing to stay and do their best despite the considerable uncertainty about their future.

But again, most of the detailees, and the reason we went from 135 to 30 almost overnight, is that it’s pretty standard for the detailees to go back to their home agencies and wait for the next administration to decide what set of detailees it wants to advance their objects.

So there’s nothing shocking that most of the detailees went back to their home agencies. The people who stayed are mostly employed directly by OSTP. What’s shocking is that, this far into the new administration, that number hasn’t gone back up. That is, they have only five more people than they had on January 20 [2017].

As I had been wondering about the OSTP and about the President’s Council of Advisors on Science and Technology (PCAST), it was good to get an update.

On a more parochial note, we in Canada are still waiting for an announcement about who our Chief Science Advisor might be.

The Canadian science scene and the 2017 Canadian federal budget

There’s not much happening in the 2017-18 budget in terms of new spending according to Paul Wells’ March 22, 2017 article for TheStar.com,

This is the 22nd or 23rd federal budget I’ve covered. And I’ve never seen the like of the one Bill Morneau introduced on Wednesday [March 22, 2017].

Not even in the last days of the Harper Conservatives did a budget provide for so little new spending — $1.3 billion in the current budget year, total, in all fields of government. That’s a little less than half of one per cent of all federal program spending for this year.

But times are tight. The future is a place where we can dream. So the dollars flow more freely in later years. In 2021-22, the budget’s fifth planning year, new spending peaks at $8.2 billion. Which will be about 2.4 per cent of all program spending.

He’s not alone in this 2017 federal budget analysis; CBC (Canadian Broadcasting Corporation) pundits, Chantal Hébert, Andrew Coyne, and Jennifer Ditchburn said much the same during their ‘At Issue’ segment of the March 22, 2017 broadcast of The National (news).

Before I focus on the science and technology budget, here are some general highlights from the CBC’s March 22, 2017 article on the 2017-18 budget announcement (Note: Links have been removed,

Here are highlights from the 2017 federal budget:

  • Deficit: $28.5 billion, up from $25.4 billion projected in the fall.
  • Trend: Deficits gradually decline over next five years — but still at $18.8 billion in 2021-22.
  • Housing: $11.2 billion over 11 years, already budgeted, will go to a national housing strategy.
  • Child care: $7 billion over 10 years, already budgeted, for new spaces, starting 2018-19.
  • Indigenous: $3.4 billion in new money over five years for infrastructure, health and education.
  • Defence: $8.4 billion in capital spending for equipment pushed forward to 2035.
  • Care givers: New care-giving benefit up to 15 weeks, starting next year.
  • Skills: New agency to research and measure skills development, starting 2018-19.
  • Innovation: $950 million over five years to support business-led “superclusters.”
  • Startups: $400 million over three years for a new venture capital catalyst initiative.
  • AI: $125 million to launch a pan-Canadian Artificial Intelligence Strategy.
  • Coding kids: $50 million over two years for initiatives to teach children to code.
  • Families: Option to extend parental leave up to 18 months.
  • Uber tax: GST to be collected on ride-sharing services.
  • Sin taxes: One cent more on a bottle of wine, five cents on 24 case of beer.
  • Bye-bye: No more Canada Savings Bonds.
  • Transit credit killed: 15 per cent non-refundable public transit tax credit phased out this year.

You can find the entire 2017-18 budget here.

Science and the 2017-18 budget

For anyone interested in the science news, you’ll find most of that in the 2017 budget’s Chapter 1 — Skills, Innovation and Middle Class jobs. As well, Wayne Kondro has written up a précis in his March 22, 2017 article for Science (magazine),

Finance officials, who speak on condition of anonymity during the budget lock-up, indicated the budgets of the granting councils, the main source of operational grants for university researchers, will be “static” until the government can assess recommendations that emerge from an expert panel formed in 2015 and headed by former University of Toronto President David Naylor to review basic science in Canada [highlighted in my June 15, 2016 posting ; $2M has been allocated for the advisor and associated secretariat]. Until then, the officials said, funding for the Natural Sciences and Engineering Research Council of Canada (NSERC) will remain at roughly $848 million, whereas that for the Canadian Institutes of Health Research (CIHR) will remain at $773 million, and for the Social Sciences and Humanities Research Council [SSHRC] at $547 million.

NSERC, though, will receive $8.1 million over 5 years to administer a PromoScience Program that introduces youth, particularly unrepresented groups like Aboriginal people and women, to science, technology, engineering, and mathematics through measures like “space camps and conservation projects.” CIHR, meanwhile, could receive modest amounts from separate plans to identify climate change health risks and to reduce drug and substance abuse, the officials added.

… Canada’s Innovation and Skills Plan, would funnel $600 million over 5 years allocated in 2016, and $112.5 million slated for public transit and green infrastructure, to create Silicon Valley–like “super clusters,” which the budget defined as “dense areas of business activity that contain large and small companies, post-secondary institutions and specialized talent and infrastructure.” …

… The Canadian Institute for Advanced Research will receive $93.7 million [emphasis mine] to “launch a Pan-Canadian Artificial Intelligence Strategy … (to) position Canada as a world-leading destination for companies seeking to invest in artificial intelligence and innovation.”

… Among more specific measures are vows to: Use $87.7 million in previous allocations to the Canada Research Chairs program to create 25 “Canada 150 Research Chairs” honoring the nation’s 150th year of existence, provide $1.5 million per year to support the operations of the office of the as-yet-unappointed national science adviser [see my Dec. 7, 2016 post for information about the job posting, which is now closed]; provide $165.7 million [emphasis mine] over 5 years for the nonprofit organization Mitacs to create roughly 6300 more co-op positions for university students and grads, and provide $60.7 million over five years for new Canadian Space Agency projects, particularly for Canadian participation in the National Aeronautics and Space Administration’s next Mars Orbiter Mission.

Kondros was either reading an earlier version of the budget or made an error regarding Mitacs (from the budget in the “A New, Ambitious Approach to Work-Integrated Learning” subsection),

Mitacs has set an ambitious goal of providing 10,000 work-integrated learning placements for Canadian post-secondary students and graduates each year—up from the current level of around 3,750 placements. Budget 2017 proposes to provide $221 million [emphasis mine] over five years, starting in 2017–18, to achieve this goal and provide relevant work experience to Canadian students.

As well, the budget item for the Pan-Canadian Artificial Intelligence Strategy is $125M.

Moving from Kondros’ précis, the budget (in the “Positioning National Research Council Canada Within the Innovation and Skills Plan” subsection) announces support for these specific areas of science,

Stem Cell Research

The Stem Cell Network, established in 2001, is a national not-for-profit organization that helps translate stem cell research into clinical applications, commercial products and public policy. Its research holds great promise, offering the potential for new therapies and medical treatments for respiratory and heart diseases, cancer, diabetes, spinal cord injury, multiple sclerosis, Crohn’s disease, auto-immune disorders and Parkinson’s disease. To support this important work, Budget 2017 proposes to provide the Stem Cell Network with renewed funding of $6 million in 2018–19.

Space Exploration

Canada has a long and proud history as a space-faring nation. As our international partners prepare to chart new missions, Budget 2017 proposes investments that will underscore Canada’s commitment to innovation and leadership in space. Budget 2017 proposes to provide $80.9 million on a cash basis over five years, starting in 2017–18, for new projects through the Canadian Space Agency that will demonstrate and utilize Canadian innovations in space, including in the field of quantum technology as well as for Mars surface observation. The latter project will enable Canada to join the National Aeronautics and Space Administration’s (NASA’s) next Mars Orbiter Mission.

Quantum Information

The development of new quantum technologies has the potential to transform markets, create new industries and produce leading-edge jobs. The Institute for Quantum Computing is a world-leading Canadian research facility that furthers our understanding of these innovative technologies. Budget 2017 proposes to provide the Institute with renewed funding of $10 million over two years, starting in 2017–18.

Social Innovation

Through community-college partnerships, the Community and College Social Innovation Fund fosters positive social outcomes, such as the integration of vulnerable populations into Canadian communities. Following the success of this pilot program, Budget 2017 proposes to invest $10 million over two years, starting in 2017–18, to continue this work.

International Research Collaborations

The Canadian Institute for Advanced Research (CIFAR) connects Canadian researchers with collaborative research networks led by eminent Canadian and international researchers on topics that touch all humanity. Past collaborations facilitated by CIFAR are credited with fostering Canada’s leadership in artificial intelligence and deep learning. Budget 2017 proposes to provide renewed and enhanced funding of $35 million over five years, starting in 2017–18.

Earlier this week, I highlighted Canada’s strength in the field of regenerative medicine, specifically stem cells in a March 21, 2017 posting. The $6M in the current budget doesn’t look like increased funding but rather a one-year extension. I’m sure they’re happy to receive it  but I imagine it’s a little hard to plan major research projects when you’re not sure how long your funding will last.

As for Canadian leadership in artificial intelligence, that was news to me. Here’s more from the budget,

Canada a Pioneer in Deep Learning in Machines and Brains

CIFAR’s Learning in Machines & Brains program has shaken up the field of artificial intelligence by pioneering a technique called “deep learning,” a computer technique inspired by the human brain and neural networks, which is now routinely used by the likes of Google and Facebook. The program brings together computer scientists, biologists, neuroscientists, psychologists and others, and the result is rich collaborations that have propelled artificial intelligence research forward. The program is co-directed by one of Canada’s foremost experts in artificial intelligence, the Université de Montréal’s Yoshua Bengio, and for his many contributions to the program, the University of Toronto’s Geoffrey Hinton, another Canadian leader in this field, was awarded the title of Distinguished Fellow by CIFAR in 2014.

Meanwhile, from chapter 1 of the budget in the subsection titled “Preparing for the Digital Economy,” there is this provision for children,

Providing educational opportunities for digital skills development to Canadian girls and boys—from kindergarten to grade 12—will give them the head start they need to find and keep good, well-paying, in-demand jobs. To help provide coding and digital skills education to more young Canadians, the Government intends to launch a competitive process through which digital skills training organizations can apply for funding. Budget 2017 proposes to provide $50 million over two years, starting in 2017–18, to support these teaching initiatives.

I wonder if BC Premier Christy Clark is heaving a sigh of relief. At the 2016 #BCTECH Summit, she announced that students in BC would learn to code at school and in newly enhanced coding camp programmes (see my Jan. 19, 2016 posting). Interestingly, there was no mention of additional funding to support her initiative. I guess this money from the federal government comes at a good time as we will have a provincial election later this spring where she can announce the initiative again and, this time, mention there’s money for it.

Attracting brains from afar

Ivan Semeniuk in his March 23, 2017 article (for the Globe and Mail) reads between the lines to analyze the budget’s possible impact on Canadian science,

But a between-the-lines reading of the budget document suggests the government also has another audience in mind: uneasy scientists from the United States and Britain.

The federal government showed its hand at the 2017 #BCTECH Summit. From a March 16, 2017 article by Meera Bains for the CBC news online,

At the B.C. tech summit, Navdeep Bains, Canada’s minister of innovation, said the government will act quickly to fast track work permits to attract highly skilled talent from other countries.

“We’re taking the processing time, which takes months, and reducing it to two weeks for immigration processing for individuals [who] need to come here to help companies grow and scale up,” Bains said.

“So this is a big deal. It’s a game changer.”

That change will happen through the Global Talent Stream, a new program under the federal government’s temporary foreign worker program.  It’s scheduled to begin on June 12, 2017.

U.S. companies are taking notice and a Canadian firm, True North, is offering to help them set up shop.

“What we suggest is that they think about moving their operations, or at least a chunk of their operations, to Vancouver, set up a Canadian subsidiary,” said the company’s founder, Michael Tippett.

“And that subsidiary would be able to house and accommodate those employees.”

Industry experts says while the future is unclear for the tech sector in the U.S., it’s clear high tech in B.C. is gearing up to take advantage.

US business attempts to take advantage of Canada’s relative stability and openness to immigration would seem to be the motive for at least one cross border initiative, the Cascadia Urban Analytics Cooperative. From my Feb. 28, 2017 posting,

There was some big news about the smallest version of the Cascadia region on Thursday, Feb. 23, 2017 when the University of British Columbia (UBC) , the University of Washington (state; UW), and Microsoft announced the launch of the Cascadia Urban Analytics Cooperative. From the joint Feb. 23, 2017 news release (read on the UBC website or read on the UW website),

In an expansion of regional cooperation, the University of British Columbia and the University of Washington today announced the establishment of the Cascadia Urban Analytics Cooperative to use data to help cities and communities address challenges from traffic to homelessness. The largest industry-funded research partnership between UBC and the UW, the collaborative will bring faculty, students and community stakeholders together to solve problems, and is made possible thanks to a $1-million gift from Microsoft.

Today’s announcement follows last September’s [2016] Emerging Cascadia Innovation Corridor Conference in Vancouver, B.C. The forum brought together regional leaders for the first time to identify concrete opportunities for partnerships in education, transportation, university research, human capital and other areas.

A Boston Consulting Group study unveiled at the conference showed the region between Seattle and Vancouver has “high potential to cultivate an innovation corridor” that competes on an international scale, but only if regional leaders work together. The study says that could be possible through sustained collaboration aided by an educated and skilled workforce, a vibrant network of research universities and a dynamic policy environment.

It gets better, it seems Microsoft has been positioning itself for a while if Matt Day’s analysis is correct (from my Feb. 28, 2017 posting),

Matt Day in a Feb. 23, 2017 article for the The Seattle Times provides additional perspective (Note: Links have been removed),

Microsoft’s effort to nudge Seattle and Vancouver, B.C., a bit closer together got an endorsement Thursday [Feb. 23, 2017] from the leading university in each city.

The partnership has its roots in a September [2016] conference in Vancouver organized by Microsoft’s public affairs and lobbying unit [emphasis mine.] That gathering was aimed at tying business, government and educational institutions in Microsoft’s home region in the Seattle area closer to its Canadian neighbor.

Microsoft last year [2016] opened an expanded office in downtown Vancouver with space for 750 employees, an outpost partly designed to draw to the Northwest more engineers than the company can get through the U.S. guest worker system [emphasis mine].

This was all prior to President Trump’s legislative moves in the US, which have at least one Canadian observer a little more gleeful than I’m comfortable with. From a March 21, 2017 article by Susan Lum  for CBC News online,

U.S. President Donald Trump’s efforts to limit travel into his country while simultaneously cutting money from science-based programs provides an opportunity for Canada’s science sector, says a leading Canadian researcher.

“This is Canada’s moment. I think it’s a time we should be bold,” said Alan Bernstein, president of CIFAR [which on March 22, 2017 was awarded $125M to launch the Pan Canada Artificial Intelligence Strategy in the Canadian federal budget announcement], a global research network that funds hundreds of scientists in 16 countries.

Bernstein believes there are many reasons why Canada has become increasingly attractive to scientists around the world, including the political climate in the United States and the Trump administration’s travel bans.

Thankfully, Bernstein calms down a bit,

“It used to be if you were a bright young person anywhere in the world, you would want to go to Harvard or Berkeley or Stanford, or what have you. Now I think you should give pause to that,” he said. “We have pretty good universities here [emphasis mine]. We speak English. We’re a welcoming society for immigrants.”​

Bernstein cautions that Canada should not be seen to be poaching scientists from the United States — but there is an opportunity.

“It’s as if we’ve been in a choir of an opera in the back of the stage and all of a sudden the stars all left the stage. And the audience is expecting us to sing an aria. So we should sing,” Bernstein said.

Bernstein said the federal government, with this week’s so-called innovation budget, can help Canada hit the right notes.

“Innovation is built on fundamental science, so I’m looking to see if the government is willing to support, in a big way, fundamental science in the country.”

Pretty good universities, eh? Thank you, Dr. Bernstein, for keeping some of the boosterism in check. Let’s leave the chest thumping to President Trump and his cronies.

Ivan Semeniuk’s March 23, 2017 article (for the Globe and Mail) provides more details about the situation in the US and in Britain,

Last week, Donald Trump’s first budget request made clear the U.S. President would significantly reduce or entirely eliminate research funding in areas such as climate science and renewable energy if permitted by Congress. Even the National Institutes of Health, which spearheads medical research in the United States and is historically supported across party lines, was unexpectedly targeted for a $6-billion (U.S.) cut that the White House said could be achieved through “efficiencies.”

In Britain, a recent survey found that 42 per cent of academics were considering leaving the country over worries about a less welcoming environment and the loss of research money that a split with the European Union is expected to bring.

In contrast, Canada’s upbeat language about science in the budget makes a not-so-subtle pitch for diversity and talent from abroad, including $117.6-million to establish 25 research chairs with the aim of attracting “top-tier international scholars.”

For good measure, the budget also includes funding for science promotion and $2-million annually for Canada’s yet-to-be-hired Chief Science Advisor, whose duties will include ensuring that government researchers can speak freely about their work.

“What we’ve been hearing over the last few months is that Canada is seen as a beacon, for its openness and for its commitment to science,” said Ms. Duncan [Kirsty Duncan, Minister of Science], who did not refer directly to either the United States or Britain in her comments.

Providing a less optimistic note, Erica Alini in her March 22, 2017 online article for Global News mentions a perennial problem, the Canadian brain drain,

The budget includes a slew of proposed reforms and boosted funding for existing training programs, as well as new skills-development resources for unemployed and underemployed Canadians not covered under current EI-funded programs.

There are initiatives to help women and indigenous people get degrees or training in science, technology, engineering and mathematics (the so-called STEM subjects) and even to teach kids as young as kindergarten-age to code.

But there was no mention of how to make sure Canadians with the right skills remain in Canada, TD’s DePratto {Toronto Dominion Bank} Economics; TD is currently experiencing a scandal {March 13, 2017 Huffington Post news item}] told Global News.

Canada ranks in the middle of the pack compared to other advanced economies when it comes to its share of its graduates in STEM fields, but the U.S. doesn’t shine either, said DePratto [Brian DePratto, senior economist at TD .

The key difference between Canada and the U.S. is the ability to retain domestic talent and attract brains from all over the world, he noted.

To be blunt, there may be some opportunities for Canadian science but it does well to remember (a) US businesses have no particular loyalty to Canada and (b) all it takes is an election to change any perceived advantages to disadvantages.

Digital policy and intellectual property issues

Dubbed by some as the ‘innovation’ budget (official title:  Building a Strong Middle Class), there is an attempt to address a longstanding innovation issue (from a March 22, 2017 posting by Michael Geist on his eponymous blog (Note: Links have been removed),

The release of today’s [march 22, 2017] federal budget is expected to include a significant emphasis on innovation, with the government revealing how it plans to spend (or re-allocate) hundreds of millions of dollars that is intended to support innovation. Canada’s dismal innovation record needs attention, but spending our way to a more innovative economy is unlikely to yield the desired results. While Navdeep Bains, the Innovation, Science and Economic Development Minister, has talked for months about the importance of innovation, Toronto Star columnist Paul Wells today delivers a cutting but accurate assessment of those efforts:

“This government is the first with a minister for innovation! He’s Navdeep Bains. He frequently posts photos of his meetings on Twitter, with the hashtag “#innovation.” That’s how you know there is innovation going on. A year and a half after he became the minister for #innovation, it’s not clear what Bains’s plans are. It’s pretty clear that within the government he has less than complete control over #innovation. There’s an advisory council on economic growth, chaired by the McKinsey guru Dominic Barton, which periodically reports to the government urging more #innovation.

There’s a science advisory panel, chaired by former University of Toronto president David Naylor, that delivered a report to Science Minister Kirsty Duncan more than three months ago. That report has vanished. One presumes that’s because it offered some advice. Whatever Bains proposes, it will have company.”

Wells is right. Bains has been very visible with plenty of meetings and public photo shoots but no obvious innovation policy direction. This represents a missed opportunity since Bains has plenty of policy tools at his disposal that could advance Canada’s innovation framework without focusing on government spending.

For example, Canada’s communications system – wireless and broadband Internet access – falls directly within his portfolio and is crucial for both business and consumers. Yet Bains has been largely missing in action on the file. He gave approval for the Bell – MTS merger that virtually everyone concedes will increase prices in the province and make the communications market less competitive. There are potential policy measures that could bring new competitors into the market (MVNOs [mobile virtual network operators] and municipal broadband) and that could make it easier for consumers to switch providers (ban on unlocking devices). Some of this falls to the CRTC, but government direction and emphasis would make a difference.

Even more troubling has been his near total invisibility on issues relating to new fees or taxes on Internet access and digital services. Canadian Heritage Minister Mélanie Joly has taken control of the issue with the possibility that Canadians could face increased costs for their Internet access or digital services through mandatory fees to contribute to Canadian content.  Leaving aside the policy objections to such an approach (reducing affordable access and the fact that foreign sources now contribute more toward Canadian English language TV production than Canadian broadcasters and distributors), Internet access and e-commerce are supposed to be Bains’ issue and they have a direct connection to the innovation file. How is it possible for the Innovation, Science and Economic Development Minister to have remained silent for months on the issue?

Bains has been largely missing on trade related innovation issues as well. My Globe and Mail column today focuses on a digital-era NAFTA, pointing to likely U.S. demands on data localization, data transfers, e-commerce rules, and net neutrality.  These are all issues that fall under Bains’ portfolio and will impact investment in Canadian networks and digital services. There are innovation opportunities for Canada here, but Bains has been content to leave the policy issues to others, who will be willing to sacrifice potential gains in those areas.

Intellectual property policy is yet another area that falls directly under Bains’ mandate with an obvious link to innovation, but he has done little on the file. Canada won a huge NAFTA victory late last week involving the Canadian patent system, which was challenged by pharmaceutical giant Eli Lilly. Why has Bains not promoted the decision as an affirmation of how Canada’s intellectual property rules?

On the copyright front, the government is scheduled to conduct a review of the Copyright Act later this year, but it is not clear whether Bains will take the lead or again cede responsibility to Joly. The Copyright Act is statutorily under the Industry Minister and reform offers the chance to kickstart innovation. …

For anyone who’s not familiar with this area, innovation is often code for commercialization of science and technology research efforts. These days, digital service and access policies and intellectual property policies are all key to research and innovation efforts.

The country that’s most often (except in mainstream Canadian news media) held up as an example of leadership in innovation is Estonia. The Economist profiled the country in a July 31, 2013 article and a July 7, 2016 article on apolitical.co provides and update.

Conclusions

Science monies for the tri-council science funding agencies (NSERC, SSHRC, and CIHR) are more or less flat but there were a number of line items in the federal budget which qualify as science funding. The $221M over five years for Mitacs, the $125M for the Pan-Canadian Artificial Intelligence Strategy, additional funding for the Canada research chairs, and some of the digital funding could also be included as part of the overall haul. This is in line with the former government’s (Stephen Harper’s Conservatives) penchant for keeping the tri-council’s budgets under control while spreading largesse elsewhere (notably the Perimeter Institute, TRIUMF [Canada’s National Laboratory for Particle and Nuclear Physics], and, in the 2015 budget, $243.5-million towards the Thirty Metre Telescope (TMT) — a massive astronomical observatory to be constructed on the summit of Mauna Kea, Hawaii, a $1.5-billion project). This has lead to some hard feelings in the past with regard to ‘big science’ projects getting what some have felt is an undeserved boost in finances while the ‘small fish’ are left scrabbling for the ever-diminishing (due to budget cuts in years past and inflation) pittances available from the tri-council agencies.

Mitacs, which started life as a federally funded Network Centre for Excellence focused on mathematics, has since shifted focus to become an innovation ‘champion’. You can find Mitacs here and you can find the organization’s March 2016 budget submission to the House of Commons Standing Committee on Finance here. At the time, they did not request a specific amount of money; they just asked for more.

The amount Mitacs expects to receive this year is over $40M which represents more than double what they received from the federal government and almost of 1/2 of their total income in the 2015-16 fiscal year according to their 2015-16 annual report (see p. 327 for the Mitacs Statement of Operations to March 31, 2016). In fact, the federal government forked over $39,900,189. in the 2015-16 fiscal year to be their largest supporter while Mitacs’ total income (receipts) was $81,993,390.

It’s a strange thing but too much money, etc. can be as bad as too little. I wish the folks Mitacs nothing but good luck with their windfall.

I don’t see anything in the budget that encourages innovation and investment from the industrial sector in Canada.

Finallyl, innovation is a cultural issue as much as it is a financial issue and having worked with a number of developers and start-up companies, the most popular business model is to develop a successful business that will be acquired by a large enterprise thereby allowing the entrepreneurs to retire before the age of 30 (or 40 at the latest). I don’t see anything from the government acknowledging the problem let alone any attempts to tackle it.

All in all, it was a decent budget with nothing in it to seriously offend anyone.

Nanoelectronic thread (NET) brain probes for long-term neural recording

A rendering of the ultra-flexible probe in neural tissue gives viewers a sense of the device’s tiny size and footprint in the brain. Image credit: Science Advances.

As long time readers have likely noted, I’m not a big a fan of this rush to ‘colonize’ the brain but it continues apace as a Feb. 15, 2017 news item on Nanowerk announces a new type of brain probe,

Engineering researchers at The University of Texas at Austin have designed ultra-flexible, nanoelectronic thread (NET) brain probes that can achieve more reliable long-term neural recording than existing probes and don’t elicit scar formation when implanted.

A Feb. 15, 2017 University of Texas at Austin news release, which originated the news item, provides more information about the new probes (Note: A link has been removed),

A team led by Chong Xie, an assistant professor in the Department of Biomedical Engineering in the Cockrell School of Engineering, and Lan Luan, a research scientist in the Cockrell School and the College of Natural Sciences, have developed new probes that have mechanical compliances approaching that of the brain tissue and are more than 1,000 times more flexible than other neural probes. This ultra-flexibility leads to an improved ability to reliably record and track the electrical activity of individual neurons for long periods of time. There is a growing interest in developing long-term tracking of individual neurons for neural interface applications, such as extracting neural-control signals for amputees to control high-performance prostheses. It also opens up new possibilities to follow the progression of neurovascular and neurodegenerative diseases such as stroke, Parkinson’s and Alzheimer’s diseases.

One of the problems with conventional probes is their size and mechanical stiffness; their larger dimensions and stiffer structures often cause damage around the tissue they encompass. Additionally, while it is possible for the conventional electrodes to record brain activity for months, they often provide unreliable and degrading recordings. It is also challenging for conventional electrodes to electrophysiologically track individual neurons for more than a few days.

In contrast, the UT Austin team’s electrodes are flexible enough that they comply with the microscale movements of tissue and still stay in place. The probe’s size also drastically reduces the tissue displacement, so the brain interface is more stable, and the readings are more reliable for longer periods of time. To the researchers’ knowledge, the UT Austin probe — which is as small as 10 microns at a thickness below 1 micron, and has a cross-section that is only a fraction of that of a neuron or blood capillary — is the smallest among all neural probes.

“What we did in our research is prove that we can suppress tissue reaction while maintaining a stable recording,” Xie said. “In our case, because the electrodes are very, very flexible, we don’t see any sign of brain damage — neurons stayed alive even in contact with the NET probes, glial cells remained inactive and the vasculature didn’t become leaky.”

In experiments in mouse models, the researchers found that the probe’s flexibility and size prevented the agitation of glial cells, which is the normal biological reaction to a foreign body and leads to scarring and neuronal loss.

“The most surprising part of our work is that the living brain tissue, the biological system, really doesn’t mind having an artificial device around for months,” Luan said.

The researchers also used advanced imaging techniques in collaboration with biomedical engineering professor Andrew Dunn and neuroscientists Raymond Chitwood and Jenni Siegel from the Institute for Neuroscience at UT Austin to confirm that the NET enabled neural interface did not degrade in the mouse model for over four months of experiments. The researchers plan to continue testing their probes in animal models and hope to eventually engage in clinical testing. The research received funding from the UT BRAIN seed grant program, the Department of Defense and National Institutes of Health.

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

Ultraflexible nanoelectronic probes form reliable, glial scar–free neural integration by Lan Luan, Xiaoling Wei, Zhengtuo Zhao, Jennifer J. Siegel, Ojas Potnis, Catherine A Tuppen, Shengqing Lin, Shams Kazmi, Robert A. Fowler, Stewart Holloway, Andrew K. Dunn, Raymond A. Chitwood, and Chong Xie. Science Advances  15 Feb 2017: Vol. 3, no. 2, e1601966 DOI: 10.1126/sciadv.1601966

This paper is open access.

You can get more detail about the research in a Feb. 17, 2017 posting by Dexter Johnson on his Nanoclast blog (on the IEEE [International Institute for Electrical and Electronics Engineers] website).

Hopes for nanocellulose in the fields of medicine and green manufacturing

Initially this seemed like an essay extolling the possibilities for nanocellulose but it is also a research announcement. From a Nov. 7, 2016 news item on Nanowerk,

What if you could take one of the most abundant natural materials on earth and harness its strength to lighten the heaviest of objects, to replace synthetic materials, or use it in scaffolding to grow bone, in a fast-growing area of science in oral health care?

This all might be possible with cellulose nanocrystals, the molecular matter of all plant life. As industrial filler material, they can be blended with plastics and other synthetics. They are as strong as steel, tough as glass, lightweight, and green.

“Plastics are currently reinforced with fillers made of steel, carbon, Kevlar, or glass. There is an increasing demand in manufacturing for sustainable materials that are lightweight and strong to replace these fillers,” said Douglas M. Fox, associate professor of chemistry at American University.
“Cellulose nanocrystals are an environmentally friendly filler. If there comes a time that they’re used widely in manufacturing, cellulose nanocrystals will lessen the weight of materials, which will reduce energy.”

A Nov. 7, 2016 American University news release on EurekAlert, which originated the news item, continues into the research,

Fox has submitted a patent for his work with cellulose nanocrystals, which involves a simple, scalable method to improve their performance. Published results of his method can be found in the chemistry journal ACS Applied Materials and Interfaces. Fox’s method could be used as a biomaterial and for applications in transportation, infrastructure and wind turbines.

The power of cellulose

Cellulose gives stems, leaves and other organic material in the natural world their strength. That strength already has been harnessed for use in many commercial materials. At the nano-level, cellulose fibers can be broken down into tiny crystals, particles smaller than ten millionths of a meter. Deriving cellulose from natural sources such as wood, tunicate (ocean-dwelling sea cucumbers) and certain kinds of bacteria, researchers prepare crystals of different sizes and strengths.

For all of the industry potential, hurdles abound. As nanocellulose disperses within plastic, scientists must find the sweet spot: the right amount of nanoparticle-matrix interaction that yields the strongest, lightest property. Fox overcame four main barriers by altering the surface chemistry of nanocrystals with a simple process of ion exchange. Ion exchange reduces water absorption (cellulose composites lose their strength if they absorb water); increases the temperature at which the nanocrystals decompose (needed to blend with plastics); reduces clumping; and improves re-dispersal after the crystals dry.

Cell growth

Cellulose nanocrystals as a biomaterial is yet another commercial prospect. In dental regenerative medicine, restoring sufficient bone volume is needed to support a patient’s teeth or dental implants. Researchers at the National Institute of Standards and Technology [NIST], through an agreement with the National Institute of Dental and Craniofacial Research of the National Institutes of Health, are looking for an improved clinical approach that would regrow a patient’s bone. When researchers experimented with Fox’s modified nanocrystals, they were able to disperse the nanocrystals in scaffolds for dental regenerative medicine purposes.

“When we cultivated cells on the cellulose nanocrystal-based scaffolds, preliminary results showed remarkable potential of the scaffolds for both their mechanical properties and the biological response. This suggests that scaffolds with appropriate cellulose nanocrystal concentrations are a promising approach for bone regeneration,” said Martin Chiang, team leader for NIST’s Biomaterials for Oral Health Project.

Another collaboration Fox has is with Georgia Institute of Technology and Owens Corning, a company specializing in fiberglass insulation and composites, to research the benefits to replace glass-reinforced plastic used in airplanes, cars and wind turbines. He also is working with Vireo Advisors and NIST to characterize the health and safety of cellulose nanocrystals and nanofibers.

“As we continue to show these nanomaterials are safe, and make it easier to disperse them into a variety of materials, we get closer to utilizing nature’s chemically resistant, strong, and most abundant polymer in everyday products,” Fox said.

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

Simultaneously Tailoring Surface Energies and Thermal Stabilities of Cellulose Nanocrystals Using Ion Exchange: Effects on Polymer Composite Properties for Transportation, Infrastructure, and Renewable Energy Applications by Douglas M. Fox, Rebeca S. Rodriguez, Mackenzie N. Devilbiss, Jeremiah Woodcock, Chelsea S. Davis, Robert Sinko, Sinan Keten, and Jeffrey W. Gilman. ACS Appl. Mater. Interfaces, 2016, 8 (40), pp 27270–27281 DOI: 10.1021/acsami.6b06083 Publication Date (Web): September 14, 2016

Copyright © 2016 American Chemical Society

This paper is behind a paywall.