Tag Archives: University of California at Berkeley

It’s a very ‘carbony’ time: graphene jacket, graphene-skinned airplane, and schwarzite

In August 2018, I been stumbled across several stories about graphene-based products and a new form of carbon.

Graphene jacket

The company producing this jacket has as its goal “… creating bionic clothing that is both bulletproof and intelligent.” Well, ‘bionic‘ means biologically-inspired engineering and ‘intelligent‘ usually means there’s some kind of computing capability in the product. This jacket, which is the first step towards the company’s goal, is not bionic, bulletproof, or intelligent. Nonetheless, it represents a very interesting science experiment in which you, the consumer, are part of step two in the company’s R&D (research and development).

Onto Vollebak’s graphene jacket,

Courtesy: Vollebak

From an August 14, 2018 article by Jesus Diaz for Fast Company,

Graphene is the thinnest possible form of graphite, which you can find in your everyday pencil. It’s purely bi-dimensional, a single layer of carbon atoms that has unbelievable properties that have long threatened to revolutionize everything from aerospace engineering to medicine. …

Despite its immense promise, graphene still hasn’t found much use in consumer products, thanks to the fact that it’s hard to manipulate and manufacture in industrial quantities. The process of developing Vollebak’s jacket, according to the company’s cofounders, brothers Steve and Nick Tidball, took years of intensive research, during which the company worked with the same material scientists who built Michael Phelps’ 2008 Olympic Speedo swimsuit (which was famously banned for shattering records at the event).

The jacket is made out of a two-sided material, which the company invented during the extensive R&D process. The graphene side looks gunmetal gray, while the flipside appears matte black. To create it, the scientists turned raw graphite into something called graphene “nanoplatelets,” which are stacks of graphene that were then blended with polyurethane to create a membrane. That, in turn, is bonded to nylon to form the other side of the material, which Vollebak says alters the properties of the nylon itself. “Adding graphene to the nylon fundamentally changes its mechanical and chemical properties–a nylon fabric that couldn’t naturally conduct heat or energy, for instance, now can,” the company claims.

The company says that it’s reversible so you can enjoy graphene’s properties in different ways as the material interacts with either your skin or the world around you. “As physicists at the Max Planck Institute revealed, graphene challenges the fundamental laws of heat conduction, which means your jacket will not only conduct the heat from your body around itself to equalize your skin temperature and increase it, but the jacket can also theoretically store an unlimited amount of heat, which means it can work like a radiator,” Tidball explains.

He means it literally. You can leave the jacket out in the sun, or on another source of warmth, as it absorbs heat. Then, the company explains on its website, “If you then turn it inside out and wear the graphene next to your skin, it acts like a radiator, retaining its heat and spreading it around your body. The effect can be visibly demonstrated by placing your hand on the fabric, taking it away and then shooting the jacket with a thermal imaging camera. The heat of the handprint stays long after the hand has left.”

There’s a lot more to the article although it does feature some hype and I’m not sure I believe Diaz’s claim (August 14, 2018 article) that ‘graphene-based’ hair dye is perfectly safe ( Note: A link has been removed),

Graphene is the thinnest possible form of graphite, which you can find in your everyday pencil. It’s purely bi-dimensional, a single layer of carbon atoms that has unbelievable properties that will one day revolutionize everything from aerospace engineering to medicine. Its diverse uses are seemingly endless: It can stop a bullet if you add enough layers. It can change the color of your hair with no adverse effects. [emphasis mine] It can turn the walls of your home into a giant fire detector. “It’s so strong and so stretchy that the fibers of a spider web coated in graphene could catch a falling plane,” as Vollebak puts it in its marketing materials.

Not unless things have changed greatly since March 2018. My August 2, 2018 posting featured the graphene-based hair dye announcement from March 2018 and a cautionary note from Dr. Andrew Maynard (scroll down ab out 50% of the way for a longer excerpt of Maynard’s comments),

Northwestern University’s press release proudly announced, “Graphene finds new application as nontoxic, anti-static hair dye.” The announcement spawned headlines like “Enough with the toxic hair dyes. We could use graphene instead,” and “’Miracle material’ graphene used to create the ultimate hair dye.”

From these headlines, you might be forgiven for getting the idea that the safety of graphene-based hair dyes is a done deal. Yet having studied the potential health and environmental impacts of engineered nanomaterials for more years than I care to remember, I find such overly optimistic pronouncements worrying – especially when they’re not backed up by clear evidence.

These studies need to be approached with care, as the precise risks of graphene exposure will depend on how the material is used, how exposure occurs and how much of it is encountered. Yet there’s sufficient evidence to suggest that this substance should be used with caution – especially where there’s a high chance of exposure or that it could be released into the environment.

The full text of Dr. Maynard’s comments about graphene hair dyes and risk can be found here.

Bearing in mind  that graphene-based hair dye is an entirely different class of product from the jacket, I wouldn’t necessarily dismiss risks; I would like to know what kind of risk assessment and safety testing has been done. Due to their understandable enthusiasm, the brothers Tidball have focused all their marketing on the benefits and the opportunity for the consumer to test their product (from graphene jacket product webpage),

While it’s completely invisible and only a single atom thick, graphene is the lightest, strongest, most conductive material ever discovered, and has the same potential to change life on Earth as stone, bronze and iron once did. But it remains difficult to work with, extremely expensive to produce at scale, and lives mostly in pioneering research labs. So following in the footsteps of the scientists who discovered it through their own highly speculative experiments, we’re releasing graphene-coated jackets into the world as experimental prototypes. Our aim is to open up our R&D and accelerate discovery by getting graphene out of the lab and into the field so that we can harness the collective power of early adopters as a test group. No-one yet knows the true limits of what graphene can do, so the first edition of the Graphene Jacket is fully reversible with one side coated in graphene and the other side not. If you’d like to take part in the next stage of this supermaterial’s history, the experiment is now open. You can now buy it, test it and tell us about it. [emphasis mine]

How maverick experiments won the Nobel Prize

While graphene’s existence was first theorised in the 1940s, it wasn’t until 2004 that two maverick scientists, Andre Geim and Konstantin Novoselov, were able to isolate and test it. Through highly speculative and unfunded experimentation known as their ‘Friday night experiments,’ they peeled layer after layer off a shaving of graphite using Scotch tape until they produced a sample of graphene just one atom thick. After similarly leftfield thinking won Geim the 2000 Ig Nobel prize for levitating frogs using magnets, the pair won the Nobel prize in 2010 for the isolation of graphene.

Should you be interested, in beta-testing the jacket, it will cost you $695 (presumably USD); order here. One last thing, Vollebak is based in the UK.

Graphene skinned plane

An August 14, 2018 news item (also published as an August 1, 2018 Haydale press release) by Sue Keighley on Azonano heralds a new technology for airplans,

Haydale, (AIM: HAYD), the global advanced materials group, notes the announcement made yesterday from the University of Central Lancashire (UCLAN) about the recent unveiling of the world’s first graphene skinned plane at the internationally renowned Farnborough air show.

The prepreg material, developed by Haydale, has potential value for fuselage and wing surfaces in larger scale aero and space applications especially for the rapidly expanding drone market and, in the longer term, the commercial aerospace sector. By incorporating functionalised nanoparticles into epoxy resins, the electrical conductivity of fibre-reinforced composites has been significantly improved for lightning-strike protection, thereby achieving substantial weight saving and removing some manufacturing complexities.

Before getting to the photo, here’s a definition for pre-preg from its Wikipedia entry (Note: Links have been removed),

Pre-preg is “pre-impregnated” composite fibers where a thermoset polymer matrix material, such as epoxy, or a thermoplastic resin is already present. The fibers often take the form of a weave and the matrix is used to bond them together and to other components during manufacture.

Haydale has supplied graphene enhanced prepreg material for Juno, a three-metre wide graphene-enhanced composite skinned aircraft, that was revealed as part of the ‘Futures Day’ at Farnborough Air Show 2018. [downloaded from https://www.azonano.com/news.aspx?newsID=36298]

A July 31, 2018 University of Central Lancashire (UCLan) press release provides a tiny bit more (pun intended) detail,

The University of Central Lancashire (UCLan) has unveiled the world’s first graphene skinned plane at an internationally renowned air show.

Juno, a three-and-a-half-metre wide graphene skinned aircraft, was revealed on the North West Aerospace Alliance (NWAA) stand as part of the ‘Futures Day’ at Farnborough Air Show 2018.

The University’s aerospace engineering team has worked in partnership with the Sheffield Advanced Manufacturing Research Centre (AMRC), the University of Manchester’s National Graphene Institute (NGI), Haydale Graphene Industries (Haydale) and a range of other businesses to develop the unmanned aerial vehicle (UAV), which also includes graphene batteries and 3D printed parts.

Billy Beggs, UCLan’s Engineering Innovation Manager, said: “The industry reaction to Juno at Farnborough was superb with many positive comments about the work we’re doing. Having Juno at one the world’s biggest air shows demonstrates the great strides we’re making in leading a programme to accelerate the uptake of graphene and other nano-materials into industry.

“The programme supports the objectives of the UK Industrial Strategy and the University’s Engineering Innovation Centre (EIC) to increase industry relevant research and applications linked to key local specialisms. Given that Lancashire represents the fourth largest aerospace cluster in the world, there is perhaps no better place to be developing next generation technologies for the UK aerospace industry.”

Previous graphene developments at UCLan have included the world’s first flight of a graphene skinned wing and the launch of a specially designed graphene-enhanced capsule into near space using high altitude balloons.

UCLan engineering students have been involved in the hands-on project, helping build Juno on the Preston Campus.

Haydale supplied much of the material and all the graphene used in the aircraft. Ray Gibbs, Chief Executive Officer, said: “We are delighted to be part of the project team. Juno has highlighted the capability and benefit of using graphene to meet key issues faced by the market, such as reducing weight to increase range and payload, defeating lightning strike and protecting aircraft skins against ice build-up.”

David Bailey Chief Executive of the North West Aerospace Alliance added: “The North West aerospace cluster contributes over £7 billion to the UK economy, accounting for one quarter of the UK aerospace turnover. It is essential that the sector continues to develop next generation technologies so that it can help the UK retain its competitive advantage. It has been a pleasure to support the Engineering Innovation Centre team at the University in developing the world’s first full graphene skinned aircraft.”

The Juno project team represents the latest phase in a long-term strategic partnership between the University and a range of organisations. The partnership is expected to go from strength to strength following the opening of the £32m EIC facility in February 2019.

The next step is to fly Juno and conduct further tests over the next two months.

Next item, a new carbon material.

Schwarzite

I love watching this gif of a schwarzite,

The three-dimensional cage structure of a schwarzite that was formed inside the pores of a zeolite. (Graphics by Yongjin Lee and Efrem Braun)

An August 13, 2018 news item on Nanowerk announces the new carbon structure,

The discovery of buckyballs [also known as fullerenes, C60, or buckminsterfullerenes] surprised and delighted chemists in the 1980s, nanotubes jazzed physicists in the 1990s, and graphene charged up materials scientists in the 2000s, but one nanoscale carbon structure – a negatively curved surface called a schwarzite – has eluded everyone. Until now.

University of California, Berkeley [UC Berkeley], chemists have proved that three carbon structures recently created by scientists in South Korea and Japan are in fact the long-sought schwarzites, which researchers predict will have unique electrical and storage properties like those now being discovered in buckminsterfullerenes (buckyballs or fullerenes for short), nanotubes and graphene.

An August 13, 2018 UC Berkeley news release by Robert Sanders, which originated the news item, describes how the Berkeley scientists and the members of their international  collaboration from Germany, Switzerland, Russia, and Italy, have contributed to the current state of schwarzite research,

The new structures were built inside the pores of zeolites, crystalline forms of silicon dioxide – sand – more commonly used as water softeners in laundry detergents and to catalytically crack petroleum into gasoline. Called zeolite-templated carbons (ZTC), the structures were being investigated for possible interesting properties, though the creators were unaware of their identity as schwarzites, which theoretical chemists have worked on for decades.

Based on this theoretical work, chemists predict that schwarzites will have unique electronic, magnetic and optical properties that would make them useful as supercapacitors, battery electrodes and catalysts, and with large internal spaces ideal for gas storage and separation.

UC Berkeley postdoctoral fellow Efrem Braun and his colleagues identified these ZTC materials as schwarzites based of their negative curvature, and developed a way to predict which zeolites can be used to make schwarzites and which can’t.

“We now have the recipe for how to make these structures, which is important because, if we can make them, we can explore their behavior, which we are working hard to do now,” said Berend Smit, an adjunct professor of chemical and biomolecular engineering at UC Berkeley and an expert on porous materials such as zeolites and metal-organic frameworks.

Smit, the paper’s corresponding author, Braun and their colleagues in Switzerland, China, Germany, Italy and Russia will report their discovery this week in the journal Proceedings of the National Academy of Sciences. Smit is also a faculty scientist at Lawrence Berkeley National Laboratory.

Playing with carbon

Diamond and graphite are well-known three-dimensional crystalline arrangements of pure carbon, but carbon atoms can also form two-dimensional “crystals” — hexagonal arrangements patterned like chicken wire. Graphene is one such arrangement: a flat sheet of carbon atoms that is not only the strongest material on Earth, but also has a high electrical conductivity that makes it a promising component of electronic devices.

schwarzite carbon cage

The cage structure of a schwarzite that was formed inside the pores of a zeolite. The zeolite is subsequently dissolved to release the new material. (Graphics by Yongjin Lee and Efrem Braun)

Graphene sheets can be wadded up to form soccer ball-shaped fullerenes – spherical carbon cages that can store molecules and are being used today to deliver drugs and genes into the body. Rolling graphene into a cylinder yields fullerenes called nanotubes, which are being explored today as highly conductive wires in electronics and storage vessels for gases like hydrogen and carbon dioxide. All of these are submicroscopic, 10,000 times smaller than the width of a human hair.

To date, however, only positively curved fullerenes and graphene, which has zero curvature, have been synthesized, feats rewarded by Nobel Prizes in 1996 and 2010, respectively.

In the 1880s, German physicist Hermann Schwarz investigated negatively curved structures that resemble soap-bubble surfaces, and when theoretical work on carbon cage molecules ramped up in the 1990s, Schwarz’s name became attached to the hypothetical negatively curved carbon sheets.

“The experimental validation of schwarzites thus completes the triumvirate of possible curvatures to graphene; positively curved, flat, and now negatively curved,” Braun added.

Minimize me

Like soap bubbles on wire frames, schwarzites are topologically minimal surfaces. When made inside a zeolite, a vapor of carbon-containing molecules is injected, allowing the carbon to assemble into a two-dimensional graphene-like sheet lining the walls of the pores in the zeolite. The surface is stretched tautly to minimize its area, which makes all the surfaces curve negatively, like a saddle. The zeolite is then dissolved, leaving behind the schwarzite.

soap bubble schwarzite structure

A computer-rendered negatively curved soap bubble that exhibits the geometry of a carbon schwarzite. (Felix Knöppel image)

“These negatively-curved carbons have been very hard to synthesize on their own, but it turns out that you can grow the carbon film catalytically at the surface of a zeolite,” Braun said. “But the schwarzites synthesized to date have been made by choosing zeolite templates through trial and error. We provide very simple instructions you can follow to rationally make schwarzites and we show that, by choosing the right zeolite, you can tune schwarzites to optimize the properties you want.”

Researchers should be able to pack unusually large amounts of electrical charge into schwarzites, which would make them better capacitors than conventional ones used today in electronics. Their large interior volume would also allow storage of atoms and molecules, which is also being explored with fullerenes and nanotubes. And their large surface area, equivalent to the surface areas of the zeolites they’re grown in, could make them as versatile as zeolites for catalyzing reactions in the petroleum and natural gas industries.

Braun modeled ZTC structures computationally using the known structures of zeolites, and worked with topological mathematician Senja Barthel of the École Polytechnique Fédérale de Lausanne in Sion, Switzerland, to determine which of the minimal surfaces the structures resembled.

The team determined that, of the approximately 200 zeolites created to date, only 15 can be used as a template to make schwarzites, and only three of them have been used to date to produce schwarzite ZTCs. Over a million zeolite structures have been predicted, however, so there could be many more possible schwarzite carbon structures made using the zeolite-templating method.

Other co-authors of the paper are Yongjin Lee, Seyed Mohamad Moosavi and Barthel of the École Polytechnique Fédérale de Lausanne, Rocio Mercado of UC Berkeley, Igor Baburin of the Technische Universität Dresden in Germany and Davide Proserpio of the Università degli Studi di Milano in Italy and Samara State Technical University in Russia.

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

Generating carbon schwarzites via zeolite-templating by Efrem Braun, Yongjin Lee, Seyed Mohamad Moosavi, Senja Barthel, Rocio Mercado, Igor A. Baburin, Davide M. Proserpio, and Berend Smit. PNAS August 14, 2018. 201805062; published ahead of print August 14, 2018. https://doi.org/10.1073/pnas.1805062115

This paper appears to be open access.

I found it at the movies: a commentary on/review of “Films from the Future”

Kudos to anyone who recognized the reference to Pauline Kael (she changed film criticism forever) and her book “I Lost it at the Movies.” Of course, her book title was a bit of sexual innuendo, quite risqué for an important film critic in 1965 but appropriate for a period (the 1960s) associated with a sexual revolution. (There’s more about the 1960’s sexual revolution in the US along with mention of a prior sexual revolution in the 1920s in this Wikipedia entry.)

The title for this commentary is based on an anecdote from Dr. Andrew Maynard’s (director of the Arizona State University [ASU] Risk Innovation Lab) popular science and technology book, “Films from the Future: The Technology and Morality of Sci-Fi Movies.”

The ‘title-inspiring’ anecdote concerns Maynard’s first viewing of ‘2001: A Space Odyssey, when as a rather “bratty” 16-year-old who preferred to read science fiction, he discovered new ways of seeing and imaging the world. Maynard isn’t explicit about when he became a ‘techno nerd’ or how movies gave him an experience books couldn’t but presumably at 16 he was already gearing up for a career in the sciences. That ‘movie’ revelation received in front of a black and white television on January 1,1982 eventually led him to write, “Films from the Future.” (He has a PhD in physics which he is now applying to the field of risk innovation. For a more detailed description of Dr. Maynard and his work, there’s his ASU profile webpage and, of course, the introduction to his book.)

The book is quite timely. I don’t know how many people have noticed but science and scientific innovation is being covered more frequently in the media than it has been in many years. Science fairs and festivals are being founded on what seems to be a daily basis and you can now find science in art galleries. (Not to mention the movies and television where science topics are covered in comic book adaptations, in comedy, and in standard science fiction style.) Much of this activity is centered on what’s called ’emerging technologies’. These technologies are why people argue for what’s known as ‘blue sky’ or ‘basic’ or ‘fundamental’ science for without that science there would be no emerging technology.

Films from the Future

Isn’t reading the Table of Contents (ToC) the best way to approach a book? (From Films from the Future; Note: The formatting has been altered),

Table of Contents
Chapter One
In the Beginning 14
Beginnings 14
Welcome to the Future 16
The Power of Convergence 18
Socially Responsible Innovation 21
A Common Point of Focus 25
Spoiler Alert 26
Chapter Two
Jurassic Park: The Rise of Resurrection Biology 27
When Dinosaurs Ruled the World 27
De-Extinction 31
Could We, Should We? 36
The Butterfly Effect 39
Visions of Power 43
Chapter Three
Never Let Me Go: A Cautionary Tale of Human Cloning 46
Sins of Futures Past 46
Cloning 51
Genuinely Human? 56
Too Valuable to Fail? 62
Chapter Four
Minority Report: Predicting Criminal Intent 64
Criminal Intent 64
The “Science” of Predicting Bad Behavior 69
Criminal Brain Scans 74
Machine Learning-Based Precognition 77
Big Brother, Meet Big Data 79
Chapter Five
Limitless: Pharmaceutically-enhanced Intelligence 86
A Pill for Everything 86
The Seduction of Self-Enhancement 89
Nootropics 91
If You Could, Would You? 97
Privileged Technology 101
Our Obsession with Intelligence 105
Chapter Six
Elysium: Social Inequity in an Age of Technological
Extremes 110
The Poor Shall Inherit the Earth 110
Bioprinting Our Future Bodies 115
The Disposable Workforce 119
Living in an Automated Future 124
Chapter Seven
Ghost in the Shell: Being Human in an
Augmented Future 129
Through a Glass Darkly 129
Body Hacking 135
More than “Human”? 137
Plugged In, Hacked Out 142
Your Corporate Body 147
Chapter Eight
Ex Machina: AI and the Art of Manipulation 154
Plato’s Cave 154
The Lure of Permissionless Innovation 160
Technologies of Hubris 164
Superintelligence 169
Defining Artificial Intelligence 172
Artificial Manipulation 175
Chapter Nine
Transcendence: Welcome to the Singularity 180
Visions of the Future 180
Technological Convergence 184
Enter the Neo-Luddites 190
Techno-Terrorism 194
Exponential Extrapolation 200
Make-Believe in the Age of the Singularity 203
Chapter Ten
The Man in the White Suit: Living in a Material World 208
There’s Plenty of Room at the Bottom 208
Mastering the Material World 213
Myopically Benevolent Science 220
Never Underestimate the Status Quo 224
It’s Good to Talk 227
Chapter Eleven
Inferno: Immoral Logic in an Age of
Genetic Manipulation 231
Decoding Make-Believe 231
Weaponizing the Genome 234
Immoral Logic? 238
The Honest Broker 242
Dictating the Future 248
Chapter Twelve
The Day After Tomorrow: Riding the Wave of
Climate Change 251
Our Changing Climate 251
Fragile States 255
A Planetary “Microbiome” 258
The Rise of the Anthropocene 260
Building Resiliency 262
Geoengineering the Future 266
Chapter Thirteen
Contact: Living by More than Science Alone 272
An Awful Waste of Space 272
More than Science Alone 277
Occam’s Razor 280
What If We’re Not Alone? 283
Chapter Fourteen
Looking to the Future 288
Acknowledgments 293

The ToC gives the reader a pretty clue as to where the author is going with their book and Maynard explains how he chose his movies in his introductory chapter (from Films from the Future),

“There are some quite wonderful science fiction movies that didn’t make the cut because they didn’t fit the overarching narrative (Blade Runner and its sequel Blade Runner 2049, for instance, and the first of the Matrix trilogy). There are also movies that bombed with the critics, but were included because they ably fill a gap in the bigger story around emerging and converging technologies. Ultimately, the movies that made the cut were chosen because, together, they create an overarching narrative around emerging trends in biotechnologies, cybertechnologies, and materials-based technologies, and they illuminate a broader landscape around our evolving relationship with science and technology. And, to be honest, they are all movies that I get a kick out of watching.” (p. 17)

Jurassic Park (Chapter Two)

Dinosaurs do not interest me—they never have. Despite my profound indifference I did see the movie, Jurassic Park, when it was first released (someone talked me into going). And, I am still profoundly indifferent. Thankfully, Dr. Maynard finds meaning and a connection to current trends in biotechnology,

Jurassic Park is unabashedly a movie about dinosaurs. But it’s also a movie about greed, ambition, genetic engineering, and human folly—all rich pickings for thinking about the future, and what could possibly go wrong. (p. 28)

What really stands out with Jurassic Park, over twenty-five years later, is how it reveals a very human side of science and technology. This comes out in questions around when we should tinker with technology and when we should leave well enough alone. But there is also a narrative here that appears time and time again with the movies in this book, and that is how we get our heads around the sometimes oversized roles mega-entrepreneurs play in dictating how new tech is used, and possibly abused. These are all issues that are just as relevant now as they were in 1993, and are front and center of ensuring that the technologyenabled future we’re building is one where we want to live, and not one where we’re constantly fighting for our lives.  (pp. 30-1)

He also describes a connection to current trends in biotechnology,

De-Extinction

In a far corner of Siberia, two Russians—Sergey Zimov and his son Nikita—are attempting to recreate the Ice Age. More precisely, their vision is to reconstruct the landscape and ecosystem of northern Siberia in the Pleistocene, a period in Earth’s history that stretches from around two and a half million years ago to eleven thousand years ago. This was a time when the environment was much colder than now, with huge glaciers and ice sheets flowing over much of the Earth’s northern hemisphere. It was also a time when humans
coexisted with animals that are long extinct, including saber-tooth cats, giant ground sloths, and woolly mammoths.

The Zimovs’ ambitions are an extreme example of “Pleistocene rewilding,” a movement to reintroduce relatively recently extinct large animals, or their close modern-day equivalents, to regions where they were once common. In the case of the Zimovs, the
father-and-son team believe that, by reconstructing the Pleistocene ecosystem in the Siberian steppes and elsewhere, they can slow down the impacts of climate change on these regions. These areas are dominated by permafrost, ground that never thaws through
the year. Permafrost ecosystems have developed and survived over millennia, but a warming global climate (a theme we’ll come back to in chapter twelve and the movie The Day After Tomorrow) threatens to catastrophically disrupt them, and as this happens, the impacts
on biodiversity could be devastating. But what gets climate scientists even more worried is potentially massive releases of trapped methane as the permafrost disappears.

Methane is a powerful greenhouse gas—some eighty times more effective at exacerbating global warming than carbon dioxide— and large-scale releases from warming permafrost could trigger catastrophic changes in climate. As a result, finding ways to keep it in the ground is important. And here the Zimovs came up with a rather unusual idea: maintaining the stability of the environment by reintroducing long-extinct species that could help prevent its destruction, even in a warmer world. It’s a wild idea, but one that has some merit.8 As a proof of concept, though, the Zimovs needed somewhere to start. And so they set out to create a park for deextinct Siberian animals: Pleistocene Park.9

Pleistocene Park is by no stretch of the imagination a modern-day Jurassic Park. The dinosaurs in Hammond’s park date back to the Mesozoic period, from around 250 million years ago to sixty-five million years ago. By comparison, the Pleistocene is relatively modern history, ending a mere eleven and a half thousand years ago. And the vision behind Pleistocene Park is not thrills, spills, and profit, but the serious use of science and technology to stabilize an increasingly unstable environment. Yet there is one thread that ties them together, and that’s using genetic engineering to reintroduce extinct species. In this case, the species in question is warm-blooded and furry: the woolly mammoth.

The idea of de-extinction, or bringing back species from extinction (it’s even called “resurrection biology” in some circles), has been around for a while. It’s a controversial idea, and it raises a lot of tough ethical questions. But proponents of de-extinction argue
that we’re losing species and ecosystems at such a rate that we can’t afford not to explore technological interventions to help stem the flow.

Early approaches to bringing species back from the dead have involved selective breeding. The idea was simple—if you have modern ancestors of a recently extinct species, selectively breeding specimens that have a higher genetic similarity to their forebears can potentially help reconstruct their genome in living animals. This approach is being used in attempts to bring back the aurochs, an ancestor of modern cattle.10 But it’s slow, and it depends on
the fragmented genome of the extinct species still surviving in its modern-day equivalents.

An alternative to selective breeding is cloning. This involves finding a viable cell, or cell nucleus, in an extinct but well-preserved animal and growing a new living clone from it. It’s definitely a more appealing route for impatient resurrection biologists, but it does mean getting your hands on intact cells from long-dead animals and devising ways to “resurrect” these, which is no mean feat. Cloning has potential when it comes to recently extinct species whose cells have been well preserved—for instance, where the whole animal has become frozen in ice. But it’s still a slow and extremely limited option.

Which is where advances in genetic engineering come in.

The technological premise of Jurassic Park is that scientists can reconstruct the genome of long-dead animals from preserved DNA fragments. It’s a compelling idea, if you think of DNA as a massively long and complex instruction set that tells a group of biological molecules how to build an animal. In principle, if we could reconstruct the genome of an extinct species, we would have the basic instruction set—the biological software—to reconstruct
individual members of it.

The bad news is that DNA-reconstruction-based de-extinction is far more complex than this. First you need intact fragments of DNA, which is not easy, as DNA degrades easily (and is pretty much impossible to obtain, as far as we know, for dinosaurs). Then you
need to be able to stitch all of your fragments together, which is akin to completing a billion-piece jigsaw puzzle without knowing what the final picture looks like. This is a Herculean task, although with breakthroughs in data manipulation and machine learning,
scientists are getting better at it. But even when you have your reconstructed genome, you need the biological “wetware”—all the stuff that’s needed to create, incubate, and nurture a new living thing, like eggs, nutrients, a safe space to grow and mature, and so on. Within all this complexity, it turns out that getting your DNA sequence right is just the beginning of translating that genetic code into a living, breathing entity. But in some cases, it might be possible.

In 2013, Sergey Zimov was introduced to the geneticist George Church at a conference on de-extinction. Church is an accomplished scientist in the field of DNA analysis and reconstruction, and a thought leader in the field of synthetic biology (which we’ll come
back to in chapter nine). It was a match made in resurrection biology heaven. Zimov wanted to populate his Pleistocene Park with mammoths, and Church thought he could see a way of
achieving this.

What resulted was an ambitious project to de-extinct the woolly mammoth. Church and others who are working on this have faced plenty of hurdles. But the technology has been advancing so fast that, as of 2017, scientists were predicting they would be able to reproduce the woolly mammoth within the next two years.

One of those hurdles was the lack of solid DNA sequences to work from. Frustratingly, although there are many instances of well preserved woolly mammoths, their DNA rarely survives being frozen for tens of thousands of years. To overcome this, Church and others
have taken a different tack: Take a modern, living relative of the mammoth, and engineer into it traits that would allow it to live on the Siberian tundra, just like its woolly ancestors.

Church’s team’s starting point has been the Asian elephant. This is their source of base DNA for their “woolly mammoth 2.0”—their starting source code, if you like. So far, they’ve identified fifty plus gene sequences they think they can play with to give their modern-day woolly mammoth the traits it would need to thrive in Pleistocene Park, including a coat of hair, smaller ears, and a constitution adapted to cold.

The next hurdle they face is how to translate the code embedded in their new woolly mammoth genome into a living, breathing animal. The most obvious route would be to impregnate a female Asian elephant with a fertilized egg containing the new code. But Asian elephants are endangered, and no one’s likely to allow such cutting edge experimentation on the precious few that are still around, so scientists are working on an artificial womb for their reinvented woolly mammoth. They’re making progress with mice and hope to crack the motherless mammoth challenge relatively soon.

It’s perhaps a stretch to call this creative approach to recreating a species (or “reanimation” as Church refers to it) “de-extinction,” as what is being formed is a new species. … (pp. 31-4)

This selection illustrates what Maynard does so very well throughout the book where he uses each film as a launching pad for a clear, readable description of relevant bits of science so you understand why the premise was likely, unlikely, or pure fantasy while linking it to contemporary practices, efforts, and issues. In the context of Jurassic Park, Maynard goes on to raise some fascinating questions such as: Should we revive animals rendered extinct (due to obsolescence or inability to adapt to new conditions) when we could develop new animals?

General thoughts

‘Films for the Future’ offers readable (to non-scientific types) science, lively writing, and the occasional ‘memorish’ anecdote. As well, Dr. Maynard raises the curtain on aspects of the scientific enterprise that most of us do not get to see.  For example, the meeting  between Sergey Zimov and George Church and how it led to new ‘de-extinction’ work’. He also describes the problems that the scientists encountered and are encountering. This is in direct contrast to how scientific work is usually presented in the news media as one glorious breakthrough after the next.

Maynard does discuss the issues of social inequality and power and ownership. For example, who owns your transplant or data? Puzzlingly, he doesn’t touch on the current environment where scientists in the US and elsewhere are encouraged/pressured to start up companies commercializing their work.

Nor is there any mention of how universities are participating in this grand business experiment often called ‘innovation’. (My March 15, 2017 posting describes an outcome for the CRISPR [gene editing system] patent fight taking place between Harvard University’s & MIT’s [Massachusetts Institute of Technology] Broad Institute vs the University of California at Berkeley and my Sept. 11, 2018 posting about an art/science exhibit in Vancouver [Canada] provides an update for round 2 of the Broad Institute vs. UC Berkeley patent fight [scroll down about 65% of the way.) *To read about how my ‘cultural blindness’ shows up here scroll down to the single asterisk at the end.*

There’s a foray through machine-learning and big data as applied to predictive policing in Maynard’s ‘Minority Report’ chapter (my November 23, 2017 posting describes Vancouver’s predictive policing initiative [no psychics involved], the first such in Canada). There’s no mention of surveillance technology, which if I recall properly was part of the future environment, both by the state and by corporations. (Mia Armstrong’s November 15, 2018 article for Slate on Chinese surveillance being exported to Venezuela provides interesting insight.)

The gaps are interesting and various. This of course points to a problem all science writers have when attempting an overview of science. (Carl Zimmer’s latest, ‘She Has Her Mother’s Laugh: The Powers, Perversions, and Potential of Heredity’] a doorstopping 574 pages, also has some gaps despite his focus on heredity,)

Maynard has worked hard to give an comprehensive overview in a remarkably compact 279 pages while developing his theme about science and the human element. In other words, science is not monolithic; it’s created by human beings and subject to all the flaws and benefits that humanity’s efforts are always subject to—scientists are people too.

The readership for ‘Films from the Future’ spans from the mildly interested science reader to someone like me who’s been writing/blogging about these topics (more or less) for about 10 years. I learned a lot reading this book.

Next time, I’m hopeful there’ll be a next time, Maynard might want to describe the parameters he’s set for his book in more detail that is possible in his chapter headings. He could have mentioned that he’s not a cinéaste so his descriptions of the movies are very much focused on the story as conveyed through words. He doesn’t mention colour palates, camera angles, or, even, cultural lenses.

Take for example, his chapter on ‘Ghost in the Shell’. Focused on the Japanese animation film and not the live action Hollywood version he talks about human enhancement and cyborgs. The Japanese have a different take on robots, inanimate objects, and, I assume, cyborgs than is found in Canada or the US or Great Britain, for that matter (according to a colleague of mine, an Englishwoman who lived in Japan for ten or more years). There’s also the chapter on the Ealing comedy, The Man in The White Suit, an English film from the 1950’s. That too has a cultural (as well as, historical) flavour but since Maynard is from England, he may take that cultural flavour for granted. ‘Never let me go’ in Chapter Two was also a UK production, albeit far more recent than the Ealing comedy and it’s interesting to consider how a UK production about cloning might differ from a US or Chinese or … production on the topic. I am hearkening back to Maynard’s anecdote about movies giving him new ways of seeing and imagining the world.

There’s a corrective. A couple of sentences in Maynard’s introductory chapter cautioning that in depth exploration of ‘cultural lenses’ was not possible without expanding the book to an unreadable size followed by a sentence in each of the two chapters that there are cultural differences.

One area where I had a significant problem was with regard to being “programmed” and having  “instinctual” behaviour,

As a species, we are embarrassingly programmed to see “different” as “threatening,” and to take instinctive action against it. It’s a trait that’s exploited in many science fiction novels and movies, including those in this book. If we want to see the rise of increasingly augmented individuals, we need to be prepared for some social strife. (p. 136)

These concepts are much debated in the social sciences and there are arguments for and against ‘instincts regarding strangers and their possible differences’. I gather Dr. Maynard hies to the ‘instinct to defend/attack’ school of thought.

One final quandary, there was no sex and I was expecting it in the Ex Machina chapter, especially now that sexbots are about to take over the world (I exaggerate). Certainly, if you’re talking about “social strife,” then sexbots would seem to be fruitful line of inquiry, especially when there’s talk of how they could benefit families (my August 29, 2018 posting). Again, there could have been a sentence explaining why Maynard focused almost exclusively in this chapter on the discussions about artificial intelligence and superintelligence.

Taken in the context of the book, these are trifling issues and shouldn’t stop you from reading Films from the Future. What Maynard has accomplished here is impressive and I hope it’s just the beginning.

Final note

Bravo Andrew! (Note: We’ve been ‘internet acquaintances/friends since the first year I started blogging. When I’m referring to him in his professional capacity, he’s Dr. Maynard and when it’s not strictly in his professional capacity, it’s Andrew. For this commentary/review I wanted to emphasize his professional status.)

If you need to see a few more samples of Andrew’s writing, there’s a Nov. 15, 2018 essay on The Conversation, Sci-fi movies are the secret weapon that could help Silicon Valley grow up and a Nov. 21, 2018 article on slate.com, The True Cost of Stain-Resistant Pants; The 1951 British comedy The Man in the White Suit anticipated our fears about nanotechnology. Enjoy.

****Added at 1700 hours on Nov. 22, 2018: You can purchase Films from the Future here.

*Nov. 23, 2018: I should have been more specific and said ‘academic scientists’. In Canada, the great percentage of scientists are academic. It’s to the point where the OECD (Organization for Economic Cooperation and Development) has noted that amongst industrialized countries, Canada has very few industrial scientists in comparison to the others.

Mixing the unmixable for all new nanoparticles

This news comes out of the University of Maryland and the discovery could led to nanoparticles that have never before been imagined. From a March 29, 2018 news item on ScienceDaily,

Making a giant leap in the ‘tiny’ field of nanoscience, a multi-institutional team of researchers is the first to create nanoscale particles composed of up to eight distinct elements generally known to be immiscible, or incapable of being mixed or blended together. The blending of multiple, unmixable elements into a unified, homogenous nanostructure, called a high entropy alloy nanoparticle, greatly expands the landscape of nanomaterials — and what we can do with them.

This research makes a significant advance on previous efforts that have typically produced nanoparticles limited to only three different elements and to structures that do not mix evenly. Essentially, it is extremely difficult to squeeze and blend different elements into individual particles at the nanoscale. The team, which includes lead researchers at University of Maryland, College Park (UMD)’s A. James Clark School of Engineering, published a peer-reviewed paper based on the research featured on the March 30 [2018] cover of Science.

A March 29, 2018 University of Maryland press release (also on EurekAlert), which originated the news item, delves further (Note: Links have been removed),

“Imagine the elements that combine to make nanoparticles as Lego building blocks. If you have only one to three colors and sizes, then you are limited by what combinations you can use and what structures you can assemble,” explains Liangbing Hu, associate professor of materials science and engineering at UMD and one of the corresponding authors of the paper. “What our team has done is essentially enlarged the toy chest in nanoparticle synthesis; now, we are able to build nanomaterials with nearly all metallic and semiconductor elements.”

The researchers say this advance in nanoscience opens vast opportunities for a wide range of applications that includes catalysis (the acceleration of a chemical reaction by a catalyst), energy storage (batteries or supercapacitors), and bio/plasmonic imaging, among others.

To create the high entropy alloy nanoparticles, the researchers employed a two-step method of flash heating followed by flash cooling. Metallic elements such as platinum, nickel, iron, cobalt, gold, copper, and others were exposed to a rapid thermal shock of approximately 3,000 degrees Fahrenheit, or about half the temperature of the sun, for 0.055 seconds. The extremely high temperature resulted in uniform mixtures of the multiple elements. The subsequent rapid cooling (more than 100,000 degrees Fahrenheit per second) stabilized the newly mixed elements into the uniform nanomaterial.

“Our method is simple, but one that nobody else has applied to the creation of nanoparticles. By using a physical science approach, rather than a traditional chemistry approach, we have achieved something unprecedented,” says Yonggang Yao, a Ph.D. student at UMD and one of the lead authors of the paper.

To demonstrate one potential use of the nanoparticles, the research team used them as advanced catalysts for ammonia oxidation, which is a key step in the production of nitric acid (a liquid acid that is used in the production of ammonium nitrate for fertilizers, making plastics, and in the manufacturing of dyes). They were able to achieve 100 percent oxidation of ammonia and 99 percent selectivity toward desired products with the high entropy alloy nanoparticles, proving their ability as highly efficient catalysts.

Yao says another potential use of the nanoparticles as catalysts could be the generation of chemicals or fuels from carbon dioxide.

“The potential applications for high entropy alloy nanoparticles are not limited to the field of catalysis. With cross-discipline curiosity, the demonstrated applications of these particles will become even more widespread,” says Steven D. Lacey, a Ph.D. student at UMD and also one of the lead authors of the paper.

This research was performed through a multi-institutional collaboration of Prof. Liangbing Hu’s group at the University of Maryland, College Park; Prof. Reza Shahbazian-Yassar’s group at University of Illinois at Chicago; Prof. Ju Li’s group at the Massachusetts Institute of Technology; Prof. Chao Wang’s group at Johns Hopkins University; and Prof. Michael Zachariah’s group at the University of Maryland, College Park.

What outside experts are saying about this research:

“This is quite amazing; Dr. Hu creatively came up with this powerful technique, carbo-thermal shock synthesis, to produce high entropy alloys of up to eight different elements in a single nanoparticle. This is indeed unthinkable for bulk materials synthesis. This is yet another beautiful example of nanoscience!,” says Peidong Yang, the S.K. and Angela Chan Distinguished Professor of Energy and professor of chemistry at the University of California, Berkeley and member of the American Academy of Arts and Sciences.

“This discovery opens many new directions. There are simulation opportunities to understand the electronic structure of the various compositions and phases that are important for the next generation of catalyst design. Also, finding correlations among synthesis routes, composition, and phase structure and performance enables a paradigm shift toward guided synthesis,” says George Crabtree, Argonne Distinguished Fellow and director of the Joint Center for Energy Storage Research at Argonne National Laboratory.

More from the research coauthors:

“Understanding the atomic order and crystalline structure in these multi-element nanoparticles reveals how the synthesis can be tuned to optimize their performance. It would be quite interesting to further explore the underlying atomistic mechanisms of the nucleation and growth of high entropy alloy nanoparticle,” says Reza Shahbazian-Yassar, associate professor at the University of Illinois at Chicago and a corresponding author of the paper.

“Carbon metabolism drives ‘living’ metal catalysts that frequently move around, split, or merge, resulting in a nanoparticle size distribution that’s far from the ordinary, and highly tunable,” says Ju Li, professor at the Massachusetts Institute of Technology and a corresponding author of the paper.

“This method enables new combinations of metals that do not exist in nature and do not otherwise go together. It enables robust tuning of the composition of catalytic materials to optimize the activity, selectivity, and stability, and the application will be very broad in energy conversions and chemical transformations,” says Chao Wang, assistant professor of chemical and biomolecular engineering at Johns Hopkins University and one of the study’s authors.

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

Carbothermal shock synthesis of high-entropy-alloy nanoparticles by Yonggang Yao, Zhennan Huang, Pengfei Xie, Steven D. Lacey, Rohit Jiji Jacob, Hua Xie, Fengjuan Chen, Anmin Nie, Tiancheng Pu, Miles Rehwoldt, Daiwei Yu, Michael R. Zachariah, Chao Wang, Reza Shahbazian-Yassar, Ju Li, Liangbing Hu. Science 30 Mar 2018: Vol. 359, Issue 6383, pp. 1489-1494 DOI: 10.1126/science.aan5412

This paper is behind a paywall.

My name is Steve and I’m a sub auroral ion drift

Photo: The Aurora Named STEVE Couresty: NASA Goddard

That stunning image is one of a series, many of which were taken by amateur photographers as noted in a March 14, 2018 US National Aeronautics and Space Agency (NASA)/Goddard Space Flight Center news release (also on EurekAlert) by Kasha Patel about how STEVE was discovered,

Notanee Bourassa knew that what he was seeing in the night sky was not normal. Bourassa, an IT technician in Regina, Canada, trekked outside of his home on July 25, 2016, around midnight with his two younger children to show them a beautiful moving light display in the sky — an aurora borealis. He often sky gazes until the early hours of the morning to photograph the aurora with his Nikon camera, but this was his first expedition with his children. When a thin purple ribbon of light appeared and starting glowing, Bourassa immediately snapped pictures until the light particles disappeared 20 minutes later. Having watched the northern lights for almost 30 years since he was a teenager, he knew this wasn’t an aurora. It was something else.

From 2015 to 2016, citizen scientists — people like Bourassa who are excited about a science field but don’t necessarily have a formal educational background — shared 30 reports of these mysterious lights in online forums and with a team of scientists that run a project called Aurorasaurus. The citizen science project, funded by NASA and the National Science Foundation, tracks the aurora borealis through user-submitted reports and tweets.

The Aurorasaurus team, led by Liz MacDonald, a space scientist at NASA’s Goddard Space Flight Center in Greenbelt, Maryland, conferred to determine the identity of this mysterious phenomenon. MacDonald and her colleague Eric Donovan at the University of Calgary in Canada talked with the main contributors of these images, amateur photographers in a Facebook group called Alberta Aurora Chasers, which included Bourassa and lead administrator Chris Ratzlaff. Ratzlaff gave the phenomenon a fun, new name, Steve, and it stuck.

But people still didn’t know what it was.

Scientists’ understanding of Steve changed that night Bourassa snapped his pictures. Bourassa wasn’t the only one observing Steve. Ground-based cameras called all-sky cameras, run by the University of Calgary and University of California, Berkeley, took pictures of large areas of the sky and captured Steve and the auroral display far to the north. From space, ESA’s (the European Space Agency) Swarm satellite just happened to be passing over the exact area at the same time and documented Steve.

For the first time, scientists had ground and satellite views of Steve. Scientists have now learned, despite its ordinary name, that Steve may be an extraordinary puzzle piece in painting a better picture of how Earth’s magnetic fields function and interact with charged particles in space. The findings are published in a study released today in Science Advances.

“This is a light display that we can observe over thousands of kilometers from the ground,” said MacDonald. “It corresponds to something happening way out in space. Gathering more data points on STEVE will help us understand more about its behavior and its influence on space weather.”

The study highlights one key quality of Steve: Steve is not a normal aurora. Auroras occur globally in an oval shape, last hours and appear primarily in greens, blues and reds. Citizen science reports showed Steve is purple with a green picket fence structure that waves. It is a line with a beginning and end. People have observed Steve for 20 minutes to 1 hour before it disappears.

If anything, auroras and Steve are different flavors of an ice cream, said MacDonald. They are both created in generally the same way: Charged particles from the Sun interact with Earth’s magnetic field lines.

The uniqueness of Steve is in the details. While Steve goes through the same large-scale creation process as an aurora, it travels along different magnetic field lines than the aurora. All-sky cameras showed that Steve appears at much lower latitudes. That means the charged particles that create Steve connect to magnetic field lines that are closer to Earth’s equator, hence why Steve is often seen in southern Canada.

Perhaps the biggest surprise about Steve appeared in the satellite data. The data showed that Steve comprises a fast moving stream of extremely hot particles called a sub auroral ion drift, or SAID. Scientists have studied SAIDs since the 1970s but never knew there was an accompanying visual effect. The Swarm satellite recorded information on the charged particles’ speeds and temperatures, but does not have an imager aboard.

“People have studied a lot of SAIDs, but we never knew it had a visible light. Now our cameras are sensitive enough to pick it up and people’s eyes and intellect were critical in noticing its importance,” said Donovan, a co-author of the study. Donovan led the all-sky camera network and his Calgary colleagues lead the electric field instruments on the Swarm satellite.

Steve is an important discovery because of its location in the sub auroral zone, an area of lower latitude than where most auroras appear that is not well researched. For one, with this discovery, scientists now know there are unknown chemical processes taking place in the sub auroral zone that can lead to this light emission.

Second, Steve consistently appears in the presence of auroras, which usually occur at a higher latitude area called the auroral zone. That means there is something happening in near-Earth space that leads to both an aurora and Steve. Steve might be the only visual clue that exists to show a chemical or physical connection between the higher latitude auroral zone and lower latitude sub auroral zone, said MacDonald.

“Steve can help us understand how the chemical and physical processes in Earth’s upper atmosphere can sometimes have local noticeable effects in lower parts of Earth’s atmosphere,” said MacDonald. “This provides good insight on how Earth’s system works as a whole.”

The team can learn a lot about Steve with additional ground and satellite reports, but recording Steve from the ground and space simultaneously is a rare occurrence. Each Swarm satellite orbits Earth every 90 minutes and Steve only lasts up to an hour in a specific area. If the satellite misses Steve as it circles Earth, Steve will probably be gone by the time that same satellite crosses the spot again.

In the end, capturing Steve becomes a game of perseverance and probability.

“It is my hope that with our timely reporting of sightings, researchers can study the data so we can together unravel the mystery of Steve’s origin, creation, physics and sporadic nature,” said Bourassa. “This is exciting because the more I learn about it, the more questions I have.”

As for the name “Steve” given by the citizen scientists? The team is keeping it as an homage to its initial name and discoverers. But now it is STEVE, short for Strong Thermal Emission Velocity Enhancement.

Other collaborators on this work are: the University of Calgary, New Mexico Consortium, Boston University, Lancaster University, Athabasca University, Los Alamos National Laboratory and the Alberta Aurora Chasers Facebook group.

If you live in an area where you may see STEVE or an aurora, submit your pictures and reports to Aurorasaurus through aurorasaurus.org or the free iOS and Android mobile apps. To learn how to spot STEVE, click here.

There is a video with MacDonald describing the work and featuring more images,

Katherine Kornei’s March 14, 2018 article for sciencemag.org adds more detail about the work,

Citizen scientists first began posting about Steve on social media several years ago. Across New Zealand, Canada, the United States, and the United Kingdom, they reported an unusual sight in the night sky: a purplish line that arced across the heavens for about an hour at a time, visible at lower latitudes than classical aurorae, mostly in the spring and fall. … “It’s similar to a contrail but doesn’t disperse,” says Notanee Bourassa, an aurora photographer in Saskatchewan province in Canada [Regina as mentioned in the news release is the capital of the province of Saskatchewan].

Traditional aurorae are often green, because oxygen atoms present in Earth’s atmosphere emit that color light when they’re bombarded by charged particles trapped in Earth’s magnetic field. They also appear as a diffuse glow—rather than a distinct line—on the northern or southern horizon. Without a scientific theory to explain the new sight, a group of citizen scientists led by aurora enthusiast Chris Ratzlaff of Canada’s Alberta province [usually referred to as Canada’s province of Alberta or simply, the province of Alberta] playfully dubbed it Steve, after a line in the 2006 children’s movie Over the Hedge.

Aurorae have been studied for decades, but people may have missed Steve because their cameras weren’t sensitive enough, says Elizabeth MacDonald, a space physicist at NASA Goddard Space Flight Center in Greenbelt, Maryland, and leader of the new research. MacDonald and her team have used data from a European satellite called Swarm-A to study Steve in its native environment, about 200 kilometers up in the atmosphere. Swarm-A’s instruments revealed that the charged particles in Steve had a temperature of about 6000°C, “impressively hot” compared with the nearby atmosphere, MacDonald says. And those ions were flowing from east to west at nearly 6 kilometers per second, …

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

New science in plain sight: Citizen scientists lead to the discovery of optical structure in the upper atmosphere by Elizabeth A. MacDonald, Eric Donovan, Yukitoshi Nishimura, Nathan A. Case, D. Megan Gillies, Bea Gallardo-Lacourt, William E. Archer, Emma L. Spanswick, Notanee Bourassa, Martin Connors, Matthew Heavner, Brian Jackel, Burcu Kosar, David J. Knudsen, Chris Ratzlaff, and Ian Schofield. Science Advances 14 Mar 2018:
Vol. 4, no. 3, eaaq0030 DOI: 10.1126/sciadv.aaq0030

This paper is open access. You’ll note that Notanee Bourassa is listed as an author. For more about Bourassa, there’s his Twitter feed (@DJHardwired) and his YouTube Channel. BTW, his Twitter bio notes that he’s “Recently heartbroken,” as well as, “Seasoned human male. Expert storm chaser, aurora photographer, drone flyer and on-air FM radio DJ.” Make of that what you will.

Body-on-a-chip (10 organs)

Also known as human-on-a-chip, the 10-organ body-on-a-chip was being discussed at the 9th World Congress on Alternatives to Animal Testing in the Life Sciences in 2014 in Prague, Czech Republic (see this July 1, 2015 posting for more). At the time, scientists were predicting success at achieving their goal of 10 organs on-a-chip in 2017 (the best at the time was four organs). Only a few months past that deadline, scientists from the Massachusetts Institute of Technology (MIT) seem to have announced a ’10 organ chip’ in a March 14, 2018 news item on ScienceDaily,

MIT engineers have developed new technology that could be used to evaluate new drugs and detect possible side effects before the drugs are tested in humans. Using a microfluidic platform that connects engineered tissues from up to 10 organs, the researchers can accurately replicate human organ interactions for weeks at a time, allowing them to measure the effects of drugs on different parts of the body.

Such a system could reveal, for example, whether a drug that is intended to treat one organ will have adverse effects on another.

A March 14, 2018 MIT news release (also on EurekAlert), which originated the news item, expands on the theme,

“Some of these effects are really hard to predict from animal models because the situations that lead to them are idiosyncratic,” says Linda Griffith, the School of Engineering Professor of Teaching Innovation, a professor of biological engineering and mechanical engineering, and one of the senior authors of the study. “With our chip, you can distribute a drug and then look for the effects on other tissues, and measure the exposure and how it is metabolized.”

These chips could also be used to evaluate antibody drugs and other immunotherapies, which are difficult to test thoroughly in animals because they are designed to interact with the human immune system.

David Trumper, an MIT professor of mechanical engineering, and Murat Cirit, a research scientist in the Department of Biological Engineering, are also senior authors of the paper, which appears in the journal Scientific Reports. The paper’s lead authors are former MIT postdocs Collin Edington and Wen Li Kelly Chen.

Modeling organs

When developing a new drug, researchers identify drug targets based on what they know about the biology of the disease, and then create compounds that affect those targets. Preclinical testing in animals can offer information about a drug’s safety and effectiveness before human testing begins, but those tests may not reveal potential side effects, Griffith says. Furthermore, drugs that work in animals often fail in human trials.

“Animals do not represent people in all the facets that you need to develop drugs and understand disease,” Griffith says. “That is becoming more and more apparent as we look across all kinds of drugs.”

Complications can also arise due to variability among individual patients, including their genetic background, environmental influences, lifestyles, and other drugs they may be taking. “A lot of the time you don’t see problems with a drug, particularly something that might be widely prescribed, until it goes on the market,” Griffith says.

As part of a project spearheaded by the Defense Advanced Research Projects Agency (DARPA), Griffith and her colleagues decided to pursue a technology that they call a “physiome on a chip,” which they believe could offer a way to model potential drug effects more accurately and rapidly. To achieve this, the researchers needed new equipment — a platform that would allow tissues to grow and interact with each other — as well as engineered tissue that would accurately mimic the functions of human organs.

Before this project was launched, no one had succeeded in connecting more than a few different tissue types on a platform. Furthermore, most researchers working on this kind of chip were working with closed microfluidic systems, which allow fluid to flow in and out but do not offer an easy way to manipulate what is happening inside the chip. These systems also require external pumps.

The MIT team decided to create an open system, which essentially removes the lid and makes it easier to manipulate the system and remove samples for analysis. Their system, adapted from technology they previously developed and commercialized through U.K.-based CN BioInnovations, also incorporates several on-board pumps that can control the flow of liquid between the “organs,” replicating the circulation of blood, immune cells, and proteins through the human body. The pumps also allow larger engineered tissues, for example tumors within an organ, to be evaluated.

Complex interactions

The researchers created several versions of their chip, linking up to 10 organ types: liver, lung, gut, endometrium, brain, heart, pancreas, kidney, skin, and skeletal muscle. Each “organ” consists of clusters of 1 million to 2 million cells. These tissues don’t replicate the entire organ, but they do perform many of its important functions. Significantly, most of the tissues come directly from patient samples rather than from cell lines that have been developed for lab use. These so-called “primary cells” are more difficult to work with but offer a more representative model of organ function, Griffith says.

Using this system, the researchers showed that they could deliver a drug to the gastrointestinal tissue, mimicking oral ingestion of a drug, and then observe as the drug was transported to other tissues and metabolized. They could measure where the drugs went, the effects of the drugs on different tissues, and how the drugs were broken down. In a related publication, the researchers modeled how drugs can cause unexpected stress on the liver by making the gastrointestinal tract “leaky,” allowing bacteria to enter the bloodstream and produce inflammation in the liver.

Kevin Healy, a professor of bioengineering and materials science and engineering at the University of California at Berkeley, says that this kind of system holds great potential for accurate prediction of complex adverse drug reactions.

“While microphysiological systems (MPS) featuring single organs can be of great use for both pharmaceutical testing and basic organ-level studies, the huge potential of MPS technology is revealed by connecting multiple organ chips in an integrated system for in vitro pharmacology. This study beautifully illustrates that multi-MPS “physiome-on-a-chip” approaches, which combine the genetic background of human cells with physiologically relevant tissue-to-media volumes, allow accurate prediction of drug pharmacokinetics and drug absorption, distribution, metabolism, and excretion,” says Healy, who was not involved in the research.

Griffith believes that the most immediate applications for this technology involve modeling two to four organs. Her lab is now developing a model system for Parkinson’s disease that includes brain, liver, and gastrointestinal tissue, which she plans to use to investigate the hypothesis that bacteria found in the gut can influence the development of Parkinson’s disease.

Other applications include modeling tumors that metastasize to other parts of the body, she says.

“An advantage of our platform is that we can scale it up or down and accommodate a lot of different configurations,” Griffith says. “I think the field is going to go through a transition where we start to get more information out of a three-organ or four-organ system, and it will start to become cost-competitive because the information you’re getting is so much more valuable.”

The research was funded by the U.S. Army Research Office and DARPA.

Caption: MIT engineers have developed new technology that could be used to evaluate new drugs and detect possible side effects before the drugs are tested in humans. Using a microfluidic platform that connects engineered tissues from up to 10 organs, the researchers can accurately replicate human organ interactions for weeks at a time, allowing them to measure the effects of drugs on different parts of the body. Credit: Felice Frankel

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

Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies by Collin D. Edington, Wen Li Kelly Chen, Emily Geishecker, Timothy Kassis, Luis R. Soenksen, Brij M. Bhushan, Duncan Freake, Jared Kirschner, Christian Maass, Nikolaos Tsamandouras, Jorge Valdez, Christi D. Cook, Tom Parent, Stephen Snyder, Jiajie Yu, Emily Suter, Michael Shockley, Jason Velazquez, Jeremy J. Velazquez, Linda Stockdale, Julia P. Papps, Iris Lee, Nicholas Vann, Mario Gamboa, Matthew E. LaBarge, Zhe Zhong, Xin Wang, Laurie A. Boyer, Douglas A. Lauffenburger, Rebecca L. Carrier, Catherine Communal, Steven R. Tannenbaum, Cynthia L. Stokes, David J. Hughes, Gaurav Rohatgi, David L. Trumper, Murat Cirit, Linda G. Griffith. Scientific Reports, 2018; 8 (1) DOI: 10.1038/s41598-018-22749-0 Published online:

This paper which describes testing for four-, seven-, and ten-organs-on-a-chip, is open access. From the paper’s Discussion,

In summary, we have demonstrated a generalizable approach to linking MPSs [microphysiological systems] within a fluidic platform to create a physiome-on-a-chip approach capable of generating complex molecular distribution profiles for advanced drug discovery applications. This adaptable, reusable system has unique and complementary advantages to existing microfluidic and PDMS-based approaches, especially for applications involving high logD substances (drugs and hormones), those requiring precise and flexible control over inter-MPS flow partitioning and drug distribution, and those requiring long-term (weeks) culture with reliable fluidic and sampling operation. We anticipate this platform can be applied to a wide range of problems in disease modeling and pre-clinical drug development, especially for tractable lower-order (2–4) interactions.

Congratulations to the researchers!

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)

CRISPR-Cas12a as a new diagnostic tool

Similar to Cas9, Cas12a is has an added feature as noted in this February 15, 2018 news item on ScienceDaily,

Utilizing an unsuspected activity of the CRISPR-Cas12a protein, researchers created a simple diagnostic system called DETECTR to analyze cells, blood, saliva, urine and stool to detect genetic mutations, cancer and antibiotic resistance and also diagnose bacterial and viral infections. The scientists discovered that when Cas12a binds its double-stranded DNA target, it indiscriminately chews up all single-stranded DNA. They then created reporter molecules attached to single-stranded DNA to signal when Cas12a finds its target.

A February 15, 2018 University of California at Berkeley (UC Berkeley) news release by Robert Sanders and which originated the news item, provides more detail and history,

CRISPR-Cas12a, one of the DNA-cutting proteins revolutionizing biology today, has an unexpected side effect that makes it an ideal enzyme for simple, rapid and accurate disease diagnostics.

blood in test tube

(iStock)

Cas12a, discovered in 2015 and originally called Cpf1, is like the well-known Cas9 protein that UC Berkeley’s Jennifer Doudna and colleague Emmanuelle Charpentier turned into a powerful gene-editing tool in 2012.

CRISPR-Cas9 has supercharged biological research in a mere six years, speeding up exploration of the causes of disease and sparking many potential new therapies. Cas12a was a major addition to the gene-cutting toolbox, able to cut double-stranded DNA at places that Cas9 can’t, and, because it leaves ragged edges, perhaps easier to use when inserting a new gene at the DNA cut.

But co-first authors Janice Chen, Enbo Ma and Lucas Harrington in Doudna’s lab discovered that when Cas12a binds and cuts a targeted double-stranded DNA sequence, it unexpectedly unleashes indiscriminate cutting of all single-stranded DNA in a test tube.

Most of the DNA in a cell is in the form of a double-stranded helix, so this is not necessarily a problem for gene-editing applications. But it does allow researchers to use a single-stranded “reporter” molecule with the CRISPR-Cas12a protein, which produces an unambiguous fluorescent signal when Cas12a has found its target.

“We continue to be fascinated by the functions of bacterial CRISPR systems and how mechanistic understanding leads to opportunities for new technologies,” said Doudna, a professor of molecular and cell biology and of chemistry and a Howard Hughes Medical Institute investigator.

DETECTR diagnostics

The new DETECTR system based on CRISPR-Cas12a can analyze cells, blood, saliva, urine and stool to detect genetic mutations, cancer and antibiotic resistance as well as diagnose bacterial and viral infections. Target DNA is amplified by RPA to make it easier for Cas12a to find it and bind, unleashing indiscriminate cutting of single-stranded DNA, including DNA attached to a fluorescent marker (gold star) that tells researchers that Cas12a has found its target.

The UC Berkeley researchers, along with their colleagues at UC San Francisco, will publish their findings Feb. 15 [2018] via the journal Science’s fast-track service, First Release.

The researchers developed a diagnostic system they dubbed the DNA Endonuclease Targeted CRISPR Trans Reporter, or DETECTR, for quick and easy point-of-care detection of even small amounts of DNA in clinical samples. It involves adding all reagents in a single reaction: CRISPR-Cas12a and its RNA targeting sequence (guide RNA), fluorescent reporter molecule and an isothermal amplification system called recombinase polymerase amplification (RPA), which is similar to polymerase chain reaction (PCR). When warmed to body temperature, RPA rapidly multiplies the number of copies of the target DNA, boosting the chances Cas12a will find one of them, bind and unleash single-strand DNA cutting, resulting in a fluorescent readout.

The UC Berkeley researchers tested this strategy using patient samples containing human papilloma virus (HPV), in collaboration with Joel Palefsky’s lab at UC San Francisco. Using DETECTR, they were able to demonstrate accurate detection of the “high-risk” HPV types 16 and 18 in samples infected with many different HPV types.

“This protein works as a robust tool to detect DNA from a variety of sources,” Chen said. “We want to push the limits of the technology, which is potentially applicable in any point-of-care diagnostic situation where there is a DNA component, including cancer and infectious disease.”

The indiscriminate cutting of all single-stranded DNA, which the researchers discovered holds true for all related Cas12 molecules, but not Cas9, may have unwanted effects in genome editing applications, but more research is needed on this topic, Chen said. During the transcription of genes, for example, the cell briefly creates single strands of DNA that could accidentally be cut by Cas12a.

The activity of the Cas12 proteins is similar to that of another family of CRISPR enzymes, Cas13a, which chew up RNA after binding to a target RNA sequence. Various teams, including Doudna’s, are developing diagnostic tests using Cas13a that could, for example, detect the RNA genome of HIV.

infographic about DETECTR system

(Infographic by the Howard Hughes Medical Institute)

These new tools have been repurposed from their original role in microbes where they serve as adaptive immune systems to fend off viral infections. In these bacteria, Cas proteins store records of past infections and use these “memories” to identify harmful DNA during infections. Cas12a, the protein used in this study, then cuts the invading DNA, saving the bacteria from being taken over by the virus.

The chance discovery of Cas12a’s unusual behavior highlights the importance of basic research, Chen said, since it came from a basic curiosity about the mechanism Cas12a uses to cleave double-stranded DNA.

“It’s cool that, by going after the question of the cleavage mechanism of this protein, we uncovered what we think is a very powerful technology useful in an array of applications,” Chen said.

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

CRISPR-Cas12a target binding unleashes indiscriminate single-stranded DNase activity by Janice S. Chen, Enbo Ma, Lucas B. Harrington, Maria Da Costa, Xinran Tian, Joel M. Palefsky, Jennifer A. Doudna. Science 15 Feb 2018: eaar6245 DOI: 10.1126/science.aar6245

This paper is behind a paywall.

AI (artificial intelligence) for Good Global Summit from May 15 – 17, 2018 in Geneva, Switzerland: details and an interview with Frederic Werner

With all the talk about artificial intelligence (AI), a lot more attention seems to be paid to apocalyptic scenarios: loss of jobs, financial hardship, loss of personal agency and privacy, and more with all of these impacts being described as global. Still, there are some folks who are considering and working on ‘AI for good’.

If you’d asked me, the International Telecommunications Union (ITU) would not have been my first guess (my choice would have been United Nations Educational, Scientific and Cultural Organization [UNESCO]) as an agency likely to host the 2018 AI for Good Global Summit. But, it turns out the ITU is a UN (United Nations agency) and, according to its Wikipedia entry, it’s an intergovernmental public-private partnership, which may explain the nature of the participants in the upcoming summit.

The news

First, there’s a May 4, 2018 ITU media advisory (received via email or you can find the full media advisory here) about the upcoming summit,

Artificial Intelligence (AI) is now widely identified as being able to address the greatest challenges facing humanity – supporting innovation in fields ranging from crisis management and healthcare to smart cities and communications networking.

The second annual ‘AI for Good Global Summit’ will take place 15-17 May [2018] in Geneva, and seeks to leverage AI to accelerate progress towards the United Nations’ Sustainable Development Goals and ultimately benefit humanity.

WHAT: Global event to advance ‘AI for Good’ with the participation of internationally recognized AI experts. The programme will include interactive high-level panels, while ‘AI Breakthrough Teams’ will propose AI strategies able to create impact in the near term, guided by an expert audience of mentors representing government, industry, academia and civil society – through interactive sessions. The summit will connect AI innovators with public and private-sector decision-makers, building collaboration to take promising strategies forward.

A special demo & exhibit track will feature innovative applications of AI designed to: protect women from sexual violence, avoid infant crib deaths, end child abuse, predict oral cancer, and improve mental health treatments for depression – as well as interactive robots including: Alice, a Dutch invention designed to support the aged; iCub, an open-source robot; and Sophia, the humanoid AI robot.

WHEN: 15-17 May 2018, beginning daily at 9 AM

WHERE: ITU Headquarters, 2 Rue de Varembé, Geneva, Switzerland (Please note: entrance to ITU is now limited for all visitors to the Montbrillant building entrance only on rue Varembé).

WHO: Confirmed participants to date include expert representatives from: Association for Computing Machinery, Bill and Melinda Gates Foundation, Cambridge University, Carnegie Mellon, Chan Zuckerberg Initiative, Consumer Trade Association, Facebook, Fraunhofer, Google, Harvard University, IBM Watson, IEEE, Intellectual Ventures, ITU, Microsoft, Massachusetts Institute of Technology (MIT), Partnership on AI, Planet Labs, Shenzhen Open Innovation Lab, University of California at Berkeley, University of Tokyo, XPRIZE Foundation, Yale University – and the participation of “Sophia” the humanoid robot and “iCub” the EU open source robotcub.

The interview

Frederic Werner, Senior Communications Officer at the International Telecommunication Union and** one of the organizers of the AI for Good Global Summit 2018 kindly took the time to speak to me and provide a few more details about the upcoming event.

Werner noted that the 2018 event grew out of a much smaller 2017 ‘workshop’ and first of its kind, about beneficial AI which this year has ballooned in size to 91 countries (about 15 participants are expected from Canada), 32 UN agencies, and substantive representation from the private sector. The 2017 event featured Dr. Yoshua Bengio of the University of Montreal  (Université de Montréal) was a featured speaker.

“This year, we’re focused on action-oriented projects that will help us reach our Sustainable Development Goals (SDGs) by 2030. We’re looking at near-term practical AI applications,” says Werner. “We’re matchmaking problem-owners and solution-owners.”

Academics, industry professionals, government officials, and representatives from UN agencies are gathering  to work on four tracks/themes:

In advance of this meeting, the group launched an AI repository (an action item from the 2017 meeting) on April 25, 2018 inviting people to list their AI projects (from the ITU’s April 25, 2018? AI repository news announcement),

ITU has just launched an AI Repository where anyone working in the field of artificial intelligence (AI) can contribute key information about how to leverage AI to help solve humanity’s greatest challenges.

This is the only global repository that identifies AI-related projects, research initiatives, think-tanks and organizations that aim to accelerate progress on the 17 United Nations’ Sustainable Development Goals (SDGs).

To submit a project, just press ‘Submit’ on the AI Repository site and fill in the online questionnaire, providing all relevant details of your project. You will also be asked to map your project to the relevant World Summit on the Information Society (WSIS) action lines and the SDGs. Approved projects will be officially registered in the repository database.

Benefits of participation on the AI Repository include:

WSIS Prizes recognize individuals, governments, civil society, local, regional and international agencies, research institutions and private-sector companies for outstanding success in implementing development oriented strategies that leverage the power of AI and ICTs.

Creating the AI Repository was one of the action items of last year’s AI for Good Global Summit.

We are looking forward to your submissions.

If you have any questions, please send an email to: ai@itu.int

“Your project won’t be visible immediately as we have to vet the submissions to weed out spam-type material and projects that are not in line with our goals,” says Werner. That said, there are already 29 projects in the repository. As you might expect, the UK, China, and US are in the repository but also represented are Egypt, Uganda, Belarus, Serbia, Peru, Italy, and other countries not commonly cited when discussing AI research.

Werner also pointed out in response to my surprise over the ITU’s role with regard to this AI initiative that the ITU is the only UN agency which has 192* member states (countries), 150 universities, and over 700 industry members as well as other member entities, which gives them tremendous breadth of reach. As well, the organization, founded originally in 1865 as the International Telegraph Convention, has extensive experience with global standardization in the information technology and telecommunications industries. (See more in their Wikipedia entry.)

Finally

There is a bit more about the summit on the ITU’s AI for Good Global Summit 2018 webpage,

The 2nd edition of the AI for Good Global Summit will be organized by ITU in Geneva on 15-17 May 2018, in partnership with XPRIZE Foundation, the global leader in incentivized prize competitions, the Association for Computing Machinery (ACM) and sister United Nations agencies including UNESCO, UNICEF, UNCTAD, UNIDO, Global Pulse, UNICRI, UNODA, UNIDIR, UNODC, WFP, IFAD, UNAIDS, WIPO, ILO, UNITAR, UNOPS, OHCHR, UN UniversityWHO, UNEP, ICAO, UNDP, The World Bank, UN DESA, CTBTOUNISDRUNOG, UNOOSAUNFPAUNECE, UNDPA, and UNHCR.

The AI for Good series is the leading United Nations platform for dialogue on AI. The action​​-oriented 2018 summit will identify practical applications of AI and supporting strategies to improve the quality and sustainability of life on our planet. The summit will continue to formulate strategies to ensure trusted, safe and inclusive development of AI technologies and equitable access to their benefits.

While the 2017 summit sparked the first ever inclusive global dialogue on beneficial AI, the action-oriented 2018 summit will focus on impactful AI solutions able to yield long-term benefits and help achieve the Sustainable Development Goals. ‘Breakthrough teams’ will demonstrate the potential of AI to map poverty and aid with natural disasters using satellite imagery, how AI could assist the delivery of citizen-centric services in smart cities, and new opportunities for AI to help achieve Universal Health Coverage, and finally to help achieve transparency and explainability in AI algorithms.

Teams will propose impactful AI strategies able to be enacted in the near term, guided by an expert audience of mentors representing government, industry, academia and civil society. Strategies will be evaluated by the mentors according to their feasibility and scalability, potential to address truly global challenges, degree of supporting advocacy, and applicability to market failures beyond the scope of government and industry. The exercise will connect AI innovators with public and private-sector decision-makers, building collaboration to take promising strategies forward.

“As the UN specialized agency for information and communication technologies, ITU is well placed to guide AI innovation towards the achievement of the UN Sustainable Development ​Goals. We are providing a neutral close quotation markplatform for international dialogue aimed at ​building a ​common understanding of the capabilities of emerging AI technologies.​​” Houlin Zhao, Secretary General ​of ITU​

Should you be close to Geneva, it seems that registration is still open. Just go to the ITU’s AI for Good Global Summit 2018 webpage, scroll the page down to ‘Documentation’ and you will find a link to the invitation and a link to online registration. Participation is free but I expect that you are responsible for your travel and accommodation costs.

For anyone unable to attend in person, the summit will be livestreamed (webcast in real time) and you can watch the sessions by following the link below,

https://www.itu.int/en/ITU-T/AI/2018/Pages/webcast.aspx

For those of us on the West Coast of Canada and other parts distant to Geneva, you will want to take the nine hour difference between Geneva (Switzerland) and here into account when viewing the proceedings. If you can’t manage the time difference, the sessions are being recorded and will be posted at a later date.

*’132 member states’ corrected to ‘192 member states’ on May 11, 2018 at 1500 hours PDT.

*Redundant ‘and’ removed on July 19, 2018.

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.

Cyborg bacteria to reduce carbon dioxide

This video is a bit technical but then it is about work being presented to chemists at the American Chemical Society’s (ACS) at the 254th National Meeting & Exposition Aug. 20 -24, 2017,

For a more plain language explanation, there’s an August 22, 2017 ACS news release (also on EurekAlert),

Photosynthesis provides energy for the vast majority of life on Earth. But chlorophyll, the green pigment that plants use to harvest sunlight, is relatively inefficient. To enable humans to capture more of the sun’s energy than natural photosynthesis can, scientists have taught bacteria to cover themselves in tiny, highly efficient solar panels to produce useful compounds.

“Rather than rely on inefficient chlorophyll to harvest sunlight, I’ve taught bacteria how to grow and cover their bodies with tiny semiconductor nanocrystals,” says Kelsey K. Sakimoto, Ph.D., who carried out the research in the lab of Peidong Yang, Ph.D. “These nanocrystals are much more efficient than chlorophyll and can be grown at a fraction of the cost of manufactured solar panels.”

Humans increasingly are looking to find alternatives to fossil fuels as sources of energy and feedstocks for chemical production. Many scientists have worked to create artificial photosynthetic systems to generate renewable energy and simple organic chemicals using sunlight. Progress has been made, but the systems are not efficient enough for commercial production of fuels and feedstocks.

Research in Yang’s lab at the University of California, Berkeley, where Sakimoto earned his Ph.D., focuses on harnessing inorganic semiconductors that can capture sunlight to organisms such as bacteria that can then use the energy to produce useful chemicals from carbon dioxide and water. “The thrust of research in my lab is to essentially ‘supercharge’ nonphotosynthetic bacteria by providing them energy in the form of electrons from inorganic semiconductors, like cadmium sulfide, that are efficient light absorbers,” Yang says. “We are now looking for more benign light absorbers than cadmium sulfide to provide bacteria with energy from light.”

Sakimoto worked with a naturally occurring, nonphotosynthetic bacterium, Moorella thermoacetica, which, as part of its normal respiration, produces acetic acid from carbon dioxide (CO2). Acetic acid is a versatile chemical that can be readily upgraded to a number of fuels, polymers, pharmaceuticals and commodity chemicals through complementary, genetically engineered bacteria.

When Sakimoto fed cadmium and the amino acid cysteine, which contains a sulfur atom, to the bacteria, they synthesized cadmium sulfide (CdS) nanoparticles, which function as solar panels on their surfaces. The hybrid organism, M. thermoacetica-CdS, produces acetic acid from CO2, water and light. “Once covered with these tiny solar panels, the bacteria can synthesize food, fuels and plastics, all using solar energy,” Sakimoto says. “These bacteria outperform natural photosynthesis.”

The bacteria operate at an efficiency of more than 80 percent, and the process is self-replicating and self-regenerating, making this a zero-waste technology. “Synthetic biology and the ability to expand the product scope of CO2 reduction will be crucial to poising this technology as a replacement, or one of many replacements, for the petrochemical industry,” Sakimoto says.

So, do the inorganic-biological hybrids have commercial potential? “I sure hope so!” he says. “Many current systems in artificial photosynthesis require solid electrodes, which is a huge cost. Our algal biofuels are much more attractive, as the whole CO2-to-chemical apparatus is self-contained and only requires a big vat out in the sun.” But he points out that the system still requires some tweaking to tune both the semiconductor and the bacteria. He also suggests that it is possible that the hybrid bacteria he created may have some naturally occurring analog. “A future direction, if this phenomenon exists in nature, would be to bioprospect for these organisms and put them to use,” he says.

For more insight into the work, check out Dexter Johnson’s Aug. 22, 2017 posting on his Nanoclast blog (on the IEEE [Institute of Electrical and Electronics Engineers] website),

“It’s actually a natural, overlooked feature of their biology,” explains Sakimoto in an e-mail interview with IEEE Spectrum. “This bacterium has a detoxification pathway, meaning if it encounters a toxic metal, like cadmium, it will try to precipitate it out, thereby detoxifying it. So when we introduce cadmium ions into the growth medium in which M. thermoacetica is hanging out, it will convert the amino acid cysteine into sulfide, which precipitates out cadmium as cadmium sulfide. The crystals then assemble and stick onto the bacterium through normal electrostatic interactions.”

I’ve just excerpted one bit, there’s more in Dexter’s posting.