Tag Archives: US

New nanomapping technology: CRISPR-CAS9 as a programmable nanoparticle

A November 21, 2017 news item on Nanowerk describes a rather extraordinary (to me, anyway) approach to using CRRISP ( Clustered Regularly Interspaced Short Palindromic Repeats)-CAS9 (Note: A link has been removed),

A team of scientists led by Virginia Commonwealth University physicist Jason Reed, Ph.D., have developed new nanomapping technology that could transform the way disease-causing genetic mutations are diagnosed and discovered. Described in a study published today [November 21, 2017] in the journal Nature Communications (“DNA nanomapping using CRISPR-Cas9 as a programmable nanoparticle”), this novel approach uses high-speed atomic force microscopy (AFM) combined with a CRISPR-based chemical barcoding technique to map DNA nearly as accurately as DNA sequencing while processing large sections of the genome at a much faster rate. What’s more–the technology can be powered by parts found in your run-of-the-mill DVD player.

A November 21, 2017 Virginia Commonwealth University news release by John Wallace, which originated the news item, provides more detail,

The human genome is made up of billions of DNA base pairs. Unraveled, it stretches to a length of nearly six feet long. When cells divide, they must make a copy of their DNA for the new cell. However, sometimes various sections of the DNA are copied incorrectly or pasted together at the wrong location, leading to genetic mutations that cause diseases such as cancer. DNA sequencing is so precise that it can analyze individual base pairs of DNA. But in order to analyze large sections of the genome to find genetic mutations, technicians must determine millions of tiny sequences and then piece them together with computer software. In contrast, biomedical imaging techniques such as fluorescence in situ hybridization, known as FISH, can only analyze DNA at a resolution of several hundred thousand base pairs.

Reed’s new high-speed AFM method can map DNA to a resolution of tens of base pairs while creating images up to a million base pairs in size. And it does it using a fraction of the amount of specimen required for DNA sequencing.

“DNA sequencing is a powerful tool, but it is still quite expensive and has several technological and functional limitations that make it difficult to map large areas of the genome efficiently and accurately,” said Reed, principal investigator on the study. Reed is a member of the Cancer Molecular Genetics research program at VCU Massey Cancer Center and an associate professor in the Department of Physics in the College of Humanities and Sciences.

“Our approach bridges the gap between DNA sequencing and other physical mapping techniques that lack resolution,” he said. “It can be used as a stand-alone method or it can complement DNA sequencing by reducing complexity and error when piecing together the small bits of genome analyzed during the sequencing process.”

IBM scientists made headlines in 1989 when they developed AFM technology and used a related technique to rearrange molecules at the atomic level to spell out “IBM.” AFM achieves this level of detail by using a microscopic stylus — similar to a needle on a record player — that barely makes contact with the surface of the material being studied. The interaction between the stylus and the molecules creates the image. However, traditional AFM is too slow for medical applications and so it is primarily used by engineers in materials science.

“Our device works in the same fashion as AFM but we move the sample past the stylus at a much greater velocity and use optical instruments to detect the interaction between the stylus and the molecules. We can achieve the same level of detail as traditional AFM but can process material more than a thousand times faster,” said Reed, whose team proved the technology can be mainstreamed by using optical equipment found in DVD players. “High-speed AFM is ideally suited for some medical applications as it can process materials quickly and provide hundreds of times more resolution than comparable imaging methods.”

Increasing the speed of AFM was just one hurdle Reed and his colleagues had to overcome. In order to actually identify genetic mutations in DNA, they had to develop a way to place markers or labels on the surface of the DNA molecules so they could recognize patterns and irregularities. An ingenious chemical barcoding solution was developed using a form of CRISPR technology.

CRISPR has made a lot of headlines recently in regard to gene editing. CRISPR is an enzyme that scientists have been able to “program” using targeting RNA in order to cut DNA at precise locations that the cell then repairs on its own. Reed’s team altered the chemical reaction conditions of the CRISPR enzyme so that it only sticks to the DNA and does not actually cut it.

“Because the CRISPR enzyme is a protein that’s physically bigger than the DNA molecule, it’s perfect for this barcoding application,” Reed said. “We were amazed to discover this method is nearly 90 percent efficient at bonding to the DNA molecules. And because it’s easy to see the CRISPR proteins, you can spot genetic mutations among the patterns in DNA.”

To demonstrate the technique’s effectiveness, the researchers mapped genetic translocations present in lymph node biopsies of lymphoma patients. Translocations occur when one section of the DNA gets copied and pasted to the wrong place in the genome. They are especially prevalent in blood cancers such as lymphoma but occur in other cancers as well.

While there are many potential uses for this technology, Reed and his team are focusing on medical applications. They are currently developing software based on existing algorithms that can analyze patterns in sections of DNA up to and over a million base pairs in size. Once completed, it would not be hard to imagine this shoebox-sized instrument in pathology labs assisting in the diagnosis and treatment of diseases linked to genetic mutations.

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

DNA nanomapping using CRISPR-Cas9 as a programmable nanoparticle by Andrey Mikheikin, Anita Olsen, Kevin Leslie, Freddie Russell-Pavier, Andrew Yacoot, Loren Picco, Oliver Payton, Amir Toor, Alden Chesney, James K. Gimzewski, Bud Mishra, & Jason Reed. Nature Communications 8, Article number: 1665 (2017) doi:10.1038/s41467-017-01891-9 Published online: 21 November 2017

This paper is open access.

China is world leader in nanotechnology and in other fields too?

State of Chinese nanoscience/nanotechnology

China claims to be the world leader in the field in a white paper announced in an August 29, 2017 Springer Nature press release,

Springer Nature, the National Center for Nanoscience and Technology, China and the National Science Library of the Chinese Academy of Sciences (CAS) released in both Chinese and English a white paper entitled “Small Science in Big China: An overview of the state of Chinese nanoscience and technology” at NanoChina 2017, an international conference on nanoscience and technology held August 28 and 29 in Beijing. The white paper looks at the rapid growth of China’s nanoscience research into its current role as the world’s leader [emphasis mine], examines China’s strengths and challenges, and makes some suggestions for how its contribution to the field can continue to thrive.

The white paper points out that China has become a strong contributor to nanoscience research in the world, and is a powerhouse of nanotechnology R&D. Some of China’s basic research is leading the world. China’s applied nanoscience research and the industrialization of nanotechnologies have also begun to take shape. These achievements are largely due to China’s strong investment in nanoscience and technology. China’s nanoscience research is also moving from quantitative increase to quality improvement and innovation, with greater emphasis on the applications of nanotechnologies.

“China took an initial step into nanoscience research some twenty years ago, and has since grown its commitment at an unprecedented rate, as it has for scientific research as a whole. Such a growth is reflected both in research quantity and, importantly, in quality. Therefore, I regard nanoscience as a window through which to observe the development of Chinese science, and through which we could analyze how that rapid growth has happened. Further, the experience China has gained in developing nanoscience and related technologies is a valuable resource for the other countries and other fields of research to dig deep into and draw on,” said Arnout Jacobs, President, Greater China, Springer Nature.

The white paper explores at China’s research output relative to the rest of the world in terms of research paper output, research contribution contained in the Nano database, and finally patents, providing insight into China’s strengths and expertise in nano research. The white paper also presents the results of a survey of experts from the community discussing the outlook for and challenges to the future of China’s nanoscience research.

China nano research output: strong rise in quantity and quality

In 1997, around 13,000 nanoscience-related papers were published globally. By 2016, this number had risen to more than 154,000 nano-related research papers. This corresponds to a compound annual growth rate of 14% per annum, almost four times the growth in publications across all areas of research of 3.7%. Over the same period of time, the nano-related output from China grew from 820 papers in 1997 to over 52,000 papers in 2016, a compound annual growth rate of 24%.

China’s contribution to the global total has been growing steadily. In 1997, Chinese researchers co-authored just 6% of the nano-related papers contained in the Science Citation Index (SCI). By 2010, this grew to match the output of the United States. They now contribute over a third of the world’s total nanoscience output — almost twice that of the United States.

Additionally, China’s share of the most cited nanoscience papers has kept increasing year on year, with a compound annual growth rate of 22% — more than three times the global rate. It overtook the United States in 2014 and its contribution is now many times greater than that of any other country in the world, manifesting an impressive progression in both quantity and quality.

The rapid growth of nanoscience in China has been enabled by consistent and strong financial support from the Chinese government. As early as 1990, the State Science and Technology Committee, the predecessor of the Ministry of Science and Technology (MOST), launched the Climbing Up project on nanomaterial science. During the 1990s, the National Natural Science Foundation of China (NSFC) also funded nearly 1,000 small-scale projects in nanoscience. In the National Guideline on Medium- and Long-Term Program for Science and Technology Development (for 2006−2020) issued in early 2006 by the Chinese central government, nanoscience was identified as one of four areas of basic research and received the largest proportion of research budget out of the four areas. The brain boomerang, with more and more foreign-trained Chinese researchers returning from overseas, is another contributor to China’s rapid rise in nanoscience.

The white paper clarifies the role of Chinese institutions, including CAS, in driving China’s rise to become the world’s leader in nanoscience. Currently, CAS is the world’s largest producer of high impact nano research, contributing more than twice as many papers in the 1% most-cited nanoscience literature than its closest competitors. In addition to CAS, five other Chinese institutions are ranked among the global top 20 in terms of output of top cited 1% nanoscience papers — Tsinghua University, Fudan University, Zhejiang University, University of Science and Technology of China and Peking University.

Nano database reveals advantages and focus of China’s nano research

The Nano database (http://nano.nature.com) is a comprehensive platform that has been recently developed by Nature Research – part of Springer Nature – which contains nanoscience-related papers published in 167 peer-reviewed journals including Advanced Materials, Nano Letters, Nature, Science and more. Analysis of the Nano database of nanomaterial-containing articles published in top 30 journals during 2014–2016 shows that Chinese scientists explore a wide range of nanomaterials, the five most common of which are nanostructured materials, nanoparticles, nanosheets, nanodevices and nanoporous materials.

In terms of the research of applications, China has a clear leading edge in catalysis research, which is the most popular area of the country’s quality nanoscience papers. Chinese nano researchers also contributed significantly to nanomedicine and energy-related applications. China is relatively weaker in nanomaterials for electronics applications, compared to other research powerhouses, but robotics and lasers are emerging applications areas of nanoscience in China, and nanoscience papers addressing photonics and data storage applications also see strong growth in China. Over 80% of research from China listed in the database explicitly mentions applications of the nanostructures and nanomaterials described, notably higher than from most other leading nations such as the United States, Germany, the UK, Japan and France.

Nano also reveals the extent of China’s international collaborations in nano research. China has seen the percentage of its internationally collaborated papers increasing from 36% in 2014 to 44% in 2016. This level of international collaboration, similar to that of South Korea, is still much lower than that of the western countries, and the rate of growth is also not as fast as those in the United States, France and Germany.

The United States is China’s biggest international collaborator, contributing to 55% of China’s internationally collaborated papers on nanoscience that are included in the top 30 journals in the Nano database. Germany, Australia and Japan follow in a descending order as China’s collaborators on nano-related quality papers.

China’s patent output: topping the world, mostly applied domestically

Analysis of the Derwent Innovation Index (DII) database of Clarivate Analytics shows that China’s accumulative total number of patent applications for the past 20 years, amounting to 209,344 applications, or 45% of the global total, is more than twice as many as that of the United States, the second largest contributor to nano-related patents. China surpassed the United States and ranked the top in the world since 2008.

Five Chinese institutions, including the CAS, Zhejiang University, Tsinghua University, Hon Hai Precision Industry Co., Ltd. and Tianjin University can be found among the global top 10 institutional contributors to nano-related patent applications. CAS has been at the top of the global rankings since 2008, with a total of 11,218 patent applications for the past 20 years. Interestingly, outside of China, most of the other big institutional contributors among the top 10 are commercial enterprises, while in China, research or academic institutions are leading in patent applications.

However, the number of nano-related patents China applied overseas is still very low, accounting for only 2.61% of its total patent applications for the last 20 years cumulatively, whereas the proportion in the United States is nearly 50%. In some European countries, including the UK and France, more than 70% of patent applications are filed overseas.

China has high numbers of patent applications in several popular technical areas for nanotechnology use, and is strongest in patents for polymer compositions and macromolecular compounds. In comparison, nano-related patent applications in the United States, South Korea and Japan are mainly for electronics or semiconductor devices, with the United States leading the world in the cumulative number of patents for semiconductor devices.

Outlook, opportunities and challenges

The white paper highlights that the rapid rise of China’s research output and patent applications has painted a rosy picture for the development of Chinese nanoscience, and in both the traditionally strong subjects and newly emerging areas, Chinese nanoscience shows great potential.

Several interviewed experts in the survey identify catalysis and catalytic nanomaterials as the most promising nanoscience area for China. The use of nanotechnology in the energy and medical sectors was also considered very promising.

Some of the interviewed experts commented that the industrial impact of China’s nanotechnology is limited and there is still a gap between nanoscience research and the industrialization of nanotechnologies. Therefore, they recommended that the government invest more in applied research to drive the translation of nanoscience research and find ways to encourage enterprises to invest more in R&D.

As more and more young scientists enter the field, the competition for research funding is becoming more intense. However, this increasing competition for funding was not found to concern most interviewed young scientists, rather, they emphasized that the soft environment is more important. They recommended establishing channels that allow the suggestions or creative ideas of the young to be heard. Also, some interviewed young researchers commented that they felt that the current evaluation system was geared towards past achievements or favoured overseas experience, and recommended the development of an improved talent selection mechanism to ensure a sustainable growth of China’s nanoscience.

I have taken a look at the white paper and found it to be well written. It also provides a brief but thorough history of nanotechnology/nanoscience even adding a bit of historical information that was new to me. As for the rest of the white paper, it relies on bibliometrics (number of published papers and number of citations) and number of patents filed to lay the groundwork for claiming Chinese leadership in nanotechnology. As I’ve stated many times before, these are problematic measures but as far as I can determine they are almost the only ones we have. Frankly, as a Canadian, it doesn’t much matter to me since Canada no matter how you slice or dice it is always in a lower tier relative to science leadership in major fields. It’s the Americans who might feel inclined to debate leadership with regard to nanotechnology and other major fields and I leave it to to US commentators to take up the cudgels should they be inclined. The big bonuses here are the history, the glimpse into the Chinese perspective on the field of nanotechnology/nanoscience, and the analysis of weaknesses and strengths.

Coming up fast on Google and Amazon

A November 16, 2017 article by Christina Bonnington for Slate explores the possibility that a Chinese tech giant, Baidu,  will provide Google and Amazon serious competition in their quests to dominate world markets (Note: Links have been removed,

raven_h
The company took a playful approach to the form—but it has functional reasons for the design, too. Baidu

 

One of the most interesting companies in tech right now isn’t based in Palo Alto, or San Francisco, or Seattle. Baidu, a Chinese company with headquarters in Beijing, is taking on America’s biggest and most innovative tech titans—with style.

Baidu, a titan in its own right, leapt onto the scene as a competitor to Google in the search engine space. Since then, the company, largely underappreciated here in the U.S., has focused on beefing up its artificial intelligence efforts. Former AI chief Andrew Ng, upon leaving the company in March, credited Baidu’s CEO Robin Li on being one of the first technology leaders to fully appreciate the value of deep learning. Baidu now has a 1,300 person AI group, and that investment in AI has helped the company catch up to older, more established companies like Google and Amazon—both in emerging spaces, such as autonomous vehicles, and in consumer tech, as its latest announcement shows.

On Thursday [November 16, 2017], Baidu debuted its entrants to the popular virtual assistant space: a connected speaker and two robots. Baidu aims for the speaker to compete against options such as Amazon’s Echo line, Google Home, and Apple HomePod. Inside, the $256 device will utilize Baidu’s DuerOS conversational artificial intelligence platform, which is already used in more than 100 different smart home brands’ products. DuerOS will let you use your voice to do things like ask the speaker for information, play music, or hail a cab. Called the Raven H, the speaker includes high-end audio components from Tymphany and a unique design jointly created by acquired startup Raven Tech and Swedish consumer electronics company Teenage Engineering.

While the focus is on exciting new technology products from Baidu, the subtext, such as it is, suggests US companies had best keep an eye on its Chinese competitor(s).

Dutch/Chinese partnership to produce nanoparticles at the touch of a button

Now back to China and nanotechnology leadership and the production of nanoparticles. This announcement was made in a November 17, 2017 news item on Azonano,

Delft University of Technology [Netherlands] spin-off VSPARTICLE enters the booming Chinese market with a radical technology that allows researchers to produce nanoparticles at the push of a button. VSPARTICLE’s nanoparticle generator uses atoms, the worlds’ smallest building blocks, to provide a controllable source of nanoparticles. The start-up from Delft signed a distribution agreement with Bio-Sun to make their VSP-G1 nanoparticle generator available in China.

A November 16, 2017 VSPARTICLE press release, which originated the news item,

“We are honoured to cooperate with VSPARTICLE and bring the innovative VSP-G1 nanoparticle generator into the Chinese market. The VSP-G1 will create new possibilities for researchers in catalysis, aerosol, healthcare and electronics,” says Yinghui Cai, CEO of Bio-Sun.

With an exponential growth in nanoparticle research in the last decade, China is one of the leading countries in the field of nanotechnology and its applications. Vincent Laban, CFO of VSPARTICLE, explains: “Due to its immense investments in IOT, sensors, semiconductor technology, renewable energy and healthcare applications, China will eventually become one of our biggest markets. The collaboration with Bio-Sun offers a valuable opportunity to enter the Chinese market at exactly the right time.”

NANOPARTICLES ARE THE BUILDING BLOCKS OF THE FUTURE

Increasingly, scientists are focusing on nanoparticles as a key technology in enabling the transition to a sustainable future. Nanoparticles are used to make new types of sensors and smart electronics; provide new imaging and treatment possibilities in healthcare; and reduce harmful waste in chemical processes.

CURRENT RESEARCH TOOLKIT LACKS A FAST WAY FOR MAKING SPECIFIC BUILDING BLOCKS

With the latest tools in nanotechnology, researchers are exploring the possibilities of building novel materials. This is, however, a trial-and-error method. Getting the right nanoparticles often is a slow struggle, as most production methods take a substantial amount of effort and time to develop.

VSPARTICLE’S VSP-G1 NANOPARTICLE GENERATOR

With the VSP-G1 nanoparticle generator, VSPARTICLE makes the production of nanoparticles as easy as pushing a button. . Easy and fast iterations enable researchers to fast forward their research cycle, and verify their hypotheses.

VSPARTICLE

Born out of the research labs of Delft University of Technology, with over 20 years of experience in the synthesis of aerosol, VSPARTICLE believes there is a whole new world of possibilities and materials at the nanoscale. The company was founded in 2014 and has an international sales network in Europe, Japan and China.

BIO-SUN

Bio-Sun was founded in Beijing in 2010 and is a leader in promoting nanotechnology and biotechnology instruments in China. It serves many renowned customers in life science, drug discovery and material science. Bio-Sun has four branch offices in Qingdao, Shanghai, Guangzhou and Wuhan City, and a nationwide sale network.

That’s all folks!

Book commentaries: The Science of Orphan Black: The Official Companion and Star Trek Treknology; The Science of Star Trek from Tricorders to Warp Drive

I got more than I expected from both books (“The Science of Orphan Black: The Official Companion” by Casey Griffin and Nina Nesseth and “Star Trek Treknology; The Science of Star Trek from Tricorders to Warp Drive” by Ethan Siegel) I’m going to discuss by changing my expectations.

The Science of Orphan Black: The Official Companion

I had expected a book about the making of the series with a few insider stories about the production along with some science. Instead, I was treated to a season by season breakdown of the major scientific and related ethical issues in the fields of cloning and genetics.I don’t follow those areas exhaustively but from my inexpert perspective, the authors covered everything I could have hoped for (e.g., CRISPR/CAS9, Henrietta Lacks, etc.) in an accessible but demanding writing style  In other words, it’s a good read but it’s not a light read.

There are many, many pictures of Tatiana Maslany as one of her various clone identities in the book. Unfortunately, the images do not boast good reproduction values. This was disconcerting as it can lead a reader (yes, that was me) to false expectations (e.g., this is a picture book) concerning the contents. The boxed snippets from the scripts and explanatory notes inset into the text helped to break up some of the more heavy going material while providing additional historical/scripting/etc. perspectives. One small niggle, the script snippets weren’t always as relevant to the discussion at hand as the authors no doubt hoped.

I suggest reading both the Foreword by Cosima Herter, the series science consultant, and (although it could have done with a little editing) The Conversation between Cosima Herter and Graeme Manson (one of the producers). That’s where you’ll find that the series seems to have been incubated in Vancouver, Canada. It’s also where you’ll find out how much of Cosima Herter’s real life story is included in the Cosima clone’s life story.

The Introduction tells you how the authors met (as members of ‘the clone club’) and started working together as recappers for the series. (For anyone unfamiliar with the phenomenon or terminology, episodes of popular series are recapitulated [recapped] on one or more popular websites. These may or may not be commercial, i.e., some are fan sites.)

One of the authors, Casey Griffin, is a PhD candidate at the University of Southern California (USC) studying in the field of developmental and stem cell biology. I was not able to get much more information but did find her LinkedIn profile. The other author also has a science background. Nina Nesseth is described as a science communicator on the back cover of the book but she’s described as a staff scientist for Science North, a science centre located in Sudbury, Ontario, Canada. Her LinkedIn profile lists an honours Bachelor of Science (Biological and Medical Sciences) from Laurentian University, also located in Sudbury, Ontario.

It’s no surprise, given the authors’ educational background, that a bibliography (selected) has been included. This is something I very much appreciated. Oddly, given that Nesseth lists a graduate certificate in publishing as one of her credentials (on LinkedIn), there is no index (!?!). Unusually, the copyright page is at the back of the book instead of the front and boasts a fairly harsh copyright notice (summary: don’t copy anything, ever … unless you get written permission from ECW Press and the other copyright owners; Note: Herter is the copyright owner of her Foreword while the authors own the rest).

There are logos on the copyright page—more than I’m accustomed to seeing. Interestingly, two of them are government logos. It seems that taxpayers contributed to the publication of this book. The copyright notice seems a little facey to me since taxpayers (at least partially) subsidized the book, as well, Canadian copyright law has a concept called fair dealing (in the US, there’s something similar: fair use). In other words, if I chose, I could copy portions of the text without asking for permission if there’s no intent to profit from it and as long as I give attributions.

How, for example, could anyone profit from this?

In fact, in January 2017, Jun Wu and colleagues published their success in creating pig-human hybrids. (description of real research on chimeras on p. 98)

Or this snippet of dialogue,

[Charlotte] You’re my big sister.

[Sarah] How old are you? (p. 101)

All the quoted text is from “The Science of Orphan Black: The Official Companion” by Casey Griffin and Nina Nesseth (paperback published August 22, 2017).

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,

Getting back to the book, copyright silliness aside, it’s a good book for anyone interested in some of the  science and the issues associated with biotechnology, synthetic biology, genomes, gene editing technologies, chimeras, and more. I don’t think you need to have seen the series in order to appreciate the book.

Star Trek Treknology; The Science of Star Trek from Tricorders to Warp Drive

This looks and feels like a coffee table book. The images in this book are of a much higher quality than those in the ‘Orphan Black’ book. With thicker paper and extensive ink coverage lending to its glossy, attractive looks, it’s a physically heavy book. The unusually heavy use of black ink  would seem to be in service of conveying the feeling that you are exploring the far reaches of outer space.

It’s clear that “Star Trek Treknology; The Science of Star Trek from Tricorders to Warp Drive’s” author, Ethan Siegel, PhD., is a serious Star Trek and space travel fan. All of the series and movies are referenced at one time or another in the book in relationship to technology (treknology).

Unlike Siegel, while I love science fiction and Star Trek, I have never been personally interested in space travel. Regardless, Siegel did draw me in with his impressive ability to describe and explain physics-related ideas. Unfortunately, his final chapter on medical and biological ‘treknology’ is not as good. He covers a wide range of topics but no one is an expert on everything.

Siegel has a Wikipedia entry, which notes this (Note: Links have been removed),

Ethan R. Siegel (August 3, 1978, Bronx)[1] is an American theoretical astrophysicist and science writer, who studies Big Bang theory. He is a professor at Lewis & Clark College and he blogs at Starts With a Bang, on ScienceBlogs and also on Forbes.com since 2016.

By contrast with the ‘Orphan Black’ book, the tone is upbeat. It’s one of the reasons Siegel appreciates Star Trek in its various iterations,

As we look at the real-life science and technology behind the greatest advances anticipated by Star Trek, it’s worth remembering that the greatest legacy of the show is its message of hope. The future can be brighter and better than our past or present has ever been. It’s our continuing mission to make it so. (p. 6)

All the quoted text is from “Star Trek Treknology; The Science of Star Trek from Tricorders to Warp Drive” by Ethan Siegel (hard cover published October 15, 2017).

This book too has one of those copyright notices that fail to note you don’t need permission when it’s fair dealing to copy part of the text. While it does have an index, it’s on the anemic side and, damningly, there are neither bibliography nor reference notes of any sort. If Siegel hadn’t done such a good writing job, I might not have been so distressed.

For example, it’s frustrating for someone like me who’s been trying to get information on cortical/neural  implants and finds this heretofore unknown and intriguing tidbit in Siegel’s text,

In 2016, the very first successful cortical implant into a patient with ALS [amyotrophic lateral sclerosis] was completed, marking the very first fully implanted brain-computer interface in a human being. (p. 180)

Are we talking about the Australia team, which announced human clinical trials for their neural/cortical implant (my February 15, 2016 posting) or was it preliminary work by a team in Ohio (US) which later (?) announced a successful implant for a quadriplegic (also known as tetraplegic) patient who was then able to move hands and fingers (see my April 19, 2016 posting)? Or is it an entirely different team?

One other thing, I was a bit surprised to see no mention of quantum or neuromorphic computing in the chapter on computing. I don’t believe either was part of the Star Trek universe but they (neuromorphic and quantum computing) are important developments and Siegel makes a point, on at least a few occasions, of contrasting present day research with what was and wasn’t ‘predicted’ by Star Trek.

As for the ‘predictions’, there’s a longstanding interplay between storytellers and science and sometimes it can be a little hard to figure out which came first. I think Siegel might have emphasized that give and take a bit more.

Regardless of my nitpicking, Siegel is a good writer and managed to put an astonishing amount of ‘educational’ material into a lively and engaging book. That is not easy.

Final thoughts

I enjoyed both books and am very excited to see grounded science being presented along with the fictional stories of both universes (Star Trek and Orphan Black).

Yes, both books have their shortcomings (harsh copyright notices, no index, no bibliography, no reference notes, etc.) but in the main they offer adults who are sufficiently motivated a wealth of current scientific and technical information along with some elucidation of ethical issues.

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

MIT (Massachusetts Institute of Technology) researchers have developed a new nonviral means of delivering CRISPR ((clustered regularly interspaced short palindromic repeats)-CAS9 gene therapy according to a November 13, 2017 news item on Nanowerk,

In a new study, MIT researchers have developed nanoparticles that can deliver the CRISPR genome-editing system and specifically modify genes in mice. The team used nanoparticles to carry the CRISPR components, eliminating the need to use viruses for delivery.

Using the new delivery technique, the researchers were able to cut out certain genes in about 80 percent of liver cells, the best success rate ever achieved with CRISPR in adult animals.

In a new study, MIT researchers have developed nanoparticles that can deliver the CRISPR genome-editing system and specifically modify genes, eliminating the need to use viruses for delivery. Image: MIT News

A November 13, 2017 MIT news release (also on EurekAlert), which originated the news item, provides more details about the research and a good description of and comparison between using a viral system and using a nanoparticle-based system to deliver CRISPR-CAS9,

“What’s really exciting here is that we’ve shown you can make a nanoparticle that can be used to permanently and specifically edit the DNA in the liver of an adult animal,” says Daniel Anderson, an associate professor in MIT’s Department of Chemical Engineering and a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science (IMES).

One of the genes targeted in this study, known as Pcsk9, regulates cholesterol levels. Mutations in the human version of the gene are associated with a rare disorder called dominant familial hypercholesterolemia, and the FDA recently approved two antibody drugs that inhibit Pcsk9. However these antibodies need to be taken regularly, and for the rest of the patient’s life, to provide therapy. The new nanoparticles permanently edit the gene following a single treatment, and the technique also offers promise for treating other liver disorders, according to the MIT team.

Anderson is the senior author of the study, which appears in the Nov. 13 [2017] issue of Nature Biotechnology. The paper’s lead author is Koch Institute research scientist Hao Yin. Other authors include David H. Koch Institute Professor Robert Langer of MIT, professors Victor Koteliansky and Timofei Zatsepin of the Skolkovo Institute of Science and Technology [Russia], and Professor Wen Xue of the University of Massachusetts Medical School.

Targeting disease

Many scientists are trying to develop safe and efficient ways to deliver the components needed for CRISPR, which consists of a DNA-cutting enzyme called Cas9 and a short RNA that guides the enzyme to a specific area of the genome, directing Cas9 where to make its cut.

In most cases, researchers rely on viruses to carry the gene for Cas9, as well as the RNA guide strand. In 2014, Anderson, Yin, and their colleagues developed a nonviral delivery system in the first-ever demonstration of curing a disease (the liver disorder tyrosinemia) with CRISPR in an adult animal. However, this type of delivery requires a high-pressure injection, a method that can also cause some damage to the liver.

Later, the researchers showed they could deliver the components without the high-pressure injection by packaging messenger RNA (mRNA) encoding Cas9 into a nanoparticle instead of a virus. Using this approach, in which the guide RNA was still delivered by a virus, the researchers were able to edit the target gene in about 6 percent of hepatocytes, which is enough to treat tyrosinemia.

While that delivery technique holds promise, in some situations it would be better to have a completely nonviral delivery system, Anderson says. One consideration is that once a particular virus is used, the patient will develop antibodies to it, so it couldn’t be used again. Also, some patients have pre-existing antibodies to the viruses being tested as CRISPR delivery vehicles.

In the new Nature Biotechnology paper, the researchers came up with a system that delivers both Cas9 and the RNA guide using nanoparticles, with no need for viruses. To deliver the guide RNAs, they first had to chemically modify the RNA to protect it from enzymes in the body that would normally break it down before it could reach its destination.

The researchers analyzed the structure of the complex formed by Cas9 and the RNA guide, or sgRNA, to figure out which sections of the guide RNA strand could be chemically modified without interfering with the binding of the two molecules. Based on this analysis, they created and tested many possible combinations of modifications.

“We used the structure of the Cas9 and sgRNA complex as a guide and did tests to figure out we can modify as much as 70 percent of the guide RNA,” Yin says. “We could heavily modify it and not affect the binding of sgRNA and Cas9, and this enhanced modification really enhances activity.”

Reprogramming the liver

The researchers packaged these modified RNA guides (which they call enhanced sgRNA) into lipid nanoparticles, which they had previously used to deliver other types of RNA to the liver, and injected them into mice along with nanoparticles containing mRNA that encodes Cas9.

They experimented with knocking out a few different genes expressed by hepatocytes, but focused most of their attention on the cholesterol-regulating Pcsk9 gene. The researchers were able to eliminate this gene in more than 80 percent of liver cells, and the Pcsk9 protein was undetectable in these mice. They also found a 35 percent drop in the total cholesterol levels of the treated mice.

The researchers are now working on identifying other liver diseases that might benefit from this approach, and advancing these approaches toward use in patients.

“I think having a fully synthetic nanoparticle that can specifically turn genes off could be a powerful tool not just for Pcsk9 but for other diseases as well,” Anderson says. “The liver is a really important organ and also is a source of disease for many people. If you can reprogram the DNA of your liver while you’re still using it, we think there are many diseases that could be addressed.”

“We are very excited to see this new application of nanotechnology open new avenues for gene editing,” Langer adds.

The research was funded by the National Institutes of Health (NIH), the Russian Scientific Fund, the Skoltech Center, and the Koch Institute Support (core) Grant from the National Cancer Institute.

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

Structure-guided chemical modification of guide RNA enables potent non-viral in vivo genome editing by Hao Yin, Chun-Qing Song, Sneha Suresh, Qiongqiong Wu, Stephen Walsh, Luke Hyunsik Rhym, Esther Mintzer, Mehmet Fatih Bolukbasi, Lihua Julie Zhu, Kevin Kauffman, Haiwei Mou, Alicia Oberholzer, Junmei Ding, Suet-Yan Kwan, Roman L Bogorad, Timofei Zatsepin, Victor Koteliansky, Scot A Wolfe, Wen Xue, Robert Langer, & Daniel G Anderson. Nature Biotechnology doi:10.1038/nbt.4005 Published online: 13 November 2017

This paper is behind a paywall.

Why don’t you CRISPR yourself?

It must have been quite the conference. Josiah Zayner plunged a needle into himself and claimed to have changed his DNA (deoxyribonucleic acid) while giving his talk. (*Segue: There is some Canadian content if you keep reading.*) From an Oct. 10, 2017 article by Adele Peters for Fast Company (Note: A link has been removed),

“What we’ve got here is some DNA, and this is a syringe,” Josiah Zayner tells a room full of synthetic biologists and other researchers. He fills the needle and plunges it into his skin. “This will modify my muscle genes and give me bigger muscles.”

Zayner, a biohacker–basically meaning he experiments with biology in a DIY lab rather than a traditional one–was giving a talk called “A Step-by-Step Guide to Genetically Modifying Yourself With CRISPR” at the SynBioBeta conference in San Francisco, where other presentations featured academics in suits and the young CEOs of typical biotech startups. Unlike the others, he started his workshop by handing out shots of scotch and a booklet explaining the basics of DIY [do-it-yourwelf] genome engineering.

If you want to genetically modify yourself, it turns out, it’s not necessarily complicated. As he offered samples in small baggies to the crowd, Zayner explained that it took him about five minutes to make the DNA that he brought to the presentation. The vial held Cas9, an enzyme that snips DNA at a particular location targeted by guide RNA, in the gene-editing system known as CRISPR. In this case, it was designed to knock out the myostatin gene, which produces a hormone that limits muscle growth and lets muscles atrophy. In a study in China, dogs with the edited gene had double the muscle mass of normal dogs. If anyone in the audience wanted to try it, they could take a vial home and inject it later. Even rubbing it on skin, Zayner said, would have some effect on cells, albeit limited.

Peters goes on to note that Zayner has a PhD in molecular biology and biophysics and worked for NASA (US National Aeronautics and Space Administration). Zayner’s Wikipedia entry fills in a few more details (Note: Links have been removed),

Zayner graduated from the University of Chicago with a Ph.D. in biophysics in 2013. He then spent two years as a researcher at NASA’s Ames Research Center,[2] where he worked on Martian colony habitat design. While at the agency, Zayner also analyzed speech patterns in online chat, Twitter, and books, and found that language on Twitter and online chat is closer to how people talk than to how they write.[3] Zayner found NASA’s scientific work less innovative than he expected, and upon leaving in January 2016, he launched a crowdfunding campaign to provide CRISPR kits to let the general public experiment with editing bacterial DNA. He also continued his grad school business, The ODIN, which sells kits to let the general public experiment at home. As of May 2016, The ODIN had four employees and operates out of Zayner’s garage.[2]

He refers to himself as a biohacker and believes in the importance in letting the general public participate in scientific experimentation, rather than leaving it segregated to labs.[2][4][1] Zayner found the biohacking community exclusive and hierarchical, particularly in the types of people who decide what is “safe”. He hopes that his projects can let even more people experiment in their homes. Other scientists responded that biohacking is inherently privileged, as it requires leisure time and money, and that deviance from the safety rules of concern would lead to even harsher regulations for all.[5] Zayner’s public CRISPR kit campaign coincided with wider scrutiny over genetic modification. Zayner maintained that these fears were based on misunderstandings of the product, as genetic experiments on yeast and bacteria cannot produce a viral epidemic.[6][7] In April 2015, Zayner ran a hoax on Craigslist to raise awareness about the future potential of forgery in forensics genetics testing.[8]

In February 2016, Zayner performed a full body microbiome transplant on himself, including a fecal transplant, to experiment with microbiome engineering and see if he could cure himself from gastrointestinal and other health issues. The microbiome from the donors feces successfully transplanted in Zayner’s gut according to DNA sequencing done on samples.[2] This experiment was documented by filmmakers Kate McLean and Mario Furloni and turned into the short documentary film Gut Hack.[9]

In December 2016, Zayner created a fluorescent beer by engineering yeast to contain the green fluorescent protein from jellyfish. Zayner’s company, The ODIN, released kits to allow people to create their own engineered fluorescent yeast and this was met with some controversy as the FDA declared the green fluorescent protein can be seen as a color additive.[10] Zayner, views the kit as a way that individual can use genetic engineering to create things in their everyday life.[11]

I found the video for Zayner’s now completed crowdfunding campaign,

I also found The ODIN website (mentioned in the Wikipedia essay) where they claim to be selling various gene editing and gene engineering kits including the CRISPR editing kits mentioned in Peters’ article,

In 2016, he [Zayner] sold $200,000 worth of products, including a kit for yeast that can be used to brew glowing bioluminescent beer, a kit to discover antibiotics at home, and a full home lab that’s roughly the cost of a MacBook Pro. In 2017, he expects to double sales. Many kits are simple, and most buyers probably aren’t using the supplies to attempt to engineer themselves (many kits go to classrooms). But Zayner also hopes that as people using the kits gain genetic literacy, they experiment in wilder ways.

Zayner sells a full home biohacking lab that’s roughly the cost of a MacBook Pro. [Photo: The ODIN]

He questions whether traditional research methods, like randomized controlled trials, are the only way to make discoveries, pointing out that in newer personalized medicine (such as immunotherapy for cancer, which is personalized for each patient), a sample size of one person makes sense. At his workshop, he argued that people should have the choice to self-experiment if they want to; we also change our DNA when we drink alcohol or smoke cigarettes or breathe in dirty city air. Other society-sanctioned activities are more dangerous. “We sacrifice maybe a million people a year to the car gods,” he said. “If you ask someone, ‘Would you get rid of cars?’–no.” …

US researchers both conventional and DIY types such as Zayner are not the only ones who are editing genes. The Chinese study mentioned in Peters’ article was written up in an Oct. 19, 2015 article by Antonio Regalado for the MIT [Massachusetts Institute of Technology] Technology Review (Note: Links have been removed),

Scientists in China say they are the first to use gene editing to produce customized dogs. They created a beagle with double the amount of muscle mass by deleting a gene called myostatin.

The dogs have “more muscles and are expected to have stronger running ability, which is good for hunting, police (military) applications,” Liangxue Lai, a researcher with the Key Laboratory of Regenerative Biology at the Guangzhou Institutes of Biomedicine and Health, said in an e-mail.

Lai and 28 colleagues reported their results last week in the Journal of Molecular Cell Biology, saying they intend to create dogs with other DNA mutations, including ones that mimic human diseases such as Parkinson’s and muscular dystrophy. “The goal of the research is to explore an approach to the generation of new disease dog models for biomedical research,” says Lai. “Dogs are very close to humans in terms of metabolic, physiological, and anatomical characteristics.”

Lai said his group had no plans breed to breed the extra-muscular beagles as pets. Other teams, however, could move quickly to commercialize gene-altered dogs, potentially editing their DNA to change their size, enhance their intelligence, or correct genetic illnesses. A different Chinese Institute, BGI, said in September it had begun selling miniature pigs, created via gene editing, for $1,600 each as novelty pets.

People have been influencing the genetics of dogs for millennia. By at least 36,000 years ago, early humans had already started to tame wolves and shape the companions we have today. Charles Darwin frequently cited dog breeding in The Origin of Species to demonstrate how evolution gradually occurs by a process of selection. With CRISPR, however, evolution is no longer gradual or subject to chance. It is immediate and under human control.

It is precisely that power that is stirring wide debate and concern over CRISPR. Yet at least some researchers think that gene-edited dogs could put a furry, friendly face on the technology. In an interview this month, George Church, a professor at Harvard University who leads a large effort to employ CRISPR editing, said he thinks it will be possible to augment dogs by using DNA edits to make them live longer or simply make them smarter.

Church said he also believed the alteration of dogs and other large animals could open a path to eventual gene editing of people. “Germline editing of pigs or dogs offers a line into it,” he said. “People might say, ‘Hey, it works.’ ”

In the meantime, Zayner’s ideas are certainly thought provoking. I’m not endorsing either his products or his ideas but it should be noted that early science pioneers such as Humphrey Davy and others experimented on themselves. For anyone unfamiliar with Davy, (from the Humphrey Davy Wikipedia entry; Note: Links have been removed),

Sir Humphry Davy, 1st Baronet PRS MRIA FGS (17 December 1778 – 29 May 1829) was a Cornish chemist and inventor,[1] who is best remembered today for isolating a series of substances for the first time: potassium and sodium in 1807 and calcium, strontium, barium, magnesium and boron the following year, as well as discovering the elemental nature of chlorine and iodine. He also studied the forces involved in these separations, inventing the new field of electrochemistry. Berzelius called Davy’s 1806 Bakerian Lecture On Some Chemical Agencies of Electricity[2] “one of the best memoirs which has ever enriched the theory of chemistry.”[3] He was a Baronet, President of the Royal Society (PRS), Member of the Royal Irish Academy (MRIA), and Fellow of the Geological Society (FGS). He also invented the Davy lamp and a very early form of incandescent light bulb.

Canadian content*

A Nov. 11, 2017 posting on the Canadian Broadcasting Corporation’s (CBC) Quirks and Quarks blog notes that self-experimentation has a long history and goes on to describe Zayner’s and others biohacking exploits before describing the legality of biohacking in Canada,

With biohackers entering into the space traditionally held by scientists and clinicians, it begs questions. Professor Timothy Caulfield, a Canada research chair in health, law and policy at the University of Alberta, says when he hears of somebody giving themselves biohacked gene therapy, he wonders: “Is this legal? Is this safe? And if it’s not safe, is there anything that we can do about regulating it? And to be honest with you that’s a tough question and I think it’s an open question.”

In Canada, Caulfield says, Health Canada focuses on products. “You have to have something that you are going to regulate or you have to have something that’s making health claims. So if there is a product that is saying I can cure X, Y, or Z, Health Canada can say, ‘Well let’s make sure the science really backs up that claim.’ The problem with these do-it-yourself approaches is there isn’t really a product. You know these people are experimenting on themselves with something that may or may not be designed for health purposes.”

According to Caufield, if you could buy a gene therapy kit that was being marketed to you to biohack yourself, that would be different. “Health Canada could jump in. But right here that’s not the case,” he says.

There are places in the world that do regulate biohacking, says Caulfield. “Germany, for example, they have specific laws for it. And here in Canada we do have a regulatory framework that says that you cannot do gene therapy that will alter the germ line. In other words, you can’t do gene therapy or any kind of genetic editing that will create a change that you will pass on to your offspring. So that would be illegal, but that’s not what’s happening here. And I don’t think there’s a regulatory framework that adequately captures it.”

Infectious disease and policy experts aren’t that concerned yet about the possibility of a biohacker unleashing a genetically modified super germ into the population.

“I think in the future that could be a problem,”says Caulfield, “but this isn’t something that would be easy to do in your garage. I think it’s complicated science. But having said that, the science is moving quickly. We need to think about how we are going to control the potential harms.”

You can find out more about the ‘wild’ people (mostly men) of early science in Richard Holmes’ 2008 book, The Age of Wonder: How the Romantic Generation Discovered the Beauty and Terror of Science.

Finally, should you be interested in connecting with synthetic biology enthusiasts, entrepreneurs, and others, SynBioBeta is more than a conference; it’s also an activity hub.

ETA January 25, 2018 (five minutes later): There are some CRISPR/CAS9 events taking place in Toronto, Canada on January 24 and 25, 2018. One is a workshop with Portuguese artist, Marta de Menezes, and the other is a panel discussion. See my January 10, 2018 posting for more details.

*’Segue: There is some Canadian content if you keep reading.’ and ‘Canadian content’ added January 25, 2018 six minutes later.

Nano-neurons from a French-Japanese-US research team

This news about nano-neurons comes from a Nov. 8, 2017 news item on defenceweb.co.za,

Researchers from the Joint Physics Unit CNRS/Thales, the Nanosciences and Nanotechnologies Centre (CNRS/Université Paris Sud), in collaboration with American and Japanese researchers, have developed the world’s first artificial nano-neuron with the ability to recognise numbers spoken by different individuals. Just like the recent development of electronic synapses described in a Nature article, this electronic nano-neuron is a breakthrough in artificial intelligence and its potential applications.

A Sept. 19, 2017 Thales press release, which originated the news item, expands on the theme,

The latest artificial intelligence algorithms are able to recognise visual and vocal cues with high levels of performance. But running these programs on conventional computers uses 10,000 times more energy than the human brain. To reduce electricity consumption, a new type of computer is needed. It is inspired by the human brain and comprises vast numbers of miniaturised neurons and synapses. Until now, however, it had not been possible to produce a stable enough artificial nano-neuron which would process the information reliably.

Today [Sept. 19, 2017 or July 27, 2017 when the paper was published in Nature?]], for the first time, researchers have developed a nano-neuron with the ability to recognise numbers spoken by different individuals with 99.6% accuracy. This breakthrough relied on the use of an exceptionally stable magnetic oscillator. Each gyration of this nano-compass generates an electrical output, which effectively imitates the electrical impulses produced by biological neurons. In the next few years, these magnetic nano-neurons could be interconnected via artificial synapses, such as those recently developed, for real-time big data analytics and classification.

The project is a collaborative initiative between fundamental research laboratories and applied research partners. The long-term goal is to produce extremely energy-efficient miniaturised chips with the intelligence needed to learn from and adapt to the constantly ever-changing and ambiguous situations of the real world. These electronic chips will have many practical applications, such as providing smart guidance to robots or autonomous vehicles, helping doctors in their diagnosis’ and improving medical prostheses. This project included researchers from the Joint Physics Unit CNRS/Thales, the AIST, the CNS-NIST, and the Nanosciences and Nanotechnologies Centre (CNRS/Université Paris-Sud).

About the CNRS
The French National Centre for Scientific Research is Europe’s largest public research institution. It produces knowledge for the benefit of society. With nearly 32,000 employees, a budget exceeding 3.2 billion euros in 2016, and offices throughout France, the CNRS is present in all scientific fields through its 1100 laboratories. With 21 Nobel laureates and 12 Fields Medal winners, the organization has a long tradition of excellence. It carries out research in mathematics, physics, information sciences and technologies, nuclear and particle physics, Earth sciences and astronomy, chemistry, biological sciences, the humanities and social sciences, engineering and the environment.

About the Université Paris-Saclay (France)
To meet global demand for higher education, research and innovation, 19 of France’s most renowned establishments have joined together to form the Université Paris-Saclay. The new university provides world-class teaching and research opportunities, from undergraduate courses to graduate schools and doctoral programmes, across most disciplines including life and natural sciences as well as social sciences. With 9,000 masters students, 5,500 doctoral candidates, an equivalent number of engineering students and an extensive undergraduate population, some 65,000 people now study at member establishments.

About the Center for Nanoscale Science & Technology (Maryland, USA)
The CNST is a national user facility purposely designed to accelerate innovation in nanotechnology-based commerce. Its mission is to operate a national, shared resource for nanoscale fabrication and measurement and develop innovative nanoscale measurement and fabrication capabilities to support researchers from industry, academia, NIST and other government agencies in advancing nanoscale technology from discovery to production. The Center, located in the Advanced Measurement Laboratory Complex on NIST’s Gaithersburg, MD campus, disseminates new nanoscale measurement methods by incorporating them into facility operations, collaborating and partnering with others and providing international leadership in nanotechnology.

About the National Institute of Advanced Industrial Science and Technology (Japan)
The National Institute of Advanced Industrial Science and Technology (AIST), one of the largest public research institutes in Japan, focuses on the creation and practical realization of technologies useful to Japanese industry and society, and on bridging the gap between innovative technological seeds and commercialization. For this, AIST is organized into 7 domains (Energy and Environment, Life Science and Biotechnology, Information Technology and Human Factors, Materials and Chemistry, Electronics and Manufacturing, Geological

About the Centre for Nanoscience and Nanotechnology (France)
Established on 1 June 2016, the Centre for Nanosciences and Nanotechnologies (C2N) was launched in the wake of the joint CNRS and Université Paris-Sud decision to merge and gather on the same campus site the Laboratory for Photonics and Nanostructures (LPN) and the Institut d’Electronique Fondamentale (IEF). Its location in the École Polytechnique district of the Paris-Saclay campus will be completed in 2017 while the new C2N buildings are under construction. The centre conducts research in material science, nanophotonics, nanoelectronics, nanobiotechnologies and microsystems, as well as in nanotechnologies.

There is a video featuring researcher Julie Grollier discussing their work but you will need your French language skills,

(If you’re interested, there is an English language video published on youtube on Feb. 19, 2017 with Julie Grollier speaking more generally about the field at the World Economic Forum about neuromorphic computing,  https://www.youtube.com/watch?v=Sm2BGkTYFeQ

Here’s a link to and a citation for the team’s July 2017 paper,

Neuromorphic computing with nanoscale spintronic oscillators by Jacob Torrejon, Mathieu Riou, Flavio Abreu Araujo, Sumito Tsunegi, Guru Khalsa, Damien Querlioz, Paolo Bortolotti, Vincent Cros, Kay Yakushiji, Akio Fukushima, Hitoshi Kubota, Shinji Yuasa, Mark D. Stiles, & Julie Grollier. Nature 547, 428–431 (27 July 2017) doi:10.1038/nature23011 Published online 26 July 2017

This paper is behind a paywall.

What human speech, jazz, and whale song have in common

Credit: iStock/Velvetfish

Seeing connections between what seem to be unrelated activities such as human speech, jazz, and whale song is fascinating to me and I’m not alone. Scientists at the University of California at Merced (UC Merced) have delivered handily on that premise according to an Oct. 13, 2017 news item on phys.org,

Jazz musicians riffing with each other, humans talking to each other and pods of killer whales all have interactive conversations that are remarkably similar to each other, new research reveals.

Cognitive science researchers at UC Merced have developed a new method for analyzing and comparing the sounds of speech, music and complex animal vocalizations like whale song and bird song. The paper detailing their findings is being published today [Oct. 12, 2017] in the Journal of the Royal Society Interface.

Their method is based on the idea that these sounds are complex because they have multiple layers of structure. Every language, for instance, has individuals sounds, roughly corresponding to letters, that combine to form syllables, words, phrases, sentences and so on. It’s a hierarchy that everyone understands intuitively. Musical compositions have their own temporal hierarchies, but until now there hasn’t been a way to directly compare the hierarchies of speech and music, or test whether similar hierarchies might exist in bird song and whale song.

An Oct. 12, 2017 UC Merced news release by Lorena Anderson, which originated the news item, provides more details about the investigation (Note: Links have been removed),

“Playing jazz music has been likened to a conversation among musicians, and killer whales are highly social creatures who vocalize as if they are talking to each other. But does jazz music really sound like a conversation, and do killer whales really sound like they are talking?” asked lead researcher and UC Merced professor Chris Kello. “We know killer whales are highly social and intelligent, but it’s hard to tell that they are interacting when you listen to recordings of them. Our method shows how much their sound patterns are like people talking, but not like other, less social whales or birds.”

The researchers figured out a way to measure and compare sound recordings by converting them into “barcodes” that capture clusters of sound energy, and clusters of clusters, across levels of a hierarchy. These barcodes allowed the researchers to directly compare temporal hierarchies in more than 200 recordings of different kinds of speech in six different languages, different kinds of popular and classical music, four different species of birds and whales singing their songs, and even thunderstorms.

Kello and his colleagues have been using the barcode method for several years. They first developed it in studies of conversations. The study published today is the first time that they applied the method to music and animal vocalizations.

“The method allows us to ask questions about language and music and animal songs that we couldn’t ask without a way to see and compare patterns in all these recordings,” Kello said.

A common song

The researchers compared barcode-style visualizations of recorded sounds.
Credit: UC Merced

Kello, fellow UC Merced cognitive science professor Ramesh Balasubramaniam, graduate student Butovens Me´de´ [or Médé] and collaborator professor Simone Dalla Bella also discovered that the haunting songs of huge humpback whales are remarkably similar to the beautiful songs of tiny nightingales and hermit thrushes in terms of their temporal hierarchies.

“Humpbacks, nightingales and hermit thrushes are solitary singers,” Kello said. “The barcodes show that their songs have similar layers of structure, but we don’t know what it means — yet.”

The idea for this project came from Kello’s sabbatical at the University of Montpellier in France, where he worked and discussed ideas with Dalla Bella. Balasubramaniam, who studies how music is perceived, is in the School of Social Sciences, Humanities and Arts with Kello, who studies speech and language processing. The project was a natural collaboration and is part of a growing research focus at UC Merced that was enabled by the National Science Foundation-funded CHASE summer school on Music and Language in 2014, and a Google Faculty Award to Kello.

Balasubramaniam is interested in continuing the work to better understand how brains distinguish between music and speech, while Kello said there are many different avenues to pursue.

For instance, the researchers found nearly identical temporal hierarchies for six different languages, which may suggest something universal about human speech. However, because this result was based on recordings of TED Talks — which have a common style and progression — Kello said it will be important to keep looking at other forms of speech and language.

One of his graduate students, Sara Schneider, is using the method to study the convergence of Spanish and English barcodes in bilingual conversations. Another graduate student, Adolfo Ramirez-Aristizabal, is working with Kello and Balasubramaniam to study whether the barcode method may shed light on how brains process speech and other complex sounds.

“Listening to music and speech, we can hear some of what we see in the barcodes, and the information may be useful for automatic classification of audio recordings. But that doesn’t mean that our brains process music and speech using these barcodes,” Kello said. “It’s intriguing, but we need to keep asking questions and go where the data lead us.”

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

Hierarchical temporal structure in music, speech and animal vocalizations: jazz is like a conversation, humpbacks sing like hermit thrushes by Christopher T. Kello, Simone Dalla Bella, Butovens Médé, Ramesh Balasubramaniam. Journal of the Royal Society Interface DOI: 10.1098/rsif.2017.0231 Published 11 October 2017

This paper appears to be open access.*

*”This paper is behind a paywall” was changed to “… appears to be open access.” at 1700 hours on January 23, 2018.

Alberta adds a newish quantum nanotechnology research hub to the Canada’s quantum computing research scene

One of the winners in Canada’s 2017 federal budget announcement of the Pan-Canadian Artificial Intelligence Strategy was Edmonton, Alberta. It’s a fact which sometimes goes unnoticed while Canadians marvel at the wonderfulness found in Toronto and Montréal where it seems new initiatives and monies are being announced on a weekly basis (I exaggerate) for their AI (artificial intelligence) efforts.

Alberta’s quantum nanotechnology hub (graduate programme)

Intriguingly, it seems that Edmonton has higher aims than (an almost unnoticed) leadership in AI. Physicists at the University of Alberta have announced hopes to be just as successful as their AI brethren in a Nov. 27, 2017 article by Juris Graney for the Edmonton Journal,

Physicists at the University of Alberta [U of A] are hoping to emulate the success of their artificial intelligence studying counterparts in establishing the city and the province as the nucleus of quantum nanotechnology research in Canada and North America.

Google’s artificial intelligence research division DeepMind announced in July [2017] it had chosen Edmonton as its first international AI research lab, based on a long-running partnership with the U of A’s 10-person AI lab.

Retaining the brightest minds in the AI and machine-learning fields while enticing a global tech leader to Alberta was heralded as a coup for the province and the university.

It is something U of A physics professor John Davis believes the university’s new graduate program, Quanta, can help achieve in the world of quantum nanotechnology.

The field of quantum mechanics had long been a realm of theoretical science based on the theory that atomic and subatomic material like photons or electrons behave both as particles and waves.

“When you get right down to it, everything has both behaviours (particle and wave) and we can pick and choose certain scenarios which one of those properties we want to use,” he said.

But, Davis said, physicists and scientists are “now at the point where we understand quantum physics and are developing quantum technology to take to the marketplace.”

“Quantum computing used to be realm of science fiction, but now we’ve figured it out, it’s now a matter of engineering,” he said.

Quantum computing labs are being bought by large tech companies such as Google, IBM and Microsoft because they realize they are only a few years away from having this power, he said.

Those making the groundbreaking developments may want to commercialize their finds and take the technology to market and that is where Quanta comes in.

East vs. West—Again?

Ivan Semeniuk in his article, Quantum Supremacy, ignores any quantum research effort not located in either Waterloo, Ontario or metro Vancouver, British Columbia to describe a struggle between the East and the West (a standard Canadian trope). From Semeniuk’s Oct. 17, 2017 quantum article [link follows the excerpts] for the Globe and Mail’s October 2017 issue of the Report on Business (ROB),

 Lazaridis [Mike], of course, has experienced lost advantage first-hand. As co-founder and former co-CEO of Research in Motion (RIM, now called Blackberry), he made the smartphone an indispensable feature of the modern world, only to watch rivals such as Apple and Samsung wrest away Blackberry’s dominance. Now, at 56, he is engaged in a high-stakes race that will determine who will lead the next technology revolution. In the rolling heartland of southwestern Ontario, he is laying the foundation for what he envisions as a new Silicon Valley—a commercial hub based on the promise of quantum technology.

Semeniuk skips over the story of how Blackberry lost its advantage. I came onto that story late in the game when Blackberry was already in serious trouble due to a failure to recognize that the field they helped to create was moving in a new direction. If memory serves, they were trying to keep their technology wholly proprietary which meant that developers couldn’t easily create apps to extend the phone’s features. Blackberry also fought a legal battle in the US with a patent troll draining company resources and energy in proved to be a futile effort.

Since then Lazaridis has invested heavily in quantum research. He gave the University of Waterloo a serious chunk of money as they named their Quantum Nano Centre (QNC) after him and his wife, Ophelia (you can read all about it in my Sept. 25, 2012 posting about the then new centre). The best details for Lazaridis’ investments in Canada’s quantum technology are to be found on the Quantum Valley Investments, About QVI, History webpage,

History-bannerHistory has repeatedly demonstrated the power of research in physics to transform society.  As a student of history and a believer in the power of physics, Mike Lazaridis set out in 2000 to make real his bold vision to establish the Region of Waterloo as a world leading centre for physics research.  That is, a place where the best researchers in the world would come to do cutting-edge research and to collaborate with each other and in so doing, achieve transformative discoveries that would lead to the commercialization of breakthrough  technologies.

Establishing a World Class Centre in Quantum Research:

The first step in this regard was the establishment of the Perimeter Institute for Theoretical Physics.  Perimeter was established in 2000 as an independent theoretical physics research institute.  Mike started Perimeter with an initial pledge of $100 million (which at the time was approximately one third of his net worth).  Since that time, Mike and his family have donated a total of more than $170 million to the Perimeter Institute.  In addition to this unprecedented monetary support, Mike also devotes his time and influence to help lead and support the organization in everything from the raising of funds with government and private donors to helping to attract the top researchers from around the globe to it.  Mike’s efforts helped Perimeter achieve and grow its position as one of a handful of leading centres globally for theoretical research in fundamental physics.

Stephen HawkingPerimeter is located in a Governor-General award winning designed building in Waterloo.  Success in recruiting and resulting space requirements led to an expansion of the Perimeter facility.  A uniquely designed addition, which has been described as space-ship-like, was opened in 2011 as the Stephen Hawking Centre in recognition of one of the most famous physicists alive today who holds the position of Distinguished Visiting Research Chair at Perimeter and is a strong friend and supporter of the organization.

Recognizing the need for collaboration between theorists and experimentalists, in 2002, Mike applied his passion and his financial resources toward the establishment of The Institute for Quantum Computing at the University of Waterloo.  IQC was established as an experimental research institute focusing on quantum information.  Mike established IQC with an initial donation of $33.3 million.  Since that time, Mike and his family have donated a total of more than $120 million to the University of Waterloo for IQC and other related science initiatives.  As in the case of the Perimeter Institute, Mike devotes considerable time and influence to help lead and support IQC in fundraising and recruiting efforts.  Mike’s efforts have helped IQC become one of the top experimental physics research institutes in the world.

Quantum ComputingMike and Doug Fregin have been close friends since grade 5.  They are also co-founders of BlackBerry (formerly Research In Motion Limited).  Doug shares Mike’s passion for physics and supported Mike’s efforts at the Perimeter Institute with an initial gift of $10 million.  Since that time Doug has donated a total of $30 million to Perimeter Institute.  Separately, Doug helped establish the Waterloo Institute for Nanotechnology at the University of Waterloo with total gifts for $29 million.  As suggested by its name, WIN is devoted to research in the area of nanotechnology.  It has established as an area of primary focus the intersection of nanotechnology and quantum physics.

With a donation of $50 million from Mike which was matched by both the Government of Canada and the province of Ontario as well as a donation of $10 million from Doug, the University of Waterloo built the Mike & Ophelia Lazaridis Quantum-Nano Centre, a state of the art laboratory located on the main campus of the University of Waterloo that rivals the best facilities in the world.  QNC was opened in September 2012 and houses researchers from both IQC and WIN.

Leading the Establishment of Commercialization Culture for Quantum Technologies in Canada:

In the Research LabFor many years, theorists have been able to demonstrate the transformative powers of quantum mechanics on paper.  That said, converting these theories to experimentally demonstrable discoveries has, putting it mildly, been a challenge.  Many naysayers have suggested that achieving these discoveries was not possible and even the believers suggested that it could likely take decades to achieve these discoveries.  Recently, a buzz has been developing globally as experimentalists have been able to achieve demonstrable success with respect to Quantum Information based discoveries.  Local experimentalists are very much playing a leading role in this regard.  It is believed by many that breakthrough discoveries that will lead to commercialization opportunities may be achieved in the next few years and certainly within the next decade.

Recognizing the unique challenges for the commercialization of quantum technologies (including risk associated with uncertainty of success, complexity of the underlying science and high capital / equipment costs) Mike and Doug have chosen to once again lead by example.  The Quantum Valley Investment Fund will provide commercialization funding, expertise and support for researchers that develop breakthroughs in Quantum Information Science that can reasonably lead to new commercializable technologies and applications.  Their goal in establishing this Fund is to lead in the development of a commercialization infrastructure and culture for Quantum discoveries in Canada and thereby enable such discoveries to remain here.

Semeniuk goes on to set the stage for Waterloo/Lazaridis vs. Vancouver (from Semeniuk’s 2017 ROB article),

… as happened with Blackberry, the world is once again catching up. While Canada’s funding of quantum technology ranks among the top five in the world, the European Union, China, and the US are all accelerating their investments in the field. Tech giants such as Google [also known as Alphabet], Microsoft and IBM are ramping up programs to develop companies and other technologies based on quantum principles. Meanwhile, even as Lazaridis works to establish Waterloo as the country’s quantum hub, a Vancouver-area company has emerged to challenge that claim. The two camps—one methodically focused on the long game, the other keen to stake an early commercial lead—have sparked an East-West rivalry that many observers of the Canadian quantum scene are at a loss to explain.

Is it possible that some of the rivalry might be due to an influential individual who has invested heavily in a ‘quantum valley’ and has a history of trying to ‘own’ a technology?

Getting back to D-Wave Systems, the Vancouver company, I have written about them a number of times (particularly in 2015; for the full list: input D-Wave into the blog search engine). This June 26, 2015 posting includes a reference to an article in The Economist magazine about D-Wave’s commercial opportunities while the bulk of the posting is focused on a technical breakthrough.

Semeniuk offers an overview of the D-Wave Systems story,

D-Wave was born in 1999, the same year Lazaridis began to fund quantum science in Waterloo. From the start, D-Wave had a more immediate goal: to develop a new computer technology to bring to market. “We didn’t have money or facilities,” says Geordie Rose, a physics PhD who co0founded the company and served in various executive roles. …

The group soon concluded that the kind of machine most scientists were pursing based on so-called gate-model architecture was decades away from being realized—if ever. …

Instead, D-Wave pursued another idea, based on a principle dubbed “quantum annealing.” This approach seemed more likely to produce a working system, even if the application that would run on it were more limited. “The only thing we cared about was building the machine,” says Rose. “Nobody else was trying to solve the same problem.”

D-Wave debuted its first prototype at an event in California in February 2007 running it through a few basic problems such as solving a Sudoku puzzle and finding the optimal seating plan for a wedding reception. … “They just assumed we were hucksters,” says Hilton [Jeremy Hilton, D.Wave senior vice-president of systems]. Federico Spedalieri, a computer scientist at the University of Southern California’s [USC} Information Sciences Institute who has worked with D-Wave’s system, says the limited information the company provided about the machine’s operation provoked outright hostility. “I think that played against them a lot in the following years,” he says.

It seems Lazaridis is not the only one who likes to hold company information tightly.

Back to Semeniuk and D-Wave,

Today [October 2017], the Los Alamos National Laboratory owns a D-Wave machine, which costs about $15million. Others pay to access D-Wave systems remotely. This year , for example, Volkswagen fed data from thousands of Beijing taxis into a machine located in Burnaby [one of the municipalities that make up metro Vancouver] to study ways to optimize traffic flow.

But the application for which D-Wave has the hights hope is artificial intelligence. Any AI program hings on the on the “training” through which a computer acquires automated competence, and the 2000Q [a D-Wave computer] appears well suited to this task. …

Yet, for all the buzz D-Wave has generated, with several research teams outside Canada investigating its quantum annealing approach, the company has elicited little interest from the Waterloo hub. As a result, what might seem like a natural development—the Institute for Quantum Computing acquiring access to a D-Wave machine to explore and potentially improve its value—has not occurred. …

I am particularly interested in this comment as it concerns public funding (from Semeniuk’s article),

Vern Brownell, a former Goldman Sachs executive who became CEO of D-Wave in 2009, calls the lack of collaboration with Waterloo’s research community “ridiculous,” adding that his company’s efforts to establish closer ties have proven futile, “I’ll be blunt: I don’t think our relationship is good enough,” he says. Brownell also point out that, while  hundreds of millions in public funds have flowed into Waterloo’s ecosystem, little funding is available for  Canadian scientists wishing to make the most of D-Wave’s hardware—despite the fact that it remains unclear which core quantum technology will prove the most profitable.

There’s a lot more to Semeniuk’s article but this is the last excerpt,

The world isn’t waiting for Canada’s quantum rivals to forge a united front. Google, Microsoft, IBM, and Intel are racing to develop a gate-model quantum computer—the sector’s ultimate goal. (Google’s researchers have said they will unveil a significant development early next year.) With the U.K., Australia and Japan pouring money into quantum, Canada, an early leader, is under pressure to keep up. The federal government is currently developing  a strategy for supporting the country’s evolving quantum sector and, ultimately, getting a return on its approximately $1-billion investment over the past decade [emphasis mine].

I wonder where the “approximately $1-billion … ” figure came from. I ask because some years ago MP Peter Julian asked the government for information about how much Canadian federal money had been invested in nanotechnology. The government replied with sheets of paper (a pile approximately 2 inches high) that had funding disbursements from various ministries. Each ministry had its own method with different categories for listing disbursements and the titles for the research projects were not necessarily informative for anyone outside a narrow specialty. (Peter Julian’s assistant had kindly sent me a copy of the response they had received.) The bottom line is that it would have been close to impossible to determine the amount of federal funding devoted to nanotechnology using that data. So, where did the $1-billion figure come from?

In any event, it will be interesting to see how the Council of Canadian Academies assesses the ‘quantum’ situation in its more academically inclined, “The State of Science and Technology and Industrial Research and Development in Canada,” when it’s released later this year (2018).

Finally, you can find Semeniuk’s October 2017 article here but be aware it’s behind a paywall.

Whither we goest?

Despite any doubts one might have about Lazaridis’ approach to research and technology, his tremendous investment and support cannot be denied. Without him, Canada’s quantum research efforts would be substantially less significant. As for the ‘cowboys’ in Vancouver, it takes a certain temperament to found a start-up company and it seems the D-Wave folks have more in common with Lazaridis than they might like to admit. As for the Quanta graduate  programme, it’s early days yet and no one should ever count out Alberta.

Meanwhile, one can continue to hope that a more thoughtful approach to regional collaboration will be adopted so Canada can continue to blaze trails in the field of quantum research.

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.

Gold’s origin in the universe due to cosmic collision

An hypothesis for gold’s origins was first mentioned here in a May 26, 2016 posting,

The link between this research and my side project on gold nanoparticles is a bit tenuous but this work on the origins for gold and other precious metals being found in the stars is so fascinating and I’m determined to find a connection.

An artist's impression of two neutron stars colliding. (Credit: Dana Berry / Skyworks Digital, Inc.) Courtesy: Kavli Foundation

An artist’s impression of two neutron stars colliding. (Credit: Dana Berry / Skyworks Digital, Inc.) Courtesy: Kavli Foundation

From a May 19, 2016 news item on phys.org,

The origin of many of the most precious elements on the periodic table, such as gold, silver and platinum, has perplexed scientists for more than six decades. Now a recent study has an answer, evocatively conveyed in the faint starlight from a distant dwarf galaxy.

In a roundtable discussion, published today [May 19, 2016?], The Kavli Foundation spoke to two of the researchers behind the discovery about why the source of these heavy elements, collectively called “r-process” elements, has been so hard to crack.

From the Spring 2016 Kavli Foundation webpage hosting the  “Galactic ‘Gold Mine’ Explains the Origin of Nature’s Heaviest Elements” Roundtable ,

Astronomers studying a galaxy called Reticulum II have just discovered that its stars contain whopping amounts of these metals—collectively known as “r-process” elements (See “What is the R-Process?”). Of the 10 dwarf galaxies that have been similarly studied so far, only Reticulum II bears such strong chemical signatures. The finding suggests some unusual event took place billions of years ago that created ample amounts of heavy elements and then strew them throughout the galaxy’s reservoir of gas and dust. This r-process-enriched material then went on to form Reticulum II’s standout stars.

Based on the new study, from a team of researchers at the Kavli Institute at the Massachusetts Institute of Technology, the unusual event in Reticulum II was likely the collision of two, ultra-dense objects called neutron stars. Scientists have hypothesized for decades that these collisions could serve as a primary source for r-process elements, yet the idea had lacked solid observational evidence. Now armed with this information, scientists can further hope to retrace the histories of galaxies based on the contents of their stars, in effect conducting “stellar archeology.”

Researchers have confirmed the hypothesis according to an Oct. 16, 2017 news item on phys.org,

Gold’s origin in the Universe has finally been confirmed, after a gravitational wave source was seen and heard for the first time ever by an international collaboration of researchers, with astronomers at the University of Warwick playing a leading role.

Members of Warwick’s Astronomy and Astrophysics Group, Professor Andrew Levan, Dr Joe Lyman, Dr Sam Oates and Dr Danny Steeghs, led observations which captured the light of two colliding neutron stars, shortly after being detected through gravitational waves – perhaps the most eagerly anticipated phenomenon in modern astronomy.

Marina Koren’s Oct. 16, 2017 article for The Atlantic presents a richly evocative view (Note: Links have been removed),

Some 130 million years ago, in another galaxy, two neutron stars spiraled closer and closer together until they smashed into each other in spectacular fashion. The violent collision produced gravitational waves, cosmic ripples powerful enough to stretch and squeeze the fabric of the universe. There was a brief flash of light a million trillion times as bright as the sun, and then a hot cloud of radioactive debris. The afterglow hung for several days, shifting from bright blue to dull red as the ejected material cooled in the emptiness of space.

Astronomers detected the aftermath of the merger on Earth on August 17. For the first time, they could see the source of universe-warping forces Albert Einstein predicted a century ago. Unlike with black-hole collisions, they had visible proof, and it looked like a bright jewel in the night sky.

But the merger of two neutron stars is more than fireworks. It’s a factory.

Using infrared telescopes, astronomers studied the spectra—the chemical composition of cosmic objects—of the collision and found that the plume ejected by the merger contained a host of newly formed heavy chemical elements, including gold, silver, platinum, and others. Scientists estimate the amount of cosmic bling totals about 10,000 Earth-masses of heavy elements.

I’m not sure exactly what this image signifies but it did accompany Koren’s article so presumably it’s a representation of colliding neutron stars,

NSF / LIGO / Sonoma State University /A. Simonnet. Downloaded from: https://www.theatlantic.com/science/archive/2017/10/the-making-of-cosmic-bling/543030/

An Oct. 16, 2017 University of Warwick press release (also on EurekAlert), which originated the news item on phys.org, provides more detail,

Huge amounts of gold, platinum, uranium and other heavy elements were created in the collision of these compact stellar remnants, and were pumped out into the universe – unlocking the mystery of how gold on wedding rings and jewellery is originally formed.

The collision produced as much gold as the mass of the Earth. [emphasis mine]

This discovery has also confirmed conclusively that short gamma-ray bursts are directly caused by the merging of two neutron stars.

The neutron stars were very dense – as heavy as our Sun yet only 10 kilometres across – and they collided with each other 130 million years ago, when dinosaurs roamed the Earth, in a relatively old galaxy that was no longer forming many stars.

They drew towards each other over millions of light years, and revolved around each other increasingly quickly as they got closer – eventually spinning around each other five hundred times per second.

Their merging sent ripples through the fabric of space and time – and these ripples are the elusive gravitational waves spotted by the astronomers.

The gravitational waves were detected by the Advanced Laser Interferometer Gravitational-Wave Observatory (Adv-LIGO) on 17 August this year [2017], with a short duration gamma-ray burst detected by the Fermi satellite just two seconds later.

This led to a flurry of observations as night fell in Chile, with a first report of a new source from the Swope 1m telescope.

Longstanding collaborators Professor Levan and Professor Nial Tanvir (from the University of Leicester) used the facilities of the European Southern Observatory to pinpoint the source in infrared light.

Professor Levan’s team was the first one to get observations of this new source with the Hubble Space Telescope. It comes from a galaxy called NGC 4993, 130 million light years away.

Andrew Levan, Professor in the Astronomy & Astrophysics group at the University of Warwick, commented: “Once we saw the data, we realised we had caught a new kind of astrophysical object. This ushers in the era of multi-messenger astronomy, it is like being able to see and hear for the first time.”

Dr Joe Lyman, who was observing at the European Southern Observatory at the time was the first to alert the community that the source was unlike any seen before.

He commented: “The exquisite observations obtained in a few days showed we were observing a kilonova, an object whose light is powered by extreme nuclear reactions. This tells us that the heavy elements, like the gold or platinum in jewellery are the cinders, forged in the billion degree remnants of a merging neutron star.”

Dr Samantha Oates added: “This discovery has answered three questions that astronomers have been puzzling for decades: what happens when neutron stars merge? What causes the short duration gamma-ray bursts? Where are the heavy elements, like gold, made? In the space of about a week all three of these mysteries were solved.”

Dr Danny Steeghs said: “This is a new chapter in astrophysics. We hope that in the next few years we will detect many more events like this. Indeed, in Warwick we have just finished building a telescope designed to do just this job, and we expect it to pinpoint these sources in this new era of multi-messenger astronomy”.

Congratulations to all of the researchers involved in this work!

Many, many research teams were  involved. Here’s a sampling of their news releases which focus on their areas of research,

University of the Witwatersrand (South Africa)

https://www.eurekalert.org/pub_releases/2017-10/uotw-wti101717.php

Weizmann Institute of Science (Israel)

https://www.eurekalert.org/pub_releases/2017-10/wios-cns101717.php

Carnegie Institution for Science (US)

https://www.eurekalert.org/pub_releases/2017-10/cifs-dns101217.php

Northwestern University (US)

https://www.eurekalert.org/pub_releases/2017-10/nu-adc101617.php

National Radio Astronomy Observatory (US)

https://www.eurekalert.org/pub_releases/2017-10/nrao-ru101317.php

Max-Planck-Gesellschaft (Germany)

https://www.eurekalert.org/pub_releases/2017-10/m-gwf101817.php

Penn State (Pennsylvania State University; US)

https://www.eurekalert.org/pub_releases/2017-10/ps-stl101617.php

University of California – Davis

https://www.eurekalert.org/pub_releases/2017-10/uoc–cns101717.php

The American Association for the Advancement of Science’s (AAAS) magazine, Science, has published seven papers on this research. Here’s an Oct. 16, 2017 AAAS news release with an overview of the papers,

https://www.eurekalert.org/pub_releases/2017-10/aaft-btf101617.php

I’m sure there are more news releases out there and that there will be many more papers published in many journals, so if this interests, I encourage you to keep looking.

Two final pieces I’d like to draw your attention to: one answers basic questions and another focuses on how artists knew what to draw when neutron stars collide.

Keith A Spencer’s Oct. 18, 2017 piece on salon.com answers a lot of basic questions for those of us who don’t have a background in astronomy. Here are a couple of examples,

What is a neutron star?

Okay, you know how atoms have protons, neutrons, and electrons in them? And you know how protons are positively charged, and electrons are negatively charged, and neutrons are neutral?

Yeah, I remember that from watching Bill Nye as a kid.

Totally. Anyway, have you ever wondered why the negatively-charged electrons and the positively-charged protons don’t just merge into each other and form a neutral neutron? I mean, they’re sitting there in the atom’s nucleus pretty close to each other. Like, if you had two magnets that close, they’d stick together immediately.

I guess now that you mention it, yeah, it is weird.

Well, it’s because there’s another force deep in the atom that’s preventing them from merging.

It’s really really strong.

The only way to overcome this force is to have a huge amount of matter in a really hot, dense space — basically shove them into each other until they give up and stick together and become a neutron. This happens in very large stars that have been around for a while — the core collapses, and in the aftermath, the electrons in the star are so close to the protons, and under so much pressure, that they suddenly merge. There’s a big explosion and the outer material of the star is sloughed off.

Okay, so you’re saying under a lot of pressure and in certain conditions, some stars collapse and become big balls of neutrons?

Pretty much, yeah.

So why do the neutrons just stick around in a huge ball? Aren’t they neutral? What’s keeping them together? 

Gravity, mostly. But also the strong nuclear force, that aforementioned weird strong force. This isn’t something you’d encounter on a macroscopic scale — the strong force only really works at the type of distances typified by particles in atomic nuclei. And it’s different, fundamentally, than the electromagnetic force, which is what makes magnets attract and repel and what makes your hair stick up when you rub a balloon on it.

So these neutrons in a big ball are bound by gravity, but also sticking together by virtue of the strong nuclear force. 

So basically, the new ball of neutrons is really small, at least, compared to how heavy it is. That’s because the neutrons are all clumped together as if this neutron star is one giant atomic nucleus — which it kinda is. It’s like a giant atom made only of neutrons. If our sun were a neutron star, it would be less than 20 miles wide. It would also not be something you would ever want to get near.

Got it. That means two giant balls of neutrons that weighed like, more than our sun and were only ten-ish miles wide, suddenly smashed into each other, and in the aftermath created a black hole, and we are just now detecting it on Earth?

Exactly. Pretty weird, no?

Spencer does a good job of gradually taking you through increasingly complex explanations.

For those with artistic interests, Neel V. Patel tries to answer a question about how artists knew what draw when neutron stars collided in his Oct. 18, 2017 piece for Slate.com,

All of these things make this discovery easy to marvel at and somewhat impossible to picture. Luckily, artists have taken up the task of imagining it for us, which you’ve likely seen if you’ve already stumbled on coverage of the discovery. Two bright, furious spheres of light and gas spiraling quickly into one another, resulting in a massive swell of lit-up matter along with light and gravitational waves rippling off speedily in all directions, towards parts unknown. These illustrations aren’t just alluring interpretations of a rare phenomenon; they are, to some extent, the translation of raw data and numbers into a tangible visual that gives scientists and nonscientists alike some way of grasping what just happened. But are these visualizations realistic? Is this what it actually looked like? No one has any idea. Which is what makes the scientific illustrators’ work all the more fascinating.

“My goal is to represent what the scientists found,” says Aurore Simmonet, a scientific illustrator based at Sonoma State University in Rohnert Park, California. Even though she said she doesn’t have a rigorous science background (she certainly didn’t know what a kilonova was before being tasked to illustrate one), she also doesn’t believe that type of experience is an absolute necessity. More critical, she says, is for the artist to have an interest in the subject matter and in learning new things, as well as a capacity to speak directly to scientists about their work.

Illustrators like Simmonet usually start off work on an illustration by asking the scientist what’s the biggest takeaway a viewer should grasp when looking at a visual. Unfortunately, this latest discovery yielded a multitude of papers emphasizing different conclusions and highlights. With so many scientific angles, there’s a stark challenge in trying to cram every important thing into a single drawing.

Clearly, however, the illustrations needed to center around the kilonova. Simmonet loves colors, so she began by discussing with the researchers what kind of color scheme would work best. The smash of two neutron stars lends itself well to deep, vibrant hues. Simmonet and Robin Dienel at the Carnegie Institution for Science elected to use a wide array of colors and drew bright cracking to show pressure forming at the merging. Others, like Luis Calcada at the European Southern Observatory, limited the color scheme in favor of emphasizing the bright moment of collision and the signal waves created by the kilonova.

Animators have even more freedom to show the event, since they have much more than a single frame to play with. The Conceptual Image Lab at NASA’s [US National Aeronautics and Space Administration] Goddard Space Flight Center created a short video about the new findings, and lead animator Brian Monroe says the video he and his colleagues designed shows off the evolution of the entire process: the rising action, climax, and resolution of the kilonova event.

The illustrators try to adhere to what the likely physics of the event entailed, soliciting feedback from the scientists to make sure they’re getting it right. The swirling of gas, the direction of ejected matter upon impact, the reflection of light, the proportions of the objects—all of these things are deliberately framed such that they make scientific sense. …

Do take a look at Patel’s piece, if for no other reason than to see all of the images he has embedded there. You may recognize Aurore Simmonet’s name from the credit line in the second image I have embedded here.