Tag Archives: Harvard University

Physics of a singing saw could lead to applications in sensing, nanoelectronics, photonics, etc.

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I’d forgotten how haunting a musical saw can sound,

An April 22, 2022 news item on Nanowerk announces research into the possibilities of a singing saw,

The eerie, ethereal sound of the singing saw has been a part of folk music traditions around the globe, from China to Appalachia, since the proliferation of cheap, flexible steel in the early 19th century. Made from bending a metal hand saw and bowing it like a cello, the instrument reached its heyday on the vaudeville stages of the early 20th century and has seen a resurgence thanks, in part, to social media.

As it turns out, the unique mathematical physics of the singing saw may hold the key to designing high quality resonators for a range of applications.

In a new paper, a team of researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and the Department of Physics used the singing saw to demonstrate how the geometry of a curved sheet, like curved metal, could be tuned to create high-quality, long-lasting oscillations for applications in sensing, nanoelectronics, photonics and more.

An April 21, 2022 Harvard University John A. Paulson School of Engineering and Applied Sciences (SEAS) news release by Leah Burrows (also on EurekAlert but published on April 22, 2022) delves further into physics of singing saws,

“Our research offers a robust principle to design high-quality resonators independent of scale and material, from macroscopic musical instruments to nanoscale devices, simply through a combination of geometry and topology,” said L Mahadevan, the Lola England de Valpine Professor of Applied Mathematics, of Organismic and Evolutionary Biology, and of Physics and senior author of the study.

…

While all musical instruments are acoustic resonators of a kind, none work quite like the singing saw.

“How the singing saw sings is based on a surprising effect,” said Petur Bryde, a graduate student at SEAS and co-first author of the paper. “When you strike a flat elastic sheet, such as a sheet of metal, the entire structure vibrates. The energy is quickly lost through the boundary where it is held, resulting in a dull sound that dissipates quickly. The same result is observed if you curve it into a J-shape. But, if you bend the sheet into an S-shape, you can make it vibrate in a very small area, which produces a clear, long-lasting tone.”

The geometry of the curved saw creates what musicians call the sweet spot and what physicists call localized vibrational modes — a confined area on the sheet which resonates without losing energy at the edges.

Importantly, the specific geometry of the S-curve doesn’t matter. It could be an S with a big curve at the top and a small curve at the bottom or visa versa. 

“Musicians and researchers have known about this robust effect of geometry for some time, but the underlying mechanisms have remained a mystery,” said Suraj Shankar, a Harvard Junior Fellow in Physics and SEAS and co-first author of the study.  “We found a mathematical argument that explains how and why this robust effect exists with any shape within this class, so that the details of the shape are unimportant, and the only fact that matters is that there is a reversal of curvature along the saw.”

Shankar, Bryde and Mahadevan found that explanation via an analogy to very different class of physical systems — topological insulators. Most often associated with quantum physics, topological insulators are materials that conduct electricity in their surface or edge but not in the middle and no matter how you cut these materials, they will always conduct on their edges.

“In this work, we drew a mathematical analogy between the acoustics of bent sheets and these quantum and electronic systems,” said Shankar.

By using the mathematics of topological systems, the researchers found that the localized vibrational modes in the sweet spot of singing saw were governed by a topological parameter that can be computed and which relies on nothing more than the existence of two opposite curves in the material. The sweet spot then behaves like an internal “edge” in the saw.

“By using experiments, theoretical and numerical analysis, we showed that the S-curvature in a thin shell can localize topologically-protected modes at the ‘sweet spot’ or inflection line, similar to exotic edge states in topological insulators,” said Bryde. “This phenomenon is material independent, meaning it will appear in steel, glass or even graphene.”

The researchers also found that they could tune the localization of the mode by changing the shape of the S-curve, which is important in applications such as sensing, where you need a resonator that is tuned to very specific frequencies.

Next, the researchers aim to explore localized modes in doubly curved structures, such as bells and other shapes.

…

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

Geometric control of topological dynamics in a singing saw by Suraj Shankar, Petur Bryde, and L. Mahadevan. The Proceedings of the National Academy of Sciences (PNAS) April 21, 2022 | 119 (17) e2117241119 DOI: https://doi.org/10.1073/pnas.2117241119

This paper is open (free) access.

Ancient Namibian gemstone could be key to new light-based quantum computers

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Researchers in Scotland, the US, Australia, and Denmark have a found a solution to a problem with creating light-based computers according to an April 15, 2022 news item on phys.org,

A special form of light made using an ancient Namibian gemstone could be the key to new light-based quantum computers, which could solve long-held scientific mysteries, according to new research led by the University of St Andrews.

The research, conducted in collaboration with scientists at Harvard University in the US, Macquarie University in Australia and Aarhus University in Denmark and published in Nature Materials, used a naturally mined cuprous oxide (Cu2O) gemstone from Namibia to produce Rydberg polaritons, the largest hybrid particles of light and matter ever created.

…

Cuprous oxide – the mined crystal from Namibia used for making Rydberg polaritons. Courtesy: University of St. Andrews

An April 15, 2022 University of St. Andrews press release, which originated the news item, describes Rydberg polaritons and explains why they could be the key to light-based quantum computing,

Rydberg polaritons switch continually from light to matter and back again. In Rydberg polaritons, light and matter are like two sides of a coin, and the matter side is what makes polaritons interact with each other.

This interaction is crucial because this is what allows the creation of quantum simulators, a special type of quantum computer, where information is stored in quantum bits. These quantum bits [qubits], unlike the binary bits in classical computers that can only be 0 or 1, can take any value between 0 and 1. They can therefore store much more information and perform several processes simultaneously.

This capability could allow quantum simulators to solve important mysteries of physics, chemistry and biology, for example, how to make high-temperature superconductors for highspeed trains, how cheaper fertilisers could be made potentially solving global hunger, or how proteins fold making it easier to produce more effective drugs.

Project lead Dr Hamid Ohadi, of the School of Physics and Astronomy at the University of St Andrews, said: “Making a quantum simulator with light is the holy grail of science. We have taken a huge leap towards this by creating Rydberg polaritons, the key ingredient of it.”

To create Rydberg polaritons, the researchers trapped light between two highly reflective mirrors. A cuprous oxide crystal from a stone mined in Namibia was then thinned and polished to a 30-micrometer thick slab (thinner than a strand of human hair) and sandwiched between the two mirrors to make Rydberg polaritons 100 times larger than ever demonstrated before.

One of the leading authors Dr Sai Kiran Rajendran, of the School of Physics and Astronomy at the University of St Andrews, said: “Purchasing the stone on eBay was easy. The challenge was to make Rydberg polaritons that exist in an extremely narrow colour range.”

The team is currently further refining these methods in order to explore the possibility of making quantum circuits, which are the next ingredient for quantum simulators.

The research was funded by UK Engineering and Physical Sciences Research Council (EPSRC).

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

Rydberg exciton–polaritons in a Cu2O microcavity by Konstantinos Orfanakis, Sai Kiran Rajendran, Valentin Walther, Thomas Volz, Thomas Pohl & Hamid Ohadi. Nature Materials (2022) DOI: DOIhttps://doi.org/10.1038/s41563-022-01230-4 Published: 14 April 2022

This paper is behind a paywall.

Xenobots (living robots) that can reproduce

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Xenobots (living robots made from African frog (Xenopus laevis) frog cells) can now self-replicate. First mentioned here in a June 21, 2021 posting, xenobots have captured the imagination of various media outlets including the Canadian Broadcasting Corporation’s (CBC) Quirks and Quarks radio programme and blog where Amanda Buckiewicz posted a December 3, 2021 article about the latest xenobot development (Note: Links have been removed),

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In a new study, Bongard [Joshua Bongard, a computer scientist at the University of Vermont] and his colleagues from Tufts University and Harvard’s Wyss Institute for Biologically Inspired Engineering found that the xenobots would autonomously collect loose single cells in their environment, gathering hundreds of cells together until new xenobots had formed.

“This took a little bit for us to wrap our minds around,” he said. “There’s no programming here. Instead, we’re designing or shaping these xenobots, and what they do, the way they behave, is based on shape.”

…

“We take a couple of thousand of those frog cells and we squish them together into a ball and put that in the bottom of a petri dish,” Bongard told Quirks & Quarks host Bob McDonald. 

“If you were to look into the dish, you would see some very small, what look like specks of pepper, moving about in the bottom of the petri dish.”

The xenobots initially received no instruction from humans on how to replicate. But when researchers added extra cells to the dish containing xenobots, they observed that the xenobots would assemble them into piles.

“Cells early in development are sticky,” said Bongard. “If the pile is large enough and the cells stick together, the outer ones on the surface will grow very small hairs, which are called cilia. And eventually, after four days, those cilia will start to beat back and forth like flexible oars, and the pile will start moving.”

“And that’s a child xenobot.” 

…

A November 29, 2021 Wyss Institute news release by Joshua Brown describes the process a little differently,

To persist, life must reproduce. Over billions of years, organisms have evolved many ways of replicating, from budding plants to sexual animals to invading viruses.

Now scientists at the University of Vermont, Tufts University, and the Wyss Institute for Biologically Inspired Engineering at Harvard University have discovered an entirely new form of biological reproduction—and applied their discovery to create the first-ever, self-replicating living robots.

The same team that built the first living robots (“Xenobots,” assembled from frog cells—reported in 2020) has discovered that these computer-designed and hand-assembled organisms can swim out into their tiny dish, find single cells, gather hundreds of them together, and assemble “baby” Xenobots inside their Pac-Man-shaped “mouth”—that, a few days later, become new Xenobots that look and move just like themselves.

And then these new Xenobots can go out, find cells, and build copies of themselves. Again and again.

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In a Xenopus laevis frog, these embryonic cells would develop into skin. “They would be sitting on the outside of a tadpole, keeping out pathogens and redistributing mucus,” says Michael Levin, Ph.D., a professor of biology and director of the Allen Discovery Center at Tufts University and co-leader of the new research. “But we’re putting them into a novel context. We’re giving them a chance to reimagine their multicellularity.” Levin is also an Associate Faculty member at the Wyss Institute.

And what they imagine is something far different than skin. “People have thought for quite a long time that we’ve worked out all the ways that life can reproduce or replicate. But this is something that’s never been observed before,” says co-author Douglas Blackiston, Ph.D., the senior scientist at Tufts University and the Wyss Institute who assembled the Xenobot “parents” and developed the biological portion of the new study.

“This is profound,” says Levin. “These cells have the genome of a frog, but, freed from becoming tadpoles, they use their collective intelligence, a plasticity, to do something astounding.” In earlier experiments, the scientists were amazed that Xenobots could be designed to achieve simple tasks. Now they are stunned that these biological objects—a computer-designed collection of cells—will spontaneously replicate. “We have the full, unaltered frog genome,” says Levin, “but it gave no hint that these cells can work together on this new task,” of gathering and then compressing separated cells into working self-copies.

“These are frog cells replicating in a way that is very different from how frogs do it. No animal or plant known to science replicates in this way,” says Sam Kriegman, Ph.D.,  the lead author on the new study, who completed his Ph.D. in Bongard’s lab at UVM and is now a post-doctoral researcher at Tuft’s Allen Center and Harvard University’s Wyss Institute for Biologically Inspired Engineering.

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Both Buckiewicz’s December 3, 2021 article and Brown’s November 29, 2021 Wyss Institute news release are good reads with liberal used of embedded images. If you have time, start with Buckiewicz as she provides a good introduction and follow up with Brown who gives more detail and has an embedded video of a December 1, 2021 panel discussion with the scientists behind the xenobots.

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

Kinematic self-replication in reconfigurable organisms by Sam Kriegman, Douglas Blackiston, Michael Levin, and Josh Bongard. PNAS [Proceedings of the National Academy of Sciences] December 7, 2021 118 (49) e2112672118; https://doi.org/10.1073/pnas.2112672118

This paper appears to be open access.

Cellulose nanocrystals (CNC), protein, and starch eletrospun to develop ‘smart’ food packaging

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A December 29, 2021 news item on ScienceDaily announces research into ;smart’ sustainable packaging from a joint Nanyang Technical University and Harvard University,

A team of scientists from Nanyang Technological University, Singapore (NTU Singapore) and Harvard T.H. Chan School of Public Health, US, has developed a ‘smart’ food packaging material that is biodegradable, sustainable and kills microbes that are harmful to humans. It could also extend the shelf-life of fresh fruit by two to three days.

The waterproof food packaging is made from a type of corn protein called zein, starch and other naturally derived biopolymers, infused with a cocktail of natural antimicrobial compounds. These include oil from thyme, a common herb used in cooking, and citric acid, which is commonly found in citrus fruits.

…

A December 28, 2021 Nanyang Technological University press release (PDF), also on EurekAlert but published December 27, 2021, which originated the news item, offers a few more details about the research (Note 1: Links have been removed; Note 2: I had to dig into the abstract to find the cellulose nanocrystals),

In lab experiments, when exposed to an increase in humidity or enzymes from harmful bacteria, the fibres in the packaging have been shown to release the natural antimicrobial compounds, killing common dangerous bacteria that contaminate food, such as E. Coli and Listeria, as well as fungi.

The packaging is designed to release the necessary miniscule amounts of antimicrobial compounds only in response to the presence of additional humidity or bacteria. This ensures that the packaging can endure several exposures, and last for months.

As the compounds combat any bacteria that grow on the surface of the packaging as well as on the food product itself, it has the potential to be used for a large variety of products, including ready-to-eat foods, raw meat, fruits, and vegetables.

In an experiment, strawberries that were wrapped in the packaging stayed fresh for seven days before developing mould, compared to counterparts that were kept in mainstream fruit plastic boxes, which only stayed fresh for four days.

The invention is the result of the collaboration by scientists from the NTU-Harvard T. H. Chan School of Public Health Initiative for Sustainable Nanotechnology (NTU-Harvard SusNano), which brings together NTU and Harvard Chan School researchers to work on cutting edge applications in agriculture and food, with an emphasis on developing non-toxic and environmentally safe nanomaterials.

The development of this advanced food packaging material is part of the University’s efforts to promote sustainable food tech solutions, that is aligned with the NTU 2025 strategic plan, which aims to develop sustainable solutions to address some of humanity’s pressing grand challenges.

Professor Mary Chan, Director of NTU’s Centre of Antimicrobial Bioengineering, who co-led the project, said: “This invention would serve as a better option for packaging in the food industry, as it has demonstrated superior antimicrobial qualities in combatting a myriad of food-related bacteria and fungi that could be harmful to humans. The packaging can be applied to various produces such as fish, meat, vegetables, and fruits. The smart release of antimicrobials only when bacteria or high humidity is present, provides protection only when needed thus minimising the use of chemicals and preserving the natural composition of foods packaged.”

Professor Philip Demokritou, Adjunct Professor of Environmental Health at Harvard Chan School, who is also Director of Nanotechnology and Nanotoxicology Center and Co-director of NTU-Harvard Initiative on Sustainable Nanotechnology, who co-led the study, said: “Food safety and waste have become a major societal challenge of our times with immense public health and economic impact which compromises food security. One of the most efficient ways to enhance food safety and reduce spoilage and waste is to develop efficient biodegradable non-toxic food packaging materials. In this study, we used nature-derived compounds including biopolymers, non-toxic solvents, and nature-inspired antimicrobials and develop scalable systems to synthesise smart antimicrobial materials which can be used not only to enhance food safety and quality but also to eliminate the harm to the environment and health and reduce the use of non-biodegradable plastics at global level and promote sustainable agri-food systems.” 

Providing an independent assessment of the work done by the NTU research team, Mr Peter Barber, CEO of ComCrop, a Singapore company that pioneered urban rooftop farming, said: “The NTU-Harvard Chan School food packaging material would serve as a sustainable solution for companies like us who want to cut down on the usage of plastic and embrace greener alternatives. As ComCrop looks to ramp up product to boost Singapore’s food production capabilities, the volume of packaging we need will increase in sync, and switching to a material such as this would help us have double the impact. The wrapping’s antimicrobial properties, which could potentially extend the shelf life of our vegetables, would serve us well. The packaging material holds promise to the industry, and we look forward to learning more about the wrapping and possibly adopting it for our usage someday.”

The results of the study were published in the peer-reviewed academic journal ACS Applied Materials & Interfacesin October [2021].

Cutting down on packaging waste

The packaging industry is the largest and growing consumer of synthetic plastics derived from fossil fuels, with food packaging plastics accounting for the bulk of plastic waste that are polluting the environment.

In Singapore, packaging is a major source of trash, with data from Singapore’s National Environment Agency showing that out of the 1.76 million tonnes of waste disposed of by domestic sources in 2018, one third of it was packaging waste, and over half of it (55 per cent) was plastic.

The smart food package material, when scaled up, could serve as an alternative to cut down on the amount of plastic waste, as it is biodegradable. Its main ingredient, zein, is also produced from corn gluten meal, which is a waste by-product from using corn starch or oils in order to produce ethanol.

The food packaging material is produced by electrospinning[1] the zein, the antimicrobial compounds with cellulose, a natural polymer starch that makes up plant cell walls, and acetic acid, which is commonly found in vinegar.

Prof Mary Chan added: “The sustainable and biodegradable active food packaging, which has inbuilt technology to keep bacteria and fungus at bay, is of great importance to the food industry. It could serve as an environmentally friendly alternative to petroleum-based polymers used in commercial food packaging, such as plastic, which have a significant negative environmental impact.”

Prof Demokritou added: “Due to the globalisation of food supply and attitude shift towards a healthier lifestyle and environmentally friendly food packaging, there is a need to develop biodegradable, non-toxic and smart/responsive materials to enhance food safety and quality. Development of scalable synthesis platforms for developing food packaging materials that are composed of nature derived, biodegradable biopolymers and nature inspired antimicrobials, coupled with stimuli triggered approaches will meet the emerging societal needs to reduce food waste and enhance food safety and quality.”

The team of NTU and Harvard Chan School researchers hope to scale up their technology with an industrial partner, with the aim of commercialisation within the next few years.

They are also currently working on developing other technologies to develop biopolymer-based smart food package materials to enhance food safety and quality.

Here’s a link to and a citation for the paper, followed by the key (nanocellulose crystal mention) sentences in the abstract,

Enzyme- and Relative Humidity-Responsive Antimicrobial Fibers for Active Food Packaging by Zeynep Aytac, Jie Xu, Suresh Kumar Raman Pillai, Brian D. Eitzer, Tao Xu, Nachiket Vaze, Kee Woei Ng, Jason C. White, Mary B. Chan-Park, Yaguang Luo, and Philip Demokritou. ACS Appl. Mater. Interfaces 2021, 13, 42, 50298–50308 I: https://doi.org/10.1021/acsami.1c12319 Publication Date: October 14, 2021 Copyright © 2021 American Chemical Society

This paper is behind a paywall.

Excerpt from abstract,

Active food packaging materials that are sustainable, biodegradable, and capable of precise delivery of antimicrobial active ingredients (AIs) are in high demand. Here, we report the development of novel enzyme- and relative humidity (RH)-responsive antimicrobial fibers with an average diameter of 225 ± 50 nm, which can be deposited as a functional layer for packaging materials. Cellulose nanocrystals (CNCs) [emphasis mine], zein (protein), and starch were electrospun to form multistimuli-responsive fibers that incorporated a cocktail of both free nature-derived antimicrobials such as thyme oil, citric acid, and nisin and cyclodextrin-inclusion complexes (CD-ICs) of thyme oil, sorbic acid, and nisin. …

I have been following the CNC story for some time. If you’re curious, just use ‘cellulose nanocrystal(s)’ as your search term. You can find out more about ComCrop here.

Council of Canadian Academies (CCA) Appoints Expert Panel on International Science and Technology Partnerships

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Now the Council of Canadian Academies (CCA) has announced its expert panel for the “International Science and Technology Partnership Opportunities” project, I offer my usual guess analysis of the connections between the members of the panle.

This project first was mentioned in my March 2, 2022 posting, scroll down to the “Council of Canadian Academies launches four projects” subhead. One comment before launching into the expert panel, the word innovation, which you’ll see in the announcement, is almost always code for commercialization, business and/or entrepreneurship.

A May 9, 2022 CCA news release (received via email) announced the members of expert panel,

CCA Appoints Expert Panel on International Science and Technology Partnerships

May 9, 2022 – Ottawa, ON

Canada has numerous opportunities to pursue beneficial international partnerships focused on science, technology, and innovation (STI), but finite resources to support them. At the request of Global Affairs Canada, the Council of Canadian Academies (CCA) has formed an Expert Panel to examine best practices and identify key elements of a rigorous, data-enabled approach to selecting international STI partnership opportunities. Monica Gattinger, Director of the Institute for Science, Society and Policy at the University of Ottawa, will serve as Chair of the Expert Panel.

“International STI partnerships can be crucial to advancing Canada’s interests, from economic growth to public health, sustainability, and security,” said Dr. Gattinger. “I look forward to leading this important assessment and working with panel members to develop clear, comprehensive and coherent approaches for evaluating partnership opportunities.”

As Chair, Dr. Gattinger will lead a multidisciplinary group with expertise in science diplomacy, global security, economics and trade, international research collaboration, and program evaluation. The Panel will answer the following question:

In a post-COVID world, how can Canadian public, private and academic organizations evaluate and prioritize STI partnership opportunities with foreign countries to achieve key national objectives, using indicators supported by objective data where possible?

“I’m delighted that an expert of Dr. Gattinger’s experience and knowledge has agreed to chair this panel,” said Eric M. Meslin, PhD, FRSC, FCAHS, President and CEO of the CCA. “I look forward to the report’s findings for informing the use of international partnerships in science, technology, and innovation.”

More information can be found here.

The Expert Panel on International Science and Technology Partnerships:

Monica Gattinger (Chair), Director of the Institute for Science, Society and Policy at the University of Ottawa

David Audretsch, Distinguished Professor; Ameritech Chair of Economic Development; Director, Institute for Development Strategies, Indiana University

Stewart Beck, Distinguished Fellow, Asia Pacific Foundation of Canada

Paul Arthur Berkman, Faculty Associate, Program on Negotiation, Harvard Law School, and Associate Director, Science Diplomacy Centre, Harvard-MIT Public Disputes Program, Harvard University; Associated Fellow, United Nations Institute for Training and Research

Karen Croteau, Partner, Goss Gilroy

Paul Dufour, Principal, PaulicyWorks

Meredith Lilly, Associate Professor, Simon Reisman Chair in International Economic Policy, Norman Paterson School of International Affairs, Carleton University [located in Ottawa]

David Perry, President, Canadian Global Affairs Institute

Peggy Van de Plassche, Managing Partner, Roar Growth

Caroline S. Wagner, Professor, John Glenn College of Public Affairs, The Ohio State University

Jennifer M. Welsh, Professor; Canada 150 Research Chair in Global Governance and Security; Director, Centre for International Peace and Security Studies, McGill University

Given the discussion of pronouns and identification, I note that the panel of 11 experts includes six names commonly associated with women and five names commonly associated with men, which suggests some of the gender imbalance (male/female) I’ve noticed in the past is not present in the makeup of this panel.

There are three ‘international’ members and all are from the US. Based on past panels, international members tend to be from the US or the UK or, occasionally, from Australia or Europe.

Geographically, we have extraordinarily high representation (Monica Gattinger, David Perry, Meredith Lilly, Paul Dufour, and Karen Croteau) from people who are linked to Ottawa, Ontario, either educated or working at the University of Ottawa or Carleton University. (Thank goodness; it’s not as if the nation’s capital dominates almost every discussion about Canada. Ottawa, represent!)

As usual, there is no Canadian representing the North. This seems a bit odd given the very high international interest in the Arctic regions.

Ottawa connections

Here are some of the links (that I’ve been able to find) to Ottawa,

Monica Gattinger (from her Institute of Governance profile page),

…

Dr. Gattinger is an award-winning researcher and highly sought-after speaker, adviser and media commentator in the energy and arts/cultural [emphasis mine] policy sectors….

Gattinger is Fellow at the Canadian Global Affairs Institute, … She holds a Ph.D. in public policy from Carleton University. [emphases mine]

You’ll note David Perry is president of the Canadian Global Affairs Institute and Meredith Lilly is currently at Carleton University.

Perry is a professor at the University of Calgary where the Canadian Global Affairs Institute is headquartered (and it has offices in Ottawa). Here’s more from Perry’s institute profile page,

… He received his PhD in political science from Carleton University [emphasis mine] where his dissertation examined the link between defence budgeting and defence procurement. He is an adjunct professor at the Centre for Military and Strategic Studies at the University of Calgary and a research fellow of the Centre for the Study of Security and Development at Dalhousie University. …

Paul Dufour also has an Ottawa connection, from his 2017 CCA profile page,

Paul Dufour is a Fellow and Adjunct Professor at the Institute for Science, Society and Policy in the University of Ottawa [emphasis mine] and science policy Principal with PaulicyWorks in Gatineau, Québec. He is on the Board of Directors of the graduate student led Science Policy Exchange based in Montréal [emphasis mine], and is [a] member of the Investment Committee for Grand Challenges Canada.

Paul Dufour has been senior advisor in science policy with several Canadian agencies and organizations over the course of the past 30 years. Among these: Senior Program Specialist with the International Development Research Centre, and interim Executive Director at the former Office of the National Science Advisor to the Canadian Government advising on international S&T matters and broad questions of R&D policy directions for the country.

Born in Montréal, Mr. Dufour was educated at McGill University [emphasis mine], the Université de Montréal, and Concordia University in the history of science and science policy, …

…

Role: Steering Committee Member

Report: Science Policy: Considerations for Subnational Governments (April 2017)

Finally, there’s Karen Croteau a partner at Goss Gilroy. Here’s more from her LinkedIn profile page,

A seasoned management consultant professional and Credentialed Evaluator with more than 18 years experience in a variety of areas including: program evaluation, performance measurement, organizational/ resource review, benefit/cost analysis, reviews of regulatory management programs, organizational benchmarking, business case development, business process improvement, risk management, change management and project/ program management.

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Experience

Partner

Goss Gilroy Inc

Jul 2019 – Present 2 years 11 months

Ottawa, Ontario [emphasis mine]

…

Education

Carleton University [emphasis mine]

Carleton University [emphasis mine]
Master’s Diploma Public Policy and Program Evaluation

The east coast

I think of Toronto, Ottawa, and Montréal as a kind of East Coast triangle.

Interestingly, Jennifer M. Welsh is at McGill University in Montréal where Paul Dufour was educated.

Representing the third point, Toronto, is Peggy Van de Plassche (judging by her accent in her YouTube videos, she’s from France), from her LinkedIn profile page,

I am a financial services and technology expert, corporate director, business advisor, investor, entrepreneur, and public speaker, fluent in French and English.

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Prior to starting Roar Growth, I led innovation for CIBC [Canadian Imperial Bank of Commerce], allocated several billions of capital to technology projects on behalf of CGI and BMO [Bank of Montreal], managed a European family office, and started 2 Fintechs.

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Education

Harvard Business School [emphasis mine]

Executive Education – Investment

IÉSEG School of Management [France]

Master of Science (MSc) – Business Administration and Management, General

…

IÉSEG School of Management

Bachelor of Business Administration (BBA) – Accounting and Finance

…

I didn’t find any connections to the Ottawa or Montréal panel members but I was mildly interested to see that one of the US members Paul Arthur Berkman is from Harvard University. Otherwise, Van de Plassche stands mostly alone.

The last of my geographical comments

David Perry manages to connect Alberta via his adjunct professorship at the University of Calgary, Ottawa (as noted previously) and Nova Scotia via his fellowship at Dalhousie University.

In addition to Montréal and the ever important Québec connection, Jennifer M. Welsh could be said to connect another prairie province while adding a little more international flair to this panel (from her McGill University profile page,

Professor Jennifer M. Welsh is the Canada 150 Research Chair in Global Governance and Security at McGill University (Montreal, Canada). She was previously Professor and Chair in International Relations at the European University Institute (Florence, Italy) [emphasis mine] and Professor in International Relations at the University of Oxford, [emphasis mine] where she co-founded the Oxford Institute for Ethics, Law and Armed Conflict. From 2013-2016, she served as the Special Adviser to the UN Secretary General, Ban Ki-moon, on the Responsibility to Protect.

… She has a BA from the University of Saskatchewan (Canada),[emphasis mine] and a Masters and Doctorate from the University of Oxford (where she studied as a Rhodes Scholar).

…

Stewart Beck seems to be located in Vancouver, Canada which gives the panel one West Coast connection, here’s more from his LinkedIn profile page,

As a diplomat, a trade commissioner, and a policy expert, I’ve spent the last 40 years as one of the foremost advocates of Canada’s interests in the U.S. and Asia. From 2014 to 2021 (August), I was the President and CEO of the Asia Pacific Foundation of Canada [APF] [emphasis mine], Canada’s leading research institution on Asia. Under my leadership, the organization added stakeholder value through applied research and as a principal convener on Asia topics, a builder of enviable networks of public and private sector stakeholders, and a leader of conversations on crucial regional issues. Before joining APF Canada, I led a distinguished 30+ year career with Canada’s diplomatic corps. With postings in the U.S. and Asia, culminating with an assignment as Canada’s High Commissioner to India (Ambassador) [emphasis mine], I gained the knowledge and experience to be one of Canada’s recognized experts on Asia and innovation policy. Along the way, I also served in many senior foreign policy and trade positions, including as Canada’s most senior trade and investment development official, Consul General to Shanghai [emphasis mine]and Consul General to San Francisco. Today, Asia is vitally critical to Canada’s economic security, both financially and technologically. Applying my understanding and navigating the challenging geopolitical, economic, and trade environment is the value I bring to strategic conversations on the region. An established network of senior private and public sector officials in Canada and Asia complements the experience I’ve gained over the many years living and working in Asia.

He completed undergraduate and graduate degrees at Queen’s University in Ontario and, given his career in diplomacy, I expect there are many Ottawa connections.

David Audretsch and Caroline S. Wagner of Indiana University and Ohio State University, respectively, are a little unusual. Most of the time, US members are from the East Coast or the West Coast not from one of the Midwest states.

One last comment about Paul Arthur Berkman, his profile page on the Harvard University website reveals unexpected polar connections,

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Fulbright Arctic Chair [emphasis mine] 2021-2022, United States Department of State and Norwegian Ministry of Foreign Affairs

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Paul Arthur Berkman is science diplomat, polar explorer and global thought leader applying international, interdisciplinary and inclusive processes with informed decisionmaking to balance national interests and common interests for the benefit of all on Earth across generations. Paul wintered in Antarctica [emphasis mine] when he was twenty-two, SCUBA diving throughout the year under the ice, and then taught a course on science into policy as a Visiting Professor at the University of California Los Angeles the following year, visiting all seven continents before the age of thirty.

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Hidden diversity

While the panel is somewhat Ottawa-centric with a strong bias towards the US and Europe, there are some encouraging signs.

Beck’s experience in Asia and Berkman’s in the polar regions is good to see. Dufour has written the Canada chapter in two (2015 and 2021) UNESCO Science Reports and offers an excellent overview of the Canadian situation within a global context in the 2021 edition (I haven’t had the time to view the 2015 report).

Economist Audretsch and FinTech entrepreneur Van de Plassche, offer academic and practical perspectives for ‘innovation’ while Perry and Welsh both offer badly needed (Canada has been especially poor in this area; see below) security perspectives.

The rest of the panel offers what you’d expect, extensive science policy experience. I hope Gattinger’s experience with arts/cultural policy will enhance this project.

This CCA project comes at a time when Canada is looking at establishing closer links to the European Union’s science programmes as per my May 11, 2022 posting: Canada’s exploratory talks about joining the European Union’s science funding programme (Horizon Europe).

This project also comes at about the same time the Canadian federal government announced in its 2022 federal budget (covered in my April 19, 2022 posting, scroll down about 25% of the way; you’ll recognize the subhead) a new Canadian investment and Innovation Agency.

Notes on security

Canada has stumbled more than once in this area.The current war waged by Russia in Ukraine offers one of the latest examples of how state actors can wage damage not just in the obvious physical sense but also with cyberattacks. The US suffered a notable attack in May 2021 which forced the shutdown of a major gas pipeline (May 9, 2021 NBC news report).

As for Canada, there is a July 9, 2014 Canadian Broadcasting Corporation news report about a cyberattack on the National Research Council (NRC),

A “highly sophisticated Chinese state-sponsored actor” recently managed to hack into the computer systems at Canada’s National Research Council, according to Canada’s chief information officer, Corinne Charette.

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For its part, the NRC says in a statement released Tuesday morning that it is now attempting to rebuild its computer infrastructure and this could take as much a year.

The NRC works with private businesses to advance and develop technological innovations through science and research.

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This is not the first time the Canadian government has fallen victim to a cyberattack that seems to have originated in China — but it is the first time the Canadian government has unequivocally blamed China for the attack.

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In September 2021 an announcement was made about a new security alliance where Canada was not included (from my September 17, 2021 posting),

Wednesday, September 15, 2021 an announcement of a new alliance in the Indo-Pacific region, the Three Eyes (Australia, UK, and US or AUKUS) was made.

Interestingly all three are part of the Five Eyes intelligence alliance comprised of Australia, Canada, New Zealand, UK, and US. Hmmm … Canada and New Zealand both border the Pacific and last I heard, the UK is still in Europe.

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I mention other security breaches such as the Cameron Ortis situation and the Winnipeg-based National Microbiology Lab (NML), the only level 4 lab in Canada in the September 17, 2021 posting under the ‘What is public safety?’ subheading.

It seems like there might be some federal movement on the issues assuming funding for “Securing Canada’s Research from Foreign Threats” in the 2022 federal budget actually appears. It’s in my April 19, 2022 posting about 45% of the way down under the subheading Research security.

I wish the panel good luck.

Update on Charles Lieber (former Harvard professor) has been convicted

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That was quick. Lieber went on trial Tuesday, December 14, 2021 and he was found guilty of two charges one week later on Tuesday, December 21, 2021. (You can see my December 20, 2021 posting for mention of the trial and a description of the events leading up to it.)

As for the conviction, here’s more from a December 23, 2021 posting by Brian Liu and Raquel Leslie for the Law Fare blog (Note: Links have been removed),

The Justice Department announced on Tuesday [December 21, 2921] that Charles Lieber, former chair of Harvard’s Chemistry and Chemical Biology Department, was convicted by a federal jury in connection with his ties to China’s Thousand Talents Program. Lieber was convicted for failing to report income and making false statements to authorities regarding his affiliation with the Wuhan University of Technology (WUT). The conviction is a significant chapter in the story of the department’s China Initiative, which has recently come under fire by groups who allege that the program has led to racial profiling and amounts to prosecutorial overreach. 

The jury convicted Lieber of knowingly and willfully making a materially false statement to federal authorities regarding his work with China’s Thousand Talents Program. The program, launched in 2008, began with the aim of reversing brain drain by enticing Chinese scientists overseas to return to China. Over time, the program evolved to also recruit foreigners with expertise in key technologies. The program provided Lieber with $50,000 a month to work at WUT, in addition to up to $150,000 in living expenses and more than $1.5 million in grants. Though it is not illegal to participate in Chinese recruitment programs, federal prosecutors alleged that Lieber had failed to report these payments as required of scientists receiving federal funding.

This is why Lieber’s prosecution is such a big deal (from the December 23, 2021 posting),

Lieber was seen by some as a potential Nobel Prize winner [emphasis mine] for his work in nanotechnology. Nanotechnology, the manipulation of materials at a near-atomic level, is a strategically important field with civilian and military application in medicine, green energy, computing and propulsion. In 2012, China’s Academy of Sciences launched a Strategic Pioneering Programme dedicated to nanotechnology research, investing one billion yuan ($152 million) over five years. As a result of the investment, China now ranks first worldwide for the number of patents and articles published on nanotechnology.

Both Liu and Leslie are JD (Juris Doctor) candidates (JD is an advanced law degree) at Yale Law School. Their posting is well worth reading in its entirety as they go on to discuss China and US tensions with regard to science and technology advancements. They also provide links to further commentaries at the end of their posting.

At this point (given limited information and from my admittedly amateur perspective), it looks more like a tax evasion case than anything else.

Charles Lieber, nanoscientist, and the US Dept. of Justice

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Charles Lieber, professor at Harvard University and one of the world’s leading researchers in nanotechnology went on trial on Tuesday, December 14, 2021.

Accused of hiding his ties to a People’s Republic of China (PRC)-run recruitment programme, Lieber is probably the highest profile academic and one of the few who was not born in China or has familial origins in China to be charged under the auspices of the US Department of Justice’s ‘China Initiative’.

This US National Public Radio (NPR) December 14, 2021 audio excerpt provides a brief summary of the situation by Ryan Lucas,

A December 14, 2021 article by Jess Aloe, Eileen Guo, and Antonio Regalado for the Massachusetts Institute of Technology (MIT) Technology Review lays out the situation in more detail (Note: A link has been removed),

In January of 2020, agents arrived at Harvard University looking for Charles Lieber, a renowned nanotechnology researcher who chaired the school’s department of chemistry and chemical biology. They were there to arrest him on charges of hiding his financial ties with a university in China. By arresting Lieber steps from Harvard Yard, authorities were sending a loud message to the academic community: failing to disclose such links is a serious crime.

Now Lieber is set to go on trial beginning December 14 [2021] in federal court in Boston. He has pleaded not guilty, and hundreds of academics have signed letters of support. In fact, some critics say it’s the Justice Department’s China Initiative—a far-reaching effort started in 2018 to combat Chinese economic espionage and trade-secret theft—that should be on trial, not Lieber. They are calling the prosecutions fundamentally flawed, a witch hunt that misunderstands the open-book nature of basic science and that is selectively destroying scientific careers over financial misdeeds and paperwork errors without proof of actual espionage or stolen technology.

For their part, prosecutors believe they have a tight case. They allege that Lieber was recruited into China’s Thousand Talents Plan—a program aimed at attracting top scientists—and paid handsomely to establish a research laboratory at the Wuhan University of Technology, but hid the affiliation from US grant agencies when asked about it (read a copy of the indictment here). Lieber is facing six felony charges: two counts of making false statements to investigators, two counts of filing a false tax return, and two counts of failing to report a foreign bank account. [emphases mine; Note: None of these charges have been proved in court]

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The case against Lieber could be a bellwether for the government, which has several similar cases pending against US professors alleging that they didn’t disclose their China affiliations to granting agencies.

As for the China Initiative (from the MIT Technology Review December 14, 2021 article),

The China Initiative was announced in 2018 by Jeff Sessions, then the Trump administration’s attorney general, as a central component of the administration’s tough stance toward China.

An MIT Technology Review investigation published earlier this month [December 2021] found that the China Initiative is an umbrella for various types of prosecutions somehow connected to China, with targets ranging from a Chinese national who ran a turtle-smuggling ring to state-sponsored hackers believed to be behind some of the biggest data breaches in history. In total, MIT Technology Review identified 77 cases brought under the initiative; of those, a quarter have led to guilty pleas or convictions, but nearly two-thirds remain pending.

The government’s prosecution of researchers like Lieber for allegedly hiding ties to Chinese institutions has been the most controversial, and fastest-growing, aspect of the government’s efforts. In 2020, half of the 31 new cases brought under the China Initiative were cases against scientists or researchers. These cases largely did not accuse the defendants of violating the Economic Espionage Act.

… hundreds of academics across the country, from institutions including Stanford University and Princeton University,signed a letter calling on Attorney General Merrick Garland to end the China Initiative. The initiative, they wrote, has drifted from its original mission of combating Chinese intellectual-property theft and is instead harming American research competitiveness by discouraging scholars from coming to or staying in the US.

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Lieber’s case is the second [emphasis mine] China Initiative prosecution of an academic to end up in the courtroom. The only previous person to face trial [emphasis mine] on research integrity charges, University of Tennessee–Knoxville professor Anming Hu, was acquitted of all charges [emphasis mine] by a judge in June [2021] after a deadlocked jury led to a mistrial.

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Ken Dilanian wrote an October 19, 2021 article for (US) National Broadcasting Corporation’s (NBC) news online about Hu’s eventual acquittal and about the China Inititative (Note: Dilanian’s timeline for the acquittal differs from the timeline in the MIT Technology Review),

The federal government brought the full measure of its legal might against Anming Hu, a nanotechnology expert at the University of Tennessee.

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But the Justice Department’s efforts to convict Hu as part of its program to crack down on illicit technology transfer to China failed — spectacularly. A judge acquitted him last month [September 2021] after a lengthy trial offered little evidence of anything other than a paperwork misunderstanding, according to local newspaper coverage. It was the second trial, after the first ended in a hung jury.

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“The China Initiative has turned up very little by way of clear espionage and the transfer of genuinely strategic information to the PRC,” said Robert Daly, a China expert at the Wilson Center, referring to the country by its formal name, the People’s Republic of China. “They are mostly process crimes, disclosure issues. A growing number of voices are calling for an end to the China initiative because it’s seen as discriminatory.”

The China Initiative began under President Donald Trump’s attorney general, Jeff Sessions, in 2018. But concerns about Chinese espionage in the United States — and the transfer of technology to China through business and academic relationships — are bipartisan.

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John Demers, who departed in June [2021] as head of the Justice Department’s National Security Division, said in an interview that the problem of technology transfer at universities is real. But he said he also believes conflict of interest and disclosure rules were not rigorously enforced for many years. For that reason, he recommended an amnesty program offering academics with undisclosed foreign ties a chance to come clean and avoid penalties. So far, the Biden administration has not implemented such a program.

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When I first featured the Lieber case in a January 28, 2020 posting I was more focused on the financial elements,

ETA January 28, 2020 at 1645 hours: I found a January 28, 2020 article by Antonio Regalado for the MIT Technology Review which provides a few more details about Lieber’s situation,

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Big money: According to the charging document, Lieber, starting in 2011,  agreed to help set up a research lab at the Wuhan University of Technology and “make strategic visionary and creative research proposals” so that China could do cutting-edge science.

He was well paid for it. Lieber earned a salary when he visited China worth up to $50,000 per month, as well as $150,000 a year in expenses in addition to research funds. According to the complaint, he got paid by way of a Chinese bank account but also was known to send emails asking for cash instead.

Harvard eventually wised up to the existence of a Wuhan lab using its name and logo, but when administrators confronted Lieber, he lied and said he didn’t know about a formal joint program, according to the government complaint.

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This is messy not least because Lieber and the members of his Harvard lab have done some extraordinary work as per my November 15, 2019 (Human-machine interfaces and ultra-small nanoprobes) posting about injectable electronics.

Tough colour and the flower beetle

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The flower beetle Torynorrhina flammea. [downloaded from https://www.nanowerk.com/nanotechnology-news2/newsid=58269.php]

That is one gorgeous beetle and a June 17, 2021 news item on Nanowerk reveals that it features in a structural colour story (i.e, how structures rather than pigments create colour),

The unique mechanical and optical properties found in the exoskeleton of a humble Asian beetle has the potential to offer a fascinating new insight into how to develop new, effective bio-inspired technologies.

Pioneering new research by a team of international scientists, including Professor Pete Vukusic from the University of Exeter, has revealed a distinctive, and previously unknown property within the carapace of the flower beetle – a member of the scarab beetle family.

The study showed that the beetle has small micropillars within the carapace – or the upper section of the exoskeleton – that give the insect both strength and flexibility to withstand damage very effectively.

Crucially, these micropillars are incorporated into highly regular layering in the exoskeleton that concurrently give the beetle an intensely bright metallic colour appearance.

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A June 18, 2021 University of Exeter press release (also on EurekAlert but published June 17, 2021), delves further into the researchers’ new insights,

For this new study, the scientists used sophisticated modelling techniques to determine which of the two functions – very high mechanical strength or conspicuously bright colour – were more important to the survival of the beetle.

They found that although these micropillars do create a highly enhanced toughness of the beetle shell, they were most beneficial for optimising the scattering of coloured light that generates its conspicuous appearance.

The research is published this week in the leading journal, Proceedings of the National Academy of Sciences, PNAS.

Professor Vukusic, one of three leads of the research along with Professor Li at Virginia Tech and Professor Kolle at MIT [Massachusetts Institute of Technology], said: “The astonishing insights generated by this research have only been possible through close collaborative work between Virginia Tech, MIT, Harvard and Exeter, in labs that trailblaze the fields of materials, mechanics and optics. Our follow-up venture to make use of these bio-inspired principles will be an even more exciting journey.”.

The seeds of the pioneering research were sown more than 16 years ago as part of a short project created by Professor Vukusic in the Exeter undergraduate Physics labs. Those early tests and measurements, made by enthusiastic undergraduate students, revealed the possibility of intriguing multifunctionality.

The original students examined the form and structure of beetles’ carapce to try to understand the simple origin of their colour. They noticed for the first time, however, the presence of strength-inducing micropillars.

Professor Vukusic ultimately carried these initial findings to collaborators Professor Ling Li at Virginia Tech and Professor Mathias Kolle at Harvard and then MIT who specialise in the materials sciences and applied optics. Using much more sophisticated measurement and modelling techniques, the combined research team were also to confirm the unique role played by the micropillars in enhancing the beetles’ strength and toughness without compromising its intense metallic colour.

The results from the study could also help inspire a new generation of bio-inspired materials, as well as the more traditional evolutionary research.

By understanding which of the functions provides the greater benefit to these beetles, scientists can develop new techniques to replicate and reproduce the exoskeleton structure, while ensuring that it has brilliant colour appearance with highly effective strength and toughness.

Professor Vukusic added: “Such natural systems as these never fail to impress with the way in which they perform, be it optical, mechanical or in another area of function. The way in which their optical or mechanical properties appear highly tolerant of all manner of imperfections too, continues to offer lessons to us about scientific and technological avenues we absolutely should explore. There is exciting science ahead of us on this journey.”

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

Microstructural design for mechanical–optical multifunctionality in the exoskeleton of the flower beetle Torynorrhina flammea by Zian Jia, Matheus C. Fernandes, Zhifei Deng, Ting Yang, Qiuting Zhang, Alfie Lethbridge, Jie Yin, Jae-Hwang Lee, Lin Han, James C. Weaver, Katia Bertoldi, Joanna Aizenberg, Mathias Kolle, Pete Vukusic, and Ling Li. PNAS June 22, 2021 118 (25) e2101017118; DOI: https://doi.org/10.1073/pnas.2101017118

This paper is behind a paywall.

Follow up to the Charles M. Lieber affair and US government efforts to prosecute nanotech scientists

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Rebecca Trager in a March 5, 2021 news article for Chemistry World highlights support for Charles M. Lieber (Harvard professor and chair of the chemistry department) from his colleagues (Note: Links have been removed),

More than a year after the chair of Harvard University’s chemistry department was arrested for allegedly hiding his receipt of millions of dollars in research funding from China from his university and the US government, dozens of prominent researchers – including many Nobel Prize winners – are coming to Charles Lieber’s defence. They are calling the US Department of Justice (DOJ) case against him ‘unjust’ and urging the agency to drop it.

Following his January 2020 arrest, Lieber was placed on ‘indefinite’ paid administrative leave. The nanoscience pioneer was indicted in June [2020] on charges of making false statements to federal authorities regarding his participation in China’s Thousand Talents plan – the country’s programme to attract, recruit and cultivate high-level scientific talent from abroad. Lieber faces up to five years in prison and a fine of $250,000 (£179,000) if convicted.

A 1 March [2021] open letter, drafted and coordinated by Harvard chemist Stuart Schreiber, co-founder of the Broad Institute, and professor emeritus Elias Corey, winner of the 1990 chemistry Nobel prize, says Lieber became the target of a ‘tragically misguided government campaign’. The letter refers to Lieber as ‘one of the great scientist of his generation’ and warns such government actions are discouraging US scientists from collaborating with peers in other countries, particularly China. The open letter also notes that Lieber is fighting to salvage his reputation while suffering from incurable lymphoma.

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Ferguson goes on to contrast Lieber’s treatment by Harvard to another embattled colleague’s treatment by his home institution (Note: Links have been removed),

Harvard’s treatment of Lieber stands in contrast to how the Massachusetts Institute of Technology (MIT) handled the more recent case of nanotechnologist Gang Chen, who was arrested in January [2021] for failing to report his ties to the Chinese government. MIT agreed to cover his legal fees, and more than 100 faculty members signed a letter to their university’s president that picked apart the DOJ’s allegations against Chen.

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I have more details about the case against Lieber (as it was presented at the time) in a January 28, 2020 posting.

As for Professor Chen, I found this MIT statement dated January 14, 2021 (the date of his arrest) and this January 14, 2021 statement from The United States District Attorney’s Office District of Massachusetts.

Precision targeting of the liver for gene editing

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Apparently the magic is in the lipid nanoparticles. A March 1, 2021 news item on Nanowerk announced research into lipid nanoparticles as a means to deliver CRISPR (clustered regularly interspaced short palindromic repeats) to specific organs (Note: A link has been removed),

The genome editing technology CRISPR has emerged as a powerful new tool that can change the way we treat disease. The challenge when altering the genetics of our cells, however, is how to do it safely, effectively, and specifically targeted to the gene, tissue and organ that needs treatment.

Scientists at Tufts University and the Broad Institute of Harvard [University] and MIT [Massachusetts Institute of Technology] have developed unique nanoparticles comprised of lipids — fat molecules — that can package and deliver gene editing machinery specifically to the liver.

In a study published in the Proceedings of the National Academy of Sciences [PNAS] (“Lipid nanoparticle-mediated codelivery of Cas9 mRNA and single-guide RNA achieves liver-specific in vivo genome editing of Angptl3”), they have shown that they can use the lipid nanoparticles (LNPs) to efficiently deliver the CRISPR machinery into the liver of mice, resulting in specific genome editing and the reduction of blood cholesterol levels by as much as 57% — a reduction that can last for at least several months with just one shot.

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A March 2, 2021 Tufts University news release (also on EurekAlert but published March 1, 2021), which originated the news item, provides greater insight into and technical detail about the research,

The problem of high cholesterol plagues more than 29 million Americans, according to the Centers for Disease Control and Prevention. The condition is complex and can originate from multiple genes as well as nutritional and lifestyle choices, so it is not easy to treat. The Tufts and Broad researchers, however, have modified one gene that could provide a protective effect against elevated cholesterol if it can be shut down by gene editing.

The gene that the researchers focused on codes for the angiopoietin-like 3 enzyme (Angptl3). That enzyme tamps down the activity of other enzymes – lipases – that help break down cholesterol. If researchers can knock out the Angptl3 gene, they can let the lipases do their work and reduce levels of cholesterol in the blood. It turns out that some lucky people have a natural mutation in their Angptl3 gene, leading to consistently low levels of triglycerides and low-density lipoprotein (LDL) cholesterol, commonly called “bad” cholesterol, in their bloodstream without any known clinical downsides.

“If we can replicate that condition by knocking out the angptl3 gene in others, we have a good chance of having a safe and long term solution to high cholesterol,” said Qiaobing Xu, associate professor of biomedical engineering at Tufts’ School of Engineering and corresponding author of the study. “We just have to make sure we deliver the gene editing package specifically to the liver so as not to create unwanted side effects.”

Xu’s team was able to do precisely that in mouse models. After a single injection of lipid nanoparticles packed with mRNA coding for CRISPR-Cas9 and a single-guide RNA targeting Angptl3, they observed a profound reduction in LDL cholesterol by as much as 57% and triglyceride levels by about 29 %, both of which remained at those lowered levels for at least 100 days. The researchers speculate that the effect may last much longer than that, perhaps limited only by the slow turnover of cells in the liver, which can occur over a period of about a year. The reduction of cholesterol and triglycerides is dose dependent, so their levels could be adjusted by injecting fewer or more LNPs in the single shot, the researchers said.

By comparison, an existing, FDA [US Food and Drug Administration]-approved version of CRISPR mRNA-loaded LNPs could only reduce LDL cholesterol by at most 15.7% and triglycerides by 16.3% when it was tested in mice, according to the researchers.

The trick to making a better LNP was in customizing the components – the molecules that come together to form bubbles around the mRNA. The LNPs are made up of long chain lipids that have a charged or polar head that is attracted to water, a carbon chain tail that points toward the middle of the bubble containing the payload, and a chemical linker between them. Also present are polyethylene glycol, and yes, even some cholesterol – which has a normal role in lipid membranes to make them less leaky – to hold their contents better.

The researchers found that the nature and relative ratio of these components appeared to have profound effects on the delivery of mRNA into the liver, so they tested LNPs with many combinations of heads, tails, linkers and ratios among all components for their ability to target liver cells. Because the in vitro potency of an LNP formulation rarely reflects its in vivo performance, they directly evaluated the delivery specificity and efficacy in mice that have a reporter gene in their cells that lights up red when genome editing occurs. Ultimately, they found a CRISPR mRNA-loaded LNP that lit up just the liver in mice, showing that it could specifically and efficiently deliver gene-editing tools into the liver to do their work.

The LNPs were built upon earlier work at Tufts, where Xu and his team developed LNPs with as much as 90% efficiency in delivering mRNA into cells. A unique feature of those nanoparticles was the presence of disulfide bonds between the long lipid chains. Outside the cells, the LNPs form a stable spherical structure that locks in their contents. When they are inside a cell, the environment within breaks the disulfide bonds to disassemble the nanoparticles. The contents are then quickly and efficiently released into the cell. By preventing loss outside the cell, the LNPs can have a much higher yield in delivering their contents.

“CRISPR is one of the most powerful therapeutic tools for the treatment of diseases with a genetic etiology. We have recently seen the first human clinical trail for CRISPR therapy enabled by LNP delivery to be administered systemically to edit genes inside the human body. Our LNP platform developed here holds great potential for clinical translation,” said Min Qiu, post-doctoral researcher in Xu’s lab at Tufts.  “We envision that with this LNP platform in hand, we could now make CRISPR a practical and safe approach to treat a broad spectrum of liver diseases or disorders,” said Zachary Glass, graduate student in the Xu lab. Qiu and Glass are co-first authors of the study.

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

Lipid nanoparticle-mediated codelivery of Cas9 mRNA and single-guide RNA achieves liver-specific in vivo genome editing of Angptl3 by Min Qiu, Zachary Glass, Jinjin Chen, Mary Haas, Xin Jin, Xuewei Zhao, Xuehui Rui, Zhongfeng Ye, Yamin Li, Feng Zhang, and Qiaobing Xu. PNAS March 9, 2021 118 (10) e2020401118 DOI: https://doi.org/10.1073/pnas.2020401118

This paper appears to be behind a paywall.