Category Archives: medicine

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.

CRISPR/Cas9 as a tool for artists (Art/sci Salon January 2018 events in Toronto, Canada) and an event in Winnipeg, Canada

The Art/Sci Salon in Toronto, Canada is offering a workshop and a panel discussion (I think) on the topic of CRISPR( (clustered regularly interspaced short palindromic repeats)/Cas9.

CRISPR Cas9 Workshop with Marta De Menezes

From its Art/Sci Salon event page (on Eventbrite),

This is a two day intensive workshop on

Jan. 24 5:00-9:00 pm
and
Jan. 25 5:00-9:00 pm

This workshop will address issues pertaining to the uses, ethics, and representations of CRISPR-cas9 genome editing system; and the evolution of bioart as a cultural phenomenon . The workshop will focus on:

1. Scientific strategies and ethical issues related to the modification of organisms through the most advanced technology;

2. Techniques and biological materials to develop and express complex concepts into art objects.

This workshop will introduce knowledge, methods and living material from the life sciences to the participants. The class will apply that novel information to the creation of art. Finally, the key concepts, processes and knowledge from the arts will be discussed and related to scientific research. The studio-­‐lab portion of the course will focus on the mastering and understanding of the CRISPR – Cas9 technology and its revolutionary applications. The unparalleled potential of CRISPR ‐ Cas9 for genome editing will be directly assessed as the participants will use the method to make artworks and generate meaning through such a technique. The participants will be expected to complete one small project by the end of the course. In developing and completing these projects, participants will be asked to present their ideas/work to the instructors and fellow participants. As part of the course, participants are expected to document their work/methodology/process by keeping a record of processes, outcomes, and explorations.

This is a free event. Go here to register.

Do CRISPR monsters dream of synthetic futures?

This second event in Toronto seems to be a panel discussion; here’s more from its Art/Sci Salon event page (on Eventbrite),

The term CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) refers to a range of novel gene editing systems which can be programmed to edit DNA at precise locations. It allows the permanent modification of the genes in cells of living organisms. CRISPR enables novel basic research and promises a wide range of possible applications from biomedicine and agriculture to environmental challenges.

The surprising simplicity of CRISPR and its potentials have led to a wide range of reactions. While some welcome it as a gene editing revolution able to cure diseases that are currently fatal, others urge for a worldwide moratorium, especially when it comes to human germline modifications. The possibility that CRISPR may allow us to intervene in the evolution of organisms has generated particularly divisive thoughts: is gene editing going to cure us all? Or is it opening up a new era of designer babies and new types of privileges measured at the level of genes? Could the relative easiness of the technique allow individuals to modify bodies, identities, sexuality, to create new species and races? will it create new monsters? [emphasis mine] These are all topics that need to be discussed. With this panel/discussion, we wish to address technical, ethical, and creative issues arising from the futuristic scenarios promised by CRISPR.

Our Guests:

Marta De Menezes, Director, Cultivamos Cultura

Dalila Honorato, Assistant Professor, Ionian University

Mark Lipton, Professor, University of Guelph

Date: January 26, 2018

Time: 6:00-8:00 pm

Location: The Fields Institute for Research in Mathematical Sciences
222 College Street, Toronto, ON

Events Facilitators: Roberta Buiani and Stephen Morris (ArtSci Salon) and Nina Czegledy (Leonardo Network)

Bios:

Marta de Menezes is a Portuguese artist (b. Lisbon, 1975) with a degree in Fine Arts by the University in Lisbon, a MSt in History of Art and Visual Culture by the University of Oxford, and a PhD candidate at the University of Leiden. She has been exploring the intersection between Art and Biology, working in research laboratories demonstrating that new biological technologies can be used as new art medium. Her work has been presented internationally in exhibitions, articles and lectures. She is currently the artistic director of Ectopia, an experimental art laboratory in Lisbon, and Director of Cultivamos Cultura in the South of Portugal. http://martademenezes.com

Dalila Honorato, Ph.D., is currently Assistant Professor in Media Aesthetics and Semiotics at the Ionian University in Greece where she is one of the founding members of the Interactive Arts Lab. She is the head of the organizing committee of the conference “Taboo-Transgression-Transcendence in Art & Science” and developer of the studies program concept of the Summer School in Hybrid Arts. She is a guest faculty at the PhD studies program of the Institutum Studiorum Humanitatis in Alma Mater Europaea, Slovenia, and a guest member of the Science Art Philosophy Lab integrated in the Center of Philosophy of Sciences of the University of Lisbon, Portugal. Her research focus is on embodiment in the intersection of performing arts and new media.

Mark Lipton works in the College of Arts; in the School of English and Theatre Studies, and Guelph’s Program in Media Studies. Currently, his work focuses on queering media ecological perspectives of technology’s role in education, with emerging questions about haptics and the body in performance contexts, and political outcomes of neo-liberal economics within Higher Education.

ArtSci Salon thanks the Fields Institute and the Bonham Center for Sexual Diversity Studies (U of T), and the McLuhan Centre for Culture and Technology for their support. We are grateful to the members of DIYBio Toronto and Hacklab for hosting Marta’s workshop.

This series of event is promoted and facilitated as part of FACTT Toronto

LASER – Leonardo Art Science Evening Rendezvous is a project of Leonardo® /ISAST (International Society for the Arts Sciences and Technology)

Go here to click on the Register button.

For anyone who didn’t recognize (or, like me, barely remembers what it means) the title’s reference is to a famous science fiction story by Philip K. Dick. Here’s more from the Do Androids Dream of Electric Sheep? Wikipedia entry (Note: Links have been removed),

Do Androids Dream of Electric Sheep? (retitled Blade Runner: Do Androids Dream of Electric Sheep? in some later printings) is a science fiction novel by American writer Philip K. Dick, first published in 1968. The novel is set in a post-apocalyptic San Francisco, where Earth’s life has been greatly damaged by nuclear global war. Most animal species are endangered or extinct from extreme radiation poisoning, so that owning an animal is now a sign of status and empathy, an attitude encouraged towards animals. The book served as the primary basis for the 1982 film Blade Runner, and many elements and themes from it were used in its 2017 sequel Blade Runner 2049.

The main plot follows Rick Deckard, a bounty hunter who is tasked with “retiring” (i.e. killing) six escaped Nexus-6 model androids, while a secondary plot follows John Isidore, a man of sub-par IQ who aids the fugitive androids. In connection with Deckard’s mission, the novel explores the issue of what it is to be human. Unlike humans, the androids are said to possess no sense of empathy.

I wonder why they didn’t try to reference Orphan Black (its Wikipedia entry)? That television series was all about biotechnology. If not Orphan Black, what about a Frankenstein reference? It’s the 200th anniversary this year (2018) of the publication of the book which is the forerunner to all the cautionary tales that have come after.

Nano- and neuro- together for nanoneuroscience

This is not the first time I’ve posted about nanotechnology and neuroscience (see this April 2, 2013 piece about then new brain science initiative in the US and Michael Berger’s  Nanowerk Spotlight article/review of an earlier paper covering the topic of nanotechnology and neuroscience).

Interestingly, the European Union (EU) had announced its two  $1B Euro research initiatives, the Human Brain Project and the Graphene Flagship (see my Jan. 28, 2013 posting about it),  months prior to the US brain research push. For those unfamiliar with the nanotechnology effort, graphene is a nanomaterial and there is high interest in its potential use in biomedical technology, thus partially connecting both EU projects.

In any event, Berger is highlighting a nanotechnology and neuroscience connection again in his Oct. 18, 2017 Nanowerk Spotlight article, or overview of, a new paper, which updates our understanding of the potential connections between the two fields (Note: A link has been removed),

Over the past several years, nanoscale analysis tools and in the design and synthesis of nanomaterials have generated optical, electrical, and chemical methods that can readily be adapted for use in neuroscience and brain activity mapping.

A review paper in Advanced Functional Materials (“Nanotechnology for Neuroscience: Promising Approaches for Diagnostics, Therapeutics and Brain Activity Mapping”) summarizes the basic concepts associated with neuroscience and the current journey of nanotechnology towards the study of neuron function by addressing various concerns on the significant role of nanomaterials in neuroscience and by describing the future applications of this emerging technology.

The collaboration between nanotechnology and neuroscience, though still at the early stages, utilizes broad concepts, such as drug delivery, cell protection, cell regeneration and differentiation, imaging and surgery, to give birth to novel clinical methods in neuroscience.

Ultimately, the clinical translation of nanoneuroscience implicates that central nervous system (CNS) diseases, including neurodevelopmental, neurodegenerative and psychiatric diseases, have the potential to be cured, while the industrial translation of nanoneuroscience indicates the need for advancement of brain-computer interface technologies.

Future Developing Arenas in Nanoneuroscience

The Brain Activity Map (BAM) Project aims to map the neural activity of every neuron across all neural circuits with the ultimate aim of curing diseases associated with the nervous system. The announcement of this collaborative, public-private research initiative in 2013 by President Obama has driven the surge in developing methods to elucidate neural circuitry. Three current developing arenas in the context of nanoneuroscience applications that will push such initiative forward are 1) optogenetics, 2) molecular/ion sensing and monitoring and 3) piezoelectric effects.

In their review, the authors discuss these aspects in detail.

Neurotoxicity of Nanomaterials

By engineering particles on the scale of molecular-level entities – proteins, lipid bilayers and nucleic acids – we can stereotactically interface with many of the components of cell systems, and at the cutting edge of this technology, we can begin to devise ways in which we can manipulate these components to our own ends. However, interfering with the internal environment of cells, especially neurons, is by no means simple.

“If we are to continue to make great strides in nanoneuroscience, functional investigations of nanomaterials must be complemented with robust toxicology studies,” the authors point out. “A database on the toxicity of materials that fully incorporates these findings for use in future schema must be developed. These databases should include information and data on 1) the chemical nature of the nanomaterials in complex aqueous environments; 2) the biological interactions of nanomaterials with chemical specificity; 3) the effects of various nanomaterial properties on living systems; and 4) a model for the simulation and computation of possible effects of nanomaterials in living systems across varying time and space. If we can establish such methods, it may be possible to design nanopharmaceuticals for improved research as well as quality of life.”

“However, challenges in nanoneuroscience are present in many forms, such as neurotoxicity; the inability to cross the blood-brain barrier [emphasis mine]; the need for greater specificity, bioavailability and short half-lives; and monitoring of disease treatment,” the authors conclude their review. “The nanoneurotoxicity surrounding these nanomaterials is a barrier that must be overcome for the translation of these applications from bench-to-bedside. While the challenges associated with nanoneuroscience seem unending, they represent opportunities for future work.”

I have a March 26, 2015 posting about Canadian researchers breaching the blood-brain barrier and an April 13, 2016 posting about US researchers at Cornell University also breaching the blood-brain barrier. Perhaps the “inability” mentioned in this Spotlight article means that it can’t be done consistently or that it hasn’t been achieved on humans.

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

Nanotechnology for Neuroscience: Promising Approaches for Diagnostics, Therapeutics and Brain Activity Mapping by Anil Kumar, Aaron Tan, Joanna Wong, Jonathan Clayton Spagnoli, James Lam, Brianna Diane Blevins, Natasha G, Lewis Thorne, Keyoumars Ashkan, Jin Xie, and Hong Liu. Advanced Functional Materials Volume 27, Issue 39, October 19, 2017 DOI: 10.1002/adfm.201700489 Version of Record online: 14 AUG 2017

© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

I took a look at the authors’ information and found that most of these researchers are based in  China and in the UK, with a sole researcher based in the US.

Nanopatch more effective with poliovirus

No more needles or syringes that’s the Nanopatch promise and its one I’ve been writing about since 2009. It seems 2017 marks another step closer to seeing this idea become a product. From an Oct. 5, 2017 news item on ScienceDaily,

Efforts to rid the world of polio have taken another significant step, thanks to research led by University of Queensland [UQ] bioscience experts and funding from the World Health Organisation (WHO).

A fresh study of the Nanopatch — a microscopic vaccine delivery platform first developed by UQ researchers — has shown the device more effectively combats poliovirus than needles and syringes.

Here’s a prototype,

Caption: This is an image of the intended commercial product. Credit: Courtesy Vaxxas Pty Ltd

An Oct. 5, 2017 University of Queensland press release (also on EurekAlert), which originated the news item, provides more detail (Note: Links have been removed),

Head of UQ’s School of Chemistry and Molecular Biosciences Professor Paul Young said the breakthrough provided the next step in consigning polio to history.

“Polio was one of the most dreaded childhood diseases of the 20th century, resulting in limb disfigurement and irreversible paralysis in tens of millions of cases,” Professor Young said.

“This most recent study showed the Nanopatch enhanced responses to all three types of inactivated poliovirus vaccines (IPV) – a necessary advancement from using the current live oral vaccine.

“We are extremely grateful to the WHO for providing funding to Vaxxas Pty Ltd, the biotechnology company commercialising the Nanopatch.

“The support specifically assists pre-clinical studies and good manufacturing practices.”

Patch inventor Professor Mark Kendall said the study exhibited a key advantage of the Nanopatch.

“It targets the abundant immune cell populations in the skin’s outer layers, rather than muscle, resulting in a more efficient vaccine delivery system,” Professor Kendall said.

“The ease of administration, coupled with dose reduction observed in this study suggests that the Nanopatch could facilitate inexpensive vaccination of inactivated poliovirus vaccines.”

UQ Australian Institute for Biotechnology and Nanotechnology researcher Dr David Muller said effectively translating the dose could dramatically reduce the cost.

“A simple, easy-to-administer polio Nanopatch vaccine could increase the availability of the IPV vaccine and facilitate its administration in door-to-door and mass vaccination campaigns,” said Dr Muller.

“As recently as 1988, more than 350,000 cases occurred every year in more than 125 endemic countries.

“Concerted efforts to eradicate the disease have reduced incidence by more than 99 per cent.”

“Efforts are being intensified to eradicate the remaining strains of transmission once and for all.”

Data from the study encourages efforts by Vaxxas – established by UQ’s commercialisation company UniQuest – to bring the technology to use for human vaccinations.

“The research we are undertaking in conjunction with UQ and WHO can improve the reach of life-saving vaccines to children everywhere,” Vaxxas chief executive officer David Hoey said.

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

High-density microprojection array delivery to rat skin of low doses of trivalent inactivated poliovirus vaccine elicits potent neutralising antibody responses by David A. Muller, Germain J. P. Fernando, Nick S. Owens, Christiana Agyei-Yeboah, Jonathan C. J. Wei, Alexandra C. I. Depelsenaire, Angus Forster, Paul Fahey, William C. Weldon, M. Steven Oberste, Paul R. Young, & Mark A. F. Kendall. Scientific Reports 7, Article number: 12644 (2017) doi:10.1038/s41598-017-13011-0 Published online: 03 October 2017

This paper is open access.

Should you be interested in seeing previous posts, just use ‘Nanopatch’ as your search term in the blog search engine.

Tracks of my tears could power smartphone?

So far the researchers aren’t trying to power anything with tears but they have discovered that tears could be used to generate electricity (from an Oct. 2, 2017 news item on phys.org),

A team of Irish scientists has discovered that applying pressure to a protein found in egg whites and tears can generate electricity. The researchers from the Bernal Institute, University of Limerick (UL), Ireland, observed that crystals of lysozyme, a model protein that is abundant in egg whites of birds as well as in the tears, saliva and milk of mammals can generate electricity when pressed. Their report is published today (October 2) in the journal, Applied Physics Letters.

An Oct. 2, 2017 University of Limerick press release (also on EurekAlert), which originated the news item, offers additional detail,

The ability to generate electricity by applying pressure, known as direct piezoelectricity, is a property of materials such as quartz that can convert mechanical energy into electrical energy and vice versa. Such materials are used in a variety of applications ranging from resonators and vibrators in mobile phones to deep ocean sonars and ultrasound imaging. Bone, tendon and wood are long known to possess piezoelectricity.

“While piezoelectricity is used all around us, the capacity to generate electricity from this particular protein had not been explored. The extent of the piezoelectricity in lysozyme crystals is significant. It is of the same order of magnitude found in quartz. However, because it is a biological material, it is non toxic so it could have many innovative applications such as electroactive anti-microbial coatings for medical implants,” explained Aimee Stapleton, the lead author and an Irish Research Council EMBARK Postgraduate Fellow in the Department of Physics and Bernal Institute of UL.

Crystals of lysozyme are easy to make from natural sources. “The high precision structure of lysozyme crystals has been known since 1965,” said structural biologist at UL and co-author Professor Tewfik Soulimane.
“In fact, it is the second protein structure and the first enzyme structure that was ever solved,” he added, “but we are the first to use these crystals to show the evidence of piezoelectricity”.

According to team leader Professor Tofail Syed of UL’s Department of Physics, “Crystals are the gold-standard for measuring piezoelectricity in non-biological materials. Our team has shown that the same approach can be taken in understanding this effect in biology. This is a new approach as scientists so far have tried to understand piezoelectricity in biology using complex hierarchical structures such as tissues, cells or polypeptides rather than investigating simpler fundamental building blocks”.

The discovery may have wide reaching applications and could lead to further research in the area of energy harvesting and flexible electronics for biomedical devices. Future applications of the discovery may include controlling the release of drugs in the body by using lysozyme as a physiologically mediated pump that scavenges energy from its surroundings. Being naturally biocompatible and piezoelectric, lysozyme may present an alternative to conventional piezoelectric energy harvesters, many of which contain toxic elements such as lead.

Professor Luuk van der Wielen, Director of Bernal Institute and Bernal Professor of Biosystems Engineering and Design expressed his delight at this breakthrough by UL scientists.

“The €109-million Bernal Institute has the ambition to impact the world on the basis of top science in an increasingly international context. The impact of this discovery in the field of biological piezoelectricity will be huge and Bernal scientists are leading from the front the progress in this field,” he said.

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

The direct piezoelectric effect in the globular protein lysozyme featured by A. Stapleton, M. R. Noor, J. Sweeney, V. Casey, A. L. Kholkin, C. Silien, A. A. Gandhi, T. Soulimane, and S. A. M. Tofail. Appl. Phys. Lett. 111, 142902 (2017); doi: http://dx.doi.org/10.1063/1.4997446

This paper is open access.

As for Tracks of My Tears,

Llama-derived nanobodies are good for solving crystal structure

This work comes from Denmark, not a locale I associate with llamas (from an Oct. 2, 2017 news item on Nanowerk; Note: A link has been removed),

Aarhus University [Denmark] scientists have developed miniature antibodies (nanobodies) that can be labelled on certain amino acids (Acta Crystallographica Section D, “Introducing site-specific cysteines into nanobodies for mercury labelling allows de novo phasing of their crystal structures”).

This provides a direct route for solving new X-ray crystal structures of protein complexes important for gaining mechanistic understanding of cellular processes, which is important in the development of drugs.

An Oct. 2, 2017 Aarhus University press release on EurekAlert, which originated the news item, provides more detail,

Nanobodies are miniature antibodies derived from naturally circulating heavy-chain only antibodies in llamas. Over the past years, nanobodies and their applications have expanded enormously, both in basic research but also in drug development.

Nanobodies have proven to be well suited as protein stabilizers, which is particularly important during crystallization of a protein where millions of molecules have to arrange in a well-defined lattice. In this way, nanobodies can act as crystallization chaperones.

In an X-ray diffraction experiment, a critical piece of information – called the phases – is lost, which makes it difficult to determine new crystal structures. To overcome this phase problem in crystallography, heavy atoms are needed in the crystal. However, it is challenging to insert heavy atoms into a crystal. The scientists at Aarhus University used a nanobody as the vehicle for introducing mercury atoms. They developed a method to site-specifically label the nanobody with a heavy atom, and in this way, they could overcome the phase problem.

Since the scientists know which specific residues in the nanobodies can be modified and labelled, the technique used at Aarhus University opens for a range of other application. One exciting perspective is the insertion of fluorescent dyes into the nanobody to follow the location and distribution of target proteins in living organisms, which can give essential information on functional and regulatory processes.

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

Introducing site-specific cysteines into nanobodies for mercury labelling allows de novo phasing of their crystal structures by S. B. Hansen, N. S. Laursen, G. R. Andersen and K. R. Andersen. Acta Cryst. (2017). D73 https://doi.org/10.1107/S2059798317013171

This paper is open access.

Here’s an image illustrating the work,

Caption: Nanobodies have proven to be well suited as protein stabilizers, which is particularly important during crystallization of a protein where millions of molecules have to arrange in a well-defined lattice. Credit: Kasper Røjkjær Andersen

Popping (nano)bubbles!

Who doesn’t love to pop bubbles? Well, there’s probably someone out there but it does seem to be a near universal delight (especially with the advent of bubble wrap which I’ve seen more than one person happily popping). Scientists are no more immune to that impulse than the rest of us although they approach the whole endeavour from a more technical perspective where popping bubbles becomes destabilization and bubble rupture. From a Sept. 28, 2017 American Institute of Physics (AIP) news release (also on EurekAlert),

Nanobubbles have recently gained popularity for their unique properties and expansive applications. Their large surface area and high stability in saturated liquids make nanobubbles ideal candidates for food science, medicine and environmental advancements. Nanobubbles also have long lifetimes of hours or days, and greater applicability than traditional macrobubbles, which typically only last for seconds.

The stability of nanobubbles is well understood, but the mechanisms causing their eventual destabilization are still in question. Using molecular dynamics simulations (MDS), researchers from the Beijing University of Chemical Technology explored the effect of surfactants — components that lower surface tension — on the stabilization of nanobubbles. They report their findings on the surprising mechanisms of destabilization [emphasis mine] for both soluble and insoluble surfactants this week [Sept. 25-29, 2017] in Applied Physics Letters, from AIP Publishing.

Researchers investigated the differences between soluble and insoluble surfactants and their varying influence on nanobubble stability using MDS software. They created a controled model system where the only variables that could be manipulated were the number of surfactants and the interaction between the surfactant and the substrate, the base of the model where the bubble is formed, to measure the direct influence of surfactants on nanobubble stability.

Analyzing both soluble and insoluble surfactants, the group focused on two possible mechanisms of destabilization: contact line depinning, where the surfactant flexibility reduces the forces responsible for stabilizing the bubble shape, causing it to rupture from lack of inner surface force; and surface tension reduction, causing a liquid to vapor phase transition.

The found soluble surfactants initiated nanobubble depinning when a large amount, roughly 80 percent, of the surfactant was adsorbed by the substrate, eventually causing the nanobubbles to burst.

“However, when small concentrations of soluble surfactant were introduced it remained dissolved, and adsorption onto the substrate was insignificant, generating a negligible effect on nanobubble stability,” said Xianren Zhang at Beijing University of Chemical Technology.

Simulations with insoluble surfactants showed comparable results to soluble surfactants when interacting heavily with substrates, but a new mechanism was discovered demonstrating a liquid-to-vapor transition model of bubble rupture [emphasis mine].

The transition is similar to how we traditionally envision bubbles popping, occurring when a surfactant significantly reduces the surface tension on the outside of the nanobubble. Nanobubbles destabilize in this fashion when a large amount of surfactant is present, but little — around 40 percent — surfactant-substrate interaction occurs.

These findings are critical to understanding nanobubble stability and have implications for nanobubble interaction with other molecules, including proteins and contaminants. Nanobubble applications could revolutionize aspects of modern medicine such as ultrasound techniques, expand functions in food science, and improve waste water treatment. But better characterizing basic properties like instability is essential to fully utilizing their potential in these applications.

There researchers have made this image illustrating their work available,

Several typical snapshots for nanobubbles losing their stability with various concentrations of surfactants and levels of interaction with substrates. In each picture, top panel shows evolution of the system with all involved particles, while in the bottom panel, solvent molecules are not shown to clarify the effect of surfactants. CREDIT: Qianxiang Xiao, Yawei Liu, Zhenjiang Guo, Zhiping Liu, and Xianren Zhang

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

How nanobubbles lose stability: Effects of surfactants featured by Qianxiang Xiao, Yawei Liu, Zhenjiang Guo, Zhiping Liua, and Xianren Zhang. Appl. Phys. Lett. 111, 131601 (2017); doi: http://dx.doi.org/10.1063/1.5000831

This paper is open access.

Calligraphy ink and cancer treatment

Courtesy of ACS Omega and the researchers

Nice illustration! I wish I could credit the artist. For anyone who needs a little text to make sense of it, there’s a Sept. 27, 2017 news item on Nanowerk (Note: A link has been removed),

For hundreds of years, Chinese calligraphers have used a plant-based ink to create beautiful messages and art. Now, one group reports in ACS Omega (“New Application of Old Material: Chinese Traditional Ink for Photothermal Therapy of Metastatic Lymph Nodes”) that this ink could noninvasively and effectively treat cancer cells that spread, or metastasize, to lymph nodes.

A Sept. 27, 2017 American Chemical Society (ACS) news release, which originated the news item, reveals more about the research,

As cancer cells leave a tumor, they frequently make their way to lymph nodes, which are part of the immune system. In this case, the main treatment option is surgery, but this can result in complications. Photothermal therapy (PTT) is an emerging noninvasive treatment option in which nanomaterials are injected and accumulate in cancer cells. A laser heats up the nanomaterials, and this heat kills the cells. Many of these nanomaterials are expensive, difficult-to-make and toxic. However, a traditional Chinese ink called Hu-Kaiwen ink (Hu-ink) has similar properties to the nanomaterials used in PTT. For example, they are the same color, and are both carbon-based and stable in water. So Wuli Yang and colleagues wanted to see if Hu-ink could be a good alternative material for PTT.

The researchers analyzed Hu-ink and found that it consists of nanoparticles and thin layers of carbon. When Hu-ink was heated with a laser, its temperature rose by 131 degrees Fahrenheit, much higher than current nanomaterials. Under PPT conditions, the Hu-ink killed cancer cells in a laboratory dish, but under normal conditions, the ink was non-toxic. This was also the scenario observed in mice with tumors. The researchers also noted that Hu-ink could act as a probe to locate tumors and metastases because it absorbs near-infrared light, which goes through skin.

Being a little curious about Hu-ink’s similarity to nanomaterial, I looked for more detail in the the paper (Note: Links have been removed), From the: Introduction,

Photothermal therapy (PTT) is an emerging tumor treatment strategy, which utilizes hyperthermia generated from absorbed near-infrared (NIR) light energy by photoabsorbing agents to kill tumor cells.(7-13) Different from chemotherapy, surgical treatment, and radiotherapy, PTT is noninvasive and more efficient.(7, 14, 15) In the past decade, PTT with diverse nanomaterials to eliminate cancer metastases lymph nodes has attracted extensive attention by several groups, including our group.(3, 16-20) For instance, Liu and his co-workers developed a treatment method based on PEGylated single-walled carbon nanotubes for PTT of tumor sentinel lymph nodes and achieved remarkably improved treatment effect in an animal tumor model.(21) To meet the clinical practice, the potential metastasis of deeper lymph nodes was further ablated in our previous work, using magnetic graphene oxide as a theranostic agent.(22) However, preparation of these artificial nanomaterials usually requires high cost, complicated synthetic process, and unavoidably toxic catalyst or chemicals,(23, 24) which impede their future clinical application. For the clinical application, exploring an environment-friendly material with simple preparation procedure, good biocompatibility, and excellent therapeutic efficiency is still highly desired. [emphases mine]

From the: Preparation and Characterization of Hu-Ink

To obtain an applicable sample, the condensed Hu-ink was first diluted into aqueous dispersion with a lower concentration. The obtained Hu-ink dispersion without any further treatment was black in color and stable in physiological environment, including water, phosphate-buffered saline (PBS), and Roswell Park Memorial Institute (RPMI) 1640; furthermore, no aggregation was observed even after keeping undisturbed for 3 days (Figure 2a). The nanoscaled morphology of Hu-ink was examined by transmission electron microscopy (TEM) (Figure 2b), which demonstrates that Hu-ink mainly exist in the form of small aggregates. These small aggregates consist of a few nanoparticles with diameter of about 20–50 nm. Dynamic light scattering (DLS) measurement (Figure 2c) further shows that Hu-ink aqueous dispersion possesses a hydrodynamic diameter of about 186 nm (polydispersity index: 0.18), which was a crucial prerequisite for biomedical applications.(29) In the X-ray diffraction (XRD) pattern, no other characteristic peaks are found except carbon peak (Figure S1, Supporting Information), which confirms that the main component of Hu-ink is carbon.(25) Raman spectroscopy was a common tool to characterize graphene-related materials.(30) D band (∼1300 cm–1, corresponding to the defects) and G band (∼1600 cm–1, related to the sp2 carbon sites) peaks could be observed in Figure 2d with the ratio ID/IG = 0.96, which confirms the existence of graphene sheetlike structure in Hu-ink.(31) The UV–vis–NIR spectra (Figure 2e) also revealed that Hu-ink has high absorption in the NIR region around 650–900 nm, in which hemoglobin and water, the major absorbers of biological tissue, have their lowest absorption coefficient.(32) The high NIR absorption capability of Hu-ink encouraged us to investigate its photothermal properties.(33-35) Hu-ink dispersions with different concentrations were irradiated under an 808 nm laser (the commercial and widely used wavelength in photothermal therapy).(8-13) [emphases mine]

Curiosity satisfied! For those who’d like to investigate even further, here’s a link to and a citation for the paper,

New Application of Old Material: Chinese Traditional Ink for Photothermal Therapy of Metastatic Lymph Nodes by Sheng Wang, Yongbin Cao, Qin Zhang, Haibao Peng, Lei Liang, Qingguo Li, Shun Shen, Aimaier Tuerdi, Ye Xu, Sanjun Cai, and Wuli Yang. ACS Omega, 2017, 2 (8), pp 5170–5178 DOI: 10.1021/acsomega.7b00993 Publication Date (Web): August 30, 2017

Copyright © 2017 American Chemical Society

This paper appears to be open access.

Could CRISPR (clustered regularly interspaced short palindromic repeats) be weaponized?

On the occasion of an American team’s recent publication of research where they edited the germline (embryos), I produced a three-part series about CRISPR (clustered regularly interspaced short palindromic repeats), sometimes referred to as CRISPR/Cas9, (links offered at end of this post).

Somewhere in my series, there’s a quote about how CRISPR could be used as a ‘weapon of mass destruction’ and it seems this has been a hot topic for the last year or so as James Revill, research fellow at the University of Sussex, references in his August 31, 2017 essay on theconversation.com (h/t phys.org August 31, 2017 news item), Note: Links have been removed,

The gene editing technique CRISPR has been in the limelight after scientists reported they had used it to safely remove disease in human embryos for the first time. This follows a “CRISPR craze” over the last couple of years, with the number of academic publications on the topic growing steadily.

There are good reasons for the widespread attention to CRISPR. The technique allows scientists to “cut and paste” DNA more easily than in the past. It is being applied to a number of different peaceful areas, ranging from cancer therapies to the control of disease carrying insects.

Some of these applications – such as the engineering of mosquitoes to resist the parasite that causes malaria – effectively involve tinkering with ecosystems. CRISPR has therefore generated a number of ethical and safety concerns. Some also worry that applications being explored by defence organisations that involve “responsible innovation in gene editing” may send worrying signals to other states.

Concerns are also mounting that gene editing could be used in the development of biological weapons. In 2016, Bill Gates remarked that “the next epidemic could originate on the computer screen of a terrorist intent on using genetic engineering to create a synthetic version of the smallpox virus”. More recently, in July 2017, John Sotos, of Intel Health & Life Sciences, stated that gene editing research could “open up the potential for bioweapons of unimaginable destructive potential”.

An annual worldwide threat assessment report of the US intelligence community in February 2016 argued that the broad availability and low cost of the basic ingredients of technologies like CRISPR makes it particularly concerning.

A Feb. 11, 2016 news item on sciencemagazine.org offers a précis of some of the reactions while a February 9, 2016 article by Antonio Regalado for the Massachusetts Institute of Technology’s MIT Technology Review delves into the matter more deeply,

Genome editing is a weapon of mass destruction.

That’s according to James Clapper, [former] U.S. director of national intelligence, who on Tuesday, in the annual worldwide threat assessment report of the U.S. intelligence community, added gene editing to a list of threats posed by “weapons of mass destruction and proliferation.”

Gene editing refers to several novel ways to alter the DNA inside living cells. The most popular method, CRISPR, has been revolutionizing scientific research, leading to novel animals and crops, and is likely to power a new generation of gene treatments for serious diseases (see “Everything You Need to Know About CRISPR’s Monster Year”).

It is gene editing’s relative ease of use that worries the U.S. intelligence community, according to the assessment. “Given the broad distribution, low cost, and accelerated pace of development of this dual-use technology, its deliberate or unintentional misuse might lead to far-reaching economic and national security implications,” the report said.

The choice by the U.S. spy chief to call out gene editing as a potential weapon of mass destruction, or WMD, surprised some experts. It was the only biotechnology appearing in a tally of six more conventional threats, like North Korea’s suspected nuclear detonation on January 6 [2016], Syria’s undeclared chemical weapons, and new Russian cruise missiles that might violate an international treaty.

The report is an unclassified version of the “collective insights” of the Central Intelligence Agency, the National Security Agency, and half a dozen other U.S. spy and fact-gathering operations.

Although the report doesn’t mention CRISPR by name, Clapper clearly had the newest and the most versatile of the gene-editing systems in mind. The CRISPR technique’s low cost and relative ease of use—the basic ingredients can be bought online for $60—seems to have spooked intelligence agencies.

….

However, one has to be careful with the hype surrounding new technologies and, at present, the security implications of CRISPR are probably modest. There are easier, cruder methods of creating terror. CRISPR would only get aspiring biological terrorists so far. Other steps, such as growing and disseminating biological weapons agents, would typically be required for it to become an effective weapon. This would require additional skills and places CRISPR-based biological weapons beyond the reach of most terrorist groups. At least for the time being.

A July 5, 2016 opinion piece by Malcolm Dando for Nature argues for greater safeguards,

In Geneva next month [August 2016], officials will discuss updates to the global treaty that outlaws the use of biological weapons. The 1972 Biological Weapons Convention (BWC) was the first agreement to ban an entire class of weapons, and it remains a crucial instrument to stop scientific research on viruses, bacteria and toxins from being diverted into military programmes.

The BWC is the best route to ensure that nations take the biological-weapons threat seriously. Most countries have struggled to develop and introduce strong and effective national programmes — witness the difficulty the United States had in agreeing what oversight system should be applied to gain-of-function experiments that created more- dangerous lab-grown versions of common pathogens.

As scientific work advances — the CRISPR gene-editing system has been flagged as the latest example of possible dual-use technology — this treaty needs to be regularly updated. This is especially important because it has no formal verification system. Proposals for declarations, monitoring visits and inspections were vetoed by the United States in 2001, on the grounds that such verification threatened national security and confidential business information.

Even so, issues such as the possible dual-use threat from gene-editing systems will not be easily resolved. But we have to try. Without the involvement of the BWC, codes of conduct and oversight systems set up at national level are unlikely to be effective. The stakes are high, and after years of fumbling, we need strong international action to monitor and assess the threats from the new age of biological techniques.

Revill notes the latest BWC agreement and suggests future directions,

This convention is imperfect and lacks a way to ensure that states are compliant. Moreover, it has not been adequately “tended to” by its member states recently, with the last major meeting unable to agree a further programme of work. Yet it remains the cornerstone of an international regime against the hostile use of biology. All 178 state parties declared in December of 2016 their continued determination “to exclude completely the possibility of the use of (biological) weapons, and their conviction that such use would be repugnant to the conscience of humankind”.

These states therefore need to address the hostile potential of CRISPR. Moreover, they need to do so collectively. Unilateral national measures, such as reasonable biological security procedures, are important. However, preventing the hostile exploitation of CRISPR is not something that can be achieved by any single state acting alone.

As such, when states party to the convention meet later this year, it will be important to agree to a more systematic and regular review of science and technology. Such reviews can help with identifying and managing the security risks of technologies such as CRISPR, as well as allowing an international exchange of information on some of the potential benefits of such technologies.

Most states supported the principle of enhanced reviews of science and technology under the convention at the last major meeting. But they now need to seize the opportunity and agree on the practicalities of such reviews in order to prevent the convention being left behind by developments in science and technology.

Experts (military, intelligence, medical, etc.) are not the only ones concerned about CRISPR according to a February 11, 2016 article by Sharon Begley for statnews.com (Note: A link has been removed),

Most Americans oppose using powerful new technology to alter the genes of unborn babies, according to a new poll — even to prevent serious inherited diseases.

They expressed the strongest disapproval for editing genes to create “designer babies” with enhanced intelligence or looks.

But the poll, conducted by STAT and Harvard T.H. Chan School of Public Health, found that people have mixed, and apparently not firm, views on emerging genetic techniques. US adults are almost evenly split on whether the federal government should fund research on editing genes before birth to keep children from developing diseases such as cystic fibrosis or Huntington’s disease.

“They’re not against scientists trying to improve [genome-editing] technologies,” said Robert Blendon, professor of health policy and political analysis at Harvard’s Chan School, perhaps because they recognize that one day there might be a compelling reason to use such technologies. An unexpected event, such as scientists “eliminating a terrible disease” that a child would have otherwise inherited, “could change people’s views in the years ahead,” Blendon said.

But for now, he added, “people are concerned about editing the genes of those who are yet unborn.”

A majority, however, wants government regulators to approve gene therapy to treat diseases in children and adults.

The STAT-Harvard poll comes as scientists and policy makers confront the ethical, social, and legal implications of these revolutionary tools for changing DNA. Thanks to a technique called CRISPR-Cas9, scientists can easily, and with increasing precision, modify genes through the genetic analog of a computer’s “find and replace” function.

I find it surprising that there’s resistance to removing diseases found in the germline (embryos). When they were doing public consultations on nanotechnology, the one area where people tended to be quite open to research was health and medicine. Where food was concerned however, people had far more concerns.

If you’re interested in the STAT-Harvard poll, you can find it here. As for James Revill, he has written a more substantive version of this essay as a paper, which is available here.

On a semi-related note, I found STAT (statnews.com) to be a quite interesting and accessibly written online health science journal. Here’s more from the About Us page (Note: A link has been removed),

What’s STAT all about?
STAT is a national publication focused on finding and telling compelling stories about health, medicine, and scientific discovery. We produce daily news, investigative articles, and narrative projects in addition to multimedia features. We tell our stories from the places that matter to our readers — research labs, hospitals, executive suites, and political campaigns.

Why did you call it STAT?
In medical parlance, “stat” means important and urgent, and that’s what we’re all about — quickly and smartly delivering good stories. Read more about the origins of our name here.

Who’s behind the new publication?
STAT is produced by Boston Globe Media. Our headquarters is located in Boston but we have bureaus in Washington, New York, Cleveland, Atlanta, San Francisco, and Los Angeles. It was started by John Henry, the owner of Boston Globe Media and the principal owner of the Boston Red Sox. Rick Berke is executive editor.

So is STAT part of The Boston Globe?
They’re distinct properties but the two share content and complement one another.

Is it free?
Much of STAT is free. We also offer STAT Plus, a premium subscription plan that includes exclusive reporting about the pharmaceutical and biotech industries as well as other benefits. Learn more about it here.

Who’s working for STAT?
Some of the best-sourced science, health, and biotech journalists in the country, as well as motion graphics artists and data visualization specialists. Our team includes talented writers, editors, and producers capable of the kind of explanatory journalism that complicated science issues sometimes demand.

Who’s your audience?
You. Even if you don’t work in science, have never stepped foot in a hospital, or hated high school biology, we’ve got something for you. And for the lab scientists, health professionals, business leaders, and policy makers, we think you’ll find coverage here that interests you, too. The world of health, science, and medicine is booming and yielding fascinating stories. We explore how they affect us all.

….

As promised, here are the links to my three-part series on CRISPR,

Part 1 opens the series with a basic description of CRISPR and the germline research that occasioned the series along with some of the other (non-weapon) ethical issues and patent disputes that are arising from this new technology. CRISPR and editing the germline in the US (part 1 of 3): In the beginning

Part 2 covers three critical responses to the reporting and between them describe the technology in more detail and the possibility of ‘designer babies’.  CRISPR and editing the germline in the US (part 2 of 3): ‘designer babies’?

Part 3 is all about public discussion or, rather, the lack of and need for according to a couple of social scientists. Informally, there is some discussion via pop culture and Joelle Renstrom notes although she is focused on the larger issues touched on by the television series, Orphan Black and as I touch on in my final comments. CRISPR and editing the germline in the US (part 3 of 3): public discussions and pop culture

Finally, I hope to stumble across studies from other countries about how they are responding to the possibilities presented by CRISPR/Cas9 so that I can offer a more global perspective than this largely US perspective. At the very least, it would be interesting to find it if there differences.

What helps you may hurt you (titanium dioxide nanoparticles and orthopedic implants)

From a Sept. 16, 2017 news item on Nanotechnology Now,

Researchers from the Mayo Clinic have proposed that negative cellular responses to titanium-based nanoparticles released from metal implants interfere in bone formation and resorption at the site of repair, resulting in implant loosening and joint pain. [emphasis mine]Their review of recent scientific evidence and call for further research to characterize the biological, physical, and chemical interactions between titanium dioxide nanoparticles and bone-forming cells is published in BioResearch Open Access, a peer-reviewed open access journal from Mary Ann Liebert, Inc., publishers. The article is available free on theBioResearch Open Access website.

A Sept. 14, 2017 Mary Anne Liebert (Publishing) news release, which originated the news item,  mentions the authors,

Jie Yao, Eric Lewallen, PhD, David Lewallen, MD, Andre van Wijnen, PhD, and colleagues from the Mayo Clinic, Rochester, MN and Second Affiliated Hospital of Soochow University, China, coauthored the article entitled “Local Cellular Responses to Titanium Dioxide from Orthopedic Implants The authors examined the results of recently published studies of titanium-based implants, focusing on the direct and indirect effects of titanium dioxide nanoparticles on the viability and behavior of multiple bone-related cell types. They discuss the impact of particle size, aggregation, structure, and the specific extracellular and intracellular (if taken up by the cells) effects of titanium particle exposure.

“The adverse effects of metallic orthopedic particles generated from implants are of significant clinical interest given the large number of procedures carried out each year. This article reviews our current understanding of the clinical issues and highlights areas for future research,” says BioResearch Open Access Editor Jane Taylor, PhD, MRC Centre for Regenerative Medicine, University of Edinburgh, Scotland.

Before getting to the abstract, here’s a link to and a citation for the paper,

Local Cellular Responses to Titanium Dioxide from Orthopedic Implants by Yao, Jie J.; Lewallen, Eric A.; Trousdale, William H.; Xu, Wei; Thaler, Roman; Salib, Christopher G.; Reina, Nicolas; Abdel, Matthew P.; Lewallen, David G.; and van Wijnenm, Andre J.. BioResearch Open Access. July 2017, 6(1): 94-103. https://doi.org/10.1089/biores.2017.0017 Published July 1, 2017

This paper is open access.